Costs of resistance: genetic correlations and potential trade-offs in an insect immune system

Theory predicts that natural selection will erode additive genetic variation in fitness-related traits. However, numerous studies have found considerable heritable variation in traits related to immune function, which should be closely linked to fitness. This could be due to trade-offs maintaining variation in these traits. We used the Egyptian cotton leafworm, Spodoptera littoralis, as a model system to examine the quantitative genetics of insect immune function. We estimated the heritabilities of several different measures of innate immunity and the genetic correlations between these immune traits and a number of life history traits. Our results provide the first evidence for a potential genetic trade-off within the insect immune system, with antibacterial activity (lysozyme-like) exhibiting a significant negative genetic correlation with haemocyte density, which itself is positively genetically correlated with both haemolymph phenoloxidase activity and cuticular melanization. We speculate on a potential trade-off between defence against parasites and predators, mediated by larval colour, and its role in maintaining genetic variation in traits under natural selection.

Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA stud

Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions.

Optimal proportional-integral-derivative control of shape memory alloy actuators using genetic algorithm and the Preisach model

Shape memory alloy (SMA) actuators, which have the ability to return to a predetermined shape when heated, have many potential applications in aeronautics, surgical tools, robotics, and so on. Although the number of applications is increasing, there has been limited success in precise motion control owing to the hysteresis effect of these smart actuators. The present paper proposes an optimization of the proportional-integral-derivative (PID) control method for SMA actuators by using genetic algorithm and the Preisach hysteresis model.

Modelling and Control of Shape Memory Alloy Actuators by using Preisach Model, Genetic Algorithm and Fuzzy Logic

Shapememoryalloy (SMA) actuators, which have the ability to return to a predetermined shape when heated, have many potential applications in aeronautics, surgical tools, robotics and so on. Nonlinearity hysteresis effects existing in SMA actuators present a problem in the motion control of these smart actuators. This paper investigates the control problem of SMA actuators in both simulation and experiment. In the simulation, the numerical Preisachmodel with geometrical interpretation is used for hysteresis modeling of SMA actuators. This model is then incorporated in a closed loop PID control strategy. The optimal values of PID parameters are determined by using geneticalgorithm to minimize the mean squared error between desired output displacement and simulated output. However, the control performance is not good compared with the simulation results when these parameters are applied to the real SMA control since the system is disturbed by unknown factors and changes in the surrounding environment of the system. A further automated readjustment of the PID parameters using fuzzylogic is proposed for compensating the limitation. To demonstrate the effectiveness of the proposed controller, real time control experiment results are presented.

Implementation and testing of Lanczos-based algorithms for Random-Phase Approximation eigenproblems

The treatment of the Random-Phase Approximation Hamiltonians, encountered in different frameworks, like time-dependent density functional theory or Bethe-Salpeter equation, is complicated by their non-Hermicity. Compared to their Hermitian Hamiltonian counterparts, computational methods for the treatment of non-Hermitian Hamiltonians are often less efficient and less stable, sometimes leading to the breakdown of the method. Recently [Gruning et al. Nano Lett. 8 (2009) 28201, we have identified that such Hamiltonians are usually pseudo-Hermitian. Exploiting this property, we have implemented an algorithm of the Lanczos type for Random-Phase Approximation Hamiltonians that benefits from the same stability and computational load as its Hermitian counterpart, and applied it to the study of the optical response of carbon nanotubes. We present here the related theoretical grounds and technical details, and study the performance of the algorithm for the calculation of the optical absorption of a molecule within the Bethe-Salpeter equation framework. (C) 2011 Elsevier B.V. All rights reserved.

Clinical and testing protocols for the analysis of epidermal growth factor receptor mutations in East Asian patients with non-small cell lung cancer:a combined clinical-molecular pathological approach

Several randomized phase III studies in advanced stage non-small cell lung cancer (NSCLC) confirmed the superior response rate and progression-free survival of using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor as first-line therapy compared with chemotherapy in patients with activating EGFR mutations. Despite the need for EGFR mutation tests to guide first-line therapy in East Asian NSCLC, there are no current standard clinical and testing protocols.

Design and testing of transonic linear cascade tunnel with optimized slotted walls

In linear cascade wind tunnel tests, a high level of pitchwise periodicity is desirable to reproduce the azimuthal periodicity in the stage of an axial compressor or turbine. Transonic tests in a cascade wind tunnel with open jet boundaries have been shown to suffer from spurious waves, reflected at the jet boundary, that compromise the flow periodicity in pitch. This problem can be tackled by placing at this boundary a slotted tailboard with a specific wall void ratio s and pitch angle a. The optimal value of the s-a pair depends on the test section geometry and on the tunnel running conditions. An inviscid two-dimensional numerical method has been developed to predict transonic linear cascade flows, with and without a tailboard, and quantify the nonperiodicity in the discharge. This method includes a new computational boundary condition to model the effects of the tailboard slots on the cascade interior flow. This method has been applied to a six-blade turbine nozzle cascade, transonically tested at the University of Leicester. The numerical results identified a specific slotted tailboard geometry, able to minimize the spurious reflected waves and regain some pitchwise flow periodicity. The wind tunnel open jet test section was redesigned accordingly. Pressure measurements at the cascade outlet and synchronous spark schlieren visualization of the test section, with and without the optimized slotted tailboard, have confirmed the gain in pitchwise periodicity predicted by the numerical model. Copyright © 2006 by ASME.

A specific pathway can be identified between genetic characteristics and behaviour profiles in Prader-Willi syndrome via cognitive, environmental and physiological mechanisms

Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences. However, relationships between different aspects of behavioural phenotypes have been less frequently researched and although recent interest in potential cognitive phenotypes or endophenotypes has increased, these are frequently studied independently of the behavioural phenotypes.

Taking Prader-Willi syndrome (PWS) as an example, we discuss evidence suggesting specific relationships between apparently distinct aspects of the PWS behavioural phenotype and relate these to specific endophenotypic characteristics.

The framework we describe progresses through biological, cognitive, physiological and behavioural levels to develop a pathway from genetic characteristics to behaviour with scope for interaction with the environment at any stage.

We propose this multilevel approach as useful in setting out hypotheses in order to structure research that can more rapidly advance theory.

Genetic polymorphisms and kidney transplant outcomes

Purpose of review: Gene polymorphism studies are growing at a quasiexponential rate and aim to improve immediate and long-term outcomes in renal transplantation. This review highlights recent evidence and potential future directions for genetic research studies.

Recent findings: Studies are largely based on immunity, inflammation and pharmacogenetics, investigating mostly 'surrogate' outcomes with sometimes conflicting results. However, the last 12 months has also heralded the emergence of important genome-wide association studies on transplantation, more robust replicated multicentre analyses of candidate gene variants, meta-analyses, and an increasing interest in copy number variation and donor genetics.

Summary: These studies set the scene for further investigation, aiming to understand pathways of disease and biomarkers of risk, and are leading to a greater understanding of the biology of transplantation. Future studies will require focus on donor : recipient and gene : environment interactions, and an integrated approach of 'transplantomics' to evaluate long-term outcomes in multinational collaborations.