Integrating models and simulations of continuous dynamic system behavior into SysML

Contemporary systems engineering problems are becoming increasingly complex as they are handled by geographically distributed design teams, constrained by the objectives of multiple stakeholders, and inundated by large quantities of design information. According to the principles of model-based systems engineering (MBSE), engineers can effectively manage increasing complexity by replacing document-centric design methods with computerized, model-based approaches. In this thesis, modeling constructs from SysML and Modelica are integrated to improve support for MBSE. The Object Management Group has recently developed the Systems Modeling Language (OMG SysML ) to provide a comprehensive set constructs for modeling many common aspects of systems engineering problems (e.g. system requirements, structures, functions). Complementing these SysML constructs, the Modelica language has emerged as a standard for modeling the continuous dynamics (CD) of systems in terms of hybrid discrete- event and differential algebraic equation systems. The integration of SysML and Modelica is explored from three different perspectives: the definition of CD models in SysML; the use of graph transformations to automate the transformation of SysML CD models into Modelica models; and the integration of CD models and other SysML models (e.g. structural, requirements) through the depiction of simulation experiments and engineering analyses. Throughout the thesis, example models of a car suspension and a hydraulically-powered excavator are used for demonstration. The core result of this work is the provision of modeling abilities that do not exist independently in SysML or Modelica. These abilities allow systems engineers to prescribe necessary system analyses and relate them to stakeholder concerns and other system aspects. Moreover, this work provides a basis for model integration which can be generalized and re-specialized for integrating other modeling formalisms into SysML.M.S.Committee Chair: Chris Paredis; Committee Member: Dirk Schaefer; Committee Member: Russell Pea

Development of a Bond Graph Based Model of Computation for SystemC-AMS

The modelling and simulation capabilities of SystemC-AMS concerning conservative continuous time systems involving the interaction of several physical domains and with digital control components are currently limited. Bond graphs unify the description of multi-domain systems by modelling the energy flow between the electrical and non-electrical components. They integrate well with block diagrams describing the signal processing part of a system. The goal of this work is to integrate the bond graph formalism as a new Model of Computation (MoC) into the SystemC-AMS prototype

Model Reduction for Vehicle Systems Modelling

The full model of a double-wishbone suspension has more than 30 differential-algebraic equations which takes a remarkably long time to simulate. By contrast, the look-up table for the same suspension is simulated much faster, but may not be very accurate. Therefore, developing reduced models that approximate complex systems is necessary because model reduction decreases the simulation time in comparison with the original model, enables real time applications, and produces acceptable accuracy. In this research, we focus on model reduction techniques for vehicle systems such as suspensions and how they are approximated by models having lower degrees of freedom. First, some existing model reduction techniques, such as irreducible realization procedures, balanced truncation, and activity-based reduction, are implemented to some vehicle suspensions. Based on the application of these techniques, their disadvantages are revealed. Then, two methods of model reduction for multi-body systems are proposed. The first proposed method is 2-norm power-based model reduction (2NPR) that combines 2-norm of power and genetic algorithms to derive reduced models having lower degrees of freedom and fewer number of components. In the 2NPR, some components such as mass, damper, and spring are removed from the original system. Afterward, the values of the remaining components are adjusted by the genetic algorithms. The most important advantage of the 2NPR is keeping the topology of multi-body systems which is useful for design purposes. The second method uses proper orthogonal decomposition. First, the equations of motion for a multi-body system are converted to explicit second-order differential equations. Second, the projection matrix is obtained from simulation or experimental data by proper orthogonal decomposition. Finally, the equations of motion are transferred to a lower-dimensional state coordinate system. The implementation of the 2NPR to two double-wishbone suspensions and the comparison with other techniques such as balanced truncation and activity-based model reduction also demonstrate the efficiency of the new reduction technique

Molecular requirements involving the human platelet protease-activated receptor-4 mechanism of activation by peptide analogues of its tetheredligand

Thrombin is the most potent agonist of human platelets and its effects are primarily mediated through the protease-activated receptors (PARs)-1 and -4. Although PAR-1 has higher affinity for thrombin than PAR-4, both receptors contribute to thrombin-mediated actions on platelets. Recently, a potent and selective PAR-1 antagonist (vorapaxar) was approved for clinical use in selected patients. In contrast, despite the fact that several PAR-4 antagonists have been developed, few of them have been tested in clinical trials. The aim of the present study was to elucidate the molecular requirements involving the PAR-4 mechanism of activation by peptide analogues of its tethered-ligand. Eight synthetic PAR-4 tethered-ligand peptide analogues were synthesized and studied for their agonistic/antagonistic potency and selectivity toward human washed platelet aggregation, using light transmittance aggregometry. In addition, in silico studies were conducted to describe the receptor–peptide interactions that are developed following PAR-4 exposure to the above analogues. To provide a first structure-activity relationship rationale on the bioactivity profiles recorded for the studied analogues, molecular docking was applied in a homology model of PAR-4, derived using the crystal structure of PAR-1. The following peptide analogues were synthesized: AYPGKF-NH2 (1), GYPGKF-NH2 (2), AcAYPGKF-NH2 (3), trans-cinnamoyl-AYPGKF-NH2 (4), YPGKF-NH2 (5), Ac-YPGKF-NH2 (6), transcinnamoyl-YPGKF-NH2 (7), and caffeoyl-YPGKF-NH2 (8). Peptide (1) is a selective PAR-4 agonist inducing platelet aggregation with an IC50 value of 26.2 μM. Substitution of Ala-1 with Gly-1 resulted in peptide (2), which significantly reduces the agonistic potency of peptide (1) by 25- fold. Importantly, substitution of Ala-1 with trans-cinnamoyl-1 resulted in peptide (7), which completely abolishes the agonistic activity of peptide (1) and renders it with a potent antagonistic activity toward peptide (1)-induced platelet aggregation. All other peptides tested were inactive. Tyr-2, residue, along with its neighboring environment was a key determinant in the PAR-4 recognition mode. When the neighboring residues to Tyr-2 provided an optimum spatial ability for the ligand to enter into the binding site of the transmembrane receptor, a biological response was propagated. These results were compared with the predicted binding poses of small molecule antagonists of PAR-4, denoted as YD-3, ML-354, and BMS-986120. π–π stacking interaction with Tyr-183 appears to be critical and common for both small molecules antagonists and the peptide trans-cinnamoyl-YPGKFNH2. Conclusively, the lipophilicity, size, and aromatic nature of the residue preceding Tyr-2 are determining factors on whether a human platelet PAR-4 tethered-ligand peptide analogue will exert an agonistic or antagonistic activit

Realizing Adaptive Process-aware Information Systems with ADEPT2

In dynamic environments it must be possible to quickly implement new business processes, to enable ad-hoc deviations from the defined business processes on-demand (e.g., by dynamically adding, deleting or moving process activities), and to support dynamic process evolution (i.e., to propagate process schema changes to already running process instances). These fundamental requirements must be met without affecting process consistency and robustness of the process-aware information system. In this paper we describe how these challenges have been addressed in the ADEPT2 process management system. Our overall vision is to provide a next generation technology for the support of dynamic processes, which enables full process lifecycle management and which can be applied to a variety of application domains

A systematic re-examination of processing of MHCI-bound antigenic peptide precursors by ER aminopeptidase 1

Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims antigenic peptide precursors to generate mature antigenic peptides for presentation by major histocompatibility complex class I (MHCI) molecules and regulates adaptive immune responses. ERAP1 has been proposed to trim peptide precursors both in solution and in pre-formed MHCI-peptide complexes, but which mode is more relevant to its biological function remains controversial. Here, we compared ERAP1-mediated trimming of antigenic peptide precursors in solution or when bound to three MHCI alleles, HLA-B*58, HLA-B*08 and HLA-A*02. For all MHCI-peptide combinations, peptide binding onto MHCI protected against ERAP1-mediated trimming. In only a single MHCI-peptide combination, trimming of an HLA-B*08-bound 12mer progressed at a considerable rate, albeit still slower than in solution. Results from thermodynamic, kinetic and computational analyses suggested that this 12mer is highly labile and that apparent on-MHC trimming rates are always slower than that of MHCI-peptide dissociation. Both ERAP2 and leucine aminopeptidase, an enzyme unrelated to antigen processing, could trim this labile peptide from pre-formed MHCI complexes as efficiently as ERAP1. A pseudopeptide analogue with high affinity for both HLA-B*08 and the ERAP1 active site could not promote the formation of a ternary ERAP1-MHCI-peptide complex. Similarly, no interactions between ERAP1 and purified peptide loading complex (PLC) were detected in the absence or presence of a pseudopeptide trap. We conclude that MHCI binding protects peptides from ERAP1 degradation and that trimming in solution, along with the dynamic nature of peptide binding to MHCI, are sufficient to explain ERAP1 processing of antigenic peptide precursors

Towards a mesoscale rheology model for aqueous particulate suspensions

Particulate suspensions are ubiquitous and diverse; pharmaceutical formulations, biological fluids, magma and foodstuffs are just few of numerous examples. In many cases, the flow behaviour (rheology) of the suspension is critical to its function. A key rheological property is viscosity; a measure of a substance’s resistance to flow. This work aims to understand molecular-level mechanisms responsible for determining flow behaviour in moderately dense suspensions; 35% particles by volume (i.e., volume fraction 0.35). The industrial application of interest to this thesis is catalysis; namely, the ‘washcoat’, a key component in the performance of catalytic converters. A typical washcoat formulation is an aqueous suspension, comprising a high surface-area support powder, an active catalyst material, together with organic additives and certain salts used to optimise properties of the washcoat; including its flow behaviour. Of these components, this work investigates ‘salt-specific effects’; i.e. the influence of differing salt-types. Investigation is conducted at molecular and macroscopic resolution via simulations and experiments, respectively. The research approach probes the constituents of a suspension: the aqueous phase, the particle-aqueous phase interface, and particle interactions. Molecular dynamics simulations are employed as the foundation of this analysis, with experiments - rheology, nuclear magnetic resonance and dynamic light scattering - utilised alongside. A final set of rheology experiments is conducted on particulate suspensions of 35% volume fraction, in pure water and the aqueous salt solutions of interest. At all stages of analysis, results suggest that macroscopic behaviours are a cumulative manifestation of phenomena at molecular resolution. However, such phenomena are varied; the challenge lies in identifying which mechanisms are relevant to the behaviour of interest, how they work together, and how they manifest cumulatively. Towards a mesoscale rheology model for aqueous particulate suspensions, results are discussed in terms of input for such a model, which would predict rheology as a function of particle loading, ionic strength and possibly other factors, in future work

Proceedings of the ECCOMAS Thematic Conference on Multibody Dynamics 2015

This volume contains the full papers accepted for presentation at the ECCOMAS Thematic Conference on Multibody Dynamics 2015 held in the Barcelona School of Industrial Engineering, Universitat Politècnica de Catalunya, on June 29 - July 2, 2015. The ECCOMAS Thematic Conference on Multibody Dynamics is an international meeting held once every two years in a European country. Continuing the very successful series of past conferences that have been organized in Lisbon (2003), Madrid (2005), Milan (2007), Warsaw (2009), Brussels (2011) and Zagreb (2013); this edition will once again serve as a meeting point for the international researchers, scientists and experts from academia, research laboratories and industry working in the area of multibody dynamics. Applications are related to many fields of contemporary engineering, such as vehicle and railway systems, aeronautical and space vehicles, robotic manipulators, mechatronic and autonomous systems, smart structures, biomechanical systems and nanotechnologies. The topics of the conference include, but are not restricted to: ● Formulations and Numerical Methods ● Efficient Methods and Real-Time Applications ● Flexible Multibody Dynamics ● Contact Dynamics and Constraints ● Multiphysics and Coupled Problems ● Control and Optimization ● Software Development and Computer Technology ● Aerospace and Maritime Applications ● Biomechanics ● Railroad Vehicle Dynamics ● Road Vehicle Dynamics ● Robotics ● Benchmark ProblemsPostprint (published version

Advances in combined architecture, plant, and control design

The advancement of many engineering systems relies on novel design methodologies, design formulations, design representations, and other advancements. In this dissertation, we consider three broad design domains: architecture, plant, and control. These domains cover most of the potential design decision elements in an actively-controlled engineering system. In this dissertation, strategic aspects of this combined problem are addressed. The task of representing and generating candidate architectures is addressed with methods developed based on colored graphs built by enumerating all perfect matchings of a specified catalog of components. The proposed approach captures all architectures under specific assumptions. General combined plant and control design (or co-design) problems are examined. Previous work in co-design theory imposed restrictions on the type of problems that could be posed. Here many of those restrictions are lifted. The problem formulations and optimality conditions for both the simultaneous and nested solution strategies are given along with a detailed discussion of the two methods. Direct transcription is also discussed as it enables the solution of general co-design problems by approximating the problem. Motivated primarily by the need for efficient methods to solve certain control problems that emerge using the nested co-design method, an automated problem generation procedure is developed to support easy specification of linear-quadratic dynamic optimization problems using direct transcription and quadratic programming. Pseudospectral and single-step methods (including the zero-order hold) are all implemented in this unified framework and comparisons are made. Three detailed engineering design case studies are presented. The results from the enumeration and evaluation of all passive analog circuits with up to a certain number of components are used to synthesize low-pass filters and circuits that match a certain magnitude response. Advantages and limitations of enumerative approaches are highlighted in this case study, along with comparisons to circuits synthesized via evolutionary computation; many similarities are found in the topologies. The second case study tackles a complex co-design problem with the design of strain-actuated solar arrays for spacecraft precision pointing and jitter reduction. Nested co-design is utilized along with a linear-quadratic inner loop problem to obtain solutions efficiently. A simpler, scaled problem is analyzed to gain general insights into these results. This is accomplished with a unified theory of scaling in dynamic optimization. The final case study involves the design of active vehicle suspensions. All three design domains are considered in this problem. A class of architecture, plant, and control design problems which utilize linear physical elements is discussed. This problem class can be solved using the methods in this dissertation