Confined granular packings: structure, stress, and forces

The structure and stresses of static granular packs in cylindrical containers are studied using large-scale discrete element molecular dynamics simulations in three dimensions. We generate packings by both pouring and sedimentation and examine how the final state depends on the method of construction. The vertical stress becomes depth-independent for deep piles and we compare these stress depth-profiles to the classical Janssen theory. The majority of the tangential forces for particle-wall contacts are found to be close to the Coulomb failure criterion, in agreement with the theory of Janssen, while particle-particle contacts in the bulk are far from the Coulomb criterion. In addition, we show that a linear hydrostatic-like region at the top of the packings unexplained by the Janssen theory arises because most of the particle-wall tangential forces in this region are far from the Coulomb yield criterion. The distributions of particle-particle and particle-wall contact forces $P(f)$ exhibit exponential-like decay at large forces in agreement with previous studies.Comment: 11 pages, 11 figures, submitted to PRE (v2) added new references, fixed typo

The position of graptolites within Lower Palaeozoic planktic ecosystems.

An integrated approach has been used to assess the palaeoecology of graptolites both as a discrete group and also as a part of the biota present within Ordovician and Silurian planktic realms. Study of the functional morphology of graptolites and comparisons with recent ecological analogues demonstrates that graptolites most probably filled a variety of niches as primary consumers, with modes of life related to the colony morphotype. Graptolite coloniality was extremely ordered, lacking any close morphological analogues in Recent faunas. To obtain maximum functional efficiency, graptolites would have needed varying degrees of coordinated automobility. A change in lifestyle related to ontogenetic changes was prevalent within many graptolite groups. Differing lifestyle was reflected by differing reproductive strategies, with synrhabdosomes most likely being a method for rapid asexual reproduction. Direct evidence in the form of graptolithophage 'coprolitic' bodies, as well as indirect evidence in the form of probable defensive adaptations, indicate that graptolites comprised a food item for a variety of predators. Graptolites were also hosts to a variety of parasitic organisms and provided an important nutrient source for scavenging organisms

Geometric Challenges in Designing Parts for Machining using Wire-fed DED

Wire-fed DED using MIG welding systems allows for high deposition rates above 30lbs/hr, enabling much larger parts to be printed than would be possible on other DED systems. However, a drawback to this high deposition rate is a relatively low bead resolution on the printed part. Post-processing using machining is usually required on any mating surfaces printed using wire-fed DED. Problems such as residual stress in the build plate and printed part, underbuilding, and path interpolations can all lead to insufficient material deposition and deviation from the desired shape. These areas where the printed part varies from the model can leave defects on post-processed surfaces. This paper will cover common geometry issues that can arise from wire-fed DED and design changes that can be made to ensure that the printed design contains the required material to achieve the finished part.Mechanical Engineerin

Dysfunctional Dopaminergic Neurones in Mouse Models of Huntington's Disease: A Role for SK3 Channels

Background: Huntington's disease (HD) is a late-onset fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene coding for the protein huntingtin and is characterised by progressive motor, psychiatric and cognitive decline. We previously demonstrated that normal synaptic function in HD could be restored by application of dopamine receptor agonists, suggesting that changes in the release or bioavailability of dopamine may be a contributing factor to the disease process. Objective: In the present study, we examined the properties of midbrain dopaminergic neurones and dopamine release in presymptomatic and symptomatic transgenic HD mice. Methods and Results:Using intracellular sharp recordings and immunohistochemistry, we found that neuronal excitability was increased due to a loss of slow afterhyperpolarisation and that these changes were related to an apparent functional loss and abnormal distribution of SK3 channels (KCa2.3 encoded by the KCNN3 gene), a class of small-conductance calcium-activated potassium channels. Electrochemical detection of dopamine showed that this observation was associated with an enhanced dopamine release in presymptomatic transgenic mice and a drastic reduction in symptomatic animals. These changes occurred in the context of a progressive expansion in the CAG repeat number and nuclear localisation of mutant protein within the substantia nigra pars compacta. Conclusions: Dopaminergic neuronal dysfunction is a key early event in HD disease progression. The initial increase in dopamine release appears to be related to a loss of SK3 channel function, a protein containing a polyglutamine tract. Implications for polyglutamine-mediated sequestration of SK3 channels, dopamine-associated DNA damage and CAG expansion are discussed in the context of HD.</br

Enhanced pressure drop, planar contraction flows and continuous spectrum models

This study addresses a rheological problem that has been outstanding now for the past few decades, raised by the experimental findings of Binding and Walters [1]. There, it was established experimentally that planar contraction flows for some Boger fluids could display enhanced pressure-drops above Newtonian flows, as was the case for their tubular counterparts. Nevertheless, flow-structures to achieve this result were reported to be markedly different, planar to circular. In this article, it is shown how predictive differential-viscoelastic solutions with continuum models can replicate these observations. Key to this success has been the derivation of a new definition for the third-invariant of the rate-of-deformation tensor in planar flows, mimicking that of the circular case [2], [3]. This provides a mechanism to successfully incorporate dissipation within planar flows, as performed earlier for tubular flows. Still, to reach the necessary large deformation-rates to achieve planar enhanced pressure-drops, and whilst maintaining steady flow-conditions, it has been found crucial to invoke a continuous-spectrum relaxation-time model [3]. The rheological power and flexibility of such a model is clearly demonstrated, over its counterpart Maxwellian single-averaged relaxation-time approximation; the latter transcending the boundaries of steady-to-unsteady flow to manifest equivalent levels of enhanced pressure-drops. Then, the role of extensional viscosity and first normal-stress difference, each play their part to achieve such planar enhanced pressure-drops. As a by-product, the distinctive planar ‘bulb-flow’ structures discovered by Binding and Walters [1], absent in tubular flows, are also predicted under the associated regime of high deformation-rates where enhanced pressure-drop arise

Hyperbolic contraction measuring systems for extensional flow

In this paper an experimental method for extensional measurements on medium viscosity fluids in contraction flow is evaluated through numerical simulations and experimental measurements. This measuring technique measures the pressure drop over a hyperbolic contraction, caused by fluid extension and fluid shear, where the extensional component is assumed to dominate. The present evaluative work advances our previous studies on this experimental method by introducing several contraction ratios and addressing different constitutive models of varying shear and extensional response. The constitutive models included are those of the constant viscosity Oldroyd-B and FENE-CR models, and the shear-thinning LPTT model. Examining the results, the impact of shear and first normal stress difference on the measured pressure drop are studied through numerical pressure drop predictions. In addition, stream function patterns are investigated to detect vortex development and influence of contraction ratio. The numerical predictions are further related to experimental measurements for the flow through a 15:1 contraction ratio with three different test fluids. The measured pressure drops are observed to exhibit the same trends as predicted in the numerical simulations, offering close correlation and tight predictive windows for experimental data capture. This result has demonstrated that the hyperbolic contraction flow is well able to detect such elastic fluid properties and that this is matched by numerical predictions in evaluation of their flow response. The hyperbolical contraction flow technique is commended for its distinct benefits: it is straightforward and simple to perform, the Hencky strain can be set by changing contraction ratio, non-homogeneous fluids can be tested, and one can directly determine the degree of elastic fluid behaviour. Based on matching of viscometric extensional viscosity response for FENE-CR and LPTT models, a decline is predicted in pressure drop for the shear-thinning LPTT model. This would indicate a modest impact of shear in the flow since such a pressure drop decline is relatively small. It is particularly noteworthy that the increase in pressure drop gathered from the experimental measurements is relatively high despite the low Deborah number range explored

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding