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Software developers build complex systems using plenty of third-party libraries. Documentation is key to understand and use the functionality provided via the libraries’ APIs. Therefore, functionality is the main focus of contemporary API documentation, while cross-cutting concerns such as security are almost never considered at all, especially when the API itself does not provide security features. Documentations of JavaScript libraries for use in web applications, e.g., do not specify how to add or adapt a Content Security Policy (CSP) to mitigate content injection attacks like Cross-Site Scripting (XSS). This is unfortunate, as security-relevant API documentation might have an influence on secure coding practices and prevailing major vulnerabilities such as XSS. For the first time, we study the effects of integrating security-relevant information in non-security API documentation. For this purpose, we took CSP as an exemplary study object and extended the official Google Maps JavaScript API documentation with security-relevant CSP information in three distinct manners. Then, we evaluated the usage of these variations in a between-group eye-tracking lab study involving N=49 participants. Our observations suggest: (1) Developers are focused on elements with code examples. They mostly skim the documentation while searching for a quick solution to their programming task. This finding gives further evidence to results of related studies. (2) The location where CSP-related code examples are placed in non-security API documentation significantly impacts the time it takes to find this security-relevant information. In particular, the study results showed that the proximity to functional-related code examples in documentation is a decisive factor. (3) Examples significantly help to produce secure CSP solutions. (4) Developers have additional information needs that our approach cannot meet.
Overall, our study contributes to a first understanding of the impact of security-relevant information in non-security API documentation on CSP implementation. Although further research is required, our findings emphasize that API producers should take responsibility for adequately documenting security aspects and thus supporting the sensibility and training of developers to implement secure systems. This responsibility also holds in seemingly non-security relevant contexts.
3-Hydroxyisobutyrate Dehydrogenase (HIBADH) deficiency - a novel disorder of valine metabolism
(2021)
3-Hydroxyisobutyric acid (3HiB) is an intermediate in the degradation of the branched-chain amino acid valine. Disorders in valine degradation can lead to 3HiB accumulation and its excretion in the urine. This article describes the first two patients with a new metabolic disorder, 3-hydroxyisobutyrate dehydrogenase (HIBADH) deficiency, its phenotype and its treatment with a low-valine diet. The detected mutation in the HIBADH gene leads to nonsense-mediated mRNA decay of the mutant allele and to a complete loss-of-function of the enzyme. Under strict adherence to a low-valine diet a rapid decrease of 3HiB excretion in the urine was observed. Due to limited patient numbers and intrafamilial differences in phenotype with one affected and one unaffected individual, the clinical phenotype of HIBADH deficiency needs further evaluation.
Animal models are often needed in cancer research but some research questions may be answered with other models, e.g., 3D replicas of patient-specific data, as these mirror the anatomy in more detail. We, therefore, developed a simple eight-step process to fabricate a 3D replica from computer tomography (CT) data using solely open access software and described the method in detail. For evaluation, we performed experiments regarding endoscopic tumor treatment with magnetic nanoparticles by magnetic hyperthermia and local drug release. For this, the magnetic nanoparticles need to be accumulated at the tumor site via a magnetic field trap. Using the developed eight-step process, we printed a replica of a locally advanced pancreatic cancer and used it to find the best position for the magnetic field trap. In addition, we described a method to hold these magnetic field traps stably in place. The results are highly important for the development of endoscopic tumor treatment with magnetic nanoparticles as the handling and the stable positioning of the magnetic field trap at the stomach wall in close proximity to the pancreatic tumor could be defined and practiced. Finally, the detailed description of the workflow and use of open access software allows for a wide range of possible uses.
A qualitative study of Machine Learning practices and engineering challenges in Earth Observation
(2021)
Machine Learning (ML) is ubiquitously on the advance. Like many domains, Earth Observation (EO) also increasingly relies on ML applications, where ML methods are applied to process vast amounts of heterogeneous and continuous data streams to answer socially and environmentally relevant questions. However, developing such ML- based EO systems remains challenging: Development processes and employed workflows are often barely structured and poorly reported. The application of ML methods and techniques is considered to be opaque and the lack of transparency is contradictory to the responsible development of ML-based EO applications. To improve this situation a better understanding of the current practices and engineering-related challenges in developing ML-based EO applications is required. In this paper, we report observations from an exploratory study where five experts shared their view on ML engineering in semi-structured interviews. We analysed these interviews with coding techniques as often applied in the domain of empirical software engineering. The interviews provide informative insights into the practical development of ML applications and reveal several engineering challenges. In addition, interviewees participated in a novel workflow sketching task, which provided a tangible reflection of implicit processes. Overall, the results confirm a gap between theoretical conceptions and real practices in ML development even though workflows were sketched abstractly as textbook-like. The results pave the way for a large-scale investigation on requirements for ML engineering in EO.
The article explores SME (Small and Medium Sized Enterprises) brand strategies as a means to position and successfully engage in competitive markets. A derived typology of brand strategy types deals with social profiling and sheds light on brand strategy internalization of two current managerial paradigms—sustainability and co-creation. N = 895 German SME wineries were examined, leaning on a netnographic analysis of predominantly websites and social media interactions. A two-step clustering method thereby identified eight winery SME brand strategy types. The importance of sustainability across the identified eight brand strategy types is significant. Co-creation turned out to be a key profiling trait characterizing one brand strategy type. The typology illustrates strategic richness, with brand strategies leaning predominantly on traditional values, on sustainability, on external reputation, or on more innovative customer centric concepts such as co-creation. Hereby, the typology and the identified brand levers invite to strategically design brand management, governance, and sustainability. Wineries which focus on traditional positioning and legitimacy were found to be cautious in deploying co-creation through social media. Winery brands that are characterized by engagement in digital co-creation apparently either tend to expand their scope or partially combine it with traditional values, making them the most diverse type identified. Sustainability obviously needs to be addressed by all brand strategies. Despite industry and country focus, the analyses illustrate the relevance of socially-oriented profiling and highlights that sustainability has reached a status of a fundamental business approach still allowing to differentiate thereon. Furthermore, the business models of the SMEs need to deliver communicated values.
The clear-sky radiative effect of aerosol–radiation interactions is of relevance for our understanding of the climate system. The influence of aerosol on the surface energy budget is of high interest for the renewable energy sector. In this study, the radiative effect is investigated in particular with respect to seasonal and regional variations for the region of Germany and the year 2015 at the surface and top of atmosphere using two complementary approaches.
First, an ensemble of clear-sky models which explicitly consider aerosols is utilized to retrieve the aerosol optical depth and the surface direct radiative effect of aerosols by means of a clear-sky fitting technique. For this, short-wave broadband irradiance measurements in the absence of clouds are used as a basis. A clear-sky detection algorithm is used to identify cloud-free observations. Considered are measurements of the short-wave broadband global and diffuse horizontal irradiance with shaded and unshaded pyranometers at 25 stations across Germany within the observational network of the German Weather Service (DWD). The clear-sky models used are the Modified MAC model (MMAC), the Meteorological Radiation Model (MRM) v6.1, the Meteorological–Statistical solar radiation model (METSTAT), the European Solar Radiation Atlas (ESRA), Heliosat-1, the Center for Environment and Man solar radiation model (CEM), and the simplified Solis model. The definition of aerosol and atmospheric characteristics of the models are examined in detail for their suitability for this approach.
Second, the radiative effect is estimated using explicit radiative transfer simulations with inputs on the meteorological state of the atmosphere, trace gases and aerosol from the Copernicus Atmosphere Monitoring Service (CAMS) reanalysis. The aerosol optical properties (aerosol optical depth, Ångström exponent, single scattering albedo and asymmetry parameter) are first evaluated with AERONET direct sun and inversion products. The largest inconsistency is found for the aerosol absorption, which is overestimated by about 0.03 or about 30 % by the CAMS reanalysis. Compared to the DWD observational network, the simulated global, direct and diffuse irradiances show reasonable agreement within the measurement uncertainty. The radiative kernel method is used to estimate the resulting uncertainty and bias of the simulated direct radiative effect. The uncertainty is estimated to −1.5 ± 7.7 and 0.6 ± 3.5 W m−2 at the surface and top of atmosphere, respectively, while the annual-mean biases at the surface, top of atmosphere and total atmosphere are −10.6, −6.5 and 4.1 W m−2, respectively.
The retrieval of the aerosol radiative effect with the clear-sky models shows a high level of agreement with the radiative transfer simulations, with an RMSE of 5.8 W m−2 and a correlation of 0.75. The annual mean of the REari at the surface for the 25 DWD stations shows a value of −12.8 ± 5 W m−2 as the average over the clear-sky models, compared to −11 W m−2 from the radiative transfer simulations. Since all models assume a fixed aerosol characterization, the annual cycle of the aerosol radiation effect cannot be reproduced. Out of this set of clear-sky models, the largest level of agreement is shown by the ESRA and MRM v6.1 models.
Alleine Bowling spielen?
(2021)
Womöglich ist das social distancing dieser Tage gar kein soziales sondern einfach nur ein körperliches, ein body distancing. Sozial können wir heute auch sein, ohne uns physisch zu begegnen. Wir können sogar "gemeinsam einsam" musizieren oder im Chor singen. Trotzdem geht etwas verloren - und am Ende wissen wir Zusammenkünfte in Vereinen welcher Art auch immer vielleicht wieder besonders zu schätzen.
Many workers experience their jobs as effortful or even stressful, which can result in strain. Although recovery from work would be an adaptive strategy to prevent the adverse effects of work-related strain, many workers face problems finding enough time to rest and to mentally disconnect from work during nonwork time. What goes on in workers’ minds after a stressful workday? What is it about their jobs that makes them think about their work? This special issue aims to bridge the gap between research on recovery processes mainly examined in Occupational Health Psychology, and research on work stress and working hours, often investigated in the field of Human Resource Management. We first summarize conceptual and theoretical streams from both fields of research. In the following, we discuss the contributions of the five special issue papers and conclude with key messages and directions for further research.
The analysis of used engine oils from industrial engines enables the study of engine wear and oil degradation in order to evaluate the necessity of oil changes. As the matrix composition of an engine oil strongly depends on its intended application, meaningful diagnostic oil analyses bear considerable challenges. Owing to the broad spectrum of available oil matrices, we have evaluated the applicability of using an internal standard and/or preceding sample digestion for elemental analysis of used engine oils via inductively coupled plasma optical emission spectroscopy (ICP OES). Elements originating from both wear particles and additives as well as particle size influence could be clearly recognized by their distinct digestion behaviour. While a precise determination of most wear elements can be achieved in oily matrix, the measurement of additives is performed preferably after sample digestion. Considering a dataset of physicochemical parameters and elemental composition for several hundred used engine oils, we have further investigated the feasibility of predicting the identity and overall condition of an unknown combustion engine using the machine learning system XGBoost. A maximum accuracy of 89.6% in predicting the engine type was achieved, a mean error of less than 10% of the observed timeframe in predicting the oil running time and even less than 4% for the total engine running time, based purely on common oil check data. Furthermore, obstacles and possibilities to improve the performance of the machine learning models were analysed and the factors that enabled the prediction were explored with SHapley Additive exPlanation (SHAP). Our results demonstrate that both the identification of an unknown engine as well as a lifetime assessment can be performed for a first estimation of the actual sample without requiring meticulous documentation.
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%).
Introduction: Chronic pain is a frequent severe disease and often associated with anxiety, depression, insomnia, disability, and reduced quality of life. This maladaptive condition is further characterized by sensory loss, hyperalgesia, and allodynia. Blue light has been hypothesized to modulate sensory neurons and thereby influence nociception.
Objectives: Here, we compared the effects of blue light vs red light and thermal control on pain sensation in a human experimental pain model.
Methods: Pain, hyperalgesia, and allodynia were induced in 30 healthy volunteers through high-density transcutaneous electrical stimulation. Subsequently, blue light, red light, or thermal control treatment was applied in a cross-over design. The nonvisual effects of the respective light treatments were examined using a well-established quantitative sensory testing protocol. Somatosensory parameters as well as pain intensity and quality were scored.
Results: Blue light substantially reduced spontaneous pain as assessed by numeric rating scale pain scoring. Similarly, pain quality was significantly altered as assessed by the German counterpart of the McGill Pain Questionnaire. Furthermore, blue light showed antihyperalgesic, antiallodynic, and antihypesthesic effects in contrast to red light or thermal control treatment.
Conclusion: Blue-light phototherapy ameliorates pain intensity and quality in a human experimental pain model and reveals antihyperalgesic, antiallodynic, and antihypesthesic effects. Therefore, blue-light phototherapy may be a novel approach to treat pain in multiple conditions.
This article provides insights into the modalities of business-model change and innovation. On the basis of an analysis of empirical data of small and medium enterprises, a transition from wine production centrism to its expanded use in hospitality and tourism is explored. Previous research on wine tourism and hospitality predominantly focuses on a destination perspective, neglecting the organizational winery perspective. The article deploys a mixed methods approach, combining netnography and a content analysis for data collection with grounded research and clustering for theory building. The sample size included 885 German wineries. Data stemmed from two distinct sources (websites and a secondary publication in form of a wine guide) and has been analyzed through a two-step clustering algorithm as well as a Principal Component Analysis (PCA). The two-step clustering algorithm resulted in nine different business models while the PCA analysis grouped the variables into the following two categories: basic winery business model (BM) and BM extension into hospitality and tourism, thereby validating the difference between the two constructs. The results point to the diverse nature of business model extensions of wineries in tourism and hospitality, depending on their organizational type and size. This study offers a classification of small and medium sized enterprise’s strategic business model expansion, and explores the expansion of the wine industry through wine hospitality and tourism services, starting with the winery organizational perspective, which has not been done before.
Many people do not consume as much healthy food as recommended. Nudging has been identified as a promising intervention strategy to increase the consumption of healthy food. The present study analyzed the effects of three body shape nudges (thin, thick, or Giacometti artwork) on food ordering and assessed the mediating role of being aware of the nudge. Students (686) and employees (218) of a German university participated in an online experimental study. After randomization, participants visited a realistic online cafeteria and composed a meal for themselves. Under experimental conditions, participants were exposed to one out of three nudges while choosing dishes: (1) thin body shape, (2) thick body shape, and (3) the Giacometti artwork nudge. The Giacometti nudge resulted in more orders for salad among employees. The thin and thick body shape nudges did not change dish orders. Awareness of the nudge mediated the numbers of calories ordered when using the Giacometti or thin body shape nudges. These findings provide useful insights for health interventions in occupational and public health sectors using nudges. Our study contributes to the research on the Giacometti nudge by showing its effectiveness when participants are aware (it is effective under conditions where it is consciously perceived).
The promotion of sustainable packaging is part of the European Green Deal and plays a key role in the EU’s social and political strategy. One option is the use of renewable resources and biomass waste as raw materials for polymer production. Lignocellulose biomass from annual and perennial industrial crops and agricultural residues are a major source of polysaccharides, proteins, and lignin and can also be used to obtain plant-based extracts and essential oils. Therefore, these biomasses are considered as potential substitute for fossil-based resources. Here, the status quo of bio-based polymers is discussed and evaluated in terms of properties related to packaging applications such as gas and water vapor permeability as well as mechanical properties. So far, their practical use is still restricted due to lower performance in fundamental packaging functions that directly influence food quality and safety, the length of shelf life, and thus the amount of food waste. Besides bio-based polymers, this review focuses on plant extracts as active packaging agents. Incorporating extracts of herbs, flowers, trees, and their fruits is inevitable to achieve desired material properties that are capable to prolong the food shelf life. Finally, the adoption potential of packaging based on polymers from renewable resources is discussed from a bioeconomy perspective.
Cysticfibrosis (CF) arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in progressiveand life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterized. Our aims were to describe theclinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individu-als harboring R751L (2 patients with G551D/R751L and 1 with F508del/R751L). Assessment of R751L-CFTR function was made inprimary human bronchial epithelial cultures (HBEs) andXenopusoocytes. Molecular properties of R751L-CFTR were investigatedin the presence of known CFTR modulators. Although sweat chloride was elevated in all three patients, the clinical phenotypeassociated with R751L was mild. Chloride secretion in F508del/R751L HBEs was reduced compared with non-CF HBEs and asso-ciated with a reduction in sodium absorption by the epithelial sodium channel (ENaC). However, R751L-CFTR function inXenopusoocytes, together with folding and cell surface transport of R751L-CFTR, was not different from wild-type CFTR. Overall,R751L-CFTR was associated with reduced sodium chloride absorption but had functional properties similar to wild-type CFTR.This is thefirst report of R751L-CFTR that combines clinical phenotype with characterization of functional and biological proper-ties of the mutant channel. Our work will build upon existing knowledge of mutations within this region of CFTR and, importantly,inform approaches for clinical management. Elevated sweat chloride and reduced chloride secretion in HBEs may be due to al-ternative non-CFTR factors, which require further investigation.
Cancer is a complex disease where resistance to therapies and relapses often pose a serious clinical challenge. The scenario is even more complicated when the cancer type itself is heterogeneous in nature, e.g., lymphoma, a cancer of the lymphocytes which constitutes more than 70 different subtypes. Indeed, the treatment options continue to expand in lymphomas. Herein, we provide insights into lymphoma-specific clinical trials based on cytokine-induced killer (CIK) cell therapy and other pre-clinical lymphoma models where CIK cells have been used along with other synergetic tumor-targeting immune modules to improve their therapeutic potential. From a broader perspective, we will highlight that CIK cell therapy has potential, and in this rapidly evolving landscape of cancer therapies its optimization (as a personalized therapeutic approach) will be beneficial in lymphomas.
The identification of energetic materials in containments is an important challenge for analytical methods in the field of safety and security. Opening a package without knowledge of its contents and the resulting hazards is highly involved with risks and should be avoided whenever possible. Therefore, preferable methods work non-destructive with minimal interaction and are capable of identifying target substances in a containment quickly and reliably. Most spectroscopic methods find their limits, if the target substance is shielded by a covering material. To solve this problem, a combined laser drilling method with subsequent identification of the target substance by means of Raman spectroscopic measurements through microscopic bore holes of the covering material is presented. A pulsed laser beam is used for both the drilling process and as an excitation source for Raman measurements in the same optical setup. Results show the ability of this new method to gain high-quality spectra even when performed through microscopic small bore channels. With the laser parameters chosen right, the method can even be performed on highly sensitive explosives like triacetone triperoxide (TATP). Another advantageous effect arises in an observed reduction in unwanted fluorescence signal in the spectral data, resulting from the confocal-like measurement setup with the bore hole acting as aperture.
Off-lattice Boltzmann methods increase the flexibility and applicability of lattice Boltzmann methods by decoupling the discretizations of time, space, and particle velocities. However, the velocity sets that are mostly used in off-lattice Boltzmann simulations were originally tailored to on-lattice Boltzmann methods. In this contribution, we show how the accuracy and efficiency of weakly and fully compressible semi-Lagrangian off-lattice Boltzmann simulations is increased by velocity sets derived from cubature rules, i.e. multivariate quadratures, which have not been produced by the Gauß-product rule. In particular, simulations of 2D shock-vortex interactions indicate that the cubature-derived degree-nine D2Q19 velocity set is capable to replace the Gauß-product rule-derived D2Q25. Likewise, the degree-five velocity sets D3Q13 and D3Q21, as well as a degree-seven D3V27 velocity set were successfully tested for 3D Taylor–Green vortex flows to challenge and surpass the quality of the customary D3Q27 velocity set. In compressible 3D Taylor–Green vortex flows with Mach numbers on-lattice simulations with velocity sets D3Q103 and D3V107 showed only limited stability, while the off-lattice degree-nine D3Q45 velocity set accurately reproduced the kinetic energy provided by literature.
Das Windenergie-auf-See-Gesetz und das Verfassungsrecht: Eine Vervollständigung in drei Etappen
(2021)
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.
Fabry disease (FD) is an X‐linked lysosomal storage disorder. Deficiency of the lysosomal enzyme alpha‐galactosidase (GLA) leads to accumulation of potentially toxic globotriaosylceramide (Gb3) on a multisystem level. Cardiac and cerebrovascular abnormalities as well as progressive renal failure are severe, life‐threatening long‐term complications. The complete pathophysiology of chronic kidney disease (CKD) in FD and the role of tubular involvement for its progression are unclear.
We established human renal tubular epithelial cell lines from the urine of male FD patients and male controls. The renal tubular system is rich in mitochondria and involved in transport processes at high energy costs. Our studies revealed fragmented mitochondria with disrupted cristae structure in FD patient cells. Oxidative stress levels were elevated and oxidative phosphorylation was up‐regulated in FD pointing at enhanced energetic needs. Mitochondrial homeostasis and energy metabolism revealed major changes as evidenced by differences in mitochondrial number, energy production and fuel consumption. The changes were accompanied by activation of the autophagy machinery in FD. Sirtuin1, an important sensor of (renal) metabolic stress and modifier of different defense pathways, was highly expressed in FD.
Our data show that lysosomal FD impairs mitochondrial function and results in severe disturbance of mitochondrial energy metabolism in renal cells. This insight on a tissue‐specific level points to new therapeutic targets which might enhance treatment efficacy.
Design of a Medium Voltage Generator with DC-Cascade for High Power Wind Energy Conversion Systems
(2021)
This paper shows a new concept to generate medium voltage (MV) in wind power application to avoid an additional transformer. Therefore, the generator must be redesigned with additional constraints and a new topology for the power rectifier system by using multiple low voltage (LV) power rectifiers connected in series and parallel to increase the DC output voltage. The combination of parallel and series connection of rectifiers is further introduced as DC-cascade. With the resulting DC-cascade, medium output voltage is achieved with low voltage rectifiers and without a bulky transformer. This approach to form a DC-cascade reduces the effort required to achieve medium DC voltage with a simple rectifier system. In this context, a suitable DC-cascade control was presented and verified with a laboratory test setup. A gearless synchronous generator, which is highly segmented so that each segment can be connected to its own power rectifier, is investigated. Due to the mixed AC and DC voltage given by the DC-cascade structure, it becomes more demanding to the design of the generator insulation, which influences the copper fill factor and the design of the cooling system. A design strategy for the overall generator design is carried out considering the new boundary conditions.
Background: Atypical myopathy (AM), an acquired multiple acyl-CoA dehydrogenase deficiency (MADD) in horses, induce changes in mitochondrial metabolism. Only few veterinary laboratories offer diagnostic testing for this disease. Inborn and acquired MADD exist in humans, therefore determination of organic acids (OA) in urine and acylcarnitines (AC) in blood by assays available in medical laboratories can serve as AM diagnostics. The evolution of OA and AC profiles in surviving horses is unreported.
Methods: AC profiles using electrospray ionization tandem mass spectrometry (ESI-MS/MS) and OA in urine using gas chromatography mass spectrometry (GC–MS) were determined in dried blot spots (DBS, n = 7) and urine samples (n = 5) of horses with AM (n = 7) at disease presentation and in longitudinal samples from 3/4 survivors and compared to DBS (n = 16) and urine samples (n = 7) from control horses using the Wilcoxon test.
Results: All short- (C2-C5) and medium-chain (C6-C12) AC in blood differed significantly (p < 0.008) between horses with AM and controls, except for C5:1 (p = 0.45) and C5OH + C4DC (p = 0.06). In AM survivors the AC concentrations decreased over time but were still partially elevated after 7 days. 14/62 (23%) of OA differed significantly between horses with AM and control horses. Concentrations of ethylmalonic acid, 2-hydroxyglutaric acid and the acylglycines (butyryl-, valeryl-, and hexanoylglycine) were highly elevated in the urine of all horses with AM at the day of disease presentation. In AM survivors, concentrations of those metabolites were initially lower and decreased during remission to approach normalization after 7 days.
Conclusion: OA and AC profiling by specialized human medical laboratories was used to diagnose AM in horses. Elevation of specific metabolites were still evident several days after disease presentation, allowing diagnosis via analysis of samples from convalescent animals.
Diversity of Insects in Nature protected Areas (DINA): an interdisciplinary German research project
(2021)
Insect declines and biodiversity loss have attracted much attention in recent years, but lack of comprehensive data, conflicting interests among stakeholders and insufficient policy guidance hinder progress in preserving biodiversity. The project DINA (Diversity of Insects in Nature protected Areas) investigates insect communities in 21 nature reserves in Germany. All selected conservation sites border arable land, with agricultural practices assumed to influence insect populations. We taught citizen scientists how to manage Malaise traps for insect collection, and subsequently used a DNA metabarcoding approach for species identification. Vegetation surveys, plant metabarcoding as well as geospatial and ecotoxicological analyses will help to unravel contributing factors for the deterioration of insect communities. As a pioneering research project in this field, DINA includes a transdisciplinary dialogue involving relevant stakeholders such as local authorities, policymakers, and farmers, which aims at a shared understanding of conservation goals and action pathways. Stakeholder engagement combined with scientific results will support the development of sound policy recommendations to improve legal frameworks, landscape planning, land use, and conservation strategies. With this transdisciplinary approach, we aim to provide the background knowledge to implement policy strategies that will halt further decline of insects in German protected areas.
Intimate swabs taken for examination in sexual assault cases typically yield mixtures of sperm and epithelial cell types. While powerful, differential extraction protocols to overcome such cell type mixtures by separate lysis of epithelial cells and spermatozoa can still prove ineffective, in particular if only few sperm cells are present or if swabs contain sperm from more than one individual leading to complex low level DNA mixtures. A means to avoid such mixtures consists in the analysis of single micromanipulated sperm cells. However, the quantity of DNA from single sperm cells is not sufficient for conventional STR analysis. Here, we describe a simple method for micromanipulating individual sperm cells from intimate swabs and show that whole genome amplification can generate sufficient amounts of DNA from single cells for subsequent DNA profiling. We recovered over 80% of alleles of haploid autosomal STR profiles from the majority of individual sperm cells. Furthermore, we demonstrate that in mixtures of sperm from two contributors, Y-STR and X-STR profiles of individual sperm cells can be used to sort the haploid autosomal profiles to develop the diploid consensus STR profiles of the individual donors. Finally, by analysing single sperm cells from mock sexual assault swabs with one or two sperm donors, we showed that our protocols enabled the identification of the unknown male contributors.
For several decades, farmers have been mixing rock powders with livestock slurry to reduce its NH3 emissions and increase its nutrient content. However, mixing rock powders with slurry is controversial, and there is currently no scientific evidence for its effects on NH3 and greenhouse gas (GHG) emissions or on changes in its nutrient content due to element release from rock powders. The major aim of this study was therefore to analyse the effects of mixing two commercially established rock powders with cattle slurry on NH3, CO2, N2O and CH4 emissions, and on nutrient release over a course of 46 days. We found that rock powders did not significantly affect CO2 emission rates. NH3 and N2O emission rates did not differ significantly up until the end of the trial, when the emission rates of the rock powder treatments significantly increased for NH3 and significantly decreased for N2O, respectively, which coincided with a reduction of the slurry crust. Cumulative NH3 emissions did not, however, differ significantly between treatments. Unexpected and significant increases in CH4 emission rates occurred for the rock powder treatments. Rock powders increased the macro- and micronutrient content of the slurry. The conflicting results are discussed and future research directions are proposed.
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.
Kompetenzen auf dem Gebiet der Datenbanken gehören zum Pflichtbereich der Informatik. Das Angebot an Lehrbüchern, Vorlesungsformaten und Tools lässt sich jedoch für Lehrende oft nur eingeschränkt in die eigene Lehre integrieren. In diesem Aufsatz schildern wir unsere Erfahrungen in der Nutzung (frei) verfügbarer und der Entwicklung eigener digitaler Inhalte für grundlegende Datenbankveranstaltungen. Die Präferenzen der Studierenden werden mittels Nutzungsanalysen und Befragungen ermittelt. Wir stellen die Anforderungen auf, wie die nicht selten aufwendig herzustellenden digitalen Materialien von Lehrenden in ihre Lehr- und Lernumgebungen integriert werden können. Als konstruktive Antwort auf diese Herausforderung wird das Konzept EILD zur Entwicklung von Inhalten für die Lehre im Fach Datenbanken vorgestellt. Die Inhalte sollen in vielfältigen Lernszenarien eingesetzt werden können und mit einer Creative Commons (CC) Lizenzierung als OER (open educational resources) frei zur Verfügung stehen.
Different analyses and feasibility studies have been conducted on the plant extracts of thyme (Thymus vulgaris), European horse chestnut (Aesculus hippocastanum), Nordmann fir (Abies nordmanniana), and snowdrop (Galanthus elwesii) to evaluate bio‐based alternatives to common petrol‐based stabilisers. For this purpose, in this study, plant extracts were incorporated into poly‐lactic acid films (PLA) at different concentrations. The films’ UV absorbance and migration into packed food was analysed via photometric assays (ABTS radical cation scavenging capacity assay, β‐carotene assay) and GC–MS analysis. Furthermore, the synergistic antioxidant effects of various combinations of extracts and isolated active compounds were determined. This way, antioxidant effects can be increased, allowing for a highly effective use of resources. All extracts were successfully incorporated into PLA films and showed notable photoabsorbing effects, while no migration risk was observed. Depending on extract combinations, high synergistic effects of up to 726% can be utilised to improve the effectiveness of bio‐based extracts. This applies particularly to tomato paste and Aesculus hippocastanum extracts, which overall show high synergistic and antioxidant effects in combination with each other and with isolated active compounds. The study shows that it is possible to create safe bio‐based antioxidant films which show even improved properties when using highlighted target combinations.
Applied privacy research has so far focused mainly on consumer relations in private life. Privacy in the context of employment relationships is less well studied, although it is subject to the same legal privacy framework in Europe. The European General Data Protection Regulation (GDPR) has strengthened employees’ right to privacy by obliging that employers provide transparency and intervention mechanisms. For such mechanisms to be effective, employees must have a sound understanding of their functions and value. We explored possible boundaries by conducting a semistructured interview study with 27 office workers in Germany and elicited mental models of the right to informational self-determination, which is the European proxy for the right to privacy. We provide insights into (1) perceptions of different categories of data, (2) familiarity with the legal framework regarding expectations for privacy controls, and (3) awareness of data processing, data flow, safeguards, and threat models. We found that legal terms often used in privacy policies used to describe categories of data are misleading. We further identified three groups of mental models that differ in their privacy control requirements and willingness to accept restrictions on their privacy rights. We also found ignorance about actual data flow, processing, and safeguard implementation. Participants’ mindsets were shaped by their faith in organizational and technical measures to protect privacy. Employers and developers may benefit from our contributions by understanding the types of privacy controls desired by office workers and the challenges to be considered when conceptualizing and designing usable privacy protections in the workplace.
Although work events can be regarded as pivotal elements of organizational life, only a few studies have examined how positive and negative events relate to and combine to affect work engagement over time. Theory suggests that, to better understand how current events affect work engagement (WE), we have to account for recent events that have preceded these current events. We present competing theoretical views on how recent and current work events may affect employees (e.g., getting used to a high frequency of negative events or becoming more sensitive to negative events). Although the occurrence of events implies discrete changes in the experience of work, prior research has not considered whether work events actually accumulate to sustained mid-term changes in WE. To address these gaps in the literature, we conducted a week-level longitudinal study across a period of 15 consecutive weeks among 135 employees, which yielded 849 weekly observations. While positive events were associated with higher levels of WE within the same week, negative events were not. Our results support neither satiation nor sensitization processes. However, a high frequency of negative events in the preceding week amplified the beneficial effects of positive events on WE in the current week. Growth curve analyses show that the benefits of positive events accumulate to sustain high levels of WE. WE dissipates in the absence of a continuous experience of positive events. Our study adds a temporal component by highlighting that positive events affect work engagement, particularly in light of recent negative events. Our study informs research that has taken a feature-oriented perspective on the dynamic interplay of job demands and resources.
New sustainable, environmentally friendly materials for thermal insulation of buildings are necessary to reduce their carbon footprints. In this study, Miscanthus fiber-reinforced geopolymer composites, foamed with sodium dodecyl sulfate (SDS), were developed using fly ash as a geopolymer precursor. The effects of fiber content, fiber size, curing temperature, foaming agent content, fumed silica specific surface area and fumed silica content on thermal conductivity and compressive strength were evaluated using a Plackett-Burman design of experiment. Furthermore, the microstructure of geopolymer composites was investigated using X-ray diffraction (XRD), X-ray micro-computed tomography (μCT) and scanning electron microscopy (SEM). The measured characteristic values were in the following ranges: Thermal conductivity 0.057 W (m K)−1 to 0.127 W (m K)−1, compressive strength 0.007 MPa–0.719 MPa and porosity 49 vol% to 76 vol%. The results reveal an enhancement of thermal conductivity by elevated fiber size and foaming agent content. In contrast, the compressive strength is enhanced by high fiber content. Additionally, SEM images indicate a good interaction between the fibers and the geopolymer matrix, because nearly the whole fiber surface is covered by the geopolymer.
In thyroid carcinoma cells, the soluble βgalactosidespecific lectin, galectin3, is extra and intracellularly expressed and plays a significant role in thyroid cancer diagnosis. The functional relevance of this molecule, particularly in its extracellular environment however, warrants further elucidation. To gain insight into this topic, the present study characterized principal functional properties of galectin3 in 3 commonly used thyroid carcinoma cell lines (BCPAP, Cal62 and FTC133) that express the molecule intra and extracellulary. Cellintrinsic galectin3 harbors a functional carbohydrate recognition domain as determined by affinity purification. Moreover, cell surface expressed galectin3 can be partially removed by treatment with lactose or asialofetuin, but not with sucrose. Thyroid carcinoma cells adhere to substratebound galectin3 in a βgalactosidespecific manner, whereby only cell adhesion, but not cell migration is promoted. Thus, thyroid tumor cells harbor functional active galectin3 that, inter alia, specifically interacts with cell surfaceexpressed molecular ligands in a βgalactosidedependent manner, whereby the molecule can at least interfere with cell adhesion. The modulation of galectin3 expression level or its ligands in such tumor cells could be of therapeutic interest and needs further experimental clarification.
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.
Turbulent compressible flows are traditionally simulated using explicit time integrators applied to discretized versions of the Navier-Stokes equations. However, the associated Courant-Friedrichs-Lewy condition severely restricts the maximum time-step size. Exploiting the Lagrangian nature of the Boltzmann equation’s material derivative, we now introduce a feasible three-dimensional semi-Lagrangian lattice Boltzmann method (SLLBM), which circumvents this restriction. While many lattice Boltzmann methods for compressible flows were restricted to two dimensions due to the enormous number of discrete velocities in three dimensions, the SLLBM uses only 45 discrete velocities. Based on compressible Taylor-Green vortex simulations we show that the new method accurately captures shocks or shocklets as well as turbulence in 3D without utilizing additional filtering or stabilizing techniques other than the filtering introduced by the interpolation, even when the time-step sizes are up to two orders of magnitude larger compared to simulations in the literature. Our new method therefore enables researchers to study compressible turbulent flows by a fully explicit scheme, whose range of admissible time-step sizes is dictated by physics rather than spatial discretization.
BACKGROUND
Biallelic loss-of-function variants in NCF1 lead to reactive oxygen species deficiency and chronic granulomatous disease (CGD). Heterozygosity for the p.Arg90His variant in NCF1 has been associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome in adult patients. This study demonstrates the association of the homozygous p.Arg90His variant with interferonopathy with features of autoinflammation and autoimmunity in a pediatric patient.
CASE PRESENTATION
A 5-year old female of Indian ancestry with early-onset recurrent fever and headache, and persistently elevated antinuclear, anti-Ro, and anti-La antibodies was found to carry the homozygous p.Arg90His variant in NCF1 through exome sequencing. Her unaffected parents and three other siblings were carriers for the mutant allele. Because the presence of two NCF1 pseudogenes, this variant was confirmed by independent genotyping methods. Her intracellular neutrophil oxidative burst and NCF1 expression levels were normal, and no clinical features of CGD were apparent. Gene expression analysis in peripheral blood detected an interferon gene expression signature, which was further supported by cytokine analyses of supernatants of cultured patient's cells. These findings suggested that her inflammatory disease is at least in part mediated by type I interferons. While her fever episodes responded well to systemic steroids, treatment with the JAK inhibitor tofacitinib resulted in decreased serum ferritin levels and reduced frequency of fevers.
CONCLUSION
Homozygosity for p.Arg90His in NCF1 should be considered contributory in young patients with an atypical systemic inflammatory antecedent phenotype that may evolve into autoimmunity later in life. The complex genomic organization of NCF1 poses a difficulty for high-throughput genotyping techniques and variants in this gene should be carefully evaluated when using the next generation and Sanger sequencing technologies. The p.Arg90His variant is found at a variable allele frequency in different populations, and is higher in people of South East Asian ancestry. In complex genetic diseases such as SLE, other rare and common susceptibility alleles might be necessary for the full disease expressivity.
The solvent exchange as one of the most important steps during the manufacturing process of organic aerogels was investigated. This step is crucial as a preparatory step for the supercritical drying, since the pore solvent must be soluble in supercritical carbon dioxide to enable solvent extraction. The development and subsequent optimization of a suitable system with a peristaltic pump for automatic solvent exchange proved to be a suitable approach. In addition, the influence of zeolites on the acceleration of the process was found to be beneficial. To investigate the process, the water content in acetone was determined at different times using Karl Fischer titration. The shrinkage, densities, as well as the surface areas of the aerogels were analyzed. Based on these, the influence of various process parameters on the final structure of the obtained aerogels was investigated and evaluated. Modeling on diffusion in porous materials completes this study.
The modern concept of the evolution of Mars assumes that life could potentially have originated on the planet Mars, possibly during the end of the late heavy bombardment, and could then be transferred to other planets. Since then, physical and chemical conditions on Mars changed and now strongly limit the presence of terrestrial-like life forms. These adverse conditions include scarcity of liquid water (although brine solutions may exist), low temperature and atmospheric pressure, and cosmic radiation. Ionizing radiation is very important among these life-constraining factors because it damages DNA and other cellular components, particularly in liquid conditions where radiation-induced reactive oxidants diffuse freely. Here, we investigated the impact of high doses (up to 2 kGy) of densely-ionizing (197.6 keV/µm), space-relevant iron ions (corresponding on the irradiation that reach the uppermost layer of the Mars subsurface) on the survival of an extremophilic terrestrial organism-Cryomyces antarcticus-in liquid medium and under atmospheric conditions, through different techniques. Results showed that it survived in a metabolically active state when subjected to high doses of Fe ions and was able to repair eventual DNA damages. It implies that some terrestrial life forms can withstand prolonged exposure to space-relevant ion radiation.
Intersectoral collaborations are an integral component of the prevention and control of diseases in a complex health system. On the one hand, One Health (OH) is promoting the establishment of intersectoral collaborations for prevention at the human-animal-environment interface. On the other hand, operationalising OH can only be realized through intersectoral collaborations.
This work contributes to broadening the knowledge of the process for operationalising OH by analysing the governance structures behind different initiatives that tackle health problems at the human-animal-environment interface. The cases taken as examples for the analysis are the control and response to rabies and avian influenza under “classical OH”, and the management of floods and droughts for insights into “extended OH”. Data from Ghana and India were collected and compared to identify the key elements that enable ISC for OH.
Despite the case studies being heterogeneous in terms of their geographic, economic, social, cultural, and historical contexts, strong similarities were identified on how intersectoral collaborations in OH were initiated, managed, and taken to scale.
The actions documented for rabies prevention and control were historically based on one sector being the leader and implementer of activities, while avian influenza management relied more on intersectoral collaborations with clearly defined sectoral responsibilities. The management of the impact of flood and droughts on health provided a good example of intersectoral collaborations achieved by sectoral integration; however, the human health component was only involved in the response stage in the case of Ghana, while for India, there were broader schemes of intersectoral collaborations for prevention, adaptation, and response concerning climate change and disaster.
Because the robust and rapid determination of spoilage microorganisms is becoming increasingly important in industry, the use of IR microspectroscopy, and the establishment of robust and versatile chemometric models for data processing and classification, is gaining importance. To further improve the chemometric models, bacterial stress responses were induced, to study the effect on the IR spectra and to improve the chemometric model. Thus, in this work, nine important food-relevant microorganisms were subjected to eight stress conditions, besides the regular culturing as a reference. Spectral changes compared to normal growth conditions without stressors were found in the spectral regions of 900–1500 cm−1 and 1500–1700 cm−1. These differences might stem from changes in the protein secondary structure, exopolymer production, and concentration of nucleic acids, lipids, and polysaccharides. As a result, a model for the discrimination of the studied microorganisms at the genus, species and strain level was established, with an accuracy of 96.6%. This was achieved despite the inclusion of various stress conditions and times after incubation of the bacteria. In addition, a model was developed for each individual microorganism, to separate each stress condition or regular treatment with 100% accuracy.
In this study, we investigate the thermo-mechanical relaxation and crystallization behavior of polyethylene using mesoscale molecular dynamics simulations. Our models specifically mimic constraints that occur in real-life polymer processing: After strong uniaxial stretching of the melt, we quench and release the polymer chains at different loading conditions. These conditions allow for free or hindered shrinkage, respectively. We present the shrinkage and swelling behavior as well as the crystallization kinetics over up to 600 ns simulation time. We are able to precisely evaluate how the interplay of chain length, temperature, local entanglements and orientation of chain segments influences crystallization and relaxation behavior. From our models, we determine the temperature dependent crystallization rate of polyethylene, including crystallization onset temperature.
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.
Soweit grundsätzlich als gemeinnützig anerkannte Sportvereine neben dem Betrieb einer Abteilung mit ideeller und gemeinnütziger Zwecksetzung (Kinder- und Jugendfußball) auch einen wirtschaftlichen Geschäftsbetrieb (erste Fußballmannschaft in der Regionalliga, Bistro) unterhalten, entfällt die Befreiung von den Umlagen zum Lastenausgleich und zur Lastenverteilung in diesem Umfang.
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.
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.
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.
Die Kommunikation der Gegenwart ist dominant digital geleitet. Die Benutzung der Zeichen ist hier an mediale Artefakte gebunden, denen dabei das Kriterium des Mikroformatischen sowohl im Hinblick auf ihre Objektivationen als auch in Hinsicht auf ihre Inhalte zukommt. Der Beitrag nimmt diese Beobachtung zum Ausgang, um am Beispiel von WhatsApp eine Kommunikationspraktik medienästhetisch zu betrachten, die ihrerseits vehement die Gegenwärtigkeit der Kommunikation bestimmt.
Multi-epoch searches for relativistic binary pulsars and fast transients in the Galactic Centre
(2021)
In recent years, there has been an increasing interest in psychological need satisfaction and its role in promoting optimal functioning. The DRAMMA model integrates existing need and recovery models to explain why leisure is connected to optimal functioning (i.e., high well-being and low ill-being). It encompasses six psychological needs: detachment, relaxation, autonomy, mastery, meaning, and affiliation (DRAMMA). While the individual needs of the DRAMMA model have been previously shown to relate to different aspects of optimal functioning, a longitudinal study examining the entire model has not been conducted before. In this longitudinal field study covering leisure and work episodes, we tested the within-person reliability and (construct and criterion) validity of the operationalization of the DRAMMA model in a sample of 279 German employees. Participants filled out measures of DRAMMA need satisfaction and optimal functioning at five measurement times before, during, and after vacation periods in 2016 and 2017. The six-factor model showed good fit to the data. In the multilevel models, relaxation, detachment, autonomy, and mastery had the most consistent within-person effects on optimal functioning, while the relationships between optimal functioning, meaning, and affiliation were considerably weaker. In conclusion, DRAMMA need satisfaction can aid and nurture employees’ optimal functioning.
Cultivation of Miscanthus x giganteus L. (Mis) with annual harvest of biomass could provide an additional C source for farmers. To test the potential of Mis-C for immobilizing inorganic N from slurry or manure and as a C source for soil organic matter build-up in comparison to wheat (Triticum aestivum L.) straw (WS), a greenhouse experiment was performed. Pot experiments with ryegrass (Lolium perenne L.) were set up to investigate the N dynamics of two organic fertilisers based on Mis at Campus Klein-Altendorf, Germany. The two fertilisers, a mixture of cattle slurry and Mis as well as cattle manure from Mis-bedding material resulted in a slightly higher N immobilisation. Especially at the 1st and 2nd harvest, they were partly significantly different compared with the WS treatments. The fertilisers based on Mis resulted in a slightly higher microbial biomass C and microbial biomass N and thus can be identified as an additional C source to prevent nitrogen losses and for the build-up of soil organic matter (SOM) in the long-term.
Cytokine-induced killer (CIK) cells are an ex vivo expanded heterogeneous cell population with an enriched NK-T phenotype (CD3+CD56+). Due to the convenient and relatively inexpensive expansion capability, together with low incidence of graft versus host disease (GVHD) in allogeneic cancer patients, CIK cells are a promising candidate for immunotherapy. It is well known that natural killer group 2D (NKG2D) plays an important role in CIK cell-mediated antitumor activity; however, it remains unclear whether its engagement alone is sufficient or if it requires additional co-stimulatory signals to activate the CIK cells. Likewise, the role of 2B4 has not yet been identified in CIK cells. Herein, we investigated the individual and cumulative contribution of NKG2D and 2B4 in the activation of CIK cells. Our analysis suggests that (a) NKG2D (not 2B4) is implicated in CIK cell (especially CD3+CD56+ subset)-mediated cytotoxicity, IFN-γ secretion, E/T conjugate formation, and degranulation; (b) NKG2D alone is adequate enough to induce degranulation, IFN-γ secretion, and LFA-1 activation in CIK cells, while 2B4 only provides limited synergy with NKG2D (e.g., in LFA-1 activation); and (c) NKG2D was unable to costimulate CD3. Collectively, we conclude that NKG2D engagement alone suffices to activate CIK cells, thereby strengthening the idea that targeting the NKG2D axis is a promising approach to improve CIK cell therapy for cancer patients. Furthermore, CIK cells exhibit similarities to classical invariant natural killer (iNKT) cells with deficiencies in 2B4 stimulation and in the costimulation of CD3 with NKG2D. In addition, based on the current data, the divergence in receptor function between CIK cells and NK (or T) cells can be assumed, pointing to the possibility that molecular modifications (e.g., using chimeric antigen receptor technology) on CIK cells may need to be customized and optimized to maximize their functional potential.
The purpose of this paper is to examine the impact that various types of business model extensions (hospitality and tourism, online sales platforms, and sustainability) have on the winery business. The research is based on company data and online observations of N = 886 German wineries and deploys a content analysis, netnography, and structural equation modeling (SEM) in order to test the hypothesis on business model extensions of wineries, which have been set forth in the previous literature. The findings indicate that business model extensions related to online sales platforms have a positive impact on winery business size. These results mean that developing online sales platforms enlarges the winery BM (business model) size and type (manager-run, state-owned, or cooperatives). The paper presents in detail the impact of winery BM extensions on winery BM model type and size, thereby contributing to the literature on business model innovation.
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.
The synthesis and characterization of a new class of 1,2,4-oxadiazolylpyridinium as a cationic scaffold for fluorinated ionic liquid crystals is herein described. A series of 12 fluorinated heterocyclic salts based on a 1,2,4-oxadiazole moiety, connected through its C(5) or C(3) to an N-alkylpyridinium unit and a perfluoroheptyl chain, differing in the length of the alkyl chain and counterions, has been synthesized. As counterions iodide, bromide and bis(trifluoromethane)sulfonimide have been considered. The synthesis, structure, and liquid crystalline properties of these compounds are discussed on the basis of the tuned structural variables. The thermotropic properties of this series of salts have been investigated by differential scanning calorimetry and polarized optical microscopy. The results showed the existence of an enantiotropic mesomorphic smectic liquid crystalline phase for six bis(trifluoromethane)sulfonimide salts.
İnsanlar yeryüzünün doğal kaynaklarını onun bunları yenileyebileceğinden daha hızlı tüketmektedirler. İnsanların bu tutumlarının bedelini gelecek kuşaklar ödeyeceklerdir. Gelecek kuşaklara bu bedeli ödetmemek için artık parasal kârları ençoklamak, niceliksel olarak büyümek ve bolluk yaratmak doğrultusunda işleyen şimdiki ekonomik faaliyetleri bir başka biçime dönüştürmek kaçınılmazdır. Peren Teoremi göstermektedir ki Dünya örneğinde de olduğu gibi kapalı bir sistem doğal kaynak tüketimi eş düzeyde bir doğal kaynak üretimi ile yaşayabilir. Üretim ile tüketim arasındaki denge çok uzun bir süre bozulursa gezegen doğal bir ölüm ile karşılaşır. Bunu sağlamak üzere Dünya üzerinde yaşayan ve/veya dünya sayesinde yaşayan tüm insanların kişi başına doğal kaynak tüketimlerini artan küresel nüfusla orantılı bir biçimde azaltmak gerekir.