Design of an Event Based Messaging System

B2B document handling is moving from paper to electronic networks and electronic domain very rapidly. Moving, handling and transforming large electronic business documents requires a lot from the systems handling them. This paper explores new technologies such as SOA, event-driven systems and ESB and a scalable, event-driven enterprise service bus is created to demonstrate these new approaches to message handling. As an end result, we have a small but fully functional messaging system with several different components. This is the first larger Java-project done in-house, so on the side we developed our own set of best practices of Java development, setting up configurations, tools, code repositories and class naming and much more.

A new approach to evaluate immobilization of β-galactosidase on Eupergit® C: structural, kinetic, and thermal characterization

This study aimed to evaluate β-galactosidase immobilization. For this purpose, the ionic strength of the buffer, reaction time, amount of the immobilization support, and pH were evaluated by a central composite design. Assay 8, which consisted of 1.5 mol L-1 phosphate buffer (pH 7.5) and a reaction time of 2 h, produced the maximum yield. Eupergit® C (400 mg) was subsequently used as an immobilization support. Immobilization kinetics wereinvestigated, and a significant increase in the yield was obtained after immobilization compared with that obtained from assay 8 (22.0 U mL-1 vs. 15.6 U mL-1). The enzyme efficiency of actuation was evaluated using o-nitrophenyl-β-D-galactopyranoside and lactose, with lactose providing better results. The reuse of β-galactosidase was evaluated, and more than 50% of the initial enzyme activity was maintained after five cycles of use. Enzyme characterization revealed that immobilization improved some aspects of the thermostability of β-galactosidase.

Structural bioinformatics study of cyclin-dependent kinases complexed with inhibitors

The present work describes molecular models for the binary complexes CDK9, CDK5 and CDK1 complexed with Flavopiridol and Roscovitine. These structural models indicate that the inhibitors strongly bind to the ATP-binding pocket of CDKs and the structural comparison with the complexes CDK2:Flavopiridol and CDK2:Roscovitine correlates the structural differences with differences in inhibition of these CDKs by the inhibitors. These structures open the possibility of testing new inhibitor families, in addition to new substituents for the already known lead structures such as flavones and adenine derivatives.

DPS-Like Peroxide Resistance Protein: Structural and Functional Studies on a Versatile Nanocontainer

Oxidative stress is a constant threat to almost all organisms. It damages a number of biomolecules and leads to the disruption of many crucial cellular functions. It is caused by reactive oxygen species (ROS), such as hydrogen peroxide (H2O₂), superoxide (•O₂ -), and hydroxyl radical (•OH). The most harmful of these compounds is •OH, which is only formed in cells in the presence of redox-cycling transition metals, such as iron and copper. Bacteria have developed a number of mechanisms to cope with ROS. One of the most widespread means employed by bacteria is the DNA-binding proteins from starved cells (Dps). Dps proteins protect the cells by binding and oxidizing Fe2+, thus greatly reducing the production of •OH. The oxidized iron is stored inside the protein as an iron core. In addition, Dps proteins bind directly to DNA forming a protective coating that shields DNA from harmful agents. Moreover, Dps proteins have been found to elicit other protective functions in cells and to participate in bacterial virulence. Dps proteins are of special importance to Streptococci owing to the lack of catalase in this genus of bacteria.This study was focused on structural and functional characterization of streptococcal Dpslike peroxide resistance (Dpr) proteins. Initially, crystal structures of Streptococcus pyogenes Dpr were determined. The data confirmed the presence of a di-metal ferroxidase center (FOC) in Dpr proteins and revealed the presence of a novel N-terminal helix as well as a surface metal-binding site. The crystal structures of Streptococcus suis Dpr complexed with transition metals demonstrated the metal specificity of the FOC. Solution binding studies also indicated the presence of a di-metal FOC. These results suggested a possible role for Dpr in the detoxification of various metals. Iron was found to mineralize inside the protein as ferrihydrite based on X-ray absorption spectroscopy data. The iron core was found to exhibit clear superparamagnetic behaviour using magnetic and Mössbauer measurements. The results from this study are expected to further increase our understanding on the binding, oxidation, and mineralization of iron and other metals in Dpr proteins. In particular, the structural and magnetic properties of the iron core can form a basis for potential new applications in nanotechnology. From the streptococcal viewpoint, the results would help in understanding better the complicated picture of bacterial pathogenesis. Dpr proteins may also provide a novel target for drug design due to their tight involvement in bacterial virulence.

Design and characterization of large area position sensitive radiation detectors

Planar, large area, position sensitive silicon detectors are widely utilized in high energy physics research and in medical, computed tomography (CT). This thesis describes author's research work relating to development of such detector components. The key motivation and objective for the research work has been the development of novel, position sensitive detectors improving the performance of the instruments they are intended for. Silicon strip detectors are the key components of barrel-shaped tracking instruments which are typically the innermost structures of high energy physics experimental stations. Particle colliders such as the former LEP collider or present LHC produce particle collisions and the silicon strip detector based trackers locate the trajectories of particles emanating from such collisions. Medical CT has become a regular part of everyday medical care in all developed countries. CT scanning enables x-ray imaging of all parts of the human body with an outstanding structural resolution and contrast. Brain, chest and abdomen slice images with a resolution of 0.5 mm are possible and latest CT machines are able to image whole human heart between heart beats. The two application areas are presented shortly and the radiation detection properties of planar silicon detectors are discussed. Fabrication methods and preamplifier electronics of the planar detectors are presented. Designs of the developed, large area silicon detectors are presented and measurement results of the key operating parameters are discussed. Static and dynamic performance of the developed silicon strip detectors are shown to be very satisfactory for experimental physics applications. Results relating to the developed, novel CT detector chips are found to be very promising for further development and all key performance goals are met.

Simulation of structural stress history based on dynamic analysis

Modern machine structures are often fabricated by welding. From a fatigue point of view, the structural details and especially, the welded details are the most prone to fatigue damage and failure. Design against fatigue requires information on the fatigue resistance of a structure’s critical details and the stress loads that act on each detail. Even though, dynamic simulation of flexible bodies is already current method for analyzing structures, obtaining the stress history of a structural detail during dynamic simulation is a challenging task; especially when the detail has a complex geometry. In particular, analyzing the stress history of every structural detail within a single finite element model can be overwhelming since the amount of nodal degrees of freedom needed in the model may require an impractical amount of computational effort. The purpose of computer simulation is to reduce amount of prototypes and speed up the product development process. Also, to take operator influence into account, real time models, i.e. simplified and computationally efficient models are required. This in turn, requires stress computation to be efficient if it will be performed during dynamic simulation. The research looks back at the theoretical background of multibody dynamic simulation and finite element method to find suitable parts to form a new approach for efficient stress calculation. This study proposes that, the problem of stress calculation during dynamic simulation can be greatly simplified by using a combination of floating frame of reference formulation with modal superposition and a sub-modeling approach. In practice, the proposed approach can be used to efficiently generate the relevant fatigue assessment stress history for a structural detail during or after dynamic simulation. In this work numerical examples are presented to demonstrate the proposed approach in practice. The results show that approach is applicable and can be used as proposed.

A Design Methodology for the Compensation of Positioning Deviation in Gantry Manipulators

This work presents recent results concerning a design methodology used to estimate the positioning deviation for a gantry (Cartesian) manipulator, related mainly to structural elastic deformation of components during operational conditions. The case-study manipulator is classified as gantry type and its basic dimensions are 1,53m x 0,97m x 1,38m. The dimensions used for the calculation of effective workspace due to end-effector path displacement are: 1m x 0,5m x 0,5m. The manipulator is composed by four basic modules defined as module X, module Y, module Z and terminal arm, where is connected the end-effector. Each module controlled axis performs a linear-parabolic positioning movement. The planning path algorithm has the maximum velocity and the total distance as input parameters for a given task. The acceleration and deceleration times are the same. Denavit-Hartemberg parameterization method is used in the manipulator kinematics model. The gantry manipulator can be modeled as four rigid bodies with three degrees-of-freedom in translational movements, connected as an open kinematics chain. Dynamic analysis were performed considering inertial parameters specification such as component mass, inertia and center of gravity position of each module. These parameters are essential for a correct manipulator dynamic modelling, due to multiple possibilities of motion and manipulation of objects with different masses. The dynamic analysis consists of a mathematical modelling of the static and dynamic interactions among the modules. The computation of the structural deformations uses the finite element method (FEM).

A Model-Based Development and Verification Framework for Distributed System-on-Chip Architecture

The capabilities and thus, design complexity of VLSI-based embedded systems have increased tremendously in recent years, riding the wave of Moore’s law. The time-to-market requirements are also shrinking, imposing challenges to the designers, which in turn, seek to adopt new design methods to increase their productivity. As an answer to these new pressures, modern day systems have moved towards on-chip multiprocessing technologies. New architectures have emerged in on-chip multiprocessing in order to utilize the tremendous advances of fabrication technology. Platform-based design is a possible solution in addressing these challenges. The principle behind the approach is to separate the functionality of an application from the organization and communication architecture of hardware platform at several levels of abstraction. The existing design methodologies pertaining to platform-based design approach don’t provide full automation at every level of the design processes, and sometimes, the co-design of platform-based systems lead to sub-optimal systems. In addition, the design productivity gap in multiprocessor systems remain a key challenge due to existing design methodologies. This thesis addresses the aforementioned challenges and discusses the creation of a development framework for a platform-based system design, in the context of the SegBus platform - a distributed communication architecture. This research aims to provide automated procedures for platform design and application mapping. Structural verification support is also featured thus ensuring correct-by-design platforms. The solution is based on a model-based process. Both the platform and the application are modeled using the Unified Modeling Language. This thesis develops a Domain Specific Language to support platform modeling based on a corresponding UML profile. Object Constraint Language constraints are used to support structurally correct platform construction. An emulator is thus introduced to allow as much as possible accurate performance estimation of the solution, at high abstraction levels. VHDL code is automatically generated, in the form of “snippets” to be employed in the arbiter modules of the platform, as required by the application. The resulting framework is applied in building an actual design solution for an MP3 stereo audio decoder application.

Modelling of hydrogen stratification and gas mixing in containment using the APROS code

Hydrogen stratification and atmosphere mixing is a very important phenomenon in nuclear reactor containments when severe accidents are studied and simulated. Hydrogen generation, distribution and accumulation in certain parts of containment may pose a great risk to pressure increase induced by hydrogen combustion, and thus, challenge the integrity of NPP containment. The accurate prediction of hydrogen distribution is important with respect to the safety design of a NPP. Modelling methods typically used for containment analyses include both lumped parameter and field codes. The lumped parameter method is universally used in the containment codes, because its versatility, flexibility and simplicity. The lumped parameter method allows fast, full-scale simulations, where different containment geometries with relevant engineering safety features can be modelled. Lumped parameter gas stratification and mixing modelling methods are presented and discussed in this master’s thesis. Experimental research is widely used in containment analyses. The HM-2 experiment related to hydrogen stratification and mixing conducted at the THAI facility in Germany is calculated with the APROS lump parameter containment package and the APROS 6-equation thermal hydraulic model. The main purpose was to study, whether the convection term included in the momentum conservation equation of the 6-equation modelling gives some remarkable advantages compared to the simplified lumped parameter approach. Finally, a simple containment test case (high steam release to a narrow steam generator room inside a large dry containment) was calculated with both APROS models. In this case, the aim was to determine the extreme containment conditions, where the effect of convection term was supposed to be possibly high. Calculation results showed that both the APROS containment and the 6-equation model could model the hydrogen stratification in the THAI test well, if the vertical nodalisation was dense enough. However, in more complicated cases, the numerical diffusion may distort the results. Calculation of light gas stratification could be probably improved by applying the second order discretisation scheme for the modelling of gas flows. If the gas flows are relatively high, the convection term of the momentum equation is necessary to model the pressure differences between the adjacent nodes reasonably.

Design and validation of stateful composite RESTful web services

A web service is a software system that provides a machine-processable interface to the other machines over the network using different Internet protocols. They are being increasingly used in the industry in order to automate different tasks and offer services to a wider audience. The REST architectural style aims at producing scalable and extensible web services using technologies that play well with the existing tools and infrastructure of the web. It provides a uniform set of operation that can be used to invoke a CRUD interface (create, retrieve, update and delete) of a web service. The stateless behavior of the service interface requires that every request to a resource is independent of the previous ones facilitating scalability. Automated systems, e.g., hotel reservation systems, provide advanced scenarios for stateful services that require a certain sequence of requests that must be followed in order to fulfill the service goals. Designing and developing such services for advanced scenarios with REST constraints require rigorous approaches that are capable of creating web services that can be trusted for their behavior. Systems that can be trusted for their behavior can be termed as dependable systems. This thesis presents an integrated design, analysis and validation approach that facilitates the service developer to create dependable and stateful REST web services. The main contribution of this thesis is that we provide a novel model-driven methodology to design behavioral REST web service interfaces and their compositions. The behavioral interfaces provide information on what methods can be invoked on a service and the pre- and post-conditions of these methods. The methodology uses Unified Modeling Language (UML), as the modeling language, which has a wide user base and has mature tools that are continuously evolving. We have used UML class diagram and UML state machine diagram with additional design constraints to provide resource and behavioral models, respectively, for designing REST web service interfaces. These service design models serve as a specification document and the information presented in them have manifold applications. The service design models also contain information about the time and domain requirements of the service that can help in requirement traceability which is an important part of our approach. Requirement traceability helps in capturing faults in the design models and other elements of software development environment by tracing back and forth the unfulfilled requirements of the service. The information about service actors is also included in the design models which is required for authenticating the service requests by authorized actors since not all types of users have access to all the resources. In addition, following our design approach, the service developer can ensure that the designed web service interfaces will be REST compliant. The second contribution of this thesis is consistency analysis of the behavioral REST interfaces. To overcome the inconsistency problem and design errors in our service models, we have used semantic technologies. The REST interfaces are represented in web ontology language, OWL2, that can be part of the semantic web. These interfaces are used with OWL 2 reasoners to check unsatisfiable concepts which result in implementations that fail. This work is fully automated thanks to the implemented translation tool and the existing OWL 2 reasoners. The third contribution of this thesis is the verification and validation of REST web services. We have used model checking techniques with UPPAAL model checker for this purpose. The timed automata of UML based service design models are generated with our transformation tool that are verified for their basic characteristics like deadlock freedom, liveness, reachability and safety. The implementation of a web service is tested using a black-box testing approach. Test cases are generated from the UPPAAL timed automata and using the online testing tool, UPPAAL TRON, the service implementation is validated at runtime against its specifications. Requirement traceability is also addressed in our validation approach with which we can see what service goals are met and trace back the unfulfilled service goals to detect the faults in the design models. A final contribution of the thesis is an implementation of behavioral REST interfaces and service monitors from the service design models. The partial code generation tool creates code skeletons of REST web services with method pre and post-conditions. The preconditions of methods constrain the user to invoke the stateful REST service under the right conditions and the post condition constraint the service developer to implement the right functionality. The details of the methods can be manually inserted by the developer as required. We do not target complete automation because we focus only on the interface aspects of the web service. The applicability of the approach is demonstrated with a pedagogical example of a hotel room booking service and a relatively complex worked example of holiday booking service taken from the industrial context. The former example presents a simple explanation of the approach and the later worked example shows how stateful and timed web services offering complex scenarios and involving other web services can be constructed using our approach.

Virtual Testing of Active Magnetic Bearing Systems based on Design Guidelines given by the Standards

Active Magnetic Bearings offer many advantages that have brought new applications to the industry. However, similarly to all new technology, active magnetic bearings also have downsides and one of those is the low standardization level. This thesis is studying mainly the ISO 14839 standard and more specifically the system verification methods. These verifying methods are conducted using a practical test with an existing active magnetic bearing system. The system is simulated with Matlab using rotor-bearing dynamics toolbox, but this study does not include the exact simulation code or a direct algebra calculation. However, this study provides the proof that standardized simulation methods can be applied in practical problems.

Liposomes: from biophysics to the design of peptide vaccines

Liposomes (lipid-based vesicles) have been widely studied as drug delivery systems due to their relative safety, their structural versatility concerning size, composition and bilayer fluidity, and their ability to incorporate almost any molecule regardless of its structure. Liposomes are successful in inducing potent in vivo immunity to incorporated antigens and are now being employed in numerous immunization procedures. This is a brief overview of the structural, biophysical and pharmacological properties of liposomes and of the current strategies in the design of liposomes as vaccine delivery systems.

VVER-440 Thermal Hydraulics as a Computer Code Validation Challenge

This thesis concentrates on the validation of a generic thermal hydraulic computer code TRACE under the challenges of the VVER-440 reactor type. The code capability to model the VVER-440 geometry and thermal hydraulic phenomena specific to this reactor design has been examined and demonstrated acceptable. The main challenge in VVER-440 thermal hydraulics appeared in the modelling of the horizontal steam generator. The major challenge here is not in the code physics or numerics but in the formulation of a representative nodalization structure. Another VVER-440 specialty, the hot leg loop seals, challenges the system codes functionally in general, but proved readily representable. Computer code models have to be validated against experiments to achieve confidence in code models. When new computer code is to be used for nuclear power plant safety analysis, it must first be validated against a large variety of different experiments. The validation process has to cover both the code itself and the code input. Uncertainties of different nature are identified in the different phases of the validation procedure and can even be quantified. This thesis presents a novel approach to the input model validation and uncertainty evaluation in the different stages of the computer code validation procedure. This thesis also demonstrates that in the safety analysis, there are inevitably significant uncertainties that are not statistically quantifiable; they need to be and can be addressed by other, less simplistic means, ultimately relying on the competence of the analysts and the capability of the community to support the experimental verification of analytical assumptions. This method completes essentially the commonly used uncertainty assessment methods, which are usually conducted using only statistical methods.

The use of protein structure/activity relationships in the rational design of stable particulate delivery systems

The recombinant heat shock protein (18 kDa-hsp) from Mycobacterium leprae was studied as a T-epitope model for vaccine development. We present a structural analysis of the stability of recombinant 18 kDa-hsp during different processing steps. Circular dichroism and ELISA were used to monitor protein structure after thermal stress, lyophilization and chemical modification. We observed that the 18 kDa-hsp is extremely resistant to a wide range of temperatures (60% of activity is retained at 80ºC for 20 min). N-Acylation increased its ordered structure by 4% and decreased its ß-T1 structure by 2%. ELISA demonstrated that the native conformation of the 18 kDa-hsp was preserved after hydrophobic modification by acylation. The recombinant 18 kDa-hsp resists to a wide range of temperatures and chemical modifications without loss of its main characteristic, which is to be a source of T epitopes. This resistance is probably directly related to its lack of organization at the level of tertiary and secondary structures.

VAP-1 as drug target in inflammation : structural features determining ligand interactions

Vascular adhesion protein-1 (VAP-1), which belongs to the copper amine oxidases (CAOs), is a validated drug target in inflammatory diseases. Inhibition of VAP-1 blocks the leukocyte trafficking to sites of inflammation and alleviates inflammatory reactions. In this study, a novel set of potent pyridazinone inhibitors is presented together with their X-ray structure complexes with VAP-1. The crystal structure of serum VAP-1 (sVAP-1) revealed an imidazole binding site in the active site channel and, analogously, the pyridazinone inhibitors were designed to bind into the channel. This is the first time human VAP-1 has been crystallized with a reversible inhibitor and the structures reveal detailed information of the binding mode on the atomic level. Similarly to some earlier studied inhibitors of human VAP-1, the designed pyridazinone inhibitors bind rodent VAP-1 with a lower affinity than human VAP-1. Therefore, we made homology models of rodent VAP-1 and compared human and rodent enzymes to determine differences that might affect the inhibitor binding. The comparison of the crystal structures of the human VAP-1 and the mouse VAP-1 homology model revealed key differences important for the species specific binding properties. In general, the channel in mouse VAP-1 is more narrow and polar than the channel in human VAP-1, which is wider and more hydrophobic. The differences are located in the channel leading to the active site, as well as, in the entrance to the active site channel. The information obtained from these studies is of great importance for the development and design of drugs blocking the activity of human VAP-1, as rodents are often used for in vivo testing of candidate drugs. In order to gain more insight into the selective binding properties of the different CAOs in one species a comprehensive evolutionary study of mammalian CAOs was performed. We found that CAOs can be classified into sub-families according to the residues X1 and X2 of the Thr/Ser-X1-X2-Asn-Tyr-Asp active site motif. In the phylogenetic tree, CAOs group into diamine oxidase, retina specific amine oxidase and VAP-1/serum amine oxidase clades based on the residue in the position X2. We also found that VAP-1 and SAO can be further differentiated based on the residue in the position X1. This is the first large-scale comparison of CAO sequences, which explains some of the reasons for the unique substrate specificities within the CAO family.