239 research outputs found

    341: Allogeneic Antibodies Specifically Target AML Antigen NuSAP1 after Bone Marrow Transplantation

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    Nonuniversal scaling behavior of Barkhausen noise

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    We simulate Barkhausen avalanches on fractal clusters in a two-dimensional diluted Ising ferromagnet with an effective Gaussian random field. We vary the concentration of defect sites cc and find a scaling region for moderate disorder, where the distribution of avalanche sizes has the form D(s,c,L)=s(1+τ(c))D(sLDs(c))D(s,c,L) = s^{-(1+\tau (c))}{\cal{D}}(sL^{-D_s(c)}). The exponents τ(c)\tau (c) for size and α(c)\alpha (c) for length distribution, and the fractal dimension of avalanches Ds(c)D_s(c) satisfy the scaling relation Ds(c)τ(c)=α(c)D_s(c)\tau (c) =\alpha (c). For fixed disorder the exponents vary with driving rate in agreement with experiments on amorphous Si-Fe alloys.Comment: 5 pages, Latex, 4 PostScript figures include

    Increases in sampling support the southern Gondwanan hypothesis for the origin of dinosaurs

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    Dinosaurs were ubiquitous in terrestrial ecosystems through most of the Mesozoic and are still diversely represented in the modern fauna in the form of birds. Recent efforts to better understand the origins of the group have resulted in the discovery of many new species of early dinosaurs and their closest relatives (dinosauromorphs). In addition, recent re-examinations of early dinosaur phylogeny have highlighted uncertainties regarding the interrelationships of the main dinosaur lineages (Sauropodomorpha, Theropoda and Ornithischia), and questioned the traditional hypothesis that the group originated in South Gondwana and gradually dispersed over Pangaea. Here, we use a historical approach to examine the impact of new fossil discoveries and changing phylogenetic hypotheses on biogeographic scenarios for dinosaur origins over 20 years of research time, and analyse the results in the light of different fossil record sampling regimes. Our results consistently optimize South Gondwana as the ancestral area for Dinosauria, as well as for more inclusive clades including Dinosauromorpha, and show that this hypothesis is robust to increased taxonomic and geographic sampling and divergent phylogenetic results. Our results do not find any support for the recently proposed Laurasian origin of dinosaurs and suggest that a southern Gondwanan origin is by far the most plausible given our current knowledge of the diversity of early dinosaurs and non-dinosaurian dinosauromorphs

    Disorder-Induced Critical Phenomena in Hysteresis: Numerical Scaling in Three and Higher Dimensions

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    We present numerical simulations of avalanches and critical phenomena associated with hysteresis loops, modeled using the zero-temperature random-field Ising model. We study the transition between smooth hysteresis loops and loops with a sharp jump in the magnetization, as the disorder in our model is decreased. In a large region near the critical point, we find scaling and critical phenomena, which are well described by the results of an epsilon expansion about six dimensions. We present the results of simulations in 3, 4, and 5 dimensions, with systems with up to a billion spins (1000^3).Comment: Condensed and updated version of cond-mat/9609072,``Disorder-Induced Critical Phenomena in Hysteresis: A Numerical Scaling Analysis'

    Hysteresis, Avalanches, and Disorder Induced Critical Scaling: A Renormalization Group Approach

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    We study the zero temperature random field Ising model as a model for noise and avalanches in hysteretic systems. Tuning the amount of disorder in the system, we find an ordinary critical point with avalanches on all length scales. Using a mapping to the pure Ising model, we Borel sum the 6ϵ6-\epsilon expansion to O(ϵ5)O(\epsilon^5) for the correlation length exponent. We sketch a new method for directly calculating avalanche exponents, which we perform to O(ϵ)O(\epsilon). Numerical exponents in 3, 4, and 5 dimensions are in good agreement with the analytical predictions.Comment: 134 pages in REVTEX, plus 21 figures. The first two figures can be obtained from the references quoted in their respective figure captions, the remaining 19 figures are supplied separately in uuencoded forma

    Genome-wide Characterization of Shared and Distinct Genetic Components that Influence Blood Lipid Levels in Ethnically Diverse Human Populations

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    Blood lipid concentrations are heritable risk factors associated with atherosclerosis and cardiovascular diseases. Lipid traits exhibit considerable variation among populations of distinct ancestral origin as well as between individuals within a population. We performed association analyses to identify genetic loci influencing lipid concentrations in African American and Hispanic American women in the Women’s Health Initiative SNP Health Association Resource. We validated one African-specific high-density lipoprotein cholesterol locus at CD36 as well as 14 known lipid loci that have been previously implicated in studies of European populations. Moreover, we demonstrate striking similarities in genetic architecture (loci influencing the trait, direction and magnitude of genetic effects, and proportions of phenotypic variation explained) of lipid traits across populations. In particular, we found that a disproportionate fraction of lipid variation in African Americans and Hispanic Americans can be attributed to genomic loci exhibiting statistical evidence of association in Europeans, even though the precise genes and variants remain unknown. At the same time, we found substantial allelic heterogeneity within shared loci, characterized both by population-specific rare variants and variants shared among multiple populations that occur at disparate frequencies. The allelic heterogeneity emphasizes the importance of including diverse populations in future genetic association studies of complex traits such as lipids; furthermore, the overlap in lipid loci across populations of diverse ancestral origin argues that additional knowledge can be gleaned from multiple populations

    Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines

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    BACKGROUND: To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery. METHODOLOGY/PRINCIPAL FINDINGS: We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy. CONCLUSIONS/SIGNIFICANCE: For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery

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

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    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
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