Developmentally regulated IL6-type cytokines signal to germ cells in the human fetal ovary

Fetal ovarian development and primordial follicle formation are imperative for adult fertility in the female. Data suggest the interleukin (IL)6-type cytokines, leukaemia inhibitory factor (LIF), IL6, oncostatin M (OSM) and ciliary neurotrophic factor (CNTF), are able to regulate the survival, proliferation and differentiation of fetal murine germ cells (GCs) in vivo and in vitro. We postulated that these factors may play a similar role during early human GC development and primordial follicle formation. To test this hypothesis, we have investigated the expression and regulation of IL6-type cytokines, using quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Expression of transcripts encoding OSM increased significantly across the gestational range examined (8-20 weeks), while expression of IL6 increased specifically between the first (8-11 weeks) and early second (12-16 weeks) trimesters, co-incident with the initiation of meiosis. LIF and CNTF expression remained unchanged. Expression of the genes encoding the LIF and IL6 receptors, and their common signalling subunit gp130, was also found to be developmentally regulated, with expression increasing significantly with increasing gestation. LIF receptor and gp130 proteins localized exclusively to GCs, including oocytes in primordial follicles, indicating this cell type to be the sole target of IL6-type cytokine signalling in the human fetal ovary. These data establish that IL6-type cytokines and their receptors are expressed in the human fetal ovary and may directly influence GC development at multiple stages of maturation.

Received Signal Characteristics of the Indoor Off-Body Communications Channel at 5.8 GHz

In this paper we investigate the received signal characteristics of a mobile chest-worn transmitter at 5.8 GHz within a high multipath indoor environment. The off-body channel measurements considered both the co- and cross-polarized received signal for both line-of-sight (LOS) and non-LOS (NLOS) conditions. A straightforward channel model based upon the estimated path loss, a lognormal slow fading component and Ricean small-scale fading contribution is developed and used to perform simulations which allow the generation of first order received signal power characteristics.

Improving signal reliability in outdoor body-to-body communications using front and back positioned antenna diversity

It has previously been shown that human body shadowing can have a considerable impact on body-to-body communications channels in low multipath environments. Signal degradation directly attributable to shadowing when one user's body obstructs the main line of sight can be as great as 40 dB. When both people's bodies obstruct the direct line of sight path, the communications link can be lost altogether even at very short distances of a few metres. In this paper, using front and back positioned antennas, we investigate the utility of a simple selection combination diversity combining scheme with the aim of mitigating human body shadowing in outdoor body-to-body communications channels at 2.45 GHz. Early results from this work are extremely promising, indicating substantial diversity gains, as great as 29 dB, may be achieved in a number of everyday scenarios likely to be encountered in body-to-body networking. © 2012 IEEE.

A co-operative formation-based collision avoidance approach for a group of autonomous vehicles (Special Issue on Adaptive Control and Signal Processing in Marine System)

This paper employs a unique decentralised cooperative control method to realise a formation-based collision avoidance strategy for a group of autonomous vehicles. In this approach, the vehicles' role in the formation and their alert and danger areas are first defined, and the formation-based intra-group and external collision avoidance methods are then proposed to translate the collision avoidance problem into the formation stability problem. The extension–decomposition–aggregation formation control method is next employed to stabilise the original and modified formations, whilst manoeuvring, and subsequently solve their collision avoidance problem indirectly. Simulation study verifies the feasibility and effectiveness of the intra-group and external collision avoidance strategy. It is demonstrated that both formation control and collision avoidance problems can be simultaneously solved if the stability of the expanded formation including external obstacles can be satisfied.

Identification of Small Signal Oscillation Mode Parameters from Simulated and Actual PMU Ringdown Data

This paper presents the practical use of Prony Analysis to identify small signal oscillation mode parameters from simulated and actual phasor measurement unit (PMU) ringdown data. A well-known two-area four-machine power system was considered as a study case while the latest PMU ringdown data were collected from a double circuit 275 kV main interconnector on the Irish power system. The eigenvalue analysis and power spectral density were also conducted for the purpose of comparison. The capability of Prony Analysis to identify the mode parameters from three different types of simulated PMU ringdown data has been shown successfully. Furthermore, the results indicate that the Irish power system has dominant frequency modes at different frequencies. However, each mode has good system damping.

Streaming Elements for FPGA Signal and Image Processing Accelerators

Field programmable gate array devices boast abundant resources with which custom accelerator components for signal, image and data processing may be realised; however, realising high performance, low cost accelerators currently demands manual register transfer level design. Software-programmable ’soft’ processors have been proposed as a way to reduce this design burden but they are unable to support performance and cost comparable to custom circuits. This paper proposes a new soft processing approach for FPGA which promises to overcome this barrier. A high performance, fine-grained streaming processor, known as a Streaming Accelerator Element, is proposed which realises accelerators as large scale custom multicore networks. By adopting a streaming execution approach with advanced program control and memory addressing capabilities, typical program inefficiencies can be almost completely eliminated to enable performance and cost which are unprecedented amongst software-programmable solutions. When used to realise accelerators for fast fourier transform, motion estimation, matrix multiplication and sobel edge detection it is shown how the proposed architecture enables real-time performance and with performance and cost comparable with hand-crafted custom circuit accelerators and up to two orders of magnitude beyond existing soft processors.

Signal Reliability Improvement Using Selection Combining Based Macro-Diversity for Off-Body Communications At 868 MHz

This paper investigates the potential improvement in signal reliability for outdoor short-range off-body communications channels at 868 MHz using the macro-diversity offered by multiple co-located base stations. In this study, ten identical hypothetical base stations were positioned equidistantly around the perimeter of a rectangle of length 6.67 m and width 3.3 m. A body worn node was placed on the central chest region of an adult male. Five scenarios, each considering different user trajectories, were then analyzed to test the efficacy of using macro-diversity when the desired link is subject to shadowing caused by the human body. A number of selection combining based macro-diversity configurations consisting of four and then ten base stations were considered. It was found that using a macro-diversity system consisting of four base stations (or equivalently signal branches), a maximum diversity gain of 22.5 dB could be obtained while implementing a 10-base station setup this figure could be improved to 25.2 dB.

Signal Reception Characteristics in the Proximity of Alice and Bob for Secure Indoor Peer-to-Peer Communications At 2.45 GHz

Mutual variation of the received signal which occurs as a consequence of the channel reciprocity property has recently been proposed as a viable method for secret key generation. However, this cannot be strictly maintained in practice as the property is applicable only in the absence of interference. To ensure the propagation defined key remains secret, one requirement is that there remain high degrees of uncertainty between the legitimate users channel response and that of any eavesdropper's. In this paper, we investigate whether such de-correlation occurs for an indoor point-to-point link at 2.45 GHz. This is achieved by computing the localized correlation coefficient between the simultaneous channel response measured by the legitimate users and that of multiple distributed eavesdroppers for static and dynamic scenarios.

Real-Time Channel Model Selection Using Windowed Received Signal Strength Measurements

This paper investigates the potential for using the windowed variance of the received signal strength to select from a set of predetermined channel models for a wireless ranging or localization system. An 868 MHz based measurement system was used to characterize the received signal strength (RSS) of the off-body link formed between two wireless nodes attached to either side of a human thorax and six base stations situated in the local surroundings.

Specific role of neuronal nitric-oxide synthase when tethered to the plasma membrane calcium pump in regulating the beta-adrenergic signal in the myocardium

The cardiac neuronal nitric-oxide synthase (nNOS) has been described as a modulator of cardiac contractility. We have demonstrated previously that isoform 4b of the sarcolemmal calcium pump (PMCA4b) binds to nNOS in the heart and that this complex regulates beta-adrenergic signal transmission in vivo. Here, we investigated whether the nNOS-PMCA4b complex serves as a specific signaling modulator in the heart. PMCA4b transgenic mice (PMCA4b-TG) showed a significant reduction in nNOS and total NOS activities as well as in cGMP levels in the heart compared with their wild type (WT) littermates. In contrast, PMCA4b-TG hearts showed an elevation in cAMP levels compared with the WT. Adult cardiomyocytes isolated from PMCA4b-TG mice demonstrated a 3-fold increase in Ser(16) phospholamban (PLB) phosphorylation as well as Ser(22) and Ser(23) cardiac troponin I (cTnI) phosphorylation at base line compared with the WT. In addition, the relative induction of PLB phosphorylation and cTnI phosphorylation following isoproterenol treatment was severely reduced in PMCA4b-TG myocytes, explaining the blunted physiological response to the beta-adrenergic stimulation. In keeping with the data from the transgenic animals, neonatal rat cardiomyocytes overexpressing PMCA4b showed a significant reduction in nitric oxide and cGMP levels. This was accompanied by an increase in cAMP levels, which led to an increase in both PLB and cTnI phosphorylation at base line. Elevated cAMP levels were likely due to the modulation of cardiac phosphodiesterase, which determined the balance between cGMP and cAMP following PMCA4b overexpression. In conclusion, these results showed that the nNOS-PMCA4b complex regulates contractility via cAMP and phosphorylation of both PLB and cTnI.

A BRCA1 deficient, NFκB driven immune signal predicts good outcome in triple negative breast cancer

Triple negative (TNBCs) and the closely related Basal-like (BLBCs) breast cancers are a loosely defined collection of cancers with poor clinical outcomes. Both show strong similarities with BRCA1-mutant breast cancers and BRCA1 dysfunction, or 'BRCAness', is observed in a large proportion of sporadic BLBCs. BRCA1 expression and function has been shown in vitro to modulate responses to radiation and chemotherapy. Exploitation of this knowledge in the treatment of BRCA1-mutant patients has had varying degrees of success. This reflects the significant problem of accurately detecting those patients with BRCA1 dysfunction. Moreover, not all BRCA1 mutations/loss of function result in the same histology/pathology or indeed have similar effects in modulating therapeutic responses. Given the poor clinical outcomes and lack of targeted therapy for these subtypes, a better understanding of the biology underlying these diseases is required in order to develop novel therapeutic strategies.We have discovered a consistent NFκB hyperactivity associated with BRCA1 dysfunction as a consequence of increased Reactive Oxygen Species (ROS). This biology is found in a subset of BRCA1-mutant and triple negative breast cancer cases and confers good outcome. The increased NFκB signalling results in an anti-tumour microenvironment which may allow CD8+ cytotoxic T cells to suppress tumour progression. However, tumours lacking this NFκB-driven biology have a more tumour-promoting environment and so are associated with poorer prognosis. Tumour-derived gene expression data and cell line models imply that these tumours may benefit from alternative treatment strategies such as reprogramming the microenvironment and targeting the IGF and AR signalling pathways.

Inexact-aware architecture design for ultra-low power bio-signal analysis

This study introduces an inexact, but ultra-low power, computing architecture devoted to the embedded analysis of bio-signals. The platform operates at extremely low voltage supply levels to minimise energy consumption. In this scenario, the reliability of static RAM (SRAM) memories cannot be guaranteed when using conventional 6-transistor implementations. While error correction codes and dedicated SRAM implementations can ensure correct operations in this near-threshold regime, they incur in significant area and energy overheads, and should therefore be employed judiciously. Herein, the authors propose a novel scheme to design inexact computing architectures that selectively protects memory regions based on their significance, i.e. their impact on the end-to-end quality of service, as dictated by the bio-signal application characteristics. The authors illustrate their scheme on an industrial benchmark application performing the power spectrum analysis of electrocardiograms. Experimental evidence showcases that a significance-based memory protection approach leads to a small degradation in the output quality with respect to an exact implementation, while resulting in substantial energy gains, both in the memory and the processing subsystem.

Phytochelatin signal tranduction and cadmium chelation in plants

As plantas utilizam diversas estratégias de sinalização para reconhecer e responder aos stresses ambientais. A maioria das vias de transdução de sinais partilham um sinal genérico, normalmente a modulação dos níveis intracelulares de Ca2+. Esta por sua vez pode iniciar uma cascata de fosforilação proteica que finalmente afecta as proteínas directamente envolvidas na protecção celular ou culmina em factores de transcrição que vão determinar a resposta fisiológica ao stresse. A percepção destes sinais e a compreensão de como estes podem activar as respostas adaptativas são factores-chave para a tolerância das plantas a stresses abióticos. Um dos principais stresses abóticos que restrigem o crescimento das plantas é a presença de metais pesados. A produção de fitoquelatinas e a subsequente quelação dos metais é o mecanismo mais conhecido de tolerância ao stresse metálico em plantas. Fitoquelatinas (PCs) são péptidos com grupos tiol que são sintetizados através da transpeptidação da glutationa (GSH), pela acção da enzima fitoquelatina sintase (PCS). No entanto, até ao momento, as vias de sinalização que levam à síntese de fitoquelatinas e à percepção do stresse metálico são pouco compreendidas. Dentro deste contexto, o presente trabalho foi elaborado com o intuito de elucidar a via de sinalização através da qual o cádmio é detectado pelas células vegetais e induz a síntese de PCs. Quase todos, os estudos de stresses abióticos em plantas apontam para o facto de a sua sinalização se basear nos mesmos tipos de sinais moleculares, nomeadamente a sinalização por cálcio, a fosforilação proteica e a indução de espécies reactivas de oxigénio (ROS). Trabalhos recentes sugerem que a sinalização de PCs poderá envolver todos estes parâmetros. Assim, uma primeira abordagem foi efectuada para compreender a síntese de PCs na espécie Arabidopsis thaliana, através da monitorizaçção da actividade de enzimas relacionadas, a γ-EC sintetase, GSH sintetase e a PC sintase (PCS), assim como o tempo necessário para o elongamento das PCs e a sua acumulação. Seguidamente, ao longo deste processo foi analisada a expressão de sinais específicos, associados com sinais de cálcio, fosforilação proteica e sinalização por ROS. A importância destes factores na síntese de PCs foi também avaliada através do uso de moduladores farmacológicos de cálcio e fosfatases proteicas e também pela indução de stresse oxidativo. Os resultados demonstraram novos dados sobre o papel do cálcio e da fosforilação proteica na produção de PCs e na síntese de GSH, revelando que a actvidade da PCS é regulada por fosforilação e que a sinalização de cálcio pode mediar a síntese de GSH. O envolvimento da sinalização de ROS na síntese de GSH, atráves de crosstalk com a sinalização de cálcio também foi proposta. Assim, os resultados aqui apresentados descrevem uma possível via de sinalização de cádmio nas plantas e da indução de fitoquelatinas. Este trabalho poderá ser portanto muito útil na implementação de novas metodologias de agricultura sustentável e práticas de fitorremediação em solos contaminados com metais pesados.

Photonic devices for optical and RF signal processing

O presente trabalho tem por objectivo o estudo de novos dispositivos fotónicos aplicados a sistemas de comunicações por fibra óptica e a sistemas de processamento de sinais RF. Os dispositivos apresentados baseiam-se em processamento de sinal linear e não linear. Dispositivos lineares ópticos tais como o interferómetro de Mach-Zehnder permitem adicionar sinais ópticos com pesos fixos ou sintonizáveis. Desta forma, este dispositivo pode ser usado respectivamente como um filtro óptico em amplitude com duas saídas complementares, ou, como um filtro óptico de resposta de fase sintonizável. O primeiro princípio de operação serve como base para um novo sistema fotónico de medição em tempo real da frequência de um sinal RF. O segundo princípio de operação é explorado num novo sistema fotónico de direccionamento do campo eléctrico radiado por um agregado de antenas, e também num novo compensador sintonizável de dispersão cromática. O processamento de sinal é não linear quando sinais ópticos são atrasados e posteriormente misturados entre si, em vez de serem linearmente adicionados. Este princípio de operação está por detrás da mistura de um sinal eléctrico com um sinal óptico, que por sua vez é a base de um novo sistema fotónico de medição em tempo real da frequência de um sinal RF. A mistura de sinais ópticos em meios não lineares permite uma operação eficiente numa grande largura espectral. Tal operação é usada para realizar conversão de comprimento de onda sintonizável. Um sinal óptico com multiplexagem no domínio temporal de elevada largura de banda é misturado com duas bombas ópticas não moduladas com base em processos não lineares paramétricos num guia de ondas de niobato de lítio com inversão periódica da polarização dos domínios ferroeléctricos. Noutro trabalho, uma bomba pulsada em que cada pulso tem um comprimento de onda sintonizável serve como base a um novo conversor de sinal óptico com multiplexagem no domínio temporal para um sinal óptico com multiplexagem no comprimento de onda. A bomba é misturada com o sinal óptico de entrada através de um processo não linear paramétrico numa fibra óptica com parâmetro não linear elevado. Todos os dispositivos fotónicos de processamento de sinal linear ou não linear propostos são experimentalmente validados. São também modelados teoricamente ou através de simulação, com a excepção dos que envolvem mistura de sinais ópticos. Uma análise qualitativa é suficiente nestes últimos dispositivos.