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  • 1
    Publication Date: 2005-12-13
    Description: Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor-alpha and interleukin-1alpha, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular "basis axes") within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janes, Kevin A -- Albeck, John G -- Gaudet, Suzanne -- Sorger, Peter K -- Lauffenburger, Douglas A -- Yaffe, Michael B -- GM059281/GM/NIGMS NIH HHS/ -- P50-GM68762/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Dec 9;310(5754):1646-53.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Biological Engineering Division, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16339439" target="_blank"〉PubMed〈/a〉
    Keywords: *Apoptosis ; Autocrine Communication ; Cell Survival ; Cytokines/*physiology ; Epidermal Growth Factor/physiology ; HT29 Cells ; Humans ; Insulin/physiology ; Interleukin-1/physiology ; JNK Mitogen-Activated Protein Kinases/metabolism ; Least-Squares Analysis ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/metabolism ; Models, Biological ; *Signal Transduction ; *Systems Biology ; Systems Theory ; Transforming Growth Factor alpha/physiology ; Tumor Necrosis Factor-alpha/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2009-04-14
    Description: In microorganisms, noise in gene expression gives rise to cell-to-cell variability in protein concentrations. In mammalian cells, protein levels also vary and individual cells differ widely in their responsiveness to uniform physiological stimuli. In the case of apoptosis mediated by TRAIL (tumour necrosis factor (TNF)-related apoptosis-inducing ligand) it is common for some cells in a clonal population to die while others survive-a striking divergence in cell fate. Among cells that die, the time between TRAIL exposure and caspase activation is highly variable. Here we image sister cells expressing reporters of caspase activation and mitochondrial outer membrane permeabilization after exposure to TRAIL. We show that naturally occurring differences in the levels or states of proteins regulating receptor-mediated apoptosis are the primary causes of cell-to-cell variability in the timing and probability of death in human cell lines. Protein state is transmitted from mother to daughter, giving rise to transient heritability in fate, but protein synthesis promotes rapid divergence so that sister cells soon become no more similar to each other than pairs of cells chosen at random. Our results have implications for understanding 'fractional killing' of tumour cells after exposure to chemotherapy, and for variability in mammalian signal transduction in general.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858974/" 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/PMC2858974/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spencer, Sabrina L -- Gaudet, Suzanne -- Albeck, John G -- Burke, John M -- Sorger, Peter K -- CA112967/CA/NCI NIH HHS/ -- GM68762/GM/NIGMS NIH HHS/ -- P50 GM068762/GM/NIGMS NIH HHS/ -- P50 GM068762-06/GM/NIGMS NIH HHS/ -- U54 CA112967/CA/NCI NIH HHS/ -- U54 CA112967-05/CA/NCI NIH HHS/ -- England -- Nature. 2009 May 21;459(7245):428-32. doi: 10.1038/nature08012. Epub 2009 Apr 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cell Decision Processes, Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19363473" target="_blank"〉PubMed〈/a〉
    Keywords: Apoptosis/*physiology ; BH3 Interacting Domain Death Agonist Protein/metabolism ; Caspases/metabolism ; Cell Division ; Cell Line ; Enzyme Activation ; Fluorescence Resonance Energy Transfer ; Genes, Reporter ; HeLa Cells ; Humans ; Mitochondrial Membranes/metabolism ; Models, Biological ; Permeability ; Probability ; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism ; Signal Transduction ; TNF-Related Apoptosis-Inducing Ligand/*metabolism ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-05-30
    Description: Cell-to-cell variability in cell death: can systems biology help us make sense of it all? Cell Death and Disease 5, e1261 (May 2014). doi:10.1038/cddis.2014.199 Authors: X Xia, M S Owen, R E C Lee & S Gaudet
    Keywords: cell-to-cell variabilitycomputational modelingsignaling dynamicsapoptosis
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Computational mechanics 21 (1998), S. 461-476 
    ISSN: 1432-0924
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract A numerical method for simulating the extensional dynamics of elongating filaments of non-Newtonian fluids in a filament stretching rheometer is presented. The boundary element method, in conjunction with either the Oldroyd-B or the generalized multimode Upper-Convected Maxwell constitutive model, is used to calculate the transient evolution of the liquid interface, the applied force on the stationary end plate and the polymeric stresses. The numerical results are compared to experimental results and are in excellent agreement at low Hencky strains (Newtonian response) but provide less accurate modeling of the stress growth observed in experiments at higher strains. A comparison of different methods for measuring the apparent extensional viscosity from global measurements of the net force and the mid-point radius of the filament is presented. At large strains calculations show that the fluid motion in these devices closely approximates ideal uniaxial elongation.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2315
    Keywords: Human animation ; Composition ; Complexity ; Design ; Human interface ; Creative design ; Aesthetic design ; Dance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Insights gained from an interdisciplinary study of the creative processes involved in dance composition are the basis for developing computer-based tools to support dance composition and animation. The system that has been developed, Life Forms, provides an interactive hierarchical environment where the user can reduce the complexity of the task by flexibly switching between spatial and temporal views of the composition. Realistic animation of the final result is also available. Life Forms, which is implemented on IRIS and Macintosh workstations, has proven itself to be of real value in dance composition. It is now being tested as the front end of a conventional animation system for use in animating multiple articulated figures.
    Type of Medium: Electronic Resource
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  • 6
    Publication Date: 2018-06-08
    Description: We talk about the NEPTUNE project under development (North East Pacific Time-series Underwater Networked Experiment).
    Keywords: Lunar and Planetary Science and Exploration
    Type: 2001 MTS IEEE; Honolulu, HI; United States
    Format: text
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  • 7
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Physics of Fluids 8 (1996), S. 2568-2579 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A numerical investigation is presented of axisymmetric, static and elongating, viscous Newtonian liquid bridges confined between identical circular disks. The time-dependent interface shapes and applied forces on the end plates, which separate at a constant prescribed velocity, are calculated as functions of the capillary number, the viscosity ratio between the inner and outer fluids, and an initial bridge configuration characterized by the aspect ratio. The numerical simulations are in excellent agreement with available experimental data and provide useful insight into the different dynamical responses of extending liquid bridge configurations. In particular, liquid bridges surrounded by fluids of a relatively small viscosity deform in a fore-aft symmetrical manner and undergo breakup sooner than in the case of relatively viscous outer fluids, which also require a greater applied force on the end plates to maintain the desired motion. Decreasing the capillary number (increasing interfacial tension) and the initial aspect ratio result in shorter bridge lengths prior to breakup and an increase in the applied forces on the end plates. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Physics of Fluids 10 (1998), S. 2489-2499 
    ISSN: 1089-7666
    Source: AIP Digital Archive
    Topics: Physics
    Notes: In this paper numerical simulations of the irrotational fluid flow associated with the entry of circular disks of a given mass into a semi-infinite fluid domain in the limits of very low to moderate Froude numbers are reported. This work is motivated by an experimental study performed by Glasheen and McMahon who investigated the low-Froude-number water entry of circular disks and found a linear relationship between the cavity seal depth and the Froude number and also showed that a single value of a modified drag coefficient is sufficient to predict the drag force on the disk. The numerical calculations performed in this paper confirm these experimental findings for steady cavity regimes and identify the ranges of Froude number and dimensionless mass values for which these results hold. Excellent agreement between the numerical computations and analytical velocity predictions, as well as the experimental cavity seal depth measurements, are obtained although the agreement between the measured and the computed drag coefficient values is not as good. The cavity seal depth and the drag coefficient are also found to depend on the disk mass and the numerical results in this paper show that for any disk of dimensionless mass M there exists a value of the Froude number for which the cavity dynamics are steady. Also, a very low-Froude-number regime in which gravitational forces are dominant and for which the cavity dynamics are qualitatively different than for low-to-moderate-Froude-number cases is also numerically explored in this paper. Finally, a bifurcation in the cavity seal mechanism from deep seal to surface seal was found at a Froude number F=105. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 9
    Publication Date: 2013-08-31
    Description: STARCAT, the Space Telescope ARchive and CATalogue user interface has been along for a number of years already. During this time it has been enhanced and augmented in a number of different fields. This time, we would like to dwell on a new capability allowing geographically distributed user interfaces to connect to geographically distributed data servers. This new concept permits users anywhere on the internet running STARCAT on their local hardware to access e.g., whichever of the 3 existing HST archive sites is available, or get information on the CFHT archive through a transparent connection to the CADC in BC or to get the La Silla weather by connecting to the ESO database in Munich during the same session. Similarly PreView (or quick look) images and spectra will also flow directly to the user from wherever it is available. Moving towards an 'X'-based STARCAT is another goal being pursued: a graphic/image server and a help/doc server are currently being added to it. They should further enhance the user independence and access transparency.
    Keywords: DOCUMENTATION AND INFORMATION SCIENCE
    Type: NASA, Washington, Second Annual Conference on Astronomical Data Analysis Software and Systems. Abstracts; p 38
    Format: application/pdf
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  • 10
    Publication Date: 2014-11-12
    Description: The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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