Millimetre wave dielectric characterisation of multilayer LTCC substrate

The paper reports on the mm-wave characterization of a low temperature co-fired ceramic (LTCC) substrate. A substrate integrated resonator (SIW) method is presented for robust extraction of both permittivity and loss tangent of the substrate. The data obtained allow full characterization of the substrate in the 71 GHz – 95 GHz frequency range suitable for accurate modelling of E-and W-band printed circuits.

The Art of Dying

Invited annual international lecture

Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer

Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a major regulator of this process, but its activation under normoxic conditions, termed pseudohypoxia, is not well documented. Here, using an integrative approach combining the first genome-wide mapping of chromatin binding for an endocytic adaptor, ARRB1, both in vitro and in vivo with gene expression profiling, we demonstrate that nuclear ARRB1 contributes to this metabolic shift in prostate cancer cells via regulation of HIF1A transcriptional activity under normoxic conditions through regulation of succinate dehydrogenase A (SDHA) and fumarate hydratase (FH) expression. ARRB1-induced pseudohypoxia may facilitate adaptation of cancer cells to growth in the harsh conditions that are frequently encountered within solid tumours. Our study is the first example of an endocytic adaptor protein regulating metabolic pathways. It implicates ARRB1 as a potential tumour promoter in prostate cancer and highlights the importance of metabolic alterations in prostate cancer.

The androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man

The androgen receptor (AR) regulates prostate cell growth in man, and prostate cancer is the commonest cancer in men in the UK. We present a comprehensive analysis of AR binding sites in human prostate cancer tissues, including castrate-resistant prostate cancer (CRPC). We identified thousands of AR binding sites in CRPC tissue, most of which were not identified in PC cell lines. Many adjacent genes showed AR regulation in xenografts but not in cultured LNCaPs, demonstrating an in-vivo-restricted set of AR-regulated genes. Functional studies support a model of altered signaling in vivo that directs AR binding. We identified a 16 gene signature that outperformed a larger in-vitro-derived signature in clinical data sets, showing the importance of persistent AR signaling in CRPC.

Nuclear trafficking and functions of endocytic proteins implicated in oncogenesis

A subset of proteins predominantly associated with early endosomes or implicated in clathrin-mediated endocytosis can shuttle between the cytoplasm and the nucleus. Although the endocytic functions of these proteins have been extensively studied, much less effort has been expended in exploring their nuclear roles. Membrane trafficking proteins can affect signalling and proliferation and this can be achieved either at a nuclear or endocytic level. Furthermore, some proteins, such as Huntingtin interacting protein 1, are known as cancer biomarkers. This review will highlight the limits of our understanding of their nuclear functions and the relevance of this to signalling and oncogenesis.

Putting chromatin immunoprecipitation into context

Chromatin immunoprecipitation (ChIP), when paired with sequencing or arrays, has become a method of choice for the unbiased identification of genomic-binding sites for transcription factors and epigenetic marks in various model systems. The data generated is often then interpreted by groups seeking to link these binding sites to the expression of adjacent or distal genes, and more broadly to the evolution of species, cell fate/differentiation or even cancer development. Against this backdrop is an ongoing debate over the relative importance DNA sequence versus chromatin structure and modification in the regulation of gene expression (Anon. 2008a Nature 454: 795; Anon. 2008b Nature 454: 711-715; Henikoff et al. 2008 Science 322: 853; Madhani et al. 2008 Science 322: 43-44). Rationally there is a synergy between the two and the goal of a biologist is to characterise both comprehensively enough to explain a cellular phenotype or a developmental process. If this is truly our goal then the critical factor in good science is an awareness of the constraints and potential of the biological models used. The reality however is often that this discussion is polarised by funding imperatives and the need to align to a transcription factor or epigenetic camp. This article will discuss the extrapolations involved in using ChIP data to draw conclusions about these themes and the discoveries that have resulted.

Colocalization of synapsin and actin during synaptic vesicle recycling

It has been hypothesized that in the mature nerve terminal, interactions between synapsin and actin regulate the clustering of synaptic vesicles and the availability of vesicles for release during synaptic activity. Here, we have used immunogold electron microscopy to examine the subcellular localization of actin and synapsin in the giant synapse in lamprey at different states of synaptic activity. In agreement with earlier observations, in synapses at rest, synapsin immunoreactivity was preferentially localized to a portion of the vesicle cluster distal to the active zone. During synaptic activity, however, synapsin was detected in the pool of vesicles proximal to the active zone. In addition, actin and synapsin were found colocalized in a dynamic filamentous cytomatrix at the sites of synaptic vesicle recycling, endocytic zones. Synapsin immunolabeling was not associated with clathrin-coated intermediates but was found on vesicles that appeared to be recycling back to the cluster. Disruption of synapsin function by microinjection of antisynapsin antibodies resulted in a prominent reduction of the cytomatrix at endocytic zones of active synapses. Our data suggest that in addition to its known function in clustering of vesicles in the reserve pool, synapsin migrates from the synaptic vesicle cluster and participates in the organization of the actin-rich cytomatrix in the endocytic zone during synaptic activity.

Cooperative Beamforming and User Selection for Improving the Security of Relay-aided Systems

A relay network in which a source wishes to convey a confidential message to a legitimate destination with the assistance of trusted relays is considered. In particular, cooperative beamforming and user selection techniques are applied to protect the confidential message. The secrecy rate (SR) and secrecy outage probability (SOP) of the network are investigated first, and a tight upper bound for the SR and an exact formula for the SOP are derived. Next, asymptotic approximations for the SR and SOP in the high signal-to-noise ratio (SNR) regime are derived for two different schemes: i) cooperative beamforming and ii) multiuser selection. Further, a new concept of cooperative diversity gain, namely, adapted cooperative diversity gain (ACDG), which can be used to evaluate security level of a cooperative relaying network, is investigated. It is shown that the ACDG of cooperative beamforming is equal to the conventional cooperative diversity gain of traditional multiple-input single-output networks, while the ACDG of the multiuser scenario is equal to that of traditional single-input multiple-output networks.

Multilayer Dielectric Stack Parameter Modelling for FSS Design

This paper discusses modelling multilayer dielectric stacks for use as substrate support for frequency selective surface. A method of a fast simulation of multilayer dielectric stack as a complementary tool for FSS design is proposed. Using the method analysis of effect of different parts of the multilayer stack has been performed. The tool has also been used for extraction of material parameters from the measured results. Measured transmission and reflection of a sample manufactured material stack show good agreement with the simulated results obtained for extracted material parameters.

Analysis of the Second Harmonic Effect on Power Amplifier Intermodulation Products

A theoretical analysis is reported in this paper to investigate the effect that a second harmonic signal which might be present at an amplifier’s input has on generating additional intermodulation products, particularly the third-order intermodulation (IM3) products. The analysis shows that the amplitude of an extra generated IM3 component is equal to the product of the fundamental amplitude, the second harmonic amplitude, and the second order Taylor series coefficient. The effect of the second order harmonic on the IM3 is examined through a simulated example of a 2.22-GHz 10-W Class-EF amplifier whereby the IM3 levels have been reduced by 2-3 dB after employing a second harmonic termination stub at the input.

Towards generalized Doherty power amplifier design for multiband operation

This paper presents a new variant of broadband Doherty power amplifier that employs a novel output combiner. A new parameter ∝ is introduced to permit a generalized analysis of the recently reported Parallel Doherty power amplifier (PDPA),and hence offer design flexibility. The circuit prototype of the new DPA fabricated using GaN devices exhibits maximum drain efficiency of 85% at 43-dBm peak power and 63% at 6-dB backoff power (BOP). Measured drain efficiency of >60% at peak power across 500-MHz frequency range and >50% at 6-dB BOP across 480-MHz frequency range were achieved, confirming the  theoretical wideband characteristics of the new DPA.

Propagation Characteristics of Groove Gap Waveguide Below and Above Cutoff

Recently, gap waveguides have been shown as a potential alternative to conventional waveguides in the millimeterwave band. Until now, Groove Gap Waveguide (GGW) has been studied through direct correspondence with rectangular waveguide with the same physical dimensions. However there have been observed differences in the above cutoff propagation characteristics between these two waveguide types. Furthermore, the behavior of GGW below cutoff remains unknown. This work presents a discussion of both below and above cutoff propagation characteristics of GGW, and introduces a simple model that explains the observed GGW behavior and establishes well its propagation characteristics. Two TRL calibration kits have been manufactured, and the measurements have good agreement with the proposed analysis model results.

Resonantly loaded apertures for high-resolution near field surface imaging

A novel type of microwave probes based on the loaded aperture geometry has been proposed and experimentally evaluated for dielectrics characterisation and high-resolution near-field imaging. Experimental results demonstrate the possibility of very accurate microwave spectroscopic characterisation of thin lossy dielectric samples and biological materials containing water. High-resolution images of the subwavelength lossy dielectric strips and wet and dry leaves have been obtained with amplitude contrast around 10-20 dB and spatial resolution better than one-tenth of a wavelength in the near-field zone. A microwave imaging scenario for the early-stage skin cancer identification based on the artificial dielectric model has also been explored. This model study shows that the typical resolution of an artificial malignant tumour with a characteristic size of one-tenth of a wavelength can be discriminated with at least 6 dB amplitude and 50° phase contrast from the artificial healthy skin and with more than 3 dB contrast from a benign lesion of the same size. It has also been demonstrated that the proposed device can efficiently deliver microwave energy to very small, subwavelength, focal areas which is highly sought in the microwave hyperthermia applications.

Increasing the TRL of an L band Retrodirective array for Type Approved SATCOM applications

Retrodirective, self-steering, antennas have the advantage of being able to automatically return a signal back in the direction along from which it originated. The tracking is real time and is carried out in the analogue domain which results in simple circuits which can be accommodated, planar-form, behind the antenna elements. The main objective of this paper is to detail the continuation of the work on L band retrodirective antennas which has the ambition of increasing the TRL such that a minimal viable product can be produced, suitable for type approval as an L band SATCOM user terminal. The focus will be the technical challenges that have arisen as the retrodirective antenna is moved up the TRL chain. Some of these aspects include the ability to track very weak modulated signals (S/N tending to 0dB), TX/RX filter and duplexer specifications, PA and LNA considerations. The resultant retrodirective architecture will be compared against typical specifications of L band satellite ground terminals, showing that the retrodirective antenna offers a simple and effective real time tracking antenna architecture.