Implementation and Validation of Finite Element Framework for Passive and Active Membrane Transport in Deformable Multiphasic Models of Biological Tissues and Cells

The chondrocyte is the only cell type in articular cartilage, and its role is to maintain cartilage integrity by synthesizing and releasing macromolecules into the extracellular matrix (ECM) or breaking down its damaged constituents (Stockwell, 1991). The two major constituents of the ECM are type II collagen and aggrecans (aggregating proteoglycans). Proteoglycans have a high negative charge which attracts cations and increases the osmolarity, while also lowering the pH of the interstitial fluid. The fibrillar collagen matrix constrains ECM swelling that results from the Donnan osmotic pressure produced by proteoglycans (Wilkins et al., 2000). Activities of daily living produce fluctuating mechanical loads on the tissue which also alter the mechano-electro-chemical environment of chondrocytes embedded in the ECM. These conditions affect the physiology and function of chondrocytes directly (Wilkins et al., 2000; Guilak et al., 1995; Guilak et al., 1999). Relatively few studies of in situ chondrocyte mechanics have been reported in the biomechanics literature, in contrast to the more numerous experimental studies of the mechanobiological response of live cartilage explants to various culture and loading conditions. Analyses of chondrocyte mechanics can shed significant insights in the interpretation of experimental mechanobiological responses. Predictions from carefully formulated biomechanics models may also generate hypotheses about the mechanisms that transduce signals to chondrocytes via mechanical, electrical and chemical pathways. Therefore, computational tools that can model the response of cells, embedded within a charged hydrated ECM, to various loading conditions may serve a valuable role in mechanobiological studies. Computational modeling has become a necessary tool to study biomechanics with complex geometries and mechanisms (De et al., 2010). Usually, theoretical and computational models of cell physiology and biophysics are formulated in 1D, deriving solutions by solving ordinary differential equations, such as cell volume regulation (Tosteson and Hoffman, 1960), pH regulation (Boron and De Weer, 1976), and Ca2+ regulation (Schuster et al., 2002). Cell modeling software, such as The Virtual Cell (vcell.org Moraru et al. (2008)), analyze stationary cell shapes and isolated cells. To model the cell-ECM system while accounting for ECM deformation, the fibrillar nature of the ECM, interstitial fluid flow, solute transport, and electrical potential arising from Donnan or streaming effects, we adopt the multiphasic theory framework (Ateshian, 2007). This framework serves as the foundation of multiphasic analyses in the open source finite element software FEBio (Maas et al., 2012; Ateshian et al., 2013), which was developed specifically for biomechanics and biophysics, and offers a suitable environment to solve complex models of cell-ECM interactions in 3D. In the studies proposed here, we will extend the functionality of FEBio to further investigate the cell-ECM system. These extensions and studies are summarized in the following chapters: Chapter 1: This introductory chapter provides the general background and specific aims of this dissertation. Chapter 2: Cell-ECM interactions depend significantly on the ECM response to external loading conditions. For fibrillar soft tissues such as articular cartilage, it has been shown that modeling the ECM using a continuous fiber distribution produces much better agreement with experimental measurements of its response to loading. However, evaluating the stress and elasticity tensors for such distributions is computationally very expensive in a finite element analysis. In this aim we develop a new numerical integration scheme to calculate these tensors more efficiently than standard techniques, only accounting for fibers that are in tension. Chapter 3: Cell-ECM interactions also depend significantly on accurate modeling of selective transport across the cell membrane. However, the thickness of this membrane is typically three orders of magnitude smaller than the cell size, which poses significant numerical challenges when modeling the membrane using the finite element method, such as element locking. To date, no existing finite element software offers a multiphasic membrane element. In this aim, we formulate and implement a new membrane element in FEBio, which can accommodate fluid and solute transport within the biphasic and multiphasic framework, to model passive and selective transport across the cell membrane. Chapter 4: This aim extends Aim 2 to incorporate reactions across multiphasic membrane elements in FEBio, to model the conformational reactions of cell membrane transporters, such as carrier-mediated transporters and membrane pumps. This implementation is verified against standard models for the regulation of cell volume, pH, and Ca2+. Chapter 5: This final chapter provides a summary of the advances contributed in this dissertation, along with suggestions for future aims related to the topics covered here. With the completion of these aims, we have extended the modeling capabilities for cell physiology and mechanobiology to more complex multicellular systems embedded within their ECM, while subjected to a range of varying mechanical, electrical or chemical loading conditions

Roadmap on measurement technologies for next generation structural health monitoring systems

Structural health monitoring (SHM) is the automation of the condition assessment process of an engineered system. When applied to geometrically large components or structures, such as those found in civil and aerospace infrastructure and systems, a critical challenge is in designing the sensing solution that could yield actionable information. This is a difficult task to conduct cost-effectively, because of the large surfaces under consideration and the localized nature of typical defects and damages. There have been significant research efforts in empowering conventional measurement technologies for applications to SHM in order to improve performance of the condition assessment process. Yet, the field implementation of these SHM solutions is still in its infancy, attributable to various economic and technical challenges. The objective of this Roadmap publication is to discuss modern measurement technologies that were developed for SHM purposes, along with their associated challenges and opportunities, and to provide a path to research and development efforts that could yield impactful field applications. The Roadmap is organized into four sections: distributed embedded sensing systems, distributed surface sensing systems, multifunctional materials, and remote sensing. Recognizing that many measurement technologies may overlap between sections, we define distributed sensing solutions as those that involve or imply the utilization of numbers of sensors geometrically organized within (embedded) or over (surface) the monitored component or system. Multi-functional materials are sensing solutions that combine multiple capabilities, for example those also serving structural functions. Remote sensing are solutions that are contactless, for example cell phones, drones, and satellites. It also includes the notion of remotely controlled robots

Novel Covalent Organic Frameworks (COFs) for Electrochemical Energy Storage and Conversion

Covalent Organic Frameworks (COFs) are a new type of crystalline porous organic materials composed of covalently linked organic molecular modules. They possess the advantages of ordered channels, nano-scale pore structures, large specific surface areas and high crystallinity. Meanwhile, unlike traditional linear polymerization leading to uncontrolled product structures, COFs can be designed to form highly regular structures in two or even three dimensions. In addition, rigid structures can provide excellent stability for COFs. Furthermore, the designable structure allows functional groups to be introduced into COFs to meet the specific requirements of devices. As a result, COFs have been widely used in various fields. In particular, COFs have been found to be suitable for electrochemical energy conversion and storage applications. In this thesis, I present two conceptual applications of COFs as electrochemical active material in supercapacitors for energy storage and as electrocatalysts bearing the metal-nitrogen-carbon single-atom structure for the oxygen reduction reaction. The results demonstrated in this thesis represent the specific applications of COFs in electrochemistry, offering further possibilities and new ideas for developing novel materials for electrochemical energy storage and conversion

Active thermography for the investigation of corrosion in steel surfaces

The present work aims at developing an experimental methodology for the analysis of corrosion phenomena of steel surfaces by means of Active Thermography (AT), in reflexion configuration (RC). The peculiarity of this AT approach consists in exciting by means of a laser source the sound surface of the specimens and acquiring the thermal signal on the same surface, instead of the corroded one: the thermal signal is then composed by the reflection of the thermal wave reflected by the corroded surface. This procedure aims at investigating internal corroded surfaces like in vessels, piping, carters etc. Thermal tests were performed in Step Heating and Lock-In conditions, by varying excitation parameters (power, time, number of pulse, ….) to improve the experimental set up. Surface thermal profiles were acquired by an IR thermocamera and means of salt spray testing; at set time intervals the specimens were investigated by means of AT. Each duration corresponded to a surface damage entity and to a variation in the thermal response. Thermal responses of corroded specimens were related to the corresponding corrosion level, referring to a reference specimen without corrosion. The entity of corrosion was also verified by a metallographic optical microscope to measure the thickness variation of the specimens

Roadmap on measurement technologies for next generation structural health monitoring systems

Structural health monitoring (SHM) is the automation of the condition assessment process of an engineered system. When applied to geometrically large components or structures, such as those found in civil and aerospace infrastructure and systems, a critical challenge is in designing the sensing solution that could yield actionable information. This is a difficult task to conduct cost-effectively, because of the large surfaces under consideration and the localized nature of typical defects and damages. There have been significant research efforts in empowering conventional measurement technologies for applications to SHM in order to improve performance of the condition assessment process. Yet, the field implementation of these SHM solutions is still in its infancy, attributable to various economic and technical challenges. The objective of this Roadmap publication is to discuss modern measurement technologies that were developed for SHM purposes, along with their associated challenges and opportunities, and to provide a path to research and development efforts that could yield impactful field applications. The Roadmap is organized into four sections: distributed embedded sensing systems, distributed surface sensing systems, multifunctional materials, and remote sensing. Recognizing that many measurement technologies may overlap between sections, we define distributed sensing solutions as those that involve or imply the utilization of numbers of sensors geometrically organized within (embedded) or over (surface) the monitored component or system. Multi-functional materials are sensing solutions that combine multiple capabilities, for example those also serving structural functions. Remote sensing are solutions that are contactless, for example cell phones, drones, and satellites. It also includes the notion of remotely controlled robots

LIVING CAPACITORS: FUNCTIONAL CHARACTERIZATION OF A NOVEL CYTOCHROME ACTING AS A NANOWIRE

In an Era where environmental issues are a growing concern, microorganisms that have remarkable features, such as extracellular electron transfer (EET) ability, present major opportunities in diverse biotechnological fields. Geobacter bacteria have shown an extraordinary respiratory flexibility, with its dissimilatory metal reduction ability and EET to electrode surfaces, and numerous c-type cytochromes were pointed as key players. However, the understanding of the mechanisms involved and hence, the advances in practical applications, are still in its early days and it is crucial to move further and unveil not only the components involved, but also their roles and partners in electron transfer. The dodecaheme GSU1996, composed of four similar triheme domains (A–D), was proposed to work as a natural nanowire, owing to its linear structure and large number of hemes. In this work, the in vitro functional characterization of the GSU1996 was attempted, in a modular characterization based strategy. Here, the triheme domains C and D assisted in the characterization of the C-terminal end of GSU1996, the hexaheme fragment CD. The first step encompassed the assignment of the heme groups signals in the nuclear magnetic resonance spectra of the triheme domains and of the hexaheme fragment, which is the protein with the highest number of hemes assigned to date. The second step comprised the determination of the microscopic thermodynamic parameters of fragment CD. This provided mechanistic information on the dominant microstates and included the determination of the reduction potentials of the hemes, redox interactions between hemes and ionizable centers and among neighboring hemes. The third and final step consisted in the determination of the microscopic kinetic parameters of fragment CD. This unveiled details about the reactivity of the heme groups and included the calculation of the reference rate constants for each heme in the reduction/oxidation process. All combined, the data revealed that a heme located at the end of the C-terminal edge of GSU1996 shows the necessary skills to accept electrons from redox partners. In vitro interaction studies performed between GSU1996 and the periplasmic cytochrome PpcA and its homologues (PpcC–E), revealed that it is possible that GSU1996 and PpcA may be redox partners in G. sulfurreducens, as they form a transient redox complex that involves the C-terminal fragment of GSU1996. Work has also been started to disclose other electron transfer components of G. sulfurreducens, namely, the outer membrane tetraheme cytochrome OmcE; the hexaheme OmcS and the nanowire cytochrome GSU2210. New constructs and expression systems were tested, based in the pBAD vector, albeit none of the attempts have been successful. Although in vitro studies provide information and allow the evaluation of the functional properties of these proteins, in vivo studies are essential to assess the actual roles and interacting partners in the cells. Therefore, a novel approach was also tested towards the in vivo labeling of c-type cytochromes, based in the attachment of a tetracysteine tag that is fluorescent upon binding with commercially available biarsenical dyes. However, no expression of the model tagged protein was accomplished

12th EASN International Conference on "Innovation in Aviation & Space for opening New Horizons"

Epoxy resins show a combination of thermal stability, good mechanical performance, and durability, which make these materials suitable for many applications in the Aerospace industry. Different types of curing agents can be utilized for curing epoxy systems. The use of aliphatic amines as curing agent is preferable over the toxic aromatic ones, though their incorporation increases the flammability of the resin. Recently, we have developed different hybrid strategies, where the sol-gel technique has been exploited in combination with two DOPO-based flame retardants and other synergists or the use of humic acid and ammonium polyphosphate to achieve non-dripping V-0 classification in UL 94 vertical flame spread tests, with low phosphorous loadings (e.g., 1-2 wt%). These strategies improved the flame retardancy of the epoxy matrix, without any detrimental impact on the mechanical and thermal properties of the composites. Finally, the formation of a hybrid silica-epoxy network accounted for the establishment of tailored interphases, due to a better dispersion of more polar additives in the hydrophobic resin