Tesi sul tema "Agence de design"

Cette thèse prend place au sein d'une agence digitale qui met en œuvre des méthodes de design qui permettent d'impliquer ses client.e.s dans la conception. Ce terrain me permet d'observer des situations de co-conception qui rassemblent une agence et une organisation cliente, situations peu étudiées dans la littérature. Notre immersion et notre engagement en tant que designeure nous a permis de faire l'expérience des temporalités du travail en agence et de revenir en particulier sur ce que le vocabulaire et les méthodes dites de “sprint” supposent de rapport au temps dans la conception. C'est une thèse pluridisciplinaire qui réunit les sciences de l'information et de la communication et du design. Elles permettent d'analyser ensemble les situations de communication et de design ainsi que les supports qui les soutiennent.Il nous a ainsi paru important de comprendre la situation de co-conception moins à travers le concept d'espace (qui a tendance à prédominer) qu'à travers celui du temps.Notre hypothèse est que l'on peut considérer l'activité de design comme l'organisation de formats temporels qui ont des effets sur la participation mais aussi qui présupposent des modèles de la conception. La thèse porte attention aux dynamiques d'émergence. Ces dernières font intervenir un autre rapport au temps fondé sur des inter-relations en mouvement. Cette hypothèse nous a ainsi plus particulièrement conduit à étudier la méthode du “sprint” comme un format temporel mais également à être attentive à ce qui émerge au cœur de ces situations “formatées” et à la façon dont l'expertise du design noue et dénoue des temporalités. Nous observons finalement que la situation de design ouvre un espace transitionnel, un “dispositif bienveillant”, où le temps est “dynamiquement suspendu” pour justement permettre de tisser des liens entre la pluralité des temporalités qui traverse le projet entre passé, présent et futur
This thesis takes place within a digital agency that implements design methods that allow its clients to be involved in the design. This field allows me to observe co-design situations that bring together an agency and a client organization, situations that have been little studied in the literature. Our immersion and our commitment as a designer allowed us to experience the temporalities of agency work and to come back in particular to what the vocabulary and the so-called “sprint” methods imply in relation to time in design. It is a multidisciplinary thesis that brings together the sciences of information and communication and design. They make it possible to jointly analyze communication and design situations as well as the supports that support them.It therefore seemed important to us to understand the co-design situation less through the concept of space (which tends to predominate) than through that of time.Our hypothesis is that we can consider the activity of design as the organization of temporal formats which have effects on participation but also which presuppose models of design. The thesis pays attention to the dynamics of emergence. These latter involve another relationship to time based on moving inter-relations. This hypothesis thus more particularly led us to study the “sprint” method as a temporal format but also to be attentive to what emerges at the heart of these “formatted” situations and to the way in which design expertise ties and unties temporalities. Finally, we observe that the design situation opens up a transitional space, a “benevolent device”, where time is “dynamically suspended” precisely to allow links to be forged between the plurality of temporalities that crosses the project between past, present and future

Apprendre à porter un regard et à adopter une posture ethnologique pour élucider notre contemporain, pour comprendre les autres et soi-même. Une agence de design est ici le terrain d'une approche ethnologique, celle d'une ergonome réalisant une observation participante; et qui s'ouvrant à l'ethnologie et à l'ethnométhodologie, cherche à identifier les allants-de-soi, les croyances et les pratiques de ses membres. Quels sont les sens que les individus appartenant à une culture multiple donnent à leurs activités quotidiennes ? IP est une agence de design et d'innovation particulière. La croyance sur laquelle elle se base est celle de l'alliance entre les sciences humaines et sociales et le design. Pendant près de quatre ans, des designers et une ergonome ont travaillé dans cette agence, sur des projets d'innovation produit. Ces derniers ont été les supports observables des croyances et des pratiques des membres et ils illustrent ici leurs évolutions afin de répondre à l'alliance entre observation et création. Le travail des individus est passé d'une activité cloisonnée entre des métiers différents qui se méconnaissaient, à celle d'une équipe dans laquelle se sont constitués des allants-de-soi, des pratiques communes, des échanges et des partages, vers une co-construction de la méthode de l'agence, vers un travail de construction identitaire. La recherche traite du processus réel de travail de création, des rapports de coopération et la mobilisation des pratiques et des subjectivités pour passer de la notion de métier à celle d'individus, posture essentielle pour penser une amélioration de la démarche collaborative multidisciplinaire et l'intégration des métiers en conception
Learning how to carry a glance and to adopt an ethnological posture to elucidate our contemporary, to understand the others and oneself Here,a design agency is the ground for an ethnological approach, that of an ergonomist carrying out a participating observation; and who open to ethnology and ethnomethodology, is giving an attempt to identify the obvious concepts, the beliefs and the practices of its members. What are the directions that the individuals belonging to a multiple culture give to their daily activities? IP is a particular agency of design and innovation. The belief on which it is based is that of an alliance between social sciences and desjgn. During nearly four years, designers and an ergonomist have worked in this agency, on projects of products innovation. Those were the observable supports of the beliefs and of the practices of the members and they illustrate here their evolutions in order to answer to the alliance between observation and creation. The work of the individuals went from an activity partitioned between different professions, which fail to recognize each other well, with that of a team in which the obvious concepts, the common practices, the exchanges and the divisions constituted themselves, towards a co-construction of the method of the agency, towards an identity construction work. The research deals with the real process of creation work, of the relations of co-operation and the mobilization of the practices and subjectivities to go from the concept of profession to the one of individuals, an essential posture to consider an improvement of the multidisciplinary collaborative process and the integration of the professions in design

Les nouvelles technologies se succèdent dans la formation sans que de véritables réponses aux problématiques de la formation continue en ligne soient apportées. Et pourtant, à chaque introduction d’une nouvelle technologie, des travaux de recherche sont menés sur les apprenants, la théorisation du design ou encore la caractérisation des dispositifs créés. Mais il manque une analyse sur le terrain du design pour envisager des évolutions positives et l’introduction de résultats de recherche dans les pratiques.A l’ère des MOOC et de leur utilisation par les entreprises, comment les formations continues en ligne sont-elles « designées » ? Dans le contexte spécifique de la création de MOOC en agence, nous décrivons le design des formations en ligne sous deux angles : celui de l’activité de design et celui des expériences produites.Bénéficiant d’un statut particulier de Doctorante salariée d’une agence spécialisée en formation en ligne, des « scènes de vie » issues d’une participation observante ont permis d’établir un modèle de design, selon la Théorie de l’Activité.Pour l’étude d’expériences, quatre projets MOOC de l’agence ont servi d’études de cas. Après la présentation des choix de conception spécifiques à chaque projet et des résultats quantitatifs obtenus, les représentations issues d’expériences sont analysées suite à la réalisation d’entretiens semi-directifs.Ces travaux proposent finalement une méthode de description du design et d’analyse conjointe du design et des expériences. Dans le cadre du terrain observé, de nouvelles perspectives dans le design de ces formations sont soulevées concernant la médiation des savoirs, ses dimensions stratégique et évolutive
In the domain of training, new technologies have come and gone but have not provided real answers to the problems of online continuing training. And yet, with each introduction of a new technology, research is conducted into the learners, the theoretical aspects of course design and the characterization of the devices created. What is lacking seems to be an analysis of design in the field; such an analysis would make it possible to imagine positive developments and to implement research results in hands-on practice.In the era of MOOC and their use by companies, how are online continuing training courses designed ? In the specific context of the creation MOOC by an agency, we set out to describe the design of online training from two perspectives : that of the design activity and that of the experiences that the training brings about.For this research I had the advantage of being at the same time a PhD student and a salaried employee of an agency specialized in online training and was thus able to collect « scenes of life » as both participant and observer and these were used to establish a model of design, according to the Theory of Activity.For the study of the experiences, four MOOC projects of the agency served as case studies. After a presentation of the design choices specific to each project and the quantitative results obtained, the representations resulting from the experiences are analyzed based on the semi-directive interviews that we carried out.Finally, this work proposes a descriptive method of design and joint analysis of design and experiences. As part of the observed field, new perspectives related to the design of online training were raised concerning the mediation of knowledge, its strategic and evolutionary dimensions

Cette thèse porte sur les spécificités du secteur public et leurs impacts sur les incitations et la performance. Elle mobilise les outils microéconomiques de la théorie des contrats et l’analyse économétrique. Parmi ces caractéristiques, une attention particulière est portée sur les problématiques de surveillance, de gestion de l’information et de contraintes budgétaires. Le premier chapitre de cette thèse contribue au débat sur la transparence dans le secteur public en considérant l’une de ses caractéristiques majeure : un budget limité. Cette question est étudiée comme un problème de design informationnel et utilise un modèle principal agent sous aléa moral pour montrer que la transparence a plus de chance d’être sélectionnée par le principal lorsque que le budget disponible et la valeur de la tache sont faibles. Le deuxième chapitre s’attache à offrir une nouvelle explication théorique à l’intuition associant un accroissement de la pression bureaucratique à une baisse de la qualité. Dans ce but, l’idée d’«extra-mile» est introduite dans un modèle principal agent classique sous aléa-moral. Le management bureaucratique est caractérisé par l’introduction d’une procédure définie comme l’association d’une codification et d’une vérification. Une telle procédure permet une vérification plus précise de l’action de l’agent mais est source d’inefficience sociale. Le dernier chapitre, dans une démarche théorique et empirique, propose une nouvelle explication de la différence des prix de l’eau en France en se fondant sur des arguments organisationnels
This thesis focuses on the structural specificities of the public sector and how they impact incentives and performance. It uses the microeconomic tools of contract theory and econometric analysis. Among these characteristics, special attention is paid to monitoring, information management and budget constraints by applying a theoretical lens, that allows to provide new insights into the incentive systems in place in the public sector. The first chapter contributes to the debate on transparency in the public sector by considering one of its major features, i.e. a limited budget. This issue is studied as an information design problem and employ a principal-agent model with moral hazard to show that if the principal has to choose between total transparency and total opacity, then transparency is more likely to be optimal when tasks are least valuable and budgets are lowest. The second chapter aims at capturing a new theoretical explanation for the widespread intuition that more bureaucracy could lead to less effort and quality despite improved control. To that end, the idea of “the extra mile” is introduced in a classic principal-agent model with moral hazard. Bureaucratic management is characterized by the use of procedures, defined as the association of codification and verification. A procedure allows for more accurate verification of the agent’s action, but is socially inefficient. In the third chapter, using both theory and regression analysis, we propose a new explanation for price differences in the French water industry based on organizational arguments

Ce travail porte sur la conception du « durable » dans le milieu de l'architecture en Inde. Il s'appuie, notamment, sur deux séjours effectués en 2011 et en 2012, dans une agence d'architecture dans la ville d'Ahmedabad (dans l’État du Gujarat) et dans un bureau d'études dans la ville de Bombay (dans l’État du Maharashtra). L'arrivée des labels sur le marché de l'immobilier et de la construction permet de mettre au goût du jour l'idée de « durabilité » dans la conception architecturale et de raviver un débat typiquement local. La polémique concerne, plus précisément, la mise en œuvre des labels « LEED » d'origine nord-américaine. Ce « durable » « occidental » et procédural, qui sert des logiques économique et de marketing, ne représente pas, selon les architectes, l'« authentique ». Or, l'Inde est le pays, par excellence, du « durable » : il suffit de regarder autour de soi les modes de vie, la culture indienne, ou évidemment, l'architecture « traditionnelle » et « vernaculaire ». Au delà de cette rhétorique entre tradition et modernité, en suivant dans les petits détails des projets d'architecture en train de se faire, l'enquête ethnographique montre les similarités entre ces deux lieux de conception. Le devenir du « durable » est lié, d'une manière ou d'une autre, à l'idée d'engagement et de conviction. L'idéal de « durabilité » ne repose pas tant sur une certitude (qui demeure pour le reste toujours plus ou moins relative selon les acteurs), mais sur le quotidien et les pratiques qui tendent à le faire vivre et à lui donner corps le plus possible
This work explores the making of sustainability in the field of architecture in India. It is based on two ethnographical studies made in 2011 and 2012, in an architectural studio in the city of Ahmedabad (in the State of Gujarat) and in an consultancy firm in the city of Bombay (in the State of Maharashtra). The arrival of labels on the real estate and construction markets makes it possible to date the idea of sustainability in architectural design and rekindle a typical local debate. The controversy more specifically concerns the implementation of LEED certifications of American origin. This “Western” and procedural sustainability, which serves economic and marketing logics, does not represent, according to the architects, the “authentic” one. But then, India is said to be, par excellence, the country of sustainability: just look the lifestyles, Indian culture, or of course, the “traditional” and “vernacular” architecture. Beyond the rhetoric between tradition and modernity, the ethnographic investigation follows the small details of architectural projects in the making and shows the similarities between the studio and the consultancy firm. The fate of sustainability is related, in one way or another, to ideas of commitment and conviction. The ideal of sustainability is not lying so much on a certainty (which still more or less depends on the actors), but on the daily life and on the practices that tend to give it life and the most substance possible

This research aims at developing a different kind of virtual world that is dynamically designed and implemented as needed. Currently, most virtual world designs are considered static. Similar to the physical world, these worlds are pre-defined prior to their use. The resultant environments serve certain purposes but do not take into consideration possible changes to the purposes during their use, changes which often occur when the occupants interact with the environments and with each other. Virtual worlds as networked environments can be flexibly configured and programmed. This flexibility makes it possible to consider virtual world designs in terms of dynamics and autonomy, reflecting the changing needs of different moments. To achieve dynamic designs of virtual worlds, this study applies a computational approach using rational design agents. A Generative Design Agent (GDA) model is developed that specifies computational processes for reasoning and designing in virtual worlds. The GDAs serve as personal design agents to the virtual world occupants. Design formalisms for virtual worlds are also addressed. The design component of a GDA is supported by the application of a generative design grammar. On one hand, generative design grammars serve as the generative force to be applied by the GDAs for virtual world design automation. On the other hand, each grammar defines coherent stylistic characterisations shared by the virtual world designs it generates. The technical outcomes of the research consist of the GDA model and a generative design grammar framework. The framework provides guidelines and strategies to designers for developing generative design grammars that produce different design languages for virtual worlds, rather than predefine every detail of all possible virtual world designs. GDAs monitor the virtual worlds and the various activities that occur in the worlds, interpret the occupants’ needs in the virtual worlds and the state of the worlds based on these observations, hypothesise design goals in order to satisfy these needs, and finally apply generative design grammars to provide virtual world designs for the moment, or initiate other actions in the worlds, according to the current design goals, on behalf of the occupants. The development of the GDA model and the generative design grammar framework provides new perspectives for understanding and developing virtual worlds. The GDA model challenges the conventional way that virtual worlds are designed and implemented, and this leads to dynamic designs of virtual worlds. The generative design grammar framework provides a computational approach to formally defining design languages for virtual worlds.

Doctor of Philosophy (PhD)
This research aims at developing a different kind of virtual world that is dynamically designed and implemented as needed. Currently, most virtual world designs are considered static. Similar to the physical world, these worlds are pre-defined prior to their use. The resultant environments serve certain purposes but do not take into consideration possible changes to the purposes during their use, changes which often occur when the occupants interact with the environments and with each other. Virtual worlds as networked environments can be flexibly configured and programmed. This flexibility makes it possible to consider virtual world designs in terms of dynamics and autonomy, reflecting the changing needs of different moments. To achieve dynamic designs of virtual worlds, this study applies a computational approach using rational design agents. A Generative Design Agent (GDA) model is developed that specifies computational processes for reasoning and designing in virtual worlds. The GDAs serve as personal design agents to the virtual world occupants. Design formalisms for virtual worlds are also addressed. The design component of a GDA is supported by the application of a generative design grammar. On one hand, generative design grammars serve as the generative force to be applied by the GDAs for virtual world design automation. On the other hand, each grammar defines coherent stylistic characterisations shared by the virtual world designs it generates. The technical outcomes of the research consist of the GDA model and a generative design grammar framework. The framework provides guidelines and strategies to designers for developing generative design grammars that produce different design languages for virtual worlds, rather than predefine every detail of all possible virtual world designs. GDAs monitor the virtual worlds and the various activities that occur in the worlds, interpret the occupants’ needs in the virtual worlds and the state of the worlds based on these observations, hypothesise design goals in order to satisfy these needs, and finally apply generative design grammars to provide virtual world designs for the moment, or initiate other actions in the worlds, according to the current design goals, on behalf of the occupants. The development of the GDA model and the generative design grammar framework provides new perspectives for understanding and developing virtual worlds. The GDA model challenges the conventional way that virtual worlds are designed and implemented, and this leads to dynamic designs of virtual worlds. The generative design grammar framework provides a computational approach to formally defining design languages for virtual worlds.

This thesis project opens up an interaction design space in the InfoSec domain concerning raising awareness of common vulnerabilities and facilitating counter practices through seamful design.This combination of raising awareness coupled with boosting possibilities for deliberate action (or non-action) together account for augmenting agency. This augmentation takes the form of bottom up micro-movements and daily gestures contributing to opportunities for greater agency in the increasingly fraught InfoSec domain.

In the field of digital media, the study of interactive narratives holds the aesthetics of agency and dramatic agency as core to digital design. These principles hold that users must reliably be able to navigate the interface and the narrative elements of the artifact in order to have a lasting appeal. However, due to recent academic and critical discussions several digital artifacts are being focused on as possible new ways of engaging users. These artifacts do not adhere to the design aesthetics foundational to digital media, but represent a movement away from the principle of dramatic agency in interactive narratives. In an attempt to understand this separation and offer a solution to this developing issue, another non-digital interactive medium was studied: tabletop role-playing games. The designers of this medium were studied to understand the techniques and methods they employed to create dramatic interactive narratives for their users. These case studies suggested the designers used a third design aesthetic, design agency, to help balance the tension between agency and dramatic agency of the users of their medium. This design aesthetic could provide a balancing force to the current issues arising within interactive narrative.

Though the topic of learner agency has received relatively little discussion in the literature of educational technology, it is nevertheless a significant and actually omnipresent concern of both scholars and practitioners. Through the journal-ready articles contained herein, I show how theories of learning and certain practices of instructional designers reflect implicit positions on the agency of learners. I also discuss agency in more concrete terms as the responsibility for learning that is shared with learners in instructional design contexts. In addition, I provide practical suggestions to help designers keep the learner at the forefront of their design thinking. Through this research, I hope to make the broad philosophical concept of agency more accessible and practical, and to outline some initial directions for further inquiry and practical application in the field of educational technology.

South African democracy is perceived and evidenced to be under duress. This research questions how design, when underpinned by transdisciplinarity and abduction, can articulate and address this problem. The literature is reviewed to map how designed objects, processes, and philosophy enable and hamper notions of democracy. Within this literature, two concepts are identified as key to a South African context, and require further research - Indigenous Knowledge Systems (IKS) and cosmopolitanism. The African concept of Ubuntu, a subset of IKS, is argued to function as an authentic context, however, its ability to influence urban and diverse environments is questioned. Cosmopolitan theory, and Dewey's focus on experimentation, is argued to promote normative organisation, and its application to facilitate urban and dynamic participation is questioned. The Cape Town precinct - Long Street - provides a case study with which to unpack these two key concepts, and obtain empirical data to answer the research questions. Qualitative data is firstly obtained, from key informants who have the authority to influence the case study delineation. Based on this data, an Abductive instrument (Ai), based on Experience Design (XD) and Designing For Participation (DFP) methods, obtains quantitative data from public actors. Findings from the research include: political philosophy is increasingly enabled and countered by design; design is required to deconstruct and not fortify South African democracy; design is capable of operationalising decolonisation as a constructive, and not reductive, act; indigeneity is being reclaimed in urban contexts, and reinterpreted by design; reflective participation, and not historical assimilation, is a fundamental challenge for political studies; publics experiment with, and not on, themselves. The key implication of the research is designing critical representation, which is at the intersection of design, IKS, and cosmopolitanism. Here, empowerment is an indigenous imperative, design synthesises direct and representative democracy, and design intent is hyper-transparent.

This thesis is about incentive design in presence of agents who exhibit reciprocity and it is composed by four papers, each corresponding to a self-contained chapter. The first one presents a theoretical analysis of the optimal compensation scheme design in presence of workers who are motivated both by reciprocity toward the principal and the colleagues. The third and the fourth ones apply the methodology of laboratory experiment to investigate, respectively, the presence of spillovers effects across alternative incentive systems and a different but simultaneous social dilemma; and the relevance of (useless) peer information under a piece rate incentive scheme in which workers can observe each other. Finally, the last chapter empirically analyzes the effectiveness of alternatives incentives designed for waste sorting and recycling and applied in the Treviso district from 1999 to 2008. In recent years, a growing literature analyzes the factors which impact incentives’ effectiveness at individual as well as group level (e.g. organizations, communities, etc). Indeed, besides a considerable number of studies documenting that incentives works (Gibbons, (1997), Lazear (2000)) a recent growing literature reports evidences from field and laboratory experiments about cases in which incentives are not effective (Angrist and Lavy, 2009) or even detrimental, leading to undesired results and crowding-out of intrinsic motivation (see for instance, Ariely et al., 2009; Frey and Oberholzer-Gee, 1997; Gneezy and Rustichini, 2000). In particular, it is not obvious that incentives designed under the assumption that individuals are self interested, result equally effective even in those cases in which agents exhibit other regarding preferences, Gintis et al. (2005). If incentives and motivations are substitute, incentives results to be ineffective or even counterproductive. In these situations we observe the so called crowding out of intrinsic motivation or over-justification effect, Bénabou and Tirole, (2003). Symmetrically, incentives may reinforce intrinsic motivation, acting as a complement, as documented by Bowles (2010), Galbiati and Vetrova (2009). In the first chapter we analyze a principal two agents model. Relying on the relevance of other-regarding preferences in workplaces, the chapter provides a behavioral explanation for the extra-effort provision in organizations (i.e. overtime, additional task, etc) when workers exhibit horizontal reciprocity concerns. In particular the chapter shows that a profit maximizing employer may find it convenient to offer employees a relative compensation scheme, which, by exploiting negative horizontal reciprocity, induces extra effort exertion but does not pay any monetary compensation in equilibrium. This result is robust to the introduction of vertical reciprocity concerns which cannot be neglected in many organizations. Chapter 2 contains a laboratory experiment which investigates how different incentive systems interact with individuals’ willingness to cooperate in social dilemmas, highlighting the mechanisms which induce crowding out of voluntary cooperation. In particular the chapter investigates the impact of different incentives on simultaneous public good contributions in economically unrelated games. The results show that tournaments, but not simple piece rate schemes, reduce contributions by about 40%. However, the effect is brittle. The incentivized elicitation of beliefs eliminates the effect. It also vanishes immediately if the games are played sequentially rather than simultaneously. Therefore, the designers of competitive incentive schemes must pay close attention to the framing of the scheme in order to avoid negative spillovers. Chapter 3 presents results from a laboratory experiment which tests the impact of peers’ effect on individual productivity under piece rate incentives. Along 15 repetitions, being informed about their productivity, participants choose an initial effort level which they can revise after a feedback on result. Knowing that the optimal effort choice may differ across subjects, half of the participants received also a feedback about the initial choice and the results of another participant in the room without knowing her/his productivity. Despite the fact that information about peer is useless in determining the individual optimal effort, we find that individuals manifest selective attention to information about peer. In particular, those subjects informed that the peer obtained a higher result have a higher probability to revise their initial choice and a higher probability to revise it optimally. The fourth chapter is an empirical analysis of the effectiveness of incentives for waste recycling. We use data on the amount of waste produced in each of the 95 municipalities in the district of Treviso (Italy) for the period 1999-2008. The specificity of local regulative frame has created conditions for a quasi-natural experiment. Our dataset is unique for three reasons. First, in our sample the incentive mechanism is randomly assigned to the municipalities. Second, our data show wide heterogeneity of policies over the years. Third, its panel structure allows us to control for potential increasing concern for the environment, and to isolate potential “learning effects” of incentives over time. We find that the introduction of economic incentives has a significant and positive net effect of around 12% on the recycling waste ratio, that is complementary to the positive effect induced by door-to-door collection. The effect of PAYT is obtained by increasing the production of sorted waste (+10%), while the production of total waste remains unchanged. We therefore conclude that economic incentives are an effective tool to reach the desired goal.
Abstract [In Italian] Incentive Design with Reciprocal Agents La presente tesi analizza la definizione ottimale di incentivi in presenza di agenti economici caratterizzati da other regarding preferences, e in particolare preferenze per la reciprocità. Recentemente, una crescente letteratura in ambito economico analizza i fattori in grado di influenzare l’efficacia dei sistemi di incentivazione sia a livello individuale che di gruppo (es. organizzazioni, comunità, etc). Accanto a una corposa letteratura che documenta il corretto funzionamento degli incentivi, es. Gibbons, (1997), Lazear (2000), infatti, un filone di studi in crescita riporta evidenze di casi in cui gli incentivi sembrano non essere efficaci, (Angrist and Lavy, 2009) o addirittura controproducenti, determinando il crowding out delle motivazioni intrinseche (si veda, tra gli altri Ariely et al., 2009; Frey e Oberholzer-Gee, 1997; Gneezy e Rustichini, 2000). In particolare, non è ovvio che incentivi disegnati partendo dall’assunzione che gli agenti economici siano motivati esclusivamente da self-interest siano ugualmente efficaci nei casi in cui gli individui presentano c.d. other regarding preferences, Gintis et al. (2005), Bowles (2009). Nei casi in cui risultino sostituti delle motivazioni, gli incentivi economici saranno inefficaci o addirittura controproducenti. In queste situazioni osserveremo il c.d crowding out delle motivazioni intrinseche o un over-justification effect, Bénabou and Tirole, (2003). Ci sono però anche dei casi in cui gli incentivi rinforzano le motivazioni intrinseche, manifestando un effetto complementare, come documentato da Bowles (2009), Galbiati and Vetrova (2009). La tesi è composta da quattro capitoli, facenti riferimento a quattro articoli autonomi. Il primo capitolo è un modello teorico che spiega la presenza di lavoro straordinario non (adeguatamente) ricompensato documentato in molte organizzazioni e in quasi tutti i paesi industrializzati. Quando i lavoratori sono motivati da reciprocità sia verso il proprio datore di lavoro (o in generale verso un superiore gerarchico) sia verso i colleghi, un manager interessato a massimizzare il profitto troverà conveniente offrire ai lavoratori uno schema di compensazione competitivo che induca i dipendenti a fare lavoro straordinario senza essere (totalmente) compensati. I lavoratori saranno motivati da reciprocità negativa verso i colleghi e vorranno impedire loro di segnalarsi agli occhi del datore di lavoro. Il secondo capitolo utilizza la metodologia sperimentale per analizzare la presenza di effetti di spillover tra due contesti decisionali diversi ma in cui i soggetti partecipano simultaneamente. Un contesto decisionale è sempre identico in ognuno dei tre trattamenti, e presenta i caratteri del dilemma sociale. Il secondo contesto decisionale varia in ogni trattamento e fa riferimento a diverse tipologie di sistemi di incentivi: incentivi di team, tornei e piece rate. Spesso, infatti, si è simultaneamente coinvolti in più interazioni con diverse persone. In ambito lavorativo, per esempio, il lavoratore compete con alcuni colleghi (es. per avanzamenti di carriera) e deve collaborare con altri. Mentre alcuni ambiti di interazioni possono essere oggetto di diverse forme di incentivazione, esiste una dimensione in cui la cooperazione volontaria è necessaria ma non può essere imposta. Il lavoro evidenzia che quando i soggetti sono contemporaneamente esposti a tornei e contesti di dilemma sociale, il livello medio di cooperazione volontaria sarà minore del caso in cui i soggetti siano esposti a un incentivo di team. Questa evidenza suggerisce di incorporare anche considerazioni legate agli effetti di spillover nel valutare l’efficacia dei sistemi di incentivazione. Il terzo capitolo analizza sperimentalmente la rilevanza di informazioni (inutili) su pari (es. colleghi in un’organizzazione) in presenza di schemi di compensazione di tipo individuale. In molti contesti organizzativi, infatti, i lavoratori possono osservarsi reciprocamente non è chiaro quale sia il livello ottimale di comunicazione e trasparenza interna che debba essere promosso da parte dei manager. I risultati di questo lavoro dimostrano che avere informazioni su soggetti simili aumenta la probabilità di rivedere le proprie scelte in maniera ottimale ma questo effetto è rilevante solo se l’informazione veicolata informa il soggetto di essere in una situazione peggiore del suo pari. I soggetti, pertanto, manifestano una forma di attenzione selettiva alle informazioni sugli altri. Infine, l’ultimo capitolo presenta un’analisi empirica sull’efficacia di sistemi di incentivi alternativi finalizzati ad aumentare la percentuale di raccolta differenziata. Lo studio utilizza dati sulla produzione annuale di rifiuti di 95 comuni nella provincia di Treviso dal 1999 al 2008. In seguito a un provvedimento legislativo regionale i paesi della provincia sono stati assegnati a tre consorzi che hanno perseguito strategie differenti per la gestione dei rifiuti urbani. In particolare, mentre quasi tutti i comuni hanno un programma di raccolta dei rifiuti porta a porta (DtD) solo un sottogruppo di comuni ha adottato una metodologia di pagamento che lega la produzione di rifiuti all’ammontare effettivo pagato, c.d. Pay as you throw (PAYT). La nostra analisi dimostra che sia la DtT che la PAYT aumentano sensibilmente la percentuale di raccolta differenziata, la tariffa ha un effetto che cresce significativamente nel tempo. Inoltre, sebbene sia documentato un significativo spostamento dei rifiuti dai comuni che adottano la PAYT a quelli limitrofi che non hanno la DtD, a livello di municipalità questo effetto è trascurabile dal momento che l’effetto netto associato all’adozione della PAYT è positivo.

This study focuses on the role of structured derivative securities to meet diverse corporate financing objectives in the light of agency theory and asymmetric information. The focus is on the nonconvertible callable-puttable fixed-coupon bonds. The primary objective is to discern the marginal role of the put and put-deferred features in addressing the agency issues and asymmetric information. A sample of (159) securities issued over the period (1977-2005) are examined using Merton's (1974) structural contingent claims valuation model. The put option as well as the deferred put option incorporated in these securities is found to mitigate the asset substitution issue. It is also found that these contract features provide considerable insurance against the asymmetric information about the firm's downside risk. Specifically, the effects of asset substitution are mitigated because the put option reduces sensitivity of the security's value to the changes in the firm's volatility. Prior to this study, this effect was believed to be driven primarily by the conversion feature in the convertible bonds and the preferred stocks. In addition, the long-term performance of the underlying common stock indicates systematic negative performance for the protracted periods both prior and subsequent to the issuance, yet it is found that this decline in the equity value has only a limited negative impact on the security.
Ph.D.
Department of Finance
Business Administration
Business Administration PhD

This essay is a look into the future of games with new technology at hand, it serves as acloser look at new challenges and ways to overcome those challenges in VR game design.What new untapped way of acting on immersive storytelling can we convey with thisinteractive medium and how can we treat our players sense of agency within a VR world withthe necessary respect it deserves. This paper will dive into the idea of walking a mile insomeone else’s shoes and how to create a believable, narrative driven, non-restrictive gameexperience using aesthetic choices, world interactions and environmental storytelling as ourdesign tools. Aesthetic choices aren’t just a matter of achieving the highest realism thoughgraphical fidelity, instead it requires us to go deeper and look at a more traditional way ofdesigning our games art, to deeper convey immersion through minimalism and environmentaldesign to name a few. The goal is to understand how a world’s environments and the gameart in that environment could affect agency, all to support a more deeply focused, curious andin the end more immersive session of play.A virtual reality game called Norn have been produced alongside this paper to showcasethese features come into play. Norn is a narrative driven experience set in a stylistic old norsesetting where you play as a 18 year old girl named Thora and her sister Eira in a coming ofage story told in a different way.We have concluded that methods like the “Weenie”-method help to produce ways to guideplayers subconsciously but need carefully iterative improvements to work. We have also useddesign methods such as Bartle’s (1996) taxonomy of player types and Schell’s´(2008)“Pleasures” to build an inviting game environment and gameplay around to achieve personalagency. All while streamlining the games art both to overcome technical challenges but alsoto show how stylized environments can help accentuate the intended experiences compared toa realistic one.

The present thesis deals with the playful exploration of fermentation as a practice of care. Fermentation has a lot of positive impacts and can be seen as a practice of care in relation to human self-care, caring with human others, relationships to non-human beings, like microorganisms, and caring with the planet Earth. Based on the question ‘What can game design do to explore fermentation as a practice beyond human (self-) care?’ I developed an Online Fermentation Game. The game functioned as a conversational framework to explore together with co-creators the possibilities of more careful and sustainability-oriented food practices on the example of fermentation. The game involved the step by step and hands-on fermentation of fruits and vegetables while exploring the complexity of care in relation to fermentation.  With this project, I aimed to offer a co-learning space to explore together with co-learners the possibilities of more careful and sustainable food practices on the example of fermentation in a playful way. To create a dialogue about more than human care in relation to food, in particular fermentation. To inspire the co-learners to question their relationships around food and discover which actors to care with. Beyond this project and in a larger context, I aim for a paradigm shift from the individualistic human benefit towards a notion of more than human care. This shift can make a huge difference regarding a more sustainability-oriented future of food. With this thesis project, I strived to make a small contribution to this long term vision. Starting from the human need for healthy food, the blind spot of acknowledging fermentation as a sustainability-oriented practice beyond human care, that the majority of other fermentation workshops is missing, was explored in a playful way. The global Coronavirus (COVID-19) pandemic that this project happened to be situated in challenged me in creating a safe and comfortable co-learning space. Therefore, this project focused on creating a digital- and home-based game experience. To hand over, other design practitioners and change agents can apply and transform the game as part of their fermentation projects. On a broader perspective, the concept of this explorative design game can be adapted inside but also outside the food sector. The project serves as inspiration for a playful and at the same time careful approach to design and change-making. Moreover, it shows an example of shifting community spaces provoked by crises.

The ethics training program of the United States Army Corps of Engineers (USACE), Alaska District, a recipient of the Office of Government Ethics (OGE) 2010 Education and Communication Award, was studied to determine if the training fostered employee awareness of unethical situations within the workplace. The study fills a gap in scholarly literature in that never before had a peer-review study been done to examine how ethics training fosters awareness within an award-winning federal agency. The method and design used for collecting the data was the qualitative exploratory case study. Seven data sources were analyzed using NVivo 10 ^® software and Microsoft Excel and conclusions drawn by use of data source triangulation. Two primary data sources used were responses from two sets of interview questions: one set with 15 employees and another set with two ethics training coordinators. The other five sources of data evidence used were the OGE 2009 Education and Commission Awards Announcement, the OGE 2009 Education and Communication Award Application Form submitted by Alaska District to OGE, samples of the Ethics Monthly Treats, and comments made by the interviewees on the 2-minute ethics video (Secret Ethics Man), and brownbag lunches. The framework for this study was Gagne’s theoretical instructional design model. The three emerging themes were: ethics information was distributed frequently, innovative delivery methods, and content of ethics instruction. The results of the study indicate that the design, delivery, and components of the training program may have been effective in fostering employee awareness of unethical situations within the workplace.

The Glucagon-like peptide 1 receptor (GLP-1R) belongs to the pharmaceutically important Class B family of G-protein coupled receptors (GPCRs) and its incretin peptide ligand GLP-1 analogs are adopted drugs for the treatment of type 2 diabetes (T2D). Despite remarkable anti-diabetic effects, Glucagon Like Peptide-1 (GLP-1) peptide-based drugs are limited by the need of injection or high cost oral formulation. On the other hand, developing non-peptide small molecule drugs targeting GLP-1R remains elusive likely due to the large nature of the orthosteric binding site on GLP-1R. A promising approach is to develop small molecule agonistic positive allosteric modulators (ago-PAMs) or positive allosteric modulators (PAMs) of GLP-1R by targeting the potential allosteric sites in the transmembrane (TM) domain of human GLP-1R.

As the first step of taking this approach, we constructed a three-dimensional structure model of the TM domain of human GLP-1R using homology modeling and conformational sampling techniques. Next, a potential allosteric binding site on the TM domain was predicted computationally. In silico screening of drug-like compounds against this predicted allosteric site has identified nine compounds as potential GLP-1R agonists. The independent agonistic activity of two compounds was subsequently confirmed using cyclic adenosine monophosphate (cAMP) response element (CRE)-based luciferase reporting system. One compound was also shown to stimulate insulin secretion through in vitro assay. In addition, this compound synergized with GLP-1 to activate human GLP-1R.

In 2017, the crystal structures of GLP-1R in its active state (PDB ID: 5VAI) became available. Hence, we have performed another round of in silico screening employing this structure. First, the potential ligand binding sites in 5VAI were identified using computational tools and in silico screening procedure as described above was carried out again. A new small 8 molecule with low molecular weight and logP was identified. In vitro studies of this compound confirmed that it acts as the ago-Positive Allosteric Modulator (PAM) of GLP-1R that improves GLP-1's affinity and efficacy towards GLP-1R. When used in combination with GLP-1, this compound improves insulin secretion than using GLP-1 alone. Site specific mutagenesis studies confirmed its binding site as predicted in the TM domain of GLP-1R.

Finally, this ago-PAM molecule was further optimized to improve its potency and specificity towards GLP-1R using structure-based optimization strategy and medicinal synthesis. The newly designed compound, whose molecular weight was less than the parental compound, was found to act as the PAM of GLP-1R and showed improvement in the specificity than the parental compound. Thus, this new compound could be further exploited in the drug development for T2D treatment.

These results demonstrated that allosteric regulation exists in GLP-1R and can be exploited for developing small molecule agonists. The success of this work will help pave the way for small molecule drug discovery targeting other Class B GPCRs through allosteric regulations.

After decades of exorbitant antibiotic misuse and overuse in human medicine, agriculture and livestock industry, multidrug resistant bacteria (MDR) have become a major medical concern. In this regard, the design of new, safe, and effective antimicrobials, particularly against Gram-negative bacteria is an urgent need. Polymyxins are antimicrobial lipopeptides, highly active and selective against Gram- negative bacteria which were discovered in 1947, but their use was abandoned in the 1970s due to nephro- and neurotoxicity issues. In the last decades, polymyxins have been rescued as last line therapy in hospitals due to the antibiotic crisis. In that regard, 31 new polymyxin-based compounds were designed, synthesized, and characterized during this work. Furthermore, their biological activity and mechanism of action were evaluated using diverse microbiological and biophysical assays. Finally, two compounds were selected as promising candidates for further development, they presented comparable in vitro and in vivo potency to that displayed by natural polymyxin and outstandingly low nephrotoxic effects in vivo. On the other hand, the ability to form pores on bacterial membranes of BP100 was studied. BP100 is an 11-residue antimicrobial peptide derived from the well-known cecropin A and melittin. By studying a series of BP100 analogues with different lengths ranging from 4 to 24 amino acids, it was possible to determine its potential mechanism of action, which consists in a dynamic carpet mechanism, where BP100 gets inserted dynamically into the membrane, perturbating the bilayer, increasing the membrane permeability and ultimately producing the cell death.
Després de dècades d'excessiu ús d'antibiòtics en la medicina humana, l'agricultura i la indústria ramadera, els bacteris multiresistents (resistents a molts o tots els antibiòtics convencionals) s'han convertit en un important problema de salut pública de primer ordre a escala mundial. En aquest sentit, és de gran importància el disseny de nous antimicrobians, segurs i efectius, especialment contra els bacteris Gram-negatius. Les polimixines són lipopèptids antimicrobians, altament actius i selectius contra bacteris Gram-negatius que es van descobrir l'any 1947, però el seu ús es va abandonar a la dècada dels 70 a causa de la seva nefro- i neurotoxicitat. En les últimes dècades, les polimixines han estat rescatades com a teràpia d'últim recurs als hospitals a causa de la crisi dels antibiòtics. Per aquest motiu, durant aquesta tesi es van dissenyar, sintetitzar i caracteritzar 31 nous compostos basats en polimixina. A més, es va avaluar la seva activitat biològica i el seu mecanisme d'acció mitjançant diversos assajos microbiològics i biofísics. Finalment, es van seleccionar dos compostos com a candidats més prometedors per al seu posterior desenvolupament. Aquests presentaven una activitat in vitro i in vivo comparable a la mostrada per la polimixina natural i uns efectes nefrotòxics in vivo excepcionalment baixos. D'altra banda, es va estudiar la capacitat de formar porus a les membranes bacterianes per part del BP100. El BP100 és un pèptid antimicrobià d'11 aminoàcids derivat de cecropina A i melitina. Mitjançant l'estudi d'una sèrie d'anàlegs de BP100 amb diferents longituds que anaven de 4 a 24 aminoàcids, es va poder determinar el seu potencial mecanisme d'acció, que consisteix en un mecanisme de “dynamic carpet” on el BP100 s'insereix dinàmicament a la membrana, pertorbant la bicapa, augmentant la permeabilitat d’aquesta de manera que finalment es produeix la mort cel·lular.

Master thesis focuses on issues of corporate identity of advertising agency NIOSPORT agency, a.s. The aim of this thesis is to analyze corporate identity of company NIOSPORT agency, a.s. In the theoretical part is explained what is a corporate identity, which elements are included and why it is so important for companies. Then there is a definition of an image with an emphasis on its distinction from the concept of corporate identity, explained the interdependence between corporate identity and corporate strategy, and then is paid attention on advertising agencies in general. The practical part consists of a description of a particular advertising agency NIOSPORT agency, a.s., the results of empirical research, evaluation of the image of agency and finally of recommendations for the future, arising from the theoretical part, analyzing corporate documents and of the depth interviews with the director, staff and clients of advertising agency.

This research aimed to develop a deeper understanding of trust and non-profit agency website design, and specifically focussed on the ‘Donate Now’ button. Two experiments investigated the effects of varying levels of consumer certainty, manipulated by providing varying levels of donation relevant information on the web homepage donation buttons, on aid agency trust and donation compliance. Both experiments were based on Study 1, a preliminary survey of website donation button design. Experiment 1 investigated the effects of iconic manipulation of the ‘Donate Now’ button. Results suggested that varying levels of consumer certainty through iconic manipulation of the website donation button design did not effect aid agency trust and donation compliance. Experiment 2 extended the research of Burt and Dunham (2009) to investigate the effects of varying consumer certainty levels through the provision of crisis/need and response photographs on the donation buttons. Results suggested that whilst there was no effect of level of certainty on donation compliance, there was an effect on aid agency trust. Participants’ rated aid agency trust was increased to the greatest extent in the level of greatest certainty, when the donation button contained photographs of both the crisis/need and agency response. Collectively, these results suggest that aid agency trust can be enhanced through the considered manipulation of donation button design. Subsequently photographic images may be a more effective means with which to portray donation-relevant information and reduce uncertainty. Furthermore, in both experiments results showed that those individuals who reported higher aid agency trust also reported significantly higher donation intention. Thus, the current research has implications for the non-profit sector, suggesting that whilst the internet is a viable fundraising tool, the commercially driven process of online donation generation should not be isolated from the psychological concept of trust.

Earth as a fundamental aspect of the existing conditions of a site has/can/should have agency in design, both historically and today. The aim of this study is to describe the agency of earth in design as a common premise between the disciplines of architecture and landscape architecture. The thesis question is "how can the earth on site have agency on the design?" Thinking of the physical earth, specifically the topography, as one of the basic structures of the existing conditions, the earth should be taken as the most important condition that both architecture and landscape architecture use and share; both disciplines have to deal with context; they both have to deal with surroundings, and then work within systems that exist around them. As landscape architecture has been incredibly important to civilization throughout history, this project looks at different ways that earth has agency in design through important periods of history, from Greeks to contemporary design. While there are many examples in which designers have worked with the existing topography, there are other cases across cultures where people have drastically altered topography. Thinking about those designs, there are many possible answers to this thesis question from using existing hills to making mountains. This thesis explores the creation of an artificial mound, as a monument to indigenous people, in order to revive the missed parts of the earth and empower the ground. The thesis rethinks the whole ground, protecting the earth by turning excavated soil into an important earthwork. The design is not only about creating an earthwork for people, it also transforms invisible earth into a visible structure. Based on the practices of Native American mound builders, the earthwork stands for the values of diversity and equality in the US, creating a gathering space for all people made of the native earth/soil.
Master of Landscape Architecture
Earth as one of the existing materials of a site constantly affects the process of the design. This study focuses on describing and improving the use and understanding this material shared by the disciplines of architecture and landscape architecture. As landscape architecture has been incredibly important to civilization throughout history, this project looks at different ways that earth has affected design through important periods of history, from Greeks to modern design. Considering many examples in which designers have worked with the current land, there are other cases across cultures where people have changed earth. Thinking about different designs, there are many possible answers to this thesis question from using existing hills to making mountains. This design is an artificial mound as a monument to indigenous people and it is about reviving the missed parts of the earth in order to empower the ground, rethinking the whole earth and protecting it, turning it into an important earthwork that is not only about something for people but also making it into something which in invisible situations it cannot be. Based on the tradition of Native American mound builders, part of this thesis is to affirm the value of diversity and equality in the US, through creating a gathering space for all people that pays special attention to indigenous culture.

Despite educational directives advocating the integrated use of technology, some staff remain resistant to the adoption of computer-mediated classroom practice. As resistance is sometimes akin to lack of confidence or understanding, this thesis sought to illuminate the nature of work for teachers and students in a digital environment. It reports on a descriptive and interpretive case study on the classroom experiences of teachers and senior secondary school students in two humanities subjects where technology use was integrated with literacy practices for learning (technoliteracy). Findings suggest that there is a role for technology in the learning process and that student learning might be enhanced by constructivist-based, computer-mediated activities. These findings seem to confirm the important role of teacher agency in designing classroom experiences that capitalise on the potential of new technologies of communication for effective student learning. Furthermore, this thesis has synthesised key ideas from constructivism, educational technology and learning theory with study findings to generate a supportive framework that might encourage techno-reluctant teachers to engage productively with technology in meaningful ways. It develops a grounded model for technoliteracy that gains its dynamism from the notion of design. With its related constructs of "teacher-as-designer" of classroom digital learning environment and "students-as-designers" of electronic representations of knowledge, this model suggests a purposeful integration of technology and literacy practices towards a more critical appreciation of subject content. The thesis also offers practical guidelines for applying constructivist principles to promote technoliteracy and a digital learning culture. The evaluative criteria developed from the SOLO Taxonomy and specially designed for analysing the student-created electronic artefacts also offer possibilities for reconceiving the choice of texts, activities and assessment for students of the 21st century. From the theoretical and practical perspectives shaping this study, this thesis could prompt other teachers to imagine new possibilities for digital learning and to pioneer new models for teaching and learning in increasingly borderless classrooms in the knowledge age. It could encourage techno-reluctant staff to engage in computer-mediated learning practices.

Thrombosis is the most important pathological process underlying many cardiovascular diseases, which are responsible for high mortality worldwide. In this theses the computer-aided design of new anti-thrombotic agents able to inhibit two types of receptors located on the surface of the platelets has been applied. The first one - αIIbβ3 - is responsible for the interaction of activated platelets with fibrinogen to form clots, whereas the second one - thromboxane A2 - is responsible for platelet activation by one of agonists excreted by activated platelets. To achieve this, different types of models have been developed using experimentally available information and structure of protein-ligand complexes. This concerns: QSAR models, structure-based and ligand-based 3D pharmacophore models, 2D pharmacophore models, shape-based and molecular field-based models. The ensemble of the developed models were used in virtual screening. This study resulted in suggestion of new potential antagonists of αIIbβ3 and thromboxane A2 receptors. Suggested antagonists of αIIbβ3 able to bind either open or closed form of the receptor have been synthesized and tested experimentally. Experiments show that they display high activity; moreover some of theoretically designed compounds are more efficient than Tirofiban - the commercialized drug molecule. The recommended antagonists of thromboxane A2 receptor have been already synthesized but biological tests have not been completed yet.

Thesis (MSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: Malaria is a pestilent disease associated with massive socioeconomic burden of sub-Saharan Africa. This disease is caused by a blood infection of the single cellular parasite of the Plasmodium genus. Two enzymes of this parasite have been identified to be essential to the survival of this parasite, notably Spermidine Synthase and Protein Farnesyltransferase. The goal of this dissertation was to search for and synthesise novel inhibitors of these two enzymes with a strong focus towards understanding their structure/activity relationships. To achieve the first goal, molecular modelling was employed. An in-depth discussion is presented to describe the underlying principles relevant to this branch of computational chemistry. This ensures that the experiments using these methods are set-up correctly and results are interpreted within context. Two virtual high-throughput screens were then performed using prepared crystallographic structures of Spermidine Synthase. The first was pharmacophore based method and the second based on LibDock. The database used, containing 7.1 million compounds, was filtered using a custom developed tool prior to screening. Finally, CDOCKER was then used to investigate the activity of potential hit compounds. Spermidine Synthase has a natural affinity for adenosine and this trait was exploited by derivatising analogues to synthesise potential inhibitors of the enzyme. This was to be achieved by the incorporation of both electrophilic and nucleophilic moieties at selected positions, including the use of a high yielding Mitsunobu reaction. A number of additional residues were then synthesised and joined to the adenosine which were proposed to increase the active site occupancy and increase affinity to the enzyme. For the second enzyme targeted for inhibition, Protein Farnesyltransferase, indole was used as a starting scaffold to synthesise potential hits de novo. It was aimed to derivatise the indole at the Nʹ and 3ʹ positions. The crystal structure of one of the intermediates was published. Furthermore, a synthetic sequence which culminated in a palladium catalysed Suzuki coupling was performed.
AFRIKAANSE OPSOMMING: Malaria is ‘n peslike siekte wat geassosieer word met beduinde sosio-ekonomiese implikasies vir sub-Sahara Afrika. Die siekte word veroorsaak deur ‘n bloed infeksie van die enkel sellulêre parasiet van die Plasmodium genus. Twee ensieme, naamlik Spermidien Sintetase en Protein Farnesieltransferase, is geïdentifiseer om noodsaaklik te wees vir die oorlewing van die parasiet. Die doelwit van hierdie verhandeling is die soektog en sintese van oorspronklike inhibeerders van hierdie twee ensieme met ‘n sterk fokus daarop om struktuur/aktiwiteit interaksies te verstaan. Om die eerste doelwit te bereik is molekulêre modellering toegepas. ‘n Indiepte ondersoek word voorgestel om die onderliggende beginsels relevant tot hierdie tak van berekenkundige chemie te beskryf. Dit verseker dat eksperimente wat op hierdie tegnieke berus korrek opgestel word en dat die resultate binne konteks geïnterpreteer word. Twee virtuele hoë-deurset skerms was deurgevoer op voorbereide kristallografiese strukture van Spermidien Sintetase. Die eerste het berus op ‘n pharmakoforiese metode en die tweede op LibDock. ‘n Self-ontwikkelde sagteware gereedskap stuk is gebruik om a databasis van 7.1 miljoen verbindings te filtreer voor dit gebruik is in hoë-deurset skerms. Uiteindelik is CDOCKER gebruik om die potensiele aktiwiteit van “treffer” verbindings te beraam. Spermidien syntetase het ‘n natuurlike affiniteit vir adenosien en hierdie eienskap is benut deur analoeë af te lei na potensiële inhibeerders teen die ensiem. Dit is bewerkstellig deur die insluiting van beide elektrofiliese asook nukleifielese funksionele groepe op gekose posisies. Dit het die gebruik van ‘n hoë opbrengs Mitsunobu reaksie ingesluit. ‘n Aantal ander addisionele residueë is toe gesintetiseer en geheg aan die afgeleide adenosien om die ensiem setel te vul en sodoende die affinitieit te verhoog. Vir die tweede ensiem wat geteiken is vir inhibisie, Protein Farnesieltransferase, is indool benuttig as ‘n begin steier te dien om potensiële treffers de novo te sintetiseer. Dit is geteiken om die indool af te lei op die Nʹ en 3ʹ posisies en die kristal struktuur van een van hierdie tussengangers is gepubliseer. Verder is ‘n sintetiese weg, wat uitgeloop het op ‘n palladium gekataliseerde Suzuki koppeling, uitgevoer.

A series of pyridine-2-, pyridine-3-, pyridine-4-, pyrazine and quinoline-2-carboxamidrazone derivatives and new classes of carboxamidrazone were prepared. Over nine hundred synthesized compounds were screened for their antimycobacterial activity against M. fortutium (NCTC 10394) as a surrogate for M. tuberculosis. The new classes of amidrazones were also screened against tuberculosis H37 Rv. Fifteen tested compounds were found to provide 90-100% inhibition of mycobacterium growth of M. tuberculosis H37 Rv in the primary screen at 6.25 μg mL-1. The most active compound in the carboxamidrazone amide series had an MIC value of 0.1-2 μg mL-1 against M. fortutium. The x-ray structure of DHFR from M. tuberculosis and human DHFR were found to have differences in substrate binding site. The presence of glycerol molecule in the X-ray structure from M. tuberculosis DHFR provided opportunity to design new antifolates. The new antifolates were designed to retain the pharmocophore of pyrimethamine (2,4-diamino-5(4-chlorophenyl)-6-ethylpyrimidine), but encompassing a range of polar groups that might interact with the M. tuberculosis DHFR glycerol binding pockets. Finally, the research describes the preparation of molecularly imprinted polymers for the recognition of 2,4-diaminopyrimidine for the binding of the target. Having proven that 2,4-diaminopyrimidine interacts strongly with the model 5-(4-tert-butyl-benzylidene)-pyrimidine-2,4,6-trione, 2,4-diaminopyrimidine-imprinted polymers were prepared using a novel cyclobarbital derived functional monomer, acrylic acid 4-(2,4,6-trioxo-tetrahydro-pyrimidin-5-ylidenemethyl)phenyl ester, capable of multiple hydrogen bond formation with the 2,4-diaminopyrimidine. The recognition property of the respective polymers toward the templates and other test compounds was evaluated. The polymers showed dose dependent enhancement of fluorescence emissions. Synthesized MIPs have higher 2,4-diaminopyrimidine binding ability as compared with corresponding non-imprinting polymers.

Chorismate mutase is one of the essential enzymes in the shikimate pathway and is key to the survival of the organism Mycobacterium tuberculosis. The x-ray crystal structure of this enzyme from Mycobacterium tuberculosis was manipulated to prepare an initial set of in silico protein models of the active site. Known inhibitors of the enzyme were docked into the active site using the flexible ligand / flexible active site side chains approach implemented in CAChe Worksystem (Fujitsu Ltd). The resulting complexes were refined by molecular dynamics studies in explicit water using Amber 9. This yielded a further set of protein models that were used for additional rounds of ligand docking. A binding hypothesis was established for the enzyme and this was used to screen a database of commercially available drug-like compounds. From these results new potential ligands were designed that fitted appropriately into the active site and matched the functional groups and binding motifs founds therein. Some of these compounds and close analogues were then synthesized and submitted for biological evaluation. As a separate part of this thesis, analogues of very active anti-tuberculosis pyridylcarboxamidrazone were also prepared. This was carried out by the addition and the deletion of the substitutions from the lead compound thereby preparing heteroaryl carboxamidrazone derivatives and related compounds. All these compounds were initially evaluated for biological activity against various gram positive organisms and then sent to the TAACF (USA) for screening against Mycobacterium tuberculosis. Some of the new compounds proved to be at least as potent as the original lead compound but less toxic.

The latest data on antimicrobial resistance (AMR) related mortality is alarming. A conservative estimate places current global death due to AMR infections at 700,000 annually and projections anticipate that this could rise to 10 million by 2050. Over 50 major initiatives have emerged from the European Union (EU), United Kingdom (UK) and the United States of America (US) since 2007 aimed at improving surveillance, stewardship, and refreshing the drug development pipeline. The identification of priority pathogens, such as the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens has also assisted in directing global attention and efforts towards developing agents against these dangerous microbes. However, despite the FDA approval of 17 new antimicrobial agents since 2013, no novel class of Gram negative active agents has been introduced. Concerning the antibacterials in the drug development pipeline which are currently in phase 3 development or near obtaining approval (fourteen), only one (cefiderocol, a cephalosporin derivative) displays broad activity against priority Gram negative pathogens whilst seven display very specific activity against the same – none of these are new classes. Fragment-based drug discovery (FBDD) is an efficient strategy to utilise in this research. FBDD involves virtual screening of exceptionally small ligands, termed fragments, against the crystal structure of the target protein. Fragments are known to sample chemical space more efficiently than conventional virtual screening ligand libraries. Fragment hits may have low affinity initially but demonstrate a good amount of free energy of binding per heavy atom, referred to as ligand efficiency. It is then necessary to optimise the best scoring fragments by introducing structural modifications to improve affinity and pharmacokinetic properties towards more drug-like leads. Chapter 2 of this thesis details the design of novel Extended Spectrum β-lactamase (ESBL) inhibitors through FBDD. This begins with a discussion regarding the benefits and rationale of virtual screening, followed by details of the software and methods used by the candidate to generate drug-like small molecules against protein crystal structures of the target carbapenemase, New Delhi Metallo-β-lactamase 1 (NDM-1). Careful and rational optimisation of high scoring fragments resulted in a structurally diverse set of lead compounds with anticipated ability to restore carbapenem activity in pathogenic bacterial which express NDM-1. Furthermore, we aimed to synthesise a structural extension of lead compounds to provide a prodrug form which we hypothesised could improve effectiveness of the lead compound in Gram negative bacteria. Previously published bacteria detection and identification research by the Groundwater research group targeted an aminopeptidase widely distributed in Gram negative bacteria for differentiating between Gram negative and Gram positive species from clinical isolates. This enzyme, L-alanyl aminopeptidase, cleaved chromogenic compounds containing a terminal L-alanine amino acid residue, which released the chromophore and produced colouration of the colony. Therefore, these ‘L-alanyl precursors’ allowed for distinction between Gram positive and Gram negative bacteria in clinical isolates. We proposed that L-alanyl derivatives of the lead compounds could produce the same effect, effectively targeting the antibacterial agents towards Gram negative species, which are of greater clinical urgency. The compounds which were successfully synthesised were tested by international collaborators and, separately, by the candidate against two clinically important Gram negative pathogens. Inhibition of the target carbapenemase was determined by observed improvement of carbapenem MIC (in this case meropenem) and, therefore, required testing of the synthesised inhibitors in tandem with the carbapenem, by simultaneous broth microdilution. All synthesised compounds displayed the ability to improve meropenem MIC by at least two-fold (that is, the MIC of meropenem halved in the presence of a test inhibitor) and demonstrated no growth inhibition in the absence of meropenem at the concentrations tested. Particularly noteworthy was the performance of L-proline-based compounds, derived from fragment 1, which displayed impressive activity. The thiol-containing L-proline derivative 8 was able to improve the MIC of meropenem by sixteen-fold (i.e. from 64 µg/mL to 4 µg/mL). The L-alanyl prodrug forms of the lead compounds also, generally, demonstrated greater potency than their respective parent lead compounds. In the case of one pair, the prodrug form was seven-times more effective than the corresponding lead compound. Chapter 3 of this thesis details the use of rational structure modification to generate improved antibacterials based on agents discovered by previous PhD candidates (Dr Liao and Dr Lin) within the research group. The target of this work was Filamenting temperature-sensitive mutant Z (FtsZ), an enzyme ubiquitous in bacteria which is critical for successful cell division and replication. FtsZ inhibitors are a validated antibacterial target, with one such inhibitor, TXA707 and its prodrug TXA709, currently in Phase 1 clinical trials. Research by Dr Liao and Dr Lin identified curcumin-based compounds 88 and 89 respectively which were successful antibacterial agents in Bacillus subtilis, a Gram positive species. The work described in Chapter 3 of this thesis aimed to introduce structural modifications to these compounds to produce less chemically reactive derivatives which retained, or, ideally, improved antibacterial activity. This resulted in the phenolic derivatives which demonstrated comparable activity against B. subtilis. However, these compounds demonstrated no significant activity against a Gram negative species of bacteria, Escherichia coli. Consequently, an L-alanyl prodrug form of the lead phenol 94 was vehemently pursued. In summary, this thesis details the exploration of a diverse range of synthetic reactions which produced structurally diverse potential antibacterial agents. Many of these compounds exhibited encouraging antimicrobial activity, either by inhibiting a resistance-conferring enzyme (NDM-1) or by inhibiting an enzyme critical for bacterial division (FtsZ).

2010 - 2011
I develop an overview on the impact of intrinsic motivation on the individu- als’ choice in several economic environments. I start by considering a public good problem in which individuals can be intrinsically motivated. Even if the intrinsic motivation has a positive impact on the levels of public good contributed, it seems difficult to achieve the socially optimal level of contribution. When intrinsic mo- tivations alone are not sufficient to supply the socially optimal level, a principal’s intervention is necessary. The intervention usually takes the form of monetary in- centives. These incentives may conflict with individuals’ intrinsic motivation. I analyze the interaction between intrinsic motivation and monetary incentives in or- der to understand how people respond to incentives. In this sense, this work is related to the literature on psychological incentives in organizations (B´enabou and Tirole, 2003, 2006; Gneezy and Rustichini, 2000a, 2000b). A key prediction of this literature is that motivation is effective in stimulating effort even in the absence of a monetary compensation. This overview is also related to the literature on the self-selection of motivated employees in different sectors (see for instance Besley and Ghatak, 2005, and Prendergast, 2007). This literature suggests that the public sector pays lower incentives to attract motivated employees. This review exam- ines implications regarding the design of optimal incentives and public policy, the selection of motivated agents and its interaction with monetary rewards.I develop a multi-agent model where the individuals are the agents who are asked to contribute to the public good. The individuals may be interested not only in their own utility but also in the well-being of the others. Namely, individuals may or may not be intrinsically motivated. Whether they are motivated or not is their private information. I investigate the possibility of implementing a mecha- nism compatible with individual incentives that simultaneously results in efficient decisions, the voluntary participation of the individuals, and the feasibility of the budget. Under asymmetric information on the individuals’ intrinsic motivation, the principal has to offer different transfers to different agents in order to attain sepa- ration of types. The transfers are made as a function of their degree of motivation. Both individuals will be taxed but motivated individuals pay lower taxes than un- motivated individuals. This is because the principal pays an information rent to motivated individuals in order to elicit higher levels of effort. Monetary incentives are necessary to compensate motivated individuals in order to increase the levels of contribution.I study whether the presence of motivated teachers benefits public and private schools in a competitive environment. The quality is influenced by the effort exerted by the teachers. Teachers’ motivation may have a positive impact on the levels of effort and, then, on the quality. The effect of motivation strictly depends on the degree of differentiation of the programmes offered by the two schools. When both schools offer similar programmes, the Nash equilibrium is the one in which both schools hire motivated teachers. This is because teachers’ motivation plays an important role in the students’ choice between the two school. In contrast, when the two schools offer significantly different programmes, the Nash equilibrium is the one in which both schools hire selfish teachers. The increase in the students’ utility due to the higher quality provided by the motivated teachers is more than offset by the reduction in the profits earned by the two schools. [edited by author]
X n.s.

"Current approaches to design are often serial and iterative in nature, leading to poor quality of design and reduced productivity. Complex artifacts are designed by groups of experts, each with his/her own area of expertise. Hence design can be modeled as a cooperative multi-agent problem-solving task, where different agents possess different expertise and evaluation criteria. New techniques for Concurrent Design, which emphasize parallel interaction among design experts involved, are needed. During this concurrent design process, disagreements may arise among the expert agents as the design is being produced. The process by which these differences are resolve to arrive at a common set of design decisions is called Negotiation. The main issues associated with the negotiation process are, whether negotiation should be centralized or distributed, the language of communication and the negotiation strategy. The goals of this thesis are to study the work done by various researchers in this field, to do a comarative analysis of their work and to design and implement an approach to handle negotiation between expert agents in an existing Concurrent Engineering Design System."

"Design is a very complicated and ill-defined problem solving activity. Routine parametric design is a more restricted and well-defined version of design problems. Even this restricted version requires many different kinds of expert knowledge and the ability to perform a variety of tasks. One approach to solving this restricted version is to use Single Function Agents (SiFAs), each of which can perform a very specialized task, from a single point of view. The ability to represent expertise with different points of view is very important in design. These different points of view usually cause conflicts among agents, and these conflicts need to be resolved in order for the design process to be successful. Therefore, agents need to be capable of detecting and resolving these conflicts. This thesis presents a model of conflicts and negotiations in the SiFA framework. Some extensions to the present state of the SiFA paradigm are introduced. A hierarchy of possible conflicts is proposed and the steps of the negotiation process are discussed. The ability of agents to negotiation in order to resolve conflicts makes SiFA-based design systems more versatile, less brittle, and easier to construct and maintain. Also, the extended SiFA paradigm, where agents have negotiation capabilities leads to many interesting directions for further research. "

This research aims to examine the extent to which cultural agency can be seen to ‘act’ in an ecopolitical context and how its operations urge a rethinking of the processes that govern the production of urban subjects and environment(s). Responding to the fact that in recent decades, art and architectural cultures have converged around a shared concern for ‘ecological matters’ and that discourses in visual/spatial culture have become increasingly ‘ecologized’, this research broadens the points of reference for the term ‘ecology’ beyond that which simply reinforces an essentialist perspective on ‘nature’. The thesis re-directs the focus of current theoretical discourse on ‘ecological art’ towards a more rigorous engagement with its frames of reference and how it uses them to evaluate the role of cultural production in enacting ways of thinking and acting eco-logically. In doing so it develops an eco-logical mode of analysis for mapping and probing the attribution of cultural agency, how it intervenes in the production of the commons and how it discloses the participants and mechanisms of a nascent political ecology. Setting cultural agency within a more expansive and multivalent field of action, means that the nexus of agency (and intentionality) is dislocated and translated between ‘things’. Reconfigured in this way, ‘an ecology of agencing’ demonstrates the profound implications this has for any ‘bodies’ of action, cultural or otherwise. Locating this exploration within the socio-natural environment(s) found in urban spatialities this thesis attends to the relatively under-theorised, but highly significant area (in eco-logical terms) of aesthetic praxis operating at the interstices of art and architecture. Pressing at the boundaries of the formal and conceptual enterprises of both disciplines, critical spatial practices represent a distinctive form of eco-praxis being cultivated ‘on the ground’. Through a series of encounters with its operations this research looks to the ways in which practice and theory, in relation to the question of ecology, are becoming increasingly co-constituted.

Human-Computer Interaction (HCI) research has suggested that there has been a general shift away from more traditional aspects of design, such as usability, and the focus is now more pleasure, or emotion, based. Jordan (2000) states that pleasurebased design is associated with more hedonic aspects, such as enjoyment, and the interaction between the user and the product. A number of studies have investigated the relationship between the user and product in relation to agents (e.g. DeAngeli, Lynch & Johnson, 2002). While it has been widely acknowledged that the use of agents enhances the user experience (e.g. Lester, Converse, Stone, Kahler & Barlow, 1997; DeAngeli et al, 2002), these agents have mainly been fully animated, which may influence perceptions as they are considered more 'human-like'. Conversely, other studies (e.g. Koda & Maes, 1996) have found that the appearance of an agent has little influence on user perceptions of attributes such as intelligence, but only if an interaction has taken place. A series of experiments were conducted in order to investigate user perceptions of agents, or more specifically the influence of aesthetics, context and interaction. Experimental work investigated rating of agents, on a variety of different attributes, in an implied financial context. It was found that there was a general positive regard for female agents, but it was unclear whether stereotypes relating to the context were driving these judgements. Additional work showed that this positive view of female agents was consistent when no context was implied. Further investigation of the role of context indicated that while context (compared to imagined context and no context) had an overall detrimental influence on perceptions of agents, there was a high general regard for both attractive agents and female agents. However, to ensure that this result did not simply arise from the choice of website (financial), additional studies investigated the extent of occupational stereotypes and whether these occupational stereotypes extended to agents. This was found to be the case. However, although the most appropriate agent for a given occupation was one that was gender-congruent with the occupation, there was still a general positive regard for attractive agents. Finally, the influence of interaction was explored, and it was found that the aesthetics, or even presence, of an agent had no effect on user perceptions. This suggests that the quality of interaction may be the most salient aspect of agent perception. These findings are discussed in relation to the literature and future studies are considered.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Economics, 2012.
Cataloged from PDF version of thesis.
Includes bibliographical references.
This dissertation ties together three papers on mechanism design with boundedly rational agents. These papers explore theoretically whether, and to what extent, limitations on agents' ability to strategically misrepresent their preferences can help a mechanism designer achieve outcomes that she could not achieve with perfectly rational agents. The first chapter investigates whether local incentive constraints are sufficient to logically imply full incentive-compatibility, in a variety of mechanism design settings. This can be motivated by a boundedly rational model in which agents cannot contemplate all possible misrepresentations, but can consider those that are close to their true preferences. This chapter offers a unified approach that covers both continuous and discrete type spaces, showing that in many commonly studied cases, local incentive-compatibility (suitably defined) implies full incentive-compatibility. The second chapter advances the methodology of looking quantitatively at incentives for strategic behavior, motivated by the premise that agents will be truthful if the incentive to be strategic is small enough. This chapter defines a mechanism's susceptibility to manipulation as the maximum amount of expected utility any agent can ever gain from strategic misrepresntation. This measure of susceptibility is then applied to anonymous voting rules. One set of results estimates the susceptibility of specific voting rules; an important finding is that several voting systems previously identified as resistant to manipulation are actually more susceptible than simple plurality rule, by the measure proposed here. A second set of results gives asymptotic lower bounds on susceptibility for any possible voting rule, under various combinations of efficiency, regularity, and informational conditions. These results illustrate how one can quantitatively explore the tradeoffs between susceptibility and other properties of the voting rule. The third chapter carries the methodology of the second chapter to a market environment: unit-demand, private-value double auction markets. This chapter quantitatively studies the tradeoff between inefficiency and susceptibility to manipulation, among all possible mechanisms for such markets. The main result approximately locates the possibility frontier, pinning it down within a factor that is logarithmic in the size of the market.
by Gabriel D. Carroll.
Ph.D.

Thesis (MSc (Chemistry and Polymer Science))--University of Stellenbosch, 2005.
This thesis begins with the description of the preparation of thirteen dithioesters (of the form Z- (C=S)-S-R) which were characterized via Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR) and ultraviolet spectroscopy (UV). The dithioesters were then used as reversible addition-fragmentation chain transfer (RAFT) mediating agents in the bulk polymerization of styrene, in order to observe differences in the kinetic behaviour of the polymerizations and, as a result, the efficiencies of the dithioesters in mediating the polymerizations.