The ability to predict the skin sensitization potential of small organic molecules is of high importance to the development and safe application of cosmetics, drugs and pesticides. One of the most widely accepted methods for predicting this hazard is the rodent local lymph node assay (LLNA). The goal of this work was to develop in silico models for the prediction of the skin sensitization potential of small molecules that go beyond the state of the art, with larger LLNA data sets and, most importantly, a robust and intuitive definition of the applicability domain, paired with additional indicators of the reliability of predictions. We explored a large variety of molecular descriptors and fingerprints in combination with random forest and support vector machine classifiers. The most suitable models were tested on holdout data, on which they yielded competitive performance (Matthews correlation coefficients up to 0.52; accuracies up to 0.76; areas under the receiver operating characteristic curves up to 0.83). The most favorable models are available via a public web service at https://nerdd.zbh.uni-hamburg.de/skinDoctor/ that, in addition to predictions, provides assessments of the applicability domain and indicators of the reliability of the individual predictions.

Finite element (FE) modeling is commonly used as a method to investigate the influence of medical devices, such as implants and screws and their effects on the biomechanical behavior of the spine. Another simulation method is a multi-body simulation (MBS), where the model is composed of several non-deformable bodies. MBS solvers generally require a very short computing time for dynamic tasks compared to an FE analysis. Considering this computational advantage, in this study, we examine whether parameters whose values are not known a priory can be determined with sufficient accuracy using MBS model. Therefore, we propose a Many-at-a-time sensitivity analysis method that allows approximating these a priory unknown parameters without requiring long simulation times. This method enables a high degree of MBS model optimization to be achieved in an iterative process. The sensitivity analysis method is applied to a simplified screw-vertebra model, consisting of an anterior anchor implant screw and vertebral body of C4. An experiment described in the literature is used as a basis for developing and assessing the potential of the method for sensitivity analysis and to validate the models action. The optimal model parameters for the MBS model were determined to be c=823224N/m for stiffness and d=488Ns/m for damping. The presented method of parameter identification can be used in studies including more complex MBS spine models or to set initial parameter values that are not available as initial values for FE models.

Input reconstruction problem is usually encountered in the areas such as virtual sensing, image restoration, sensor linearization, and communications. The input reconstruction problem can be seen as an inverse problem. Given a nominal system, two types of approaches are commonly used for solving the inverse problem. The first one is to directly invert the nominal system, and the second one is to derive an inversion of the nominal system in an indirect way. However, for the first type of approaches, system inversion cannot be directly conducted under some conditions such as there exist nonminimum-phase zeros in the nominal system, while for the second type of approaches, simultaneously guaranteeing stability and causality of the obtained inversion is still not solved well. In order to avoid the drawbacks existing in the two types of approaches, an alternative approach is proposed for input reconstruction. In this approach, the input signal is first modeled as the output of a state-space model, afterwards two Kalman filters for the model resulted by combining the input signal model and the nominal system model are implemented alternatively such that the input signal can be sequentially reconstructed in an infinite horizon. The proposed input reconstruction approach is applied in two examples, and simulation results can illustrate the effectiveness of the proposed approach.

Blood-derived products (BP) like citrate-platelet-rich plasma (CPRP) or hyperacute serum (HAS) are known to contain many growth factors. Combined mitogenic and DNA damaging stimuli might lead to increased senescent cell burden and altered senescence-associated secretory pheno-type (SASP). Therefore, the senescent state was extensively tested by γH2AX staining, p21 Q-PCR and western blot, growth curves and senescence associated ß-galactosidase staining. Two main treatments with BP were performed early (immediately after etoposide) and late (after addition-al 11days). Effects of the BP treatment was evaluated by IL-6 and IL-8 measurement as well as collagen (COL1) and p21 mRNA expression. Additionally, XTT assays, cell size measurements, viability assays, and cell number calculations were performed. HAS treated cells in early treat-ment had the lowest observed IL-6 and IL-8. In contrast, there was a clear inflammatory response for IL-8 on HAS and CPRP treated cells in late treatment. For COL1 expression an upregulation in early treatment could be shown, meanwhile cells in the late treatment group remained unaf-fected. In CPRP treated cells, the COL1 expression decreased. All in all, BP treatment seems to have slightly positive effects regarding skin rejuvenation.

The inverse system identification toolbox named INVSID 1.0 for MATLAB, which is used to identify the inversion of single-input single-output systems, is developed. The complete process of developing the toolbox is demonstrated. Afterwards, a numerical example is illustrated to describe how the toolbox can be used to solve inverse identification problems. Simulation results demonstrate the effectiveness of the toolbox.

SORL1 gene encodes LR11/SorLA, a protein that binds -amyloid precursor protein (bAPP) and drives its intracellular trafficking. SORL1 mutations occurring frequently in a subset of familial cases of Alzheimer’s disease (AD) have been documented but their pathogenic potential is not yet clear and questions remain concerning their putative influence on the physiopathological processing of bAPP. We have assessed the influence of three SORL1 mutations that were described as likely disease-causing and that were associated with either benign (SorLA924) or severe (SorLA141 and SorLA511) AD phenotypes. We examined the influence of wild-type and mutants SorLA in transiently transfected HEK293 cells expressing either wild-type or Swedish mutated bAPP on bAPP expression, secreted Ab and sAPPa levels, intracellular Ab40 and Ab42 peptides, APP-CTFs (C99 and C83) expressions, a-, b- and g-secretases expressions and activities as well as Ab and CTFs-degrading enzymes. These paradigms were studied in control conditions or after pharmacological proteasomal modulation. We also established stably transfected CHO cells expressing wild-type SorLA and established the colocalization of wild-type SorLA and bAPP. Overall, although we mostly confirmed previous data concerning the influence of wild-type SorLA on bAPP processing, we were unable to evidence significant alterations triggered by our set of SorLA mutants, whatever the cells or pharmacological conditions examined. Our study however does not rule out the possibility that other AD-linked SORL1 mutations could indeed affect bAPP processing and that pathogenic mutations examined in the present study could interfere with other cellular pathways/triggers in AD.

A key in controlling the SARS-CoV-2 pandemic is the assessment of the immune status of the population. We explored the utility of SARS-CoV-2 virus-like particles (VLPs) as antigens to detect specific humoral immune reactions in an enzyme-linked immunosorbent assay (ELISA). For this purpose, SARS-CoV-2 VLPs were produced from an engineered cell line and characterized by western blot, ELISA and nanoparticle tracking analysis. Subsequently, we collected 42 serum samples from before the pandemic (2014), 89 samples from healthy-, and 38 samples from vaccinated subjects. Seventeen samples were collected less than three weeks after infection, and 44 samples more than three weeks after infection. All serum samples were characterized for their reactivity with VLPs and the SARS-CoV-2 N- and S-protein. Finally, we compared the performance of the VLP-based ELISA with a certified in vitro diagnostic device (IVD). In the applied set of samples, we determined a sensitivity of 95.5 % and a specificity of 100 % for the certified IVD. There were 7 samples with an uncertain outcome. Our VLP-ELISA showed superior performance with a sensitivity of 97.5 %, a specificity of 100 %, and only 3 uncertain outcomes. This result warrants further research to develop a certified IVD based on SARS-CoV-2 VLPs as an antigen.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Different factors seemingly account for the emergence of present-day languages in our species. Human self-domestication has been recently invoked as one important force favouring language complexity mostly via a cultural mechanism. As a consequence, evolutionary changes impacting on aggression levels are expected to have fostered this process. Here we hypothesise about a positive effect of dog-human interactions on aggression management and more generally, on our self-domestication, ultimately, contributing to aspects of language evolution. We review evidence of diverse sort (ethological mostly, but also archaeological, genetic, and physiological) supporting a positive feedback loop between dog domestication and human-self domestication that might have favoured the mechanisms promoting structural complexity in human languages.

(1) Background: There is not much research about obesity in nursing homes although knowledge will help us to develop customized treatment plans and prevention strategies, which may help to decrease the burden for all persons involved. The objective of conducting this study was to describe the prevalence of obesity and the association between obesity and care problems in nursing home patients. (2) Methods: This study is a secondary data analysis of data collected in an annually performed cross-sectional study called “Nursing Quality Measurement 2.0”. A standardized and tested questionnaire was used to collect data. (3) Results: 1236 nursing home patients took part and 16.7% of them were obese. The multivariate logistic regression analysis results show that urinary incontinence is significantly associated with the presence of obesity (OR 2.111). The other care problems of pressure injuries, fecal and double incontinence, physical restraints, falls and pain were not associated with obesity. (4) Conclusion: The results indicate that, in the nursing home setting, health care staff should pay special attention to the patients’ nutritional and continence status and help patients maintain a normal, healthy weight. Conducting more studies with larger sample sizes is recommended, as this will allow differentiation among different obesity classes.

The sustainable management of water scarcity is a global crucial issue. Germany has es- tablished efficient water management systems, but the agricultural sector still struggles with water scarcity as the demand surpasses the available water supply. The primary aim is to establish a framework for making water accessible for irrigation and additional use on households through the effective utilization of recycled water from wastewater treatment facilities. The research inquiries are focused on evaluating the changes in the agricultural irrigation model in CROPWAT, determining the spatial distribution of zonal severity, estimating the capacity of urban roof catchments, and evaluating the reduction volume of efficient water required from the existing wastewater treatment plant supply. According to the findings, the annual amount of water required for agriculture in the designated study location is approximately 2.9 million m3. Although there is no initial need for irrigation water, yet the demand for irrigation water increases during the development, active growth, and mature stages of maize, winter wheat, and wine grapes, reaching around 189mm, 225mm, and 62mm, respectively. According to our observation, the annual water supply in Weinstadt is around 4 million m3. On the other hand, the amount of water calculated from urban roof rainfall is estimated 0.8 million m3, which is considered valuable from an economic standpoint. This economically efficient volume of water would reduce the current treated water supply passes an opportunity for enhanced agricultural irrigation

A geometric Planck-scale model of quantum electrodynamics is tested against observations. Based on Dirac’s proposal to describe spin 1/2 particles as tethered objects, elementary fermions are conjectured to be fluctuating rational tangles with unobservable tethers. As Battey-Pratt and Racey showed, when such tangles propagate, they obey the free Dirac equation. Classifying rational tangles yields the observed spectrum of elementary fermions. Classifying deformations of tangle cores yields exactly three types of gauge interactions. They exchange three types of elementary gauge bosons and have the symmetry groups U(1), broken SU(2) and SU(3). The possible rational tangles for fermions, Higgs and gauge bosons allow only the observed Feynman diagrams. The complete Lagrangian of the standard model arises, including the Lagrangian of quantum electrodynamics. Over 50 tests of the tangle model are deduced. They include details on the perturbation expansion of the g-factor and the existence of limit values for electric and magnetic fields. Measurements agree with most tests, though this could change in the future. Some tests are genuine predictions that still need to be checked. In particular, the geometry of the process occurring at QED interaction vertices suggests an ab-initio estimate for the fine structure constant. In addition, the average geometric shapes of the elementary particle tangles suggest ab-initio lower and upper limits for the mass values of the electron and the other leptons.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment - surgery, radiation, and chemotherapy - on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.

Extracorporeal shock wave therapy (ESWT) is a well investigated and widely used treatment modality for a number of musculoskeletal disorders. A limitation of ESWT is its potential painfulness at higher, clinically relevant energy flux density (EFD), which may limit its applicability and, thus, effectiveness. Various studies in the literature demonstrated that neither application of a higher number of extracorporeal shock waves with lower EFD nor use of local anesthesia may solve this problem. Based on the results of several other studies in the literature it is hypothesized here that in patients suffering from musculoskeletal disorders that can be treated with ESWT, pretreatment with a pulsed, high power laser with a wavelength of 904 or 905 nanometers (hereafter: "laser pretreatment") does not only allow to apply higher EFDs in subsequent ESWT but actually results in faster and/or better treatment outcome than ESWT without laser pretreatment. Accordingly, it is hypothesized here that combining ESWT with laser pretreatment leads to synergistic effects and, thus, is superior to either treatment modality alone. Confirming this hypothesis in preclinical and clinical research may raise significance and increase the use of ESWT in physical and rehabilitation medicine, with immediate benefit for patients.

The study of order patterns of three equally spaced values $x_t,x_{t+d},x_{t+2d}$ in a time series is a powerful tool. The lag $d$ is changed in a wide range so that differences of frequencies of order patterns become autocorrelation functions. Similar to a spectrogram in speech analysis, four ordinal autocorrelation functions are used to visualize big data series, as for instance heart and brain activity over many hours. The method applies to real data without preprocessing, outliers and missing data do not matter. On the theoretical side, we study properties of order correlation functions and show that the four autocorrelation functions are orthogonal in a certain sense. An analysis of variance of a modified permutation entropy can be performed with four variance components associated with the functions.

A rapid synthesis of chiral sulfoxide-functionalized meta-terphenyl derivatives by a 2,5-[C4+C2] ring transformation reaction of pyrylium salts with in-situ generated enantio-merically pure .alpha.-sulfinylacetaldehydes is described. This synthetic method demonstrates for the first time the use of .alpha.-sulfinylacetaldehydes in a reaction sequence initiated by nu-cleophilic attack of pyrylium salts by .alpha.-sulfinylcarbanions to generate chiral aromatic systems. The method presented shows broad applicability starting with various methyl sulfoxides and a number of functionalized pyrylium salts, furnishing meta-terphenyls with complex substitution patterns from readily accessible starting compounds.

Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.

Natural products (NPs) have been the centre of attention of the scientific community in the last decencies and the interest around them continues to grow incessantly. As a consequence, in the last 20 years, there was a rapid multiplication of various databases and collections as generalistic or thematic resources for NP information. In this review, we establish a complete overview of these resources, and the numbers are overwhelming: over 120 different NP databases and collections were published and re-used since 2000. 98 of them are still somehow accessible and only 50 are open access. The latter include not only databases but also big collections of NPs published as supplementary material in scientific publications and collections that were backed up in the ZINC database for commercially-available compounds. Some databases, even published relatively recently are already not accessible anymore, which leads to a dramatic loss of data on NPs. The data sources are presented in this manuscript, together with the comparison of the content of open ones. With this review, we also compiled the open-access natural compounds in one single dataset a COlleCtion of Open NatUral producTs (COCONUT), which is available on Zenodo and contains structures and sparse annotations for over 400000 non-redundant NPs, which makes it the biggest open collection of NPs available to this date.

The automatic recognition of scanned Medieval manuscripts still represents a challenge due to degradation, non standard layouts, or notations. This paper focuses on the Medieval square notation developed around the 11th century which is composed of staff lines, clefs, accidentals, and neumes which are basically connected single notes. We present a novel approach to tackle the automatic transcription by applying CNN/LSTM networks that are trained using the segmentation-free CTC-loss-function which considerably facilitates the GT-production. For evaluation, we use three different manuscripts and achieve a dSAR of 86.0% on the most difficult book and 92.2% on the cleanest one. To further improve the results, we apply a neume dictionary during decoding which yields a relative improvement of about 5%.

The evolving collective psyche of humanity reveals a shift from predominantly masculine to increasingly feminine characteristics since around 1500 A.D. This transformation, termed 'trans-genderization,' is attributed to identified psychological factors. Remarkably, the collective psyche has undergone similar transitions in the past since the emergence of humanity.

This article is a commentary on the publication Guo J, Hai H, Ma Y. Application of extracorporeal shock wave therapy in nervous system diseases: A review. Front Neurol. (2022) 13:963849. doi: 10.3389/fneur.2022.963849 (1). In the opinion of the authors of this commentary the information provided in the Section "Principles of ESWT" in (1) is partly incorrect and misleading. This is due to the fact that important, published knowledge regarding focused extracorporeal shock wave therapy (fESWT) and radial extracorporeal shock wave therapy (rESWT) was disregarded in (1).

Special machinery engineering is of great importance to the manufacturing industry and makes a comparatively large contribution to many economies. Digital transformation is already well advanced in many producing industries, and modern ICT technologies such as agents, service orientation, digital twins and artificial intelligence are being used with increasing success. In addition to improving specific product characteristics such as reliability or flexibility, the adoption of modern ICT technologies to ensure sustainability is being intensively discussed. So far, however, there has been little uptake of these technologies in the special machinery industry; sustainability receives little attention. This article examines in detail the reasons for and impediments to the adoption of modern ICT technologies based on a study among special machinery manufacturers. Observations of existing challenges were gathered during daily work, described in detail, and used to derive conclusions about causal barriers. From this, detailed requirements are derived to promote the adoption of modern ICT technologies in the special machinery engineering sector and, ultimately, to bring sustainability more into focus.

The choice of parameters for laser beams used in the treatment of musculoskeletal diseases is of great importance. First, to reach high penetration depths into biological tissue and, secondly, to achieve the required effects on a molecular level. The penetration depth depends on the wavelength since there are multiple light-absorbing and scattering molecules in tissue with different absorption spectra. The present study is the first comparing the penetration depth of 1064 nm laser light with light of a smaller wavelength (905 nm) using high-fidelity laser measurement technology. Penetration depths in two types of tissue (porcine skin and bovine muscle) were investigated. The transmittance of 1064 nm light through both tissue types was consistently higher than of 905 nm light. The largest differences (up to 5.9%) were seen in the upper 10 mm of tissue, while the difference vanished with increasing tissue thickness. The higher penetration was most likely due to a combination of lower absorption in hemoglobin and less scattering at larger wavelengths, and not due to absorption in melanin. Overall, differences in penetration depth were comparably small and high peak power and short pulse lengths of laser light seem to be more important to efficiently treat deep musculoskeletal diseases.

In this contribution, we aim to show that opinion dynamics and population balance modeling can benefit from an exchange of problems and methods. To support this claim, the Deffuant-Weisbuch model, a classical approach in opinion dynamics, is formulated as a population balance model. This new formulation is subsequently analyzed in terms of moment equations, and conservation of the first and second order moment is shown. Exemplary results obtained by our formulation are presented and agreement with the original model is found. Also the influence of the initial distribution is studied. Additionally, the Deffuant-Weisbuch model is transferred to engineering and interpreted as mass transfer between liquid droplets which results in a more flexible formulation compared to alternatives from the literature. On the one hand, it is concluded that the transfer of opinion-dynamics problems to the domain of population balance modeling offers some interesting insights as well as stimulating challenges for the population-balance community. On the other hand, it is inferred that population-balance methods can contribute to the solution of problems in opinion dynamics. In a broad outlook, some further possibilities of how the two fields can possibly benefit from a close interaction are outlined.

Knowledge about laminar-turbulent transition on operating multi-megawatt wind turbine blades needs sophisticated equipment like hot-films or microphone arrays. Contrarily thermographic pictures can easily be taken from the ground and temperature differences indicate different states of the boundary layer. The accuracy however, still is an open question, so that an aerodynamic glove known from experimental research on aero-planes was used to classify the boundary-layer state of a 2 megawatt wind turbine blade operating in the orthern part of Schleswig-Holstein, Germany. State-of-the-art equipment for measurering static surface pressure was used for monitoring the lift distribution. To distinguish laminar and turbulent parts of the boundary layer (suction side only) 48 microphones were applied together with ground-based thermographic cameras from two teams. Additionally, an optical camera mounted on the hub was used to survey vibrations. During start-up (from 0 to 9 rpm) extended, but irregularly shaped regions of a laminar boundary layer were observed which had the same extension measured both with microphones and Thermography. When an approximately constant rotor rotation (9 rpm corresponding to approximately 6 m/s wind-speed) was achieved, a flow transition was visible at the expected position of 40 % chord length on the rotor blade, which was fouled with dense turbulent wedges and an almost complete turbulent state on the glove was detected. In all observations, quantitative determination of the flow transition positions from thermography and microphones agree well within their accuracy.

Snow is a vital environmental parameter and dynamically responsive to climate change, particularly in mountainous regions. Snow cover can be monitored at variable spatial scales using Earth Observation (EO) data. Long-lasting remote sensing missions enable the generation of multi-decadal time series and thus the detection of long-term trends. However, there have been few attempts to use these to model future snow cover dynamics. In this study, we therefore explore the potential of such time series to forecast the Snow Line Elevation (SLE) in the European Alps. We generate monthly SLE time series from the entire Landsat archive (1985-2021) in 43 Alpine catchments. Positive long-term SLE change rates are detected, with the highest rates (5-8 m/y) in the Western and Central Alps. We utilize this SLE dataset to implement and evaluate seven uni-variate time series modeling and forecasting approaches. The best results were achieved by Random Forests, with a Nash-Sutcliffe efficiency (NSE) of 0.79 and a Mean Absolut Error (MAE) of 258 m, Telescope (0.76, 268 m), and seasonal ARIMA (0.75, 270 m). Since the model performance varies strongly with the input data, we developed a Combined forecast based on the best performing methods in each catchment. This approach was then used to forecast the SLE for the years 2022-2029. In the majority of the catchments the shift of the forecast median SLE level retained the sign of the long-term trend. In cases where a deviating SLE dynamic is forecast a discussion based on the unique properties of the catchment and past SLE dynamics is required. In the future, we expect major improvements in our SLE forecasting efforts by including external predictor variables in a multi-variate modeling approach.

This paper deals with a generic methodology to evaluate the magnetic parameters of contactless power transfer systems. Neumann's integral has been used to create a matrix method that can model the magnetics of single coils (circle, square, rectangle). The principle of superposition has been utilised to extend the theory to multi-coil geometries such as double circular, double rectangle and double rectangle quadrature assuming linearity of magnetics. Numerical and experimental validation has been performed to validate the analytical models developed. A rigorous application of the analysis has been carried out to study misalignment and hence the efficacy of various geometries to misalignment tolerance. Comparison of single-coil and multi-coil shapes considering coupling variation with misalignment, power transferred and maximum efficiency is carried out.

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and treatment response are typ-ically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences in tumor take, with GL261 Red-FLuc cells requiring immunocompromised mice for 100% engraftment. Immuno-histochemistry and MRI revealed distinct tumor characteristics: GL261 Red-FLuc tumors were well-demarcated with densely packed cells, high mitotic activity, and vascularization. In con-trast, TRP-mCherry-FLuc tumors were large, invasive, and necrotic, with perivascular invasion. Quantifying tumor volume using the HALO® AI analysis platform yielded results comparable to manual measurements, providing a standardized and efficient approach for reliable high-throughput analysis of luciferase-expressing tumors. Our study highlights the importance of considering tumor engraftment when using luciferase-expressing GBM models, providing in-sights for preclinical research design.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

(1) Background: Sensing of critical events or flow signatures in nature often presents itself as a coupled interaction between a fluid and arrays of slender flexible beams, such a wind-hairs or whiskers. It is hypothesized that important information is gained in highly noisy environments by the inter-correlation within the array. (2) Methods: The present study uses a model sea lion head with artificial whiskers in the form of slender beams (optical fibres), which are subjected to a mean flow with overlaid turbulent structures generated in the wake of a cylinder. Motion tracking of the array of fibres is used to analyse the correlation of the bending deformations of pairs of fibres. (3) Results: Cross-correlation of the bending signal from tandem pairs of whiskers proves that the detection of vortices and their passage along the animals head is possible even in noisy environments. The underlying pattern, during passage of a vortex core, is a jerk-like response of the whiskers, which can be found at later arrival-times in similar form in the downstream whisker's response. (4) Conclusion: Coherent vortical structures can be detected from cross-correlation of pairs of cantilever-beam like sensors even in highly turbulent flows. Such vortices carry important information within the environment, e.g. the underlying convection velocity. More importantly in nature, these vortices are characteristic elementary signals left by prey and predators. The present work can help to further develop flow, or critical event, sensory systems which can overcome high noise levels due to the proposed correlation principle.

A recent study published in Nature Medicine (Mautner et al., Nat Med 2023 Nov 2. doi: 10.1038/s41591-023-02632-w. Epub ahead of print) reported findings regarding a four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients, aimed at comparing the therapeutic effectiveness of orthobiologic interventions against corticosteroid injections for the treatment of knee osteoarthritis (OA). The study concluded that, one-year post-treatment, all orthobiologic therapies examined were equivalent in effectiveness to each other and to corticosteroid injections. While we commend the scope and methodological rigor of the trial, the publication could be enhanced by a more comprehensive presentation of data to support the conclusions drawn. Particularly, the omission of baseline data for primary outcomes, the missing context to evaluate absolute values, the lack of discussion regarding interindividual variability, and the unexpectedly favorable results for corticosteroids that contrast the established literature, are areas that merit additional examination and insight. Here we aim to highlight these points for consideration, and advocate for the release of supplementary data to facilitate a comprehensive understanding and utilization of this rich dataset.

Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote proinflammatory pathways also contributing to procoagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing molecular and clinical effects of inflammatory processes on the micro- and microvas-culature with a focus on peripheral artery disease.

Many patients with Coronavirus disease 2019 (COVID-19) suffer from shortness of breath and severe chest pain. Here we report successful therapy of a patient with diagnosis of COVID-19, severe chest pain and significant shortness of breath, using radial extracorporeal shock wave therapy (rESWT). The latter started seven days after beginning of symptoms and drug therapy without success, and involved daily application of 15.000 to 20.000 radial extracorporeal shock waves over the intercostal muscles as well as the paravertebral muscles of the thoracic and lumbar spine, diaphragm and flanks. Immediately after the first rESWT session the patient experienced significant pain relief and improvement of breathing. Four days later the pain had completely subsided and breathing was largely normalized. This type of noninvasive, non-pharmacologic treatment could help many COVID-19 patients or patients who still suffer from breathing problems weeks after having been infected with SARS-CoV-2, giving them back quality of life.

Background: Spine shape parameters, such as leg length, kyphotic or lordotic angle, are influenced by low back pain. There is also evidence that the thoracolumbar fascia plays a role in such pa-thologies. This study examined the immediate effects of a myofascial release technique (MFR) on the thoracolumbar fascia and of an osteopathic treatment (OMT) on postural parameters in pa-tients with acute low back pain (aLBP). Methods: This study was a single-blind randomized pla-cebo-controlled trial. Seventy-one subjects (43.8 ± 10.5 years) suffering from aLBP were randomly and blinded assigned to three groups to be treated with MFR, OMT or a placebo intervention. Spinal shape parameters (functional leg length discrepancy (fLLD), kyphotic angle, lordotic an-gle) were measured before and after the intervention using video raster stereography. Results: Within the MFR group, fLLD reduced by 5.2 mm, p < 0.001 and kyphotic angle by 8.2 degrees, p < 0.001. Within the OMT group, fLLD reduced by 4.5 mm, p < 0.001 and kyphotic angle by 8.4 °, p = 0.007. Conclusion: MFR and OMT have an influence on fLLD and the kyphotic angle in aLBP patients. The interventions could have a regulating effect on the impaired neuromotor control of the lumbar muscles.

With the advent of real-time MRI, the motion and passage of cerebrospinal fluid can be visualized without gating and exclusion of low-frequency waves. This imaging modality gives insights into low-volume, rapidly oscillating cardiac-driven movement as well as sustained, high-volume, slowly oscillating inspiration-driven movement.Inspiration means a spontaneous or artificial increase in the intrathoracic dimensions independent of body position. Alterations in thoracic diameter enable the thoracic and spinal epidural venous compartments to be emptied and filled, producing an upward surge of cerebrospinal fluid inside the spine during inspiration; this surge counterbalances the downward pooling of venous blood toward the heart.Real-time MRI, as a macroscale in vivo observation method, could expand our knowledge of neurofluid dynamics, including how astrocytic fluid preloading is adjusted and how brain buoyancy and turgor are maintained in different postures and zero gravity.Along with these macroscale findings, new microscale insights into aquaporin-mediated fluid transfer, its sensing by cilia and its tuning by nitric oxide will be reviewed. By incorporating clinical knowledge spanning several disciplines, certain disorders—congenital hydrocephalus with Chiari malformation, idiopathic intracranial hypertension and adult idiopathic hydrocephalus—are interpreted and reviewed according to current concepts, from the basics of the interrelated systems to their pathology.

Objectives: To compare the volumes and shapes of the coagulation zone (CZ) of a multi-probe RFA system (three RFA electrodes) and a single-probe MWA system from the same vendor in an ex-vivo bovine liver model. Material &amp; Methods: A total of 48 CZs were obtained in bovine liver specimens with three different ablation system configurations (single-probe MWA vs. multi-probe RFA with 20 mm inter-probe distance [confluent CZ] vs. multi-probe RFA with 50 mm inter-probe distance [three individual CZ]) at 4-, 6-, 8-, and 10-min ablation time using a fixed ablation protocol. Ablation diameters were measured and ellipticity indices (EI) and volumes calculated. Calculations for all systems/configurations were compared. Results: Volumes and diameters increased with ablation time for all configurations. At 4- and 6-min ablation time volumes obtained with the RFA 50 mm setup, and at 8 and 10 min with the RFA 20 mm setup were the largest with 26.5 ± 4.1 mL, 38.1 ± 5.8 mL, 46.3 ± 4.9 mL, 48.4 ± 7.3 mL, respectively. The single-probe MWA could not reach the volumes of the RFA setups for any of the ablation times evaluated. EI were very similar and almost round for RFA 20 mm and single-probe MWA and differed significantly to the more ovoid ones for the RFA 50 mm configuration. Conclusion: The multi-probe RFA system employing three electrodes achieved significantly larger ablation volumes in both configurations (confluent CZ and three individual CZ) per time as compared to a single-probe MWA system in this ex-vivo bovine liver model.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

The synthesis and crystal structure of pyrazine-2,5-diyldimethanol (pzydmH2, C8H8N2O2) a new symmetric water-soluble N,O-chelating tetra-dentate organic ligand is reported and an environmentally friendly method was used to synthesize coordination compounds in water under ambient conditions from the reaction of pzydmH2 with the halide salts of Cu(II), Zn(II), Hg(II) and Cd(II): {[Cu(pzydmH2)0.5(µ-Br)(Br)(H2O)]·H2O}n 1, {[Zn2(pzydmH2)(µ-Cl)(Cl)3(H2O)]·H2O}n 2, [Hg2(pzydmH2)0.5(µ-Cl)2(Cl)2]n 3, {[Cd2(pzydmH2)(µ-Cl)4]·H2O}n 4, and {[Cd2(pzydmH2)(µ-Br)4]·H2O}n 5. Single-crystal X-ray diffraction analysis revealed that 1-3 are 1D coordination polymers and 4 and 5 are 3D coordination networks, all constructed by bridging pyrazine-2,5-diyldimethanol and halogen ions. The hydroxyl groups in the organic linker extend the 1D chains to non-covalent 3D networks. In all non-covalent and covalent 3D networks water molecules were trapped by strong hydrogen bond interactions. Supramolecular analysis revealed strong O-H···O, O-H···N, O-H···X and week of C-H···O, C-H···X (X = Cl, Br) hydrogen bonds, as well as π-π(pyrazine ring), metal-halogen···π(pyrazine ring) and O-H···ring(5-membered chelate ring) interactions. Also X···O weak halogen bonds are present in 1-5 (X = Cl and Br).

This study investigated the factors that influence consumer acceptance of fungus-resistant grape varieties (FRGV) in Germany. The qualitative research methodology involved conducting semi-structured interviews including sensory evaluation test with focus groups consisting of 48 consumers, and the data were evaluated using content analysis. The findings revealed that the attractiveness of a grape variety is determined by four distinct attributes. Furthermore, FRGV can be made more attractive to consumers by using denominations based on established grape varieties or by using and associating them with their sensory patterns. The sensory acceptance of FRGV varies significantly across consumer segments and vinification methods. Providing relevant information about the benefits of resistant grape varieties has a positive impact on consumer acceptance, and the level of interest and relevance varies by the target group. The study suggests that it is possible to enhance consumer acceptance by offering attractive grape varieties, targeting group-specific sensory profiles and engaging in storytelling campaigns that educate consumers about the advantages of resistant grapes.

Laser therapy devices (LTDs) operating with near-infrared laser light are increasingly being used in sports medicine. For several reasons the users cannot evaluate whether or not such devices emit laser beams according to the specifications provided by the manufacturer and the settings of the device. In this study the laser beams from two different LTDs that can be used in sports medicine were thoroughly characterized by measuring the emitted power, pulse shapes and lengths, and spatial intensity distributions using professional, high-fidelity laser measurement technology. This was repeated for three units of each LDT independently to distinguish problems of individual units from potential intrinsic instrument design errors. The laser beams from the units of one LTD agreed with the settings at the device, with the measured average power for these units being within 3.3% of the set power. In contrast, the laser beams from the units of the other LTD showed large deviations between the settings and the actual emitted light. This device came with three laser diodes that could be used independently and simultaneously. The average power differed greatly between the units as well as between the laser diodes within each unit. Some laser diodes emitted essentially no light, which could lead to a lack of treatment of patients. Other laser diodes emitted much more power than set at the device (up to 230%) that could result in skin irritations or burnings of patients. These findings indicate a need for better standardization and consistency of therapeutic laser light sources.

There is increasing interest in the application of near-infrared (NIR) laser light for the treatment of various musculoskeletal disorders. The present study thoroughly examined the physical characteristics of laser beams from two different laser therapy devices that are commercially available for the treatment of musculoskeletal disorders. Then, these laser beams were used to measure the penetration depth in various biological tissues from different animal species. The key result of the present study was the finding that for all investigated tissues, most of the initial light energy was lost in the first one to two millimeters, more than 90% of the light energy was absorbed within the first ten millimeters, and there was hardly any light energy left after 15 – 20 mm of tissue. Furthermore, the investigated laser therapy devices fundamentally differed in several laser beam parameters that can have an influence on how light is transmitted through tissue. Overall, the present study showed that a laser therapy device that is supposed to reach deep layers of tissue for treatments of musculoskeletal disorders should operate with a wavelength between 800 nm and 905 nm, a top-hat beam profile, and it should emit very short pulses with a large peak power.

Ultrafast chip nanocalorimetry opens up remarkable possibilities in materials science by allowing samples to be cooled and heated at extremely high rates. Due to heat transfer limitations, controlled ultrafast cooling and heating can only be achieved for tiny samples in calorimeters with a micron-thick membrane. Even if ultrafast heating can be controlled under quasi-adiabatic conditions, ultrafast controlled cooling can be performed if the calorimetric cell is located in a heat-conducting gas. It was found that the maximum possible cooling rate increases as 1/r0 with decreasing radius r0 of the hot zone of the membrane. The possibility of increasing the maximum cooling rate with decreasing r0 was successfully implemented in many experiments. In this regard, it is interesting to answer the question: what is the maximum possible cooling rate in such experiments if r0 tends to zero? Indeed, on submicron scales, the mean free path of gas molecules lmfp becomes comparable to r0, and the temperature jump that exists at the membrane/gas interface becomes significant. Considering the limitation associated with thermal resistance at the membrane/gas interface and considering the transfer of heat through the membrane, we show that the controlled cooling rate can reach billions of K/s, up to 1010 K/s.

Phosphorus is required by laying hens for a variety of biological functions. It is usually provided in excess, in a readily digestible inorganic form in diet formulations. However, this does not represent an efficient use of a finite resource and can result in water pollution. Plant bound phosphorus in phytate, is common in commercial poultry diets, and represents an alternate source of phosphorus, however poultry lacks the enzyme to digest it. By adding enzymes to their diets, the availability of this phytate-bound phosphorus can be increased allowing for the reduced inclusion of inorganic P in the diet formulation. Therefore, this study was conducted to examine the effect of a natural enzyme complex that contains phytase and xylanase in layer diets. Novogen Brown Classic layers (n=314) were fed one of two diets: (T1) control diet or (T2) control diet plus a natural mixed-enzyme product with both, phytase and xylanase. Experimental diets were provided for 12 days after which the excreta from each pen were collected for an additional three days to determine total retention and ileal digestibility of phosphorus and gross energy. At the end of the trial the birds were euthanized, and their ileal contents were collected. Productivity parameters were also recorded over the course of the study. The amount of phosphorus detected in the excreta of the control group was significantly higher than the amount detected in the enzyme-supplemented group (P<0.05). Both phosphorus retention and phosphorus ileal digestibility were significantly higher in the enzyme-supplemented birds (P<0.001). Gross energy digestibility was significantly higher in the enzyme-supplemented birds for both the total tract and ileal samples (P<0.001). There were only numerical improvements, not significant, in the layer productivity parameters. This study showed that the enzyme supplement can improve total retention and ileal digestibility of phosphorus and gross energy in older layers.

Mapping and prediction of inundated areas is increasingly important for climate change adaptation and emergency preparedness. Flood forecasting tools and flood risk models have to be compared to observed flooding patterns for training, calibration, validation and benchmarking. At regional to continental scale, satellite earth observation is the established method for surface water extent (SWE) mapping and several operational global-scale data products are available. However, the spatial resolution of satellite-derived SWE maps remains a limiting factor, especially in low-lying areas with complex hydrography, such as Denmark. We collected thermal imagery using an unmanned airborne system (UAS) for three areas in Denmark shortly after major flooding events. We combined the thermal imagery with an airborne lidar-derived high-resolution digital surface model of the country to retrieve high-resolution (40 cm) SWE maps. The resulting SWE maps were compared to low-resolution SWE maps derived from satellite earth observation (EO). We conclude that UAS have significant potential for SWE mapping at intermediate scales, can bridge the scale gap between ground observations and satellite EO and can be used to benchmark and validate SWE mapping products derived from satellite EO as well as models predicting inundation.

Even today, the automatic digitisation of scanned documents in general but especially the automatic optical music recognition (OMR) of historical manuscripts still remain an enormous challenge, since both handwritten musical symbols and text have to be identified. This paper focuses on the Medieval so-called square notation developed in the 11th-12th century, which is already composed of staff lines, staves, clefs, accidentals, and neumes, that are roughly spoken connected single notes. The aim is to develop an algorithm that captures both the neume and pitch, that is melody information that can be used to reconstruct the original writing. Our pipeline is similar to the standard OMR approach and comprises a novel staff line and symbol detection algorithm, based on deep Fully Convolutional Networks (FCN), which perform pixel-based predictions for either staff lines or symbols and their respective types. Then, the staff line detection combines the extracted lines to staves and yields an F1-score of over 99% for both detecting lines and complete staves. For the music symbol detection we choose a novel approach that skips the step to identify neumes and instead directly predicts note components (NCs) and their respective affiliation to a neume. Furthermore, the algorithm detects clefs and accidentals. Our algorithm recognises these symbols with an F1-score of over 96% if the type is ignored and predicts the true symbol sequence of a staff with a diplomatic symbol accuracy rate (dSAR) of about 87%. If only the NCs without their respective connection to a neume, all clefs, and accidentals are of interest the algorithm reaches an harmonic symbol accuracy rate (hSAR) of approximately 90%.

Surface velocity is traditionally measured with in situ techniques such as velocity probes (in shallow rivers) or Acoustic Doppler Current Profilers (in deeper water). In the last years, researchers have developed remote sensing techniques, both optical (e.g., image-based velocimetry techniques) and microwave (e.g., Doppler radar). These techniques can be deployed from Unmanned Aerial Systems (UAS), which ensure fast and low-cost surveys also in remotely-accessible locations. We compare the results obtained with a UAS-borne Doppler radar and UAS-borne Particle Image Velocimetry (PIV) in different rivers, which presented different hydraulic–morphological conditions (width, slope, surface roughness and sediment material). The Doppler radar was a commercial 24 GHz instrument, developed for static deployment, adapted for UAS integration. PIV was applied with natural seeding (e.g., foam, debris) when possible, or with artificial seeding (woodchips) in the stream where the density of natural particles was insufficient. PIV reconstructed the velocity profile with high accuracy typically in the order of a few cm s⁻¹ and a coefficient of determination (R²) typically larger than 0.7 (in half of the cases larger than 0.85), when compared with acoustic Doppler current profiler (ADCP) or velocity probe, in all investigated rivers. However, UAS-borne Doppler radar measurements show low reliability because of UAS vibrations, large instrument sampling footprint, large required sampling time and difficult-to-interpret quality indicators suggesting that additional research is needed to measure surface velocity from UAS-borne Doppler radar.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

The inherent dependency of deep learning models to labeled data is a well-known problem and one of the barriers that slows down the integration of such methods into different fields of applied sciences and engineering, in which experimental and numerical methods can easily generate a colossal amount of unlabeled data. This paper proposes an unsupervised domain adaptation methodology that mimics the peer review process to label new observations in a different domain from the training set. The approach evaluates the validity of a hypothesis using domain knowledge acquired from the training set through a similarity analysis, exploring the projected feature space to examine the class centroid shifts. The methodology is tested on a binary classification problem, where synthetic images of cubes and cylinders in different orientations are generated. The methodology improves the accuracy of the object classifier from 60% to around 90% in the case of a domain shift in physical feature space without human labeling.

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (N=271, 7 sites), to compare volumes of hippocampus, amygdala, and their subfields/nuclei between help-seeking subjects divided in risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2– 74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0– 71.9) for leave-one-site-out. Structural altera-tions of hippocampus and amygdala may not be as pronounced in young people at risk, nonetheless, ma-chine learning can predict estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.

Deterioration of concrete subjected to freezing and thawing climatic conditions is one of most important factors affecting the durability of concrete infrastructure in cold climates. The freeze-thaw resistance of cementitious materials like concrete and mortar can be determined by the CDF test (Capillary Suction of De-icing chemicals and Freeze-Thaw Test). Here, concrete specimens are subjected to repeated freeze-thaw cycles with simultaneous addition of de-icing salt and the amount of material weathered near the surface is determined. For concretes with adequate freeze-thaw resistance, this test method works very well. However, specimens with inadequate or unknown performance often experience increased edge weathering, which is caused by the detachment of the lateral isolation tape. The increasing edge influence thus leads to a falsification of the results and consequently to an underestimation of the actual freeze-thaw resistance of the material. In materials research in particular, however, concretes with high levels of weathering are studied in order to be able to investigate various factors of influence on the freeze-thaw resistance of concretes in a targeted manner. This paper presents a novel methodology that delivers new information regarding the weathering of CDF test samples and the associated distribution function of the height decrease using high resolution 3D scan data. The results indicate a correlation between the progression of the distribution function and the sample's maximum aggregate size. The change of the sample volume can be used to support the weathering results of the standard CDF methodology. The increase of the surface area is used to estimate the tortuosity of the sample surface. It indicates an asymptotic curve approaching a specific maximum value, which is dependent on the the weathering depth of the sample.

In the theoretical treatment of crystallization it is commonly assumed that relaxation processes of the liquid proceed fast as compared to crystal nucleation and growth processes. Actually, it is supposed that the liquid is located always in the metastable state corresponding to the current values of pressure and temperature. However, near and below the glass transition temperature, Tg, this condition is commonly not fulfilled. In such cases, in the treatment of crystallization, deviations of the state of the liquid from the respective metastable equilibrium state have to be accounted for in determining the kinetic coefficients governing the crystallization kinetics, the thermodynamic driving force of crystallization, and the surface tension of the aggregates of the newly evolving crystal phase including the surface tension of critical clusters affecting considerably the crystal nucleation rate. These factors may considerably influence the course of the overall crystallization process. A theoretical analysis of the resulting effects is given in the present paper by numerical solutions of the J(ohnson)–M(ehl)–A(vrami)–K(olmogorov)–equation employed as the tool to model the overall crystallization kinetics and by analytical estimates of the crystallization peak temperatures in dependence on cooling and heating rates. The results are shown to be in good agreement with experimental data. Possible extensions of the theory to be explored in future analysis are anticipated.

Coronaviruses are a large family of diverse enveloped RNA viruses found in numerous animal species. They are well-known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in human populations. In contrast, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we discuss the significance and perspectives of broad-spectrum therapeutics and vaccines.

(1) Background: Globally, neck pain is prevalent, affecting around thirty percent of the population annually. To better understand the influence of pain on the myofascial layers, the present study investigated these on the upper trapezius muscle in unilateral, more severe neck pain. (2) Methods: This study was a cross-sectional study. Forty patients (42.2 ± 14.7) with a confirmed diagnosis of unilateral neck pain were examined using durometry and indentometry. The study evaluated stiffness, elasticity, and pressure pain threshold of both sides of the neck (symptomatic side: SS; healthy side: HS). Furthermore, the range of motion of the cervical spine (lateral flexion, rotation) was quantified using a digital goniometer. (3) Results: A significant lateral discrepancy was observed in stiffness between groups (durometry: SS – 33.76 ± 7.78, HS – 29.75 ± 7.45, p&lt;0.001; indentometry: SS – 59.73 ± 33.93, HS – 4.18 ± 12.69, p=0.024). In contrast, no differences were found between the comparison sides of the upper trapezius for the parameter’s elasticity (SS – 0.101 ± 1.09, HS – -0.006 ± 0.29, p=0.416), cervical spine mobility (lateral flexion: SS – 37.08 ± 8.15, HS – 37.73 ± 7.61, p=0.559; rotation: SS – 73.55 ± 12.37, HS – 72.85 ± 11.10, p=0.660) and algometry (SS – 36.41 ± 17.53, HS – 37.22 ± 17.00, p=0.657). (4) Conclusion: Overall, it can be concluded that more severe neck pain unilaterally shows differences in stiffness on the same side. Future research is needed to investigate the links.

Atmospheric corrosion of aluminum aircraft structures occurs due to numerous reasons. A typical phenomenon leading to corrosion is the deliquescence of contaminants such as salts due to changes in relative humidity (RH) caused by aircraft operation at different altitudes and climate zones. Currently, corrosion of aircrafts is controlled by scheduled inspections. In contrast, the present contribution aims for a continuous monitoring approach by using the acoustic emission (AE) method to detect and further evaluate atmospheric corrosion. The AE method is frequently used for corrosion detection at typically immersion-like conditions or for corrosion types where stress-induced cracking is involved. However, it has not yet been demonstrated for atmospheric corrosion at unloaded aluminum structures. To address this question, the present investigation uses small droplets of a corrosive sodium chloride (NaCl) solution to induce atmospheric corrosion on aluminum alloy AA2024-T351. Operating conditions of an aircraft are simulated by a controlled variation in RH. In addition, videos of the corrosion site are recorded to visually observe the corrosion process. Pitting corrosion is generated and clearly measurable AE signals are detected. An automatic video processing algorithm looking for sudden changes on the corrosion site mainly detects hydrogen bubbles formed when aluminum reacts with aqueous solutions. A clear correlation between the observed pitting corrosion, the AE and the hydrogen bubble activity and the RH, i.e., the electrolyte present at the aluminum surface, is found. Thus, the findings demonstrate the applicability of the AE method for monitoring atmospheric corrosion of aluminum aircraft structures by today’s measurement equipment. Numerous potential effects that can cause measurable AE signals are investigated and discussed. Among these, bubble activity is clearly considered to be the most emissive one.

We point out that field equations of general relativity are implied by a maximal force given by c⁴/4G, analogous to the way that special relativity is implied by a maximal speed given by c. We present some of the arguments for this equivalence. The maxi-mal force naturally plays the role of an elastic constant for space-time. Implications of the maximal force for gravitational wave measurements, cosmology and black holes are highlighted. Quantum aspects of the maximal force are discussed.

This case study investigates the heart rate (HR) and heart rate variability (HRV) in a patient with coronavirus disease 2019 (COVID-19). We report the case of a 58-year old male who contracted COVID-19. During his disease, 24-hour Holter electrocardiography (ECG) was performed continuously. For comparison, his 24-hour Holter ECGs from the previous 10 years were available. In this patient, COVID-19 was associated with a decrease in HR and a paradoxical decline in HRV. An abrupt decline in HRV and a decrease in HR may signal the onset of COVID-19 before common symptoms such as dry cough or fever appear. In addition, HRV and HR measurements may help to evaluate the course of the disease.

Digital federated platforms and data cooperatives for secure, trusted and sovereign data exchange will play a central role in the construction industry of the future. With the help of platforms, cooperatives and their novel value creation, the digital transformation and the degree of organization of the construction value chain can be taken to a new level of collaboration. The goal of this research project was to develop an experimental prototype for a federated innovation data platform along with a suitable exemplary use case. The prototype is to serve the construction industry as a demonstrator for further developments and form the basis for an innovation platform. It exemplifies how an overall concept is concretely implemented along one or more use cases that address high-priority industry pain points. This concept will create a blueprint and a framework for further developments, which will then be further established in the market. The research project illuminates the perspective of various governance innovations to increase industry collaboration, productivity and capital project performance and transparency as well as the overall potential of possible platform business models. However, a comprehensive expert survey revealed that there are considerable obstacles to trust-based data exchange between the key stakeholders in the industry value network. The obstacles to cooperation are predominantly not of a technical nature, but of a competitive, predominantly trust-related nature. To overcome these obstacles and create a pre-competitive space of trust, the authors therefore propose the governance structure of a data cooperative model, which is discussed in detail in this paper.

Extracorporeal shock wave therapy (ESWT) is a safe and effective treatment option for various pathologies of the musculoskeletal system. Many studies addressed the molecular and cellular mechanisms of action of ESWT. However, no uniform concept could be established in this matter until now. We performed a systematic review of the effects of exposure of musculoskeletal tissue to extracorporeal shock waves (ESWs) reported in the literature. The key results were as follows: (i) compared to the effects of many other forms of therapy, the clinical benefit of ESWT does not appear to be based on a single mechanism; (ii) different tissues respond to the same mechanical stimulus in different ways; (iii) just because a mechanism of action of ESWT was described in a study does not automatically mean that this mechanism was relevant to the observed clinical effect; (iv) focused ESWs and radial ESWs seem to act in a similar way; and (v) even the most sophisticated research into the effects of exposure of musculoskeletal tissue to ESWs cannot substitute clinical research in order to determine the optimum intensity, treatment frequency and localization of ESWT.

The synthesis and structure of the 4,4′-dipyridyl N,N′-donor ligand with a central thiazolo[5,4-d]thiazole (tztz) unit, named Dptztz is presented. With the linker Dptztz and isophthalate (benzene-1,3-dicarboxylate, 1,3-BDC²⁻) the mixed-linker, two-dimensional coordination network [Zn(1,3-BDC)Dptztz]·DMF could be obtained (DMF = dimethylformamide), which belongs to the class of coordination polymers with interdigitated structures (CIDs). The incorporated DMF solvent molecules can be removed through solvent exchange and evacuation such that the supramolecular 3D packing of the 2D networks retains porosity for CO₂ adsorption in activated [Zn(1,3-BDC)Dptztz]. The first sorption study of a tztz-functionalized porous metal-organic framework material yields a BET surface of 417 m²/g from CO₂ adsorption. The heat of adsorption for CO₂ exhibits a relative maximum with 27.7 kJ/mol at adsorbed CO₂ of about 4 cm³/g STP which is interpreted as a gate-opening effect.

Accurately estimating the current state of local traffic scenes is one of the key problems in the development of software components for automated vehicles. In addition to details on free space and drivability, static and dynamic traffic participants, information on the semantics may also be included in the desired representation. Multi-layer grid maps allow to include all this information in a common representation. However, most existing grid mapping approaches only process range sensor measurements such as LIDAR and Radar and solely model occupancy without semantic states. In order to add sensor redundancy and diversity it is desired to add vision based sensor setups in a common grid map representation. In this work, we present a semantic evidential grid mapping pipeline including estimates for eight semantic classes that is designed for straightforward fusion with range sensor data. Unlike in other publication our representation explicitly models uncertainties in the evdiential model. We present results of our grid mapping pipeline based on a monocular vision setup and a stereo vision setup. Our mapping resulsts are accurate and dense mapping due to the incorporation of a disparity- or depth-based ground surface estimation in the inverse perspective mapping. We conclude this paper by providing a detailed quantitative evaluation based on real traffic scenarios in the Kitti odometry benchmark and demonstrating the advantages compared to other semantic grid mapping approaches.

We report a novel dual-band barrier infrared detector (DBIRD) design using type-II superlattices (T2SLs). The DBIRD structure consists of back-to-back barrier diodes: a "blue channel" (BC) diode which has an nBp architecture, an n-type layer of larger bandgap for absorbing blue band infrared/barrier/p-type layer, and a "red channel" (RC) diode which has an pBn architecture, a p-type layer of smaller bandgap for absorbing red band infrared/barrier/n-type layer. Each has a unipolar barrier using a T2SL lattice matched to a GaSb substrate to impede the flow of majority carriers from the absorbing layer. Each channel in the DBIRD can be independently accessed with a low bias voltage, as is preferable for high-speed thermal imaging. Device modeling of DBIRDs and simulation results of the current-voltage characteristics under dark and illuminated conditions are also presented. They predict that dual-band operation of the DBIRD will produce low dark currents and 27-33% quantum efficiencies for the in-band photons in the BC with λc=5.58 μm, and a nearly-constant 33% in the RC with λc=8.05 μm. The spectral quantum efficiency of the BC for 500 K blackbody radiation is approximately 20% over the range of λ=3 − 4.2 μm, while that of the RC has a peak of 42% at 5.7 μm. The DBIRD may provide improved high-speed dual-band imaging in comparison with NBn dual-band detectors.

Proposal: Pineal region cysts (PCs) may affect the tectum and aqueduct and cause deep central vein congestion and endocrine dysfunction. In addition to headaches, PC often causes a broad range of symptoms, leading to prolonged diagnosis and therapy. The aims of this study are to reveal parameters that might explain the ambiguity of the symptoms and to identify factors association with the respiration driven neurofluid preload system. Methods: This retrospective study included 28 paediatric patients (mean age 11.6 years) who received surgical treatment for pineal region cysts and 18 patients (mean age 11.3 years) who were followed conservatively. Multiple clinical patient characteristics, such as symptoms, time to neuroimaging diagnosis, cyst size, ventricular indices, head circumference and postoperative outcome, were analysed. Four patients were investigated for CSF dynamics with real-time MRI. The mean follow-up time was 1.6 years. Results: The most common early onset symptoms were headaches (92%), blurred vision (42.8%), sleep disturbances (39.3%) and vertigo (32.1%). Tectum contact was observed in 82% of patients, and MRI examinations revealed that imaging flow void signals were absent in 32.1% of patients. The mean cyst diameters were 13.7 mm for the axial axis and 15.6 mm for the longitudinal axis. Together with a postoperative flow void signal, 4 patients recovered their respiration-driven CSF upward flow, which was not detectable before OP. After operation in 92.1% of patients, the leading symptoms improved without any mortality or morbidity. Conclusion: Despite proximity to the tectum and aqueduct with frequently absent aqueductal flow void signals, hydrocephalic ventricular enlargement was never detected. Data from real-time MRI depicted a reduced preoperative filling of the ventricular CSF compartments, indicating a diminished fluid preload, which recovered postoperatively.

Purpose: ETV is indicated for treating obstructions of major CSF pathways. The outcome evaluation often yields success rates of only +- 70% for shunt independency. Hence, compromised CSF absorption seems to occur more often than expected. We searched for parameters suitable to assess the involved CSF dynamics. Material and Methods: This was a prospective study in 58 paediatric patients (7.7 yrs. mean age) between 2000 and 2020 with aqueductal stenosis (11/58), obstruction of the aqueduct due to tumor growth (22/58),and connatal hydrocephalus (9/58). The average follow-up interval was 4.7 years. Head circumferences, Evans- and fronto-occipital horn ratios before and 3 months after ETV were obtained as Delta-indices. Furthermore ETV success score (ETVSS), the patency of the aqueduct pre- and postoperatively as well as of the stoma were assessed by flow void signs on MRI. Evaluation on MRI also included the shape of the floor of the 3^rd ventricle and whether or not the septum pellucidum showed signs of perforation. Four patients were analysed pre- and postoperatively via real-time MRI. At least the educational status regarding protected or unprotected education was analyzed. Results:The prevalence of a bowing of the floor of the 3^rd ventricle was 72%, and the ETVSS was 71.0%. In 26 children a septal perforations or an open aqueduct prior to ETV (19) could be identified. Mean ER and FOHR were reduced by 0.03 and 0.05 , respectively. Maintained open (flow void on postop MRI) or perforation could successfully be carried out during endoscopic surgery in 44 patients (79%). The disproportionate increase of head circumference abated in 79.4% of patients. New shunt insertion occurred in 16 patients (27.5%). Intraoperatively upward CSF flow was detected in all cases. Statistical analyses(ANOVA) showed significant results for unprotected education, postoperative ER and FOHR but not for open stoma. Conclusion: The identification of flow through the stoma on postoperative MRI seems to be a necessary but not sufficient condition for ETV success. In our study, ventricular volumes were used as parameters to determine success rates as well as unprotected education. Furthermore, enabling upward CSF flow driven by inspiration seems crucial for successful ETV.

ZnO has many technological applications which largely depend on its properties that can be tuned by controlled synthesis. Ideally, the most convenient ZnO synthesis is carried out at room temperature in aqueous solvent. However, the correct temperature values are often loosely defined. In the current paper we performed synthesis of ZnO in aqueous solvent, by varying reaction and drying temperature by 10°C steps and monitored the synthesis products primarily by XRD. We found out that a simple direct synthesis of ZnO, without additional surfactant, pumping of freezing, required both a reaction (TP) and a drying (TD) temperature of 40°C. Higher temperatures also afford ZnO, but lowering any of the TP or TD below the threshold value results either in the achievement of Zn(OH)2 or in a mixture of Zn(OH)2/ZnO. A more detailed Rietveld analysis of the ZnO samples reveals a density variation with the synthesis temperature and an increase of the nanoparticles average size also verified by SEM images. The optical properties of ZnO obtained by UV-Vis reflectance spectroscopy indicate a red shift of the band gap by ~0.1 eV.

The sensitivity of macroscopic mechanical and thermal properties of grey cast iron is computationally investigated for a variety of graphite microstructures over a wide temperature range. In order to represent common graphite microstructures according to DIN EN ISO 945-1, a synthetic approach is used to algorithmically generate simulation domains. The developed mechanical and thermal model is applied in a large simulation study. The study includes statistical volume elements of the graphite microstructures classes GG-15 and IA2 to IA5, with 10 v.-%, 11 v.-% and 12 v.-% graphite, respectively, for a temperature range from 20 °C to 750 °C. Homogenized macroscopic quantities such as the Young's moduli, Poisson's ratios, yield strengths and thermal conductivities are predicted for the different microstructure classes by applying simulation and data analysis tools of the research data infrastructure Kadi4Mat.

(1) Background: The proportion of fully mechanized harvesting systems in Austria is constantly increasing especially because of the technological development of the machines, which allows them to drive on increasingly steep terrain. This leads to additional challenges and potential hazards for the operators, which may also cause higher stress levels. The purpose of this study is to develop and debate a new set of methodologies for determining time and space resolved psychophysiology data to analyze stressful and non-stressful work situations for harvester and forwarder operators; (2) Methods: we suggest a study protocol to analyze a) tasks performed by the driver, b) environmental factors, like slope gradient, c) the psychophysiological response of experts during these tasks, and d) evaluate the worker´s subjective stress and fatigue before and after a harvest operation. (3) Results: Within this manuscript we present a study protocol based on quantitative and qualitative methods, like time and space resolved psychophysiology, questionnaires, qualitative interviews, as well as video and sensor-based analysis of environmental and machine data. The first results from real measurements of a forwarder driver are presented; (4) Conclusions: This multimodal research protocol serves to explore the relationship between stress, fatigue, and performed tasks. Through our quantitative and qualitative methodology, researchers can improve the health and safety of forest workers at work, improve their productivity and reduce damage to remaining trees.

Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including the regulation of local inflammation and activation of further bone-remodeling cells. Previous studies suggested the growth differentiation factor 15 (GDF15) as important pro-inflammatory regulator during the PdLFs mechanoresponse. However, the precise mechanism remains to be clarified, as GDF15 may act both intracrine and by receptor binding, potentially also in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we detected an altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLFs differentiation and their mechanoresponse.

Chitosan treatment results in significantly lower serum LDL cholesterol concentrations. To assess the working mechanism of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol) corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m²) were studied under chitosan (n=61) and placebo treatment (n=55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (P=0.0252) under chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increase in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment was not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption nor with an increases of markers for cholesterol and bile acid synthesis.

In this work, a small-strain phase-field model is presented, which is able to predict crack propagation in systems with anisotropic brittle and ductile constituents. To model the anisotropic brittle crack propagation, an anisotropic critical energy release rate is used. The brittle constituents behave linear-elastically, in a transversely isotropic manner. Ductile crack growth is realised by a special crack degradation function, depending on the accumulated plastic strain, which is calculated by following the J2-plasticity theory. The mechanical jump conditions are applied in solid-solid phase transition regions. The influence of the relevant model parameters on a crack, propagating through a planar brittle-ductile interface, and furthermore a crack developing in a domain with a single anisotropic brittle ellipsoid, embedded in a ductile matrix, is investigated. We demonstrate that important properties, concerning the mechanical behaviour of grey cast iron, such as the favoured growth of cracks along the graphite lamellae and the tension-compression load asymmetry of the stress-strain response, are covered by the model. The behaviour is analysed on basis of a simulation domain consisting of three differently oriented elliptical inclusions, embedded in a ductile matrix, which is subjected to tensile and compressive load. The used material parameters correspond to graphite lamellae and pearlite.

Background: The thoracolumbar fascia (TLF) is thought to play a role in the development of LBP, but it is not yet clear which factor of TLF changes is a cause and which is an effect. Therefore, some studies used the cross-correlation function (CCR) to reveal time-dependent relationships between biomechanical and neuromotor factors. Methods: Ten patients with acute low back pain (aLBP) were matched to healthy controls. Simultaneous recording of surface electromyography (sEMG) of the erector spinae muscle (ES) and dynamic ultrasound (US) images of TLF deformation were performed during trunk extension. CCR functions and Granger causality were used to describe the relationship between the two measures. Results: CCR time lags were significant higher in the aLBP group (p = 0.04). Granger causality (GC) showed a direct effect of TLF deformation on ES activation only in the aLBP group (p &lt; 0.03). Conclusions: The results suggest that in aLBP, ES activity is significantly affected by TLF, whereas this relation-ship is completely random in healthy subjects studied with CCR and GC comparisons of dynamic US imaging and sEMG data signals. Fascia-related disturbances in neuromotor control, particularly due to altered muscle spindle functions, are suspected as a possible mechanism behind this.

Using the unique combination of atomically resolved atom probe tomography (APT) and volume averaged neutron (resonance) spin echo (NRSE and NSE) experiments, the influence of nano-scaled clusters on the spin relaxation in spin glasses was studied. For this purpose, the phase transition from the paramagnetic phase to the spin glass phase in a Fe-Cr spin glass with a composition of Fe_17.8Cr_82.2 was studied in detail by means of NRSE. The microstructure was characterised by APT measurements, which show local concentration fluctuations of Fe and Cr on a length scale of 2 to 5 nm, which lead i) to the coexistence of ferro- and anti-ferromagnetic clusters and ii) a change of the magnetic properties of the whole sample, even in the spin glass phase, where spins are supposed to be randomly frozen. We show that a generalized spin glass relaxation function, which was successfully used to describe the phase transition in diluted spin glasses, can also be used for fitting the spin dynamics in spin glasses with significant concentration fluctuations.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, rheumatoid arthritis or cancer. Inflammation in the brain is marked by the upregulation of the translocator protein (TSPO) in microglia. Moreover, high TSPO levels are found, for example in macrophages during rheumatoid arthritis and in malignant tumor cells compared to its relatively low physiological expression. The same applies for cycloxygenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable to monitor the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases like rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

Remote sensing data are essential for monitoring Earth’s surface waters, especially since the number of publicly available in-situ data is declining. Satellite altimetry provides valuable information on water level and its variations for lakes, reservoirs, and rivers. In combination with satellite imagery, the derived time series allow for monitoring lake storage changes and river discharge. However, satellite altimetry is limited in spatial resolution due to its measurement geometry, only providing information in nadir direction beneath the satellite’s orbit. In a case study in the Mississippi River Basin (MRB), this study investigates the potential and the limitations of past and current satellite missions to monitor basin-wide storage changes. For that purpose an automated target detection is developed and the extracted lake surfaces are merged with the satellites’ tracks. This reveals that the current altimeter configuration misses about 80% of all lakes larger than 0.1 km2 in the MRB, and still 20% of lakes larger than 10 km2, corresponding to 30% and 7% of surface area, respectively. Past altimetry configurations perform even worse. From the water bodies represented by a global hydrology model, at least 91% of targets and 98% of storage changes are captured by the current altimeter configuration. This will significantly improve with the launch of the planned SWOT mission.

Providing data on usage patterns is key to assessing the reduced-risk potential of novel tobacco and nicotine products at a population level. We performed a nationwide cross-sectional survey of the general population in Japan to assess usage patterns after the introduction of tobacco heating products (THPs). Eligible participants were Japanese residents, aged 20 years or older who consented to complete the survey. Individuals living in institutions were excluded. A three-stage probability sampling method was applied that was geographically stratified by street blocks proportionate to population density. Respondents self-reported patterns of product use and reasons for THP use. Complete responses were available from 5,306 individuals, of whom 933.5 (17.6%) were current users, 984.2 (18.5%) were former users and 3388.4 (63.9%) were never users of tobacco products. Cigarettes were used by 14.6% of current tobacco product users and THPs by 5.3%. Cigarettes and THPs were used exclusively by 64.5% and 12.2%, respectively, and both were used by 12.7%. The most common reasons reported for THP use were perceived reduction in harm to self and others compared to cigarettes. While the prevalence of cigarette use in Japan is decreasing, THPs seem to be increasingly used as long-term alternatives to cigarette smoking.

The aim of this study is to study the effect of aging in different media (deionized water and artificial saliva) on the force/torque generation by thermoplastic orthodontic aligners. Ten thermoformed aligners made of Essix ACE® thermoplastic sheets were aged in deionized water and in artificial saliva over two weeks at 37 C, five in each medium. The force/torque generated on upper second premolar (Tooth 25) of a resin model was measured at day 0 (before aging), 2, 4, 6, 10, and 14, using a biomechanical test set-up. The results showed that the thermocycling of aligners has no significant impact on their force/torque decay. No significant differences were also found in force/torque between the aligners stored in deionized water nor artificial saliva. The vertical extrusion-intrusion forces were measured in the range of 1.4 to 4.6 N, the horizontal oro-vestibular forces were 1.3 to 2.5 N, while the torques on mesio-distal rotation were 5.4 to 41.7 Nmm. It could be concluded that the influence of saliva on the mechanical properties can be classified as insignificant, and no significant difference between artificial aging in deionized water or artificial saliva was observed.

The Selective Paste Intrusion (SPI) method is a layer-by-layer additive manufacturing technique that allows for the production of complex geometries in concrete elements by selectively bonding aggregates with cement paste in a particle bed. To create reinforced concrete, the Wire and Arc Additive Manufacturing (WAAM) process shall be integrated into SPI. This technique allows the production of almost free-formed reinforcement and thus complements the advantage of SPI to produce free-formed structures of almost any geometry. However, integration of WAAM into SPI poses a considerable challenge, as high temperatures are generated during the welding process. These temperatures can negatively affect the rheological properties of the cement paste, in turn the penetration behavior of the paste in the particle bed and, subsequently, the mechanical properties of the hardened concrete. A possible passive cooling strategy is to increase the protruding length of the reinforcement bars out of the particle-bed. This requires that the distance of the print nozzle to the particle bed is as well increased, since it must be possible to move it across the reinforcement. The objective was thus to investigate the effect of that distance on print quality and to quantify a maximum allowable distance for an adequate print quality (for the printer setting used) in terms of shape accuracy and concrete strength. Compressive and flexural strength tests as well as geometrical measurements using a 3D scanning method were performed on specimen, printed with varying print nozzle to particle bed distances. It can be stated that for the used SPI print-heads, nozzle-types and parameter settings, the distance between the nozzle and the particle bed should not exceed 50 mm to ensure sufficient print quality in both shape accuracy and mechanical strength.

Background: Health inequity (HI) remains a major challenge in public health. Improving the health of children with low socioeconomic status (SES) can help to reduce overall HI in children. Childhood obesity is a global problem, entailing several adverse health effects. It is crucial to assess influencing factors for adoption, implementation and sustainment of interventions. This review aims to identify articles reporting about influencing factors for the implementation of school-based interventions promoting obesity prevention behaviors in children with low SES. It aims to critically appraise the articles’ quality, assess influencing factors, categorize and evaluate them, and to discuss possible implications. Methods: A systematic search was conducted in 7 databases with the following main inclusion criteria: 1) school-based interventions and 2) target group aged 5–14 years. The Consolidated Framework for Implementation Research, its five domains (intervention characteristics, inner setting, outer setting, characteristics of individuals, process) along with 39 constructs within these domains were used to deductively analyze the data. We grouped the articles with regard to the characteristics of the interventions in simple and complex interventions. For each domain, and for the groups of simple and complex interventions, the most commonly reported influencing factors are identified. Results: 6452 articles were screened, and 16 met all eligibility criteria. Included articles applied mixed methods (n=10), qualitative (n=5) and quantitative design (n=1). Of these, five were considered to report simple interventions and eleven were considered to report complex interventions. In total, 295 influencing factors were assessed. Aspects of the inner setting were reported in every study, aspects of the outer setting were the least reported domain, and in the group of simple interventions not reported at all. In the inner setting, most reported influencing factors were time (n=7), scheduling (n=6) and communication (n=6). Conclusion: This review found a wide range of influencing factors for implementation. Most important influencing factors need to be assessed for every setting. Including all stakeholders involved in the implementation process enhances the prioritization of the most important influencing factors for the specific setting. More empirical research and practical guidance are needed to promote obesity prevention behaviors among children with low SES.

Two-wheeler vehicles are the most significant mode of transportation for Kenyans in both rural and urban regions thereby contributing to local air pollution, and greenhouse gas emissions (GHG). The transition to electric two-wheeler vehicles can make a significant contribution to reducing GHG and improving the socio-economic lives of people living in rural Kenya. Re-newable energy systems can considerably contribute to the charging of electric two-wheeled vehicles, thus leading to the reduction of carbon emissions and the expansion of renewable energy penetration in rural Kenya. Therefore, this paper focuses on integrating and modelling electric two-wheeled vehicles (e-bikes) into an off-grid photovoltaic Water-Energy Hub located in the Lake Victoria Region of Western Kenya using the Conventional and Renewable Energy Opti-mization (CARNOT) Toolbox in MATLAB / Simulink. Electricity demand data obtained from the Water-Energy Hub was investigated and analysed. Potential solar energy surplus was identified and electric two-wheeler vehicles were integrated based on the surplus. A field measurement investigation on the energy consumption of the electric two-wheeler vehicles based on the rider’s driving behaviour was also carried. The annual electricity demand of 27,267 kWh, photovoltaic (PV) electricity production of 37,785 kWh with an electricity deficit of 370 kWh were obtained from the simulation results. To reduce the electricity deficit, a load optimisation algorithm was de-veloped to optimally integrate the electric 2-wheeler vehicle into the Water-Energy Hub. It was found that using the load optimisation algorithm, the annual electricity deficit was reduced to 1 kWh and the annual electricity demand was increased by 11% (30,767 kWh) which is enough to charge 4 additional electric two-wheeler batteries daily.

Structure quality of LuFeO3 epitaxial layers grown by pulsed-laser deposition on sapphire substrates with and without platinum interlayers has been investigated by in-situ high-resolution x-ray diffraction (reciprocal-space mapping). The parameters of the structure such as size and misorientation of mosaic blocks have been determined as functions of the thickness of LuFeO3 during the PLD growth and for different platinum interlayers thicknesses up to 40 nm. The x-ray diffraction results combined with ex-situ scanning electron microscopy and high-resolution transmission electron microscopy demonstrate that the Pt interlayer significantly improves the structure of LuFeO3 by reducing the misfit of the LuFeO3 lattice with respect to the material underneath.

Iron-containing nickel sulfides, selenides, and sulfoselenides were synthesized via a simple two-step hydrothermal reaction (temperature 160 °C) for their application as electrocatalysts in the oxygen evolution reaction (OER) in an alkaline solution (1 mol L–1 KOH). The study demonstrated that iron-containing nickel cobalt sulfides and selenides exhibit superior OER performance with lower overpotentials compared to iron-free nickel cobalt sulfide and selenide, which highlights the significant role of iron in enhancing OER nickel cobalt electrocatalysts: Fe0.1Ni1.4Co2.9(S0.87O0.13)4, η50 = 318 mV; Fe0.2Ni1.5Co2.8(S0.9O0.1)4, η50 = 310 mV; Fe0.3Ni1.2Co2.5(S0.9O0.1)4, η50 = 294 mV; Fe0.6Ni1.2Co2.5(S0.83O0.17)4, η50 = 294 mV, Fe0.4Ni0.7Co1.6(Se0.81O0.19)4, η50 = 306 mV compared to Ni1.0Co2.1(S0.9O0.1)4, η50 = 346 mV and Ni0.7Co1.4(Se0.85O0.15)4, η50 = 355 mV (all values at current densities η50 of 50 mA cm–2). Furthermore, the iron-containing nickel cobalt sulfoselenide Fe0.5Ni1.0Co2.0(S0.57Se0.25O0.18)4 displayed exceptional OER performance with η50 = 277 mV, surpassing the benchmark RuO2 electrode with η50 = 299 mV. The superior performance of the sulfoselenide was attributed to its low charge transfer resistance (Rct) of 0.8 Ω at 1.5 V vs. the reversible hydrogen electrode (RHE). Moreover, the sulfoselenide demonstrated remarkable stability, with only a minimal increase in overpotential (η50) from 277 mV to 279 mV after a 20 h chronopotentiometry test. These findings suggest that trimetallic iron, nickel and cobalt sulfide, selenide and especially sulfoselenide materials hold promise as high-performance, cost-effective, and durable electrocatalysts for sustainable OER reactions. This study provides a valuable approach for the development of efficient electrocatalytic materials, contributing to the advancement of renewable energy technologies.

In this paper, we present a method for detecting and quantifying pathogens in water samples. The method proposes a portable dark field imaging and analysis system for quantifying E. coli concentrations in water after being labeled with magnetic particles. The system utilizes the tracking of moving micro/nano objects close to or below the optical resolution limit confined in small sample volumes (~ 10 µl). In particular, the system analyzes the effect of volumetric changes due to bacteria conjugation to magnetic microparticles (MP) on their Brownian motion while being suspended in liquid buffer solution. The method allows for a simple inexpensive implementation and the possibility to be used as point-of-need testing system. Indeed, a work-ing prototype is demonstrated with the capacity of quantifying E. coli colony forming units (CFU) at a range of 1x10³ - 6x10³ CFU/mL.

The chemical graph theory is a subfield of mathematical chemistry which applies classic graph theory to chemical entities and phenomena. Chemical graphs are main data structures to represent chemical structures in cheminformatics. Computable properties of graphs lay the foundation for (quantitative) structure activity and structure property predictions - a core discipline of cheminformatics. It has a historic relevance for natural sciences, such as chemistry, biochemistry and biology, and is in the heart of modern disciplines, such as cheminformatics and bioinformatics. This review first covers the history of chemical graph theory, then provides an overview of its various techniques and applications for CASE, and finally summarises modern tools using chemical graph theory for CASE.

The emergence of carbapenemase-producing Enterobacteriaceae has limited therapeutic options and presents a major public health problem. Resistances against carbapenems in this bacterial family are mostly conveyed by metallo-beta-lactamases (MBL) including VIM, which are often encoded on resistance plasmids. We characterized four VIM-positive isolates that were obtained as part of a routine diagnostic screening from two laboratories in north-eastern Germany be-tween June and August 2020. Whole-genome sequences were generated to address a) their phylo-genetic properties, b) their plasmid content, and c) the underlying mechanisms of resistance and virulence. In addition, we performed phenotypic antibiotic and mercury resistance analyses. The genomic analysis revealed three different bacterial species including C. freundii, E. coli and K. oxytoca with four different sequence types. All isolates were geno- and phenotypically multi-drug-resistant (MDR). Three isolates of four carried identical VIM-1-resistance plasmids, which – in addition – encoded for a mercury resistance operon and showed some similarity to two ex-ternal plasmid sequences. The distribution of virulence features among the genomes was limited. Our results highlight the circulation of an identical VIM-1-resistance plasmid in three of four bacterial isolates of different Enterobacteriaceae in north-eastern Germany.

We developed a novel machine learning algorithm to augment clinical diagnosis of prostate cancer utilizing first and second-order texture analysis metrics and novel application of machine learning radiomics analysis. We successfully discriminated between significant prostate cancers versus non-tumor regions and provided accurate prediction between Gleason score cohorts with statistical sensitivity of greater than 0.91 sensitivity across three separate cohorts. Tumor heterogeneity and prediction between GS cohorts were quantified using two feature selection approaches and two classifiers with tuned hyperparameters (including grid search and randomized search). There was a total of 71 patients analyzed in this study. Multiparametric MRI, incorporating T2WI and the ADC maps, were used to derive radiomics features. Recursive feature elimination (RFE), the least absolute shrinkage and selection operator (LASSO), and two classification approaches, including a support vector machine (SVM) (with grid search) and random forest (RF) (with randomized search), were utilized to differentiate between non-tumor regions versus significant cancer and prediction among Gleason score groups. In T2WI images, the RFE feature selection approach combined with RF and SVM classifiers outperformed LASSO with SVM and RF classifiers regarding performance. The detection precision of the radiomics framework depending on multiple imaging modalities was lower than the diagnostic accuracy of single imaging modality model with every machine learning approach assessed. The best performance was achieved by combining LASSO and SVM into a model that used both T2WI and ADC. This model had an area under the curve (AUC) of 0.91. Radiomic features computed from ADC and T2WI images were used to predict three groups of Gleason score using two kinds of feature selection methods (RFE and LASSO), RF and SVM classifier models with tuned hyperparameters. Using combined sequences (T2WI and ADC map images) and combined radiomics (1st and GLCM features), LASSO, with a feature selection method with RF, was able to predict G3 with the highest sensitivity at a level AUC of 0.92. To predict G3 for single sequence (T2WI images) using GLCM features, LASSO with SVM achieved the highest sensitivity with an AUC of 0.92.

The detection and enrichment of circulating melanoma cells is a challenge as the cells are very heterogeneous in terms of their biomechanical properties and surface markers. In addition, there is a lack of valid and reliable biomarkers that predict progress and therapeutic response. We here analyzed the elasticity of A375 melanoma cells applying force spectroscopy and a microfluidic method. To identify and eventually separate circulating tumor cells, it is crucial to precisely know their physical properties. First, we used standard AFM force spectroscopy, where the elasticity of the cells is calculated from indentation with a pyramidal tip. To extend the limits of measurement with a tip, we then used cantilevers without a tip to press on the cells over a large area. The resulting Young’s moduli are slightly lower and vary less without tip presumably because of the inhomogeneity of the cells. Finally, we implemented our microfluidic method. We measured single cell elasticity by analyzing its deformation in high-speed micrographs while passing a stenosis. Combining the force field and the change in shape provides the basis for a stress strain diagram. The results from microfluidic deformation analysis were in accordance with the results from force spectroscopy. The microfluidic method provides advantages over conventional methods, since it is less invasive and less likely to harm the cell during the measurement, and the whole cell is measured as one entity without contact to a stiff substrate, while force spectroscopy is limited to the contact area of the tip, and in some cases dependent of the cell substrate interaction. Consequently, microfluidic deformation analysis allows to predict the overall elastic behavior of the whole inhomogeneous cell in three-dimensional force fields. This method may contribute to improve the detection of circulation melanoma cells in the clinical practice.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

Metal-organic frameworks (MOFs) are investigated for the oxygen evolution reaction (OER) due to their structure diversity, high specific surface area, adjustable pore size and abundant active sites. However, the poor conductivity of most MOFs restricts this application. Herein, through a facile one-step solvothermal method, the Ni-based pillared metal-organic framework [Ni2(BDC)2DABCO] (BDC = 1,4-benzenedicarboxylate, DABCO = 1,4-diazabicyclo[2.2.2]octane), its bimetallic nickel-iron form [Ni(Fe)(BDC)2DABCO] and their modified Ketjenblack (mKB) composites were synthesized and tested towards OER in an alkaline medium (KOH 1 mol L–1). A synergistic effect of the bimetallic nickel-iron MOF and the conductive mKB additive enhance the catalytic activity of the MOF/mKB composites. All MOF/mKB composite samples (7, 14, 22, 34 wt.% mKB) indicated much higher OER performances than the MOFs and mKB alone. The Ni-MOF/mKB14 composite (14 wt. % of mKB) demonstrated an overpotential of 294 mV at a current density of 10 mA cm–2 and Tafel slope of 32 mV dec–1, which is comparable with commercial RuO2 commonly used as a benchmark material for OER. The catalytic performance of Ni(Fe)MOF/mKB14 (0.57 wt% Fe) was improved further to an overpotential of 279 mV at a current density of 10 mA cm–2. The low Tafel slope of 25 mV dec–1 as well as a low reaction resistance due to electrochemical impedance spectroscopy (EIS) measurement confirm the excellent OER performance of the Ni(Fe)MOF/mKB14 composite. For practical applications, the Ni(Fe)MOF/mKB14 electrocatalyst was impregnated into commercial nickel foam (NF), where overpotentials of 247 and 291 mV at current densities of 10 and 50 mA cm–2, respectively, were realized. The activity was maintained for 30 h at the applied current density of 50 mA cm–2. The electrocatalytic system consisting of earth-abundant Ni and Fe metals only would be attractive for the development of efficient, practical and economical energy conversion materials for efficient OER activity.

Education outside the classroom (EOtC) can be beneficial for students. The relationship between biological stress markers and sedentary behavior (SB) plus physical activity (PA) is insufficiently evaluated in school settings. This exploratory study aims to evaluate the association between students’ cortisol, plus circulating cell-free deoxyribonucleic acid (cfDNA) levels, and their SB, light PA (LPA) and moderate-to-vigorous PA (MVPA) during outdoor and indoor classes in different seasons. We assessed data from an education outside the classroom (EOtC) program (n = 48; intervention group [IG], n = 37; control group [CG], n = 11). We sampled data on 3 school-days in three seasons (fall, spring, and summer) in normal teaching indoors (CG) and outdoor lessons (IG) in the forest. SB and PA were evaluated by accelerometry, and cortisol and cfDNA levels by saliva samples. The compositional data analysis approach analyzed SB and PA. Fitted Bayesian hierarchical linear models evaluated the association between cortisol and cfDNA, and SB/LPA/MVPA. A steady decline of cortisol in the outdoor setting is associated with relatively high levels of LPA. SB and MVPA tended to exhibit a similar effect in the indoor setting. CfDNA is positively associated with a relatively high amount of SB in the IG, the same association is likely for LPA and MVPA in both groups. LPA seems to support a healthy cortisol decrease in children during outdoor lessons. The relevance of SB/PA as a composition in relation to students stress response in school should be emphasized. This study facilitates the formulation of straightforward and directed hypotheses for further research.

Thin supported inorganic mesoporous membranes are used for removal of salts, small molecules (PFAS, dyes, polyanions) and particulate species (oil droplets) from aqueous sources with high flux and selectivity. Nano-filtration membranes can reject simple salts with 80-100% selectivity through a space charge mechanism. Rejection by size selectivity can be near 100% since the membranes can have a very narrow size distribution. Mesoporous membranes have received par-ticular interest due to their (potential) stability at operational conditions and defouling operations. More recently membranes with extreme stability became interesting with the advent of in-situ fouling mitigation by means of ultrasound, emitted from within the membrane structure. For this reason we explored the stability of available and new membranes with accelerated lifetime tests in aqueous solutions at various temperatures and pH values. Of the available ceria, titania, mag-netite membranes none were actually stable at all test conditions. In earlier work, it was already established that meso-porous alumina membranes have very poor stability. A new nano-filtration membrane was made of cubic zirconia membranes that exhibited a near perfect stability. A new ultra-filtration membrane was made of amorphous silica that was fully stable in ultrapure water at 80°C. This work provides details of membrane synthesis, stability characterization and actual sta-bility data.

The availability of high quality surface observations of precipitation and volume observations by polarimetric operational radars make it possible to constrain, evaluate and validate numerical models with a wide variety of microphysical schemes. In this article, a novel particle-based Monte-Carlo microphysical model (called “McSnow”) is used to simulate the outer rain bands of Hurricane Dorian which traversed the densely instrumented precipitation research facility operated by NASA at Wallops Island, Virginia. The rain bands showed steady stratiform vertical profiles with radar signature of dendritic growth layers near −15 °C and peak reflectivity in the bright band of 55 dBZ along with polarimetric signatures of wet snow with sizes inferred to exceed 15 mm. A 2D-video disdrometer measured frequent occurrences of large drops &gt;5 mm and combined with an optical array probe the drop size distribution was well-documented in spite of uncertainty for drops &lt;0.5 mm due to high wind gusts and turbulence. The 1D McSnow control run and four numerical “experiments” were conducted and compared with observations. One of the main findings is that even at the moderate rain rate of 10 mm/h collisional breakup is essential for the shape of the drop size distribution.

Lipophilic oligonucleotide derivatives are a potent approach to the intracellular delivery of nucleic acids. The binding of these derivatives to serum albumin is a major determinant of their fate in the body, as its structure contains several sites of high affinity for hydrophobic compounds. This study focuses on the features of self-association and non-covalent interactions with human serum albumin of novel self-penetrating oligonucleotide derivatives. The study revealed that the introduction of a triazinyl phosphoramidate modification bearing two dodecyl groups at the 3' end region of the oligonucleotide sequence has a negligible effect on its affinity for the complementary sequence. Dynamic light scattering verified that the amphiphilic oligonucleotides under study can self-assemble into micelle-like particles ranging from 8 to 15 nm in size. The oligonucleotides with dodecyl groups form stable complexes with human serum albumin with a dissociation constant of approximately 10-6 M. The oligonucleotide micelles are simultaneously destroyed upon binding to albumin. Using an electrophoretic mobility shift assay and affinity modification, we examined the ability of DNA duplexes containing triazinyl phosphoramidate oligonucleotides to interact with Ku antigen and PARP1, as well as the mutual influence of PARP1 and albumin or Ku antigen and albumin upon interaction with DNA duplexes. These findings, together with the capability of dodecyl-containing derivatives to effectively penetrate different cells, such as HEK293 and T98G, indicate that the oligonucleotides under study can be considered as a platform for the development of therapeutic preparations with a target effect.

In this paper an overview of waste materials in underground coal mines is presented, whereas waste materials can be of anthropogenic or geogenic origin. Complex interactions with mine water and waste materials take place, especially during mine water level rebound. Bearing in mind that under the increasing societal pressure most, if not all underground coal mines are going to be closed rather sooner than later, it is important to understand these interactions and to predict the composition and dynamics of mine water lever rebound in underground coal mines to prevent adverse effects to the environment, especially receiving waters and drinking water resources. The second part of this article focusses on the experiences gained in the Ruhr area, a closed underground coal mining region in Western Germany, where mine water rebound has been ongoing for decades. In this regard, the modelling program DMT-Boxmodel has been developed and applied to predict the hydrodynamics and hydrogeochemical development of the water rebound. As an example, simulation results of water rebound as well as solute and PCB transport in central province of Ruhr mining area are compared to the monitoring data, and predictions over 3 decades are given. The experiences gained in the mine water management in Ruhr area can be applied in mining areas worldwide.

High-resolution laboratory-based thermal infrared spectroscopy is an up-and-coming tool in the field of geological remote sensing. Its spatial resolution allows for detailed analyses at centimeter to sub-millimeter scale. However, this increase in resolution creates challenges with sample characteristics such as grain size, surface roughness and porosity that can influence the spectral signature. This research explores the effect of rock sample surface preparation on the TIR spectral signatures. We applied three surface preparation methods (split, saw and polish) to determine how the resulting differences in surface roughness affects both the spectral shape as well as the spectral contrast. The selected samples are a pure quartz sandstone, a quartz sandstone containing a small percentage of kaolinite, and an intermediate-grained gabbro. To avoid instrument or measurement type biases we conducted measurements on three TIR instruments, resulting in directional hemispherical reflectance spectra, emissivity spectra and bi-directional reflectance images. Surface imaging and analyses were performed with scanning electron microscopy and profilometer measurements. We demonstrate that surface preparation affects the TIR spectral signatures influencing both the spectral contrast as well as the spectral shape. The results show that polished surfaces predominantly display a high spectral contrast while the sawed and split surfaces display up to 25% lower reflectance values. Furthermore, the sawed and split surfaces display spectral signature shape differences at specific wavelengths, which we link to mineral transmission features, surface orientation effects and multiple reflections in fine-grained minerals. Hence, the influence of rock surface preparation should be taken in consideration to avoid an inaccurate geological interpretation.

As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxicants to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the blood stream resulting in rapid distribution in the body. Consequently, mucosal barriers present in nose, buccal and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where a) different cultivation conditions such as air-liquid interface or submerged cultures, b) varying barrier maturity and c) diverse media substitutes have been used. The current comparative nanotoxicological study therefore aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions and tissue type using standard Transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and Presto Blue assays of immature (e.g. 5 days) and mature (e.g. 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular responses to increasing nanoparticle exposures are highly cell type specific, where bronchial mucosal cell barriers models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures. Additionally, stronger toxicities are found using early mucosa barriers compared to later barrier models being maturated under air-liquid cultivation conditions.

This study introduces a compact Raman spectrometer with a 1064 nm excitation laser coupled with a fiber probe and an inexpensive motorized stage, offering a promising alternative to widely used Raman imaging instruments with 785 nm excitation lasers. The benefits of 1064 nm excitation for biomedical applications include further suppression of fluorescence background and deeper tissue penetration. The performance of the 1064 nm instrument in detecting cancer in human bladder resectates is demonstrated. Raman images with 1064 nm excitation were collected ex vivo from 10 human tumor and non-tumor bladder specimens and the results are compared to previously published Raman images with 785 nm excitation. K-Means cluster (KMC) analysis is used after pre-processing to identify Raman signatures of control, tumor, necrosis, and lipid-rich tissues. Hierarchical cluster analysis (HCA) groups the KMC centroids of all specimens as input. The tools for data processing and hyperspectral analysis were compiled in an open source Python library called SpectraMap (SpMap). In conclusion, the 1064 nm Raman system can differentiate between tumor and non-tumor bladder tissues in a similar way to 785 nm Raman spectroscopy. These findings hold promise for future clinical hyperspectral imaging.

New experimental and clinical findings question the historic view of hydrocephalus and its 100-year-old classification. In particular, real-time MRI evaluation of CSF flow and detailed insights into brain water regulation on the molecular scale indicate the existence of at least three main mechanisms that determine the dynamics of neurofluids. (i) Inspiration is a major driving force (ii) Adequate filling of brain ventricles by balanced cerebrospinal fluid upsurge is sensed by cilia (iii) The perivascular glial network connects the ependymal surface to the pericapillary Virchow-Robin spaces. Hitherto, these aspects have not been considered a common physiologic framework improving knowledge and therapy for severe disorders of normal-pressure and post-haemorrhagic hydrocephalus, spontaneous intracranial hypotension and spaceflight disease.

The aim of the study is to investigate the effects of artificial aging by thermocycling and mechanical loading on force/torque delivery by thermoplastic orthodontic aligners. Ten thermoformed aligners made of Zendura™ thermoplastic polyurethane sheets were aged over two weeks in deionized water by thermocycling alone (n=5) and by both thermocycling and mechanical loading (n=5). The force/torque generated on upper second premolar (Tooth 25) of a plastic model was measured before aging (as control), and after 2, 4, 6, 10, and 14 days of aging, using a biomechanical set-up. Before aging, the extrusion-intrusion forces were in the range of 2.4 to 3.0 N, the oro-vestibular forces were 1.8 to 2.0 N, and the torques on mesio-distal rotation were 13.6 to 40.0 Nmm. Pure thermocycling had no significant effect on the force decay of the aligners. However, there was a significant decrease in force/torque after 2 days of aging for both thermocycling and mechanical loading aging group, which is no longer significant over 14 days of aging. In conclusion, artificial aging of aligners in deionized water with thermocycling and mechanical loading results in a significant decrease in force/torque generation. However, the mechanical loading of aligners has a greater impact than thermocycling alone.

The objective of this paper is to investigate the debonding behavior of the interface between continuously and discontinuously fiber reinforced thermoplastics using the climbing drum peel test. The study emphasizes the importance of considering different climatic boundary conditions due to the properties of thermoplastics. Specimens with varying moisture contents are prepared and tested. It is observed that an increase in moisture content initially results in a higher fracture surface energy being required to separate the two materials, but a further increase results in a decrease of the required energy. The study presents an explanatory model of increasing plasticization of the polymer due to increased polymer chain mobility, which results in more deformation energy being required to propagate the crack. The experiment is also modeled numerically for the first time with cohesive surfaces, which successfully reproduces the force-displacement curve in the experiment.

We synthesized iron(II)-triazole spin crossover compounds of the type [Fe(atrz)3]X2 and incorporated and deposited them on electrospun polymer nanofibers. In view of possible applications, we chose iron(II)-triazole-complexes that are known to exhibit spin crossover close to ambient temperature. Therefore we used the complexes [Fe(atrz)3]Cl2 and [Fe(atrz)3](2ns)2 (2ns = 2Naphthalenesulfonate) and analyzed them with IR-, UV/Vis and Mossbauer spectroscopy and with a SQUID magnetometer. The synthesized complexes were then in one attempt deposited on fibers of polymethylmethacrylate (PMMA) and in another attempt incorporated into core-shell like PMMA fiber structures. This was done via two different electrospinning methods. Deposition was performed by uniaxial electrospinning and incorporation was performed by coaxial electrospinning. The obtained polymer-complex-composites were then further investitgated by the same methods as the pure complexes as well as by SEM pictures and EDX measurements. The analysis by UV/Vis spectroscopy, Mössbauer spectroscopy and temperature-depended magnetic measurements with the SQUID magnetometer showed that the spin crossover properties were maintained and were not changed after the electrospinning processes and that the complexes were not harmed during the procedure.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.