Eric Sembrat's Test Bonanza

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Cells are sensitive to mechanical signals produced either by application of exogenous force, or by the resistance to cell-generated forces caused by the viscoelastic properties of the materials to which they adhere. The range of stiffness over which different cell types respond can vary over a wide range and generally reflects the elastic modulus of the tissue from which these cells were isolated. Many cell types can alter their own stiffness to match that of the substrate to which they adhere. The maximal elastic modulus that cells can attain is similar to that of crosslinked actin networks at the concentrations in the cell cortex. Mechanosensing appears to require an elastic connection between cell and substrate, mediated by transmembrane proteins. The viscoelastic properties of different extracellular matrices and cytoskeletal elements strongly influence the response of cells to mechanical signals, and the unusual non-linear elasticity of many biopolymer gels, characterized by strain-stiffening, leads to novel mechanisms by which cells alter their stiffness by engagement of molecular motors that produce internal stresses.

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Curative cancer treatment requires radiotherapy (RT) in almost 2/3rd of all cases. Unfortunately, children are highly susceptible to the development of debilitating toxicities and secondary malignancies from RT. Normal tissue sparing with hadron-beam therapy is being actively investigated to reduce RT side-effects. The objective of this talk is to describe conventional and novel normal tissue-sparing applications of photon and proton beam therapy, respectively; radiobiological interplay with the tumor microenvironment will also be discussed.

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Physicist and adventurer Francis Slakey describes his decade long journey that led to his becoming the first person to both summit the highest mountain on every continent and surf every ocean.  The talk reviews some of the people he encounters and the challenges he endures – a Lama who gives him an amulet etched with “life’s meaning”, an ambush in the jungles of Indonesia, a life-or-death choice atop Everest – that culminate in a recognition that science is the most powerful tool we have to build a better world.  He will describe how that perspective now informs his work for the American Physical Society and Georgetown University.

Biography:

Francis Slakey received his PhD in physics from the University of Illinois, Urbana-Champaign in 1992.  He is the Associate Director of Public Affairs for the American Physical Society where he oversees APS legislative activities, specializing in energy and security policy.  He is also The Upjohn Lecturer on Physics and Public Policy and the Co-Director of the Program on Science in the Public Interest at Georgetown University.  He is a Fellow of the APS, a Fellow of the AAAS, a MacArthur Scholar, and a Lemelson Research Associate of the Smithsonian Institution.  In recognition of his adventures, in 2002, he was chosen to run the Olympic Torch from the steps of the US Capitol.  He recounts his global journey in his best-selling adventure memoir, To The Last Breath.

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Most of the mass in the Universe is of some unknown form of matter. While we have some guesses what it might be we are not sure. In this talk for a non-specialist audience, Professor Abel will explain how observations using telescopes convinced the scientists that Dark Matter must exist. He will also show how without it we would not even be here. Using videos produced from his supercomputer calculations we can see how stars and galaxies are formed in virtual universes that have a striking resemblance to our own. Without dark matter none of this would work. The talk will also explain current experiments on the way that have the hope of discovering what this dominant part of the Universe may be made of.

About the Speaker:

Dr. Tom Abel of the Kavli Institute for Particle Astrophysics and Cosmology is a man with a mission: "My long term goal is to build a galaxy, one star at a time" (via computer modeling, of course). Among Abel's research interests are the processes and events of "the dark ages", the first few hundred million years after the Big Bang. Abel & colleagues' visualizations and simulations of dark ages events, in addition to some 100 publications in the technical literature, have been featured on PBS and The Discovery Channel and in numerous newspapers and magazines, including the covers of Discover in December 2002 and of National Geographic in February 2003. Dr. Abel studied at the Max Planck Institut fuer Astrophysik at Garching and the National Center for Supercomputing Applications at Urbana/Champaign prior to earning a PhD in physics in 2000 from Ludwig-Maximilians-Universitat, Munich, Germany. Abel was a post-doctoral fellow at the Institute of Astronomy at Cambridge, England and at the Harvard Smithsonian Center for Astrophysics in Cambridge, Massachusetts. He was a Wempe Lecturer at the Astrophysikalisches Institut Potsdam, Potsdam, Germany, in 2001, and merited a CAREER Award from the National Science Foundation, Arlington, Virginia, 2002. Dr. Abel served as an Assistant and then Associate Professor for 2.5 years at The Pennsylvania State University in the Department of Astronomy and Astrophysics. He is now an Associate Professor of Physics in the Kavli Institute for Particle Astrophysics and Cosmology at both the Stanford University Physics Department and the Stanford Linear Accelerator Center, Stanford and Menlo Park, California.

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In this paper we present recent results obtained in the Nanobiotechnology and Spintronics group of  the LNEES research center of Politecnico di Milano, partially in cooperation with the nanoGUNE center in Spain, in the field of lab-on-chip devices based on magnetic nanostructures.

Manipulation of biological entities:

A few years ago the LNESS group discovered, in cooperation with nanoGUNE, that the controlled propagation of constrained magnetic domain walls (DWs)  in magnetic stripes can be used for finely manipulating magnetic particles in suspension over them. This approach relies on the precise control of the motion of DWs that can be achieved in ferromagnetic stripes (magnetic conduits) [1] and on the robust coupling between a DW and a magnetic particle in suspension over the conduits.[2] In this way the injection, displacement, and annihilation of a single DW in a ferromagnetic stripe results in the capture, displacement, and release of a particle. The method has been successfully applied to the manipulation of both biomolecules [3] attached to a magnetic carrier and of cells decorated with magnetic particles [4]. As an example, in figure 1 we show two frames from a video taken during the manipulation of a yeast cell via displacement of a DW between two adjacent corners in a square ring.

 R. Bertacco (1), D. Petti (1), M. Cantoni (1), A. Torti (1), E. Albisetti (1), M. Donolato (2), P. Vavassori (2) (1) LNESS and CNISM, Dipartimento di Fisica Politecnico di Milano, via Anzani 42,22100 Como (Italy)  (2) CIC nanoGUNE Consolider, Tolosa Hiribidea 76, San Sebastian, 20009, Spain

 

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School Chair's Annual Address to the School.

Reception immediately following in the East courtyard of Howey (between main building and lecture rooms on first floor).

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Coherent manipulation of atoms by strong electromagnetic radiation can be used to engineer new optical properties of matter. The technique of using a strong control field to manipulate the transmission of a weak probe field, such as it is done in Autler-Townes splitting, has recently been extended to control the transmission of x rays.

If a strong femtosecond pulse is used to control the transmission of an isolated attosecond extreme ultraviolet pulse, then basic assumptions of traditional quantum optics break down. The rotating wave approximation becomes invalid, and the sub-cycle timing of the attosecond pulse within the optical cycle of the control pulse influences the transmission dramatically. Furthermore the transmitted radiation is modulated over a wide frequency spectrum when the Rabi frequency exceeds the frequency of the strong control field. This effect is observed in a transient absorption experiment with Xenon atoms and can be explained in the framework of a few-level quantum model.

The transmitted spectrum also reveals information about the valence electron motion in the remaining ion if the control pulse is strong enough to induce strong field ionization. Attosecond transient absorption, that has already been used to observe the valence electron motion in singly charged ions, could be used to monitor the dynamics in doubly charged ions. This observation could give useful information to understand the role of electron correlation in strong field double ionization by circularly polarized fields, a topic that is currently heavily debated.

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Directed locomotion requires coordinated motor activity throughout an animal’s body. The nematode C. elegans, with only 302 neurons, offers an opportunity to understand how locomotion is organized by an entire motor system. We discovered that the mechanism that organizes undulatory locomotion in C. elegans is a novel form of sensory feedback within the motor circuit. Stretch-sensory feedback simply compels each body segment to bend in the same direction and shortly after the bending of the adjacent anterior segment. Remarkably, the entire sensorimotor loop operates is contained within a single (particularly sophisticated) type of neuron. We used microfluidics, optogenetics, calcium imaging, and modeling to show how stretch-sensory feedback is integrated into the motor circuit and how it explains the propagation of undulatory waves from head to tail. Our results point to a new framework for the organization of swimming and crawling gaits in worm undulatory locomotion.

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The challenge of predicting velocity and stress fields in any flowing granular material has proven to be a difficult one, from both computational and theoretical perspectives.  Indeed, researchers are still in search of the ``Navier-Stokes"-equivalent for flowing granular materials.   Granular flows can be adequately predicted using grain-by-grain discrete element methods (DEM), but these approaches become computationally unrealistic for large bodies of material and long times.   A robust continuum model, once identified, would have the practical benefit that it could be implemented at a meso-scale saving many orders of magnitude in computation time compared to DEM.

Here, we begin by synthesizing a 3D elasto-viscoplastic law for steady granular flow, merging an existing "frictional fluid" relation with a nonlinear granular elasticity relation to close the system.  The flow rate vanishes within a frictional (Drucker-Prager) yield surface and the elastic response is based on a mean-field model generalizing Hertz's contact law. The resulting form is general, able to produce flow and stress predictions  in any well-posed boundary value problem.  We implement it using ABAQUS/Explicit finite-element package and run test simulations in multiple geometries. The solutions are shown to compare favorably against a number of experiments and DEM simulations.

While this relation appears to function well for rapid flows, experimental results can often differ from the predictions in regions of slower flows.  We have been able to attribute many of these phenomena to nonlocal effects stemming from the finite-ness of the grain size.  To correct this, we consider the addition of a simple nonlocal term to the rheology in a fashion similar to recent nonlocal flow models in the emulsions community.  The results of this extended model are compared against many DEM steady-flow simulations in three different 2D geometries.  Quantitative agreement is found for all geometries and over various geometrical/loading parameters.  By natural extension, the nonlocal model is then converted to three dimensions with minimal changes, and is implemented numerically as a User-Element in the ABAQUS package.  We show that a single calibration of the 3D model quantitatively predicts hundreds of experimental flows in different geometries, including, for the first time, the wide-shear zones observed in the split-bottom annular couette cell, a geometry made infamous for resisting a theoretical treatment for almost a decade.

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EVO link:  http://evo.caltech.edu/evoNext/koala.jnlp?meeting=MtM8Ma2t2DD8Du9s92Ds9t

Defibrillation is a medical treatment used to terminate ventricular fibrillation or pulseless ventricular tachycardia. An electrical device via a pair of electrodes delivers controlled amount of electrical energy to the heart in order to reestablish the normal heart rhythm. First generation of defibrillators applied monophasic shock, in which electrodes did not change polarity during the application of the shock. Later it was found that changing the polarity of the electrodes during the shock leads to better result with less energy applied. Optimal monophasic and biphasic shock release approximately 200 J and 150 J, respectively. It is desirable to use as less energetic shock as possible in order to reduce the damage done to the tissue by the strong electric current. However, to this day, there is no full understanding why biphasic shocks are better than monophasic shocks. To assess this question, we have used a bidomain model for cardiac tissue with modified Beeler-Reuter model for transmembrane currents. Modifications account for anode break phenomena and electroporation effect known to happen during defibrillation. We have studied three different types of protocols for shock application (i.e. monophasic; symmetric biphasic; and asymmetric biphasic shock) in a one-dimensional ring of cardiac tissue. The size of the ring was chosen to exhibit a discordant-alternans dynamics.

Results of the numerical simulations reveal that monophasic shocks defibrillate with higher rate of success than the two biphasic shock protocols at lower energies. On the contrary for higher shock energies, the biphasic shock are significantly more efficient than monophasic shocks. This latter result confirms the medical common wisdom about defibrillators. Moreover, in this study, we were able to identify and classify the different defibrillation mechanisms that happen in this system. One identifies four different types: direct block, delayed block, annihilation and direct activation. Which defibrillation mechanism prevails depends on the energy level, the current dynamic state of the system and the shock protocol. This study has permitted to uncover and confirm the experimental fact stating that biphasic shocks are more efficient (at high energy) than monophasic shock to defibrillate cardiac tissue.

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