Ruthenium dioxide (RuO2) thin films were synthesized by Chemical Solution Deposition (CSD) on silicon substrates using only water and acetic acid as solvents. The microstructure, phase purity, electrical and optical properties as well as the thermal stability of the thin films have been characterized. The microstructure of the thin films strongly depends on the annealing temperature: A smooth thin film was achieved at an annealing temperature of 600 °C. Higher annealing temperatures (800 °C) led to radial grain growth and an inhomogeneous thin film. A very low resistivity of 0.89 µΩm was measured for a 220 nm-thick thin film prepared at 600 °C. The resistivity of the thin films increases with temperature, which indicates metallic behavior. Phase purity of the thin films was confirmed with X-ray Diffraction (XRD) measurements, X-ray Photoelectron Spectroscopy (XPS) and Raman spectroscopy. Transmission and reflectivity measurements indicate that RuO2 efficiently blocks the UV-VIS and IR wavelengths. The optical constants determined via spectroscopic ellipsometry show high absorption in the near-IR region as well as a lower one in the UV-VIS region. The thermal stability was investigated by post-annealing, confirming that the thin films are stable up to 750 °C in synthetic air. Graphical Abstract
Four pinaceae pine resins analyzed in this study: black pine, shore pine, Baltic amber, and rosin demonstrate excellent dielectric properties, outstanding film forming, and ease of processability from ethyl alcohol solutions. Their trap‐free nature allows fabrication of virtually hysteresis‐free organic field effect transistors operating in a low voltage window with excellent stability under bias stress. Such green constituents represent an excellent choice of materials for applications targeting biocompatibility and biodegradability of electronics and sensors, within the overall effort of sustainable electronics development and environmental friendliness.
The COVID-19 pandemic exposed and reinforced the structural crisis in paid and unpaid care work. On the one hand, pandemic-related closures of schools and childcare facilities increased the fragility of unpaid care arrangements, which are mainly organised by women. On the other hand, high infection and hospitalisation rates exacerbated the difficult working conditions in health-care professions, ranging from low wages and long working hours to high levels of mental and physical stress. Drawing on interviews conducted in an ongoing project in the German and Austrian health-care sector, this article investigates, from a gender perspective, how employees in health-care professions, who are at the very centre of both the unpaid and paid care crises, experienced this precarious situation during the pandemic. We suggest that the female-dominated sectors of paid and unpaid care work experienced further devaluation during the COVID-19 pandemic, while attempts to valorise their work were rather short-lived. We further argue that the structural crisis in paid care work is threatening the functionality of the health-care sector.
Burn wounds are a common challenge for medical professionals. Current burn wound models hold several limitations, including a lack of comparability due to the heterogeneity of wounds and differences in individual wound healing. Hence, there is a need for reproducible in vivo models. In this study, we established a new burn wound model using the chorioallantoic membrane assay (CAM) as a surrogate model for animal experiments. The new experimental setup was tested by investigating the effects on burn wound healing of the auspicious biophysical therapy photobiomodulation (PBM), which has been shown to positively influence wound healing through vascular proliferative effects and the increased secretion of chemotactic substances. The easily accessible burn wounds can be treated with various therapies. The model enables the analysis of ingrowing blood vessels (angiogenesis) and diameter and area of the wounds. The established model was used to test the effects of PBM on burn wound healing. PBM promoted angiogenesis in burn wounds on day 4 (p = .005). Furthermore, there was a not significant trend toward a higher number of vessels for day 6 (p = .065) in the irradiated group. Changes in diameter (p = .129) and the burn area (p = .131) were not significant. Our results suggest that CAM can be a suitable model for studying burn wounds. The novel experimental design enables reproducible and comparable studies on burn wound treatment.
Ski tourism is a substantial component of the economy of mountainous regions in Europe and is highly vulnerable to snow scarcity, which is increasing due to climate change. However, the climate change snow supply risk to ski tourism has not been quantified in a consistent way throughout Europe, including the influence and environmental footprint of snowmaking. Here we show that the snow supply risk to ski tourism increases with global warming level, heterogeneously within and across mountain areas and countries. Without snowmaking, 53% and 98% of the 2,234 ski resorts studied in 28 European countries are projected to be at very high risk for snow supply under global warming of 2 °C and 4 °C, respectively. By contrast, assuming a snowmaking fractional coverage of 50% leads to corresponding proportions of 27% and 71%, but with increasing water and electricity demand (and related carbon footprint) of snowmaking. While it represents a modest fraction of the overall carbon footprint of ski tourism, snowmaking is an inherent part of the ski tourism industry and epitomizes some of the key challenges at the nexus between climate change adaptation, mitigation and sustainable development in the mountains, with their high social-ecological vulnerability.
Aims: Drivers of the drug tolerant proliferative persister (DTPP) state have not been well investigated. Histone H3 lysine-4 trimethylation (H3K4me3), an active histone mark, might enable slow cycling drug tolerant persisters (DTP) to regain proliferative capacity. This study aimed to determine H3K4me3 transcriptionally active sites identifying a key regulator of DTPPs. Methods: Deploying a model of adaptive cancer drug tolerance, H3K4me3 ChIP-Seq data of DTPPs guided identification of top transcription factor binding motifs. These suggested involvement of O-linked N-acetylglucosamine transferase (OGT), which was confirmed by metabolomics analysis and biochemical assays. OGT impact on DTPPs and adaptive resistance was explored in vitro and in vivo. Results: H3K4me3 remodeling was widespread in CPG island regions and DNA binding motifs associated with O-GlcNAc marked chromatin. Accordingly, we observed an upregulation of OGT, O-GlcNAc and its binding partner TET1 in chronically treated cancer cells. Inhibition of OGT led to loss of H3K4me3 and downregulation of genes contributing to drug resistance. Genetic ablation of OGT prevented acquired drug resistance in in vivo models. Upstream of OGT, we identified AMPK as an actionable target. AMPK activation by acetyl salicylic acid downregulated OGT with similar effects on delaying acquired resistance. Conclusion: Our findings uncover a fundamental mechanism of adaptive drug resistance that governs cancer cell reprogramming towards acquired drug resistance, a process that can be exploited to improve response duration and patient outcomes.
Facial skin cancer (FSC) is prone to incomplete excision due to the sophisticated anatomy and the aesthetic importance of the face. In this study, we sought to investigate to what extent sex-specific differences and other operation-, patient-, and cancer-specific factors influence the re-resection rate in FSC surgery, in order to provide personalized treatment strategies to patients. In this retrospective study, patients (>18 years) undergoing surgical excision of an FSC were enrolled. Each patient’s demographic data, cancer location, the surgical team, primary and secondary surgeries were analyzed. Overall, 469 patients (819 surgeries) were included. The mean age was 69 ± 15 years. No significant association between sex-specific factors (surgeon’s sex (OR: 1.09, 95% CI: 0.76–1.56) or patient’s sex (OR: 0.85, 95% CI: 0.62–1.17), surgeon–patient sex concordance and discordance) and the likelihood of secondary surgery were found. However, healing by secondary intention (OR: 4.28; 95% CI: 1.94–9.45) and cancer location showed an increased re-resection rate. In conclusion, FSC surgery is a safe method unaffected by sex-specific factors, which had no impact on the re-resection rate. However, in further analysis, the likelihood of a re-resection was influenced by other factors such as healing by secondary intention and cancer location. This knowledge might be useful to provide an algorithm for personalized treatment strategies in the future.
Measuring the shear viscosity of polymeric melts is an extensive effort frequently performed in high-pressure capillary rheometers, where the pressures required to push the melt through a capillary at various temperatures and volumetric flow rates are recorded. Then, the viscosity values are obtained through Bagley and Weissenberg–Rabinowitsch corrections involving parameter fitting. However, uncertainties in those conversions due to pressure variations and measurement inaccuracies (random errors) affect the accuracy of the consequently calculated viscosities. This paper proposes quantifying them through a propagation of uncertainties calculation. This has been experimentally demonstrated for a polycarbonate melt. In addition, the derived viscosity uncertainties were used for the weighted residual sum of squares parameter estimation of the Cross-WLF viscosity model and compared with the coefficients obtained using the standard residual sum of squares minimization approach. The motivation was that, by comparison, individual poorly measured viscosity values should have a less negative impact on the overall fit quality of the former. For validation, the rheometer measurements were numerically simulated with both fits. The simulations based on the Cross-WLF fit, including the derived viscosity uncertainties, matched the measured pressures ~16% more closely for shear rates below 1500 1/s. Considering the uncertainties led to more precise coefficients. However, both fits showed substantial deviations at higher shear rates, probably due to substantial non-isothermal flow conditions that prevailed during these measurements. A capillary rheometer experiment was also simulated using arbitrarily chosen Cross-WLF parameters to exclude such systematic errors. A normally distributed error was then applied to the simulated pressures before re-fitting the parameters. Again, taking advantage of the derived viscosity uncertainties, the fit could recover the initial parameters better.
Smart sensor systems are increasingly pervading all kind of application fields such as in industry, ambient assisted living, or lifestyle accessories. In this work, a smart system for position-oriented human fall detection is investigated using various machine-learning algorithms for data processing and evaluation. Data from an inertial measurement unit is combined with data from visible light positioning methods to achieve position-based fall detection. Furthermore, an experimental setup and test methods were created to generate appropriate datasets for this analysis. The classification accuracy is compared with three machine-learning algorithms commonly used for such tasks, which are Decision Tree, Naïve Bayes and Support Vector Machine. It is demonstrated that the combination of data from the two sensor systems can improve the recognition accuracy beyond 99% in the best case.
The European Tertiary Education Register (ETER) is the reference dataset on European Higher Education Institutions (HEIs). ETER provides data on nearly 3,500 HEIs in about 40 European countries, including descriptive information, geographical information, students and graduates (with various breakdowns), revenues and expenditures, personnel, and research activities; as of March 2023, data cover the years from 2011–2020. ETER complies with OECD-UNESCO-EUROSTAT standards for educational statistics; most data are collected from National Statistical Authorities (NSAs) or ministries of participating countries and are subject to extensive checks and harmonization. The development of ETER has been funded by the European Commission and is part of the current efforts to establish a European Higher Education Sector Observatory; it is closely connected to the establishment of a broader data infrastructure in the field of science and innovation studies (RISIS). The ETER dataset is widely used in the scholarly literature on higher education and science policy, as well as for policy reports and analyses.
The increasing relevance of improved therapeutic monoclonal antibodies (mAbs) to treat neurodegenerative diseases has strengthened the need to reliably measure their brain pharmacokinetic (PK) profiles. The aim of this study was, therefore, to absolutely quantify the therapeutic antibody ocrelizumab (OCR) as a model antibody in mouse brain interstitial fluid (ISF), and to record its PK profile by using cerebral open flow microperfusion (cOFM). Further, to monitor the blood-brain barrier (BBB) integrity using an endogenous antibody with a similar molecular size as OCR. The study was conducted on 13 male mice. Direct and absolute OCR quantification was performed with cOFM in combination with zero flow rate, and subsequent bioanalysis of the obtained cerebral ISF samples. For PK profile recording, cerebral ISF samples were collected bi-hourly, and brain tissue and plasma were collected once at the end of the sampling period. The BBB integrity was monitored during the entire PK profile recording by using endogenous mouse immunoglobulin G1. We directly and absolutely quantified OCR and recorded its brain PK profile over 96 h. The BBB remained intact during the PK profile recording. The resulting data provide the basis for reliable PK assessment of therapeutic antibodies in the brain thus favoring the further development of therapeutic monoclonal antibodies.
Successful treatment of herpes simplex viruses is currently limited by the lack of effective topical drugs. Commonly used topical acyclovir products only reduce the duration of lesions by a few days. Optimizing topical formulations to achieve an enhanced acyclovir solubility and penetration could increase the efficacy of topically applied acyclovir but new formulations need to show reliable acyclovir delivery into at least the epidermis/dermis and need to provide sustained acyclovir release for extended time periods. The aim of this study was to compare pharmacokinetic data from in-vitro permeation testing (IVPT) and preclinical dermal open flow microperfusion (dOFM) experiments regarding the penetration behaviour of different acyclovir formulations relative to the reference product Zovirax® 5% cream. Four test formulations that delivered the best penetration data in IVPT were further tested using continuous dOFM in vivo dermal sampling. The use of dOFM identified one of the four tested formulations to perform significantly better than the other three tested formulations and the reference product. In vivo dOFM data showed differences in the dermal acyclovir concentration that had not been detected by using IVPT. Improved acyclovir delivery to the dermis was likely achieved by the new formulation that uses a much lower drug load compared to the reference product. This optimized formulation was able to achieve a dermal concentration similar to oral application and can thus provide the opportunity of more efficacious topical HSV-1 treatment with less side effects than oral systemic treatment.
Glucose is the primary energy source of human cells. Therefore, monitoring glucose inside microphysiological systems (MPS) provides valuable information on the viability and metabolic state of the cultured cells. However, continuous glucose monitoring inside MPS is challenging due to a lack of suitable miniaturized sensors. Here we present an enzymatic, optical glucose sensor element for measurement inside microfluidic systems. The miniaturized glucose sensor (Ø 1 mm) is fabricated together with a reference oxygen sensor onto biocompatible, pressure-sensitive adhesive tape for easy integration inside microfluidic systems. Furthermore, the proposed microfluidic system can be used as plug and play sensor system with existing MPS. It was characterized under cell culture conditions (37 °C and pH 7.4) for five days, exhibiting minor drift (3% day-1). The influence of further cell culture parameters like oxygen concentration, pH, flow rate, and sterilization methods was investigated. The plug-and-play system was used for at-line measurements of glucose levels in (static) cell culture and achieved good agreement with a commercially available glucose sensor. In conclusion, we developed an optical glucose sensor element that can be easily integrated in microfluidic systems and is able to perform stable glucose measurements under cell culture conditions.
Old-growth forests (OGF) provide valuable ecosystem services such as habitat provision, carbon sequestration or recreation maintaining biodiversity, carbon storage, or human well-being. Long-term human pressure caused OGFs in Europe to be rare and scattered. Their detailed extent and current status are largely unknown. This review aims to identify potential methods to map temperate old-growth forests (tOGF) by remote sensing (RS) technology, highlights the potentials and benefits, and identifies main knowledge gaps requesting further research. RS offers a wide range of data and methods to map forests and their properties, applicable from local to continental scale. We structured existing mapping approaches in three main groups. First, parameter-based approaches, which are based on forest parameters and usually applied on local to regional scale using detailed data, often from airborne laser scanning (ALS). Second, direct approaches, usually employing machine learning algorithms to generate information from RS data, with high potential for large-area mapping but so far lacking operational applications and related sound accuracy assessment. Finally, indirect approaches integrating various existing data sets to predict OGF existence. These approaches have also been used for large area mapping with a main drawback of missing physical evidence of the identified areas to really hold OGFs as compared to the likelihood of OGF existence. In conclusion, studies dealing with the mapping of OGF using remote sensing are quite limited, but there is a huge amount of knowledge from other forestry-related applications that is yet to be leveraged for OGF identification. We discuss two scenarios, where different data and approaches are suitable, recognizing that one single system cannot serve all potential needs. These may be hot spot identification, detailed area delineation, or status assessment. Further, we pledge for a combined method to overcome the identified limitations of the individual approaches.
Reversible and sub-lethal stresses to the mitochondria elicit a program of compensatory responses that ultimately improve mitochondrial function, a conserved anti-aging mechanism termed mitohormesis. Here, we show that harmol, a member of the beta-carbolines family with anti-depressant properties, improves mitochondrial function and metabolic parameters, and extends healthspan. Treatment with harmol induces a transient mitochondrial depolarization, a strong mitophagy response, and the AMPK compensatory pathway both in cultured C2C12 myotubes and in male mouse liver, brown adipose tissue and muscle, even though harmol crosses poorly the blood–brain barrier. Mechanistically, simultaneous modulation of the targets of harmol monoamine-oxidase B and GABA-A receptor reproduces harmol-induced mitochondrial improvements. Diet-induced pre-diabetic male mice improve their glucose tolerance, liver steatosis and insulin sensitivity after treatment with harmol. Harmol or a combination of monoamine oxidase B and GABA-A receptor modulators extend the lifespan of hermaphrodite Caenorhabditis elegans or female Drosophila melanogaster. Finally, two-year-old male and female mice treated with harmol exhibit delayed frailty onset with improved glycemia, exercise performance and strength. Our results reveal that peripheral targeting of monoamine oxidase B and GABA-A receptor, common antidepressant targets, extends healthspan through mitohormesis.
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