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During the race towards the4th generation (4G) cellular-based digital communication systems, a growth in the demand for high capacity, multi-media capable, improved Quality-of-Service (QoS) mobile communication systems have caused the developing mobile communications world to turn towards betterMultiple Access (MA) techniques, like Code Division Multiple Access (CDMA) [5]. The demand for higher throughput and better QoS in future 4G systems have also given rise to a scheme that is becoming ever more popular for use in these so-called ‘bandwidth-on-demand’ systems. This scheme is known as adaptive channel coding, and gives a system the ability to firstly sense changes in conditions, and secondly, to adapt to these changes, exploiting the fact that under good channel conditions, a very simple or even no channel coding scheme can be used for Forward Error Correction(FEC). This will ultimately result in better system throughput utilization. One such scheme, known as incremental redundancy, is already implemented in the Enhanced Data Rates for GSM Evolution (EDGE) standard. This study presents an extensive simulation study of a Multi-User (MU), adaptive channel coded Direct Sequence Spread Spectrum Multiple Access (DS/SSMA) communication system. This study firstly presents and utilizes a complex Base Band(BB) DS/SSMA transmitter model, aimed at user data diversity [6] in order to realize the MU input data to the system. This transmitter employs sophisticated double-sideband (DSB)Constant-Envelope Linearly Interpolated Root-of-Unity (CE-LI-RU) filtered General Chirp-Like (GCL) sequences [34, 37, 38] to band limit and spread user data. It then utilizes a fully user-definable, complex Multipath Fading Channel Simulator(MFCS), first presented by Staphorst [3], which is capable of reproducing all of the physical attributes of realistic mobile fading channels. Next, this study presents a matching DS/SSMA receiver structure that aims to optimally recover user data from the channel, ensuring the achievement of data diversity. In order to provide the basic channel coding functionality needed by the system of this study, three simple, but well-known channel coding schemes are investigated and employed. These are: binary Hamming (7,4,3) block code, (15,7,5) binary Bose-Chadhuri-Hocquenghem (BCH) block code and a rate 1/3 <i.Non-Systematic (NS) binary convolutional code [6]. The first step towards the realization of any adaptive channel coded system is the ability to measure channel conditions as fast as possible, without the loss of accuracy or inclusion of known data. In 1965, Gooding presented a paper in which he described a technique that measures communication conditions at the receiving end of a system through a device called a Performance Monitoring Unit (PMU) [12, 13]. This device accelerates the system’sBit Error Rate (BER) to a so-called Pseudo Error Rate(PER) through a process known as threshold modification. It then uses a simple PER extrapolation algorithm to estimate the system’s true BER with moderate accuracy and without the need for known data. This study extends the work of Gooding by applying his technique to the DS/SSMA system that utilizes a generic Soft-Output Viterbi Algorithm(SOVA) decoder [39] structure for the trellis decoding of the binary linear block codes [3, 41-50], as well as binary convolutional codes mentioned, over realistic MU frequency selective channel conditions. This application will grant the system the ability to sense changes in communication conditions through real-time BER measurement and, ultimately, to adapt to these changes by switching to different channel codes. Because no previous literature exists on this application, this work is considered novel. Extensive simulation results also investigate the linearity of the PER vs. modified threshold relationship for uncoded, as well as all coded cases. These simulations are all done for single, as well as multiple user systems. This study also provides extensive simulation results that investigate the calculation accuracy and speed advantages that Gooding’s technique possesses over that of the classic Monte-Carlo technique for BER estimation. These simulations also consider uncoded and coded cases, as well as single and multiple users. Finally, this study investigates the experimental real-time performance of the fully functional MU, adaptive coded, DS/SSMA communication system over varying channel conditions. During this part of the study, the channel conditions are varied over time, and the system’s adaptation (channel code switching) performance is observed through a real-time observation of the system’s estimated BER. This study also extends into cases with multiple system users. Since the adaptive coded system of this study does not require known data sequences (training sequences), inclusion of Gooding’s technique for real-time BER estimation through threshold modification and PER extrapolation in future 4G adaptive systems will enable better Quality-of-Service (QoS) management without sacrificing throughput. Furthermore, this study proves that when Gooding’s technique is applied to a coded system with a soft-output, it can be an effective technique for QoS monitoring, and should be considered in 4G systems of the future. / Dissertation (MEng (Computer Engineering))--University of Pretoria, 2007. / Electrical, Electronic and Computer Engineering / MEng / unrestricted

This diploma thesis deals with design and realization of a module for a digital signal procesor, for handheld RFID reader working in UHF band. It utilises a special chip EM4298 for RFID signals processing. Module is controlled by the microcontroller ATmega32L, which communicates with the PC through USB bus. Settings in EM4298 is made by a service program which processes received identifying data obtained from tags. Source codes for microcontroller are created in AVR Studio 4.13 program. Source codes for microcontroller are created in C++ Builder 6.0 program. Further thing is Desing and realization of analog interface and a UHF transceiver for wireless communication with tags. A Webench program was used for the analog interface design, which is freely available on the internet. For verification of parameters of the analog interface it was used PSpice 10.0 program. The UHF transceiver is build-up with a MAX2903 chip (transmitter) and AD8347 (receiver) and transmitting and receiving antennae.

Prostate cancer is one of the most frequently diagnosed cancers and failure to manage localized disease contributes to the majority of deaths. Radiation therapy (RT) is a common treatment for localized prostate cancer and uses ionizing radiation (IR) to damage DNA. Although RT is potentially curative, tumors often recur and progress to terminal disease. The cellular response to RT is multidimensional. For example, cells respond to a single dose of IR by activating the DNA damage response (DDR) to repair the DNA. Targeting proteins involved in the DDR is an effective clinical strategy to sensitize cancer cells to RT. However, multiple radiation treatments, as in fractionated ionizing radiation (FIR), can promote neuroendocrine differentiation (NED). FIR-induced NED is an emerging resistance mechanism to RT and tumors that undergo NED are highly aggressive and remain incurable.<br><br> Currently, the only clinical approach that improves RT for prostate cancer treatment is androgen deprivation therapy (ADT). ADT blocks androgen receptor (AR) signaling which inhibits the repair of DNA damage. In 2017, my lab reported that targeting Protein arginine methyltransferase 5 (PRMT5) blocks AR protein expression. Therefore, targeting PRMT5 may also sensitize prostate cancer cells to RT via a novel mechanism of action.<br><br> This dissertation focuses on the role of PRMT5 in the cellular response to IR and the goal of my work is to validate PRMT5 as a therapeutic target to enhance RT for prostate cancer treatment. I demonstrate that PRMT5 has several roles in the cellular response to IR. Upon a single dose of IR, PRMT5 cooperates with pICln to function as a master epigenetic activator of DDR genes and efficiently repair IR-induced DNA damage. There is an assumption in the field that the methyltransferase activity and epigenetic function of PRMT5 is dependent on the cofactor MEP50. I demonstrate that PRMT5 can function independently of MEP50 and identify pICln as a novel epigenetic cofactor of PRMT5. During FIR, PRMT5, along with both cofactors MEP50 and pICln, are essential for initiation of NED, maintenance of NED, and cell survival. Targeting PRMT5 also sensitizes prostate cancer xenograft tumors in mice to RT, significantly reduces and delays tumor recurrence, and prolongs overall survival. Incredibly, while 100% of control mice died due to tumor burden, targeting PRMT5 effectively cured ~85% of mice from their xenograft tumor. Overall, this work provides strong evidence for PRMT5 as a therapeutic target and suggests that targeting PRMT5 during RT should be assessed clinically.<br>

Les microtubules sont de longs polymères cylindriques de la protéine α, β tubuline, utilisés dans les cellules pour construire le cytosquelette, le fuseau mitotique et les axonèmes. Ces polymères creux sont cruciaux pour de nombreuses fonctions cellulaires, y compris le transport intracellulaire et la ségrégation chromosomique pendant la division cellulaire. Au fur et à mesure que les cellules se développent, se divisent et se différencient, les microtubules passent par un processus, appelé instabilité dynamique, ce qui signifie qu’ils basculent constamment entre les états de croissance et de rétrécissement. Cette caractéristique conservée et fondamentale des microtubules est étroitement régulée par des familles de protéines associées aux microtubules. Les protéines de kinésine-13 sont une famille de facteurs régulateurs de microtubules qui dépolymérisent catalytiquement les extrémités des microtubules. Cette thèse traite d’abord des concepts mécanistiques sur le cycle catalytique de la kinésine-13. Afin de mieux comprendre le mécanisme moléculaire par lequel les protéines de kinésine-13 induisent la dépolymérisation des microtubules, nous rapportons la structure cristalline d’un monomère de kinésine-13 catalytiquement actif (Kif2A) en complexe avec deux hétérodimères αβ-tubuline courbés dans un réseau tête-à-queue. Nous démontrons également l’importance du « cou » spécifique à la classe de kinésine-13 dans la dépolymérisation catalytique des microtubules. Ensuite, nous avons cherché à fournir la base moléculaire de l’hydrolyse tubuline-guanosine triphosphate (GTP) et son rôle dans la dynamique des microtubules. Dans le modèle que nous présentons ici, l’hydrolyse tubuline-GTP pourrait être déclenchée par les changements conformationnels induits par les protéines kinésine-13 ou par l’agent chimique stabilisant paclitaxel. Nous fournissons également des preuves biochimiques montrant que les changements conformationnels des dimères de tubuline précèdent le renouvellement de la tubuline-GTP, ce qui indique que ce processus est déclenché mécaniquement. Ensuite, nous avons identifié la kinésine de microtubule Kif2C comme une protéine associée à des modèles d’ADN imitant la rupture double brin (DSB) et à d’autres protéines de réparation DSB connues dans les extraits d’œufs de Xenope et les cellules de mammifères. Les cassures double brin d’ADN (DSB) sont un type majeur de lésions d’ADN ayant les effets les plus cytotoxiques. En raison de leurs graves impacts sur la survie cellulaire et la stabilité génomique, les DSB d’ADN sont liés à de nombreuses maladies humaines, y compris le cancer. Nous avons constaté que les activités PARP et ATM étaient toutes deux nécessaires pour le recrutement de Kif2C sur les sites de réparation de l’ADN. Kif2C knockout ou inhibition de son activité de dépolymérisation des microtubules a conduit à l’hypersensibilité des dommages à l’ADN et à une réduction de la réparation du DSB via la jonction terminale non homologue et la recombinaison homologue. Dans l’ensemble, notre modèle suggère que les protéines de kinésine-13 peuvent interagir avec les dimères de tubuline aux extrémités microtubules et modifier leurs conformations, moduler l’étendue des extrêmités tubuline-GTP dans les cellules et déclencher le désassemblage des microtubules. Ces deux modèles pourraient être des clés pour démêler les mécanismes impliqués dans le nouveau rôle de Kif2C dans la réparation de l’ADN DSB sans s’associer à des polymères de microtubules. / Microtubules are long, cylindrical polymers of the proteins α, β tubulin, used in cells to construct the cytoskeleton, the mitotic spindle and axonemes. These hollow polymers are crucial for many cellular functions including intracellular transport and chromosome segregation during cell division. As cells grow, divide, and differentiate, microtubules go through a process, called dynamic instability, which means they constantly switch between growth and shrinkage states. This conserved and fundamental feature of microtubules is tightly regulated by families of microtubule-associated proteins (MAPs). Kinesin-13 proteins are a family of microtubule regulatory factors that catalytically depolymerize microtubule ends. This thesis first discusses mechanistic insights into the catalytic cycle of kinesin-13. In order to better understand the molecular mechanism by which kinesin-13 proteins induce microtubule depolymerization, we report the crystal structure of a catalytically active kinesin-13 monomer (Kif2A) in complex with two bent αβ-tubulin heterodimers in a head-to-tail array. We also demonstrate the importance of the kinesin-13 class-specific “neck” in modulating Adenosine triphosphate (ATP) turnover and catalytic depolymerization of microtubules. Then, we aimed to provide the molecular basis for tubulin-Guanosine triphosphate (GTP) hydrolysis and its role in microtubule dynamics. Although it has been known for decades that tubulin-GTP turnover is linked to microtubule dynamics, its precise role in the process and how it is driven are now well understood. In the model we are presenting here, tubulin-GTP hydrolysis could be triggered via the conformational changes induced by kinesin-13 proteins or by the stabilizing chemical agent paclitaxel. We also provide biochemical evidence showing that conformational changes of tubulin dimers precedes the tubulin-GTP turnover, which indicates that this process is triggered mechanically. Next, we identified microtubule kinesin Kif2C as a protein associated with double strand break (DSB)-mimicking DNA templates and other known DSB repair proteins in Xenopus egg extracts and mammalian cells. DNA double strand breaks (DSBs) are a major type of DNA lesions with the most cytotoxic effects. Due to their sever impacts on cell survival and genomic stability, DNA DSBs are related to many human diseases including cancer. Here we found that PARP and ATM activities were both required for the recruitment of Kif2C to DNA repair sites. Kif2C knockdown/knockout or inhibition of its microtubule depolymerizing activity led to accumulation of endogenous DNA damage, DNA damage hypersensitivity, and reduced DSB repair via both non-homologous end-joining (NHEJ) and homologous recombination (HR). Interestingly, genetic depletion of KIF2C, or inhibition of its microtubule depolymerase activity, reduced the mobility of DSBs, impaired the formation of DNA damage foci, and decreased the occurrence of foci fusion and resolution. Altogether, our findings shed light on the mechanisms involved in kinesin-13 catalyzed microtubule depolymerization. Our tubulin-GTP hydrolysis model suggests that kinesin-13 proteins may interact with tubulin dimers at microtubules ends and alter their conformations, modulate the extent of the GTP caps in cells and trigger microtubule disassembly. These two models could be keys to unravel the mechanisms involved in the novel role of Kif2C in DNA DSB repair without associating with microtubule polymers.