El desarrollo y la progresión de los cánceres de mama, y especialmente de aquellos que son hormono-dependientes están ampliamente influenciados y determinados por los receptores de estrógenos y progesterona (ER y PR respectivamente). Aproximadamente un 70% de todos los cánceres mamarios son ER+ y más de la mitad también son PR+. Está aceptado ampliamente que el estado del ER es un importante factor predictivo de buena respuesta a las terapias endocrinas (TEs), sin embargo la positividad del ER no es una garantía de la sensibilidad al tratamiento ya que algunos tumores ER+ no presentan una buena respuesta. Las observaciones clínicas indican que los tumores ER+PR- presentan una pobre respuesta a la TE y un fenotipo más agresivo que los ER+PR+. El objetivo de este estudio es identificar diferencias genéticas entre los subtipos de tumores ER+PR+ y ER+PR-. La técnica de CGH-array fue aplicada a 25 tumores ER+PR+ y 23 tumores ER+PR-. Los genes de interés obtenidos a partir del análisis de los resultados de dicha técnica fueron analizados por la técnica de hibridación in situ fluorescente (FISH) en una serie de validación formada por 50 tumores ER+PR+ y 50 tumores ER+PR- localizados en varios arrays de tejidos (TMAs). Como resultado se observó que los tumores ER+PR- tienen un ligero pero diferente perfil genético respecto a los tumores ER+PR+. Los tumores ER+PR- presentaban un mayor perfil genómico aberrante, con los cromosomas 17 y 20 como los más diferentemente alterados con ganancias solapadas, y los cromosomas 3, 8, 9, 14, 17, 21 y 22 como los más diferentemente alterados con pérdidas solapadas respecto al grupo ER+PR+. Las regiones ganadas solapadas 17q23.2-q23.3 y 20q13.12, y las regiones perdidas solapadas 3p21.32-p12.3, 9pter-p13.2, 17pter-p12 y 21tel-q21.1 estaban alteradas de forma estadísticamente significativa en los tumores ER+PR-. Las regiones de pérdida incluyen genes (RASSF1A, FHIT, CDKN2A, TP53 y BTG3) con funciones supresoras de tumores y están involucrados en apoptosis, mitosis, angiogénesis y dispersión celular. Mientras que las regiones de ganancia incluyen genes (MAP3K3, RPS6KB1 y ZNF217) involucrados en el control del ciclo celular, angiogénesis, resistencia a la apoptosis, metástasis y dispersión celular y en la activación de las vías de señalización de la PI3K/Akt/mTOR. Todas estas alteraciones podrían contribuir, al menos en algunos casos, a explicar la mayor inestabilidad genómica, la pérdida de la expresión del PR, el fenotipo más agresivo y la mayor resistencia a las ETs, todo ello tradicionalmente observado en los tumores ER+PR-. / Development and progression of all types of breast cancer, and especially the hormone-dependent ones are widely influenced and determined by estrogen and progesterone receptors (ER and PR, respectively). Approximately 70% of all breast cancers are ER+ and more than half of them are also PR+. It is widely accepted that ER status is a strong predictive factor of good response to endocrine therapy (ET), but ER positivity is not a guarantee of sensitivity to the treatment and some tumors fail to respond. Clinical observations indicate that ER+PR- breast cancers present a poorer response to ET and more aggressive phenotype than ER+PR+ ones. The aim of this study was to identify genetic differences between ER+PR+ and ER+PR- subgroups. An array CGH technique was applied to 25 ER+PR+ breast tumors and 23 ER+PR- ones. Genes of interest were analyzed by Fluorescence in situ hybridization (FISH) in a validation series composed by 50 ER+PR+ tumors and 50 ER+PR- ones on TMAs. As a result, it was observed that ER+PR- breast tumors have a smaller but different genetic profile. ER+PR- group presented a higher genomic aberrant profile with chromosomes 17 and 20 as the most differently altered with overlapped gains, and chromosomes 3, 8, 9, 14, 17, 21 and 22 as the most differently altered with overlapped losses respect to ER+PR+ group. The overlapped gained regions 17q23.2-q23.3 and 20q13.12, and the overlapped lost regions 3p21.32-p12.3, 9pter-p13.2, 17pter-p12 and 21tel-q21.1 were found in a significant way in ER+PR- breast tumors. Significant lost regions included genes (RASSF1A, FHIT, CDKN2A, TP53 and BTG3) with tumor suppressor functions and involved in apoptosis, mitosis, angiogenesis and cell spreading. Significant gained regions included genes (MAP3K3, RPS6KB1 and ZNF217) involved in cell cycle control, angiogenesis, resistance to apoptosis, metastasis and cellular spread, and activation of PI3K/Akt/mTOR pathways. All these alterations could contribute, at least in some cases, to explain the higher genomic instability, loss of PR expression, more aggressive phenotype and higher resistance to ETs, traditionally observed in ER+/PR- tumors.

Future radars require more flexible and faster radar signal processing chain than commercial radars of today. This means that the demands on the processors in a radar signal system, and the desire to be able to compute larger amount of data in lesser time, is constantly increasing. This thesis focuses on commercial micro-processors of today that can be used for Active Electronically Scanned Array Antenna (AESA) based radar, their physical size, power consumption and performance must to be taken into consideration. The evaluation is based on theoretical comparisons among some of the latest processors provided by PACT, PicoChip, Intrinsity, Clearspeed and IBM. The project also includes a benchmark made on PowerPC G5 from IBM, which shows the calculation time for different Fast Fourier Transforms (FFTs). The benchmark on the PowerPC G5 shows that it is up to 5 times faster than its predecessor PowerPC G4 when it comes to calculate FFTs, but it only consumes twice the power. This is due to the fact that PowerPC G5 has a double word length and almost twice the frequency. Even if this seems as a good result, all the PowerPC´s that are needed to reach the performance for an AESA radar chain would consume too much power. The thesis ends up with a discussion about the traditional architectures and the new multi-core architectures. The future belongs with almost certainty to some kind of multicore processor concept, because of its higher performance per watt. But the traditional single core processor is probably the best choice for more moderate-performance systems of today, if you as developer looking for a traditional way of programing processors.

The aim of this pro ject was to evaluate the use of SIMD array architectures in radar signal processing. This has been done by implementing one of the most demanding parts of the radar signal processing chain for airborne radar on the CSX600 architecture devel- oped by Clearspeed Technologies. The CSX600 architecture is a SIMD processor with 96 processing elements which can be arranged either as a linera array or as a ring. The QR- decomposition, which was the part chosen for implementation, is the most performance demanding part of the STAP stage. In order to create a relevant test case the well known RT STAP benchmark from Mitre Corporation has been used. Two different algorithms for performing QR-decompositions have been implemented and verified. In both cases it has been concluded that either longer (> ≈256) or shorter (< ≈32) processor array lengths would, in general, yield a higher utilization ratio. The FLOP count and utiliza- tion has been measured for both algorithms, and it has been concluded that at least eight CSX600 processors are needed to meet the real-time demand of the benchmark.

As phosphorylation represents the pivotal mechanism for regulation of biological processes, kinases belong to one of the most biologically significant enzyme classes. The development of analytical techniques for characterization of kinase activity, in particular at a global scale, is a central priority for proteomic and cell biology researchers. In order to facilitate global analysis of cellular phosphorylation, a new paradigm of microarray technology which focuses on analysis of total cellular kinase activity, kinome, has emerged in the past few years. As the specificity of many kinases is dictated primarily by recognition of residues immediately surrounding the site of phosphorylation a logical methodology is to employ peptides representing these immediate sequences as experimental substrates. Microarray chips carrying hundreds of such substrate targets have been developed for human kinome analysis, however, lack of similar tools for species outside research mainstream has limited kinome analysis in these species.<p> Based on sequence alignment of orthologous phosphoproteins from mammalian species, conservation of amino acid identity is reported to be 80 %. Accordingly, the potential exists to utilize phosphorylation sequence databases to extrapolate phosphorylation sites in other species based on their genomic sequence information. Peptides representing these proposed phosphorylation sites can then be utilized as substrates to quantify the activity of the corresponding kinase. Based on these principles, a bovine microarray of 300 unique peptide targets was constructed. The bovine phosphorylation targets were selected to represent a spectrum of cellular events but with focus on processes related to innate immunity. Initial application and validation of the bovine peptide arrays was carried out for kinome analysis of bovine blood monocytes stimulated with either lipopolysaccharide (LPS) or CpG-ODNs; ligands for Toll-like receptors (TLR) 4 and 9, respectively. The arrays confirmed activation of the known TLR signaling pathway as well as identifying receptor-specific phosphorylation events. Phosphorylation events not previously attributed to TLR activation were also identified and validated by independent bioassays. This investigation offers insight into the complexity of TLR signaling and more importantly verifies the potential to use bioinformatics approaches to create tools for species-specific kinome analysis based on genomic information.

Given a certain transmission frequency, Shannon spatial sampling limit de¯nes an upper bound for the antenna element spacing. Beyond this bound, the exceeded ambiguity avoids correct estimation of the signal parameters (i.e., array manifold crossing). This spacing limit is inversely proportional to the frequency of transmis- sion. Therefore, to meet a wider spectral support, the element spacing should be decreased. However, practical implementations of closely spaced elements result in a detrimental increase in electromagnetic mutual couplings among the sensors. Further- more, decreasing the spacing reduces the array angle resolution. In this dissertation, the problem of Direction of Arrival (DOA) estimation of broadband sources is ad- dressed when the element spacing of a Uniform Array Antenna (ULA) is inordinate. It is illustrated that one can resolve the aliasing ambiguity by utilizing the frequency diversity of the broadband sources. An algorithm, based on Maximum Likelihood Estimator (MLE), is proposed to estimate the transmitted data signal and the DOA of each source. In the sequel, a subspace-based algorithm is developed and the prob- lem of order estimation is discussed. The adopted signaling framework assumes a subband hopping transmission in order to resolve the problem of source associations and system identi¯cation. The proposed algorithms relax the stringent maximum element-spacing constraint of the arrays pertinent to the upper-bound of frequency transmission and suggest that, under some mild constraints, the element spacing can be conveniently increased. An approximate expression for the estimation error has also been developed to gauge the behavior of the proposed algorithms. Through con- ¯rmatory simulation, it is shown that the performance gain of the proposed setup is potentially signi¯cant, speci¯cally when the transmitters are closely spaced and under low Signal to Noise Ratio (SNR), which makes it applicable to license-free communication.

The research presented within this dissertation explores the photocatalytic deposition of metal carried out within sealed microfluidic channels. Micro scale patterning of metals inside sealed microchannels is investigated as well as nanoscale control over the surface morphology of the nanoparticles making up the patterns. This is achieved by controlling solution conditions during deposition. Finally, the nanoparticle patterns are used in fabricating a sensor device, which demonstrates the ability to address multiple patches within a sealed channel with different surface chemistries. Also presented here is the construction of the first epifluorescence/total internal reflection macroscope. Its ability to carry out high numerical aperture imaging of large arrays of solid supported phospholipid bilayers is explored. For this, three experiments are carried out. First, imaging of a 63 element array where every other box contains a different bilayer is preformed, demonstrating the ability to address large scale arrays by hand. Next, a protein binding experiment is preformed using two different arrays of increasing ligand density on the same chip. Finally, a two-dimensional array of mixed fluorescent dyes contained within solid supported lipid bilayers is imaged illustrating the ability of the instrument to acquire fluorescent resonance energy transfer data. Additionally, the design and fabrication of an improved array chip and addressing method is presented. Using this new array chip and addressing method in conjunction with the epifluorescence/total internal reflection macroscope should provide an efficient platform for high throughput screening of important biological processes which occur at the surfaces of cell membranes.

Cognitive radio networks require the use of computational resources to reconfigure transmit/receive parameters to improve communication quality of service or efficiency. Recent emergence of smart phones has made these resources more accessible and mobile, combining sensors, geolocation, memory and processing power into a single device. Thus, this work examines an integration of a smart phone into a complex radio network that controls the beam direction of a phased array using a conventional method, but utilizes the phone's internal sensors as an enhancement to generate beam direction information, Bluetooth channel to relay information to control circuitry, and Global Position System (GPS) to track an object in motion. The research and experiments clearly demonstrate smart phone's ability to utilize internal sensors to generate information used to control beam direction from a phased array. Computational algorithms in a network of microcontrollers map this information into a DC bias voltage which is applied to individual phase shifters connected to individual array elements. To test algorithms and control theory, a 4 by 4 microstrip patch array is designed and fabricated to operate at a frequency of 2.4 GHz. Simulations and tests of the array provide successful antenna design results with satisfactory design parameters. Smart phone control circuitry is designed and tested with the array. Anechoic test results yield successful beam steering capability scanning 90 degrees at 15 degree intervals with 98% accuracy in all cases. In addition, the system achieves successful beam steering operable over a bandwidth of 100 MHz around resonance. Furthermore, these results demonstarate the capability of the smart phone controlled system to be used in testing further array formations to achieve beam steering in 3-Dimensional space. It is further noted that the system extends capabilities of integrating other control methods which use the smart phone to process information.

Wireless communication systems are limited in performance and capacity by the major impairments of multipath fading and co-channel interference. Smart antenna can combat the impairments, thereby enhancing the system capacity and alleviating the problem of bandwidth limitation. In general, there are two main types of smart antennas; these are switched beam systems and adaptive array systems. An antenna array, which consists of a group of several antenna elements and digital signal processing units, can form several independent beams in different angles. Smart antennas aim the main beam in the direction of the target mobile user and locate the nulls in the direction of the interfering signals from other mobile users to enhance the signal-to-interference power ratio and system capacity. One of the most important parts in adaptive array antenna systems is the adaptive algorithm to adjust the weights of an array. These algorithms include unconstrained as well as constrained LMS, normalized LMS, structured gradient, RLS, CMA, and conjugate gradient method. In this thesis, we propose a new algorithm based on weight-partition RLS method to reduce the computational complexity. The major concept of our algorithm is decreasing the dimension size of data matrix. Performance and complexity of the proposed algorithm is evaluated and compared with traditional WRLS algorithm.

Oligo array is a high throughput technology and is widely used in many scopes of biology and medical researches for quantitative and highly parallel measurements of gene expression. When one faulty step occurs during the synthesis process, it affects all probes using the faulty step. In this thesis, a two-phase genetic algorithm (GA) is proposed to design optimal quality control of oligo array for detecting any single faulty step. The first phase performs the wide search to obtain the approximate solutions and the second phase performs the local search on the approximate solutions to achieve the optimal solution. Besides, the proposed algorithm could hold many non-duplicate individuals and parallelly search multiple regions simultaneously. The superior searching capability of the two-phase GA helps us to find out the 275 nonequireplicate cases that settled by the hill-climbing algorithm. Furthermore, the proposed algorithm also discovers five more open issues.

For the requirements of high-speed signal transmission has been increasing, the fiber array in the communication system has a lot of advantages which can not be replaced. But the loss of coupling efficiency is a difficult problem as the distance of communication is getting longer and longer. For the sake of solving this problem, the system needs to use optic amplifier for enlarging the coupling efficiency in every long distance. The receiver can receive the correct signal by using optic amplifier. In order to reduce the using amount of optic amplifier for decreasing the cost, producing the fiber array with high coupling efficiency can reach the goal. This paper chooses quadrangular-pyramid-shaped fiber endface (QPSFE) which has better coupling efficiency than flattened-end fiber to research. Among those different manufacturing methods and different precision for fiber array packaging, the research chooses the method of grinding to manufacture the shape of surface. The research can raise the accuracy of manufacture for increasing the coupling efficiency of QPSFE by external equipments.