Detection of selective sweeps in structured populations : a comparison of recent methods

This work was supported by the Marie-Curie Initial Training Network INTERCROSSING (European Commission FP7). OEG was further supported by the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). Date of Acceptance: 25/08/2015Identifying genomic regions targeted by positive selection has been a longstanding interest of evolutionary biologists. This objective was difficult to achieve until the recent emergence of Next Generation Sequencing, which is fostering the development of large-scale catalogs of genetic variation for increasing number of species. Several statistical methods have been recently developed to analyze these rich datasets but there is still a poor understanding of the conditions under which these methods produce reliable results. This study aims at filling this gap by assessing the performance of genome-scan methods that consider explicitly the physical linkage among SNPs surrounding a selected variant. Our study compares the performance of seven recent methods for the detection of selective sweeps (iHS, nSL, EHHST, xp-EHH, XP-EHHST, XPCLR and hapFLK). We use an individual-based simulation approach to investigate the power and accuracy of these methods under a wide range of population models under both hard and soft sweeps. Our results indicate that XPCLR and hapFLK perform best and can detect soft sweeps under simple population structure scenarios if migration rate is low. All methods perform poorly with moderate to high migration rates, or with weak selection and very poorly under a hierarchical population structure. Finally, no single method is able to detect both starting and nearly completed selective sweeps. However, combining several methods (XPCLR or hapFLK with iHS or nSL) can greatly increase the power to pinpoint the selected region.PostprintPeer reviewe

Chiral phase transitions and quantum critical points of the D3/D7(D5) system with mutually perpendicular E and B fields at finite temperature and density

We study chiral symmetry restoration with increasing temperature and density in gauge theories subject to mutually perpendicular electric and magnetic fields using holography. We determine the chiral symmetry breaking phase structure of the D3/D7 and D3/D5 systems in the temperature-density-electric field directions. A magnetic field may break the chiral symmetry and an additional electric field induces Ohm and Hall currents as well as restoring the chiral symmetry. At zero temperature the D3/D5 system displays a line of holographic BKT phase transitions in the density-electric field plane, while the D3/D7 system shows a mean-field phase transition. At intermediate temperatures, the transitions in the density-electric field plane are of first order at low density, transforming to second order at critical points as density rises. At high temperature the transition is only ever first order.Comment: 15 pages, 7 figures, v2: Added a referenc

Moduli Spaces of Cold Holographic Matter

We use holography to study (3+1)-dimensional N=4 supersymmetric Yang-Mills theory with gauge group SU(Nc), in the large-Nc and large-coupling limits, coupled to a single massless (n+1)-dimensional hypermultiplet in the fundamental representation of SU(Nc), with n=3,2,1. In particular, we study zero-temperature states with a nonzero baryon number charge density, which we call holographic matter. We demonstrate that a moduli space of such states exists in these theories, specifically a Higgs branch parameterized by the expectation values of scalar operators bilinear in the hypermultiplet scalars. At a generic point on the Higgs branch, the R-symmetry and gauge group are spontaneously broken to subgroups. Our holographic calculation consists of introducing a single probe Dp-brane into AdS5 times S^5, with p=2n+1=7,5,3, introducing an electric flux of the Dp-brane worldvolume U(1) gauge field, and then obtaining explicit solutions for the worldvolume fields dual to the scalar operators that parameterize the Higgs branch. In all three cases, we can express these solutions as non-singular self-dual U(1) instantons in a four-dimensional space with a metric determined by the electric flux. We speculate on the possibility that the existence of Higgs branches may point the way to a counting of the microstates producing a nonzero entropy in holographic matter. Additionally, we speculate on the possible classification of zero-temperature, nonzero-density states described holographically by probe D-branes with worldvolume electric flux.Comment: 56 pages, 8 PDF images, 4 figure

2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry

Objectives: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. Background: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. Methods: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. Results: During the current observation 37788 doses of Gadolinium based contrast agent were administered to 37788 patients. The mean dose was 24.7 ml (range 5–80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12 %). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05 % (linear non-ionic agent gadodiamide) to 0.42 % (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05 % (risk stratification in suspected CAD) to 0.22 % (viability in known CAD). Conclusions: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the “off-label” use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events

Mesons from global Anti-de Sitter space

In the context of gauge/gravity duality, we study both probe D7-- and probe D5--branes in global Anti-de Sitter space. The dual field theory is N=4 theory on R x S^3 with added flavour. The branes undergo a geometrical phase transition in this geometry as function of the bare quark mass m_q in units of 1/R with R the S^3 radius. The meson spectra are obtained from fluctuations of the brane probes. First, we study them numerically for finite quark mass through the phase transition. Moreover, at zero quark mass we calculate the meson spectra analytically both in supergravity and in free field theory on R x S^3 and find that the results match: For the chiral primaries, the lowest level is given by the zero point energy or by the scaling dimension of the operator corresponding to the fluctuations, respectively. The higher levels are equidistant. Similar results apply to the descendents. Our results confirm the physical interpretation that the mesons cannot pair-produce any further when their zero-point energy exceeds their binding energy.Comment: 43 pages, 8 figures, references edited, few typos corrected, updated to match the published versio

Collective Excitations of Holographic Quantum Liquids in a Magnetic Field

We use holography to study N=4 supersymmetric SU(Nc) Yang-Mills theory in the large-Nc and large-coupling limits coupled to a number Nf << Nc of (n+1)-dimensional massless supersymmetric hypermultiplets in the Nc representation of SU(Nc), with n=2,3. We introduce a temperature T, a baryon number chemical potential mu, and a baryon number magnetic field B, and work in a regime with mu >> T,\sqrt{B}. We study the collective excitations of these holographic quantum liquids by computing the poles in the retarded Green's function of the baryon number charge density operator and the associated peaks in the spectral function. We focus on the evolution of the collective excitations as we increase the frequency relative to T, i.e. the hydrodynamic/collisionless crossover. We find that for all B, at low frequencies the tallest peak in the spectral function is associated with hydrodynamic charge diffusion. At high frequencies the tallest peak is associated with a sound mode similar to the zero sound mode in the collisionless regime of a Landau Fermi liquid. The sound mode has a gap proportional to B, and as a result for intermediate frequencies and for B sufficiently large compared to T the spectral function is strongly suppressed. We find that the hydrodynamic/collisionless crossover occurs at a frequency that is approximately B-independent.Comment: 45 pages, 8 png and 47 pdf images in 22 figure

Inverse magnetic catalysis in dense holographic matter

We study the chiral phase transition in a magnetic field at finite temperature and chemical potential within the Sakai-Sugimoto model, a holographic top-down approach to (large-N_c) QCD. We consider the limit of a small separation of the flavor D8-branes, which corresponds to a dual field theory comparable to a Nambu-Jona Lasinio (NJL) model. Mapping out the surface of the chiral phase transition in the parameter space of magnetic field strength, quark chemical potential, and temperature, we find that for small temperatures the addition of a magnetic field decreases the critical chemical potential for chiral symmetry restoration - in contrast to the case of vanishing chemical potential where, in accordance with the familiar phenomenon of magnetic catalysis, the magnetic field favors the chirally broken phase. This "inverse magnetic catalysis" (IMC) appears to be associated with a previously found magnetic phase transition within the chirally symmetric phase that shows an intriguing similarity to a transition into the lowest Landau level. We estimate IMC to persist up to 10^{19} G at low temperatures.Comment: 42 pages, 11 figures, v3: extended discussion; new appendix D; references added; version to appear in JHE

Holographic DC conductivities from the open string metric

We study the DC conductivities of various holographic models using the open string metric (OSM), which is an effective metric geometrizing density and electromagnetic field effect. We propose a new way to compute the nonlinear conductivity using OSM. As far as the final conductivity formula is concerned, it is equivalent to the Karch-O'Bannon's real-action method. However, it yields a geometrical insight and technical simplifications. Especially, a real-action condition is interpreted as a regular geometry condition of OSM. As applications of the OSM method, we study several holographic models on the quantum Hall effect and strange metal. By comparing a Lifshitz background and the Light-Cone AdS, we show how an extra parameter can change the temperature scaling behavior of conductivity. Finally we discuss how OSM can be used to study other transport coefficients, such as diffusion constant, and effective temperature induced by the effective world volume horizon.Comment: 33 page

Enhanced cosmic-ray flux toward zeta Persei inferred from laboratory study of H3+ - e- recombination rate

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many interstellar molecules. In dense clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density, and temperature. On the other hand, observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. However, diffuse cloud models have been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons, the electron fraction, and the cosmic-ray ionisation rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards zeta Persei) where the electron fraction is already known. Taken together, these results allow us to derive the value of the third uncertain model parameter: we find that the cosmic-ray ionisation rate in this sightline is forty times faster than previously assumed. If such a high cosmic-ray flux is indeed ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.Comment: 6 pages, Nature, in pres