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Now showing items 1 - 16 of 28

  • Network-based integration of multi-omics data for prioritizing cancer genes

    Dimitrakopoulos, Christos   Kumar Hindupur, Sravanth   H?fliger, Luca   Behr, Jonas   Montazeri, Hesam   Hall, Michael N   Beerenwinkel, Niko   Birol, Inanc  

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  • Network-based integration of multi-omics data for prioritizing cancer genes.

    Dimitrakopoulos, Christos   Hindupur, Sravanth Kumar   Hafliger, Luca   Behr, Jonas   Montazeri, Hesam   Hall, Michael N   Beerenwinkel, Niko  

    Motivation: Several molecular events are known to be cancer-related, including genomic aberrations, hypermethylation of gene promoter regions and differential expression of microRNAs. These aberration events are very heterogeneous across tumors and it is poorly understood how they affect the molecular makeup of the cell, including the transcriptome and proteome. Protein interaction networks can help decode the functional relationship between aberration events and changes in gene and protein expression.; Results: We developed NetICS (Network-based Integration of Multi-omics Data), a new graph diffusion-based method for prioritizing cancer genes by integrating diverse molecular data types on a directed functional interaction network. NetICS prioritizes genes by their mediator effect, defined as the proximity of the gene to upstream aberration events and to downstream differentially expressed genes and proteins in an interaction network. Genes are prioritized for individual samples separately and integrated using a robust rank aggregation technique. NetICS provides a comprehensive computational framework that can aid in explaining the heterogeneity of aberration events by their functional convergence to common differentially expressed genes and proteins. We demonstrate NetICS' competitive performance in predicting known cancer genes and in generating robust gene lists using TCGA data from five cancer types.; Availability and implementation: NetICS is available at; Supplementary information: Supplementary data are available at Bioinformatics online.=20
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  • Graphene-based microfluidics for serial crystallography

    Sui, Shuo   Wang, Yuxi   Kolewe, Kristopher W.   Srajer, Vukica   Henning, Robert   Schiffman, Jessica D.   Dimitrakopoulos, Christos   Perry, Sarah L.  

    Microfluidic strategies to enable the growth and subsequent serial crystallographic analysis of microcrystals have the potential to facilitate both structural characterization and dynamic structural studies of protein targets that have been resistant to single-crystal strategies. However, adapting microfluidic crystallization platforms for micro-crystallography requires a dramatic decrease in the overall device thickness. We report a robust strategy for the straightforward incorporation of single-layer graphene into ultra-thin microfluidic devices. This architecture allows for a total material thickness of only similar to 1 mu m, facilitating on-chip X-ray diffraction analysis while creating a sample environment that is stable against significant water loss over several weeks. We demonstrate excellent signal-to-noise in our X-ray diffraction measurements using a 1.5 mu s polychromatic X-ray exposure, and validate our approach via on-chip structure determination using hen egg white lysozyme (HEWL) as a model system. Although this work is focused on the use of graphene for protein crystallography, we anticipate that this technology should find utility in a wide range of both X-ray and other lab on a chip applications.
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  • Layer-Resolved Graphene Transfer via Engineered Strain Layers

    Kim, Jeehwan   Park, Hongsik   Hannon, James B.   Bedell, Stephen W.   Fogel, Keith   Sadana, Devendra K.   Dimitrakopoulos, Christos  

    The performance of optimized graphene devices is ultimately determined by the quality of the graphene itself. Graphene grown on copper foils is often wrinkled, and the orientation of the graphene cannot be controlled. Graphene grown on SiC(0001) via the decomposition of the surface has a single orientation, but its thickness cannot be easily limited to one layer. We describe a method in which a graphene film of one or two monolayers grown on SiC is exfoliated via the stress induced with a Ni film and transferred to another substrate. The excess graphene is selectively removed with a second exfoliation process with a Au film, resulting in a monolayer graphene film that is continuous and single-oriented.
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    Disclosed is a ribbon of graphene less than 3 run wide, more preferably less than 1 nm wide. In a more preferred embodiment, there are multiple ribbons of graphene each with a width of one of the following dimensions: the length of 2 phenyl rings fused together, the length of 3 phenyl rings fused together, the length of 4 phenyl rings fused together, and the length of 5 phenyl rings fused together. In another preferred embodiment the edges of the ribbons are parallel to each other. In another preferred embodiment, the ribbons have at least one arm chair edge and may have wider widths.
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  • State-of-the-Art Graphene High-Frequency Electronics

    Wu, Yanqing   Jenkins, Keith A.   Valdes-Garcia, Alberto   Farmer, Damon B.   Zhu, Yu   Bol, Ageeth A.   Dimitrakopoulos, Christos   Zhu, Wenjuan   Xia, Fengnian   Avouris, Phaedon   Lin, Yu-Ming  

    High-performance graphene transistors for radio frequency applications have received much attention and significant progress has been achieved. However, devices based on large-area synthetic graphene, which have direct technological relevance, are still typically outperformed by those based on mechanically exfoliated graphene. Here, we report devices with intrinsic cutoff frequency above 300 GHz, based on both wafer-scale CVD grown graphene and epitaxial graphene on SiC, thus surpassing previous records on any graphene material. We also demonstrate devices with optimized architecture exhibiting voltage and power gains reaching 20 dB and a wafer-scale integrated graphene amplifier circuit with voltage amplification.
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  • Infrared Spectroscopy of Wafer-Scale Graphene

    Yan, Hugen   Xia, Fengnian   Zhu, Wenjuan   Freitag, Marcus   Dimitrakopoulos, Christos   Bol, Ageeth A.   Tulevski, George   Avouris, Phaedon  

    We report spectroscopy results from the mid- to far-infrared on wafer-scale graphene, grown either epitaxially on silicon carbide or by chemical vapor deposition. The free carrier absorption (Drude peak) Is simultaneously obtained with the universal optical conductivity (due to interband transitions) and the wavelength at which Pauli blocking occurs due to band filling. From these, the graphene layer number, doping level, sheet resistivity, carrier mobility, and scattering rate can be inferred. The mid-IR absorption of epitaxial two-layer graphene shows a less pronounced peak at 0.37 +/- 0.02 eV compared to that in exfoliated bilayer graphene. In heavily chemically doped single-layer graphene, a record high transmission reduction due to free carriers approaching 40% at 250 mu m (40 cm(-1)) is measured in this atomically thin material, supporting the great potential of graphene in far-infrared and terahertz optoelectronics.
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  • Scale-space measures for graph topology link protein network architecture to function.

    Hulsman, Marc   Dimitrakopoulos, Christos   de Ridder, Jeroen  

    MOTIVATION: The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an important shortcoming: they do not take into account that interactions occur across different scales. This is important because some cellular functions may involve a single direct protein interaction (small scale), whereas others require more and/or indirect interactions, such as protein complexes (medium scale) and interactions between large modules of proteins (large scale).; RESULTS: In this work, we derive generalized scale-aware versions of known graph topological measures based on diffusion kernels. We apply these to characterize the topology of networks across all scales simultaneously, generating a so-called graph topological scale-space. The comprehensive physical interaction network in yeast is used to show that scale-space based measures consistently give superior performance when distinguishing protein functional categories and three major types of functional interactions-genetic interaction, co-expression and perturbation interactions. Moreover, we demonstrate that graph topological scale spaces capture biologically meaningful features that provide new insights into the link between function and protein network architecture.; AVAILABILITY AND IMPLEMENTATION: Matlab(TM) code to calculate the scale-aware topological measures (STMs) is available at =C2=A9 The Author 2014. Published by Oxford University Press.
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  • Multicarrier transport in epitaxial multilayer graphene RID C-9737-2009

    Lin, Yu-Ming   Dimitrakopoulos, Christos   Farmer, Damon B.   Han, Shu-Jen   Wu, Yanqing   Zhu, Wenjuan   Gaskill, D. Kurt   Tedesco, Joseph L.   Myers-Ward, Rachael L.   Eddy, Charles R., Jr.   Grill, Alfred   Avouris, Phaedon  

    Variable-field Hall measurements were performed on epitaxial graphene grown on Si-face and C-face SiC. The carrier transport involves essentially a single-type of carrier in few-layer graphene, regardless of SiC face. However, in multilayer graphene (MLG) grown on C-face SiC, the Hall measurements indicated the existence of several groups of carriers with distinct mobilities. Electrical transport in MLG can be properly described by invoking three independent conduction channels in parallel. Two of these are n- and p-type, while the third involves nearly intrinsic graphene. The carriers in this lightly doped channel have significantly higher mobilities than the other two. (c) 2010 American Institute of Physics. [doi:10.1063/1.3485671]
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  • Enhanced Performance in Epitaxial Graphene FETs With Optimized Channel Morphology

    Lin, Yu-Ming   Farmer, Damon B.   Jenkins, Keith A.   Wu, Yanqing   Tedesco, Joseph L.   Myers-Ward, Rachael L.   Eddy, Charles R., Jr.   Gaskill, D. Kurt   Dimitrakopoulos, Christos   Avouris, Phaedon  

    This letter reports the impact of surface morphology on the carrier transport and radio-frequency performance of graphene FETs formed on epitaxial graphene synthesized on SiC substrates. Such graphene exhibits long terrace structures with widths between 3-5 mu m and steps of 10 +/- 2 nm in height. While a carrier mobility value above 3000 cm(2)/V . s at a carrier density of 10(12) cm(-2) is obtained in a single graphene terrace, the step edges can result in a step resistance of similar to 21 k Omega . mu m. By orienting the transistor layout so that the entire channel lies within a single graphene terrace and by reducing the access resistance associated with the ungated part of the channel, a cutoff frequency above 200 GHz is achieved for graphene FETs with channel lengths of 210 nm, i.e., the highest value reported on epitaxial graphene thus far.
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  • N-Doped Zwitterionic Fullerenes as Interlayers in Organic and Perovskite Photovoltaic Devices

    Duzhko, Volodimyr V.   Dunham, Brandon   Rosa, Stephen J.   Cole, Marcus D.   Paul, Abhijit   Page, Zachariah A.   Dimitrakopoulos, Christos   Emrick, Todd  

    The efficient operation of polymer-and perovskite-based photovoltaic devices depends on selective charge extraction layers that are placed between the active layer and electrodes. Herein, we demonstrate that integration of a tetra-n-butyl ammonium iodide-doped zwitterionic fulleropyrrolidine derivative, C-60-SB, as a cathode modification interlayer significantly improves the photovoltaic device performance. Compared to the intrinsic (undoped) zwitterionic material, which is an efficient interlayer itself, the doped interlayers further improve average power conversion efficiencies from 8.37% to 9.68% in polymer-based devices and from 12.53% to 15.31% in perovskite-based devices. Ultraviolet photoelectron spectroscopy revealed that doping increases the interfacial dipole at the C-60-SB/Ag interface, i.e., reduces the effective work function of the resultant composite cathode. This effect originates from the population of negative polaron states in C-60-SB by extrinsic charges that prevent directional charge transfer from Ag to the integer charge-transfer states in C-60-SB, pinning the Fermi level at higher energy. The reduced resistivity of the doped interlayer, as measured by impedance spectroscopy, enables efficient device operation with a broad range of interlayer thicknesses, thus simplifying the solution-based device fabrication process.
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  • Layer Number Determination and Thickness-Dependent Properties of Graphene Grown on SiC

    Zhu, Wenjuan   Dimitrakopoulos, Christos   Freitag, Marcus   Avouris, Phaedon  

    The electronic properties of few-layer graphene grown on the carbon face of silicon carbide (SiC) are found to be strongly dependent on the number of layers. The carrier mobility is larger in thicker graphene because substrate-related scattering is reduced in the higher layers. The carrier density dependence of the mobility is qualitatively different in thin and thick graphene, with the transition occurring at about 2 layers. The mobility increases with carrier density in thick graphene, similar to multilayer graphene exfoliated from natural graphite, suggesting that the individual layers are still electrically coupled in spite of reports recording non-Bernal stacking order in C-face grown graphene. The Hall coefficient peak value is reduced in thick graphene due to the increased density of states. A reliable and rapid characterization tool for the layer number is, therefore, highly desirable. To date, atomic force microscopy height determination and Raman scattering are typically used since the optical contrast of graphene on SiC is weak. However, both methods suffer from low throughput. We showthat the scanning electron microscopy (SEM) contrast can give similar results with much higher throughput.
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  • A Graphene-Based Microfluidic Platform for Electrocrystallization and In Situ X-ray Diffraction

    Sui, Shuo   Wang, Yuxi   Dimitrakopoulos, Christos   Perry, Sarah L.  

    Here, we describe a novel microfluidic platform for use in electrocrystallization experiments. The device incorporates ultra-thin graphene-based films as electrodes and as X-ray transparent windows to enable in situ X-ray diffraction analysis. Furthermore, large-area graphene films serve as a gas barrier, creating a stable sample environment over time. We characterize different methods for fabricating graphene electrodes, and validate the electrical capabilities of our device through the use of methyl viologen, a redox-sensitive dye. Proof-of-concept electrocrystallization experiments using an internal electric field at constant potential were performed using hen egg-white lysozyme (HEWL) as a model system. We observed faster nucleation and crystal growth, as well as a higher signal-to-noise for diffraction data obtained from crystals prepared in the presence of an applied electric field. Although this work is focused on the electrocrystallization of proteins for structural biology, we anticipate that this technology should also find utility in a broad range of both X-ray technologies and other applications of microfluidic technology.
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  • Enhanced Quality CVD-Grown Graphene via a Double-Plateau Copper Surface Planarization Methodology

    Griep, Mark H.   Tumlin, Travis M.   Smith, Joshua T.   Oida, Satoshi   Sano, Tomoko   Demaree, Derek   Dimitrakopoulos, Christos  

    Two-dimensional (2D) nanomaterials have been of intense interest in recent years because of their exceptional electronic, thermal, and mechanical properties. Tailoring these novel properties toward their intrinsic potential requires precise control of the atomic layer growth process and the underlying catalytic growth substrate, as the morphology and purity of the catalytic surface plays a critical role on the shape, size, and growth kinetics of the 2D nanomaterial. In this work, we present a systematic study on the role of the catalytic surface morphology and interface properties on the subsequent carrier mobility properties of CVDgrown graphene. A modified electropolishing methodology results in a dramatic reduction of over 99% in Cu surface roughness that enhances the carrier mobility of the CVD-grown graphene by as much as 125% compared to unpolished and lower planarization level growth substrates, providing a clear correlation between the smoothness of the Cu growth substrate and the resulting electrical properties of the graphene. Mobility measurements also reveal a systematic and controllable reduction in carrier concentration for increased electropolishing time. In addition to enhanced transport properties, the 100-fold reduction in the copper surface roughness leads to the ability to grow high-quality graphene at lower process temperatures.
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  • Ectopic expression of Msx2 in mammalian myotubes recapitulates aspects of amphibian muscle dedifferentiation.

    Yilmaz, Atilgan   Engeler, Rachel   Constantinescu, Simona   Kokkaliaris, Konstantinos D   Dimitrakopoulos, Christos   Schroeder, Timm   Beerenwinkel, Niko   Paro, Renato  

    In contrast to urodele amphibians and teleost fish, mammals lack the regenerative responses to replace large body parts. Amphibian and fish regeneration uses dedifferentiation, i.e., reversal of differentiated state, as a means to produce progenitor cells to eventually replace damaged tissues. Therefore, induced activation of dedifferentiation responses in mammalian tissues holds an immense promise for regenerative medicine. Here we demonstrate that ectopic expression of Msx2 in cultured mouse myotubes recapitulates several aspects of amphibian muscle dedifferentiation. We found that MSX2, but not MSX1, leads to cellularization of myotubes and downregulates the expression of myotube markers, such as MHC, MRF4 and myogenin. RNA sequencing of myotubes ectopically expressing Msx2 showed downregulation of over 500 myotube-enriched transcripts and upregulation of over 300 myoblast-enriched transcripts. MSX2 selectively downregulated expression of Ptgs2 and Ptger4, two members of the prostaglandin pathway with important roles in myoblast fusion during muscle differentiation. Ectopic expression of Msx2, as well as Msx1, induced partial cell cycle re-entry of myotubes by upregulating CyclinD1 expression but failed to initiate S-phase. Finally, MSX2-induced dedifferentiation in mouse myotubes could be recapitulated by a pharmacological treatment with trichostatin A (TSA), bone morphogenetic protein 4 (BMP4) and fibroblast growth factor 1 (FGF1). Together, these observations indicate that MSX2 is a major driver of dedifferentiation in mammalian muscle cells. Copyright =C2=A9 2015 The Authors. Published by Elsevier B.V. All rights reserved.
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  • Effect of SiC wafer miscut angle on the morphology and Hall mobility of epitaxially grown graphene

    Dimitrakopoulos, Christos   Grill, Alfred   McArdle, Timothy J.   Liu, Zihong   Wisnieff, Robert   Antoniadis, Dimitri A.  

    We show that the surface morphology and electrical properties of graphene grown on SiC(0001) wafers depend strongly on miscut angle, even for nominally ldquoon-axisrdquo wafers. Graphene grown on pit-free surfaces with narrow terraces (miscut above 0.28deg) shows substantially lower Hall mobility than graphene on surfaces with miscut angles below 0.1deg that have wider terraces with some pits. The effect of pits on mobility is not detrimental if flat, pit-free areas with dimensions larger than the carrier mean free path remain between pits. Using these results, we optimized the growth process, achieving room-temperature mobility up to 3015 cm 2/V s at N = 2.0 times 10 12 cm -2.
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