Mating-system evolution in Euplotes, from the Mendelian to a molecular approach.

Euplotes evolved multiple mating systems which have for long been assumed to be determined by "open" series of alleles at a single mat locus. Families of mating type-specific pheromones and of their mat coding genes have been extensively characterized from Euplotes species lying in different positions of Euplotes phylogenetic tree, and this characterization permitted the study of Euplotes mating systems to evolve from a Mendelian to a molecular approach. While early branching species (e.g. E. raikovi) show a mating-type determination at a single mat locus in accord with Mendelian genetics, late branching species (e.g. E. crassus) revealed, in disagreement with Mendelian genetics, a mating-type determination at two distinct mat loci implying an event of mat-gene locus duplication. One locus (orthologous) appears to be multi-allelic and deputed to synthesize pheromones distinctive of different mating types, and the second one (paralogous) deputed to synthesize pheromones that are structurally identical among different mating types

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

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

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

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

Stride: a flexible software platform for high-performance ultrasound computed tomography

BACKGROUND AND OBJECTIVE: Advanced ultrasound computed tomography techniques like full-waveform inversion are mathematically complex and orders of magnitude more computationally expensive than conventional ultrasound imaging methods. This computational and algorithmic complexity, and a lack of open-source libraries in this field, represent a barrier preventing the generalised adoption of these techniques, slowing the pace of research, and hindering reproducibility. Consequently, we have developed Stride, an open-source Python library for the solution of large-scale ultrasound tomography problems. METHODS: On one hand, Stride provides high-level interfaces and tools for expressing the types of optimisation problems encountered in medical ultrasound tomography. On the other, these high-level abstractions seamlessly integrate with high-performance wave-equation solvers and with scalable parallelisation routines. The wave-equation solvers are generated automatically using Devito, a domain-specific language, and the parallelisation routines are provided through the custom actor-based library Mosaic. RESULTS: We demonstrate the modelling accuracy achieved by our wave-equation solvers through a comparison (1) with analytical solutions for a homogeneous medium, and (2) with state-of-the-art modelling software applied to a high-contrast, complex skull section. Additionally, we show through a series of examples how Stride can handle realistic numerical and experimental tomographic problems, in 2D and 3D, and how it can scale robustly from a local multi-processing environment to a multi-node high-performance cluster. CONCLUSIONS: Stride enables researchers to rapidly and intuitively develop new imaging algorithms and to explore novel physics without sacrificing performance and scalability. This will lead to faster scientific progress in this field and will significantly ease clinical translation

Antarctic and Arctic populations of the ciliate Euplotes nobilii show common pheromone-mediated cell-cell signaling and cross-mating.

Wild-type strains of the protozoan ciliate Euplotes collected from different locations on the coasts of Antarctica, Tierra del Fuego and the Arctic were taxonomically identified as the morpho-species Euplotes nobilii, based on morphometric and phylogenetic analyses. Subsequent studies of their sexual interactions revealed that mating combinations of Antarctic and Arctic strains form stable pairs of conjugant cells. These conjugant pairs were isolated and shown to complete mutual gene exchange and cross-fertilization. The biological significance of this finding was further substantiated by demonstrating that close homology exists among the threedimensional structures determined by NMR of the water-borne signaling pheromones that are constitutively secreted into the extracellular space by these interbreeding strains, in which these molecules trigger the switch between the growth stage and the sexual stage of the life cycle. The fact that Antarctic and Arctic E. nobilii populations share the same gene pool and belong to the same biological species provides new support to the biogeographic model of global distribution of eukaryotic microorganisms, which had so far been based exclusively on studies of morphological and phylogenetic taxonomy

Towards self-verification in finite difference code generation

Code generation from domain-specific languages is becoming increasingly popular as a method to obtain optimised low-level code that performs well on a given platform and for a given problem instance. Ensuring the correctness of generated codes is crucial. At the same time, testing or manual inspection of the code is problematic, as the generated code can be complex and hard to read. Moreover, the generated code may change depending on the problem type, domain size, or target platform, making conventional code review or testing methods impractical. As a solution, we propose the integration of formal verification tools into the code generation process. We present a case study in which the CIVL verification tool is combined with the Devito finite difference framework that generates optimised stencil code for PDE solvers from symbolic equations. We show a selection of properties of the generated code that can be automatically specified and verified during the code generation process. Our approach allowed us to detect a previously unknown bug in the Devito code generation tool