Os gliomas compreendem mais de 70% de todos os tumores cerebrais primários. Mesmo com tratamento agressivo, a média de sobrevivência relatada para estes tumores é geralmente menor do que 1 ano após o diagnóstico. A quimioterapia baseada em agentes alquilantes, como a temozolomida (TMZ), tem mostrado, em média, uma modesta resposta e pequeno aumento da sobrevida. As principais lesões causadas pela TMZ são os aductos N7-metil-G e N3-metil-A, que são processados pelo reparo por excisão de base (BER), compreendendo mais de 80% das lesões induzidas no DNA pela TMZ. Há evidência de que a resistência a este quimioterápico pode ser causada em parte por um eficiente processo de reparo via BER, mas poucos estudos têm focalizado essa abordagem. Metoxiamina (MX) é um inibidor do reparo via BER que tem sido atualmente investigado como um possível aliado no combate a vários tipos de tumores, aumentando os efeitos citotóxicos de drogas, tais como a TMZ. No presente trabalho, foram avaliadas as respostas celulares de células de glioblastoma (GBM) ao tratamento com a TMZ, associada ou não à MX. Foram analisados parâmetros como citotoxicidade (24 h, Kit XTT), sobrevivência celular (120 h, Kit XTT) e clonogênica (10 dias após o tratamento), danos no DNA pelo Ensaio Cometa (2, 6, 12 e 24 h), a indução de apoptose (24, 48 e 72 h) e alterações na expressão gênica e transcricional (24, 48 e 72h) de genes envolvidos na via de reparo por BER. Sob tratamento das linhagens de GBM (U87, U343, U251, U138 e T98G) a diferentes concentrações de TMZ (100 a 1000 M), o efeito citotóxico foi observado em células analisadas após 120 h, sendo que a linhagem T98G foi a mais resistente ao tratamento com TMZ e foi a única a apresentar diferenças significativas entre o tratamento sozinho e combinado (p 0,05). Assim, foi selecionada a linhagem T98G para os demais experimentos e estudar as possíveis vias implicadas na resistência a essa droga. A sobrevivência clonogênica das células T98G foi reduzida, sob tratamento com a TMZ (100 a 800 M), com diferença significativas para as concentrações superiores a 400 M. Observou-se que o efeito da TMZ foi acentuado quando associada ao inibidor, com diferenças significativas para todas as concentrações testadas. A droga induziu uma maior porcentagem de danos no DNA (Ensaio Cometa) para ambos os tratamentos (400 e 600 M) e nos tempos de 2 e 6 h, com diferenças significativas entre os tratamentos (TMZ e TMZ+MX), somente na concentração de 600 M/2 h. Entretanto esses danos se equipararam nos tempos seguintes. A indução de apoptose analisada nas células T98G mostrou a freqüência máxima de 24,2% no tempo de 72h, na concentração de 600 M de TMZ, enquanto que uma maior indução de apoptose (47,7%) foi observada para a mesma concentração no tratamento combinado (TMZ + MX), resultando em diferenças significativas. A análise de expressão gênica realizada para os genes APE1, FEN1 e XRCC1, mostraram que houve uma menor indução dos genes APE1 e FEN1 no tratamento combinado. A expressão da proteína APE1 (analisada por Western blot) foi menos intensa em todos os tempos de tratamento combinado (TMZ + MX), possivelmente pelo bloqueio dos sítios AP causado pelo inibidor MX. A proteína FEN1 mostrou-se menos expressa na comparação dos tratamentos, nos tempos de 48 e 72 h, indicando uma inibição de proteínas da via BER downstream à remoção de sítios AP por APE1, possivelmente pela ligação de MX. PCNA teve sua expressão protéica aumentada no tratamento combinado, nos tempos de 24 h, e principalmente em 48 h, sugerindo uma indução devida a um aumento de danos no DNA. Portanto, os resultados dos ensaios realizados com a associação da TMZ à MX demonstraram a influência do tratamento combinado sobre a expressão de proteínas envolvidas no reparo via BER, o que contribuiu para uma redução da capacidade proliferativa das células T98G em decorrência da maior indução de danos por aductos DNA-MX não reparados, resultando também em aumento de morte celular apoptótica. Esses dados mostram que a modulação do reparo via BER pode constituir uma estratégia promissora para aumentar a eficácia do tratamento com a TMZ, o que poderá futuramente embasar a escolha de procedimentos terapêuticos que resultem numa maior eficácia do tratamento de gliomas com agentes alquilantes. / Gliomas represent more than 70% of primary brain tumors. Even following an aggressive therapies, the mean survival rate of patients with these tumors is less than one year after diagnosis. Chemotherapy based on alkyklating agents, such as temozolomide (TMZ) has been reported to increase the survival rate. N7-metyl-G and N3-metyl-A adducts comprise more than 80% of the DNA lesions induced by TMZ and are processed by the base excision repair process (BER). There is evidence in the literature suggesting that the resistance to TMZ could be caused, in part, by an efficient repair by BER pathway, although few studies have focused on this subject. Metoxiamine (MX) is an effective BER inhibitor, which has been investigated as a conceivable treatment for different kinds of tumor, due to its synergistic effect with antitumoral drugs, such as TMZ. In the present study, the cellular responses to TMZ treatment associated or not with MX were evaluated in giloblastoma (GBM) cell lines. Several parameters were analyzed, such as cytotoxicity (24 h), cellular survival (120 h) and clonogenic efficiency (10 days after treatment), DNA damage and repair kinetics (after 2, 6, 12 and 24 h of recovery time), apoptosis induction (24, 48 and 72 h) and alterations in gene expression (24, 48 e 72h) for genes playing role in BER pathway. The treatment with TMZ 100 -1000 M (during 24 h) was cytotoxic for all GBM cell lines tested (U87, U343, U251, U138 and T98G), as analyzed after 120 h, with the T98G cell line being be the most resistant to TMZ; besides, T98G was the only one to present significant differences (p 0,05) in survival rates measured between TMZ treatment and TMZ combined with MX. Thus, T98G cells were selected for the subsequent experiments and for the study of the pathways implicated in TMZ resistance. The clonogenic efficiency of T98G cells was reduced under TMZ treatment (100 - 800 M) with significant differences for treatments above 400 M. In addition, the combined treatment TMZ plus MX significantly increased the cytotoxic effects, even for the lowest concentration. The comet assay showed higher percentage of DNA damage for both treatment modalities (TMZ and TMZ+MX) at 2 and 6 h of recovery, with significant differences between treatments for 2 h. Following 12 and 24 h of recovery, the amount of DNA damage reached the control levels, indicating the repair of DNA breaks. Apoptosis induction in T98G cells showed the highest frequency (24.2%) at 72h for 600 M TMZ, while the highest apoptosis induction (47.7%) was observed for the same concentration combined to MX. Quantitative gene expression analysis performed for three genes, APE1, FEN1 and XRCC1, showed a reduced expression of APE1 and FEN1 for the combined treatment. Western blot analysis demonstrated that APE1 was less expressed for all kind of treatments, probably due to AP-sites blockade caused by the inhibitor MX. In addition, FEN1 showed low levels of expression at 48h and 72h, indicating the inhibition of BER pathway downstream to the AP removal by APE1. On the other hand, PCNA expression was higher for the combined treatment (24h and mainly 48h), suggesting its induction probably due to increased DNA damage. Therefore, the present results demonstrated that the association of TMZ with MX interfered with the expression of proteins involved in BER, thus, reducing the clonogenic efficiency of T98G cells, probably as a consequence of the high production of unrepaired DNA-MX adducts, leading to cell death, including apoptosis. These data show that the modulation of BER is a promising strategy for magnifying the therapeutic impact of TMZ, and in the next future, this strategy may embrace the option to establish novel and efficient therapy protocols for the treatment of gliomas with alkylating agents.

International Telemetering Conference Proceedings / October 25-28, 1999 / Riviera Hotel and Convention Center, Las Vegas, Nevada / Three different demodulators applicable to the coherent demodulation of binary Gaussian Minimum Shift Keying (GMSK) signal are described and their performance compared. These include a near-optimal trellis demodulator, which utilizes two matched filters and Viterbi algorithm to carry out maximum likelihood sequence estimation, and a singlefilter threshold demodulator with and without pulse equalization. The performance of these demodulators in noise and adjacent channel interference (ACI) are compared for several signal BT products. The equalized threshold demodulator is shown to perform nearly as well as the near-optimal trellis demodulator in additive white Gaussian noise (AWGN), and substantially outperform the trellis demodulator under severe ACI condition.

International Telemetering Conference Proceedings / October 25-28, 1999 / Riviera Hotel and Convention Center, Las Vegas, Nevada / The design, implementation, and performance of a digital modem employing Gaussian minimum shift keying (GMSK) is described. The GMSK modem is implemented in field programmable gate array (FPGA) chips, and a laboratory test setup was developed to validate its performance for a signal BT value of 1/5. The measured spectrum of the GMSK modem and its bit error rate (BER) performance, which are found in very close agreement with those of theory and simulation, are presented in this paper.

International Telemetering Conference Proceedings / October 26-29, 1998 / Town & Country Resort Hotel and Convention Center, San Diego, California / In computer simulations of communication systems, linear congruential generators and shift registers are typically used to model noise and data sources. These generators are often assumed to be close to ideal (i.e. delta correlated), and an insignificant source of error in the simulation results. The samples generated by these algorithms have non-ideal autocorrelation functions, which may cause a non-uniform distribution in the data or noise signals. This error may cause the simulation bit-error-rate (BER) to be artificially high or low. In this paper, the problem is described through the use of confidence intervals. Tests are performed on several pseudo-random generators to access which ones are acceptable for computer simulation.

International Telemetering Conference Proceedings / October 26-29, 1987 / Town and Country Hotel, San Diego, California / The three axis stabilized Indian Remote Sensing Satellite will image the earth from a 904 Km polar - sun synchronous orbit. The payload is a set of CCD cameras which collect data in four bands visible and near infra-red region. This payload data from two cameras, each at 10.4 megabits per sec is transmitted in a balanced QPSK in X Band. The payload data before transmission is formatted by adopting Major and Minor frame synchronizing codes. The formatted two streams of data are differentially encoded to take care of 4-phase ambiguity due to QPSK transmission. This paper describes the design and development aspects related to such a Data Handling System. It also highlights the environmental qualification tests that were carried out to meet the requirement of three years operational life of the satellite.

International Telemetering Conference Proceedings / October 23-26, 2000 / Town & Country Hotel and Conference Center, San Diego, California / The interoperability of Feher-patented Quadrature Phase Shift Keying (FQPSK) systems with future and legacy data links is discussed in this paper. In particular, the benefits of “forward” interoperability with 3G (3rd Generation) wireless systems such as WCDMA (Wideband Code Division Multiple Access) up to 40 Mchips/sec are highlighted. Other proposals of forward interoperability with future data links include an enhanced, ultra-bandwidth efficient FQPSK and 16-state FQAM (Feher’s Quadrature Amplitude Modulation) architectures. In addition, since FQPSK based systems have been proven in “dual use” systems and extensively tested and evaluated by the Department of Defense (DoD) and NASA, the analysis of “backward” interoperability with legacy data links such as GSM is also included in this paper.

No description available.

Clustered damage to DNA is a signature mark of radiation-induced damage, which involves damage to the nucleobases and/or DNA backbone. Double-strand breaks created by damaging agents are detrimental to cell survival leading to chromosomal translocations. Normal cells employ Non-homologous end-joining because of its faster kinetics, to suppress chromosomal translocations. However, the presence of complex DNA ends constitutes a significant challenge to NHEJ. Location of Thymine glycol (Tg) at DSB ends was a potential hindrance to end joining. The substrate with Tg at the third position (Tg3) from the DSB joined better than when present at the fifth position (Tg5). However, hNTH1 assay showed Tg5 to be a better substrate than Tg3 for BER, potentially explaining the increased Tg removal and decreased end joining of Tg5 in extracts. Nonetheless, there appeared to be no preference in the susceptibility of 5’-Tg substrates with Tg at the second and third positions from DSB ends. Polynucleotide kinase phosphatase is crucial in restoring the 3′ hydroxyl, and 5′ phosphate ends at strand breaks. No other enzyme is known to possess PNKP’s activity in mammalian cells at DSBs. Experiments done with PNKP knockout cells have shown some activity similar to PNKP, which appeared to be a part of NHEJ and was not pharmacologically inhibited by PNKP inhibitor. Additionally, core NHEJ factors XRCC4 and XLF influenced the activities of PNKP. Overall, these experiments suggest that Tg repair is dependent on the position from DSB and an alternative enzyme processes 3′- PO, and 5′-OH ends.

Wireless sensor network, which is constitute of autonomous sensors, is used for monitoring physical or environmental conditions like temperature, sound, pressure, and so on. The dispersed sensors or nodes will respectively pass their data through the network to the main location. Currently, several standards are ratified or in developing for wireless sensor network, like Wireless Hart, ISA, 100.11a, WIA-PAA, IEEE 802.15.4, etc. Among the standards, Zigbee is often used in industrial applications that require short-range and low-rate wireless transfer. In the research, all the data is collected under industrial environment using IEEE 802.15.4 compliant physical layer, some packets are interfered only by multi-path fading while others are also interfered by Wi-Fi interference. The goal of the thesis is to find out the dependence between the received power (RSS), correlation value (CORR) and bit error rate (BER) of the received message, and their distribution in situations both when the packet is lost or not. Besides, the performance of bit error rate such as the distribution and the features of burst error length under Wi-Fi interference or not will also be tested. All of them are based on a precise statistical processing.

Αξιοσημείωτη επίδραση στην εξέλιξη και ανάπτυξη των επικοινωνιακών συστημάτων έχει παρουσιάσει το όριο χωρητικότητας διαύλου, το οποίο εισήγαγε ο Claude Shannon. Σήμερα γνωρίζουμε αρκετούς κώδικες διόρθωσης σφαλμάτων οι οποίοι προσεγγίζουν αρκετά τη μέγιστη χωρητικότητα του διαύλου. Ανάμεσα σε αυτούς, εξέχουσα θέση κατέχουν οι Turbo και οι LDPC κώδικες, οι οποίοι ανήκουν στην κατηγορία των κωδίκων τύπου-Turbo. Στην παρούσα διπλωματική εργασία γίνεται ανάλυση της λειτουργίας και της επίδοσης των LDPC κωδίκων σε AWGN δίαυλο. Συγκεκριμένα, υπολογίζεται ο ρυθμός σφάλματος ψηφίου (BER) ενός σήματος που μεταδίδεται διαμέσου ενός AWGN διαύλου και τα αποτελέσματα που προκύπτουν συγκρίνονται με τα αντίστοιχα ενός σήματος που δεν έχει υποστεί κωδικοποίηση. Επίσης, μελετάται η απόδοση του κώδικα για διάφορες τιμές επαναλήψεων του αλγορίθμου αποκωδικοποίησης. / The channel capacity limit, which was determined by Claude Shannon, has caused a great impact on the evolution of communication systems. We know of error correction codes that closely approach this limit. Turbo codes and LDPC codes, which are a class of Turbo-like codes, are of great significance. The present thesis analyses the performance of LDPC codes in an AWGN channel. Particularly, it studies the bit error rate (BER) of a signal which is conveyed through an AWGN channel and compares the results with the ones of the corresponding uncoded signal. Furthermore, the thesis studies the performance of the code for a number of iterations of the decoding algorithm.