High fidelity imaging and high performance computing in nonlinear EIT

We show that nonlinear EIT provides images with well defined characteristics when smoothness of the image is used as a constraint in the reconstruction process. We use the gradient of the logarithm of resistivity as an effective measure of image smoothness, which has the advantage that resistivity and conductivity are treated with equal weight. We suggest that a measure of the fidelity of the image to the object requires the explicit definition and application of such a constraint. The algorithm is applied to the simulation of intra-ventricular haemorrhaging (IVH) in a simple head model. The results indicate that a 5% increase in the blood content of the ventricles would be easily detectable with the noise performance of contemporary instrumentation. The possible implementation of the algorithm in real time via high performance computing is discussed

Comparative analyses of genetic trends and prospects for selection against hip and elbow dysplasia in 15 UK dog breeds

BACKGROUND: Hip dysplasia remains one of the most serious hereditary diseases occurring in dogs despite long-standing evaluation schemes designed to aid selection for healthy joints. Many researchers have recommended the use of estimated breeding values (EBV) to improve the rate of genetic progress from selection against hip and elbow dysplasia (another common developmental orthopaedic disorder), but few have empirically quantified the benefits of their use. This study aimed to both determine recent genetic trends in hip and elbow dysplasia, and evaluate the potential improvements in response to selection that publication of EBV for such diseases would provide, across a wide range of pure-bred dog breeds. RESULTS: The genetic trend with respect to hip and elbow condition due to phenotypic selection had improved in all breeds, except the Siberian Husky. However, derived selection intensities are extremely weak, equivalent to excluding less than a maximum of 18% of the highest risk animals from breeding. EBV for hip and elbow score were predicted to be on average between 1.16 and 1.34 times more accurate than selection on individual or both parental phenotypes. Additionally, compared to the proportion of juvenile animals with both parental phenotypes, the proportion with EBV of a greater accuracy than selection on such phenotypes increased by up to 3-fold for hip score and up to 13-fold for elbow score. CONCLUSIONS: EBV are shown to be both more accurate and abundant than phenotype, providing more reliable information on the genetic risk of disease for a greater proportion of the population. Because the accuracy of selection is directly related to genetic progress, use of EBV can be expected to benefit selection for the improvement of canine health and welfare. Public availability of EBV for hip score for the fifteen breeds included in this study will provide information on the genetic risk of disease in nearly a third of all dogs annually registered by the UK Kennel Club, with in excess of a quarter having an EBV for elbow score as well

Genetic Evaluation of the Nine Component Features of Hip Score in UK Labrador Retrievers

The aim of this study was to explore the genetic relationship between the nine component traits comprising the British Veterinary Association (BVA) total hip score in UK registered Labrador Retrievers. Data consisted of 11,928 single records of trait scores of dogs aged between one and four years (365–1459 days) old, from radiographs evaluated between 2000 and 2007. Pedigree information was provided by the UK Kennel Club. The distribution of trait scores showed only small numbers of dogs with visible malformation in the six traits that were scored according to the severity of osteoarthritis. Linear mixed models were fitted using ASREML. Estimates of heritability ranged from 0.15 to 0.38, and litter effects from 0.04 to 0.10. Genetic correlations between all nine traits were extremely high ranging from 0.71 to 1.0, implying considerable genetic similarity. The decomposition demonstrated that aggregate scores of only the 3 traits indicative of laxity in one year old dogs was predictive of the phenotype of the remaining six scored on osteoarthritic severity in dogs at 4+ years old. The application of selection index methodology in selecting against hip dysplasia using the trait scores was explored and potential improvements in accuracy (directly related to response to selection) of over 10% are reported compared to the current total hip score. This study demonstrates that traits descriptive of joint laxity are valuable early-age predictors of osteoarthritis and shows that there is scope for improvement in the way data from the UK hip score scheme are used for selection against hip dysplasia in Labradors. This was verified via use of selection indices, which identified substantial increases in accuracy, not only via optimum coefficients, but also through an easily applicable aggregate of scores of just two or three traits only compared with the current total hip score

Implementing Neural Network-Based Equalizers in a Coherent Optical Transmission System Using Field-Programmable Gate Arrays

In this work, we demonstrate the offline FPGA realization of both recurrent and feedforward neural network (NN)-based equalizers for nonlinearity compensation in coherent optical transmission systems. First, we present a realization pipeline showing the conversion of the models from Python libraries to the FPGA chip synthesis and implementation. Then, we review the main alternatives for the hardware implementation of nonlinear activation functions. The main results are divided into three parts: a performance comparison, an analysis of how activation functions are implemented, and a report on the complexity of the hardware. The performance in Q-factor is presented for the cases of bidirectional long-short-term memory coupled with convolutional NN (biLSTM + CNN) equalizer, CNN equalizer, and standard 1-StpS digital back-propagation (DBP) for the simulation and experiment propagation of a single channel dual-polarization (SC-DP) 16QAM at 34 GBd along 17x70km of LEAF. The biLSTM+CNN equalizer provides a similar result to DBP and a 1.7 dB Q-factor gain compared with the chromatic dispersion compensation baseline in the experimental dataset. After that, we assess the Q-factor and the impact of hardware utilization when approximating the activation functions of NN using Taylor series, piecewise linear, and look-up table (LUT) approximations. We also show how to mitigate the approximation errors with extra training and provide some insights into possible gradient problems in the LUT approximation. Finally, to evaluate the complexity of hardware implementation to achieve 400G throughput, fixed-point NN-based equalizers with approximated activation functions are developed and implemented in an FPGA.Comment: Invited paper at Journal of Lightwave Technology - IEE

Size-associated Variation and Factors Affecting the Morphology of Brown Bodies in Glycera tridactyla (Polychaeta:Glyceridae)

Size-associated variations in brown body morphology (size and shape) were studied from the individuals of Glycera tridactyla. Variables related to size, length (BL) and width (BW) of the brown bodies were measured. On the basis of these measurements, other variables such as the surface area (SA), volume (V), surface area/volume ratio (SA/V) and elongation degree (ED) were calculated. Brown body shape was quantified by the elongation degree. The immature brown bodies were significantly smaller than the mature bodies, and therefore the smaller bodies had a higher SA/V. Results obtained from the regression analysis showed that there was a significant relationship between all the variables with the exception of SA/V:BW for the immature bodies and ED: BL for both groups of the bodies. The body size (proboscis length) of the worm and the sampling time (months) were the affecting factors on size and shape of the brown body. Brown bodies tend to be elongated as the proboscis length increased. The variation in size and/or shape of the brown bodies could refer to an adaptation to the movement along the coelomic fluid

Quantitative trait loci mapping for canine hip dysplasia and its related traits in UK Labrador Retrievers

BACKGROUND: Canine hip dysplasia (CHD) is characterised by a malformation of the hip joint, leading to osteoarthritis and lameness. Current breeding schemes against CHD have resulted in measurable but moderate responses. The application of marker-assisted selection, incorporating specific markers associated with the disease, or genomic selection, incorporating genome-wide markers, has the potential to dramatically improve results of breeding schemes. Our aims were to identify regions associated with hip dysplasia or its related traits using genome and chromosome-wide analysis, study the linkage disequilibrium (LD) in these regions and provide plausible gene candidates. This study is focused on the UK Labrador Retriever population, which has a high prevalence of the disease and participates in a recording program led by the British Veterinary Association (BVA) and The Kennel Club (KC). RESULTS: Two genome-wide and several chromosome-wide QTLs affecting CHD and its related traits were identified, indicating regions related to hip dysplasia. CONCLUSION: Consistent with previous studies, the genetic architecture of CHD appears to be based on many genes with small or moderate effect, suggesting that genomic selection rather than marker-assisted selection may be an appropriate strategy for reducing this disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-833) contains supplementary material, which is available to authorized users

The utility of low-density genotyping for imputation in the Thoroughbred horse

BACKGROUND: Despite the dramatic reduction in the cost of high-density genotyping that has occurred over the last decade, it remains one of the limiting factors for obtaining the large datasets required for genomic studies of disease in the horse. In this study, we investigated the potential for low-density genotyping and subsequent imputation to address this problem. RESULTS: Using the haplotype phasing and imputation program, BEAGLE, it is possible to impute genotypes from low- to high-density (50K) in the Thoroughbred horse with reasonable to high accuracy. Analysis of the sources of variation in imputation accuracy revealed dependence both on the minor allele frequency of the single nucleotide polymorphisms (SNPs) being imputed and on the underlying linkage disequilibrium structure. Whereas equidistant spacing of the SNPs on the low-density panel worked well, optimising SNP selection to increase their minor allele frequency was advantageous, even when the panel was subsequently used in a population of different geographical origin. Replacing base pair position with linkage disequilibrium map distance reduced the variation in imputation accuracy across SNPs. Whereas a 1K SNP panel was generally sufficient to ensure that more than 80% of genotypes were correctly imputed, other studies suggest that a 2K to 3K panel is more efficient to minimize the subsequent loss of accuracy in genomic prediction analyses. The relationship between accuracy and genotyping costs for the different low-density panels, suggests that a 2K SNP panel would represent good value for money. CONCLUSIONS: Low-density genotyping with a 2K SNP panel followed by imputation provides a compromise between cost and accuracy that could promote more widespread genotyping, and hence the use of genomic information in horses. In addition to offering a low cost alternative to high-density genotyping, imputation provides a means to combine datasets from different genotyping platforms, which is becoming necessary since researchers are starting to use the recently developed equine 70K SNP chip. However, more work is needed to evaluate the impact of between-breed differences on imputation accuracy

A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses

Fractures caused by bone overloading are a leading cause of euthanasia in Thoroughbred racehorses. The risk of fatal fracture has been shown to be influenced by both environmental and genetic factors but, to date, no specific genetic mechanisms underpinning fractures have been identified. In this study, we utilised a genome-wide polygenic risk score to establish an in vitro cell system to study bone gene regulation in horses at high and low genetic risk of fracture. Candidate gene expression analysis revealed differential expression of COL3A1 and STAT1 genes in osteoblasts derived from high- and low-risk horses. Whole-genome sequencing of two fracture cases and two control horses revealed a single-nucleotide polymorphism (SNP) upstream of COL3A1 that was confirmed in a larger cohort to be significantly associated with fractures. Bioinformatics tools predicted that this SNP may impact the binding of the transcription factor SOX11. Gene modulation demonstrated SOX11 is upstream of COL3A1, and the region binds to nuclear proteins. Furthermore, luciferase assays demonstrated that the region containing the SNP has promoter activity. However, the specific effect of the SNP depends on the broader genetic background of the cells and suggests other factors may also be involved in regulating COL3A1 expression. In conclusion, we have identified a novel SNP that is significantly associated with fracture risk and provide new insights into the regulation of the COL3A1 gene

Fas Signalling Promotes Intercellular Communication in T Cells

Cell-to-cell communication is a fundamental process for development and maintenance of multicellular organisms. Diverse mechanisms for the exchange of molecular information between cells have been documented, such as the exchange of membrane fragments (trogocytosis), formation of tunneling nanotubes (TNTs) and release of microvesicles (MVs). In this study we assign to Fas signalling a pivotal role for intercellular communication in CD4+ T cells. Binding of membrane-bound FasL to Fas expressing target cells triggers a well-characterized pro-apoptotic signalling cascade. However, our results, pairing up flow cytometric studies with confocal microscopy data, highlight a new social dimension for Fas/FasL interactions between CD4+ T cells. Indeed, FasL enhances the formation of cell conjugates (8 fold of increase) in an early time-frame of stimulation (30 min), and this phenomenon appears to be a crucial step to prime intercellular communication. Our findings show that this communication mainly proceeds along a cytosolic material exchange (ratio of exchange >10, calculated as ratio of stimulated cells signal divided by that recorded in control cells) via TNTs and MVs release. In particular, inhibition of TNTs genesis by pharmacological agents (Latruculin A and Nocodazole) markedly reduced this exchange (inhibition percentage: >40% and >50% respectively), suggesting a key role for TNTs in CD4+ T cells communication. Although MVs are present in supernatants from PHA-activated T cells, Fas treatment also leads to a significant increase in the amount of released MVs. In fact, the co-culture performed between MVs and untreated cells highlights a higher presence of MVs in the medium (1.4 fold of increase) and a significant MVs uptake (6 fold of increase) by untreated T lymphocytes. We conclude that Fas signalling induces intercellular communication in CD4+ T cells by different mechanisms that seem to start concomitantly with the main pathway (programmed cell death) promoted by FasL