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Human bestrophin-1 (hBest1) is a transmembrane Ca2+- dependent anion channel, associated with the transport of Cl−, HCO3- ions, γ-aminobutiric acid (GABA), glutamate (Glu), and regulation of retinal homeostasis. Its mutant forms cause retinal degenerative diseases, defined as Bestrophinopathies. Using both physicochemical - surface pressure/mean molecular area (π/A) isotherms, hysteresis, compressibility moduli of hBest1/sphingomyelin (SM) monolayers, Brewster angle microscopy (BAM) studies, and biological approaches - detergent membrane fractionation, Laurdan (6-dodecanoyl-N,N-dimethyl-2-naphthylamine) and immunofluorescence staining of stably transfected MDCK-hBest1 and MDCK II cells, we report:
1) Ca2+, Glu and GABA interact with binary hBest1/SM monolayers at 35 °C, resulting in changes in hBest1 surface conformation, structure, self-organization and surface dynamics. The process of mixing in hBest1/SM monolayers is spontaneous and the effect of protein on binary films was defined as “fluidizing”, hindering the phase-transition of monolayer from liquid-expanded to intermediate (LE-M) state;
2) in stably transfected MDCK-hBest1 cells, bestrophin-1 was distributed between detergent resistant (DRM) and detergent-soluble membranes (DSM) - up to 30 % and 70 %, respectively; in alive cells, hBest1 was visualized in both liquid-ordered (Lo) and liquid-disordered (Ld) fractions, quantifying protein association up to 35 % and 65 % with Lo and Ld. Our results indicate that the spontaneous miscibility of hBest1 and SM is a prerequisite to diverse protein interactions with membrane domains, different structural conformations and biological functions.
The Twelfth International Conference on Advances in Databases, Knowledge, and Data Applications (DBKDA 2020) continued a series of events covering a large spectrum of topics related to advances in fundamentals on databases, evolution of relation between databases and other domains, data base technologies and content processing, as well as specifics in applications domains databases. Advances in different technologies and domains related to databases triggered substantial improvements for content processing, information indexing, and data, process and knowledge mining. The push came from Web services, artificial intelligence, and agent technologies, as well as from the generalization of the XML adoption. High-speed communications and computations, large storage capacities, and load-balancing for distributed databases access allow new approaches for content processing with incomplete patterns, advanced ranking algorithms and advanced indexing methods. Evolution on e-business, ehealth and telemedicine, bioinformatics, finance and marketing, geographical positioning systems put pressure on database communities to push the ‘de facto’ methods to support new requirements in terms of scalability, privacy, performance, indexing, and heterogeneity of both content and technology.
Steady state efficiency optimization techniques for induction motors are state of the art and various methods have already been developed. This paper provides new insights in the efficiency optimized operation in dynamic regime. The paper proposes an anticipative flux modification in order to decrease losses during torque and speed transients. These trajectories are analyzed based on a numerical study for different motors. Measurement results for one motor are given as well.
The shift of populations to cities is creating challenges in many respects, thus leading to increasing demand for smart solutions of urbanization problems. Smart city applications range from technical and social to economic and ecological. The main focus of this work is to provide a systematic literature review of smart city research to answer two main questions: (1) How is current research on smart cities structured? and (2) What directions are relevant for future research on smart cities? To answer these research questions, a text-mining approach is applied to a large number of publications. This provides an overview and gives insights into relevant dimensions of smart city research. Although the main dimensions of research are already described in the literature, an evaluation of the relevance of such dimensions is missing. Findings suggest that the dimensions of environment and governance are popular, while the dimension of economy has received only limited attention.
Purpose: Despite growing interest in the intersection of supply chain management (SCM) and management accounting (MA) in the academic debate, there is a lack of understanding regarding both the content and the delimitation of this topic. As of today, no common conceptualization of supply chain management accounting (SCMA) exists. The purpose of this study is to provide an overview of the research foci of SCMA in the scholarly debate of the past two decades. Additionally, it analyzes whether and to what extent the academic discourse of MA in SCs has already found its way into both SCM and MA higher education, respectively.
Design/methodology/approach: A content analysis is conducted including 114 higher education textbooks written in English or in German language.
Findings: The study finds that SC-specific concepts of MA are seldom covered in current textbooks of both disciplines. The authors conclude that although there is an extensive body of scholarly research about SCMA concepts, there is a significant discrepancy with what is taught in higher education textbooks.
Practical implications: There is a large discrepancy between the extensive knowledge available in scholarly research and what we teach in both disciplines. This implies that graduates of both disciplines lack important knowledge and skills in controlling and accounting for SCs. To bring about the necessary change, MA and SCM in higher education must be more integrative.
Originality/value: To the best of the authors knowledge, this study is first of its kind comprising a large textbook sample in both English and German languages. It is the first substantiated assessment of the current state of integration between SCM and MA in higher education.
Driven by digital transformation, manufacturing systems are heading towards autonomy. The implementation of autonomous elements in manufacturing systems is still a big challenge. Especially small and medium sized enterprises (SME) often lack experience to assess the degree of Autonomous Production. Therefore, a description model for the assessment of stages for Autonomous Production has been identified as a core element to support such a transformation process. In contrast to existing models, the developed SME-tailored model comprises different levels within a manufacturing system, from single manufacturing cells to the factory level. Furthermore, the model has been validated in several case studies.
Process quality has reached a high level on mass production, utilizing well known methods like the DoE. The drawback of the unterlying statistical methods is the need for tests under real production conditions, which cause high costs due to the lost output. Research over the last decade let to methods for correcting a process by using in-situ data to correct the process parameters, but still a lot of pre-production is necessary to get this working. This paper presents a new approach in improving the product quality in process chains by using context data - which in part are gathered by using Industry 4.0 devices - to reduce the necessary pre-production.
In recent years, machine learning algorithms have made a huge development in performance and applicability in industry and especially maintenance. Their application enables predictive maintenance and thus offers efficiency increases. However, a successful implementation of such solutions still requires high effort in data preparation to obtain the right information, interdisciplinarity in teams as well as a good communication to employees. Here, small and medium sized enterprises (SME) often lack in experience, competence and capacity. This paper presents a systematic and practice-oriented method for an implementation of machine learning solutions for predictive maintenance in SME, which has already been validated.
The chemical synthesis of polysiloxanes from monomeric starting materials involves a series of hydrolysis, condensation and modification reactions with complex monomeric and oligomeric reaction mixtures. Real-time monitoring and precise process control of the synthesis process is of great importance to ensure reproducible intermediates and products and can readily be performed by optical spectroscopy. In chemical reactions involving rapid and simultaneous functional group transformations and complex reaction mixtures, however, the spectroscopic signals are often ambiguous due to overlapping bands, shifting peaks and changing baselines. The univariate analysis of individual absorbance signals is hence often only of limited use. In contrast, batch modelling based on the multivariate analysis of the time course of principal components (PCs) derived from the reaction spectra provides a more efficient tool for real time monitoring. In batch modelling, not only single absorbance bands are used but information over a broad range of wavelengths is extracted from the evolving spectral fingerprints and used for analysis. Thereby, process control can be based on numerous chemical and morphological changes taking place during synthesis. “Bad” (or abnormal) batches can quickly be distinguished from “normal” ones by comparing the respective reaction trajectories in real time. In this work, FTIR spectroscopy was combined with multivariate data analysis for the in-line process characterization and batch modelling of polysiloxane formation. The synthesis was conducted under different starting conditions using various reactant concentrations. The complex spectral information was evaluated using chemometrics (principal component analysis, PCA). Specific spectral features at different stages of the reaction were assigned to the corresponding reaction steps. Reaction trajectories were derived based on batch modelling using a wide range of wavelengths. Subsequently, complexity was reduced again to the most relevant absorbance signals in order to derive a concept for a low-cost process spectroscopic set-up which could be used for real-time process monitoring and reaction control.
The automation of work by means of disruptive technologies such as Artificial Intelligence (AI) and Robotic Process Automation (RPA) is currently intensely discussed in business practice and academia. Recent studies indicate that many tasks manually conducted by humans today will not in the future. In a similar vein, it is expected that new roles will emerge. The aim of this study is to analyze prospective employment opportunities in the context of RPA in order to foster our understanding of the pivotal qualifications, expertise and skills necessary to find an occupation in a completely changing world of work. This study is based on an explorative, content analysis of 119 job advertisements related to RPA in Germany. The data was collected from major German online job platforms, qualitatively coded, and subsequently analyzed quantitatively. The research indicates that there indeed are employment opportunities, especially in the consulting sector. The positions require different technological expertise such as specific programming languages and knowledge in statistics. The results of this study provide guidance for organizations and individuals on reskilling requirements for future employment. As many of the positions require profound IT expertise, the generally accepted perspective that existing employees affected by automation can be retrained to work in the emerging positions has to be seen extremely critical. This paper contributes to the body of knowledge by providing a novel perspective on the ongoing discussion of employment opportunities, and reskilling demands of the existing workforce in the context of recent technological developments and automation.
Despite strong political efforts in Europe, industrial small- and medium sized enterprises (SMEs) seem to neglect adopting practices for energy effciency. By taking a cultural perspective, this study investigated what drives the establishment of energy effciency and corresponding practices in SMEs. Based on 10 ethnographic case studies and a quantitative survey among 500 manufacturing SMEs, the results indicate the importance of everyday employee behavior in achieving energy savings. The studied enterprises value behavior related measures as similarly important as technical measures. Raising awareness for energy issues within the organization, therefore, constitutes an essential leadership task that is oftentimes perceived as challenging and frustrating. It was concluded that the embedding of energy efficiency in corporate strategy, the use of a broad spectrum of different practices, and the empowerment and involvement of employees serve as major drivers in establishing energy effciency within SMEs. Moreover, the findings reveal institutional influences on shaping the meanings of energy effciency for the SMEs by raising attention for energy effciency in the enterprises and making energy effciency decisions more likely. The main contribution of the paper is to offer an alternative perspective on energy effciency in SMEs beyond the mere adoption of energy-effcient technology.
In recent years, the development and application of decellularized extracellular matrices (ECMs) for use as biomaterials have grown rapidly. These cell-derived matrices (CDMs) represent highly bioactive and biocompatible materials consisting of a complex assembly of biomolecules. Even though CDMs mimic the natural microenvironment of cells in vivo very closely, they still lack specifically addressable functional groups, which are often required to tailor a biomaterial functionality by bioconjugation. To overcome this limitation, metabolic glycoengineering has emerged as a powerful tool to equip CDMs with chemical groups such as azides. These small chemical handles are known for their ability to undergo bioorthogonal click reactions, which represent a desirable reaction type for bioconjugation. However, ECM insolubility makes its processing very challenging. In this contribution, we isolated both the unmodified ECM and azide-modified clickECM by osmotic lysis. In a first step, these matrices were concentrated to remove excessive water from the decellularization step. Next, the hydrogel-like ECM and clickECM films were mechanically fragmentized, resulting in easy to pipette suspensions with fragment sizes ranging from 7.62 to 31.29 μm (as indicated by the mean d90 and d10 values). The biomolecular composition was not impaired as proven by immunohistochemistry. The suspensions were used for the reproducible generation of surface coatings, which proved to be homogeneous in terms of ECM fragment sizes and coating thicknesses (the mean coating thickness was found to be 33.2 ± 7.3 μm). Furthermore, they were stable against fluid-mechanical abrasion in a laminar flow cell. When primary human fibroblasts were cultured on the coated substrates, an increased bioactivity was observed. By conjugating the azides within the clickECM coatings with alkyne-coupled biotin molecules, a bioconjugation platform was obtained, where the biotin–streptavidin interaction could be used. Its applicability was demonstrated by equipping the bioactive clickECM coatings with horseradish peroxidase as a model enzyme.
The extracellular matrix (ECM) naturally surrounds cells in humans, and therefore represents the ideal biomaterial for tissue engineering. ECM from different tissues exhibit different composition and physical characteristics. Thus, ECM provides not only physical support but also contains crucial biochemical signals that influence cell adhesion, morphology, proliferation and differentiation. Next to native ECM from mature tissue, ECM can also be obtained from the in vitro culture of cells. In this study, we aimed to highlight the supporting effect of cell-derived- ECM (cdECM) on adipogenic differentiation. ASCs were seeded on top of cdECM from ASCs (scdECM) or pre-adipocytes (acdECM). The impact of ECM on cellular activity was determined by LDH assay, WST I assay and BrdU assay. A supporting effect of cdECM substrates on adipogenic differentiation was determined by oil red O staining and subsequent quantification. Results revealed no effect of cdECM substrates on cellular activity. Regarding adipogenic differentiation a supporting effect of cdECM substrates was obtained compared to control. With these results, we confirm cdECM as a promising biomaterial for adipose tissue engineering.
Bone tissue is highly vascularized. The crosstalk of vascular and osteogenic cells is not only responsible for the formation of the strongly divergent tissue types but also for their physiological maintenance and repair. Extrusion-based bioprinting presents a promising fabrication method for bone replacement. It allows for the production of large-volume constructs, which can be tailored to individual tissue defect geometries. In this study, we used the all-gelatin-based toolbox of methacryl-modified gelatin (GM), non-modified gelatin (G) and acetylated GM (GMA) to tailor both the properties of the bioink towards improved printability, and the properties of the crosslinked hydrogel towards enhanced support of vascular network formation by simple blending. The vasculogenic behavior of human dermal microvascular endothelial cells (HDMECs) and human adipose-derived stem cells (ASCs) was evaluated in the different hydrogel formulations for 14 days. Co-culture constructs including a vascular component and an osteogenic component (i.e. a bone bioink based on GM, hydroxyapatite and ASCs) were fabricated via extrusion-based bioprinting. Bioprinted co-culture constructs exhibited functional tissue-specific cells whose interplay positively affected the formation and maintenance of vascular-like structures. The setup further enabled the deposition of bone matrix associated proteins like collagen type I, fibronectin and alkaline phosphatase within the 30-day culture.
Improvement of a three-layered in vitro skin model for topical application of irritating substances
(2020)
In the field of skin tissue engineering, the development of physiologically relevant in vitro skin models comprising all skin layers, namely epidermis, dermis, and subcutis, is a great challenge. Increasing regulatory requirements and the ban on animal experiments for substance testing demand the development of reliable and in vivo-like test systems, which enable high-throughput screening of substances. However, the reproducibility and applicability of in vitro testing has so far been insufficient due to fibroblast-mediated contraction. To overcome this pitfall, an advanced 3-layered skin model was developed. While the epidermis of standard skin models showed an 80% contraction, the initial epidermal area of our advanced skin models was maintained. The improved barrier function of the advanced models was quantified by an indirect barrier function test and a permeability assay. Histochemical and immunofluorescence staining of the advanced model showed well-defined epidermal layers, a dermal part with distributed human dermal fibroblasts and a subcutis with round-shaped adipocytes. The successful response of these advanced 3-layered models for skin irritation testing demonstrated the suitability as an in vitro model for these clinical tests: only the advanced model classified irritative and non-irritative substances correctly. These results indicate that the advanced set up of the 3-layered in vitro skin model maintains skin barrier function and therefore makes them more suitable for irritation testing.
Different types of raw cotton were investigated by a commercial ultraviolet-visible/near infrared (UV-Vis/NIR) spectrometer (210–2200 nm) as well as on a home-built setup for NIR hyperspectral imaging (NIR-HSI) in the range 1100–2200 nm. UV-Vis/NIR reflection spectroscopy reveals the dominant role proteins, hydrocarbons and hydroxyl groups play in the structure of cotton. NIR-HSI shows a similar result. Experimentally obtained data in combination with principal component analysis (PCA) provides a general differentiation of different cotton types. For UV-Vis/NIR spectroscopy, the first two principal components (PC) represent 82 % and 78 % of the total data variance for the UV-Vis and NIR regions, respectively. Whereas, for NIR-HSI, due to the large amount of data acquired, two methodologies for data processing were applied in low and high lateral resolution. In the first method, the average of the spectra from one sample was calculated and in the second method the spectra of each pixel were used. Both methods are able to explain ≥90 % of total variance by the first two PCs. The results show that it is possible to distinguish between different cotton types based on a few selected wavelength ranges. The combination of HSI and multivariate data analysis has a strong potential in industrial applications due to its short acquisition time and low-cost development. This study opens a novel possibility for a further development of this technique towards real large-scale processes.
This book presents an empirical investigation of the efforts that multinational pharmaceutical companies take in order to find a business model that allows for a profitable access to the Bottom of the Pyramid (BoP) markets. The Bottom of the Pyramid in Africa is frequently mentioned as an attractive market due to its sheer size. Yet most companies struggle to access it because of the low price level, difficult physical market access and challenges when it comes to payment.
More specifically, the book investigates the following business model-related questions: Do pharmaceutical companies provide products that meet the needs of the BoP? What characterizes the value generation of the company? What revenue model leads to a profitable business, and what role does a network of partners play in the business model?
Findings reveal that there is no ‘one-size-fits-all’ answer to these questions. Providing continuous availability, affordability at a good quality of goods and services, creating health awareness, as well as localizing business to achieve a level of inclusivenessare essential prerequisites for success. In the last chapter this book provides a business model prototype that accounts for these key success factors for business at the Bottom of the Pyramid and points to further research topics.
Here, we report the mechanical and water sorption properties of a green composite based on Typha latifolia fibres. The composite was prepared either completely binder-less or bonded with 10% (w/w) of a bio-based resin which was a mixture of an epoxidized linseed oil and a tall-oil based polyamide. The flexural modulus of elasticity, the flexural strength and the water absorption of hot pressed Typha panels were measured and the influence of pressing time and panel density on these properties was investigated. The cure kinetics of the biobased resin was analyzed by differential scanning calorimetry (DSC) in combination with the iso-conversional kinetic analysis method of Vyazovkin to derive the curing conditions required for achieving completely cured resin. For the binderless Typha panels the best technological properties were achieved for panels with high density. By adding 10% of the binder resin the flexural strength and especially the water absorption were improved significantly.
Here, we report the continuous peroxide-initiated grafting of vinyltrimethoxysilane (VTMS) onto a standard polyolefin by means of reactive extrusion to produce a functionalized liquid ethylene propylene copolymer (EPM). The effects of the process parameters governing the grafting reaction and their synergistic interactions are identified, quantified and used in a mathematical model of the extrusion process. As process variables the VTMS and peroxide concentrations and the extruder temperature setting were systematically studied for their influence on the grafting and the relative grafting degree using a face-centered central composite design (FCD). The grafting degree was quantified by 1H NMR spectroscopy. Response surface methodology (RSM) was used to calculate the most efficient grafting process in terms of chemical usage and graft yield. With the defined processing window, it was possible to make precise predictions about the grafting degree with at the same time highest possible relative degree of grafting.