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The extracellular matrix (ECM) is the non-cellular part of tissues and represents the natural environment of the cells. Next to structural stability, it provides various physical, chemical, and mechanical cues that strongly regulate and influence cellular behavior and are required for tissue morphogenesis, differentiation, and homeostasis. Due to its promising characteristics, ECM is used in a wide range of tissue engineering and regenerative medicine approaches as a biomaterial for coatings and scaffolds. To date, there are two sources for ECM material. First, native ECM is generated by the removal of the residing cells of a tissue or organ (decellularized ECM; dECM). Secondly, cell-derived ECM (cdECM) can be generated by and isolated from in vitro cultured cells. Although both types of ECM were intensively used for tissue engineering and regenerative medicine approaches, studies directly characterizing and comparing them are rare. Hence, in the first part of this thesis, dECM from adipose tissue and cdECM from stem cells and adipogenic differentiated stem cells from adipose tissue (ASCs) were characterized towards their macromolecular composition, structural features, and biological purity. The dECM was found to exhibit higher levels of collagens and lower levels of sulfated glycosaminoglycans compared to cdECMs. Structural characteristics revealed an immature state of collagen fibers in cdECM samples. The obtained results revealed differences between the two ECMs that can relevantly impact cellular behavior and subsequently experimental outcome and should therefore be considered when choosing a biomaterial for a specific application. The establishment of a functional vascular system in tissue constructs to realize an adequate nutrient supply remains challenging. In the second part, the supporting effect of cdECM on the self‐assembled formation of prevascular‐like structures by microvascular endothelial cells (mvECs) was investigated. It could be observed that cdECM, especially adipogenic differentiated cdECM, enhanced the formation of prevascular-like structures. An increased concentration of proangiogenic factors was found in cdECM substrates. The demonstration of cdECMs capability to induce the spontaneous formation of prevascular‐like structures by mvECs highlights cdECM as a promising biomaterial for adipose tissue engineering. Depending on the purpose of the ECM material chemical modification might be necessary. In the third and last part, the chemical functionalization of cdECM with dienophiles (terminal alkenes, cyclopropene) by metabolic glycoengineering (MGE) was demonstrated. MGE allows the chemical functionalization of cdECM via the natural metabolism of the cells and without affecting the chemical integrity of the cdECM. The incorporated dienophile chemical groups can be specifically addressed via catalysts-free, cell-friendly inverse electron-demand Diels‐Alder reaction. Using this system, the successful modification of cdECM from ASCs with an active enzyme could be shown. The possibility to modify cdECM via a cell-friendly chemical reaction opens up a wide range of possibilities to improve cdECM depending on the purpose of the material. Altogether, this thesis highlighted the differences between adipose dECM and cdECM from ASCs and demonstrated cdECM as a promising alternative to native dECM for application in tissue engineering and regenerative medicine approaches.
Over the last decades, a tremendous change toward using information technology in almost every daily routine of our lives can be perceived in our society, entailing an incredible growth of data collected day-by-day on Web, IoT, and AI applications.
At the same time, magneto-mechanical HDDs are being replaced by semiconductor storage such as SSDs, equipped with modern Non-Volatile Memories, like Flash, which yield significantly faster access latencies and higher levels of parallelism. Likewise, the execution speed of processing units increased considerably as nowadays server architectures comprise up to multiple hundreds of independently working CPU cores along with a variety of specialized computing co-processors such as GPUs or FPGAs.
However, the burden of moving the continuously growing data to the best fitting processing unit is inherently linked to today’s computer architecture that is based on the data-to-code paradigm. In the light of Amdahl's Law, this leads to the conclusion that even with today's powerful processing units, the speedup of systems is limited since the fraction of parallel work is largely I/O-bound.
Therefore, throughout this cumulative dissertation, we investigate the paradigm shift toward code-to-data, formally known as Near-Data Processing (NDP), which relieves the contention on the I/O bus by offloading processing to intelligent computational storage devices, where the data is originally located.
Firstly, we identified Native Storage Management as the essential foundation for NDP due to its direct control of physical storage management within the database. Upon this, the interface is extended to propagate address mapping information and to invoke NDP functionality on the storage device. As the former can become very large, we introduce Physical Page Pointers as one novel NDP abstraction for self-contained immutable database objects.
Secondly, the on-device navigation and interpretation of data are elaborated. Therefore, we introduce cross-layer Parsers and Accessors as another NDP abstraction that can be executed on the heterogeneous processing capabilities of modern computational storage devices. Thereby, the compute placement and resource configuration per NDP request is identified as a major performance criteria. Our experimental evaluation shows an improvement in the execution durations of 1.4x to 2.7x compared to traditional systems. Moreover, we propose a framework for the automatic generation of Parsers and Accessors on FPGAs to ease their application in NDP.
Thirdly, we investigate the interplay of NDP and modern workload characteristics like HTAP. Therefore, we present different offloading models and focus on an intervention-free execution. By propagating the Shared State with the latest modifications of the database to the computational storage device, it is able to process data with transactional guarantees. Thus, we achieve to extend the design space of HTAP with NDP by providing a solution that optimizes for performance isolation, data freshness, and the reduction of data transfers. In contrast to traditional systems, we experience no significant drop in performance when an OLAP query is invoked but a steady and 30% faster throughput.
Lastly, in-situ result-set management and consumption as well as NDP pipelines are proposed to achieve flexibility in processing data on heterogeneous hardware. As those produce final and intermediary results, we continue investigating their management and identified that an on-device materialization comes at a low cost but enables novel consumption modes and reuse semantics. Thereby, we achieve significant performance improvements of up to 400x by reusing once materialized results multiple times.
Advancements in Internet of Things (IoT), cloud and mobile computing have fostered the digital enrichment—or “digitization”—of physical products, which are gaining increasing relevance in practice. According to recent studies, global IoT spending will exceed USD 1 Trillion by 2021 and there will be over 25 billion IoT connections (KPMG, 2018). Porter and Heppelmann (2014) state that IT is “revolutionizing products [as …] IT is becoming an integral part of the product itself.” Senior business executives like GE’s former CEO Jeff Immelt (2015) are even proposing that “every industrial company in the coming age is also going to become a software and analytics company.” This reflects the increasing relevance of IT components’ (i.e., software, data analytics, cloud computing) integration into previously purely physical products. We call IT-enriched physical products, “digitized” products to differentiate them from purely intangible “digital” products, such as digital music, e-books, and software. Examples of digitized products include the Philips Hue smartphone-controllable lightbulb, Audi Connect internet-connected cars, or Rolls-Royce’s sensor-enabled pay per use jet engines.
Digitized products provide their producers with a wide range of opportunities to offer new functionality and product capabilities (e.g., autonomy) that traditional, physical products do not exhibit (Porter and Heppelmann, 2014). In addition, the digitization of products allows producers to continuously repurpose their offerings, by extending and/or changing the product functionality and, thus, enabling new value creation opportunities. Based on their re-programmability and connectivity, digitized products “remain essentially incomplete […] throughout their lifetime as users continue to add and delete […] and change […] functional capabilities” (Yoo, 2013). For instance, the Philips Hue connected lightbulb enables remote control of basic functions (e.g., switching on and off the light) as well as setting more advanced light scenes for day-to-day tasks (e.g., relax, read) via Amazon’s Alexa artificial intelligence assistant (Signify, 2019), offerings that were not intended use cases when Signify (previously known as Philips Lighting) created Hue in 2012. Thus, digitized products present limitless potentials for new functionality and unforeseen use cases, which provides them with a huge innovation capacity.
Despite the limitless potentials offered by digitized products, there has been a slow uptake of digitized products by businesses so far (Jernigan et al., 2016; Mocker et al., 2019). According to a 2016 MIT Sloan Management Review report (Jernigan et al., 2016) only 24% of the investigated firms were actively using IoT technologies – a key technology for digitized products. In a more recent research study Mocker et al. (2019) found that the median revenue share from digital offerings (i.e., solutions based on IT enriched products) in large companies only accounted for 5% of the total revenue of the investigated companies.
The slow uptake of digitized products might be explained by the challenges that firms face regarding the changing nature of digitized products. Pervasive digital technologies (such as IoT) change the nature of products by adding new functionality that was previously not part of the value proposition of the products/services (e.g., a pair of shoes embedded with sensors and connectivity allows joggers to have access to data regarding their run distance, speed, etc.) (Yoo et al., 2012). The addition of new functionality and use cases of digitized products makes it harder for producers to design and develop relevant products (Hui 2014). As described in the paper ‘Do Your Customers Actually Want a “Smart” Version of Your Product?’, “just because [firms] can make something with IoT technology doesn’t mean people will want it.” (Smith, 2017).
The shift in digitized products’ nature poses new challenges for producers along the entire product development process (Porter and Heppelmann, 2015; Yoo et al., 2012) and create a paradox in product digitization, described by Yoo et al. (2012) as the paradox of pace: while technology accelerates the rate of innovation, companies need to spend more time to digitize their products, extending time to market. The production of these digitized products also becomes more challenging, e.g., as companies need to deal with different clock-speeds of software and hardware development (Porter and Heppelman, 2015). The above-mentioned challenges suggest that producers need to better understand how they can generate value from their digitized products’ generative potentials.
The body of literature on digitized products has been growing in recent years. For instance, Herterich et al. (2016) investigate how digitized product affordances (i.e., potentials) enable industrial service innovation; Nicolescu et al. (2018) explore the emerging meanings of value associated with IoT; and Benbunan-Fich (2019) studies the impact of basic wearable sensors on the quality of the user experience. However, it remains unclear what it takes for firms to generate value with their digitized product potentials. This dissertation investigates this research gap.