Cette thèse se place dans le cadre de l'étude in silico, c'est-à-dire assistée par ordinateur, des liens qui unissent la séquence d'une protéine à la (ou aux) structure(s) tri-dimensionnelle(s) qu'elle adopte. Le décryptage de ces liens présente de nombreuses applications dans divers domaines et constitue sans doute l'une des problématiques les plus fascinantes de la recherche en biologie moléculaire. Le premier aspect de notre travail concerne le développement de potentiels statistiques dérivés de bases de données de protéines dont les structures sont connues. Ces potentiels présentent plusieurs avantages: ils peuvent être aisément adaptés à des représentations structurales simplifiées, et permettent de définir un nombre limité de fonctions énergétiques qui incarnent l'ensemble complexe d'interactions gouvernant la structure et la stabilité des protéines, et qui incluent également certaines contributions entropiques. Cependant, leur signification physique reste assez nébuleuse, car l'impact des diverses hypothèses nécessaires à leur dérivation est loin d'être clairement établi. Nous nous sommes attachés à l'étude de certaines limitations des ces potentiels: leur dépendance en la taille des protéines incluses dans la base de données, la non-additivité des termes de potentiels, et l'importance souvent négligée de l'environnement protéique spécifique ressenti par chaque résidu. Nous avons ainsi mis en évidence que l'influence de la taille des protéines de la base de données sur les potentiels de distance entre résidus est spécifique à chaque paire d'acides aminés, peut être relativement importante, et résulte essentiellement de la répartition inhomogène des résidus hydrophobes et hydrophiles entre le coeur et la surface des protéines. Ces résultats ont guidé la mise au point de fonctions correctives qui permettent de tenir compte de cette influence lors de la dérivation des potentiels. Par ailleurs, la définition d'une procédure générale de dérivation de potentiels et de termes de couplage a rendu possible la création d'une fonction énergétique qui tient compte simultanément de plusieurs descripteurs de séquence et de structure (la nature des résidus, leurs conformations, leurs accessibilités au solvant, ainsi que les distances qui les séparent dans l'espace et le long de la séquence). Cette fonction énergétique présente des performances nettement améliorées par rapport aux potentiels originaux, et par rapport à d'autres potentiels décrits dans la littérature. Le deuxième aspect de notre travail concerne l'application de programmes basés sur des potentiels statistiques à l'étude de protéines qui adoptent des structures alternatives. La permutation de domaines est un phénomène qui affecte diverses protéines et qui implique la génération d'un oligomère suite à l'échange de fragments structuraux entre monomères identiques. Nos résultats suggèrent que la présence de "faiblesses structurales", c'est-à-dire de régions qui ne sont pas optimales vis-à-vis de la stabilité de la structure native ou qui présentent une préférence marquée pour une conformation non-native en absence d'interactions tertiaires, est intimement liée aux mécanismes de permutation. Nous avons également mis en évidence l'importance des interactions de type cation-{pi}, qui sont fréquemment observées dans certaines zones clés de la permutation. Finalement, nous avons sélectionné un ensemble de mutations susceptibles de modifier sensiblement la propension de diverses protéines à permuter. L'étude expérimentale de ces mutations devrait permettre de valider, ou de raffiner, les hypothèses que nous avons proposées quant au rôle joué par les faiblesses structurales et les interactions de type cation-{pi}. Nous avons également analysé une autre protéine soumise à d'importants réarrangements conformationnels: l'{alpha}1-antitrypsine. Dans le cas de cette protéine, les modifications structurales sont indispensables à l'exécution de l'activité biologique normale, mais peuvent sous certaines conditions mener à la formation de polymères insolubles et au développement de maladies. Afin de contribuer à une meilleure compréhension des mécanismes responsables de la polymérisation, nous avons cherché à concevoir rationnellement des protéines mutantes qui présentent une propension à polymériser contrôlée. Des tests expérimentaux ont été réalisés par le groupe australien du Professeur S.P. Bottomley, et ont permis de valider nos prédictions de manière assez remarquable. ---------------------------------------------------------------------------------------------------- The work presented in this thesis concerns the computational study of the relationships between the sequence of a protein and its three-dimensional structure(s). The unravelling of these relationships has many applications in different domains and is probably one of the most fascinating issues in molecular biology. The first part of our work is devoted to the development of statistical potentials derived from databases of known protein structures. These potentials allow to define a limited number of energetic functions embodying the complex ensemble of interactions that rule protein folding and stability (including some entropic contributions), and can be easily adapted to simplified representations of protein structures. However, their physical meaning remains unclear since several hypotheses and approximations are necessary, whose impact is far from clearly understood. We studied some of the limitations of these potentials: their dependence on the size of the proteins included in the database, the non-additivity of the different potential terms, and the importance of the specific environment of each residue. Our results show that residue-based distance potentials are affected by the size of the database proteins, and that this effect can be quite strong, is residue-specific, and seems to result mostly from the inhomogeneous partition of hydrophobic and hydrophilic residues between the surface and the core of proteins. On the basis of these observations, we defined a set of corrective functions in order to take protein size into account while deriving the potentials. On the other hand, we developed a general procedure of derivation of potentials and coupling terms and consequently created an energetic function describing the correlations between several sequence and structure descriptors (the nature of each residue, the conformation of its main chain, its solvent accessibility, and the distances that separate it from other residues, in space and along the sequence). This energetic function presents a strongly improved predictive power, in comparison with the original potentials and with other potentials described in the literature. The second part describes the application of different programs, based on statistical potentials, to the study of proteins that adopt alternative structures. Domain swapping involves the exchange of a structural element between identical proteins, and leads to the generation of an oligomeric unit. We showed that the presence of “structural weaknesses”, regions that are not optimal with respect to the folding mechanisms or to the stability of the native structure, seems to be intimately linked with the swapping mechanisms. In addition, cation-{pi} interactions were frequently detected in some key locations and might also play an important role. Finally, we designed a set of mutations that are likely to affect the swapping propensities of different proteins. The experimental study of these mutations should allow to validate, or refine, our hypotheses concerning the importance of structural weaknesses and cation-{pi} interactions. We also analysed another protein that undergoes large conformational changes: {alpha}1-antitrypsin. In this case, the structural modifications are necessary to the proper execution of the biological activity. However, under certain circumstances, they lead to the formation of insoluble polymers and the development of diseases. With the aim of reaching a better understanding of the mechanisms that are responsible for this polymerisation, we tried to design mutant proteins that display a controlled polymerisation propensity. An experimental study of these mutants was conducted by the group of Prof. S.P. Bottomley, and remarkably confirmed our predictions.

Inspiré par l'algèbre d’échange et birapport de rang n introduit par F. Labourie, nous construisons un anneau muni de la structure de Poisson--- l’algèbre d’échangée de rang n Zn(P) pour étudier les espaces de modules de birapports . Nous prouvons que Zn(P) hérite d'une structure de Poisson provenant de l’algèbre d’échangée. Pour tenir compte des “birapports” dans l’anneau de fraction, en interprétant Zn(P) par un modèle géométrique dans l'étude de la géométrie théorie des invariants, nous montrons que Zn(P) est intègre. Ensuite, nous considérons l'anneau Bn(P) engendreré par les birapports dans l'anneau de fraction de Zn(P). Pour n = 2,3, nous trouvons un homomorphisme injectif poissonienne de l'anneau engendré par coordonnées de Fock-Goncharovde sur l'espace des configurations de drapeaux dans Rn vers Bn(P). En étudiant le système intégrable discret pour l'espace des configurations de polygones N-tordus dans RP1, à une transformation de Fourier discrète, nous rapportons asymptotiquement l'algèbre d’échangée à l'algèbre de Virasoro sur une hypersurface de MN, 1. / Inspired by the swapping algebra and the rank n cross-ratio introduced by F. Labourie, we construct a ring equipped with the swapping Poisson structure---the rank n swapping algebra Zn(P) to study the moduli spaces of cross ratios. We prove that Zn(P) inherits a Poisson structure form the swapping bracket. To consider the "cross-ratios" in the fraction ring, by interpreting Zn(P) by a geometric model in the study of geometry invariant theory, we prove that Zn(P) is an integral domain. Then we consider the ring Bn(P) generated by the cross ratios in the fraction ring of Zn(P). For n = 2,3, we embed in a Poisson way the ring generated by Fock-Goncharov coordinates for configuration space of flags in Rn into Bn(P). By studying the discrete integrable system for the configuration space MN,1 of N-twisted polygons in RP1, up to a discrete Fourier transformation, we asymptotically relate the swapping algebra to the Virasoro algebra on a hypersurface of MN,1.

In the last two decades a drive for sustainable fashion emerged, grew and ultimately failed. In its beginnings the boom of green fashion and the saturation of labelled so-called sustainable garments, followed by the realization that most of the labelling did not hold any consistency behind it, overwhelmed consumers and made them immune to the effects of green marketing. This occurred because of the approach the fashion industry took regarding the topic. They needed to sell their products no matter what, and if a green tag with a recycling logo and a “green is the new black” motto would help them, they would embrace it. However, after several scandals and inquiries about the validity of the sustainable claims advertised, consumers grew rapidly disappointed and eventually unconcerned, falling back into their usual consumption habits without regard for ethical and environmental aspects. Nevertheless, once uncovered, the issues emerging from the production of garments could not be hidden once again, and companies were then required to take regulatory measures in order to mitigate the effects of the industry, if only to satisfy the general public’s knowledge and perceptions of the brands. As is well known this is not yet standard procedure and the ideal scenario for sustainable fashion production is still a road that continues on, but a small battle was won in the sustainability agenda and corporate social responsibility is nowadays common practice within large enterprises, again, if only for the sake of their stakeholders view. The truth, however, proves to be that this is not enough. Of the main environmental issues caused by clothing, not production, but use and consumption proved to be the most critical points in the larger picture. The amount of water, energy and waste created by laundering alone poses one of the biggest threats to the sustainable fashion notion, as well as the ever increasing textile waste in landfills. These issues are related entirely to each individual user and their actions, but the endeavor of making the large public aware of this issue is being undertaken by several, relatively small enterprises both private and public that don’t seem to be succeeding according to the studies. The public is not going to voluntarily wake up and undertake the quest for consuming and disposing sustainably unless they become aware first of their actions, and are given enough infrastructure to do so. This thesis concentrates on the problematic of consumer awareness regarding both use and disposal phases as well as the existing or possible solutions that help mitigate the devastating effects on the environment clothing is causing nowadays. / Program: Master programme in Fashion Management

Inspired by the swapping algebra and the rank n cross-ratio introduced by F. Labourie, we construct a ring equipped with the swapping Poisson structure---the rank n swapping algebra Zn(P) to study the moduli spaces of cross ratios. We prove that Zn(P) inherits a Poisson structure form the swapping bracket. To consider the "cross-ratios" in the fraction ring, by interpreting Zn(P) by a geometric model in the study of geometry invariant theory, we prove that Zn(P) is an integral domain. Then we consider the ring Bn(P) generated by the cross ratios in the fraction ring of Zn(P). For n = 2,3, we embed in a Poisson way the ring generated by Fock-Goncharov coordinates for configuration space of flags in Rn into Bn(P). By studying the discrete integrable system for the configuration space MN,1 of N-twisted polygons in RP1, up to a discrete Fourier transformation, we asymptotically relate the swapping algebra to the Virasoro algebra on a hypersurface of MN,1.

As small-form factor drones grow more intelligent, they increasingly require more sophisticated capabilities to record sensor data and system state, ensuring safe and improved operation. Already regulations for black boxes, electronic data recorders (EDRs), for determining liabilities and improving the safety of large-form factor autonomous vehicles are becoming established. Conventional techniques use hardened memory storage units that conserve all sensor (visual) and system operational state; and N-way redundant models for detecting uncertainty in system operation. For small-form factor drones, which are highly limited by weight, power, and computational resources, these techniques become increasingly prohibitive. In this paper, we propose a safety architecture for resource constrained autonomous vehicles that enables the development of safer and more efficient nano-drone systems. The insight for the proposed safety architecture is that the regular structure of data-driven models used to control drones can be exploited to efficiently compress and identify key events that should be conserved in the EDR subsystem. We describe an implementation of the architecture, including hardware and software support, and quantify the benefits of the approach. We show that the proposed techniques can increase the amount of recorded flight time by over 10x and reduce energy usage by over 10x for high-resolution systems.

The transition towards sustainable energy in the construction machinery sector is gaining momentum due to the urgent need to reduce greenhouse gas emissions and operational costs. Despite the benefits of electric construction machinery, challenges such as high initial investment costs, infrastructure requirements, and the practicality of battery swapping systems hinder widespread adoption. Understanding the economic feasibility and practical implications of implementing battery swapping in different construction scenarios is crucial for facilitating this transition. This study contributes to the existing body of knowledge by conducting a detailed Total Cost of Ownership (TCO) analysis for various energy sources —diesel, built-in batteries, and battery swapping systems — in two distinct construction settings: Big Quarry and Small Construction site. It provides a comparative evaluation of these options, highlighting the economic and environmental benefits of battery swapping. A comprehensive TCO analysis was performed, encompassing costs related to machine purchase, fuel/electricity consumption, maintenance, and infrastructure. Sensitivity analyses were conducted to identify critical cost drivers and assess the impact of fluctuating fuel and battery prices on the overall cost-effectiveness of each energy solution.  The findings indicate that battery swapping is the most cost-effective option across both construction sites, offering substantial savings compared to diesel and built-in batteries. Sensitivity analyses further showed that even with increased battery costs, electric machinery maintained stable economic performance, underscoring its viability as a sustainable alternative.

A unique mechanism of protein oligomerization is domain swapping. It is a feature found in some proteins wherein a dimer or a higher oligomer is formed by the exchange of identical structural segments between protomers. Domain swapping is thought to have played a key role in the evolution of stable oligomeric proteins and in oligomerization of amyloid proteins. This thesis deals with studies to understand the significance of hinges involved in domain swapping for protein oligomerization and function. The stationary phase survival protein SurE from Salmonella typhimurium (StSurE) and Sesbania mosaic virus (SeMV) coat protein have been used as models for studies on domain swapping. This thesis has been divided into eight chapters. Chapter 1 provides a brief introduction to domain swapping, while Chapters 2 to 6 describes the studies carried out on StSurE protein, Chapter 7 deals with studies on SeMV coat protein. The final Chapter 8 provides brief descriptions of various experimental techniques employed during these investigations. Chapter 1 deals with a brief introduction to domain swapping in proteins. Examples where different domains are exchanged are cited. Then it describes physiological relevance of domain swapping in proteins and probable factors which promote swapping. Finally it also discusses the uncertainties that are inevitable in protein structure prediction and design. Chapter 2 describes the structure of Salmonella typhimurium SurE (StSurE; Pappachan et al., 2008) determined at a higher resolution. The chapter also deals with the sequence and structure based comparison of StSurE with other known SurE homolog structures. A comparative analysis of the relative conservation of N- and C-terminal halves of SurE protomer and variations observed in the quaternary structures of SurE homologs are presented. Then a brief introduction is provided on function of StSurE. The conserved active site of StSurE that might be important for its phosphatase activity is described. A plausible mechanism for the phosphatase activity as proposed by Pappachan et al. (2008) is presented. Crystal structures of StSurE bound with AMP, pNPP and pNP that was determined with the view of better understanding the mechanism of enzyme function is presented. These structures provide structural evidence for the mechanism proposed by Pappachan et al. (2008). Finally a substrate entry channel inferred from these structures is discussed. SurE from Salmonella typhimurium (StSurE) was selected for studies on domain swapping as there is at least one homologous structure (Pyrobaculum aerophilum - PaSurE) in which swapping of the C-terminal helices appears to have been avoided without leading to the loss of oligomeric structure or function. It was of interest to examine if an unswapped dimer of StSurE resembling PaSurE dimer could be constructed by mutagenesis. To achieve this objective, a crucial hydrogen bond in the hinge involved in C-terminal helix swapping was abolished by mutagenesis. These mutants were constructed with the intention of increasing the flexibility of the hinge which might bring the C-terminal helices closer to the respective protomer as in PaSurE. Chapter 3 presents a comparative analysis of the hinges involved in C-terminal helix swapping in PaSurE and StSurE. Based on the comparison of structure and sequence, crucial residues important for C-terminal helix swapping in StSurE were identified as D230 and H234. The chapter describes the construction of mutants obtained by substituting D230 and H234 by alanine and their biophysical characterization. Finally it describes structural studies carried out on these mutants. The mutation H234A and D230A/H234A resulted in highly distorted dimers, although helix swapping was not avoided. Comparative analysis of the X-ray crystal structures of native StSurE and mutants H234A and D230A/H234A reveal large structural changes in the mutants relative to the native structure. However the crystal structures do not provide information on the changes in dynamics of the protein resulting from these mutations. To gain better insights into the dynamics involved in the native and mutants H234A and D230A/H234A, MD simulations were carried on using GROMACS 4.0.7. Chapter 4 deals with a brief description of the theory of molecular dynamics, followed by results of simulation studies carried out on monomeric and dimeric forms of StSurE and dimeric forms of its mutants H234A and D230A/H234A. The conformational changes and dynamics of different swapped segments are discussed. Crystal structures of H234A and D230A/H234A mutants reveal that they form highly distorted dimers with altered dimeric interfaces. Chapter 5 focuses on comparison of dimeric interfaces of the native StSurE and hinge mutants H234A and D230A/H234A. Based on the analysis, three sets of interactions were selected to investigate the importance of the interface formed by swapped segments in StSurE mutants H234A and D230A/H234A. One of the selected sites corresponds to a novel interaction involving tetramerization loop in the hinge mutants H234A and D230A/H234A resulting in a salt bridge between E112 – R179’ and E112’ – H180 (prime denotes residue from the other chain of the dimeric protein). This salt bridge seems to stabilize the distorted dimer. It is shown by structural studies that the loss of this salt bridge due to targeted mutation restores symmetry and dimeric organization of the mutants. Loss of a crucial hydrogen bond in the hinge region involved in C-terminal helix swapping in SurE not only leads to large structural changes but also alters the conformation of a loop near the active site. It is of interest to understand functional consequences of these structural changes. StSurE is a phosphatase, and its activity could be conveniently monitored using the synthetic substrate para nitrophenyl phosphate (pNPP) at pH 7 and 25 ºC. Chapter 6 deals with the functional studies carried out with various StSurE mutants. The studies suggest that there is a drastic loss in phosphatase activity in hinge mutants D230A, H234A and D230A/H234A, while in the salt bridge mutants the function seems to have been restored. Few of these mutants also exhibit positive cooperativity, which could probably be due to altered dynamics of domains. Sesbania mosaic virus (SeMV) is a plant virus, belonging to genus sobemovirus. SeMV is a T=3 icosahedral virus (532 symmetry) made up of 180 coat protein (CP) subunits enclosing a positive-sense RNA genome. The asymmetric unit of the icosahedral capsid is composed of chemically identical A, B and C subunits occupying quasi-equivalent environments. Residues 48 – 59 of the N-terminal arms of the C subunits interact at the nearby icosahedral three-fold axes through a network of hydrogen bonds to form a structure called the “β-annulus”. Residues 60 – 73 form the “βA-arm” that connects the N-terminal β-annulus to the rest of the protomer. Various studies on SeMV-CP suggest that different lengths of the N-terminal segments affect the assembly of virus. It might be possible to exploit this flexibility of the N-terminus in SeMV-CP to introduce swapping of this segment between two 2-fold related C subunits as is found in Rice yellow mottle virus (RYMV), another sobemovirus, with which SeMV shares significant sequence similarity. Chapter 7 focuses on attempts made to examine the mutational effects planned to introduce domain swapping. The strategy used for introducing swapping in SeMV-CP was based on the sequence of the βA-arm or the hinge involved in swapping of β-annulus in RYMV. TEM images of the mutant virus like particles obtained suggest that they are heterogeneous. These mutants could not be crystallized, probably due to the heterogeneity. However, the assembly of the expressed proteins to virus like particles was profoundly influenced by the mutations. Chapter 8 discusses various crystallographic, biophysical and biochemical techniques used during these investigations. Finally the thesis concludes with Conclusions and Future perspectives of the various studies reported in the thesis. In summary, I have addressed the importance of amino acid residues and interactions of hinges involved in domain swapping for the quaternary structure and function of proteins.

Domain swapping is a wide spread phenomenon which involves the association between two or more protein subunits such that intra-molecular interactions between domains in each subunit are replaced by equivalent inter-molecular interactions between the same domains in different subunits. This thesis is devoted to the analysis of the factors that drive proteins to undergo such association modes. The specific system analyzed is the monomer to swapped dimer formation of the B1 domain of the immunoglobulin G binding protein (GB1). The formation of this dimer was shown to be fostered by 4 amino acid substitutions (L5V, F30V, Y33F, A34F) (Byeon et al. 2003). In this work, computational protein design and molecular dynamics simulations, both with detailed atomic models, were used to gain insight into how these 4 mutations may promote the domain swapping reaction.<p>The stability of the wt and quadruple mutant GB1 monomers was assessed using the software DESIGNER, a fully automatic procedure that selects amino acid sequences likely to stabilize a given backbone structure (Wernisch et al. 2000). Results suggest that 3 of the mutations (L5V, F30V, A34F) have a destabilizing effect. The first mutation (L5V) forms destabilizing interactions with surrounding residues, while the second (F30V) is engaged in unfavorable interactions with the protein backbone, consequently causing local strain. Although the A34F substitution itself is found to contribute favorably to the stability of the monomer, this is achieved only at the expense of forcing the wild type W43 into a highly strained conformation concomitant with the formation of unfavorable interactions with both W43 and V54.<p>Finally, we also provide evidence that A34F mutation stabilizes the swapped dimer structure. Although we were unable to perform detailed protein design calculations on the dimer, due to the lower accuracy of the model, inspection of its 3D structure reveals that the 34F side chains pack against one another in the core of the swapped structure, thereby forming extensive non-native interactions that have no counterparts in the individual monomers. Their replacement by the much smaller Ala residue is suggested to be significantly destabilizing by creating a large internal cavity, a phenomenon, well known to be destabilizing in other proteins. Our analysis hence proposes that the A34F mutation plays a dual role, that of destabilizing the GB1 monomer structure while stabilizing the swapped dimer conformation.<p>In addition to the above study, molecular dynamics simulations of the wild type and modeled quadruple mutant GB1 structures were carried out at room and elevated temperatures (450 K) in order to sample the conformational landscape of the protein near its native monomeric state, and to characterize the deformations that occur during early unfolding. This part of the study was aimed at investigating the influence of the amino acid sequence on the conformational properties of the GB1 monomer and the possible link between these properties and the swapping process. Analysis of the room temperature simulations indicates that the mutant GB1 monomer fluctuates more than its wild type counter part. In addition, we find that the C-terminal beta-hairpin is pushed away from the remainder of the structure, in agreement with the fact that this hairpin is the structural element that is exchanged upon domain swapping. The simulations at 450 K reveal that the mutant protein unfolds more readily than the wt, in agreement with its decreased stability. Also, among the regions that unfold early is the alpha-helix C-terminus, where 2 out of the 4 mutations reside. NMR experiments by our collaborators have shown this region to display increased flexibility in the monomeric state of the quadruple mutant.<p>Our atomic scale investigation has thus provided insights into how sequence modifications can foster domain swapping of GB1. Our findings indicate that the role of the amino acid substitutions is to decrease the stability of individual monomers while at the same time increase the stability of the swapped dimer, through the formation of non-native interactions. Both roles cooperate to foster swapping. / Doctorat en sciences, Spécialisation biologie moléculaire / info:eu-repo/semantics/nonPublished

The deterministic generation and manipulation of quantum states has attracted much interest ever since the rise of quantum mechanics. Large-scale, distributed quantum states are the basis for novel applications such as quantum communication, quantum remote sensing, distributed quantum computing or quantum voting protocols. The necessary infrastructure will be provided by distributed quantum networks, allowing for quantum bit processing and storage at single nodes. Quantum states of light then allow for inter-node transmission of quantum information. Transmission losses in optical fibers may be overcome by quantum repeaters, the quantum equivalent of classical signal amplifiers. The fragility of quantum superposition states makes building such networks very challenging. Hybrid solutions combine the strengths of different physical systems: Efficient quantum memories can be realized using alkali atoms such as rubidium. Leading in the deterministic generation of single photons and polarization entangled photon pairs are semiconductor InAs/GaAs quantum dots grown by the Stranski-Krastanov method. Despite remarkable progress in the last twenty years, complex quantum optical protocols could not be realized due to low degree of entanglement, low brightness and broad wavelength distribution. In this work, an emerging family of epitaxially grown GaAs/AlGaAs quantum dots obtained by droplet etching and nanohole infilling is studied. Under pulsed resonant two-photon excitation, they emit single pairs of entangled photons with high purity and unprecedented degree of entanglement. Entanglement fidelities up to f = 0.94 are observed, which are only limited by the optical setup or a residual exciton fine structure. The samples exhibit a very narrow wavelength distribution at rubidium memory transitions. Strain tuning is applied via piezoelectric actuators to allow for reversible fine-tuning of the emission frequency. In a next step, active feedback is employed to stabilize the frequency of single photons emitted by two separate quantum dots to an atomic rubidium standard. The transmission of a rubidium-based Faraday filter serves as the error signal for frequency stabilization. A residual frequency deviation of < 30MHz is achieved, which is less than 1.5% of the quantum dot linewidth. Long-term stability is demonstrated by Hong-Ou-Mandel interference between photons from the two quantum dots. Their internal dephasing limits the expected visibility to V = 40%. For frequency-stabilized dots, V = (41 ± 5)% is observed as opposed to V = (31 ± 7)% for free-running emission. This technique reaches the maximally expected visibility for the given system and therefore facilitates quantum networks with indistinguishable photons from distributed sources. Based on the presented techniques and improved emission quality, pivotal quantum communication protocols can now be implemented with quantum dots, such as transferring entanglement between photon pairs. Embedding quantum dots in a dielectric antenna ensures a bright emission. For the first time, entanglement swapping between two pairs of photons emitted by a single quantum dot is realized. A joint Bell measurement heralds the successful generation of the Bell state Ψ+ with a fidelity of up to (0.81 ± 0.04). The state's nonlocal nature is confirmed by violating the CHSH-Bell inequality with S = (2.28 ± 0.13). The photon source is tuned into resonance with rubidium transitions, facilitating implementation of hybrid quantum repeaters. This work thus represents a major step forward for the application of semiconductor based entangled photon sources in real-world scenarios.

The purpose of this thesis is to investigate how tractor swapping can be implemented in Vehicle Routing Problems (VRP) with electric heavy goods vehicles, and to evaluate how a model that allows for tractor swapping performs, in terms of schedule cost, against a model that does not. Hence, this thesis introduces a new rich VRP variant which includes tractor swapping, as well as time windows, pickup and delivery, and electric vehicles. The model is named Electric Tractor Swap Vehicle Routing Problem (E-TSVRP) and is formulated as a mixed integer linear program. As for the solver, Gurobi is used. The results show that utilizing tractor swapping can reduce the total cost of serving customers significantly by reducing en-route charging and utilizing drivers more efficiently. Specifically, it is shown that the cost reduction comes mainly from reducing driver work time. By demonstrating how tractor swapping works and how the results can be visualized on smaller cases, this thesis aims to serve as a foundation for future research within the field. To be able to fully implement the model for large logistics problem instances however, alternative solution methods such as heuristics or metaheuristics should be developed so that the problems can be solved in a reasonable amount of time. / Syftet med denna uppsats är att undersöka hur traktorbyten kan implementeras i "Vehicle Routing Problem" (VRP) med tunga, elektriska lastfordon, och att utvärdera hur en modell som tillåter traktorbyten presterar mot en modell som inte tillåter det, med avseende på den totala schemakostnaden. I uppsatsen introduceras därför en ny och generell VRP som har stöd för traktorbyten, men som också modellerar energikonsumtion och laddning av elektriska lastbilar, samt tillåter tidsfönster för när leveranser kan levereras och hämtas upp på godtyckliga platser. Modellen kallas för "Electric Tractor Swap Vehicle Routing Problem" (E-TSVRP) och formuleras som ett linjärt, blandat heltalsprogram. Programmet löses sedan med lösaren Gurobi. Resultaten visar att utnyttjandet av traktorbyten kan märkbart minska den totala kostnaden av att leverera varor till kunder genom att minska tiden som föraren väntar på att traktorn laddar. Mer specifikt tillåts möjligheten att byta till en ny traktor när den tidigare får slut på energi, vilket möjliggör en högre utnyttjandegrad av förarna, och den fakturerade tiden associerad till förarna kan minskas. Detta sker genom en avvägning mellan å ena sidan högre hårdvarukostnader för fler traktorer och å andra sidan lägre förarkostnader. Genom att demonstrera hur traktorbyten fungerar och hur resultaten kan visualiseras på mindre transportproblem, strävar denna uppsats efter att verka som en grund för framtida forskning. För att modellen ska kunna användas för stora logistikproblem bör dock alternativa lösningsmetoder som till exempel lösningsheuristiker eller metaheuristiker utvecklas så att problemen kan lösas inom en rimlig tid.