Genes envolvidos com a interação hospedeiro-patógeno são fortemente afetados pela seleção natural positiva. O gene codificante do antígeno sangüíneo Duffy, também conhecido como DARC (Duffy Antigen Receptor for Chemokines), tem um importante papel na invasão dos eritrócitos pelos parasitas causadores da malária, Plasmodium vivax em humanos e Plasmodium knowlesi em outros primatas. A estrutura do gene DARC já é conhecida, estando este presente na região 1q22q23 do cromossomo 1, e sendo composto por dois éxons separados por um grande íntron. Em uma população africana a deleção de um nucleotídeo no domínio GATA-1 da região promotora do gene é responsável pela não expressão de DARC nos eritrócitos e pela resistência à invasão pelo P. Vivax. Além disso, o antígeno DARC age como um receptor promíscuo de quimiocinas, sendo expresso nos eritrócitos, células endoteliais de vênulas e outros tecidos. Devido a esse papel dual, no presente estudo seqüenciou-se regiões homólogas do gene DARC em macacos do Novo e Velho Mundo e utilizando métodos estatísticos procurou-se indícios da seleção natural positiva na sua história evolutiva. Nenhuma nova mutação foi encontrada no promotor ou na região codificante. As árvores filogenéticas pelos métodos de máxima parcimônia, máxima verossimilhança e neighbor-join apresentaram topologias semelhantes com três grande clados monofiléticos reconhecíveis e com a espécie Macaca fascicularis apresentando um perfil polifilético. O teste de seleção positiva pelos métodos de Nei-Gojobori, máxima verossimilhança por ramos e máxima verossimilhança por sítios não demonstraram, estatisticamente, à ação da seleção positiva sobre o gene DARC. Porém, o teste de máxima verossimilhança por sítio em domínios demonstrou que existem regiões do gene DARC sujeitas à diferentes pressões seletivas, mas também falhou em detectar a assinatura da seleção positiva. Os resultados indicam a presença da seleção darwiniana sobre a região de ligação do P. vivax, porém os testes de máxima verossimilhança utilizados, aparentemente, não possuem poder suficiente para detectar a sua assinatura. Além disso, os resultados sugerem que a região de ligação do P. vivax está sob influência de duas pressões seletivas antagônicas (seleção positiva exercida pelo parasita e seleção purificadora exercida pelas quimiocinas) o que pode, também, explicar a não detecção da seleção positiva. / Genes involved in pathogen-host interactions are strongly affected by positive natural selection. The gene of blood Duffy antigen, also known as DARC (Duffy Antigen Receptor for Chemokines), has an important role in the invasion of red blood cells by the parasites that cause malaria, Plasmodium vivax in humans and Plasmodium knowlesi in other primates. The structure of the DARC gene is known, it was mapped in 1q22-q23 region of chromosome 1, and is composed by two exons separated by a large intron. In an African population a nucleic acid deletion in GATA-1 of the gene promoter is responsible for the non-expression of DARC on red blood cells and the resistance to invasion by P. vivax. Moreover, the DARC antigen acts as a promiscuous receptor for chemokines and is expressed in red blood cells, endothelial venules cells and other tissues. Because of this dual role, in this study we sequenced homologous regions of the DARC gene in monkeys of the New and Old World and using statistical methods we tried to detect positive natural selection in their evolutionary history. New mutations were not found at promoter or in coding region. The phylogenetic trees by the methods of maximum parsimony, maximum likelihood and neighbor-join showed similar topologies with three large monophyletic clades recognizable and with the Macaca fascicularis showing a poliphyletic profile. The test of positive selection by the methods of Nei-Gojobori, maximum likelihood by branchs and maximum likelihood by sites not shown, statistically, the action of positive selection on the DARC gene. But the maximum likelihood test using sites divided in domains showed that some regions of the DARC gene are subject to different selective pressures, but also failed to detect the signature of positive selection. The results indicate the presence of darwinian selection on P. vivax binding region, but the maximum likelihood tests used, apparently, do not have enough power to detect its signature. Moreover, the results suggest that P. vivax binding region is under the influence of two opposing selective pressures (positive selection exerted by the parasite and purifying selection exerced by chemokines) that can also explain the non-detection of positive selection.

Genes envolvidos com a interação hospedeiro-patógeno são fortemente afetados pela seleção natural positiva. O gene codificante do antígeno sangüíneo Duffy, também conhecido como DARC (Duffy Antigen Receptor for Chemokines), tem um importante papel na invasão dos eritrócitos pelos parasitas causadores da malária, Plasmodium vivax em humanos e Plasmodium knowlesi em outros primatas. A estrutura do gene DARC já é conhecida, estando este presente na região 1q22q23 do cromossomo 1, e sendo composto por dois éxons separados por um grande íntron. Em uma população africana a deleção de um nucleotídeo no domínio GATA-1 da região promotora do gene é responsável pela não expressão de DARC nos eritrócitos e pela resistência à invasão pelo P. Vivax. Além disso, o antígeno DARC age como um receptor promíscuo de quimiocinas, sendo expresso nos eritrócitos, células endoteliais de vênulas e outros tecidos. Devido a esse papel dual, no presente estudo seqüenciou-se regiões homólogas do gene DARC em macacos do Novo e Velho Mundo e utilizando métodos estatísticos procurou-se indícios da seleção natural positiva na sua história evolutiva. Nenhuma nova mutação foi encontrada no promotor ou na região codificante. As árvores filogenéticas pelos métodos de máxima parcimônia, máxima verossimilhança e neighbor-join apresentaram topologias semelhantes com três grande clados monofiléticos reconhecíveis e com a espécie Macaca fascicularis apresentando um perfil polifilético. O teste de seleção positiva pelos métodos de Nei-Gojobori, máxima verossimilhança por ramos e máxima verossimilhança por sítios não demonstraram, estatisticamente, à ação da seleção positiva sobre o gene DARC. Porém, o teste de máxima verossimilhança por sítio em domínios demonstrou que existem regiões do gene DARC sujeitas à diferentes pressões seletivas, mas também falhou em detectar a assinatura da seleção positiva. Os resultados indicam a presença da seleção darwiniana sobre a região de ligação do P. vivax, porém os testes de máxima verossimilhança utilizados, aparentemente, não possuem poder suficiente para detectar a sua assinatura. Além disso, os resultados sugerem que a região de ligação do P. vivax está sob influência de duas pressões seletivas antagônicas (seleção positiva exercida pelo parasita e seleção purificadora exercida pelas quimiocinas) o que pode, também, explicar a não detecção da seleção positiva. / Genes involved in pathogen-host interactions are strongly affected by positive natural selection. The gene of blood Duffy antigen, also known as DARC (Duffy Antigen Receptor for Chemokines), has an important role in the invasion of red blood cells by the parasites that cause malaria, Plasmodium vivax in humans and Plasmodium knowlesi in other primates. The structure of the DARC gene is known, it was mapped in 1q22-q23 region of chromosome 1, and is composed by two exons separated by a large intron. In an African population a nucleic acid deletion in GATA-1 of the gene promoter is responsible for the non-expression of DARC on red blood cells and the resistance to invasion by P. vivax. Moreover, the DARC antigen acts as a promiscuous receptor for chemokines and is expressed in red blood cells, endothelial venules cells and other tissues. Because of this dual role, in this study we sequenced homologous regions of the DARC gene in monkeys of the New and Old World and using statistical methods we tried to detect positive natural selection in their evolutionary history. New mutations were not found at promoter or in coding region. The phylogenetic trees by the methods of maximum parsimony, maximum likelihood and neighbor-join showed similar topologies with three large monophyletic clades recognizable and with the Macaca fascicularis showing a poliphyletic profile. The test of positive selection by the methods of Nei-Gojobori, maximum likelihood by branchs and maximum likelihood by sites not shown, statistically, the action of positive selection on the DARC gene. But the maximum likelihood test using sites divided in domains showed that some regions of the DARC gene are subject to different selective pressures, but also failed to detect the signature of positive selection. The results indicate the presence of darwinian selection on P. vivax binding region, but the maximum likelihood tests used, apparently, do not have enough power to detect its signature. Moreover, the results suggest that P. vivax binding region is under the influence of two opposing selective pressures (positive selection exerted by the parasite and purifying selection exerced by chemokines) that can also explain the non-detection of positive selection.

<p>DARC är ett sätt att sända digital information via FM-rundradionätet. Moduleringsmetoden för DARC är GMSK. Målsättningen var att jämföra kostnad/komplexitet och strömförbrukning för olika sätt att demodulera GMSK. Tre icke-koherenta demodulatorer och en koherent demodulator har jämförts. Man vill veta hur stor resursanvändningen var för olika FPGAer. De olika demodulatorerna har beskrivits med VHDL.</p>

DARC är ett sätt att sända digital information via FM-rundradionätet. Moduleringsmetoden för DARC är GMSK. Målsättningen var att jämföra kostnad/komplexitet och strömförbrukning för olika sätt att demodulera GMSK. Tre icke-koherenta demodulatorer och en koherent demodulator har jämförts. Man vill veta hur stor resursanvändningen var för olika FPGAer. De olika demodulatorerna har beskrivits med VHDL.

Rutiner skrivna i Verilog har utvecklats för avkodning av en frekvensmodulerad signal givet ett Analog Devices AD9874-chip. Olika metoder för I/Q-demodulation har utvärderats och av dessa har CORDIC valts och implementerats i Verilog. Koden har till viss del testats på en IGLOO nano-FPGA men framförallt simulerats och verifierats i ModelSim. / Routines written in Verilog have been developed to perform I/Q-demodulation of a frequency modulated signal given valuesfrom a Analog Devices AD9874 chip. Different methods for I/Q-demodulation have been evaluated and among theseCORDIC has been chosen and implemented in Verilog. The code has to some extent been tested on a IGLOO nano FPGA but foremost been simulated and verified in ModelSim.

Malaria is one of the oldest parasitic diseases known to man, and the disease has played a role in shaping civilizations and the success of human populations over many centuries. While the malaria is well studied, it still remains a worldwide killer--claiming about 600,000 lives annually with children under the age of five representing a disproportionate population of those lethally infected. Malaria is caused by the protozoan parasite Plasmodium, which is introduced to the human body through the bite of a female Anopheles mosquito. The most lethal form of the disease is carried by the parasite Plasmodium falciparum, while the most widespread form of malaria is caused by Plasmodium vivax, the latter of which has a specific mode of entry and life cycle that makes it difficult to eradicate. The entry of P. vivax into human reticulocytes is based on the presence of the Duffy antigen chemokine receptor (DARC), which is uniquely absent in two-thirds of the Black population and populations of immediate African descent making it rare in the African region while endemic in Western and Asian countries. Inability to culture the parasite P. vivax in vitro and exhaustible tissue samples makes an accurate model of P. vivax malaria difficult to maintain ex vivo. The current study focuses on overcoming those limitations by modeling the mode of entry of P. vivax into patient-specific, induced pluripotent stem cell (iPSC)-derived erythrocyte-lineage cells by showing firstly that DARC is a measurable marker of susceptibility in vitro via FACS analysis, and that secondly, P. vivax cell culture limitations can be bypassed by creating a lentivirus designed to specifically infect DARC-expressing cells. To demonstrate the potency of this system, we show that a virus expressing the conserved region of the Duffy binding ligand, Duffy binding protein II (DBPII), can selectively infect peripheral blood mononuclear cells (PBMCs) that express DARC. Moreover, our current study focuses on the development of an iPSC-based disease model using patient samples derived from DARC expressing patients (DARC+) and DARC negative Sickle Cell Disease (SCD) patients (DARC-). We show that DARC+ iPSC-derived erythroid lineage cells express a transient population of DARC-expressing cells via FACS analysis, and we explore different protocols to stabilize this unique population. We hypothesize that DARC is a stage-specific marker for erythrocyte maturation, and we believe that any subset of cells expressing DARC consists of more mature erythrocyte-lineage cells. This study then, provides a novel platform by which to study malaria infection in a patient-specific manner while bypassing the limitations of culturing P. vivax in an in vitro culture system, as well as introducing a new way to measure erythrocyte maturation. Successful establishment of such a disease model has great implications for in-depth drug screenings for novel therapeutics that target the blood stage of the parasitic disease that were previously difficult to validate due to the limitations of currently existing models.

<p>The Swedish National Testing and Research Institute is maintaining the Swedish realization of the world time scale UTC, called UTC(SP). One area of research and development for The Swedish National Laboratory of Time and Frequency is time synchronization and how UTC(SP) can be distributed in Sweden. Dissemination of time information by SP is in Sweden mainly performed via Internet using the Network Time Protocol (NTP) as well as via a modem dial up service and a speaking clock (Fröken Ur). In addition to these services, time information from the Global Positioning System (GPS) and from the long-wave transmitter DCF77 in Germany, is also available in Sweden. </p><p>This master’s thesis considers how different available commercial communication systems could be used for multicast time distribution. DECT, Bluetooth, Mobile Telecommunication and Radio Broadcasting are different techniques that are investigated. One application of Radio Broadcasting, DARC, was found to be interesting for a more detailed study. A theoretical description of how DARC could be used for national time distribution is accomplished and a practical implementation of a test system is developed to evaluate the possibilities to use DARC for multicast time distribution. </p><p>The tests of DARC and the radio broadcast system showed that these could be interesting techniques to distribute time with an accuracy of a couple of milliseconds. This quality level is not obtained today but would be possible with some alterations of the system.</p>

<p>DARC is a technique for data broadcasting over the FM radio network. Sectra Wireless Technologies AB has developed a handheld DARC receiver known as the Sectra CitySurfer. The CitySurfer is equipped with a high-resolution display along with buttons and a joystick that allows the user to view and navigate through various types of information received over DARC. </p><p>Sectra Wireless Technologies AB has, among other services, also developed a paging system that enables personal message transmission over DARC. The background of this thesis is a wish to be able to send fax documents using the paging system and to be able to view received fax documents in the CitySurfer. </p><p>The presented solution is a central PC-based fax server. The fax server is responsible for receiving standard fax transmissions and converting the fax documents before redirecting them to the right receiver in the DARC network. The topics discussed in this thesis are fax document routing, fax document conversion and fax server system design.</p>

The Swedish National Testing and Research Institute is maintaining the Swedish realization of the world time scale UTC, called UTC(SP). One area of research and development for The Swedish National Laboratory of Time and Frequency is time synchronization and how UTC(SP) can be distributed in Sweden. Dissemination of time information by SP is in Sweden mainly performed via Internet using the Network Time Protocol (NTP) as well as via a modem dial up service and a speaking clock (Fröken Ur). In addition to these services, time information from the Global Positioning System (GPS) and from the long-wave transmitter DCF77 in Germany, is also available in Sweden. This master’s thesis considers how different available commercial communication systems could be used for multicast time distribution. DECT, Bluetooth, Mobile Telecommunication and Radio Broadcasting are different techniques that are investigated. One application of Radio Broadcasting, DARC, was found to be interesting for a more detailed study. A theoretical description of how DARC could be used for national time distribution is accomplished and a practical implementation of a test system is developed to evaluate the possibilities to use DARC for multicast time distribution. The tests of DARC and the radio broadcast system showed that these could be interesting techniques to distribute time with an accuracy of a couple of milliseconds. This quality level is not obtained today but would be possible with some alterations of the system.

DARC is a technique for data broadcasting over the FM radio network. Sectra Wireless Technologies AB has developed a handheld DARC receiver known as the Sectra CitySurfer. The CitySurfer is equipped with a high-resolution display along with buttons and a joystick that allows the user to view and navigate through various types of information received over DARC. Sectra Wireless Technologies AB has, among other services, also developed a paging system that enables personal message transmission over DARC. The background of this thesis is a wish to be able to send fax documents using the paging system and to be able to view received fax documents in the CitySurfer. The presented solution is a central PC-based fax server. The fax server is responsible for receiving standard fax transmissions and converting the fax documents before redirecting them to the right receiver in the DARC network. The topics discussed in this thesis are fax document routing, fax document conversion and fax server system design.