No / Phortress is a novel, potent, and selective experimental antitumor agent. Its mechanism of action involves induction of CYP1A1-catalyzed biotransformation of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) to generate electrophilic species, which covalently bind to DNA, exacting lethal damage to sensitive tumor cells, in vitro and in vivo. Herein, we investigate the effects of DNA adduct formation on cellular DNA integrity and progression through cell cycle and examine whether a relevant pharmacodynamic end point may be exploited to probe the clinical mechanism of action of Phortress and predict tumor response. Single cell gel electrophoresis (SCGE) was applied to quantify DNA damage and cell cycle analyses conducted upon 5F 203 treatment of benzothiazole-sensitive MCF-7 and inherently resistant MDA-MB-435 breast carcinoma cells. Following treatment of xenograft-bearing mice and mice possessing hollow fiber implants containing MCF-7 or MDA-MB-435 cells with Phortress (20 mg/kg, i.p., 24 hours), tumor cells and xenografts were recovered for analyses by SCGE. Dose- and time-dependent DNA single and double strand breaks occurred exclusively in sensitive cells following treatment with 5F 203 in vitro (10 nmol/L¿10 ¿mol/L; 24¿72 hours). In vivo, Phortress-sensitive and Phortress-resistant tumor cells were distinct; moreover, DNA damage in xenografts, following treatment of mice with Phortress, could be determined. Interrogation of the mechanism of action of 5F 203 in silico by self-organizing map-based cluster analyses revealed modulation of phosphatases and kinases associated with cell cycle regulation, corroborating observations of selective cell cycle perturbation by 5F 203 in sensitive cells. By conducting SCGE, tumor sensitivity to Phortress, an agent currently undergoing clinical evaluation, may be determined.

Many chaotic and complicated systems cannot be analysed by traditional methods. In 1987 P.Bak, C.Tang, and K.A.Wiesenfeld developed a new concept called Self-Organised Criticality (SOC) to explain the behaviour of composite systems containing a large number of elements that interact over a short range. In general this theory applies to complex systems that naturally evolve to a critical state in which a minor event starts a chain reaction that can affect any number of elements in the system. It was later shown that many complex phenomena such as flux pinning in superconductors, dynamics of granular systems, earthquakes, droplet formation and biological evolution show signs of SOC. The dynamics of complex systems in nature often occurs in terms of punctuation, or avalanches rather than following a smooth, gradual path. Extremal dynamics is used to model the temporal evolution of many different complex systems. Specifically the Bak-Sneppen evolution model, the Sneppen interface depinning model, the Zaitsev flux creep model, invasion percolation, and several other depinning models. This thesis considers extremal dynamics at constant flux where M>1 smallest barriers are simultaneously updated as opposed to models in the limit of zero flux where only the smallest barrier is updated. For concreteness, we study the Bak-Sneppen (BS) evolution model [Phys. Rev. Lett. 71, 4083 (1993)]. M=1 corresponds to the original BS model. The aim of the present work is to understand analytically through mean field theory the random neighbour version of the generalised BS model and verify the results against the computer simulations. This is done in order to scrutinise the trustworthiness of our numerical simulations. The computer simulations are found to be identical with results obtained from the analytical approach. Due to this agreement, we know that our simulations will produce reliable results for the nearest neighbour version of the generalised BS model. Since the nearest neighbour version of the generalised BS model cannot be solved analytically, we have to rely on simulations. We investigate the critical behaviour of both versions of the model using the scaling theory. We look at various distributions and their scaling properties, and also measure the critical exponents accurately verifying whether the scaling relations holds. The effect of increasing from M=1 to M>1 is surprising with dramatic decrease in size of the scaling regime.

The brain is a complex system par excellence. Its intricate structure has become clearer recently, and it has been reported that it shares some properties common to complex networks, such as the small-world property, the presence of hubs, and assortative mixing, among others. These properties provide the brain with a robust architecture appropriate for efficient information transmission across different brain regions. Nevertheless, how these topological properties emerge in neural networks is still an open question. Moreover, in the last decade the observation of neuronal avalanches in neocortical circuits suggested the presence of self-organised criticality in neural systems. The occurrence of this kind of dynamics implies several benefits to neural computation. However, the mechanisms that give rise to critical behaviour in these systems, and how they interact with other neuronal processes such as synaptic plasticity are not fully understood. In this thesis, we study self-organised criticality and neural systems in the context of complex networks. Our work differs from other similar approaches by stressing the importance of analysing the influence of hubs, high clustering coefficients, and synaptic plasticity into the collective dynamics of the system. Additionally, we introduce a metric that we call node success to assess the effectiveness of a spike in terms of its capacity to trigger cascading behaviour. We present a synaptic plasticity rule based on this metric, which enables the system to reach the critical state of its collective dynamics without the need to fine-tune any control parameter. Our results suggest that retro-synaptic signals could be responsible for the emergence of self-organised criticality in brain networks. Furthermore, based on the measure of node success, we find what kind of topology allows nodes to be more successful at triggering cascades of activity. Our study comprises four different scenarios: i) static synapses, ii) dynamic synapses under spike-timing-dependent plasticity (STDP), iii) dynamic synapses under node-success-driven plasticity (NSDP), and iv) dynamic synapses under both NSDP and STDP mechanisms. We observe that small-world structures emerge when critical dynamics are combined with STDP mechanisms in a particular type of topology. Moreover, we go beyond simple spike pairs of STDP, and implement spike triplets to assess their influence on the dynamics of the system. To the best of our knowledge this is the first study that implements this version of STDP in the context of critical dynamics in complex networks.

We are at that moment of network evolution when we have realised that our telecommunication systems should mimic features of human kind, e.g., the ability to understand the medium and take advantage of its changes. Looking towards the future, the mobile industry envisions the use of fully automatised cells able to self-organise all their parameters and procedures. A fully self-organised network is the one that is able to avoid human involvement and react to the fluctuations of network, traffic and channel through the automatic/autonomous nature of its functioning. Nowadays, the mobile community is far from this fully self-organised kind of network, but they are taken the first steps to achieve this target in the near future. This thesis hopes to contribute to the automatisation of cellular networks, providing models and tools to understand the behaviour of these networks, and algorithms and optimisation approaches to enhance their performance. This work focuses on the next generation of cellular networks, in more detail, in the DownLink (DL) of Orthogonal Frequency Division Multiple Access (OFDMA) based networks. Within this type of cellular system, attention is paid to interference mitigation in self-organising macrocell scenarios and femtocell deployments. Moreover, this thesis investigates the interference issues that arise when these two cell types are jointly deployed, complementing each other in what is currently known as a two-tier network. This thesis also provides new practical approaches to the inter-cell interference problem in both macro cell and femtocell OFDMA systems as well as in two-tier networks by means of the design of a novel framework and the use of mathematical optimisation. Special attention is paid to the formulation of optimisation problems and the development of well-performing solving methods (accurate and fast).

Dieses Paper beschreibt die Entwicklung und die Erprobung eines Fragebogens, der bisherige Untersuchungsinstrumente im Kontext der Lernstrategie-Forschung durch die Fokussierung auf selbstorganisiertes Lernen bei der Verwendung von Social Software ergänzt. Dazu wird im Anschluss an die Darstellung der Motivation selbstorganisiertes Lernen defi niert sowie hierzu bestehende Fragebogeninventare vorgestellt, bevor auf die veränderten Lernstrategien im Social Web eingegangen wird. In den weiteren Abschnitten werden die Entwicklung des ergänzenden Inventars zur Messung selbstorganisierten Lernens im Social Web sowie bisherige Ergebnisse des Einsatzes dieses Inventars dargestellt. Diese weisen überwiegend sehr hohe Reliabilitätswerte auf, was darauf hindeutet, dass die explorativ erschlossenen Items die jeweiligen Dimensionen abbilden. Allerdings lassen die z.T. hohen Korrelationswerte zwischen einigen Skalen vermuten, dass diese sich nicht klar voneinander abtrennen lassen. Der folgende Aufsatz stellt somit einen Beitrag zur Diskussion über die Messung selbstorganisierten Lernens im Social Web dar.

Within the parameters of the development, since the 1970s, of the National Teacher Appraisal Scheme, and the current changes in Education, a research programme of observation, video-recording and analysis of teaching performance is described and evaluated. The aim was to ascertain, by means of specific techniques, the value and benefits to teachers in developing their personal and professional levels of experience on the path to becoming self-organised learners. The potential of two specific methods of appraising teachers' classroom performance to generate developmental Learning Conversations is examined and compared. Using video-recordings of their lessons, two groups of ten teachers in one secondary school, individually reflected, discussed and evaluated their own performance with the researcher, by using either conversational repertory grid or conversational rating scale techniques, as the basis for an extended focused Learning Conversation. A third group of ten teachers was intended as a control group. The immediate and longer term developmental effects on the individual teachers, and on the school, were examined as the research activities gradually evolved from an original positivist experimental research paradigm to a conversational action research paradigm. Parallel to the account of the changes and developments in the research project, the impact of the research journey on the personal and professional development of the researcher is also related.

Dieses Paper beschreibt die Entwicklung und die Erprobung eines Fragebogens, der bisherige Untersuchungsinstrumente im Kontext der Lernstrategie-Forschung durch die Fokussierung auf selbstorganisiertes Lernen bei der Verwendung von Social Software ergänzt. Dazu wird im Anschluss an die Darstellung der Motivation selbstorganisiertes Lernen defi niert sowie hierzu bestehende Fragebogeninventare vorgestellt, bevor auf die veränderten Lernstrategien im Social Web eingegangen wird. In den weiteren Abschnitten werden die Entwicklung des ergänzenden Inventars zur Messung selbstorganisierten Lernens im Social Web sowie bisherige Ergebnisse des Einsatzes dieses Inventars dargestellt. Diese weisen überwiegend sehr hohe Reliabilitätswerte auf, was darauf hindeutet, dass die explorativ erschlossenen Items die jeweiligen Dimensionen abbilden. Allerdings lassen die z.T. hohen Korrelationswerte zwischen einigen Skalen vermuten, dass diese sich nicht klar voneinander abtrennen lassen. Der folgende Aufsatz stellt somit einen Beitrag zur Diskussion über die Messung selbstorganisierten Lernens im Social Web dar.

Above true strain rates of $10^4$ s$^{-1}$ FCC metals exhibit a rapid increase in strength. Understanding of the physical mechanisms behind this strength transition is hindered by the number and interdependence of candidate mechanisms. Broadly, contributions to strength can be split into `instantaneous' effects and the more permanent `structural' ones. In this thesis a series of experiments are presented which are designed to separate the two types of contribution. Chapter 2 outlines the basics of dislocation plasticity, based on the seminal works of Taylor and Orowan. It then progresses on to discuss recent experimental and theoretical work on the understanding of slip as avalanche behaviour. Chapter 3 summarises traditional modelling approaches for instantaneous strength contributions which are routinely applied below $10^4$ s$^{-1}$. It then continues on to outline a number of different approaches which have been adopted to attempt to explain and model the strength transition. Chapter 4 outlines the methods used in the earliest stages of the study: Instron and split Hopkinson pressure bar methods. Both methods are well established, and cover the majority of the range of rates under study. Emphasis is made on minimising experimental sources of error, and subsequently accounting for those which are unavoidable. Finally, the specimen material is introduced and is shown to be fit for purpose. Chapter 5 presents a set of mechanical tests of specimens at strain rates between $10^4-10^5$~s$^{-1}$. The softening of the specimens with increased temperature is observed to increase with strain rate, both in absolute terms and when normalised to the 300 K measurement for each strain rate. The observations are most easily explained if the strength transition is due to an increase in early stage work hardening, however, some anomalous behaviours remain. Chapter 6 introduces a new experimental technique; direct impact Hopkinson pressure bars, required to perform experiments shown to be necessary by the results of Chapter 5. Photon Doppler velocimetry is applied to the projectiles used in experiments, removing one of the most significant flaws of the technique, and creating a more confident basis with which to perform further experimental work. Chapter 7 presents a series of `jump tests' at ambient temperatures. Specimens are deformed at strain rates ranging from $10^{-2}$ to $10^5$~s$^{-1}$ to a fixed strain of 0.1, then reloaded to yield at a strain rate of $10^{-1}$. The yield point at reload is shown to have the same rapid upturn as seen when the specimens were deforming at high rates, providing strong evidence that the increase in strength is due to changes in the underlying dislocation structure, rather than a dynamic effect, as it remains even when the high strain rate is removed. Chapter 8 continues on from the conclusions of Chapter 7. Jump tests are expanded to a variety of temperatures and strains, to provide a more complete characterisation of metal behaviour. No dramatic change in the saturation of work hardening is observed to coincide with the increase in early stage work hardening. Chapter 9 discusses discrepancies between contemporary high rate models and recent developments in the understanding of plasticity being an avalanche process. Potential consequences of incorporating avalanche plasticity into high rate models are explored. Particular attention is paid to Brown's observation that based on quasi static observations of avalanche behaviour, the formation of dislocation avalanches will begin to fail at strain rates of approximately $10^4$ s$^{-1}$. Consequences of the progressive breakdown of avalanche behaviour are discussed with respect to the experimental observations presented in earlier chapters. In Chapter 10, we will discuss the key conclusions of the work. Finally, a number of avenues are proposed for building upon the current work both theoretically and experimentally.

För att bli konkurrenskraftiga behöver organisationer bli agila. Genom nya arbetssätt och tankesätt rusta upp sig för framtiden där de anpassar till dagens snabbrörliga värld, som är avgörande för organisationens överlevnad. En viktig förutsättning för att lyckas skapa agila organisationer är ett genuint ledarskap där ledaregenskaper som att leda sig själv och att skapa självorganiserade team är viktiga faktorer. Telekommunikationsföretaget som denna studie undersöker, arbetar till en viss del agilt men har fortfarande det traditionella ledarskapet kvar. De arbetar med att beslut ska kunna fattas där arbetet sker, vilket kan skapas genom att arbeta agilt där teamen är självorganiserade och kan leda sig själva. Studiens syfte är att se nuläget med ledarskapet på Telia och vilka egenskaper som skulle behöva utvecklas för att komma närmare ett agilt ledarskap. Studien tillämpar en kvalitativ forskningsmetodik, diskursanalys där data tolkats på mjuka värden så som inspelade videofilmer, information på webben, empiri från Telia samt litteratur. Teorier inom industriell teknik som delar av hörnstensmodellen och ledarskapsstilar tillämpas för att analysera och dra slutsats. Slutsatsen är att Telia behöver fokusera på att utveckla ledaregenskaper som att skapa tillit, transparens, anpassningsbarhet, delegering samt utveckla självtillit, självkännedom och självinsikt. Utifrån slutsatsen har förbättringsförslag tagits fram som att ständigt utveckla självkännedom, självinsikt och självtillit som ledare så att teamen och medarbetare blir säkra på sitt eget agerande och egna beslut. Samt att utveckla engagemang, ödmjukhet, framtid tänkande och förmågan att anpassa sig snabbt till förändringar. / To be competitive, organizations need to become agile. Through new ways of working and thinking, they prepare for the future where they adapt to today's fast-moving and changing world, which is crucial for the organization's survival. An important prerequisite for succeeding in creating agile organizations is genuine leadership, where leadership characteristics such as leading oneself and creating self-organized teams are important. The telecommunications company that this study examines, works to some extent agile but still retains the traditional leadership. They make decisions where the work takes place, which can be created by working agile where the teams are self-organized and can lead themselves. The purpose of the study is to see the current state of leadership at Telia and what characteristics would need to be developed to get closer to agile leadership. The study applies a qualitative research methodology, discourse analysis where data has been interpreted on soft values such as recorded videos, information on the web, empirical data from Telia and literature. Theories in industrial technology as parts of the cornerstone model and leadership styles are applied to analyze and draw conclusions. The conclusion is that Telia needs to focus on developing leadership characteristics such as creating trust, transparency, adaptability, delegation and developing self-confidence, selfawareness and self-insight. Based on the conclusion, improvement proposals have been developed such as constantly developing self-knowledge, self-insight and self-confidence as leaders so that the teams and employees become confident in their own actions and decisions. As well as developing commitment, humility, future thinking and the ability to adapt quickly to change.

The long-term evolution (LTE) network has been proposed to provide better network capacity than the earlier 3G network. Driven by the market, the conventional LTE (3G) network standard could not achieve the expectations of the international mobile telecommunications advanced (IMT-Advanced) standard. To satisfy this gap, the LTE-Advanced was introduced with additional network functionalities to meet up with the IMT-Advanced Standard. In addition, due to the need to minimize operational expenditure (OPEX) and reduce human interventions, the wireless cellular networks are required to be self-aware, self-reconfigurable, self-adaptive and smart. An example of such network involves transceiver base stations (BTSs) within a self-organizing network (SON). Besides these great breakthroughs, the conventional LTE and LTE-Advanced networks have not been designed with the intelligence of scalable capacity output especially in sudden demographic changes, namely during events of football, malls, worship centres or during religious and cultural festivals. Since most of these events cannot be predicted, modern cellular networks must be scalable in terms of capacity and coverage in such unpredictable demographic surge. Thus, the use of dynamic BTSs is proposed to be used in modern and future cellular networks for crowd and demographic change managements. Dynamic BTSs are complements of the capability of SONs to search, determine and deploy less crowded/idle BTSs to densely crowded cells for scalable capacity management. The mobile BTSs will discover areas of dark coverages and fill-up the gap in terms of providing cellular services. The proposed network relieves the LTE network from overloading thus reducing packet loss, delay and improves fair load sharing. In order to trail the best (least) path, a bio-inspired optimization algorithm based on swarm-particle optimization is proposed over the dynamic BTS network. It uses the ant-colony optimization algorithm (ACOA) to find the least path. A comparison between an optimized path and the un-optimized path showed huge gain in terms of delay, fair load sharing and the percentage of packet loss.