ALBERT

Description: The cores of Arp 220, the closest ultraluminous infrared starburst galaxy, provide an opportunity to study interactions of cosmic rays under extreme conditions. In this paper, we model the populations of cosmic rays produced by supernovae in the central molecular zones of both starburst nuclei. We find that ~65–100 per cent of cosmic rays are absorbed in these regions due to their huge molecular gas contents, and thus, the nuclei of Arp 220 nearly complete proton calorimeters. As the cosmic ray protons collide with the interstellar medium, they produce secondary electrons that are also contained within the system and radiate synchrotron emission. Using results from 2 tests between the model and the observed radio spectral energy distribution, we predict the emergent -ray and high-energy neutrino spectra and find the magnetic field to be at milligauss levels. Because of the extremely intense far-infrared radiation fields, the -ray spectrum steepens significantly at TeV energies due to – absorption.

Description: We present a detailed analysis of an astrophysical mechanism that generates cosmological magnetic fields during the Epoch of Reionization. It is based on the photoionization of the intergalactic medium by the first sources formed in the Universe. First the induction equation is derived, then the characteristic length and time-scales of the mechanism are identified, and finally numerical applications are carried out for first stars, primordial galaxies and distant powerful quasars. In these simple examples, the strength of the generated magnetic fields varies between the order of 10 –23  G on hundreds of kiloparsecs and 10 –19  G on hundreds of parsecs in the neutral intergalactic medium between the Strömgren spheres of the sources. Thus, this mechanism contributes to the premagnetization of the whole Universe before large-scale structures are in place. It operates with any ionizing source, at any time during the Epoch of Reionization. Finally, the generated fields possess a characteristic spatial configuration which may help discriminate these seeds from those produced by different mechanisms.

Description: We report the identification of elongated (triaxial or prolate) galaxies in cosmological simulations at z ~= 2. These are preferentially low-mass galaxies ( M * ≤ 10 9.5 M ), residing in dark matter (DM) haloes with strongly elongated inner parts, a common feature of high-redshift DM haloes in the cold dark matter cosmology. Feedback slows formation of stars at the centres of these haloes, so that a dominant and prolate DM distribution gives rise to galaxies elongated along the DM major axis. As galaxies grow in stellar mass, stars dominate the total mass within the galaxy half-mass radius, making stars and DM rounder and more oblate. A large population of elongated galaxies produces a very asymmetric distribution of projected axis ratios, as observed in high- z galaxy surveys. This indicates that the majority of the galaxies at high redshifts are not discs or spheroids but rather galaxies with elongated morphologies.

Description: There is much evidence that planet formation is occurring in the disc around the Herbig Be star HD100546. To learn more about the processes occurring in this disc, we conducted high-resolution imaging at 43/45 GHz with the Australia Telescope Compact Array. Multiple array configurations were used, providing a best spatial resolution of ~0.15 arcsec, or 15 au at HD100546's distance of ~100 pc. Significant structure is revealed, but its precise form is dependent on the u – v plane sampling used for the image reconstruction. At a resolution of ≤30 au, we detected an inner gap in the disc with a radius of ~25 au and a position angle approximately along the known disc major axis. With different weighting, and an achieved resolution of ~15 au, emission appears at the centre and the disc takes on the shape of an incomplete ring, much like a horseshoe, again with a gap radius of ~25 au. The position angle of the disc major axis and its inclination from face-on are determined to be 140° ± 5° and 40° ± 5°, respectively. The ~25 au gap radius is confirmed by a null in the real part of the binned visibilities at 320 ± 10 k, whilst the non-axisymmetric nature is also confirmed through significant structure in the imaginary component. The emission mechanism at the central peak is most likely to be free–free emission from a stellar or disc wind. Overall our data support the picture of at least one, but probably several, giant planets orbiting HD100546 within 25 au.

Description: We present a fast iterative fast Fourier transform (FFT) based reconstruction algorithm that allows for non-parallel redshift-space distortions (RSDs). We test our algorithm on both N -body dark matter simulations and mock distributions of galaxies designed to replicate galaxy survey conditions. We compare solenoidal and irrotational components of the redshift distortion and show that an approximation of this distortion leads to a better estimate of the real-space potential (and therefore faster convergence) than ignoring the RSD when estimating the displacement field. Our iterative reconstruction scheme converges in two iterations for the mock samples corresponding to Baryon Oscillation Spectroscopic Survey CMASS Data Release 11 when we start with an approximation of the RSD. The scheme takes six iterations when the initial estimate, measured from the redshift-space overdensity, has no RSD correction. Slower convergence would be expected for surveys covering a larger angle on the sky. We show that this FFT based method provides a better estimate of the real-space displacement field than a configuration space method that uses finite difference routines to compute the potential for the same grid resolution. Finally, we show that a lognormal transform of the overdensity, used as a proxy for the linear overdensity, is beneficial in estimating the full displacement field from a dense sample of tracers. However, the lognormal transform of the overdensity does not perform well when estimating the displacements from sparser simulations with a more realistic galaxy density.

Description: Natural gas is an extremely important bridge fuel to a low-carbon energy economy for improving local air quality. Coal to synthetic natural gas (SNG) is an effective way to convert the high-carbon energy (coal) into the low-carbon energy with rich hydrogen (natural gas). For the modern coal to SNG industry, the high-temperature methanation (HTM) catalyst plays an important role, and the advanced evaluation process should necessitate the elimination of mass transfer effect. Some simple but effective model catalysts, such as slab and sphere, can be very helpful in defining the reaction conditions, and thus facilitating the evaluation process for real HTM catalysts. In this work, slab and sphere model catalysts were adopted to derive mass transfer and reaction-coupled equations, the numerical methods were used to solve the coupled equations for the concentration profiles in catalysts, and the effectiveness factors were accordingly calculated. By taking advantage of the Thiele module and the Weisz–Prater module , the criteria for the elimination of mass transfer effect in the HTM catalyst evaluation process were successfully defined. This work also complements the Weisz–Prater criterion by incorporating ‘negative reaction orders’.

Description: Gene expression evolution occurs through changes in cis - or trans -regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus ) and within species (comparing two closely related S. cerevisiae strains).

Description: Gene duplication is a key factor contributing to phenotype diversity across and within species. Although the availability of complete genomes has led to the extensive study of genomic duplications, the dynamics and variability of gene duplications mediated by retrotransposition are not well understood. Here, we predict mRNA retrotransposition and use comparative genomics to investigate their origin and variability across primates. Analyzing seven anthropoid primate genomes, we found a similar number of mRNA retrotranspositions (~7,500 retrocopies) in Catarrhini (Old Word Monkeys, including humans), but a surprising large number of retrocopies (~10,000) in Platyrrhini (New World Monkeys), which may be a by-product of higher long interspersed nuclear element 1 activity in these genomes. By inferring retrocopy orthology, we dated most of the primate retrocopy origins, and estimated a decrease in the fixation rate in recent primate history, implying a smaller number of species-specific retrocopies. Moreover, using RNA-Seq data, we identified approximately 3,600 expressed retrocopies. As expected, most of these retrocopies are located near or within known genes, present tissue-specific and even species-specific expression patterns, and no expression correlation to their parental genes. Taken together, our results provide further evidence that mRNA retrotransposition is an active mechanism in primate evolution and suggest that retrocopies may not only introduce great genetic variability between lineages but also create a large reservoir of potentially functional new genomic loci in primate genomes.

Description: The energy expended for conditioning buildings around the world is worryingly large and increasing every year. Currently, almost half of houses around the world use some type of energy-expensive conventional air-conditioning system. These systems are high emitters of gases such as carbon dioxide and so high contributors to climate change. Consequently, alternatives must be considered. Earth–air heat exchangers (EAHEs) and phase-change materials (PCMs) may be options; they have, however, limitations. This paper proposes a novel hybrid space-conditioning system combining EAHEs with PCMs, which uses surfaces as sources of heating or cooling to provide better temperature distribution across a space and comfort enhancement with low energy use. The idea is to use an EAHE to provide cool air to discharge the PCM, consequently helping to overcome most of the limitations of both strategies. Two of a series of experiments undertaken to test the proposed system are reported in this article. The EAHE + PCM system compared with a reference room could decrease temperature swings by up to 47%. The system was proved to work although further work is required to make it commercially viable.

Description: The design of a future building with very high-energy efficiency demands from the architect to study the available solar resources in this urban environment. The purpose of the presented methodology is to study the variations in all components of the incident solar radiation daily, monthly and seasonally for all building facades. This is realized in the computer program 3D–SOLARIA. In the focus of the paper is the estimation of the background component of the incident diffuse solar irradiation on a building facade under orthogonally obstructed sky, using anisotropic sky view factors.

Description: The assessment of building envelope sustainability using existing building performance assessment methods is still a challenge and yet to be fully addressed. This is due to the single-dimensional nature and lack of integration of sustainable performance values. Besides, the issue of sustainability assessment in the building envelope requires considering many factors including life cycle considerations. As such, in an effort to develop an integrated approach that combines relevant sustainable development factors and life cycles, an integrated performance model (IPM) was developed. The IPM is an essential tool developed to aid the sustainable design of the residential building envelope that can reduce carbon emission and whole residential building energy consumption and ensure sustainable performance of the building envelope.

Description: The results and considerations on one self-consumption photovoltaic installation with net balance in Granada (South of Spain) are presented and discussed in this paper. The use of the building (one faculty) makes it optimal for this kind of consumption. Finally, the potential benefits and problems of self-consumption with net balance are presented.

Description: Passive convective heat transfer enhancement can be achieved by improving the thermo-physical properties of the working fluid, changing flow geometry or both. This work presents a numerical study to investigate the combined effect of using helical coils and nanofluids on the heat transfer characteristics and pressure losses in turbulent flow regime. The developed computational fluid dynamics models were validated against published experimental data and empirical correlations. Results have shown that combining the effects of alumina (Al 2 O 3 ) nanoparticles and tube coiling could enhance the heat transfer coefficient by up to 60% compared with that of pure water in straight tube at the same Reynolds number. Also, results showed that the pressure drop in helical coils using Al 2 O 3 nanofluid for volume fraction of 3% was six times that of water in straight tubes (80% of the pressure drop increase is due to nanoparticles addition), while the effect of Reynolds number on the pressure drop penalty factor was found to be insignificant.

Description: The demand for better indoor environment has led to a wide use of heating, ventilating and air conditioning (HVAC) systems. However, this demanding cannot be sustained without a strategy to reduce the energy consumption of HVAC systems. Employing advanced HVAC control is one of the strategies to maintain high-quality indoor thermal comfort with low energy consumption. This paper reviews the development of control technologies for HVAC systems. It summarizes the problems in existing reviews and gives a future perspective on HVAC control systems for occupant comfort and energy efficiency.

Description: While the kinematics of Anatolia plate and the North Anatolian Fault System (NAFS) has been studied extensively, the slip rate and locking depth along the NAFS are usually assumed constant in the analyses due to the lack of sufficient data. This is also partly due to the reasonably good fit of Euler small circle and partly due to the lack of spatial resolution of observations to determine slip rates independently from locking depths. On the other hand, recent geodetic studies show a contrast for locking depth between Marmara and other parts of the NAFS, implying a non-uniform locking depth across the NAFS. In this study, we analyse new GPS data and homogenously combine available data sets covering the eastern part of the NAFS to form the most complete data set. In particular, we incorporate the first results of Turkish Real-Time Kinematic GPS Network (CORS-TR) into our data set. A detailed analysis of three profiles within the NAFS reveals an increase of locking depth in the middle profile to 19.1 ± 3.4 km from 11.9 ± 3.5 km in the easternmost profile while the slip rate is nearly constant (20–22 mm yr –1 ), which implies a variation of strain rate of ~100 nanostrain yr –1 . Assuming a constant locking depth throughout whole NAFS gives an average locking depth of 14.3 ± 1.7 km. Our best estimates of slip rates in block modelling which takes the variation of locking depths into account are in the range between 22.5 and 22.8 mm yr –1 over eastern part of the NAFS.

Description: Seismic waves sensitive to the outermost part of the Earth's liquid core seem to be affected by a stably stratified layer at the core–mantle boundary. Such a layer could have an observable signature in both long-term and short-term variations of the magnetic field of the Earth, which are used to probe the flow at the top of the core. Indeed, with the recent SWARM mission, it seems reasonable to be able to identify waves propagating in the core with period of several months, which may play an important role in the large-scale dynamics. In this paper, we characterize the influence of a stratified layer at the top of the core on deep quasi-geostrophic (Rossby) waves. We compute numerically the quasi-geostrophic eigenmodes of a rapidly rotating spherical shell, with a stably stratified layer near the outer boundary. Two simple models of stratification are taken into account, which are scaled with commonly adopted values of the Brunt–Väisälä frequency in the Earth's core. In the absence of magnetic field, we find that both azimuthal wavelength and frequency of the eigenmodes control their penetration into the stratified layer: the higher the phase speed, the higher the permeability of the stratified layer to the wave motion. We also show that the theory developed by Takehiro & Lister for thermal convection extends to the whole family of Rossby waves in the core. Adding a magnetic field, the penetrative behaviour of the quasi-geostrophic modes (the so-called fast branch) is insensitive to the imposed magnetic field and only weakly sensitive to the precise shape of the stratification. Based on these results, the large-scale and high-frequency modes (1–2 month periods) may be detectable in the geomagnetic data measured at the Earth's surface, especially in the equatorial area where the modes can be trapped.

Description: We investigate the properties of dark matter haloes and subhaloes in an f ( R ) gravity model with | f R 0 | = 10 –6 , using a very-high-resolution N -body simulation. The model is a borderline between being cosmologically interesting and yet still consistent with current data. We find that the halo mass function in this model has a maximum 20 per cent enhancement compared with the -cold-dark-matter (CDM) predictions between z  = 1 and 0. Because of the chameleon mechanism which screens the deviation from standard gravity in dense environments, haloes more massive than 10 13 h –1 M in this f ( R ) model have very similar properties to haloes of similar mass in CDM, while less massive haloes, such as that of the Milky Way, can have steeper inner density profiles and higher velocity dispersions due to their weaker screening. The halo concentration is remarkably enhanced for low-mass haloes in this model due to a deepening of the total gravitational potential. Contrary to the naive expectation, the halo formation time z f is later for low-mass haloes in this model, a consequence of these haloes growing faster than their counterparts in CDM at late times and the definition of z f . Subhaloes, especially those less massive than 10 11 h –1 M , are substantially more abundant in this f ( R ) model for host haloes less massive than 10 13 h –1 M . We discuss the implications of these results for the Milky Way satellite abundance problem. Although the overall halo and subhalo properties in this borderline f ( R ) model are close to their CDM predictions, our results suggest that studies of the Local Group and astrophysical systems, aided by high-resolution simulations, can be valuable for further tests of it.

Description: Mass-to-light versus colour relations (MLCRs), derived from stellar population synthesis models, are widely used to estimate galaxy stellar masses ( M * ), yet a detailed investigation of their inherent biases and limitations is still lacking. We quantify several potential sources of uncertainty, using optical and near-infrared (NIR) photometry for a representative sample of nearby galaxies from the Virgo cluster. Our method for combining multiband photometry with MLCRs yields robust stellar masses, while errors in M * decrease as more bands are simultaneously considered. The prior assumptions in one's stellar population modelling dominate the error budget, creating a colour-dependent bias of up to 0.6 dex if NIR fluxes are used (0.3 dex otherwise). This matches the systematic errors associated with the method of spectral energy distribution (SED) fitting, indicating that MLCRs do not suffer from much additional bias. Moreover, MLCRs and SED fitting yield similar degrees of random error (~0.1–0.14 dex) when applied to mock galaxies and, on average, equivalent masses for real galaxies with M *  ~ 10 8–11 M . The use of integrated photometry introduces additional uncertainty in M * measurements, at the level of 0.05–0.07 dex. We argue that using MLCRs, instead of time-consuming SED fits, is justified in cases with complex model parameter spaces (involving, for instance, multiparameter star formation histories) and/or for large data sets. Spatially resolved methods for measuring M * should be applied for small sample sizes and/or when accuracies less than 0.1 dex are required. An appendix provides our MLCR transformations for 10 colour permutations of the grizH filter set.

Description: The inverse Compton catastrophe is defined as a dramatic rise in the luminosity of inverse Compton scattered photons. It is described by a non-linear loop of radiative processes that sets in for high values of the electron compactness and is responsible for the efficient transfer of energy from electrons to photons, predominantly through inverse Compton scatterings. We search for the conditions that drive a magnetized non-thermal source to the inverse Compton catastrophe regime and study its multiwavelength (MW) photon spectrum. We develop a generic analytical framework and use numerical calculations as a backup to the analytical predictions. We find that the escaping radiation from a source in the Compton catastrophe regime bears some unique features. The MW photon spectrum is a broken power law with a break at ~ m e c 2 due to the onset of the Klein–Nishina suppression. The spectral index below the break energy depends on the electron and magnetic compactnesses logarithmically, while it is independent of the electron power-law index ( s ). The maximum radiating power emerges typically in the -ray regime, at energies ~ m e c 2 (~ max m e c 2 ) for s  〉 2 ( s   2), where max is the maximum Lorentz factor of the injected electron distribution. We apply the principles of the inverse Compton catastrophe to blazars and -ray bursts using the analytical framework we developed, and show how these can be used to impose robust constraints on the source parameters.

Description: We construct equilibrium configurations of magnetized, two-fluid neutron stars using an iterative numerical method. Working in Newtonian framework we assume that the neutron star has two regions: the core, which is modelled as a two-component fluid consisting of type-II superconducting protons and superfluid neutrons, and the crust, a region composed of normal matter. Taking a new step towards more complete equilibrium models, we include the effect of entrainment, which implies that a magnetic force acts on neutrons, too. We consider purely poloidal field cases and present improvements to an earlier numerical scheme for solving equilibrium equations, by introducing new convergence criteria. We find that entrainment results in qualitative differences in the structure of field lines along the magnetic axis.

Description: We prove a spectral flow formula for one-parameter families of Hamiltonian systems under homoclinic boundary conditions, which relates the spectral flow to the relative Maslov index of a pair of curves of Lagrangians induced by the stable and unstable subspaces, respectively. Finally, we deduce sufficient conditions for bifurcation of homoclinic trajectories of one-parameter families of non-autonomous Hamiltonian vector fields.

Description: We present an analysis of the 3–79 keV NuSTAR spectrum of the low-luminosity active galactic nucleus NGC 7213. In agreement with past observations, we find a lower limit to the high-energy cut-off of E c  〉 140 keV, no evidence for a Compton-reflected continuum and the presence of an iron K α complex, possibly produced in the broad-line region. From the application of the mytorus model, we find that the line-emitting material is consistent with the absence of a significant Compton reflection if arising from a Compton-thin torus of gas with a column density of $5.0^{+2.0}_{-1.6}\times 10^{23}$ cm –2 . We report variability of the equivalent width of the iron lines on the time-scale of years using archival observations from XMM–Newton , Chandra and Suzaku . This analysis suggests a possible contribution from dusty gas. A fit with a Comptonization model indicates the presence of a hot corona with a temperature kT e  〉 40 keV and an optical depth   1, assuming a spherical geometry.

Description: PSR J1357–6429 is a young and energetic radio pulsar detected in X-rays and -rays. It powers a compact pulsar wind nebula with a jet visible in X-rays and a large-scale plerion detected in X-ray and TeV ranges. Previous multiwavelength studies suggested that the pulsar has a significant proper motion of about 180 mas yr –1 , implying an extremely high transverse velocity of about 2000 km s –1 . In order to verify this, we performed radio-interferometric observations of PSR J1357–6429 with the Australia Telescope Compact Array (ATCA) in the 2.1-GHz band. We detected the pulsar with a mean flux density of 212 ± 5 μJy and obtained the most accurate pulsar position: RA =  $13^{\rm h}57^{\rm m}02{^{\rm s}_{.}}525(14)$ , Dec. = –64°29 ' 29 ${^{\prime\prime}_{.}}$ 89(15). Using both new and archival ATCA data, we did not find any proper motion and estimated its 90 per cent upper limit as μ 〈 106 mas yr –1 . The pulsar shows a highly polarized single pulse, as was observed earlier at 1.4 GHz. Spectral analysis revealed a shallow spectral index α  = 0.5 ± 0.1. Based on our new radio position of the pulsar, we discount the claim of an optical counterpart candidate reported previously.

Description: We consider the Schur–Horn problem for normal operators in von Neumann algebras, which is the problem of characterizing the possible diagonal values of a given normal operator based on its spectral data. For normal matrices, this problem is well known to be extremely difficult, and in fact, it remains open for matrices of size greater than $3$ . We show that the infinite-dimensional version of this problem is more tractable, and establish approximate solutions for normal operators in von Neumann factors of type I $_\infty$ , II, and III. A key result is an approximation theorem that can be seen as an approximate multivariate analogue of Kadison's Carpenter Theorem.

Description: We study the rate of convergence to zero of the tail entropy of $C^\infty$ maps. We give an upper bound of this rate in terms of the growth in $k$ of the derivative of order $k$ and give examples showing the optimality of the established rate of convergence. We also consider the case of multimodal maps of the interval. Finally, we prove that homoclinic tangencies give rise to $C^r$ $(r\geqslant 2)$ robustly non- $h$ -expansive dynamical systems.

Description: Let ${{\mathscr {C}}}^0_{{{\mathfrak {g}}}}$ be the category of finite-dimensional integrable modules over the quantum affine algebra $U_{q}'({{\mathfrak {g}}})$ and let $R^{A_\infty }{\mbox {-}\mathrm {gmod}}$ denote the category of finite-dimensional graded modules over the quiver Hecke algebra of type $A_{\infty }$ . In this paper, we investigate the relationship between the categories ${{\mathscr {C}}}^0_{A_{N-1}^{(1)}}$ and ${{\mathscr {C}}}^0_{A_{N-1}^{(2)}}$ by constructing the generalized quantum affine Schur–Weyl duality functors ${\mathcal {F}}^{(t)}$ from $R^{A_\infty }{\mbox {-}\mathrm {gmod}}$ to ${{\mathscr {C}}}^0_{A_{N-1}^{(t)}}\ (t=1,2)$ .

Description: We present new constructions of complex and $p$ -adic Darmon points on elliptic curves over base fields of arbitrary signature. We conjecture that these points are global and present numerical evidence to support our conjecture.

Description: Viruses rely completely on the hosts’ machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response.

Description: We address the problem of line confusion in intensity-mapping surveys and explore the possibility to mitigate line foreground contamination by progressively masking the brightest pixels in the observed map. We consider experiments targeting CO(1–0) at z  = 3, Ly α at z  = 7, and C  ii at z  = 7, and use simulated intensity maps, which include both clustering and shot-noise components of the signal and possible foregrounds, in order to test the efficiency of our method. We find that for CO and Ly α, it is quite possible to remove most of the foreground contribution from the maps via only 1–3 per cent pixel masking. The C  ii maps will be more difficult to clean, however, due to instrumental constraints and the high-intensity foreground contamination involved. While the masking procedure sacrifices much of the astrophysical information present in our maps, we demonstrate that useful cosmological information in the targeted lines can be successfully retrieved.

Description: We analyse the Suzaku X-ray Imaging Spectrometer data of the central region of supernova remnant G332.5-5.6. The X-ray data are well described by a single non-equilibrium ionization thermal model, vnei , with an absorbing hydrogen column density of 1.4 $^{+0.4}_{-0.1}$   x  10 21  cm –2 . The plasma is characterized by an electron temperature of 0.49 $^{+0.08}_{-0.06}$ keV with subsolar abundances for O (0.58 $^{+0.06}_{-0.05}$ solar value) and Fe (0.72 $^{+0.06}_{-0.05}$ solar value) and slightly overabundance for Mg (1.23 $^{+0.14}_{-0.14}$ solar value). It seems that the central X-ray emission originates from a projection effect or evaporation of residual clouds inside G332.5-5.6. We estimate a distance of 3.0 ± 0.8 kpc for G332.5-5.6 based on the extinction–distance relation. G332.5-5.6 has an age of 7–9 kyr.

Description: In interstellar media, stable hydrogen-containing molecules, like CH 3 OH, may be easily dissociated following irradiation by energetic cosmic rays, to form either stable or unstable chemical species. Laboratory experiments have already proved that when ices containing CH 3 OH are irradiated with high-energy photons or energetic particles, many chemical primary fragments are formed, due to the dissociation of C-H or O-H bonds. Are these hydrogen-containing molecules chemically stable in dark dust clouds? What is the behaviour of molecules like CH 3 OH in non-energy-induced processes? An understanding of the thermal reactions between methanol and radical species in their ground states at cryogenic temperatures is of primary importance in the astrochemical context. We experimentally show that the reaction between ground-state nitrogen atoms and CH 3 OH leads to dehydrogenation processes of methanol to form CH 3 O, H 2 CO and HCO chemical fragments via thermal chemistry initiated at temperatures below 10 K. These results underline the problem of the low chemical stability of some species formed and destroyed in interstellar media without any contribution of cosmic ray particles or high-energy photons.

Description: With a total area of several million hectares, mountain forests of Norway spruce ( Picea abies (L.) Karst.), silver fir ( Abies alba Mill.) and European beech ( Fagus sylvatica L.) connect the beech-covered lowlands and spruce-dominated alpine regions and still represent the most natural though managed forests in Europe. For sustaining their unique functions and services, their natural gap dynamics are emulated by the combined shelterwood–femel-coupe system. In the 1970s, 22 long-term experimental plots were established in the Bavarian Alps in order to substantiate the formerly mainly experience-based silvicultural prescriptions. After more than 40 years of successive surveys including the integrated evaluation of the old stands and the measurement of natural regeneration, analyses reveal: (1) The reduction of overstorey density is generally associated with a proportional reduction of the overstorey stand growth. So, the recommended 20–40 per cent density reduction of a combined shelterwood–femel coupe may reduce the mean annual increment also by ~20–40 per cent, but part of this loss is compensated by the additional growth of the regeneration. (2) Over time, the natural regeneration is continuously augmented by new recruitment of seedlings and saplings. (3) However, even 40 years after initiating regeneration, spruce is rare in the regeneration compared with fir, beech and other broadleaved species. Further observation will show whether spruce will catch up with the other species or whether it requires either larger disturbances than gap and femel coupes, or possibly planting. Based on these findings, a refined shelterwood–femel-coupe system is proposed and its advantages and disadvantages are discussed.

Description: Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by brain atrophy particularly in striatum leading to personality changes, chorea and dementia. Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase in the crossroad of many signaling pathways that is highly pleiotropic as it phosphorylates more than hundred substrates including structural, metabolic, and signaling proteins. Increased GSK-3 activity is believed to contribute to the pathogenesis of neurodegenerative diseases like Alzheimer's disease and GSK-3 inhibitors have been postulated as therapeutic agents for neurodegeneration. Regarding HD, GSK-3 inhibitors have shown beneficial effects in cell and invertebrate animal models but no evident efficacy in mouse models. Intriguingly, those studies were performed without interrogating GSK-3 level and activity in HD brain. Here we aim to explore the level and also the enzymatic activity of GSK-3 in the striatum and other less affected brain regions of HD patients and of the R6/1 mouse model to then elucidate the possible contribution of its alteration to HD pathogenesis by genetic manipulation in mice. We report a dramatic decrease in GSK-3 levels and activity in striatum and cortex of HD patients with similar results in the mouse model. Correction of the GSK-3 deficit in HD mice, by combining with transgenic mice with conditional GSK-3 expression, resulted in amelioration of their brain atrophy and behavioral motor and learning deficits. Thus, our results demonstrate that decreased brain GSK-3 contributes to HD neurological phenotype and open new therapeutic opportunities based on increasing GSK-3 activity or attenuating the harmful consequences of its decrease.

Description: Spinocerebellar ataxia type 6 (SCA6) is dominantly inherited neurodegenerative disease, caused by an expansion of CAG repeat encoding a polyglutamine (PolyQ) tract in the Ca v 2.1 voltage-gated calcium channel. Its key pathological features include selective degeneration of the cerebellar Purkinje cells (PCs), a common target for PolyQ-induced toxicity in various SCAs. Mutant Ca v 2.1 confers toxicity primarily through a toxic gain-of-function mechanism; however, its molecular basis remains elusive. Here, we studied the cerebellar gene expression patterns of young Sca6 -MPI 118Q/118Q knockin (KI) mice, which expressed mutant Ca v 2.1 from an endogenous locus and recapitulated many phenotypic features of human SCA6. Transcriptional signatures in the MPI 118Q/118Q mice were distinct from those in the Sca1 154Q/2Q mice, a faithful SCA1 KI mouse model. Temporal expression profiles of the candidate genes revealed that the up-regulation of genes associated with microglial activation was initiated before PC degeneration and was augmented as the disease progressed. Histological analysis of the MPI 118Q/118Q cerebellum showed the predominance of M1-like pro-inflammatory microglia and it was concomitant with elevated expression levels of tumor necrosis factor, interleukin-6, Toll-like receptor (TLR) 2 and 7. Genetic ablation of MyD88, a major adaptor protein conveying TLR signaling, altered expression patterns of M1/M2 microglial phenotypic markers in the MPI 118Q/118Q cerebellum. More importantly, it ameliorated PC loss and partially rescued motor impairments in the early disease phase. These results suggest that early neuroinflammatory response may play an important role in the pathogenesis of SCA6 and its modulation could pave the way for slowing the disease progression during the early stage of the disease.

Description: The attenuation and velocity dispersion of sonic waves contain valuable information on the mechanical and hydraulic properties of the probed medium. An inherent complication arising in the interpretation of corresponding measurements is, however, that there are multiple physical mechanisms contributing to the energy dissipation and that the relative importance of the various contributions is difficult to unravel. To address this problem for the practically relevant case of terrestrial alluvial sediments, we analyse the attenuation and velocity dispersion characteristics of broad-band multifrequency sonic logs with dominant source frequencies ranging between 1 and 30 kHz. To adequately compensate for the effects of geometrical spreading, which is critical for reliable attenuation estimates, we simulate our experimental setup using a correspondingly targeted numerical solution of the poroelastic equations. After having applied the thus inferred corrections, the broad-band sonic log data set, in conjunction with a comprehensive suite of complementary logging data, allows for assessing the relative importance of a range of pertinent attenuation mechanisms. In doing so, we focus on the effects of wave-induced fluid flow over a wide range of scales. Our results indicate that the levels of attenuation due to the presence of mesoscopic heterogeneities in unconsolidated clastic sediments fully saturated with water are expected to be largely negligible. Conversely, Monte-Carlo-type inversions indicate that Biot's classical model permits to explain most of the considered data. Refinements with regard to the fitting of the observed attenuation and velocity dispersion characteristics are locally provided by accounting for energy dissipation at the microscopic scale, although the nature of the underlying physical mechanism remains speculative.

Description: We present a detailed clustering analysis of the young stellar population across the star-forming ring galaxy NGC 6503, based on the deep Hubble Space Telescope photometry obtained with the Legacy ExtraGalactic UV Survey. We apply a contour-based map analysis technique and identify in the stellar surface density map 244 distinct star-forming structures at various levels of significance. These stellar complexes are found to be organized in a hierarchical fashion with 95 per cent being members of three dominant super-structures located along the star-forming ring. The size distribution of the identified structures and the correlation between their radii and numbers of stellar members show power-law behaviours, as expected from scale-free processes. The self-similar distribution of young stars is further quantified from their autocorrelation function, with a fractal dimension of ~1.7 for length-scales between ~20 pc and 2.5 kpc. The young stellar radial distribution sets the extent of the star-forming ring at radial distances between 1 and 2.5 kpc. About 60 per cent of the young stars belong to the detected stellar structures, while the remaining stars are distributed among the complexes, still inside the ring of the galaxy. The analysis of the time-dependent clustering of young populations shows a significant change from a more clustered to a more distributed behaviour in a time-scale of ~60 Myr. The observed hierarchy in stellar clustering is consistent with star formation being regulated by turbulence across the ring. The rotational velocity difference between the edges of the ring suggests shear as the driving mechanism for this process. Our findings reveal the interesting case of an inner ring forming stars in a hierarchical fashion.

Description: We used a new generation of asymptotic giant branch (AGB) stellar models that include dust formation in the stellar winds to find the links between evolutionary models and the observed properties of a homogeneous sample of Large Magellanic Cloud (LMC) planetary nebulae (PNe). Comparison between the evolutionary yields of elements such as CNO and the corresponding observed chemical abundances is a powerful tool to shed light on evolutionary processes such as hot bottom burning (HBB) and third dredge-up (TDU). We found that the occurrence of HBB is needed to interpret the nitrogen-enriched (log (N/H) + 12 〉 8) PNe. In particular, N-rich PNe with the lowest carbon content are nicely reproduced by AGB models of mass M  ≥ 6 M , whose surface chemistry reflects the pure effects of HBB. PNe with log (N/H) + 12 〈 7.5 correspond to ejecta of stars that have not experienced HBB, with initial mass below ~3 M . Some of these stars show very large carbon abundances, owing to the many TDU episodes experienced. We found from our LMC PN sample that there is a threshold to the amount of carbon accumulated at AGB surfaces, log (C/H) + 12 〈 9. Confirmation of this constraint would indicate that, after the C-star stage is reached, AGBs experience only a few thermal pulses, which suggests a rapid loss of the external mantle, probably owing to the effects of radiation pressure on carbonaceous dust particles present in the circumstellar envelope. The implications of these findings for AGB evolution theories and the need to extend the PN sample currently available are discussed.

Description: Young tidal dwarf galaxies (TDGs) are observed in the tidal debris of gas-rich interacting galaxies. In contrast to what is generally assumed to be the case for isolated dwarf galaxies, TDGs are not embedded in their own dark matter (DM) sub-halo. Hence, they are more sensitive to stellar feedback and could be disrupted on a short time-scale. Detailed numerical and observational studies demonstrate that isolated DM-dominated dwarf galaxies can have lifetimes of more than 10 Gyr. For TDGs that evolve in a tidal field with compressing accelerations equal to the gravitational acceleration within a DM sub-halo typical of an isolated dwarf galaxy, a similar survival time is expected. The tidal acceleration profile depends on the virial mass of the host galaxy and the distance between the TDG and its host. We analytically compare the tidal compression to the gravitational acceleration due to either cuspy or cored DM sub-haloes of various virial masses. For example, the tidal field at a distance of 100 kpc to a host halo of 10 13 M can be as stabilizing as a 10 9 M DM sub-halo. By linking the tidal field to the equivalent gravitational field of a DM sub-halo, we can use existing models of isolated dwarfs to estimate the survivability of TDGs. We show that part of the unexpectedly high dynamical masses inferred from observations of some TDGs can be explained by tidal compression and hence TDGs require to contain less unobservable matter to understand their rotation curves.

Description: Near-IR (NIR) spectroscopy is presented for Nova Scorpii 2014. It is shown that the outburst occurred in a symbiotic binary system – an extremely rare configuration for a classical nova outburst to occur in but appropriate for the eruption of a recurrent nova of the T CrB class. We estimate the spectral class of secondary as M5III ± (two sub-classes). The maximum magnitude versus rate of decline relations give an unacceptably large value of 37.5 kpc for the distance. The spectra are typical of the He/N class of novae with strong He  i and H lines. The profiles are broad and flat topped with full width at zero intensities approaching 9000–10 000 km s –1 and also have a sharp narrow component superposed which is attributable to emission from the giant's wind. Hot shocked gas, accompanied by X-rays and -rays, is expected to form when the high-velocity ejecta from the nova ploughs into the surrounding giant wind. Although X-ray emission was observed no -ray emission was reported. It is also puzzling that no signature of a decelerating shock is seen in the NIR, seen in similar systems like RS Oph, V745 Sco and V407 Cyg, as rapid narrowing of the line profiles. The small outburst amplitude and the giant secondary strongly suggest that Nova Sco 2014 could be a recurrent nova.

Description: We investigate the abundance of galactic molecular hydrogen (H 2 ) in the ‘Evolution and Assembly of GaLaxies and their Environments’ (EAGLE) cosmological hydrodynamic simulations. We assign H 2 masses to gas particles in the simulations in post-processing using two different prescriptions that depend on the local dust-to-gas ratio and the interstellar radiation field. Both result in H 2 galaxy mass functions that agree well with observations in the local and high-redshift Universe. The simulations reproduce the observed scaling relations between the mass of H 2 and the stellar mass, star formation rate and stellar surface density. Towards high redshifts, galaxies in the simulations display larger H 2 mass fractions and lower H 2 depletion time-scales, also in good agreement with observations. The comoving mass density of H 2 in units of the critical density, $\Omega _{\rm H_2}$ , peaks at z   1.2–1.5, later than the predicted peak of the cosmic star formation rate activity, at z   2. This difference stems from the decrease in gas metallicity and increase in interstellar radiation field with redshift, both of which hamper H 2 formation. We find that the cosmic H 2 budget is dominated by galaxies with $M_{\rm H_2} 〉 10^9\,\rm M_{{\odot }}$ , star formation rates $ 〉 \,\!\!10\,\rm M_{{\odot }}\,\rm yr^{-1}$ and stellar masses M stellar 〉 10 10 M , which are readily observable in the optical and near-IR. The match between the H 2 properties of galaxies that emerge in the simulations and observations is remarkable, particularly since H 2 observations were not used to adjust parameters in EAGLE.

Description: The detection of planar structures within the satellite systems of both the Milky Way (MW) and Andromeda (M31) has been reported as being in stark contradiction to the predictions of the standard cosmological model ( cold dark matter – CDM). Given the ambiguity in defining a planar configuration, it is unclear how to interpret the low incidence of the MW and M31 planes in CDM. We investigate the prevalence of satellite planes around galactic mass haloes identified in high-resolution cosmological simulations. We find that planar structures are very common, and that ~10 per cent of CDM haloes have even more prominent planes than those present in the Local Group. While ubiquitous, the planes of satellite galaxies show a large diversity in their properties. This precludes using one or two systems as small-scale probes of cosmology, since a large sample of satellite systems is needed to obtain a good measure of the object-to-object variation. This very diversity has been misinterpreted as a discrepancy between the satellite planes observed in the Local Group and CDM predictions. In fact, ~10 per cent of CDM galactic haloes have planes of satellites that are as infrequent as the MW and M31 planes. The look-elsewhere effect plays an important role in assessing the detection significance of satellite planes and accounting for it leads to overestimating the significance level by a factor of 30 and 100 for the MW and M31 systems, respectively.

Description: We use a suite of cooling halo simulations to study a new mechanism for rapid accretion of hot halo gas on to star-forming galaxies. Correlated supernova (SN) events create converging ‘superbubbles’ in the halo gas. Where these collide, the density increases, driving cooling filaments of low-metallicity gas that feed the disc. At our current numerical resolution (~20 pc; m gas = 4 x 10 4 M ) we are only able to resolve the most dramatic events; however, as we increase the numerical resolution, we find that the filaments persist for longer, driving continued late-time star formation. This suggests that SN-driven accretion could act as an efficient mechanism for extracting cold gas from the hot halo, driving late-time star formation in disc galaxies. We show that such filament feeding leads to a peak star formation rate of ~3 M yr –1 , consistent with estimates for the Milky Way (MW). The filaments we resolve extend to ~50 kpc, reaching column densities of N ~ 10 18  cm –2 . We show that such structures can plausibly explain the broad dispersion in Mg  ii absorption seen along sightlines to quasars. Our results suggest a dual role for stellar feedback in galaxy formation, suppressing hot-mode accretion while promoting cold-mode accretion along filaments. Finally, since the filamentary gas has higher angular momentum than that coming from hot-mode accretion, we show that this leads to the formation of substantially larger gas discs.

Description: It is often argued that the unintended consequences of science policy transformation over the last 50 years—increased role of fixed-term project funding, evaluation and temporary contracts—are short-termism, fragmentation and limited freedom to choose research topics and collaborators. This paper focuses on a phenomenon that should be highly unlikely in this context: long-term international research collaborations lasting over 10 and 20 years which remain creative and productive. To shed light on the little studied topic of why and how long-term international research collaborations evolve, the paper develops a mid-range theory from multiple longitudinal case studies. It suggests that long-term collaborations combining formal and informal interactions operate as virtuous circles whereas earlier results ensure feedback loops and thematic and organisational continuity, but renewal is crucial. The emergent theory is built from multiple data sources and methods analysing international collaborations in the emerging field of nanosciences in Europe.

Description: Motivation: Stem cell differentiation is largely guided by master transcriptional regulators, but it also depends on the expression of other types of genes, such as cell cycle genes, signaling genes, metabolic genes, trafficking genes, etc. Traditional approaches to understanding gene expression patterns across multiple conditions, such as principal components analysis or K-means clustering, can group cell types based on gene expression, but they do so without knowledge of the differentiation hierarchy. Hierarchical clustering can organize cell types into a tree, but in general this tree is different from the differentiation hierarchy itself. Methods: Given the differentiation hierarchy and gene expression data at each node, we construct a weighted Euclidean distance metric such that the minimum spanning tree with respect to that metric is precisely the given differentiation hierarchy. We provide a set of linear constraints that are provably sufficient for the desired construction and a linear programming approach to identify sparse sets of weights, effectively identifying genes that are most relevant for discriminating different parts of the tree. Results: We apply our method to microarray gene expression data describing 38 cell types in the hematopoiesis hierarchy, constructing a weighted Euclidean metric that uses just 175 genes. However, we find that there are many alternative sets of weights that satisfy the linear constraints. Thus, in the style of random-forest training, we also construct metrics based on random subsets of the genes and compare them to the metric of 175 genes. We then report on the selected genes and their biological functions. Our approach offers a new way to identify genes that may have important roles in stem cell differentiation. Contact: tperkins@ohri.ca Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Principal component analysis (PCA) is a basic tool often used in bioinformatics for visualization and dimension reduction. However, it is known that PCA may not consistently estimate the true direction of maximal variability in high-dimensional, low sample size settings, which are typical for molecular data. Assuming that the underlying signal is sparse, i.e. that only a fraction of features contribute to a principal component (PC), this estimation consistency can be retained. Most existing sparse PCA methods use L1-penalization, i.e. the lasso , to perform feature selection. But, the lasso is known to lack variable selection consistency in high dimensions and therefore a subsequent interpretation of selected features can give misleading results. Results: We present S4VDPCA, a sparse PCA method that incorporates a subsampling approach, namely stability selection. S4VDPCA can consistently select the truly relevant variables contributing to a sparse PC while also consistently estimate the direction of maximal variability. The performance of the S4VDPCA is assessed in a simulation study and compared to other PCA approaches, as well as to a hypothetical oracle PCA that ‘knows’ the truly relevant features in advance and thus finds optimal, unbiased sparse PCs. S4VDPCA is computationally efficient and performs best in simulations regarding parameter estimation consistency and feature selection consistency. Furthermore, S4VDPCA is applied to a publicly available gene expression data set of medulloblastoma brain tumors. Features contributing to the first two estimated sparse PCs represent genes significantly over-represented in pathways typically deregulated between molecular subgroups of medulloblastoma. Availability and implementation: Software is available at https://github.com/mwsill/s4vdpca . Contact: m.sill@dkfz.de Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. Comparative structural studies of biological molecules provide useful insight into their biological relationships. However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. Results: A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. Benchmark tests against the Protein Data Bank (PDB) N -linked glycan library and PDB homologous/non-homologous N -glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. Availability and implementation: http://www.glycanstructure.org/gsalign . Contact: wonpil@ku.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Motivation: Impedance-based technologies are advancing methods for measuring proliferation of adherent cell cultures non-invasively and in real time. The analysis of the resulting data has so far been hampered by inappropriate computational methods and the lack of systematic data to evaluate the characteristics of the assay. Results: We used a commercially available system for impedance-based growth measurement (xCELLigence) and compared the reported cell index with data from microscopy. We found that the measured signal correlates linearly with the cell number throughout the time of an experiment with sufficient accuracy in subconfluent cell cultures. The resulting growth curves for various colon cancer cells could be well described with the empirical Richards growth model, which allows for extracting quantitative parameters (such as characteristic cycle times). We found that frequently used readouts like the cell index at a specific time or the area under the growth curve cannot be used to faithfully characterize growth inhibition. We propose to calculate the average growth rate of selected time intervals to accurately estimate time-dependent IC50 values of drugs from growth curves. Contact: nils.bluethgen@charite.de Supplementary information: Supplementary data are available at Bioinformatics online.

Description: The STInno project, which was part of the EU Framework Programme 7 aimed to minimise the distance between south–north regions in Europe with a specific focus on wastewater treatment clusters. Three triple helix collaborations from three different countries participated, using their knowledge to work on a case study of olive mill wastewaters. The objective of this paper was to study how the triple helix functioned in practice. Results showed that a management model of the triple helix is somewhat different from the analytical model. A shift between these two views occurred during the project and the participants had to relate to this, as it had an effect on the outcomes. Concepts of social capital and trust are used to further elaborate on this by emphasising the importance of the people side of the triple helix and how the original, analytical model can be limiting when used in management practice.

Description: We empirically study how the characteristics of research and innovation systems influence the openness of national research funding programmes as regards the availability of funding to non-resident researchers. Based on a unique data set of national R&D programmes in the EU27 we identify a number of country-specific factors. These factors determine the degrees of programme openness observed when controlling for programme features in a hierarchical estimation model. Interestingly, we find that the quality and performance of national research add to the explanation of programme openness, whereas national integration into EU funding and research collaboration does not.

Description: Spliceosomal introns are a hallmark of eukaryotic genes that are hypothesized to play important roles in genome evolution but have poorly understood origins. Although most introns lack sequence homology to each other, new families of spliceosomal introns that are repeated hundreds of times in individual genomes have recently been discovered in a few organisms. The prevalence and conservation of these introner elements (IEs) or introner-like elements in other taxa, as well as their evolutionary relationships to regular spliceosomal introns, are still unknown. Here, we systematically investigate introns in the widespread marine green alga Micromonas and report new families of IEs, numerous intron presence–absence polymorphisms, and potential intron insertion hot-spots. The new families enabled identification of conserved IE secondary structure features and establishment of a novel general model for repetitive intron proliferation across genomes. Despite shared secondary structure, the IE families from each Micromonas lineage bear no obvious sequence similarity to those in the other lineages, suggesting that their appearance is intimately linked with the process of speciation. Two of the new IE families come from an Arctic culture ( Micromonas Clade E2) isolated from a polar region where abundance of this alga is increasing due to climate induced changes. The same two families were detected in metagenomic data from Antarctica—a system where Micromonas has never before been reported. Strikingly high identity between the Arctic isolate and Antarctic coding sequences that flank the IEs suggests connectivity between populations in the two polar systems that we postulate occurs through deep-sea currents. Recovery of Clade E2 sequences in North Atlantic Deep Waters beneath the Gulf Stream supports this hypothesis. Our research illuminates the dynamic relationships between an unusual class of repetitive introns, genome evolution, speciation, and global distribution of this sentinel marine alga.

Description: Cellular Ca 2+ homeostasis is tightly regulated and is pivotal to life. Inositol 1,4,5-trisphosphate receptors (IP 3 Rs) and ryanodine receptors (RyRs) are the major ion channels that regulate Ca 2+ release from intracellular stores. Although these channels have been extensively investigated in multicellular organisms, an appreciation of their evolution and the biology of orthologs in unicellular organisms is largely lacking. Extensive phylogenetic analyses reveal that the IP 3 R gene superfamily is ancient and diverged into two subfamilies, IP 3 R-A and IP 3 R-B/RyR, at the dawn of Opisthokonta. IP 3 R-B/RyR further diversified into IP 3 R-B and RyR at the stem of Filozoa. Subsequent evolution and speciation of Holozoa is associated with duplication of IP 3 R-A and RyR genes, and loss of IP 3 R-B in the vertebrate lineages. To gain insight into the properties of IP 3 R important for the challenges of multicellularity, the IP 3 R-A and IP 3 R-B family orthologs were cloned from Capsaspora owczarzaki, a close unicellular relative to Metazoa (designated as CO.IP 3 R-A and CO.IP 3 R-B). Both proteins were targeted to the endoplasmic reticulum. However, CO.IP 3 R-A, but strikingly not CO.IP 3 R-B, bound IP 3 , exhibited robust Ca 2+ release activity and associated with mammalian IP 3 Rs. These data indicate strongly that CO.IP 3 R-A as an exemplar of ancestral IP 3 R-A orthologs forms bona fide IP 3 -gated channels. Notably, however, CO.IP 3 R-A appears not to be regulated by Ca 2+ , ATP or Protein kinase A-phosphorylation. Collectively, our findings explore the origin, conservation, and diversification of IP 3 R gene families and provide insight into the functionality of ancestral IP 3 Rs and the added specialization of these proteins in Metazoa.

Description: Marriage rules, the community prescriptions that dictate who an individual can or cannot marry, are extremely diverse and universally present in traditional societies. A major focus of research in the early decades of modern anthropology, marriage rules impose social and economic forces that help structure societies and forge connections between them. However, in those early anthropological studies, the biological benefits or disadvantages of marriage rules could not be determined. We revisit this question by applying a novel simulation framework and genome-wide data to explore the effects of Asymmetric Prescriptive Alliance, an elaborate set of marriage rules that has been a focus of research for many anthropologists. Simulations show that strict adherence to these marriage rules reduces genetic diversity on the autosomes, X chromosome and mitochondrial DNA, but relaxed compliance produces genetic diversity similar to random mating. Genome-wide data from the Indonesian community of Rindi, one of the early study populations for Asymmetric Prescriptive Alliance, are more consistent with relaxed compliance than strict adherence. We therefore suggest that, in practice, marriage rules are treated with sufficient flexibility to allow social connectivity without significant degradation of biological diversity.

Description: The environment has profound effects on the expression of many traits and reaction norms describe the expression dynamics of a trait across a broad range of environmental conditions. Here, we analyze gene expression in Drosophila melanogaster across four different developmental temperatures (13–29 °C). Gene expression is highly plastic with 83.3% of the genes being differentially expressed. We distinguished three components of plasticity: 1) Dynamics of gene expression intensity (sum of change), 2) direction of change, and 3) curvature of the reaction norm (linear vs. quadratic). Studying their regulatory architecture we found that all three plasticity components were most strongly affected by the number of different transcription factors (TFs) binding to the target gene. More TFs were found in genes with less expression changes across temperatures. Although the effect of microRNAs was weaker, we consistently noted a trend in the opposite direction. The most plastic genes were regulated by fewer TFs and more microRNAs than less plastic genes. Different patterns of plasticity were also reflected by their functional characterization based on gene ontology. Our results suggest that reaction norms provide an important key to understand the functional requirements of natural populations exposed to variable environmental conditions.

Description: Recent advances in paleogenomic technologies have enabled an increasingly detailed understanding of the evolutionary relationships of now-extinct mammalian taxa. However, a number of enigmatic Quaternary species have never been characterized with molecular data, often because available fossils are rare or are found in environments that are not optimal for DNA preservation. Here, we analyze paleogenomic data extracted from bones attributed to the late Pleistocene western camel, Camelops cf. hesternus, a species that was distributed across central and western North America until its extinction approximately 13,000 years ago. Despite a modal sequence length of only around 35 base pairs, we reconstructed high-coverage complete mitochondrial genomes and low-coverage partial nuclear genomes for each specimen. We find that Camelops is sister to African and Asian bactrian and dromedary camels, to the exclusion of South American camelids (llamas, guanacos, alpacas, and vicuñas). These results contradict previous morphology-based phylogenetic models for Camelops , which suggest instead a closer relationship between Camelops and the South American camelids. The molecular data imply a Late Miocene divergence of the Camelops clade from lineages that separately gave rise to the extant camels of Eurasia. Our results demonstrate the increasing capacity of modern paleogenomic methods to resolve evolutionary relationships among distantly related lineages.

Description: Recent developments in the analysis of amino acid covariation are leading to breakthroughs in protein structure prediction, protein design, and prediction of the interactome. It is assumed that observed patterns of covariation are caused by molecular coevolution, where substitutions at one site affect the evolutionary forces acting at neighboring sites. Our theoretical and empirical results cast doubt on this assumption. We demonstrate that the strongest coevolutionary signal is a decrease in evolutionary rate and that unfeasibly long times are required to produce coordinated substitutions. We find that covarying substitutions are mostly found on different branches of the phylogenetic tree, indicating that they are independent events that may or may not be attributable to coevolution. These observations undermine the hypothesis that molecular coevolution is the primary cause of the covariation signal. In contrast, we find that the pairs of residues with the strongest covariation signal tend to have low evolutionary rates, and that it is this low rate that gives rise to the covariation signal. Slowly evolving residue pairs are disproportionately located in the protein’s core, which explains covariation methods’ ability to detect pairs of residues that are close in three dimensions. These observations lead us to propose the "coevolution paradox": The strength of coevolution required to cause coordinated changes means the evolutionary rate is so low that such changes are highly unlikely to occur. As modern covariation methods may lead to breakthroughs in structural genomics, it is critical to recognize their biases and limitations.

Description: We present a modified GPU (graphics processing unit) version of MrBayes, called ta(MC) 3 (GPU MrBayes V3.1), for Bayesian phylogenetic inference on protein data sets. Our main contributions are 1) utilizing 64-bit variables, thereby enabling ta(MC) 3 to process larger data sets than MrBayes; and 2) to use Kahan summation to improve accuracy, convergence rates, and consequently runtime. Versus the current fastest software, we achieve a speedup of up to around 2.5 (and up to around 90 vs. serial MrBayes), and more on multi-GPU hardware. GPU MrBayes V3.1 is available from http://sourceforge.net/projects/mrbayes-gpu/ .

Description: Understanding the genetic and molecular bases of the ability to distinguish self from nonself (allorecognition) and mechanisms underlying evolution of allorecognition systems is an important endeavor for understanding cases where it becomes dysfunctional, such as in autoimmune disorders. In filamentous fungi, allorecognition can result in vegetative or heterokaryon incompatibility, which is a type of programmed cell death that occurs following fusion of genetically different cells. Allorecognition is genetically controlled by het loci, with coexpression of any combination of incompatible alleles triggering vegetative incompatibility. Herein, we identified, characterized, and inferred the evolutionary history of candidate het loci in the filamentous fungus Neurospora crassa . As characterized het loci encode proteins carrying an HET domain, we annotated HET domain genes in 25 isolates from a natural population along with the N. crassa reference genome using resequencing data. Because allorecognition systems can be affected by frequency-dependent selection favoring rare alleles (i.e., balancing selection), we mined resequencing data for HET domain loci whose alleles displayed elevated levels of variability, excess of intermediate frequency alleles, and deep gene genealogies. From these analyses, 34 HET domain loci were identified as likely to be under balancing selection. Using transformation, incompatibility assays and genetic analyses, we determined that one of these candidates functioned as a het locus ( het-e ). The het-e locus has three divergent allelic groups that showed signatures of positive selection, intra- and intergroup recombination, and trans-species polymorphism. Our findings represent a compelling case of balancing selection functioning on multiple alleles across multiple loci potentially involved in allorecognition.

Description: Scoring the impact of noncoding variation on the function of cis -regulatory regions, on their chromatin state, and on the qualitative and quantitative expression levels of target genes is a fundamental problem in evolutionary genomics. A particular challenge is how to model the divergence of quantitative traits and to identify relationships between the changes across the different levels of the genome, the chromatin activity landscape, and the transcriptome. Here, we examine the use of the Ornstein–Uhlenbeck (OU) model to infer selection at the level of predicted cis -regulatory modules (CRMs), and link these with changes in transcription factor binding and chromatin activity. Using publicly available cross-species ChIP-Seq and STARR-Seq data we show how OU can be applied genome-wide to identify candidate transcription factors for which binding site and CRM turnover is correlated with changes in regulatory activity. Next, we profile open chromatin in the developing eye across three Drosophila species. We identify the recognition motifs of the chromatin remodelers, Trithorax-like and Grainyhead as mostly correlating with species-specific changes in open chromatin. In conclusion, we show in this study that CRM scores can be used as quantitative traits and that motif discovery approaches can be extended towards more complex models of divergence.

Description: How populations that inhabit the same geographical area become genetically differentiated is not clear. To investigate this, we characterized phenotypic and genetic differences between two populations of Saccharomyces cerevisiae that in some cases inhabit the same environment but show relatively little gene flow. We profiled stress sensitivity in a group of vineyard isolates and a group of oak-soil strains and found several niche-related phenotypes that distinguish the populations. We performed bulk-segregant mapping on two of the distinguishing traits: The vineyard-specific ability to grow in grape juice and oak-specific tolerance to the cell wall damaging drug Congo red. To implicate causal genes, we also performed a chemical genomic screen in the lab-strain deletion collection and identified many important genes that fell under quantitative trait loci peaks. One gene important for growth in grape juice and identified by both the mapping and the screen was SSU1 , a sulfite-nitrite pump implicated in wine fermentations. The beneficial allele is generated by a known translocation that we reasoned may also serve as a genetic barrier. We found that the translocation is prevalent in vineyard strains, but absent in oak strains, and presents a postzygotic barrier to spore viability. Furthermore, the translocation was associated with a fitness cost to the rapid growth rate seen in oak-soil strains. Our results reveal the translocation as a dual-function locus that enforces ecological differentiation while producing a genetic barrier to gene flow in these sympatric populations.

Description: Species tree reconstruction has been a subject of substantial research due to its central role across biology and medicine. A species tree is often reconstructed using a set of gene trees or by directly using sequence data. In either of these cases, one of the main confounding phenomena is the discordance between a species tree and a gene tree due to evolutionary events such as duplications and losses. Probabilistic methods can resolve the discordance by coestimating gene trees and the species tree but this approach poses a scalability problem for larger data sets. We present MixTreEM-DLRS: A two-phase approach for reconstructing a species tree in the presence of gene duplications and losses. In the first phase, MixTreEM, a novel structural expectation maximization algorithm based on a mixture model is used to reconstruct a set of candidate species trees, given sequence data for monocopy gene families from the genomes under study. In the second phase, PrIME-DLRS, a method based on the DLRS model (Åkerborg O, Sennblad B, Arvestad L, Lagergren J. 2009. Simultaneous Bayesian gene tree reconstruction and reconciliation analysis. Proc Natl Acad Sci U S A. 106(14):5714–5719), is used for selecting the best species tree. PrIME-DLRS can handle multicopy gene families since DLRS, apart from modeling sequence evolution, models gene duplication and loss using a gene evolution model (Arvestad L, Lagergren J, Sennblad B. 2009. The gene evolution model and computing its associated probabilities. J ACM. 56(2):1–44). We evaluate MixTreEM-DLRS using synthetic and biological data, and compare its performance with a recent genome-scale species tree reconstruction method PHYLDOG ( Boussau B, Szöllősi GJ, Duret L, Gouy M, Tannier E, Daubin V. 2013 . Genome-scale coestimation of species and gene trees. Genome Res. 23(2):323–330) as well as with a fast parsimony-based algorithm Duptree (Wehe A, Bansal MS, Burleigh JG, Eulenstein O. 2008. Duptree: a program for large-scale phylogenetic analyses using gene tree parsimony. Bioinformatics 24(13):1540–1541). Our method is competitive with PHYLDOG in terms of accuracy and runs significantly faster and our method outperforms Duptree in accuracy. The analysis constituted by MixTreEM without DLRS may also be used for selecting the target species tree, yielding a fast and yet accurate algorithm for larger data sets. MixTreEM is freely available at http://prime.scilifelab.se/mixtreem/ .

Description: Contrasting with birds and mammals, poikilothermic vertebrates often have homomorphic sex chromosomes, possibly resulting from high rates of sex-chromosome turnovers and/or occasional X–Y recombination. Strong support for the latter mechanism was provided by four species of European tree frogs, which inherited from a common ancestor (~5 Ma) the same pair of homomorphic sex chromosomes (linkage group 1, LG1), harboring the candidate sex-determining gene Dmrt1. Here, we test sex linkage of LG1 across six additional species of the Eurasian Hyla radiation with divergence times ranging from 6 to 40 Ma. LG1 turns out to be sex linked in six of nine resolved cases. Mapping the patterns of sex linkage to the Hyla phylogeny reveals several transitions in sex-determination systems within the last 10 My, including one switch in heterogamety. Phylogenetic trees of DNA sequences along LG1 are consistent with occasional X–Y recombination in all species where LG1 is sex linked. These patterns argue against one of the main potential causes for turnovers, namely the accumulation of deleterious mutations on nonrecombining chromosomes. Sibship analyses show that LG1 recombination is strongly reduced in males from most species investigated, including some in which it is autosomal. Intrinsically low male recombination might facilitate the evolution of male heterogamety, and the presence of important genes from the sex-determination cascade might predispose LG1 to become a sex chromosome.

Description: It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from subjects aged 18–83 years, as part of a health survey of the Danish population that focussed on lifestyle factors. The level of DNA repair activity was measured as incisions on potassium bromate-damaged DNA by the comet assay. There was an inverse association between age and DNA repair activity with a 0.65% decline in activity per year from age 18 to 83 (95% confidence interval: 0.16–1.14% per year). Univariate regression analysis also indicated inverse associations between DNA repair activity and waist-hip ratio ( P 〈 0.05) and plasma concentrations of glycosylated hemoglobin ( P = 0.07). However, multivariate regression analysis only showed an inverse association between age and DNA repair activity ( P 〈 0.05), indicating that the decline in repair activity was not mediated by metabolic risk factors. In summary, the results show an inverse association between age and DNA repair activity of oxidatively damaged DNA.

Description: We have coupled a fast, parametrized star cluster evolution code to a Markov Chain Monte Carlo code to determine the distribution of probable initial conditions of observed star clusters, that may serve as a starting point for future N -body calculations. In this paper, we validate our method by applying it to a set of star clusters which have been studied in detail numerically with N -body simulations and Monte Carlo methods: the Galactic globular clusters M4, 47 Tucanae, NGC 6397, M22, Centauri, Palomar 14 and Palomar 4, the Galactic open cluster M67, and the M31 globular cluster G1. For each cluster, we derive a distribution of initial conditions that, after evolution up to the cluster's current age, evolves to the currently observed conditions. We find that there is a connection between the morphology of the distribution of initial conditions and the dynamical age of a cluster and that a degeneracy in the initial half-mass radius towards small radii is present for clusters that have undergone a core collapse during their evolution. We find that the results of our method are in agreement with N -body and Monte Carlo studies for the majority of clusters. We conclude that our method is able to find reliable posteriors for the determined initial mass and half-mass radius for observed star clusters, and thus forms an suitable starting point for modelling an observed cluster's evolution.

Description: We present a panoramic study of the Fornax dwarf spheroidal galaxy, using data obtained as part of the VLT Survey Telescope (VST) ATLAS Survey. The data presented here – a subset of the full survey – uniformly cover a region of 25 deg 2 centred on the galaxy, in g , r and i bands. This large area coverage reveals two key differences to previous studies of Fornax. First, data extending beyond the nominal tidal radius of the dwarf highlight the presence of a second distinct red giant branch population. This bluer red giant branch appears to be co-eval with the horizontal branch population. Secondly, a shell structure located approximately 1 $_{.}^{\circ}$ 4 from the centre of Fornax is shown to be a mis-identified background overdensity of galaxies. This last result casts further doubt on the hypothesis that Fornax underwent a gas-rich merger in its relatively recent past.

Description: Far-infrared (FIR)–radio correlation is a well-established empirical connection between continuum radio and dust emission of star-forming galaxies, often used as a tool in determining star formation rates. Here we expand the point made by Murphy that in the case of some interacting star-forming galaxies there is a non-thermal emission from the gas bridge in between them, which might cause a dispersion in this correlation. Galactic interactions and mergers have been known to give rise to tidal shocks and disrupt morphologies especially in the smaller of the interacting components. Here we point out that these shocks can also heat the gas and dust and will inevitably accelerate particles and result in a tidal cosmic ray population in addition to standard galactic cosmic rays in the galaxy itself. This would result in a non-thermal emission not only from the gas bridges of interacting systems, but from interacting galaxies as a whole in general. Thus both tidal heating and additional non-thermal radiation will obviously affect the FIR–radio correlation of these systems, the only question is how much. In this scenario the FIR–radio correlation is not stable in interacting galaxies, but rather evolves as the interaction/merger progresses. To test this hypothesis and probe the possible impact of tidal cosmic ray population, we have analysed a sample of 43 infrared-bright star-forming interacting galaxies at different merger stages. We have found that their FIR–radio correlation parameter and radio emission spectral index vary noticeably over different merger stages and behave as it would be expected from our tidal-shock scenario. Important implications of departure of interacting galaxies from the FIR–radio correlation are discussed.

Description: We report the alignment and shape of dark matter, stellar, and hot gas distributions in the EAGLE (Evolution and Assembly of GaLaxies and their Environments) and cosmo-OWLS (OverWhelmingly Large Simulations) simulations. The combination of these state-of-the-art hydrodynamical cosmological simulations enables us to span four orders of magnitude in halo mass (11 ≤ log 10 ( M 200 /[ h –1 M ]) ≤ 15), a wide radial range (–2.3 ≤ log 10 ( r /[ h –1 Mpc]) ≤ 1.3) and redshifts 0 ≤  z  ≤ 1. The shape parameters of the dark matter, stellar and hot gas distributions follow qualitatively similar trends: they become more aspherical (and triaxial) with increasing halo mass, radius, and redshift. We measure the misalignment of the baryonic components (hot gas and stars) of galaxies with their host halo as a function of halo mass, radius, redshift, and galaxy type (centrals versus satellites and early- versus late-type). Overall, galaxies align well with the local distribution of the total (mostly dark) matter. However, the stellar distributions on galactic scales exhibit a median misalignment of about 45–50 deg with respect to their host haloes. This misalignment is reduced to 25–30 deg in the most massive haloes (13 ≤ log 10 ( M 200 /[ h –1 M ]) ≤ 15). Half of the disc galaxies in the EAGLE simulations have a misalignment angle with respect to their host haloes larger than 40 deg. We present fitting functions and tabulated values for the probability distribution of galaxy–halo misalignment to enable a straightforward inclusion of our results into models of galaxy formations based on purely collisionless N -body simulations.

Description: We develop a simple dynamical model for the evolution of gas in the centres of barred spiral galaxies, using the Milky Way's Central Molecular Zone (CMZ, i.e. the central few hundred pc) as a case study. We show that, in the presence of a galactic bar, gas in a disc in the central regions of a galaxy will be driven inwards by angular momentum transport induced by acoustic instabilities within the bar's inner Lindblad resonance. This transport process drives turbulence within the gas that temporarily keeps it strongly gravitationally stable and prevents the onset of rapid star formation. However, at some point the rotation curve must transition from approximately flat to approximately solid body, and the resulting reduction in shear reduces the transport rates and causes gas to build up, eventually producing a gravitationally unstable region that is subject to rapid and violent star formation. For the observed rotation curve of the Milky Way, the accumulation happens ~100 pc from the centre of the Galaxy, in good agreement with the observed location of gas clouds and young star clusters in the CMZ. The characteristic time-scale for gas accumulation and star formation is of the order of 10–20 Myr. We argue that similar phenomena should be ubiquitous in other barred spiral galaxies.

Description: Exposure to traffic-related particulate matter (PM) has been associated with increased risk of lung disease, cancer and cardiovascular disease especially in elderly and overweight subjects. The proposed mechanisms involve intracellular production of reactive oxygen species (ROS), inflammation and oxidation-induced DNA damage studied mainly in young normal-weight subjects. We performed a controlled cross-over, randomised, single-blinded, repeated-measure study where 60 healthy subjects (25 males and 35 females) with age 55–83 years and body mass index above 25kg/m 2 were exposed for 5h to either particle-filtered or sham-filtered air from a busy street with number of concentrations and PM 2.5 levels of 1800/cm 3 versus 23 000/cm 3 and 3 µg/m 3 versus 24 µg/m 3 , respectively. Peripheral blood mononuclear cells (PBMCs) were collected and assayed for production of ROS with and without ex vivo exposure to nanosized carbon black as well as expression of genes related to inflammation ( chemokine (C-C motif) ligand 2 , interleukin-8 and tumour necrosis factor ), oxidative stress response ( heme oxygenase (decycling)-1 ) and DNA repair ( oxoguanine DNA glycosylase ). DNA strand breaks and oxidised purines were assayed by the alkaline comet assay. No statistically significant differences were found for any biomarker immediately after exposure to PM from urban street air although strand breaks and oxidised purines combined were significantly associated with the particle number concentration during exposure. In conclusion, 5h of controlled exposure to PM from urban traffic did not change the gene expression related to inflammation, oxidative stress or DNA repair, ROS production or oxidatively damaged DNA in PBMCs from elderly overweight human subjects.

Description: Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only ( P 〈 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice.

Description: Individualized treatment rules recommend treatments on the basis of individual patient characteristics. A high-quality treatment rule can produce better patient outcomes, lower costs and less treatment burden. If a treatment rule learned from data is to be used to inform clinical practice or provide scientific insight, it is crucial that it be interpretable; clinicians may be unwilling to implement models they do not understand, and black-box models may not be useful for guiding future research. The canonical example of an interpretable prediction model is a decision tree. We propose a method for estimating an optimal individualized treatment rule within the class of rules that are representable as decision trees. The class of rules we consider is interpretable but expressive. A novel feature of this problem is that the learning task is unsupervised, as the optimal treatment for each patient is unknown and must be estimated. The proposed method applies to both categorical and continuous treatments and produces favourable marginal mean outcomes in simulation experiments. We illustrate it using data from a study of major depressive disorder.

Description: Sufficient dimension reduction in regression aims to reduce the predictor dimension by replacing the original predictors with some set of linear combinations of them without loss of information. Numerous dimension reduction methods have been developed based on this paradigm. However, little effort has been devoted to diagnostic studies within the context of dimension reduction. In this paper we introduce methods to check goodness-of-fit for a given dimension reduction subspace. The key idea is to extend the so-called distance correlation to measure the conditional dependence relationship between the covariates and the response given a reduction subspace. Our methods require minimal assumptions, which are usually much less restrictive than the conditions needed to justify the original methods. Asymptotic properties of the test statistic are studied. Numerical examples demonstrate the effectiveness of the proposed approach.

Description: We propose a geometric framework to assess sensitivity of Bayesian procedures to modelling assumptions based on the nonparametric Fisher–Rao metric. While the framework is general, the focus of this article is on assessing local and global robustness in Bayesian procedures with respect to perturbations of the likelihood and prior, and on the identification of influential observations. The approach is based on a square-root representation of densities, which enables analytical computation of geodesic paths and distances, facilitating the definition of naturally calibrated local and global discrepancy measures. An important feature of our approach is the definition of a geometric $\epsilon$ -contamination class of sampling distributions and priors via intrinsic analysis on the space of probability density functions. We demonstrate the applicability of our framework to generalized mixed-effects models and to directional and shape data.

Description: With the discovery of an increasing number of causal genes for complex human disorders, it is crucial to assess the genetic risk of disease onset for individuals who are carriers of these causal mutations and to compare the distribution of the age-at-onset for such individuals with the distribution for noncarriers. In many genetic epidemiological studies that aim to estimate causal gene effect on disease, the age-at-onset of disease is subject to censoring. In addition, the mutation carrier or noncarrier status of some individuals may be unknown, due to the high cost of in-person ascertainment by collecting DNA samples or because of the death of older individuals. Instead, the probability of such individuals’ mutation status can be obtained from various other sources. When mutation status is missing, the available data take the form of censored mixture data. Recently, various methods have been proposed for risk estimation using such data, but none is efficient for estimating a nonparametric distribution. We propose a fully efficient sieve maximum likelihood estimation method, in which we estimate the logarithm of the hazard ratio between genetic mutation groups using B-splines, while applying nonparametric maximum likelihood estimation to the reference baseline hazard function. Our estimator can be calculated via an expectation-maximization algorithm which is much faster than existing methods. We show that our estimator is consistent and semiparametrically efficient and establish its asymptotic distribution. Simulation studies demonstrate the superior performance of the proposed method, which is used to estimate the distribution of the age-at-onset of Parkinson's disease for carriers of mutations in the leucine-rich repeat kinase 2, LRRK2, gene.

Description: Smoothing splines provide flexible nonparametric regression estimators. However, the high computational cost of smoothing splines for large datasets has hindered their wide application. In this article, we develop a new method, named adaptive basis sampling, for efficient computation of smoothing splines in super-large samples. Except for the univariate case where the Reinsch algorithm is applicable, a smoothing spline for a regression problem with sample size n can be expressed as a linear combination of n basis functions and its computational complexity is generally O ( n 3 ). We achieve a more scalable computation in the multivariate case by evaluating the smoothing spline using a smaller set of basis functions, obtained by an adaptive sampling scheme that uses values of the response variable. Our asymptotic analysis shows that smoothing splines computed via adaptive basis sampling converge to the true function at the same rate as full basis smoothing splines. Using simulation studies and a large-scale deep earth core-mantle boundary imaging study, we show that the proposed method outperforms a sampling method that does not use the values of response variables.

Description: We propose tests for nonlinear serial dependence in time series under the null hypothesis of general linear dependence, in contrast to the more widely studied null hypothesis of independence. The approach is based on combining an entropy dependence metric, which possesses many desirable properties and is used as a test statistic, with a suitable extension of surrogate data methods, a class of Monte Carlo distribution-free tests for nonlinearity, and a smoothed sieve bootstrap scheme. We show how, in the same way as the autocorrelation function is used for linear models, our tests can in principle be employed to detect the lags at which a significant nonlinear relationship is present. We prove the asymptotic validity of the proposed procedures and the corresponding inferences. The small-sample performance of the tests in terms of power and size is assessed through a simulation study. Applications to real datasets of different kinds are also presented.

Description: Contamination caused by outliers is inevitable in data analysis, and robust statistical methods are often needed. In this paper we develop a new approach for robust data analysis on the basis of scoring rules. A scoring rule is a discrepancy measure to assess the quality of probabilistic forecasts. We propose a simple method of estimating not only parameters in the statistical model but also the contamination ratio, i.e., the ratio of outliers. The outliers are detected based on the estimated contamination ratio. For this purpose, we use scoring rules with extended statistical models called unnormalized models. Regression problems are also considered. We study complex heterogeneous contamination wherein the contamination ratio in a response variable may depend on covariate variables, and propose a simple method to estimate a robust regression function and expected contamination ratio. Simulation studies demonstrate the effectiveness of our method.

Description: The sample covariance matrix, which is well known to be highly nonrobust, plays a central role in many classical multivariate statistical methods. A popular way of making such multivariate methods more robust is to replace the sample covariance matrix with some robust scatter matrix. The aim of this paper is to point out that multivariate methods often require that certain properties of the covariance matrix hold also for the robust scatter matrix in order for the corresponding robust plug-in method to be a valid approach, but that not all scatter matrices possess the desired properties. Plug-in methods for independent components analysis, observational regression and graphical modelling are considered in more detail. For each case, it is shown that replacing the sample covariance matrix with a symmetrized robust scatter matrix yields a valid robust multivariate procedure.

Description: So-called big data are likely to have complex structure, in particular implying that estimates of precision obtained by applying standard statistical procedures are likely to be misleading, even if the point estimates of parameters themselves may be reasonably satisfactory. While this possibility is best explored in the context of each special case, here we outline a fairly general representation of the accretion of error in large systems and explore the possible implications for the estimation of regression coefficients. The discussion raises issues broadly parallel to the distinction between short-range and long-range dependence in time series theory.

Description: This paper extends the classical two-regime threshold autoregressive model by introducing hysteresis to its regime-switching structure, which leads to a new model: the hysteretic autoregressive model. The proposed model enjoys the piecewise linear structure of a threshold model but has a more flexible regime switching mechanism. A sufficient condition is given for geometric ergodicity. Conditional least squares estimation is discussed, and the asymptotic distributions of its estimators and information criteria for model selection are derived. Simulation results and an example support the model.

Description: This paper points out an error in Davidov and Iliopoulos's ( Biometrika 100 , 778–80) proof of convergence of an iterative algorithm for the proportional likelihood ratio model. It is shown that the iterative algorithm increases the likelihood in each iteration and converges under mild additional conditions when the odds ratio function is bounded.

Description: One of the major sources of the X-ray emitting hot gas around galaxies is the feedback from supernovae (SNe), but most of this metal-enriched feedback material is often not directly detected in X-ray observations. This missing galactic feedback problem is extremely prominent in early-type galaxy bulges, where there is little cool gas to make the Type Ia SNe ejecta radiate at lower temperature beyond the X-ray domain. We herein present a deep Suzaku observation of an S0 galaxy NGC 5866, which is relatively rich in molecular gas as an S0 galaxy and shows significant evidence of cool–hot gas interaction. By jointly analysing the Suzaku and an archival Chandra data, we measure the Fe/O abundance ratio to be $\rm 7.63_{-5.52}^{+7.28}$ relative to solar values. This abundance ratio is much higher than those of spiral galaxies, and even among the highest ones of S0 and elliptical galaxies. NGC 5866 also simultaneously has the highest Fe/O abundance ratio and molecular gas mass among a small sample of gas-poor early-type galaxies. An estimation of the Fe budget indicates that NGC 5866 could preserve a larger than usual fraction, but far from the total amount of Fe injected by Type Ia SNe. We also find that the hot gas temperature increases from inner to outer haloes, with the inner region has a temperature of ~ 0.25 keV, clearly lower than that expected from Type Ia SNe heating. This low temperature could be most naturally explained by additional cooling processes related to the cool–hot gas interaction as being indicated by the existence of many extraplanar dusty filaments. Our results indicate that the large cool gas content and the presence of cool–hot gas interaction in the inner region of NGC 5866 have significantly reduced the specific energy of the SN ejecta and so the velocity of the galactic outflow. The galaxy could thus preserve a considerable fraction of the metal-enriched feedback material from being blown out.

Description: According to the standard cosmological scenario, superclusters are objects that have just passed the turn-around point and are collapsing. The dynamics of very few superclusters have been analysed up to now. In this paper, we study the supercluster SC0028-0005, at redshift 0.22, identify the most prominent groups and/or clusters that make up the supercluster, and investigate the dynamic state of this structure. For the membership identification, we have used photometric and spectroscopic data from Sloan Digital Sky Survey Data Release 10, finding six main structures in a flat spatial distribution. We have also used a deep multiband observation with MegaCam/Canada–France–Hawaii Telescope to estimate de mass distribution through the weak-lensing effect. For the dynamical analysis, we have determined the relative distances along the line of sight within the supercluster using the Fundamental Plane of early-type galaxies. Finally, we have computed the peculiar velocities of each of the main structures. The 3D distribution suggests that SC0028-005 is indeed a collapsing supercluster, supporting the formation scenario of these structures. Using the spherical collapse model, we estimate that the mass within r  = 10 Mpc should lie between 4 and 16  x  10 15 M . The farthest detected members of the supercluster suggest that within ~60 Mpc the density contrast is  ~ 3 with respect to the critical density at z  = 0.22, implying a total mass of ~4.6–16  x  10 17 M , most of which in the form of low-mass galaxy groups or smaller substructures.

Description: We present CCD UBVRI photometry of the field of the open cluster NGC 6866. Structural parameters of the cluster are determined utilizing the stellar density profile of the stars in the field. We calculate the probabilities of the stars being physical members of the cluster, using their astrometric data, and perform further analyses using only the most probable members. The reddening and metallicity of the cluster were determined by independent methods. The LAMOST spectra and the ultraviolet excess of the F- and G-type main-sequence stars in the cluster indicate that the metallicity of the cluster is about the solar value. We estimated the reddening E ( B – V ) = 0.074 ± 0.050 mag using the U – B versus B – V two-colour diagram. The distance modula, the distance and the age of NGC 6866 were derived as μ = 10.60 ± 0.10 mag, d  = 1189 ± 75 pc and t  = 813 ± 50 Myr, respectively, by fitting colour–magnitude diagrams of the cluster with the PARSEC isochrones. The Galactic orbit of NGC 6866 indicates that the cluster is orbiting in a slightly eccentric orbit with e  = 0.12. The mass function slope x  = 1.35 ± 0.08 was derived by using the most probable members of the cluster.

Description: The mean absolute extinction towards the central parsec of the Milky Way is A K ~= 3 mag, including both foreground and Galactic Centre dust. Here we present a measurement of dust extinction within the Galactic old nuclear star cluster (NSC), based on combining differential extinctions of NSC stars with their l proper motions along Galactic longitude. Extinction within the NSC preferentially affects stars at its far side, and because the NSC rotates, this causes higher extinctions for NSC stars with negative l , as well as an asymmetry in the l -histograms. We model these effects using an axisymmetric dynamical model of the NSC in combination with simple models for the dust distribution. Comparing the predicted asymmetry to data for ~7100 stars in several NSC fields, we find that dust associated with the Galactic Centre mini-spiral with extinction A K ~= 0.15–0.8 mag explains most of the data. The largest extinction A K ~= 0.8 mag is found in the region of the Western arm of the mini-spiral. Comparing with total A K determined from stellar colours, we determine the extinction in front of the NSC. Finally, we estimate that for a typical extinction of A K ~= 0.4 the statistical parallax of the NSC changes by ~0.4 per cent.

Description: Regardless of the physical origin of stellar magnetic fields – fossil or dynamo induced - an inclination angle between the magnetic and rotation axes is very often observed. Absence of observational evidence in this direction in the solar case has led to generally assume that its global magnetic field and rotation axes are well aligned. We present the detection of a monthly periodic signal of the photospheric solar magnetic field at all latitudes, and especially near the poles, revealing that the main axis of the Sun's magnetic field is not aligned with the surface rotation axis. This result reinforces the view of our Sun as a common intermediate-mass star. Furthermore, this detection challenges and imposes a strong observational constraint to modern solar dynamo theories.

Description: Motivation: The storage and transmission of high-throughput sequencing data consumes significant resources. As our capacity to produce such data continues to increase, this burden will only grow. One approach to reduce storage and transmission requirements is to compress this sequencing data. Results: We present a novel technique to boost the compression of sequencing that is based on the concept of bucketing similar reads so that they appear nearby in the file. We demonstrate that, by adopting a data-dependent bucketing scheme and employing a number of encoding ideas, we can achieve substantially better compression ratios than existing de novo sequence compression tools, including other bucketing and reordering schemes. Our method, Mince, achieves up to a 45% reduction in file sizes (28% on average) compared with existing state-of-the-art de novo compression schemes. Availability and implementation : Mince is written in C++11, is open source and has been made available under the GPLv3 license. It is available at http://www.cs.cmu.edu/~ckingsf/software/mince . Contact: carlk@cs.cmu.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Description: : Current methods for motif discovery from chromatin immunoprecipitation followed by sequencing (ChIP-seq) data often identify non-targeted transcription factor (TF) motifs, and are even further limited when peak sequences are similar due to common ancestry rather than common binding factors. The latter aspect particularly affects a large number of proteins from the Cys 2 His 2 zinc finger (C2H2-ZF) class of TFs, as their binding sites are often dominated by endogenous retroelements that have highly similar sequences. Here, we present recognition code-assisted discovery of regulatory elements (RCADE) for motif discovery from C2H2-ZF ChIP-seq data. RCADE combines predictions from a DNA recognition code of C2H2-ZFs with ChIP-seq data to identify models that represent the genuine DNA binding preferences of C2H2-ZF proteins. We show that RCADE is able to identify generalizable binding models even from peaks that are exclusively located within the repeat regions of the genome, where state-of-the-art motif finding approaches largely fail. Availability and implementation: RCADE is available as a webserver and also for download at http://rcade.ccbr.utoronto.ca/ . Supplementary information: Supplementary data are available at Bioinformatics online. Contact: t.hughes@utoronto.ca

Description: Motivation: Phylogenetic estimates from published studies can be archived using general platforms like Dryad (Vision, 2010) or TreeBASE (Sanderson et al. , 1994). Such services fulfill a crucial role in ensuring transparency and reproducibility in phylogenetic research. However, digital tree data files often require some editing (e.g. rerooting) to improve the accuracy and reusability of the phylogenetic statements. Furthermore, establishing the mapping between tip labels used in a tree and taxa in a single common taxonomy dramatically improves the ability of other researchers to reuse phylogenetic estimates. As the process of curating a published phylogenetic estimate is not error-free, retaining a full record of the provenance of edits to a tree is crucial for openness, allowing editors to receive credit for their work and making errors introduced during curation easier to correct. Results : Here, we report the development of software infrastructure to support the open curation of phylogenetic data by the community of biologists. The backend of the system provides an interface for the standard database operations of creating, reading, updating and deleting records by making commits to a git repository. The record of the history of edits to a tree is preserved by git’s version control features. Hosting this data store on GitHub ( http://github.com/ ) provides open access to the data store using tools familiar to many developers. We have deployed a server running the ‘phylesystem-api’, which wraps the interactions with git and GitHub. The Open Tree of Life project has also developed and deployed a JavaScript application that uses the phylesystem-api and other web services to enable input and curation of published phylogenetic statements. Availability and implementation : Source code for the web service layer is available at https://github.com/OpenTreeOfLife/phylesystem-api . The data store can be cloned from: https://github.com/OpenTreeOfLife/phylesystem . A web application that uses the phylesystem web services is deployed at http://tree.opentreeoflife.org/curator . Code for that tool is available from https://github.com/OpenTreeOfLife/opentree . Contact : mtholder@gmail.com

Description: Motivation: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) detects genome-wide DNA–protein interactions and chromatin modifications, returning enriched regions (ERs), usually associated with a significance score. Moderately significant interactions can correspond to true, weak interactions, or to false positives; replicates of a ChIP-seq experiment can provide co-localised evidence to decide between the two cases. We designed a general methodological framework to rigorously combine the evidence of ERs in ChIP-seq replicates, with the option to set a significance threshold on the repeated evidence and a minimum number of samples bearing this evidence. Results : We applied our method to Myc transcription factor ChIP-seq datasets in K562 cells available in the ENCODE project. Using replicates, we could extend up to 3 times the ER number with respect to single-sample analysis with equivalent significance threshold. We validated the ‘rescued’ ERs by checking for the overlap with open chromatin regions and for the enrichment of the motif that Myc binds with strongest affinity; we compared our results with alternative methods (IDR and jMOSAiCS), obtaining more validated peaks than the former and less peaks than latter, but with a better validation. Availability and implementation : An implementation of the proposed method and its source code under GPLv3 license are freely available at http://www.bioinformatics.deib.polimi.it/MSPC/ and http://mspc.codeplex.com/ , respectively. Contact : marco.morelli@iit.it Supplementary information: Supplementary Material are available at Bioinformatics online.

Description: : We announce the release of kSNP3.0, a program for SNP identification and phylogenetic analysis without genome alignment or the requirement for reference genomes. kSNP3.0 is a significantly improved version of kSNP v2. Availability and implementation : kSNP3.0 is implemented as a package of stand-alone executables for Linux and Mac OS X under the open-source BSD license. The executable packages, source code and a full User Guide are freely available at https://sourceforge.net/projects/ksnp/files/ Contact: barryghall@gmail.com

Description: Motivation: We have created an R package named phylogeo that provides a set of geographic utilities for sequencing-based microbial ecology studies. Although the geographic location of samples is an important aspect of environmental microbiology, none of the major software packages used in processing microbiome data include utilities that allow users to map and explore the spatial dimension of their data. phylogeo solves this problem by providing a set of plotting and mapping functions that can be used to visualize the geographic distribution of samples, to look at the relatedness of microbiomes using ecological distance, and to map the geographic distribution of particular sequences. By extending the popular phyloseq package and using the same data structures and command formats, phylogeo allows users to easily map and explore the geographic dimensions of their data from the R programming language. Availability and Implementation: phylogeo is documented and freely available http://zachcp.github.io/phylogeo Contact : zcharlop@rockefeller.edu

Description: : Gener is a development module for programming chemical controllers based on DNA strand displacement. Gener is developed with the aim of providing a simple interface that minimizes the opportunities for programming errors: Gener allows the user to test the computations of the DNA programs based on a simple two-domain strand displacement algebra, the minimal available so far. The tool allows the user to perform stepwise computations with respect to the rules of the algebra as well as exhaustive search of the computation space with different options for exploration and visualization. Gener can be used in combination with existing tools, and in particular, its programs can be exported to Microsoft Research’s DSD tool as well as to LaTeX. Availability and implementation : Gener is available for download at the Cosbi website at http://www.cosbi.eu/research/prototypes/gener as a windows executable that can be run on Mac OS X and Linux by using Mono. Contact : ozan@cosbi.eu

Description: Motivation: Molecular dynamics simulations provide atomic insight into the physicochemical characteristics of lipid membranes and hence, a wide range of force field families capable of modelling various lipid types have been developed in recent years. To model membranes in a biologically realistic lipid composition, simulation systems containing multiple different lipids must be assembled. Results: We present a new web service called MemGen that is capable of setting up simulation systems of heterogenous lipid membranes. MemGen is not restricted to certain lipid force fields or lipid types, but instead builds membranes from uploaded structure files which may contain any kind of amphiphilic molecule. MemGen works with any all-atom or united-atom lipid representation. Availability and implementation: MemGen is freely available without registration at http://memgen.uni-goettingen.de . Contact: jhub@gwdg.de Supplementary information: Supplementary data are available at Bioinformatics online.

Description: Hydrocarbon reservoir pressure depletion leads to stress changes inside the reservoir and ground deformation which is registered at the surface as subsidence. As reservoirs are often overlain by layers of rocksalt (or other evaporites), which are materials that flow so as to relax stresses inside them, there is the potential for time-varying surface subsidence. This work focuses on understanding the macroscopic mechanisms that lead to rocksalt flow-induced ground displacements. A Finite Element Model is used for this purpose in which the rocksalt layer is represented by a viscoelastic Maxwell material. Two distinct mechanisms that lead to displacement are observed. These are active during different stages of the deformation and have different timescales associated with them. An important observation is that the timescale for deformation that is measured at the ground surface is not equal to the timescale for deformation of a viscoelastic material element, but can be many times larger than that. The sensitivity of the response to the thickness and location of the rocksalt layer is also presented. Conclusions are drawn which allow for the relative importance of the presence of the rocksalt layer to be assessed and for a framework for understanding time-dependent subsidence above producing hydrocarbon reservoirs to be developed. Finally the changes in stress distribution around a producing reservoir are also briefly discussed.

Description: Environmental control of flowering allows plant reproduction to occur under optimal conditions and facilitates adaptation to different locations. At high latitude, flowering of many plants is controlled by seasonal changes in day length. The photoperiodic flowering pathway confers this response in the Brassicaceae, which colonized temperate latitudes after divergence from the Cleomaceae, their subtropical sister family. The CONSTANS (CO) transcription factor of Arabidopsis thaliana , a member of the Brassicaceae, is central to the photoperiodic flowering response and shows characteristic patterns of transcription required for day-length sensing. CO is believed to be widely conserved among flowering plants; however, we show that it arose after gene duplication at the root of the Brassicaceae followed by divergence of transcriptional regulation and protein function. CO has two close homologs, CONSTANS-LIKE1 ( COL1 ) and COL2 , which are related to CO by tandem duplication and whole-genome duplication, respectively. The single CO homolog present in the Cleomaceae shows transcriptional and functional features similar to those of COL1 and COL2 , suggesting that these were ancestral. We detect cis -regulatory and codon changes characteristic of CO and use transgenic assays to demonstrate their significance in the day-length-dependent activation of the CO target gene FLOWERING LOCUS T. Thus, the function of CO as a potent photoperiodic flowering switch evolved in the Brassicaceae after gene duplication. The origin of CO may have contributed to the range expansion of the Brassicaceae and suggests that in other families CO genes involved in photoperiodic flowering arose by convergent evolution.

Description: The high regulatory complexity of vertebrates has been related to two rounds of whole genome duplication (2R-WGD) that occurred before the divergence of the major vertebrate groups. Following these events, many developmental transcription factors (TFs) were retained in multiple copies and subsequently specialized in diverse functions, whereas others reverted to their singleton state. TFs are known to be generally rich in amino acid repeats or low-complexity regions (LCRs), such as polyalanine or polyglutamine runs, which can evolve rapidly and potentially influence the transcriptional activity of the protein. Here we test the hypothesis that LCRs have played a major role in the diversification of TF gene duplicates. We find that nearly half of the TF gene families originated during the 2R-WGD contains LCRs. The number of gene duplicates with LCRs is 155 out of 550 analyzed (28%), about twice as many as the number of single copy genes with LCRs (15 out of 115, 13%). In addition, duplicated TFs preferentially accumulate certain LCR types, the most prominent of which are alanine repeats. We experimentally test the role of alanine-rich LCRs in two different TF gene families, PHOX2A/PHOX2B and LHX2/LHX9. In both cases, the presence of the alanine-rich LCR in one of the copies (PHOX2B and LHX2) significantly increases the capacity of the TF to activate transcription. Taken together, the results provide strong evidence that LCRs are important driving forces of evolutionary change in duplicated genes.

Description: Studies of species with continental distributions continue to identify intraspecific lineages despite continuous habitat. Lineages may form due to isolation by distance, adaptation, divergence across barriers, or genetic drift following range expansion. We investigated lineage diversification and admixture within American black bears ( Ursus americanus ) across their range using 22 k single nucleotide polymorphisms and mitochondrial DNA sequences. We identified three subcontinental nuclear clusters which we further divided into nine geographic regions: Alaskan (Alaska-East), eastern (Central Interior Highlands, Great Lakes, Northeast, Southeast), and western (Alaska-West, West, Pacific Coast, Southwest). We estimated that the western cluster diverged 67 ka, before eastern and Alaskan divergence 31 ka; these divergence dates contrasted with those from the mitochondrial genome where clades A and B diverged 1.07 Ma, and clades A-east and A-west diverged 169 ka. We combined estimates of divergence timing with hindcast species distribution models to infer glacial refugia for the species in Beringia, Pacific Northwest, Southwest, and Southeast. Our results show a complex arrangement of admixture due to expansion out of multiple refugia. The delineation of the genomic population clusters was inconsistent with the ranges for 16 previously described subspecies. Ranges for U. a. pugnax and U. a. cinnamomum were concordant with admixed clusters, calling into question how to order taxa below the species level. Additionally, our finding that U. a. floridanus has not diverged from U. a. americanus also suggests that morphology and genetics should be reanalyzed to assess taxonomic designations relevant to the conservation management of the species.

Description: Deinococcus bacteria are extremely resistant to radiation, oxidation, and desiccation. Resilience to these factors has been suggested to be due to enhanced damage prevention and repair mechanisms, as well as highly efficient antioxidant protection systems. Here, using mutation-accumulation experiments, we find that the GC-rich Deinococcus radiodurans has an overall background genomic mutation rate similar to that of E. coli , but differs in mutation spectrum, with the A/T to G/C mutation rate (based on a total count of 88 A:T-〉G:C transitions and 82 A:T-〉C:G transversions) per site per generation higher than that in the other direction (based on a total count of 157 G:C-〉A:T transitions and 33 G:C-〉T:A transversions). We propose that this unique spectrum is shaped mainly by the abundant uracil DNA glycosylases reducing G:C-〉A:T transitions, adenine methylation elevating A:T-〉C:G transversions, and absence of cytosine methylation decreasing G:C-〉A:T transitions. As opposed to the greater than 100 x elevation of the mutation rate in MMR – (DNA Mismatch Repair deficient) strains of most other organisms, MMR – D. radiodurans only exhibits a 4-fold elevation, raising the possibility that other DNA repair mechanisms compensate for a relatively low-efficiency DNA MMR pathway. As D. radiodurans has plentiful insertion sequence (IS) elements in the genome and the activities of IS elements are rarely directly explored, we also estimated the insertion (transposition) rate of the IS elements to be 2.50 x 10 –3 per genome per generation in the wild-type strain; knocking out MMR did not elevate the IS element insertion rate in this organism.