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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.
Für den Unternehmer wichtig ist, binnen welcher Fristen er als Käufer seine Rechte bei Sachmängeln geltend machen muss. Ist der Unternehmer Verkäufer, kann er sich erst nach Verjährungsvollendung endgültig zurücklehnen und sicher sein, dass keine Gewährleistungsansprüche gegen ihn mehr geltend gemacht werden können. Im nationalen Rechtsverkehr hat man sich auf Verkäufer- und Käuferseite mittlerweile an die zweijährige Regelfrist im BGB gewöhnt. Welche Fristen im Auslandsgeschäft gelten, ist dagegen oft unklar, weil sich die nationalen Verjährungsfristen oft unterscheiden: Allein in Europa gibt es bei der kaufrechtlichen Gewährleistung Verjährungsfristen zwischen sechs Monaten und sechs Jahren.
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.
nKV in action: accelerating KVstores on native computational storage with NearData processing
(2020)
Massive data transfers in modern data intensive systems resulting from low data-locality and data-to-code system design hurt their performance and scalability. Near-data processing (NDP) designs represent a feasible solution, which although not new, has yet to see widespread use.
In this paper we demonstrate various NDP alternatives in nKV, which is a key/value store utilizing native computational storage and near-data processing. We showcase the execution of classical operations (GET, SCAN) and complex graph-processing algorithms (Betweenness Centrality) in-situ, with 1.4x-2.7x better performance due to NDP. nKV runs on real hardware - the COSMOS+ platform.
Massive data transfers in modern key/value stores resulting from low data-locality and data-to-code system design hurt their performance and scalability. Near-data processing (NDP) designs represent a feasible solution, which although not new, have yet to see widespread use.
In this paper we introduce nKV, which is a key/value store utilizing native computational storage and near-data processing. On the one hand, nKV can directly control the data and computation placement on the underlying storage hardware. On the other hand, nKV propagates the data formats and layouts to the storage device where, software and hardware parsers and accessors are implemented. Both allow NDP operations to execute in host-intervention-free manner, directly on physical addresses and thus better utilize the underlying hardware. Our performance evaluation is based on executing traditional KV operations (GET, SCAN) and on complex graph-processing algorithms (Betweenness Centrality) in-situ, with 1.4×-2.7× better performance on real hardware – the COSMOS+ platform.
Massive data transfers in modern data intensive systems resulting from low data-locality and data-to-code system design hurt their performance and scalability. Near-data processing (NDP) and a shift to code-to-data designs may represent a viable solution as packaging combinations of storage and compute elements on the same device has become viable.
The shift towards NDP system architectures calls for revision of established principles. Abstractions such as data formats and layouts typically spread multiple layers in traditional DBMS, the way they are processed is encapsulated within these layers of abstraction. The NDP-style processing requires an explicit definition of cross-layer data formats and accessors to ensure in-situ executions optimally utilizing the properties of the underlying NDP storage and compute elements. In this paper, we make the case for such data format definitions and investigate the performance benefits under NoFTL-KV and the COSMOS hardware platform.
The tale of 1000 cores: an evaluation of concurrency control on real(ly) large multi-socket hardware
(2020)
In this paper, we set out the goal to revisit the results of “Starring into the Abyss [...] of Concurrency Control with [1000] Cores” and analyse in-memory DBMSs on today’s large hardware. Despite the original assumption of the authors, today we do not see single-socket CPUs with 1000 cores. Instead multi-socket hardware made its way into production data centres. Hence, we follow up on this prior work with an evaluation of the characteristics of concurrency control schemes on real production multi-socket hardware with 1568 cores. To our surprise, we made several interesting findings which we report on in this paper.
In this paper, we present a new approach for achieving robust performance of data structures making it easier to reuse the same design for different hardware generations but also for different workloads. To achieve robust performance, the main idea is to strictly separate the data structure design from the actual strategies to execute access operations and adjust the actual execution strategies by means of so-called configurations instead of hard-wiring the execution strategy into the data structure. In our evaluation we demonstrate the benefits of this configuration approach for individual data structures as well as complex OLTP workloads.
Modern mixed (HTAP)workloads execute fast update-transactions and long running analytical queries on the same dataset and system. In multi-version (MVCC) systems, such workloads result in many short-lived versions and long version-chains as well as in increased and frequent maintenance overhead.
Consequently, the index pressure increases significantly. Firstly, the frequent modifications cause frequent creation of new versions, yielding a surge in index maintenance overhead. Secondly and more importantly, index-scans incur extra I/O overhead to determine, which of the resulting tuple versions are visible to the executing transaction (visibility-check) as current designs only store version/timestamp information in the base table – not in the index. Such index-only visibility-check is critical for HTAP workloads on large datasets.
In this paper we propose the Multi Version Partitioned B-Tree (MV-PBT) as a version-aware index structure, supporting index-only visibility checks and flash-friendly I/O patterns. The experimental evaluation indicates a 2x improvement for analytical queries and 15% higher transactional throughput under HTAP workloads. MV-PBT offers 40% higher tx. throughput compared to WiredTiger’s LSM-Tree implementation under YCSB.
Customer orientation should be the core engine of every organisation while IT can be considered as the enabler to generate competitive advantages along customer processes in marketing, sales and service. Research shows that customer relationship management (CRM) enables organisations to perform better and experience indicates that organisations that focus on customer orientation are more successful. With marketplace organisations such as Amazon, Alibaba or Conrad shaping the future of customer centricity and information technology, German B2B organisations need to shift their value contribution from product-centric to customer-centric. While these organisations are currently attempting to implement CRM software and putting their customers more into focus, the question remains how organisations are approaching the implementation of CRM and whether these attempts are paying off in terms of business performance.
Here, we study resin cure and network formation of solid melamine formaldehyde pre-polymer over a large temperature range viadynamic temperature curing profiles. Real-time infrared spectroscopy is used to analyze the chemical changes during network formation and network hardening. By applying chemometrics (multivariate curve resolution,MCR), the essential chemical functionalities that constitute the network at a given stage of curing are mathematically extracted and tracked over time. The three spectral components identified by MCR were methylol-rich, ether linkages-rich and methylene linkages-rich resin entities. Based on dynamic changes of their characteristic spectral patterns in dependence of temperature, curing is divided into five phases: (I) stationary phase with free methylols as main chemical feature, (II) formation of flexible network cross-linked by ether linkages, (III) formation of rigid, ether-cross-linked network, (IV) further hardening via transformation of methylols and ethers into methylene-cross-linkages, and (V) network consolidation via transformation of ether into methylene bridges. The presented spectroscopic/chemometric approach can be used as methodological basis for the functionality design of MF-based surface films at the stage of laminate pressing, i.e., for tailoring the technological property profile of cured MF films using a causal understanding of the underlying chemistry based on molecular markers and spectroscopic fingerprints.
Dieser Beitrag gibt einen Überblick über die verschiedenen Möglichkeiten der Bilanzierung einens Initial Coin Offerings (ICO) beim Emittenten auf der Passivseite nach den Regelungen der IFRS. Ziel ist es, die bilanzielle Einordnung anhand verschiedenenr Arten von Token zu erörtern und den Emittenten bei der Ausgestaltung der Token sowie der anschließenden Bilanzierung zu unterstützen. Die Ergebnisse zeigen, dass die Standards für die bilanzielle Einordnung von ICO-Token zwar ausreichen, allerdings eine große Bandbreite der Bilanzierung zu berücksichtigen ist und eine detaillierte Regelung durch einen eigenen IFRS daher schwierig erscheint.
Das Value-Engineering in der Kundenkommunikation ist eine strukturierte Methode, Kommunikationsprozesse zwischen Unternehmen zu verbessern. Das Konzept greift bewährte Elemente der technischen Wertanalyse und der Gemeinkosten-Wertanalyse auf und überträgt sie auf die Kundenkommunikation. Der Ansatz bietet eine systematische Vorgehensweise, Kommunikationsprozesse zwischen Anbieter und Kunde zu durchleuchten und neu zu gestalten. Value-Engineering in der Kundenkommunikation schafft somit Wettbewerbsvorteile durch eine Optimierung der Kommunikation.
The article studies a novel approach of inflation modeling in economics. We utilize a stochastic differential equation (SDE) of the form dXt=aXtdt+bXtdBtH, where dBtH is a fractional Brownian motion in order to model inflationary dynamics. Standard economic models do not capture the stochastic nature of inflation in the Eurozone. Thus, we develop a new stochastic approach and take into consideration fractional Brownian motions as well as Lévy processes. The benefits of those stochastic processes are the modeling of interdependence and jumps, which is equally confirmed by empirical inflation data. The article defines and introduces the rules for stochastic and fractional processes and elucidates the stochastic simulation output.