We develop a machine learning (ML) approach for improving the accuracy of the horizontal dis-tribution of the aerosol optical depth (AOD) simulated by the CHIMERE chemistry-transport model over Northern Africa using Moderate-Resolution Imaging Spectroradiometer (MODIS) AOD satellite observations. These observations are used during the training phase of the ML method for deriving a regional bias correction of AODs simulated by CHIMERE. The results are daily maps of regional bias corrected AODs with full horizontal coverage over Northern Africa. We test four types of ML models: multiple linear regression (MLR), random forests (RF), gradi-ent boosting (XGB), and multiple layer perceptron networks (NN). We perform comparisons with satellite and independent ground-based observations of AOD that are not used in the training phase. They suggest that all models have overall comparable performances with a slight advantage of the RF model which expresses less spatial artifacts. While the method slightly underestimates the very high AODs, it significantly reduces biases and absolute errors, and clearly enhances linear correlations with respect to independent observations. This im-provement for deriving the AOD is particularly relevant for high dust pollution regions like the Sahara Desert, which dramatically lack ground-based measurements for validations of chemis-try-transport modeling which currently remains challenging and imprecise.

We identified six natural "control knobs" for global weather and climate, which clearly regulate, increase and decrease global temperatures, thus performing a true temperature "control" on Earth. Identified control knobs act as Earth's orbital forcing. We present a detailed Earth orbital model, from where the analysis proceeds. Based on our orbital model, we compare meteorological data from all over the globe, in order to detect orbital forcing fingerprints. Ninety temperature graphs and bar charts demonstrate the results. Empirical meteorological data covers the Pacific ocean, the Atlantic ocean, Arctic and Antarctic sea ice extent, and presents land based meteorological measurements from all continents for the year 2020, as well as multi-decadal data from global daily temperature datasets. A supplementary file provides another 100 additional graphs of weather data and temperature charts. The global orbital "temperature control" is clearly observable in all graphs and charts. Until today, orbital forcing has not been integrated in weather models and CMIP6 climate models.It is concluded that the proposed new orbital forcing should be part of weather and climate forecasting models.

The paper concerns with the identification of current communication technologies and software functionalities from the field of digitalization and Industry 4.0, from the point of view of benefits and applicability for the machine manufacturer. In order to identify the relevant technologies and functionalities, both a descriptive and statistical literature research was carried out. As a result, both the currently most widespread technologies and eleven IT functionalities relevant to mechanical engineers were identified and described in terms of their application and implementation. In addition, a knowledge gap in the area of industry transfer in the field of Industry 4.0 / Digitalization was identified

Background: New open-source electric-grid planning models have the potential to improve power system planning and bring a wider range of stakeholders into the planning process for next-generation, high-renewable power systems. However, it has not yet been established whether open-source models perform similarly to the more established commercial models for power system analysis. This reduces their credibility and attractiveness to stakeholders, postponing the benefits they could offer. In this paper, we report the first model intercomparison between an open-source power system model and an established commercial production cost model. Results: We compare the open-source Switch 2.0 to GE Energy Consulting’s Multi Area Production Simulation (MAPS) for production-cost modeling, considering hourly operation under 17 scenarios of renewable energy adoption in Hawaii. We find that after configuring Switch with similar inputs to MAPS, the two models agree closely on hourly and annual production from all power sources. Comparing production gave a coefficient of determination of 0.996 across all energy sources and scenarios, indicating that the two models agree on 99.6% of the variation. For individual energy sources, the coefficient of determination was 69–100. Conclusions: Although some disagreement remains between the two models, this work indicates that Switch is a viable choice for renewable integration modeling, at least for the small power systems considered here. Although some disagreement remains between the two models, this work indicates that Switch is a viable choice for renewable integration modeling, at least for the small power systems considered here.

Of the roughly 20,000 canonical human protein sequences, as of September 15, 2020, 6,937 proteins have had their full or partial, medium- to high-resolution structures determined by x-ray crystallography or other methods. Which of these proteins dominate the Protein Data Bank (the PDB) and why? In this paper, we list the 273 top human protein structures based on the number of their PDB entries. This set of proteins accounts for more than 40% of all available human PDB entries and represent past trends as well as current status for protein structural biology. We briefly discuss the relationship which some of the prominent protein structures have with protein research as a whole and mention their relevance to human diseases. The top-10 soluble and membrane proteins are all well-known (most of their first structures being deposited more than 30 years ago). Overall, there is no dramatic change in recent trends in the PDB. Remarkably, the number of structure depositions has grown nearly exponentially over the last 10 or more years (with a doubling time of 7 yrs for proteins from all organisms). Growth in human protein structures is slightly faster (at 5.9 yrs, while E.Coli and Mouse+Rat protein structures accumulate more slowly, Zebrafish protein structures are growing most, at a doubling every 3.7 years, albeit starting from only approx. 100 structure entries in 2010). The information may be informative to senior scientists but also inspire researchers who are new to protein science, providing the year 2020 snap-shot for the state of protein structural biology.

Dynamic crossflow filtration (DCF) is the state-of-the-art technology for solid-liquid separation from viscous and sensitive feed streams in the food and biopharma industry. Up to now, the potential of industrial processes is often not fully exploited because fixed recipes are usually applied to run the processes. Therefore, a digital twin has been developed to optimize an industrial brownfield DCF plant. The core of the digital twin is a mechanistic-empirical process model combining fundamental filtration laws with process expert knowledge. The effect of variation of selected process and model parameters on plant productivity has been assessed using a model-based design-of-experiments approach and a regression metamodel has been trained with the data. A cyclic program that bidirectionally communicates with the DCF asset serves as frame of the digital twin. It monitors the process dynamics membrane torque and transmembrane pressure and feeds back the optimum permeate flow rate setpoint to the physical asset in almost real-time during process runs. The presented digital twin framework is a simple example how an industrial established process can be controlled by a hybrid model-based algorithm. With a digital process dynamics model at hand, the presented metamodel optimization approach can be easily transferred to other (bio)chemical processes.

A new model predictive control (MPC) algorithm is used to select optimal air conditioning setpoints for a commercial office building, considering variable electricity prices, weather, occupancy and lighting. This algorithm, Cost-Comfort Particle Swarm Optimization (CCPSO), is the first to combine a realistic, smooth representation of occupants’ willingness to pay for thermal comfort with a bottom-up, non-linear model of the building and air conditioning system under control. We find that using a quadratic preference function for temperature can yield solutions that are both more comfortable and lower-cost than previous work that used a ``brick wall'' preference function with no preference for further cooling within an allowed temperature band and infinite aversion to going outside the allowed band. Using historical pricing data for a summer month in Chicago, CCPSO provided a 3\% reduction in costs vs. a ``brick-wall'' MPC approach with similar comfort and 13\% reduction in costs vs. a standard night setback strategy. CCPSO also reduced peak-hours demand by 3\% vs. the ``brick-wall'' strategy and 15\% vs. standard night-setback. At the same time, the CCPSO strategy increased off-peak energy consumption by 15\% vs. the ``brick-wall'' strategy. This may be valuable for power systems integrating large amounts of renewable power, which can otherwise become uneconomic due to saturation of demand during off-peak hours.

Lead optimization in drug discovery is a crucial phase where initial hits are refined into compounds with improved pharmacological properties. While traditional methods rely on manual experimentation and modifications, AI-driven techniques have revolutionized this process by leveraging big data and predictive modeling. This review explores how AI-driven approaches accelerate lead optimization, showcasing examples like deep neural networks and reinforcement learning. Integration of multi-omic data and experimental validation further enhances AI-driven strategies. The future lies in refining these AI methods, democratizing tools, and interdisciplinary collaboration to streamline drug discovery and address medical needs efficiently.

This paper discusses the potential and limitations of the Normalized Difference Vegetation Index (NDVI) in environmental justice, health and inequality studies in urban areas. Very often the NDVI is correlated with socioeconomic and/or sociodemographic data to demonstrate the inequality in environmental settings that themselves influence individual health and questions of environmental justice. This paper addresses the limits of the NDVI for such applications and as well its potential, if applied properly. The overall goal is to make people of disciplines other than those that are geo-related aware of the characteristics, limits and potentials of satellite image-based information layers such as NDVI.

Greenhouse gas (GHG) emissions from human activities have climbed significantly above pre-pandemic levels and reached record highs that unequivocally accelerate global warming. Industry has a significant impact on climate change, emitting at least 21 % of global GHGs and making little overall progress toward its reduction until now. Reducing industry’s emissions requires coordinated action along the value chains in order to promote mitigation options, such as energy and material efficiency, circular material flows, and transformative changes within production processes. The authors analyzed the GHG emissions generated during the manufacturing of three different products of automotive suppliers located in Austria. Despite previous efforts toward an environmentally compatible fabrication, additional and significant reduction potentials were identified. These measures for product carbon footprint (PCF) reduction included the sourcing of low-carbon materials (which are already available on the market), more extensive use of renewable energy, and changes towards more resource efficient manufacturing processes and machinery. Depending on the materials used, the PCF can be reduced by up to 80 %. The findings serve to prepare for future PCF reporting regulations and illustrate reduction potentials to achieve future market advantages, especially when PCFs become an awarding criterion.

Controversial hypotheses to explain consciousness exist in many fields of science, psychology and philosophy. Recent experimental findings in quantum cognition and magnetic resonance imaging have added new controversies to the field, suggesting that the mind may be based on quantum computing. Quantum computers process information in quantum bits (qubits) using quantum gates. At a first glance, it seems unrealistic or impossible that the brain can meet the challenges to provide either of these. Nevertheless, we show here why the brain has the incredible ability to perform quantum computing and how that may be realized.

Biohydrogen is a versatile energy carrier for the generation of electric energy from renewable sources. Hydrogenases can be used in enzymatic fuel cells to oxidize dihydrogen. The rate of electron transfer (ET) at the anodic side between the [NiFe]-hydrogenase enzyme distal iron-sulfur cluster and the electrode surface can be described by the Marcus equation. All parameters for the Marcus equation are accessible from DFT calculations. The distal cubane FeS-cluster has a three cysteine and one histidine coordination [Fe₄S₄](His)(Cys)₃ first ligation sphere. The reorganization energy (inner- and outer-sphere) is almost unchanged upon a histidine-to-cysteine substitution. Differences in rates of electron transfer between the wild-type enzyme and the all-cysteine mutant can be rationalized by a diminished electronic coupling between the donor and acceptor molecules in the [Fe₄S₄](Cys)₄ case. The fast and efficient electron transfer from the distal iron-sulfur cluster is realized by a fine-tuned protein environment which facilitates the flow of electrons. This study enables the design and control of electron transfer rates and pathways by protein engineering.

There are compelling evidences that the immune system is to confer protection not only against foreign pathogens but also against cancer. But if the immune system can’t detect every malignant cell, and at the same time a suitable tumor microenvironment (TME) is formed by inflammatory processes, a carcinogenesis is not longer to be blocked. Once the tumor cells have found their niche, the tumor cells are trained by immune cells turned inside out in how to deal with the immune system "out there". The TME is a training camp and protected space for tumor cells. The Corona crisis has revived a therapeutic approach that was thought to be almost dead: RNA vaccines. Despite decades of research and many clinical studies, no registered RNA cancer vaccine exists today. But the SARS-CoV-2 RNA vaccines against COVID-19 disease have demonstrated their dangerous weaknesses. RNA vaccines manipulate the innate immunity and make the body susceptible to any viral infection. There is also the possibility of integration into the genome. The few approved therapeutic cancer vaccines show little effect. Despite some successes, immunotherapies remain ineffective for most patients with cancer. Powerful therapeutic cancer vaccines remain an unfulfilled dream, a misconception.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

Time-domain spectroscopy (TDS) in the Terahertz (THz) frequency range is gaining in importance in nondestructive testing of dielectric materials. One application is the layer thickness measurement of a coating layer. To determine the thickness from the measurement data, the refractive index of the coating layer must be known in the surveyed frequency range. For perpendicular incidence of the radiation, methods exist to extract the refractive index from the measurement data itself without prior knowledge. This paper extends these methods for non-perpendicular incidence, where the polarization of the radiation becomes important. Furthermore, modifications considering effects of surface roughness of the coating are introduced. The new methods are verified using measurement data of a sample of Inconel steel coated with yttria-stabilized zirconia (YSZ) and with COMSOL simulations of the measurement setup. To validate the thickness measurements, scanning electron microscopy (SEM) images of the layer structure are used. The results show good agreement with an average error of 1% for the simulation data and under 4% for the experimental data compared to reference measurements.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

This paper presents a comprehensive simulation study of Automated Guided Vehicles (AGVs) in a fabricated production environment for toy car assembly. This paper uses Petri Nets for modeling and the General Petri Net Simulator (GPenSIM) for model implementation on MATLAB and simulation. The primary focus of this research is to analyze the operational efficiency of AGVs under varying conditions, particularly examining the impact of battery charge reduction rates and the strategic placement of charging stations within the production line. By employing Colored Petri Nets (CPN) within GPenSIM, we have developed a detailed and dynamic model that captures the intricate movements and interactions of AGVs in a simulated manufacturing setting. By presenting an approach to simulating AGVs in a production environment, this paper specifically focuses on two critical operational parameters: the battery charge reduction rate of AGVs and the number of charging stations available in the production line. Unlike previous studies that have primarily concentrated on general path planning or bottleneck detection in manufacturing systems, this paper delves into the intricate balance between AGV operational efficiency and the logistical constraints imposed by battery life and charging infrastructure.

Jakarta belongs to the cities with the highest flood risk in the world. Its flood hazard is driven by land subsidence, soil sealing, changes in river discharge and increasingly sea level rise. As all of these trends are set to continue, Jakarta’s flood hazard is expected to intensify in the future. Designing and implementing risk reduction and adaption measures is therefore of utmost importance. Against the background, the paper draws on a discourse analysis and original empirical household survey data to review and evaluate current adaptation measures and to analyze in how far they describe a path that is transformative from previous risk reduction approaches. The results show that the focus is clearly on engineering solutions, foremost in the Giant Sea Wall project. The project is likely to transform the city’s flood hydrology. However, it cements rather than transforms the current risk management paradigm which gravitates around the goal of controlling flood symptoms, rather than addressing their anthropogenic root causes. The results also show that the planned measures are heavily contested due to concerns about ecological impacts, social costs, distributional justice, public participation and long-term effectiveness. On the outlook, the results therefore suggest that the more the flood hazard will intensify in the future, the deeper a societal debate will be needed about the desired pathway in flood risk reduction and overall development planning – particularly with regards to the accepted level of transformation, such as partial retreat from the most flood-affected areas.

The purpose is to verify trends of scientific production from 2010 to 2020, considering the best universities of the United States, China, the European Union (EU) and private companies. The top 30 universities in 2020 in China, the EU, and the US and private companies were selected from the SCImago institutions ranking (SIR). The positions in 2020, 2015, 2010 in SIR and three sub-indicators were analyzed by means of non-parametric statistics, taking into consideration the effect of time and group on rankings. American and European Union universities have lost positions to Chinese universities and even more to private companies, which have improved. In 2020, private companies have surpassed all other groups considering Innovation as sub-indicator. The loss of leadership of European and partly American universities mainly concerns research linked to the production of patents. This can lead to future risks of monopoly that may elude public control and cause a possible loss of importance of research not linked to innovation.

The term “risk” is connoted with divergent meanings in natural hazard risk research and the practice of risk management. Whilst the technical definition is accurately defined, in practice, the term “risk” is often synonymously used with “danger”. Considering this divergence as a deficiency, risk communication often aims to correct laypersons’ understanding. We suggest in reference to Breakwell (2001) to treat the variety of meanings as a resource for risk communication strategies instead. However, there is no investigation so far, of what laypersons’ meanings of risk actually comprise. To address this gap, we examine the meanings of risk applying a social representations approach (Moscovici, 2001) in a qualitative case study design. Results of the study among inhabitants of Swiss mountain villages show that differences in meanings were found according to hazard experience and community size. We found commonly shared core representations, and single peripheral ones. We conclude with suggestions on how to make usage of the knowledge on SR in risk communication.

This paper reports a new control strategy to improve sharing of unbalanced currents in islanded LV microgrids. This technique provides fast and effective sharing of positive-, negative- and zero-sequence currents, and is the first example of zero-sequence current sharing in the literature. The controllers are designed in the stationary frame. The control structure consists of four loops; 1)~the current controller; 2)~the voltage controller; 3)~the droop controller and the 4)~negative and zero sequence current controllers. The output current is considered unknown for the controller and is added to the control system as a disturbance. The proposed controller features a high gain in fundamental and harmonic frequencies, hence a good voltage quality is obtained in the presence of unbalanced and nonlinear loads. To this aim, a proportional-resonant (PR) controller is adopted as the current controller. By using a multi-resonant controller as current controller, a unified control structure is obtained which is suitable for both grid-connected and islanded modes. The voltage controller is designed using a resonant controller so that the voltage can have low VUF and THD in the presence of unbalanced and nonlinear loads. Furthermore, in this paper droop method is applied to the control structure to share real and reactive powers. Simulation studies show that the conventional droop method cannot share the oscillatory part of the output power that is due to the presence of unbalanced loads in the microgrid. This paper relies on using zero and negative sequence virtual impedance controller to share the oscillatory part of output power. By using zero-sequence virtual impedance controller (ZSVIC) and negative-sequence virtual impedance controller (NSVIC), the zero and negative sequence currents in the microgrid are controlled and shared effectively. By compensating zero- and negative-sequence currents locally, the flow of these currents in the microgrid is minimized, and the overall power quality of the islanded LV microgrid is improved.

This article delves into the intersection of generative AI and digital twins within drug discovery, exploring their synergistic potential to revolutionize pharmaceutical research and development. Through various instances and examples, we illuminate how generative AI algorithms, capable of simulating vast chemical spaces and predicting molecular properties, are increasingly integrated with digital twins of biological systems to expedite drug discovery. By harnessing the power of computational models and machine learning, researchers can design novel compounds tailored to specific targets, optimize drug candidates, and simulate their behavior within virtual biological environments. This paradigm shift offers unprecedented opportunities for accelerating drug development, reducing costs, and, ultimately, improving patient outcomes. As we navigate this rapidly evolving landscape, collaboration between interdisciplinary teams and continued innovation will be paramount in realizing the promise of generative AI and digital twins in advancing drug discovery.

Arylmagnesium and -calcium reagents are easily accessible, however, ether degradation processes limit the storability especially of the calcium-based heavy Grignard reagents. Ortho-bound substituents with phosphanyl donor sites usually block available coordination sites and stabilize such complexes. The reaction of bromo-2,6-bis(diphenylphosphanylmethyl)benzene (1a) with magnesium in tetrahydrofuran yields [Mg{C₆H₃-2,6-(CH₂PPh₂)₂}₂] (2) after recrystallization from 1,2-dimethoxyethane. However, the similarly performed reduction of bromo- (1a) and iodo-2,6-bis(diphenylphosphanylmethyl)benzene (1b) with calcium leads to ether cleavage and subsequent degradation products. α-Deprotonation of THF yields 1,3-bis(diphenylphosphanylmethyl)benzene. Furthermore, the insoluble THF adducts of dimeric calcium diphenylphosphinate halides, [(thf)₃Ca(X)(µ-O₂PPh₂)]₂ [X = Br (3a), I (3b)], precipitate verifying ether decomposition and cleavage of P-C bonds. Ether adducts of calcium halides [such as [(dme)₂(thf)CaBr₂] (4)] form supporting the initial Grignard reaction and a subsequent Schlenk-type dismutation reaction.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Transmembrane transport of small organic and inorganic molecules is one of the cornerstones of cellular metabolism. Among transmembrane transporters, solute carrier (SLC) proteins form the largest, albeit very diverse, superfamily with over 400 members. It has been early on recognized that xenobiotics can directly interact with SLCs and that this interaction can fundamentally determine their efficacy, including bioavailability and intertissue distribution. Apart from the well-established prodrug strategy, the chemical ligation of transporter substrates to nanoparticles of various chemical composition has recently been used as a means to enhance their targeting or absorption. In this review, we summarize efforts in drug design exploiting interactions with specific SLC transporters to optimize their therapeutic effects. Furthermore, we describe current and future challenges as well as new directions for the advanced development of therapeutics that target SLC transporters.

Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical mitochondrial carrier family SLC25, the past decade led to the discovery of additional protein families that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins and mitochondrial cation/H+ exchangers that have been linked to vital physiological functions and disease. Their structures and transport mechanisms are still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combined sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanism and structure of these novel mitochondrial carriers.

For more than twenty years chemists use peptidic organocatalysts to transfer acyl groups onto alcohols. The goal was and still is the increase of selectivity towards the substrate of choice. One carefully designed example is a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols. Until now, the intermediate responsible for the acyl transfer of this tetrapeptide has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this organocatalyst and its high enantioselectivity.

Peptide/Histidine Transporter PHT1 (SLC15A4) is expressed in lysosomal membranes of immune cells where it plays an important role in metabolic and inflammatory signaling. PHT1 is an H+-coupled/histidine symporter that can transport a broad range of oligopeptides, including a variety of bacterial-derived peptides. Moreover, it enables the scaffolding of various metabolic signaling molecules and interacts with key regulatory elements of the immune response. Therefore, it is not surprising that PHT1 is associated with the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Unfortunately, the pharmacological development of PHT1 has been hampered by the lack of appropriate transport assays. With the aim to address this shortcoming, a novel transport assay based on solid supported membrane-based electrophysiology (SSME) is presented. Key findings of the present SSME studies include the first recordings of electrophysiological properties, a pH dependence analysis, an assessment of PHT1 substrate selectivity, as well as the transport kinetics of the identified substrates. In contrast to previous works, PHT1 is studied its native lysosomal environment. Moreover, observed substrate selectivity is validated by molecular docking. Overall, this new SSME-based assay is expected to contribute to unlock the pharmacological potential of PHT1 and to deepen the understanding of its functional properties.

Friction has long been an important issue in multibody dynamics. Static friction models apply appropriate regularization techniques to convert the stick inequality and the non-smooth stick-slip transition of Coulomb’s approach into a continuous and smooth function of the sliding velocity. However, a regularized friction force is not able to maintain long-term stick. That is why, dynamic friction models were developed in the last decades. The friction force depends herein not only on the sliding velocity but also on internal states. The probably best known representative, the LuGre friction model, is based on a fictitious bristle but realizes a too simple approximation. The recently published second order dynamic friction model describes the dynamics of a fictitious bristle more accurately. Its performance is compared here to stick-slip friction models, developed and launched not long ago by commercial multibody software packages.

Thunderstorms are among the most common and most dangerous meteorological hazards in the world. They cause lightning and can lead to strong wind gusts, squall lines, hail and heavy precipitation combined with flooding, and therefore pose a threat to health and life, can cause enormous property damage and also endanger flight savety. Monitoring and forecast of thunderstorms are therefore important topics. In this work a novel method for the detection and forecast of thunderstorms and strong convection is presented. The detection is based on the global GLD360 lightning data in combination with satellite information from the satellite series Meteosat, HIMAWAARI and GOES, covering the complete geostationary ring. Three severity levels are defined depending on the occurrence of lightning and the brightness temperature difference of the water vapour channels and the infrared window channel (∼ 10.8 μm). The detection of thunderstorms and strong convection is the basis for the nowcasting up to 2 hours, which is performed with the optical flow method TV-L1. This method provides the needed atmospheric motion vectors for the extrapolation of the thunderstorm movement. Both, the validation results as well as the feedback of the customers show the great value of the new NowCastSat-Aviation (NCS-A) method. For example, the Critical Success Index (CSI) is with 0.64 still quite high for the 60 minute forecast of severe thunderstorms. The method is operated 24/7 by the German Weather Service (DWD) and used to provide thunderstorm information to aviation customers and the central weather forecast unit of DWD.

: This study examines the prospects of residential water demand management policy regulations in Ethiopia and their implications for sustainable water resource management. This study aims to evaluate the existing policy regulations and analyze their effectiveness in promoting efficient water use and conservation practices in residential areas. By considering the potential challenges and opportunities associated with these regulations, the research provides insights into the future of residential water demand management in Ethiopia and suggests strategies for enhancing sustainable water resource management. Integrated literature and policy document review, alongside observation and interviews, was used to assess the viability of residential water demand management policies. The assessment of current policy regulations for residential water demand management in Ethiopian urban towns has revealed significant shortcomings in promoting water conservation activities. Hence, there is a need for significant improvements in the current water resource policy guidelines, which lack specificity, particularly in residential water demand management conservation strategies. The lack of awareness among residents regarding the importance of conserving their limited water resources is evident. To address these challenges and ensure the sustainability of the water supply, the government and policy developers must engage with various stakeholders, including the community, in the process of revising current policy documents. A more precise and tailored approach is necessary for its effective implementation.

Alzheimer's disease (AD) remains a significant challenge in the field of neurodegenerative disor-ders, even nearly a century after its discovery, due to the elusive nature of its causes. The develop-ment of drugs that target multiple aspects of the disease has emerged as a promising strategy to address the complexities of AD and related conditions. The immune system's role, particularly in AD, has gained considerable interest, with nanobodies representing a new frontier in biomedical research. Advances in targeting antibodies against amyloid-β (Aβ) and using messenger RNA for genetic translation have revolutionized the production of antibodies and drug development, open-ing new possibilities for treatment. Despite these advancements, conventional treatments for AD, such as Cognex, Exelon, Razadyne, and Aricept, often have limited long-term effectiveness, under-scoring the need for innovative solutions. This necessity has led to the incorporating of advanced technologies like artificial intelligence and machine learning into the drug discovery process for neurodegenerative diseases. These technologies help identify therapeutic targets and optimize lead compounds, offering a more effective approach to addressing the challenges of AD and similar conditions.

The relative paucity of donor livers suitable for transplantation has sparked innovations to preserve and recondition organs to expand the pool of transplantable organs. Currently, machine perfusion techniques have led to the improvement of the quality of marginal livers and to prolonged cold ischemia time and allowed for the prediction of graft function through analysis of the organ during perfusion, improving the rate of organ use. In the future, the implementation of organ modulation might expand the scope of machine perfusion beyond its current usage. The aim of this review was to provide an overview of the current clinical use of machine perfusion devices in liver transplantation and provide a perspective for future clinical use, including therapeutic interventions in perfused donor liver grafts.

The ongoing challenge to ensure a sustainable and affordable energy supply forces industrial companies to implement appropriate measures. These measures typically lead to an increased system complexity, which has to be addressed during operation. Whereas existing approaches from the field of supervisory and optimal control appear to be capable of mastering this issue, these are still not adopted in industry. Therefore, this work presents a procedure model for the systematic development of application-oriented operating strategies for industrial energy supply systems. The procedure model combines research approaches from the fields of sequencing control and approximate MPC to extract rule-based operating strategies. By splitting the procedure model into five phases, expert knowledge can be integrated in a target-oriented manner. Subsequently to the description, the procedure model is exemplary applied to the example of an industrial heating supply system. Throughout an optimization study, the developed operating strategy is compared to a MPC strategy as well as a baseline strategy. Whereas the conventional MPC approach is the upper bound with regard to optimality, the developed operating strategy is able to generate comparable results. Compared to the baseline strategy, a relative reduction in operating expenses of 5.4 % to 37.0 % are achieved in this specific use case.

A new requirement for the manufacturing companies in Industry 4.0 is to be flexible with respect to changes in demands, requiring them to react rapidly and efficiently on the production capacities. Together with the trend to use Service-Oriented Architectures (SOA), this requirement induces a need for agile collaboration among supply chain partners, but also between different divisions or branches of the same company. In order to address this collaboration challenge, we~propose a novel pragmatic approach for the process analysis, implementation and execution. This~is achieved through sets of semantic annotations of business process models encoded into BPMN 2.0 extensions. Building blocks for such manufacturing processes are the individual available services, which are also semantically annotated according to the Everything-as-a-Service (XaaS) principles and stored into a common marketplace. The optimization of such manufacturing processes combines pattern-based semantic composition of services with their non-functional aspects. This is achieved by means of Quality-of-Service (QoS)-based Constraint Optimization Problem (COP) solving, resulting in an automatic implementation of service-based manufacturing processes. The produced solution is mapped back to the BPMN 2.0 standard formalism by means of the introduced extension elements, fully detailing the enactable optimal process service plan produced. This approach allows enacting a process instance, using just-in-time service leasing, allocation of resources and dynamic replanning in the case of failures. This proposition provides the best compromise between external visibility, control and flexibility. In this way, it provides an optimal approach for business process models' implementation, with a full service-oriented taste, by implementing user-defined QoS metrics, just-in-time execution and basic dynamic repairing capabilities. This paper presents the described approach and the technical architecture and depicts one initial industrial application in the manufacturing domain of aluminum forging for bicycle hull body forming, where the advantages stemming from the main capabilities of this approach are sketched.

It was the aim of this study to compare the ratio of salbutamol and its major metabolite salbutamol-4’-O-sulfate as well as the quantity excreted renally after oral and inhalative administration. Additionally, the excretion pattern after application of racemic salbutamol opposed to the pure enantiomer levosalbutamol was evaluated. For quantitation of the sulfonated metabolite of salbutamol, reference material was synthesized and characterized by NMR and HRMS. Urine samples were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Salbutamol is mainly metabolized by sulfotransferase 1A3 (SULT1A3), which is most abundantly found in the jejunum. A high first pass effect occurs upon oral administration, which leads to a higher amount of salbutamol-4’-O-sulfate in urine compared to unchanged salbutamol excreted within the first hour post administration. Thus, when administered orally, the proportion of metabolite to total salbutamol was higher than for inhalative administration in the early urinary excretion. Levosalbutamol is the favored enantiomer of SULT1A3 and therefore metabolized at a higher rate whereas racemic salbutamol shows a reduced proportion between metabolite and parent compound. The amount of sulfoconjugate was found higher than that of the parent compound for all urine samples except for those excreted in the first hour after inhalative administration.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten time to antibiotic administration in the Emergency Department. We retrospectively evaluated all patients above 18 years of age that were diagnosed with sepsis or severe infection in our Emergency Department between 2018 and 2020. We recorded the suspected diagnosis at time of presentation, type of referring healthcare provider and time until initiation of antibiotic treatment. Differences between groups were calculated using Kruskal-Wallis rank sum test. Of the 277 patients that were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well described outcome benefits to early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce time to antibiotic administration and improve patient outcomes.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

Creating new business models is crucial for the implementation of clean technologies for industrial decarbonization. With incomplete knowledge of market processes and uncertain conditions, assessing the prospects of a technology-based business model is challenging. This study combines business model innovation, system dynamics and exploratory model analysis to identify new business opportunities in a context of socio-technical transition and assess their prospects through simulation experiments. Furthermore, insights are visualized in a roadmap to coordinate action among the actors involved. This combination of methods is applied to the case of a business model aiming at ensuring stability of the electrical grid by centralizing the management of flexible loads in industrial companies. A system dynamics model was set up to simulate the diffusion of flexible electrification technologies. Through scenario definition and sensitivity analysis, the influence of internal and external factors on diffusion was assessed. Results highlight the central role of energy costs and customer perception. The chosen combination of methods allowed the formulation of concrete recommendation for coordinated action, explicitly accounting for the various sources of uncertainty. We suggest testing this approach in further business model innovation contexts.

Creating new business models is crucial for the implementation of clean technologies for industrial decarbonization. With incomplete knowledge of market processes and uncertain conditions, assessing the prospects of a technology-based business model is challenging. This study combines business model innovation, system dynamics and exploratory model analysis to identify new business opportunities in a context of socio-technical transition and assess their prospects through simulation experiments. Furthermore, insights are visualized in a roadmap to coordinate action among the actors involved. This combination of methods is applied to the case of a business model aiming at ensuring stability of the electrical grid by centralizing the management of flexible loads in industrial companies. A system dynamics model was set up to simulate the diffusion of flexible electrification technologies. Through scenario definition and sensitivity analysis, the influence of internal and external factors on diffusion was assessed. Results highlight the central role of energy costs and customer perception. The chosen combination of methods allowed the formulation of concrete recommendation for coordinated action, explicitly accounting for the various sources of uncertainty. We suggest testing this approach in further business model innovation contexts.

Pharmacophores are an established concept for the modelling of ligand-receptor interactions based on the abstract representations of stereoelectronic molecular features. They became widely popular as filters for the fast virtual screening of large compound libraries. Until today a lot of effort has been put into the development of sophisticated algorithms and strategies to increase the computational efficiency of the screening process. However, hardly any focus was put on the development of automated procedures that optimise pharmacophores towards higher discriminatory power, which until today still has to be done manually by a human expert. In the age of machine learning, the researcher has become the decision-maker at the top level, outsourcing analysis tasks and recurrent work to advanced algorithms and automation workflows. Here we propose an algorithm for the automated selection of features driving pharmacophore model quality using SAR information extracted from validated QPhAR models. By integrating the developed method into an end-to-end workflow, we present a fully automated method that is able to derive best-quality pharmacophores from a given input dataset. Finally, we show how the QPhAR-generated models can be used to guide the researcher with insights regarding (un-)favourable interactions for compounds of interest.

The present contribution provides the first agro-economic and ecological account of the in-furrow application of a mineral and an organomineral microgranular fertilizer in comparison to a wide spread mineral band fertilizer in temperate climate regions. The reduction of phosphorus inputs while maintaining the yield of maize plants (Zea mays) is the focus of the study. In a three-year field trial, the dry matter yields gained with the two phosphorus-reduced microgranular fertilizers and standard diammonium phosphate (DAP) fertilization were examined. The application of the organomineral microgranular fertilizer resulted in dry matter yields that were 15% higher (2.8 tons per hectare) than the DAP variant, while higher yields using the mineral microgranular fertilizer occurred only in a single year. The higher yield of the organomineral microgranular fertilizer and the lower phosphorus amounts applied with that product resulted in a moderate phosphorus excess of 2.7 kg P ha-1, while DAP fertilization resulted in a surplus of 25.5 kg per hectare. A similar pattern of phosphorus balance was observed on the plots fertilized with the mineral microgranular fertilizer. We conclude that both tested microgranular fertilizers provide an adequate alternative to the wide-spread DAP fertilization in maize cultivation on fertile soils.

(1) Background: New sensor technologies in wearables and other consumer health devices open up promising opportunities to collect real-world data. As cardiovascular diseases remain reason number one for disease and mortality worldwide, cardiology offers potent monitoring use-cases with patients in their out-of-hospital daily routine. Therefore, the aim of this systematic review is to investigate the status quo of studies monitoring patients with cardiovascular risks and patients suffering from cardiovascular diseases in a telemedical setting using not only a smartphone-based app, but also consumer health devices such as wearables and other sensor-based devices. (2) Methods: A literature search was conducted across five databases and the results were examined according to the study protocols, technical approaches and qualitative and quantitative parameters measured. (3) Results: Out of 166 articles, 8 studies were included in this systematic review. These cover interventional and observational monitoring approaches in the area of cardiovascular diseases, heart failure and atrial fibrillation using various app, wearable and health device combination. (4) Conclusions: Depending on the researcher’s motivation a fusion of apps, patient reported outcome measures and non-invasive sensors can be orchestrated in a meaningful way adding major contributions to monitoring concepts for both, individual patients and larger cohorts.

The developments of confirmed daily Sars-CoV-2 infections can be modeled a posteriori in a comparatively simple and satisfactory way by means of a special exponential function: its exponential coefficient varies exponentially with time itself. This property enables the function to directly simulate the „daily case“ curve fragments observed for the first waves of the current epidemics in a number of counties and countries. Linear combinations of two or more of the functions allow for the modeling of the complete curves observed in the vast majority of all regions for which case number developments have been tabulated.

The study investigates the role of NWP filtering for the remote sensing of Cumulonimbus Clouds (Cbs) by implementation of 14 different experiments, covering Central Europe. These experiments compiles different stability filter settings as well as the use of different channels for the InfraRed (IR) brightness temperatures. As stability filter parameters from Numerical Weather Prediction (NWP) are used. The brightness temperature information results from the IR SEVIRI instrument on-board of Meteosat Second Generation satellite and enables the detection of very cold and high clouds close to the tropopause. The satellite only approaches (no NWP filtering) result in the detection of Cbs with a relative high probability of detection, but unfortunately combined with a large False Alarm Rate (FAR), leading to a Critical Success Index (CSI) below 60 %. The false alarms results from other types of very cold and high clouds. It is shown that the false alarms can be significantly decreased by application of an appropriate NWP stability filter, leading to the increase of CSI to about 70 % . A brief review and reflection of the literature clarifies that the this function of the NWP filter can not be replaced by MSG IR spectroscopy. Thus, NWP filtering is strongly recommended to increase the quality of satellite based Cb detection. Further, it has been shown that the well established convective available potential energy (CAPE) and the convection index (KO) works well as stability filter.

Vitamins are essential compounds obtained through diet that are necessary for normal devel-opment and function in an organism. One of the most important vitamins for human physiology is Vitamin A, a group of retinoid compounds and carotenoids which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids like β-carotene, or preformed vitamin A such as retinyl esters are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carote-noid cleavage oxygenases (CCOs), such as BCO1, to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein receptor 2 (RBPR2) in systemic tissues (e.g. in the retina and the liver respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to review literature re-garding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.

Symmetry, as a key concept in geometry and the foundational principle of mathematical concepts, is a fundamental part of geometry and nature, creating patterns that help us conceptually organize our world. It is often linked with aesthetic beauty and can be observed in both natural phenomena and human-made objects, such as artworks and manufactured products, across the globe. The automorphism group of a graph is a mathematical structure that captures all the symmetries of the graph. symmetry refers to the property of a graph, indicating that it can be transformed without changing its structure, while the automorphism group is the collection of all permutations of the vertices that preserve the graph's adjacency relationships. In graph theory, the concepts of symmetry group and automorphism group play fundamental roles in understanding the symmetries and structural properties of graphs. This paper aims to explore the relationship between symmetry groups and automorphism groups, shedding light on their interconnected nature and their significance in graph theory. We delve into the definitions and properties of both symmetry groups and automorphism groups, highlighting their similarities and distinctions. Furthermore, we discuss their applications in various fields, including computer science, chemistry, and network analysis. Through this exploration, we aim to provide a comprehensive understanding of the relationship between symmetry groups and automorphism groups, deepening our comprehension of the symmetries and structures inherent in graphs.

Methods to handle uncertainty in economic evaluation have gained much attention in the literature and the cost-effectiveness acceptability curve (CEAC) is the most widely used method to summarize and present uncertainty associated with program costs and effects in cost-effectiveness analysis. Some researchers have emphasized the limitations of the CEAC for informing decision and policy makers as the CEAC is insensitive to radial shifts of the joint distribution of incremental costs and effects in the North-East and South-West quadrants of the cost-effective plane (CEP). Furthermore, it has been pointed out that the CEAC does not incorporate risk-aversion in valuing uncertain costs and effects. In the present article we show that the cost-effectiveness affordability curve (CEAFC) captures both dimensions of the joint distribution of incremental costs and effects on the CEP and is therefore sensitive to radial shifts of the joint distribution on the CEP. Furthermore, the CEAFC also informs about the budget impact of a new intervention as it estimates the joint probability an intervention is both affordable and cost-effective. Moreover, we show that the cost-effectiveness risk-aversion curve (CERAC) allows to incorporate risk-aversion into the analysis and can therefore be used to inform decision-makers who are risk-averse. We use data from a published cost-effectiveness model of palbociclib in addition to letrozole versus letrozole alone for the treatment of oestrogen-receptor positive, HER-2 negative, advanced breast cancer to demonstrate the differences between CEAC, CEAFC and CERAC and show how these can jointly be used to inform decision and policy makers.

Energy storage systems will play a key role for individual users in the future smart grid. They serve two purposes: (i) handling the intermittent nature of renewable energy resources for a more reliable and efficient system, and (ii) preventing the impact of blackouts on users and allowing for more independence from the grid, while saving money through load-shifting. In this paper we investigate the latter scenario by looking at a neighbourhood of 25 households whose demand is satisfied by one utility company. Assuming the users possess lithium-ion batteries, we answer the question of how each household can make the best use of their individual storage system given a real-time pricing policy. To this end, each user is modelled as a player of a non-cooperative scheduling game. The novelty of the game lies in the advanced battery model, which incorporates charging and discharging characteristics of lithium-ion batteries. The action set for each player comprises day-ahead schedules of their respective battery usage. We analyse different user behavior and are able to obtain a realistic and applicable understanding of the potential of these systems. As a result, we show the correlation between the efficiency of the battery and the outcome of the game.

The detection performance of small objects in remote sensing images has not been satisfactory compared to large objects, especially in low-resolution and noisy images. A generative adversarial network (GAN)-based model called enhanced super-resolution GAN (ESRGAN) showed remarkable image enhancement performance, but reconstructed images usually miss high-frequency edge information. Therefore, object detection performance showed degradation for small objects on recovered noisy and low-resolution remote sensing images. Inspired by the success of edge enhanced GAN (EEGAN) and ESRGAN, we applied a new edge-enhanced super-resolution GAN (EESRGAN) to improve the quality of remote sensing images and used different detector networks in an end-to-end manner where detector loss was backpropagated into the EESRGAN to improve the detection performance. We proposed an architecture with three components: ESRGAN, EEN, and Detection network. We used residual-in-residual dense blocks (RRDB) for both the ESRGAN and EEN, and for the detector network, we used a faster region-based convolutional network (FRCNN) (two-stage detector) and a single-shot multibox detector (SSD) (one stage detector). Extensive experiments on a public (car overhead with context) dataset and another self-assembled (oil and gas storage tank) satellite dataset showed superior performance of our method compared to the standalone state-of-the-art object detectors.

The fatigue life of welded joints under cyclic loading is a complex process that can be roughly divided into fatigue crack initiation, crack propagation and final fracture. Usually, these phases are evaluated separately. Several methods are available to estimate the extent of the different phases in welded components, such as stress-based fatigue concepts for crack initiation or linear elastic fracture mechanics for crack propagation; however, distinguishing these phases in welded components is a complex procedure and often relies on assumptions such as transition crack sizes. The objective of this study is to investigate the relationship between fatigue crack initiation and propagation in welded joints using artificially notched specimens with welded joints characteristics of different notch acuity (different radii and opening angle). The experiments show that the investigated relationship basically depends on the notch acuity, the load level and the stress ratio.

Using digital media has become the most popular leisure activity for children and adolescents. The effects of digital media use on the developing brain and cognitive processes of children are subject to debate. Here, we examine the effect of digital media use on attention subdomains in children aged 6 to 10 years. In total, 77 children participated in the study. Selective and divided attention as well as switching between attentional demands were quantified by the SwAD task. Parents were asked to assess the screen time of their children (TV, smartphone, laptop/PC, game console, tablet). Results show no main or interaction effects of screen time on any of the attention conditions investigated. Based on the present findings, as well as previous studies, we suggest a possible non-linear relationship between the amount of screen time and attention function. Furthermore, we emphasize the relevance of considering the socio-economic background of children and a need for longitudinal studies.

Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. After the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“Oral Turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights on the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations of the D-ring.

This study presents a novel approach for the early detection of developing thunderstorms. To date, methods for the detection of developing thunderstorms usually rely on accurate atmospheric motion vectors (AMVs) for the estimation of cooling rate of convective clouds, which corresponds to the updraft strength of the cloud objects. In this study we present a method for the estimation of the updraft strength that does not rely on AMVs. The updraft strength is derived directly from the satellite observations in the SEVIRI water vapor channels. For this purpose the absolute value of the vector product of two vectors derived from the observed radiances emitted by the water vapor channels in 2 subsequent satellite images is calculated. The x and y components of the vectors consists of the temporal change of the spatial brightness temperature gradients in x- and y-direction, the z component consists of the temporal variation of the brightness temperature at pixel level. The absolute value of the vector product is referred to as normalized updraft strength (NUS). The performance of the method has been investigated for 2 summer periods in 2016 and 2017 by validation with lightning data. Values of the Critical Success Index (CSI) of about 66 % for the 2016 period and 62 % for the 2017 period demonstrate the good performance of the method. The POD values for the experiments with the highest CSI values are 90.3 for 2016 period and 87.6 for the 2017 period, respectively The corresponding FAR values are 28.2% (2016) and 32.5 % (2017), respectively. In summary, the method has the potential to reduce the forecast lead time significantly, and can be quite useful in regions without a well maintained radar network.

Numerous researchers and institutions have been developing in ovo sexing technologies to improve animal welfare by identifying male embryos in an early embryonic stage and disposing of them before pain perception. This review gives a complete overview of the technological approaches reported in papers and patents by performing a thorough search using Web of Science and Patstat databases for papers and patents, respectively. Based on a total of 45 papers and 100 patent families up until 2021 reported worldwide, 11 technology categories were defined: six non-optical and five optical techniques. Every category was described for its characteristics while assessing its potential for application. Next, the dynamics of the publications of in ovo sexing techniques in both paper and patent fields were described through growth curves, and the interest or actual status was visualized using the number of paper citations and the actual legal status of the patents. When comparing the reported technologies in papers to those in patents, scientific gaps were observed, as some of the patented technologies were not reported in the scientific literature, e.g., ion mobility and mass spectrometry approaches. Generally, more diverse approaches in all categories were found in patents, although they do require more scientific evidence through papers or industrial adoption to prove their robustness. Moreover, although there is a recent trend for non-invasive techniques, invasive methods like analyzing DNA through PCR or hormones through immunosensing are still being reported (and might continue to be) in papers and patents. It was also observed that none of the technologies complies with all the industry requirements. Thus, more research and harmony between consumers, industry, and governments is necessary.

The pulse duration in short-pulse schemes for Self-Amplified Spontaneous Emission Free Electron Lasers (SASE FELs) is limited by the FEL coherence time. A recently proposed concept allows to overcome the coherence time barrier and to get much shorter pulses. When the lasing part of an electron bunch is much shorter than the coherence time, one can suppress the radiation in the long main undulator while preserving microbunching within that short lasing slice. Then a short radiation pulse is produced in a relatively short radiator. A possible suppression method, an excessive reverse undulator taper, is discussed and illustrated numerically in this paper. We also performed first experimental tests of this method at the soft X-ray FEL user facility FLASH. The measured pulse duration approaches 1 fs (FWHM) at the wavelength of 5 nm.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Recent in-vitro studies have investigated the effects of CytoSorb hemoadsorption on endothelial function in sepsis showing a reduction in markers of endothelial dysfunction, but to this day there is a lack of clinical studies showing whether this approach could actually positively influence the disturbed vascular barrier function in septic conditions. We analyzed the data on administered fluid volumes and catecholamines to determine the potential benefit of CytoSorb hemoadsorption therapy on endothelial function in a clinical scenario. We performed a retrospective analysis of 124 septic shock patients who had undergone adjunctive treatment with CytoSorb hemadsorption therapy. We collected volume requirements, and calculated the volume balance within different time periods to obtain an assumption on the stability of the vascular barrier. We also calculated catecholamine requirements. With regard to the entire study cohort our findings revealed a significant reduction in fluid balance at 72 hours (T72) compared to both baseline (T0) and the 24-hour mark (T24). Fluid balances from T72 – T0 were significantly lower in hospital survivors compared to non-survivors. Patients who received a second catecholamine had a significantly lower in-hospital mortality. Our findings showed that use of hemoadsorption therapy results in a reduced positive fluid balance paralleled by reductions in vasopressor needs suggesting a positive effect on endothelial integrity. These results, derived from a large cohort of patients, provide valuable insights that may greatly improve our understanding of the multiple effects of hemoadsorption treatment in septic shock patients.

The recent setbacks in the withdrawal and approval delays of antibody treatments of neurodegenerative disorders (NDs) can be attributed to their poor entry across the blood-brain barrier (BBB). While several invasive and noninvasive approaches can be used to make the BBB more permeable, their inconsistency makes them a poor choice; however, if an antibody is chemically modified to attach a transferrin molecule that enhances its permeation across the BBB, this could be the most practical and useful modification that can transform the science of ND treatment. Antibodies can be conjugated with transferrin in vitro, but preferably through mRNA, as we propose to convert current treatments to bring faster treatment options. The mRNA technology yields products at a meager cost, which is a consideration for the affordability of these drugs globally. This paper provides complete details with templates to convert the current medicines and those under development into mRNA delivery systems to ensure clinical success, avoiding the current failures in their efficacy, more specifically the products that have demonstrated efficacy but are being removed from the market.

Suppose G is a graph with vertex-orbits O1,1 O2, . . . ,Ot, and jOi j denotes the cardinallity of Oi. Then OG (x) = åt 2 i=1 xjOi j is called as orbit polynomial. It is well-known that this polynomial 3 has a unique positive zero d in the interval [0, 1]. The aim of this paper is to study the specific 4 properties of this polynomial and then we determine the location of this root for several classes of 5 complex networks to compare with other graphical measures. Besides, we compare the unique 6 positive zero measure with several well-known centrality graph measures.

This study presents a case report demonstrating an anomalous origin of the right subclavian artery from the aortic arch, accompanied by proximal dilation and a retro-esophageal course, characteristic of arteria lusoria and Kommerell's diverticulum. The research highlights the clinical significance of this anomaly and discusses its management strategies, emphasizing the importance of precise surgical intervention in addressing this condition.

The ability to efficiently recognize the emotions on others’ faces is something that most of us take for granted. Children with callous-unemotional (CU) traits and impulsivity/conduct problems (ICP), such as attention-deficit hyperactivity disorder, have been previously described as being “fear blind”. This is also associated with looking less at the eye regions of fearful faces, which are highly diagnostic. Previous attempts to intervene into emotion recognition strategies have not had lasting effects on participants’ fear recognition abilities. Here we present both (a) additional evidence that there is a two-part causal chain, from personality traits to face recognition strategies using the eyes, then from strategies to rates of recognizing fear in others; and (b) a pilot intervention that had persistent effects for weeks after the end of instruction. Further, the intervention led to more change in those with the highest CU traits. This both clarifies the specific mechanisms linking personality to emotion recognition and shows that the process is fundamentally malleable. It is possible that such training could promote empathy and reduce the rates of antisocial behavior in specific populations in the future.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

We present the prototype and analytical model of a miniaturized impact actuation mechanism, providing a fast out-of-plane displacement to accelerate objects against gravity, allowing for freely moving objects and hence for large displacements without the need of cantilevers. To achieve the necessary high speed, we chose a piezo electric stack actuator driven by a high-current pulse generator, connected to a rigid support and a rigid three-point contact with the object. We describe this mechanism with a spring-mass model and compare various inertial masses, all of them spheres, from different diameters and materials. As expected, we found that larger flight heights are achieved by harder projectiles, achieving, e.g., approx. 3 mm displacement for a 3 mm steel sphere using a 3x3x2 mm³ piezo stack.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, the trafficking of rod opsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for visual function. Two key mechanisms of this process are emphasized in this manuscript: Ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene opsin to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

In systems biology, biological phenomena are often modeled by ODE and distributed in the de facto standard file format SBML. The primary analyses performed with such models are dynamic simulation, steady-state analysis, and parameter estimation. These methodologies are mathematically formalized, and libraries for such analyses have been published. Several tools exist to create, simulate, or visualize models encoded in SBML. However, setting up and establishing analysis environments is a crucial hurdle for non-modelers. Therefore, easy access to perform fundamental analyses of ODE models is a significant challenge. We developed SBMLWebApp, a web-based service to execute SBML-based simulations, steady-state analysis, and parameter estimation directly in the browser without the need for any setup or prior knowledge to address this issue. SBMLWebApp visualizes the result and numerical table of each analysis and provides a download of the results. SBMLWebApp allows users to select and analyze SBML models directly from the BioModels Database. Taken together, SBMLWebApp provides barrier-free access to an SBML analysis environment for simulation, steady-state analysis, and parameter estimation for SBML models. SBMLWebApp is implemented in Java™ based on an Apache Tomcat® web server using COPASI, the SBSCL, and LibSBMLSim as simulation engines. SBMLWebApp is licensed under MIT with source code available from https://github.com/TakahiroYamada/SBMLWebApp. The program runs online at http://simulate-biology.org.

The application of instrumented indentation to assess material properties like Young’s modulus and micro-hardness has become a standard method. In recent developments, indentation experiments and simulations have been combined to inverse methods, from which further material parameters as yield strength, work hardening rate, and tensile strength can be determined. In this work, an inverse method is introduced by which material parameters for cyclic plasticity, i.e. kinematic hardening parameters, can be determined. To accomplish this, cyclic Vickers indentation experiments are combined with finite element simulations of the indentation with unknown material properties, which are then determined by inverse analysis. To validate the proposed method, these parameters are subsequently applied to predict the uniaxial stress-strain response of a material with success. The method has been validated successfully for a quenched and tempered martensitic steel and for technically pure copper, where an excellent agreement between measured and predicted cyclic stress-strain-curves has been achieved. Hence, the proposed inverse method based on cyclic nanoindentation, as a quasi-non-destructive method, could complement or even substitute the resource-intensive conventional fatigue testing in the future for some applications.

Energy system optimization models (ESOM) are widely used to inform about energy transition strategies. The heterogeneity of consumers, especially in the heat sector, is rarely considered in these model types. Integrating consumer heterogeneity and behavioral factors into ESOMs may generate new insights for energy policy. In this study a literature review was conducted, identifying empirical data on consumer behavior for adopting residential heating systems. This data was integrated into an ESOM for the German heat sector, combining established methods for integrating consumer heterogeneity and a novel approach for calculating indirect costs, representing behavioral factors. The incorporation of consumer choice leads to a higher diversity in technology market shares in a business as usual and an ambitious measures scenario. Especially, the future role of log wood technologies in the private household sector may have been underestimated in previous studies and should be discussed, when designing policies. Still, these findings need to be handled with care, since the empirical data basis and the methodological basis is limited.

Three-dimensional nanocomposite networks consisting of percolated Si nanowires in a SiO₂ matrix, Si:SiO₂, were studied. The structures were obtained by reactive ion beam sputter deposition of SiO_x (x ≈ 0.6) thin films at 450 °C and subsequent crystallization using conventional oven as well as millisecond line focus laser annealing. Rutherford backscattering spectrometry, Raman spectroscopy, X-ray diffraction, cross-sectional and energy-filtered transmission electron microscopy were applied for sample characterization. While oven annealing resulted in a mean Si wire diameter of 10 nm and a crystallinity of 72 % within the Si volume, almost single-domain Si structures with 30 nm in diameter and almost free of amorphous Si were obtained by millisecond laser application. The structural differences are attributed to the different crystallization processes: Conventional oven tempering proceeds via solid state, millisecond laser application via liquid phase crystallization of Si. The 5 orders of magnitude larger diffusion constant in the liquid phase is responsible for the three times larger Si nanostructure diameter. In conclusion, laser annealing offers not only significantly shorter process times but moreover a superior structural order of nano-Si compared to conventional heating.

Lightweight component design is effectively achievable through the sandwich structures, many past research studies in the aerospace and racing sectors (since 1920s) has proven it. To extend their application into automotive and other transport industries, the manufacturing cycle times must be reduced. This can be achieved by thermoplastic sandwich materials of continuous fibre-reinforced thermoplastic (CFRTP) cover layers and thermoplastic honeycomb cores. To widespread the application of flat thermoplastic-based sandwich panels into complex parts, a novel forming technology was developed by the Fraunhofer Institute of Microstructure of Materials and Systems (IMWS). For an increase in reproducibility of the sandwich component production and a decrease in manufacturing defects, numerical modelling methods and experimental validation are needed. The finite element (FE) modelling of this thermoforming process is a thermo-mechanical assignment with all three: material, geometry, and boundary non-linearities. In the scope of this work, the material behavior of different sandwich components (cover layers, honeycomb core, interface) under thermo-mechanical loads is characterized in detail, and a complex numerical model is developed to describe the thermoforming process of thermoplastic-based sandwich laminate. The critical forming condition like wrinkling that occurs due to friction in a sandwich or poor intra-ply shear in cross-ply studied, validated, and optimized. A thermoplastic sandwich made of polypropylene (PP) honeycomb core and polypropylene glass fibre (PP/GF) cross-ply as cover layers was used for this study, and numerical modelling was executed in LS-DYNA software.

β₂-m, β₂-microglobulin; CAF, cancer associated fibroblast; CSC, cancer stem cell; CTL, cytotoxic T lymphocyte; DC, dendritic cell; ECM, extracellular matrix; EGF-R, epidermal growth factor receptor; ER, endoplasmic reticulum; FDA, Food and Drug Administration; HLA, human leukocyte antigen; HNSCC, head and neck squamous cell carcinoma; HPV, human papilloma virus; ICP immune checkpoint; ICPi, immune checkpoint inhibitor; IFN, interferon; LMP, low molecular weight protein; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; mTOR, mammalian target of rapamycin; MSI, multispectral imaging; NK, natural killer; OS, overall survival; PBL, peripheral blood lymphocytes; PBMNC, peripheral blood mononuclear cells; PD1, programmed death receptor 1; PD-L1, programmed death ligand 1; PFS, progression-free survival; PI3K, phosphatidyl-linositol-3-kinase; R/M, recurrence and or metastatic; STAT, signal transducer and activator of transcription; TAA, tumor-associated antigen; TAM, tumor associated macrophages; TAP, transporter associated with antigen processing; TCR, T cell receptor; TIL, tumor-infiltrating lymphocyte; TLS, tertiary lymphoid structure; TME, tumor microenvironment; Treg, regulatory T cell; TSA, tumor-specific antigen; VEGF, vascular endothelial growth factor; VEGF-R, vascular endothelial growth factor receptor.

In this paper, a novel synthesis for a chemical precursor for nanocrystalline VO2 coatings is elaborated. The compatibility of the precursor towards the substrate is optimized for spin coating. This is done by subjecting multiple solvents to contact angle measurements. A suitable thermal treatment is developed to densify the coating and to induce crystallization. Afterwards the microstructure of the coating is investigated using X-Ray diffraction, electron microscopy and ellipsometry techniques. To assess the thermochromic properties of the fabricated device, optical transmission experiments were conducted both at room temperature and at elevated temperature. A correlation between these thermochromic properties and coating thickness was investigated in order to obtain an optimized thermochromic device, where both high visual transparency and prominent thermochromic switching abilities are aimed for. In this work, an optimal coating thickness is proposed for a thermochromic coating with high switching ability and solar modulation.

In order to harmonize supply and demand of green energy, new future-proof technologies are needed. Here, hydrogen plays a key role. Within the current framework conditions, the production of green hydrogen is not yet economically viable. The use of the oxygen produced and the possible increase in efficiency associated with it mostly remains unconsidered. The aim is to demonstrate that the economic efficiency of a power-to-gas (PtG) project can be increased by using the by-product oxygen. In this research project, a water electrolyser connected to grid is powered to supply hydrogen to a hydrogen refuelling station. By utilising the by-product oxygen from water electrolysis for a wastewater treatment plant (WWTP), it is shown that the net present value (NPV) of the project can be improved by up to 13 % compared to the initial scenario. If a photovoltaic (PV) system is used in addition to grid electricity for higher green hydrogen production, the NPV can be further improved by up to 58 %. The levelized cost of hydrogen (LCOH) is calculated for different scenarios with and without oxygen configuration. A sensitivity analysis is then performed to find important parameters.

As the COVID-19 pandemic progresses, new variants of SARS-CoV-2 continue to emerge. This underscores the need to develop optimized tools to study such variants, as well as new coronaviruses that may arise in the future, and to use them for antiviral drug development. Here we introduce microscale thermophoresis (MST) as a reliable and versatile tool for coronavirus research, which we demonstrate through three different applications described in this report: 1) binding of the SARS-CoV-2 spike receptor binding domain (RBD) to peptides as a strategy to prevent virus entry, 2) binding of the RBD to the viral receptor ACE2, and 3) binding of the RBD to ACE2 in complex with the amino acid transporter SLC6A20/SIT1 or its allelic variant rs61731475 (p.Ile529Val). Our results demonstrate that MST is a highly precise approach to study protein-protein and/or protein-ligand interactions in coronavirus research, making it an ideal tool for studying viral variants and developing antiviral agents. The ability to measure interactions with proteins in their near-native plasma membrane environment is a unique advantage of the MST assay over other available binding assays.

Physical distancing and wearing a face mask are key interventions to prevent COVID-19. While this remains difficult to practice for millions of firefighters in fire engines responding to emergencies, the delayed forthcoming of evidence on the physical effectiveness of such safety interventions in this setting presents a major problem. In this field experimental study, we provided initial evidence to close this gap. We examined total aerosol burden in the cabin of a fire engine whilst manipulating crew size, natural ventilation, use of FFP2 respirators and use of SCBA full-face masks during 15-minute driving periods. At the same time, we controlled for crew activity and speaking, vehicle speed, cabin air temperature, pressure and humidity. Limiting the crew size, using FFP2 respirators and not donning SCBA full-face masks was associated with a reduction of the arithmetic mean of total aerosol burden of up to 49%. Natural ventilation as tested in this study was associated with both an increase and a decrease of total aerosol burden. This study provided initial evidence on the physical effectiveness of safety interventions in fire engines to reduce potential airborne transmission of SARS-CoV-2 through aerosols. More research about the physical and clinical effectiveness of such safety interventions is needed.

Aircraft heat exchangers play a crucial role in maintaining thermal balance and ensuring that essential components operate efficiently and safely. In this context, it is highly relevant to gain knowledge about the deterioration and the predominant damage mechanisms of these components. In this study, two different non-destructive methods are employed to analyze the damage initiation of a heat exchanger part during fatigue test. On the one hand, Acoustic Emission technique is employed using membrane-free microphones capable of capturing a broad bandwidth. The acoustic events were classified by a machine learning algorithm to determine their source and damage mechanisms. On the other side, Digital Image Correlation (DIC) allowed the measurement of the strain evolution along the test and more precisely, redistributions were considered as damage indicators. As a result, it was identified that AE served as early damage indicator as the cumulative number of events was in good agreement with the severity of the damage. With respect to classification two clear clusters ascribed to different type of events were identified. In the case of DIC, strain redistributions gave clear indications of damage or deterioration but at a later stage compared to AE

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Interdisciplinary research into the underlying neural processes of music therapy (MT) and subjective experiences of patients and therapists are largely lacking. The aim of the current study was to assess the feasibility of newly developed procedures (including EEG/ECG hyperscanning, synchronous audio-video monitoring, and qualitative interviews) to study the personal experiences and neuronal dynamics of moments of interest during MT with stroke survivors. The feasibility of our mobile set-up and procedures as well as their clinical implementation in a rehabilitation centre and an acute hospital ward were tested with four phase C patients. Protocols and interviews were used for the documentation and analysis of the feasibility. Recruiting patients for MT sessions was feasible, although data collection on three consecutive weeks was not always possible due to organisational constraints, especially in the hospital with acute ward routines. Research procedures were successfully implemented, and according to interviews, none of the patients reported any burden, tiredness or increased stress due to the research procedures, which lasted approx. 3 hours (ranging from 135min to 209min) for each patient. Implementing the research procedures in a rehabilitation unit with stroke patients was feasible and only small adaptations were made for further research.

The aim of the study was the comparison of conventional sintering versus additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A "critical" bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects but it has its limitations. Alloplastic bone grafting using synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly and current research was focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the thereby produced β-TCP implants. The 3D-printed β-TCP hybrid structure implant was fabricated using two components, a column structure and a freeze-foam, which were sintered together. The conventionally manufactured ceramics were made by pouring. Both scaffolds were characterized according to porosity, mechanical properties and biocompatibility. The hybrid structure had a total porosity of 74.4 ± 0.5%. Microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, significantly lower than the microporous β-TCP implant’s with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all β-TCP implants, with minimal cytotoxicity. This study provides valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects.

: Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metallopro-teinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "biorector," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and pro-liferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wound. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.

A major challenge for the dissemination, replication, and reuse of epidemiological forecasting studies during COVID-19 pandemics is the lack of clear guidelines and platforms to exchange models in a Findable, Accessible, Interoperable, and Reusable (FAIR) manner, facilitating reproducibility of research outcomes. During the beginning of pandemics, models were developed in diverse tools that were not interoperable, opaque without traceability and semantics, and scattered across various platforms - making them hard to locate, infer and reuse. In this work, we demonstrate that implementing the standards developed by the systems biology community to encode and share COVID-19 epidemiological models can serve as a roadmap to implement models as a tool in medical informatics, in general. As a proof-of-concept, we encoded and shared 24 epidemiological models using the standard format for model exchange in systems biology, annotated them with cross-references to data resources, packed up all associated files in COMBINE archives for easy sharing, and finally, disseminated the models through BioModels repository to significantly enhance their reproducibility and repurposing potential. We recommend the use of systems biology standards to encode and share models of epidemic and pandemic forecasts to improve their findability, accessibility, interoperability, reusability, and reproducibility.

Despite energy-related financial concerns and the growing demand for sustainability, many energy efficiency measures are not being implemented in industrial practice. There are a number of reasons for this, including a lack of knowledge about energy efficiency potentials and the assessment of energy savings as well as the high workloads of employees. This article describes the systematic development of an expert system, which offers a chance to overcome these obstacles and contribute significantly to increasing the energy efficiency of production machines. The system employs data-driven regression models to identify inefficient parameter settings, calculate achievable energy savings, and prioritize actions based on a fuzzy rule base. Proposed measures are first applied to an analytical real-time simulation model of a production machine to verify that constraints required for the specified product quality are met. This provides the machine operator with the expert means to apply proposed energy efficiency measures to the physical entity. We demonstrate the development and application of the system for a throughput parts cleaning machine in the metalworking industry.

Detector-based spectral CT offers the possibility of obtaining spectral information from which discrete acquisitions at different energy levels can be derived, yielding so-called virtual monoenergetic images (VMI). In this study, we aimed to develop a jointly optimized deep learning framework based on dual-energy CT pulmonary angiography (DE-CTPA) data to generate synthetic monoenergetic images (SMI) for improving automatic pulmonary embolism (PE) detection in single-energy CTPA scans. For this purpose, we used two data sets: our institutional DE-CTPA data set D1 comprising polyenergetic arterial series and the corresponding VMI at low-energy levels (40 keV) with 7,892 image pairs, and a 10% subset of the 2020 RSNA Pulmonary Embolism Detection Challenge data set D2, which consisted of 161,253 polyenergetic images with dichotomous slice-wise annotations (PE/no PE). We trained a fully convolutional encoder-decoder on D1 to generate SMI from single-energy CTPA scans of D2, which were then fed into a ResNet50 network for training of the downstream PE classification task. The quantitative results on the reconstruction ability of our framework revealed high-quality visual SMI predictions with reconstruction results of 0.984 ± 0.002 (structural similarity) and 41.706 ± 0.547 dB (peak-signal-to-noise ratio). PE classification resulted in an AUC of 0.84 for our model, which achieved improved performance compared to other naive approaches with AUCs up to 0.81. Our study stresses the role of using joint optimization strategies for deep learning algorithms to improve automatic PE detection. The proposed pipeline may prove to be beneficial for computer-aided detection systems and could help rescue CTPA studies with suboptimal opacification of the pulmonary arteries from single-energy CT scanners.

The threats of climate change and the sustainable supply of clean energy are global challenges that require an international approach to the energy supply. Utilizing the wind and solar energy potential of regions where these renewable sources are especially viable to produce hydrogen by means of water electrolysis represents an attractive option to counter the above-mentioned challenges. Within the scope of this techno economic analysis of a worldwide hydrogen supply infrastructure based on renewable energy, selected regions are assessed on the basis of their wind or solar energy potential. In contrast to established analyses of hydrogen infrastructures, this paper introduces a worldwide allocation approach to the supply hydrogen from strong wind and solar regions to different demand regions on the premise of a global supply cost minimum. The allocation results show a significant dependence of hydrogen export volumes and the oversea transport distances of potential trading partners. Hence, the transnational trading flows of hydrogen derived from wind and solar energy are concentrated in continental regions.

In the last two decades, variably doped strontium barium niobate (SBN) has attracted a lot of scientific interest mainly due to its specific non-linear optical response. Comparably, the parental compound, i.e., undoped SBN, appears to be less studied so far. Here, two different cuts of single-crystalline nominally pure strontium barium niobate in the composition Sr0.61Ba0.39Nb2O6 (SBN61) are comprehensively studied and analyzed with regard to their photoconductive responses. We present conductivity measurements under systematically varied illumination conditions along either the polar z-axis or perpendicular to it (x-cut). Apart from a pronounced photoconductivity (PC) already under daylight and a large effect upon super-bandgap illumination in general, we observe (i) distinct spectral features when sweeping the excitation wavelength over the sub-bandgap region as then discussed in the context of deep and shallow trap states, (ii) extremely slow long-term relaxation for both light-on and light-off transients in the range of hours and days, (iii) a critical dependence of the photoresponse on the pre-illumination history of the sample, and (iv) a current-voltage hysteresis depending on both the illumination and the electrical-measurement conditions in a complex manner.

Cross-institutional secondary use of medical data benefits from structured semantic annotation, which, ideally, enables matching and merging semantically related data items from different sources and sites. While numerous medical terminologies and ontologies, as well as some tooling, exist to support such annotation, cross-institutional data usage based on independently annotated datasets is challenging for multiple reasons: the annotation process is resource intensive and requires a combination of medical and technical expertise since it often requires judgment calls to resolve ambiguities resulting from non-uniqueness of potential mappings to various levels of ontological hierarchies and relational and representational systems. Divergent resolution of such ambiguities can inhibit joint cross-institutional data usage based on semantic annotation since data items with related content from different sites will not be identifiable based on their respective annotations if different choices were made without further steps such as ontological inference, which is still an active area of research. We hypothesize that a collaborative approach to semantic annotation of medical data can contribute to more resource efficient and high-quality annotation by utilizing prior annotational choices of others to inform the annotation process, thus both speeding up the annotation itself and fostering a consensus approach to resolving annotational ambiguities by enabling annotators to discover and follow pre-existing annotational choices. Therefore, we have implemented a prototypical Collaborative Annotation Tool (CoAT), evaluated its usability, and present first inter-institutional experiences with this novel approach to promoting practically relevant interoperability driven by use of standardized ontologies.

Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.

Lyme disease is the most common tick-borne illness in the United States, Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes Lyme disease in the U.S. If untreated, Lyme arthritis, carditis, and meningitis will occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus vaccine vector, BNSP333, and an outer surface borrelial protein BBI39. To incorporate BBI39 into the RABV virion, we generated a chimeric BBI39 antigen, BBI39RVG, by fusing it with the final amino acids of the RABV glycoprotein. Here we demonstrated that BBI39RVG antigen was incorporated into the RABV virion, and mice vaccinated with our RABV-BBI39RVG vaccine induced high amounts of BBI39-specific antibodies which are maintained long-term. The BBI39 antibodies neutralized Borrelia in vaccinated mice when challenged with Borrelia burgdorferi by either syringe injection or infected ticks, and reduced Lyme disease pathology.

The focus of recent research shifts towards complex ‘whole organism’ responses (i.e., in multiple functional traits) in adaptation to or to defend against stressors under complex environmental conditions. This increasing complexity is challenging to analyse and demands sophisticated tools to drive meaningful conclusions from those data. Trait-based regression models, multivariate analyses, like principal component analyses, and plasticity indices can be used to tackle challenges with those complex investigations. But those methods have substantial limitations, like the need for high sample size, multi-dimensionality of results or the need for trait coordination in high-dimensional space, or the calculation on the population level, which might buffer or cover the de facto occurring individual effects. To improve and simplify studies on ‘whole organism’ responses, analyses, and their interpretation, we developed the Index for Adaptive Responses. This straightforward framework can unite all traits of an organism in one number. A newly developed transformation method, included in this framework, comprises a normalisation and standardisation to a baseline or control without changing the data or variance structure of the original data. We assessed the performance and accuracy of the framework with an application in an extensive predator-prey case study, with simulations and application examples using literature data. We show that the Index for Adaptive Responses respects adaptations as well as maladaptations and outperforms established approaches. The framework is robust against outliers and non-gaussian distribution. We further show that the qualitative prediction of the adaptiveness of included traits is highly accurate, even under challenging conditions, e.g., low replicate numbers. Functions and algorithms of the framework are provided with an R package but can easily be translated into other programming languages. The Index for Adaptive Responses will simplify future research on complex adaptive responses and improves our understanding of these responses’ ecological as well as evolutionary implications.

Driver drowsiness is one of the leading causes of traffic accidents. This paper proposes a new method for classifying driver drowsiness using deep convolution neural networks trained by wavelet scalogram images of electrocardiogram (ECG) signals. Three different classes were de-fined for drowsiness based on video observation of driving tests performed in a simulator for manual and automated modes. The Bayesian optimization method is employed to optimize the hyperparameters of the designed neural networks, such as the learning rate and the number of neurons in every layer. To assess the results of the deep network method, Heart Rate Variability (HRV) data is derived from the ECG signals, some features are extracted from this data, and finally, random forest and k-nearest neighbors (KNN) classifiers are used as two traditional methods to classify the drowsiness levels. Results show that the trained deep network achieves balanced accuracies of about 77% and 79% in the manual and automated modes, respectively. However, the best obtained balanced accuracies using traditional methods are about 62% and 64%. We conclude that designed deep networks working with wavelet scalogram images of ECG signals significantly outperform KNN and random forest classifiers which are trained on HRV-based features.

Summary: Studying biological systems generally relies on computational modeling and simulation, e.g., for model-driven discovery and hypothesis testing. Progress in standardization efforts led to the development of interrelated file formats to exchange and reuse models in systems biology, such as SBML, the Simulation Experiment Description Markup Language (SED-ML), or the Open Modeling EXchange format (OMEX). Conducting simulation experiments based on these formats requires efficient and reusable implementations to make them accessible to the broader scientific community and to ensure the reproducibility of the results. The Systems Biology Simulation Core Library (SBSCL) provides interpreters and solvers for these standards as a versatile open-source API in Java™. The library simulates even complex bio-models and supports deterministic Ordinary Differential Equations (ODEs); Stochastic Differential Equations (SDEs); constraint-based analyses; recent SBML and SED-ML versions; exchange of results, and visualization of in silico experiments; open modeling exchange formats (COMBINE archives); hierarchically structured models; and compatibility with standard testing systems, including the Systems Biology Test Suite and published models from the BioModels and BiGG databases. Availability and implementation: SBSCL is freely available at https://draeger-lab.github.io/SBSCL/.

A new strategy to nanoengineer gold/fluorocarbon multilayer (ML) nanostructures is reported. We have investigated the morphological changes occuring at the metal-polymer interface in multilayer structures with varying volume fraction of gold (Au) and the kinetic growth aspect of the microscale properties of nano-sized Au in plasma polymer fluorocarbon (PPFC). Investigations were carried out at various temperatures and annealing time by means of grazing incidence small-angle and wide-angle X-ray scattering (GISAXS and GIWAXS). We have fabricated a series of multilayers with variying volume fraction (0.12, 0.27, 0.38) of Au and bilayer periodicity in ML structure. They show an interesting granular structure consisting of nearly spherical shaped nanoparticles within the polymer layer. The nanoparticle (NP) morphology changes due to the collective effects of NPs diffusion within ensembles in the in-plane vicinity and inter-layer with increasing temperature. The in-plane NPs size distinctly increases (from 1.9 to 4 nm) with increasing temperature. The NPs become more spherical thus reducing the surface energy. Linear growth of NPs with temperature and time shows diffusion-controled growth of NPs in the ML structure. The structural stability of the multilayer is controlled by the volume ratio of the metal in polymer. At room temperature UV-Vis shows a blueshift of the plasmon peak from 560 nm in ML Au/PTFE_1 to 437 nm in Au/PTFE_3. We have identified the fabrication and post-deposition annealing conditions to limit the Local Surface Plasmon resonance (LSPR) shift (from 〖∆λ〗_LSPR=180 nm (Au/PTFE_1) to 〖∆λ〗_LSPR=67 nm (Au/PTFE_3 ML)) and their optical response over a wide visible wavelength range. A variation in the dielectric constant of the polymer in precence of varying Au inclusion is found to be the main factor affecting the LSPR frequency. Our finding may provide insights in Nano engineering ML structure can be useful to systematically control the growth of NPs in polymer matrix.

Due to its time effective, joint friendly and highly customizable character whole-body-electromyostimulation (WB-EMS) is regarded as a feasible solution for a large variety of training issues particularly in the area of non-athletic application. To identify gaps in research and summarize prevalent evidence we conducted an evidence map on outcomes addressed by WB-EMS trials in middle-aged to older, non-athletic adults. Based on a comprehensive systematic search in five databases and two study registers according to PRISMA, 54 projects published in 80 articles were included. More than 90% of the studies reported outcomes related to the physical fitness or function domain. Body composition parameters were addressed by two thirds of the projects. Health-related outcomes addressed by WB-EMS included cancer/neoplasm (n=7), endocrine regulation (n=8), glucose metabolism (15), nervous system diseases (n=2), cardiovascular system diseases (n=22), non-specific chronic low back pain (n=4), osteopenia (n=5) and diseases of the renal system (n=12). Outcomes related to inflammation were addressed 18 times. Of importance, no studies reported clinically relevant adverse effects related to the WB-EMS intervention. In summary, while considerable evidence on outcomes related to fitness/function and body composition is prevalent, evidence gaps of WB-EMS research were particular evident for diseases of the nervous and cerebrovascular system.

Whole-body electromyostimulation (WB-EMS) can be considered as a time-efficient, joint-friendly and highly customizable training technology that attracts a wide range of users. The present evidence map aimed to provide an overview of different non-athletic cohorts addressed by WB-EMS research. Based on a comprehensive systematic search according to PRISMA, eighty-six eligible longitudinal trials were identified that correspond with our eligibility criteria. In summary, WB-EMS research sufficiently covers all adult age categories in males and females. Most cohorts addressed (58%) were predominately or exclusively overweight/obese and in about 60% of them, diseases or conditions were inclusion criteria for the trials. Cohorts specifically addressed by WB-EMS trials suffer from cancer/neoplasm (n=7), obesity (n=6), diabetes mellitus (n=5), the metabolic syndrome (n=2), nervous system diseases (n=2), chronic heart failure (n=4), stroke (n=1), peripheral arterial diseases (n=2), knee arthrosis (n=1), sarcopenia (n=3), chronic unspecific low back pain (n=4), and osteopenia (n=3). Chronic kidney disease was an eligibility criterion in five WB-EMS trials. Finally, three studies included only critically ill patients, two further studies considered frailty as an inclusion criterion. Of importance, no adverse effects of the WB-EMS intervention were reported. In summary, evidence gaps of WB-EMS research were particular evident for cohorts with diseases of the nervous and cerebrovascular system.

5G low-earth orbit satellite communications offer enhanced wireless coverage beyond the reach of 5G terrestrial networks, with important implications, particularly for automated and connected vehicles. Such wireless automotive mass-market applications demand well-designed compact user equipment antenna terminals offering non-terrestrial jointly with terrestrial communications. The antenna should be low-profile, conformal, and meet specific parameter values for gain and operational frequency bandwidth, tailored to the intended applications, in line with the aesthetic design requirements of passenger cars. This work presents an original concept for a dual-band nested circularly polarized automotive user terminal that operates at the S-band frequencies around 3.5 GHz and Ka-band frequencies around 28 GHz, namely within the 5G new-radio bands n78 and n257, respectively. The proposed terminal is designed to be integrated into the plastic components of a passenger vehicle. The arrays consist of 2×2 aperture-coupled corner-truncated microstrip slot patch antenna elements for the n78 band and of 4×4 single-layer edge-truncated microstrip circular slot patch antenna elements for the n257 band. The embedded arrays offer, across the two bands, respectively 9.9 and 13.7 dBi measured realized gain and 3-dB axial ratio bandwidths of 100 and 1500 MHz for the n78 and n257 bands along the broadside direction. Detailed link budget calculations anticipate uplink data rates of 21 and 6 Mbit/s, respectively, deeming it suitable for various automotive mobility and internet-of-things applications.

Background: External beam radiation therapy requires a sophisticated and laborious planning procedure. To improve the efficiency and quality of the planning procedure, machine learning predictions of the dose distributions have been introduced to speed up the planning procedure and to serve as quality assurance. The most recent dose prediction models are based on deep learning U-Nets that give good approximations of the dose in 3D almost instantly. It is our purpose to train a 3D dose prediction for glioblastoma VMAT treatment and test its robustness and sensitivity for the purpose of quality assurance of automatic contouring. Methods: From a cohort of 125 glioblastoma (GBM) patients, VMAT plans were created according to a clinical protocol. The initial model was trained on a concatenated 3D U-Net. A total of 60 cases were used for training, 15 for validation and 20 for testing. The prediction model was tested for sensitivity to dose changes according to realistic contour variations. Additionally, the model was tested for robustness by exposing it to a worst-case test set containing out-of-distribution cases.Results: The initially trained prediction model had a dose score of 0.94 Gy and a mean DVH score for all structures of 1.95 Gy. In terms of sensitivity, the model was able to predict the dose changes that occurred due to the contour variations with a mean error of 1.38 Gy.Conclusions: We obtained a 3D VMAT dose prediction model for GBM with limited data, providing good sensitivity to realistic contour variations. We tested and improved the model's robustness, by targeted updating the training set, making it a useful technique for dose awareness in the contouring evaluation and quality assurance.

The artificial intelligence chatbot ChatGPT can answer questions and solve tasks posed by the user within seconds. Using an exemplary task, this study investigates the reliability and con-sistency of the answers given by ChatGPT. For this purpose, it was analyzed whether the an-swers differ when a question is asked repeatedly and whether selected content categories and associated word combinations coincide with those from scientific literature. ChatGPT was asked 400 times, how the connectedness between humans and nature can be increased. The responses were classified into a categorization system and the most frequently occurring word combina-tions for each category were extracted. These word combinations were used for a search of re-lated scientific literature. In addition, the Normalized Mutual Information (NMI) between the 400 individual responses was calculated. The results show that the phrases used by ChatGPT within the categories are also found in the scientific literature, however, the number of mentions between scientific literature and ChatGPT differs. In addition, the NMI suggested that there are large differences between the categories mentioned in the individual answers. These results in-dicate that ChatGPT currently still has difficulties in answering complex questions and cannot yet replace scientific literature research or academic writing.

This study explores the integration of Building Information Modelling (BIM) and Virtual Tours in the Architecture Engineering and Construction (AEC) industry, focusing on Facility Management (FM) and Computerized Maintenance Management Systems (CMMS). The research addresses the need for different levels of detail in BIMs across various building phases and the potential of Virtual Tours as a complement to BIMs in IoT-based FM. The study’s methodology includes a literature review, a pilot-demonstrator case study, installation of monitoring and IoT control devices, execution of BIMs and Virtual Tour models, and development of links between system elements. The case study is based on the Controlled Environments for Living Lab Studies (CELLS), a unique facility designed for flexible monitoring and remote-control processes. The findings of this research could provide valuable insights into the potential of Virtual Tours to complement and connect to BIMs within a life cycle perspective, enhancing the usability of digital twins for nontrained users and contributing to the evolution of the AEC industry.

Offshore wind farms are increasingly built in the North Sea and the number of HVDC systems transmitting the wind power to shore increases as well. To connect offshore wind farms to adjacent AC transmission systems, onshore and offshore modular multilevel converters transform the transmitted power from AC to DC and vice versa. Besides, modern wind farms mainly use wind turbines connected to the offshore point of common coupling via voltage source converters. However, converters and their control systems can cause unwanted interactions, referred to as converter-driven stability problems. The resulting instabilities can be predicted by applying an impedance-based analysis in the frequency domain. Considering that the converter models and system data are often confidential and cannot be exchanged in real systems, this paper proposes an enhanced impedance measurement method suitable for black-box applications to investigate the interactions. The proposed method is applied to assess an offshore HVDC system’s converter-driven stability, using impedance measurements of laboratory converters and a wind turbine converter controller replica. The results show that the onshore modular multilevel converter’s interactions with AC grids of moderate short-circuit ratios can lead to instabilities. The offshore system analysis reveals that considering the offshore grid topology is crucial for assessing interactions between the wind turbine controllers and the offshore modular multilevel converter. It is shown that different stability margins result from varying offshore grid layouts.

In this study, we investigate the influence of control type and strain rate on the lifetime of specimens manufactured from 50CrMo4. This influence is described by a strain rate dependent method that uses cyclic stress strain curves to correct displacement controlled cyclic test results. The objective of this correction is to eliminate the stress related differences between displacement controlled cyclic test results and force controlled cyclic test results. The method is applied to the results of ultrasonic fatigue tests of six different combinations of heat treatment, specimen geometry (notch factor) and atmosphere. The corrected results show an improved agreement with test results obtained on conventional fatigue testing equipment with similar specimens: the standard deviation in combined data sets is significantly reduced (p=4.1%). We discuss the literature on intrinsic and extrinsic strain rate effects in carbon steels.

Background/Objectives: We defined the value of a machine learning algorithm to distinguish between the EEG response to no light or any light stimulation, and between red or green light stimulation in awake volunteers with closed eyelids. This new method of EEG analysis is visionary in the understanding of visual signal processing and will facilitate anaesthetic depth research. Methods: X-gradient boosting models were used to classify the cortical response to VEP stimulation (no light vs. any light stimulation; red vs. green light stimulation). For each of the two classifications, three scenarios were tested: training and prediction in all participants (all), training and prediction in one participant (individual), training across all but one participant with prediction in the participant left out (one out). Results: Ninety-four Caucasian adults were included. The machine learning algorithm had a very high predictive value and accuracy in differentiating between no light and any light stimulation (AUCROCall: 0.96; accuracyall: 0.94; AUCROCindividual: 0.96±0.05, accuracyindividual: 0.94±0.05; AUCROConeout: 0.98±0.04; accuracyo-neout:0.96±0.04). The machine learning algorithm was highly predictive and accurate in distinguishing between green and red colour stimulation (AUCROCall: 0.97; accuracyall: 0.91; AUCROCin-dividual: 0.98±0.04, accuracyindividual: 0.96±0.04; AUCROConeout: 0.96±0.05; accuracyoneout: 0.93±0.06). The predictive value and accuracy of both classification tasks was comparable between males and females. Conclusions: Machine learning algorithms could almost continuously and reliably differentiate between the cortical EEG responses to no light or any light stimulation and between green or red colour stimulation using VEPs in awake female and male volunteers with eyes closed. Our findings may open new possibilities for using VEPs in the intraoperative setting.