c-FLIP: A Key Regulator of Colorectal Cancer Cell Death

c-FLIP is an inhibitor of apoptosis mediated by the death receptors Fas, DR4 and DR5 and is expressed as long (c-FLIPL) and short (c-FLIPS) splice forms. We found that siRNA-mediated silencing of c-FLIP induced spontaneous apoptosis in a panel of p53 wild-type, mutant and null colorectal cancer (CRC) cell lines and that this apoptosis was mediated by caspase 8 and FADD. Further analyses indicated the involvement of DR5 and/or Fas (but not DR4) in regulating apoptosis induced by c-FLIP siRNA. Interestingly, these effects were not dependent on activation of DR5 or Fas by their ligands TRAIL and FasL. Overexpression of c-FLIPL, but not c-FLIPS, significantly decreased spontaneous and chemotherapy-induced apoptosis in HCT116 cells. Further analyses with splice form-specific siRNAs indicated that c-FLIPL was the more important splice form in regulating apoptosis in HCT116, H630 and LoVo cells, although specific knock down of c-FLIPS induced more apoptosis in the HT29 cell line. Importantly, intra-tumoral delivery of c-FLIP-targeted siRNA duplexes induced apoptosis and inhibited the growth of HCT116 xenografts in Balb/c SCID mice. In addition, the growth of c-FLIPL overexpressing CRC xenografts was more rapid than control xenografts, an effect that was significantly enhanced in the presence of chemotherapy. These results indicate that c-FLIP inhibits spontaneous death ligand-independent, death receptor-mediated apoptosis in CRC cells and that targeting c-FLIP may have therapeutic potential for the treatment of colorectal cancer.

A method for determining generators’ shares in loads, line flows and losses

This paper presents a new method for calculating the individual generators’ shares in line flows, line losses and loads. The method is described and illustrated on active power flows, but it can be applied in the same way to reactive power flows. Starting from a power flow solution, the line flow matrix is formed. This matrix is used for identifying node types, tracing the power flow from generators downstream to loads, and to determine generators’ participation factors to lines and loads. Neither exhaustive search nor matrix inversion is required. Hence, the method is claimed to be the least computationally demanding amongst all of the similar methods.

The impact of the intrinsic and extrinsic resistances of double gate SOI on RF performance

In this paper, the analogue performance of a 65 nm node double gate Sol (DGSOI) is qualitatively investigated using MixedMode simulation. The intrinsic resistance of the device is optimised by evaluating the impact of the source/drain engineering using variation of spacers and doping profile on the RF key figures of merit such as f(T), and f(MAX). It is evident that longer spacers, which approach the length of the gate offer better RF performance irrespective of the profile as long as the doping gradient at the gate edge is <7 nm/decade. Analytical expressions, which reflect the dependence of f(T), and fMAX on extrinsic source, drain and gate resistances R-S, R-D and R-G have been derived. While R-D and R-S have equal effect on f(T), R-D appears to be more influential than R-S in reducing f(MAX). The sensitivity of f(MAX) to R-S and R-D. has been shown to be greater than to R-G. (c) 2006 Elsevier Ltd. All rights reserved.

Engineering source/drain extension regions in nanoscale double gate (DG) SOI MOSFETs: Analytical model and design considerations

In this paper, we propose for the first time, an analytical model for short channel effects in nanoscale source/drain extension region engineered double gate (DG) SOI MOSFETs. The impact of (i) lateral source/drain doping gradient (d), (ii) spacer width (s), (iii) spacer to doping gradient ratio (s/d) and (iv) silicon film thickness (T-si), on short channel effects - threshold voltage (V-th) and subthreshold slope (S), on-current (I-on), off-current (I-on) and I-on/I-off is extensively analysed by using the analytical model and 2D device simulations. The results of the analytical model confirm well with simulated data over the entire range of spacer widths, doping gradients and effective channel lengths. Results show that lateral source/drain doping gradient along with spacer width can not only effectively control short channel effects, thus presenting low off-current, but can also be optimised to achieve high values of on-currents. The present work provides valuable design insights in the performance of nanoscale DG Sol devices with optimal source/drain engineering and serves as a tool to optimise important device and technological parameters for 65 nm technology node and below. (c) 2006 Elsevier Ltd. All rights reserved.

Open-ended microwave oven for flip-chip assembly

A novel open-ended waveguide cavity resonator for the microwave curing of bumps, underfills and encapsulants is described. The open oven has the potential to provide fast alignment of devices during flip-chip assembly, direct chip attach, surface mount assembly or wafer-scale level packaging. The prototype microwave oven was designed to operate at X-band for ease of testing, although a higher frequency version is planned. The device described in the paper takes the form of a waveguide cavity resonator. It is approximately square in cross-section and is filled with a low-loss dielectric with a relative permittivity of 6. It is excited by end-fed probes in order to couple power preferentially into the TM3,3,k mode with the object of forming nine 'hot-spots' in the open end. Low power tests using heat sensitive film demonstrate clearly that selective heating in multiple locations in the open end of the oven is achievable.

Geometric bonding effects in the X2A1, A2∑+u, and B2IIg states of Li2F

Published ab-initio and pseudopotential calculations for the dialkali halide systems suggest that the preferred co-linear geometry is for the metal to approach the metal end of the alkali halide. Here, ab-initio calculations on the Li2F system reveal that the well depth on the halide side in this radical is much deeper and is a local saddle-point associated with the ionic non-linear global minima. Although many features of the pseudopotential surfaces are confirmed, significant differences are apparent including the existence of a linear excited state instead of a triangular one, a considerably deeper global minimum some 50% lower in energy and a close approach between the X2A1 and the states, with the minimum 87 kJ mol-1 below the ground state asymptote. All the results can be rationalised as the avoided crossings between a long range, covalent potential dominant within the LiLiF geometry and an ionic state that forms the global minimum. Calculations on the 3rd 2A' potential indicate that even for Li + LiF collisions at ultracold temperatures the collision dynamics could involve as many as three electronic states.

Effect of Selfish Node Behavior on Efficient Topology Design

The problem of topology control is to assign per-node transmission power such that the resulting topology is energy efficient and satisfies certain global properties such as connectivity. The conventional approach to achieve these objectives is based on the fundamental assumption that nodes are socially responsible. We examine the following question: if nodes behave in a selfish manner, how does it impact the overall connectivity and energy consumption in the resulting topologies? We pose the above problem as a noncooperative game and use game-theoretic analysis to address it. We study Nash equilibrium properties of the topology control game and evaluate the efficiency of the induced topology when nodes employ a greedy best response algorithm. We show that even when the nodes have complete information about the network, the steady-state topologies are suboptimal. We propose a modified algorithm based on a better response dynamic and show that this algorithm is guaranteed to converge to energy-efficient and connected topologies. Moreover, the node transmit power levels are more evenly distributed, and the network performance is comparable to that obtained from centralized algorithms.

Cooperative transmission protocol with full diversity and iterative detection

The authors propose a three-node full diversity cooperative protocol, which allows the retransmission of all symbols. By allowing multiple nodes to transmit simultaneously, relaying transmission only consumes limited bandwidth resource. To facilitate the performance analysis of the proposed cooperative protocol, the lower and upper bounds of the outage probability are first developed, and then the high signal-to-noise ratio behaviour is studied. Our analytical results show that the proposed strategy can achieve full diversity. To achieve the performance gain promised by the cooperative diversity, at the relays decode-and-forward strategy is adopted and an iterative soft-interference-cancellation minimum mean-squared error equaliser is developed. The simulation results compare the bit-error-rate performance of the proposed protocol with the non-cooperative scheme and the scheme presented by Azarian et al. ( 2005).

An Antennas and Propagation Approach to Improving Physical Layer Performance in Wireless Body Area Networks

A combined antennas and propagation study has been undertaken with a view to directly improving link conditions for wireless body area networks. Using tissue-equivalent numerical and experimental phantoms representative of muscle tissue at 2.45 GHz, we show that the node to node [S-21] path gain performance of a new wearable integrated antenna (WIA) is up to 9 dB better than a conventional compact Printed-F antenna, both of which are suitable for integration with wireless node circuitry. Overall, the WIA performed extremely well with a measured radiation efficiency of 38% and an impedance bandwidth of 24%. Further benefits were also obtained using spatial diversity, with the WIA providing up to 7.7 dB of diversity gain for maximal ratio combining. The results also show that correlation was lower for a multipath environment leading to higher diversity gain. Furthermore, a diversity implementation with the new antenna gave up to 18 dB better performance in terms of mean power level and there was a significant improvement in level crossing rates and average fade durations when moving from a single-branch to a two-branch diversity system.

Turbo channel estimation and equalisation for a superposition-based cooperative system

This study investigates the superposition-based cooperative transmission system. In this system, a key point is for the relay node to detect data transmitted from the source node. This issued was less considered in the existing literature as the channel is usually assumed to be flat fading and a priori known. In practice, however, the channel is not only a priori unknown but subject to frequency selective fading. Channel estimation is thus necessary. Of particular interest is the channel estimation at the relay node which imposes extra requirement for the system resources. The authors propose a novel turbo least-square channel estimator by exploring the superposition structure of the transmission data. The proposed channel estimator not only requires no pilot symbols but also has significantly better performance than the classic approach. The soft-in-soft-out minimum mean square error (MMSE) equaliser is also re-derived to match the superimposed data structure. Finally computer simulation results are shown to verify the proposed algorithm.

Priming of CD8+ and CD4+ T Cells in Experimental Leishmaniasis Is Initiated by Different Dendritic Cell Subtypes

The biological role of Langerin(+) dendritic cells (DCs) such as Langerhans cells and a subset of dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact of Langerin(+) DCs in adaptive T cell-mediated immunity toward Leishmania major parasites in a Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation of The biological role of Langerin+ dendritic cells (DCs) such as Langerhans cells and a subset of dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact of Langerin+ DCs in adaptive T cell-mediated immunity toward Leishmania major parasites in a Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation of Langerin+ DCs in vivo. For the first time, infection experiments with DT-treated Lang-DTR mice revealed that proliferation of L. major-specific CD8+ T cells is significantly reduced during the early phase of the immune response following depletion of Langerin+ DCs. Consequently, the total number of activated CD8+ T cells within the draining lymph node and at the site of infection is diminished. Furthermore, we show that the impaired CD8+ T cell response is due to the absence of Langerin+ dDCs and not Langerhans cells. Nevertheless, the CD4+ T cell response is not altered and the infection is cleared as effectively in DT-treated Lang-DTR mice as in control mice. This clearly demonstrates that Langerin+ DCs are, in general, dispensable for an efficient adaptive immune response against L. major parasites. Thus, we propose a novel concept that, in the experimental model of leishmaniasis, priming of CD4+ T cells is mediated by Langerin− dDCs, whereas Langerin+ dDCs are involved in early priming of CD8+ T cells.

Pattern Switching Compact Patch Antenna for On-body and Off-body Communications at 2.45 GHz

The ability to switch between propagating modes is important for body-centric applications such as medical body area networks where a single node may need to be able to optimise communications for either on-body sensor links or off-body links to the wider network. Therefore, we present a compact 2.45 GHz active mode-switching wearable antenna for both on-body and off-body wireless communications. The single-layer patch antenna was pattern-switched using shorting pins and had an impedance bandwidth of 253 MHz and 217 MHz for the on-body and off-body radiating modes, respectively. An efficiency of 57 % and 56.8 % was obtained for on-body and off-body mode respectively when placed in close proximity to a phantom that represents a muscle issue at 2.45 GHz.

Data mining approach identifies research priorities and data requirements for resolving the red algal tree of life

Background. The assembly of the tree of life has seen significant progress in recent years but algae and protists have been largely overlooked in this effort. Many groups of algae and protists have ancient roots and it is unclear how much data will be required to resolve their phylogenetic relationships for incorporation in the tree of life. The red algae, a group of primary photosynthetic eukaryotes of more than a billion years old, provide the earliest fossil evidence for eukaryotic multicellularity and sexual reproduction. Despite this evolutionary significance, their phylogenetic relationships are understudied. This study aims to infer a comprehensive red algal tree of life at the family level from a supermatrix containing data mined from GenBank. We aim to locate remaining regions of low support in the topology, evaluate their causes and estimate the amount of data required to resolve them. Results. Phylogenetic analysis of a supermatrix of 14 loci and 98 red algal families yielded the most complete red algal tree of life to date. Visualization of statistical support showed the presence of five poorly supported regions. Causes for low support were identified with statistics about the age of the region, data availability and node density, showing that poor support has different origins in different parts of the tree. Parametric simulation experiments yielded optimistic estimates of how much data will be needed to resolve the poorly supported regions (ca. 103 to ca. 104 nucleotides for the different regions). Nonparametric simulations gave a markedly more pessimistic image, some regions requiring more than 2.8 105 nucleotides or not achieving the desired level of support at all. The discrepancies between parametric and nonparametric simulations are discussed in light of our dataset and known attributes of both approaches. Conclusions. Our study takes the red algae one step closer to meaningful inclusion in the tree of life. In addition to the recovery of stable relationships, the recognition of five regions in need of further study is a significant outcome of this work. Based on our analyses of current availability and future requirements of data, we make clear recommendations for forthcoming research.

Stability and dynamical behavior in a lake-model and implications for regime shifts in real lakes

A modified abstract version of the Comprehensive Aquatic Simulation Model (CASM) is found to exhibit three types of folded bifurcations due to nutrient loading. The resulting bifurcation diagrams account for nonlinear dynamics such as regime shifts and cyclic changes between clear-water state and turbid state that have actually been observed in real lakes. In particular, pulse-perturbation simulations based on the model presented suggest that temporal behaviors of real lakes after biomanipulations can be explained by pulse-dynamics in complex ecosystems, and that not only the amplitude (manipulated abundance of organisms) but also the phase (timing) is important for restoring lakes by biomanipulation. Ecosystem management in terms of possible irreversible changes in ecosystems induced by regime shifts is also discussed. (c) 2007 Elsevier B.V All rights reserved.