Asymptotic analysis and analytical solutions of a model of cardiac excitation.

The original publication is available at www.springerlink.com - http://link.springer.com/article/10.1007/s11538-007-9267-0Journal ArticleCopyright © SpringerWe describe an asymptotic approach to gated ionic models of single-cell cardiac excitability. It has a form essentially different from the Tikhonov fast-slow form assumed in standard asymptotic reductions of excitable systems. This is of interest since the standard approaches have been previously found inadequate to describe phenomena such as the dissipation of cardiac wave fronts and the shape of action potential at repolarization. The proposed asymptotic description overcomes these deficiencies by allowing, among other non-Tikhonov features, that a dynamical variable may change its character from fast to slow within a single solution. The general asymptotic approach is best demonstrated on an example which should be both simple and generic. The classical model of Purkinje fibers (Noble in J. Physiol. 160:317-352, 1962) has the simplest functional form of all cardiac models but according to the current understanding it assigns a physiologically incorrect role to the Na current. This leads us to suggest an "Archetypal Model" with the simplicity of the Noble model but with a structure more typical to contemporary cardiac models. We demonstrate that the Archetypal Model admits a complete asymptotic solution in quadratures. To validate our asymptotic approach, we proceed to consider an exactly solvable "caricature" of the Archetypal Model and demonstrate that the asymptotic of its exact solution coincides with the solutions obtained by substituting the "caricature" right-hand sides into the asymptotic solution of the generic Archetypal Model. This is necessary, because, unlike in standard asymptotic descriptions, no general results exist which can guarantee the proximity of the non-Tikhonov asymptotic solutions to the solutions of the corresponding detailed ionic model

Maximum gradient embeddings and monotone clustering

Let (X,d_X) be an n-point metric space. We show that there exists a distribution D over non-contractive embeddings into trees f:X-->T such that for every x in X, the expectation with respect to D of the maximum over y in X of the ratio d_T(f(x),f(y)) / d_X(x,y) is at most C (log n)^2, where C is a universal constant. Conversely we show that the above quadratic dependence on log n cannot be improved in general. Such embeddings, which we call maximum gradient embeddings, yield a framework for the design of approximation algorithms for a wide range of clustering problems with monotone costs, including fault-tolerant versions of k-median and facility location.Comment: 25 pages, 2 figures. Final version, minor revision of the previous one. To appear in "Combinatorica

Fast Distributed Approximation for Max-Cut

Finding a maximum cut is a fundamental task in many computational settings. Surprisingly, it has been insufficiently studied in the classic distributed settings, where vertices communicate by synchronously sending messages to their neighbors according to the underlying graph, known as the $\mathcal{LOCAL}$ or $\mathcal{CONGEST}$ models. We amend this by obtaining almost optimal algorithms for Max-Cut on a wide class of graphs in these models. In particular, for any $\epsilon > 0$, we develop randomized approximation algorithms achieving a ratio of $(1-\epsilon)$ to the optimum for Max-Cut on bipartite graphs in the $\mathcal{CONGEST}$ model, and on general graphs in the $\mathcal{LOCAL}$ model. We further present efficient deterministic algorithms, including a $1/3$-approximation for Max-Dicut in our models, thus improving the best known (randomized) ratio of $1/4$. Our algorithms make non-trivial use of the greedy approach of Buchbinder et al. (SIAM Journal on Computing, 2015) for maximizing an unconstrained (non-monotone) submodular function, which may be of independent interest

Microarray profiling reveals the integrated stress response is activated by halofuginone in mammary epithelial cells

<p>Abstract</p> <p>Background</p> <p>The small molecule Halofuginone (HF) is a potent regulator of extracellular matrix (ECM ) gene expression and is unique in its therapeutic potential. While the basis for HF effects is unknown, inhibition of TGFβ signaling and activation of the amino acid restriction response (AAR) have been linked to HF transcriptional control of a number of ECM components and amelioration of fibrosis and alleviation of autoimmune disease by regulation of Th17 cell differentiation, respectively. The aim of this study was to generate a global expression profile of HF targets in epithelial cells to identify potential mediators of HF function in this cell type.</p> <p>Results</p> <p>We report that HF modulation of the expression of the ECM remodeling protein Mmp13 in epithelial cells is separable from previously reported effects of HF on TGFβ signal inhibition, and use microarray expression analysis to correlate this with transcriptional responses characteristic of the Integrated Stress Response (ISR).</p> <p>Conclusions</p> <p>Our findings suggest activation of the ISR may be a common mechanism underlying HF biological effects.</p

Performing Place: A Rhythmanalysis of the City of London

Through its focus on the City of London as a particular work sector and setting, this paper emphasizes the symbolic and material significance of place to understanding the lived experiences of power relations within organizational life. The socio-cultural and material aspects of the City are explored through an analysis of the rhythms of place, as well through interview data. Using a methodological approach based on Lefebvre’s Rhythmanalysis in order to develop an embodied, immersive sense of how the City is experienced as a workplace, the paper makes a methodological, empirical and theoretical contribution to an understanding of the way in which rhythms shape how place is performed. Using rhythmanalysis as a method, the paper shows the relationship between rhythms and the performances of place, foregrounding a subjective, embodied and experiential way of researching the places and spaces of organizing

Recovering critique in an age of datafication

This article starts out from the need for critical work on processes of datafication and their consequences for the constitution of social knowledge and the social world. Current social science work on datafication has been greatly shaped by the theoretical approach of Bruno Latour, as reflected in the work of Actor Network Theory and Science and Technology Studies (ANT/STS). The article asks whether this approach, given its philosophical underpinnings, provides sufficient resources for the critical work that is required in relation to datafication. Drawing on Latour’s own reflections about the flatness of the social, it concludes that it does not, since key questions, in particular about the nature of social order cannot be asked or answered within ANT. In the article’s final section, three approaches from earlier social theory are considered as possible supplements to ANT/STS for a social science serious about addressing the challenges that datafication poses for society

Local algorithms : Self-stabilization on speed

Non peer reviewe

The GTPase Activating Rap/RanGAP Domain-Like 1 Gene Is Associated with Chicken Reproductive Traits

BACKGROUND: Abundant evidence indicates that chicken reproduction is strictly regulated by the hypothalamic-pituitary-gonad (HPG) axis, and the genes included in the HPG axis have been studied extensively. However, the question remains as to whether any other genes outside of the HPG system are involved in regulating chicken reproduction. The present study was aimed to identify, on a genome-wide level, novel genes associated with chicken reproductive traits. METHODOLOGY/PRINCIPAL FINDING: Suppressive subtractive hybridization (SSH), genome-wide association study (GWAS), and gene-centric GWAS were used to identify novel genes underlying chicken reproduction. Single marker-trait association analysis with a large population and allelic frequency spectrum analysis were used to confirm the effects of candidate genes. Using two full-sib Ningdu Sanhuang (NDH) chickens, GARNL1 was identified as a candidate gene involved in chicken broodiness by SSH analysis. Its expression levels in the hypothalamus and pituitary were significantly higher in brooding chickens than in non-brooding chickens. GWAS analysis with a NDH two tail sample showed that 2802 SNPs were significantly associated with egg number at 300 d of age (EN300). Among the 2802 SNPs, 2 SNPs composed a block overlapping the GARNL1 gene. The gene-centric GWAS analysis with another two tail sample of NDH showed that GARNL1 was strongly associated with EN300 and age at first egg (AFE). Single marker-trait association analysis in 1301 female NDH chickens confirmed that variation in this gene was related to EN300 and AFE. The allelic frequency spectrum of the SNP rs15700989 among 5 different populations supported the above associations. Western blotting, RT-PCR, and qPCR were used to analyze alternative splicing of the GARNL1 gene. RT-PCR detected 5 transcripts and revealed that the transcript, which has a 141 bp insertion, was expressed in a tissue-specific manner. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that the GARNL1 gene contributes to chicken reproductive traits

Using Noun Phrases for Navigating Biomedical Literature on Pubmed: How Many Updates Are We Losing Track of?

Author-supplied citations are a fraction of the related literature for a paper. The “related citations” on PubMed is typically dozens or hundreds of results long, and does not offer hints why these results are related. Using noun phrases derived from the sentences of the paper, we show it is possible to more transparently navigate to PubMed updates through search terms that can associate a paper with its citations. The algorithm to generate these search terms involved automatically extracting noun phrases from the paper using natural language processing tools, and ranking them by the number of occurrences in the paper compared to the number of occurrences on the web. We define search queries having at least one instance of overlap between the author-supplied citations of the paper and the top 20 search results as citation validated (CV). When the overlapping citations were written by same authors as the paper itself, we define it as CV-S and different authors is defined as CV-D. For a systematic sample of 883 papers on PubMed Central, at least one of the search terms for 86% of the papers is CV-D versus 65% for the top 20 PubMed “related citations.” We hypothesize these quantities computed for the 20 million papers on PubMed to differ within 5% of these percentages. Averaged across all 883 papers, 5 search terms are CV-D, and 10 search terms are CV-S, and 6 unique citations validate these searches. Potentially related literature uncovered by citation-validated searches (either CV-S or CV-D) are on the order of ten per paper – many more if the remaining searches that are not citation-validated are taken into account. The significance and relationship of each search result to the paper can only be vetted and explained by a researcher with knowledge of or interest in that paper