Evolution of mating systems in Euplotes

Ciliates control their sexual phenomenon of conjugation (or mating) through a genetic mechanism of mating types, which may either be only two within a species (recalling the duality of sexes in animals), or multiple (recalling self/non-self compatibility systems in plants and fungi). The nearly one hundred species of the most ubiquitously distributed ciliate, Euplotes, all evolved multiple mating types. Based on analyses of Mendelian genetics, these mating types have for long been assumed to be determined by multi-allelic series of genes inherited at a single genetic locus (i.e., the mating-type or mat locus) and responsible for the synthesis of mating type-pecific signaling proteins. The chemical characterization of these signaling proteins (known as pheromones) from an array of Euplotes species has now permitted us to evolve in the study of Euplotes mating types from an approach of Mendelian genetics to an approach of molecular genetics. In this new experimental context, we have cloned and characterized structurally the pheromone (mating-type) gene families of Euplotes species that take different positions in the phylogenetic tree of the genus Euplotes. It appeared that, in accord with the prediction of the Mendelian genetics, early branching species (e.g., E. polaris, E. raikovi and E. nobilii) inherit their mating types at a single multi-allelic locus. However, in disagreement with the prediction of the Mendelian genetics, late branching species (e.g., E. crassus and E. focardii) inherit their mating types at two distinct loci that are likely the result of an event of gene duplication in the germinal (micronuclear) genome. One locus appears to be structurally and functionally homologous with the multi-allelic locus of the early branching species, while the second locus appears to be structurally homologous but functionally divergent

Temporal blocking of finite-difference stencil operators with sparse "off-the-grid" sources

Stencil kernels dominate a range of scientific applications, including seismic and medical imaging, image processing, and neural networks. Temporal blocking is a performance optimization that aims to reduce the required memory bandwidth of stencil computations by re-using data from the cache for multiple time steps. It has already been shown to be beneficial for this class of algorithms. However, applying temporal blocking to practical applications' stencils remains challenging. These computations often consist of sparsely located operators not aligned with the computational grid (“off-the-grid”). Our work is motivated by modelling problems in which source injections result in wavefields that must then be measured at receivers by interpolation from the grided wavefield. The resulting data dependencies make the adoption of temporal blocking much more challenging. We propose a methodology to inspect these data dependencies and reorder the computation, leading to performance gains in stencil codes where temporal blocking has not been applicable. We implement this novel scheme in the Devito domain-specific compiler toolchain. Devito implements a domain-specific language embedded in Python to generate optimized partial differential equation solvers using the finite-difference method from high-level symbolic problem definitions. We evaluate our scheme using isotropic acoustic, anisotropic acoustic, and isotropic elastic wave propagators of industrial significance. After auto-tuning, performance evaluation shows that this enables substantial performance improvement through temporal blocking over highly-optimized vectorized spatially-blocked code of up to 1.6x

Combining checkpointing and data compression for large scale seismic inversion

Seismic inversion and imaging are adjoint-based optimization problems that processes up to terabytes of data, regularly exceeding the memory capacity of available computers. Data compression is an effective strategy to reduce this memory requirement by a certain factor, particularly if some loss in accuracy is acceptable. A popular alternative is checkpointing, where data is stored at selected points in time, and values at other times are recomputed as needed from the last stored state. This allows arbitrarily large adjoint computations with limited memory, at the cost of additional recomputations. In this paper we combine compression and checkpointing for the first time to compute a realistic seismic inversion. The combination of checkpointing and compression allows larger adjoint computations compared to using only compression, and reduces the recomputation overhead significantly compared to using only checkpointing

Assessment of myocardial extracellular volume on body computed tomography in breast cancer patients treated with anthracyclines

Background: Cancer treatment with anthracyclines may lead to an increased incidence of cardiac disease due to cardiotoxicity, as they may cause irreversible myocardial fibrosis. So far, the proposed methods for screening patients for cardiotoxicity have led to only limited success, while the analysis of myocardial extracellular volume (mECV) at cardiac magnetic resonance (CMR) has shown promising results, albeit requiring a dedicated exam. Recent studies have found strong correlations between mECV values obtained through computed tomography (CT), and those derived from CMR. Thus, our purpose was to evaluate the feasibility of estimating mECV on thoracic contrast-enhanced CT performed for staging or follow-up in breast cancer patients treated with anthracyclines, and, if feasible, to assess if a rise in mECV is associated with chemotherapy, and persistent over time. Methods: After ethics committee approval, female patients with breast cancer who had undergone at least 2 staging or follow-up CT examinations at our institution, one before and one shortly after the end of chemotherapy including anthracyclines were retrospectively evaluated. Patients without available haematocrit, with artefacts in CT images, or who had undergone radiation therapy of the left breast were excluded. Follow-up CT examinations at longer time intervals were also analysed, when available. mECV was calculated on scans obtained at 1, and 7 min after contrast injection. Results: Thirty-two female patients (aged 57\ub113 years) with pre-treatment haematocrit 38%\ub14%, and ejection fraction 64%\ub16% were analysed. Pre-treatment mECV was 27.0%\ub12.9% at 1 min, and 26.4%\ub13.8% at 7 min, similar to values reported for normal subjects in the literature. Post-treatment mECV (median interval: 89 days after treatment) was 31.1%\ub14.9%, and 30.0%\ub15.1%, respectively, values significantly higher than pre-treatment values at all times (P<0.005). mECV at follow-up (median interval: 135 days after post-treatment CT) was 31.0%\ub14.5%, and 27.7%\ub13.7%, respectively, without significant differences (P>0.548) when compared to post-treatment values. Conclusions: mECV values from contrast-enhanced CT scans could play a role in the assessment of myocardial condition in breast cancer patients undergoing anthracycline-based chemotherapy. CT-derived ECV could be an imaging biomarker for the monitoring of therapy-related cardiotoxicity, allowing for potential secondary prevention of cardiac damage, using data derived from an examination that could be already part of patients\u2019 clinical workflow

Evidence for Gene Duplication and Allelic Codominance (not Hierarchical Dominance) at the Mating-Type Locus of the Ciliate, Euplotes crassus.

The high-multiple mating system of Euplotes crassus is known to be controlled by multiple alleles segregating at a single locus and manifesting relationships of hierarchical dominance, so that heterozygous cells would produce a single mating-type substance (pheromone). In strain L-2D, now known to be homozygous at the mating-type locus, we previously identified two pheromones (Ec-α and Ec-1) characterized by significant variations in their amino acid sequences and structure of their macronuclear coding genes. In this study, pheromones and macronuclear coding genes have been analyzed in strain POR-73 characterized by a heterozygous genotype and strong mating compatibility with L-2D strain. It was found that POR-73 cells contain three distinct pheromone coding genes and, accordingly, secrete three distinct pheromones. One pheromone revealed structural identity in amino acid sequence and macronuclear coding gene to the Ec-α pheromone of L-2D cells. The other two pheromones were shown to be new and were designated Ec-2 and Ec-3 to denote their structural homology with the Ec-1 pheromone of L-2D cells. We interpreted these results as evidence of a phenomenon of gene duplication at the E. crassus mating-type locus, and lack of hierarchical dominance in the expression of the macronuclear pheromone genes in cells with heterozygous genotypes

Full-waveform inversion, Part 3: Optimization

This tutorial is the third part of a full-waveform inversion (FWI) tutorial series with a step-by-step walkthrough of setting up forward and adjoint wave equations and building a basic FWI inversion framework. For discretizing and solving wave equations, we use Devito (http://www.opesci.org/devito-public), a Python-based domain-specific language for automated generation of finite-difference code (Lange et al., 2016). The first two parts of this tutorial (Louboutin et al., 2017, 2018) demonstrated how to solve the acoustic wave equation for modeling seismic shot records and how to compute the gradient of the FWI objective function using the adjoint-state method. With these two key ingredients, we will now build an inversion framework that can be used to minimize the FWI least-squares objective function