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ItemMultiscale Modeling and Simulation: The Interplay Beween Mathematics and Engineering Applications(Georgia Institute of Technology, 2009-10-26) Hou, Thomas Y.Many problems of fundamental and practical importance contain multiple scale solutions. Composite and nano materials, flow and transport in heterogeneous porous media, and turbulent flow are examples of this type. Direct numerical simulations of these multiscale problems are extremely difficult due to the wide range of length scales in the underlying physical problems. Direct numerical simulations using a fine grid are very expensive. Developing effective multiscale methods that can capture accurately the large scale solution on a coarse grid has become essential in many engineering applications. In this talk, I will use two examples to illustrate how multiscale mathematics analysis can impact engineering applications. The first example is to develop multiscale computational methods to upscale multi-phase flows in strongly heterogeneous porous media. Multi-phase flows arise in many applications, ranging from petroleum engineering, contaminant transport, and fluid dynamics applications. Multiscale computational methods guided by multiscale analysis have already been adopted by the industry in their flow simulators. In the second example, we will show how to develop a systematic multiscale analysis for incompressible flows in three space dimensions. Deriving a reliable turbulent model has a significant impact in many engineering applications, including the aircraft design. This is known to be an extremely challenging problem. So far, most of the existing turbulent models are based on heuristic closure assumption and involve unknown parameters which need to be fitted by experimental data. We will show that how multiscale analysis can be used to develop a systematic multiscale method that does not involve any closure assumption and there are no adjustable parameters.
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ItemTwistor Theory, Then and Now(Georgia Institute of Technology, 2009-03-25) Penrose, RogerTwistor theory is now over 45 years old. In December 1963, I proposed the initial ideas of this scheme, based on complex-number geometry, which presents an alternative perspective to that of standard 4-dimensional space-time, for the basic arena in which (quantum) physics takes place. Over the succeeding years, there were numerous intriguing developments. But many of these were primarily mathematical, and there was little interest expressed by the physics community. Things changed rather dramatically, in December 2003, when E.Witten produced a 99-page article initiating the subject of “twistor-string theory” this providing a novel approach to high-energy scattering processes. In this talk, I shall provide an account of the original geometrical and physical ideas, and also outline various recent developments, some of which may help our understandings of the seeming paradoxes of quantum mechanics.
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ItemAeons Before the Big Bang?(Georgia Institute of Technology, 2009-03-24) Penrose, RogerThere is much impressive observational evidence, mainly from the cosmic microwave background (CMB), for an enormously hot and dense early stage of the universe referred to as the Big Bang. Observations of the CMB are now very detailed, but this very detail presents new puzzles of various kinds, one of the most blatant being an apparent paradox in relation to the second law of thermodynamics. The hypothesis of inflationary cosmology has long been argued to explain away some of these puzzles, but it does not resolve some key issues, including that raised by the second law. In this talk, I describe a quite different proposal, which posits a succession of universe aeons prior to our own. The expansion of the universe never reverses in this scheme, but the space-time geometry is nevertheless made consistent through a novel geometrical conception. Some very recent analysis of the CMB data, obtained from the WMAP satellite, will be described, this having a profound but tantalizing bearing on these issues.
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ItemHow to Explain the Universe in Two Minutes or Less(Georgia Institute of Technology, 2009-03-11) Palca, JoeSince joining NPR in 1992, Joe Palca has covered everything from biomedical research to astronomy. He began his journalism career in television in 1982, working as a health producer for the CBS affiliate in Washington, DC, after receiving a Ph.D. in psychology from the University of California at Santa Cruz where he worked on human sleep physiology. He has won numerous awards, including the National Academies Communications Award, the Science-in-Society Award of the National Association of Science Writers, the American Association for the Advancement of Science Journalism Prize, and the 2008 Victor Cohn Prize for Excellence in Medical Science Reporting. Recently he prepared a series of reports on the work of Charles Darwin in honor of the great naturalist’s bicentenary.
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ItemGenetics under geothermal conditions: Homologous recombination in the archaeon Sulfolobus acidocaldarius(Georgia Institute of Technology, 2008-10-23) Grogan, DennisHyperthermophilic archaea differ radically from all model organisms with respect to their evolutionary history and the severe environmental conditions they require. This divergence raises questions as to whether their genetic processes also have unusual properties; but few of these processes have been analyzed in vivo. In the extreme thermoacidophile Sulfolobus acidocaldarius, a conjugational mechanism of DNA transfer enables recombination between chromosomal mutations to be quantified. Early studies of this system suggested a non-reciprocal mechanism in which donor sequences become incorporated into the recipient genome as short segments. Subsequent studies using electroporation found that synthetic oligonucleotides can recombine into this genome. When similar experiments used longer, duplex DNAs containing multiple, silent markers, the resulting recombinants often contained multiple replacement tracts, consistent with an unusual, "short-patch" mode of homologous recombination.
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ItemRNA Enzymes: From Folding to Function in Living Cells(Georgia Institute of Technology, 2008-03-25) Fedor, Martha J.Our research aims to generate fundamental insights into catalysis by RNA enzymes and into the pathways through which RNAs form specific functional structures. RNA catalysis remains an intriguing puzzle that has grown in significance since the recent discoveries that the ribosome itself is an RNA enzyme and that human and bacterial mRNAs contain self-cleaving ribozymes. The hairpin ribozyme catalyzes a reversible self-cleavage reaction in which nucleophilic attack of a ribose 2’ hydroxyl on an adjacent phosphorus proceeds through a trigonal bipyramidal trasition state that leads to the formation of 2’,3’-cyclic phosphate and 2’ hydroxyl termini. The metal cation independence of activity and the availability of high-resolution active site structures have made the hairpin ribozyme the prototype for nucleobase-mediated catalytic chemistry. A network of stacking and hydrogen bonding interactions align the reactive phosphate in the appropriate orientation for an SN2-type nucleophilic attack and orient nucleotide base functional groups near the reactive phosphate to facilitate catalytic chemistry. Two active site nucleobases, G8 and A38, adopt orientations reminiscent of the histidine residues that mediate general acid base catalysis in ribonuclease A, a protein enzyme that catalyzes the same phosphodiester cleavage chemistry. However, our biochemical experiments argue against analogous roles for G8 and A38 in hairpin ribozyme catalysis and suggest that these residues contribute to catalysis through positioning and orientation and electrostatic stabilization of the electronegative transition site. Ribozymes are useful model systems for investigation of RNA folding, since self-cleavage reflects the assembly of a precise functional structure. To learn how structure-function principles revealed through in vitro experiments translate to the behavior of RNA in living cells, we devised a way to evaluate RNA assembly in vivo using RNA self-cleavage rates to quantify assembly of functional RNA structures. Results of these studies show that intracellular RNA folding kinetics and equilibria are indistinguishable from RNA folding behavior in vitro, provided that in vitro folding reactions approximate the ionic conditions characteristic of an intracellular environment. These studies contribute basic knowledge of RNA structure and function and provide a framework for developing technical and therapeutic application involving RNAs as targets and reagents.
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ItemNew RNA-binding peptidomimetic structures that repress HIV viral replication by specifically inhibiting transcriptional activation(Georgia Institute of Technology, 2008-03-18) Varani, GabrieleThe Interaction between the human immunodeficiency virus (HIV-1) transactivator protein Tat and its response element TAR plays an essential role in viral replication by controlling HIV transcription. Previous attempts to inhibit this interaction have failed to yield molecules with sufficient potency and specificity to warrant pharmaceutical development. We have shown that comformationally constrained cyclic peptide structural mimics of Tat provide nM inhibitors of the Tat-TAR interaction. These peptidomimetics are proteolytically stable, penetrate cells efficiently and have no cytotoxicity. They specifically inhibit Tat-dependent activation of transcription in cells and repress replication of a wide variety of viral strains representing all the major HIV clades in primary human lymphocytes. The potency and selectivity observed for this family of peptides is unprecedented among Tat inhibitors and suggest that these types of compounds may be widely useful for the pharmacological inhibition of other protein-RNA interactions.
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ItemThe Crossroads of Science and the Arts(Georgia Institute of Technology, 2008-03-05) Lightman, AlanAlan Lightman, Adjunct Professor of Humanities at MIT, is a novelist, essayist, physicist, and educator. Lightman received his PhD in theoretical physics from the California Institute of Technology in 1974. In his scientific work, Lightman has made fundamental contributions to the theory of astrophysical processes under conditions of extreme temperatures and densities. In particular, his research has focused on relativistic gravitation theory, the structure and behavior of accretion disks, stellar dynamics, radiative processes, and relativistic plasmas. His research articles have appeared in The Physical Review, The Astrophysical Journal, Reviews of Modern Physics, Nature, and other journals of physics and astrophysics. For his contributions to physics, he was elected a fellow of the American Physical Society in 1989 and a fellow of the American Association for the Advancement of Science the same year. In 1990, he chaired the science panel of the National Academy of Sciences Astronomy and Astrophysics Survey Committee for the 1990s. He is a past chair of the High Energy Division of the American Astronomical Society. In 1981, Lightman began publishing essays about science, the human side of science, and the "mind of science," beginning with Smithsonian Magazine and moving to Science 82, The New Yorker, and other magazines. Since that time, Lightman's essays, short fiction, and reviews have appeared in The American Scholar, The Atlantic Monthly, Boston Review, Daedalus, Discover, Exploratorium, Granta, Harper's, Harvard Magazine, Inc Technololgy, Nature, The New Yorker, The New York Review of Books, The New York Times, Smithsonian, Story, Technology Review, and World Monitor. His novel Einstein's Dreams was an international bestseller and has been translated into thirty languages. In 1989, Lightman was appointed professor of science and writing, and senior lecturer in physics, at the Massachusetts Institute of Technology. From 1991 to 1997, he headed the Program in Writing and Humanistic Studies at MIT.
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ItemPositive Selection on Non-coding Sequences During Human Evolution: From Genome to Nucleotide(Georgia Institute of Technology, 2008-03-04) Wray, Gregory
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ItemBetter living through biosensors(Georgia Institute of Technology, 2008-02-19) Plaxco, KevinThe ideal sensor will be sensitive, specific, versatile, small enough to hold in your hand, and selective enough to work even when faced with complex, contaminant-ridden samples. Given the affinity, specificity and generalizability of biomolecular recognition, biosensors have been widely touted for their potential to meet these challenging goals. To date, however, the translation of protein- and DNA-binding events into convenient, highly selective sensing platforms has proven problematic. We have solved this problem by employing the ligand-induced folding of proteins, peptides and DNA as a robust signal transduction mechanism. Our folding-based sensors are rapid (minutes to seconds), sensitive (micromolar to femtomolar), fully electronic, and generalizable to an enormous range of protein, nucleic acid and small molecule targets. The sensors are also reagentless, greater than 99% reusable, and selective enough to be employed in (and re-used from) blood, soil and other grossly contaminated materials. Because of their sensitivity, background suppression, operational convenience and impressive scalability folding-based biosensors appear ideally suited for electronic, on-chip applications in pathogen detection, proteomics and genomics.