Optimization strategies for fast detection of positive selection on phylogenetic trees.

MOTIVATION: The detection of positive selection is widely used to study gene and genome evolution, but its application remains limited by the high computational cost of existing implementations. We present a series of computational optimizations for more efficient estimation of the likelihood function on large-scale phylogenetic problems. We illustrate our approach using the branch-site model of codon evolution. RESULTS: We introduce novel optimization techniques that substantially outperform both CodeML from the PAML package and our previously optimized sequential version SlimCodeML. These techniques can also be applied to other likelihood-based phylogeny software. Our implementation scales well for large numbers of codons and/or species. It can therefore analyse substantially larger datasets than CodeML. We evaluated FastCodeML on different platforms and measured average sequential speedups of FastCodeML (single-threaded) versus CodeML of up to 5.8, average speedups of FastCodeML (multi-threaded) versus CodeML on a single node (shared memory) of up to 36.9 for 12 CPU cores, and average speedups of the distributed FastCodeML versus CodeML of up to 170.9 on eight nodes (96 CPU cores in total).Availability and implementation: ftp://ftp.vital-it.ch/tools/FastCodeML/. CONTACT: [email protected] or [email protected]

ELM triggering conditions for the integrated modeling of H-mode plasmas

Recent advances in the integrated modeling of ELMy H-mode plasmas are presented. A model for the H-mode pedestal and for the triggering of ELMs predicts the height, width, and shape of the H-mode pedestal and the frequency and width of ELMs. Formation of the pedestal and the L-H transition is the direct result of ExB flow shear suppression of anomalous transport. The periodic ELM crashes are triggered by either the ballooning or peeling MHD instabilities. The BALOO, DCON, and ELITE ideal MHD stability codes are used to derive a new parametric expression for the peeling-ballooning threshold. The new dependence for the peeling-ballooning threshold is implemented in the ASTRA transport code. Results of integrated modeling of DIII-D like discharges are presented and compared with experimental observations. The results from the ideal MHD stability codes are compared with results from the resistive MHD stability code NIMROD.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

Development of a full-size divertor cassette prototype for ITER

Production of a full-size divertor cassette involves eight major components. All of the components are mounted on the cassette body. Inner divertor channel components for the vertical target design are being provided by the Japan Home Team. Outer divertor channel components for the vertical target design are being provided by the European and United States Home Teams. Gas box liners are being provided by the Russian Home Team. The full-size components manufactured by the four parties will be shipped to the US Home Team for assembly into a full size divertor cassette. The techniques for assembly and maintenance of the cassette will be demonstrated during this process. The assembled cassette will be tested for proper flow distribution and proof of the filling and draining procedures. The testing will include vacuum leak tightness at full temperature and pressure, cyclic heating to 150 {degrees}C, verification of dimensional accuracy of the assembled components, and application of thermal gradients to measure dimensional stability. The development of the divertor for the International Thermonuclear Experimental Reactor (ITER) depends on successful R&D efforts on materials, joining, and plasma materials interactions. Results of the development program are presented. The scale-up of the processes developed in the basic research and development tasks is accomplished by producing and high-heat-flux testing medium and full-scale mock- ups. The design of the mock-ups is discussed

Role of A2A adenosine receptors in regulation of opsonized E. coli-induced macrophage function

Adenosine is a biologically active molecule that is formed at sites of metabolic stress associated with trauma and inflammation, and its systemic level reaches high concentrations in sepsis. We have recently shown that inactivation of A2A adenosine receptors decreases bacterial burden as well as IL-10, IL-6, and MIP-2 production in mice that were made septic by cecal ligation and puncture (CLP). Macrophages are important in both elimination of pathogens and cytokine production in sepsis. Therefore, in the present study, we questioned whether macrophages are responsible for the decreased bacterial load and cytokine production in A2A receptor-inactivated septic mice. We showed that A2A KO and WT peritoneal macrophages obtained from septic animals were equally effective in phagocytosing opsonized E. coli. IL-10 production induced by opsonized E. coli was decreased in macrophages obtained from septic A2A KO mice as compared to WT counterparts. In contrast, the release of IL-6 and MIP-2 induced by opsonized E. coli was higher in septic A2A KO macrophages than WT macrophages. These results suggest that peritoneal macrophages are not responsible for the decreased bacterial load and diminished MIP-2 and IL-6 production that are observed in septic A2A KO mice. In contrast, peritoneal macrophages may contribute to the suppressive effect of A2A receptor inactivation on IL-10 production during sepsis

Interacting spinor and scalar fields in Bianchi type-I Universe filled with viscous fluid: exact and numerical solutions

We consider a self-consistent system of spinor and scalar fields within the framework of a Bianchi type I gravitational field filled with viscous fluid in presence of a $\Lambda$ term. Exact self-consistent solutions to the corresponding spinor, scalar and BI gravitational field equations are obtained in terms of $\tau$, where $\tau$ is the volume scale of BI universe. System of equations for $\tau$ and \ve, where \ve is the energy of the viscous fluid, is deduced. Some special cases allowing exact solutions are thoroughly studied.Comment: 18 pages, 6 figure

Nonlinear spinor field in Bianchi type-I Universe filled with viscous fluid: numerical solutions

We consider a system of nonlinear spinor and a Bianchi type I gravitational fields in presence of viscous fluid. The nonlinear term in the spinor field Lagrangian is chosen to be $\lambda F$, with $\lambda$ being a self-coupling constant and $F$ being a function of the invariants $I$ an $J$ constructed from bilinear spinor forms $S$ and $P$. Self-consistent solutions to the spinor and BI gravitational field equations are obtained in terms of $\tau$, where $\tau$ is the volume scale of BI universe. System of equations for $\tau$ and \ve, where \ve is the energy of the viscous fluid, is deduced. This system is solved numerically for some special cases.Comment: 15 pages, 4 figure

A multiscale hybrid model for pro-angiogenic calcium signals in a vascular endothelial cell

Cytosolic calcium machinery is one of the principal signaling mechanisms by which endothelial cells (ECs) respond to external stimuli during several biological processes, including vascular progression in both physiological and pathological conditions. Low concentrations of angiogenic factors (such as VEGF) activate in fact complex pathways involving, among others, second messengers arachidonic acid (AA) and nitric oxide (NO), which in turn control the activity of plasma membrane calcium channels. The subsequent increase in the intracellular level of the ion regulates fundamental biophysical properties of ECs (such as elasticity, intrinsic motility, and chemical strength), enhancing their migratory capacity. Previously, a number of continuous models have represented cytosolic calcium dynamics, while EC migration in angiogenesis has been separately approached with discrete, lattice-based techniques. These two components are here integrated and interfaced to provide a multiscale and hybrid Cellular Potts Model (CPM), where the phenomenology of a motile EC is realistically mediated by its calcium-dependent subcellular events. The model, based on a realistic 3-D cell morphology with a nuclear and a cytosolic region, is set with known biochemical and electrophysiological data. In particular, the resulting simulations are able to reproduce and describe the polarization process, typical of stimulated vascular cells, in various experimental conditions.Moreover, by analyzing the mutual interactions between multilevel biochemical and biomechanical aspects, our study investigates ways to inhibit cell migration: such strategies have in fact the potential to result in pharmacological interventions useful to disrupt malignant vascular progressio

Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD