Quantitative genetic modeling and inference in the presence of nonignorable missing data.

Natural selection is typically exerted at some specific life stages. If natural selection takes place before a trait can be measured, using conventional models can cause wrong inference about population parameters. When the missing data process relates to the trait of interest, a valid inference requires explicit modeling of the missing process. We propose a joint modeling approach, a shared parameter model, to account for nonrandom missing data. It consists of an animal model for the phenotypic data and a logistic model for the missing process, linked by the additive genetic effects. A Bayesian approach is taken and inference is made using integrated nested Laplace approximations. From a simulation study we find that wrongly assuming that missing data are missing at random can result in severely biased estimates of additive genetic variance. Using real data from a wild population of Swiss barn owls Tyto alba, our model indicates that the missing individuals would display large black spots; and we conclude that genes affecting this trait are already under selection before it is expressed. Our model is a tool to correctly estimate the magnitude of both natural selection and additive genetic variance

On estimation and identifiability issues of sex-linked inheritance with a case study of pigmentation in Swiss barn owl (Tyto alba)

Genetic evaluation using animal models or pedigree-based models generally assume only autosomal inheritance. Bayesian animal models provide a flexible framework for genetic evaluation, and we show how the model readily can accommodate situations where the trait of interest is influenced by both autosomal and sex-linked inheritance. This allows for simultaneous calculation of autosomal and sex-chromosomal additive genetic effects. Inferences were performed using integrated nested Laplace approximations (INLA), a nonsampling-based Bayesian inference methodology. We provide a detailed description of how to calculate the inverse of the X- or Z-chromosomal additive genetic relationship matrix, needed for inference. The case study of eumelanic spot diameter in a Swiss barn owl (Tyto alba) population shows that this trait is substantially influenced by variation in genes on the Z-chromosome (sigma(2)(z) = 0.2719 and sigma(2)(a) = 0.4405). Further, a simulation study for this study system shows that the animal model accounting for both autosomal and sex-chromosome-linked inheritance is identifiable, that is, the two effects can be distinguished, and provides accurate inference on the variance components

Soap Bubbles in Outer Space: Interaction of a Domain Wall with a Black Hole

We discuss the generalized Plateau problem in the 3+1 dimensional Schwarzschild background. This represents the physical situation, which could for instance have appeared in the early universe, where a cosmic membrane (thin domain wall) is located near a black hole. Considering stationary axially symmetric membranes, three different membrane-topologies are possible depending on the boundary conditions at infinity: 2+1 Minkowski topology, 2+1 wormhole topology and 2+1 black hole topology. Interestingly, we find that the different membrane-topologies are connected via phase transitions of the form first discussed by Choptuik in investigations of scalar field collapse. More precisely, we find a first order phase transition (finite mass gap) between wormhole topology and black hole topology; the intermediate membrane being an unstable wormhole collapsing to a black hole. Moreover, we find a second order phase transition (no mass gap) between Minkowski topology and black hole topology; the intermediate membrane being a naked singularity. For the membranes of black hole topology, we find a mass scaling relation analogous to that originally found by Choptuik. However, in our case the parameter $p$ is replaced by a 2-vector $\vec{p}$ parametrizing the solutions. We find that $Mass\propto|\vec{p}-\vec{p}_*|^\gamma$ where $\gamma\approx 0.66$. We also find a periodic wiggle in the scaling relation. Our results show that black hole formation as a critical phenomenon is far more general than expected.Comment: 15 pages, Latex, 4 figures include

A parton picture of de Sitter space during slow-roll inflation

It is well-known that expectation values in de Sitter space are afflicted by infra-red divergences. Long ago, Starobinsky proposed that infra-red effects in de Sitter space could be accommodated by evolving the long-wavelength part of the field according to the classical field equations plus a stochastic source term. I argue that--when quantum-mechanical loop corrections are taken into account--the separate-universe picture of superhorizon evolution in de Sitter space is equivalent, in a certain leading-logarithm approximation, to Starobinsky's stochastic approach. In particular, the time evolution of a box of de Sitter space can be understood in exact analogy with the DGLAP evolution of partons within a hadron, which describes a slow logarithmic evolution in the distribution of the hadron's constituent partons with the energy scale at which they are probed.Comment: 36 pages; uses iopart.cls and feynmp.sty. v2: Minor typos corrected. Matches version published in JCA

Unitarity bounds on low scale quantum gravity

We study the unitarity of models with low scale quantum gravity both in four dimensions and in models with a large extra-dimensional volume. We find that models with low scale quantum gravity have problems with unitarity below the scale at which gravity becomes strong. An important consequence of our work is that their first signal at the Large Hadron Collider would not be of a gravitational nature such as graviton emission or small black holes, but rather linked to the mechanism which fixes the unitarity problem. We also study models with scalar fields with non minimal couplings to the Ricci scalar. We consider the strength of gravity in these models and study the consequences for inflation models with non-minimally coupled scalar fields. We show that a single scalar field with a large non-minimal coupling can lower the Planck mass in the TeV region. In that model, it is possible to lower the scale at which gravity becomes strong down to 14 TeV without violating unitarity below that scale.Comment: 15 page

A type III complement factor D deficiency: Structural insights for inhibition of the alternative pathway.

Abstract Background: Complement factor D (FD) is the rate-limiting enzyme of the alternative complement pathway. Previous reports of FD deficiency featured absent plasma FD (type I deficiency) and susceptibility to meningococcal infection. A new FD mutant, which is non-functional but fully expressed, was identified in a patient with invasive meningococcal disease. Objectives: We sought to investigate the molecular features of this novel FD mutant. Methods: We performed complement haemolytic assays, western blot analysis of serum FD and Sanger sequencing of the CFD gene. Recombinant mutant FD was assessed by in vitro catalytic assays, circular dichroism, thermal shift assays, esterolytic assays and surface plasmon resonance. Molecular dynamics simulation was used to visualise the structural changes in mutant FD. Results: A homozygous single-nucleotide variation of the CFD gene in the patient and their sibling resulted in an arginine to proline (R176P) substitution in FD. While R176P FD was stable and fully expressed in blood, it had minimal catalytic activity. Mutation R176P caused key FD-C3bB binding exosite loop 156-162 to lose its binding-competent conformation and stabilised the inactive conformation of FD. Consequently, R176P FD was unable to bind its natural substrate, C3bB. Neither patient nor sibling demonstrated the glucose homeostasis impairment that occurs in FD-null mice. Conclusions: Here, we report the first genetically confirmed functional, or type III, deficiency of an activating complement serine protease. This novel mechanism of FD inhibition can inform further development of alternative pathway inhibitors to treat common inflammatory diseases such as age-related macular degeneration

Effect of stress level on the high temperature deformation and fracture mechanisms of Ti-45Al-2Nb-2Mn-0.8 vol. pct TiB²: an 'In Situ' experimental study

The effect of the applied stress on the deformation and crack nucleation and propagation mechanisms of a gamma-TiAl intermetallic alloy (Ti-45Al-2Nb-2Mn (at. pct)-0.8 vol. pct TiB2) was examined by means of in situ tensile (constant strain rate) and tensile-creep (constant load) experiments performed at 973 K (700 °C) using a scanning electron microscope. Colony boundary cracking developed during the secondary stage in creep tests at 300 and 400 MPa and during the tertiary stage of the creep tests performed at higher stresses. Colony boundary cracking was also observed in the constant strain rate tensile test. Interlamellar ledges were only found during the tensile-creep tests at high stresses (sigma > 400 MPa) and during the constant strain rate tensile test. Quantitative measurements of the nature of the crack propagation path along secondary cracks and along the primary crack indicated that colony boundaries were preferential sites for crack propagation under all the conditions investigated. The frequency of interlamellar cracking increased with stress, but this fracture mechanism was always of secondary importance. Translamellar cracking was only observed along the primary crack.Funding from the Spanish Ministry of Science and Innovation through projects (MAT2009-14547-C02-01 and MAT2009-14547-C02-02) is acknowledged. The Madrid Regional Government partially supported this project through the ESTRUMAT grant (P2009/MAT-1585). CJB acknowledges the support from the Spanish Ministry of Education for his sabbatical stay in Madrid (SAB2009-0045).Publicad

Effects of climate and atmospheric nitrogen deposition on early to mid-term stage litter decomposition across biomes

Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1-3.5% and of the more stable substrates by 3.8-10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4-2.2% and that of low-quality litter by 0.9-1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate

The handbook for standardised field and laboratory measurements in terrestrial climate-change experiments and observational studies

Climate change is a worldwide threat to biodiversity and ecosystem structure, functioning, and services. To understand the underlying drivers and mechanisms, and to predict the consequences for nature and people, we urgently need better understanding of the direction and magnitude of climate‐change impacts across the soil–plant–atmosphere continuum. An increasing number of climate‐change studies is creating new opportunities for meaningful and high‐quality generalisations and improved process understanding. However, significant challenges exist related to data availability and/or compatibility across studies, compromising opportunities for data re‐use, synthesis, and upscaling. Many of these challenges relate to a lack of an established “best practice” for measuring key impacts and responses. This restrains our current understanding of complex processes and mechanisms in terrestrial ecosystems related to climate change