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In this paper, the performance evaluation of Frequency Modulated Chaotic On-Off Keying (FM-COOK) in AWGN, Rayleigh and Rician fading channels is given. The simulation results show that an improvement in BER can be gained by incorporating the FM modulation with COOK for SNR values less than 10dB in AWGN case and less than 6dB for Rayleigh and Rician fading channels.
YAWL (Yet Another Workflow Language) is an open source Business Process Management System, first released in 2003. YAWL grew out of a university research environment to become a unique system that has been deployed worldwide as a laboratory environment for research in Business Process Management and as a productive system in other scientific domains.
When users in virtual reality cannot physically walk and self-motions are instead only visually simulated, spatial updating is often impaired. In this paper, we report on a study that investigated if HeadJoystick, an embodied leaning-based flying interface, could improve performance in a 3D navigational search task that relies on maintaining situational awareness and spatial updating in VR. We compared it to Gamepad, a standard flying interface. For both interfaces, participants were seated on a swivel chair and controlled simulated rotations by physically rotating. They either leaned (forward/backward, right/left, up/down) or used the Gamepad thumbsticks for simulated translation. In a gamified 3D navigational search task, participants had to find eight balls within 5 min. Those balls were hidden amongst 16 randomly positioned boxes in a dark environment devoid of any landmarks. Compared to the Gamepad, participants collected more balls using the HeadJoystick. It also minimized the distance travelled, motion sickness, and mental task demand. Moreover, the HeadJoystick was rated better in terms of ease of use, controllability, learnability, overall usability, and self-motion perception. However, participants rated HeadJoystick could be more physically fatiguing after a long use. Overall, participants felt more engaged with HeadJoystick, enjoyed it more, and preferred it. Together, this provides evidence that leaning-based interfaces like HeadJoystick can provide an affordable and effective alternative for flying in VR and potentially telepresence drones.
Airborne and spaceborne platforms are the primary data sources for large-scale forest mapping, but visual interpretation for individual species determination is labor-intensive. Hence, various studies focusing on forests have investigated the benefits of multiple sensors for automated tree species classification. However, transferable deep learning approaches for large-scale applications are still lacking. This gap motivated us to create a novel dataset for tree species classification in central Europe based on multi-sensor data from aerial, Sentinel-1 and Sentinel-2 imagery. In this paper, we introduce the TreeSatAI Benchmark Archive, which contains labels of 20 European tree species (i.e., 15 tree genera) derived from forest administration data of the federal state of Lower Saxony, Germany. We propose models and guidelines for the application of the latest machine learning techniques for the task of tree species classification with multi-label data. Finally, we provide various benchmark experiments showcasing the information which can be derived from the different sensors including artificial neural networks and tree-based machine learning methods. We found that residual neural networks (ResNet) perform sufficiently well with weighted precision scores up to 79 % only by using the RGB bands of aerial imagery. This result indicates that the spatial content present within the 0.2 m resolution data is very informative for tree species classification. With the incorporation of Sentinel-1 and Sentinel-2 imagery, performance improved marginally. However, the sole use of Sentinel-2 still allows for weighted precision scores of up to 74 % using either multi-layer perceptron (MLP) or Light Gradient Boosting Machine (LightGBM) models. Since the dataset is derived from real-world reference data, it contains high class imbalances. We found that this dataset attribute negatively affects the models' performances for many of the underrepresented classes (i.e., scarce tree species). However, the class-wise precision of the best-performing late fusion model still reached values ranging from 54 % (Acer) to 88 % (Pinus). Based on our results, we conclude that deep learning techniques using aerial imagery could considerably support forestry administration in the provision of large-scale tree species maps at a very high resolution to plan for challenges driven by global environmental change. The original dataset used in this paper is shared via Zenodo (https://doi.org/10.5281/zenodo.6598390, Schulz et al., 2022). For citation of the dataset, we refer to this article.
Agiles IT-Controlling
(2022)
Während im IT-Projektmanagement agile Methoden seit vielen Jahren in der Praxis Zuspruch finden, werden im IT-Controlling überwiegend noch klassische Methoden eingesetzt. Der Beitrag untersucht die Fragestellung, ob und wie die im IT-Controlling eingesetzten Methoden auch agilen Paradigmen folgen und Methoden des agilen IT-Projektmanagements adaptiert werden können.
A company's financial documents use tables along with text to organize the data containing key performance indicators (KPIs) (such as profit and loss) and a financial quantity linked to them. The KPI’s linked quantity in a table might not be equal to the similarly described KPI's quantity in a text. Auditors take substantial time to manually audit these financial mistakes and this process is called consistency checking. As compared to existing work, this paper attempts to automate this task with the help of transformer-based models. Furthermore, for consistency checking it is essential for the table's KPIs embeddings to encode the semantic knowledge of the KPIs and the structural knowledge of the table. Therefore, this paper proposes a pipeline that uses a tabular model to get the table's KPIs embeddings. The pipeline takes input table and text KPIs, generates their embeddings, and then checks whether these KPIs are identical. The pipeline is evaluated on the financial documents in the German language and a comparative analysis of the cell embeddings' quality from the three tabular models is also presented. From the evaluation results, the experiment that used the English-translated text and table KPIs and Tabbie model to generate table KPIs’ embeddings achieved an accuracy of 72.81% on the consistency checking task, outperforming the benchmark, and other tabular models.
The epithelial sodium channel (ENaC) is a heterotrimeric ion channel that plays a key role in sodium and water homeostasis in tetrapod vertebrates. In the aldosterone-sensitive distal nephron, hormonally controlled ENaC expression matches dietary sodium intake to its excretion. Furthermore, ENaC mediates sodium absorption across the epithelia of the colon, sweat ducts, reproductive tract, and lung. ENaC is a constitutively active ion channel and its expression, membrane abundance, and open probability (PO) are controlled by multiple intracellular and extracellular mediators and mechanisms [9]. Aberrant ENaC regulation is associated with severe human diseases, including hypertension, cystic fibrosis, pulmonary edema, pseudohypoaldosteronism type 1, and nephrotic syndrome [9].
Lignocellulose feedstock (LCF) provides a sustainable source of components to produce bioenergy, biofuel, and novel biomaterials. Besides hard and soft wood, so-called low-input plants such as Miscanthus are interesting crops to be investigated as potential feedstock for the second generation biorefinery. The status quo regarding the availability and composition of different plants, including grasses and fast-growing trees (i.e., Miscanthus, Paulownia), is reviewed here. The second focus of this review is the potential of multivariate data processing to be used for biomass analysis and quality control. Experimental data obtained by spectroscopic methods, such as nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR), can be processed using computational techniques to characterize the 3D structure and energetic properties of the feedstock building blocks, including complex linkages. Here, we provide a brief summary of recently reported experimental data for structural analysis of LCF biomasses, and give our perspectives on the role of chemometrics in understanding and elucidating on LCF composition and lignin 3D structure.
Antioxidant activity is an essential aspect of oxygen-sensitive merchandise and goods, such as food and corresponding packaging, cosmetics, and biomedicine. Technical lignin has not yet been applied as a natural antioxidant, mainly due to the complex heterogeneous structure and polydispersity of lignin. This report presents antioxidant capacity studies completed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The influence of purification on lignin structure and activity was investigated. The purification procedure showed that double-fold selective extraction is the most efficient (confirmed by ultraviolet-visible (UV/Vis), Fourier transform infrared (FTIR), heteronuclear single quantum coherence (HSQC) and 31P nuclear magnetic resonance spectroscopy, size exclusion chromatography, and X-ray diffraction), resulting in fractions of very narrow polydispersity (3.2⁻1.6), up to four distinct absorption bands in UV/Vis spectroscopy. Due to differential scanning calorimetry measurements, the glass transition temperature increased from 123 to 185 °C for the purest fraction. Antioxidant capacity is discussed regarding the biomass source, pulping process, and degree of purification. Lignin obtained from industrial black liquor are compared with beech wood samples: antioxidant activity (DPPH inhibition) of kraft lignin fractions were 62⁻68%, whereas beech and spruce/pine-mixed lignin showed values of 42% and 64%, respectively. Total phenol content (TPC) of the isolated kraft lignin fractions varied between 26 and 35%, whereas beech and spruce/pine lignin were 33% and 34%, respectively. Storage decreased the TPC values but increased the DPPH inhibition.
The antiradical and antimicrobial activity of lignin and lignin-based films are both of great interest for applications such as food packaging additives. The polyphenolic structure of lignin in addition to the presence of O-containing functional groups is potentially responsible for these activities. This study used DPPH assays to discuss the antiradical activity of HPMC/lignin and HPMC/lignin/chitosan films. The scavenging activity (SA) of both binary (HPMC/lignin) and ternary (HPMC/lignin/chitosan) systems was affected by the percentage of the added lignin: the 5% addition showed the highest activity and the 30% addition had the lowest. Both scavenging activity and antimicrobial activity are dependent on the biomass source showing the following trend: organosolv of softwood > kraft of softwood > organosolv of grass. Testing the antimicrobial activities of lignins and lignin-containing films showed high antimicrobial activities against Gram-positive and Gram-negative bacteria at 35 °C and at low temperatures (0-7 °C). Purification of kraft lignin has a negative effect on the antimicrobial activity while storage has positive effect. The lignin release in the produced films affected the activity positively and the chitosan addition enhances the activity even more for both Gram-positive and Gram-negative bacteria. Testing the films against spoilage bacteria that grow at low temperatures revealed the activity of the 30% addition on HPMC/L1 film against both B. thermosphacta and P. fluorescens while L5 was active only against B. thermosphacta. In HPMC/lignin/chitosan films, the 5% addition exhibited activity against both B. thermosphacta and P. fluorescens.
This paper presents the preliminary results of the Socialist Republic of Vietnam country case study conducted as part of the research project Sustainable Labour Migration implemented by the University of Applied Science Bonn-Rhein-Sieg. The project focuses on stakeholder perspectives on countries of origin benefits and the sustainability of different transnational skill partnership schemes. Existing and ongoing small-scale initiatives indicate that opportunities exist for all three types of labour mobility pathways, from recruiting youth for apprenticeships and subsequent skilled work to recruitment and recognition of skilled 'professionals' certificates for direct work contracts to initial vocational education and training programs in a dual-track approach. While the latter has the highest potential to be more beneficial than other approaches, pursuing and supporting the scaling up of all three pathways in parallel will have additional, mutually reinforcing and supporting effects. The potential for benefits over and above those already realised by existing skill partnerships appears high, especially considering the favourable framework conditions specific to the long-standing German-Vietnamese relationship. If the potential of well-managed skill partnerships was realised, such sustainable models of skilled labour migration could serve as a unique selling point in the international competition for skilled labour.
SLC6A14 (ATB0,+) is unique among SLC proteins in its ability to transport 18 of the 20 proteinogenic (dipolar and cationic) amino acids and naturally occurring and synthetic analogues (including anti-viral prodrugs and nitric oxide synthase (NOS) inhibitors). SLC6A14 mediates amino acid uptake in multiple cell types where increased expression is associated with pathophysiological conditions including some cancers. Here, we investigated how a key position within the core LeuT-fold structure of SLC6A14 influences substrate specificity. Homology modelling and sequence analysis identified the transmembrane domain 3 residue V128 as equivalent to a position known to influence substrate specificity in distantly related SLC36 and SLC38 amino acid transporters. SLC6A14, with and without V128 mutations, was heterologously expressed and function determined by radiotracer solute uptake and electrophysiological measurement of transporter-associated current. Substituting the amino acid residue occupying the SLC6A14 128 position modified the binding pocket environment and selectively disrupted transport of cationic (but not dipolar) amino acids and related NOS inhibitors. By understanding the molecular basis of amino acid transporter substrate specificity we can improve knowledge of how this multi-functional transporter can be targeted and how the LeuT-fold facilitates such diversity in function among the SLC6 family and other SLC amino acid transporters.
Pipeline transport is an efficient method for transporting fluids in energy supply and other technical applications. While natural gas is the classical example, the transport of hydrogen is becoming more and more important; both are transmitted under high pressure in a gaseous state. Also relevant is the transport of carbon dioxide, captured in the places of formation, transferred under high pressure in a liquid or supercritical state and pumped into underground reservoirs for storage. The transport of other fluids is also required in technical applications. Meanwhile, the transport equations for different fluids are essentially the same, and the simulation can be performed using the same methods. In this paper, the effect of control elements such as compressors, regulators and flaptraps on the stability of fluid transport simulations is studied. It is shown that modeling of these elements can lead to instabilities, both in stationary and dynamic simulations. Special regularization methods were developed to overcome these problems. Their functionality also for dynamic simulations is demonstrated for a number of numerical experiments.
Farming communities confronted with climate change adopt formal and informal adaptation strategies to mitigate the effects of climate change. While the environmental and social effects of climate change are well documented, there is still a dearth of literature on girl-child marriage (formal marriage or informal union between a child under the age of 18 and an adult or another child) as a response to the effects of climate change. In this research, we ask if girl-child marriage is promoted as a social protection mechanism first, rather than as simply a response to climate-induced poverty. We use qualitative semi-structured interviews and focus group discussions to explore this question in a rural farming community in Northern Ghana. Our findings reveal that climate change shocks result in poverty and compel farmers to marry off their young daughters. The unmarried girl-child is perceived as an ‘extra mouth to feed’, a liability whose marriage becomes a strategy for protecting the family, the family’s reputation, and the girl child. The emphasis in girl-child marriage is not on the girl-child as an individual but on the family as a group. Hence, what is good for the family is assumed to be in the best interest of the girl-child. We place our analysis at the intersection of climate change, social protection, and the incidence of girl-child marriages. We argue that understanding this link is crucial and can contribute significantly to our knowledge of girl-child marriage as well as our ability to address this in Sub-Saharan Africa.
Among the celestial bodies in the Solar System, Mars currently represents the main target for the search for life beyond Earth. However, its surface is constantly exposed to high doses of cosmic rays (CRs) that may pose a threat to any biological system. For this reason, investigations into the limits of resistance of life to space relevant radiation is fundamental to speculate on the chance of finding extraterrestrial organisms on Mars. In the present work, as part of the STARLIFE project, the responses of dried colonies of the black fungus Cryomyces antarcticus Culture Collection of Fungi from Extreme Environments (CCFEE) 515 to the exposure to accelerated iron (LET: 200 keV/μm) ions, which mimic part of CRs spectrum, were investigated. Samples were exposed to the iron ions up to 1000 Gy in the presence of Martian regolith analogues. Our results showed an extraordinary resistance of the fungus in terms of survival, recovery of metabolic activity and DNA integrity. These experiments give new insights into the survival probability of possible terrestrial-like life forms on the present or past Martian surface and shallow subsurface environments.
A biodegradable blend of PBAT—poly(butylene adipate-co-terephthalate)—and PLA—poly(lactic acid)—for blown film extrusion was modified with four multi-functional chain extending cross-linkers (CECL). The anisotropic morphology introduced during film blowing affects the degradation processes. Given that two CECL increased the melt flow rate (MFR) of tris(2,4-di-tert-butylphenyl)phosphite (V1) and 1,3-phenylenebisoxazoline (V2) and the other two reduced it (aromatic polycarbodiimide (V3) and poly(4,4-dicyclohexylmethanecarbodiimide) (V4)), their compost (bio-)disintegration behavior was investigated. It was significantly altered with respect to the unmodified reference blend (REF). The disintegration behavior at 30 and 60 °C was investigated by determining changes in mass, Young’s moduli, tensile strengths, elongations at break and thermal properties. In order to quantify the disintegration behavior, the hole areas of blown films were evaluated after compost storage at 60 °C to calculate the kinetics of the time dependent degrees of disintegration. The kinetic model of disintegration provides two parameters: initiation time and disintegration time. They quantify the effects of the CECL on the disintegration behavior of the PBAT/PLA compound. Differential scanning calorimetry (DSC) revealed a pronounced annealing effect during storage in compost at 30 °C, as well as the occurrence of an additional step-like increase in the heat flow at 75 °C after storage at 60 °C. The disintegration consists of processes which affect amorphous and crystalline phase of PBAT in different manner that cannot be understood by a hydrolytic chain degradation only. Furthermore, gel permeation chromatography (GPC) revealed molecular degradation only at 60 °C for the REF and V1 after 7 days of compost storage. The observed losses of mass and cross-sectional area seem to be attributed more to mechanical decay than to molecular degradation for the given compost storage times.
Process-induced changes in the morphology of biodegradable polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA) blends modified with various multifunctional chainextending cross-linkers (CECLs) are presented. The morphology of unmodified and modified films produced with blown film extrusion is examined in an extrusion direction (ED) and a transverse direction (TD). While FTIR analysis showed only small peak shifts indicating that the CECLs modify the molecular weight of the PBAT/PLA blend, SEM investigations of the fracture surfaces of blown extrusion films revealed their significant effect on the morphology formed during the processing. Due to the combined shear and elongation deformation during blown film extrusion, rather spherical PLA islands were partly transformed into long fibrils, which tended to decay to chains of elliptical islands if cooled slowly. The CECL introduction into the blend changed the thickness of the PLA fibrils, modified the interface adhesion, and altered the deformation behavior of the PBAT matrix from brittle to ductile. The results proved that CECLs react selectively with PBAT, PLA, and their interface. Furthermore, the reactions of CECLs with PBAT/PLA induced by the processing depended on the deformation directions (ED and TD), thus resulting in further non-uniformities of blown extrusion films.
This study investigates the effects of four multifunctional chain-extending cross-linkers (CECL) on the processability, mechanical performance, and structure of polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA) blends produced using film blowing technology. The newly developed reference compound (M·VERA® B5029) and the CECL modified blends are characterized with respect to the initial properties and the corresponding properties after aging at 50 °C for 1 and 2 months. The tensile strength, seal strength, and melt volume rate (MVR) are markedly changed after thermal aging, whereas the storage modulus, elongation at the break, and tear resistance remain constant. The degradation of the polymer chains and crosslinking with increased and decreased MVR, respectively, is examined thoroughly with differential scanning calorimetry (DSC), with the results indicating that the CECL-modified blends do not generally endure thermo-oxidation over time. Further, DSC measurements of 25 µm and 100 µm films reveal that film blowing pronouncedly changes the structures of the compounds. These findings are also confirmed by dynamic mechanical analysis, with the conclusion that tris(2,4-di-tert-butylphenyl)phosphite barely affects the glass transition temperature, while with the other changes in CECL are seen. Cross-linking is found for aromatic polycarbodiimide and poly(4,4-dicyclohexylmethanecarbodiimide) CECL after melting of granules and films, although overall the most synergetic effect of the CECL is shown by 1,3-phenylenebisoxazoline.
This review is divided into two interconnected parts, namely a biological and a chemical one. The focus of the first part is on the biological background for constructing tissue-engineered vascular grafts to promote vascular healing. Various cell types, such as embryonic, mesenchymal and induced pluripotent stem cells, progenitor cells and endothelial- and smooth muscle cells will be discussed with respect to their specific markers. The in vitro and in vivo models and their potential to treat vascular diseases are also introduced. The chemical part focuses on strategies using either artificial or natural polymers for scaffold fabrication, including decellularized cardiovascular tissue. An overview will be given on scaffold fabrication including conventional methods and nanotechnologies. Special attention is given to 3D network formation via different chemical and physical cross-linking methods. In particular, electron beam treatment is introduced as a method to combine 3D network formation and surface modification. The review includes recently published scientific data and patents which have been registered within the last decade.
(1) Background: Autologous bone is supposed to contain vital cells that might improve the osseointegration of dental implants. The aim of this study was to investigate particulate and filtered bone chips collected during oral surgery intervention with respect to their osteogenic potential and the extent of microbial contamination to evaluate its usefulness for jawbone reconstruction prior to implant placement. (2) Methods: Cortical and cortical-cancellous bone chip samples of 84 patients were collected. The stem cell character of outgrowing cells was characterized by expression of CD73, CD90 and CD105, followed by osteogenic differentiation. The degree of bacterial contamination was determined by Gram staining, catalase and oxidase tests and tests to evaluate the genera of the found bacteria (3) Results: Pre-surgical antibiotic treatment of the patients significantly increased viability of the collected bone chip cells. No significant difference in plasticity was observed between cells isolated from the cortical and cortical-cancellous bone chip samples. Thus, both types of bone tissue can be used for jawbone reconstruction. The osteogenic differentiation was independent of the quantity and quality of the detected microorganisms, which comprise the most common bacteria in the oral cavity. (4) Discussion: This study shows that the quality of bone chip-derived stem cells is independent of the donor site and the extent of present common microorganisms, highlighting autologous bone tissue, assessable without additional surgical intervention for the patient, as a useful material for dental implantology.
MOTIVATION
The majority of biomedical knowledge is stored in structured databases or as unstructured text in scientific publications. This vast amount of information has led to numerous machine learning-based biological applications using either text through natural language processing (NLP) or structured data through knowledge graph embedding models (KGEMs). However, representations based on a single modality are inherently limited.
RESULTS
To generate better representations of biological knowledge, we propose STonKGs, a Sophisticated Transformer trained on biomedical text and Knowledge Graphs (KGs). This multimodal Transformer uses combined input sequences of structured information from KGs and unstructured text data from biomedical literature to learn joint representations in a shared embedding space. First, we pre-trained STonKGs on a knowledge base assembled by the Integrated Network and Dynamical Reasoning Assembler (INDRA) consisting of millions of text-triple pairs extracted from biomedical literature by multiple NLP systems. Then, we benchmarked STonKGs against three baseline models trained on either one of the modalities (i.e., text or KG) across eight different classification tasks, each corresponding to a different biological application. Our results demonstrate that STonKGs outperforms both baselines, especially on the more challenging tasks with respect to the number of classes, improving upon the F1-score of the best baseline by up to 0.084 (i.e., from 0.881 to 0.965). Finally, our pre-trained model as well as the model architecture can be adapted to various other transfer learning applications.
AVAILABILITY
We make the source code and the Python package of STonKGs available at GitHub (https://github.com/stonkgs/stonkgs) and PyPI (https://pypi.org/project/stonkgs/). The pre-trained STonKGs models and the task-specific classification models are respectively available at https://huggingface.co/stonkgs/stonkgs-150k and https://zenodo.org/communities/stonkgs.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including regenerative therapies, the complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary efforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible scaffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized scaffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.
The temperature of photovoltaic modules is modelled as a dynamic function of ambient temperature, shortwave and longwave irradiance and wind speed, in order to allow for a more accurate characterisation of their efficiency. A simple dynamic thermal model is developed by extending an existing parametric steady-state model using an exponential smoothing kernel to include the effect of the heat capacity of the system. The four parameters of the model are fitted to measured data from three photovoltaic systems in the Allgäu region in Germany using non-linear optimisation. The dynamic model reduces the root-mean-square error between measured and modelled module temperature to 1.58 K on average, compared to 3.03 K for the steady-state model, whereas the maximum instantaneous error is reduced from 20.02 to 6.58 K.
Solar photovoltaic power output is modulated by atmospheric aerosols and clouds and thus contains valuable information on the optical properties of the atmosphere. As a ground-based data source with high spatiotemporal resolution it has great potential to complement other ground-based solar irradiance measurements as well as those of weather models and satellites, thus leading to an improved characterisation of global horizontal irradiance. In this work several algorithms are presented that can retrieve global tilted and horizontal irradiance and atmospheric optical properties from solar photovoltaic data and/or pyranometer measurements. The method is tested on data from two measurement campaigns that took place in the Allgäu region in Germany in autumn 2018 and summer 2019, and the results are compared with local pyranometer measurements as well as satellite and weather model data. Using power data measured at 1 Hz and averaged to 1 min resolution along with a non-linear photovoltaic module temperature model, global horizontal irradiance is extracted with a mean bias error compared to concurrent pyranometer measurements of 5.79 W m−2 (7.35 W m−2) under clear (cloudy) skies, averaged over the two campaigns, whereas for the retrieval using coarser 15 min power data with a linear temperature model the mean bias error is 5.88 and 41.87 W m−2 under clear and cloudy skies, respectively.
During completely overcast periods the cloud optical depth is extracted from photovoltaic power using a lookup table method based on a 1D radiative transfer simulation, and the results are compared to both satellite retrievals and data from the Consortium for Small-scale Modelling (COSMO) weather model. Potential applications of this approach for extracting cloud optical properties are discussed, as well as certain limitations, such as the representation of 3D radiative effects that occur under broken-cloud conditions. In principle this method could provide an unprecedented amount of ground-based data on both irradiance and optical properties of the atmosphere, as long as the required photovoltaic power data are available and properly pre-screened to remove unwanted artefacts in the signal. Possible solutions to this problem are discussed in the context of future work.
Object-Based Trace Model for Automatic Indicator Computation in the Human Learning Environments
(2021)
This paper proposes a traces model in the form of an object or class model (in the UML sense) which allows the automatic calculation of indicators of various kinds and independently of the computer environment for human learning (CEHL). The model is based on the establishment of a trace-based system that encompasses all the logic of traces collecting and indicators calculation. It is im-plemented in the form of a trace database. It is an important contribution in the field of the exploitation of the traces of apprenticeship in a CEHL because it pro-vides a general formalism for modeling the traces and allowing the calculation of several indicators at the same time. Also, with the inclusion of calculated indica-tors as potential learning traces, our model provides a formalism for classifying the various indicators in the form of inheritance relationships, which promotes the reuse of indicators already calculated. Economically, the model can allow organi-zations with different learning platforms to invest only in one traces Management System. At the social level, it can allow a better sharing of trace databases be-tween the various research institutions in the field of CEHL.
Telepresence robots allow users to be spatially and socially present in remote environments. Yet, it can be challenging to remotely operate telepresence robots, especially in dense environments such as academic conferences or workplaces. In this paper, we primarily focus on the effect that a speed control method, which automatically slows the telepresence robot down when getting closer to obstacles, has on user behaviors. In our first user study, participants drove the robot through a static obstacle course with narrow sections. Results indicate that the automatic speed control method significantly decreases the number of collisions. For the second study we designed a more naturalistic, conference-like experimental environment with tasks that require social interaction, and collected subjective responses from the participants when they were asked to navigate through the environment. While about half of the participants preferred automatic speed control because it allowed for smoother and safer navigation, others did not want to be influenced by an automatic mechanism. Overall, the results suggest that automatic speed control simplifies the user interface for telepresence robots in static dense environments, but should be considered as optionally available, especially in situations involving social interactions.
Salts and proteins comprise two of the basic molecular components of biological materials. Kosmotropic/chaotropic co-solvation and matching ion water affinities explain basic ionic effects on protein aggregation observed in simple solutions. However, it is unclear how these theories apply to proteins in complex biological environments and what the underlying ionic binding patterns are. Using the positive ion Ca2+ and the negatively charged membrane protein SNAP25, we studied ion effects on protein oligomerization in solution, in native membranes and in molecular dynamics (MD) simulations. We find that concentration-dependent ion-induced protein oligomerization is a fundamental chemico-physical principle applying not only to soluble but also to membrane-anchored proteins in their native environment. Oligomerization is driven by the interaction of Ca2+ ions with the carboxylate groups of aspartate and glutamate. From low up to middle concentrations, salt bridges between Ca2+ ions and two or more protein residues lead to increasingly larger oligomers, while at high concentrations oligomers disperse due to overcharging effects. The insights provide a conceptual framework at the interface of physics, chemistry and biology to explain binding of ions to charged protein surfaces on an atomistic scale, as occurring during protein solubilisation, aggregation and oligomerization both in simple solutions and membrane systems.
Im Zuge der Migrationsbewegung in den Jahren 2015 und 2016 hat die menschenwürdige Unterbringung von geflüchteten Menschen in Kommunen in Deutschland an Aufmerksamkeit gewonnen. Der Anstieg der Asylbewerber:innen in den Kommunen sowie die Bundesinitiative „Schutz von geflüchteten Menschen in Flüchtlingsunterkünften“ haben Veränderungen im Hinblick auf Schutzstandards in der kommunalen Unterbringung geflüchteter Menschen hervorgerufen. Der Artikel erklärt diese Veränderungen mittels einer akteurszentrierten organisationssoziologischen Herangehensweise. Grundlage sind empirische Forschungsergebnisse des Projektes „Organisational Perspectives on Human Security Standards for Refugees in Germany“ aus zwei deutschen Kommunen.
The cooperation between researchers and practitioners during the different stages of the research process is promoted as it can be of benefit to both society and research supporting processes of ‘transformation’. While acknowledging the important potential of research–practice–collaborations (RPCs), this paper reflects on RPCs from a political-economic perspective to also address potential unintended adverse effects on knowledge generation due to divergent interests, incomplete information or the unequal distribution of resources. Asymmetries between actors may induce distorted and biased knowledge and even help produce or exacerbate existing inequalities. Potential merits and limitations of RPCs, therefore, need to be gauged. Taking RPCs seriously requires paying attention to these possible tensions—both in general and with respect to international development research, in particular: On the one hand, there are attempts to contribute to societal change and ethical concerns of equity at the heart of international development research, and on the other hand, there is the relative risk of encountering asymmetries more likely.
Purpose – To describe the development of a novel polyether(meth)acrylate-based resin material class for stereolithography with alterable material characteristics.
Design/methodology/approach – A complete overview of details to composition parameters, the optimization and bandwidth of mechanical and processing parameters is given. Initial biological characterization experiments and future application felds are depicted. Process parameters are studied in a commercial 3D systems Viper stereolithography system, and a new method to determine these parameters is described herein.
Findings – Initial biological characterizations show the non-toxic behavior in a biological environment, caused mainly by the (meth)acrylate-based core components. These photolithographic resins combine an adjustable low Young’s modulus with the advantages of a non-toxic (meth)acrylate-based process material. In contrast to the mostly rigid process materials used today in the rapid prototyping industry, these polymeric formulations are able to fulfll the extended need for a soft engineering material. A short overview of sample applications is given.
Practical implications – These polymeric formulations are able to meet the growing demand for a resin class for rapid manufacturing that covers a bandwidth from softer to stiffer materials.
Originality/value – This paper gives an overview about the novel developed material class for stereolithography and should be therefore of high interest to people with interest in novel rapid manufacturing materials and technology.
Cathepsin K (CatK) is a target for the treatment of osteoporosis, arthritis, and bone metastasis. Peptidomimetics with a cyanohydrazide warhead represent a new class of highly potent CatK inhibitors; however, their binding mechanism is unknown. We investigated two model cyanohydrazide inhibitors with differently positioned warheads: an azadipeptide nitrile Gü1303 and a 3-cyano-3-aza-β-amino acid Gü2602. Crystal structures of their covalent complexes were determined with mature CatK as well as a zymogen-like activation intermediate of CatK. Binding mode analysis, together with quantum chemical calculations, revealed that the extraordinary picomolar potency of Gü2602 is entropically favoured by its conformational flexibility at the nonprimed-primed subsites boundary. Furthermore, we demonstrated by live cell imaging that cyanohydrazides effectively target mature CatK in osteosarcoma cells. Cyanohydrazides also suppressed the maturation of CatK by inhibiting the autoactivation of the CatK zymogen. Our results provide structural insights for the rational design of cyanohydrazide inhibitors of CatK as potential drugs.
When optimizing the process parameters of the acidic ethanolic organosolv process, the aim is usually to maximize the delignification and/or lignin purity. However, process parameters such as temperature, time, ethanol and catalyst concentration, respectively, can also be used to vary the structural properties of the obtained organosolv lignin, including the molecular weight and the ratio of aliphatic versus phenolic hydroxyl groups, among others. This review particularly focuses on these influencing factors and establishes a trend analysis between the variation of the process parameters and the effect on lignin structure. Especially when larger data sets are available, as for process temperature and time, correlations between the distribution of depolymerization and condensation reactions are found, which allow direct conclusions on the proportion of lignin's structural features, independent of the diversity of the biomass used. The newfound insights gained from this review can be used to tailor organosolv lignins isolated for a specific application.
Miscanthus crops possess very attractive properties such as high photosynthesis yield and carbon fixation rate. Because of these properties, it is currently considered for use in second-generation biorefineries. Here we analyze the differences in chemical composition between M. x giganteus, a commonly studied Miscanthus genotype, and M. nagara, which is relatively understudied but has useful properties such as increased frost resistance and higher stem stability. Samples of M. x giganteus (Gig35) and M. nagara (NagG10) have been separated by plant portion (leaves and stems) in order to isolate the corresponding lignins. The organosolv process was used for biomass pulping (80% ethanol solution, 170 °C, 15 bar). Biomass composition and lignin structure analysis were performed using composition analysis, Fourier-transform infrared (FTIR), ultraviolet-visible (UV-Vis) and nuclear magnetic resonance (NMR) spectroscopy, thermogravimetric analysis (TGA), size exclusion chromatography (SEC) and pyrolysis gas-chromatography/mass spectrometry (Py-GC/MS) to determine the 3D structure of the isolated lignins, monolignol ratio and most abundant linkages depending on genotype and harvesting season. SEC data showed significant differences in the molecular weight and polydispersity indices for stem versus leaf-derived lignins. Py-GC/MS and hetero-nuclear single quantum correlation (HSQC) NMR revealed different monolignol compositions for the two genotypes (Gig35, NagG10). The monolignol ratio is slightly influenced by the time of harvest: stem-derived lignins of M. nagara showed increasing H and decreasing G unit content over the studied harvesting period (December–April).
As a low-input crop, Miscanthus offers numerous advantages that, in addition to agricultural applications, permits its exploitation for energy, fuel, and material production. Depending on the Miscanthus genotype, season, and harvest time as well as plant component (leaf versus stem), correlations between structure and properties of the corresponding isolated lignins differ. Here, a comparative study is presented between lignins isolated from M. x giganteus, M. sinensis, M. robustus and M. nagara using a catalyst-free organosolv pulping process. The lignins from different plant constituents are also compared regarding their similarities and differences regarding monolignol ratio and important linkages. Results showed that the plant genotype has the weakest influence on monolignol content and interunit linkages. In contrast, structural differences are more significant among lignins of different harvest time and/or season. Analyses were performed using fast and simple methods such as nuclear magnetic resonance (NMR) spectroscopy. Data was assigned to four different linkages (A: β-O-4 linkage, B: phenylcoumaran, C: resinol, D: β-unsaturated ester). In conclusion, A content is particularly high in leaf-derived lignins at just under 70% and significantly lower in stem and mixture lignins at around 60% and almost 65%. The second most common linkage pattern is D in all isolated lignins, the proportion of which is also strongly dependent on the crop portion. Both stem and mixture lignins, have a relatively high share of approximately 20% or more (maximum is M. sinensis Sin2 with over 30%). In the leaf-derived lignins, the proportions are significantly lower on average. Stem samples should be chosen if the highest possible lignin content is desired, specifically from the M. x giganteus genotype, which revealed lignin contents up to 27%. Due to the better frost resistance and higher stem stability, M. nagara offers some advantages compared to M. x giganteus. Miscanthus crops are shown to be very attractive lignocellulose feedstock (LCF) for second generation biorefineries and lignin generation in Europe.
Miscanthus x giganteus Stem Versus Leaf-Derived Lignins Differing in Monolignol Ratio and Linkage
(2019)
As a renewable, Miscanthus offers numerous advantages such as high photosynthesis activity (as a C4 plant) and an exceptional CO2 fixation rate. These properties make Miscanthus very attractive for industrial exploitation, such as lignin generation. In this paper, we present a systematic study analyzing the correlation of the lignin structure with the Miscanthus genotype and plant portion (stem versus leaf). Specifically, the ratio of the three monolignols and corresponding building blocks as well as the linkages formed between the units have been studied. The lignin amount has been determined for M. x giganteus (Gig17, Gig34, Gig35), M. nagara (NagG10), M. sinensis (Sin2), and M. robustus (Rob4) harvested at different time points (September, December, and April). The influence of the Miscanthus genotype and plant component (leaf vs. stem) has been studied to develop corresponding structure-property relationships (i.e., correlations in molecular weight, polydispersity, and decomposition temperature). Lignin isolation was performed using non-catalyzed organosolv pulping and the structure analysis includes compositional analysis, Fourier transform infradred (FTIR), ultraviolet/visible (UV-Vis), hetero-nuclear single quantum correlation nuclear magnetic resonsnce (HSQC-NMR), thermogravimetric analysis (TGA), and pyrolysis gaschromatography/mass spectrometry (GC/MS). Structural differences were found for stem and leaf-derived lignins. Compared to beech wood lignins, Miscanthus lignins possess lower molecular weight and narrow polydispersities (<1.5 Miscanthus vs. >2.5 beech) corresponding to improved homogeneity. In addition to conventional univariate analysis of FTIR spectra, multivariate chemometrics revealed distinct differences for aromatic in-plane deformations of stem versus leaf-derived lignins. These results emphasize the potential of Miscanthus as a low-input resource and a Miscanthus-derived lignin as promising agricultural feedstock.
Human butyrylcholinesterase (BChE) is a glycoprotein capable of bioscavenging toxic compounds such as organophosphorus (OP) nerve agents. For commercial production of BChE, it is practical to synthesize BChE in non-human expression systems, such as plants or animals. However, the glycosylation profile in these systems is significantly different from the human glycosylation profile, which could result in changes in BChE's structure and function. From our investigation, we found that the glycan attached to ASN241 is both structurally and functionally important due to its close proximity to the BChE tetramerization domain and the active site gorge. To investigate the effects of populating glycosylation site ASN241, monomeric human BChE glycoforms were simulated with and without site ASN241 glycosylated. Our simulations indicate that the structure and function of human BChE are significantly affected by the absence of glycan 241.
Dried serum spots that are well prepared can be attractive alternatives to frozen serum samples for shelving specimens in a medical or research center's biobank and mailing freshly prepared serum to specialized laboratories. During the pre-analytical phase, complications can arise which are often challenging to identify or are entirely overlooked. These complications can lead to reproducibility issues, which can be avoided in serum protein analysis by implementing optimized storage and transfer procedures. With a method that ensures accurate loading of filter paper discs with donor or patient serum, a gap in dried serum spot preparation and subsequent serum analysis shall be filled. Pre-punched filter paper discs with a 3 mm diameter are loaded within seconds in a highly reproducible fashion (approximately 10% standard deviation) when fully submerged in 10 μl of serum, named the "Submerge and Dry" protocol. Such prepared dried serum spots can store several hundred micrograms of proteins and other serum components. Serum-borne antigens and antibodies are reproducibly released in 20 μl elution buffer in high yields (approximately 90%). Dried serum spot-stored and eluted antigens kept their epitopes and antibodies their antigen binding abilities as was assessed by SDS-PAGE, 2D gel electrophoresis-based proteomics, and Western blot analysis, suggesting pre-punched filter paper discs as handy solution for serological tests.
While humans can effortlessly pick a view from multiple streams, automatically choosing the best view is a challenge. Choosing the best view from multi-camera streams poses a problem regarding which objective metrics should be considered. Existing works on view selection lack consensus about which metrics should be considered to select the best view. The literature on view selection describes diverse possible metrics. And strategies such as information-theoretic, instructional design, or aesthetics-motivated fail to incorporate all approaches. In this work, we postulate a strategy incorporating information-theoretic and instructional design-based objective metrics to select the best view from a set of views. Traditionally, information-theoretic measures have been used to find the goodness of a view, such as in 3D rendering. We adapted a similar measure known as the viewpoint entropy for real-world 2D images. Additionally, we incorporated similarity penalization to get a more accurate measure of the entropy of a view, which is one of the metrics for the best view selection. Since the choice of the best view is domain-dependent, we chose demonstration-based training scenarios as our use case. The limitation of our chosen scenarios is that they do not include collaborative training and solely feature a single trainer. To incorporate instructional design considerations, we included the trainer’s body pose, face, face when instructing, and hands visibility as metrics. To incorporate domain knowledge we included predetermined regions’ visibility as another metric. All of those metrics are taken into account to produce a parameterized view recommendation approach for demonstration-based training. An online study using recorded multi-camera video streams from a simulation environment was used to validate those metrics. Furthermore, the responses from the online study were used to optimize the view recommendation performance with a normalized discounted cumulative gain (NDCG) value of 0.912, which shows good performance with respect to matching user choices.
Several species of (poly)saccharides and organic acids can be found often simultaneously in various biological matrices, e.g., fruits, plant materials, and biological fluids. The analysis of such matrices sometimes represents a challenging task. Using Aloe vera (A. vera) plant materials as an example, the performance of several spectroscopic methods (80 MHz benchtop NMR, NIR, ATR-FTIR and UV-Vis) for the simultaneous analysis of quality parameters of this plant material was compared. The determined parameters include (poly)saccharides such as aloverose, fructose and glucose as well as organic acids (malic, lactic, citric, isocitric, acetic, fumaric, benzoic and sorbic acids). 500 MHz NMR and high-performance liquid chromatography (HPLC) were used as the reference methods.
UV-VIS data can be used only for identification of added preservatives (benzoic and sorbic acids) and drying agent (maltodextrin) and semiquantitative analysis of malic acid. NIR and MIR spectroscopies combined with multivariate regression can deliver more informative overview of A. vera extracts being able to additionally quantify glucose, aloverose, citric, isocitric, malic, lactic acids and fructose. Low-field NMR measurements can be used for the quantification of aloverose, glucose, malic, lactic, acetic, and benzoic acids. The benchtop NMR method was successfully validated in terms of robustness, stability, precision, reproducibility and limit of detection (LOD) and quantification (LOQ), respectively.
All spectroscopic techniques are useful for the screening of (poly)saccharides and organic acids in plant extracts and should be applied according to its availability as well as information and confidence required for the specific analytical goal. Benchtop NMR spectroscopy seems to be the most feasible solution for quality control of A. vera products.
Pollution with anthropogenic waste, particularly persistent plastic, has now reached every remote corner of the world. The French Atlantic coast, given its extensive coastline, is particularly affected. To gain an overview of current plastic pollution, this study examined a stretch of 250 km along the Silver Coast of France. Sampling was conducted at a total of 14 beach sections, each with five sampling sites in a transect. At each collection site, a square of 0.25 m2 was marked. The top 5 cm of beach sediment was collected and sieved on-site using an analysis sieve (mesh size 1 mm), resulting in a total of approximately 0.8 m3 of sediment, corresponding to a total weight of 1300 kg of examined beach sediment. A total of 1972 plastic particles were extracted and analysed using infrared spectroscopy, corresponding to 1.5 particles kg−1 of beach sediment. Pellets (885 particles), polyethylene as the polymer type (1349 particles), and particles in the size range of microplastics (943 particles) were most frequently found. The significant pollution by pellets suggests that the spread of plastic waste is not primarily attributable to tourism (in February/March 2023). The substantial accumulation of meso- and macro-waste (with 863 and 166 particles) also indicates that research focusing on microplastics should be expanded to include these size categories, as microplastics can develop from them over time.
Bond graph modelling was devised by Professor Paynter at the Massachusetts Institute of Technology in 1959 and subsequently developed into a methodology for modelling multidisciplinary systems at a time when nobody was speaking of object-oriented modelling. On the other hand, so-called object-oriented modelling has become increasingly popular during the last few years. By relating the characteristics of both approaches, it is shown that bond graph modelling, although much older, may be viewed as a special form of object-oriented modelling. For that purpose the new object-oriented modelling language Modelica is used as a working language which aims at supporting multiple formalisms. Although it turns out that bond graph models can be described rather easily, it is obvious that Modelica started from generalized networks and was not designed to support bond graphs. The description of bond graph models in Modelica is illustrated by means of a hydraulic drive. Since VHDL-AMS as an important language standardized and supported by IEEE has been extended to support also modelling of non-electrical systems, it is briefly investigated as to whether it can be used for description of bond graphs. It turns out that currently it does not seem to be suitable.
Multidisciplinary systems are described most suitably by bond graphs. In order to determine unnormalized frequency domain sensitivities in symbolic form, this paper proposes to construct in a systematic manner a bond graph from another bond graph, which is called the associated incremental bond graph in this paper. Contrary to other approaches reported in the literature the variables at the bonds of the incremental bond graph are not sensitivities but variations (incremental changes) in the power variables from their nominal values due to parameter changes. Thus their product is power. For linear elements their corresponding model in the incremental bond graph also has a linear characteristic. By deriving the system equations in symbolic state space form from the incremental bond graph in the same way as they are derived from the initial bond graph, the sensitivity matrix of the system can be set up in symbolic form. Its entries are transfer functions depending on the nominal parameter values and on the nominal states and the inputs of the original model. The sensitivities can be determined automatically by the bond graph preprocessor CAMP-G and the widely used program MATLAB together with the Symbolic Toolbox for symbolic mathematical calculation. No particular program is needed for the approach proposed. The initial bond graph model may be non-linear and may contain controlled sources and multiport elements. In that case the sensitivity model is linear time variant and must be solved in the time domain. The rationale and the generality of the proposed approach are presented. For illustration purposes a mechatronic example system, a load positioned by a constant-excitation d.c. motor, is presented and sensitivities are determined in symbolic form by means of CAMP-G/MATLAB.
In this paper, residual sinks are used in bond graph model-based quantitative fault detection for the coupling of a model of a faultless process engineering system to a bond graph model of the faulty system. By this way, integral causality can be used as the preferred computational causality in both models. There is no need for numerical differentiation. Furthermore, unknown variables do not need to be eliminated from power continuity equations in order to obtain analytical redundancy relations (ARRs) in symbolic form. Residuals indicating faults are computed numerically as components of a descriptor vector of a differential algebraic equation system derived from the coupled bond graphs. The presented bond graph approach especially aims at models with non-linearities that make it cumbersome or even impossible to derive ARRs from model equations by elimination of unknown variables. For illustration, the approach is applied to a non-controlled as well as to a controlled hydraulic two-tank system. Finally, it is shown that not only the numerical computation of residuals but also the simultaneous numerical computation of their sensitivities with respect to a parameter can be supported by bond graph modelling.
For the case when the abstraction of instantaneous state transitions is adopted, this paper proposes to start fault detection and isolation in an engineering system from a single time-invariant causality bond graph representation of a hybrid model. To that end, the paper picks up on a long-known proposal to model switching devices by a transformer modulated by a Boolean variable and a resistor in fixed conductance causality accounting for its ON resistance. Bond graph representations of hybrid system models developed in this way have been used so far mainly for the purpose of simulation. The paper shows that they can well constitute an approach to the bond-graph-based quantitative fault detection and isolation of hybrid models. Advantages are that the standard sequential causality assignment procedure can be a used without modification. A single set of analytical redundancy relations valid for all physically feasible system modes can be (automatically) derived from the bond graph. Stiff model equations due to small values of the ON resistance in the switch model may be avoided by symbolic reformulation of equations and letting the ON resistance of some switches tend to zero, turning them into ideal switches.
First, for two examples considered in the literature, it is shown that the approach proposed in this paper can produce the same analytical redundancy relations as were obtained from a hybrid bond graph with controlled junctions and the use of a sequential causality assignment procedure especially for fault detection and isolation purpose. Moreover, the usefulness of the proposed approach is illustrated in two case studies by its application to standard switching circuits extensively used in power electronic systems and by simulation of some fault scenarios. The approach, however, is not confined to the fault detection and isolation of such systems. Analytically validated simulation results obtained by means of the program Scilab give confidence in the approach.
A bond graph representation of switching devices known for a long time has been a modulated transformer with a modulus b(t)∈{0,1}∀t≥0 in conjunction with a resistor R:Ron accounting for the ON-resistance of a switch considered non-ideal. Besides other representations, this simple model has been used in bond graphs for simulation of the dynamic behaviour of hybrid systems. A previous article of the author has proposed to use the transformer–resistor pair in bond graphs for fault diagnosis in hybrid systems. Advantages are a unique bond graph for all system modes, the application of the unmodified standard Sequential Causality Assignment Procedure, fixed computational causalities and the derivation of analytical redundancy relations incorporating ‘Boolean’ transformer moduli so that they hold for all system modes. Switches temporarily connect and disconnect model parts. As a result, some independent storage elements may temporarily become dependent, so that the number of state variables is not time-invariant. This article addresses this problem in the context of modelling and simulation of fault scenarios in hybrid systems. In order to keep time-invariant preferred integral causality at storage ports, residual sinks previously introduced by the author are used. When two storage elements become dependent at a switching time instance ts, a residual sink is activated. It enforces that the outputs of two dependent storage elements become immediately equal by imposing the conjugate3 power variable of appropriate value on their inputs. The approach is illustrated by the bond graph modelling and simulation of some fault scenarios in a standard three-phase switched power inverter supplying power into an RL-load in a delta configuration. A well-developed approach to model-based fault detection and isolation is to evaluate the residual of analytical redundancy relations. In this article, analytical redundancy relation residuals have been computed numerically by coupling a bond graph of the faulty system to one of the non-faulty systems by means of residual sinks. The presented approach is not confined to power electronic systems but can be used for hybrid systems in other domains as well. In further work, the RL-load may be replaced by a bond graph model of an alternating current motor in order to study the effect of switch failures in the power inverter on to the dynamic behaviour of the motor.
Failure prognostic builds up on constant data acquisition and processing and fault diagnosis and is an essential part of predictive maintenance of smart manufacturing systems enabling condition based maintenance, optimised use of plant equipment, improved uptime and yield and to prevent safety problems. Given known control inputs into a plant and real sensor outputs or simulated measurements, the model-based part of the proposed hybrid method provides numerical values of unknown parameter degradation functions at sampling time points by the evaluation of equations that have been derived offline from a bicausal diagnostic bond graph. These numerical values are computed concurrently to the constant monitoring of a system and are stored in a buffer of fixed length. The data-driven part of the method provides a sequence of remaining useful life estimates by repeated projection of the parameter degradation into the future based on the use of values in a sliding time window. Existing software can be used to determine the best fitting function and can account for its random parameters. The continuous parameter estimation and their projection into the future can be performed in parallel for multiple isolated simultaneous parametric faults on a multicore, multiprocessor computer.
The proposed hybrid bond graph model-based, data-driven method is verified by an offline simulation case study of a typical power electronic circuit. It can be used to implement embedded systems that enable cooperating machines in smart manufacturing to perform prognostic themselves.
Analytical redundancy relations are fundamental in model-based fault detection and isolation. Their numerical evaluation yields a residual that may serve as a fault indicator. Considering switching linear time-invariant system models that use ideal switches, it is shown that analytical redundancy relations can be systematically deduced from a diagnostic bond graph with fixed causalities that hold for all modes of operation. Moreover, as to a faultless system, the presented bond graph–based approach enables to deduce a unique implicit state equation with coefficients that are functions of the discrete switch states. Devices or phenomena with fast state transitions, for example, electronic diodes and transistors, clutches, or hard mechanical stops are often represented by ideal switches which give rise to variable causalities. However, in the presented approach, fixed causalities are assigned only once to a diagnostic bond graph. That is, causal strokes at switch ports in the diagnostic bond graph reflect only the switch-state configuration in a specific system mode. The actual discrete switch states are implicitly taken into account by the discrete values of the switch moduli. The presented approach starts from a diagnostic bond graph with fixed causalities and from a partitioning of the bond graph junction structure and systematically deduces a set of equations that determines the wanted residuals. Elimination steps result in analytical redundancy relations in which the states of the storage elements and the outputs of the ideal switches are unknowns. For the later two unknowns, the approach produces an implicit differential algebraic equations system. For illustration of the general matrix-based approach, an electromechanical system and two small electronic circuits are considered. Their equations are directly derived from a diagnostic bond graph by following causal paths and are reformulated so that they conform with the matrix equations obtained by the formal approach based on a partitioning of the bond graph junction structure. For one of the three mode-switching examples, a fault scenario has been simulated.
Bond graph software can simulate bond graph models without the user needing to manually derive equations. This offers the power to model larger and more complex systems than in the past. Multibond graphs (those with vector bonds) offer a compact model which further eases handling multibody systems. Although multibond graphs can be simulated successfully, the use of vector bonds can present difficulties. In addition, most qualitative, bond graph–based exploitation relies on the use of scalar bonds. This article discusses the main methods for simulating bond graphs of multibody systems, using a graphical software platform. The transformation between models with vector and scalar bonds is presented. The methods are then compared with respect to both time and accuracy, through simulation of two benchmark models. This article is a tutorial on the existing methods for simulating three-dimensional rigid and holonomic multibody systems using bond graphs and discusses the difficulties encountered. It then proposes and adapts methods for simulating this type of system directly from its bond graph within a software package. The value of this study is in giving practical guidance to modellers, so that they can implement the adapted method in software.
Here, we present a miR mechanism which is active in the nucleus and is essential for the production of intron included, C-terminal truncated and biologically active proteins, like e.g. Vim3. We exemplified this mechanism by miRs, miR-15a and miR-498, which are overexpressed in clear cell renal carcinoma or oncocytoma. Both miRs directly interact with DNA in an intronic region, leading to transcriptional stop, and therefore repress the full length version of the pre-mRNA, resulting in intron included truncated proteins (Mxi-2 and Vim3). A computational survey shows that this miR:DNA interactions mechanism may be generally involved in regulating the human transcriptome, with putative interaction sites in intronic regions for over 1000 genes. In this work, an entirely new mechanism is revealed how miRs can repress full length protein translation, resulting in C-terminal truncated proteins.
Increased endothelin-1 decreases PKC alpha (PKCα), resulting in high miRNA 15a levels in kidney tumors. Breast cancer cells treated with ET-1, β-estrogen, Tamoxifen, Tamoxifen + β-estrogen and Tamoxifen + ET-1 were analysed regarding miRNA 15a expression. Significantly increased miRNA 15a levels were found after ET-1, becoming further increased in Tamoxifen + ET-1 treated cells. Our group already showed that miRNA 15a induces MAPK p38 splicing resulting in a truncated product called Mxi-2, whose function has yet to be defined in tumors. We described for the first time in ET-1 induced tumor cells that Mxi-2 builds a complex with Ago2, a miRNA binding protein, which is important for the localization of miRNAs to the 3′UTR of target genes. Furthermore, we show that Mxi-2/Ago2 is important for the interaction with the miRNA 1285 which binds to the 3′end of the tumor suppressor gene p53, being responsible for the downregulation of p53. Tissue arrays from breast cancer patients were performed, analysing Mxi-2, p53 and PKCα. Since the Mxi-2 levels increase in Tamoxifen + ET-1 treated cells, we claim that increasing ET-1 levels in Tamoxifen treated breast cancer patients are responsible for decreasing p53 levels. In summary, ET-1 decreases nuclear PKCα levels, while increasing the amount of miRNA 15a. This causes high levels of Mxi-2, necessary for complex formation with Ago2. The newly identified Mxi-2/Ago2 complex interacting with miRNA 1285 leads to increased 3′UTR p53 interaction, resulting in decreased p53 levels and subsequent tumor progression. This newly identified mechanism is a possible explanation for the development of ET-1 induced tumors.
Die Motive für die Einführung von Public Cloud Services liegen oft im Bereich der Kosteneinsparung und Qualitätsverbesserung. Vielfach werden bei der erstmaligen Einführung vermeidbare Fehler gemacht, die im Nachhinein den Erfolg des Vorhabens schmälern. Der Beitrag beschreibt ein aus Sicht der Beratungspraxis bewährtes Vorgehensmodell für die Einführung und Nutzung von Public Cloud Services unter besonderer Berücksichtigung von Microsoft Cloud Services.
This work presents an open source database with suitable retention parameters for prediction and simulation of GC separations and gives a short introduction to three common retention models. Useful computer simulations play an important role to save resources and time in method development in GC. Thermodynamic retention parameters for the ABC model and the K-centric model are determined by isothermal measurements. This standardized procedure of measurements and calculations, presented in this work, have a useful benefit for all chromatographers, analytical chemists, and method developers because it can be used in their own laboratories to simplify the method development. The main benefits as simulations of temperature-programed GC separations are demonstrated and compared to measurements. The observed deviations of predicted retention times are in most cases less than 1%. The database includes more than 900 entries with a large range of compounds such as VOCs, PAHs, FAMEs, PCBs, or allergenic fragrances over 20 different GC columns.
In der heutigen Zeit nimmt die Bedeutung schlanker und effektiver Prozesse in Unternehmen vor dem Hintergrund des Wettbewerbs sowie Kostendrucks stetig zu. Um dieser Herausforderung entgegenzuwirken, fokussieren sich Unternehmen auf die Identifikation neuer innovativer Potenziale. Aufgrund der Tatsache, dass monotone und regelbasierte Prozesse durch Softwareroboter automatisiert werden können, ist das Interesse an Robotic Process Automation (RPA) in den letzten Jahren stetig gestiegen. Bevor sich Unternehmen allerdings für oder gegen den Einsatz von RPA entscheiden, ist es zunächst notwendig, dass die Entscheidungsträger ein Verständnis von RPA erlangen sowie die entsprechenden Einsatzpotenziale und Risiken einschätzen können. Dieser Artikel trägt diesem Bedürfnis Rechnung, indem es diese auf Basis einer Literaturrecherche ermittelt und bewertet. Im Ausblick wird das zukünftige Potenzial von RPA eingeschätzt.
Hydrophilic surface-enhanced Raman spectroscopy (SERS) substrates were prepared by a combination of TiO2-coatings of aluminium plates through a direct titanium tetraisopropoxide (TTIP) coating and drop coated by synthesised gold nanoparticles (AuNPs). Differences between the wettability of the untreated substrates, the slowly dried Ti(OH)4 substrates and calcinated as well as plasma treated TiO2 substrates were analysed by water contact angle (WCA) measurements. The hydrophilic behaviour of the developed substrates helped to improve the distribution of the AuNPs, which reflects in overall higher lateral SERS enhancement. Surface enhancement of the substrates was tested with target molecule rhodamine 6G (R6G) and a fibre-coupled 638 nm Raman spectrometer. Additionally, the morphology of the substrates was characterised using scanning electron microscopy (SEM) and Raman microscopy. The studies showed a reduced influence of the coffee ring effect on the particle distribution, resulting in a more broadly distributed edge region, which increased the spatial reproducibility of the measured SERS signal in the surface-enhanced Raman mapping measurements on mm scale.
Surface-enhanced Raman spectroscopy (SERS) with subsequent chemometric evaluation was performed for the rapid and non-destructive differentiation of seven important meat-associated microorganisms, namely Brochothrix thermosphacta DSM 20171, Pseudomonas fluorescens DSM 4358, Salmonella enterica subsp. enterica sv. Enteritidis DSM 14221, Listeria monocytogenes DSM 19094, Micrococcus luteus DSM 20030, Escherichia coli HB101 and Bacillus thuringiensis sv. israelensis DSM 5724. A simple method for collecting spectra from commercial paper-based SERS substrates without any laborious pre-treatments was used. In order to prepare the spectroscopic data for classification at genera level with a subsequent chemometric evaluation consisting of principal component analysis and discriminant analysis, a pre-processing method with spike correction and sum normalisation was performed. Because of the spike correction rather than exclusion, and therefore the use of a balanced data set, the multivariate analysis of the data is significantly resilient and meaningful. The analysis showed that the differentiation of meat-associated microorganisms and thereby the detection of important meat-related pathogenic bacteria was successful on genera level and a cross-validation as well as a classification of ungrouped data showed promising results, with 99.5 % and 97.5 %, respectively.
The molecular weight properties of lignins are one of the key elements that need to be analyzed for a successful industrial application of these promising biopolymers. In this study, the use of 1H NMR as well as diffusion-ordered spectroscopy (DOSY NMR), combined with multivariate regression methods, was investigated for the determination of the molecular weight (Mw and Mn) and the polydispersity of organosolv lignins (n = 53, Miscanthus x giganteus, Paulownia tomentosa, and Silphium perfoliatum). The suitability of the models was demonstrated by cross validation (CV) as well as by an independent validation set of samples from different biomass origins (beech wood and wheat straw). CV errors of ca. 7–9 and 14–16% were achieved for all parameters with the models from the 1H NMR spectra and the DOSY NMR data, respectively. The prediction errors for the validation samples were in a similar range for the partial least squares model from the 1H NMR data and for a multiple linear regression using the DOSY NMR data. The results indicate the usefulness of NMR measurements combined with multivariate regression methods as a potential alternative to more time-consuming methods such as gel permeation chromatography.
Neutral buoyancy has been used as an analog for microgravity from the earliest days of human spaceflight. Compared to other options on Earth, neutral buoyancy is relatively inexpensive and presents little danger to astronauts while simulating some aspects of microgravity. Neutral buoyancy removes somatosensory cues to the direction of gravity but leaves vestibular cues intact. Removal of both somatosensory and direction of gravity cues while floating in microgravity or using virtual reality to establish conflicts between them has been shown to affect the perception of distance traveled in response to visual motion (vection) and the perception of distance. Does removal of somatosensory cues alone by neutral buoyancy similarly impact these perceptions? During neutral buoyancy we found no significant difference in either perceived distance traveled nor perceived size relative to Earth-normal conditions. This contrasts with differences in linear vection reported between short- and long-duration microgravity and Earth-normal conditions. These results indicate that neutral buoyancy is not an effective analog for microgravity for these perceptual effects.
An internal model of self-motion provides a fundamental basis for action in our daily lives, yet little is known about its development. The ability to control self-motion develops in youth and often deteriorates with advanced age. Self-motion generates relative motion between the viewer and the environment. Thus, the smoothness of the visual motion created will vary as control improves. Here, we study the influence of the smoothness of visually simulated self-motion on an observer's ability to judge how far they have travelled over a wide range of ages. Previous studies were typically highly controlled and concentrated on university students. But are such populations representative of the general public? And are there developmental and sex effects? Here, estimates of distance travelled (visual odometry) during visually induced self-motion were obtained from 466 participants drawn from visitors to a public science museum. Participants were presented with visual motion that simulated forward linear self-motion through a field of lollipops using a head-mounted virtual reality display. They judged the distance of their simulated motion by indicating when they had reached the position of a previously presented target. The simulated visual motion was presented with or without horizontal or vertical sinusoidal jitter. Participants' responses indicated that they felt they travelled further in the presence of vertical jitter. The effectiveness of the display increased with age over all jitter conditions. The estimated time for participants to feel that they had started to move also increased slightly with age. There were no differences between the sexes. These results suggest that age should be taken into account when generating motion in a virtual reality environment. Citizen science studies like this can provide a unique and valuable insight into perceptual processes in a truly representative sample of people.
Multiwalled carbon nanotubes (MWCNTs) were easily and efficiently functionalised with highly cross-linked polyamines. The radical polymerisation of two bis-vinylimidazolium salts in the presence of pristine MWCNTs and azobisisobutyronitrile (AIBN) as a radical initiator led to the formation of materials with a high functionalisation degree. The subsequent treatment with sodium borohydride gave rise to the reduction of imidazolium moieties with the concomitant formation of secondary and tertiary amino groups. The obtained materials were characterised by thermogravimetric analysis (TGA), elemental analysis, solid state 13C-NMR, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), potentiometric titration, and temperature programmed desorption of carbon dioxide (CO2-TPD). One of the prepared materials was tested as a heterogeneous base catalyst in C–C bond forming reactions such as the Knoevenagel condensation and Henry reaction. Furthermore, two examples concerning a sequential one-pot approach involving two consecutive reactions, namely Knoevenagel and Michael reactions, were reported.
Ghana suffers from frequent power outages, which can be compensated by off-grid energy solutions. Photovoltaic-hybrid systems become more and more important for rural electrification due to their potential to offer a clean and cost-effective energy supply. However, uncertainties related to the prediction of electrical loads and solar irradiance result in inefficient system control and can lead to an unstable electricity supply, which is vital for the high reliability required for applications within the health sector. Model predictive control (MPC) algorithms present a viable option to tackle those uncertainties compared to rule-based methods, but strongly rely on the quality of the forecasts. This study tests and evaluates (a) a seasonal autoregressive integrated moving average (SARIMA) algorithm, (b) an incremental linear regression (ILR) algorithm, (c) a long short-term memory (LSTM) model, and (d) a customized statistical approach for electrical load forecasting on real load data of a Ghanaian health facility, considering initially limited knowledge of load and pattern changes through the implementation of incremental learning. The correlation of the electrical load with exogenous variables was determined to map out possible enhancements within the algorithms. Results show that all algorithms show high accuracies with a median normalized root mean square error (nRMSE) <0.1 and differing robustness towards load-shifting events, gradients, and noise. While the SARIMA algorithm and the linear regression model show extreme error outliers of nRMSE >1, methods via the LSTM model and the customized statistical approaches perform better with a median nRMSE of 0.061 and stable error distribution with a maximum nRMSE of <0.255. The conclusion of this study is a favoring towards the LSTM model and the statistical approach, with regard to MPC applications within photovoltaic-hybrid system solutions in the Ghanaian health sector.
This work proposes a novel approach for probabilistic end-to-end all-sky imager-based nowcasting with horizons of up to 30 min using an ImageNet pre-trained deep neural network. The method involves a two-stage approach. First, a backbone model is trained to estimate the irradiance from all-sky imager (ASI) images. The model is then extended and retrained on image and parameter sequences for forecasting. An open access data set is used for training and evaluation. We investigated the impact of simultaneously considering global horizontal (GHI), direct normal (DNI), and diffuse horizontal irradiance (DHI) on training time and forecast performance as well as the effect of adding parameters describing the irradiance variability proposed in the literature. The backbone model estimates current GHI with an RMSE and MAE of 58.06 and 29.33 W m−2, respectively. When extended for forecasting, the model achieves an overall positive skill score reaching 18.6 % compared to a smart persistence forecast. Minor modifications to the deterministic backbone and forecasting models enables the architecture to output an asymmetrical probability distribution and reduces training time while leading to similar errors for the backbone models. Investigating the impact of variability parameters shows that they reduce training time but have no significant impact on the GHI forecasting performance for both deterministic and probabilistic forecasting while simultaneously forecasting GHI, DNI, and DHI reduces the forecast performance.
A firm link between endoplasmic reticulum (ER) stress and tumors has been wildly reported. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α), an ER-resident thiol oxidoreductase, is confirmed to be highly upregulated in various cancer types and associated with a significantly worse prognosis. Of importance, under ER stress, the functional interplay of ERO1α/PDI axis plays a pivotal role to orchestrate proper protein folding and other key processes. Multiple lines of evidence propose ERO1α as an attractive potential target for cancer treatment. However, the unavailability of specific inhibitor for ERO1α, its molecular inter-relatedness with closely related paralog ERO1β and the tightly regulated processes with other members of flavoenzyme family of enzymes, raises several concerns about its clinical translation. Herein, we have provided a detailed description of ERO1α in human cancers and its vulnerability towards the aforementioned concerns. Besides, we have discussed a few key considerations that may improve our understanding about ERO1α in tumors.
The white ground crater by the Phiale Painter (450–440 BC) exhibited in the “Pietro Griffo” Archaeological Museum in Agrigento (Italy) depicts two scenes from Perseus myth. The vase is of utmost importance to archaeologists because the figures are drawn on a white background with remarkable daintiness and attention to detail. Notwithstanding the white ground ceramics being well documented from an archaeological and historical point of view, doubts concerning the compositions of pigments and binders and the production technique are still unsolved. This kind of vase is a valuable rarity, the use of which is documented in elitist funeral rituals. The study aims to investigate the constituent materials and the execution technique of this magnificent crater. The investigation was carried out using non-destructive and non-invasive techniques in situ. Portable X-ray fluorescence and Fourier-transform total reflection infrared spectroscopy complemented the use of visible and ultraviolet light photography to get an overview and specific information on the vase. The XRF data were used to produce false colour maps showing the location of the various elements detected, using the program SmART_scan. The use of gypsum as the material for the white ground is an important result that deserves to be further investigated in similar vases.
Novel methods for contingency analysis of gas transport networks are presented. They are motivated by the transition of our energy system where hydrogen plays a growing role. The novel methods are based on a specific method for topological reduction and so-called supernodes. Stationary Euler equations with advanced compressor thermodynamics and a gas law allowing for gas compositions with up to 100% hydrogen are used. Several measures and plots support an intuitive comparison and analysis of the results. In particular, it is shown that the newly developed methods can estimate locations and magnitudes of additional capacities (injection, buffering, storage etc.) with a reasonable performance for networks of relevant composition and size.
PURPOSE
Cervical cancer (CC) is caused by a persistent high-risk human papillomavirus (hrHPV) infection. The cervico-vaginal microbiome may influence the development of (pre)cancer lesions. Aim of the study was (i) to evaluate the new CC screening program in Germany for the detection of high-grade CC precursor lesions, and (ii) to elucidate the role of the cervico-vaginal microbiome and its potential impact on cervical dysplasia.
METHODS
The microbiome of 310 patients referred to colposcopy was determined by amplicon sequencing and correlated with clinicopathological parameters.
RESULTS
Most patients were referred for colposcopy due to a positive hrHPV result in two consecutive years combined with a normal PAP smear. In 2.1% of these cases, a CIN III lesion was detected. There was a significant positive association between the PAP stage and Lactobacillus vaginalis colonization and between the severity of CC precursor lesions and Ureaplasma parvum.
CONCLUSION
In our cohort, the new cervical cancer screening program resulted in a low rate of additional CIN III detected. It is questionable whether these cases were only identified earlier with additional HPV testing before the appearance of cytological abnormalities, or the new screening program will truly increase the detection rate of CIN III in the long run. Colonization with U. parvum was associated with histological dysplastic lesions. Whether targeted therapy of this pathogen or optimization of the microbiome prevents dysplasia remains speculative.
It has become increasingly clear that caspases, far from being merely cell death effectors, have a much wider range of functions within the cell. These functions are as diverse as signal transduction and cytoskeletal remodeling, and caspases are now known to have an essential role in cell proliferation, migration, and differentiation. There is also evidence that apoptotic cells themselves can direct the behavior of nearby cells through the caspase-dependent secretion of paracrine signaling factors. In some processes, including the differentiation of skeletal muscle myoblasts, both caspase activation in differentiating cells as well as signaling from apoptotic cells has been reported. Here, we review the non-apoptotic outcomes of caspase activity in a range of different model systems and attempt to integrate this knowledge.
Climate change is transforming the risks individuals and households face, with potentially profound socioeconomic consequences such as increased poverty, inequality, and social instability. Social protection is a policy tool that governments use to help individuals and households manage risks linked to income and livelihoods, and to achieve societal outcomes such as reducing poverty and inequality. Despite its potential as a policy response to climate change, the integration of social protection within the climate policy agenda is currently limited. While the concept of risk is key to both sectors, different understandings of the nature and scope of climate change impacts and their implications, as well as of the adequacy of social protection instruments to address them, contribute to the lack of policy and practice integration.
Our goal is to bridge this cognitive gap by highlighting the potential of social protection as a policy response to climate change. Using a comprehensive climate risk lens, we first explore how climate change drives risks that are within the realm of social protection, and their implications, including likely future trends in demand for social protection. Based on this analysis, we critically review existing arguments for what social protection can do and evidence of what it currently does to manage risks arising from climate change. From the analysis, a set of reconceptualised roles emerge for social protection to strategically contribute to climate-resilient development.
The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model. Using these model systems, various targets for potential pharmaceutical treatments have been identified and many treatments have been shown to be efficient in preclinical studies. However, all attempts to turn these findings into a therapy for patients have failed thus far. In this review, I will discuss underlying difficulties and address potential alternatives for our future research.
Intact Transition Epitope Mapping - Targeted High-Energy Rupture of Extracted Epitopes (ITEM-THREE)
(2019)
Epitope mapping, which is the identification of antigenic determinants, is essential for the design of novel antibody-based therapeutics and diagnostic tools. ITEM-THREE is a mass spectrometry-based epitope mapping method that can identify epitopes on antigens upon generating an immune complex in electrospray-compatible solutions by adding an antibody of interest to a mixture of peptides from which at least one holds the antibody's epitope. This mixture is nano-electrosprayed without purification. Identification of the epitope peptide is performed within a mass spectrometer that provides an ion mobility cell sandwiched in-between two collision cells and where this ion manipulation setup is flanked by a quadrupole mass analyzer on one side and a time-of-flight mass analyzer on the other side. In a stepwise fashion, immune-complex ions are separated from unbound peptide ions and dissociated to release epitope peptide ions. Immune complex-released peptide ions are separated from antibody ions and fragmented by collision induced dissociation. Epitope-containing peptide fragment ions are recorded, and mass lists are submitted to unsupervised data base search thereby retrieving both, the amino acid sequence of the epitope peptide and the originating antigen. ITEM-THREE was developed with antiTRIM21 and antiRA33 antibodies for which the epitopes were known, subjecting them to mixtures of synthetic peptides of which one contained the respective epitope. ITEM-THREE was then successfully tested with an enzymatic digest of His-tagged recombinant human β-actin and an antiHis-tag antibody, as well as with an enzymatic digest of recombinant human TNFα and an antiTNFα antibody whose epitope was previously unknown.
Introduction: Recovery experiences have thus far been portrayed as experiences that simply “happen” to people. However, recovery can also be understood from a crafting perspective; that is, individuals may proactively shape their work and non-work activities to recover from stress, satisfy their psychological needs, and achieve optimal functioning.
Materials and Methods: In my talk, I will present the theoretical basis of needs-based crafting based on a conceptual review of the literature. Moreover, I will present empirical findings on the validation of a newly developed off-job crafting scale.
Results: In five sub studies, we found that off-job crafting was related to optimal functioning over time. Moreover, the newly developed off-job crafting scale had good convergent and discriminant validity, internal consistency, and test-retest reliability.
Conclusions: Theoretical and empirical evidence suggests that needs-based crafting can enhance optimal functioning in different life domains and support people in performing their work duties sustainably. Proactive attempts to achieve better recovery through needs satisfaction may be beneficial in an intensified and continually changing and challenging working life. Our line of research provides important avenues for organizational research and practices regarding recovery and needs satisfaction occurring at work and outside work.
Unlimited paid time off policies are currently fashionable and widely discussed by HR professionals around the globe. While on the one hand, paid time off is considered a key benefit by employees and unlimited paid time off policies (UPTO) are seen as a major perk which may help in recruiting and retaining talented employees, on the other hand, early adopters reported that employees took less time off than previously, presumably leading to higher burnout rates. In this conceptual review, we discuss the theoretical and empirical evidence regarding the potential effects of UPTO on leave utilization, well-being and performance outcomes. We start out by defining UPTO and placing it in a historical and international perspective. Next, we discuss the key role of leave utilization in translating UPTO into concrete actions. The core of our article constitutes the description of the effects of UPTO and the two pathways through which these effects are assumed to unfold: autonomy need satisfaction and detrimental social processes. We moreover discuss the boundary conditions which facilitate or inhibit the successful utilization of UPTO on individual, team, and organizational level. In reviewing the literature from different fields and integrating existing theories, we arrive at a conceptual model and five propositions, which can guide future research on UPTO. We conclude with a discussion of the theoretical and societal implications of UPTO.
An Universitäten und Fachhochschulen ist die Mathematik-Ausbildung eines der Nadelöhre für angehende Ingenieurinnen und Ingenieure. Viele Studierende der Ingenieurwissenschaften scheitern in den ersten Studiensemestern an den Anforderungen der Mathematik. Lehrende, Fach- und Hochschuldidaktiker/innen und zunehmend auch Fachvertretungen und Verbände stellen sich die Frage, was an den Fakultäten und Fachbereichen getan werden kann, damit Studierende ihre mathematischen Fähigkeiten vergrößern und den anspruchsvollen Studienweg zur Ingenieurin oder zum Ingenieur meistern können.
Die Implementierung strategischer Erfolgsfaktoren rückt zunehmend in den Fokus kleiner und mittelständischer Unternehmen. Vor dem Hintergrund des überdurchschnittlichen Erfolgs sogenannter Hidden Champions (HC) stellt sich unter einer praxisorientierten Perspektive die Frage, welche Bedeutung mittelständische Unternehmen grundsätzlich den von Hermann Simon identifizierten Erfolgsprinzipien für HC für den Unternehmenserfolg zumessen. Die empirische Studie analysierte dazu die Bedeutung dieser Erfolgsfaktoren für mittelständische Unternehmen und untersuchte, ob Bedeutungsunterschiede zwischen erfolgreichen und weniger erfolgreichen Unternehmen der Stichprobe existieren. Im Rahmen einer explorativen, multivariaten Datenanalyse konnten außerdem zwei Cluster, die „Internationalen Innovatoren“ und die „Nationalen Traditionalisten“, im Datensatz identifiziert werden, die sich hinreichend in der Bedeutungszumessung der Erfolgsfaktoren voneinander unterschieden.
The digitization of financial activities in consumers' lives is increasing, and the digitalization of invoicing processes is expected to play a significant role, although this area is not well understood regarding the private sector. Human-Computer Interaction (HCI) and Computer Supported Cooperative Work (CSCW) research have a long history of analyzing the socio-material and temporal aspects of work practices that are relevant for the domestic domain. The socio-material structuring of invoicing work and the working styles of consumers must be considered when designing effective consumer support systems. In this ethnomethodologically-informed, design-oriented interview study, we followed 17 consumers in their daily practices of dealing with invoices to make the invisible administrative work involved in this process visible. We identified and described the meaningful artifacts that were used in a spatial-temporal process within various storage locations such as input, reminding, intermediate (for postponing cases) buffers, and archive systems. Furthermore, we identified three different working styles that consumers exhibited: direct completion, at the next opportunity, and postpone as far as possible. This study contributes to our understanding of household economics and domestic workplace studies in the tradition of CSCW and has implications for the design of electronic invoicing systems.
This study investigated the application potential of Black Soldier Fly Larva Hermetia illucens Stratiomyidae: Diptera (L.1758) for wastewater treatment and the removal potential of chemical oxygen demand, ammonia, and phosphorus of and liquid manure residue and municipal waste water containing 1% solids content. Black Soldier Fly Larva were found to reduce the concentration of chemical oxygen demand, but unfortunately, increase the concentration of ammonia and phosphorus. The ability of Black Soldier Fly Larva to feed on organic waste of Liquid manure residue showed that Black Soldier Fly Larva increase their weight by 365% in a solution with 12% solids content and by 595% in a solution having 6% solids content. The study also showed that Black Soldier Fly Larva have the ability to survive in a solution of 1% solids content and have the ability to reduce chemical oxygen demand by up to 86.4% for liquid manure residue and 46.9% for municipal wastewater after 24 hours. Generally, ammonia increased by 43.9% for Liquid manure residue and 98.6% for municipal wastewater. Total phosphorus showed an increase of 11.0% and 88.6% increase for liquid manure residue and municipal wastewater respectively over the 8-day study. Transparent environments tend to reduce the COD content more than the dark environment, both for the liquid manure residue (55.8% and 65.4%) and municipal wastewater (71.5% and 66.4%).
In this paper, a gas-to-power (GtoP) system for power outages is digitally modeled and experimentally developed. The design includes a solid-state hydrogen storage system composed of TiFeMn as a hydride forming alloy (6.7 kg of alloy in five tanks) and an air-cooled fuel cell (maximum power: 1.6 kW). The hydrogen storage system is charged under room temperature and 40 bar of hydrogen pressure, reaching about 110 g of hydrogen capacity. In an emergency use case of the system, hydrogen is supplied to the fuel cell, and the waste heat coming from the exhaust air of the fuel cell is used for the endothermic dehydrogenation reaction of the metal hydride. This GtoP system demonstrates fast, stable, and reliable responses, providing from 149 W to 596 W under different constant as well as dynamic conditions. A comprehensive and novel simulation approach based on a network model is also applied. The developed model is validated under static and dynamic power load scenarios, demonstrating excellent agreement with the experimental results.
Jet engines of airplanes are designed such that in some components damage occurs and accumulates in service without being critical up to a certain level of damage. Since maintenance, repair, and component exchange are very cost-intensive, it is necessary to predict efficiently the component lifetime with high accuracy. A former developed lifetime model, based on interpolated results of aerodynamic and structural mechanics simulations, uses material parameters estimated from literature values of standard creep experiments. For improved accuracy, an experimental procedure is developed for the characterization of the short-time creep behavior, which is relevant for the operation of turbine blades of jet engines. To consider microstructural influences resulting from the manufacturing of thin-walled single crystal turbine blades, small-scale specimens from used turbine blades are extracted and tested in short- and medium-time creep experiments. Based on experimental results and literature values, a creep model, which describes the fracture behavior for a wide range of creep loads, is calibrated and is now used for the lifetime prediction of turbine blades under real loading conditions.
Interne Audits können mehr
(2024)
Dieser Beitrag zeigt, wie das Deutsche Zentrum für Luft- und Raumfahrt e. V. (DLR) Zufriedenheitsanalysen aus zwei Sichtweisen durchführt: Aus Sicht der Auditoren und aus Sicht der Managementbeauftragten der auditierten Institute und Einrichtungen. Die Ergebnisse fließen in die jährliche Auditprogrammplanung ein. Damit wird der Nutzen von internen Audits gesteigert.
A Method for the Sustainable Documentation of Operations Processes in Parcel Distribution Centers
(2018)
There is often no common understanding on operational processes in logistics companies as they are not properly documented. Hence, people execute the same process differently and training is conducted by experienced operators on an ad-hoc basis. Furthermore, continuous process improvement is hampered as neither the ideal process nor current issues in as-is processes are visible. A major reason for the missing documentation is the complexity of existing business process modelling languages. Modelling experts are required for initially describing the processes and also for updating the models after process changes. Furthermore, operations people are usually not used to read complex process models in EPCs or BPMN diagrams. In order to overcome these limitations, a domain-specific modelling language which facilitates maintaining up-to-date process models has been designed with a large logistics company in Germany. The paper at hand briefly describes this language and illustrates the method on how to apply it in operations environments.
Contextual information is widely considered for NLP and knowledge discovery in life sciences since it highly influences the exact meaning of natural language. The scientific challenge is not only to extract such context data, but also to store this data for further query and discovery approaches. Classical approaches use RDF triple stores, which have serious limitations. Here, we propose a multiple step knowledge graph approach using labeled property graphs based on polyglot persistence systems to utilize context data for context mining, graph queries, knowledge discovery and extraction. We introduce the graph-theoretic foundation for a general context concept within semantic networks and show a proof of concept based on biomedical literature and text mining. Our test system contains a knowledge graph derived from the entirety of PubMed and SCAIView data and is enriched with text mining data and domain-specific language data using Biological Expression Language. Here, context is a more general concept than annotations. This dense graph has more than 71M nodes and 850M relationships. We discuss the impact of this novel approach with 27 real-world use cases represented by graph queries. Storing and querying a giant knowledge graph as a labeled property graph is still a technological challenge. Here, we demonstrate how our data model is able to support the understanding and interpretation of biomedical data. We present several real-world use cases that utilize our massive, generated knowledge graph derived from PubMed data and enriched with additional contextual data. Finally, we show a working example in context of biologically relevant information using SCAIView.
Comparación de perfiles de ansiedad matemática entre estudiantes mexicanos y estudiantes alemanes
(2017)
Se determinan los perfiles de ansiedad matemática de estudiantes mexicanos y estudiantes alemanes por medio de la aplicación de un cuestionario desarrollado ex profeso. La ansiedad matemática se define en términos de tres descriptores: creencias, actitudes y emociones. Los autores definen un Índice de Ansiedad Matemática, al aplicarlo encuentran que los estudiantes alemanes presentan un valor mayor de dicho Índice, lo que significa que tienen una mayor nivel de ansiedad matemática. Las diferencias en los valores del Índice de Ansiedad Matemática se interpretan en términos de diferencias culturales. La interpretación parece ser consistente con las diferencias culturales y se ajusta a los resultados obtenidos.
Purpose To investigate how completing vocational re-training influenced income and employment days of working-age people with disabilities in the first 8 years after program admission. The investigation also included the influence of vocational re-training on the likelihood of receiving an earnings incapacity pension and on social security benefit receipt. Methods This retrospective cohort study with 8 years follow up was based on data from 2399 individuals who had completed either a 1-year vocational re-training program (n = 278), or a 2-year vocational re-training program (n = 1754) or who were admitted into re-training but never completed the program (n = 367). A propensity score-based method was used to account for observed differences and establish comparability between program graduates and program dropouts. Changes in outcomes were examined using the inverse probability-weighted regression adjustment method. Results After controlling for other factors, over the 8 years after program admission, graduates of 1-year re-training, on average, were employed for an additional 405 days, 95% CI [249 days, 561 days], and had earned €24,260 more than without completed re-training, 95% CI [€12,805, €35,715]. Two-year program completers, on average, were employed for 441 additional days, 95% CI [349 days, 534 days], and had earned €35,972 more than without completed re-training, 95% CI [€27,743, €44,202]. The programs also significantly reduced the number of days on social-security and unemployment benefits and lowered the likelihood of an earnings incapacity pension. Conclusion Policies to promote the labor market re-integration of persons with disabilities should consider that vocational re-training may be an effective tool for sustainably improving work participation outcomes.
A Fourier scatterometry setup is evaluated to recover the key parameters of optical phase gratings. Based on these parameters, systematic errors in the printing process of two-photon polymerization (TPP) gray-scale lithography three-dimensional printers can be compensated, namely tilt and curvature deviations. The proposed setup is significantly cheaper than a confocal microscope, which is usually used to determine calibration parameters for compensation of the TPP printing process. The grating parameters recovered this way are compared to those obtained with a confocal microscope. A clear correlation between confocal and scatterometric measurements is first shown for structures containing either tilt or curvature. The correlation is also shown for structures containing a mixture of tilt and curvature errors (squared Pearson coefficient r2 = 0.92). This compensation method is demonstrated on a TPP printer: a diffractive optical element printed with correction parameters obtained from Fourier scatterometry shows a significant reduction in noise as compared to the uncompensated system. This verifies the successful reduction of tilt and curvature errors. Further improvements of the method are proposed, which may enable the measurements to become more precise than confocal measurements in the future, since scatterometry is not affected by the diffraction limit.
Trust your guts: fostering embodied knowledge and sustainable practices through voice interaction
(2023)
Despite various attempts to prevent food waste and motivate conscious food handling, household members find it difficult to correctly assess the edibility of food. With the rise of ambient voice assistants, we did a design case study to support households’ in situ decision-making process in collaboration with our voice agent prototype, Fischer Fritz. Therefore, we conducted 15 contextual inquiries to understand food practices at home. Furthermore, we interviewed six fish experts to inform the design of our voice agent on how to guide consumers and teach food literacy. Finally, we created a prototype and discussed with 15 consumers its impact and capability to convey embodied knowledge to the human that is engaged as sensor. Our design research goes beyond current Human-Food Interaction automation approaches by emphasizing the human-food relationship in technology design and demonstrating future complementary human-agent collaboration with the aim to increase humans’ competence to sense, think, and act.
Brentuximab vedotin (SGN-35) is an antibody–drug conjugate with a high selectivity against CD30+ cell lines and more than 300-fold less activity against antigen-negative cells. In the last years, the results of many in vitro and in vivo studies have led to the fast approval of this drug to treat lymphoma patients. Another innovative method to treat tumor cells including lymphoma cells is the use cytokine-induced killer (CIK) cells, which have also been approved and proven to be a safe treatment with only minor adverse events. In this study, a possible additive effect when combining SGN-35 with CIK cells was investigated. The combinational treatment showed that it reduces the viability of CD30+ cell lines significantly in vitro. Additionally, the amount of lymphoma cells was significantly reduced when exposed to CIK cells as well as when exposed to SGN-35. A significant negative effect of SGN-35 on the function of CIK cells could be excluded. These results lead to the assumption that SGN-35 and CIK cells in combination might achieve better results in an in vitro setting compared to the single use of SGN-35 and CIK cells. Further investigations in in vivo models must be conducted to obtain a better understanding of the exact mechanisms of both treatments when applied in combination.
The motor protein myosin drives a wide range of cellular and muscular functions by generating directed movement and force, fueled through adenosine triphosphate (ATP) hydrolysis. Release of the hydrolysis product adenosine diphosphate (ADP) is a fundamental and regulatory process during force production. However, details about the molecular mechanism accompanying ADP release are scarce due to the lack of representative structures. Here we solved a novel blebbistatin-bound myosin conformation with critical structural elements in positions between the myosin pre-power stroke and rigor states. ADP in this structure is repositioned towards the surface by the phosphate-sensing P-loop, and stabilized in a partially unbound conformation via a salt-bridge between Arg131 and Glu187. A 5 Å rotation separates the mechanical converter in this conformation from the rigor position. The crystallized myosin structure thus resembles a conformation towards the end of the two-step power stroke, associated with ADP release. Computationally reconstructing ADP release from myosin by means of molecular dynamics simulations further supported the existence of an equivalent conformation along the power stroke that shows the same major characteristics in the myosin motor domain as the resolved blebbistatin-bound myosin-II·ADP crystal structure, and identified a communication hub centered on Arg232 that mediates chemomechanical energy transduction.
Cyanobacteria are gaining considerable interest as a method of supporting the long-term presence of humans on the Moon and settlements on Mars due to their ability to produce oxygen and their potential as bio-factories for space biotechnology/synthetic biology and other applications. Since many unknowns remain in our knowledge to bridge the gap and move cyanobacterial bioprocesses from Earth to space, we investigated cell division resumption on the rehydration of dried Chroococcidiopsis sp. CCMEE 029 accumulated DNA damage while exposed to space vacuum, Mars-like conditions, and Fe-ion radiation. Upon rehydration, the monitoring of the ftsZ gene showed that cell division was arrested until DNA damage was repaired, which took 48 h under laboratory conditions. During the recovery, a progressive DNA repair lasting 48 h of rehydration was revealed by PCR-stop assay. This was followed by overexpression of the ftsZ gene, ranging from 7.5- to 9-fold compared to the non-hydrated samples. Knowing the time required for DNA repair and cell division resumption is mandatory for deep-space experiments that are designed to unravel the effects of reduced/microgravity on this process. It is also necessary to meet mission requirements for dried-sample implementation and real-time monitoring upon recovery. Future experiments as part of the lunar exploration mission Artemis and the lunar gateway station will undoubtedly help to move cyanobacterial bioprocesses beyond low Earth orbit. From an astrobiological perspective, these experiments will further our understanding of microbial responses to deep-space conditions.
While many proteins are known clients of heat shock protein 90 (Hsp90), it is unclear whether the transcription factor, thyroid hormone receptor beta (TRb), interacts with Hsp90 to control hormonal perception and signaling. Higher Hsp90 expression in mouse fibroblasts was elicited by the addition of triiodothyronine (T3). T3 bound to Hsp90 and enhanced adenosine triphosphate (ATP) binding of Hsp90 due to a specific binding site for T3, as identified by molecular docking experiments. The binding of TRb to Hsp90 was prevented by T3 or by the thyroid mimetic sobetirome. Purified recombinant TRb trapped Hsp90 from cell lysate or purified Hsp90 in pull-down experiments. The affinity of Hsp90 for TRb was 124 nM. Furthermore, T3 induced the release of bound TRb from Hsp90, which was shown by streptavidin-conjugated quantum dot (SAv-QD) masking assay. The data indicate that the T3 interaction with TRb and Hsp90 may be an amplifier of the cellular stress response by blocking Hsp90 activity.
Microarray-based experiments revealed that thyroid hormone triiodothyronine (T3) enhanced the binding of Cy5-labeled ATP on heat shock protein 90 (Hsp90). By molecular docking experiments with T3 on Hsp90, we identified a T3 binding site (TBS) near the ATP binding site on Hsp90. A synthetic peptide encoding HHHHHHRIKEIVKKHSQFIGYPITLFVEKE derived from the TBS on Hsp90 showed, in MST experiments, the binding of T3 at an EC50 of 50 μM. The binding motif can influence the activity of Hsp90 by hindering ATP accessibility or the release of ADP.
Green infrastructure improves environmental health in cities, benefits human health, and provides habitat for wildlife. Increasing urbanization has demanded the expansion of urban areas and transformation of existing cities. The adoption of compact design in urban planning is a recommended strategy to minimize environmental impacts; however, it may undermine green infrastructure networks within cities as it sets a battleground for urban space. Under this scenario, multifunctionality of green spaces is highly desirable but reconciling human needs and biodiversity conservation in a limited space is still a challenge. Through a systematic review, we first compiled urban green space's characteristics that affect mental health and urban wildlife support, and then identified potential synergies and trade-offs between these dimensions. A framework based on the One Health approach is proposed, synthesizing the interlinkages between green space quality, mental health, and wildlife support; providing a new holistic perspective on the topic. Looking at the human-wildlife-environment relationships simultaneously may contribute to practical guidance on more effective green space design and management that benefit all dimensions.
Green infrastructure has been widely recognized for the benefits to human health and biodiversity conservation. However, knowledge of the qualities and requirements of such spaces and structures for the effective delivery of the range of ecosystem services expected is still limited, as well as the identification of trade-offs between services. In this study, we apply the One Health approach in the context of green spaces to investigate how urban park characteristics affect human mental health and wildlife support outcomes and identify synergies and trade-offs between these dimensions. Here we show that perceived restorativeness of park users varies significantly across sites and is mainly affected by safety and naturalness perceptions. In turn, these perceptions are driven by objective indicators of quality, such as maintenance of facilities and vegetation structure, and subjective estimations of biodiversity levels. The presence of water bodies benefited both mental health and wildlife. However, high tree canopy coverage provided greater restoration potential whereas a certain level of habitat heterogeneity was important to support a wider range of bird species requirements. To reconcile human and wildlife needs in green spaces, cities should strategically implement a heterogeneous green infrastructure network that considers trade-offs and maximizes synergies between these dimensions.
This study contributes to the growing body of research concerning management consultancies by linking two previously disparate fields of study: (1) the examination of the effectiveness of consulting interventions and (2) the examination of the social processes that aim to create and legitimize the insights, knowledge and capabilities of management consultancies. We propose that consulting firms accumulate social authority in the course of pre-intervention discourse processes that is reflected in their reputation and celebrity. With respect to intervention, this social authority affects change recipients’ commitment to and compliance with the requirements of change implementation. We test the proposed relationships by conducting a measured variable path analysis of 117 change initiatives in German companies that were set up and implemented with the assistance of external consultancies. Our findings indicate that a consulting firm’s levels of both celebrity and reputation affect the change recipients’ commitment to proposed change strategies and thus, indirectly affect their behavioral compliance with the explicit requirements of change implementation.
Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re‐evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well‐informed decisions in the context of MMA and PA patient care.
The actomyosin system generates mechanical work with the execution of the power stroke, an ATP-driven, two-step rotational swing of the myosin-neck that occurs post ATP hydrolysis during the transition from weakly to strongly actin-bound myosin states concomitant with Pi release and prior to ADP dissociation. The activating role of actin on product release and force generation is well documented; however, the communication paths associated with weak-to-strong transitions are poorly characterized. With the aid of mutant analyses based on kinetic investigations and simulations, we identified the W-helix as an important hub coupling the structural changes of switch elements during ATP hydrolysis to temporally controlled interactions with actin that are passed to the central transducer and converter. Disturbing the W-helix/transducer pathway increased actin-activated ATP turnover and reduced motor performance as a consequence of prolonged duration of the strongly actin-attached states. Actin-triggered Pi release was accelerated, while ADP release considerably decelerated, both limiting maximum ATPase, thus transforming myosin-2 into a high-duty-ratio motor. This kinetic signature of the mutant allowed us to define the fractional occupancies of intermediate states during the ATPase cycle providing evidence that myosin populates a cleft-closure state of strong actin interaction during the weak-to-strong transition with bound hydrolysis products before accomplishing the power stroke.
Mebendazole Mediates Proteasomal Degradation of GLI Transcription Factors in Acute Myeloid Leukemia
(2021)
The prognosis of elderly AML patients is still poor due to chemotherapy resistance. The Hedgehog (HH) pathway is important for leukemic transformation because of aberrant activation of GLI transcription factors. MBZ is a well-tolerated anthelmintic that exhibits strong antitumor effects. Herein, we show that MBZ induced strong, dose-dependent anti-leukemic effects on AML cells, including the sensitization of AML cells to chemotherapy with cytarabine. MBZ strongly reduced intracellular protein levels of GLI1/GLI2 transcription factors. Consequently, MBZ reduced the GLI promoter activity as observed in luciferase-based reporter assays in AML cell lines. Further analysis revealed that MBZ mediates its anti-leukemic effects by promoting the proteasomal degradation of GLI transcription factors via inhibition of HSP70/90 chaperone activity. Extensive molecular dynamics simulations were performed on the MBZ-HSP90 complex, showing a stable binding interaction at the ATP binding site. Importantly, two patients with refractory AML were treated with MBZ in an off-label setting and MBZ effectively reduced the GLI signaling activity in a modified plasma inhibitory assay, resulting in a decrease in peripheral blood blast counts in one patient. Our data prove that MBZ is an effective GLI inhibitor that should be evaluated in combination to conventional chemotherapy in the clinical setting.
Argentina substantially contributes to the global organic agriculture and food sector due to its large areas of organically managed agricultural land. However, most of the organic production is intended for export. Overall, food supply for the domestic organic market is hardly tapped. Based on this, we investigate the current importance of organic agriculture and food production as well as consumption attitudes and behavior within the country. The novelty of the study also lies in the observation, documentation and analysis of latest stakeholder‐driven developments towards organic agriculture and food. Furthermore, the publication allows the Argentinean organic market to be significantly more visible for the international audience.