What is the effect of systemic anticancer treatment on cognitive function?

Treatment regimens for solid tumours have been extensively investigated for their physical toxic effects, but far less is known about the potential impairment of cognitive function by anticancer treatment regimens. Here, we review published studies that examined cognitive function in adult patients receiving systemic therapy for solid tumours. Our review suggests that patients can experience cognitive changes related to their treatment. However, several studies had methodological limitations, such as use of a limited sample size, lack of baseline assessment, and lack of control for potential confounding factors. Better designed clinical trials are required so that the difficulties patients face in terms of reduced cognitive function as a result of anticancer treatment can be fully elucidated. These trials should have sufficient statistical power and, importantly, should also be prospective.

Assessment of LD matrix measures for the analysis of biological pathway association.

Complex diseases will have multiple functional sites, and it will be invaluable to understand the cross-locus interaction in terms of linkage disequilibrium (LD) between those sites (epistasis) in addition to the haplotype-LD effects. We investigated the statistical properties of a class of matrix-based statistics to assess this epistasis. These statistical methods include two LD contrast tests (Zaykin et al., 2006) and partial least squares regression (Wang et al., 2008). To estimate Type 1 error rates and power, we simulated multiple two-variant disease models using the SIMLA software package. SIMLA allows for the joint action of up to two disease genes in the simulated data with all possible multiplicative interaction effects between them. Our goal was to detect an interaction between multiple disease-causing variants by means of their linkage disequilibrium (LD) patterns with other markers. We measured the effects of marginal disease effect size, haplotype LD, disease prevalence and minor allele frequency have on cross-locus interaction (epistasis). In the setting of strong allele effects and strong interaction, the correlation between the two disease genes was weak (r=0.2). In a complex system with multiple correlations (both marginal and interaction), it was difficult to determine the source of a significant result. Despite these complications, the partial least squares and modified LD contrast methods maintained adequate power to detect the epistatic effects; however, for many of the analyses we often could not separate interaction from a strong marginal effect. While we did not exhaust the entire parameter space of possible models, we do provide guidance on the effects that population parameters have on cross-locus interaction.

Parallel implementation of the recurrence method for computing the power-spectral density of thin avalanche photodiodes

A simulation program has been developed to calculate the power-spectral density of thin avalanche photodiodes, which are used in optical networks. The program extends the time-domain analysis of the dead-space multiplication model to compute the autocorrelation function of the APD impulse response. However, the computation requires a large amount of memory space and is very time consuming. We describe our experiences in parallelizing the code using both MPI and OpenMP. Several array partitioning schemes and scheduling policies are implemented and tested Our results show that the OpenMP code is scalable up to 64 processors on an SGI Origin 2000 machine and has small average errors.

Optimizing the reliability of power electronics module isolation substrates

Optimal design of a power electronics module isolation substrate is assessed using a combination of finite element structural mechanics analysis and response surface optimisation technique. Primary failure modes in power electronics modules include the loss of structural integrity in the ceramic substrate materials due to stresses induced through thermal cycling. Analysis of the influence of ceramic substrate design parameters is undertaken using a design of experiments approach. Finite element analysis is used to determine the stress distribution for each design, and the results are used to construct a quadratic response surface function. A particle swarm optimisation algorithm is then used to determine the optimal substrate design. Analysis of response surface function gradients is used to perform sensitivity analysis and develop isolation substrate design rules. The influence of design uncertainties introduced through manufacturing tolerances is assessed using a Monte-Carlo algorithm, resulting in a stress distribution histogram. The probability of failure caused by the violation of design constraints has been analyzed. Six geometric design parameters are considered in this work and the most important design parameters have been identified. Overall analysis results can be used to enhance the design and reliability of the component.

Computer simulation of crack propagation in power electronics module solder joints

A numerical modelling method for the analysis of solder joint damage and crack propagation has been described in this paper. The method is based on the disturbed state concept. Under cyclic thermal-mechanical loading conditions, the level of damage that occurs in solder joints is assumed to be a simple monotonic scalar function of the accumulated equivalent plastic strain. The increase of damage leads to crack initiation and propagation. By tracking the evolution of the damage level in solder joints, crack propagation path and rate can be simulated using Finite Element Analysis method. The discussions are focused on issues in the implementation of the method. The technique of speeding up the simulation and the mesh dependency issues are analysed. As an example of the application of this method, crack propagation in solder joints of power electronics modules under cyclic thermal-mechanical loading conditions has been analyzed and the predicted cracked area size after 3000 loading cycles is consistent with experimental results.

The assessment of a global marine ecosystem model on the basis of emergent properties and ecosystem function: a case study with ERSEM

Ecosystem models are often assessed using quantitative metrics of absolute ecosystem state, but these model-data comparisons are disproportionately vulnerable to discrepancies in the location of important circulation features. An alternative method is to demonstrate the models capacity to represent ecosystem function; the emergence of a coherent natural relationship in a simulation indicates that the model may have an appropriate representation of the ecosystem functions that lead to the emergent relationship. Furthermore, as emergent properties are large-scale properties of the system, model validation with emergent properties is possible even when there is very little or no appropriate data for the region under study, or when the hydrodynamic component of the model differs significantly from that observed in nature at the same location and time. A selection of published meta-analyses are used to establish the validity of a complex marine ecosystem model and to demonstrate the power of validation with emergent properties. These relationships include the phytoplankton community structure, the ratio of carbon to chlorophyll in phytoplankton and particulate organic matter, the ratio of particulate organic carbon to particulate organic nitrogen and the stoichiometric balance of the ecosystem. These metrics can also inform aspects of the marine ecosystem model not available from traditional quantitative and qualitative methods. For instance, these emergent properties can be used to validate the design decisions of the model, such as the range of phytoplankton functional types and their behaviour, the stoichiometric flexibility with regards to each nutrient, and the choice of fixed or variable carbon to nitrogen ratios.

Escape times for rigid Brownian rotators in a bistable potential from the time evolution of the Green function and the characteristic time of the probability evolution

The greatest relaxation time for an assembly of three- dimensional rigid rotators in an axially symmetric bistable potential is obtained exactly in terms of continued fractions as a sum of the zero frequency decay functions (averages of the Legendre polynomials) of the system. This is accomplished by studying the entire time evolution of the Green function (transition probability) by expanding the time dependent distribution as a Fourier series and proceeding to the zero frequency limit of the Laplace transform of that distribution. The procedure is entirely analogous to the calculation of the characteristic time of the probability evolution (the integral of the configuration space probability density function with respect to the position co-ordinate) for a particle undergoing translational diffusion in a potential; a concept originally used by Malakhov and Pankratov (Physica A 229 (1996) 109). This procedure allowed them to obtain exact solutions of the Kramers one-dimensional translational escape rate problem for piecewise parabolic potentials. The solution was accomplished by posing the problem in terms of the appropriate Sturm-Liouville equation which could be solved in terms of the parabolic cylinder functions. The method (as applied to rotational problems and posed in terms of recurrence relations for the decay functions, i.e., the Brinkman approach c.f. Blomberg, Physica A 86 (1977) 49, as opposed to the Sturm-Liouville one) demonstrates clearly that the greatest relaxation time unlike the integral relaxation time which is governed by a single decay function (albeit coupled to all the others in non-linear fashion via the underlying recurrence relation) is governed by a sum of decay functions. The method is easily generalized to multidimensional state spaces by matrix continued fraction methods allowing one to treat non-axially symmetric potentials, where the distribution function is governed by two state variables. (C) 2001 Elsevier Science B.V. All rights reserved.

Identification and Development of Enzymes Associated With the Sperm Inner Acrosomal Membrane and Their Function during Fertilization

In order for mammalian fertilization to transpire, spermatozoa must transit through the female reproductive tract and penetrate the outer investments of the oocyte: the cumulus oophorus and the zona pellucida. In order to penetrate the oocyte, spermatozoa must undergo the acrosome reaction. The acrosome reaction results in the exposure of the inner acrosomal membrane (IAM) and proteins that coat it to the extracellular environment. After the acrosome reaction, the IAM becomes the leading edge of spermatozoa undergoing progressive movement. Thus the enzymes which effect lysis of the oocyte investments ought to be located on the IAM. An objective of this study was to identify and characterize enzymatic activity detected on the IAM and provide evidence that they play a role in fertilization. This study also describes procedures for fractionating spermatozoa and isolating the IAM and proteins on its intra- and extra-vesicular surfaces, and describes their development during male gametogenesis. Since the IAM is exposed to the extracellular environment and oviductal milieu after the acrosome reaction, this study also sought to characterize interactions and relationships between factors in the oviductal environment and the enzymes identified on the IAM. The data presented provide evidence that MMP2 and acrosin are co-localized on the IAM, originate from the Golgi apparatus in gametogenesis, and suggest they cooperate in their function. Their localization and results of in vitro fertilization suggests they have a function in zona pellucida penetration. The data also provide evidence that plasminogen, originating from the oviductal epithelium and/or cumulus-oocyte complex, is present in the immediate environment of sperm-egg initial contact and penetration. Additionally, plasminogen interacts with MMP2 and enhances its enzymatic action on the IAM. The data also provide evidence that MMP2 has an important function in penetration of the cumulus oophorus. Holistically, this thesis provides evidence that enzymes on the IAM, originating from the Golgi apparatus in development, have an important function in penetration of the outer investments of the oocyte, and are aided in penetration by plasminogen in the female reproductive tract.

Improved power-saving medium access protocol for IEEE 802.11e QoS-enabled wireless networks

The performance of a new pointer-based medium-access control protocol that was designed to significantly improve the energy efficiency of user terminals in quality-of-service-enabled wireless local area networks was analysed. The new protocol, pointer-controlled slot allocation and resynchronisation protocol (PCSARe), is based on the hybrid coordination function-controlled channel access mode of the IEEE 802.11e standard. PCSARe reduces energy consumption by removing the need for power-saving stations to remain awake for channel listening. Discrete event network simulations were performed to compare the performance of PCSARe with the non-automatic power save delivery (APSD) and scheduled-APSD power-saving modes of IEEE 802.11e. The simulation results show a demonstrable improvement in energy efficiency without significant reduction in performance when using PCSARe. For a wireless network consisting of an access point and eight stations in power-saving mode, the energy saving was up to 39% when using PCSARe instead of IEEE 802.11e non-APSD. The results also show that PCSARe offers significantly reduced uplink access delay over IEEE 802.11e non-APSD, while modestly improving the uplink throughput. Furthermore, although both had the same energy consumption, PCSARe gave a 25% reduction in downlink access delay compared with IEEE 802.11e S-APSD.

Plasma power measurement and hysteresis in the E-H transition of a rf inductively coupled plasma system

An experimental investigation of the argon plasma behavior near the E-H transition in an inductively coupled Gaseous Electronics Conference reference cell is reported. Electron density and temperature, ion density, argon metastable density, and optical emission measurements have been made as function of input power and gas pressure. When plotted versus plasma power, applied power corrected for coil and hardware losses, no hysteresis is observed in the measured plasma parameter dependence at the E-H mode transition. This suggests that hysteresis in the E-H mode transition is due to ignoring inherent power loss, primarily in the matching system.

The 67 kDa laminin receptor: structure, function and role in disease

The 67LR (67 kDa laminin receptor) is a cell-surface receptor with high affinity for its primary ligand. Its role as a laminin receptor makes it an important molecule both in cell adhesion to the basement membrane and in signalling transduction following this binding event. The protein also plays critical roles in the metastasis of tumour cells. Isolation of the protein from either normal or cancerous cells results in a product with an approx. molecular mass of 67 kDa. This protein is believed to be derived from a smaller precursor, the 37LRP (37 kDa laminin receptor precursor). However, the precise mechanism by which cytoplasmic 37LRP becomes cell-membrane-embedded 67LR is unclear. The process may involve post-translational fatty acylation of the protein combined with either homo- or hetero-dimerization, possibly with a galectin-3-epitope-containing partner. Furthermore, it has become clear that acting as a receptor for laminin is not the only function of this protein. 67LR also acts as a receptor for viruses, such as Sindbis virus and dengue virus, and is involved with internalization of the prion protein. Interestingly, unmodified 37LRP is a ribosomal component and homologues of this protein are found in all five kingdoms. In addition, it appears to be strongly associated with histones in the eukaryotic cell nucleus, although the precise role of these interactions is not clear. Here we review the current understanding of the structure and function of this molecule, as well as highlighting areas requiring further research.

A new Jacobian matrix for optimal learning of single-layer neural networks

This paper investigates the learning of a wide class of single-hidden-layer feedforward neural networks (SLFNs) with two sets of adjustable parameters, i.e., the nonlinear parameters in the hidden nodes and the linear output weights. The main objective is to both speed up the convergence of second-order learning algorithms such as Levenberg-Marquardt (LM), as well as to improve the network performance. This is achieved here by reducing the dimension of the solution space and by introducing a new Jacobian matrix. Unlike conventional supervised learning methods which optimize these two sets of parameters simultaneously, the linear output weights are first converted into dependent parameters, thereby removing the need for their explicit computation. Consequently, the neural network (NN) learning is performed over a solution space of reduced dimension. A new Jacobian matrix is then proposed for use with the popular second-order learning methods in order to achieve a more accurate approximation of the cost function. The efficacy of the proposed method is shown through an analysis of the computational complexity and by presenting simulation results from four different examples.

Analysis of multiple aspects of a repeated signal: power and rate of rapping during shell fights in hermit crabs

Repeated activities used by animals during contests are assumed to act as signals advertising the quality of the sender. However, their exact functions are not well understood and observations fit only a limited set of the predictions made by models of signaling systems. Experimental studies of contest behavior tend to focus on analysis of the rate of signaling, but individual performances may also vary in magnitude. Both of these features can vary between outcomes and within contests. We examined changes in the rate and power of shell rapping during shell fights in hermit crabs. We show that both rate and power decline during the course of the encounter and that the duration of pauses between bouts of shell rapping increases with an index of the total effort put into each bout. This supports the idea that the vigor of shell rapping is regulated by fatigue and could therefore act as a signal of stamina. By examining different interacting components of this complex activity, we gain greater insight into its function than would be achieved by investigating a single aspect in isolation.

Time-dependent R -matrix theory for ultrafast atomic processes

We describe an ab initio nonperturbative time-dependent R-matrix theory for ultrafast atomic processes. This theory enables investigations of the interaction of few-femtosecond and -attosecond pulse lasers with complex multielectron atoms and atomic ions. A derivation and analysis of the basic equations are given, which propagate the atomic wave function in the presence of the laser field forward in time in the internal and external R-matrix regions. To verify the accuracy of the approach, we investigate two-photon ionization of Ne irradiated by an intense laser pulse and compare current results with those obtained using the R-matrix Floquet method and an alternative time-dependent method. We also verify the capability of the current approach by applying it to the study of two-dimensional momentum distributions of electrons ejected from Ne due to irradiation by a sequence of 2 as light pulses in the presence of a 780 nm laser field.

Sequential extracellular matrix-focused and baited-global cluster analysis of serial transcriptomic profiles identifies candidate modulators of renal tubulointerstitial fibrosis in murine adriamycin-induced nephropathy

Transcriptome analysis using microarray technology represents a powerful unbiased approach for delineating pathogenic mechanisms in disease. Here molecular mechanisms of renal tubulointerstitial fibrosis (TIF) were probed by monitoring changes in the renal transcriptome in a glomerular disease-dependent model of TIF ( adriamycin nephropathy) using Affymetrix (mu74av2) microarray coupled with sequential primary biological function-focused and secondary