Prebiotic Oligosaccharides Potentiate Host Protective Responses against L. Monocytogenes Infection.

Prebiotic oligosaccharides are used to modulate enteric pathogens and reduce pathogen shedding. The interactions with prebiotics that alter Listeria monocytogenes infection are not yet clearly delineated. L. monocytogenes cellular invasion requires a concerted manipulation of host epithelial cell membrane receptors to initiate internalization and infection often via receptor glycosylation. Bacterial interactions with host glycans are intimately involved in modulating cellular responses through signaling cascades at the membrane and in intracellular compartments. Characterizing the mechanisms underpinning these modulations is essential for predictive use of dietary prebiotics to diminish pathogen association. We demonstrated that human milk oligosaccharide (HMO) pretreatment of colonic epithelial cells (Caco-2) led to a 50% decrease in Listeria association, while Biomos pretreatment increased host association by 150%. L. monocytogenes-induced gene expression changes due to oligosaccharide pretreatment revealed global alterations in host signaling pathways that resulted in differential subcellular localization of L. monocytogenes during early infection. Ultimately, HMO pretreatment led to bacterial clearance in Caco-2 cells via induction of the unfolded protein response and eIF2 signaling, while Biomos pretreatment resulted in the induction of host autophagy and L. monocytogenes vacuolar escape earlier in the infection progression. This study demonstrates the capacity of prebiotic oligosaccharides to minimize infection through induction of host-intrinsic protective responses

Logic of Negation-Complete Interactive Proofs (Formal Theory of Epistemic Deciders)

We produce a decidable classical normal modal logic of internalised negation-complete and thus disjunctive non-monotonic interactive proofs (LDiiP) from an existing logical counterpart of non-monotonic or instant interactive proofs (LiiP). LDiiP internalises agent-centric proof theories that are negation-complete (maximal) and consistent (and hence strictly weaker than, for example, Peano Arithmetic) and enjoy the disjunction property (like Intuitionistic Logic). In other words, internalised proof theories are ultrafilters and all internalised proof goals are definite in the sense of being either provable or disprovable to an agent by means of disjunctive internalised proofs (thus also called epistemic deciders). Still, LDiiP itself is classical (monotonic, non-constructive), negation-incomplete, and does not have the disjunction property. The price to pay for the negation completeness of our interactive proofs is their non-monotonicity and non-communality (for singleton agent communities only). As a normal modal logic, LDiiP enjoys a standard Kripke-semantics, which we justify by invoking the Axiom of Choice on LiiP's and then construct in terms of a concrete oracle-computable function. LDiiP's agent-centric internalised notion of proof can also be viewed as a negation-complete disjunctive explicit refinement of standard KD45-belief, and yields a disjunctive but negation-incomplete explicit refinement of S4-provability.Comment: Expanded Introduction. Added Footnote 4. Corrected Corollary 3 and 4. Continuation of arXiv:1208.184

Dewetting of thin polymer films near the glass transition

Dewetting of ultra-thin polymer films near the glass transition exhibits unexpected front morphologies [G. Reiter, Phys. Rev. Lett., 87, 186101 (2001)]. We present here the first theoretical attempt to understand these features, focusing on the shear-thinning behaviour of these films. We analyse the profile of the dewetting film, and characterize the time evolution of the dry region radius, $R_{d}(t)$, and of the rim height, $h_{m}(t)$. After a transient time depending on the initial thickness, $h_{m}(t)$ grows like $\sqrt{t}$ while $R_{d}(t)$ increases like $\exp{(\sqrt{t})}$. Different regimes of growth are expected, depending on the initial film thickness and experimental time range.Comment: 4 pages, 5 figures Revised version, published in Physical Review Letters: F. Saulnier, E. Raphael and P.-G. de Gennes, Phys. Rev. Lett. 88, 196101 (2002

Dietary Variation and Evolution of Gene Copy Number among Dog Breeds

Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed-specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic α-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs

Compendium-Wide Analysis of Pseudomonas aeruginosa Core and Accessory Genes Reveals Transcriptional Patterns across Strains PAO1 and PA14.

Pseudomonas aeruginosa is an opportunistic pathogen that causes difficult-to-treat infections. Two well-studied divergent P. aeruginosa strain types, PAO1 and PA14, have significant genomic heterogeneity, including diverse accessory genes present in only some strains. Genome content comparisons find core genes that are conserved across both PAO1 and PA14 strains and accessory genes that are present in only a subset of PAO1 and PA14 strains. Here, we use recently assembled transcriptome compendia of publicly available P. aeruginosa RNA sequencing (RNA-seq) samples to create two smaller compendia consisting of only strain PAO1 or strain PA14 samples with each aligned to their cognate reference genome. We confirmed strain annotations and identified other samples for inclusion by assessing each sample\u27s median expression of PAO1-only or PA14-only accessory genes. We then compared the patterns of core gene expression in each strain. To do so, we developed a method by which we analyzed genes in terms of which genes showed similar expression patterns across strain types. We found that some core genes had consistent correlated expression patterns across both compendia, while others were less stable in an interstrain comparison. For each accessory gene, we also determined core genes with correlated expression patterns. We found that stable core genes had fewer coexpressed neighbors that were accessory genes. Overall, this approach for analyzing expression patterns across strain types can be extended to other groups of genes, like phage genes, or applied for analyzing patterns beyond groups of strains, such as samples with different traits, to reveal a deeper understanding of regulation

Detecting Generalized Synchronization Between Chaotic Signals: A Kernel-based Approach

A unified framework for analyzing generalized synchronization in coupled chaotic systems from data is proposed. The key of the proposed approach is the use of the kernel methods recently developed in the field of machine learning. Several successful applications are presented, which show the capability of the kernel-based approach for detecting generalized synchronization. It is also shown that the dynamical change of the coupling coefficient between two chaotic systems can be captured by the proposed approach.Comment: 20 pages, 15 figures. massively revised as a full paper; issues on the choice of parameters by cross validation, tests by surrogated data, etc. are added as well as additional examples and figure

Open design at the intersection of making and manufacturing

This one-day workshop aims to consider the opportunities for HCI at the intersection of maker culture and professional, industrial manufacturing. In particular, we are interested in exploring how the concept of “open design” could help support productive interactions between professional manufacturers and non-professional makers. Our proposal builds on momentum established by previous related workshops (including one at CHI2016) and aims to respond critically to several key industry and government reports published in 2015-2016 on the ‘maker movement’

The dynamics of proving uncolourability of large random graphs I. Symmetric Colouring Heuristic

We study the dynamics of a backtracking procedure capable of proving uncolourability of graphs, and calculate its average running time T for sparse random graphs, as a function of the average degree c and the number of vertices N. The analysis is carried out by mapping the history of the search process onto an out-of-equilibrium (multi-dimensional) surface growth problem. The growth exponent of the average running time is quantitatively predicted, in agreement with simulations.Comment: 5 figure