Ultrametric spaces of branches on arborescent singularities

Let $S$ be a normal complex analytic surface singularity. We say that $S$ is arborescent if the dual graph of any resolution of it is a tree. Whenever $A,B$ are distinct branches on $S$, we denote by $A \cdot B$ their intersection number in the sense of Mumford. If $L$ is a fixed branch, we define $U_L(A,B)= (L \cdot A)(L \cdot B)(A \cdot B)^{-1}$ when $A \neq B$ and $U_L(A,A) =0$ otherwise. We generalize a theorem of P{\l}oski concerning smooth germs of surfaces, by proving that whenever $S$ is arborescent, then $U_L$ is an ultrametric on the set of branches of $S$ different from $L$. We compute the maximum of $U_L$, which gives an analog of a theorem of Teissier. We show that $U_L$ encodes topological information about the structure of the embedded resolutions of any finite set of branches. This generalizes a theorem of Favre and Jonsson concerning the case when both $S$ and $L$ are smooth. We generalize also from smooth germs to arbitrary arborescent ones their valuative interpretation of the dual trees of the resolutions of $S$. Our proofs are based in an essential way on a determinantal identity of Eisenbud and Neumann.Comment: 37 pages, 16 figures. Compared to the first version on Arxiv, il has a new section 4.3, accompanied by 2 new figures. Several passages were clarified and the typos discovered in the meantime were correcte

Context Specificity in Causal Signaling Networks Revealed by Phosphoprotein Profiling.

Signaling networks downstream of receptor tyrosine kinases are among the most extensively studied biological networks, but new approaches are needed to elucidate causal relationships between network components and understand how such relationships are influenced by biological context and disease. Here, we investigate the context specificity of signaling networks within a causal conceptual framework using reverse-phase protein array time-course assays and network analysis approaches. We focus on a well-defined set of signaling proteins profiled under inhibition with five kinase inhibitors in 32 contexts: four breast cancer cell lines (MCF7, UACC812, BT20, and BT549) under eight stimulus conditions. The data, spanning multiple pathways and comprising ∼70,000 phosphoprotein and ∼260,000 protein measurements, provide a wealth of testable, context-specific hypotheses, several of which we experimentally validate. Furthermore, the data provide a unique resource for computational methods development, permitting empirical assessment of causal network learning in a complex, mammalian setting.This work was supported by the National Institutes of Health National Cancer Institute (grant U54 CA112970 to J.W.G., G.B.M., S.M., and P.T.S.). S.M.H. and S.M. were supported by the UK Medical Research Council (unit program numbers MC_UP_1302/1 and MC_UP_1302/3). S.M. was a recipient of a Royal Society Wolfson Research Merit Award. The MD Anderson Cancer Center RPPA Core Facility is funded by the National Institutes of Health National Cancer Institute (Cancer Center Core Grant CA16672)

Foodways in transition: food plants, diet and local perceptions of change in a Costa Rican Ngäbe community

Background Indigenous populations are undergoing rapid ethnobiological, nutritional and socioeconomic transitions while being increasingly integrated into modernizing societies. To better understand the dynamics of these transitions, this article aims to characterize the cultural domain of food plants and analyze its relation with current day diets, and the local perceptions of changes given amongst the Ngäbe people of Southern Conte-Burica, Costa Rica, as production of food plants by its residents is hypothesized to be drastically in recession with an decreased local production in the area and new conservation and development paradigms being implemented. Methods Extensive freelisting, interviews and workshops were used to collect the data from 72 participants on their knowledge of food plants, their current dietary practices and their perceptions of change in local foodways, while cultural domain analysis, descriptive statistical analyses and development of fundamental explanatory themes were employed to analyze the data. Results Results show a food plants domain composed of 140 species, of which 85 % grow in the area, with a medium level of cultural consensus, and some age-based variation. Although many plants still grow in the area, in many key species a decrease on local production–even abandonment–was found, with much reduced cultivation areas. Yet, the domain appears to be largely theoretical, with little evidence of use; and the diet today is predominantly dependent on foods bought from the store (more than 50 % of basic ingredients), many of which were not salient or not even recognized as ‘food plants’ in freelists exercises. While changes in the importance of food plants were largely deemed a result of changes in cultural preferences for store bought processed food stuffs and changing values associated with farming and being food self-sufficient, Ngäbe were also aware of how changing household livelihood activities, and the subsequent loss of knowledge and use of food plants, were in fact being driven by changes in social and political policies, despite increases in forest cover and biodiversity. Conclusions Ngäbe foodways are changing in different and somewhat disconnected ways: knowledge of food plants is varied, reflecting most relevant changes in dietary practices such as lower cultivation areas and greater dependence on food from stores by all families. We attribute dietary shifts to socioeconomic and political changes in recent decades, in particular to a reduction of local production of food, new economic structures and agents related to the State and globalization

Circulating Metabolites Associated with Postprandial Satiety in Overweight/Obese Participants: The SATIN Study

Scope: To identify a metabolomic profile related to postprandial satiety sensations involved in appetite control would help for a better understanding of the regulation of food intake. Methods and Results: A cross-sectional analysis of plasma metabolites was conducted over 151 overweight/obese adults from the “Satiety Innovation”-SATIN study, a randomized clinical trial of a 12-week weight-loss maintenance period. Postprandial satiety sensations (3 h-iAUC) were assessed by visual analogue scale (VAS) at the beginning and at the end of the study. Fasting plasma metabolites were profiled using a targeted multiplatform metabolomics approach before each appetite test meal. Associations between 124 metabolites and iAUC-satiety were assessed using elastic net linear regression analyses. The accuracy of the multimetabolite weighted models for iAUC-VAS was evaluated using a 10-fold cross-validation (CV) approach and the Pearson’s correlation coefficients were estimated. Five and three metabolites were selected in the first and the second assessments, respectively. Circulating glycine and linoleic acid concentrations were consistently and positively associated with higher iAUC-satiety in both visits. Sucrose and sphingomyelins (C32:2, C38:1) were negatively associated with iAUC-satiety in the first visit. The Pearson correlations coefficients between the metabolomic profiles and iAUC-satiety in the first and the second appetite assessments were 0.37 and 0.27, respectively. Conclusion: Higher glycine and linoleic acid were moderately but consistently associated with higher postprandial satiety in two different appetite assessments in overweight and obese subjects

Biology, Methodology or Chance? The Degree Distributions of Bipartite Ecological Networks

The distribution of the number of links per species, or degree distribution, is widely used as a summary of the topology of complex networks. Degree distributions have been studied in a range of ecological networks, including both mutualistic bipartite networks of plants and pollinators or seed dispersers and antagonistic bipartite networks of plants and their consumers. The shape of a degree distribution, for example whether it follows an exponential or power-law form, is typically taken to be indicative of the processes structuring the network. The skewed degree distributions of bipartite mutualistic and antagonistic networks are usually assumed to show that ecological or co-evolutionary processes constrain the relative numbers of specialists and generalists in the network. I show that a simple null model based on the principle of maximum entropy cannot be rejected as a model for the degree distributions in most of the 115 bipartite ecological networks tested here. The model requires knowledge of the number of nodes and links in the network, but needs no other ecological information. The model cannot be rejected for 159 (69%) of the 230 degree distributions of the 115 networks tested. It performed equally well on the plant and animal degree distributions, and cannot be rejected for 81 (70%) of the 115 plant distributions and 78 (68%) of the animal distributions. There are consistent differences between the degree distributions of mutualistic and antagonistic networks, suggesting that different processes are constraining these two classes of networks. Fit to the MaxEnt null model is consistently poor among the largest mutualistic networks. Potential ecological and methodological explanations for deviations from the model suggest that spatial and temporal heterogeneity are important drivers of the structure of these large networks

Na⁺ entry through heteromeric TRPC4/C1 channels mediates (-)Englerin A-induced cytotoxicity in synovial sarcoma cells

The sesquiterpene (-)Englerin A (EA) is an organic compound from the plant Phyllanthus engleri which acts via heteromeric TRPC4/C1 channels to cause cytotoxicity in some types of cancer cell but not normal cells. Here we identified selective cytotoxicity of EA in human synovial sarcoma cells (SW982 cells) and investigated the mechanism. EA induced cation channel current (Icat) in SW982 cells with biophysical characteristics of heteromeric TRPC4/C1 channels. Inhibitors of homomeric TRPC4 channels were weak inhibitors of the Icat and EA-induced cytotoxicity whereas a potent inhibitor of TRPC4/C1 channels (Pico145) strongly inhibited Icat and cytotoxicity. Depletion of TRPC1 converted Icat into a current with biophysical and pharmacological properties of homomeric TRPC4 channels and depletion of TRPC1 or TRPC4 suppressed the cytotoxicity of EA. A Na⁺ /K⁺-ATPase inhibitor (ouabain) potentiated EA-induced cytotoxicity and direct Na⁺ loading by gramicidin-A caused Pico145-resistant cytotoxicity in the absence of EA. We conclude that EA has a potent cytotoxic effect on human synovial sarcoma cells which is mediated by heteromeric TRPC4/C1 channels and Na⁺ loading

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

High Yield Production Process for Shigella Outer Membrane Particles

Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30–45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from Gram-negative bacteria