Mapping spaces in Quasi-categories

We apply the Dwyer-Kan theory of homotopy function complexes in model categories to the study of mapping spaces in quasi-categories. Using this, together with our work on rigidification from [DS1], we give a streamlined proof of the Quillen equivalence between quasi-categories and simplicial categories. Some useful material about relative mapping spaces in quasi-categories is developed along the way

Lime stabilisation: clay-metal-lime interactions

The literature review identified the current scientific understanding of element and lime interactions with clay minerals and the leaching protocols used to assess contaminant mobility. This understanding formed the basis for the mechanisms postulated for clay-contaminant-lime interactions and the appropriate methods of chemically assessing time-dependent interactions. Two refined clay minerals English China Clay (predominantly kaolinite) and Wyoming Bentonite (predominantly sodium-montmorillonite) were used to assess the time-dependent effects of mineral structural chemistry on clay-contaminant-lime interactions. (Continues...)

The mineralogy and fabric of 'Brickearths' in Kent, UK and their relationship to engineering behaviour

Mineralogical and petrographical investigation of two loessic brickearth profiles from Ospringe and Pegwell Bay in north Kent, UK have differentiated two types of brickearth fabric that can be correlated with different engineering behaviour. Both sequences comprise metastable (collapsing) calcareous brickearth, overlain by non collapsing ‘non-calcareous’ brickearth. This study has demonstrated that the two types of brickearth are discretely different sedimentary units, with different primary sedimentary characteristics and an erosional junction between the two units. A palaeosol is developed on the calcareous brickearth, and is associated with the formation of rhizolithic calcrete indicating an arid or semi-arid environment. No evidence has been found for decalcification being responsible for the fabric of the upper ‘non-calcareous’ brickearth. Optically-stimulated dates lend further support for the calcareous and ‘non-calcareous’ brickearth horizons being of different age or origins. The calcareous brickearth is metastable in that it undergoes rapid collapse settlement when wetted under applied stresses. It is characterised by an open-packed arrangement of clay-coated, silt-sized quartz particles and pelletised aggregate grains (peds) of compacted silt and clay, supported by an interped matrix of loosely packed, silt/fine-grained sand, in which the grains are held in place by a skeletal framework of illuviated clay. The illuviated clay forms bridges and pillars separating and binding the dispersed component silt/sand grains. There is little direct grain-to-grain contact and the resultant fabric has a very high voids ratio. Any applied load is largely supported by these delicate clay bridge and pillar microfabrics. Collapse of this brickearth fabric can be explained by a sequence of processes involving: (1) dispersion and disruption of the grain-bridging clay on saturation, leading to initial rapid collapse of the loose packed inter-ped silt/sand; (2) rearrangement and closer stacking of the compact aggregate silt/clay peds; (3) with increasing stress further consolidation may result from deformation and break up of the peds as they collapse into the inter-ped regions. Smectite is a significant component of the clay assemblage and will swell on wetting, further encouraging disruption and breaking of the clay bonds. In contrast, the ‘non-calcareous’ brickearth already possesses a close-packed and interlocking arrangement of silt/sand grains with only limited scope for further consolidation under load. Minor authigenic calcite and dolomite may also form meniscus cements between silt grains. These have either acted as ‘‘scaffolds’’ on which illuviated clay has subsequently been deposited or have encrusted earlier formed grain-bridging clay. In either case, the carbonate cements may help to reinforce the clay bridge fabrics. However, these carbonate features are a relatively minor feature and not an essential component of the collapsible brickearth fabric. Cryoturbation and micromorphological features indicate that the calcareous brickearth fabric has probably been developed through periglacial freeze–thaw processes. Freezing could have produced the compact silt/clay aggregates and an open porous soil framework containing significant inter-ped void space. Silt and clay were remobilised and translocated deeper into the soil profile by water percolating through the active layer of the sediment profile during thawing cycles, to form the loosed packed inter-ped silt matrix and grain-bridging meniscus clay fabrics. In contrast, the upper ‘non-calcareous’ brickearth may represent a head or solifluction deposit. Mass movement during solifluction will have destroyed any delicate grain-bridging clay microfabrics that may have been present in this material

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition

In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most change occurring in the chromosomes found in only one sex—the W and Y chromosomes1, 2, 3, 4, 5. By contrast, the sex chromosomes found in both sexes—the Z and X chromosomes—are assumed to have diverged little from their autosomal progenitors2. Here we report findings that challenge this assumption for both the chicken Z chromosome and the human X chromosome. The chicken Z chromosome, which we sequenced essentially to completion, is less gene-dense than chicken autosomes but contains a massive tandem array containing hundreds of duplicated genes expressed in testes. A comprehensive comparison of the chicken Z chromosome with the finished sequence of the human X chromosome demonstrates that each evolved independently from different portions of the ancestral genome. Despite this independence, the chicken Z and human X chromosomes share features that distinguish them from autosomes: the acquisition and amplification of testis-expressed genes, and a low gene density resulting from an expansion of intergenic regions. These features were not present on the autosomes from which the Z and X chromosomes originated but were instead acquired during the evolution of Z and X as sex chromosomes. We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety. More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females.National Science Foundation (U.S.)Howard Hughes Medical Institut

Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators

After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males are ZZ, but in mammals females are XX and males are XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly expressed regulators of key cellular processes. We propose that, like the human Y chromosome, the chicken W chromosome is essential for embryonic viability of the heterogametic sex. Unlike other sequenced sex chromosomes, the chicken W chromosome did not acquire and amplify genes specifically expressed in reproductive tissues. We speculate that the pressures that drive the acquisition of reproduction-related genes on sex chromosomes may be specific to the male germ line

Testing the sensitivity of Tract-Based Spatial Statistics to simulated treatment effects in preterm neonates

Early neuroimaging may provide a surrogate marker for brain development and outcome after preterm birth. Tract-Based Spatial Statistics (TBSS) is an advanced Diffusion Tensor Image (DTI) analysis technique that is sensitive to the effects of prematurity and may provide a quantitative marker for neuroprotection following perinatal brain injury or preterm birth. Here, we test the sensitivity of TBSS to detect diffuse microstructural differences in the developing white matter of preterm infants at term-equivalent age by modelling a 'treatment' effect as a global increase in fractional anisotropy (FA). As proof of concept we compare these simulations to a real effect of increasing age at scan. 3-Tesla, 15-direction diffusion tensor imaging (DTI) was acquired from 90 preterm infants at term-equivalent age. Datasets were randomly assigned to 'treated' or 'untreated' groups of increasing size and voxel-wise increases in FA were used to simulate global treatment effects of increasing magnitude in all 'treated' maps. 'Treated' and 'untreated' FA maps were compared using TBSS. Predictions from simulated data were then compared to exemplar TBSS group comparisons based on increasing postmenstrual age at scan. TBSS proved sensitive to global differences in FA within a clinically relevant range, even in relatively small group sizes, and simulated data were shown to predict well a true biological effect of increasing age on white matter development. These data confirm that TBSS is a sensitive tool for detecting global group-wise differences in FA in this population