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Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types.
Cancer cell lines are a cornerstone of cancer research but previous studies have shown that not all cell lines are equal in their ability to model primary tumors. Here we present a comprehensive pan-cancer analysis utilizing transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia to evaluate cell lines as models of primary tumors across 22 tumor types. We perform correlation analysis and gene set enrichment analysis to understand the differences between cell lines and primary tumors. Additionally, we classify cell lines into tumor subtypes in 9 tumor types. We present our pancreatic cancer results as a case study and find that the commonly used cell line MIA PaCa-2 is transcriptionally unrepresentative of primary pancreatic adenocarcinomas. Lastly, we propose a new cell line panel, the TCGA-110-CL, for pan-cancer studies. This study provides a resource to help researchers select more representative cell line models
Spin- and energy relaxation of hot electrons at GaAs surfaces
The mechanisms for spin relaxation in semiconductors are reviewed, and the
mechanism prevalent in p-doped semiconductors, namely spin relaxation due to
the electron-hole exchange interaction, is presented in some depth. It is shown
that the solution of Boltzmann-type kinetic equations allows one to obtain
quantitative results for spin relaxation in semiconductors that go beyond the
original Bir-Aronov-Pikus relaxation-rate approximation. Experimental results
using surface sensitive two-photon photoemission techniques show that the spin
relaxation-time of electrons in p-doped GaAs at a semiconductor/metal surface
is several times longer than the corresponding bulk spin relaxation-times. A
theoretical explanation of these results in terms of the reduced density of
holes in the band-bending region at the surface is presented.Comment: 33 pages, 12 figures; earlier submission replaced by corrected and
expanded version; eps figures now included in the tex
Low Resistance Polycrystalline Diamond Thin Films Deposited by Hot Filament Chemical Vapour Deposition
Polycrystalline diamond thin films with outgrowing diamond (OGD) grains were deposited onto silicon wafers using a hydrocarbon gas (CH4) highly diluted with H2 at low pressure in a hot filament chemical vapour deposition (HFCVD) reactor with a range of gas flow rates. X-ray diffraction (XRD) and SEM showed polycrystalline diamond structure with a random orientation. Polycrystalline diamond films with various textures were grown and (111) facets were dominant with sharp grain boundaries. Outgrowth was observed in flowerish character at high gas flow rates. Isolated single crystals with little openings appeared at various stages at low gas flow rates. Thus, changing gas flow rates had a beneficial influence on the grain size, growth rate and electrical resistivity. CVD diamond films gave an excellent performance for medium film thickness with relatively low electrical resistivity and making them potentially useful in many industrial applications
The radiation of cynodonts and the ground plan of mammalian morphological diversity
Cynodont therapsids diversified extensively after the Permo-Triassic mass extinction event, and gave rise to mammals in the Jurassic. We use an enlarged and revised dataset of discrete skeletal characters to build a new phylogeny for all main cynodont clades from the Late Permian to the Early Jurassic, and we analyse models of morphological diversification in the group. Basal taxa and epicynodonts are paraphyletic relative to eucynodonts, and the latter are divided into cynognathians and probainognathians, with tritylodonts and mammals forming sister groups. Disparity analyses reveal a heterogeneous distribution of cynodonts in a morphospace derived from cladistic characters. Pairwise morphological distances are weakly correlated with phylogenetic distances. Comparisons of disparity by groups and through time are non-significant, especially after the data are rarefied. A disparity peak occurs in the Early/Middle Triassic, after which period the mean disparity fluctuates little. Cynognathians were characterized by high evolutionary rates and high diversity early in their history, whereas probainognathian rates were low. Community structure may have been instrumental in imposing different rates on the two clades
Dual Conformal Properties of Six-Dimensional Maximal Super Yang-Mills Amplitudes
We demonstrate that the tree-level amplitudes of maximal super-Yang-Mills
theory in six dimensions, when stripped of their overall momentum and
supermomentum delta functions, are covariant with respect to the
six-dimensional dual conformal group. Using the generalized unitarity method,
we demonstrate that this property is also present for loop amplitudes. Since
the six-dimensional amplitudes can be interpreted as massive four-dimensional
ones, this implies that the six-dimensional symmetry is also present in the
massively regulated four-dimensional maximal super-Yang-Mills amplitudes.Comment: 20 pages, 3 figures, minor clarification, references update
Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end
Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process
Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids
Multicellular tumor spheroids are an important {\it in vitro} model of the
pre-vascular phase of solid tumors, for sizes well below the diagnostic limit:
therefore a biophysical model of spheroids has the ability to shed light on the
internal workings and organization of tumors at a critical phase of their
development. To this end, we have developed a computer program that integrates
the behavior of individual cells and their interactions with other cells and
the surrounding environment. It is based on a quantitative description of
metabolism, growth, proliferation and death of single tumor cells, and on
equations that model biochemical and mechanical cell-cell and cell-environment
interactions. The program reproduces existing experimental data on spheroids,
and yields unique views of their microenvironment. Simulations show complex
internal flows and motions of nutrients, metabolites and cells, that are
otherwise unobservable with current experimental techniques, and give novel
clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The
published version contains links to a supplementary text and three video
file
The scale of population structure in Arabidopsis thaliana
The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales
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