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  • 1
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    Gene selection for the reconstruction of stem cell differentiation trees: a linear programming approach (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-08
    Description: Motivation: Stem cell differentiation is largely guided by master transcriptional regulators, but it also depends on the expression of other types of genes, such as cell cycle genes, signaling genes, metabolic genes, trafficking genes, etc. Traditional approaches to understanding gene expression patterns across multiple conditions, such as principal components analysis or K-means clustering, can group cell types based on gene expression, but they do so without knowledge of the differentiation hierarchy. Hierarchical clustering can organize cell types into a tree, but in general this tree is different from the differentiation hierarchy itself. Methods: Given the differentiation hierarchy and gene expression data at each node, we construct a weighted Euclidean distance metric such that the minimum spanning tree with respect to that metric is precisely the given differentiation hierarchy. We provide a set of linear constraints that are provably sufficient for the desired construction and a linear programming approach to identify sparse sets of weights, effectively identifying genes that are most relevant for discriminating different parts of the tree. Results: We apply our method to microarray gene expression data describing 38 cell types in the hematopoiesis hierarchy, constructing a weighted Euclidean metric that uses just 175 genes. However, we find that there are many alternative sets of weights that satisfy the linear constraints. Thus, in the style of random-forest training, we also construct metrics based on random subsets of the genes and compare them to the metric of 175 genes. We then report on the selected genes and their biological functions. Our approach offers a new way to identify genes that may have important roles in stem cell differentiation. Contact: tperkins@ohri.ca Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 2
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    Discovery of very high energy gamma rays from 1ES 1440+122 (2016)
    Archambault, S., Archer, A., Barnacka, A., Behera, B., Beilicke, M., Benbow, W., Berger, K., Bird, R., Böttcher, M., Buckley, J. H., Bugaev, V., Cardenzana, J. V., Cerruti, M., Chen, X., Christiansen, J. L., Ciupik, L., Collins-Hughes, E., Connolly, M. P., Cui, W., Dickinson, H. J., Dumm, J., Eisch, J. D., Errando, M., Falcone, A., Federici, S., Feng, Q., Finley, J. P., Fleischhack, H., Fortson, L., Furniss, A., Gillanders, G. H., Godambe, S., Griffin, S., Griffiths, S. T., Grube, J., Gyuk, G., Hkansson, N., Hanna, D., Holder, J., Hughes, G., Johnson, C. A., Kaaret, P., Kar, P., Kertzman, M., Khassen, Y., Kieda, D., Krawczynski, H., Kumar, S., Lang, M. J., Madhavan, A. S., Maier, G., McArthur, S., McCann, A., Meagher, K., Millis, J., Moriarty, P., Nelson, T., Nieto, D., de Bhroithe, A. O., Ong, R. A., Otte, A. N., Park, N., Perkins, J. S., Pohl, M., Popkow, A., Prokoph, H., Pueschel, E., Quinn, J., Ragan, K., Rajotte, J., Reyes, L. C., Reynolds, P. T., Richards, G. T., Roache, E., Sembroski, G. H., Shahinyan, K., Smith, A. W., Staszak, D., Sweeney, K., Telezhinsky, I., Tucci, J. V., Tyler, J., Varlotta, A., Vassiliev, V. V., Wakely, S. P., Welsing, R., Wilhelm, A., Williams, D. A., Zitzer, B.
    Oxford University Press
    Details
    Publication Date: 2016-06-30
    Description: The BL Lacertae object 1ES 1440+122 was observed in the energy range from 85 GeV to 30 TeV by the VERITAS array of imaging atmospheric Cherenkov telescopes. The observations, taken between 2008 May and 2010 June and totalling 53 h, resulted in the discovery of -ray emission from the blazar, which has a redshift z = 0.163. 1ES 1440+122 is detected at a statistical significance of 5.5 standard deviations above the background with an integral flux of (2.8 ± 0.7 stat ± 0.8 sys ) x 10 –12  cm –2  s –1 (1.2 per cent of the Crab Nebula's flux) above 200 GeV. The measured spectrum is described well by a power law from 0.2 to 1.3 TeV with a photon index of 3.1 ± 0.4 stat ± 0.2 sys . Quasi-simultaneous multiwavelength data from the Fermi Large Area Telescope (0.3–300 GeV) and the Swift X-ray Telescope (0.2–10 keV) are additionally used to model the properties of the emission region. A synchrotron self-Compton model produces a good representation of the multiwavelength data. Adding an external-Compton or a hadronic component also adequately describes the data.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-06-06
    Description: Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, D G -- Fan, J B -- Siao, C J -- Berno, A -- Young, P -- Sapolsky, R -- Ghandour, G -- Perkins, N -- Winchester, E -- Spencer, J -- Kruglyak, L -- Stein, L -- Hsie, L -- Topaloglou, T -- Hubbell, E -- Robinson, E -- Mittmann, M -- Morris, M S -- Shen, N -- Kilburn, D -- Rioux, J -- Nusbaum, C -- Rozen, S -- Hudson, T J -- Lipshutz, R -- Chee, M -- Lander, E S -- HG00098/HG/NHGRI NIH HHS/ -- HG01323/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 1998 May 15;280(5366):1077-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9582121" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Alleles ; Chromosome Mapping/*methods ; DNA, Complementary ; Databases, Factual ; Deoxyribonucleotides/*genetics ; Dinucleoside Phosphates ; Gene Expression ; Genetic Markers ; *Genetic Techniques ; Genetic Variation ; *Genome, Human ; *Genotype ; Heterozygote ; Homozygote ; Humans ; Molecular Sequence Data ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Reproducibility of Results ; Sequence Analysis, DNA ; Sequence Tagged Sites
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-08-01
    Description: Chemoresistance is a serious limitation of cancer treatment. Until recently, almost all the work done to study this limitation has been restricted to tumour cells. Here we identify a novel molecular mechanism by which endothelial cells regulate chemosensitivity. We establish that specific targeting of focal adhesion kinase (FAK; also known as PTK2) in endothelial cells is sufficient to induce tumour-cell sensitization to DNA-damaging therapies and thus inhibit tumour growth in mice. The clinical relevance of this work is supported by our observations that low blood vessel FAK expression is associated with complete remission in human lymphoma. Our study shows that deletion of FAK in endothelial cells has no apparent effect on blood vessel function per se, but induces increased apoptosis and decreased proliferation within perivascular tumour-cell compartments of doxorubicin- and radiotherapy-treated mice. Mechanistically, we demonstrate that endothelial-cell FAK is required for DNA-damage-induced NF-kappaB activation in vivo and in vitro, and the production of cytokines from endothelial cells. Moreover, loss of endothelial-cell FAK reduces DNA-damage-induced cytokine production, thus enhancing chemosensitization of tumour cells to DNA-damaging therapies in vitro and in vivo. Overall, our data identify endothelial-cell FAK as a regulator of tumour chemosensitivity. Furthermore, we anticipate that this proof-of-principle data will be a starting point for the development of new possible strategies to regulate chemosensitization by targeting endothelial-cell FAK specifically.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533916/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533916/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tavora, Bernardo -- Reynolds, Louise E -- Batista, Silvia -- Demircioglu, Fevzi -- Fernandez, Isabelle -- Lechertier, Tanguy -- Lees, Delphine M -- Wong, Ping-Pui -- Alexopoulou, Annika -- Elia, George -- Clear, Andrew -- Ledoux, Adeline -- Hunter, Jill -- Perkins, Neil -- Gribben, John G -- Hodivala-Dilke, Kairbaan M -- 12007/Cancer Research UK/United Kingdom -- C9218/A12007/Cancer Research UK/United Kingdom -- G0901609/Medical Research Council/United Kingdom -- P01 CA081534/CA/NCI NIH HHS/ -- P01 CA95426/CA/NCI NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):112-6. doi: 10.1038/nature13541. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Adhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; 1] Adhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK [2]. ; Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; Centre for Haemato-Oncology, Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; Institute for Cell and Molecular Biosciences (ICaMB), Medical School, Newcastle University, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079333" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus/drug effects ; Animals ; Apoptosis/drug effects/radiation effects ; Cell Nucleus/drug effects/metabolism ; Cell Proliferation/drug effects/radiation effects ; Cytokines/biosynthesis ; *DNA Damage/drug effects/genetics ; Doxorubicin/pharmacology/therapeutic use ; Drug Resistance, Neoplasm/*drug effects/genetics ; Endothelial Cells/*drug effects/*enzymology/metabolism ; Focal Adhesion Protein-Tyrosine Kinases/deficiency/genetics/*metabolism ; Humans ; Mice ; NF-kappa B/metabolism ; Neoplasms/drug therapy/genetics/pathology/radiotherapy ; Phosphorylation/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Non-linear dynamic intertwining of rods with self-contact (2008)
    Details
    Publication Date: 2022-05-25
    Description: Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in International Journal of Non-Linear Mechanics 43 (2008): 65-73, doi:10.1016/j.ijnonlinmec.2007.10.004.
    Description: Twisted marine cables on the sea floor can form highly contorted three-dimensional loops that resemble tangles. Such tangles or ‘hockles’ are topologically equivalent to the plectomenes that form in supercoiled DNA molecules. The dynamic evolution of these intertwined loops is studied herein using a computational rod model that explicitly accounts for dynamic self-contact. Numerical solutions are presented for an illustrative example of a long rod subjected to increasing twist at one end. The solutions reveal the dynamic evolution of the rod from an initially straight state, through a buckled state in the approximate form of a helix, through the dynamic collapse of this helix into a near-planar loop with one site of self-contact, and the subsequent intertwining of this loop with multiple sites of self-contact. This evolution is controlled by the dynamic conversion of torsional strain energy to bending strain energy or, alternatively by the dynamic conversion of twist (Tw) to writhe (Wr).
    Description: The authors (NCP and SG) gratefully acknowledge the research support provided by the U.S. Office of Naval Research (grant N00014-00-1-0001), the Lawrence Livermore 25 National Laboratories (grant B 531085), and the U. S. National Science Foundation (grants CMS 0439574 and CMS 0510266).
    Keywords: Rod dynamics ; Self-contact ; Intertwining ; DNA Supercoiling ; Cable hockling
    Repository Name: Woods Hole Open Access Server
    Type: Preprint
    Format: application/pdf
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  • 6
    Electronic Resource
    Electronic Resource
    Photoluminescence of erbium-implanted GaN and in situ-doped GaN:Er (1998)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 72 (1998), S. 1244-1246 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The photoluminescence of in situ-doped GaN:Er during hydride vapor phase epitaxy was compared to an Er-implanted GaN sample. At 11 K, the main emission wavelength of the in situ-doped sample is shifted to shorter wavelengths by 2.5 nm and the lifetime is 2.1±0.1 ms as compared to 2.9±0.1 ms obtained for the implanted sample. The 295 K band edge luminescence of the in situ-doped sample was free of the broad band luminescence centered at 500 nm which dominated the spectrum of the implanted sample. Reversible changes in the emission intensity of the in situ-doped sample upon annealing in a N2 versus a NH3/H2 ambient indicate the probable role of hydrogen in determining the luminescence efficiency of these samples. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.121034
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  • 7
    Electronic Resource
    Electronic Resource
    A near-field scanning optical microscopy study of the photoluminescence from GaN films (1996)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 69 (1996), S. 3519-3521 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We have achieved spatially resolved photoluminescence from GaN films using a near-field scanning optical microscope (NSOM). GaN films grown by hydride vapor phase epitaxy (HVPE) and metal-organic vapor phase epitaxy (MOVPE) on sapphire substrates have been studied. We have performed spatial scans of topography, band edge, and yellow luminescence signals. Atomic force microscopy measurements were also made and compared with the NSOM topography. We have found spatial variations in photoluminescence characteristics at the submicron scale for both HVPE and MOVPE GaN. The observed enhancement of yellow luminescence at multiatomic step edges on the HVPE GaN surface suggests that the yellow luminescence is associated with chemical impurities incorporated during the growth of GaN films. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.117231
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  • 8
    Electronic Resource
    Electronic Resource
    Photoemission spectroscopy studies of the surface of GaN films grown by vapor phase epitaxy (1996)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 69 (1996), S. 3351-3353 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Surfaces of GaN films have been investigated with photoemission spectroscopy. The measured valence band is in good agreement with band structure calculations and correlates well with tunneling luminescence measurements performed on the same samples. The effect of N depletion on band structure is explored, clarifying disagreements in previous photoemission measurements. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.117303
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  • 9
    Electronic Resource
    Electronic Resource
    Room temperature epitaxy of Pd films on GaN under conventional vacuum conditions (1996)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 69 (1996), S. 1722-1724 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Pd films deposited at room temperature have been found to grow epitaxially on GaN grown by metalorganic vapor phase epitaxy (MOVPE). The Pd films were deposited on GaN substrates cleaned by chemicals only, and in a conventional e-beam evaporation system with a vacuum of ∼1×10−7 Torr. MeV 4He backscattering spectrometry and the Read x-ray camera were used to evaluate the Pd films. The effects of various chemical etchants—such as aqua regia, HCl:H2O, and HF:H2O—on the epitaxial quality of the Pd films have also been investigated. Ni and Pt films deposited on GaN in a similar manner were also found to be epitaxial. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.118009
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  • 10
    Electronic Resource
    Electronic Resource
    Scanning tunneling microscopy and tunneling luminescence of the surface of GaN films grown by vapor phase epitaxy (1996)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 68 (1996), S. 1380-1382 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We report scanning tunneling microscopy (STM) images of surfaces of GaN films and the observation of luminescence from those films induced by highly spatially localized injection of electrons or holes using STM. This combination of scanning tunneling luminescence with STM for GaN surfaces and the ability to observe both morphology and luminescence in GaN is the first step to investigate possible correlations between surface morphology and optical properties. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.116086
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