Numerical simulation of neutron radiation effects in avalanche photodiodes

A new one-dimensional (1-D) device model developed for the simulation of neutron radiation effects in silicon avalanche photodiodes is described. The model uses a finite difference technique to solve the time-independent semiconductor equations across a user specified structure. The model includes impact ionization and illumination allowing accurate simulation with minimal assumptions. The effect of neutron radiation damage is incorporated via the introduction of deep acceptor levels subject to Shockley-Read-Hall statistics. Preliminary analysis of an EG&G reverse APD structure is compared with experimental data from a commercial EG&G C30719F APD

Oilseed rape (Brassica napus) as a resource for farmland insect pollinators: quantifying floral traits in conventional varieties and breeding systems

This is the final version of the article. Available from the publisher via the DOI in this record.Oilseed rape (OSR; Brassica napus L.) is a major crop in temperate regions and provides an important source ofnutrition to many of the yield-enhancing insect flower visitors that consume floral nectar. The manipulation ofmechanisms that control various crop plant traits for the benefit of pollinators has been suggested in the bid toincrease food security, but little is known about inherent floral trait expression in contemporary OSR varieties orthe breeding systems used in OSR breeding programmes. We studied a range of floral traits in glasshouse-grown, certified conventional varieties of winter OSR to test for variation among and within breeding systems.We measured 24-h nectar secretion rate, amount, concentration and ratio of nectar sugars per flower, and sizesand number of flowers produced per plant from 24 varieties of OSR representing open-pollinated (OP), genicmale sterility (GMS) hybrid and cytoplasmic male sterility (CMS) hybrid breeding systems. Sugar concentrationwas consistent among and within the breeding systems; however, GMS hybrids produced more nectar and moresugar per flower than CMS hybrid or OP varieties. With the exception of ratio of fructose/glucose in OP vari-eties, we found that nectar traits were consistent within all the breeding systems. When scaled, GMS hybridsproduced 1.73 times more nectar resource per plant than OP varieties. Nectar production and amount of nectarsugar in OSR plants were independent of number and size of flowers. Our data show that floral traits of glass-house-grown OSR differed among breeding systems, suggesting that manipulation and enhancement of nectarrewards for insect flower visitors, including pollinators, could be included in future OSR breeding programmes.This work was fundedby the BBSRC, including support from an Insect Pollinators Ini-tiative grant awarded to GAW (BB/I000968/1) that was jointlyfunded by the BBSRC, NERC, the Wellcome Trust, Defra, andthe Scottish Government. Support was also received from HighWycombe Beekeepers’ Association. Rothamsted Researchreceives strategic funding from the Biotechnology and BiologicalSciences Research Council (BBSRC) of the UK

So near and yet so far: harmonic radar reveals reduced homing ability of Nosema infected honeybees.

© 2014 Wolf et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Citation: Wolf S, McMahon DP, Lim KS, Pull CD, Clark SJ, et al. (2014) So Near and Yet So Far: Harmonic Radar Reveals Reduced Homing Ability of Nosema Infected Honeybees. PLoS ONE 9(8): e103989. doi:10.1371/journal.pone.0103989Pathogens may gain a fitness advantage through manipulation of the behaviour of their hosts. Likewise, host behavioural changes can be a defence mechanism, counteracting the impact of pathogens on host fitness. We apply harmonic radar technology to characterize the impact of an emerging pathogen--Nosema ceranae (Microsporidia)--on honeybee (Apis mellifera) flight and orientation performance in the field. Honeybees are the most important commercial pollinators. Emerging diseases have been proposed to play a prominent role in colony decline, partly through sub-lethal behavioural manipulation of their hosts. We found that homing success was significantly reduced in diseased (65.8%) versus healthy foragers (92.5%). Although lost bees had significantly reduced continuous flight times and prolonged resting times, other flight characteristics and navigational abilities showed no significant difference between infected and non-infected bees. Our results suggest that infected bees express normal flight characteristics but are constrained in their homing ability, potentially compromising the colony by reducing its resource inputs, but also counteracting the intra-colony spread of infection. We provide the first high-resolution analysis of sub-lethal effects of an emerging disease on insect flight behaviour. The potential causes and the implications for both host and parasite are discussed.Biotechnology and Biological Sciences Research Council (BBSRC)Department for Environment Food & Rural Affairs (DEFRA)Natural Environment Research Council (NERC)The Scottish GovernmentWellcome Trus

Long-term spatiotemporal stability and dynamic changes in helminth infracommunities of bank voles (Myodes glareolus) in NE Poland

Parasites are considered to be an important selective force in host evolution but ecological studies of host-parasite systems are usually short-term providing only snap-shots of what may be dynamic systems. We have conducted four surveys of helminths of bank voles at three ecologically similar woodland sites in NE Poland, spaced over a period of 11 years, to assess the relative importance of temporal and spatial effects on helminth infracommunities. Some measures of infracom- munity structure maintained relative stability: the rank order of prevalence and abundance of Heligmosomum mixtum, Heligmosomoides glareoli and Mastophorus muris changed little between the four surveys. Other measures changed markedly: dynamic changes were evident in Syphacia petrusewiczi which declined to local extinction, while the capillariid Aonchotheca annulosa first appeared in 2002 and then increased in prevalence and abundance over the remaining three surveys. Some species are therefore dynamic and both introductions and extinctions can be expected in ecological time. At higher taxonomic levels and for derived measures, year and host-age effects and their interactions with site are import- ant. Our surveys emphasize that the site of capture is the major determinant of the species contributing to helminth community structure, providing some predictability in these systems

Flight performance of actively foraging honey bees is reduced by a common pathogen

ArticleSudden and severe declines in honey bee (Apis mellifera) colony health in the US and Europe have been attributed, in part, to emergent microbial pathogens, however, the mechanisms behind the impact are unclear. Using roundabout flight mills, we measured the flight distance and duration of actively foraging, healthy-looking honey bees sampled from standard colonies, before quantifying the level of infection by Nosema ceranae and Deformed Wing Virus complex (DWV) for each bee. Neither the presence nor quantity of N. ceranae at low, natural levels of infection had any effect on flight distance or duration, but presence of DWV reduced flight distance by two thirds and duration by one half. Quantity of DWV was shown to have a significant, but weakly positive relation with flight distance and duration, however, the low amount of variation that was accounted for suggests further investigation by dose-response assays is required. We conclude that widespread, naturally occurring levels of infection by DWV weaken the flight ability of honey bees and high levels of within-colony prevalence are likely to reduce efficiency and increase the cost of resource acquisition. Predictions of implications of pathogens on colony health and function should take account of sub-lethal effects on flight performance.This work was funded by the Insect Pollinators Initiative (IPI) grants BB/I000100/1, BB/I000097/1 and BB/I000097/2, C.B. Dennis British Beekeepers' Research Trust and the High Wycombe Beekeepers’ Association. The IPI is funded jointly by the BBSRC, Defra, NERC, The Scottish Government and The Wellcome Trust, under the LWEC Partnership. Rothamsted Research is a national institute of bioscience strategically funded by the BBSRC

Development of novel bioassays to detect soluble and aggregated Huntingtin proteins on three technology platforms

Huntington’s disease is caused by a CAG / polyglutamine repeat expansion. Mutated CAG repeats undergo somatic instability, resulting in tracts of several hundred CAGs in the brain; and genetic modifiers of Huntington’s disease have indicated that somatic instability is a major driver of age of onset and disease progression. As the CAG repeat expands, the likelihood that exon 1 does not splice to exon 2 increases, resulting in two transcripts that encode full-length huntingtin protein, as well as the highly pathogenic and aggregation-prone exon 1 huntingtin protein. Strategies that target the huntingtin gene or transcripts are a major focus of therapeutic development. It is essential that the levels of all isoforms of huntingtin protein can be tracked, to better understand the molecular pathogenesis, and to assess the impact of huntingtin protein-lowering approaches in preclinical studies and clinical trials. Huntingtin protein bioassays for soluble and aggregated forms of huntingtin protein are in widespread use on the homogeneous time-resolved fluorescence and Meso Scale Discovery platforms, but these do not distinguish between exon 1 huntingtin protein and full-length huntingtin protein. In addition, they are frequently used to quantify huntingtin protein levels in the context of highly expanded polyglutamine tracts, for which appropriate protein standards do not currently exist. Here, we set out to develop novel huntingtin protein bioassays to ensure that all soluble huntingtin protein isoforms could be distinguished. We utilized the zQ175 Huntington’s disease mouse model that has ∼190 CAGs, a CAG repeat size for which protein standards are not available. Initially, 30 combinations of six antibodies were tested on three technology platforms: homogeneous time-resolved fluorescence, amplified luminescent proximity homogeneous assay and Meso Scale Discovery, and a triage strategy was employed to select the best assays. We found that, without a polyglutamine-length-matched standard, the vast majority of soluble mutant huntingtin protein assays cannot be used for quantitative purposes, as the highly expanded polyglutamine tract decreased assay performance. The combination of our novel assays, with those already in existence, provides a tool-kit to track: total soluble mutant huntingtin protein, soluble exon 1 huntingtin protein, soluble mutant huntingtin protein (excluding the exon 1 huntingtin protein) and total soluble full-length huntingtin protein (mutant and wild type). Several novel aggregation assays were also developed that track with disease progression. These selected assays can be used to compare the levels of huntingtin protein isoforms in a wide variety of mouse models of Huntington’s disease and to determine how these change in response to genetic or therapeutic manipulations

Two distinct conformations of factor H regulate discrete complement-binding functions in the fluid phase and at cell surfaces

Factor H (FH) is the major regulator of C3b in the alternative pathway of the complement system in immunity. FH comprises 20 short complement regulator (SCR) domains, including eight glycans, and its Y402H polymorphism predisposes those who carry it for age-related macular degeneration. To better understand FH complement binding and self-association, we have studied the solution structures of both the His402 and Tyr402 FH allotypes. Analytical ultracentrifugation revealed that up to 12% of both FH allotypes self-associate, and this was confirmed by small angle X-ray scattering (SAXS), mass spectrometry and surface plasmon resonance analyses. SAXS showed that monomeric FH has a radius of gyration Rg of 7.2-7.8 nm and a length of 25 nm. Starting from known structures for the SCR domains and glycans, the SAXS data were fitted using Monte Carlo methods to determine atomistic structures for monomeric FH. The analysis of 29,715 physically realistic but randomised FH conformations resulted in 100 similar best-fit FH structures for each allotype. Two distinct molecular structures resulted that showed either an extended N-terminal domain arrangement with a folded-back C-terminus, or an extended C-terminus and folded-back N-terminus. These two structures are the most accurate to date for glycosylated full-length FH. To clarify FH functional roles in host protection, crystal structures for the FH complexes with C3b and C3dg revealed that the extended N-terminal conformation accounted for C3b fluid phase regulation, the extended C-terminal conformation accounted for C3d binding, and both conformations accounted for bivalent FH binding to glycosaminoglycans on the target cell surface

lp-Recovery of the Most Significant Subspace among Multiple Subspaces with Outliers

We assume data sampled from a mixture of d-dimensional linear subspaces with spherically symmetric distributions within each subspace and an additional outlier component with spherically symmetric distribution within the ambient space (for simplicity we may assume that all distributions are uniform on their corresponding unit spheres). We also assume mixture weights for the different components. We say that one of the underlying subspaces of the model is most significant if its mixture weight is higher than the sum of the mixture weights of all other subspaces. We study the recovery of the most significant subspace by minimizing the lp-averaged distances of data points from d-dimensional subspaces, where p>0. Unlike other lp minimization problems, this minimization is non-convex for all p>0 and thus requires different methods for its analysis. We show that if 0<p<=1, then for any fraction of outliers the most significant subspace can be recovered by lp minimization with overwhelming probability (which depends on the generating distribution and its parameters). We show that when adding small noise around the underlying subspaces the most significant subspace can be nearly recovered by lp minimization for any 0<p<=1 with an error proportional to the noise level. On the other hand, if p>1 and there is more than one underlying subspace, then with overwhelming probability the most significant subspace cannot be recovered or nearly recovered. This last result does not require spherically symmetric outliers.Comment: This is a revised version of the part of 1002.1994 that deals with single subspace recovery. V3: Improved estimates (in particular for Lemma 3.1 and for estimates relying on it), asymptotic dependence of probabilities and constants on D and d and further clarifications; for simplicity it assumes uniform distributions on spheres. V4: minor revision for the published versio

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials