Abstraction concepts based on process groups have largely dominated the design and implementation of communication patterns in message passing systems. Although such an approach seems pragmatic—given that participating processes form a ‘group’—in this dissertation, we discuss subtle issues that affect the qualitative and quantitative aspects of this approach. To address these issues, we introduce the concept of a ‘communication structure,’ which defines a communication pattern as an implicit runtime composition of localised patterns, known as ‘roles.’ During application development, communication structures are derived from the algorithm being implemented. These are then translated to an executable form by defining process specific data structures, known as ‘branching channels.’ The qualitative advantages of the communication structure approach are that the resulting programming model is non-ambiguous, uniform, expressive, and extensible. To use a pattern is to access the corresponding branching channels; to define a new pattern is simply to combine appropriate roles. The communication structure approach therefore allows immediate implementation of ad hoc patterns. Furthermore, it is guaranteed that every newly added role interfaces correctly with all of the existing roles, therefore scaling the benefit of every new addition. Quantitatively, branching channels improve performance by automatically overlapping computations and communications. The runtime system uses a receiver initiated communication protocol that allows senders to continue immediately without waiting for the receivers to respond. The advantage is that, unlike split-phase asynchronous communications, senders need not check whether the send operations were successful. Another property of branching channels is that they allow communications to be grouped, identified, and referenced. Communication structure specific parameters, such as message buffering, can therefore be specified immediately. Furthermore, a ‘commit’ based interface optimisation for send-and-forget type communications—where senders do not reuse sent data—is presented. This uses the referencing property of branching channels, allowing message buffering without incurring performance degradation due to intermediate memory copy.

We present an investigation into the design of an evolutionary mechanism for multiagent protocol constraint optimisation. Starting with a review of common population based mechanisms we discuss the properties of the mechanisms used by these search methods. We derive a novel algorithm for optimisation of vectors of real numbers and empirically validate the efficacy of the design by comparing against well known results from the literature. We discuss the application of an optimiser to a novel problem and remark upon the relevance of the no free lunch theorem. We show the relative performance of the optimiser is strong and publish details of a new best result for the Keane optimisation problem. We apply the final algorithm to the multi-agent protocol optimisation problem and show the design process was successful.

Direct fitness is measured as the number of surviving offspring. Thus adult males may try to produce as many offspring as possible or to increase the survival of their offspring. Recent findings have shown the many potential benefits of fathers’ presence and support on infants’ development and survival. However, little is known about the influence of socio-ecological factors on male-infant interactions. The main aim of this thesis was therefore to investigate male-infant interactions in wild crested macaques (Macaca nigra). In particular, we aimed to examine the affiliative and agonistic interactions taking place in this species, along with the factors influencing these interactions and offspring survival. Data collection for this thesis took place in the Tangkoko-Duasudara Reserve in Sulawesi, Indonesia, on 3 wild groups of crested macaques. For the first study, data were collected on migrations, births, disappearances, and encounters between groups over 5 years. We analyzed the influence of socio-ecological factors (e.g. rainfall, alpha-male position takeover, and male hierarchy stability) on pre- and post-natal loss. The results showed that high infant mortality was mainly associated to male alpha-position takeover, which suggests that infanticide may indeed occur in this species. In addition, we found that female within-group competition for food sources and between-group resource defense influenced fetal and infant loss. Based on these findings, we were interested to see whether fathers protected their own offspring against male attacks. Thus, in the second study, we investigated the social determinants and characteristics of male-infant affiliations. Our results indicate that adult males and infants form preferential association, and that infants initiate the majority of male-infant affiliations. Infants initiated affiliations mainly towards a high ranking male or a male in a close relationship with their mother. In addition, infants affiliated mainly with adult males in the absence of their mother, while males affiliated mostly with infants when the infants‘ mother was present in proximity. Furthermore, males initiated affiliations towards an infant when they held a high rank or when they had a strong bond with the infant‘s mother. Interestingly, paternity did not affect male-infant affiliations. In conclusion, these studies provide insights in the specifics of both infant survival strategies and male reproductive strategies. In addition, we show that infants are active agents in establishing and maintaining preferential relationships with males. This thesis, thus, confirm that male-infant interactions, although rare, have a strong influence both on males’ and infants’ direct fitness.

The nucleosome remodeling factor (NURF) is a mutli-protein complex that plays a role in the regulation of gene expression through its ability to remodel nucleosomes. The largest subunit of this complex, Bptf (Bromodomain PHD Finger Transcription Factor) is important for many cellular processes as a transcriptional regulator and improper function results in disease or malignancy. To further understand the genome-wide recruitment of the NURF complex, the interaction partner for the N-terminal PHD finger domain of Bptf was investigated through pull down assays followed by mass spectrometry. It was determined that this domain does not recognize histones; instead it recognizes a nonhistone protein, Thoc4 or Hmgb1. The expression of a cDNA corresponding to Bptf was also tested for expression in mouse ES cells after the addition of two exons found to be missing in the original cDNA. Addition of this sequence did not allow for exogenous Bptf expression in ES cells.

Les systèmes de surveillance modernes doivent coordonner leurs stratégies d’observation pour améliorer l’information obtenue lors de leurs futures mesures afin d’estimer avec précision les états des objets d’intérêt (emplacement, vitesse, apparence, etc.). Par conséquent, la gestion adaptative des capteurs consiste à déterminer les stratégies de mesure des capteurs exploitant les informations a priori afin de déterminer les actions de détection actuelles. L’une des applications la plus connue de la gestion des capteurs est le suivi multi-objet, qui fait référence au problème de l’estimation conjointe du nombre d’objets et de leurs états ou trajectoires à partir de mesures bruyantes. Cette thèse porte sur les stratégies de gestion des capteurs en temps réel afin de résoudre le problème du suivi multi-objet dans le cadre de l’approche RFS labélisée. La première contribution est la formulation théorique rigoureuse du filtre mono-capteur LPHD avec son implémentation Gaussienne. La seconde contribution est l’extension du filtre LPHD pour le cas multi-capteurs. La troisième contribution est le développement de la méthode de gestion de capteurs basée sur la minimisation du risque Bayes et formulée dans les cadres POMDP et LRFS. En outre, des analyses et des simulations des approches de gestion de capteurs existantes pour le suivi multi-objets sont fournies / Modern surveillance systems must coordinate their observation strategies to enhance the information obtained by their future measurements in order to accurately estimate the states of objects of interest (location, velocity, appearance, etc). Therefore, adaptive sensor management consists of determining sensor measurement strategies that exploit a priori information in order to determine current sensing actions. One of the most challenging applications of sensor management is the multi-object tracking, which refers to the problem of jointly estimating the number of objects and their states or trajectories from noisy sensor measurements. This thesis focuses on real-time sensor management strategies formulated in the POMDP framework to address the multi-object tracking problem within the LRFS approach. The first key contribution is the rigorous theoretical formulation of the mono-sensor LPHD filter with its Gaussian-mixture implementation. The second contribution is the extension of the mono-sensor LPHD filter for superpositional sensors, resulting in the theoretical formulation of the multi-sensor LPHD filter. The third contribution is the development of the Expected Risk Reduction (ERR) sensor management method based on the minimization of the Bayes risk and formulated in the POMDP and LRFS framework. Additionally, analyses and simulations of the existing sensor management approaches for multi-object tracking, such as Task-based, Information-theoretic, and Risk-based sensor management, are provided.

Les migrations professionnelle et étudiante ont été abordées sous l’angle des réseaux, de la socialisation ou des échanges entre les pays d’origine et la France. Cette recherche anthropologique, quant à elle, s’attache à analyser la situation professionnelle des jeunes diplômés de master ou de doctorat issus de pays n’appartenant pas à l’Union européenne. Ceux-ci souhaitent s’engager dans une activité professionnelle en France, toutefois « la question du retour au pays d’origine se pose souvent à l’issue de leurs cursus universitaire ». Pour eux, l’entrée dans le monde professionnel prend une dimension administrative très marquée. Ils se trouvent confrontés à des obligations administratives (pendant leurs études, dans la vie quotidienne ou au travail), à des contraintes d’insertion professionnelle ou de poursuite de carrière (postes réservés aux ressortissants de l’Union européenne, problèmes pour changer de statut) en passant par des difficultés à établir un projet professionnel après l’obtention de leur diplôme. Dans le cadre d’une démarche anthropologique, un travail d’immersion est mené au sein d’associations représentatives des doctorants travaillant sur la valorisation du parcours doctoral et d’associations qui informent et apportent leur soutien aux jeunes diplômés étrangers, afin d’appréhender la manière dont ils envisagent la suite de leur parcours en France et de connaître la manière dont ils le vivent. / Professional and student migrations have been considered from the point of view of networks, socialization and exchanges between countries of origin and France. For its part, this anthropological study focuses on analysis of the professional status of recent foreign graduates of a PhD or a master degree coming from non european union countries. Those foreign graduates wish to start a professional activity in France, however "the return home issue often comes up at the end of their university curriculum". For them, entering the labor market takes on a strong administrative dimension. They have to face administrative obligations (during their studies, in their everyday life or at work), constraints to integrate the labor market or to carry on with their career (reserved positions for citizens of the european union, problems to get a change of legal status) or even difficulties to determine a professional project after graduating. Within an anthropological approach, an immersion work is led in representative associations of PhD students interested in the promotion of PhD experience and in associations that provide information and support to recent foreign graduates, in order to apprehend the way they consider the continuation of their experience in France and to know how they feel about it.

The objective in this compositional research has been to create a portfolio of compositions with the goal of developing my musical language. This has been achieved through a portfolio that explores characterisation, transformation, dialogue, interaction, contrast and, latterly, timbre in the context of a teleological framework. Seven works are presented for a range of instrumental and vocal forces according to the opportunities taken throughout the research period. The majority of the works in the portfolio are under 10 minutes in duration and the final two cumulative works explore longer timeframes of c.15 and c.30 minutes respectively. The seven pieces are presented in the order of completion:1. Multiple Infection (2010) for clarinet, cello, percussion and piano.2. Contrasting Spectrum (2011) for flute, clarinet, violin, cello and piano.3. Splintering Factions (2012) for chamber orchestra.4. Chinese Whispers (2013) for violin and viola.5. Memoriam retinebimus (2014) for SATB choir and solo group (4 females and 2 males). 6. Sporos (2015) for string quartet.7. Relentless Continuum (2015-2016) for symphony orchestra. This portfolio also includes an analytical commentary in eight chapters prefaced with an opening section (part one) introducing the author and compositional research. This part also presents elements of the author's musical language including a short introduction of characterisation, teleology, transformation, dialogue, interaction, contrast and timbre with a brief discussion of notable influences that led to the implementation of these elements. Lastly, part two details the seven pieces of the portfolio in the form of musical commentaries over seven chapters, one piece being discussed in each chapter. The last chapter presents reflections and evaluations on the portfolio and future goals.

The trimeric protein known as porin, found in the outer membrane of Escherichia coli, forms ion channels which have been reported to be voltage-gated. The aim of this investigation is to increase the understanding of the function of such channels, particularly with respect to voltage-gating. To achieve this, porin was first extracted from whole cells of E. coli and then it was incorporated into lipid bilayers, made using the Montal-Mueller method, for subsequent investigation. The extraction of porin from E. coli exploited both its tight association with peptidoglycan and its high level of detergent resistance. Porin was extracted from two strains of E. coli, 0111 :B4 and K12 (a rough mutant), with the resulting samples being rich in OmpF and Ompe porins respectively. Measurement of ion flow through the porin channels was made with different transmembrane voltages and with a variety of salts and salt concentrations. Such measurements enabled the selectivity of the channels to specific ions to be determined and estimates of pore diameter to be made. Instantaneous IN characteristics were asymmetrical and non-linear for both porins and were influenced by the salt concentration, pH of the electrolyte and the number of channels in the bilayer. Based on electrostatic models of gramicidin-like channels, coupled with the available structural information on porin, it was concluded that the porinlLPS complex inserts unidirectionally into the bilayer and has a net negative charge at the LPS end. The influence of the number of channels in the bilayer on the IN characteristic, most marked for the 0111 :B4 porin, was interpreted as being due to 'clusters' of channels in close association an idea supported by the results of voltage-gating experiments. Voltage-gating in single channels was shown to occur in three well defined steps, consistent with the known trimeric structure of porin. Multi-channel membranes showed several different types of current relaxation in response to a sustained voltage application. The most common type was composed of two exponential decays, suggesting the presence of two populations of closing channels. The results from voltage-gating experiments were compared with the theoretical behaviour of a simple two-state channel. This model was also extended to include entropy changes and it was concluded that porin followed the general behaviour predicted by a simple twostate model.

Based on a retrospective survey of science and engineering (S&E) PhDs from a UK research-based university with 7-10 years job histories and the design-based non-parametric analysing methods, this thesis drew on theories on careers, organisational knowledge and learning and labour markets to explore the interrelationship between knowledge flow and careers of science and engineering PhDs. The results showed that employment outside the conventional technical occupations is the main destination for the survey respondents. This labour market segment is not only successful at retaining its members, but is also the destination of the other career types. Furthermore, S&E PhDs in the conventional technical occupations draw quite a lot of knowledge from S&E doctoral training in their jobs, even from the subject-specific dimension of it. By contrast, members in employment outside the conventional technical occupations are less likely to perceive knowledge and skills from doctoral training to be useful in their jobs, and when they do, the emphasis is more on general analytical skills and problem solving capabilities.The results also revealed the distinctive labour market features of different S&E PhD labour market segments: the sharp contrast of the core and peripheral workers in academic/public research, the highly hybrid labour market form in employment outside the conventional technical occupations and the relatively more structured labour market features in technical positions in private sector manufacturing. Regardless of the differences, nonetheless, as a whole, organisational life is still a prominent feature of the S&E PhD labour markets. Furthermore, the extent to which fluid job mobility contributes to S&E PhDs' individual knowledge flow depends on the types of knowledge under discussion. The emerging occupations associated with the knowledge economy are characterised by high inter-organisational mobility and by an emphasis of sector-specific and general knowledge. However, even for sector-specific and general knowledge, we have demonstrated that to a certain extent, these types of knowledge and skills are sticky to organisations. Hence, S&E PhD experts and knowledge workers' careers and individual knowledge flow are not really boundaryless but moderately localised within organisations.

In this work, two projects were pursued. In the first project, I investigated two different subtypes of opioid receptors, which play a key role as target for analgesia. A set of subtype specific fluorescent ligands for μ opioid receptor (MOR) and δ opioid receptor (DOR) was characterised and used to gain insights into the diffusion behaviour of those receptors. It was shown that the novel ligands hold photophysical and pharmacological properties making them suitable for single-molecule microscopy. Applying them to wild-type receptors expressed in living cells revealed that both sub-types possess a heterogeneous diffusion behaviour. Further- more, the fluorescent ligands for the MOR were used to investigate homodomerisation, a highly debated topic. The results reveal that only ≈ 5 % of the receptors are present as homodimers, and thus the majority is monomeric. G-protein coupled receptors (GPCRs) play a major role as drug targets. Accordingly, understanding the activation process is very important. For a long time GPCRs have been believed to be either active or inactive. In recent years several studies have shown, that the reality is more complex, involving more substates. [1, 2, 3, 4] In this work the α 2A AR was chosen to investigate the activation process on a single-molecule level, thus being able to distinguish also rare or short-lived events that are hidden in ensemble mea- surements. With this aim, the receptor was labelled intracellular with two fluorophores using supported membranes. Thus it was possible to acquire movies showing qualita- tively smFRET events. Unfortunately, the functionality of the used construct could not be demonstrated. To recover the functionality the CLIP-tag in the third intracellular loop was replaced successfully with an amber codon. This stop codon was used to insert an unnatural amino acid. Five different mutants were created and tested and the most promising candidate could be identified. First ensemble FRET measurements indicated that the functionality might be recovered but further improvements would be needed. Overall, I could show that single-molecule microscopy is a versatile tool to investigate the behaviour of typical class A GPCRs. I was able to show that MOR are mostly monomeric under physiological expression levels. Furthermore, I could establish intra- cellular labelling with supported membranes and acquire qualitative smFRET events. / In dieser Arbeit wurden zwei Projekte verfolgt. Im ersten Projekt wurden zwei Subtypen der Opioidrezeptoren untersucht, die eine wichtige Rolle für die Wirksamkeit von Analgetika spielen. Ein Set von subtypspezifischen fluoreszierenden Liganden für den MOR und den DOR wurde charakterisiert und eingesetzt, um Einblicke in das Diffuionsverhalten der Rezeptoren zu gewinnen. Es konnte gezeigt werden, dass die neuartigen Liganden sowohl photophysikalische als auch pharmakologische Eigenschaften besitzen, die sie für die Einzelmolekülmikroskopie interessant machen. Versuche mit Opioidrezeptoren, die in lebenden Zellen exprimiert werden, zeigten, dass beide Subtypen heterogenes Diffuionsverhalten aufweisen. Des Weiteren wurden die fluoreszierenden Liganden für den MOR genutzt um Homodimerisierung zu untersuchen, da dies ein kontrovers diskutiertes Thema ist. Die Ergebnisse zeigen, dass lediglich ≈ 5% der Rezeptoren als Homodimere vorliegen und der Großteil monomerisch ist. GPCRs sind besonderem Interesse, weil sie Angriffspunkt vieler Medikamente sind. Deshalb ist es wichtig ihren Aktivierungsmechanismus besser zu verstehen. Lange Zeit wurde angenommen, dass GPCRs entweder aktiv oder inaktiv sind. Neuere Studien zeigten jedoch, dass die Realität komplexer ist und der Prozess Zwischenschritte involviert. [1, 2, 3, 4] In dieser Arbeit wurde der α 2A Adrenorezeptor als prototypischer Klasse A GPCR gewählt, um den Aktivierungsprozess auf Einzelmoleküllevel zu untersuchen. Durch die Betrachtung einzelner Rezeptoren ist es möglich auch seltene oder sehr kurzlebige Ereignisse zu unterscheiden, die in Kollektivmessungen untergehen. Um dies zu erreichen wurde der Rezeptor erfolgreich intrazellulär mit zwei Fluorophoren markiert. Dies gelang durch die Herstellung von „supported membranes", also Zellmembranen die auf einem Objektträger fixiert wurden. Dadurch war es möglich Videos aufzunehmen, die Einzelmolekül-FRET-Ereignisse zeigen. Jedoch gelang es nicht zu zeigen, dass der Rezeptor als Ganzes noch funktional war. Um einen funktionalen Rezeptor zu erhalten, wurde das CLIP-Tag in der dritten intrazellulären Schleife erfolgreich durch ein Stopcodon ersetzt, welches für eine nicht kanonische Aminosäure kodierte. Fünf verschiedene Mutanten wurden kloniert und getestet, wobei der vielversprechendste Mutant identifiziert werden konnte. Erste FRET-Kollektivmessungen deuten darauf hin, dass dieser Mutant funktional sein könnte. Jedoch sind weitere Verbesserungen nötig. Insgesamt konnte ich zeigen, dass Einzelmolekülmikroskopie vielseitige Möglichkeiten bietet um das Verhalten von GPCRs zu untersuchen. Ich konnte nachweisen, dass MOR unter physiologischen Bedingungen hauptsächlich als Monomere vorliegen. Des Weiteren konnte ich Dank supported membranes die Markierung durch Farbstoffe im Intrazellularbereich etablieren und qualitative smFRET Ereignisse aufnehmen.