The era of whole-genome sequencing has revealed that gene copy-number changes caused by duplication and deletion events have important evolutionary, functional, and phenotypic consequences. Recent ...studies have therefore focused on revealing the extent of variation in copy-number within natural populations of humans and other species. These studies have found a large number of copy-number variants (CNVs) in humans, many of which have been shown to have clinical or evolutionary importance. For the most part, these studies have failed to detect an important class of gene copy-number polymorphism: gene duplications caused by retrotransposition, which result in a new intron-less copy of the parental gene being inserted into a random location in the genome. Here we describe a computational approach leveraging next-generation sequence data to detect gene copy-number variants caused by retrotransposition (retroCNVs), and we report the first genome-wide analysis of these variants in humans. We find that retroCNVs account for a substantial fraction of gene copy-number differences between any two individuals. Moreover, we show that these variants may often result in expressed chimeric transcripts, underscoring their potential for the evolution of novel gene functions. By locating the insertion sites of these duplicates, we are able to show that retroCNVs have had an important role in recent human adaptation, and we also uncover evidence that positive selection may currently be driving multiple retroCNVs toward fixation. Together these findings imply that retroCNVs are an especially important class of polymorphism, and that future studies of copy-number variation should search for these variants in order to illuminate their potential evolutionary and functional relevance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This work focuses on the numerical treatment of 1D flow in channels with arbitrary shape using energy balanced arguments. The system of equations is defined using the mass and momentum conservation ...equations, allowing the resolution of hydraulic jumps where energy conservation arguments are not valid. When necessary, conservation of mechanical energy takes part actively in the numerical scheme when evaluating the source terms. The numerical scheme is based on an augmented Roe solver that involves the presence of source terms by adding an extra stationary wave. The characteristics of the numerical scheme include the energy balanced property, and being only first order accurate in time and space, leads to exact numerical solutions for steady solutions with independence of the grid refinement in channels with general geometries. Riemann problems considered here involve non-prismatic channels, bed variations and the resonance regime, including the limiting situation when the Riemann data belong to the resonance hypersurface. Numerical results point out that the finite volume numerical scheme with nonconservative terms presented here, converges to the exact solution. The well balanced property is ensured, as it is a particular case of the energy balanced property in cases of quiescent equilibrium.
In this work, CFD simulation along with the site complete wind rose are used for the first time to estimate a key magnitude for the project development of a wind farm, the capacity factor, which is ...directly related with the energy yield. The large computational cost that restricted CFD simulation for such a task is drastically reduced by means of a novel interpolation-extrapolation methodology, requiring the simulation of only three inlet velocities for each wind rose sector. This methodology is based on the velocity at met mast and results of the reference velocity for each wind turbine from pre-simulated cases, which are then used to compute a wide range of cases not explicitly simulated. A comparative study is carried out, in which the measured capacity factor of an onshore wind farm in the Argentinean Patagonia is compared against different solution approaches. In the particular case of this wind farm, it is found that the separate effects of wakes and terrain produce errors in the opposite sense, and results very close to the measured value are achieved when both are considered. Also, the increase in the number of simulated direction sectors from 16 to 32 does not significantly change the results.
•A novel technique for estimating the capacity factor or the aggregated energy yield of a wind farm is developed.•CFD simulations accounting for wake and terrain effect and full wind roses are employed.•The number of CFD simulations are reduced to only 3 per wind sector, significantly saving computational effort.•The CF of an onshore wind farm is compared against different solutions with increasing level of description.•Results become very close to measurements when both wake and terrain are considered.
Damage control surgery (DCS) is a concept of abbreviated laparotomy, designed to prioritize short-term physiological recovery over anatomical reconstruction in the seriously injured and compromised ...patient. Over the last 10 yr, a new addition to the damage control paradigm has emerged, referred to as damage control resuscitation (DCR). This focuses on initial hypotensive resuscitation and early use of blood products to prevent the lethal triad of acidosis, coagulopathy, and hypothermia. This review aims to present the evidence behind DCR and its current application, and also to present a strategy of overall damage control to include DCR and DCS in conjunction. The use of DCR and DCS have been associated with improved outcomes for the severely injured and wider adoption of these principles where appropriate may allow this trend of improved survival to continue. In particular, DCR may allow borderline patients, who would previously have required DCS, to undergo early definitive surgery as their physiological derangement is corrected earlier.
This paper presents a space-time approximate diffusion-dispersion analysis of high-order, finite volume Upwind Central (UWC) and Weighted Essentially Non-Oscillatory (WENO) schemes. We perform a ...thorough study of the numerical errors to find a-priori guidelines for the computation of under-resolved turbulent flows. In particular, we study the 3-rd, 5-th and 7-th order UWC and WENO reconstructions in space, and 3-rd and 4-th order Runge-Kutta time integrators. To do so, we use the approximate von Neumann analysis for non-linear schemes introduced by Pirozzoli. Moreover, we apply the “1% rule” for the dispersion-diffusion curves proposed by Moura et al. 41 to determine the range of wavenumbers that are accurately resolved by each scheme. The dispersion-diffusion errors estimated from these analyses agree with the numerical results for the forced Burgers' turbulence problem, which we use as a benchmark. The cut-off wavenumbers defined by the “1% rule” are evidenced to serve as a good estimator of the beginning of the dissipation region of the energy cascade and they are shown to be associated to a similar level of dissipation, with independence of the scheme.
Finally, we show that WENO schemes are more diffusive than UWC schemes, leading to stable simulations at the price of more dissipative results. It is concluded both UWC and WENO schemes may be suitable schemes for iLES turbulence modeling, given their numerical dissipation level acting at the appropriate wavenumbers.
•A space-time dispersion-diffusion analysis of UWC-RK and WENO-RK is presented.•The “1% rule” determines the wavenumbers that are accurately resolved.•Cut-off wavenumbers are obtained for each scheme and different CFL numbers.•The results are supported by the forced Burgers turbulence problem.•UWC and WENO may be suitable for iLES, being WENO more dissipative than UWC.
Abstract
Background
Mutations arise in the human genome in two major settings: the germline and the soma. These settings involve different inheritance patterns, time scales, chromatin structures, and ...environmental exposures, all of which impact the resulting distribution of substitutions. Nonetheless, many of the same single nucleotide variants (SNVs) are shared between germline and somatic mutation databases, such as between the gnomAD database of 120,000 germline exomes and the TCGA database of 10,000 somatic exomes. Here, we sought to explain this overlap.
Results
After strict filtering to exclude common germline polymorphisms and sites with poor coverage or mappability, we found 336,987 variants shared between the somatic and germline databases. A uniform statistical model explains 34% of these shared variants; a model that incorporates the varying mutation rates of the basic mutation types explains another 50% of shared variants; and a model that includes extended nucleotide contexts (e.g. surrounding 3 bases on either side) explains an additional 4% of shared variants. Analysis of read depth finds mixed evidence that up to 4% of the shared variants may represent germline variants leaked into somatic call sets. 9% of the shared variants are not explained by any model. Sequencing errors and convergent evolution did not account for these. We surveyed other factors as well: Cancers driven by endogenous mutational processes share a greater fraction of variants with the germline, and recently derived germline variants were more likely to be somatically shared than were ancient germline ones.
Conclusions
Overall, we find that shared variants largely represent bona fide biological occurrences of the same variant in the germline and somatic setting and arise primarily because DNA has some of the same basic chemical vulnerabilities in either setting. Moreover, we find mixed evidence that somatic call-sets leak appreciable numbers of germline variants, which is relevant to genomic privacy regulations. In future studies, the similar chemical vulnerability of DNA between the somatic and germline settings might be used to help identify disease-related genes by guiding the development of background-mutation models that are informed by both somatic and germline patterns of variation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•A Roe solver for the simulation of non-hydrostatic pressure flows is presented.•Two different models are compared in terms of equations and numerical resolution.•Numerical details are provided to ...show the most suitable options when using a Roe solver.•The model is applied to classical dispersive test comparing with analytical and experimental data.
The aim of this work is, first of all, to extend a finite volume numerical scheme, previously designed for hydrostatic Shallow Water (SWE) formulation, to Non Hydrostatic Pressure (NHP) depth averaged model. The second objective is focused on exploring two available options in the context of previous work in this field: Hyperbolic-Elliptic (HE-NHP) formulations solved with a Pressure-Correction technique (PCM) and Hyperbolic Relaxation formulations (HR-NHP). Thus, besides providing an extension of a robust and well-proved Roe-type scheme developed for hydrostatic SWE to solve NHP systems, the work assesses the use of first order numerical schemes in the kind of phenomena typically solved with higher order methods. In particular, the relative performance and differences of both NHP numerical models are explored and analysed in detail. The performance of the models is compared using a steady flow test case with quasi-analytical solution and another unsteady case with experimental data, in which frequencies are analysed in experimental and computational results. The results highlight the need to understand the behaviour of a parameter-dependent model when using it as a prediction tool, and the importance of a proper discretization of non-hydrostatic source terms to ensure stability. On the other hand, it is proved that the incorporation of a non-hydrostatic model to a shallow water Roe solver provides good results.
A
bstract
Haloscopes are resonant cavities that serve as detectors of dark matter axions when they are immersed in a strong static magnetic field. In order to increase the volume and improve space ...compatibility with dipole or solenoid magnets for axion searches, various haloscope design techniques for rectangular geometries are discussed in this study. The volume limits of two types of haloscopes are explored: those based on single cavities and those based on multicavities. In both cases, possibilities for increasing the volume of long and/or tall structures are presented. For multicavities, 1D geometries are explored to optimise the space in the magnets. Also, 2D and 3D geometries are introduced as a first step in laying the foundations for the development of these kinds of topologies. The results prove the usefulness of the developed methods, evidencing the ample room for improvement in rectangular haloscope designs nowadays. A factor of three orders of magnitude improvement in volume compared with a single cavity based on the WR-90 standard waveguide is obtained with the design of a long and tall single cavity. Similar procedures have been applied for long and tall multicavities. Experimental measurements are shown for prototypes based on tall multicavities and 2D structures, demonstrating the feasibility of using these types of geometries to increase the volume of real haloscopes.
•The system is transformed to provide a suitable conservationlaw form.•Numerical solvers are formulated ensuring the exact well-balanced property.•Riemann problems including extreme vessel collapse ...and blockage are solved.•The extension to third order in time and space is analyzed.
In this work, numerical solvers based on extensions of the Roe and HLL schemes are adapted to deal with test cases involving extreme collapsing conditions in elastic vessels. To achieve this goal, the system is transformed to provide a conservation–law form, allowing to define Rankine–Hugoniot conditions. The approximate solvers allow to describe the inner states of the solution. Therefore, source term fixes can be used to prevent unphysical values of vessel area and, at the same time, the eigenvalues of the system control stability. Numerical solvers of different order are tested using a wide variety of Riemann problems, including extreme vessel collapse and blockage. In all cases, the robustness of the approximate solvers presented here is checked using first and third order methods in time and space, using the WENO reconstruction scheme in combination with the TVDRK3 method.
The numerical modelling of 2D shallow flows in complex geometries involving transient flow and movable boundaries has been a challenge for researchers in recent years. There is a wide range of ...physical situations of environmental interest, such as flow in open channels and rivers, tsunami and flood modelling, that can be mathematically represented by first-order non-linear systems of partial differential equations, whose derivation involves an assumption of the shallow water type. Shallow water models may include more sophisticated terms when applied to cases of not pure water floods, such as mud/debris floods, produced by landslides. Mud/debris floods are unsteady flow phenomena in which the flow changes rapidly, and the properties of the moving fluid mixture include stop and go mechanisms. The present work reports on a numerical model able to solve the 2D shallow water equations even including bed load transport over erodible bed in realistic situations involving transient flow and movable flow boundaries. The novelty is that it offers accurate and stable results in realistic problems since an appropriate discretization of the governing equations is performed. Furthermore, the present work is focused on the importance of the computational cost. Usually, the main drawback is the high computational effort required for obtaining accurate numerical solutions due to the high number of cells involved in realistic cases. However, the proposed model is able to reduce computer times by orders of magnitude making 2D applications competitive and practical for operational flood prediction. Moreover our results show that high performance code development can take advantage of general purpose and inexpensive Graphical Processing Units, allowing to run almost 100 times faster than old generation codes in some cases.
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