A 3D Cell-Free Bone Model Shows Collagen Mineralization is Driven and Controlled by the Matrix

This project was supported by an European Research Council (ERC) Advanced Investigator grant (H2020-ERC-2017-ADV-788982-COLMIN) to N.S. A.A. was in part supported by a VENI grant from the Netherlands Scientific Organization NWO (VI.Veni.192.094).Osteons, the main organizational components of human compact bone, are cylindrical structures composed of layers of mineralized collagen fibrils, called lamellae. These lamellae have different orientations, different degrees of organization, and different degrees of mineralization where the intrafibrillar and extrafibrillar minerals are intergrown into one continuous network of oriented crystals. While cellular activity is clearly the source of the organic matrix, recent in vitro studies call into question whether the cells are also involved in matrix mineralization and suggest that this process could be simply driven by the interactions of the mineral with extracellular matrix. Through the remineralization of demineralized bone matrix, the complete multiscale reconstruction of the 3D structure and composition of the osteon without cellular involvement are demonstrated. Then, this cell-free in vitro system is explored as a realistic, functional model for the in situ investigation of matrix-controlled mineralization processes. Combined Raman and electron microscopy indicate that glycosaminoglycans (GAGs) play a more prominent role than generally assumed in the matrix-mineral interactions. The experiments also show that the organization of the collagen is in part a result of its interaction with the developing mineral.European Research Council (ERC) VI.Veni.192.094Netherlands Organization for Scientific Research (NWO) H2020-ERC-2017-ADV-788982-COLMI

Systematic Procedure for Mitigating DFIG-SSR using Phase Imbalance Compensation

Replacing conventional generation by power electronics based generation changes the dynamic characteristics of the power system. This results among others in the increased susceptibility to sub synchronous oscillations (SSO). This paper proposes a systematic procedure for mitigating the interactions between a DFIG and a series compensated transmission line using the phase imbalance compensation (PIC) concept. The impact of the series and parallel PIC on the resonance behaviour of the grid is first thoroughly investigated. Then, the influence of the system strength on the capabilities of the PIC to mitigate DFIG-SSR is assessed. Based on the findings a design framework which enables the systematic assessment of the series and parallel PIC for mitigating DFIG-SSR is developed and successfully implemented in the IEEE 39 bus system. Comparison between both concepts reveals that the parallel PIC is better suited to mitigate DFIG-SSR. The impedance based stability analysis and detailed time domain electromagnetic transient (EMT) simulations are used to screen and validate the results.Intelligent Electrical Power Grid

Evaluation of PV and QV based Voltage Stability Analyses in Converter Dominated Power Systems

PV and QV analyses have been widely used in industry. It has already been proven that these steady state methods can be used to assess power system's load ability from voltage stability perspective and that their use in terms of accuracy is justified when compared to time domain simulations. However, this prior validation was carried out for conventional synchronous generator dominated power systems. With increasing levels of power electronics interfaced generation (PEIG) being integrated in power systems, the accuracy of the PV and QV methods for these `green' power systems can be challenged. This paper investigates to what extend the use of these methods is justified when the power system faces a displacement of conventional generation with PEIG. To this end, assessments with the IEEE 9 bus system and full converter wind turbine generators have been performed in this study. It is shown that, when compared to time domain simulations, the traditional PV and QV analyses do not always accurately predict the saddle-node bifurcation point. Steady state PV analyses show inaccuracies between 1.8% and 16.8% (when compared to time domain simulations) in identification of the instability point. The mismatch between steady state and time domain QV analyses is between 6.1% and 22.9%. Based on the achieved results, QV analysis is shown to be typically less accurate than PV analysis for PEIG rich systems

Parametric Evaluation of Different ANN Architectures: Forecasting Wind Power Across Different Time Horizons

The participation of volatile wind energy resources in the generation mix of power systems is increasing. It is therefore becoming more and more crucial for system operators to accurately predict the wind power generation across different short term horizons (5 to 60 minutes ahead) in order to adequately balance the system and maintain system security. This paper presents a comprehensive assessment of the influence of different parameters in artificial neural networks, such as the amount of historic data, batch size, number of hidden layers, number of neurons per hidden layer, and the amount of training data on the short term forecast accuracy. In order to identify the parameters which are most influential with respect to forecast accuracy, a sensitivity study isolating the various factors on a one-At-A-Time basis has been performed. To minimize the forecast error across the investigated forecast horizons, the developed neural networks use the feed forward back propagation algorithm. From the investigated cases it is concluded that a neural network with two hidden layers is most suitable for wind forecasting on the timeframes considered. Furthermore, with increasing forecast horizons (from 5 to 60 minutes ahead), better performance is achieved when neural networks contain increased neurons in the hidden layers and have enlarged training data sets.Intelligent Electrical Power Grid

An Organoid for Woven Bone

Bone formation (osteogenesis) is a complex process in which cellular differentiation and the generation of a mineralized organic matrix are synchronized to produce a hybrid hierarchical architecture. To study the mechanisms of osteogenesis in health and disease, there is a great need for functional model systems that capture in parallel, both cellular and matrix formation processes. Stem cell‐based organoids are promising as functional, self‐organizing 3D in vitro models for studying the physiology and pathology of various tissues. However, for human bone, no such functional model system is yet available. This study reports the in vitro differentiation of human bone marrow stromal cells into a functional 3D self‐organizing co‐culture of osteoblasts and osteocytes, creating an organoid for early stage bone (woven bone) formation. It demonstrates the formation of an organoid where osteocytes are embedded within the collagen matrix that is produced by the osteoblasts and mineralized under biological control. Alike in in vivo osteocytes, the embedded osteocytes show network formation and communication via expression of sclerostin. The current system forms the most complete 3D living in vitro model system to investigate osteogenesis, both in physiological and pathological situations, as well as under the influence of external triggers (mechanical stimulation, drug administration)

Mucolipidosis type III, a series of adult patients

Background: Mucolipidosis type III α/β or γ (MLIII) are rare autosomal recessive diseases, in which reduced activity of the enzyme UDP-N-acetyl glucosamine-1-phosphotransferase (GlcNAc-PTase) leads to intra-lysosomal accumulation of different substrates. Publications on the natural history of MLIII, especially the milder forms, are scarce. This study provides a detailed description of the disease characteristics and its natural course in adult patients with MLIII. Methods: In this retrospective chart study, the clinical, biochemical and molecular findings in adult patients with a confirmed diagnosis of MLIII from three treatment centres were collected. Results: Thirteen patients with MLIII were included in this study. Four patients (31%) were initially misdiagnosed with a type of mucopolysaccharidosis (MPS). Four patients (31%) had mild cognitive impairment. Six patients (46%) needed help with activities of daily living (ADL) or were wheelchair-dependent. All patients had dysostosis multiplex and progressive secondary osteoarthritis, characterised by cartilage destruction and bone lesions in multiple joints. All patients underwent multiple orthopaedic surgical interventions as early as the second or third decades of life, of which total hip replacement (THR) was the most common procedure (61% of patients). Carpal tunnel syndrome (CTS) was found in 12 patients (92%) and in eight patients (61%), CTS release was performed. Conclusions: Severe skeletal abnormalities, resulting from abnormal bone development and severe progressive osteoarthritis, are the hallmark of MLIII, necessitating surgical orthopaedic interventions early in life. Future therapies for this disease should focus on improving cartilage and bone quality, preventing skeletal complications and improving mobility

Parametric Evaluation of Different ANN Architectures: Forecasting Wind Power Across Different Time Horizons

The portfolio is created for the course STAT/Math380: Statistics and Applications using backward design. It is a service course on introduction statistics for undergraduate students who are not majored in statistics at University of Nebraska-Lincoln. In this portfolio, I’ll provide the detail plans on what I will teach, how it will be taught, and what is my expectation on students learning. Besides, I’ll collect data from students to analyze whether students have achieved the course expectations, from where I’ll adjust and improve the way I deliver the knowledge in the future. This portfolio will be used to help document my teaching, share with my colleagues, and prepare my promotion and tenure

Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models

Human in vitro bone models can create the possibility for investigation of physiological bone remodeling while addressing the principle of replacement, reduction and refinement of animal experiments (3R). Current in vitro models lack cell–matrix interactions and their spatiotemporal complexity. To facilitate these analyses, a bone-mimetic template is developed in this study, inspired by bone's extracellular matrix composition and organization. Silk fibroin (SF) is used as an organic matrix, poly-aspartic acid (pAsp) is used to mimic the functionality of noncollagenous proteins, and 10× simulated body fluid serves as mineralization solution. By using pAsp in the mineralization solution, minerals are guided toward the SF material resulting in mineralization inside and as a coating on top of the SF. After cytocompatibility testing, remodeling experiments are performed in which mineralized scaffold remodeling by osteoclasts and osteoblasts is tracked with nondestructive microcomputed tomography and medium analyses over a period of 42 d. The mineralized scaffolds support osteoclastic resorption and osteoblastic mineralization, in the physiological bone remodeling specific sequence. This model could therefore facilitate the investigation of cell–matrix interactions and may thus reduce animal experiments and advance in vitro drug testing for bone remodeling pathologies like osteoporosis, where cell–matrix interactions need to be targeted

Mucolipidosis type III, a series of adult patients

Background: Mucolipidosis type III α/β or γ (MLIII) are rare autosomal recessive diseases, in which reduced activity of the enzyme UDP-N-acetyl glucosamine-1-phosphotransferase (GlcNAc-PTase) leads to intra-lysosomal accumulation of different substrates. Publications on the natural history of MLIII, especially the milder forms, are scarce. This study provides a detailed description of the disease characteristics and its natural course in adult patients with MLIII. Methods: In this retrospective chart study, the clinical, biochemical and molecular findings in adult patients with a confirmed diagnosis of MLIII from three treatment centres were collected. Results: Thirteen patients with MLIII were included in this study. Four patients (31%) were initially misdiagnosed with a type of mucopolysaccharidosis (MPS). Four patients (31%) had mild cognitive impairment. Six patients (46%) needed help with activities of daily living (ADL) or were wheelchair-dependent. All patients had dysostosis multiplex and progressive secondary osteoarthritis, characterised by cartilage destruction and bone lesions in multiple joints. All patients underwent multiple orthopaedic surgical interventions as early as the second or third decades of life, of which total hip replacement (THR) was the most common procedure (61% of patients). Carpal tunnel syndrome (CTS) was found in 12 patients (92%) and in eight patients (61%), CTS release was performed. Conclusions: Severe skeletal abnormalities, resulting from abnormal bone development and severe progressive osteoarthritis, are the hallmark of MLIII, necessitating surgical orthopaedic interventions early in life. Future therapies for this disease should focus on improving cartilage and bone quality, preventing skeletal complications and improving mobility