Potentielle Steuerreformen befinden sich regelmäßig auf der Tagesordnung der politischen Diskussion in Deutschland und Europa. Die erwarteten Aufkommens- und Verteilungswirkungen von Steuerreformen werden von Simulationsmodellen quantifiziert, die damit der politischen Entscheidungsunterstützung dienen. Bisherige Simulationsmodelle basieren auf makroökonomischen oder unternehmensindividuellen Daten und führen die Analyse für einen historischen Zeitraum oder für einzelne Länder durch. Vor diesem Hintergrund stellen die Beiträge dieser Dissertation das Design, die Implementierung und die Anwendung des Mikro-Simulationsmodells ASSERT dar. ASSERT basiert auf unkonsolidierten Jahresabschlussdaten sowie Beteiligungsbeziehungen europäischer Unternehmen, länderspezifischen Parameterdaten und berücksichtigt die nationalen Besteuerungsvorschriften der europäischen Länder. Die Simulation der zukünftigen Unternehmensentwicklung erlaubt eine vorwärtsgerichtete Analyse für mögliche nationale oder europäische Steuerreformszenarien unter Unsicherheit. Dabei werden Auswirkungen auf inländische und ausländische verbundene Unternehmen berücksichtigt. Das formale und steuerliche Design von ASSERT wird in Beitrag 1 erläutert. Die Anwendung von ASSERT erfolgt dann in Beitrag 2. Ziel dieses Beitrags ist die Quantifizierung der Auswirkungen möglicher Reformszenarien zur alternativen Besteuerung der ertragsteuerlichen Organschaft in Deutschland. Die Präsentation des Entwicklungsprozesses, des optimierten IT-Designs und der Implementierung ist Gegenstand von Beitrag 3. Zunächst wurde ASSERT für eine zeitnahe Realisierung funktionenorientiert konzipiert und realisiert. Nachfolgend wurde ein ganzheitliches Datenbankdesign und ein integriertes Programm-Paket erstellt, um Verbesserungen der Performance und der Wartbarkeit zu erzielen. Da zu erwarten ist, dass unternehmerische Entscheidungen durch Steuerreformen beeinflusst werden, werden in Beitrag 4 Verhaltensreaktionen in Bezug auf die Finanzierungsstruktur berücksichtigt und die resultierenden Zweitrundeneffekte für verschiedene Szenarien ermittelt. Die Modellierung der Zielkapitalstruktur erfolgt in Abhängigkeit des tariflichen, des marginalen Steuersatzes und weiteren Konzerncharakteristika.

The Association for Computing Machinery (ACM) recognizes five computing disciplines: Computer Science (CS), Computer Engineering (CE), Information Technology (IT), Information Systems (IS), and Software Engineering (SE). Founded in 1947 the ACM is the world's largest society for computing educators, researchers, and professionals. While Computer Science has been a degree program since 1962, the other four are relatively new. This research focuses on understanding the graduate research in four of the five ACM disciplines (CS, CE, IT, and IS) using a large body of thesis and dissertation metadata. SE is not found in the metadata and graduate work in SE is not included. IS is no longer officially found in the metadata so its representative ProQuest replacement, Information Science although not an ACM recognized discipline is used based on the commonality of the associated ProQuest Classification code. The research is performed using co-word and graph analysis of author-supplied Classifications, Departments, and keywords. Similarities and differences between the disciplines are identified. Whether the computing discipline is the primary or the secondary focus of the research makes a large difference in the connections it makes with other academic disciplines. It was found that the Departments from which computing research originates varies widely but the majority come from computing-related Departments. Finally, gaps are apparent from the practitioners' views of the computing disciplines versus the public's view.

In recent years the amount of information on the web has increased dramatically. As a result, it has become a challenge for the researchers to find effective ways that can help us query and extract meaning from these large repositories. Standard document search engines try to address the problem by presenting the users a ranked list of relevant documents. In most cases, this is not enough as the end-user has to go through the entire document to find out the answer he is looking for. Question answering, which is the retrieving of answers to natural language questions from a document collection, tries to remove the onus on the end-user by providing direct access to relevant information. This thesis is concerned with open-domain complex question answering. Unlike simple questions, complex questions cannot be answered easily as they often require inferencing and synthesizing information from multiple documents. Hence, we considered the task of complex question answering as query-focused multi-document summarization. In this thesis, to improve complex question answering we experimented with both empirical and machine learning approaches. We extracted several features of different types (i.e. lexical, lexical semantic, syntactic and semantic) for each of the sentences in the document collection in order to measure its relevancy to the user query. We have formulated the task of complex question answering using reinforcement framework, which to our best knowledge has not been applied for this task before and has the potential to improve itself by fine-tuning the feature weights from user feedback. We have also used unsupervised machine learning techniques (random walk, manifold ranking) and augmented semantic and syntactic information to improve them. Finally we experimented with question decomposition where instead of trying to find the answer of the complex question directly, we decomposed the complex question into a set of simple questions and synthesized the answers to get our final result. / x, 128 leaves : ill. ; 29 cm

Detta examensarbete är utfört för Imano AB och behandlar ämnet databaser. Enorma mängder data finns lagrad i databaser världen över, men bara en bråkdel av all data används till något. Data kan förekomma i många olika former och en mängd olika typer av databaser har vuxit fram som komplement till de traditionella relationsdatabaserna. För sociala nätverk, logistiksystem, e-handel och i många andra sammanhang är relationer mellan dataposter ofta lika intressant som själva datainnehållet. När så är fallet kan grafdatabaser vara ett intressant alternativ. I en grafdatabas sparas relationer mellan enskilda dataposter som egna objekt, och denna egenskap kan användas för att ställa frågor om hur data relaterar till andra data. För att på ett effektivt sätt kunna utnyttja grafdatabasens egenskaper finns behov för ett lättillgängligt och användbart verktyg. Syftet med examensarbetet är att skapa ett verktyg, som kombinerar grafdatabasen Neo4js förmåga att hantera relationer mellan enskilda dataposter med visuell presentation av data i en webbapplikation. Studien undersöker om detta verktyg gör att användaren lättare kan få ny förståelse ur befintlig data. Denna studie är i grunden ett utvecklingsarbete som följer principerna för metoden Design Science Research. Metoden består av en utvecklingsprocess i flera steg där empirin är den kunskap som erhålls under arbetets gång. I utvecklingsprocessen ingår även kvalitativa undersökningsmetoder för att samla in data vid demonstration och utvärdering av artefakten. I rapporten jämförs grafdatabaser med relationsdatabaser. Studien avser dock endast att peka på skillnader gällande vissa egenskaper och genomför ingen fullständig jämförelse av exempelvis prestanda. Studien visar enligt utvecklarna att grafdatabasen Neo4j har egenskaper som gör den lämplig för användning där relationer mellan enskilda dataposter är viktiga som källor till kunskap. Resultatet av forskningen är att ny förståelse kan komma ur befintlig data genom användning av grafdatabas, speciellt om den kombineras med visualisering. / This thesis written in swedsh is done for Imano AB and deals with the subject databases. Huge amounts of data are stored in databases worldwide, but only a fraction of all the data is used. Data can exist in many different forms and various types of databases have emerged as a complement to the traditional relational databases. In social networking, logistics systems, e-commerce and many other contexts, relationships between data items are often as interesting as the actual data content. When this is the case, graph databases provide solutions to problems that other databases cannot handle. In a graph database relationships between individual data records are stored as own objects. Thanks to this, it is easier to ask questions about how data relate to other data. To effectively exploit the graph database’s features there is a need for an accessible and useful tool. The purpose of the project is to create a tool that combines the graph database Neo4j’s ability to manage relationships between individual data items with visual presentation of data in a web application. The study examines whether this tool allows the user to more easily gain new insights from existing data. This study is basically a software development process which follows the principles of the method of Design Science Research. The method consists of a development process in several stages where empirical data is the knowledge obtained during work. The development process also includes qualitative research methods to collect data at the demonstration and evaluation of the artifact. The study shows, according to the developers that the graph database Neo4j has properties that make it suitable for use where relationships between individual data items are important as sources of knowledge. The result of the research is that new understanding can emerge from existing data using a graph database, especially when combined with visualization

The future of networking lies within the development of low-latency and reliable networks. This development poses increased demand on the presence of edge-nodes. For a network operator to provide a low-latency edge-node resource, the physical distance from antenna-to-user needs to be small. This in turn, requires the network operator to have wide coverage of their physical antennas. An alternative solution is for network operators to share their edge-nodes within a so-called Operator Platform (OP) to reduce the cost of expanding their physical presence. In this project Design Science Research (DSR) was used to design an artifact named Master Thesis Orchestrator (MTO), to address the issue of finding and delivering shared edge-node resources between operators. An abstracted model of a realistic scenario was adopted. This model was used in evaluating the performance of the design against a baseline solution. The MTO is a decentralised algorithm using a shared memory cache. The artifact also has a randomised component which is used to control the frequency of shared memory accesses. These design choices were chosen to improve the performance in terms of scalability. A simulation of the artifact and baseline was conducted using a testbed implemented with Kubernetes/minikube. By assessing the performance on different input sizes (number of edge-nodes), the following performance metrics was gathered: success-rate (accuracy), run-time, and amount of data transmitted. The results showed that the MTO produced an average accuracy of 36% (baseline=96.8%) in terms of successful/failed user requests. The performance regarding run-time and transmitted data, varied depending on the outcome of the request. The MTO’s worst-case performance occurs for failed matches, leading to performance akin to that of the baseline’s average performance. The best-case performance of the MTO showed improvements of run-time compared to the baseline solution. The data was validated through an Analysis of variance (ANOVA)-test and the distributions are significantly (α = 5%) different from each other. The designed artifact is however not better than the baseline solution on all analysed metrics. The designed algorithm is volatile in-terms of time-needed and accuracy, but resource efficient. The poor accuracy is a significant factor into the probability that the worst-case performance would occur resulting in a slow and unreliable solution. Nevertheless, in terms of scalability, the designed artifact is showing less severe growth-rate than that of the baseline. / Framtiden för nätverk ligger i utvecklingen av tillförlitliga nätverk med låg latenstid. Denna utveckling ställer ökade krav på förekomsten av så kallade kantnoder. För att en nätoperatör ska kunna tillhandahålla en kantnodsresurs med låg latenstid måste det fysiska avståndet från antenn till användare vara litet. Detta kräver i sin tur att nätoperatören bör ha stor täckning av sina fysiska antenner. Ett alternativ till detta är att nätoperatörer delar sina resurser inom en så kallad Operatörsplatform för att minska kostnaderna för utökning av sin fysiska antennärvaro. I det här projektet användes Design Science Research för att utforma en produkt vid namn Master Thesis Orchestrator (MTO) för att lösa problemet med att hitta och leverera kantnodresurser mellan operatörer. En abstrakt modell av ett realistiskt scenario skapades. Denna modell användes för att utvärdera designens prestanda i förhållande till en baslinjelösning. MTO är en decentraliserad algoritm som använder sig av en delad minnescache. Designen har också en slumpmässig komponent som används för att styra åtkomstsfrekvensen till det delade minnet. Dessa designval gjordes för att förbättra skalbarhetsprestandan. En simulering av algoritmen och baslinjelösningen genomfördes med hjälp av en testbädd som implementerades med Kubernetes/minikube. Genom att testa prestandan på olika ingångsstorlekar (antal kantnoder) samlades följande mätetal in: framgångkvot (noggrannhet), körtid och mängden överförd data. Resultaten visade att MTO gav en genomsnittlig noggrannhet på 36% (baslinje=96,8%) gällande lyckade/felaktiga matchningar. Prestandan när det gäller körtid och överförda data varierade beroende på resultatet av matchningar. MTO:s sämsta prestanda uppstår vid misslyckade matchningar, vilket leder till ett resultat som liknar baslinjelösningens genomsnittliga prestanda. MTO:s bästa prestanda visade förbättringar av körtiden jämfört med baslinjelösningen. Testerna validerades genom ett ANOVA-test och algoritmerna skiljer sig signifikant (α = 5%) från varandra. Den utformade produkten är dock inte bättre än den baslinjelösningen för alla analyserade mätvärden. Den utformade algoritmen är volatil när det gäller tidsåtgång och noggrannhet, men resurseffektiv. Den dåliga noggrannheten är en betydande faktor för sannolikheten att den värsta möjliga prestandan skulle inträffa, vilket leder till en långsam och opålitlig lösning. När det gäller skalbarhet uppvisar den utformade produkten dock en mindre allvarlig tillväxttakt än baslinjelösningen.

Anthradithiophene (ADT) derivatives have proven to be a front-runner in the world of small molecule semiconductors for organic electronics and optoelectronics. This is mainly due to the improved stability, easy tuning of chemical and physical properties, and impressive device performance that these molecules possess, especially in organic field effect transistors (OFET) and organic photovoltaics (OPV). The second chapter of this dissertation shows that reducing the amount of alkylsilylethynyl groups, used for functionalizing and solubilizing the ADT backbone, does alter the chemical, physical and crystallographic properties of ADTs. These changes offer the opportunity to study and observe different intermolecular interactions as well as monitoring their influence on sulfur scrambling in solid state. Additionally, from the early days ADTs and functionalized ADTs have been synthesized as isomeric mixtures. In chapter three, I demonstrate a new and simple method that can separate the syn and anti isomers of the F-TES-ADT and F-TEG-ADT chromatographically. The effects of isomeric purity on crystal packing and field effect transistor performance were studied extensively. Chapter four of this dissertation reveals a new generation of acceptor (electron poor) ADT derivatives obtained by attaching cyanide as electron withdrawing group (EWG) to the ADT chromophore. An extensive study was conducted on CN-ADT (acceptor) molecules in small molecule (F-TES-ADT) donor/ small molecule (CN-ADT) acceptor binary BHJ blends as well as P3HT/CN-ADT/PCBM ternary BHJ blends. Photophysical studies of the Donor/ acceptor blends (interface, domains, and crystal orientation) were conducted to obtain a better understanding of the film morphology and its effect on solar cell performance. Finally, the last part of the dissertation, Chapter five, focus on studying singlet fission in ADT derivatives, as well as the effect of varying the size of the alkylsilylethynyl functional group (used for solubilizing the ADT backbone) on altering the electronic couplings and how can that potentially affect the singlet fission rate in these molecules. We also tried to inspect the extent of the correlation between long-range order in crystal packing and singlet fission by monitoring singlet fission rate and efficiency for ADT derivatives with different thin film morphologies.

Thesis (PhD) -- Stellenbosch University, 2014. / ENGLISH ABSTRACT: This thesis has as its focus the engineering of integrated knowledge networks (IKNs) through the use of a reference architecture. The purpose of the study is to gain a deeper understanding of the constructional principles underlying this class of collaborative networks. Although IKNs and enterprise engineering are both seen as promising approaches to the challenges of the Information Age, significant challenges still exist in the engineering of IKNs. Our globalised and commercialised society may currently be characterised by both extreme complexity and extreme rates of change. Enterprise engineering is seen as a promising approach to equip enterprises with the characteristics that are desirable in the modern economy, including flexibility and agility. Enterprise architecture contributes to this endeavour by providing a high-level design of the enterprise that allows for integrated engineering of the enterprise. From a commercial point of view, it has been widely recognised that the ability to innovate and generate new knowledge through the development of new products, services and processes is a key factor in the survival of enterprises. The latest trends in innovation management, however, show that the innovation process is no longer one that is executed inside a single enterprise, giving rise to the development of inter-organisational innovation networks. Furthermore, the importance of knowledge as a dynamic enabler of this networked innovation approach is highlighted. This has lead to the emergence of IKNs in which knowledge is created and shared between network stakeholders in order to foster sustainable innovation. The increasing rate of change means that enterprises, including IKNs, have progressively less time to react to market changes and opportunities. The emphasis is therefore on the potential of the EE and EA disciplines as tools to adapt to the dynamic landscape of the Information Age. At present, the ability to apply comprehensive enterprise engineering to IKNs is hampered by the lack of resources that describes sound constructional principles for these networks. The focus of this study is therefore on the application of the enterprise engineering discipline to IKNs through the development of a reference architecture. The reference architecture for IKNs is developed through design science research within a pragmatic and qualitative research strategy. The research problem is first identified and motivated. Various solution objectives are subsequently defined. This is followed by the design and development of the reference architecture through four iterative design cycles. A qualitative systematic review is conducted and serves as the foundation for the development of various reference models. The reference architecture for IKNs is demonstrated and evaluated through a series of illustrative scenarios, after which the utility, novelty and design rigour of the artefact is communicated. It was found that the reference architecture provides constructional principles in the engineering of IKNs, thus enabling the design, operation and research of this class of collaborative networks. The study therefore takes a first step toward extending the concept of EE to IKNs, and collaborative networks in general. This enables the greater adaptability of these networks to the dynamic environment of the Information Age. / AFRIKAANSE OPSOMMING: Hierdie tesis ondersoek die ontwikkeling van geïntegreerde kennisnetwerke (GK’s) aan die hand van ‘n verwysingsargitektuur. Die doel van die studie is om ’n beter begrip van die onderliggende ontwerpbeginsels van hierdie klas kollaborasie netwerke te kry. Alhoewel beide GK’s en ondernemingsingenieurswese beskou word as belowende benaderings tot die uitdagings van die Inligtingsera, bestaan beduidende uitdagings steeds in die ontwikkeling van GK’s. Ons geglobaliseerde, gekommersialiseerde samelewing word tans gekenmerk deur beide buitengewone kompleksiteit en buitengewone tempo-verandering. Ondernemingsingenieurswese word beskou as ’n belowende benadering om ondernemings toe te rus met die eienskappe wat in aanvraag is in die moderne ekonomie, insluitend aanpasbaarheid en vlugheid. Ondernemingsargitektuur dra by tot hierdie poging deur ’n hoëvlak ontwerp van die onderneming te voorsien wat geïntegreerde ontwikkeling van die onderneming toelaat. Vanuit ’n kommersiële oogpunt word dit ruim aanvaar dat die vermoë om te innoveer en nuwe kennis te ontwikkel deur die ontwikkeling van nuwe produkte, dienste en prosesse ’n kernfaktor in die oorlewing van ondernemings is. Die jongste benadering in innovasiebestuur toon aan dat die innovasieproses nie meer slegs in een onderneming uitgevoer word nie. Dit lei dan tot interorganisasie-innovasienetwerke. Die belangrikheid van kennis as ’n dinamiese instaatsteller van hierdie netwerk-innovasiebenadering word verder beklemtoon. Dit het gelei tot die ontstaan van GK’s waarin kennis tot stand gebring en gedeel word tussen netwerk belanghebbendes om sodoende volhoubare innovasie te bevorder. Die toenemende tempo in verandering beteken dat ondernemings, insluitende GK’s, toenemend minder tyd het om op markveranderings en -geleenthede te reageer. Die klem val daarom op die ondernemingsingenieursweseen ondernemingsargitektuur-dissiplines as hulpmiddels om by die dinamiese landskap van die Inligtingsera aan te pas. Tans word die vermoë om omvattende ondernemingsingenieurswese in GK’s te beoefen, gekniehalter deur die tekort aan hulpbronne wat grondige konstruksie-beginsels vir hierdie netwerke beskryf. Die fokus van hierdie studie is daarom die toepassing van die ondernemingsingenieurswese-dissipline op GK’s deur die ontwikkeling van ’n verwysingsargitektuur. Die verwysingsargitektuur vir GK’s word ontwikkel deur ontwerpwetenskapnavorsing binne ’n pragmatiese en kwalitatiewe navorsingstrategie. Die navorsingsprobleem word eers geïdentifiseer en gemotiveer. Verskeie oplossingsdoelwitte word vervolgens bepaal. Hierna geskied die ontwerp en ontwikkeling van die verwysingsargitektuur deur middel van die vier herhalende ontwerpsiklusse. Die verwysingsargitektuur vir GK’s word gedemonstreer en geëvalueer deur ’n reeks beeldende scenario’s, waarna die bruikbaarheid, nuutheid en ontwerpstrengheid van die artefak gekommunikeer word. Dit is bevind dat die verwysingsargitektuur konstruksiebeginsels in die ontwikkeling van GK’s voorsien en sodoende die ontwerp, werk en navorsing in hierdie klas kollaborasie netwerke moontlik maak. Dié studie neem ‘n eerste tree in die rigting om die konsep van ondernemingsingenieurswese tot GK’s uit te brei. Dit maak die groter aanpasbaarheid van hierdie netwerke by die dinamiese omgewing van die Inligtingsera moontlik.

In recent years, the causal relationship between inflammation and cancer has gained wider acknowledgement and acceptance. While various types of immune cells are involved in the process of inflammation, macrophages represent the major inflammatory component of many tumors. Derived from circulating monocytes, these cells migrate to tumor sites in response to molecular cues present within the tumor microenvironment. Once there, interactions with neoplastic cells shape the differentiation and functional orientation of macrophages into two phenotypically distinct subsets: the “classically” activated M1 macrophages and the “alternatively” activated M2 macrophages. The preeminent paradigm in macrophage-related cancer research is that within the tumor stoma, macrophages acquire an M2 phenotype characterized by production of pro-angiogenic factors, ECM degrading enzymes and up-regulation of anti-inflammatory responses, thereby promoting tumor progression. M1 macrophages, on the other hand are thought to exert anti-tumorigenic effects due to their production of pro-inflammatory cytokines, and reactive oxygen species (ROS). While the generation of ROS during immune responses is an important aspect of immune regulation and host defense, excessive ROS production has been implicated in the pathogenesis of various degenerative diseases, including cancer. Yet, despite the well-established role of M1 macrophages in generating high levels of ROS via NADPH oxidase (NOX), M1 macrophages are still largely viewed as anti-tumorigenic. Hence, this study reevaluates the complex interaction between prostate cancer (PCa) cells and tumor-associated macrophages (TAMs), and operates on the premise that PCa cells promote a pro-tumor microenvironment, denoted by increased inflammation and oxidative stress, in part, through M1 macrophage-mediated, NOX-derived ROS production. Accordingly, immunofluorescent analysis of prostate tissue microarrays demonstrated an influx of M1 macrophages in prostate carcinoma. Immature monocytes co-cultured with the poorly tumorigenic prostate cell line, LNCaP, demonstrated changes in morphology and protein expression consistent with M1 macrophage polarization. PCa cells co-cultured with M1 macrophages displayed significantly higher intracellular ROS levels. Furthermore, M1-mediated ROS generation through NOXs increased prostate cell invasiveness and anchorage-independent growth. Taken together, results from this study suggest a potentially novel pro-tumorigenic function of M1 macrophages in early PCa progression, and aid in understanding the complex role of inflammation in cancer.

Structured data stores have been the dominating technologies for the past few decades. Although dominating, structured data stores lack the functionality to handle the ‘Big Data’ phenomenon. A new technology has recently emerged which stores unstructured data and can handle the ‘Big Data’ phenomenon. This study describes the development of an artefact to aid in the analysis of NoSQL document data stores in terms of relational database model constructs. Design science research (DSR) is the methodology implemented in the study and it is used to assist in the understanding, design and development of the problem, artefact and solution. This study explores the existing literature on DSR, in addition to structured and unstructured data stores. The literature review formulates the descriptive and prescriptive knowledge used in the development of the artefact. The artefact is developed using a series of six activities derived from two DSR approaches. The problem domain is derived from the existing literature and a real application environment (RAE). The reviewed literature provided a general problem statement. A representative from NFM (the RAE) is interviewed for a situation analysis providing a specific problem statement. An objective is formulated for the development of the artefact and suggestions are made to address the problem domain, assisting the artefact’s objective. The artefact is designed and developed using the descriptive knowledge of structured and unstructured data stores, combined with prescriptive knowledge of algorithms, pseudo code, continuous design and object-oriented design. The artefact evolves through multiple design cycles into a final product that analyses document data stores in terms of relational database model constructs. The artefact is evaluated for acceptability and utility. This provides credibility and rigour to the research in the DSR paradigm. Acceptability is demonstrated through simulation and the utility is evaluated using a real application environment (RAE). A representative from NFM is interviewed for the evaluation of the artefact. Finally, the study is communicated by describing its findings, summarising the artefact and looking into future possibilities for research and application. / MSc (Computer Science), North-West University, Vaal Triangle Campus, 2014

The field of prostate cancer research is in need of biological markers that predict which cancers do not need treatment, those that can be treated successfully with a localized treatment and more specific cases in which patients are likely to have an aggressive form of cancer that will require more aggressive surgical and chemotherapeutic treatments. ZIC2 is one of five members of a family of proteins that play critical roles in neural crest and mesoderm growth in normal embryonic brain development and in the adult cerebellum of vertebrates. Found throughout the animal kingdom, ZIC1-5 genes encode five distinct ZIC proteins containing five highly conserved C2H2-type zinc finger motifs whose structural integrity is important in carrying out its function as a transcription factor. We hypothesize that ZIC2 has functional significance at the molecular and cellular levels in the initiation of prostate adenocarcinoma (PRAD) and the progression to metastatic and/or castration resistant prostate cancer (CRPC). Bioinformatic predictions suggest that the function of ZIC2 is regulated by post-translational modifications, such as phosphorylation, ubiquitination and sumoylation. This proposal further outlines the research hypothesis for investigating the role of ZIC2 in prostate cancer progression and the effects of the post-translational modification, ubiquitination, on the loss or gain of function of ZIC2.