<p>The current study aimed to describe the extent and reasons for substituting and switching HAART at the Katutura Intermediate Hospital in Windhoek, Namibia</p>

The objective of this work is to better understand themetabolism and physiology ofEscherichiacoli(W3110) in defined medium cultures with thelong-term goal of improving cell yield and recombinant proteinproductivity. The order of amino acid utilization inE. colibatch cultures was investigated in a medium with16 amino acids and glucose. Ser, Pro, Asp, Gly, Thr, Glu andAla were rapidly consumed and depleted at the end of theexponential phase, while His, Arg, Val, Met, Ile, Leu, Phe, Lysand Tyr were consumed slowly during the following linear growthphase. The uptake order correlated to the maximum specificconsumption rate. Of the rapidly consumed amino acids onlyglyine and threonine improved growth when added individually.Serine was the first amino acid to be consumed, but inhibitedglucose uptake initially, which presumably is related to thefunction of PTS. Valine inhibited cell growth could be releasedby isoleucine. The critical medium concentration of valinetoxicity was 1.5 - 3 µmol L-1. Valine uptake was associated with exchange ofisoleucine out of the cells. Glycine significantly increased the cell yield,Yx/s,and growth rate ofE. coliin batch cultures in a glucose-mineral medium.Maximum effect occurred at pH 6.8, at 6 - 12 mmol L-1glycine, and below 1.15 g dw L-1.13C NMR technique was employed to identify [1-13C], [2-13C]and [1,2-13C]acetate in the cultures supplied with [2-13C]glycine. The NMR data revealed that littledegradation of added glycine occurred, and that serine/glycinebiosynthesis was repressed below 1.15 g dw L-1, implicating that glycine was a source ofglycine, serine, one-carbon units, and threonine. Above 1.15 gdw L-1, 53% of the consumed glycine carbon was excretedas acetate. Degradation of glycine was associated with anincreased uptake rate, cleavage by GCV, and degradation of bothglycine- and glucose-derived serine to pyruvate. This switch inmetabolism appears to be regulated by quorum sensing. A cell density-dependent metabolic switch occurred also inthe central metabolism. A 2 - 3 fold decrease in mostglycolytic and TCA cycle metabolites, but an increase inacetyl-CoA, occurred after the switch. The acetate productionrate decreased throughout the culture with a temporary increaseat the switch point, but the intracellular acetate poolremained relatively constant. Two mixtures of amino acids were fed together with glucosein fed-batch cultures ofE. coliW3110 pRIT44T2, expressing the recombinantprotein ZZT2. One mixture contained 20 amino acids and theother 5 so-called 'protein amino acids': Ala, Arg, Met, His andPhe. Although the amino aids increased the cell yield anddecreased the proteolysis rate in both cases, ZZT2 productionwas decreased. A decrease of ZZT2 synthesis rate is consideredto be the reason. Further studies of the 5 amino acidsindicated that a few amino acids disturb metabolism. Carbon mass balances were calculated in glucose limitedfed-batch cultures ofE. coli. In the end, the carbon recovery was ~90% basedon biomass, CO2and acetate, but ~100% if the all carbon in themedium was included. Outer membrane (OM) constituents,lipopolysaccharide, phospholipids, and carbohydratescontributed to 63% of the extracellular carbon. Little celllysis occurred and the unidentified (~30%) carbon was assumedto constitute complex carbohydrates. A novel cultivationtechnique Temperature-Limited Fed-Batch (TLFB) is developed toprevent OM shedding in high-cell density cultures. <b>Keywords</b>: Escherichia coli, amino acids, glycine, quorumsensing, metabolic switch, metabolite pools, carbon balance,outer membrane, lipopolysaccharide, batch culture, fed-batchculture

The objective of the proposed research is to understand the design and reliability of RF front-end building blocks using SOI CMOS and SiGe BiCMOS technologies for high dynamic-range applications. This research leads to a comprehensive understanding of dynamic range in SOI CMOS devices and contributes to knowledge leading to improvement in overall dynamic range and reliability of RF building blocks. While the performance of CMOS transistors has been improving naturally with scaling, this work aims to explore the possibilities of improvement in RF performance and reliability using standard layouts (that don't need process modifications). The total-ionizing dose tolerance of SOI CMOS devices has been understood with extensive measurements. Furthermore, the role of body contacts in SOI technology is understood for dynamic range performance improvement. In this work, CMOS low-noise amplifier design for high linearity WLAN applications and its integration with RF switch on the same chip is presented. The LNA and switches designed provide state-of-the-art performance in silicon based technologies. Further, the work aims to explore applications of SiGe HBT in the context of highly linear and reliable RF building blocks. The RF reliability of SiGe HBT based RF switches is investigated and compared with CMOS counterparts. The inverse-mode operation of SiGe HBT based switches is understood to give considerably higher linearity.

Current access strategies for minimal interface (e.g., binary switch) users employ time-coded (i.e., synchronous) protocols that map unique sequences of user-generated binary digits (i.e., bits) to each of the available outcomes of a device under control. With such strategies, the user must learn and/or reproduce the timing of the protocol with a certain degree of accuracy. As a result, the number, κ, of device outcomes made accessible to the user is typically bound by the memorization capacity of the latter and by the time required to generate the appropriate bit sequences. Furthermore, synchronous access strategies introduce a minimum time delay that increases with larger κ, precluding access to control applications requiring fast user response. By turning control on its head, this thesis presents an access method that completely eliminates reliance on time-coded protocols. Instead, the proposed asynchronous access method requires users to employ their interfaces only when the behavior of the device under control does not match their intentions. In response to such event, the proposed method may then be used to select, and automatically transmit, a new outcome to the device. Such outcome is informed by historical and contextual assumptions incorporated into a recursive algorithm that provides increasingly accurate estimates of user intention. This novel approach, provides significant advantages over traditional synchronous strategies: i) the user is not required to learn any protocol, ii) there is no limit in the number of outcomes that may be made available to the user iii) there is no delay in the response of the device, iv) the expected amount of information required to achieve a particular task may be minimized, and, most importantly, v) the control of previously inaccessible devices may be enabled with minimal interfaces. This thesis presents the full mathematical development of the novel method for asynchronous control summarized above. Rigorous performance evaluations demonstrating the potential of this method in the control of complex devices, by means of minimal interfaces, are also reported.

Current access strategies for minimal interface (e.g., binary switch) users employ time-coded (i.e., synchronous) protocols that map unique sequences of user-generated binary digits (i.e., bits) to each of the available outcomes of a device under control. With such strategies, the user must learn and/or reproduce the timing of the protocol with a certain degree of accuracy. As a result, the number, κ, of device outcomes made accessible to the user is typically bound by the memorization capacity of the latter and by the time required to generate the appropriate bit sequences. Furthermore, synchronous access strategies introduce a minimum time delay that increases with larger κ, precluding access to control applications requiring fast user response. By turning control on its head, this thesis presents an access method that completely eliminates reliance on time-coded protocols. Instead, the proposed asynchronous access method requires users to employ their interfaces only when the behavior of the device under control does not match their intentions. In response to such event, the proposed method may then be used to select, and automatically transmit, a new outcome to the device. Such outcome is informed by historical and contextual assumptions incorporated into a recursive algorithm that provides increasingly accurate estimates of user intention. This novel approach, provides significant advantages over traditional synchronous strategies: i) the user is not required to learn any protocol, ii) there is no limit in the number of outcomes that may be made available to the user iii) there is no delay in the response of the device, iv) the expected amount of information required to achieve a particular task may be minimized, and, most importantly, v) the control of previously inaccessible devices may be enabled with minimal interfaces. This thesis presents the full mathematical development of the novel method for asynchronous control summarized above. Rigorous performance evaluations demonstrating the potential of this method in the control of complex devices, by means of minimal interfaces, are also reported.

Els serveis de telecomunicacions i sistemes radar estan migrant a freqüències mil•limètriques (MMW), on es disposa d 'una major amplada de banda i conseqüentment d'una major velocitat de transmissió de dades. Aquesta migració requereix de l'ús de diferents tecnologies amb capacitat d'operar a la banda de freqüències mil•limètriques (30 a 300 Ghz), i més concretament en les bandes Ka (26,5 - 40GHz), V (50 – 75GHz) i W (75 – 110GHz). En moltes aplicacions i sobretot en aquelles on l'antena forma part d'un dispositiu mòbil, es cerca poder utilitzar antenes planes, caracteritzades per tenir unes dimensions reduïdes i un baix cost de fabricació. El conjunt de requeriments es pot resumir en obtenir una antena amb capacitat de reconfigurabilitat i amb un baix nivell de pèrdues en cada una de les bandes de freqüència. Per tal d'afrontar aquests reptes, les dimensions de les antenes mil•limètriques, juntament amb els tipus de materials, toleràncies de fabricació i la capacitat de reconfigurabilitat ens porten a l'ús de processos de microfabricació. L'objectiu d'aquesta tesis doctoral és l'anàlisi dels conceptes mencionats, tipus de materials, geometries de línia de transmissió i interruptors, en el context de les freqüències mil•limètriques, així com la seva aplicació final en dissenys d'antenes compatibles amb els processos de microfabricació. Finalment, com a demostració s'han presentat dissenys específics utilitzables en tres aplicacions a freqüències mil•limètriques: Sistemes de Comunicació per Satèl•lit (SCS) a la banda Ka, Xarxes d'àrea personal inalàmbriques (WPAN) a la banda V i sistemes radar per l'automoció a la banda W. La primera part d'aquesta tesis consisteix en l'anàlisi d'algunes tecnologies circuitals a freqüències mil•limètriques. S'han presentat els materials més utilitzats a altes freqüències (Polytetrafluoroethylene or Teflon (PTFE), Quartz, Benzocyclobuten polymer (BCB) i Low Temperature Co-fired Ceramic (LTCC)) i s'han comparat en termes de permitivitat i tangent de pèrdues. També s'inclou un estudi de pèrdues a altes freqüències en les principals línies de transmissió (microstrip, stripline i CPW). Finalment, es presenta un resum dels interruptors RF-MEMS i es comparen amb els PIN diodes i els FET. En la segona part, es presenten diferents agrupacions d'antenes amb la capacitat de reconfigurar la polarització i la direcció d'apuntament. S'han dissenyat dos elements base reconfigurables en polarització: CPW Patch antena i 4-Qdime antena. La primera antena consisteix en un element singular amb interruptors RF-MEMS, dissenyada per operar a les bandes Ka i V. La segona antena consisteix en una arquitectura composta on la reconfigurabilitat en polarització s'obté mitjançant variant la fase d'alimentació de cada un dels quatre elements lineals. La fase és controlada mitjançant interruptors RF-MEMS ubicats en la xarxa de distribució. L'antena 4-Qdime s'ha dissenyat per operar en les bandes V i W. Ambdós elements base s'han utilitzat posteriorment pel disseny de dues agrupacions d'antenes amb capacitat de reconfigurar l'apuntament del feix principal. La reconfigurabilitat es dur a terme utilitzant desfasadors de fase d'1 bit. La part final de la tesis es centra en les toleràncies de fabricació i en els processo de microfabricació d'agrupacions d'antenes mil•limètriques. Les toleràncies de fabricació s'han estudiat en funció dels error d'amplitud i fase en cada element de l'agrupació, fixant-se en les pèrdues de guany, error d'apuntament, error en l'amplada de feix, errors en el nivell de lòbul secundari i en l'error en la relació axial. El procés de microfabricació de les diferents antenes dissenyades es presenta en detall. Els dissenys de l'antena CPW Patch reconfigurable en polarització i apuntament operant a les bandes Ka i V, s'han fabricat en la sala blanca del Cornell NanoScale Science & Technology Facility (CNF). Posteriorment, s'han caracteritzat l'aïllament i el temps de resposta dels interruptors RF-MEMS, i finalment, el coeficient de reflexió, el diagrama de radiació i la relació axial s'han mesurat a les bandes Ka i V per les antenes configurades en polarització lineal (LP) i circular (CP). / Telecommunication services and radar systems are migrating to Millimeter-wave (MMW) frequencies, where wider bandwidths are available. Such migration requires the use of different technologies with the capability to operate at the MMW frequency band (30 to 300GHz), and more specifically at Ka- (26.5 to 40GHz), V- (50 to 75GHz) and W-band (75 to 110GHz). For many applications and more concretely those where the antenna is part of a mobile device, it is targeted the use of planar antennas for their low profile and low fabrication cost. A wide variety of requirements is translated into a reconfiguration capability and low losses within each application frequency bandwidth. To deal with the mentioned challenges, the MMW antenna dimensions, together with the materials, fabrication tolerances and reconfigurability capability lead to microfabrication processes. The aim of this thesis is the analysis of the mentioned concepts, materials, transmission lines geometries and switches in the MMW frequencies context and their final application in antenna designs compatible with microfabrication. Finally, specific designs are presented as a demonstration for three MMW applications: Satellite Communication Systems (SCS) at Ka-band, Wireless Personal Area Network (WPAN) at V-band and Automotive Radar at W-band. The first part of this thesis consist to analyze some MMW circuit technologies. The four most used materials at MMW frequencies (Polytetrafluoroethylene or Teflon (PTFE), Quartz, Benzocyclobuten polymer (BCB) and Low Temperature Co-fired Ceramic (LTCC)) have been presented and compared in terms of permittivity (εr) and loss tangent (tanδ). An study of the main transmission lines attenuation (microstrip, stripline and CPW) at high frequencies is included. Finally, an overview of the RF-MEMS switches is presented in comparison with PIN diodes and FETS switches. The second part presents different polarization and beam pointing reconfigurable array antennas. Two polarization-reconfigurable base-elements have been designed: CPW Patch antenna and 4-Qdime antenna. The first consists of a single reconfigurable element with integrated RF-MEMS switches, designed to operate at Ka- and V-band. The second antenna presented in this thesis has a composed architecture where the polarization reconfigurability is obtained by switching the phase feeding for each of the four linear polarized elements in the feed network with RF-MEMS switches. The 4-Qdime antenna has been designed to operate at V- and W-band. The two base-elements have been used to design two beam pointing reconfigurable antenna arrays. Using phased array techniques, beamsteering is computed and implemented with 1-bit discrete phase-shifter. The final part of the thesis is focused into the fabrication tolerances and microfabrication process of Millimeter-wave antenna arrays. The fabrication tolerances have been studied as a function of the amplitude and phase errors presented at each elements array, focusing on the gain loss, beam pointing error, Half-Power Beamwidth (HPBW) error, sidelobe level error and axial ratio error. The microfabrication process for the designed antennas is presented in detail. Polarization- and pointing- reconfigurable CPW Patch antenna operating at Ka- and V- band have been fabricated in a clean-room facility at Cornell NanoScale Science & Technology Facility (CNF). The RF-MEMS switches isolation and time response have been characterized. Finally, the reflection coefficient, radiation pattern and axial ratio have been measured at Ka- and V-band for the fabricated antennas configured in Linear Polarization (LP) and Circular Polarization (CP).

Ethernet Switches are widely used in real-time distributed systems as a solution to guarantee the real-time behavior in communication. In this solution there are still some limitations which are the important obstacles obtaining timeliness in the network. These limitations are the limited number of priority levels as well as the possibility of memory overruns with consequent messages. The mentioned limitations can be eliminated using a master/slave technique along with FTT paradigm. The FTT-SE protocol which is a technique based on the master/slave and FTT methods was proposed to overcome the mentioned limitations. However, the FTT-SE protocol has been investigated for a small network architecture with a single switch and master node. Extension of this solution to larger networks is still an open issue. Three different architectures were suggested to scale the FTT-SE to large scale network. In this thesis we propose a solution that extends the FTT-SEprotocol while keeping the real-time behavior of the network. In this solution, we divided the network into a set of sub-networks, each contains one switch, set of slave nodes and one master node that connected to the associated switch in the network. Moreover, the switches are connected together directly without gateways and form a tree topology network. The solution includes both synchronous and asynchronous traffic in the network. We also show that the timeliness of the traffic can still be enforced. Moreover, to validate the solution we have designed and implemented a simulator based on the Matlab/Simulink which is a tool to evaluate different network architecture using Simulink blocks. All transmission can be visualized by the ordinary Scope block in the Simulink. Moreover, the end-to-end delay for all messages is calculated after the simulation running to show the response time of the network. Furthermore, the response time analysis is done for both synchronous and asynchronous messages in this thesis according to the proposed solution. The results from simulation and the analysis are compared together to validate the investigations.

An Adaptive Cruise Controller (ACC) is an extension of an ordinary cruise controller. In addition to maintaining a desired set velocity, an ACC can also maintain a desired time gap to the vehicle ahead. For this end, both the engine andthe brakes are controlled. The purpose with this thesis has been to develop control strategies for an ACC used in heavy vehicles. The focus of the work has been the methods used for switching between the use of engine and brake. Two different methods have been studied, a hybrid controller and an MPC-controller. For the hybrid controller, the main contribution has been to use the influence of the surroundings on the acceleration of the truck. This consists of several parts such as wind drag, road slope and rolling resistance. The estimated influence of the surroundings is used as a switch point between the use of engine and brakes. Ideally, these switch points give bumpless actuator switches. The interest in the MPC-controller as an alternative solution was to achieve automatic actuator switching, thus with no explicitly defined switch points. The MPC-controller is based on a model of the system including bounds on the control signals. Using this knowledge, the MPC-controller will choose the correct actuator for the current driving situation. Results from simulations show that both methods solve the actuator switch problem. The advantages with the hybrid controller are that it is implementable in a truck with the hardware used today and that it is relatively simple to parameterise. A drawback is that explicit switch points between the uses of the different actuators have to be included. The advantages with the MPC-controller are that no explicit switch points have to be introduced and that constraints and time delays on signals in the system can be handled in a simple way. Among the drawbacks, it can be mentioned that the variant of MPC, used in this thesis, is too complex to implement in the control system currently used in trucks. One further important drawback is that MPC demands a mathematical model of the system.

Bit-serial multiplication with a fixed coefficient is commonly used in integrated circuits, such as digital filters and FFTs. These multiplications can be implemented using basic components such as adders, subtractors and D flip-flops. Multiplication with the same coefficient can be implemented in many ways, using different structures. Other studies in this area have focused on how to minimize the number of adders/subtractors, and often assumed that the cost for D flip-flops is neglectable. That simplification has been proved to be far too great, and further not at all necessary. In digital devices low power consumption is always desirable. How to attain this in bit-serial multipliers is a complex problem. The aim of this thesis was to find a strategy on how to implement bit-serial multipliers with as low cost as possible. An important step was achieved by deriving formulas that can be used to calculate the carry switch probability in the adders/subtractors. It has also been established that it is possible to design a power model that can be applied to all possible structures of bit- serial multipliers.

<p>Cellular dynamics arise from intricate interactions among diverse components, such as metabolites, RNAs, and proteins. An in-depth understanding of these interactions requires an integrated approach to the investigation of biological systems. This task can benefit from a combination of mathematical modeling and experimental validations, which is becoming increasingly indispensable for basic and applied biological research. </p> <p>Utilizing a combination of modeling and experimentation, we investigate mammalian cell cycle entry. We begin our investigation by making predictions with a mathematical model, which is constructed based on the current knowledge of biology. To test these predictions, we develop experimental platforms for validations, which in turn can be used to further refine the model. Such iteration of model predictions and experimental validations has allowed us to gain an in-depth understanding of the cell cycle entry dynamics. </p> <p>In this dissertation, we have focused on the Myc-Rb-E2F signaling pathway and its associated pathways, dysregulation of which is associated with virtually all cancers. Our analyses of these signaling pathways provide insights into three questions in biology: 1) regulation of the restriction point (R-point) in cell cycle entry, 2) regulation of the temporal dynamics in cell cycle entry, and 3) post-translational regulation of Myc by its upstream signaling pathways. The well-studied pathways can serve as a foundation for perturbations and tight control of cell cycle entry dynamics, which may be useful in developing cancer therapeutics. </p> <p>We conclude by demonstrating how a combination of mathematical modeling and experimental validations provide mechanistic insights into the regulatory networks in cell cycle entry.</p> / Dissertation