Analytical Biases Associated with GC-Content in Molecular Evolution.

Molecular evolution is being revolutionized by high-throughput sequencing allowing an increased amount of genome-wide data available for multiple species. While base composition summarized by GC-content is one of the first metrics measured in genomes, its genomic distribution is a frequently neglected feature in downstream analyses based on DNA sequence comparisons. Here, we show how base composition heterogeneity among loci and taxa can bias common molecular evolution analyses such as phylogenetic tree reconstruction, detection of natural selection and estimation of codon usage. We then discuss the biological, technical and methodological causes of these GC-associated biases and suggest approaches to overcome them

Internal states of model isotropic granular packings. III. Elastic properties

In this third and final paper of a series, elastic properties of numerically simulated isotropic packings of spherical beads assembled by different procedures and subjected to a varying confining pressure P are investigated. In addition P, which determines the stiffness of contacts by Hertz's law, elastic moduli are chiefly sensitive to the coordination number, the possible values of which are not necessarily correlated with the density. Comparisons of numerical and experimental results for glass beads in the 10kPa-10MPa range reveal similar differences between dry samples compacted by vibrations and lubricated packings. The greater stiffness of the latter, in spite of their lower density, can hence be attributed to a larger coordination number. Voigt and Reuss bounds bracket bulk modulus B accurately, but simple estimation schemes fail for shear modulus G, especially in poorly coordinated configurations under low P. Tenuous, fragile networks respond differently to changes in load direction, as compared to load intensity. The shear modulus, in poorly coordinated packings, tends to vary proportionally to the degree of force indeterminacy per unit volume. The elastic range extends to small strain intervals, in agreement with experimental observations. The origins of nonelastic response are discussed. We conclude that elastic moduli provide access to mechanically important information about coordination numbers, which escape direct measurement techniques, and indicate further perspectives.Comment: Published in Physical Review E 25 page

Strain versus stress in a model granular material: a Devil's staircase

The series of equilibrium states reached by disordered packings of rigid, frictionless discs in two dimensions, under gradually varying stress, are studied by numerical simulations. Statistical properties of trajectories in configuration space are found to be independent of specific assumptions ruling granular dynamics, and determined by geometry only. A monotonic increase in some macroscopic loading parameter causes a discrete sequence of rearrangements. For a biaxial compression, we show that, due to the statistical importance of such events of large magnitudes, the dependence of the resulting strain on stress direction is a Levy flight in the thermodynamic limit.Comment: REVTeX, 4 pages, 5 included PostScript figures. New version altered throughout text, very close to published pape

Simulation of material consequences induced by fsw for a trigonal pin

The numerical simulation of Friction Stir Welding processes involves the coupling of a solid mechanics approach under large strains and large strain rates and heat transfer. The eulerian formalism leads to specially efficient finite element simulations of the matter flow under steady conditions. But with such a formulation, the calculation of the consequences induced by the stirring on the material (stirred state, microstructure, etc.) requires the coupling of advection equations for integrating the associated state variables. In this paper, a moving mesh strategy is proposed for the numerical simulation of Friction Stir Welding and material consequences, for complex pin’s geometries. The numerical processing is detailed and the efficiency of the proposed method is discussed on a Friction Stir Welding simulation of 7075 series aluminum alloy

Using genotyping-by-sequencing to understand Musa diversity

Poster presented at Plant and Animal Genome, PAG XXII. San Diego (USA), 11-15 Jan 201

The TheLMA project: Multi-GPU Implementation of the Lattice Boltzmann Method

International audienceIn this paper, we describe the implementation of a multi-graphical processing unit (GPU) fluid flow solver based on the lattice Boltzmann method (LBM). The LBM is a novel approach in computational fluid dynamics, with numerous interesting features from a computational, numerical, and physical standpoint. Our program is based on CUDA and uses POSIX threads to manage multiple computation devices. Using recently released hardware, our solver may therefore run eight GPUs in parallel, which allows us to perform simulations at a rather large scale. Performance and scalability are excellent, the speedup over sequential implementations being at least of two orders of magnitude. In addition, we discuss tiling and communication issues for present and forthcoming implementations

Gunshot injuries of the spine

The Acute Spinal Injury Unit, relocated from Conradie Hospital to Groote Schuur Hospital in mid-2003, admitted 162 patients in the first year of its existence. A large number of these injuries were the result of interpersonal violence, particularly gunshot wounds. Aim. To review patients with gunshot injuries to the spine, with reference to neurological injury, associated injuries, need for surgery and complications. Methods. A comprehensive database is maintained to collect data on all spinal injury admissions. These data, as well as case notes and X-rays, were reviewed for all gunshot spine patients admitted to the Acute Spinal Injury Unit over a year. Forty-nine patients were identified. Thirty-eight were male and 11 female with an average age of 27.5 years (range 15 - 51 ± 8.53). The average stay in the acute unit was 30 (4 - 109 ± 28) days. Results. The spinal injury was complete in 38 and incomplete in 8, with 3 having no neurological deficit. The level was cervical in 13, thoracic in 24 and lumbar in 12. Only 9 patients improved neurologically. The spine was considered stable in 43 cases. Stabilisation was performed in the 6 unstable cases. The bullets were removed in 11 cases as they were in the canal. There were 55 significant associated injuries, viz. 14 haemo-pneumothoraces, 16 abdominal visceral injuries, 3 vascular injuries, 4 injuries of the brachial plexus and 3 of the oesophagus, 2 tracheal injuries, 1 soft palate injury and 11 non-spinal fractures. Complications included 3 deaths and discitis in 3 cases, pneumonia in 6 and pressure sores in 6. Conclusion. Gunshot injuries of the spine are a prevalent and resource-intensive cause of paralysis. There is a high incidence of permanent severe neurological deficit, but usually the spine remains mechanically stable. Most of the management revolves around the associated injuries and consequences of the neurological deficit

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

Some anti-diabetic therapies can have adverse effects on bone health and increase fracture risk. In this study, we tested the skeletal effects of chronic administration of two Glucagon-like peptide-1 receptor agonists (GLP-1RA), increasingly used for type 2 diabetes treatment, in a model of osteoporosis associated bone loss and examined the expression and activation of GLP-1R in bone cells. Mice were ovariectomised (OVX) to induce bone loss and four weeks later they were treated with Liraglutide (LIR) 0.3 mg/kg/day, Exenatide (Ex-4) 10 μg/kg/day or saline for four weeks. Mice were injected with calcein and alizarin red prior to euthanasia, to label bone-mineralising surfaces. Tibial micro-architecture was determined by micro-CT and bone formation and resorption parameters measured by histomorphometric analysis. Serum was collected to measure calcitonin and sclerostin levels, inhibitors of bone resorption and formation, respectively. GLP-1R mRNA and protein expression were evaluated in the bone, bone marrow and bone cells using RT-PCR and immunohistochemistry. Primary osteoclasts and osteoblasts were cultured to evaluate the effect of GLP-1RA on bone resorption and formation in vitro. GLP-1RA significantly increased trabecular bone mass, connectivity and structure parameters but had no effect on cortical bone. There was no effect of GLP-1RA on bone formation in vivo but an increase in osteoclast number and osteoclast surfaces was observed with Ex-4. GLP-1R was expressed in bone marrow cells, primary osteoclasts and osteoblasts and in late osteocytic cell line. Both Ex-4 and LIR stimulated osteoclastic differentiation in vitro but slightly reduced the area resorbed per osteoclast. They had no effect on bone nodule formation in vitro. Serum calcitonin levels were increased and sclerostin levels decreased by Ex-4 but not by LIR. Thus, GLP-1RA can have beneficial effects on bone and the expression of GLP-1R in bone cells may imply that these effects are exerted directly on the tissue

Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength

Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites