Observer design for a class of nonlinear systems combining dissipativity with interconnection and damping assignment

A nonlinear observer design approach is proposed that exploits and combines port-Hamiltonian systems and dissipativity theory. First, a passivity-based observer design using interconnection and damping assignment for time variant state affine systems is presented by applying output injection to the system such that the observer error dynamics takes a port-Hamiltonian structure. The stability of the observer error system is assured by exploiting its passivity properties. Second, this setup is extended to develop an observer design approach for a class of systems with a time varying state affine forward and a nonlinear feedback contribution. For a class of nonlinear systems, the theory of dissipative observers is adapted and combined with the results for the passivity-based observer design using interconnection and damping assignment. The convergence of the compound observer design is determined by a linear matrix inequality. The performance of both observer approaches is analyzed in simulation examples

Evolution of a Lean Smart Maintenance Maturity Model towards the new Age of Industry 4.0

Over the last few years, the complexity of asset and maintenance management of industrial plants and machinery in the producing industry has risen due to higher competition and volatile environments. Smart factories, Internet of Things (IoT) and the underlying digitisation of a significant number of processes are changing the way we have to think and work in terms of asset management. Existing Lean Smart Maintenance (LSM) philosophy, which focuses on the cost-efficient (lean) and the learning organisation (smart) perspectives enables a value-oriented, dynamic, and smart maintenance/asset management. The associated LSM maturity model is the evaluation tool that contains the normative, strategic, and operational aspects of industrial asset management, based on which numerous reorganisation projects have already been carried out in industrial companies. However, due to the ever-increasing development of Industry 4.0 (I4.0), it is necessary to extend the model by selected aspects of digitisation and digitalisation. Based on a structured literature review (SLR) of state of the art I4.0 maturity models, we were able to investigate the essential maturity items for I4.0. To restructure and expand the existing LSM maturity model, the principle of design science research (DSR) was used. The architecture of the LSM maturity model was based on the structure of the Capability Maturity Model Integration (CMMI). Further development of a Lean Smart Maintenance maturity model thus covers the future requirements of I4.0 and data science. It was possible to enhance existing categories with new artefacts from the I4.0 range to represent the influence of cyber-physical systems (CPS), (big) data and information management, condition monitoring (CM) and more. Furthermore, the originally defined LSM-Model was restructured for a more simplified application in industrial use cases

Validation of a Lean Smart Maintenance Maturity Model

Rising complexity in industrial asset and maintenance management due to more volatile business environments and megatrends like Industry 4.0 has led to the need for a new perspective on these management domains. The Lean Smart Maintenance (LSM) philosophy, which focuses on both the efficient (lean) and the learning (smart) organization was introduced during the past few years, and a corresponding maturity model (MM) has been developed to guide organizations on their way to asset and maintenance excellence. This paper discusses use cases, in which the usability and the generic aspect of the LSM MM are validated by using data from three different asset management assessment projects in organizations with different types of production. Research results show that the LSM MM can be used as a basis for management system improvement, independent of production types such as one-of-a-kind industry, mass production and continuous production

Development of a Generic Framework to Assess Asset Management Maturity within Organisations

With the comprehensive Lean Smart Maintenance philosophy and its associated maturity model, organisations were given a tool to reach asset and maintenance excellence. This paper discusses the approach used to transfer the scientifically based methods and concepts of the Lean Smart Maintenance Maturity Model into an assessment structure to generate a generic tool to collect the complete and correct information necessary to determine an organisation\u27s maturity level. Research results show that a standardised assessment process combined with continuous improvement cycles, a more accurate assessment of the company\u27s maturity is possible. A well-structured MM assessment supports less experienced assessors whereby experienced assessors will not need a full questionnaire but only a well-structured list of items and their maturity levels

Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E

Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries which is usually characterized by a self-limited course. However, there is an increased risk of HEV persistence in immunocompromised risk populations, comprising patients following solid organ transplantation or hematological malignancies. Recently, chronic HEV infection following rituximab-containing treatment regimens has been described. Here we report five patients with chronic hepatitis E after prior rituximab therapy for various indications. We determined the immunological characteristics of these patients and analyzed the development of ribavirin (RBV) treatment failure-associated mutations in the HEV genome. One patient became chronically HEV-infected 110 months after administration of rituximab (RTX). Immunological characterization revealed that all patients exhibited significant hypogammaglobulinemia and CD4+ T cell lymphopenia. One patient permanently cleared HEV following weight-based ribavirin treatment while three patients failed to reach a sustained virological response. In depth mutational analysis confirmed the presence of specific mutations associated with RBV treatment failure in these patients. Our cases indicate that rituximab-containing treatment regimens might imply a relevant risk for persistent HEV infection even years after the last rituximab application. Moreover, we provide further evidence to prior observations suggesting that chronically HEV infected patients following RTX-containing treatment regimens might be difficult to treat

Eosinophilic esophagitis—established facts and new horizons

Despite dramatic advances in our understanding of the pathogenesis and course of disease in the relatively short timeframe since the discovery and first description of eosinophilic esophagitis (EoE) less than three decades ago, many open questions remain to be elucidated. For instance, we will need to better characterize atypical clinical presentations of EoE and other forms of esophageal inflammatory conditions with often similar clinical presentations, nut fulfilling current diagnostic criteria for EoE and to determine their significance and interrelationship with genuine EoE. In addition, the interrelationship of EoE with other immune-mediated diseases remains to be clarified. Hopefully, a closer look at the role of environmental factors and their interaction with genetic susceptibility often in context of atopic predisposition may enable identifying the candidate substances/agents/allergens and potentially earlier (childhood) events to trigger the condition. It appears plausible to assume that in the end—comparable to current concepts in other immune-mediated chronic diseases, such as for instance inflammatory bowel disease or asthma bronchiale—we will not be rewarded with the identification of a “one-and-only” underlying pathogenetic trigger factor, with causal responsibility for the disease in each and every EoE patient. Rather, the relative contribution and importance of intrinsic susceptibility, i.e., patient-driven factors (genetics, aberrant immune response) and external trigger factors, such as food (or aero-) allergens as well as early childhood events (e.g., infection and exposure to antibiotics and other drugs) may substantially differ among given individuals with EoE. Accordingly, selection and treatment duration of medical therapy, success rates and extent of required restriction in dietary treatment, and the need for mechanical treatment to address strictures and stenosis require an individualized approach, tailored to each patient. With the advances of emerging treatment options, the importance of such an individualized and patient-centered assessment will increase even further

A new model for preclinical testing of dermal substitutes for human skin reconstruction

Background: Currently, acellular dermal substitutes used for skin reconstruction are usually covered with split-thickness skin grafts. The goal of this study was to develop an animal model in which such dermal substitutes can be tested under standardized conditions using a bioengineered dermo-epidermal skin graft for coverage. Methods: Bioengineered grafts consisting of collagen type I hydrogels with incorporated human fibroblasts and human keratinocytes seeded on these gels were produced. Two different dermal substitutes, namely Matriderm®, and an acellular collagen type I hydrogel, were applied onto full-thickness skin wounds created on the back of immuno-incompetent rats. As control, no dermal substitute was used. As coverage for the dermal substitutes either the bioengineered grafts were used, or, as controls, human split-thickness skin or neonatal rat epidermis were used. Grafts were excised 21days post-transplantation. Histology and immunofluorescence was performed to investigate survival, epidermis formation, and vascularization of the grafts. Results: The bioengineered grafts survived on all tested dermal substitutes. Epidermis formation and vascularization were comparable to the controls. Conclusion: We could successfully use human bioengineered grafts to test different dermal substitutes. This novel model can be used to investigate newly designed dermal substitutes in detail and in a standardized wa

Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications. Keywords: biomaterials; chronic wounds; immunomodulation; intrinsic immune cell signals; regenerative medicine; skin substitutes; skin tissue engineering; wound healing

Enzymatically Crosslinked Collagen as a Versatile Matrix for In Vitro and In Vivo Co‐Engineering of Blood and Lymphatic Vasculature

Adequate vascularization is required for the successful translation of many in vitro engineered tissues. This study presents a novel collagen derivative that harbors multiple recognition peptides for orthogonal enzymatic crosslinking based on sortase A (SrtA) and Factor XIII (FXIII). SrtA-mediated crosslinking enables the rapid co-engineering of human blood and lymphatic microcapillaries and mesoscale capillaries in bulk hydrogels. Whereas tuning of gel stiffness determines the extent of neovascularization, the relative number of blood and lymphatic capillaries recapitulates the ratio of blood and lymphatic endothelial cells originally seeded into the hydrogel. Bioengineered capillaries readily form luminal structures and exhibit typical maturation markers both in vitro and in vivo. The secondary crosslinking enzyme Factor XIII is used for in situ tethering of the VEGF mimetic QK peptide to collagen. This approach supports the formation of blood and lymphatic capillaries in the absence of exogenous VEGF. Orthogonal enzymatic crosslinking is further used to bioengineer hydrogels with spatially defined polymer compositions with pro- and anti-angiogenic properties. Finally, macroporous scaffolds based on secondary crosslinking of microgels enable vascularization independent from supporting fibroblasts. Overall, this work demonstrates for the first time the co-engineering of mature micro- and meso-sized blood and lymphatic capillaries using a highly versatile collagen derivative