Development of a selective photoactivatable antagonist for corticotropin-releasing factor receptor, type 2 (CRF2)

A novel photoactivatable analog of antisauvagine-30 (aSvg-30), a specific antagonist for corticotropin-releasing factor (CRF) receptor, type 2 (CRF2), has been synthesized and characterized. The N-terminal amino-acid D-Phe in aSvg-30 [D-Phe11,His12] Svg((11-40)) was replaced by a phenyldiazirine, the 4-(1-azi-2,2,2-trifluoroethyl) benzoyl (ATB) residue. The photoactivatable aSvg-30 analog ATB-[ His12] Svg was tested for its ability to displace [I-125-Tyr0] oCRF or [I-125-Tyr0]Svg from membrane homogenates of human embryonic kidney (HEK) 293 cells stably transfected with cDNA coding for rat CRF receptor, type 1 ( rCRF(1)) or mouse CRF receptor, type 2beta (mCRF(2beta)). Furthermore, the ability of ATB- [His12] Svg((12-40)) to inhibit oCRF- or Svg-stimulated cAMP production of transfected HEK 293 cells expressing either rCRF(1) (HEK-rCRF(1) cells) or mCRF(2beta) (HEK-mCRF(2beta) cells) was determined. Unlike astressin and photo astressin, ATB- [His12]Svg((12-40)) showed high selective binding to mCRF(2beta) (K-i = 3.1 +/- 0.2 nM) but not the rCRF(1) receptor (K-i = 142. 5 +/- 22.3 nM) and decreased Svg-stimulated cAMP activity in mCRF(2beta)-expressing cells in a similar fashion as aSvg-30. A66-kDa protein was identified by SDS/PAGE, when the radioactively iodinated analog of ATB- [His12]Svg((12-40)) was covalently linked to mCRF(2beta) receptor. The specificity of the photoactivatable I-125-labeled CRF2beta antagonist was demonstrated with SDS/PAGE by the finding that this analog could be displaced from the receptor by antisauvagine-30, but not other unrelated peptides such as vasoactive intestinal peptide (VIP).

Spatial and temporal patterns in Australian wheat yield and their relationship with ENSO

Spatial and temporal variability in wheat production in Australia is dominated by rainfall occurrence. The length of historical production records is inadequate, however, to analyse spatial and temporal patterns conclusively. In this study we used modelling and simulation to identify key spatial patterns in Australian wheat yield, identify groups of years in the historical record in which spatial patterns were similar, and examine association of those wheat yield year groups with indicators of the El Nino Southern Oscillation (ENSO). A simple stress index model was trained on 19 years of Australian Bureau of Statistics shire yield data (1975-93). The model was then used to simulate shire yield from 1901 to 1999 for all wheat-producing shires. Principal components analysis was used to determine the dominating spatial relationships in wheat yield among shires. Six major components of spatial variability were found. Five of these represented near spatially independent zones across the Australian wheatbelt that demonstrated coherent temporal (annual) variability in wheat yield. A second orthogonal component was required to explain the temporal variation in New South Wales. The principal component scores were used to identify high- and low-yielding years in each zone. Year type groupings identified in this way were tested for association with indicators of ENSO. Significant associations were found for all zones in the Australian wheatbelt. Associations were as strong or stronger when ENSO indicators preceding the wheat season (April-May phases of the Southern Oscillation Index) were used rather than indicators based on classification during the wheat season. Although this association suggests an obvious role for seasonal climate forecasting in national wheat crop forecasting, the discriminatory power of the ENSO indicators, although significant, was not strong. By examining the historical years forming the wheat yield analog sets within each zone, it may be possible to identify novel climate system or ocean-atmosphere features that may be causal and, hence, most useful in improving seasonal forecasting schemes.

Description of stable pain in rheumatoid arthritis: A 6 year study

Objective. To study pain quality and variability in patients with rheumatoid arthritis (RA). Methods. Pain, disease activity, and functional status Were assessed 3 times over 6 years in an initial cohort of 120 clinic patients with chronic pain from RA. A pain visual analog scale and the McGill Pain Questionnaire (MPQ) were used to record pain intensity and quality. RA disease activity and function were measured. Results. There was no statistically significant difference in any measure over the 3 assessments. RA pain intensity was moderate. The MPQ showed that sensory components of the pain were described in terms of pressure and constriction. Pain related affect was described with adjectives suggesting positive psychological adaptation to pain. Conclusion. The. results indicate a general profile of no change in pain sensation, affect, and emotional quality in clinic monitored patients with ongoing RA and ongoing, moderate levels of disease activity and function. The MPQ provides qualitative detail to patient's report of pain severity that could be a useful addition to longterm documentation of RA outcome. Regular MPQ documentation of current pain in outpatients could indicate whether any significant change in pain levels is reflected in altered word selection that reflects physiological or psychological change, and could assist clinicians to select the most appropriate form of therapy for RA pain.

Learning the dynamics of embedded clauses

Recent work by Siegelmann has shown that the computational power of recurrent neural networks matches that of Turing Machines. One important implication is that complex language classes (infinite languages with embedded clauses) can be represented in neural networks. Proofs are based on a fractal encoding of states to simulate the memory and operations of stacks. In the present work, it is shown that similar stack-like dynamics can be learned in recurrent neural networks from simple sequence prediction tasks. Two main types of network solutions are found and described qualitatively as dynamical systems: damped oscillation and entangled spiraling around fixed points. The potential and limitations of each solution type are established in terms of generalization on two different context-free languages. Both solution types constitute novel stack implementations - generally in line with Siegelmann's theoretical work - which supply insights into how embedded structures of languages can be handled in analog hardware.

Digitally-implemented naturally sampled PWM suitable for multilevel converter control

For dynamic closed loop control of a multilevel converter with a low pulse number (ratio of switching frequency to synthesized fundamental), natural sampled pulse-width modulation (PWM) is the best form of modulation. Natural sampling does not introduce distortion or a delayed response to the modulating signal. However previous natural sampled PWM implementations have generally been analog. For a modular multilevel converter, a digital implementation has advantages of accuracy and flexibility. Re-sampled uniform PWM is a novel digital modulation technique which approaches the performance of natural PWM. Both hardware and software implementations for a five level multilevel converter phase are presented, demonstrating the improvement over uniform PWM.

The synthesis and X-ray crystal structure of 9-carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one

9-Carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one (1) was prepared and examined by X-ray crystallography to probe its potential as a new peptide scaffold/template. The crystal structure of the anhydride precursor 7-(2-acetoxyethyl)-4-methoxy-3a,4,7,7a-tetrahydro-4,7-ethanoisobenzofuran-1,3-dione (6) is also reported.

Transitory increased blood pressure after upper airway surgery for snoring and sleep apnea correlates with the apnea-hypopnea respiratory disturbance index

A transitory increase in blood pressure (BP) is observed following upper airway surgery for obstructive sleep apnea syndrome but the mechanisms implicated are not yet well understood. The objective of the present study was to evaluate changes in BP and heart rate (HR) and putative factors after uvulopalatopharyngoplasty and septoplasty in normotensive snorers. Patients (N = 10) were instrumented for 24-h ambulatory BP monitoring, nocturnal respiratory monitoring and urinary catecholamine level evaluation one day before surgery and on the day of surgery. The influence of postsurgery pain was prevented by analgesic therapy as confirmed using a visual analog scale of pain. Compared with preoperative values, there was a significant (P < 0.05) increase in nighttime but not daytime systolic BP (119 ± 5 vs 107 ± 3 mmHg), diastolic BP (72 ± 4 vs 67 ± 2 mmHg), HR (67 ± 4 vs 57 ± 2 bpm), respiratory disturbance index (RDI) characterized by apnea-hypopnea (30 ± 10 vs 13 ± 4 events/h of sleep) and norepinephrine levels (22.0 ± 4.7 vs 11.0 ± 1.3 µg l-1 12 h-1) after surgery. A positive correlation was found between individual variations of BP and individual variations of RDI (r = 0.81, P < 0.01) but not between BP or RDI and catecholamines. The visual analog scale of pain showed similar stress levels on the day before and after surgery (6.0 ± 0.8 vs 5.0 ± 0.9 cm, respectively). These data strongly suggest that the cardiovascular changes observed in patients who underwent uvulopalatopharyngoplasty and septoplasty were due to the increased postoperative RDI.

A Wireless EEG Acquisition Platform based on Embedded Systems

This paper proposes a wireless EEG acquisition platform based on Open Multimedia Architecture Platform (OMAP) embedded system. A high-impedance active dry electrode was tested for improving the scalp- electrode interface. It was used the sigma-delta ADS1298 analog-to-digital converter, and developed a “kernelspace” character driver to manage the communications between the converter unit and the OMAP’s ARM core. The acquired EEG signal data is processed by a “userspace” application, which accesses the driver’s memory, saves the data to a SD-card and transmits them through a wireless TCP/IP-socket to a PC. The electrodes were tested through the alpha wave replacement phenomenon. The experimental results presented the expected alpha rhythm (8-13 Hz) reactiveness to the eyes opening task. The driver spends about 725 μs to acquire and store the data samples. The application takes about 244 μs to get the data from the driver and 1.4 ms to save it in the SD-card. A WiFi throughput of 12.8Mbps was measured which results in a transmission time of 5 ms for 512 kb of data. The embedded system consumes about 200 mAh when wireless off and 400 mAh when it is on. The system exhibits a reliable performance to record EEG signals and transmit them wirelessly. Besides the microcontroller-based architectures, the proposed platform demonstrates that powerful ARM processors running embedded operating systems can be programmed with real-time constrains at the kernel level in order to control hardware, while maintaining their parallel processing abilities in high level software applications.

Design of improved rail-to-rail low-distortion and low-stress switches in advanced CMOS technologies

This paper describes the efficient design of an improved and dedicated switched-capacitor (SC) circuit capable of linearizing CMOS switches to allow SC circuits to reach low distortion levels. The described circuit (SC linearization control circuit, SLC) has the advantage over conventional clock-bootstrapping circuits of exhibiting low-stress, since large gate voltages are avoided. This paper presents exhaustive corner simulation results of a SC sample-and-hold (S/H) circuit which employs the proposed and optimized circuits, together with the experimental evaluation of a complete 10-bit ADC utilizing the referred S/H circuit. These results show that the SLC circuits can reduce distortion and increase dynamic linearity above 12 bits for wide input signal bandwidths.

Geração e propagação de sinais rádio sobre fibra (RoF)

As tecnologias de rádio sobre fibra associam as comunicações rádio com as comunicações ópticas, sendo estas os dois tipos de comunicações com maior desenvolvimento nos últimos anos, ao permitirem débitos e larguras de banda elevadas e simultaneamente uma elevada mobilidade. Neste sentido, no mercado das telecomunicações têm sido desenvolvidos sistemas com alta performance, tentando reduzir o quanto possível os custos associados aos sistemas, tendo assim uma especial relevância os designados sistemas de baixo custo. Nesta dissertação de Mestrado estuda-se a propagação de sinais rádio sobre fibra, variando o tipo de modulação óptica utilizada e tendo como base os sistemas de baixo custo. Estes sistemas de baixo custo são sistemas que utilizam apenas uma fonte óptica para o sentido descendente, remodulando a portadora na estação remota com o sinal do sentido ascendente. Começa-se por fazer um estudo sobre o estado da arte da tecnologia rádio sobre fibra e tecnologias envolvidas. De seguida, é apresentado um estudo teórico sobre o sistema rádio sobre fibra, desde a sua arquitectura, figuras de mérito e seus componentes. Posteriormente, são apresentadas as modulações ópticas utilizadas em sistemas rádio sobre fibra. A avaliação dos sistemas e apresentação de resultados é efectuada recorrendo a simulações. De acordo com os resultados obtidos pode verificar-se que a utilização de modulação de fase no sentido descendente e modulação de intensidade no sentido ascendente é a solução que melhores resultados apresenta como sistema de baixo custo. No entanto, caso se pretenda uma melhor performance em detrimento da redução de custos, deve-se optar por um sistema convencional com duas fontes ópticas, uma para cada sentido.

Laser scanned photodiodes (LSP) for Image sensing

An optimized ZnO:Al/a-pin SixCl1-x:H/Al configuration for the laser scanned photodiode (LSP) imaging detector is proposed. The LSP utilizes light induced depletion layers as detector and a laser beam for readout. The effect of the sensing element structure, cell configuration and light source flux are investigated and correlated with the sensor output characteristics. Experimental data reveal that the large optical gap and the low conductivity of the doped a-SixC1-x:H layers are responsible by an induced inversion layer at the illuminated interfaces which blocks the carrier collection. These insulator-like layers act as MIS gates preventing image smearing. The physical background of the LSP is discussed.

New p-i-n Si : H imager configuration for spatial resolution improvement

Amorphous glass/ZnO-Al/p(a-Si:H)/i(a-Si:H)/n(a-Si1-xCx:H)/Al imagers with different n-layer resistivities were produced by plasma enhanced chemical vapour deposition technique (PE-CVD). An image is projected onto the sensing element and leads to spatially confined depletion regions that can be readout by scanning the photodiode with a low-power modulated laser beam. The essence of the scheme is the analog readout, and the absence of semiconductor arrays or electrode potential manipulations to transfer the information coming from the transducer. The influence of the intensity of the optical image projected onto the sensor surface is correlated with the sensor output characteristics (sensitivity, linearity blooming, resolution and signal-to-noise ratio) are analysed for different material compositions (0.5 < x < 1). The results show that the responsivity and the spatial resolution are limited by the conductivity of the doped layers. An enhancement of one order of magnitude in the image intensity signal and on the spatial resolution are achieved at 0.2 mW cm(-2) light flux by decreasing the n-layer conductivity by the same amount. A physical model supported by electrical simulation gives insight into the image-sensing technique used.

Projecto de um regulador linear de tensão: LDO

Os reguladores de tensão LDO são utilizados intensivamente na actual indústria de electrónica, são uma parte essencial de um bloco de gestão de potência para um SoC. O aumento de produtos portáteis alimentados por baterias levou ao crescimento de soluções totalmente integradas, o que degrada o rendimento dos blocos analógicos que o constituem face às perturbações introduzidas na alimentação. Desta forma, surge a necessidade de procurar soluções cada vez mais optimizadas, impondo assim novas soluções, e/ou melhoramentos dos circuitos de gestão de potência, tendo como objectivo final o aumento do desempenho e da autonomia dos dispositivos electrónicos. Normalmente este tipo de reguladores tem a corrente de saída limitada, devido a problemas de estabilidade associados. Numa tentativa de evitar a instabilidade para as correntes de carga definidas e aumentar o PSRR do mesmo, é apresentado um método de implementação que tem como objectivo melhorar estas características, em que se pretende aumentar o rendimento e melhorar a resposta à variação da carga. No entanto, a técnica apresentada utiliza polarização adaptativa do estágio de potência, o que implica um aumento da corrente de consumo. O regulador LDO foi implementado na tecnologia CMOS UMC 0.18μm e ocupa uma área inferior a 0,2mm2. Os resultados da simulação mostram que o mesmo suporta uma transição de corrente 10μA para 100mA, com uma queda de tensão entre a tensão de alimentação e a tensão de saída inferior a 200mV. A estabilidade é assegurada para todas as correntes de carga. O tempo de estabelecimento é inferior a 6μs e as variações da tensão de saída relativamente a seu valor nominal são inferiores a 5mV. A corrente de consumo varia entre os 140μA até 200μA, o que permite atingir as especificações proposta para um PSRR de 40dB@10kHz.

Technical considerations concerning digital technologies

This chapter addresses technical issues concerning digital technologies. Radiological equipment and technique are briefly introduced together with a discussion about requirements and advantages of digital technologies. Digital technologies offer several advantages when compared to conventional analogical systems, or screen–film (SF) systems. While in clinical practice the practitioners should be aware of technical factors such as image acquisition, management of patient dose, and diagnostic image quality. Thus, digital technologies require an up-to-date scientific knowledge concerning their use in projection radiography. In this chapter, technical considerations concerning digital technologies are provided.

Identificação de compostos que modulam a patogénese da doença de Machado-Joseph em C.elegans: autofagia como alvo terapêutico: identification of small compounds that modulate pathogenesis of Machado-Joseph disease in a C.elegans model: targeting autophagy

A doença de Machado-Joseph (DMJ) ou ataxia espinocerebelosa do tipo 3 (SCA3), conhecida por ser a mais comum das ataxias hereditárias dominantes em todo o mundo, é uma doença neurodegenerativa autossómica dominante que leva a uma grande incapacidade motora, embora sem alterar o intelecto, culminando com a morte do doente. Atualmente não existe nenhum tratamento eficaz para esta doença. A DMJ é resultado de uma alteração genética causada pela expansão de uma sequência poliglutamínica (poliQ), na região C-terminal do gene que codifica a proteína ataxina-3 (ATXN3). Os mecanismos celulares das doenças de poliglutaminas que provocam toxicidade, bem como a função da ATXN3, não são ainda totalmente conhecidos. Neste trabalho, usamos, pela sua simplicidade e potencial genético, um pequeno animal invertebrado, o nemátode C. elegans, com o objetivo de identificar fármacos eficazes para o combate contra a patogénese da DMJ, analisando simultaneamente o seu efeito na agregação da ATXN3 mutante nas células neuronais in vivo e o seu impacto no comportamento motor dos animais. Este pequeno invertebrado proporciona grandes vantagens no estudo dos efeitos tóxicos de proteínas poliQ nos neurónios, uma vez que a transparência das suas 959 células (das quais 302 são neurónios) facilita a deteção de proteínas fluorescentes in vivo. Para além disso, esta espécie tem um ciclo de vida curto, é económica e de fácil manutenção. Neste trabalho testámos no nosso modelo transgénico da DMJ com 130Qs em C.elegans dois compostos potencialmente moduladores da agregação da ATXN3 mutante e da resultante disfunção neurológica, atuando pela via da autofagia. De modo a validar a possível importância terapêutica da ativação da autofagia os compostos candidatos escolhidos foram o Litío e o análogo da Rapamicina CCI-779, testados independentemente e em combinação. A neuroproteção conferida pelo Litío e pelo CCI-779 independentemente sugere que o uso destes fármacos possa ser considerado uma boa estratégia como terapia para a DMJ, a testar em organismos evolutivamente mais próximos do humano. A manipulação da autofagia, segundo vários autores, parece ser benéfica e pode ser a chave para o desenvolvimento de novos tratamentos para várias doenças relacionadas com a agregação proteica e o envelhecimento.