In recent years, the number of regulations an organization needs to comply with has been increasing, and organizations have to ensure that their business processes are aligned with these regulations. However, because of the complexity and intended vagueness of regulations in general, it is not possible to treat them the same way as other types of requirements. On the other hand, the cost of being non-compliant can also be fairly high; non-compliance can cause crucial harm to the organization with financial penalties or loss of reputation. Therefore, it is very important for organizations to take a systematic approach to ensuring that their compliance with related laws, regulations and standards is established and maintained. To achieve this goal, this thesis proposes a model-based compliance analysis framework for business processes called Legal-URN. This framework is composed of four layers of abstraction linked to each other. The framework exploits the User Requirements Notation (URN) as the modeling language to describe and combine legal and organizational models. In order to model legal documents, legal statements are first classified into four classes of Hohfeldian rights, and then Hohfeldian models of the regulations and their statements are created. These models are further refined into legal goal and business process models via a domain-specific version of URN called Legal URN profile. To check the well-formedness of the models and to identify instances of non-compliance, 23 Object Constraint Language (OCL) rules are provided. In this thesis, the quantitative and qualitative analysis algorithms of URN's Goal-oriented Requirement Language are extended to help analyze quantitatively and qualitatively the degree of compliance of an organization to the legal models. Furthermore, with the help of a prioritization algorithm, the framework enables one to decide, while taking the organization goals into consideration, which non-compliant instances to address first in order to provide a suitable evolution path for business processes. In addition, to assess compliance with more than one regulation, a pair-wise comparison algorithm enables organizations to identify the similarities and conflicts among regulations and incorporate them in the models. The jUCMNav tool, an Eclipse plug-in for URN modeling and analysis, was extended to support the framework and its algorithms and rules. The thesis contributions are evaluated through a gap analysis based on a systematic literature review, a comparison with closely related work, and two case studies in the healthcare domain: one with a single regulation and realistic business processes, and a second with three additional regulations. We also identify the benefits and limitations of the framework, as well as potential extensions for future work. The Legal-URN framework provides a tool-supported, rigorous approach to compliance analysis of organizations against relevant regulations.

In recent years, the number of regulations an organization needs to comply with has been increasing, and organizations have to ensure that their business processes are aligned with these regulations. However, because of the complexity and intended vagueness of regulations in general, it is not possible to treat them the same way as other types of requirements. On the other hand, the cost of being non-compliant can also be fairly high; non-compliance can cause crucial harm to the organization with financial penalties or loss of reputation. Therefore, it is very important for organizations to take a systematic approach to ensuring that their compliance with related laws, regulations and standards is established and maintained. To achieve this goal, this thesis proposes a model-based compliance analysis framework for business processes called Legal-URN. This framework is composed of four layers of abstraction linked to each other. The framework exploits the User Requirements Notation (URN) as the modeling language to describe and combine legal and organizational models. In order to model legal documents, legal statements are first classified into four classes of Hohfeldian rights, and then Hohfeldian models of the regulations and their statements are created. These models are further refined into legal goal and business process models via a domain-specific version of URN called Legal URN profile. To check the well-formedness of the models and to identify instances of non-compliance, 23 Object Constraint Language (OCL) rules are provided. In this thesis, the quantitative and qualitative analysis algorithms of URN's Goal-oriented Requirement Language are extended to help analyze quantitatively and qualitatively the degree of compliance of an organization to the legal models. Furthermore, with the help of a prioritization algorithm, the framework enables one to decide, while taking the organization goals into consideration, which non-compliant instances to address first in order to provide a suitable evolution path for business processes. In addition, to assess compliance with more than one regulation, a pair-wise comparison algorithm enables organizations to identify the similarities and conflicts among regulations and incorporate them in the models. The jUCMNav tool, an Eclipse plug-in for URN modeling and analysis, was extended to support the framework and its algorithms and rules. The thesis contributions are evaluated through a gap analysis based on a systematic literature review, a comparison with closely related work, and two case studies in the healthcare domain: one with a single regulation and realistic business processes, and a second with three additional regulations. We also identify the benefits and limitations of the framework, as well as potential extensions for future work. The Legal-URN framework provides a tool-supported, rigorous approach to compliance analysis of organizations against relevant regulations.

The employment of HIV-1 protease (PR) inhibitors (PIs) in antiviral therapy has been successful in reducing mortality of HIV/AIDS patients. However, the long-term efficacy of PIs is challenged by the rapid emergence of drug-resistant mutants of PR. To understand the underlying mechanism of drug resistance, structures and activities of HIV-1 PR and its drug resistant mutants have been extensively studied. Here, PR mutants PRR8Q, PRD30N, PRI47V, PRI50V, PRI54M, PRV82A, and PRN88D/S bearing single substitutions have been investigated by crystallography and kinetics. GRL-0519 is a potent new antiviral inhibitor of HIV-1 PR that possesses tris-tetrahydrofuran (tris-THF) as the P2 ligand. The crystal structures of GRL-0519 were determined at resolutions of 1.06-1.49 Å in complex with the mutants PRR8Q, PRD30N, PRI50V, PRI54M, and PRV82A. I50V lost its interaction with inhibitor while V82Aand I54M compensated for the mutation through the main chain shift and flexibility of 80’s loop (residues 78-82), respectively. The structural changes may account for the worst inhibition of GRL-0519 for PRI50V (60-fold decrease relative to wild-type enzyme)and moderate inhibition for PRI54M and PRV82A (6-7-fold decrease). The large tris-THF group at P2 provides a good fit in the S2 subsite and may be effective against resistant virus with mutations of residues in this subsite. SQV and DRV are two clinical inhibitors that were designed to target the wild type PR and its drug resistant mutants, respectively. The crystal structures of PR mutants PRI47V, PRN88D/s in complex with DRV and mutants PRI47V and PRN88D in complex with SQV with resolutions of 1.13-1.72 Å were also analyzed. Mutation I47V gained more hydrophobic interactions with DRV and SQV. Interestingly, the structural changes did not affect the inhibition of both inhibitors for PRI47V (relative Ki is 0.7 and 1 for DRV and SQV, respectively). DRV and SQV showed 8-fold increase in Ki for PRN88D and only very subtle local changes have been observed on the structures. DRV induced 0.3 fold reduction in Ki for PRN88S and the distal structural changes have been transferred to the active site. This study provided fundamental information for understanding drug resistance and future design of potential antiviral drugs.

Šiame magistro baigiamajame darbe yra nagrinėjama, kaip ir kokiu mastu, struktūrinant reikalavimus pagal J.A.Zachmano karkasą ir panaudojant Toronto grupės pasiūlytą nefunkcinių reikalavimų dekomponavimo metodiką (NFR), galima bent iš dalies formalizuoti reikalavimų nuleidimą iš verslo lygmens į programų sistemos lygmenį. Darbo teorinėje darbo dalyje, remiantis atliktos mokslinės literatūros analizės rezultatais, pasiūlyta kaip pritaikyti Toronto metodiką reikalavimams nuleisti iš verslo į programų sistemos lygmenį Zachmano tipo karkasuose. Darbo eksperimentinėje dalyje šie pasiūlymai patikrinti praktiškai, atliekant konkrečios sistemos reikalavimų nuleidimą iš verslo į programų sistemos lygmenį. Tyrimo rezultatai parodė, kad NFR metodika tinkama ne visų reikalavimų nuleidimui žemyn, nes joje yra per silpnos dinamikos modeliavimo priemonės. / The aim of the master thesis is to investigate possibilities to use the NFR (non-functional requirements) approach proposed by Toronto group to perform the flowdown of requirements from business to software level in the methodical requirements engineering frameworks that organize requirements in a way similar to the J.A. Zachman’s Enterprise Architecture. Using results of the library research, the theoretical part of the thesis proposes a methodology how to apply NRF approach to perform flow down of the higher level requirements to lower ones in cases when requirements are organized according to principles proposed by J.A. Zachman. The experimental part of the thesis is devoted to the validation of the proposed approach using a simplified banking system example. The main conclusion of the thesis is that the NFR approach is applicable only to some part of requirements because the modelling means provided by this approach are not sufficient to model the system dynamic.

Context: Organizations strive to improve their business processes, and adaptive business processes have recently attracted much attention in that context. However, much research in that area has a narrow focus and does not consider a comprehensive view of the organization and its goals. In addition, Business Intelligence-based monitoring methods are useful for business process improvement but they often present information in a format that is not entirely suited for decision making. Objectives: The main objectives of this thesis are to provide: • A framework to model goals, processes, performance, situations, and improvement patterns using one modeling notation, in an iterative and incremental manner; • A method for the modeling and analysis of cause-effect relationships between indicators used to measure goal satisfaction; and • A technique allowing the detection of undesirable, sub-optimal conditions and the application of improvement patterns to the context Method: We develop an iterative framework based on the User Requirements Notation (URN) for modeling, monitoring and improving business organizations and their business processes. In addition, we introduce a formula-based evaluation algorithm allowing better analysis of the relationships between the business performance model elements (namely indicators). Furthermore, we use a profiled version of the Aspect-oriented URN (AoURN) with extensions (Business Process Pattern profile), for detecting undesirable conditions and for business process adaptation. We validate the novelty and feasibility of our approach by performing a systematic literature review, by assessing it against Zellner’ mandatory elements of a method, by developing tool support, by performing a pilot experiment and by using real-life examples from different sectors (healthcare and retail). Results: The two examples show that through the framework’s iterative approach, organizations at different levels of maturity in their business improvement journey can benefit from the framework. Furthermore, our systematic literature review shows that although there are existing works that enable our vision, most of them have a narrow focus and do not cover the three organization views that are of interest in this research. AoURN allows analysts to find repeated patterns in a context and bundle goal, performance and process models as a self-contained unit. AoURN hence enables the modeling of complex circumstances together with analysis techniques for what-if analysis and process adaptation, all using a unified and integrated modeling language. Finally, the pilot experiment suggests that, with some level of documentation and training, users who are already familiar with URN can use the profiled AoURN provided in this thesis as well as the discussed improvement patterns.

Context: Organizations strive to improve their business processes, and adaptive business processes have recently attracted much attention in that context. However, much research in that area has a narrow focus and does not consider a comprehensive view of the organization and its goals. In addition, Business Intelligence-based monitoring methods are useful for business process improvement but they often present information in a format that is not entirely suited for decision making. Objectives: The main objectives of this thesis are to provide: • A framework to model goals, processes, performance, situations, and improvement patterns using one modeling notation, in an iterative and incremental manner; • A method for the modeling and analysis of cause-effect relationships between indicators used to measure goal satisfaction; and • A technique allowing the detection of undesirable, sub-optimal conditions and the application of improvement patterns to the context Method: We develop an iterative framework based on the User Requirements Notation (URN) for modeling, monitoring and improving business organizations and their business processes. In addition, we introduce a formula-based evaluation algorithm allowing better analysis of the relationships between the business performance model elements (namely indicators). Furthermore, we use a profiled version of the Aspect-oriented URN (AoURN) with extensions (Business Process Pattern profile), for detecting undesirable conditions and for business process adaptation. We validate the novelty and feasibility of our approach by performing a systematic literature review, by assessing it against Zellner’ mandatory elements of a method, by developing tool support, by performing a pilot experiment and by using real-life examples from different sectors (healthcare and retail). Results: The two examples show that through the framework’s iterative approach, organizations at different levels of maturity in their business improvement journey can benefit from the framework. Furthermore, our systematic literature review shows that although there are existing works that enable our vision, most of them have a narrow focus and do not cover the three organization views that are of interest in this research. AoURN allows analysts to find repeated patterns in a context and bundle goal, performance and process models as a self-contained unit. AoURN hence enables the modeling of complex circumstances together with analysis techniques for what-if analysis and process adaptation, all using a unified and integrated modeling language. Finally, the pilot experiment suggests that, with some level of documentation and training, users who are already familiar with URN can use the profiled AoURN provided in this thesis as well as the discussed improvement patterns.

The Swedish procedural legislation on class actions before general courts, GrL, was when coming into force in January 2003 the first generally applicable class action regime of continental Europe. However, it seems, it was never used in any notable extent. In this thesis I have analysed GrL, it’s potential flaws, how it could be affected by the ongoing EU legislative procedure of establishing a directive regarding representative actions for the protection of the collective interests of consumers, and what the Swedish legislator could potentially learn from the Dutch model being primarily based on a regime of mass settlements. The ongoing EU legislative procedure will by all accounts result in a directive requiring Swedish class action regime to be adjusted with a few minor modifications, primarily the introduction of a certification procedure of entities to allow these to initiate representative actions in disputes concerning the protection of consumers’ collective interests. Apart from adjustments of Swedish class action legislation in order to harmonise it with the directive, I have argued for several additional adjustments of proceedings under GrL in order to make it in an increased degree correspond with the reasons by which the legislation was motivated, and in order to in general function in a more effective manner. For that purpose, I have argued that the opt in mechanism should be replaced with an opt out mechanism, or that opt out should at least be introduced as a supplementing option to an opt in main rule. Independently of the issue of whether an opt in or an opt out mechanism should be used to constitute the represented group, I have furthermore argued that the mechanism used should allow group members to leave the group during the proceedings. Finally, I have argued that the courts should be encouraged to use a for the Swedish legal system untypically active direction of proceedings in class actions specifically.

Mitochondrial processing peptidase (MPP) is a heterodimeric enzyme which belongs to M16B subfamily of metaloendopeptidases. A universal function of this enzyme is in recognition and cleavage of great number of mitochondrial preprotein presequences, which differ in length and amino acid sequence. MPP consists of catalytical β-MPP and probably recognizing α-MPP. The most conservative region in α-MPP is GRL - glycine-rich loop. Its function is supposed in primary interaction with preprotein presequence. It is possible to study conformational change of GRL after binding the substrate by fluorescence experiments. In this diploma thesis the constructs coding the α-MPP with the single reporter tryptophan residue in the position 289 or 299 were prepared using site-directed mutagenesis. These forms of α-MPP were produced in E. coli BL21(DE3)+pGroESL. Activities of MPP dimer containing α-MPP with the single tryptophan residue in the reporter position were compared with MPP from wild type of S. cerevisiae. Used substrate was yeast malate dehydrogenase precursor with fused presequence (pMDH) from three organisms (yeast, mouse and melon). These presequences differ in their length. Activities of MPP dimer containing α-MPP with the single reporter tryptophan residue in the position 289 were about 70 % while...

The growing need for computer software in different sectors of activity, (health, agriculture, industries, education, aeronautic, science and telecommunication) together with the increasing reliance of the society as a whole on information technology, is placing a heavy and fast growing demand on complex and high quality software systems. In this regard, the anticipation has been on non-functional requirements (NFRs) engineering and formal methods. Despite their common objective, these techniques have in most cases evolved separately. NFRs engineering proceeds firstly, by deriving measures to evaluate the quality of the constructed software (product-oriented approach), and secondarily by improving the engineering process (process-oriented approach). With the ability to combine the analysis of both functional and non-functional requirements, Goal-Oriented Requirements Engineering (GORE) approaches have become de facto leading requirements engineering methods. They propose through refinement/operationalisation, means to satisfy NFRs encoded in softgoals at an early phase of software development. On the other side, formal methods have kept, so far, their promise to eliminate errors in software artefacts to produce high quality software products and are therefore particularly solicited for safety and mission critical systems for which a single error may cause great loss including human life. This thesis introduces the concept of Complementary Non-functional action (CNF-action) to extend the analysis and development of NFRs beyond the traditional goals/softgoals analysis, based on refinement/operationalisation, and to propagate the influence of NFRs to other software construction phases. Mechanisms are also developed to integrate the formal technique Z/Object-Z into the standardised User Requirements Notation (URN) to formalise GRL models describing functional and non-functional requirements, to propagate CNF-actions of the formalised NFRs to UCMs maps, to facilitate URN construction process and the quality of URN models. / School of Computing / D. Phil (Computer Science)

Organizations use Business Intelligence (BI) systems to monitor how well they are meeting their goals and objectives. Yet, very often BI systems do not include clear models of the organization’s goals or of how to measure whether they are satisfied or not. Several researchers now attempt to integrate goal models into BI systems, but there are still major challenges related to how to get access to the BI data to populate the part of the goal model (often indicators) used to assess goal satisfaction. This thesis explores a new approach to integrate BI systems with goal models. In particular, it explores the integration of IBM Cognos Business Intelligence, a leading BI tool, with an Eclipse-based goal modeling tool named jUCMNav. jUCMNav is an open source graphical editor for the User Requirements Notation (URN), which includes the Use Case Map notation for scenarios and processes and the Goal-oriented Requirement Language for business objectives. URN was recently extended with the concept of Key Performance Indicator (KPI) to enable performance assessment and monitoring of business processes. In jUCMNav, KPIs are currently calculated or modified manually. The new integration proposed in this thesis maps these KPIs to report elements that are generated automatically by Cognos based on the model defined in jUCMNav at runtime, with minimum effort. We are using IBM Cognos Mashup Service, which includes web services that enable the retrieval of report elements at the most granular level. This transformation provides managers and analysts with useful goal-oriented and process-oriented monitoring views fed by just-in-time BI information. This new solution also automates retrieving data from Cognos servers, which helps reducing the high costs usually caused by the amount of manual work required otherwise. The novel approach presented in this thesis avoids manual report generation and minimizes any contract with respect to the location of manually created reports, hence leading to better usability and performance. The approach and its tool support are illustrated with an ongoing example, validated with a case study, and verified through testing.