Deposition of general ellipsoidal particles

We present a systematic overview of granular deposits composed of ellipsoidal particles with different particle shapes and size polydispersities. We study the density and anisotropy of such deposits as functions of size polydispersity and two shape parameters that fully describe the shape of a general ellipsoid. Our results show that, while shape influences significantly the macroscopic properties of the deposits, polydispersity plays apparently a secondary role. The density attains a maximum for a particular family of non-symmetrical ellipsoids, larger than the density observed for prolate or oblate ellipsoids. As for anisotropy measures, the contact forces show are increasingly preferred along the vertical direction as the shape of the particles deviates for a sphere. The deposits are constructed by means of an efficient molecular dynamics method, where the contact forces are efficiently and accurately computed. The main results are discussed in the light of applications for porous media models and sedimentation processes.Comment: 7 pages, 8 figure

CCL2 modulates cytokine production in cultured mouse astrocytes

<p>Abstract</p> <p>Background</p> <p>The chemokine CCL2 (also known as monocyte chemoattractant protein-1, or MCP-1) is upregulated in patients and rodent models of traumatic brain injury (TBI), contributing to post-traumatic neuroinflammation and degeneration by directing the infiltration of blood-derived macrophages into the injured brain. Our laboratory has previously reported that <it>Ccl2</it>-/- mice show reduced macrophage accumulation and tissue damage, corresponding to improved motor recovery, following experimental TBI. Surprisingly, <it>Ccl2</it>-deficient mice also exhibited delayed but exacerbated secretion of key proinflammatory cytokines in the injured cortex. Thus we sought to further characterise CCL2's potential ability to modulate immunoactivation of astrocytes <it>in vitro</it>.</p> <p>Methods</p> <p>Primary astrocytes were isolated from neonatal wild-type and <it>Ccl2</it>-deficient mice. Established astrocyte cultures were stimulated with various concentrations of lipopolysaccharide (LPS) and interleukin (IL)-1β for up to 24 hours. Separate experiments involved pre-incubation with mouse recombinant (r)CCL2 prior to IL-1β stimulation in wild-type cells. Following stimulation, cytokine secretion was measured in culture supernatant by immunoassays, whilst cytokine gene expression was quantified by real-time reverse transcriptase polymerase chain reaction.</p> <p>Results</p> <p>LPS (0.1-100 μg/ml; 8 h) induced the significantly greater secretion of five key cytokines and chemokines in <it>Ccl2</it>-/- astrocytes compared to wild-type cells. Consistently, IL-6 mRNA levels were 2-fold higher in <it>Ccl2</it>-deficient cells. IL-1β (10 and 50 ng/ml; 2-24 h) also resulted in exacerbated IL-6 production from <it>Ccl2</it>-/- cultures. Despite this, treatment of wild-type cultures with rCCL2 alone (50-500 ng/ml) did not induce cytokine/chemokine production by astrocytes. However, pre-incubation of wild-type astrocytes with rCCL2 (250 ng/ml, 12 h) prior to stimulation with IL-1β (10 ng/ml, 8 h) significantly reduced IL-6 protein and gene expression.</p> <p>Conclusions</p> <p>Our data indicate that astrocytes are likely responsible for the exacerbated cytokine response seen <it>in vivo </it>post-injury in the absence of CCL2. Furthermore, evidence that CCL2 inhibits cytokine production by astrocytes following IL-1β stimulation, suggests a novel, immunomodulatory role for this chemokine in acute neuroinflammation. Further investigation is required to determine the physiological relevance of this phenomenon, which may have implications for therapeutics targeting CCL2-mediated leukocyte infiltration following TBI.</p

Neighborhoods of trees in circular orderings

In phylogenetics, a common strategy used to construct an evolutionary tree for a set of species X is to search in the space of all such trees for one that optimizes some given score function (such as the minimum evolution, parsimony or likelihood score). As this can be computationally intensive, it was recently proposed to restrict such searches to the set of all those trees that are compatible with some circular ordering of the set X. To inform the design of efficient algorithms to perform such searches, it is therefore of interest to find bounds for the number of trees compatible with a fixed ordering in the neighborhood of a tree that is determined by certain tree operations commonly used to search for trees: the nearest neighbor interchange (nni), the subtree prune and regraft (spr) and the tree bisection and reconnection (tbr) operations. We show that the size of such a neighborhood of a binary tree associated with the nni operation is independent of the tree’s topology, but that this is not the case for the spr and tbr operations. We also give tight upper and lower bounds for the size of the neighborhood of a binary tree for the spr and tbr operations and characterize those trees for which these bounds are attained

The genomic signature of trait-associated variants

BACKGROUND: Genome-wide association studies have identified thousands of SNP variants associated with hundreds of phenotypes. For most associations the causal variants and the molecular mechanisms underlying pathogenesis remain unknown. Exploration of the underlying functional annotations of trait-associated loci has thrown some light on their potential roles in pathogenesis. However, there are some shortcomings of the methods used to date, which may undermine efforts to prioritize variants for further analyses. Here, we introduce and apply novel methods to rigorously identify annotation classes showing enrichment or depletion of trait-associated variants taking into account the underlying associations due to co-location of different functional annotations and linkage disequilibrium. RESULTS: We assessed enrichment and depletion of variants in publicly available annotation classes such as genic regions, regulatory features, measures of conservation, and patterns of histone modifications. We used logistic regression to build a multivariate model that identified the most influential functional annotations for trait-association status of genome-wide significant variants. SNPs associated with all of the enriched annotations were 8 times more likely to be trait-associated variants than SNPs annotated with none of them. Annotations associated with chromatin state together with prior knowledge of the existence of a local expression QTL (eQTL) were the most important factors in the final logistic regression model. Surprisingly, despite the widespread use of evolutionary conservation to prioritize variants for study we find only modest enrichment of trait-associated SNPs in conserved regions. CONCLUSION: We established odds ratios of functional annotations that are more likely to contain significantly trait-associated SNPs, for the purpose of prioritizing GWAS hits for further studies. Additionally, we estimated the relative and combined influence of the different genomic annotations, which may facilitate future prioritization methods by adding substantial information

Approximate and exact nodes of fermionic wavefunctions: coordinate transformations and topologies

A study of fermion nodes for spin-polarized states of a few-electron ions and molecules with $s,p,d$ one-particle orbitals is presented. We find exact nodes for some cases of two electron atomic and molecular states and also the first exact node for the three-electron atomic system in $^4S(p^3)$ state using appropriate coordinate maps and wavefunction symmetries. We analyze the cases of nodes for larger number of electrons in the Hartree-Fock approximation and for some cases we find transformations for projecting the high-dimensional node manifolds into 3D space. The node topologies and other properties are studied using these projections. We also propose a general coordinate transformation as an extension of Feynman-Cohen backflow coordinates to both simplify the nodal description and as a new variational freedom for quantum Monte Carlo trial wavefunctions.Comment: 7 pages, 7 figure

Circular Networks from Distorted Metrics

Trees have long been used as a graphical representation of species relationships. However complex evolutionary events, such as genetic reassortments or hybrid speciations which occur commonly in viruses, bacteria and plants, do not fit into this elementary framework. Alternatively, various network representations have been developed. Circular networks are a natural generalization of leaf-labeled trees interpreted as split systems, that is, collections of bipartitions over leaf labels corresponding to current species. Although such networks do not explicitly model specific evolutionary events of interest, their straightforward visualization and fast reconstruction have made them a popular exploratory tool to detect network-like evolution in genetic datasets. Standard reconstruction methods for circular networks, such as Neighbor-Net, rely on an associated metric on the species set. Such a metric is first estimated from DNA sequences, which leads to a key difficulty: distantly related sequences produce statistically unreliable estimates. This is problematic for Neighbor-Net as it is based on the popular tree reconstruction method Neighbor-Joining, whose sensitivity to distance estimation errors is well established theoretically. In the tree case, more robust reconstruction methods have been developed using the notion of a distorted metric, which captures the dependence of the error in the distance through a radius of accuracy. Here we design the first circular network reconstruction method based on distorted metrics. Our method is computationally efficient. Moreover, the analysis of its radius of accuracy highlights the important role played by the maximum incompatibility, a measure of the extent to which the network differs from a tree.Comment: Submitte

Reconstructing pedigrees: some identifiability questions for a recombination-mutation model

Pedigrees are directed acyclic graphs that represent ancestral relationships between individuals in a population. Based on a schematic recombination process, we describe two simple Markov models for sequences evolving on pedigrees - Model R (recombinations without mutations) and Model RM (recombinations with mutations). For these models, we ask an identifiability question: is it possible to construct a pedigree from the joint probability distribution of extant sequences? We present partial identifiability results for general pedigrees: we show that when the crossover probabilities are sufficiently small, certain spanning subgraph sequences can be counted from the joint distribution of extant sequences. We demonstrate how pedigrees that earlier seemed difficult to distinguish are distinguished by counting their spanning subgraph sequences.Comment: 40 pages, 9 figure

Random tree growth by vertex splitting

We study a model of growing planar tree graphs where in each time step we separate the tree into two components by splitting a vertex and then connect the two pieces by inserting a new link between the daughter vertices. This model generalises the preferential attachment model and Ford's $\alpha$-model for phylogenetic trees. We develop a mean field theory for the vertex degree distribution, prove that the mean field theory is exact in some special cases and check that it agrees with numerical simulations in general. We calculate various correlation functions and show that the intrinsic Hausdorff dimension can vary from one to infinity, depending on the parameters of the model.Comment: 47 page

Emergence of hyperons in failed supernovae: trigger of the black hole formation

We investigate the emergence of strange baryons in the dynamical collapse of a non-rotating massive star to a black hole by the neutrino-radiation hydrodynamical simulations in general relativity. By following the dynamical formation and collapse of nascent proto-neutron star from the gravitational collapse of a 40Msun star adopting a new hyperonic EOS table, we show that the hyperons do not appear at the core bounce but populate quickly at ~0.5-0.7 s after the bounce to trigger the re-collapse to a black hole. They start to show up off center owing to high temperatures and later prevail at center when the central density becomes high enough. The neutrino emission from the accreting proto-neutron star with the hyperonic EOS stops much earlier than the corresponding case with a nucleonic EOS while the average energies and luminosities are quite similar between them. These features of neutrino signal are a potential probe of the emergence of new degrees of freedom inside the black hole forming collapse.Comment: 11 pages, 3 figures, accepted for publication in ApJ