This thesis presents numerical optimization of geometries of axially symmetric ion trap mass analyzers. The motivation for this thesis is two fold. First is to demonstrate how the automated scheme can be applied to achieve geometry parameters of axially symmetric ion traps for a desired field configuration. Second is, through the Geometries investigated in this thesis, to present practically achievable geometries for mass spectroscopists to use. Here the underlying thought has been to keep the design simple for ease of fabrication (with the possibility of miniaturization) and still ensure that the performance of these analyzers is similar to the stretched geometry Paul traps. Five geometries have been taken up for investigation: one is the well known Cylindrical ion trap (CIT), three are new geometries and the last is the Paul trap under development in our laboratory. Two of these newer geometries have a step in the region of the midline of the cylindrical ring electrode (SRIT) and the third geometry has a step in its endcap electrodes (SEIT). The optimization has been carried out around deferent objective functions composed of the desired weights of higher order multiples. The Nelder-Mead simplex method has been used to optimize trap geometries. The multipoles included in the computations are quadrupole, octopole, dodecapole, hexadecapole,ikosipole and tetraikosipole having weights A2, A4, A6, A8, A10 and A12, respectively.Poincare sections have been used to understand dynamics of ions in the traps investigated. For the CIT, it has been shown that by changing the aspect ratio of the trap the harmful ejects of negative dodecapole superposition can be eliminated, although this results in a large positive A4=A2 ratio. Improved performance of the optimized CIT is suggested by the ion dynamics as seen in Poincare sections close to the stability boundary. With respect to the SRIT, two variants have been investigated. In the first geometry, A4=A2 and A6=A2 have been optimized and in the second A4=A2, A6=A2 and A8=A2 have been optimized; in both cases, these ratios have been kept close to their values reported for stretched hyperboloid geometry Paul traps. In doing this, however, it was seen that the weights of still higher order multipole not included in the objective function, A10=A2 and A12=A2, are high; additionally, A10=A2 has a negative sign. In spite of this, for both these configurations, the Poincare sections predict good performance. In the case of the SEIT, a geometry was obtained for which A4=A2 and A6=A2 are close to their values in the stretched geometry Paul trap and the higher even multipole (A8=A2, A10=A2 and A12=A2) are all positive and small in magnitude. The Poincare sections predict good performance for this con¯guration too. Direct numerical simulations of coupled nonlinear axial/radial dynamics also predict good performance for the SEIT, which seems to be the most promising among the geometries proposed here. Finally, for the Paul trap under development in our laboratory, Poincare sections and numerical simulations of coupled ion dynamics suggest a stretch of 79:7% is the best choice.

Les polynucléaires neutrophiles (PN) sont des cellules essentielles au cours de la réponse immunitaire innée ; recrutés rapidement au site inflammatoire où ils participent à la phase aigüe, ils vont aussi contribuer à la résolution de l’inflammation. Ils peuvent en effet moduler la réponse adaptative par interaction avec les lymphocytes (Ly) ou les cellules dendritiques (DC) via des médiateurs solubles ou des interactions cellulaires directes. Les Neutrophil Extracellular Traps (NETs) libérés par les PN activés pourraient jouer un rôle important dans ce contexte. Les NETs sont des filaments de chromatine décondensée associés à des protéines issues principalement des granulations et du cytoplasme. Ils sont essentiels dans la réponse anti-infectieuse mais semblent également impliqués dans la physiopathologie de certaines maladies auto-immunes et inflammatoires. L’objectif de ce travail a été d’évaluer les effets des NETs sur la maturation des DC dans un contexte inflammatoire au cours duquel les PN et les DC peuvent co-exister, assurant ainsi un pont entre immunité innée et immunité adaptative. La première partie de ce travail a consisté à développer un modèle de production, isolement et caractérisation des NETs issus de PN sanguins humains. L’ionophore de calcium A23187 a été choisi pour induire les NETs et l'enzyme de restriction AluI a permis la récupération de fragments de NETs de taille hétérogène. Certains des composants de ces NETs sont quantifiables (ADN, élastase, histone 3 en particulier), et nous avons montré qu’ils conservaient leurs capacités bactéricides in vitro. Ces échantillons de NETs constituent donc un outil biologique standardisé, permettant d’évaluer leurs effets sur des cellules ou des tissus. Dans la deuxième partie de ce travail, nous avons mis en évidence que ces NETs purifiés régulaient négativement la maturation de moDC induites par le LPS (expression de HLA-DR, CD80, CD83, CD86 et production de TNFα, IL-12, IL-6, IL-23). De plus, les NETs diminuent la capacité de ces moDC à induire la prolifération des LyT, et leur polarisation est modulée en favorisant la production de cytokines de type Th2 (IL-5 et IL-13) aux dépens de cytokines de types Th1 (INFγ) et Th17 (IL-17). De manière intéressante, la capacité de migration des moDC activées par le LPS n’est pas modifiée en présence de NETs. En résumé, ces résultats suggèrent que les NETs pourraient jouer un rôle immunorégulateur sur la maturation des moDC dans des conditions inflammatoires. Les NETs produits par les PN activés pourraient ainsi participer à la régulation indispensable de la réponse inflammatoire. / Polymorphonuclear neutrophils (PMN) are innate immune cells rapidly recruited to the inflammatory sites where they play a major role during the acute phase response but also contribute to resolution and repair. They can also modulate the adaptive response by interacting with lymphocytes (Ly) or dendritic cells (DC) via soluble mediators or cell-cell contacts. Activated PMN release Neutrophil Extracellular Traps (NETs) that could play a role in this context. NETs are decondensed chromatin fibers associated with granule and cytoplasmic proteins. As they are mainly involved in host defense against infection, they contribute to some autoimmune and inflammatory diseases. The aim of this work was to evaluate NET effects on DC maturation in an inflammatory context where PMN and DC co-exist, thus bridging innate and adaptive immunity. We first developed a model to induce, isolate and characterize NETs from human PMN. Calcium ionophore A23187 was chosen to induce NETs and the restriction enzyme AluI allowed the recovery of heterogeneous-sized fragments of NETs. Some of their components were quantified (DNA, elastase, histone 3, in particular) and we found that they retained their bactericidal activity. These NETs samples thus constitute a new and important biological tool to study their effects on immune cells or tissues. In the second part of this work, we found that isolated NETs were able to down-regulate LPS-induced moDC maturation as evidenced by the expressions of HLA-DR, CD80, CD83, CD86 and cytokine release (TNFα, Il-6, IL-12, Il-23). Moreover, the presence of NETs during moDC maturation lead to a decrease capacity of these moDC to induce T lymphocyte proliferation and modulated polarization by promoting the production of Th2 cytokines (IL-5 and IL-13) and decreasing Th1 cytokines (INFγ) and Th17 (IL- 17). Interestingly, moDC migration capacity was not modified when moDC maturation was done in the presence of NETs. In summary, these data suggest that NETs could downregulate DC activation. NETs produced by activated PMN could thus participate to the regulation of inflammation.

No description available.

Ion traps used in mass spectrometers are of two classes. One class consists of traps having three electrode geometries which have rotational symmetry about central axis. They are called axially symmetric ion traps. Paul trap, Cylindrical Ion Trap(CIT) are examples in this class. Other class of traps contain 2D electric field inside them which has same profile along the central axis due to translational symmetry. Linear Ion Trap(LIT) and Rectilinear Ion Trap(RIT) are examples in this class. In the ideal hyperbolic geometries of Paul trap and LIT, electric field is a perfectly linear function of distance from the center of the trap. But when these ideal geometries are simplified in to simpler geometries of the CIT and the RIT for ease in machining, linearity of field, which is a specialty of Paul trap and LIT is lost. In this thesis, an effort is made to optimize the field within the traps by using split electrodes. The ring electrode of the CIT and both pairs of electrodes in the RIT are divided into more number of parts. Suitable voltages are applied on these parts to improve the linearity of the field. This thesis contains six chapters. Chapter 1 contains a background information about mass spectrometry. Chapter 2 discusses the Boundary Element Method (BEM) used to calculate charge distribution and Nelder-Mead method used for optimization. It also shows the calculation of multipoles. In Chapter 3, two new geometries namely split-electrode RIT and split-electrode CIT are considered with the objective of improving the linearity of electric field inside them. It is shown here that by applying certain external potential on various parts of split electrodes of these geometries, it is possible to improve the linearity of electric field inside them. In Chapter 4, capacitor models of new geometries proposed in chapter 3 are discussed. The use of external capacitors as a replacement to external power supply is also discussed in this chapter. InChapter5, study similar to that ofChapter3is carried out by splitting the geometries in more number of parts. The possibility of improved field profile is investigated by applying full potential to some of these parts and keeping other parts at ground potential. In Chapter 6, concluding remarks are discussed.

Driven by the goal of decreasing emissions and pollutants towards a more sustainable future, the automotive industry is undergoing a rapid transition towards battery-powered electric vehicles. This shift to sustainable transport is fast-paced, and new technical solutions are being offered on a regular basis to fulfil the future needs for electric vehicles, including battery-electric trucks. This continuously necessitates a fast development of the battery-electric truck, along with the cooling system. To validate the cooling system, Scania's preferred approaches are testing and 3D simulations. However, these approaches are time-consuming and cannot match the pace of the design or the development. This thesis addresses the implementation of using 1D Simulations (GT-Suite) to carry out coolant filling simulations as a more efficient approach by studying the filling of the battery cooling system in an electric truck and, later, validating the results obtained with a test rig. In this thesis, different cases were defined, each adding more complexity to the circuit, and the parameters studied were the filling times and the location of air traps. Finally, a case with a closed circuit and running a coolant pump was developed to study the possibilities of devising quicker deaeration techniques for the circuit. The work completed in this thesis may be used as an example of how filling simulations can be performed with GT-Suite. This thesis is a good starting point, exploring a vast potential in using 1D Simulations to simulate the coolant-air interaction in a cooling system. Nonetheless, the findings revealed that GT-Suite v2020 and v2021 lack a robust model to properly simulate the interaction of coolant and air in certain sections of the circuit. In addition, the simulation model failed to obtain a steady-state solution in some cases resulting in discrepancies between the results from the test rig and the simulations. In conclusion, it was found that 1D simulations are not an ideal way forward when individual components of the cooling circuit are being considered, for example, the cooling plates, but are much quicker and seem to be a promising method to get an overview on a system level. / Fordonsindustrin drivs av målet att minska utsläppen och föroreningarna mot en mer hållbar framtid och genomgår en snabb omställning mot batteridrivna elfordon. Övergången till hållbara transporter går snabbt och nya tekniska lösningar erbjuds regelbundet för att möta de framtida behoven av elfordon, inklusive batteridrivna lastbilar. Detta kräver kontinuerligt en snabb utveckling av den batteri-elektriska lastbilen, tillsammans med kylsystemet. För att validera kylsystemet är Scanias föredragna metoder testning och 3D-simuleringar. Dessa tillvägagångssätt är dock tidskrävande och kan inte matcha takten i designen eller utvecklingen. Denna avhandling behandlar implementeringen av att använda 1D-simuleringar (GT-Suite) för att utföra kylvätskefyllningssimuleringar som ett effektivare tillvägagångssätt genom att studera fyllningen av batterikylsystemet i en elektrisk lastbil och senare validera resultaten som erhållits med en testrigg. I denna avhandling definierades olika fall, var och en lägga till mer komplexitet till kretsen, och de undersökta parametrarna var påfyllningstiderna och platsen för luftfällor. Slutligen utvecklades ett fall med en sluten krets och kör en kylvätskepump för att studera möjligheterna att utforma snabbare deaerationstekniker för kretsen. Arbetet i denna avhandling kan användas som ett exempel på hur fyllningssimuleringar kan utföras med GT-Suite. Denna avhandling är en bra utgångspunkt och utforskar en enorm potential i att använda 1D-simuleringar för att simulera kylvätske-luftinteraktionen i ett kylsystem. Resultaten visade dock att GT-Suite v2020 och v2021 saknar en robust modell för att korrekt simulera interaktionen mellan kylvätska och luft i vissa delar av kretsen. Dessutom kunde simuleringsmodellen inte få en steady state-lösning i vissa fall vilket resulterade i skillnader mellan resultaten från testriggen och simuleringarna. Sammanfattningsvis konstaterades det att 1D-simuleringar inte är en idealisk väg framåt när enskilda komponenter i kylkretsen övervägs, till exempel kylplattorna, men är mycket snabbare och verkar vara en lovande metod för att få en översikt på systemnivå.

Neutrophile Granulozyten produzieren „Neutrophil Extracellular Traps“ (NETs), ein mit antimikrobiellen Molekülen bestücktes Netzwerk aus Chromatinfasern, das während eines Zelltodprogramms namens „NETosis“ von den sterbenden Neutrophilen ausgestoßen wird. Ihre netzartige Struktur erlaubt es ihnen, eine weitere Verbreitung des Infektionserregers zu verhindern; zudem erzeugen sie eine hohe lokale Konzentration an toxischen Molekülen, die Mikroorganismen töten können. Unter normalen Bedingungen werden NETs von Nukleasen zerkleinert und anschließend von Makrophagen entfernt. Wenn dieser Aufräummechanismus gestört ist, aktivieren NETs das Immunsystem und führen zur Produktion von Autoantikörpern oder entzündungsfördernden Zytokinen. NETs werden mit einer wachsenden Liste von inflammatorischen und Autoimmunerkrankungen in Verbindung gebracht. Wie genau dabei NETs durch das Immunsystem erkannt werden, ist noch nicht bekannt. In der vorliegenden Arbeit zeige ich, dass NETs durch den zytosolischen DNA Sensor „cyclic GMP-AMP synthase“ (cGAS) detektiert werden können und dass dadurch die Expression von Typ I Interferonen (TIIFN) induziert wird. Zu Beginn demonstriere ich, dass NETs durch rekombinantes cGAS erkannt werden und dass mit isolierten NETs stimulierte Immunzellen cGAS-abhängig TIIFN produzieren. Des Weiteren zeige ich, dass Neutrophile, die NETosis begehen, in Nachbarzellen ebenfalls cGAS-anhängig TIIFN induzieren können. Abschließend konnte ich diese Ergebnisse in einem in vivo Mausmodel für systemische NET-Produktion bestätigen. Die vorliegende Arbeit zeigt einen Mechanismus, wie NETs durch das Immunsystem erkannt werden und dadurch sowohl zur Entstehung als auch zur Progression von Krankheiten beitragen kann. Sie ermöglicht dementsprechend die Entwicklung neuer Interventionsstrategien, welche zur Heilung oder Linderung einer Vielzahl von Erkrankungen beitragen können. / The first line of cellular defense of the immune system are neutrophils. They are the most abundant white blood cell, which exert an array of antimicrobial effector functions. Neutrophils release neutrophil extracellular traps (NETs), a composite of chromatin and antimicrobial molecules, into the extracellular space during a form of regulated cell death called NETosis. Their net-like structure prevent further dissemination of the invader and establishes a high local concentration of toxic molecules that mediate pathogen killing. NETs provide a platform for undesired immune activation and contribute to the production of autoantibodies and pro-inflammatory cytokines. NETs are implicated in a growing list of inflammatory and autoimmune diseases, but the exact mechanism how NETs are recognized by the immune system is not fully understood. In this study, I demonstrate that the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) senses NETs and induces the production of type I interferons (TIIFN). I first showed that NETs are recognized by recombinant cGAS and that cells treated with isolated NETs produce TIIFN in a cGAS dependent mechanism. Secondly, I demonstrate that neutrophils undergoing NETosis are taken up by neighboring immune cells and induce cGAS-dependent TIIFN expression. Lastly, I confirmed our in vitro results in a mouse model of systemic NET induction. Wildtype mice injected with Concanavalin A significantly upregulate the expression of interferon stimulated genes, while cGAS-/- mice and Cybb-/- mice, which are incapable of producing NETs, fail to induce this response.

Text in Afrikaans / Infringement, by the executive, of the right to privacy of the individual is an everyday occurrence. Section 14 of the Constitution, Act 108 of 1996 protects the right to privacy. The Criminal Procedure Act, Act 51 of 1977 authorises the police service, to search for and seize articles, to enter premises, ascertain bodily features of accused and to employ traps and undercover operations. On the one hand the Criminal Procedure Act authorises the police to infringe the privacy of the individual but on the other hand it guarantees the privacy of the individual. The provisions of the Criminal Procedure Act are qualified by the Constitution, specifically by section 36 and 35(5). The authorisation of a police officer should be obtained before a person could be arrested without a warrant, which should, in any event, be the last resort. The written permission of an officer must be obtained prior to the making of an application for a warrant to a magistrate. A police officer should be prohibited from issuing a search warrant, as the general perception of the public is that members of the police may not be sufficiently independent. The exercising of magistrates' discretion regarding the decision as to whether a search warrant should be issued or not should be extended. A search warrant should comply with strict requirements as to who may execute the warrant, when, how and when the warrant will become invalid. Search and seizure without a warrant should not be allowed at all, except in circumstances where there is an immediate threat or danger to a person, property or the public safety. In cases of urgency, it should be made possible to obtain the telephonic permission from a magistrate to search property. Where necessary to ascertain the bodily features of an accused through surgery, a compulsory application in terms of section 37(3) should be made to the court for authorisation, irrespective of whether the accused consents to the surgery or not. More importance should be attached to the rights of the individual and the powers of the executive should be limited. / Jurisprudence / LL.D

The potential impact of quantum computing has stimulated a worldwide effort to develop the necessary experimental and theoretical resources. In the race for the quantum computer, several candidate systems have emerged, but the ultimate system is still unclear. We study theoretically how to realize atomic Fock states both for fermionic and bosonic atoms, mainly in one-dimensional optical traps. We demonstrate a new approach of quantum computing based on ultracold fermionic atomic Fock states in optical traps. With the Pauli exclusion principle, producing fermionic atomic Fock states in optical traps is straightforward. We find that laser culling of fermionic atoms in optical traps can produce a scalable number of ultra-high fidelity qubits. We show how each qubit can be independently prepared, and how to perform the required entanglement operations and detect the qubit states with spatially resolved, single-atom detection with adiabatic trap-splitting and fluorescence imaging. On the other hand, bosonic atoms have a strong tendency to stay together. One must rely on strong repulsive interactions to produce bosonic atomic Fock states. To simulate the physical conditions of producing Fock states with ultracold bosonic atoms, we study a many-boson system with arbitrary interaction strength using the Bethe ansatz method. This approach provides a general framework, enabling the study of Fock state production over a wide range of realistic experimental parameters. / text

At present there is uncertainty over the response of neotropical ecosystems to the climatic changes of the Quaternary. The majority of vegetation reconstructions from the region are derived from fossil pollen records extracted from lake sediments. However, the interpretation of these records is restricted by limited knowledge of the contemporary relationships between the vegetation and pollen rain of neotropical ecosystems, especially for more open vegetation such as savanna and dry forest. This research aims to improve the interpretation of these records by investigating the relationship between the vegetation and modern pollen rain of different savanna and seasonally dry tropical forest (SDTF) ecosystems in Bolivia using artificial pollen traps and surface lake sediments to analyse the modern pollen rain. Vegetation data is used to identify taxa that are floristically important within the different ecosystems and to allow modern pollen/vegetation ratios to be calculated. The modern pollen rain from the upland savanna is dominated by Moraceae/Urticaceae (35.1%), Poaceae (29.6%), Alchornea (6.1%) and Cecropia (4.1%), whilst the seasonally-inundated savanna sites are dominated by Moraceae/Urticaceae (30.7%), Poaceae (19.5%), Cyperaceae (14.0%) and Cecropia (7.9%). These two different savanna ecosystems are only slightly differentiated by their modern pollen rain. The main taxa in the modern pollen rain of the upland SDTF are Moraceae/Urticaceae (25.8%), Cecropia (10.5%), Acalypha (7.6%) and Combretaceae/Melastomataceae (6.7%). Seasonally-inundated SDTF is dominated by Cecropia pollen to the extent that it was removed from the pollen sum and the main non-Cecropia pollen types are Moraceae/Urticaceae (39.0%), unknown type df 61 (6.4%), Asteraceae (6.3%), Celtis (6.0%) and Physocalymma scaberrimum (4.9%). These two SDTF ecosystems are well differentiated by their modern pollen rain, implying that they may be defined in fossil pollen records. The modern pollen rain obtained from the surface lake samples is generally complementary to that obtained from the artificial pollen traps for a given ecosystem. All sites have a high Moraceae/Urticaceae pollen signal due to effective dispersal of this pollen type from areas of evergreen forest in close proximity to the study sites. The savanna sites show lower Poaceae percentages than have been previously reported in the literature by some authors and this raises the possibility than the extent of this ecosystem in the past may have been underestimated. Modern pollen/vegetation ratios show that many key vegetation types are absent/under-represented within the modern pollen rain.

Land-use history has been recognized as an important factor in shaping biological communities in clear-cuts. Many solitary bees and flower beetles (Cerambycidae: Lepturinae) are commonly found in clear-cuts, which serve as early successional habitats. I analyzed the effect of land-use history on the abundance and species richness, as well as the preference for land-use history in specific species, of solitary bees and flower beetles in coniferous clear-cuts in southern Sweden. Additionally, the effect of site-specific environmental factors was examined. Insects were caught with blue, white and yellow pan-traps in 48 clear-cuts, of which half were meadow and half were forest in the 1870s. With few exceptions, the species found did not show preference for any land-use history. Furthermore, land-use history had no significant effect on the abundance or species richness of solitary bees or flower beetles. This may be due to pan-traps being less attractive in flower-rich locations, a bias in the sampling method. However, species richness and abundance of solitary bees was higher in young clear-cuts (2-4 years old), probably best explained by more exposed soil and higher frequencies of flowering plants in newer clear-cuts. Abundance of flower beetles was higher in old clear-cuts (6-8 years old). This may be due to larger amounts of more strongly decomposed wood in older clear-cuts, which is used in the flower beetles´ larval development. I conclude that solitary bees are likely to benefit if clear-cuts, particularly with meadow history, are kept more open by introducing disturbance regimes, as suggested by previous studies.