31 research outputs found

    Uniform Boundedness of S-Units in Arithmetic Dynamics

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    Let K be a number field and let S be a finite set of places of K which contains all the Archimedean places. For any f(z) in K(z) of degree d at least 2 which is not a d-th power in \bar{K}(z), Siegel's theorem implies that the image set f(K) contains only finitely many S-units. We conjecture that the number of such S-units is bounded by a function of |S| and d (independently of K and f). We prove this conjecture for several classes of rational functions, and show that the full conjecture follows from the Bombieri--Lang conjecture

    Enhancing impact: visualization of an integrated impact assessment strategy

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    The environmental impact assessment process is over 40 years old and has dramatically expanded. Topics, such as social, health and human rights impact are now included. The main body of an impact analysis is generally hundreds of pages long and supported by countless technical appendices. For large, oil/gas, mining and water resources projects both the volume and technical sophistication of the reports has far exceeded the processing ability of host communities. Instead of informing and empowering, the reports are abstruse and overwhelming. Reinvention is required. The development of a visual integrated impact assessment strategy that utilizes remote sensing and spatial analyses is describe

    Multi-ethnic genome-wide association study for atrial fibrillation

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    Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

    Role of Pulse Pressure and Geometry of Primary Entry Tear in Acute Type B Dissection Propagation

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    The hemodynamic and geometric factors leading to propagation of acute Type B dissections are poorly understood. The objective is to elucidate whether geometric and hemodynamic parameters increase the predilection for aortic dissection propagation. A pulse duplicator set-up was used on porcine aorta with a single entry tear. Mean pressures of 100 and 180 mmHg were used, with pulse pressures ranging from 40 to 200 mmHg. The propagation for varying geometric conditions (%circumference of the entry tear: 15–65%, axial length: 0.5–3.2 cm) were tested for two flap thicknesses (1/3rd and 2/3rd of the thickness of vessel wall, respectively). To assess the effect of pulse and mean pressure on flap dynamics, the %true lumen (TL) cross-sectional area of the entry tear were compared. The % circumference for propagation of thin flap (47 ± 1%) was not significantly different (p = 0.14) from thick flap (44 ± 2%). On the contrary, the axial length of propagation for thin flap (2.57 ± 0.15 cm) was significantly different (p < 0.05) from the thick flap (1.56 ± 0.10 cm). TL compression was observed during systolic phase. For a fixed geometry of entry tear (%circumference = 39 ± 2%; axial length = 1.43 ± 0.13 cm), mean pressure did not have significant (p = 0.84) effect on flap movement. Increase in pulse pressure resulted in a significant change (p = 0.02) in %TL area (52 ± 4%). The energy acting on the false lumen immediately before propagation was calculated as 75 ± 9 J/m(2) and was fairly uniform across different specimens. Pulse pressure had a significant effect on the flap movement in contrast to mean pressure. Hence, mitigation of pulse pressure and restriction of flap movement may be beneficial in patients with type B acute dissections

    Uniform boundedness of S

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    Building synthetic chromosomes from natural DNA

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    Abstract De novo chromosome synthesis is costly and time-consuming, limiting its use in research and biotechnology. Building synthetic chromosomes from natural components is an unexplored alternative with many potential applications. In this paper, we report CReATiNG (Cloning, Reprogramming, and Assembling Tiled Natural Genomic DNA), a method for constructing synthetic chromosomes from natural components in yeast. CReATiNG entails cloning segments of natural chromosomes and then programmably assembling them into synthetic chromosomes that can replace the native chromosomes in cells. We use CReATiNG to synthetically recombine chromosomes between strains and species, to modify chromosome structure, and to delete many linked, non-adjacent regions totaling 39% of a chromosome. The multiplex deletion experiment reveals that CReATiNG also enables recovery from flaws in synthetic chromosome design via recombination between a synthetic chromosome and its native counterpart. CReATiNG facilitates the application of chromosome synthesis to diverse biological problems

    High‐throughput, microscope‐based sorting to dissect cellular heterogeneity

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    Abstract Microscopy is a powerful tool for characterizing complex cellular phenotypes, but linking these phenotypes to genotype or RNA expression at scale remains challenging. Here, we present Visual Cell Sorting, a method that physically separates hundreds of thousands of live cells based on their visual phenotype. Automated imaging and phenotypic analysis directs selective illumination of Dendra2, a photoconvertible fluorescent protein expressed in live cells; these photoactivated cells are then isolated using fluorescence‐activated cell sorting. First, we use Visual Cell Sorting to assess hundreds of nuclear localization sequence variants in a pooled format, identifying variants that improve nuclear localization and enabling annotation of nuclear localization sequences in thousands of human proteins. Second, we recover cells that retain normal nuclear morphologies after paclitaxel treatment, and then derive their single‐cell transcriptomes to identify pathways associated with paclitaxel resistance in cancers. Unlike alternative methods, Visual Cell Sorting depends on inexpensive reagents and commercially available hardware. As such, it can be readily deployed to uncover the relationships between visual cellular phenotypes and internal states, including genotypes and gene expression programs
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