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Sample records for fundamental binding forces

  1. Correlation between fundamental binding forces and clinical prognosis of Staphylococcus aureus infections of medical implants

    SciTech Connect

    Yongsunthon, Ruchirej; Fowler, Vance; Lower, Brian H.; Vellano, Francis P.; Alexander, Emily; Reller, L. Barth; Corey, G. Ralph; Lower, Steven

    2007-03-01

    Atomic force microscopy was used to “fish” for binding reactions between a fibronectin-coated probe (i.e., substrate simulating an implant device) and each of 15 different strains of S. aureus isolated from either patients with infected cardiac prosthesis (invasive group) or healthy human subjects (control group). There is a strong distinction (p=0.01) in the binding force-signature observed for the invasive vs. control populations. This observation suggests that a microorganism’s “force taxonomy” may provide a fundamental and practical indicator of the risk that bacterial infections pose to patients with implanted medical devices.

  2. Correlation between fundamental binding forces and clinical prognosis of Staphylococcus aureus infections of medical implants

    SciTech Connect

    Yongsunthon, Ruchirej; Fowler, Vance; Lower, Brian H.; Vellano, Francis P.; Alexander, Emily; Reller, L. Barth; Corey, G. Ralph; Lower, Steven

    2007-02-01

    Implanted medical devices (e.g., prosthetic heart valves, permanent pacemakers) significantly improve the quality of life for many humans. However, a common clinical observation is that such devices become colonized with potentially life-threatening Staphylococcus aureus biofilms, which are difficult to combat with host defenses or antibiotics. This study attempts to draw a correlation between the clinical outcome of patients with implanted cardiac devices and the fundamental binding forces ultimately responsible for the initiation of an S. aureus biofilm in-situ. Atomic force microscopy was used to measure forces between a fibronectin-coated probe (simulating a prosthetic implant) and 15 different strains of S. aureus isolated from either patients with infected cardiac devices (invasive population) or healthy human subjects (control population). The fibronectin-coated probe was repeatedly brought into and out of contact with a bacterium’s surface, “fishing” for a reaction with the cell’s fibronectin-binding proteins. More than 40,000 force profiles were measured on 5-10 different cells for each of the 15 clinical strains. A unique force-signature was observed for a binding event between the fibronectin-coated probe and the bacteria. When grouped by the frequency of this force-signature, there was a strong distinction (p=0.01) between the invasive and control populations of S. aureus. This discovery suggests that biofilm forming bacteria may be classified according to their “force taxonomy”, which could have a positive effect on health care as it bridges the long-standing disconnect between macroscopic, clinical investigations and nanometer-scale forces ultimately responsible for a bond between S. aureus and the surface of a prosthetic device.

  3. Unification of Fundamental Forces

    NASA Astrophysics Data System (ADS)

    Salam, Abdus; Taylor, Foreword by John C.

    2005-10-01

    Foreword John C. Taylor; 1. Unification of fundamental forces Abdus Salam; 2. History unfolding: an introduction to the two 1968 lectures by W. Heisenberg and P. A. M. Dirac Abdus Salam; 3. Theory, criticism, and a philosophy Werner Heisenberg; 4. Methods in theoretical physics Paul Adrian Maurice Dirac.

  4. Short-range Fundamental forces

    SciTech Connect

    Antoniadis, I; Baessler, Stefan; Buechner, M; Fedorov, General Victor; Hoedl, S.; Lambrecht, A; Nesvizhevsky, V.; Pignol, G; Reynaud, S.; Sobolev, Yu.

    2011-01-01

    We consider theoretical motivations to search for extra short-range fundamental forces as well as experiments constraining their parameters. The forces could be of two types: (1) spin-independent forces; and (2) spin-dependent axion-like forces. Different experimental techniques are sensitive in respective ranges of characteristic distances. The techniques include measurements of gravity at short distances, searches for extra interactions on top of the Casimir force, precision atomic and neutron experiments. We focus on neutron constraints, thus the range of characteristic distances considered here corresponds to the range accessible for neutron experiments.

  5. An Accurate Quartic Force Field, Fundamental Frequencies, and Binding Energy for the High Energy Density Material T(d)N4

    NASA Technical Reports Server (NTRS)

    Lee, Timothy J.; Martin, Jan M. L.; Kwak, Dochan (Technical Monitor)

    2002-01-01

    The CCSD(T) method has been used to compute a highly accurate quartic force field and fundamental frequencies for all N-14 and N-15 isotopomers of the high energy density material T(sub d)N(sub 4). The computed fundamental frequencies show beyond doubt that the bands observed in a matrix isolation experiment by Radziszewski and coworkers are not due to different isotopomers of T(sub d)N(sub 4). The most sophisticated thermochemical calculations to date yield a N(sub 4) -> 2N(sub 2) heat of reaction of 182.22 +/- 0.5 kcal/mol at 0 K (180.64 +/- 0.5 at 298 K). It is hoped that the data reported herein will aid in the ultimate detection of T(sub d)N(sub 4).

  6. Fundamental limits of optical force and torque

    NASA Astrophysics Data System (ADS)

    Rahimzadegan, A.; Alaee, R.; Fernandez-Corbaton, I.; Rockstuhl, C.

    2017-01-01

    Optical force and torque provide unprecedented control on the spatial motion of small particles. A valid scientific question, that has many practical implications, concerns the existence of fundamental upper bounds for the achievable force and torque exerted by a plane wave illumination with a given intensity. Here, while studying isotropic particles, we show that different light-matter interaction channels contribute to the exerted force and torque, and analytically derive upper bounds for each of the contributions. Specific examples for particles that achieve those upper bounds are provided. We study how and to which extent different contributions can add up to result in the maximum optical force and torque. Our insights are important for applications ranging from molecular sorting, particle manipulation, and nanorobotics up to ambitious projects such as laser-propelled spaceships.

  7. Redefinition of the Four Fundamental Forces,

    DTIC Science & Technology

    1980-06-01

    super-strong force. Such a force has been qualitatively predicted and attributed to Kaufman by Feynman (10, p. 609) and to Kogut, Wilson and Susskind by...Theory of Gravitation. Physical Review D, 13, 6, 1538-1560 (March 1976) 6. CHARLES W. MISNER, KIP S. THORNE, AND JOHN ARCHIBALD WHEELER . Gravitation. San...E. MEYERHOF. Elements of Nuclear Physics. New York: McGraw-Hill (1957) 216 Ala.--------- HEASTON 10. RICHARD P. FEYNMAN . Structure of the Proton

  8. Simplified fundamental force and mass measurements

    NASA Astrophysics Data System (ADS)

    Robinson, I. A.

    2016-08-01

    The watt balance relates force or mass to the Planck constant h, the metre and the second. It enables the forthcoming redefinition of the unit of mass within the SI by measuring the Planck constant in terms of mass, length and time with an uncertainty of better than 2 parts in 108. To achieve this, existing watt balances require complex and time-consuming alignment adjustments limiting their use to a few national metrology laboratories. This paper describes a simplified construction and operating principle for a watt balance which eliminates the need for the majority of these adjustments and is readily scalable using either electromagnetic or electrostatic actuators. It is hoped that this will encourage the more widespread use of the technique for a wide range of measurements of force or mass. For example: thrust measurements for space applications which would require only measurements of electrical quantities and velocity/displacement.

  9. Conformal invariance and the metrication of the fundamental forces

    NASA Astrophysics Data System (ADS)

    Mannheim, Philip D.

    2016-07-01

    We revisit Weyl’s metrication (geometrization) of electromagnetism. We show that by making Weyl’s proposed geometric connection be pure imaginary, not only are we able to metricate electromagnetism, an underlying local conformal invariance makes the geometry be strictly Riemannian and prevents observational gravity from being complex. Via torsion, we achieve an analogous metrication for axial-vector fields. We generalize our procedure to Yang-Mills theories, and achieve a metrication of all the fundamental forces. Only in the gravity sector does our approach differ from the standard picture of fundamental forces, with our approach requiring that standard Einstein gravity be replaced by conformal gravity. We show that quantum conformal gravity is a consistent and unitary quantum gravitational theory, one that, unlike string theory, only requires four spacetime dimensions.

  10. Saturation of color forces and nuclear binding

    NASA Astrophysics Data System (ADS)

    Matsuoka, Hiroshi; Sivers, Dennis

    1986-03-01

    We discuss an approach to understanding the saturation of forces in chromodynamics. Our formulation is suggested by the observation that many lattice-gauge-theory calculations give results well approximated by considering the dynamics of stringlike flux tubes. By looking at multiquark Green's functions in the strong-coupling, quenched, approximations of lattice chromodynamics we find examples of configuration mixing which can allow the binding of color-singlet hadrons into larger composite systems. We surmise that this configuration mixing is crucial to the understanding of nuclear binding. As a simple example we discuss the binding of two mesons composed of heavy, static, quarks into a deuteronlike object. Our results suggest that the magnitude of nuclear binding can be deduced by measuring a finite number of Wilson-loop configurations in lattice QCD.

  11. The Gap and the origin of the fundamental forces

    NASA Astrophysics Data System (ADS)

    Zichichi, Antonino

    2016-12-01

    The energy level where the best values of the three fundamental gauge couplings (α1,α2,α3) converge is at least two orders of magnitude below the Planck energy level. The existence of this Gap could imply that the gravitational force ‘comes into being’ before QED, QFD and QCD. The most interesting consequence of the Gap would then be the existence of matter whose charge is only the gravitational charge. If this is so, events should be detected where only gravitational waves are produced. Primordial black holes (PBHs) would be produced much more frequently than the standard black holes (SBHs) since SBHs would be ‘derivative’ effects produced later, after matter made with protons, electrons, neutrons, and stars can exist. Collisions between PBHs generating only gravitational waves should be more frequent than SBHs collisions.

  12. Air Force Officer Specialty Structure. Reviewing the Fundamentals

    DTIC Science & Technology

    2009-01-01

    documents for commercial use. For information on reprint and linking permissions, please see RAND Permissions. Limited Electronic Distribution Rights This...JUSTICE EDUCATION ENERGY AND ENVIRONMENT HEALTH AND HEALTH CARE INTERNATIONAL AFFAIRS NATIONAL SECURITY POPULATION AND AGING PUBLIC SAFETY SCIENCE AND...of RAND Project AIR FORCE for a fiscal year (FY) 2007 study, “USAF Specialty Code Restructuring.” This report should interest Air Force human

  13. Fundamental study of phosphor separation by controlling magnetic force

    NASA Astrophysics Data System (ADS)

    Wada, Kohei; Mishima, Fumihito; Akiyama, Yoko; Nishijima, Shigehiro

    2013-11-01

    The phosphor wastes consist of phosphors with different emission colors, green (LAP), red (YOX), blue (BAM) and white (HP). It is required to recover and reuse the rare earth phosphors with high market value. In this study, we tried to separate the phosphor using the magnetic separation by HTS bulk magnet utilizing the differences of magnetic susceptibility by the type of phosphors. We succeeded in the successive separation of HP with low market value from YOX and BAM including the rare earth using the magnetic Archimedes method. In this method, vertical and radial components of the magnetic force were used.

  14. The Sequential Evolution of Universes Based on Fundamental Forces

    NASA Astrophysics Data System (ADS)

    Derow, Catherine Kari

    2015-08-01

    Universes may arise as nature abhors a void. Upon ending of a universe, a new universe forms to fill a new void, forming after perhaps a period of nothingness.The nature of a new universe and the nature of formation, may be related to the nature of the previous universe and the nature of its ending, respectively, e.g., if the end of a universe was prolonged, this might be followed by a short period of nothingness and then an explosive creation of a new universe. Long approach to nothingness and a brief period of nothingness may mean a universe arises quickly and energetically in response to this long latent period of expectancy of void-filling. In terms of order in a universe, order may engender new more ordered universes, until need for chaos means a more chaotic universe arises. Ordered universes may cause new even more ordered universes to atise. The order principle dictates the type of matter organization that arises in universes in series. An ordered universe may have a latent energy of order which leads to a smaller more ordered universe. This minimizes the expectancy of a void, as a smaller more regularly filled void will then ensue in the new universe, until the energy held in by this order is released in the formation of a large much less ordered and slower forming and expanding universe, with more regions of near void. Nature may strive for a build up of intensity of focused order filling an ever- smaller void, averting the void, until the principle of chaos predominates and the energy that this requirement builds causes explosive formation of a large and disordered universe. The need to fill any void that arises and a force that favors a small void arising as void is abhorred and this void being regularly and densely filled competes with the force that favors matter tending towards chaos. These principles governs universes arising in series, until a period of nothingness can prevail until the need to create a void predominates. Nothingness is able to

  15. Biophysical characterization of DNA binding from single molecule force measurements

    PubMed Central

    Chaurasiya, Kathy R.; Paramanathan, Thayaparan; McCauley, Micah J.; Williams, Mark C.

    2010-01-01

    Single molecule force spectroscopy is a powerful method that uses the mechanical properties of DNA to explore DNA interactions. Here we describe how DNA stretching experiments quantitatively characterize the DNA binding of small molecules and proteins. Small molecules exhibit diverse DNA binding modes, including binding into the major and minor grooves and intercalation between base pairs of double-stranded DNA (dsDNA). Histones bind and package dsDNA, while other nuclear proteins such as high mobility group proteins bind to the backbone and bend dsDNA. Single-stranded DNA (ssDNA) binding proteins slide along dsDNA to locate and stabilize ssDNA during replication. Other proteins exhibit binding to both dsDNA and ssDNA. Nucleic acid chaperone proteins can switch rapidly between dsDNA and ssDNA binding modes, while DNA polymerases bind both forms of DNA with high affinity at distinct binding sites at the replication fork. Single molecule force measurements quantitatively characterize these DNA binding mechanisms, elucidating small molecule interactions and protein function. PMID:20576476

  16. Biophysical characterization of DNA binding from single molecule force measurements

    NASA Astrophysics Data System (ADS)

    Chaurasiya, Kathy R.; Paramanathan, Thayaparan; McCauley, Micah J.; Williams, Mark C.

    2010-09-01

    Single molecule force spectroscopy is a powerful method that uses the mechanical properties of DNA to explore DNA interactions. Here we describe how DNA stretching experiments quantitatively characterize the DNA binding of small molecules and proteins. Small molecules exhibit diverse DNA binding modes, including binding into the major and minor grooves and intercalation between base pairs of double-stranded DNA (dsDNA). Histones bind and package dsDNA, while other nuclear proteins such as high mobility group proteins bind to the backbone and bend dsDNA. Single-stranded DNA (ssDNA) binding proteins slide along dsDNA to locate and stabilize ssDNA during replication. Other proteins exhibit binding to both dsDNA and ssDNA. Nucleic acid chaperone proteins can switch rapidly between dsDNA and ssDNA binding modes, while DNA polymerases bind both forms of DNA with high affinity at distinct binding sites at the replication fork. Single molecule force measurements quantitatively characterize these DNA binding mechanisms, elucidating small molecule interactions and protein function.

  17. Fundamentals of large-molecule protein therapeutic bioanalysis using ligand-binding assays.

    PubMed

    Thway, Theingi M

    2016-01-01

    This article provides an overview of ligand-binding assays, including the origin and evolution of the primary concepts, in addition to reviewing commonly used assay formats. The birth of ligand-binding assays began with a radioimmunoassay developed to measure insulin in 1960. Fundamental to ligand-binding assay design is the requirement of at least one protein that interacts with the analyte of interest. Enzyme immunoassay has largely supplanted radioimmunoassay as the ligand-binding assay of choice in today's laboratory environment. This article illustrates various assay formats such as competitive, sandwich and bridging, in addition to, describing critical reagents necessary for their design. The utility of ligand-binding assays in therapeutic protein development and comparison to alternative bioanalysis platforms is discussed.

  18. Nonlinearly Additive Forces in Multivalent Ligand Binding to a Single Protein Revealed with Force Spectroscopy

    SciTech Connect

    Ratto, T V; Rudd, R E; Langry, K C; Balhorn, R L; McElfresh, M W

    2005-07-15

    We present evidence of multivalent interactions between a single protein molecule and multiple carbohydrates at a pH where the protein can bind four ligands. The evidence is based not only on measurements of the force required to rupture the bonds formed between ConcanavalinA (ConA) and {alpha}-D-mannose, but also on an analysis of the polymer-extension force curves to infer the polymer architecture that binds the protein to the cantilever and the ligands to the substrate. We find that although the rupture forces for multiple carbohydrate connections to a single protein are larger than the rupture force for a single connection, they do not scale additively with increasing number. Specifically, the most common rupture forces are approximately 46, 66, and 85 pN, which we argue corresponds to 1, 2, and 3 ligands being pulled simultaneously from a single protein as corroborated by an analysis of the linkage architecture. As in our previous work polymer tethers allow us to discriminate between specific and non-specific binding. We analyze the binding configuration (i.e. serial versus parallel connections) through fitting the polymer stretching data with modified Worm-Like Chain (WLC) models that predict how the effective stiffness of the tethers is affected by multiple connections. This analysis establishes that the forces we measure are due to single proteins interacting with multiple ligands, the first force spectroscopy study that establishes single-molecule multivalent binding unambiguously.

  19. Binding Forces and Teachers' School Life: A Recursive Model.

    ERIC Educational Resources Information Center

    Pang, Nicolas Sun-Keung

    2003-01-01

    Formulates theoretical model of four binding forces in school organizations--bureaucratic linkage, cultural linkage, tight coupling, and loose coupling--and examines their effects on teachers' feelings about school life. Finds, for example, that loose coupling had a positive effect on teachers' sense of community, job satisfaction, and commitment.…

  20. Ultra-fast force-clamp laser trapping of single molecular motors and DNA binding proteins

    NASA Astrophysics Data System (ADS)

    Capitanio, Marco; Monico, Carina; Vanzi, Francesco; Pavone, Francesco S.

    2013-09-01

    Forces play a fundamental role in a wide array of biological processes, regulating enzymatic activity, kinetics of molecular bonds, and molecular motors mechanics. Single molecule force spectroscopy techniques have enabled the investigation of such processes, but they are inadequate to probe short-lived (millisecond and sub-millisecond) molecular complexes. We developed an ultrafast force-clamp spectroscopy technique that uses a dual trap configuration to apply constant loads to a single intermittently interacting biological polymer and a binding protein. Our system displays a delay of only ˜10 μs between formation of the molecular bond and application of the force and is capable of detecting interactions as short as 100 μs. The force-clamp configuration in which our assay operates allows direct measurements of load-dependence of lifetimes of single molecular bonds. Moreover, conformational changes of single proteins and molecular motors can be recorded with sub-nanometer accuracy and few tens of microseconds of temporal resolution. We demonstrate our technique on molecular motors, using myosin II from fast skeletal muscle and on protein-DNA interaction, specifically on Lactose repressor (LacI). The apparatus is stabilized to less than 1 nm with both passive and active stabilization, allowing resolving specific binding regions along the actin filament and DNA molecule. Our technique extends single-molecule force-clamp spectroscopy to molecular complexes that have been inaccessible up to now, opening new perspectives for the investigation of the effects of forces on biological processes.

  1. The Effects of Noncellulosic Compounds on the Nanoscale Interaction Forces Measured between Carbohydrate-Binding Module and Lignocellulosic Biomass.

    PubMed

    Arslan, Baran; Colpan, Mert; Ju, Xiaohui; Zhang, Xiao; Kostyukova, Alla; Abu-Lail, Nehal I

    2016-05-09

    The lack of fundamental understanding of the types of forces that govern how cellulose-degrading enzymes interact with cellulosic and noncellulosic components of lignocellulosic surfaces limits the design of new strategies for efficient conversion of biomass to bioethanol. In a step to improve our fundamental understanding of such interactions, nanoscale forces acting between a model cellulase-a carbohydrate-binding module (CBM) of cellobiohydrolase I (CBH I)-and a set of lignocellulosic substrates with controlled composition were measured using atomic force microscopy (AFM). The three model substrates investigated were kraft (KP), sulfite (SP), and organosolv (OPP) pulped substrates. These substrates varied in their surface lignin coverage, lignin type, and xylan and acetone extractives' content. Our results indicated that the overall adhesion forces of biomass to CBM increased linearly with surface lignin coverage with kraft lignin showing the highest forces among lignin types investigated. When the overall adhesion forces were decoupled into specific and nonspecific component forces via the Poisson statistical model, hydrophobic and Lifshitz-van der Waals (LW) forces dominated the binding forces of CBM to kraft lignin, whereas permanent dipole-dipole interactions and electrostatic forces facilitated the interactions of lignosulfonates to CBM. Xylan and acetone extractives' content increased the attractive forces between CBM and lignin-free substrates, most likely through hydrogen bonding forces. When the substrates treated differently were compared, it was found that both the differences in specific and nonspecific forces between lignin-containing and lignin-free substrates were the least for OPP. Therefore, cellulase enzymes represented by CBM would weakly bind to organosolv lignin. This will facilitate an easy enzyme recovery compared to other substrates treated with kraft or sulfite pulping. Our results also suggest that altering the surface hydrophobicity

  2. Mechanical forces regulate elastase activity and binding site availability in lung elastin.

    PubMed

    Jesudason, Rajiv; Sato, Susumu; Parameswaran, Harikrishnan; Araujo, Ascanio D; Majumdar, Arnab; Allen, Philip G; Bartolák-Suki, Erzsébet; Suki, Béla

    2010-11-03

    Many fundamental cellular and extracellular processes in the body are mediated by enzymes. At the single molecule level, enzyme activity is influenced by mechanical forces. However, the effects of mechanical forces on the kinetics of enzymatic reactions in complex tissues with intact extracellular matrix (ECM) have not been identified. Here we report that physiologically relevant macroscopic mechanical forces modify enzyme activity at the molecular level in the ECM of the lung parenchyma. Porcine pancreatic elastase (PPE), which binds to and digests elastin, was fluorescently conjugated (f-PPE) and fluorescent recovery after photobleach was used to evaluate the binding kinetics of f-PPE in the alveolar walls of normal mouse lungs. Fluorescent recovery after photobleach indicated that the dissociation rate constant (k(off)) for f-PPE was significantly larger in stretched than in relaxed alveolar walls with a linear relation between k(off) and macroscopic strain. Using a network model of the parenchyma, a linear relation was also found between k(off) and microscopic strain on elastin fibers. Further, the binding pattern of f-PPE suggested that binding sites on elastin unfold with strain. The increased overall reaction rate also resulted in stronger structural breakdown at the level of alveolar walls, as well as accelerated decay of stiffness and decreased failure stress of the ECM at the macroscopic scale. These results suggest an important role for the coupling between mechanical forces and enzyme activity in ECM breakdown and remodeling in development, and during diseases such as pulmonary emphysema or vascular aneurysm. Our findings may also have broader implications because in vivo, enzyme activity in nearly all cellular and extracellular processes takes place in the presence of mechanical forces.

  3. Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

    PubMed Central

    Atherton, Joseph; Farabella, Irene; Yu, I-Mei; Rosenfeld, Steven S; Houdusse, Anne; Topf, Maya; Moores, Carolyn A

    2014-01-01

    Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles—including their nucleotide-free states—at ∼7 Å resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin–microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface. DOI: http://dx.doi.org/10.7554/eLife.03680.001 PMID:25209998

  4. Interactive Multimedia Software on Fundamental Particles and Forces. Final Technical Report

    SciTech Connect

    Jack Sculley

    1999-04-27

    Research in the SBIR Phase 2 grant number 95 ER 81944 centered on creating interactive multimedia software for teaching basic concepts in particle physics on fundamental particles and forces. The work was undertaken from February 1997 through July 1998. Overall the project has produced some very encouraging results in terms of product development, interest from the general public and interest from potential Phase 3 funders. Although the original Phase 3 publisher, McGraw Hill Home Interactive, was dissolved by its parent company, and other changes in the CD-ROM industry forced them to change their focus from CD-ROM to the Internet, there has been substantial interest from software publishers and online content providers in the content developed in the course of the Phase 2 research. Results are summarized.

  5. Unphosphorylated calponin enhances the binding force of unphosphorylated myosin to actin

    PubMed Central

    Roman, Horia Nicolae; Zitouni, Nedjma B.; Kachmar, Linda; Ijpma, Gijs; Hilbert, Lennart; Matusovskiy, Oleg; Benedetti, Andrea; Sobieszek, Apolinary; Lauzon, Anne-Marie

    2013-01-01

    Background Smooth muscle has the distinctive ability to maintain force for long periods of time and at low energy costs. While it is generally agreed that this property, called the latch-state, is due to the dephosphorylation of myosin while attached to actin, dephosphorylated-detached myosin can also attach to actin and may contribute to force maintenance. Thus, we investigated the role of calponin in regulating and enhancing the binding force of unphosphorylated tonic muscle myosin to actin. Methods To measure the effect of calponin on the binding of unphosphorylated myosin to actin, we used the laser trap assay to quantify the average force of unbinding (Funb) in the absence and presence of calponin or phosphorylated calponin. Results Funb from F-actin alone (0.12±0.01pN; mean±SE) was significantly increased in the presence of calponin (0.20±0.02pN). This enhancement was lost when calponin was phosphorylated (0.12±0.01pN). To further verify that this enhancement of Funb was due to cross-linking of actin to myosin by calponin, we repeated the measurements at high ionic strength. Indeed, the Funb obtained at a [KCl] of 25mM (0.21±0.02pN; mean±SE) was significantly decreased at a [KCl] of 150mM, (0.13±0.01pN). Conclusions This study provides direct molecular level-evidence that calponin enhances the binding force of unphosphorylated myosin to actin by cross-linking them and that this is reversed upon calponin phosphorylation. Thus, calponin might play an important role in the latch-state. General Significance This study suggests a new mechanism that likely contributes to the latch-state, a fundamental and important property of smooth muscle that remains unresolved. PMID:23747303

  6. Atomic force microscopy: Unraveling the fundamental principles governing secretion and membrane fusion in cells.

    PubMed

    Jena, Bhanu P

    2009-07-01

    The story of cell secretion and membrane fusion is as old as life itself. Without these fundamental cellular processes known to occur in yeast to humans, life would cease to exist. In the last 15 years, primarily using the atomic force microscope, a detailed understanding of the molecular process and of the molecular machinery and mechanism of secretion and membrane fusion in cells has come to light. This has led to a paradigm shift in our understanding of the underlying mechanism of cell secretion. The journey leading to the discovery of a new cellular structure the 'porosome',-the universal secretory machinery in cells, and the contributions of the AFM in our understanding of the general molecular machinery and mechanism of cell secretion and membrane fusion, is briefly discussed in this article.

  7. Fundamental Distinctions in Physics underlying Nonsteady Forcings of Wind Turbine Power vs. Drivetrain by Atmospheric Turbulence

    NASA Astrophysics Data System (ADS)

    Brasseur, James; Lavely, Adam; Nandi, Tarak

    2016-11-01

    Whereas the primary function of a wind turbine (WT) is the generation of electricity, wind farm profitability is decreased both by integrated losses in power and increases in premature failures of drivetrain components resulting from energetic nonsteady aerodynamic forcings of WT rotors by atmospheric and wake turbulence. Here we contrast the physics underlying dominant nonsteady atmospheric turbulence forcings of the bending moments in the WT rotor plane (torque/power) vs. the out-of-plane bending moments (OPBM) that underlie premature drivetrain component failure. Using an advanced actuator line model of the 5 MW NREL and the 1.5 MW GE wind turbine rotors embedded within a high-fidelity spectral LES of a typical daytime convective atmospheric boundary layer, we show that (1) the physics underlying large torque vs. OBPM fluctuations are associated with fundamentally different turbulence eddy characteristics and (2) nonsteady response centers on 4 characteristic time scales associated advection of eddies and load response of blades cutting through internal turbulence eddy structure. Supported by DOE. Computer resources by NSF/XSEDE.

  8. Fundamental Study of Local Heat Transfer in Forced Convective Boiling of Ammonia on Vertical Flat Plate

    NASA Astrophysics Data System (ADS)

    Kim, Jeong-Hun; Arima, Hirofumi; Ikegami, Yasuyuki

    In the present study, the fundamental experiments that investigate characteristics of local heat transfer in forced convective boiling on vertical flat plate with 2-mm channel height are taken to realize plate type compact evaporator for OTEC or STEC. The experiments are performed with ammonia as the working fluid. The experiments are also carried out with the following test conditions; saturated pressure = 0.7, 0.8, 0.9 MPa, mass flux = 7.5, 10, 15 kg/(m2•s), heat flux = 15, 20, 25 kW/m2 and inlet quality = 0.1 ~ 0.4 [-]. The result shows that the wall superheated temperature of forced convective boiling is lower than that of pool boiling. And the heat transfer coefficient increases with an increase in quality and the decrease in the local heat flux and saturated pressure for prescribed experimental conditions. However, local heat transfer coefficients are not affected by mass fluxes in the prescribed experimental conditions. An empirical correlation that can predict the local heat transfer coefficient on vertical flat plate within experimental conditions is also proposed.

  9. A fundamental model of mistuning for system identification and forced response prediction

    NASA Astrophysics Data System (ADS)

    Feiner, Drew M.

    The vibratory response of a turbine blade is very sensitive to small changes in the blade properties. Therefore, the variations that come from the manufacturing process and wear can significantly increase a blade's vibratory stress at resonance. This phenomenon, referred to as mistuning, can cause blades in a gas turbine engine to fail from high cycle fatigue. A new reduced order model of mistuned bladed disk vibration is presented. This new approach is shown to accurately represent the response of real turbine geometries when only a single family of modes is excited. Yet its mathematical form is even simpler than that of a mass-spring model. Because it requires only minimal input data, this model is much easier to use than previous reduced order methods. Furthermore, its simplicity allows the fundamental parameters that control mistuning to be readily identified. This model is then used to develop a set of analysis tools to assess the mistuning in an engine component and predict its vibratory response under rotating conditions. These tools include a completely experimental method of system identification which uses vibratory response measurements of the bladed disk system as a whole to infer its mistuning. As a system-based method, this approach is particularly well suited to integrally bladed rotors, whose blades cannot be removed for individual testing. Next, an analytical method is developed to adjust mistuning for the effects of centrifugal stiffening. The approach allows mistuning measured from a stationary rotor to be used to predict the part's forced response under rotating conditions. Finally, the system identification method is extended to allow forced response measurements from a rotating test to be used as input. The mistuning measured through this approach will reflect all effects present during the operating conditions. One particular advantage of this method is that it can capture the effect of centrifugal loading on the mistuning of conventionally

  10. Spatial Analysis and Quantification of the Thermodynamic Driving Forces in Protein-Ligand Binding: Binding Site Variability

    PubMed Central

    Raman, E. Prabhu; MacKerell, Alexander D.

    2015-01-01

    The thermodynamic driving forces behind small molecule-protein binding are still not well understood, including the variability of those forces associated with different types of ligands in different binding pockets. To better understand these phenomena we calculate spatially resolved thermodynamic contributions of the different molecular degrees of freedom for the binding of propane and methanol to multiple pockets on the proteins Factor Xa and p38 MAP kinase. Binding thermodynamics are computed using a statistical thermodynamics based end-point method applied on a canonical ensemble comprising the protein-ligand complexes and the corresponding free states in an explicit solvent environment. Energetic and entropic contributions of water and ligand degrees of freedom computed from the configurational ensemble provides an unprecedented level of detail into the mechanisms of binding. Direct protein-ligand interaction energies play a significant role in both non-polar and polar binding, which is comparable to water reorganization energy. Loss of interactions with water upon binding strongly compensates these contributions leading to relatively small binding enthalpies. For both solutes, the entropy of water reorganization is found to favor binding in agreement with the classical view of the “hydrophobic effect”. Depending on the specifics of the binding pocket, both energy-entropy compensation and reinforcement mechanisms are observed. Notable is the ability to visualize the spatial distribution of the thermodynamic contributions to binding at atomic resolution showing significant differences in the thermodynamic contributions of water to the binding of propane versus methanol. PMID:25625202

  11. Fundamental High-Speed Limits in Single-Molecule, Single-Cell, and Nanoscale Force Spectroscopies.

    PubMed

    Amo, Carlos A; Garcia, Ricardo

    2016-07-26

    Force spectroscopy is enhancing our understanding of single-biomolecule, single-cell, and nanoscale mechanics. Force spectroscopy postulates the proportionality between the interaction force and the instantaneous probe deflection. By studying the probe dynamics, we demonstrate that the total force acting on the probe has three different components: the interaction, the hydrodynamic, and the inertial. The amplitudes of those components depend on the ratio between the resonant frequency and the frequency at which the data are measured. A force-distance curve provides a faithful measurement of the interaction force between two molecules when the inertial and hydrodynamic components are negligible. Otherwise, force spectroscopy measurements will underestimate the value of unbinding forces. Neglecting the above force components requires the use of frequency ratios in the 50-500 range. These ratios will limit the use of high-speed methods in force spectroscopy. The theory is supported by numerical simulations.

  12. A Study on the Fundamental Mechanism and the Evolutionary Driving Forces behind Aerobic Fermentation in Yeast

    PubMed Central

    Hagman, Arne; Piškur, Jure

    2015-01-01

    Baker’s yeast Saccharomyces cerevisiae rapidly converts sugars to ethanol and carbon dioxide at both anaerobic and aerobic conditions. The later phenomenon is called Crabtree effect and has been described in two forms, long-term and short-term effect. We have previously studied under fully controlled aerobic conditions forty yeast species for their central carbon metabolism and the presence of long-term Crabtree effect. We have also studied ten steady-state yeast cultures, pulsed them with glucose, and followed the central carbon metabolism and the appearance of ethanol at dynamic conditions. In this paper we analyzed those wet laboratory data to elucidate possible mechanisms that determine the fate of glucose in different yeast species that cover approximately 250 million years of evolutionary history. We determine overflow metabolism to be the fundamental mechanism behind both long- and short-term Crabtree effect, which originated approximately 125–150 million years ago in the Saccharomyces lineage. The “invention” of overflow metabolism was the first step in the evolution of aerobic fermentation in yeast. It provides a general strategy to increase energy production rates, which we show is positively correlated to growth. The “invention” of overflow has also simultaneously enabled rapid glucose consumption in yeast, which is a trait that could have been selected for, to “starve” competitors in nature. We also show that glucose repression of respiration is confined mainly among S. cerevisiae and closely related species that diverged after the whole genome duplication event, less than 100 million years ago. Thus, glucose repression of respiration was apparently “invented” as a second step to further increase overflow and ethanol production, to inhibit growth of other microbes. The driving force behind the initial evolutionary steps was most likely competition with other microbes to faster consume and convert sugar into biomass, in niches that

  13. A study on the fundamental mechanism and the evolutionary driving forces behind aerobic fermentation in yeast.

    PubMed

    Hagman, Arne; Piškur, Jure

    2015-01-01

    Baker's yeast Saccharomyces cerevisiae rapidly converts sugars to ethanol and carbon dioxide at both anaerobic and aerobic conditions. The later phenomenon is called Crabtree effect and has been described in two forms, long-term and short-term effect. We have previously studied under fully controlled aerobic conditions forty yeast species for their central carbon metabolism and the presence of long-term Crabtree effect. We have also studied ten steady-state yeast cultures, pulsed them with glucose, and followed the central carbon metabolism and the appearance of ethanol at dynamic conditions. In this paper we analyzed those wet laboratory data to elucidate possible mechanisms that determine the fate of glucose in different yeast species that cover approximately 250 million years of evolutionary history. We determine overflow metabolism to be the fundamental mechanism behind both long- and short-term Crabtree effect, which originated approximately 125-150 million years ago in the Saccharomyces lineage. The "invention" of overflow metabolism was the first step in the evolution of aerobic fermentation in yeast. It provides a general strategy to increase energy production rates, which we show is positively correlated to growth. The "invention" of overflow has also simultaneously enabled rapid glucose consumption in yeast, which is a trait that could have been selected for, to "starve" competitors in nature. We also show that glucose repression of respiration is confined mainly among S. cerevisiae and closely related species that diverged after the whole genome duplication event, less than 100 million years ago. Thus, glucose repression of respiration was apparently "invented" as a second step to further increase overflow and ethanol production, to inhibit growth of other microbes. The driving force behind the initial evolutionary steps was most likely competition with other microbes to faster consume and convert sugar into biomass, in niches that were semi-anaerobic.

  14. Fundamental High-Speed Limits in Single-Molecule, Single-Cell, and Nanoscale Force Spectroscopies

    PubMed Central

    2016-01-01

    Force spectroscopy is enhancing our understanding of single-biomolecule, single-cell, and nanoscale mechanics. Force spectroscopy postulates the proportionality between the interaction force and the instantaneous probe deflection. By studying the probe dynamics, we demonstrate that the total force acting on the probe has three different components: the interaction, the hydrodynamic, and the inertial. The amplitudes of those components depend on the ratio between the resonant frequency and the frequency at which the data are measured. A force–distance curve provides a faithful measurement of the interaction force between two molecules when the inertial and hydrodynamic components are negligible. Otherwise, force spectroscopy measurements will underestimate the value of unbinding forces. Neglecting the above force components requires the use of frequency ratios in the 50–500 range. These ratios will limit the use of high-speed methods in force spectroscopy. The theory is supported by numerical simulations. PMID:27359243

  15. Fundamental aspects of electric double layer force-distance measurements at liquid-solid interfaces using atomic force microscopy

    SciTech Connect

    Black, Jennifer M.; Zhu, Mengyang; Zhang, Pengfei; Unocic, Raymond R.; Guo, Daqiang; Okatan, M. Baris; Dai, Sheng; Cummings, Peter T.; Kalinin, Sergei V.; Feng, Guang; Balke, Nina

    2016-09-02

    In this paper, atomic force microscopy (AFM) force-distance measurements are used to investigate the layered ion structure of Ionic Liquids (ILs) at the mica surface. The effects of various tip properties on the measured force profiles are examined and reveal that the measured ion position is independent of tip properties, while the tip radius affects the forces required to break through the ion layers as well as the adhesion force. Force data is collected for different ILs and directly compared with interfacial ion density profiles predicted by molecular dynamics. Through this comparison it is concluded that AFM force measurements are sensitive to the position of the ion with the larger volume and mass, suggesting that ion selectivity in force-distance measurements are related to excluded volume effects and not to electrostatic or chemical interactions between ions and AFM tip. Finally, the comparison also revealed that at distances greater than 1 nm the system maintains overall electroneutrality between the AFM tip and sample, while at smaller distances other forces (e.g., van der waals interactions) dominate and electroneutrality is no longer maintained.

  16. Fundamental aspects of electric double layer force-distance measurements at liquid-solid interfaces using atomic force microscopy

    DOE PAGES

    Black, Jennifer M.; Zhu, Mengyang; Zhang, Pengfei; ...

    2016-09-02

    In this paper, atomic force microscopy (AFM) force-distance measurements are used to investigate the layered ion structure of Ionic Liquids (ILs) at the mica surface. The effects of various tip properties on the measured force profiles are examined and reveal that the measured ion position is independent of tip properties, while the tip radius affects the forces required to break through the ion layers as well as the adhesion force. Force data is collected for different ILs and directly compared with interfacial ion density profiles predicted by molecular dynamics. Through this comparison it is concluded that AFM force measurements aremore » sensitive to the position of the ion with the larger volume and mass, suggesting that ion selectivity in force-distance measurements are related to excluded volume effects and not to electrostatic or chemical interactions between ions and AFM tip. Finally, the comparison also revealed that at distances greater than 1 nm the system maintains overall electroneutrality between the AFM tip and sample, while at smaller distances other forces (e.g., van der waals interactions) dominate and electroneutrality is no longer maintained.« less

  17. Fundamental aspects of electric double layer force-distance measurements at liquid-solid interfaces using atomic force microscopy.

    PubMed

    Black, Jennifer M; Zhu, Mengyang; Zhang, Pengfei; Unocic, Raymond R; Guo, Daqiang; Okatan, M Baris; Dai, Sheng; Cummings, Peter T; Kalinin, Sergei V; Feng, Guang; Balke, Nina

    2016-09-02

    Atomic force microscopy (AFM) force-distance measurements are used to investigate the layered ion structure of Ionic Liquids (ILs) at the mica surface. The effects of various tip properties on the measured force profiles are examined and reveal that the measured ion position is independent of tip properties, while the tip radius affects the forces required to break through the ion layers as well as the adhesion force. Force data is collected for different ILs and directly compared with interfacial ion density profiles predicted by molecular dynamics. Through this comparison it is concluded that AFM force measurements are sensitive to the position of the ion with the larger volume and mass, suggesting that ion selectivity in force-distance measurements are related to excluded volume effects and not to electrostatic or chemical interactions between ions and AFM tip. The comparison also revealed that at distances greater than 1 nm the system maintains overall electroneutrality between the AFM tip and sample, while at smaller distances other forces (e.g., van der waals interactions) dominate and electroneutrality is no longer maintained.

  18. Fundamental aspects of electric double layer force-distance measurements at liquid-solid interfaces using atomic force microscopy

    PubMed Central

    Black, Jennifer M.; Zhu, Mengyang; Zhang, Pengfei; Unocic, Raymond R.; Guo, Daqiang; Okatan, M. Baris; Dai, Sheng; Cummings, Peter T.; Kalinin, Sergei V.; Feng, Guang; Balke, Nina

    2016-01-01

    Atomic force microscopy (AFM) force-distance measurements are used to investigate the layered ion structure of Ionic Liquids (ILs) at the mica surface. The effects of various tip properties on the measured force profiles are examined and reveal that the measured ion position is independent of tip properties, while the tip radius affects the forces required to break through the ion layers as well as the adhesion force. Force data is collected for different ILs and directly compared with interfacial ion density profiles predicted by molecular dynamics. Through this comparison it is concluded that AFM force measurements are sensitive to the position of the ion with the larger volume and mass, suggesting that ion selectivity in force-distance measurements are related to excluded volume effects and not to electrostatic or chemical interactions between ions and AFM tip. The comparison also revealed that at distances greater than 1 nm the system maintains overall electroneutrality between the AFM tip and sample, while at smaller distances other forces (e.g., van der waals interactions) dominate and electroneutrality is no longer maintained. PMID:27587276

  19. Fundamental aspects of electric double layer force-distance measurements at liquid-solid interfaces using atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Black, Jennifer M.; Zhu, Mengyang; Zhang, Pengfei; Unocic, Raymond R.; Guo, Daqiang; Okatan, M. Baris; Dai, Sheng; Cummings, Peter T.; Kalinin, Sergei V.; Feng, Guang; Balke, Nina

    2016-09-01

    Atomic force microscopy (AFM) force-distance measurements are used to investigate the layered ion structure of Ionic Liquids (ILs) at the mica surface. The effects of various tip properties on the measured force profiles are examined and reveal that the measured ion position is independent of tip properties, while the tip radius affects the forces required to break through the ion layers as well as the adhesion force. Force data is collected for different ILs and directly compared with interfacial ion density profiles predicted by molecular dynamics. Through this comparison it is concluded that AFM force measurements are sensitive to the position of the ion with the larger volume and mass, suggesting that ion selectivity in force-distance measurements are related to excluded volume effects and not to electrostatic or chemical interactions between ions and AFM tip. The comparison also revealed that at distances greater than 1 nm the system maintains overall electroneutrality between the AFM tip and sample, while at smaller distances other forces (e.g., van der waals interactions) dominate and electroneutrality is no longer maintained.

  20. Fundamental Studies of Friction, Lubrication, and Wear by Atomic Force Microscopy

    DTIC Science & Technology

    1993-04-14

    34 If fiber interferometer is used RESULTS "*Present address: Department of Chemical Physics, Weirmann Institute The t-p- surface force normal to the...small as 30 nm. The normal force between these tips and diamond (100) and (Il 1) surfaces agrees with calculated dispersion forces . The frictional... force variation on the (100) surface are tentatively associated with a reconstructed geometry convoluted over an asymmetric tip shape, while the (11

  1. Potential of mean force in confined colloids: integral equations with fundamental measure bridge functions.

    PubMed

    Ayadim, A; Malherbe, J G; Amokrane, S

    2005-06-15

    The potential of mean force for uncharged macroparticles suspended in a fluid confined by a wall or a narrow pore is computed for solvent-wall and solvent-macroparticle interactions with attractive forces. Bridge functions taken from Rosenfeld's density-functional theory are used in the reference hypernetted chain closure of the Ornstein-Zernike integral equations. The quality of this closure is assessed by comparison with simulation. As an illustration, the role of solvation forces is investigated. When the "residual" attractive tails are given a range appropriate to "hard sphere-like" colloids, the unexpected role of solvation forces previously observed in bulk colloids is confirmed in the confinement situation.

  2. Quartic force field predictions of the fundamental vibrational frequencies and spectroscopic constants of the cations HOCO+ and DOCO+

    NASA Astrophysics Data System (ADS)

    Fortenberry, Ryan C.; Huang, Xinchuan; Francisco, Joseph S.; Crawford, T. Daniel; Lee, Timothy J.

    2012-06-01

    Only one fundamental vibrational frequency of protonated carbon dioxide (HOCO+) has been experimentally observed in the gas phase: the ν1 O-H stretch. Utilizing quartic force fields defined from CCSD(T)/aug-cc-pVXZ (X = T,Q,5) complete basis set limit extrapolated energies modified to include corrections for core correlation and scalar relativistic effects coupled to vibrational perturbation theory and vibrational configuration interaction computations, we are predicting the full set of gas phase fundamental vibrational frequencies of HOCO+. Our prediction of ν1 is within less than 1 cm-1 of the experimental value. Our computations also include predictions of the gas phase fundamental vibrational frequencies of the deuterated form of the cation, DOCO+. Additionally, other spectroscopic constants for both systems are reported as part of this study, and a search for a cis-HOCO+ minimum found no such stationary point on the potential surface indicating that only the trans isomer is stable.

  3. Supramolecular Polymers with Multiple Types of Binding Motifs: From Fundamental Studies to Multifunctional Materials

    DTIC Science & Technology

    2015-07-10

    the goal of preparing multi-responsive polymer actuators, we have incorporated liquid crystalline metal-binding Bip monomers into polymeric networks...SECURITY CLASSIFICATION OF: This research project is focused on the development and investigation of a new class of multi-stimuli-responsive polymers ...studies metallo and hydrogen bonded supramolecular polymers that exhibit defect healing characteristics and multi- 1. REPORT DATE (DD-MM-YYYY) 4

  4. Force spectroscopy of biomolecular folding and binding: theory meets experiment

    NASA Astrophysics Data System (ADS)

    Dudko, Olga

    2015-03-01

    Conformational transitions in biological macromolecules usually serve as the mechanism that brings biomolecules into their working shape and enables their biological function. Single-molecule force spectroscopy probes conformational transitions by applying force to individual macromolecules and recording their response, or ``mechanical fingerprints,'' in the form of force-extension curves. However, how can we decode these fingerprints so that they reveal the kinetic barriers and the associated timescales of a biological process? I will present an analytical theory of the mechanical fingerprints of macromolecules. The theory is suitable for decoding such fingerprints to extract the barriers and timescales. The application of the theory will be illustrated through recent studies on protein-DNA interactions and the receptor-ligand complexes involved in blood clot formation.

  5. Protonated Nitrous Oxide, NNOH(+): Fundamental Vibrational Frequencies and Spectroscopic Constants from Quartic Force Fields

    NASA Technical Reports Server (NTRS)

    Huang, Xinchuan; Fortenberry, Ryan C.; Lee, Timothy J.

    2013-01-01

    The interstellar presence of protonated nitrous oxide has been suspected for some time. Using established high-accuracy quantum chemical techniques, spectroscopic constants and fundamental vibrational frequencies are provided for the lower energy O-protonated isomer of this cation and its deuterated isotopologue. The vibrationally-averaged B0 and C0 rotational constants are within 6 MHz of their experimental values and the D(subJ) quartic distortion constants agree with experiment to within 3%. The known gas phase O-H stretch of NNOH(+) is 3330.91 cm(exp-1), and the vibrational configuration interaction computed result is 3330.9 cm(exp-1). Other spectroscopic constants are also provided, as are the rest of the fundamental vibrational frequencies for NNOH(+) and its deuterated isotopologue. This high-accuracy data should serve to better inform future observational or experimental studies of the rovibrational bands of protonated nitrous oxide in the ISM and the laboratory.

  6. Enhanced optical magnetism for reversed optical binding forces between silicon nanoparticles in the visible region.

    PubMed

    Yano, Taka-Aki; Tsuchimoto, Yuta; Zaccaria, Remo Proietti; Toma, Andrea; Portela, Alejandro; Hara, Masahiko

    2017-01-09

    We perform a comprehensive numerical analysis on the optical binding forces of a multiple-resonant silicon nanodimer induced by the normal illumination of a plane wave in the visible region. The silicon nanodimer provides either repulsive or attractive forces in water while providing only attractive forces in air. The enhancement of the magnetic dipole mode is attributed to the generation of repulsive forces. The sign (attractive/repulsive) and the amplitude of the optical forces are controlled by incident polarization and separation distance between the silicon nanoparticles. These optomechanical effects demonstrate a key step toward the optical sorting and assembly of silicon nanoparticles.

  7. Carbonic anhydrase binding site parameterization in OPLS-AA force field.

    PubMed

    Bernadat, Guillaume; Supuran, Claudiu T; Iorga, Bogdan I

    2013-03-15

    The parameterization of carbonic anhydrase binding site in OPLS-AA force field was performed using quantum chemistry calculations. Both OH2 and OH(-) forms of the binding site were considered, showing important differences in terms of atomic partial charges. Three different parameterization protocols were used, and the results obtained highlighted the importance of including an extended binding site in the charge calculation. The force field parameters were subsequently validated using standard molecular dynamics simulations. The results presented in this work should greatly facilitate the use of molecular dynamics simulations for studying the carbonic anhydrase, and more generally, the metallo-enzymes.

  8. Revised periodic boundary conditions: Fundamentals, electrostatics, and the tight-binding approximation

    NASA Astrophysics Data System (ADS)

    Kit, Oleg O.; Pastewka, Lars; Koskinen, Pekka

    2011-10-01

    Many nanostructures today are low-dimensional and flimsy, and therefore get easily distorted. Distortion-induced symmetry breaking makes conventional, translation-periodic simulations invalid, which has triggered developments for new methods. Revised periodic boundary conditions (RPBC) is a simple method that enables simulations of complex material distortions, either classically or quantum mechanically. The mathematical details of this easy-to-implement approach, however, have not been discussed before. Therefore, in this paper, we summarize the underlying theory, present the practical details of RPBC, especially related to a nonorthogonal tight-binding formulation, discuss selected features, electrostatics in particular, and suggest some examples of usage. We hope this article can give more insight into RPBC, and it will help and inspire new software implementations capable of exploring the physics and chemistry of distorted nanomaterials.

  9. Toward Improved Force-Field Accuracy through Sensitivity Analysis of Host-Guest Binding Thermodynamics

    PubMed Central

    Yin, Jian; Fenley, Andrew T.; Henriksen, Niel M.; Gilson, Michael K.

    2015-01-01

    Improving the capability of atomistic computer models to predict the thermodynamics of noncovalent binding is critical for successful structure-based drug design, and the accuracy of such calculations remains limited by non-optimal force field parameters. Ideally, one would incorporate protein-ligand affinity data into force field parametrization, but this would be inefficient and costly. We now demonstrate that sensitivity analysis can be used to efficiently tune Lennard-Jones parameters of aqueous host-guest systems for increasingly accurate calculations of binding enthalpy. These results highlight the promise of a comprehensive use of calorimetric host-guest binding data, along with existing validation data sets, to improve force field parameters for the simulation of noncovalent binding, with the ultimate goal of making protein-ligand modeling more accurate and hence speeding drug discovery. PMID:26181208

  10. Force-dependent conformational switch of α-catenin controls vinculin binding

    NASA Astrophysics Data System (ADS)

    Yao, Mingxi; Qiu, Wu; Liu, Ruchuan; Efremov, Artem K.; Cong, Peiwen; Seddiki, Rima; Payre, Manon; Lim, Chwee Teck; Ladoux, Benoit; Mège, René-Marc; Yan, Jie

    2014-07-01

    Force sensing at cadherin-mediated adhesions is critical for their proper function. α-Catenin, which links cadherins to actomyosin, has a crucial role in this mechanosensing process. It has been hypothesized that force promotes vinculin binding, although this has never been demonstrated. X-ray structure further suggests that α-catenin adopts a stable auto-inhibitory conformation that makes the vinculin-binding site inaccessible. Here, by stretching single α-catenin molecules using magnetic tweezers, we show that the subdomains MI vinculin-binding domain (VBD) to MIII unfold in three characteristic steps: a reversible step at ~5 pN and two non-equilibrium steps at 10-15 pN. 5 pN unfolding forces trigger vinculin binding to the MI domain in a 1:1 ratio with nanomolar affinity, preventing MI domain refolding after force is released. Our findings demonstrate that physiologically relevant forces reversibly unfurl α-catenin, activating vinculin binding, which then stabilizes α-catenin in its open conformation, transforming force into a sustainable biochemical signal.

  11. Going Lean: Impending Money Woes Force Tough Choices, Forecast Fundamental Shift in Community College Funding

    ERIC Educational Resources Information Center

    Joch, Alan

    2011-01-01

    The numbers were already bad, and they keep getting worse, for the Dallas County Community College District (DCCCD). Given the weak economy, administrators planned for a 5 percent reduction in state funding in the 2010-11 academic year. The actual reduction ballooned to more than 7.5 percent, an additional $13 million that DCCCD would be forced to…

  12. Going Lean: Impending Money Woes Force Tough Choices, Forecast Fundamental Shift in Community College Funding

    ERIC Educational Resources Information Center

    Joch, Alan

    2011-01-01

    The numbers were already bad, and they keep getting worse, for the Dallas County Community College District (DCCCD). Given the weak economy, administrators planned for a 5 percent reduction in state funding in the 2010-11 academic year. The actual reduction ballooned to more than 7.5 percent, an additional $13 million that DCCCD would be forced to…

  13. Investigating the binding behaviour of two avidin-based testosterone binders using molecular recognition force spectroscopy.

    PubMed

    Rangl, Martina; Leitner, Michael; Riihimäki, Tiina; Lehtonen, Soili; Hytönen, Vesa P; Gruber, Hermann J; Kulomaa, Markku; Hinterdorfer, Peter; Ebner, Andreas

    2014-02-01

    Molecular recognition force spectroscopy, a biosensing atomic force microscopy technique allows to characterise the dissociation of ligand-receptor complexes at the molecular level. Here, we used molecular recognition force spectroscopy to study the binding capability of recently developed testosterone binders. The two avidin-based proteins called sbAvd-1 and sbAvd-2 are expected to bind both testosterone and biotin but differ in their binding behaviour towards these ligands. To explore the ligand binding and dissociation energy landscape of these proteins, we tethered biotin or testosterone to the atomic force microscopy probe while the testosterone-binding protein was immobilized on the surface. Repeated formation and rupture of the ligand-receptor complex at different pulling velocities allowed determination of the loading rate dependence of the complex-rupturing force. In this way, we obtained the molecular dissociation rate (k(off)) and energy landscape distances (x(β)) of the four possible complexes: sbAvd-1-biotin, sbAvd-1-testosterone, sbAvd-2-biotin and sbAvd-2-testosterone. It was found that the kinetic off-rates for both proteins and both ligands are similar. In contrast, the x(β) values, as well as the probability of complex formations, varied considerably. In addition, competitive binding experiments with biotin and testosterone in solution differ significantly for the two testosterone-binding proteins, implying a decreased cross-reactivity of sbAvd-2. Unravelling the binding behaviour of the investigated testosterone-binding proteins is expected to improve their usability for possible sensing applications.

  14. Assembly of reconfigurable one-dimensional colloidal superlattices due to a synergy of fundamental nanoscale forces

    PubMed Central

    Young, Kaylie L.; Jones, Matthew R.; Zhang, Jian; Macfarlane, Robert J.; Esquivel-Sirvent, Raul; Nap, Rikkert J.; Wu, Jinsong; Schatz, George C.; Lee, Byeongdu; Mirkin, Chad A.

    2012-01-01

    We report that triangular gold nanoprisms in the presence of attractive depletion forces and repulsive electrostatic forces assemble into equilibrium one-dimensional lamellar crystals in solution with interparticle spacings greater than four times the thickness of the nanoprisms. Experimental and theoretical studies reveal that the anomalously large d spacings of the lamellar superlattices are due to a balance between depletion and electrostatic interactions, both of which arise from the surfactant cetyltrimethylammonium bromide. The effects of surfactant concentration, temperature, ionic strength of the solution, and prism edge length on the lattice parameters have been investigated and provide a variety of tools for in situ modulation of these colloidal superstructures. Additionally, we demonstrate a purification procedure based on our observations that can be used to efficiently separate triangular nanoprisms from spherical nanoparticles formed concomitantly during their synthesis. PMID:22308436

  15. Binding Force Dynamics of Streptococcus mutans–glucosyltransferase B to Candida albicans

    PubMed Central

    Hwang, G.; Marsh, G.; Gao, L.; Waugh, R.

    2015-01-01

    Candida albicans cells are often detected with Streptococcus mutans in plaque biofilms from children affected with early childhood caries. The coadhesion between these 2 organisms appears to be largely mediated by the S. mutans–derived exoenzyme glucosyltransferase B (GtfB); GtfB readily binds to C. albicans cells in an active form, producing glucans locally that provide enhanced binding sites for S. mutans. However, knowledge is limited about the mechanisms by which the bacterial exoenzyme binds to and functions on the fungal surface to promote this unique cross-kingdom interaction. In this study, we use atomic force microscopy to understand the strength and binding dynamics modulating GtfB–C. albicans adhesive interactions in situ. Single-molecule force spectroscopy with GtfB-functionalized atomic force microscopy tips demonstrated that the enzyme binds with remarkable strength to the C. albicans cell surface (~2 nN) and showed a low dissociation rate, suggesting a highly stable bond. Strikingly, the binding strength of GtfB to the C. albicans surface was ~2.5-fold higher and the binding stability, ~20 times higher, as compared with the enzyme adhesion to S. mutans. Furthermore, adhesion force maps showed an intriguing pattern of GtfB binding. GtfB adhered heterogeneously on the surface of C. albicans, showing a higher frequency of adhesion failure but large sections of remarkably strong binding forces, suggesting the presence of GtfB binding domains unevenly distributed on the fungal surface. In contrast, GtfB bound uniformly across the S. mutans cell surface with less adhesion failure and a narrower range of binding forces (vs. the C. albicans surface). The data provide the first insights into the mechanisms underlying the adhesive and mechanical properties governing GtfB interactions with C. albicans. The strong and highly stable GtfB binding to C. albicans could explain, at least in part, why this bacterially derived exoenzyme effectively modulates this

  16. Calculating binding free energies of host-guest systems using the AMOEBA polarizable force field.

    PubMed

    Bell, David R; Qi, Rui; Jing, Zhifeng; Xiang, Jin Yu; Mejias, Christopher; Schnieders, Michael J; Ponder, Jay W; Ren, Pengyu

    2016-11-09

    Molecular recognition is of paramount interest in many applications. Here we investigate a series of host-guest systems previously used in the SAMPL4 blind challenge by using molecular simulations and the AMOEBA polarizable force field. The free energy results computed by Bennett's acceptance ratio (BAR) method using the AMOEBA polarizable force field ranked favorably among the entries submitted to the SAMPL4 host-guest competition [Muddana, et al., J. Comput.-Aided Mol. Des., 2014, 28, 305-317]. In this work we conduct an in-depth analysis of the AMOEBA force field host-guest binding thermodynamics by using both BAR and the orthogonal space random walk (OSRW) methods. The binding entropy-enthalpy contributions are analyzed for each host-guest system. For systems of inordinate binding entropy-enthalpy values, we further examine the hydrogen bonding patterns and configurational entropy contribution. The binding mechanism of this series of host-guest systems varies from ligand to ligand, driven by enthalpy and/or entropy changes. Convergence of BAR and OSRW binding free energy methods is discussed. Ultimately, this work illustrates the value of molecular modelling and advanced force fields for the exploration and interpretation of binding thermodynamics.

  17. How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism

    PubMed Central

    Hytönen, Vesa P; Vogel, Viola

    2008-01-01

    Upon cell adhesion, talin physically couples the cytoskeleton via integrins to the extracellular matrix, and subsequent vinculin recruitment is enhanced by locally applied tensile force. Since the vinculin binding (VB) sites are buried in the talin rod under equilibrium conditions, the structural mechanism of how vinculin binding to talin is force-activated remains unknown. Taken together with experimental data, a biphasic vinculin binding model, as derived from steered molecular dynamics, provides high resolution structural insights how tensile mechanical force applied to the talin rod fragment (residues 486–889 constituting helices H1–H12) might activate the VB sites. Fragmentation of the rod into three helix subbundles is prerequisite to the sequential exposure of VB helices to water. Finally, unfolding of a VB helix into a completely stretched polypeptide might inhibit further binding of vinculin. The first events in fracturing the H1–H12 rods of talin1 and talin2 in subbundles are similar. The proposed force-activated α-helix swapping mechanism by which vinculin binding sites in talin rods are exposed works distinctly different from that of other force-activated bonds, including catch bonds. PMID:18282082

  18. Noncontact Atomic Force Microscopy: An Emerging Tool for Fundamental Catalysis Research.

    PubMed

    Altman, Eric I; Baykara, Mehmet Z; Schwarz, Udo D

    2015-09-15

    Although atomic force microscopy (AFM) was rapidly adopted as a routine surface imaging apparatus after its introduction in 1986, it has not been widely used in catalysis research. The reason is that common AFM operating modes do not provide the atomic resolution required to follow catalytic processes; rather the more complex noncontact (NC) mode is needed. Thus, scanning tunneling microscopy has been the principal tool for atomic scale catalysis research. In this Account, recent developments in NC-AFM will be presented that offer significant advantages for gaining a complete atomic level view of catalysis. The main advantage of NC-AFM is that the image contrast is due to the very short-range chemical forces that are of interest in catalysis. This motivated our development of 3D-AFM, a method that yields quantitative atomic resolution images of the potential energy surfaces that govern how molecules approach, stick, diffuse, and rebound from surfaces. A variation of 3D-AFM allows the determination of forces required to push atoms and molecules on surfaces, from which diffusion barriers and variations in adsorption strength may be obtained. Pushing molecules towards each other provides access to intermolecular interaction between reaction partners. Following reaction, NC-AFM with CO-terminated tips yields textbook images of intramolecular structure that can be used to identify reaction intermediates and products. Because NC-AFM and STM contrast mechanisms are distinct, combining the two methods can produce unique insight. It is demonstrated for surface-oxidized Cu(100) that simultaneous 3D-AFM/STM yields resolution of both the Cu and O atoms. Moreover, atomic defects in the Cu sublattice lead to variations in the reactivity of the neighboring O atoms. It is shown that NC-AFM also allows a straightforward imaging of work function variations which has been used to identify defect charge states on catalytic surfaces and to map charge transfer within an individual

  19. The effect of cigarette smoke extract on thrombomodulin-thrombin binding: an atomic force microscopy study.

    PubMed

    Wei, Yujie; Zhang, Xuejie; Xu, Li; Yi, Shaoqiong; Li, Yi; Fang, Xiaohong; Liu, Huiliang

    2012-10-01

    Cigarette smoking is a well-known risk factor for cardiovascular disease. Smoking can cause vascular endothelial dysfunction and consequently trigger haemostatic activation and thrombosis. However, the mechanism of how smoking promotes thrombosis is not fully understood. Thrombosis is associated with the imbalance of the coagulant system due to endothelial dysfunction. As a vital anticoagulation cofactor, thrombomodulin (TM) located on the endothelial cell surface is able to regulate intravascular coagulation by binding to thrombin, and the binding results in thrombosis inhibition. This work focused on the effects of cigarette smoke extract (CSE) on TM-thrombin binding by atomic force microscopy (AFM) based single-molecule force spectroscopy. The results from both in vitro and live-cell experiments indicated that CSE could notably reduce the binding probability of TM and thrombin. This study provided a new approach and new evidence for studying the mechanism of thrombosis triggered by cigarette smoking.

  20. Effects of dielectric charging on fundamental forces and reliability in capacitive microelectromechanical systems radio frequency switch contacts

    NASA Astrophysics Data System (ADS)

    Patton, Steven T.; Zabinski, Jeffrey S.

    2006-05-01

    Microelectromechanical systems (MEMS) radio frequency switches hold great promise in a myriad of commercial, aerospace, and military applications. In particular, capacitive-type switches with metal-to-dielectric contacts (typically gold-on-silicon nitride) are suitable for high frequency (>=10 GHz) applications. However, the devices are known to be unstable in their performance due to parasitic dielectric charging. Although several authors have previously reported the switch failure along with shifts in pull-down and release voltages due to charging, there is some disagreement and lack of understanding among the various reports. This study uses a switch simulator capable of measuring microscale electrostatic and adhesive forces to investigate charging and its effect on reliability and fundamental forces acting within MEMS capacitive switches. An important advantage of the switch simulator is that it can be actuated with or without a bias voltage. Electrostatic force and dielectric charging increased as surfaces were worn smooth by cycling. This is because the surface smoothening decreases separation and increases the electric field strength inside the dielectric. A simple analytical model was developed using electromagnetic theory for the electrostatic force in terms of bias voltage and the areal density of parasitic charge. Using the model and experimental data, it was determined that ``charging'' (net charge is zero) with the same polarity as the bias voltage resulted in reduced electrostatic force (under bias voltage) when a worn-in switch was actuated repeatedly at constant bias voltage >=40 V. Small electrostatic force under bias voltage can explain failure in the ``up'' position (failure to actuate and self-release). Reversing the polarity of the bias voltage between actuations prevented charge buildup and doubled the electrostatic force, which can help explain the effectiveness of bipolar actuation. The charging time constant for parasitic dielectric charge

  1. Resolving dual binding conformations of cellulosome cohesin-dockerin complexes using single-molecule force spectroscopy.

    PubMed

    Jobst, Markus A; Milles, Lukas F; Schoeler, Constantin; Ott, Wolfgang; Fried, Daniel B; Bayer, Edward A; Gaub, Hermann E; Nash, Michael A

    2015-10-31

    Receptor-ligand pairs are ordinarily thought to interact through a lock and key mechanism, where a unique molecular conformation is formed upon binding. Contrary to this paradigm, cellulosomal cohesin-dockerin (Coh-Doc) pairs are believed to interact through redundant dual binding modes consisting of two distinct conformations. Here, we combined site-directed mutagenesis and single-molecule force spectroscopy (SMFS) to study the unbinding of Coh:Doc complexes under force. We designed Doc mutations to knock out each binding mode, and compared their single-molecule unfolding patterns as they were dissociated from Coh using an atomic force microscope (AFM) cantilever. Although average bulk measurements were unable to resolve the differences in Doc binding modes due to the similarity of the interactions, with a single-molecule method we were able to discriminate the two modes based on distinct differences in their mechanical properties. We conclude that under native conditions wild-type Doc from Clostridium thermocellum exocellulase Cel48S populates both binding modes with similar probabilities. Given the vast number of Doc domains with predicted dual binding modes across multiple bacterial species, our approach opens up new possibilities for understanding assembly and catalytic properties of a broad range of multi-enzyme complexes.

  2. Evidence for a force-dependent component of calcium binding to cardiac troponin C

    SciTech Connect

    Hofmann, P.A.; Fuchs, F. )

    1987-10-01

    The duration of activation in cardiac muscle is a function of the load. On the basis of studies of Ca{sup 2+} transients in muscles subjected to quick release, it has been suggested that force or shortening-mediated changes in Ca{sup 2+}-troponin C affinity may provide a mechanism for a contraction-activation feedback. This study was designed to test the hypothesis that the formation of force-generating complexes between actin and myosin enhances the affinity of cardiac troponin C for Ca{sup 2+}. This was done by first establishing the normal relationship between Ca{sup 2+} binding and force development in chemically skinned bovine ventricular muscle bundles and then comparing the Ca{sup 2+}-saturation curves obtained with relaxed and contracting muscle bundles. A double isotope technique was used to measure Ca{sup 2+} binding during ATP-induced force generation and during relaxation maintained by the phosphate analogue vanadate. The results showed that the generation of force was associated with an enhanced binding of Ca{sup 2+} to the Ca{sup 2+}-specific regulatory site of cardiac troponin C. These data provide direct evidence that feedback between force and activation in the heart may be mediated by the Ca{sup 2+}-regulatory site of troponin C.

  3. Interplay of Multiple Interaction Forces: Binding of Norfloxacin to Human Serum Albumin.

    PubMed

    Paul, Bijan K; Ghosh, Narayani; Mukherjee, Saptarshi

    2015-10-15

    Herein, the binding interaction of a potential chemotherapeutic antibacterial drug norfloxacin (NOF) with a serum transport protein, human serum albumin (HSA), is investigated. The prototropic transformation of the drug (NOF) is found to be remarkably modified following interaction with the protein as manifested through significant modulations of the photophysics of the drug. The predominant zwitterionic form of NOF in aqueous buffer phase undergoes transformation to the cationic form within the protein-encapsulated state. This implies the possible role of electrostatic interaction force in NOF-HSA binding. This postulate is further substantiated from the effect of ionic strength on the interaction process. To this end, the detailed study of the thermodynamics of the drug-protein interaction process from isothermal titration calorimetric (ITC) experiments is found to unfold the signature of electrostatic as well as hydrophobic interaction forces underlying the binding process. Thus, interplay of more than one interaction forces is argued to be responsible for the overall drug-protein binding. The ITC results reveal an important finding in terms of enthalpy-entropy compensation (EEC) characterizing the NOF-HSA binding. The effect of drug-binding on the native protein conformation has also been evaluated from circular dichroism (CD) spectroscopy which unveils partial rupture of the protein secondary structure. In conjunction to this, the functionality of the native protein (in terms of esterase-like activity) is found to be lowered as a result of binding with NOF. The AutoDock-based docking simulation unravels the probable binding location of NOF within the hydrophilic subdomain IA of HSA. The present program also focuses on exploring the dynamical aspects of the drug-protein interaction scenario. The rotational-relaxation dynamics of the protein-bound drug reveals the not-so-common "dip-and-rise" pattern.

  4. Polypyrimidine tract binding protein homologs from Arabidopsis are key regulators of alternative splicing with implications in fundamental developmental processes.

    PubMed

    Rühl, Christina; Stauffer, Eva; Kahles, André; Wagner, Gabriele; Drechsel, Gabriele; Rätsch, Gunnar; Wachter, Andreas

    2012-11-01

    Alternative splicing (AS) generates transcript variants by variable exon/intron definition and massively expands transcriptome diversity. Changes in AS patterns have been found to be linked to manifold biological processes, yet fundamental aspects, such as the regulation of AS and its functional implications, largely remain to be addressed. In this work, widespread AS regulation by Arabidopsis thaliana Polypyrimidine tract binding protein homologs (PTBs) was revealed. In total, 452 AS events derived from 307 distinct genes were found to be responsive to the levels of the splicing factors PTB1 and PTB2, which predominantly triggered splicing of regulated introns, inclusion of cassette exons, and usage of upstream 5' splice sites. By contrast, no major AS regulatory function of the distantly related PTB3 was found. Dependent on their position within the mRNA, PTB-regulated events can both modify the untranslated regions and give rise to alternative protein products. We find that PTB-mediated AS events are connected to diverse biological processes, and the functional implications of selected instances were further elucidated. Specifically, PTB misexpression changes AS of PHYTOCHROME INTERACTING FACTOR6, coinciding with altered rates of abscisic acid-dependent seed germination. Furthermore, AS patterns as well as the expression of key flowering regulators were massively changed in a PTB1/2 level-dependent manner.

  5. Electrostatic binding and hydrophobic collapse of peptide-nucleic acid aggregates quantified using force spectroscopy.

    PubMed

    Camunas-Soler, Joan; Frutos, Silvia; Bizarro, Cristiano V; de Lorenzo, Sara; Fuentes-Perez, Maria Eugenia; Ramsch, Roland; Vilchez, Susana; Solans, Conxita; Moreno-Herrero, Fernando; Albericio, Fernando; Eritja, Ramón; Giralt, Ernest; Dev, Sukhendu B; Ritort, Felix

    2013-06-25

    Knowledge of the mechanisms of interaction between self-aggregating peptides and nucleic acids or other polyanions is key to the understanding of many aggregation processes underlying several human diseases (e.g., Alzheimer's and Parkinson's diseases). Determining the affinity and kinetic steps of such interactions is challenging due to the competition between hydrophobic self-aggregating forces and electrostatic binding forces. Kahalalide F (KF) is an anticancer hydrophobic peptide that contains a single positive charge that confers strong aggregative properties with polyanions. This makes KF an ideal model to elucidate the mechanisms by which self-aggregation competes with binding to a strongly charged polyelectrolyte such as DNA. We use optical tweezers to apply mechanical forces to single DNA molecules and show that KF and DNA interact in a two-step kinetic process promoted by the electrostatic binding of DNA to the aggregate surface followed by the stabilization of the complex due to hydrophobic interactions. From the measured pulling curves we determine the spectrum of binding affinities, kinetic barriers, and lengths of DNA segments sequestered within the KF-DNA complex. We find there is a capture distance beyond which the complex collapses into compact aggregates stabilized by strong hydrophobic forces and discuss how the bending rigidity of the nucleic acid affects this process. We hypothesize that within an in vivo context, the enhanced electrostatic interaction of KF due to its aggregation might mediate the binding to other polyanions. The proposed methodology should be useful to quantitatively characterize other compounds or proteins in which the formation of aggregates is relevant.

  6. A programmable DNA origami nanospring that reveals force-induced adjacent binding of myosin VI heads.

    PubMed

    Iwaki, M; Wickham, S F; Ikezaki, K; Yanagida, T; Shih, W M

    2016-12-12

    Mechanosensitive biological nanomachines such as motor proteins and ion channels regulate diverse cellular behaviour. Combined optical trapping with single-molecule fluorescence imaging provides a powerful methodology to clearly characterize the mechanoresponse, structural dynamics and stability of such nanomachines. However, this system requires complicated experimental geometry, preparation and optics, and is limited by low data-acquisition efficiency. Here we develop a programmable DNA origami nanospring that overcomes these issues. We apply our nanospring to human myosin VI, a mechanosensory motor protein, and demonstrate nanometre-precision single-molecule fluorescence imaging of the individual motor domains (heads) under force. We observe force-induced transitions of myosin VI heads from non-adjacent to adjacent binding, which correspond to adapted roles for low-load and high-load transport, respectively. Our technique extends single-molecule studies under force and clarifies the effect of force on biological processes.

  7. A programmable DNA origami nanospring that reveals force-induced adjacent binding of myosin VI heads

    PubMed Central

    Iwaki, M.; Wickham, S. F.; Ikezaki, K.; Yanagida, T.; Shih, W. M.

    2016-01-01

    Mechanosensitive biological nanomachines such as motor proteins and ion channels regulate diverse cellular behaviour. Combined optical trapping with single-molecule fluorescence imaging provides a powerful methodology to clearly characterize the mechanoresponse, structural dynamics and stability of such nanomachines. However, this system requires complicated experimental geometry, preparation and optics, and is limited by low data-acquisition efficiency. Here we develop a programmable DNA origami nanospring that overcomes these issues. We apply our nanospring to human myosin VI, a mechanosensory motor protein, and demonstrate nanometre-precision single-molecule fluorescence imaging of the individual motor domains (heads) under force. We observe force-induced transitions of myosin VI heads from non-adjacent to adjacent binding, which correspond to adapted roles for low-load and high-load transport, respectively. Our technique extends single-molecule studies under force and clarifies the effect of force on biological processes. PMID:27941751

  8. Determination of Base Binding Strength and Base Stacking Interaction of DNA Duplex Using Atomic Force Microscope

    PubMed Central

    Zhang, Tian-biao; Zhang, Chang-lin; Dong, Zai-li; Guan, Yi-fu

    2015-01-01

    As one of the most crucial properties of DNA, the structural stability and the mechanical strength are attracting a great attention. Here, we take advantage of high force resolution and high special resolution of Atom Force Microscope and investigate the mechanical force of DNA duplexes. To evaluate the base pair hydrogen bond strength and base stacking force in DNA strands, we designed two modes (unzipping and stretching) for the measurement rupture forces. Employing k-means clustering algorithm, the ruptured force are clustered and the mean values are estimated. We assessed the influence of experimental parameters and performed the force evaluation for DNA duplexes of pure dG/dC and dA/dT base pairs. The base binding strength of single dG/dC and single dA/dT were estimated to be 20.0 ± 0.2 pN and 14.0 ± 0.3 pN, respectively, and the base stacking interaction was estimated to be 2.0 ± 0.1 pN. Our results provide valuable information about the quantitative evaluation of the mechanical properties of the DNA duplexes. PMID:25772017

  9. Determination of base binding strength and base stacking interaction of DNA duplex using atomic force microscope.

    PubMed

    Zhang, Tian-biao; Zhang, Chang-lin; Dong, Zai-li; Guan, Yi-fu

    2015-03-16

    As one of the most crucial properties of DNA, the structural stability and the mechanical strength are attracting a great attention. Here, we take advantage of high force resolution and high special resolution of Atom Force Microscope and investigate the mechanical force of DNA duplexes. To evaluate the base pair hydrogen bond strength and base stacking force in DNA strands, we designed two modes (unzipping and stretching) for the measurement rupture forces. Employing k-means clustering algorithm, the ruptured force are clustered and the mean values are estimated. We assessed the influence of experimental parameters and performed the force evaluation for DNA duplexes of pure dG/dC and dA/dT base pairs. The base binding strength of single dG/dC and single dA/dT were estimated to be 20.0 ± 0.2 pN and 14.0 ± 0.3 pN, respectively, and the base stacking interaction was estimated to be 2.0 ± 0.1 pN. Our results provide valuable information about the quantitative evaluation of the mechanical properties of the DNA duplexes.

  10. Improving fundamental abilities of atomic force microscopy for investigating quantitative nanoscale physical properties of complex biological systems

    NASA Astrophysics Data System (ADS)

    Cartagena-Rivera, Alexander X.

    Measurements of local material properties of complex biological systems (e.g. live cells and viruses) in their respective physiological conditions are extremely important in the fields of biophysics, nanotechnology, material science, and nanomedicine. Yet, little is known about the structure-function-property relationship of live cells and viruses. In the case of live cells, the measurements of progressive variations in viscoelastic properties in vitro can provide insight to the mechanistic processes underpinning morphogenesis, mechano-transduction, motility, metastasis, and many more fundamental cellular processes. In the case of living viruses, the relationship between capsid structural framework and the role of the DNA molecule interaction within viruses influencing their stiffness, damping and electrostatic properties can shed light in virological processes like protein subunits assembly/dissassembly, maturation, and infection. The study of mechanics of live cells and viruses has been limited in part due to the lack of technology capable of acquiring high-resolution (nanoscale, subcellular) images of its heterogeneous material properties which vary widely depending on origin and physical interaction. The capabilities of the atomic force microscope (AFM) for measuring forces and topography with sub-nm precision have greatly contributed to research related to biophysics and biomechanics during the past two decades. AFM based biomechanical studies have the unique advantage of resolving/mapping spatially the local material properties over living cells and viruses. However, conventional AFM techniques such as force-volume and quasi-static force-distance curves are too low resolution and low speed to resolve interesting biophysical processes such as cytoskeletal dynamics for cells or assembly/dissasembly of viruses. To overcome this bottleneck, a novel atomic force microscopy mode is developed, that leads to sub-10-nm resolution and sub-15-minutes mapping of local

  11. Determining force dependence of two-dimensional receptor-ligand binding affinity by centrifugation.

    PubMed Central

    Piper, J W; Swerlick, R A; Zhu, C

    1998-01-01

    Analyses of receptor-ligand interactions are important to the understanding of cellular adhesion. Traditional methods of measuring the three-dimensional (3D) dissociation constant (Kd) require at least one of the molecular species in solution and hence cannot be directly applied to the case of cell adhesion. We describe a novel method of measuring 2D binding characteristics of receptors and ligands that are attached to surfaces and whose bonds are subjected to forces. The method utilizes a common centrifugation assay to quantify adhesion. A model for the experiment has been formulated, solved exactly, and tested carefully. The model is stochastically based and couples the bond force to the binding affinity. The method was applied to examine tumor cell adherence to recombinant E-selectin. Satisfactory agreement was found between predictions and data. The estimated zero-force 2D Kd for E-selectin/carbohydrate ligand binding was approximately 5 x 10(3) microm(-2), and the bond interaction range was subangstrom. Our results also suggest that the number of bonds mediating adhesion was small (<5). PMID:9449350

  12. Radii and Binding Energies in Oxygen Isotopes: A Challenge for Nuclear Forces.

    PubMed

    Lapoux, V; Somà, V; Barbieri, C; Hergert, H; Holt, J D; Stroberg, S R

    2016-07-29

    We present a systematic study of both nuclear radii and binding energies in (even) oxygen isotopes from the valley of stability to the neutron drip line. Both charge and matter radii are compared to state-of-the-art ab initio calculations along with binding energy systematics. Experimental matter radii are obtained through a complete evaluation of the available elastic proton scattering data of oxygen isotopes. We show that, in spite of a good reproduction of binding energies, ab initio calculations with conventional nuclear interactions derived within chiral effective field theory fail to provide a realistic description of charge and matter radii. A novel version of two- and three-nucleon forces leads to considerable improvement of the simultaneous description of the three observables for stable isotopes but shows deficiencies for the most neutron-rich systems. Thus, crucial challenges related to the development of nuclear interactions remain.

  13. Driving force of binding of amyloid {beta}-protein to lipid bilayers

    SciTech Connect

    Ikeda, Keisuke; Matsuzaki, Katsumi

    2008-06-06

    Amyloid {beta}-protein (A{beta}) has been reported to interact with a variety of lipid species, although the thermodynamic driving force remains unclear. We investigated the binding of A{beta}s labeled with the dye diethylaminocoumarin (DAC-A{beta}s) to lipid bilayers under various conditions. DAC-A{beta}-(1-40) electrostatically bound to anionic and cationic lipids at acidic and alkaline interfacial pH, respectively. However, at neutral pH, electroneutral A{beta} did not bind to these lipids, indicating little hydrophobic interaction between A{beta}-(1-40) and the acyl chains of lipids. In contrast, DAC-A{beta} associated with glycolipids even under electroneutral conditions. These results suggested that hydrogen-bonding as well as hydrophobic interactions with sugar groups of glycolipids drive the membrane binding of A{beta}-(1-40)

  14. Evaluating Force Field Performance in Thermodynamic Calculations of Cyclodextrin Host-Guest Binding: Water Models, Partial Charges, and Host Force Field Parameters.

    PubMed

    Henriksen, Niel M; Gilson, Michael K

    2017-08-04

    Computational prediction of noncovalent binding free energies with methods based on molecular mechanical force fields has become increasingly routine in drug discovery projects, where they promise to speed the discovery of small molecule ligands to bind targeted proteins with high affinity. Because the reliability of free energy methods still has significant room for improvement, new force fields, or modifications of existing ones, are regularly introduced with the aim of improving the accuracy of molecular simulations. However, comparatively little work has been done to systematically assess how well force fields perform, particularly in relation to the calculation of binding affinities. Hardware advances have made these calculations feasible, but comprehensive force field assessments for protein-ligand sized systems still remain costly. Here, we turn to cyclodextrin host-guest systems, which feature many hallmarks of protein-ligand binding interactions but are generally much more tractable due to their small size. We present absolute binding free energy and enthalpy calculations, using the attach-pull-release (APR) approach, on a set of 43 cyclodextrin-guest pairs for which experimental ITC data are available. The test set comprises both α- and β-cyclodextrin hosts binding a series of small organic guests, each with one of three functional groups: ammonium, alcohol, or carboxylate. Four water models are considered (TIP3P, TIP4Pew, SPC/E, and OPC), along with two partial charge assignment procedures (RESP and AM1-BCC) and two cyclodextrin host force fields. The results suggest a complex set of considerations when choosing a force field for biomolecular simulations. For example, some force field combinations clearly outperform others at the binding enthalpy calculations but not for the binding free energy. Additionally, a force field combination which we expected to be the worst performer gave the most accurate binding free energies - but the least accurate

  15. DNA interaction with DAPI fluorescent dye: Force spectroscopy decouples two different binding modes.

    PubMed

    Reis, L A; Rocha, M S

    2017-05-01

    In this work, we use force spectroscopy to investigate the interaction between the DAPI fluorescent dye and the λ-DNA molecule under high (174 mM) and low (34 mM) ionic strengths. Firstly, we have measured the changes on the mechanical properties (persistence and contour lengths) of the DNA-DAPI complexes as a function of the dye concentration in the sample. Then, we use recently developed models in order to connect the behavior of both mechanical properties to the physical chemistry of the interaction. Such analysis has allowed us to identify and to decouple two main binding modes, determining the relevant physicochemical (binding) parameters for each of these modes: minor groove binding, which saturates at very low DAPI concentrations ( CT ∼ 0.50 μM) and presents equilibrium binding constants of the order of ∼10(7) M(-1) for the two ionic strengths studied; and intercalation, which starts to play a significant role only after the saturation of the first mode, presenting much smaller equilibrium binding constants (∼10(5) M(-1) ).

  16. Electron binding energies and the fundamental gap of a push-pull dye in a polar environment: p-nitroaniline in liquid water

    NASA Astrophysics Data System (ADS)

    Cabral, Benedito J. C.

    2017-01-01

    The outer valence electron binding energies and the fundamental gap of p-nitroaniline (PNA) in water were determined by electron propagator theory. The adopted methodology relies on the calculation of electron binding energies by using configurations generated by Born-Oppenheimer molecular dynamics of PNA in water. The fundamental gap (Eg) of PNA in water was estimated from the first ionisation energy (IE) and the first vertical electron affinity VEA (Eg = IE-VEA). In liquid water Eg is predicted to be 6.5 ± 0.5 eV (OVGF), which is ∼3.3 eV greater than the experimental optical gap (3.25 eV).

  17. Effect of Ca2+ binding properties of troponin C on rate of skeletal muscle force redevelopment.

    PubMed

    Lee, Ryan S; Tikunova, Svetlana B; Kline, Kristopher P; Zot, Henry G; Hasbun, Javier E; Minh, Nguyen Van; Swartz, Darl R; Rall, Jack A; Davis, Jonathan P

    2010-11-01

    To investigate effects of altering troponin (Tn)C Ca(2+) binding properties on rate of skeletal muscle contraction, we generated three mutant TnCs with increased or decreased Ca(2+) sensitivities. Ca(2+) binding properties of the regulatory domain of TnC within the Tn complex were characterized by following the fluorescence of an IAANS probe attached onto the endogenous Cys(99) residue of TnC. Compared with IAANS-labeled wild-type Tn complex, V43QTnC, T70DTnC, and I60QTnC exhibited ∼1.9-fold higher, ∼5.0-fold lower, and ∼52-fold lower Ca(2+) sensitivity, respectively, and ∼3.6-fold slower, ∼5.7-fold faster, and ∼21-fold faster Ca(2+) dissociation rate (k(off)), respectively. On the basis of K(d) and k(off), these results suggest that the Ca(2+) association rate to the Tn complex decreased ∼2-fold for I60QTnC and V43QTnC. Constructs were reconstituted into single-skinned rabbit psoas fibers to assess Ca(2+) dependence of force development and rate of force redevelopment (k(tr)) at 15°C, resulting in sensitization of both force and k(tr) to Ca(2+) for V43QTnC, whereas T70DTnC and I60QTnC desensitized force and k(tr) to Ca(2+), I60QTnC causing a greater desensitization. In addition, T70DTnC and I60QTnC depressed both maximal force (F(max)) and maximal k(tr). Although V43QTnC and I60QTnC had drastically different effects on Ca(2+) binding properties of TnC, they both exhibited decreases in cooperativity of force production and elevated k(tr) at force levels <30%F(max) vs. wild-type TnC. However, at matched force levels >30%F(max) k(tr) was similar for all TnC constructs. These results suggest that the TnC mutants primarily affected k(tr) through modulating the level of thin filament activation and not by altering intrinsic cross-bridge cycling properties. To corroborate this, NEM-S1, a non-force-generating cross-bridge analog that activates the thin filament, fully recovered maximal k(tr) for I60QTnC at low Ca(2+) concentration. Thus TnC mutants with

  18. Binding.

    ERIC Educational Resources Information Center

    Rebsamen, Werner

    1981-01-01

    Categorizes contemporary methods of binding printed materials in terms of physical preservation--hand binding (archival restoration), edition binding (paperback, hardcover), publication binding (magazines), textbook binding (sidesewn), single-sheet binding (loose-leaf, mechanical), and library binding (oversewn, sidesewn). Seven references are…

  19. Quantum dot binding to DNA: single-molecule imaging with atomic force microscopy.

    PubMed

    Li, Kungang; Zhang, Wen; Chen, Yongsheng

    2013-01-01

    The interaction between nanoparticles (NPs) and DNA is of significance for both application and implication research of NPs. In this study, a single-molecule imaging technique based on atomic force microscopy (AFM) was employed to probe the NP-DNA interactions with quantum dots (QDs) as model NPs. Reproducible high-quality images of single DNA molecules in air and in liquids were acquired on mica by optimizing sample preparation conditions. Furthermore, the binding of QDs to DNA was explored using AFM. The DNA concentration was found to be a key factor influencing AFM imaging quality. In air and liquids, the optimal DNA concentration for imaging DNA molecules was approximately 2.5 and 0.25 μg/mL, and that for imaging DNA binding with QDs was 0.5 and 0.25 μg/mL, respectively. In the presence of QDs, the DNA conformation was altered with the formation of DNA condensates. Finally, the fine conformation of QD-DNA binding sites was examined to analyze the binding mechanisms. This work will benefit investigations of NP-DNA interactions and the understanding of the structure of NP-DNA bioconjugates. See accompanying article by Wang DOI: 10.1002/biot.201200309. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Biaxial Dielectrophoresis Force Spectroscopy: A Stoichiometric Approach for Examining Intermolecular Weak Binding Interactions.

    PubMed

    Park, In Soo; Kwak, Tae Joon; Lee, Gyudo; Son, Myeonggu; Choi, Jeong Woo; Choi, Seungyeop; Nam, Kihwan; Lee, Sei-Young; Chang, Woo-Jin; Eom, Kilho; Yoon, Dae Sung; Lee, Sangyoup; Bashir, Rashid; Lee, Sang Woo

    2016-04-26

    The direct quantification of weak intermolecular binding interactions is very important for many applications in biology and medicine. Techniques that can be used to investigate such interactions under a controlled environment, while varying different parameters such as loading rate, pulling direction, rupture event measurements, and the use of different functionalized probes, are still lacking. Herein, we demonstrate a biaxial dielectrophoresis force spectroscopy (BDFS) method that can be used to investigate weak unbinding events in a high-throughput manner under controlled environments and by varying the pulling direction (i.e., transverse and/or vertical axes) as well as the loading rate. With the BDFS system, we can quantitatively analyze binding interactions related to hydrogen bonding or ionic attractions between functionalized microbeads and a surface within a microfluidic device. Our BDFS system allowed for the characterization of the number of bonds involved in an interaction, bond affinity, kinetic rates, and energy barrier heights and widths from different regimes of the energy landscape.

  1. Understanding chemical binding using the Berlin function and the reaction force

    NASA Astrophysics Data System (ADS)

    Chakraborty, Debajit; Cárdenas, Carlos; Echegaray, Eleonora; Toro-Labbe, Alejandro; Ayers, Paul W.

    2012-06-01

    We use the derivative of the electron density with respect to the reaction coordinate, interpreted through the Berlin binding function, to identify portions of the reaction path where chemical bonds are breaking and forming. The results agree with the conventional description for SN2 reactions, but they are much more general and can be used to elucidate other types of reactions also. Our analysis offers support for, and detailed information about, the use of the reaction force profile to separate the reaction coordinates into intervals, each with characteristic extents of geometry change and electronic rearrangement.

  2. Pion tensor force and nuclear binding energy in the relativistic Hartree-Fock formalism

    NASA Astrophysics Data System (ADS)

    Marcos, S.; López-Quelle, M.; Niembro, R.; Savushkin, L. N.

    2014-03-01

    The binding energies of several isotopic families are studied within the relativistic Hartree-Fock approximation with the pseudovector coupling for the πN vertex, to find out a suitable strength for the effective pion tensor force (EPTF). An approximation for determining separately the contributions of the central and tensor forces generated by pion is considered. The results for heavy nuclei indicate that a realistic strength for the EPTF is smaller than a half of that appearing in the OPEP. This conclusion also applies to the results for the single-particle energies. Besides, it has been found that there is a genuine relativistic contribution of the EPTF in nuclear matter which is small but significant.

  3. Elementary Particles and Forces.

    ERIC Educational Resources Information Center

    Quigg, Chris

    1985-01-01

    Discusses subatomic particles (quarks, leptons, and others) revealed by higher accelerator energies. A connection between forces at this subatomic level has been established, and prospects are good for a description of forces that encompass binding atomic nuclei. Colors, fundamental interactions, screening, camouflage, electroweak symmetry, and…

  4. Elementary Particles and Forces.

    ERIC Educational Resources Information Center

    Quigg, Chris

    1985-01-01

    Discusses subatomic particles (quarks, leptons, and others) revealed by higher accelerator energies. A connection between forces at this subatomic level has been established, and prospects are good for a description of forces that encompass binding atomic nuclei. Colors, fundamental interactions, screening, camouflage, electroweak symmetry, and…

  5. Detection of metal binding sites on functional S-layer nanoarrays using single molecule force spectroscopy.

    PubMed

    Tang, Jilin; Ebner, Andreas; Kraxberger, Bernhard; Leitner, Michael; Hykollari, Alba; Kepplinger, Christian; Grunwald, Christian; Gruber, Hermann J; Tampé, Robert; Sleytr, Uwe B; Ilk, Nicola; Hinterdorfer, Peter

    2009-10-01

    Crystalline bacterial cell surface layers (S-layers) show the ability to recrystallize into highly regular pattern on solid supports. In this study, the genetically modified S-layer protein SbpA of Lysinibacillus sphaericus CCM 2177, carrying a hexa-histidine tag (His(6)-tag) at the C-terminus, was used to generate functionalized two-dimensional nanoarrays on a silicon surface. Atomic force microscopy (AFM) was applied to explore the topography and the functionality of the fused His(6)-tags. The accessibility of the His(6)-tags was demonstrated by in-situ anti-His-tag antibody binding to the functional S-layer array. The metal binding properties of the His(6)-tag was investigated by single molecule force microscopy. For this purpose, newly developed tris-NTA was tethered to the AFM tips via a flexible polyethylene glycol (PEG) linker. The functionalized tips showed specific interactions with S-layer containing His(6)-tags in the presence of nickel ions. Thus the His(6)-tag is located at the outer surface of the S-layer and can be used for stable but reversible attachment of functional tris-NTA derivatives.

  6. Influence of macrophage activation on their capacity to bind bacterial antigens studied with atomic force microscopy.

    PubMed

    Targosz, Marta; Labuda, Aleksander; Czuba, Pawel; Biedroń, Rafal; Strus, Magdalena; Gamian, Andrzej; Marcinkiewicz, Janusz; Szymoński, Marek

    2006-06-01

    In this work we studied interactions between bacterial antigens and receptors on the surface of macrophages using atomic force microscopy (AFM). We used two bacterial cell wall components: lipopolysaccharide (LPS) derived from gram-negative Escherichia coli and exopolysaccharide (EPS) derived from gram-positive Lactobacillus rhamnosus. Interactions between these bacterial antigens and immune cell receptors were studied in peritoneal macrophages derived from two strains of mice, CBA and C3H/J, in which the Toll-like receptor 4 (TLR4) is genetically disabled. We collected 500 force-distance curves for LPS-activated cells using an EPS-covered AFM tip, and for EPS-activated cells using an LPS-covered AFM tip. Nonactivated cells were tested as reference cells. The results show that LPS-primed macrophages decrease their ability to bind EPS. Surprisingly, EPS-activated macrophages maintain or even increase their ability to bind LPS. This may suggest that in vivo commensal enteric bacteria, such as lactobacilli, will enhance the defense potential of local macrophages against pathogens expressing LPS.

  7. Progressing single biomolecule force spectroscopy measurements for the screening of DNA binding agents

    NASA Astrophysics Data System (ADS)

    Zhang, Wenke; Barbagallo, Romina; Madden, Claire; Roberts, Clive J.; Woolford, Alison; Allen, Stephanie

    2005-10-01

    Recent studies have indicated that the force-extension properties of single molecules of double stranded (ds) DNA are sensitive to the presence of small molecule DNA binding agents, and also to their mode of binding. These observations raise the possibility of using this approach as a highly sensitive tool for the screening of such agents. However, particularly for studies employing the atomic force microscope (AFM), several non-trivial barriers hinder the progress of this approach to the non-specialist arena and hence also the full realization of this possibility. In this paper, we therefore address a series of key reproducibility and metrological issues associated with this type of measurement. Specifically, we present an improved immobilization method that covalently anchors one end (5' end) of a dual labelled (5'-thiol, 3'-biotin) p53 DNA molecule onto a gold substrate via gold-thiol chemistry, whilst the biotinylated 3' end is available for 'pick-up' using a streptavidin modified AFM tip. We also show that co-surface immobilization of DNA with 6-mercapto-1-hexanol (MCH) can also lead to a further increase the measured contour length. We demonstrate the impact of these improved protocols through the observation of the cooperative transition plateau in a DNA fragment of approximately 118 bp, a significantly smaller fragment than previously investigated. The results of a comparative study of the effects of a model minor groove binder (Hoechst 33258) and an intercalating drug (proflavine), alone, as a mixture and under different buffer conditions, are also presented.

  8. Multiple unfolding pathways of leucine binding protein (LBP) probed by single-molecule force spectroscopy (SMFS).

    PubMed

    Kotamarthi, Hema Chandra; Sharma, Riddhi; Narayan, Satya; Ray, Sayoni; Ainavarapu, Sri Rama Koti

    2013-10-02

    Experimental studies on the folding and unfolding of large multi-domain proteins are challenging, given the proteins' complex energy landscapes with multiple intermediates. Here, we report a mechanical unfolding study of a 346-residue, two-domain leucine binding protein (LBP) from the bacterial periplasm. Forced unfolding of LBP is a prerequisite for its translocation across the cytoplasmic membrane into the bacterial periplasm. During the mechanical stretching of LBP, we observe that 38% of the unfolding flux followed a two-state pathway, giving rise to a single unfolding force peak at ~70 pN with an unfolding contour length of 120 nm in constant-velocity single-molecule pulling experiments. The remaining 62% of the unfolding flux followed multiple three-state pathways, with intermediates having unfolding contour lengths in the range ~20-85 nm. These results suggest that the energy landscape of LBP is complex, with multiple intermediate states, and a large fraction of molecules go through intermediate states during the unfolding process. Furthermore, the presence of the ligand leucine increased the unfolding flux through the two-state pathway from 38% to 65%, indicating the influence of ligand binding on the energy landscape. This study suggests that unfolding through parallel pathways might be a general mechanism for the large two-domain proteins that are translocated to the bacterial periplasmic space.

  9. Binding Dynamics of Targeted Microbubbles in Response to Modulated Acoustic Radiation Force

    PubMed Central

    Wang, Shiying; Hossack, John A; Klibanov, Alexander L; Mauldin, F William

    2014-01-01

    Detection of molecular targeted microbubbles plays a foundational role in ultrasound-based molecular imaging and targeted gene or drug delivery. In this paper, an empirical model describing the binding dynamics of targeted microbubbles in response to modulated acoustic radiation forces in large vessels is presented and experimentally verified using tissue-mimicking flow phantoms. Higher flow velocity and microbubble concentration led to faster detaching rates for specifically bound microbubbles (p < 0.001). Higher time-averaged acoustic radiation force intensity led to faster attaching rates and a higher saturation level of specifically bound microbubbles (p < 0.05). The level of residual microbubble signal in targeted experiments after cessation of radiation forces was the only response parameter that was reliably different between targeted and control experiments (p < 0.05). A related parameter, the ratio of residual-to-saturated microbubble signal (Rresid), is proposed as a measurement that is independent of absolute acoustic signal magnitude and therefore able to reliably detect targeted adhesion independently of control measurements (p < 0.01). These findings suggest the possibility of enhanced detection of specifically bound microbubbles in real-time, using relatively short imaging protocols (approximately 3 min), without waiting for free microbubble clearance. PMID:24374866

  10. Fundamental study on transient bubble (slug) behavior by characterizing transient forces of solid particles in fluidized beds

    SciTech Connect

    Kono, H.O.

    1991-01-01

    The objective of this work is to recognize and interpret the signals of transient motion of bubbles (slugs) in fluidized beds by measuring and utilizing the signals of transient motion of solid particles. The two signals were measured simultaneously and also synchronized by using the TTL signal technique in the same fluidized beds. Also, a simultaneous study of video bubble image, transient force and pressure signals was initiated in a two dimensional fluidized bed. we successfully synchronized three signals so that the relationship of bubble behavior and force pressure signals can be identified and characterized. It has been found that bubble image can well be correlated to the transient force signal of solid particles under certain conditions in three dimensional fluidized beds. Accordingly, it seems that the transient force signals can significantly help understanding the transient motion of bubbles (slugs), which is important to design the fluidized beds.

  11. Fundamental study on transient bubble (slug) behavior by characterizing transient forces of solid particles in fluidized beds. 1990 Annual report

    SciTech Connect

    Kono, H.O.

    1991-01-01

    The objective of this work is to recognize and interpret the signals of transient motion of bubbles (slugs) in fluidized beds by measuring and utilizing the signals of transient motion of solid particles. The two signals were measured simultaneously and also synchronized by using the TTL signal technique in the same fluidized beds. Also, a simultaneous study of video bubble image, transient force and pressure signals was initiated in a two dimensional fluidized bed. we successfully synchronized three signals so that the relationship of bubble behavior and force pressure signals can be identified and characterized. It has been found that bubble image can well be correlated to the transient force signal of solid particles under certain conditions in three dimensional fluidized beds. Accordingly, it seems that the transient force signals can significantly help understanding the transient motion of bubbles (slugs), which is important to design the fluidized beds.

  12. The human peripheral subunit-binding domain folds rapidly while overcoming repulsive Coulomb forces

    PubMed Central

    Arbely, Eyal; Neuweiler, Hannes; Sharpe, Timothy D; Johnson, Christopher M; Fersht, Alan R

    2010-01-01

    Peripheral subunit binding domains (PSBDs) are integral parts of large multienzyme complexes involved in carbohydrate metabolism. PSBDs facilitate shuttling of prosthetic groups between different catalytic subunits. Their protein surface is characterized by a high density of positive charges required for binding to subunits within the complex. Here, we investigated folding thermodynamics and kinetics of the human PSBD (HSBD) using circular dichroism and tryptophan fluorescence experiments. HSBD was only marginally stable under physiological solvent conditions but folded within microseconds via a barrier-limited apparent two-state transition, analogous to its bacterial homologues. The high positive surface-charge density of HSBD leads to repulsive Coulomb forces that modulate protein stability and folding kinetics, and appear to even induce native-state movement. The electrostatic strain was alleviated at high solution-ionic-strength by Debye-Hückel screening. Differences in ionic-strength dependent characteristics among PSBD homologues could be explained by differences in their surface charge distributions. The findings highlight the trade-off between protein function and stability during protein evolution. PMID:20662005

  13. Directed Binding of Gliding Bacterium, Mycoplasma mobile, Shown by Detachment Force and Bond Lifetime

    PubMed Central

    Tanaka, Akihiro; Nakane, Daisuke; Mizutani, Masaki; Nishizaka, Takayuki

    2016-01-01

    ABSTRACT Mycoplasma mobile, a fish-pathogenic bacterium, features a protrusion that enables it to glide smoothly on solid surfaces at a velocity of up to 4.5 µm s−1 in the direction of the protrusion. M. mobile glides by a repeated catch-pull-release of sialylated oligosaccharides fixed on a solid surface by hundreds of 50-nm flexible “legs” sticking out from the protrusion. This gliding mechanism may be explained by a possible directed binding of each leg with sialylated oligosaccharides, by which the leg can be detached more easily forward than backward. In the present study, we used a polystyrene bead held by optical tweezers to detach a starved cell at rest from a glass surface coated with sialylated oligosaccharides and concluded that the detachment force forward is 1.6- to 1.8-fold less than that backward, which may be linked to a catch bond-like behavior of the cell. These results suggest that this directed binding has a critical role in the gliding mechanism. PMID:27353751

  14. Non-specific binding of Na+ and Mg2+ to RNA determined by force spectroscopy methods

    PubMed Central

    Bizarro, C. V.; Alemany, A.; Ritort, F.

    2012-01-01

    RNA duplex stability depends strongly on ionic conditions, and inside cells RNAs are exposed to both monovalent and multivalent ions. Despite recent advances, we do not have general methods to quantitatively account for the effects of monovalent and multivalent ions on RNA stability, and the thermodynamic parameters for secondary structure prediction have only been derived at 1M [Na+]. Here, by mechanically unfolding and folding a 20 bp RNA hairpin using optical tweezers, we study the RNA thermodynamics and kinetics at different monovalent and mixed monovalent/Mg2+ salt conditions. We measure the unfolding and folding rupture forces and apply Kramers theory to extract accurate information about the hairpin free energy landscape under tension at a wide range of ionic conditions. We obtain non-specific corrections for the free energy of formation of the RNA hairpin and measure how the distance of the transition state to the folded state changes with force and ionic strength. We experimentally validate the Tightly Bound Ion model and obtain values for the persistence length of ssRNA. Finally, we test the approximate rule by which the non-specific binding affinity of divalent cations at a given concentration is equivalent to that of monovalent cations taken at 100-fold concentration for small molecular constructs. PMID:22492710

  15. The Role of Caldesmon and its Phosphorylation by ERK on the Binding Force of Unphosphorylated Myosin to Actin

    PubMed Central

    Roman, Horia Nicolae; Zitouni, Nedjma B.; Kachmar, Linda; Benedetti, Andrea; Sobieszek, Apolinary; Lauzon, Anne-Marie

    2014-01-01

    Background Studies conducted at the whole muscle level have shown that smooth muscle can maintain tension with low ATP consumption. Whereas it is generally accepted that this property (latch-state) is a consequence of the dephosphorylation of myosin during its attachment to actin, free dephosphorylated myosin can also bind to actin and contribute to force maintenance. We investigated the role of caldesmon (CaD) in regulating the binding force of unphosphorylated tonic smooth muscle myosin to actin. Methods To measure the effect of CaD on the binding of unphosphorylated myosin to actin (in the presence of ATP), we used a single beam laser trap assay to quantify the average unbinding force (Funb) in the absence or presence of caldesmon, ERK-phosphorylated CaD, or CaD plus tropomyosin. Results Funb from unregulated actin (0.10 ± 0.01 pN) was significantly increased in the presence of CaD (0.17 ± 0.02 pN), tropomyosin (0.17 ± 0.02 pN) or both regulatory proteins (0.18 ± 0.02 pN). ERK phosphorylation of CaD significantly reduced the Funb (0.06 ± 0.01 pN). Inspection of the traces of the Funb as a function of time suggests that ERK phosphorylation of CaD decreases the binding force of myosin to actin or accelerates its detachment. Conclusions CaD enhances the binding force of unphosphorylated myosin to actin potentially contributing to the latch-state. ERK phosphorylation of CaD decreases this binding force to very low levels. General Significance This study suggests a mechanism that likely contributes to the latch-state and that explains the muscle relaxation from the latch-state. PMID:25108062

  16. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites

    PubMed Central

    Klotzsch, Enrico; Smith, Michael L.; Kubow, Kristopher E.; Muntwyler, Simon; Little, William C.; Beyeler, Felix; Gourdon, Delphine; Nelson, Bradley J.; Vogel, Viola

    2009-01-01

    Rather than maximizing toughness, as needed for silk and muscle titin fibers to withstand external impact, the much softer extracellular matrix fibers made from fibronectin (Fn) can be stretched by cell generated forces and display extraordinary extensibility. We show that Fn fibers can be extended more than 8-fold (>700% strain) before 50% of the fibers break. The Young's modulus of single fibers, given by the highly nonlinear slope of the stress-strain curve, changes orders of magnitude, up to MPa. Although many other materials plastically deform before they rupture, evidence is provided that the reversible breakage of force-bearing backbone hydrogen bonds enables the large strain. When tension is released, the nano-sized Fn domains first contract in the crowded environment of fibers within seconds into random coil conformations (molten globule states), before the force-bearing hydrogen bond networks that stabilize the domain's secondary structures are reestablished within minutes (double exponential). The exposure of cryptic binding sites on Fn type III modules increases steeply upon stretching. Thus fiber extension steadily up-regulates fiber rigidity and cryptic epitope exposure, both of which are known to differentially alter cell behavior. Finally, since stress-strain relationships cannot directly be measured in native extracellular matrix (ECM), the stress-strain curves were correlated with stretch-induced alterations of intramolecular fluorescence resonance energy transfer (FRET) obtained from trace amounts of Fn probes (mechanical strain sensors) that can be incorporated into native ECM. Physiological implications of the extraordinary extensibility of Fn fibers and contraction kinetics are discussed. PMID:19826086

  17. Oriented covalent immobilization of antibodies for measurement of intermolecular binding forces between zipper-like contact surfaces of split inteins

    PubMed Central

    Sorci, Mirco; Dassa, Bareket; Liu, Hongwei; Anand, Gaurav; Dutta, Amit K.; Pietrokovski, Shmuel; Belfort, Marlene; Belfort, Georges

    2013-01-01

    In order to measure the intermolecular binding forces between two halves (or partners) of naturally split protein splicing elements called inteins, a novel thiol-hydrazide linker was designed and used to orient immobilized antibodies specific for each partner. Activation of the surfaces was achieved in one step allowing direct force measurements of the formation of a peptide bond catalyzed by the binding of the two partners of the split intein (called protein trans-splicing). Through this binding process, a whole functional intein is formed resulting in subsequent splicing. Atomic force microscopy (AFM) was used to directly measure the split intein partner binding at 1µm/s between native (wild-type) and mixed pairs of C- and N-terminal partners of naturally occurring split inteins from three cyanobacteria. Native and mixed pairs exhibit similar binding forces within the error of the measurement technique (~52 pN). Bioinformatic sequence analysis and computational structural analysis discovered a zipper-like contact between the two partners with electrostatic and non-polar attraction between multiple aligned ion pairs and hydrophobic residues. Also, we tested the Jarzynski’s equality and demonstrated, as expected, that non-equilibrium dissipative measurements obtained here gave larger energies of interaction as compared with those for equilibrium. Hence, AFM coupled with our immobilization strategy and computational studies provides a useful analytical tool for the direct measurement of intermolecular association of split inteins and could be extended to any interacting protein pair. PMID:23679912

  18. Fundamental ecology is fundamental.

    PubMed

    Courchamp, Franck; Dunne, Jennifer A; Le Maho, Yvon; May, Robert M; Thébaud, Christophe; Hochberg, Michael E

    2015-01-01

    The primary reasons for conducting fundamental research are satisfying curiosity, acquiring knowledge, and achieving understanding. Here we develop why we believe it is essential to promote basic ecological research, despite increased impetus for ecologists to conduct and present their research in the light of potential applications. This includes the understanding of our environment, for intellectual, economical, social, and political reasons, and as a major source of innovation. We contend that we should focus less on short-term, objective-driven research and more on creativity and exploratory analyses, quantitatively estimate the benefits of fundamental research for society, and better explain the nature and importance of fundamental ecology to students, politicians, decision makers, and the general public. Our perspective and underlying arguments should also apply to evolutionary biology and to many of the other biological and physical sciences. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. DNA intercalation by ethidium bromide: A quantitative binding study using DNA stretching and force-induced melting

    NASA Astrophysics Data System (ADS)

    Williams, Mark C.; Rouzina, Ioulia

    2005-03-01

    The interactions between single DNA molecules and the non- covalent binding agent ethidium bromide are investigated using an optical tweezers instrument and the effects of this intercalator on the structure and mechanical stability of DNA molecules are quantitatively analyzed using our model of force- induced melting. The DNA force-extension cycles in the presence and absence of drug are recorded. It is found that the drug binds preferentially to double-stranded DNA and stabilizes the double helix. There is clear evidence of the force induced melting transition at low concentrations of drug, while at higher concentrations the drug is able to prevent the melting transition. The DNA contour length is obtained as a function of ligand concentration directly from the stretching curves. From this data we obtain the complete ethidium bromide dsDNA binding isotherm, which is used to find the binding constant and the binding site size of the intercalator. Out data also allows us to quantify directly the effect of ethidium bromide on the free energy of the helix-coil transition in dsDNA. This single molecule study brings new insights into the molecular mechanisms which drive drug-DNA complex formation.

  20. Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.

    PubMed

    Zhang, Yuxin; Huang, Xiaoqin; Han, Keli; Zheng, Fang; Zhan, Chang-Guo

    2016-11-25

    The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier (∼5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of ∼5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference (∼0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental KM values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Label-free detection of the aptamer binding on protein patterns using Kelvin probe force microscopy (KPFM).

    PubMed

    Gao, Pei; Cai, Yuguang

    2009-05-01

    Anti-lysozyme aptamers are found to preferentially bind to the edge of a tightly packed lysozyme pattern. Such edge-binding is due to the better accessibility and flexibility of the edge lysozyme molecules. Kelvin probe force microscopy (KPFM) was used to study the aptamer-lysozyme binding. Our results show that KPFM is capable of detecting the aptamer-protein binding down to the 30 nm scale. The surface potential of the aptamer-lysozyme complex is approximately 12 mV lower than that of the lysozyme. The surface potential images of the aptamer-bound lysozyme patterns have the characteristic shoulder steps around the pattern edge, which is much wider than that of a clean lysozyme pattern. These results demonstrate the potentials of KPFM as a label-free method for the detection of protein-DNA interactions.

  2. Fundamentally updating fundamentals.

    PubMed

    Armstrong, Gail; Barton, Amy

    2013-01-01

    Recent educational research indicates that the six competencies of the Quality and Safety Education for Nurses initiative are best introduced in early prelicensure clinical courses. Content specific to quality and safety has traditionally been covered in senior level courses. This article illustrates an effective approach to using quality and safety as an organizing framework for any prelicensure fundamentals of nursing course. Providing prelicensure students a strong foundation in quality and safety in an introductory clinical course facilitates early adoption of quality and safety competencies as core practice values. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. "Could charm (& τ) transitions be the `poor princess' providing a deeper understanding of fundamental dynamics ?" or: "Finding novel forces"

    NASA Astrophysics Data System (ADS)

    Bigi, Ikaros I.

    2015-06-01

    We know that our Universe is composed of only ˜ 4.5% "known" matter; therefore, our understanding is incomplete. This can be seen directly in the case of neutrino oscillations (without even considering potential other universes). Charm quarks have had considerable impact on our understanding of known matter, and quantum chromodynamics (QCD) is the only local quantum field theory to describe strong forces. It is possible to learn novel lessons concerning strong dynamics by measuring rates around the thresholds of [ Q¯ Q] states with Q = b, c. Furthermore, these states provide us with gateways towards new dynamics (ND), where we must transition from "accuracy" to "precision" eras. Finally, we can make connections with τ transitions and, perhaps, with dark matter. Charm dynamics acts as a bridge between the worlds of light- and heavy-flavor hadrons (namely, beauty hadrons), and finding regional asymmetries in many-body final states may prove to be a "game changer". There are several different approaches to achieving these goals: for example, experiments such as the Super Tau-Charm Factory, Super Beauty Factory, and the Super Z 0 Factory act as gatekeepers - and deeper thinking regarding symmetries.

  4. Force.

    ERIC Educational Resources Information Center

    Gamble, Reed

    1989-01-01

    Discusses pupil misconceptions concerning forces. Summarizes some of Assessment of Performance Unit's findings on meaning of (1) force, (2) force and motion in one dimension and two dimensions, and (3) Newton's second law. (YP)

  5. Force.

    ERIC Educational Resources Information Center

    Gamble, Reed

    1989-01-01

    Discusses pupil misconceptions concerning forces. Summarizes some of Assessment of Performance Unit's findings on meaning of (1) force, (2) force and motion in one dimension and two dimensions, and (3) Newton's second law. (YP)

  6. Water-mediated forces between the nucleotide binding domains generate the power stroke in an ABC transporter

    NASA Astrophysics Data System (ADS)

    Furukawa-Hagiya, Tomoka; Yoshida, Norio; Chiba, Shuntaro; Hayashi, Tomohiko; Furuta, Tadaomi; Sohma, Yoshiro; Sakurai, Minoru

    2014-11-01

    ATP binding cassette proteins shuttle a variety of molecules across cell membranes. The substrate transportation process is initiated by the ATP-driven dimerization of nucleotide binding domains (NBDs). Here, the integral-equation theory of liquids was applied to simulated NBD structures to analyze their dimerization process from the viewpoint of thermodynamics and the water-mediated interaction between the NBDs. It was found that a long-range hydration force of enthalpic origin drives the two NBDs to approach from a large separation. In the subsequent step, the water-mediated attraction of entropic origin brings about a structural adjustment between the two NBDs and their tighter contact.

  7. Prediction of SAMPL3 Host-Guest Binding Affinities: Evaluating the Accuracy of Generalized Force-Fields

    PubMed Central

    Muddana, Hari S.; Gilson, Michael K.

    2012-01-01

    We used the second-generation mining minima method (M2) to compute the binding affinities of the novel host-guest complexes in the SAMPL3 blind prediction challenge. The predictions were in poor agreement with experiment, and we conjectured that much of the error might derive from the force field, CHARMm with Vcharge charges. Repeating the calculations with other generalized force-fields led to no significant improvement, and we observed that the predicted affinities were highly sensitive to the choice of force-field. We therefore embarked on a systematic evaluation of a set of generalized force fields, based upon comparisons with PM6-DH2, a fast yet accurate semi-empirical quantum mechanics method. In particular, we compared gas-phase interaction energies and entropies for the host-guest complexes themselves, as well as for smaller chemical fragments derived from the same molecules. The mean deviations of the force field interaction energies from the quantum results were greater than 3 kcal/mol and 9 kcal/mol, for the fragments and host-guest systems respectively. We further evaluated the accuracy of force-fields for computing the vibrational entropies and found the mean errors to be greater than 4 kcal/mol. Given these errors in energy and entropy, it is not surprising in retrospect that the predicted binding affinities deviated from the experiment by several kcal/mol. These results emphasize the need for improvements in generalized force-fields and also highlight the importance of systematic evaluation of force-field parameters prior to evaluating different free-energy methods. PMID:22274835

  8. Nonlinear force dependence on optically bound micro-particle arrays in the evanescent fields of fundamental and higher order microfibre modes.

    PubMed

    Maimaiti, Aili; Holzmann, Daniela; Truong, Viet Giang; Ritsch, Helmut; Nic Chormaic, Síle

    2016-07-25

    Particles trapped in the evanescent field of an ultrathin optical fibre interact over very long distances via multiple scattering of the fibre-guided fields. In ultrathin fibres that support higher order modes, these interactions are stronger and exhibit qualitatively new behaviour due to the coupling of different fibre modes, which have different propagation wave-vectors, by the particles. Here, we study one dimensional longitudinal optical binding interactions of chains of 3 μm polystyrene spheres under the influence of the evanescent fields of a two-mode microfibre. The observation of long-range interactions, self-ordering and speed variation of particle chains reveals strong optical binding effects between the particles that can be modelled well by a tritter scattering-matrix approach. The optical forces, optical binding interactions and the velocity of bounded particle chains are calculated using this method. Results show good agreement with finite element numerical simulations. Experimental data and theoretical analysis show that higher order modes in a microfibre offer a promising method to not only obtain stable, multiple particle trapping or faster particle propulsion speeds, but that they also allow for better control over each individual trapped object in particle ensembles near the microfibre surface.

  9. Nonlinear force dependence on optically bound micro-particle arrays in the evanescent fields of fundamental and higher order microfibre modes

    PubMed Central

    Maimaiti, Aili; Holzmann, Daniela; Truong, Viet Giang; Ritsch, Helmut; Nic Chormaic, Síle

    2016-01-01

    Particles trapped in the evanescent field of an ultrathin optical fibre interact over very long distances via multiple scattering of the fibre-guided fields. In ultrathin fibres that support higher order modes, these interactions are stronger and exhibit qualitatively new behaviour due to the coupling of different fibre modes, which have different propagation wave-vectors, by the particles. Here, we study one dimensional longitudinal optical binding interactions of chains of 3 μm polystyrene spheres under the influence of the evanescent fields of a two-mode microfibre. The observation of long-range interactions, self-ordering and speed variation of particle chains reveals strong optical binding effects between the particles that can be modelled well by a tritter scattering-matrix approach. The optical forces, optical binding interactions and the velocity of bounded particle chains are calculated using this method. Results show good agreement with finite element numerical simulations. Experimental data and theoretical analysis show that higher order modes in a microfibre offer a promising method to not only obtain stable, multiple particle trapping or faster particle propulsion speeds, but that they also allow for better control over each individual trapped object in particle ensembles near the microfibre surface. PMID:27451935

  10. Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study

    SciTech Connect

    Lesoil, Charles; Nonaka, Takahiro; Sekiguchi, Hiroshi; Osada, Toshiya; Miyata, Makoto; Afrin, Rehana; Ikai, Atsushi

    2010-01-15

    Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349 kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the 'leg' of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70 pN. These findings strongly support the idea that Gli349 is the 'leg' protein of M. mobile, responsible for binding and also most probably force generation during gliding motility.

  11. Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study.

    PubMed

    Lesoil, Charles; Nonaka, Takahiro; Sekiguchi, Hiroshi; Osada, Toshiya; Miyata, Makoto; Afrin, Rehana; Ikai, Atsushi

    2010-01-15

    Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the "leg" of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70pN. These findings strongly support the idea that Gli349 is the "leg" protein of M. mobile, responsible for binding and also most probably force generation during gliding motility. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Effects of acoustic radiation force on the binding efficiency of BR55, a VEGFR2-specific ultrasound contrast agent.

    PubMed

    Frinking, Peter J A; Tardy, Isabelle; Théraulaz, Martine; Arditi, Marcel; Powers, Jeffry; Pochon, Sibylle; Tranquart, François

    2012-08-01

    This work describes an in vivo study analyzing the effect of acoustic radiation force (ARF) on the binding of BR55 VEGFR2-specific contrast-agent microbubbles in a model of prostatic adenocarcinoma in rat. A commercial ultrasound system was modified by implementing high duty-cycle 3.5-MHz center frequency ARF bursts in a scanning configuration. This enabled comparing the effects of ARF on binding in tumor and healthy tissue effectively in the same field of view. Bubble binding was established by measuring late-phase enhancement in amplitude modulation (AM) contrast-specific imaging mode (4 MHz, 150 kPa) 10 min after agent injection when the unbound bubbles were cleared from the circulation. Optimal experimental conditions, such as agent concentration (0.4 × 10(8)-1.6 × 10(8) bubbles/kg), acoustic pressure amplitude (26-51 kPa) and duty-cycle (20%-95%) of the ARF bursts, were evaluated in their ability to enhance binding in tumor without significantly increasing binding in healthy tissue. Using the optimal conditions (38 kPa peak-negative pressure, 95% duty cycle), ARF-assisted binding of BR55 improved significantly in tumor (by a factor of 7) at a lower agent dose compared with binding without ARF, and it had an insignificant effect on binding in healthy tissue. Thus, the high binding specificity of BR55 microbubbles for targeting VEGFR2 present at sites of active angiogenesis was confirmed by this study. Therefore, it is believed that based on the results obtained in this work, ultrasound molecular imaging using target-specific contrast-agent microbubbles should preferably be performed in combination with ARF. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  13. Fundamental study on transient bubble (slug) behavior by characterizing transient forces of solid particles in fluidized beds. Topical report, January 1991--June 1992

    SciTech Connect

    Kono, H.

    1992-10-01

    The objective of this work is to recognize and interpret the signals of transient motion of bubbles (slugs) in fluidized beds (METC/DOE) by measuring and utilizing the signals of transient gas phase pressure fluctuation, and also by taking the video pictures of transient motions of the bubbles and emulsion phase in fluidized beds. The two signals were measured simultaneously in a three dimensional fluidized bed. Correlation study on the voidage signal and pressure fluctuation was carried out. A domain concept was introduced and new bubble classification was suggested. A video recording approach was also developed to record the transient bubble motion in a two dimensional fluidized bed with a special consideration. This new approach enhances the understanding of bubble image and the physical meaning of transient particle forces. The fundamental mechanism of bubble flow was experimentally investigated and interesting new findings of the transient bubble flow were obtained.

  14. Low affinity binding in cis to P2Y2R mediates force-dependent integrin activation during hantavirus infection.

    PubMed

    Bondu, Virginie; Wu, Chenyu; Cao, Wenpeng; Simons, Peter C; Gillette, Jennifer; Zhu, Jieqing; Erb, Laurie; Zhang, X Frank; Buranda, Tione

    2017-08-23

    Pathogenic hantaviruses bind to the Plexin Semaphorin Integrin (PSI) domain of inactive, β3 integrins. Previous studies have implicated a cognate cis interaction between the bent conformation β5/β3 integrins and an RGD sequence in the first extracellular loop of P2Y2R (Erb et al., 2001). With single-molecule atomic force microscopy, we show a cognate interaction between (RGD)P2Y2R and an AFM tip decorated with recombinant αIIbβ3 integrins expressed on cell membranes. Mutation of the RGD sequence to RGE in the P2Y2R removes this interaction. Binding of inactivated and fluorescently labeled Sin Nombre virus (SNV) to the integrin PSI domain stimulates higher affinity for (RGD)P2Y2R on cells, as measured by an increase in the unbinding force. In CHO cells, stably expressing αIIbβ3 integrins, virus engagement at the integrin PSI domain, recapitulates physiologic activation of the integrin as indicated by staining with the activation specific mAB PAC1. The data also show that blocking of the Gα13 protein from binding to the cytoplasmic domain of the β3 integrin prevents outside-in signaling and infection. We propose that the cis interaction with P2Y2R provides allosteric resistance to the membrane-normal motion associated with the switchblade model of integrin activation, where the development of tensile force, yields physiological integrin activation. © 2017 by The American Society for Cell Biology.

  15. Binding affinity and adhesion force of organophosphate hydrolase enzyme with soil particles related to the isoelectric point of the enzyme.

    PubMed

    Islam, Shah Md Asraful; Yeasmin, Shabina; Islam, Md Saiful; Islam, Md Shariful

    2017-07-01

    The binding affinity of organophosphate hydrolase enzyme (OphB) with soil particles in relation to the isoelectric point (pI) was studied. Immobilization of OphB with soil particles was observed by confocal microscopy, Fourier transform infrared spectroscopy (FT-IR), and Atomic force microscopy (AFM). The calculated pI of OphB enzyme was increased from 8.69 to 8.89, 9.04 and 9.16 by the single, double and triple mutant of OphB enzyme, respectively through the replacement of negatively charged aspartate with positively charged histidine. Practically, the binding affinity was increased to 5.30%, 11.50%, and 16.80% for single, double and triple mutants, respectively. In contrast, enzyme activity of OphB did not change by the mutation of the enzyme. On the other hand, adhesion forces were gradually increased for wild type OphB enzyme (90 pN) to 96, 100 and 104 pN for single, double and triple mutants of OphB enzyme, respectively. There was an increasing trend of binding affinity and adhesion force by the increase of isoelectric point (pI) of OphB enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Computational model for nanocarrier binding to endothelium validated using in vivo, in vitro, and atomic force microscopy experiments.

    PubMed

    Liu, Jin; Weller, Gregory E R; Zern, Blaine; Ayyaswamy, Portonovo S; Eckmann, David M; Muzykantov, Vladimir R; Radhakrishnan, Ravi

    2010-09-21

    A computational methodology based on Metropolis Monte Carlo (MC) and the weighted histogram analysis method (WHAM) has been developed to calculate the absolute binding free energy between functionalized nanocarriers (NC) and endothelial cell (EC) surfaces. The calculated NC binding free energy landscapes yield binding affinities that agree quantitatively when directly compared against analogous measurements of specific antibody-coated NCs (100 nm in diameter) to intracellular adhesion molecule-1 (ICAM-1) expressing EC surface in in vitro cell-culture experiments. The effect of antibody surface coverage (σ(s)) of NC on binding simulations reveals a threshold σ(s) value below which the NC binding affinities reduce drastically and drop lower than that of single anti-ICAM-1 molecule to ICAM-1. The model suggests that the dominant effect of changing σ(s) around the threshold is through a change in multivalent interactions; however, the loss in translational and rotational entropies are also important. Consideration of shear flow and glycocalyx does not alter the computed threshold of antibody surface coverage. The computed trend describing the effect of σ(s) on NC binding agrees remarkably well with experimental results of in vivo targeting of the anti-ICAM-1 coated NCs to pulmonary endothelium in mice. Model results are further validated through close agreement between computed NC rupture-force distribution and measured values in atomic force microscopy (AFM) experiments. The three-way quantitative agreement with AFM, in vitro (cell-culture), and in vivo experiments establishes the mechanical, thermodynamic, and physiological consistency of our model. Hence, our computational protocol represents a quantitative and predictive approach for model-driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.

  17. Motion as manipulation: implementation of force-motion analogies by event-file binding and action planning.

    PubMed

    Fields, Chris

    2012-08-01

    Tool-improvisation analogies are structure-mapping inferences implemented, in many species, by event-file binding and pre-motor action planning. These processes act on multi-modal representations of currently perceived situations and eventuate in motor acts that can be directly evaluated for success or failure; they employ implicit representations of force-motion relations encoded by the pre-motor system and do not depend on explicit, language-like representations of relational concepts. A detailed reconstruction of the analogical reasoning steps involved in Rutherford's and Bohr's development of the first quantized-orbit model of atomic structure is used to show that human force-motion analogies can in general be implemented by these mechanisms. This event-file manipulation model of the implementation of force-motion analogies is distinguished from the standard view that structure-mapping analogies require the manipulation of explicit, language-like representations of relational concepts.

  18. Polypyrimidine Tract Binding Protein Homologs from Arabidopsis Are Key Regulators of Alternative Splicing with Implications in Fundamental Developmental Processes[W

    PubMed Central

    Rühl, Christina; Stauffer, Eva; Kahles, André; Wagner, Gabriele; Drechsel, Gabriele; Rätsch, Gunnar; Wachter, Andreas

    2012-01-01

    Alternative splicing (AS) generates transcript variants by variable exon/intron definition and massively expands transcriptome diversity. Changes in AS patterns have been found to be linked to manifold biological processes, yet fundamental aspects, such as the regulation of AS and its functional implications, largely remain to be addressed. In this work, widespread AS regulation by Arabidopsis thaliana Polypyrimidine tract binding protein homologs (PTBs) was revealed. In total, 452 AS events derived from 307 distinct genes were found to be responsive to the levels of the splicing factors PTB1 and PTB2, which predominantly triggered splicing of regulated introns, inclusion of cassette exons, and usage of upstream 5′ splice sites. By contrast, no major AS regulatory function of the distantly related PTB3 was found. Dependent on their position within the mRNA, PTB-regulated events can both modify the untranslated regions and give rise to alternative protein products. We find that PTB-mediated AS events are connected to diverse biological processes, and the functional implications of selected instances were further elucidated. Specifically, PTB misexpression changes AS of PHYTOCHROME INTERACTING FACTOR6, coinciding with altered rates of abscisic acid–dependent seed germination. Furthermore, AS patterns as well as the expression of key flowering regulators were massively changed in a PTB1/2 level-dependent manner. PMID:23192226

  19. Specific binding of the regulatory protein ExpG to promoter regions of the galactoglucan biosynthesis gene cluster of Sinorhizobium meliloti--a combined molecular biology and force spectroscopy investigation.

    PubMed

    Bartels, Frank Wilco; Baumgarth, Birgit; Anselmetti, Dario; Ros, Robert; Becker, Anke

    2003-08-01

    Specific protein-DNA interaction is fundamental for all aspects of gene transcription. We focus on a regulatory DNA-binding protein in the Gram-negative soil bacterium Sinorhizobium meliloti 2011, which is capable of fixing molecular nitrogen in a symbiotic interaction with alfalfa plants. The ExpG protein plays a central role in regulation of the biosynthesis of the exopolysaccharide galactoglucan, which promotes the establishment of symbiosis. ExpG is a transcriptional activator of exp gene expression. We investigated the molecular mechanism of binding of ExpG to three associated target sequences in the exp gene cluster with standard biochemical methods and single molecule force spectroscopy based on the atomic force microscope (AFM). Binding of ExpG to expA1, expG-expD1, and expE1 promoter fragments in a sequence specific manner was demonstrated, and a 28 bp conserved region was found. AFM force spectroscopy experiments confirmed the specific binding of ExpG to the promoter regions, with unbinding forces ranging from 50 to 165 pN in a logarithmic dependence from the loading rates of 70-79000 pN/s. Two different regimes of loading rate-dependent behaviour were identified. Thermal off-rates in the range of k(off)=(1.2+/-1.0) x 10(-3)s(-1) were derived from the lower loading rate regime for all promoter regions. In the upper loading rate regime, however, these fragments exhibited distinct differences which are attributed to the molecular binding mechanism.

  20. Force spectroscopy unravels the role of ionic strength on DNA-cisplatin interaction: Modulating the binding parameters

    NASA Astrophysics Data System (ADS)

    Oliveira, L.; Rocha, M. S.

    2017-09-01

    In the present work we have gone a step forward in the understanding of the DNA-cisplatin interaction, investigating the role of the ionic strength on the complexes formation. To achieve this task, we use optical tweezers to perform force spectroscopy on the DNA-cisplatin complexes, determining their mechanical parameters as a function of the drug concentration in the sample for three different buffers. From such measurements, we determine the binding parameters and study their behavior as a function of the ionic strength. The equilibrium binding constant decreases with the counterion concentration ([Na]) and can be used to estimate the effective net charge of cisplatin in solution. The cooperativity degree of the binding reaction, on the other hand, increases with the ionic strength, as a result of the different conformational changes induced by the drug on the double-helix when binding under different buffer conditions. Such results can be used to modulate the drug binding to DNA, by appropriately setting the ionic strength of the surrounding buffer. The conclusions drawn provide significant new insights on the complex cooperative interactions between the DNA molecule and the class of platinum-based compounds, much used in chemotherapies.

  1. Following aptamer-ricin specific binding by single molecule recognition and force spectroscopy measurements

    USDA-ARS?s Scientific Manuscript database

    The atomic force microscope (AFM) recognition and dynamic force spectroscopy (DFS) experiments provide both morphology and interaction information of the aptamer and protein, which can be used for the future study on the thermodynamics and kinetics properties of ricin-aptamer/antibody interactions. ...

  2. Molecular dynamics study of DNA binding by INT-DBD under a polarized force field.

    PubMed

    Yao, Xue X; Ji, Chang G; Xie, Dai Q; Zhang, John Z H

    2013-05-15

    The DNA binding domain of transposon Tn916 integrase (INT-DBD) binds to DNA target site by positioning the face of a three-stranded antiparallel β-sheet within the major groove. As the negatively charged DNA directly interacts with the positively charged residues (such as Arg and Lys) of INT-DBD, the electrostatic interaction is expected to play an important role in the dynamical stability of the protein-DNA binding complex. In the current work, the combined use of quantum-based polarized protein-specific charge (PPC) for protein and polarized nucleic acid-specific charge (PNC) for DNA were employed in molecular dynamics simulation to study the interaction dynamics between INT-DBD and DNA. Our study shows that the protein-DNA structure is stabilized by polarization and the calculated protein-DNA binding free energy is in good agreement with the experimental data. Furthermore, our study revealed a positive correlation between the measured binding energy difference in alanine mutation and the occupancy of the corresponding residue's hydrogen bond. This correlation relation directly relates the contribution of a specific residue to protein-DNA binding energy to the strength of the hydrogen bond formed between the specific residue and DNA.

  3. Cu(2+) affects amyloid-β (1-42) aggregation by increasing peptide-peptide binding forces.

    PubMed

    Hane, Francis; Tran, Gary; Attwood, Simon J; Leonenko, Zoya

    2013-01-01

    The link between metals, Alzheimer's disease (AD) and its implicated protein, amyloid-β (Aβ), is complex and highly studied. AD is believed to occur as a result of the misfolding and aggregation of Aβ. The dyshomeostasis of metal ions and their propensity to interact with Aβ has also been implicated in AD. In this work, we use single molecule atomic force spectroscopy to measure the rupture force required to dissociate two Aβ (1-42) peptides in the presence of copper ions, Cu(2+). In addition, we use atomic force microscopy to resolve the aggregation of Aβ formed. Previous research has shown that metal ions decrease the lag time associated with Aβ aggregation. We show that with the addition of copper ions the unbinding force increases notably. This suggests that the reduction of lag time associated with Aβ aggregation occurs on a single molecule level as a result of an increase in binding forces during the very initial interactions between two Aβ peptides. We attribute these results to copper ions acting as a bridge between the two peptide molecules, increasing the stability of the peptide-peptide complex.

  4. Evaluation of Selected Classical Force Fields for Alchemical Binding Free Energy Calculations of Protein-Carbohydrate Complexes.

    PubMed

    Mishra, Sushil K; Calabró, Gaetano; Loeffler, Hannes H; Michel, Julien; Koča, Jaroslav

    2015-07-14

    Protein-carbohydrate recognition is crucial in many vital biological processes including host-pathogen recognition, cell-signaling, and catalysis. Accordingly, computational prediction of protein-carbohydrate binding free energies is of enormous interest for drug design. However, the accuracy of current force fields (FFs) for predicting binding free energies of protein-carbohydrate complexes is not well understood owing to technical challenges such as the highly polar nature of the complexes, anomerization, and conformational flexibility of carbohydrates. The present study evaluated the performance of alchemical predictions of binding free energies with the GAFF1.7/AM1-BCC and GLYCAM06j force fields for modeling protein-carbohydrate complexes. Mean unsigned errors of 1.1 ± 0.06 (GLYCAM06j) and 2.6 ± 0.08 (GAFF1.7/AM1-BCC) kcal·mol(-1) are achieved for a large data set of monosaccharide ligands for Ralstonia solanacearum lectin (RSL). The level of accuracy provided by GLYCAM06j is sufficient to discriminate potent, moderate, and weak binders, a goal that has been difficult to achieve through other scoring approaches. Accordingly, the protocols presented here could find useful applications in carbohydrate-based drug and vaccine developments.

  5. Structure, mechanics, and binding mode heterogeneity of LEDGF/p75-DNA nucleoprotein complexes revealed by scanning force microscopy

    NASA Astrophysics Data System (ADS)

    Vanderlinden, Willem; Lipfert, Jan; Demeulemeester, Jonas; Debyser, Zeger; de Feyter, Steven

    2014-04-01

    LEDGF/p75 is a transcriptional coactivator implicated in the pathogenesis of AIDS and leukemia. In these contexts, LEDGF/p75 acts as a cofactor by tethering protein cargo to transcriptionally active regions in the human genome. Our study - based on scanning force microscopy (SFM) imaging - is the first to provide structural information on the interaction of LEDGF/p75 with DNA. Two novel approaches that allow obtaining insights into the DNA conformation inside nucleoprotein complexes revealed (1) that LEDGF/p75 can bind at least in three different binding modes, (2) how DNA topology and protein dimerization affect these binding modes, and (3) geometrical and mechanical aspects of the nucleoprotein complexes. These structural and mechanical details will help us to better understand the cellular mechanisms of LEDGF/p75 as a transcriptional coactivator and as a cofactor in disease.LEDGF/p75 is a transcriptional coactivator implicated in the pathogenesis of AIDS and leukemia. In these contexts, LEDGF/p75 acts as a cofactor by tethering protein cargo to transcriptionally active regions in the human genome. Our study - based on scanning force microscopy (SFM) imaging - is the first to provide structural information on the interaction of LEDGF/p75 with DNA. Two novel approaches that allow obtaining insights into the DNA conformation inside nucleoprotein complexes revealed (1) that LEDGF/p75 can bind at least in three different binding modes, (2) how DNA topology and protein dimerization affect these binding modes, and (3) geometrical and mechanical aspects of the nucleoprotein complexes. These structural and mechanical details will help us to better understand the cellular mechanisms of LEDGF/p75 as a transcriptional coactivator and as a cofactor in disease. Electronic supplementary information (ESI) available: SFM topographs of phage lambda DNA in situ, in the absence and presence of LEDGF/p75; model-independent tests for DNA chain equilibration in 2D; SFM topographs of

  6. Energetic driving force for preferential binding of self-interstitial atoms to Fe grain boundaries over vacancies

    SciTech Connect

    Tschopp, Mark A.; Horstemeyer, Mark; Gao, Fei; Sun, Xin; Khaleel, Mohammad A.

    2011-05-02

    Molecular dynamics simulations of 50 Fe grain boundaries were used to understand their interaction with vacancies and self-interstitial atoms at all atomic positions within 20 °A of the boundary, which is important for designing radiation-resistant polycrystalline materials. Site-to-site variation within the boundary of both vacancy and self-interstitial formation energies is substantial, with the majority of sites having lower formation energies than in the bulk. Comparing the vacancy and self-interstitial atom binding energies for each site shows that there is an energetic driving force for interstitials to preferentially bind to grain boundary sites over vacancies. Furthermore, these results provide a valuable dataset for quantifying uncertainty bounds for various grain boundary types at the nanoscale, which can be propagated to higher scale simulations of microstructure evolution.

  7. Exploring the binding of 4-thiothymidine with human serum albumin by spectroscopy, atomic force microscopy, and molecular modeling methods.

    PubMed

    Zhang, Juling; Gu, Huaimin; Zhang, Xiaohui

    2014-01-30

    The interaction of 4-thiothymidine (S(4)TdR) with human serum albumin (HSA) was studied by equilibrium dialysis under normal physiological conditions. In this work, the mechanism of the interaction between S(4)TdR and human serum albumin (HSA) was exploited by fluorescence, UV, CD circular, and SERS spectroscopic. Fluorescence and UV spectroscopy suggest that HSA intensities are significantly decreased when adding S(4)TdR to HAS, and the quenching mechanism of the fluorescence is static. Also, the ΔG, ΔH, and ΔS values across temperature indicated that hydrophobic interaction was the predominant binding force. The CD circular results show that there is little change in the secondary structure of HSA except the environment of amino acid changes when adding S(4)TdR to HSA. The surface-enhanced Raman scattering (SERS) shows that the interaction between S(4)TdR and HSA can be achieved through different binding sites which are probably located in the II A and III A hydrophobic pockets of HSA which correspond to Sudlow's I and II binding sites. In addition, the molecular modeling displays that S(4)TdR-HSA complex is stabilized by hydrophobic forces, which result from amino acid residues. The atomic force microscopy results revealed that the single HSA molecular dimensions were larger after interaction of 4-thiothymidine. This work would be useful to understand the state of the transportation, distribution, and metabolism of the anticancer drugs in the human body, and it could provide a useful biochemistry parameter for the development of new anti-cancer drugs and research of pharmacology mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Unraveling the motion of single-stranded DNA binding proteins on DNA using force and fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Ha, Taekjip

    2012-02-01

    Single-stranded DNA binding (SSB) proteins bind to and control the accessibility of single stranded (ss) DNA generated as a transient intermediate during a variety of cellular processes. For subsequent DNA processing, however, such a tightly wrapped, high-affinity protein--DNA complex still needs to be removed or repositioned quickly for unhindered action of other proteins. Here we show, using single-molecule two- and three-colour fluorescence resonance energy transfer, that SSB can spontaneously migrate along ssDNA. Diffusional migration of SSB helps in the local displacement of SSB by an elongating RecA filament. SSB diffusion also melts short DNA hairpins transiently and stimulates RecA filament elongation on DNA with secondary structure. This observation of diffusional movement of a protein on ssDNA introduces a new model for how an SSB protein can be redistributed, while remaining tightly bound to ssDNA during recombination and repair processes. In addition, using an optomechanical tool combining single-molecule fluorescence and force methods, we probed how proteins with such a large binding site size (˜ 65 nucleotides) can migrate rapidly on DNA and how protein-protein interactions and tension may modulate the motion. We observed force-induced progressive unravelling of ssDNA from the SSB surface between 1 and 6 pN, followed by SSB dissociation at ˜10 pN, and obtained experimental evidence of a reptation mechanism for protein movement along DNA wherein a protein slides via DNA bulge formation and propagation. SSB diffusion persists even when bound with RecO, and at forces under which the fully wrapped state is perturbed, suggesting that even in crowded cellular conditions SSB can act as a sliding platform to recruit and carry its interacting proteins for use in DNA replication, recombination and repair.

  9. Multiple stepwise pattern for potential of mean force in unfolding the thrombin binding aptamer in complex with Sr2+.

    PubMed

    Yang, Changwon; Jang, Soonmin; Pak, Youngshang

    2011-12-14

    Using all-atom molecular dynamics simulation in conjunction with umbrella sampling, we obtained the unfolding free energy and the force extension profiles of the thrombin binding DNA aptamer (15-TBA) in complex with Sr(2+) (Protein Data Bank code: 1RDE). The resulting potential of mean force (PMF) displays a multiple stepwise pattern with distinct plateau regions. The detailed analysis of the simulation result indicated that each plateau was created by the interplay of the metal ion interacting with self-arranging guanine bases and the successive uptakes of water molecules. The current PMF simulation provides a quantitative description of the unfolding process of 15-TBA DNA driven by stretching and gives molecular insight on its detailed changes of base pair interactions in the presence of the metal cation.

  10. Doublet stimulation increases Ca(2+) binding to troponin C to ensure rapid force development in skeletal muscle.

    PubMed

    Bakker, Anthony J; Cully, Tanya R; Wingate, Catherine D; Barclay, Christopher J; Launikonis, Bradley S

    2017-03-06

    Fast-twitch skeletal muscle fibers are often exposed to motor neuron double discharges (≥200 Hz), which markedly increase both the rate of contraction and the magnitude of the resulting force responses. However, the mechanism responsible for these effects is poorly understood, likely because of technical limitations in previous studies. In this study, we measured cytosolic Ca(2+) during doublet activation using the low-affinity indicator Mag-Fluo-4 at high temporal resolution and modeled the effects of doublet stimulation on sarcoplasmic reticulum (SR) Ca(2+) release, binding of Ca(2+) to cytosolic buffers, and force enhancement in fast-twitch fibers. Single isolated fibers respond to doublet pulses with two clear Ca(2+) spikes, at doublet frequencies up to 1 KHz. A 200-Hz doublet at the start of a tetanic stimulation train (70 Hz) decreases the drop in free Ca(2+) between the first three Ca(2+) spikes of the transient, maintaining a higher overall free Ca(2+) level during first 20-30 ms of the response. Doublet stimulation also increased the rate of force development in isolated fast-twitch muscles. We also modeled SR Ca(2+) release rates during doublet stimulation and showed that Ca(2+)-dependent inactivation of ryanodine receptor activity is rapid, occurring ≤1ms after initial release. Furthermore, we modeled Ca(2+) binding to the main intracellular Ca(2+) buffers of troponin C (TnC), parvalbumin, and the SR Ca(2+) pump during Ca(2+) release and found that the main effect of the second response in the doublet is to more rapidly increase the occupation of the second Ca(2+)-binding site on TnC (TnC2), resulting in earlier activation of force. We conclude that doublet stimulation maintains high cytosolic Ca(2+) levels for longer in the early phase of the Ca(2+) response, resulting in faster saturation of TnC2 with Ca(2+), faster initiation of cross-bridge cycling, and more rapid force development.

  11. Doublet stimulation increases Ca2+ binding to troponin C to ensure rapid force development in skeletal muscle

    PubMed Central

    Cully, Tanya R.; Wingate, Catherine D.

    2017-01-01

    Fast-twitch skeletal muscle fibers are often exposed to motor neuron double discharges (≥200 Hz), which markedly increase both the rate of contraction and the magnitude of the resulting force responses. However, the mechanism responsible for these effects is poorly understood, likely because of technical limitations in previous studies. In this study, we measured cytosolic Ca2+ during doublet activation using the low-affinity indicator Mag-Fluo-4 at high temporal resolution and modeled the effects of doublet stimulation on sarcoplasmic reticulum (SR) Ca2+ release, binding of Ca2+ to cytosolic buffers, and force enhancement in fast-twitch fibers. Single isolated fibers respond to doublet pulses with two clear Ca2+ spikes, at doublet frequencies up to 1 KHz. A 200-Hz doublet at the start of a tetanic stimulation train (70 Hz) decreases the drop in free Ca2+ between the first three Ca2+ spikes of the transient, maintaining a higher overall free Ca2+ level during first 20–30 ms of the response. Doublet stimulation also increased the rate of force development in isolated fast-twitch muscles. We also modeled SR Ca2+ release rates during doublet stimulation and showed that Ca2+-dependent inactivation of ryanodine receptor activity is rapid, occurring ≤1ms after initial release. Furthermore, we modeled Ca2+ binding to the main intracellular Ca2+ buffers of troponin C (TnC), parvalbumin, and the SR Ca2+ pump during Ca2+ release and found that the main effect of the second response in the doublet is to more rapidly increase the occupation of the second Ca2+-binding site on TnC (TnC2), resulting in earlier activation of force. We conclude that doublet stimulation maintains high cytosolic Ca2+ levels for longer in the early phase of the Ca2+ response, resulting in faster saturation of TnC2 with Ca2+, faster initiation of cross-bridge cycling, and more rapid force development. PMID:28209802

  12. Differential roles of regulatory light chain and myosin binding protein-C phosphorylations in the modulation of cardiac force development

    SciTech Connect

    Colson, Brett A.; Locher, Matthew R.; Bekyarova, Tanya; Patel, Jitandrakumar R.; Fitzsimons, Daniel P.; Irving, Thomas C.; Moss, Richard L.

    2010-05-25

    Phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) and myosin binding protein-C (cMyBP-C) by protein kinase A (PKA) independently accelerate the kinetics of force development in ventricular myocardium. However, while MLCK treatment has been shown to increase the Ca{sup 2+} sensitivity of force (pCa{sub 50}), PKA treatment has been shown to decrease pCa{sub 50}, presumably due to cardiac troponin I phosphorylation. Further, MLCK treatment increases Ca{sup 2+}-independent force and maximum Ca{sup 2+}-activated force, whereas PKA treatment has no effect on either force. To investigate the structural basis underlying the kinase-specific differential effects on steady-state force, we used synchrotron low-angle X-ray diffraction to compare equatorial intensity ratios (I{sub 1,1}/I{sub 1,0}) to assess the proximity of myosin cross-bridge mass relative to actin and to compare lattice spacings (d{sub 1,0}) to assess the inter-thick filament spacing in skinned myocardium following treatment with either MLCK or PKA. As we showed previously, PKA phosphorylation of cMyBP-C increases I{sub 1,1}/I{sub 1,0} and, as hypothesized, treatment with MLCK also increased I{sub 1,1}/I{sub 1,0}, which can explain the accelerated rates of force development during activation. Importantly, interfilament spacing was reduced by {approx}2 nm ({Delta} 3.5%) with MLCK treatment, but did not change with PKA treatment. Thus, RLC or cMyBP-C phosphorylation increases the proximity of cross-bridges to actin, but only RLC phosphorylation affects lattice spacing, which suggests that RLC and cMyBP-C modulate the kinetics of force development by similar structural mechanisms; however, the effect of RLC phosphorylation to increase the Ca{sup 2+} sensitivity of force is mediated by a distinct mechanism, most probably involving changes in interfilament spacing.

  13. Investigation of the binding modes between AIE-active molecules and dsDNA by single molecule force spectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, Ying; Ma, Ke; Hu, Ting; Jiang, Bo; Xu, Bin; Tian, Wenjing; Sun, Jing Zhi; Zhang, Wenke

    2015-05-01

    AIE (aggregation-induced emission)-active molecules hold promise for the labeling of biomolecules as well as living cells. The study of the binding modes of such molecules to biomolecules, such as nucleic acids and proteins, will shed light on a deeper understanding of the mechanisms of molecular interactions and eventually facilitate the design/preparation of new AIE-active bioprobes. Herein, we studied the binding modes of double-stranded DNA (dsDNA) with two types of synthetic AIE-active molecules, namely, tetraphenylethene-derived dicationic compounds (cis-TPEDPy and trans-TPEDPy) and anthracene-derived dicationic compounds (DSAI and DSABr-C6) using single molecule force spectroscopy (SMFS) and circular dichroism (CD) spectroscopy. The experimental data indicate that DSAI can strongly intercalate into DNA base pairs, while DSABr-C6 is unable to intercalate into DNA due to the steric hindrance of the alkyl side chains. Cis-TPEDPy and trans-TPEDPy can also intercalate into DNA base pairs, but the binding shows strong ionic strength dependence. Multiple binding modes of TPEDPy with dsDNA have been discussed. In addition, the electrostatic interaction enhanced intercalation of cis-TPEDPy with dsDNA has also been revealed.AIE (aggregation-induced emission)-active molecules hold promise for the labeling of biomolecules as well as living cells. The study of the binding modes of such molecules to biomolecules, such as nucleic acids and proteins, will shed light on a deeper understanding of the mechanisms of molecular interactions and eventually facilitate the design/preparation of new AIE-active bioprobes. Herein, we studied the binding modes of double-stranded DNA (dsDNA) with two types of synthetic AIE-active molecules, namely, tetraphenylethene-derived dicationic compounds (cis-TPEDPy and trans-TPEDPy) and anthracene-derived dicationic compounds (DSAI and DSABr-C6) using single molecule force spectroscopy (SMFS) and circular dichroism (CD) spectroscopy. The

  14. Analysis of adhesive binding forces between laminin-1 and C2C12 muscle cell membranes measured via high resolution force spectroscopy

    NASA Astrophysics Data System (ADS)

    Gluck, George; Gilbert, Richard; Ortiz, Christine

    2002-03-01

    Laminins are a family of glycoproteins that regulate cell differentiation, shape, and motility through interactions with various cell surface receptors. Here, we have directly measured the biomolecular adhesive binding forces between a cantilever / probe tip that was covalently attached with laminin-1 and membrane receptors on C2C12 muscle cells using the technique of high-resolution force spectroscopy (HRFS). On retraction of the probe tip away from the membrane surface, discrete, long-range adhesive unbinding events were always observed. Statistical analysis of the data revealed an initial broad distribution of heterogeneous unbinding events (occurring at separation distances, D=0-2µm from the point of maximum compression) of magnitude 92.23±37.87pN followed by a narrow distribution of homogeneous unbinding events (occurring at D > 2µm) of magnitude 38.16±9.10pN, which is suggestive of an individual biomolecular adhesive interaction. On-going studies include loading rate dependence and effect of dystroglycan mutation.

  15. Force transduction and lipid binding in MscL: A continuum-molecular approach

    DOE PAGES

    Vanegas, Juan M.; Arroyo, Marino; Fotiadis, Dimitrios

    2014-12-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, andmore » identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin.« less

  16. Force transduction and lipid binding in MscL: a continuum-molecular approach.

    PubMed

    Vanegas, Juan M; Arroyo, Marino

    2014-01-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10-13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin.

  17. Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach

    PubMed Central

    Vanegas, Juan M.; Arroyo, Marino

    2014-01-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin. PMID:25437007

  18. Force transduction and lipid binding in MscL: A continuum-molecular approach

    SciTech Connect

    Vanegas, Juan M.; Arroyo, Marino; Fotiadis, Dimitrios

    2014-12-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin.

  19. Tether fundamentals

    NASA Technical Reports Server (NTRS)

    Carroll, J. A.

    1986-01-01

    Some fundamental aspects of tethers are presented and briefly discussed. The effects of gravity gradients, dumbbell libration in circular orbits, tether control strategies and impact hazards for tethers are among those fundamentals. Also considered are aerodynamic drag, constraints in momentum transfer applications and constraints with permanently deployed tethers. The theoretical feasibility of these concepts are reviewed.

  20. Insulin binding and glucose uptake of adipocytes in rats adapted to hypergravitational force

    NASA Technical Reports Server (NTRS)

    Kobayashi, M.; Mondon, C. E.; Oyama, J.

    1980-01-01

    Rats were exposed to 4.15 g for 1 yr and weight and age matched, and lean noncentrifuged rats were used as control groups. Rats exposed to chronic hypergravity (hypergravic rats) were found to show lower ambient insulin levels, greater food intake with smaller body weight gain, and decreased size of isolated adipocytes. The ability of adipocytes from the hypergravic rats to bind insulin was increased. With Scatchard analysis, both number and affinity of receptors were increased. In contrast to the increased binding, glucose transport was found to be decreased in adipocytes from these animals. However, when the data were expressed as a percentage of maximal effect, the half maximal insulin effect for both the hypergravic and lean control groups was produced at an insulin concentration of 0.23 + or - 0.02 ng/ml, which was lower than the insulin concentration of 0.31 + or - 0.02 ng/ml for the weight-matched control group (P less than 0.05). This increased insulin sensitivity in the hypergravic group was accounted for by an increased number of receptors.

  1. Insulin binding and glucose uptake of adipocytes in rats adapted to hypergravitational force

    NASA Technical Reports Server (NTRS)

    Kobayashi, M.; Mondon, C. E.; Oyama, J.

    1980-01-01

    Rats were exposed to 4.15 g for 1 yr and weight and age matched, and lean noncentrifuged rats were used as control groups. Rats exposed to chronic hypergravity (hypergravic rats) were found to show lower ambient insulin levels, greater food intake with smaller body weight gain, and decreased size of isolated adipocytes. The ability of adipocytes from the hypergravic rats to bind insulin was increased. With Scatchard analysis, both number and affinity of receptors were increased. In contrast to the increased binding, glucose transport was found to be decreased in adipocytes from these animals. However, when the data were expressed as a percentage of maximal effect, the half maximal insulin effect for both the hypergravic and lean control groups was produced at an insulin concentration of 0.23 + or - 0.02 ng/ml, which was lower than the insulin concentration of 0.31 + or - 0.02 ng/ml for the weight-matched control group (P less than 0.05). This increased insulin sensitivity in the hypergravic group was accounted for by an increased number of receptors.

  2. Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell.

    PubMed

    Chen, Yunfeng; Liu, Baoyu; Ju, Lining; Hong, Jinsung; Ji, Qinghua; Chen, Wei; Zhu, Cheng

    2015-08-04

    Membrane receptor-ligand interactions mediate many cellular functions. Binding kinetics and downstream signaling triggered by these molecular interactions are likely affected by the mechanical environment in which binding and signaling take place. A recent study demonstrated that mechanical force can regulate antigen recognition by and triggering of the T-cell receptor (TCR). This was made possible by a new technology we developed and termed fluorescence biomembrane force probe (fBFP), which combines single-molecule force spectroscopy with fluorescence microscopy. Using an ultra-soft human red blood cell as the sensitive force sensor, a high-speed camera and real-time imaging tracking techniques, the fBFP is of ~1 pN (10(-12) N), ~3 nm and ~0.5 msec in force, spatial and temporal resolution. With the fBFP, one can precisely measure single receptor-ligand binding kinetics under force regulation and simultaneously image binding-triggered intracellular calcium signaling on a single live cell. This new technology can be used to study other membrane receptor-ligand interaction and signaling in other cells under mechanical regulation.

  3. A general intermolecular force field based on tight-binding quantum chemical calculations

    NASA Astrophysics Data System (ADS)

    Grimme, Stefan; Bannwarth, Christoph; Caldeweyher, Eike; Pisarek, Jana; Hansen, Andreas

    2017-10-01

    A black-box type procedure is presented for the generation of a molecule-specific, intermolecular potential energy function. The method uses quantum chemical (QC) information from our recently published extended tight-binding semi-empirical scheme (GFN-xTB) and can treat non-covalently bound complexes and aggregates with almost arbitrary chemical structure. The necessary QC information consists of the equilibrium structure, Mulliken atomic charges, charge centers of localized molecular orbitals, and also of frontier orbitals and orbital energies. The molecular pair potential includes model density dependent Pauli repulsion, penetration, as well as point charge electrostatics, the newly developed D4 dispersion energy model, Drude oscillators for polarization, and a charge-transfer term. Only one element-specific and about 20 global empirical parameters are needed to cover systems with nuclear charges up to radon (Z = 86). The method is tested for standard small molecule interaction energy benchmark sets where it provides accurate intermolecular energies and equilibrium distances. Examples for structures with a few hundred atoms including charged systems demonstrate the versatility of the approach. The method is implemented in a stand-alone computer code which enables rigid-body, global minimum energy searches for molecular aggregation or alignment.

  4. Regulation of protein binding toward a ligand on chromatographic matrixes by masking and forced-releasing effects using thermoresponsive polymer.

    PubMed

    Yoshizako, Kimihiro; Akiyama, Yoshikatsu; Yamanaka, Hidenori; Shinohara, Yasuro; Hasegawa, Yukio; Carredano, Enrique; Kikuchi, Akihiko; Okano, Teruo

    2002-08-15

    A novel concept of affinity regulation based on masking and forced-releasing effects using a thermoresponsive polymer was elucidated. Affinity chromatographic matrixes were prepared using either poly(glycidyl methacrylate-co-ethyleneglycol dimethacrylate) or poly(glycidyl methacrylate-co-triethyleneglycol dimethacrylate) beads immobilized with ligand molecule, Cibacron Blue F3G-A (CB), together with poly(N-isopropylacrylamide) (PIPAAm), a polymer with a cloud point of 32 degrees C. Two different lengths of spacer molecules were used for the immobilization of CB while maintaining the PIPAAm size constant. Chromatographic analyses using bovine serum albumin as a model protein showed a clear correlation between spacer length and binding capacity at temperatures lower than the lower critical solution temperature (LCST) of PIPAAm. The binding capacity under the LCST was significantly reduced only when the calculated spacer length was shorter than the mean size of the extended PIPAAm. Furthermore, the adsorbed protein could be desorbed (released) from the matrix surface by lowering the temperature to below the LCST while maintaining other factors such as pH and ion strength. Selective recovery of human albumin from human sera was demonstrated using this newly developed thermoresponsive affinity column.

  5. Entropy-enthalpy transduction caused by conformational shifts can obscure the forces driving protein-ligand binding.

    PubMed

    Fenley, Andrew T; Muddana, Hari S; Gilson, Michael K

    2012-12-04

    Molecular dynamics simulations of unprecedented duration now can provide new insights into biomolecular mechanisms. Analysis of a 1-ms molecular dynamics simulation of the small protein bovine pancreatic trypsin inhibitor reveals that its main conformations have different thermodynamic profiles and that perturbation of a single geometric variable, such as a torsion angle or interresidue distance, can select for occupancy of one or another conformational state. These results establish the basis for a mechanism that we term entropy-enthalpy transduction (EET), in which the thermodynamic character of a local perturbation, such as enthalpic binding of a small molecule, is camouflaged by the thermodynamics of a global conformational change induced by the perturbation, such as a switch into a high-entropy conformational state. It is noted that EET could occur in many systems, making measured entropies and enthalpies of folding and binding unreliable indicators of actual thermodynamic driving forces. The same mechanism might also account for the high experimental variance of measured enthalpies and entropies relative to free energies in some calorimetric studies. Finally, EET may be the physical mechanism underlying many cases of entropy-enthalpy compensation.

  6. Entropy–enthalpy transduction caused by conformational shifts can obscure the forces driving protein–ligand binding

    PubMed Central

    Fenley, Andrew T.; Muddana, Hari S.; Gilson, Michael K.

    2012-01-01

    Molecular dynamics simulations of unprecedented duration now can provide new insights into biomolecular mechanisms. Analysis of a 1-ms molecular dynamics simulation of the small protein bovine pancreatic trypsin inhibitor reveals that its main conformations have different thermodynamic profiles and that perturbation of a single geometric variable, such as a torsion angle or interresidue distance, can select for occupancy of one or another conformational state. These results establish the basis for a mechanism that we term entropy–enthalpy transduction (EET), in which the thermodynamic character of a local perturbation, such as enthalpic binding of a small molecule, is camouflaged by the thermodynamics of a global conformational change induced by the perturbation, such as a switch into a high-entropy conformational state. It is noted that EET could occur in many systems, making measured entropies and enthalpies of folding and binding unreliable indicators of actual thermodynamic driving forces. The same mechanism might also account for the high experimental variance of measured enthalpies and entropies relative to free energies in some calorimetric studies. Finally, EET may be the physical mechanism underlying many cases of entropy–enthalpy compensation. PMID:23150595

  7. Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host macromolecules.

    PubMed

    Moriarty, Tara J; Shi, Meiqing; Lin, Yi-Pin; Ebady, Rhodaba; Zhou, Hong; Odisho, Tanya; Hardy, Pierre-Olivier; Salman-Dilgimen, Aydan; Wu, Jing; Weening, Eric H; Skare, Jon T; Kubes, Paul; Leong, John; Chaconas, George

    2012-12-01

    Systemic dissemination of microbial pathogens permits microbes to spread from the initial site of infection to secondary target tissues and is responsible for most mortality due to bacterial infections. Dissemination is a critical stage of disease progression by the Lyme spirochaete, Borrelia burgdorferi. However, many mechanistic features of the process are not yet understood. A key step is adhesion of circulating microbes to vascular surfaces in the face of the shear forces present in flowing blood. Using real-time microscopic imaging of the Lyme spirochaete in living mice we previously identified the first bacterial protein (B. burgdorferi BBK32) shown to mediate vascular adhesion in vivo. Vascular adhesion is also dependent on host fibronectin (Fn) and glycosaminoglycans (GAGs). In the present study, we investigated the mechanisms of BBK32-dependent vascular adhesion in vivo. We determined that BBK32-Fn interactions (tethering) function as a molecular braking mechanism that permits the formation of more stable BBK32-GAG interactions (dragging) between circulating bacteria and vascular surfaces. Since BBK32-like proteins are expressed in a variety of pathogens we believe that the vascular adhesion mechanisms we have deciphered here may be critical for understanding the dissemination mechanisms of other bacterial pathogens. © 2012 Blackwell Publishing Ltd.

  8. Effective binding force calculation in a dimeric protein by molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Sergi, Alessandro; Ciccotti, Giovanni; Falconi, Mattia; Desideri, Alessandro; Ferrario, Mauro

    2002-04-01

    A good example of macromolecular recognition is found in the interaction of the two monomers of the dimeric superoxide dismutase protein found in Photobacterium leiognathi. We have produced, by molecular dynamics simulation techniques, a specific path for the rupture of the dimer and calculated the effective force involved in the process by extending a well established free energy calculation scheme, the molecular dynamics blue moon approach to rare events. Within this picture we have generalized the approach to a vectorial reaction coordinate and performed a number of different simulations in function of the monomer-momomer separation, at fixed relative orientation. We find a deep minimum and we compute the height of the free energy barrier to break the dimer. As for the system characterization we have found that, when the separation distance increases, the protein structure is stable and the monomer-monomer interface is uniformly hydrated. Moreover, identifying the crucial contacts for the stabilization of the dimer, we have found the sequence of the different microscopic events in the monomer-monomer recognition and we have developed a view of the process which requires a merging of standard explanations, in agreement with the recent picture of recognition as a dynamical process mixing the various mechanisms previously considered [Kimura et al., Biophys. J. 80 635 (2001)].

  9. Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host macromolecules

    PubMed Central

    Moriarty, Tara J.; Shi, Meiqing; Lin, Yi-Pin; Ebady, Rhodaba; Zhou, Hong; Odisho, Tanya; Hardy, Pierre-Olivier; Salman-Dilgimen, Aydan; Wu, Jing; Weening, Eric H.; Skare, Jon T.; Kubes, Paul; Leong, John; Chaconas, George

    2012-01-01

    SUMMARY Systemic dissemination of microbial pathogens permits microbes to spread from the initial site of infection to secondary target tissues and is responsible for most mortality due to bacterial infections. Dissemination is a critical stage of disease progression by the Lyme spirochete, Borrelia burgdorferi. However, many mechanistic features of the process are not yet understood. A key step is adhesion of circulating microbes to vascular surfaces in the face of the shear forces present in flowing blood. Using real-time microscopic imaging of the Lyme spirochete in living mice we previously identified the first bacterial protein (B. burgdorferi BBK32) shown to mediate vascular adhesion in vivo. Vascular adhesion is also dependent on host fibronectin (Fn) and glycosaminoglycans (GAGs). In the present study, we investigated the mechanisms of BBK32-dependent vascular adhesion in vivo. We determined that BBK32-Fn interactions (tethering) function as a molecular braking mechanism that permits the formation of more stable BBK32-GAG interactions (dragging) between circulating bacteria and vascular surfaces. Since BBK32-like proteins are expressed in a variety of pathogens we believe that the vascular adhesion mechanisms we have deciphered here may be critical for understanding the dissemination mechanisms of other bacterial pathogens. PMID:23095033

  10. Dialysis purification of integrase-DNA complexes provides high-resolution atomic force microscopy images: dimeric recombinant HIV-1 integrase binding and specific looping on DNA.

    PubMed

    Tsuruyama, Tatsuaki; Nakai, Tonau; Ohmori, Rei; Ozeki, Munetaka; Tamaki, Keiji; Yoshikawa, Kenichi

    2013-01-01

    It remains difficult to obtain high-resolution atomic force microscopy images of HIV-1 integrase bound to DNA in a dimeric or tetrameric fashion. We therefore constructed specific target DNAs to assess HIV-1 integrase binding and purified the complex by dialysis prior to analysis. Our resulting atomic force microscopy analyses indicated precise size of binding human immunodeficiency virus type 1 (HIV-1) recombinant integrase in a tetrameric manner, inducing formation of a loop-like or figure-eight-like secondary structure in the target DNA. Our findings regarding the target DNA secondary structure provide new insights into the intermediate states of retroviral integration.

  11. Von Willebrand factor-A1 domain binds platelet glycoprotein Ibα in multiple states with distinctive force-dependent dissociation kinetics

    PubMed Central

    Ju, Lining; Chen, Yunfeng; Zhou, Fangyuan; Lu, Hang; Cruz, Miguel A.; Zhu, Cheng

    2015-01-01

    Circulating von Willebrand factor (VWF) adopts a closed conformation that shields the platelet glycoprotein Ibα (GPIbα) binding site in the VWF-A1 domain. Immobilized at sites of vascular injury, VWF is activated by its interaction with collagen and the exertion of increased hemodynamic forces. Studies on native VWF strings and isolated A1 domains suggest the existence of multiple A1 binding states in different biophysical contexts. In this single-molecule study, we have used a biomembrane force probe (BFP) and a flow chamber to identify and characterize a collagen binding induced conformation with a higher affinity to platelet GPIbα. As force increases, our results show that collagen binding increases the stability of GPIbα bond with both VWF and isolated A1 domain. However, the collagen 2D binding affinity for VWF-A3 domain is 10 times of that for A1 domain, suggesting the initial VWF capture is mediated by A3–collagen interaction while A1–collagen regulates the subsequent VWF activation. Our results revealed the molecular mechanism of collagen-regulated, A1-mediated platelet adhesion enhancement. Characterization of different A1 states provides insights into binding heterogeneity of VWF in different scenarios of inflammation and thrombosis. PMID:26213126

  12. Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix.

    PubMed

    Gershlak, Joshua R; Black, Lauren D

    2015-01-15

    We have previously reported a unique response of traction force generation for cells grown on mature cardiac ECM, where traction force was constant over a range of stiffnesses. In this study we sought to further investigate the role of the complex mixture of ECM on this response and assess the potential mechanism behind it. Using traction force microscopy, we measured cellular traction forces and stresses for mesenchymal stem cells (MSCs) grown on polyacrylamide gels at a range of stiffnesses (9, 25, or 48 kPa) containing either adult rat heart ECM, different singular ECM proteins including collagen I, fibronectin, and laminin, or ECM mimics comprised of varying amounts of collagen I, fibronectin, and laminin. We also measured the expression of integrins on these different substrates as well as probed for β1 integrin binding. There was no significant change in traction force generation for cells grown on the adult ECM, as previously reported, whereas cells grown on singular ECM protein substrates had increased traction force generation with an increase in substrate stiffness. Cells grown on ECM mimics containing collagen I, fibronectin and laminin were found to be reminiscent of the traction forces generated by cells grown on native ECM. Integrin expression generally increased with increasing stiffness except for the β1 integrin, potentially implicating it as playing a role in the response to adult cardiac ECM. We inhibited binding through the β1 integrin on cells grown on the adult ECM and found that the inhibition of β1 binding led to a return to the typical response of increasing traction force generation with increasing stiffness. Our data demonstrates that cells grown on the mature cardiac ECM are able to circumvent typical stiffness related cellular behaviors, likely through β1 integrin binding to the complex composition. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The microtubule-binding and coiled-coil domains of Kid are required to turn off the polar ejection force at anaphase.

    PubMed

    Soeda, Shou; Yamada-Nomoto, Kaori; Ohsugi, Miho

    2016-10-01

    Mitotic chromosomes move dynamically along the spindle microtubules using the forces generated by motor proteins such as chromokinesin Kid (also known as KIF22). Kid generates a polar ejection force and contributes to alignment of the chromosome arms during prometaphase and metaphase, whereas during anaphase, Kid contributes to chromosome compaction. How Kid is regulated and how this regulation is important for chromosome dynamics remains unclear. Here, we address these questions by expressing mutant forms of Kid in Kid-deficient cells. We demonstrate that Cdk1-mediated phosphorylation of Thr463 is required to generate the polar ejection force on Kid-binding chromosomes, whereas dephosphorylation of Thr463 prevents generation of the ejection force on such chromosomes. In addition to activation of the second microtubule-binding domain through dephosphorylation of Thr463, the coiled-coil domain is essential in suspending generation of the polar ejection force, preventing separated chromosomes from becoming recongressed during anaphase. We propose that phosphorylation of Thr463 switches the mitotic chromosome movement from an anti-poleward direction to a poleward direction by converting the Kid functional mode from polar-ejection-force-ON to -OFF during the metaphase-anaphase transition, and that both the second microtubule-binding domain and the coiled-coil domain are involved in this switching process.

  14. Parallel inhibition of active force and relaxed fiber stiffness by caldesmon fragments at physiological ionic strength and temperature conditions: additional evidence that weak cross-bridge binding to actin is an essential intermediate for force generation.

    PubMed

    Kraft, T; Chalovich, J M; Yu, L C; Brenner, B

    1995-06-01

    Previously we showed that stiffness of relaxed fibers and active force generated in single skinned fibers of rabbit psoas muscle are inhibited in parallel by actin-binding fragments of caldesmon, an actin-associated protein of smooth muscle, under conditions in which a large fraction of cross-bridges is weakly attached to actin (ionic strength of 50 mM and temperature of 5 degrees C). These results suggested that weak cross-bridge attachment to actin is essential for force generation. The present study provides evidence that this is also true for physiological ionic strength (170 mM) at temperatures up to 30 degrees C, suggesting that weak cross-bridge binding to actin is generally required for force generation. In addition, we show that the inhibition of active force is not a result of changes in cross-bridge cycling kinetics but apparently results from selective inhibition of weak cross-bridge binding to actin. Together with our previous biochemical, mechanical, and structural studies, these findings support the proposal that weak cross-bridge attachment to actin is an essential intermediate on the path to force generation and are consistent with the concept that isometric force mainly results from an increase in strain of the attached cross-bridge as a result of a structural change associated with the transition from a weakly bound to a strongly bound actomyosin complex. This mechanism is different from the processes responsible for quick tension recovery that were proposed by Huxley and Simmons (Proposed mechanism of force generation in striated muscle. Nature. 233:533-538.) to represent the elementary mechanism of force generation.

  15. Binding forces between a novel Schiff base palladium(II) complex and two carrier proteins: human serum albumi and β-lactoglobulin.

    PubMed

    Shahraki, Somaye; Heydari, Ali

    2017-09-01

    Ligand binding studies on carrier proteins are crucial in determining the pharmacological properties of drug candidates. Here, a new palladium(II) complex was synthesized and characterized. The in vitro binding studies of this complex with two carrier proteins, human serum albumin (HSA), and β-lactoglobulin (βLG) were investigated by employing biophysical techniques as well as computational modeling. The experimental results showed that the Pd(II) complex interacted with two carrier proteins with moderate binding affinity (Kb ≈ .5 × 10(4) M(-1) for HSA and .2 × 10(3) M(-1) for βLG). Binding of Pd(II) complex to HSA and βLG caused strong fluorescence quenching of both proteins through static quenching mechanism. In two studied systems hydrogen bonds and van der Waals forces were the major stabilizing forces in the drug-protein complex formation. UV-Visible and FT-IR measurements indicated that the binding of above complex to HSA and βLG may induce conformational and micro-environmental changes of two proteins. Protein-ligand docking analysis confirmed that the Pd(II) complex binds to residues located in the subdomain IIA of HSA and site A of βLG. All these experimental and computational results suggest that βLG and HSA might act as carrier protein for Pd(II) complex to deliver it to the target molecules.

  16. The impact of DNA intercalators on DNA and DNA-processing enzymes elucidated through force-dependent binding kinetics

    PubMed Central

    Biebricher, Andreas S.; Heller, Iddo; Roijmans, Roel F. H.; Hoekstra, Tjalle P.; Peterman, Erwin J. G.; Wuite, Gijs J. L.

    2015-01-01

    DNA intercalators are widely used as fluorescent probes to visualize DNA and DNA transactions in vivo and in vitro. It is well known that they perturb DNA structure and stability, which can in turn influence DNA-processing by proteins. Here we elucidate this perturbation by combining single-dye fluorescence microscopy with force spectroscopy and measuring the kinetics of DNA intercalation by the mono- and bis-intercalating cyanine dyes SYTOX Orange, SYTOX Green, SYBR Gold, YO-PRO-1, YOYO-1 and POPO-3. We show that their DNA-binding affinity is mainly governed by a strongly tension-dependent dissociation rate. These rates can be tuned over a range of seven orders of magnitude by changing DNA tension, intercalating species and ionic strength. We show that optimizing these rates minimizes the impact of intercalators on strand separation and enzymatic activity. These new insights provide handles for the improved use of intercalators as DNA probes with minimal perturbation and maximal efficacy. PMID:26084388

  17. Marketing fundamentals.

    PubMed

    Redmond, W H

    2001-01-01

    This chapter outlines current marketing practice from a managerial perspective. The role of marketing within an organization is discussed in relation to efficiency and adaptation to changing environments. Fundamental terms and concepts are presented in an applied context. The implementation of marketing plans is organized around the four P's of marketing: product (or service), promotion (including advertising), place of delivery, and pricing. These are the tools with which marketers seek to better serve their clients and form the basis for competing with other organizations. Basic concepts of strategic relationship management are outlined. Lastly, alternate viewpoints on the role of advertising in healthcare markets are examined.

  18. Neutrons and Fundamental Symmetries

    SciTech Connect

    Plaster, Bradley

    2016-01-11

    The research supported by this project addressed fundamental open physics questions via experiments with subatomic particles. In particular, neutrons constitute an especially ideal “laboratory” for fundamental physics tests, as their sensitivities to the four known forces of nature permit a broad range of tests of the so-called “Standard Model”, our current best physics model for the interactions of subatomic particles. Although the Standard Model has been a triumphant success for physics, it does not provide satisfactory answers to some of the most fundamental open questions in physics, such as: are there additional forces of nature beyond the gravitational, electromagnetic, weak nuclear, and strong nuclear forces?, or why does our universe consist of more matter than anti-matter? This project also contributed significantly to the training of the next generation of scientists, of considerable value to the public. Young scientists, ranging from undergraduate students to graduate students to post-doctoral researchers, made significant contributions to the work carried out under this project.

  19. Binding Structures of tri-N-acetyl-β-glucosamine in Hen Egg White Lysozyme using Molecular Dynamics with a Polarizable Force Field

    PubMed Central

    Zhong, Yang; Patel, Sandeep

    2014-01-01

    Lysozyme is a well-studied enzyme that hydrolyzes the β-(1,4)-glycosidic linkage of N-acetyl-β-glucosamine (NAG)n oligomers. The active site of hen egg-white lysozyme (HEWL) is believed to consist of six subsites, A-F that can accommodate six sugar residues. We present studies exploring the use of polarizable force fields in conjunction with all-atom molecular dynamics simulations to analyze binding structures of complexes of lysozyme and NAG trisaccharide, (NAG)3. Molecular dynamics trajectories are applied to analyze structures and conformation of the complex as well as protein-ligand interactions, including the hydrogen-bonding network in the binding pocket. Two binding modes (ABC and BCD) of (NAG)3 are investigated independently based on a fixed-charge model and a polarizable model. We also apply MM-GBSA methods based on molecular dynamics using both non-polarizable and polarizable force fields in order to compute binding free energies. We also study the correlation between RMSD and binding free energies of the wildtype and W62Y mutant; we find that for this prototypical system, approaches using the MD trajectories coupled with implicit solvent models are equivalent for polarizable and fixed-charge models. PMID:23109228

  20. A Fundamental Relationship Between Hydrophobic Properties and Biological Activity for the Duocarmycin Class of DNA Alkylating Antitumor Drugs: Hydrophobic Binding-Driven-Bonding

    PubMed Central

    Wolfe, Amanda L.; Duncan, Katharine K.; Lajiness, James P.; Zhu, Kaicheng; Duerfeldt, Adam S.; Boger, Dale L.

    2013-01-01

    Two systematic series of increasingly hydrophilic derivatives of duocarmycin SA are described that feature the incorporation of ethylene glycol units (n = 1–5) into the methoxy substituents of the trimethoxyindole subunit. These derivatives exhibit progressively increasing water solubility, along with progressive decreases in cell growth inhibitory activity and DNA alkylation efficiency with the incremental ethylene glycol unit incorporations. A linear relationship between cLogP and –logIC50 for cell growth inhibition and –logAE (AE = cell free DNA alkylation efficiency) is observed where cLogP values span the productive range of 2.5–0.49 and –logIC50 values span the range of 11.2–6.4, representing IC50 values covering a 105 range (0.008 to 370 nM). The results quantify a fundamental role the compound hydrophobic character plays in the expression of the biological activity of members in this class, driving the intrinsically reversible DNA alkylation reaction, and define the stunning magnitude of its effect. PMID:23944748

  1. Accurate determination of pyridine-poly(amidoamine) dendrimer absolute binding constants with the OPLS-AA force field and direct integration of radial distribution functions.

    PubMed

    Peng, Yong; Kaminski, George A

    2005-08-11

    OPLS-AA force field and direct integration of intermolecular radial distribution functions (RDF) were employed to calculate absolute binding constants of pyridine molecules to amino group (NH2) and amide group hydrogen atoms in and first generation poly(amidoamine) dendrimers in chloroform. The average errors in the absolute and relative association constants, as predicted with the calculations, are 14.1% and 10.8%, respectively, which translate into ca. 0.08 and 0.06 kcal/mol errors in the absolute and relative binding free energies. We believe that this level of accuracy proves the applicability of the OPLS-AA, force field, in combination with the direct RDF integration, to reproducing and predicting absolute intermolecular association constants of low magnitudes (ca. 0.2-2.0 range).

  2. Accurate Determination of Pyridine -- Poly (Amidoamine) Dendrimer Absolute Binding Constants with the OPLS-AA Force Field and Direct Integration of Radial Distribution Functions

    NASA Astrophysics Data System (ADS)

    Peng, Yong; Kaminski, George

    2006-03-01

    OPLS-AA force field and direct integration of intermolecular radial distribution functions (RDF) were employed to calculate absolute binding constants of pyridine molecules to NH2 and amide group hydrogen atoms in 0th and 1st generation poly (amidoamine) dendrimers in chloroform. The average errors in the absolute and relative association constants, as predicted with the calculations, are 14.1% and 10.8%, respectively, which translate into ca. 0.08 kcal/mol and 0.06 kcal/mol errors in the absolute and relative binding free energies. We believe that this level of accuracy proves the applicability of the OPLS-AA, force field, in combination with the direct RDF integration, to reproducing and predicting absolute intermolecular association constants of low magnitudes (ca. 0.2 -- 2.0 range).

  3. Fundamental Physics

    NASA Image and Video Library

    2003-01-22

    Still photographs taken over 16 hours on Nov. 13, 2001, on the International Space Station have been condensed into a few seconds to show the de-mixing -- or phase separation -- process studied by the Experiment on Physics of Colloids in Space. Commanded from the ground, dozens of similar tests have been conducted since the experiment arrived on ISS in 2000. The sample is a mix of polymethylmethacrylate (PMMA or acrylic) colloids, polystyrene polymers and solvents. The circular area is 2 cm (0.8 in.) in diameter. The phase separation process occurs spontaneously after the sample is mechanically mixed. The evolving lighter regions are rich in colloid and have the structure of a liquid. The dark regions are poor in colloids and have the structure of a gas. This behavior carnot be observed on Earth because gravity causes the particles to fall out of solution faster than the phase separation can occur. While similar to a gas-liquid phase transition, the growth rate observed in this test is different from any atomic gas-liquid or liquid-liquid phase transition ever measured experimentally. Ultimately, the sample separates into colloid-poor and colloid-rich areas, just as oil and vinegar separate. The fundamental science of de-mixing in this colloid-polymer sample is the same found in the annealing of metal alloys and plastic polymer blends. Improving the understanding of this process may lead to improving processing of these materials on Earth.

  4. Healthcare fundamentals.

    PubMed

    Kauk, Justin; Hill, Austin D; Althausen, Peter L

    2014-07-01

    In order for a trauma surgeon to have an intelligent discussion with hospital administrators, healthcare plans, policymakers, or any other physicians, a basic understanding of the fundamentals of healthcare is paramount. It is truly shocking how many surgeons are unable to describe the difference between Medicare and Medicaid or describe how hospitals and physicians get paid. These topics may seem burdensome but they are vital to all business decision making in the healthcare field. The following chapter provides further insight about what we call "the basics" of providing medical care today. Most of the topics presented can be applied to all specialties of medicine. It is broken down into 5 sections. The first section is a brief overview of government programs, their influence on care delivery and reimbursement, and past and future legislation. Section 2 focuses on the compliance, care provision, and privacy statutes that regulate physicians who care for Medicare/Medicaid patient populations. With a better understanding of these obligations, section 3 discusses avenues by which physicians can stay informed of current and pending health policy and provides ways that they can become involved in shaping future legislation. The fourth section changes gears slightly by explaining how the concepts of trade restraint, libel, antitrust legislation, and indemnity relate to physician practice. The fifth, and final, section ties all of components together by describing how physician-hospital alignment can be mutually beneficial in providing patient care under current healthcare policy legislation.

  5. Fundamentals of negative refractive index optical trapping: forces and radiation pressures exerted by focused Gaussian beams using the generalized Lorenz-Mie theory.

    PubMed

    Ambrosio, Leonardo A; Hernández-Figueroa, Hugo E

    2010-11-04

    Based on the generalized Lorenz-Mie theory (GLMT), this paper reveals, for the first time in the literature, the principal characteristics of the optical forces and radiation pressure cross-sections exerted on homogeneous, linear, isotropic and spherical hypothetical negative refractive index (NRI) particles under the influence of focused Gaussian beams in the Mie regime. Starting with ray optics considerations, the analysis is then extended through calculating the Mie coefficients and the beam-shape coefficients for incident focused Gaussian beams. Results reveal new and interesting trapping properties which are not observed for commonly positive refractive index particles and, in this way, new potential applications in biomedical optics can be devised.

  6. Role of ICAM-1 polymorphisms (G241R, K469E) in mediating its single-molecule binding ability: Atomic force microscopy measurements on living cells

    SciTech Connect

    Bai, Rui; Yi, Shaoqiong; Zhang, Xuejie; Liu, Huiliang; Fang, Xiaohong

    2014-06-13

    Highlights: • We evaluated both single molecule binding ability and expression level of 4 ICAM-1 mutations. • AFM was used to measure single-molecule binding ability on living cells. • The SNP of ICAM-1 may induce changes in expressions rather than single-molecule binding ability. - Abstract: Atherosclerosis (As) is characterized by chronic inflammation and is a major cause of human mortality. ICAM-1-mediated adhesion of leukocytes in vessel walls plays an important role in the pathogenesis of atherosclerosis. Two single nucleotide polymorphisms (SNPs) of human intercellular adhesion molecule-1 (ICAM-1), G241R and K469E, are associated with a number of inflammatory diseases. SNP induced changes in ICAM-1 function rely not only on the expression level but also on the single-molecule binding ability which may be affected by single molecule conformation variations such as protein splicing and folding. Previous studies have shown associations between G241R/K469E polymorphisms and ICAM-1 gene expression. Nevertheless, few studies have been done that focus on the single-molecule forces of the above SNPs and their ligands. In the current study, we evaluated both single molecule binding ability and expression level of 4 ICAM-1 mutations – GK (G241/K469), GE (G241/E469), RK (R241/K469) and RE (R241/E469). No difference in adhesion ability was observed via cell adhesion assay or atomic force microscopy (AFM) measurement when comparing the GK, GE, RK, or RE genotypes of ICAM-1 to each other. On the other hand, flow cytometry suggested that there was significantly higher expression of GE genotype of ICAM-1 on transfected CHO cells. Thus, we concluded that genetic susceptibility to diseases related to ICAM-1 polymorphisms, G241R or K469E, might be due to the different expressions of ICAM-1 variants rather than to the single-molecule binding ability of ICAM-1.

  7. Fundamentals of negative refractive index optical trapping: forces and radiation pressures exerted by focused Gaussian beams using the generalized Lorenz-Mie theory

    PubMed Central

    Ambrosio, Leonardo A.; Hernández-Figueroa, Hugo E.

    2010-01-01

    Based on the generalized Lorenz-Mie theory (GLMT), this paper reveals, for the first time in the literature, the principal characteristics of the optical forces and radiation pressure cross-sections exerted on homogeneous, linear, isotropic and spherical hypothetical negative refractive index (NRI) particles under the influence of focused Gaussian beams in the Mie regime. Starting with ray optics considerations, the analysis is then extended through calculating the Mie coefficients and the beam-shape coefficients for incident focused Gaussian beams. Results reveal new and interesting trapping properties which are not observed for commonly positive refractive index particles and, in this way, new potential applications in biomedical optics can be devised. PMID:21258549

  8. Demonstration of specific binding of heparin to Plasmodium falciparum-infected vs. non-infected red blood cells by single-molecule force spectroscopy

    NASA Astrophysics Data System (ADS)

    Valle-Delgado, Juan José; Urbán, Patricia; Fernàndez-Busquets, Xavier

    2013-04-01

    Glycosaminoglycans (GAGs) play an important role in the sequestration of Plasmodium falciparum-infected red blood cells (pRBCs) in the microvascular endothelium of different tissues, as well as in the formation of small clusters (rosettes) between infected and non-infected red blood cells (RBCs). Both sequestration and rosetting have been recognized as characteristic events in severe malaria. Here we have used heparin and pRBCs infected by the 3D7 strain of P. falciparum as a model to study GAG-pRBC interactions. Fluorescence microscopy and fluorescence-assisted cell sorting assays have shown that exogenously added heparin has binding specificity for pRBCs (preferentially for those infected with late forms of the parasite) vs. RBCs. Heparin-pRBC adhesion has been probed by single-molecule force spectroscopy, obtaining an average binding force ranging between 28 and 46 pN depending on the loading rate. No significant binding of heparin to non-infected RBCs has been observed in control experiments. This work represents the first approach to quantitatively evaluate GAG-pRBC molecular interactions at the individual molecule level.Glycosaminoglycans (GAGs) play an important role in the sequestration of Plasmodium falciparum-infected red blood cells (pRBCs) in the microvascular endothelium of different tissues, as well as in the formation of small clusters (rosettes) between infected and non-infected red blood cells (RBCs). Both sequestration and rosetting have been recognized as characteristic events in severe malaria. Here we have used heparin and pRBCs infected by the 3D7 strain of P. falciparum as a model to study GAG-pRBC interactions. Fluorescence microscopy and fluorescence-assisted cell sorting assays have shown that exogenously added heparin has binding specificity for pRBCs (preferentially for those infected with late forms of the parasite) vs. RBCs. Heparin-pRBC adhesion has been probed by single-molecule force spectroscopy, obtaining an average binding force

  9. Hospital fundamentals.

    PubMed

    Althausen, Peter L; Hill, Austin D; Mead, Lisa

    2014-07-01

    Under the current system, orthopaedic trauma surgeons must work in some form of hospital setting as our primary service involves treatment of the trauma patient. We must not forget that just as a trauma center cannot exist without our services, we cannot function without their support. As a result, a clear understanding of the balance between physicians and hospitals is paramount. Historical perspective enables physicians and hospital personnel alike to understand the evolution of hospital-physician relationship. This process should be understood upon completion of this chapter. The relationship between physicians and hospitals is becoming increasingly complex and multiple forms of integration exist such as joint ventures, gain sharing, and co-management agreements. For the surgeon to negotiate well, an understanding of hospital governance and the role of the orthopaedic traumatologist is vital to success. An understanding of the value provided by the traumatologist includes all aspects of care including efficiency, availability, cost effectiveness, and research activities. To create effective and sustainable healthcare institutions, physicians and hospitals must be aligned over a sustained period of time. Unfortunately, external forces have eroded the historical basis for the working relationship between physicians and hospitals. Increased competition and reimbursement cuts, coupled with the increasing demands for quality, efficiency, and coordination and the payment changes outlined in healthcare reform, have left many organizations wondering how to best rebuild the relationship. The principal goal for the physician when partnering with a hospital or healthcare entity is to establish a sustainable model of service line management that protects or advances the physician's ability to make impactful improvements in quality of patient care, decreases in healthcare costs, and improvements in process efficiency through evidence-based practices and protocols.

  10. Large-scale symmetry-adapted perturbation theory computations via density fitting and Laplace transformation techniques: Investigating the fundamental forces of DNA-intercalator interactions

    NASA Astrophysics Data System (ADS)

    Hohenstein, Edward G.; Parrish, Robert M.; Sherrill, C. David; Turney, Justin M.; Schaefer, Henry F.

    2011-11-01

    Symmetry-adapted perturbation theory (SAPT) provides a means of probing the fundamental nature of intermolecular interactions. Low-orders of SAPT (here, SAPT0) are especially attractive since they provide qualitative (sometimes quantitative) results while remaining tractable for large systems. The application of density fitting and Laplace transformation techniques to SAPT0 can significantly reduce the expense associated with these computations and make even larger systems accessible. We present new factorizations of the SAPT0 equations with density-fitted two-electron integrals and the first application of Laplace transformations of energy denominators to SAPT. The improved scalability of the DF-SAPT0 implementation allows it to be applied to systems with more than 200 atoms and 2800 basis functions. The Laplace-transformed energy denominators are compared to analogous partial Cholesky decompositions of the energy denominator tensor. Application of our new DF-SAPT0 program to the intercalation of DNA by proflavine has allowed us to determine the nature of the proflavine-DNA interaction. Overall, the proflavine-DNA interaction contains important contributions from both electrostatics and dispersion. The energetics of the intercalator interaction are are dominated by the stacking interactions (two-thirds of the total), but contain important contributions from the intercalator-backbone interactions. It is hypothesized that the geometry of the complex will be determined by the interactions of the intercalator with the backbone, because by shifting toward one side of the backbone, the intercalator can form two long hydrogen-bonding type interactions. The long-range interactions between the intercalator and the next-nearest base pairs appear to be negligible, justifying the use of truncated DNA models in computational studies of intercalation interaction energies.

  11. Large-scale symmetry-adapted perturbation theory computations via density fitting and Laplace transformation techniques: investigating the fundamental forces of DNA-intercalator interactions.

    PubMed

    Hohenstein, Edward G; Parrish, Robert M; Sherrill, C David; Turney, Justin M; Schaefer, Henry F

    2011-11-07

    Symmetry-adapted perturbation theory (SAPT) provides a means of probing the fundamental nature of intermolecular interactions. Low-orders of SAPT (here, SAPT0) are especially attractive since they provide qualitative (sometimes quantitative) results while remaining tractable for large systems. The application of density fitting and Laplace transformation techniques to SAPT0 can significantly reduce the expense associated with these computations and make even larger systems accessible. We present new factorizations of the SAPT0 equations with density-fitted two-electron integrals and the first application of Laplace transformations of energy denominators to SAPT. The improved scalability of the DF-SAPT0 implementation allows it to be applied to systems with more than 200 atoms and 2800 basis functions. The Laplace-transformed energy denominators are compared to analogous partial Cholesky decompositions of the energy denominator tensor. Application of our new DF-SAPT0 program to the intercalation of DNA by proflavine has allowed us to determine the nature of the proflavine-DNA interaction. Overall, the proflavine-DNA interaction contains important contributions from both electrostatics and dispersion. The energetics of the intercalator interaction are are dominated by the stacking interactions (two-thirds of the total), but contain important contributions from the intercalator-backbone interactions. It is hypothesized that the geometry of the complex will be determined by the interactions of the intercalator with the backbone, because by shifting toward one side of the backbone, the intercalator can form two long hydrogen-bonding type interactions. The long-range interactions between the intercalator and the next-nearest base pairs appear to be negligible, justifying the use of truncated DNA models in computational studies of intercalation interaction energies.

  12. Demonstration of specific binding of heparin to Plasmodium falciparum-infected vs. non-infected red blood cells by single-molecule force spectroscopy.

    PubMed

    Valle-Delgado, Juan José; Urbán, Patricia; Fernàndez-Busquets, Xavier

    2013-05-07

    Glycosaminoglycans (GAGs) play an important role in the sequestration of Plasmodium falciparum-infected red blood cells (pRBCs) in the microvascular endothelium of different tissues, as well as in the formation of small clusters (rosettes) between infected and non-infected red blood cells (RBCs). Both sequestration and rosetting have been recognized as characteristic events in severe malaria. Here we have used heparin and pRBCs infected by the 3D7 strain of P. falciparum as a model to study GAG-pRBC interactions. Fluorescence microscopy and fluorescence-assisted cell sorting assays have shown that exogenously added heparin has binding specificity for pRBCs (preferentially for those infected with late forms of the parasite) vs. RBCs. Heparin-pRBC adhesion has been probed by single-molecule force spectroscopy, obtaining an average binding force ranging between 28 and 46 pN depending on the loading rate. No significant binding of heparin to non-infected RBCs has been observed in control experiments. This work represents the first approach to quantitatively evaluate GAG-pRBC molecular interactions at the individual molecule level.

  13. Forces and Kinetics of the Bacillus subtilis Spore Coat Proteins CotY and CotX Binding to CotE Inspected by Single Molecule Force Spectroscopy.

    PubMed

    Liu, Huiqing; Krajcikova, Daniela; Wang, Nan; Zhang, Zhe; Wang, Hongda; Barak, Imrich; Tang, Jilin

    2016-02-18

    Spores are uniquely stable cell types that are produced when bacteria encounter nutrient limitations. Spores are encased in a complex multilayered coat, which provides protection against environmental insults. The spore coat of Bacillus subtilis is composed of around 70 individual proteins that are organized into four distinct layers. Here we explored how morphogenetic protein CotE guides formation of the outermost layer of the coat, the crust, around the forespore by focusing on three proteins: CotE, CotY, and CotX. Single molecule force spectroscopy (SMFS) was used to investigate the interactions among CotE, CotY, and CotX at the single-molecule level. Direct interactions among these three proteins were observed. Additionally, the dissociation kinetics was also studied by measuring the unbinding forces of the complexes at different loading rates. A series of kinetic data of these complexes were acquired. It was found that the interaction of CotE and CotY was stronger than that of CotE and CotX.

  14. Effect of Ion-Binding and Chemical Phospholipid Structure on the Nanomechanics of Lipid Bilayers Studied by Force Spectroscopy

    PubMed Central

    Garcia-Manyes, Sergi; Oncins, Gerard; Sanz, Fausto

    2005-01-01

    The nanomechanical response of supported lipid bilayers has been studied by force spectroscopy with atomic force microscopy. We have experimentally proved that the amount of ions present in the measuring system has a strong effect on the force needed to puncture a 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer with an atomic force microscope tip, thus highlighting the role that monovalent cations (so far underestimated, e.g., Na+) play upon membrane stability. The increase in the yield threshold force has been related to the increase in lateral interactions (higher phospholipid-phospholipid interaction, decrease in area per lipid) promoted by ions bound into the membrane. The same tendency has also been observed for other phosphatidylcholine bilayers, namely, 2-dilauroyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1,2-dioleoyl-sn-3-phosphocholine, and also for phosphatidylethanolamine bilayers such as 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine. Finally, this effect has been also tested on a natural lipid bilayer (Escherichia coli lipid extract), showing the same overall tendency. The kinetics of the process has also been studied, together with the role of water upon membrane stability and its effect on membrane nanomechanics. Finally, the effect of the chemical structure of the phospholipid molecule on the nanomechanical response of the membrane has also been discussed. PMID:15980180

  15. Cardiac MyBP-C regulates the rate and force of contraction in mammalian myocardium Cardiac Myosin Binding Protein C

    PubMed Central

    Moss, Richard L.; Fitzsimons, Daniel P.; Ralphe, J. Carter

    2014-01-01

    Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that appears to contribute to the regulation of cardiac contraction through interactions with either myosin or actin or both. Several studies over the past several years have suggested that the interactions of cMyBP-C with its binding partners vary with its phosphorylation state, binding predominantly to myosin when dephosphorylated and to actin when it is phosphorylated by PKA or other kinases. Here, we summarize evidence suggesting that phosphorylation of cMyBP-C is a key regulator of the kinetics and amplitude of cardiac contraction during β-adrenergic stimulation and increased stimulus frequency. We propose a model for these effects via a phosphorylation-dependent regulation of the kinetics and extent of cooperative recruitment of cross-bridges to the thin filament – phosphorylation of cMyBP-C accelerates cross-bridge binding to actin, thereby accelerating recruitment and increasing the amplitude of the cardiac twitch. In contrast, enhanced lusitropy as a result of phosphorylation appears to be due to a direct effect of phosphorylation to accelerate cross-bridge detachment rate. Depression or elimination of one or both of these processes in a disease such as end-stage heart failure appears to contribute to the systolic and diastolic dysfunction that characterizes the disease. PMID:25552695

  16. Mechanical force effect on the two-state equilibrium of the hyaluronan-binding domain of CD44 in cell rolling

    PubMed Central

    Suzuki, Takashi; Suzuki, Miho; Ogino, Shinji; Umemoto, Ryo; Nishida, Noritaka; Shimada, Ichio

    2015-01-01

    CD44 is the receptor for hyaluronan (HA) and mediates cell rolling under fluid shear stress. The HA-binding domain (HABD) of CD44 interconverts between a low-affinity, ordered (O) state and a high-affinity, partially disordered (PD) state, by the conformational change of the C-terminal region, which is connected to the plasma membrane. To examine the role of tensile force on CD44-mediated rolling, we used a cell-free rolling system, in which recombinant HABDs were attached to beads through a C-terminal or N-terminal tag. We found that the rolling behavior was stabilized only at high shear stress, when the HABD was attached through the C-terminal tag. In contrast, no difference was observed for the beads coated with HABD mutants that constitutively adopt either the O state or the PD state. Steered molecular dynamics simulations suggested that the force from the C terminus disrupts the interaction between the C-terminal region and the core of the domain, thus providing structural insights into how the mechanical force triggers the allosteric O-to-PD transition. Based on these results, we propose that the force applied from the C terminus enhances the HABD–HA interactions by inducing the conformational change to the high-affinity PD transition more rapidly, thereby enabling CD44 to mediate lymphocyte trafficking and hematopoietic progenitor cell homing under high-shear conditions. PMID:26038553

  17. Hybrid Steered Molecular Dynamics Approach to Computing Absolute Binding Free Energy of Ligand-Protein Complexes: A Brute Force Approach That Is Fast and Accurate.

    PubMed

    Chen, Liao Y

    2015-04-14

    Computing the free energy of binding a ligand to a protein is a difficult task of essential importance for which purpose various theoretical/computational approaches have been pursued. In this paper, we develop a hybrid steered molecular dynamics (hSMD) method capable of resolving one ligand–protein complex within a few wall-clock days with high enough accuracy to compare with the experimental data. This hSMD approach is based on the relationship between the binding affinity and the potential of mean force (PMF) in the established literature. It involves simultaneously steering n (n = 1, 2, 3, ...) centers of mass of n selected segments of the ligand using n springs of infinite stiffness. Steering the ligand from a single initial state chosen from the bound state ensemble to the corresponding dissociated state, disallowing any fluctuations of the pulling centers along the way, one can determine a 3n-dimensional PMF curve connecting the two states by sampling a small number of forward and reverse pulling paths. This PMF constitutes a large but not the sole contribution to the binding free energy. Two other contributors are (1) the partial partition function containing the equilibrium fluctuations of the ligand at the binding site and the deviation of the initial state from the PMF minimum and (2) the partial partition function containing rotation and fluctuations of the ligand around one of the pulling centers that is fixed at a position far from the protein. We implement this hSMD approach for two ligand–protein complexes whose structures were determined and whose binding affinities were measured experimentally: caprylic acid binding to bovine β-lactoglobulin and glutathione binding to Schistosoma japonicum glutathione S-transferase tyrosine 7 to phenylalanine mutant. Our computed binding affinities agree with the experimental data within a factor of 1.5. The total time of computation for these two all-atom model systems (consisting of 96K and 114K atoms

  18. Different and often opposing forces drive the encapsulation and multiple exterior binding of charged guests to a M₄L₆ supramolecular vessel in water.

    PubMed

    Sgarlata, Carmelo; Mugridge, Jeffrey S; Pluth, Michael D; Zito, Valeria; Arena, Giuseppe; Raymond, Kenneth

    2017-09-12

    The supramolecular assembly [Ga₄L₆]¹²¯ acts as a nanoscale flask to mediate the reactivity of encapsulated reactive guests and also functions as a catalyst to carry out enzyme-like chemical transformations. The guest binding to the interior cavity and exterior of this host is difficult to untangle because multiple equilibria occur in solution, and only when refining simultaneously data obtained from different techniques, such as NMR, UV-vis and calorimetry, can the accurate solution thermodynamics of these host guest-systems be determined. This study reports on the driving forces for the inclusion and stepwise exterior guest binding of different aliphatic quaternary ammonium guests to the [Ga₄L₆]¹²¯assembly. Encapsulation into the host cavity was found to be an entropy driven process whereas exterior ion-association is driven either by enthalpically favorable attractive forces or by the entropy gain due to desolvation, depending on guest size and character. The analysis of the energetics of reaction may help predicting and understanding the intimate role and contribution of the transition state in those rate accelerated reactions involving this supramolecular assembly as an enzyme-like molecular flask. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. DOE Fundamentals Handbook: Classical Physics

    SciTech Connect

    Not Available

    1992-06-01

    The Classical Physics Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of physical forces and their properties. The handbook includes information on the units used to measure physical properties; vectors, and how they are used to show the net effect of various forces; Newton's Laws of motion, and how to use these laws in force and motion applications; and the concepts of energy, work, and power, and how to measure and calculate the energy involved in various applications. This information will provide personnel with a foundation for understanding the basic operation of various types of DOE nuclear facility systems and equipment.

  20. Leptospiral outer membrane lipoprotein LipL32 binding on toll-like receptor 2 of renal cells as determined with an atomic force microscope.

    PubMed

    Hsu, Shen-Hsing; Lo, Yueh-Yu; Tung, Jung-Yu; Ko, Yi-Ching; Sun, Yuh-Ju; Hung, Cheng-Chieh; Yang, Chih-Wei; Tseng, Fan-Gang; Fu, Chien-Chung; Pan, Rong-Long

    2010-07-06

    Leptopirosis is a renal disease caused by pathogenic Leptospira that primarily infects the renal proximal tubules, consequently resulting in severe tubular injuries and malfunctions. The protein extracted from the outer membrane of this pathogenic strain contains a major component of a 32 kDa lipoprotein (LipL32), which is absent in the counter membrane of nonpathogenic strains and has been identified as a crucial factor for host cell infection. Previous studies showed that LipL32 induced inflammatory responses and interacted with the extracellular matrix (ECM) of the host cell. However, the exact relationship between LipL32-mediated inflammatory responses and ECM binding is still unknown. In this study, an atomic force microscope with its tip modified by purified LipL32 was used to assess the interaction between LipL32 and cell surface receptors. Furthermore, an antibody neutralization technique was employed to identify Toll-like receptor 2 (TLR2) but not TLR4 as the major target of LipL32 attack. The interaction force between LipL32 and TLR2 was measured as approximately 59.5 +/- 8.7 pN, concurring with the theoretical value for a single-pair molecular interaction. Moreover, transformation of a TLR deficient cell line with human TLR2 brought the interaction force from the basal level to approximately 60.4 +/- 11.5 pN, confirming unambiguously TLR2 as counter receptor for LipL32. The stimulation of CXCL8/IL-8 expression by full-length LipL32 as compared to that without the N-terminal signal peptide domain suggests a significant role of the signal peptide of the protein in the inflammatory responses. This study provides direct evidence that LipL32 binds to TLR2, but not TLR4, on the cell surface, and a possible mechanism for the virulence of leptospirosis is accordingly proposed.

  1. Fundamental studies of polymer filtration

    SciTech Connect

    Smith, B.F.; Lu, M.T.; Robison, T.W.; Rogers, Y.C.; Wilson, K.V.

    1998-12-31

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The objectives of this project were (1) to develop an enhanced fundamental understanding of the coordination chemistry of hazardous-metal-ion complexation with water-soluble metal-binding polymers, and (2) to exploit this knowledge to develop improved separations for analytical methods, metals processing, and waste treatment. We investigated features of water-soluble metal-binding polymers that affect their binding constants and selectivity for selected transition metal ions. We evaluated backbone polymers using light scattering and ultrafiltration techniques to determine the effect of pH and ionic strength on the molecular volume of the polymers. The backbone polymers were incrementally functionalized with a metal-binding ligand. A procedure and analytical method to determine the absolute level of functionalization was developed and the results correlated with the elemental analysis, viscosity, and molecular size.

  2. A look at ligand binding thermodynamics in drug discovery.

    PubMed

    Claveria-Gimeno, Rafael; Vega, Sonia; Abian, Olga; Velazquez-Campoy, Adrian

    2017-04-01

    Drug discovery is a challenging endeavor requiring the interplay of many different research areas. Gathering information on ligand binding thermodynamics may help considerably in reducing the risk within a high uncertainty scenario, allowing early rejection of flawed compounds and pushing forward optimal candidates. In particular, the free energy, the enthalpy, and the entropy of binding provide fundamental information on the intermolecular forces driving such interaction. Areas covered: The authors review the current status and recent developments in the application of ligand binding thermodynamics in drug discovery. The thermodynamic binding profile (Gibbs energy, enthalpy, and entropy of binding) can be used for lead selection and optimization (binding enthalpy, selectivity, and adaptability). Expert opinion: Binding thermodynamics provides fundamental information on the forces driving the formation of the drug-target complex. It has been widely accepted that binding thermodynamics may be used as a decision criterion along the ligand optimization process in drug discovery and development. In particular, the binding enthalpy may be used as a guide when selecting and optimizing compounds over a set of potential candidates. However, this has been recently called into question by arguing certain difficulties and in the light of certain experimental examples.

  3. Mitochondrial motility in axons: membranous organelles may interact with the force generating system through multiple surface binding sites.

    PubMed

    Martz, D; Lasek, R J; Brady, S T; Allen, R D

    1984-01-01

    In living tissue, membrane-bound organelles, including mitochondria, move along parallel cytoplasmic pathways. Motion is directed and tends to be confined to a single path. Deviations from this single path motion are rare. When present, however, they tend to occur at points of intersection of cytoskeletal linear elements (LE). Such intersections are relatively uncommon in intact axons and extruded axoplasm. However, we have found that such intersections can be produced in extruded preparations by shear forces directed tangential to the axoplasmic surface. We have studied the detailed behavior of mitochondria in extruded squid axoplasm. Special attention was directed to the relationship between mitochondrial shape changes and orientation of cytoskeletal LE. The most striking of these changes in shape is branching. In this process, the mitochondrion transiently assumes a triradial (three-ended) shape. This appearance may be maintained for seconds to minutes before the normal cylindrical shape is resumed by absorption of either the newly formed end or, more commonly, one of the original ends. The frequency of branching appears to be dependent on the degree of cytoskeletal organization. It becomes more common as the number of apparent intersections between cytoskeletal LE increases. Further, the formation of new ends seems to occur along paths defined by cytoskeletal elements. These observations suggest that the mitochondrial membrane is multivalent. That is, it contains multiple sites capable of interacting with the axonal force generation apparatus. Furthermore, LE in the cytoskeleton may indicate the paths along which these interactions are permissible.

  4. Non-uniform binding of single-stranded DNA binding proteins to hybrids of single-stranded DNA and single-walled carbon nanotubes observed by atomic force microscopy in air and in liquid

    NASA Astrophysics Data System (ADS)

    Umemura, Kazuo; Ishizaka, Kei; Nii, Daisuke; Izumi, Katsuki

    2016-12-01

    Using atomic force spectroscopy (AFM), we observed hybrids of single-stranded DNA (ssDNA) and single-walled carbon nanotubes (SWNTs) with or without protein molecules in air and in an aqueous solution. This is the first report of ssDNA-SWNT hybrids with proteins in solution analyzed by AFM. In the absence of protein, the height of the ssDNA-SWNT hybrids was 1.1 ± 0.3 nm and 2.4 ± 0.6 nm in air and liquid, respectively, suggesting that the ssDNA molecules adopted a flexible structure on the SWNT surface. In the presence of single-stranded DNA binding (SSB) proteins, the heights of the hybrids in air and liquid increased to 6.4 ± 3.1 nm and 10.0 ± 4.5 nm, respectively. The AFM images clearly showed binding of the SSB proteins to the ssDNA-SWNT hybrids. The morphology of the SSB-ssDNA-SWNT hybrids was non-uniform, particularly in aqueous solution. The variance of hybrid height was quantitatively estimated by cross-section analysis along the long-axis of each hybrid. The SSB-ssDNA-SWNT hybrids showed much larger variance than the ssDNA-SWNT hybrids.

  5. Elevated rates of force development and MgATP binding in F764L and S532P myosin mutations causing dilated cardiomyopathy.

    PubMed

    Palmer, Bradley M; Schmitt, Joachim P; Seidman, Christine E; Seidman, J G; Wang, Yuan; Bell, Stephen P; Lewinter, Martin M; Maughan, David W

    2013-04-01

    Dilated cardiomyopathy (DCM) is a disease characterized by dilation of the ventricular chambers and reduced contractile function. We examined the contractile performance of chemically-skinned ventricular strips from two heterozygous murine models of DCM-causing missense mutations of myosin, F764L/+ and S532P/+, in an α-myosin heavy chain (MyHC) background. In Ca(2+)-activated skinned myocardial strips, the maximum developed tension in F764L/+ was only ~50% that of litter-mate controls (+/+). The F764L/+ also exhibited significantly reduced rigor stiffness, loaded shortening velocity and power output. Corresponding indices for S532P/+ strips were not different from controls. Manipulation of MgATP concentration in conjunction with measures of viscoelasticity, which provides estimates of myosin detachment rate 2πc, allowed us to probe the molecular basis of changes in crossbridge kinetics that occur with the myosin mutations. By examining the response of detachment rate to varying MgATP we found the rate of MgADP release was unaffected by the myosin mutations. However, MgATP binding rate was higher in the DCM groups compared to controls (422±109mM(-1)·s(-1) in F764L/+, 483±74mM(-1)·s(-1) in S532P/+ and 303±18mM(-1)·s(-1) in +/+). In addition, the rate constant of force development, 2πb, was significantly higher in DCM groups compared to controls (at 5mM MgATP: 36.9±4.9s(-1) in F764L/+, 32.9±4.5s(-1) in S532P/+ and 18.2±1.7s(-1) in +/+). These results suggest that elevated rates of force development and MgATP binding are features of cardiac myofilament function that underlie the development of DCM.

  6. Binding and Release between Polymeric Carrier and Protein Drug: pH Mediated Interplay of Coulomb forces, Hydrogen Bonding, van der Waals Interactions and Entropy.

    PubMed

    De Luca, Sergio; Chen, Fan; Seal, Prasenjit; Stenzel, Martina H; Smith, Sean C

    2017-09-07

    The accelerating search for new types of drugs and delivery strategies poses the challenge to understand the mechanism of delivery. To this end, a detailed atomistic picture of binding between the drug and the carrier is quintessential. While many studies focus on the electrostatics of drug-vector interactions, it has also been pointed out that entropic factors relating to water and counter ions can play an important role. By carrying out extensive molecular dynamics simulations and subsequently validating with experiment, we shed light herein on the binding in aqueous solution between a protein drug and a polymeric carrier. We examined the complexation between the polymer, poly (ethylene glycol) methyl ether acrylate-b-poly(carboxyethyl acrylate (PEGMEA-b-PCEA) and the protein, egg white lysozyme, a system that acts as a model for polymer-vector / protein-drug delivery systems. The complexation has been visualized and characterized using contact maps and hydrogen bonding analyses for five independent simulations of the complex, each running over 100 ns. Binding at physiological pH is, as expected, mediated by coulombic attraction between the positively charged protein and negatively charged carboxylate groups on the polymer. However, we find that consideration of electrostatics alone is insufficient to explain the complexation behaviour at low pH. Intra-complex hydrogen bonds, van der Waals interactions also water-water interactions dictate that the polymer does not release the protein at pH 4.8 or indeed at pH 3.2, even though the Coulombic attractions are largely removed as carboxylate groups on the polymer become titrated. Experiments in aqueous solution carried out at pH = 7.0, 4.5, and 3.0 confirm the veracity of the computed binding behaviour. Overall, these combined simulation and experimental results illustrate that coulomb interactions need to be complemented with consideration of other entropic forces, mediated by van der Waals interactions and hydrogen

  7. Combustion Fundamentals Research

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Increased emphasis is placed on fundamental and generic research at Lewis Research Center with less systems development efforts. This is especially true in combustion research, where the study of combustion fundamentals has grown significantly in order to better address the perceived long term technical needs of the aerospace industry. The main thrusts for this combustion fundamentals program area are as follows: analytical models of combustion processes, model verification experiments, fundamental combustion experiments, and advanced numeric techniques.

  8. Jewish Fundamentalism in Israel.

    DTIC Science & Technology

    1986-11-01

    1 Jewish Fundamentalism in Israeli Society ........................ 3 Definitions , Terminology, and Historical Background...discussed. ad2 .4 .4.o Lustick Jewish Fundamentalism Jewish Fundamentalism in Israeli Society Definitions , Terminology, and Historical Background...fundamentalist movement, requires the application of a broader, but carefully construed definition of "fundamentalist." For the purposes of this study a belief

  9. Exchange Rates and Fundamentals.

    ERIC Educational Resources Information Center

    Engel, Charles; West, Kenneth D.

    2005-01-01

    We show analytically that in a rational expectations present-value model, an asset price manifests near-random walk behavior if fundamentals are I (1) and the factor for discounting future fundamentals is near one. We argue that this result helps explain the well-known puzzle that fundamental variables such as relative money supplies, outputs,…

  10. Exchange Rates and Fundamentals.

    ERIC Educational Resources Information Center

    Engel, Charles; West, Kenneth D.

    2005-01-01

    We show analytically that in a rational expectations present-value model, an asset price manifests near-random walk behavior if fundamentals are I (1) and the factor for discounting future fundamentals is near one. We argue that this result helps explain the well-known puzzle that fundamental variables such as relative money supplies, outputs,…

  11. Mannose-Binding Lectin Inhibits the Motility of Pathogenic Salmonella by Affecting the Driving Forces of Motility and the Chemotactic Response

    PubMed Central

    Nakamura, Shuichi; Islam, Md. Shafiqul; Guo, Yijie; Ihara, Kohei; Tomioka, Rintaro; Masuda, Mizuki; Yoneyama, Hiroshi; Isogai, Emiko

    2016-01-01

    Mannose-binding lectin (MBL) is a key pattern recognition molecule in the lectin pathway of the complement system, an important component of innate immunity. MBL functions as an opsonin which enhances the sequential immune process such as phagocytosis. We here report an inhibitory effect of MBL on the motility of pathogenic bacteria, which occurs by affecting the energy source required for motility and the signaling pathway of chemotaxis. When Salmonella cells were treated with a physiological concentration of MBL, their motile fraction and free-swimming speed decreased. Rotation assays of a single flagellum showed that the flagellar rotation rate was significantly reduced by the addition of MBL. Measurements of the intracellular pH and membrane potential revealed that MBL affected a driving force for the Salmonella flagellum, the electrochemical potential difference of protons. We also found that MBL treatment increased the reversal frequency of Salmonella flagellar rotation, which interfered with the relative positive chemotaxis toward an attractive substrate. We thus propose that the motility inhibition effect of MBL may be secondarily involved in the attack against pathogens, potentially facilitating the primary role of MBL in the complement system. PMID:27104738

  12. A combined atomic force microscopy imaging and docking study to investigate the complex between p53 DNA binding domain and Azurin.

    PubMed

    Bizzarri, Anna Rita; Di Agostino, Silvia; Andolfi, Laura; Cannistraro, Salvatore

    2009-01-01

    The tumor suppressor p53 interacts with the redox copper protein Azurin (AZ) forming a complex which is of some relevance in biomedicine and cancer therapy. To obtain information on the spatial organization of this complex when it is immobilized on a substrate, we have used tapping mode-atomic force microscopy (TM-AFM) imaging combined with computational docking. The vertical dimension and the bearing volume of the DNA binding domain (DBD) of p53, anchored to functionalized gold substrate through exposed lysine residues, alone and after deposing AZ, have been measured by TM-AFM. By a computational docking approach, a three-dimensional model for the DBD of p53, before and after addition of AZ, have been predicted. Then we have calculated the possible arrangements of these biomolecular systems on gold substrate by finding a good agreement with the related experimental distribution of the height. The potentiality of the approach combining TM-AFM imaging and computational docking for the study of biomolecular complexes immobilized on substrates is briefly discussed.

  13. Fundamental Limits to Cellular Sensing

    NASA Astrophysics Data System (ADS)

    ten Wolde, Pieter Rein; Becker, Nils B.; Ouldridge, Thomas E.; Mugler, Andrew

    2016-03-01

    In recent years experiments have demonstrated that living cells can measure low chemical concentrations with high precision, and much progress has been made in understanding what sets the fundamental limit to the precision of chemical sensing. Chemical concentration measurements start with the binding of ligand molecules to receptor proteins, which is an inherently noisy process, especially at low concentrations. The signaling networks that transmit the information on the ligand concentration from the receptors into the cell have to filter this receptor input noise as much as possible. These networks, however, are also intrinsically stochastic in nature, which means that they will also add noise to the transmitted signal. In this review, we will first discuss how the diffusive transport and binding of ligand to the receptor sets the receptor correlation time, which is the timescale over which fluctuations in the state of the receptor, arising from the stochastic receptor-ligand binding, decay. We then describe how downstream signaling pathways integrate these receptor-state fluctuations, and how the number of receptors, the receptor correlation time, and the effective integration time set by the downstream network, together impose a fundamental limit on the precision of sensing. We then discuss how cells can remove the receptor input noise while simultaneously suppressing the intrinsic noise in the signaling network. We describe why this mechanism of time integration requires three classes (groups) of resources—receptors and their integration time, readout molecules, energy—and how each resource class sets a fundamental sensing limit. We also briefly discuss the scheme of maximum-likelihood estimation, the role of receptor cooperativity, and how cellular copy protocols differ from canonical copy protocols typically considered in the computational literature, explaining why cellular sensing systems can never reach the Landauer limit on the optimal trade

  14. The fundamental ribosomal RNA transcription initiation factor-IB (TIF-IB, SL1, factor D) binds to the rRNA core promoter primarily by minor groove contacts.

    PubMed

    Geiss, G K; Radebaugh, C A; Paule, M R

    1997-11-14

    Acanthamoeba castellanii transcription initiation factor-IB (TIF-IB) is the TATA-binding protein-containing transcription factor that binds the rRNA promoter to form the committed complex. Minor groove-specific drugs inhibit TIF-IB binding, with higher concentrations needed to disrupt preformed complexes because of drug exclusion by bound TIF-IB. TIF-IB/DNA interactions were mapped by hydroxyl radical and uranyl nitrate footprinting. TIF-IB contacts four minor grooves in its binding site. TIF-IB and DNA wrap around each other in a right-handed superhelix of high pitch, so the upstream and downstream contacts are on opposite faces of the helix. Dimethyl sulfate protection assays revealed limited contact with a few guanines in the major groove. This detailed analysis suggests significant DNA conformation dependence of the interaction.

  15. Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens.

    PubMed

    Pliakas, A M; Carlson, R R; Neve, R L; Konradi, C; Nestler, E J; Carlezon, W A

    2001-09-15

    Drugs of abuse regulate the transcription factor cAMP response element-binding protein (CREB) in striatal regions, including the nucleus accumbens (NAc). To explore how regulation of CREB in the NAc affects behavior, we used herpes simplex virus (HSV) vectors to elevate CREB expression in this region or to overexpress a dominant-negative mutant CREB (mCREB) that blocks CREB function. Rats treated with HSV-mCREB in place conditioning studies spent more time in environments associated with cocaine, indicating increased cocaine reward. Conversely, rats treated with HSV-CREB spent less time in cocaine-associated environments, indicating increased cocaine aversion. Studies in which drug-environment pairings were varied to coincide with either the early or late effects of cocaine suggest that CREB-associated place aversions reflect increased cocaine withdrawal. Because cocaine withdrawal can be accompanied by symptoms of depression, we examined how altered CREB function in the NAc affects behavior in the forced swim test (FST). Elevated CREB expression increased immobility in the FST, an effect that is opposite to that caused by standard antidepressants and is consistent with a link between CREB and dysphoria. Conversely, overexpression of mCREB decreased immobility, an effect similar to that caused by antidepressants. Moreover, the kappa opioid receptor antagonist nor-Binaltorphimine decreased immobility in HSV-CREB- and HSV-mCREB-treated rats, suggesting that CREB-mediated induction of dynorphin (an endogenous kappa receptor ligand) contributes to immobility behavior in the FST. Exposure to the FST itself dramatically increased CREB function in the NAc. These findings raise the possibility that CREB-mediated transcription within the NAc regulates dysphoric states.

  16. Fundamental Physical Constants

    National Institute of Standards and Technology Data Gateway

    SRD 121 CODATA Fundamental Physical Constants (Web, free access)   This site, developed in the Physics Laboratory at NIST, addresses three topics: fundamental physical constants, the International System of Units (SI), which is the modern metric system, and expressing the uncertainty of measurement results.

  17. Fundamentals of Physics

    NASA Astrophysics Data System (ADS)

    Halliday, David; Resnick, Robert; Walker, Jearl

    2003-01-01

    No other book on the market today can match the success of Halliday, Resnick and Walker's Fundamentals of Physics! In a breezy, easy-to-understand style the book offers a solid understanding of fundamental physics concepts, and helps readers apply this conceptual understanding to quantitative problem solving.

  18. Single-Cell Force Spectroscopy of Als-Mediated Fungal Adhesion

    PubMed Central

    Alsteens, David; Beaussart, Audrey; Derclaye, Sylvie; El-Kirat-Chatel, Sofiane; Park, Hye Rim; Lipke, Peter N.; Dufrêne, Yves F.

    2013-01-01

    Macroscopic assays that are traditionally used to investigate the adhesion behaviour of microbial cells provide averaged information obtained on large populations of cells and do not measure the fundamental forces driving single-cell adhesion. Here, we use single-cell force spectroscopy (SCFS) to quantify the specific and non-specific forces engaged in the adhesion of the human fungal pathogen Candida albicans. Saccharomyces cerevisiae cells expressing the C. albicans adhesion protein Als5p were attached on atomic force microscopy tipless cantilevers using a bioinspired polydopamine wet polymer, and force-distance curves were recorded between the obtained cell probes and various solid surfaces. Force signatures obtained on hydrophobic substrates exhibited large adhesion forces (1.25 ± 0.2 nN) with extended rupture lengths (up to 400 nm), attributed to the binding and stretching of the hydrophobic tandem repeats of Als5p. Data collected on fibronectin (Fn) -coated substrates featured strong adhesion forces (2.8 ± 0.6 nN), reflecting specific binding between Fn and the N-terminal immunoglobulin-like regions of Als5p, followed by weakly adhesive macromolecular bonds. Both hydrophobic and Fn adhesion forces increased with contact time, emphasizing the important role that time plays in strengthening adhesion. Our SCFS methodology provides a versatile platform in biomedicine for understanding the fundamental forces driving adhesion and biofilm formation in fungal pathogens. PMID:23956795

  19. Water clusters in an argon matrix: infrared spectra from molecular dynamics simulations with a self-consistent charge density functional-based tight binding/force-field potential.

    PubMed

    Simon, Aude; Iftner, Christophe; Mascetti, Joëlle; Spiegelman, Fernand

    2015-03-19

    The present theoretical study aims at investigating the effects of an argon matrix on the structures, energetics, dynamics, and infrared (IR) spectra of small water clusters (H2O)n (n = 1-6). The potential energy surface is obtained from a hybrid self-consistent charge density functional-based tight binding/force-field approach (SCC-DFTB/FF) in which the water clusters are treated at the SCC-DFTB level and the matrix is modeled at the FF level by a cluster consisting of ∼340 Ar atoms with a face centered cubic (fcc) structure, namely (H2O)n/Ar. With respect to a pure FF scheme, this allows a quantum description of the molecular system embedded in the matrix, along with all-atom geometry optimization and molecular dynamics (MD) simulations of the (H2O)n/Ar system. Finite-temperature IR spectra are derived from the MD simulations. The SCC-DFTB/FF scheme is first benchmarked on (H2O)Arn clusters against correlated wave function results and DFT calculations performed in the present work, and against FF data available in the literature. Regarding (H2O)n/Ar systems, the geometries of the water clusters are found to adapt to the fcc environment, possibly leading to intermolecular distortion and matrix perturbation. Several energetical quantities are estimated to characterize the water clusters in the matrix. In the particular case of the water hexamer, substitution and insertion energies for the prism, bag, and cage are found to be lower than that for the 6-member ring isomer. Finite-temperature MD simulations show that the water monomer has a quasifree rotation motion at 13 K, in agreement with experimental data. In the case of the water dimer, the only large-amplitude motion is a distortion-rotation intermolecular motion, whereas only vibration motions around the nuclei equilibrium positions are observed for clusters with larger sizes. Regarding the IR spectra, we find that the matrix environment leads to redshifts of the stretching modes and almost no shift of the

  20. The selective glucocorticoid receptor antagonist ORG 34116 decreases immobility time in the forced swim test and affects cAMP-responsive element-binding protein phosphorylation in rat brain.

    PubMed

    Bachmann, Cornelius G; Bilang-Bleuel, Alicia; De Carli, Sonja; Linthorst, Astrid C E; Reul, Johannes M H M

    2005-01-01

    Glucocorticoid receptor (GR) antagonists can block the retention of the immobility response in the forced swimming test. Recently, we showed that forced swimming evokes a distinct spatiotemporal pattern of cAMP-responsive element-binding protein (CREB) phosphorylation in the dentate gyrus (DG) and neocortex. In the present study, we found that chronic treatment of rats with the selective GR antagonist ORG 34116 decreased the immobility time in the forced swim test, increased baseline levels of phosphorylated CREB (P-CREB) in the DG and neocortex and affected the forced swimming-induced changes in P-CREB levels in a time- and site-specific manner. Overall, we observed that, in control rats, forced swimming evoked increases in P-CREB levels in the DG and neocortex, whereas in ORG 34116-treated animals a major dephosphorylation of P-CREB was observed. These observations underscore an important role of GRs in the control of the phosphorylation state of CREB which seems to be of significance for the immobility response in the forced swim test and extend the molecular mechanism of action of GRs in the brain.

  1. Measurement systems for cell adhesive forces.

    PubMed

    Zhou, Dennis W; García, Andrés J

    2015-02-01

    Cell adhesion to the extracellular matrix (ECM) involves integrin receptor-ligand binding and clustering to form focal adhesion (FA) complexes, which mechanically link the cell's cytoskeleton to the ECM and regulate fundamental cell signaling pathways. Although elucidation of the biochemical events in cell-matrix adhesive interactions is rapidly advancing, recent studies show that the forces underlying cell-matrix adhesive interactions are also critical to cell responses. Therefore, multiple measurement systems have been developed to quantify the spatial and temporal dynamics of cell adhesive forces, and these systems have identified how mechanical events influence cell phenotype and FA structure-function relationships under physiological and pathological settings. This review focuses on the development, methodology, and applications of measurement systems for probing (a) cell adhesion strength and (b) 2D and 3D cell traction forces.

  2. The Strong Nuclear Force

    SciTech Connect

    Lincoln, Don

    2016-05-24

    Scientists are aware of four fundamental forces- gravity, electromagnetism, and the strong and weak nuclear forces. Most people have at least some familiarity with gravity and electromagnetism, but not the other two. How is it that scientists are so certain that two additional forces exist? In this video, Fermilab’s Dr. Don Lincoln explains why scientists are so certain that the strong force exists.

  3. The Strong Nuclear Force

    ScienceCinema

    Lincoln, Don

    2016-07-12

    Scientists are aware of four fundamental forces- gravity, electromagnetism, and the strong and weak nuclear forces. Most people have at least some familiarity with gravity and electromagnetism, but not the other two. How is it that scientists are so certain that two additional forces exist? In this video, Fermilab’s Dr. Don Lincoln explains why scientists are so certain that the strong force exists.

  4. Fundamentals of the dwarf fundamental plane

    NASA Astrophysics Data System (ADS)

    McCall, M. L.; Vaduvescu, O.; Pozo Nunez, F.; Barr Dominguez, A.; Fingerhut, R.; Unda-Sanzana, E.; Li, B.; Albrecht, M.

    2012-04-01

    Aims: Star-forming dwarfs are studied to elucidate the physical underpinnings of their fundamental plane. Processes controlling dynamics are evaluated, connections between quiescent and bursting dwarfs are examined, and the viability of using structural properties of dwarfs to determine distances is assessed. Methods: Deep surface photometry in Ks is presented for 19 star-forming dwarfs. The data are amalgamated with previously published observations to create a sample of 66 galaxies suitable for exploring how global properties and kinematics are connected. Results: It is confirmed that residuals in the Tully-Fisher relation are correlated with surface brightness, but that even after accomodating the surface brightness dependence through the dwarf fundamental plane, residuals in absolute magnitude are far larger than expected from observational errors. Rather, a morefundamental plane is identified which connects the potential to HI line width and surface brightness. Residuals correlate with the axis ratio in a way which can be accommodated by recognizing the galaxies to be oblate spheroids viewed at varying angles. Correction of surface brightnesses to face-on leads to a correlation among the potential, line width, and surface brightness for which residuals are entirely attributable to observational uncertainties. The mean mass-to-light ratio of the diffuse component of the galaxies is constrained to be 0.88 ± 0.20 in Ks. Blue compact dwarfs lie in the same plane as dwarf irregulars. The dependence of the potential on line width is less strong than expected for virialized systems, but this may be because surface brightness is acting as a proxy for variations in the mass-to-light ratio from galaxy to galaxy. Altogether, the observations suggest that gas motions are predominantly disordered and isotropic, that they are a consequence of gravity, not turbulence, and that the mass and scale of dark matter haloes scale with the amount and distribution of luminous matter

  5. Arguing against fundamentality

    NASA Astrophysics Data System (ADS)

    McKenzie, Kerry

    This paper aims to open up discussion on the relationship between fundamentality and naturalism, and in particular on the question of whether fundamentality may be denied on naturalistic grounds. A historico-inductive argument for an anti-fundamentalist conclusion, prominent within the contemporary metaphysical literature, is examined; finding it wanting, an alternative 'internal' strategy is proposed. By means of an example from the history of modern physics - namely S-matrix theory - it is demonstrated that (1) this strategy can generate similar (though not identical) anti-fundamentalist conclusions on more defensible naturalistic grounds, and (2) that fundamentality questions can be empirical questions. Some implications and limitations of the proposed approach are discussed.

  6. Monte Carlo fundamentals

    SciTech Connect

    Brown, F.B.; Sutton, T.M.

    1996-02-01

    This report is composed of the lecture notes from the first half of a 32-hour graduate-level course on Monte Carlo methods offered at KAPL. These notes, prepared by two of the principle developers of KAPL`s RACER Monte Carlo code, cover the fundamental theory, concepts, and practices for Monte Carlo analysis. In particular, a thorough grounding in the basic fundamentals of Monte Carlo methods is presented, including random number generation, random sampling, the Monte Carlo approach to solving transport problems, computational geometry, collision physics, tallies, and eigenvalue calculations. Furthermore, modern computational algorithms for vector and parallel approaches to Monte Carlo calculations are covered in detail, including fundamental parallel and vector concepts, the event-based algorithm, master/slave schemes, parallel scaling laws, and portability issues.

  7. Fundamentals of fluid lubrication

    NASA Technical Reports Server (NTRS)

    Hamrock, Bernard J.

    1991-01-01

    The aim is to coordinate the topics of design, engineering dynamics, and fluid dynamics in order to aid researchers in the area of fluid film lubrication. The lubrication principles that are covered can serve as a basis for the engineering design of machine elements. The fundamentals of fluid film lubrication are presented clearly so that students that use the book will have confidence in their ability to apply these principles to a wide range of lubrication situations. Some guidance on applying these fundamentals to the solution of engineering problems is also provided.

  8. Fundamentals of fluid sealing

    NASA Technical Reports Server (NTRS)

    Zuk, J.

    1976-01-01

    The fundamentals of fluid sealing, including seal operating regimes, are discussed and the general fluid-flow equations for fluid sealing are developed. Seal performance parameters such as leakage and power loss are presented. Included in the discussion are the effects of geometry, surface deformations, rotation, and both laminar and turbulent flows. The concept of pressure balancing is presented, as are differences between liquid and gas sealing. Mechanisms of seal surface separation, fundamental friction and wear concepts applicable to seals, seal materials, and pressure-velocity (PV) criteria are discussed.

  9. Homeschooling and Religious Fundamentalism

    ERIC Educational Resources Information Center

    Kunzman, Robert

    2010-01-01

    This article considers the relationship between homeschooling and religious fundamentalism by focusing on their intersection in the philosophies and practices of conservative Christian homeschoolers in the United States. Homeschooling provides an ideal educational setting to support several core fundamentalist principles: resistance to…

  10. Basic Publication Fundamentals.

    ERIC Educational Resources Information Center

    Savedge, Charles E., Ed.

    Designed for students who produce newspapers and newsmagazines in junior high, middle, and elementary schools, this booklet is both a scorebook and a fundamentals text. The scorebook provides realistic criteria for judging publication excellence at these educational levels. All the basics for good publications are included in the text of the…

  11. The Fundamental Property Relation.

    ERIC Educational Resources Information Center

    Martin, Joseph J.

    1983-01-01

    Discusses a basic equation in thermodynamics (the fundamental property relation), focusing on a logical approach to the development of the relation where effects other than thermal, compression, and exchange of matter with the surroundings are considered. Also demonstrates erroneous treatments of the relation in three well-known textbooks. (JN)

  12. Fundamentals of Library Instruction

    ERIC Educational Resources Information Center

    McAdoo, Monty L.

    2012-01-01

    Being a great teacher is part and parcel of being a great librarian. In this book, veteran instruction services librarian McAdoo lays out the fundamentals of the discipline in easily accessible language. Succinctly covering the topic from top to bottom, he: (1) Offers an overview of the historical context of library instruction, drawing on recent…

  13. Food Service Fundamentals.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    Developed as part of the Marine Corps Institute (MCI) correspondence training program, this course on food service fundamentals is designed to provide a general background in the basic aspects of the food service program in the Marine Corps; it is adaptable for nonmilitary instruction. Introductory materials include specific information for MCI…

  14. Fundamentals of soil science

    USDA-ARS?s Scientific Manuscript database

    This study guide provides comments and references for professional soil scientists who are studying for the soil science fundamentals exam needed as the first step for certification. The performance objectives were determined by the Soil Science Society of America's Council of Soil Science Examiners...

  15. Fundamentals of Chemical Processes.

    ERIC Educational Resources Information Center

    Moser, William R.

    1985-01-01

    Describes a course that provides students with a fundamental understanding of the chemical, catalytic, and engineering sciences related to the chemical reactions taking place in a variety of reactors of different configurations. Also describes the eight major lecture topics, course examinations, and term papers. The course schedule is included.…

  16. Sales Fundamentals Guide.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Vocational Education.

    This curriculum guide is designed as a resource for marketing education teachers in planning and teaching a course on sales fundamentals for students in grades 10-12 who are interested in a sales career. Internships, simulations, and co-op experiences may be used to expand practical application of the course. The student course objectives are to…

  17. Fundamental research data base

    NASA Technical Reports Server (NTRS)

    1983-01-01

    A fundamental research data base containing ground truth, image, and Badhwar profile feature data for 17 North Dakota, South Dakota, and Minnesota agricultural sites is described. Image data was provided for a minimum of four acquisition dates for each site and all four images were registered to one another.

  18. Laser Fundamentals and Experiments.

    ERIC Educational Resources Information Center

    Van Pelt, W. F.; And Others

    As a result of work performed at the Southwestern Radiological Health Laboratory with respect to lasers, this manual was prepared in response to the increasing use of lasers in high schools and colleges. It is directed primarily toward the high school instructor who may use the text for a short course in laser fundamentals. The definition of the…

  19. Reading Is Fundamental, 1977.

    ERIC Educational Resources Information Center

    Smithsonian Institution, Washington, DC. National Reading is Fun-damental Program.

    Reading Is Fundamental (RIF) is a national, nonprofit organization designed to motivate children to read by making a wide variety of inexpensive books available to them and allowing the children to choose and keep books that interest them. This annual report for 1977 contains the following information on the RIF project: an account of the…

  20. Fundamentals of Diesel Engines.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    This student guide, one of a series of correspondence training courses designed to improve the job performance of members of the Marine Corps, deals with the fundamentals of diesel engine mechanics. Addressed in the three individual units of the course are the following topics: basic principles of diesel mechanics; principles, mechanics, and…

  1. Fundamentals of Solid Lubrication

    DTIC Science & Technology

    2012-03-01

    NOTES 14. ABSTRACT During this program, we have worked to develop a fundamental understanding of the chemical and tribological issues related to...approach, tribological measurements performed over a range of length scales, and the correlation of the two classes of information. Research activities...correlated measurements of surface composition and environmentally specific tribological performance of thin film solid lubricants. • Correlate shear

  2. Fundamentals of Electromagnetic Phenomena

    NASA Astrophysics Data System (ADS)

    Lorrain, Paul; Corson, Dale R.; Lorrain, Francois

    Based on the classic Electromagnetic Fields and Waves by the same authors, Fundamentals of Electromagnetic Phenomena capitalizes on the older text's traditional strengths--solid physics, inventive problems, and an experimental approach--while offering a briefer, more accessible introduction to the basic principles of electromagnetism.

  3. The Vα14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode

    PubMed Central

    Li, Yali; Girardi, Enrico; Wang, Jing; Yu, Esther Dawen; Painter, Gavin F.; Kronenberg, Mitchell

    2010-01-01

    Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-α–dependent structural changes in the F′ roof of CD1d; these changes resemble those occurring in the absence of TCR engagement when the highly potent synthetic antigen α-galactosylceramide (α-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi α–galactosyl diacylglycerol–CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles α-GalCer. The TCR-dependent reorientation of the sugar, together with the induced CD1d fit, may explain the weaker potency of the microbial antigens compared with α-GalCer. We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes. PMID:20921281

  4. Binding of an antibody mimetic of the human low density lipoprotein receptor to apolipoprotein E is governed through electrostatic forces. Studies using site-directed mutagenesis and molecular modeling.

    PubMed

    Raffaï, R; Weisgraber, K H; MacKenzie, R; Rupp, B; Rassart, E; Hirama, T; Innerarity, T L; Milne, R

    2000-03-10

    Monoclonal antibody 2E8 is specific for an epitope that coincides with the binding site of the low density lipoprotein receptor (LDLR) on human apoE. Its reactivity with apoE variants resembles that of the LDLR: it binds well with apoE3 and poorly with apoE2. The heavy chain complementarity-determining region (CDRH) 2 of 2E8 shows homology to the ligand-binding domain of the LDLR. To define better the structural basis of the 2E8/apoE interaction and particularly the role of electrostatic interactions, we generated and characterized a panel of 2E8 variants. Replacement of acidic residues in the 2E8 CDRHs showed that Asp(52), Glu(53), and Asp(56) are essential for high-affinity binding. Although Asp(31) (CDRH1), Glu(58) (CDRH2), and Asp(97) (CDRH3) did not appear to be critical, the Asp(97) --> Ala variant acquired reactivity with apoE2. A Thr(57) --> Glu substitution increased affinity for both apoE3 and apoE2. The affinities of wild-type 2E8 and variants for apoE varied inversely with ionic strength, suggesting that electrostatic forces contribute to both antigen binding and isoform specificity. We propose a model of the 2E8.apoE immune complex that is based on the 2E8 and apoE crystal structures and that is consistent with the apoE-binding properties of wild-type 2E8 and its variants. Given the similarity between the LDLR and 2E8 in terms of specificity, the LDLR/ligand interaction may also have an important electrostatic component.

  5. Fundamentals of Polarized Light

    NASA Technical Reports Server (NTRS)

    Mishchenko, Michael

    2003-01-01

    The analytical and numerical basis for describing scattering properties of media composed of small discrete particles is formed by the classical electromagnetic theory. Although there are several excellent textbooks outlining the fundamentals of this theory, it is convenient for our purposes to begin with a summary of those concepts and equations that are central to the subject of this book and will be used extensively in the following chapters. We start by formulating Maxwell's equations and constitutive relations for time- harmonic macroscopic electromagnetic fields and derive the simplest plane-wave solution that underlies the basic optical idea of a monochromatic parallel beam of light. This solution naturally leads to the introduction of such fundamental quantities as the refractive index and the Stokes parameters. Finally, we define the concept of a quasi-monochromatic beam of light and discuss its implications.

  6. Fundamental properties of resonances

    PubMed Central

    Ceci, S.; Hadžimehmedović, M.; Osmanović, H.; Percan, A.; Zauner, B.

    2017-01-01

    All resonances, from hydrogen nuclei excited by the high-energy gamma rays in deep space to newly discovered particles produced in Large Hadron Collider, should be described by the same fundamental physical quantities. However, two distinct sets of properties are used to describe resonances: the pole parameters (complex pole position and residue) and the Breit-Wigner parameters (mass, width, and branching fractions). There is an ongoing decades-old debate on which one of them should be abandoned. In this study of nucleon resonances appearing in the elastic pion-nucleon scattering we discover an intricate interplay of the parameters from both sets, and realize that neither set is completely independent or fundamental on its own. PMID:28345595

  7. Fundamental properties of resonances.

    PubMed

    Ceci, S; Hadžimehmedović, M; Osmanović, H; Percan, A; Zauner, B

    2017-03-27

    All resonances, from hydrogen nuclei excited by the high-energy gamma rays in deep space to newly discovered particles produced in Large Hadron Collider, should be described by the same fundamental physical quantities. However, two distinct sets of properties are used to describe resonances: the pole parameters (complex pole position and residue) and the Breit-Wigner parameters (mass, width, and branching fractions). There is an ongoing decades-old debate on which one of them should be abandoned. In this study of nucleon resonances appearing in the elastic pion-nucleon scattering we discover an intricate interplay of the parameters from both sets, and realize that neither set is completely independent or fundamental on its own.

  8. Fundamentals of Polarized Light

    NASA Technical Reports Server (NTRS)

    Mishchenko, Michael

    2003-01-01

    The analytical and numerical basis for describing scattering properties of media composed of small discrete particles is formed by the classical electromagnetic theory. Although there are several excellent textbooks outlining the fundamentals of this theory, it is convenient for our purposes to begin with a summary of those concepts and equations that are central to the subject of this book and will be used extensively in the following chapters. We start by formulating Maxwell's equations and constitutive relations for time- harmonic macroscopic electromagnetic fields and derive the simplest plane-wave solution that underlies the basic optical idea of a monochromatic parallel beam of light. This solution naturally leads to the introduction of such fundamental quantities as the refractive index and the Stokes parameters. Finally, we define the concept of a quasi-monochromatic beam of light and discuss its implications.

  9. Fundamental studies in geodynamics

    NASA Technical Reports Server (NTRS)

    Anderson, D. L.; Hager, B. H.; Kanamori, H.

    1981-01-01

    Research in fundamental studies in geodynamics continued in a number of fields including seismic observations and analysis, synthesis of geochemical data, theoretical investigation of geoid anomalies, extensive numerical experiments in a number of geodynamical contexts, and a new field seismic volcanology. Summaries of work in progress or completed during this report period are given. Abstracts of publications submitted from work in progress during this report period are attached as an appendix.

  10. Fundamentals of petroleum maps

    SciTech Connect

    Mc Elroy, D.P.

    1986-01-01

    It's a complete guide to the fundamentals of reading, using, and making petroleum maps. The topics covered are well spotting, lease posting, contouring, hanging cross sections, and ink drafting. This book not only tells the how of petroleum mapping, but it also tells the why to better understand the principles and techniques. The books does not teach ''drafting,'' but does describe the proper care and use of drafting equipment for those who are totally new to the task.

  11. Phacoemulsification. Technology and fundamentals.

    PubMed

    Gilger, B C

    1997-09-01

    The number one rule of phacoemulsification and aspiration cataract surgery is to know your machine. This chapter is designed to help the surgeon who is currently using phacoemulsification, or those who wish to understand more about technique, learn the basics and technology of the various types of phacoemulsification machines. Fluidics, pump design, handpiece mechanics, phacoemulsification needles, and fundamentals of phacoemulsification of cataracts will be reviewed.

  12. Redefining the Fundamental Questions

    ERIC Educational Resources Information Center

    Crain, Margaret Ann

    2006-01-01

    Every researcher must make some fundamental questions. A researcher's questions should include the following: (1) What is the nature of the reality that I wish to study? (2) How will I know it? (3) What must I do to know it? (4) Who am I? (5) Where is God in this? and (6) For religious educators--How does my research lead to a world of peace and…

  13. Fundamentals of Monte Carlo

    SciTech Connect

    Wollaber, Allan Benton

    2016-06-16

    This is a powerpoint presentation which serves as lecture material for the Parallel Computing summer school. It goes over the fundamentals of the Monte Carlo calculation method. The material is presented according to the following outline: Introduction (background, a simple example: estimating π), Why does this even work? (The Law of Large Numbers, The Central Limit Theorem), How to sample (inverse transform sampling, rejection), and An example from particle transport.

  14. Fundamentals of neurobiology.

    PubMed

    Greg Hall, D

    2011-01-01

    Session 1 of the 2010 STP/IFSTP Joint Symposium on Toxicologic Neuropathology, titled "Fundamentals of Neurobiology," was organized to provide a foundation for subsequent sessions by presenting essential elements of neuroanatomy and nervous system function. A brief introduction to the session titled "Introduction to Correlative Neurobiology" was provided by Dr. Greg Hall (Eli Lilly and Company, Indianapolis, IN). Correlative neurobiology refers to considerations of the relationships between the highly organized and compartmentalized structure of nervous tissues and the functioning within this system.

  15. Fundamentals of Structural Geology

    NASA Astrophysics Data System (ADS)

    Pollard, David D.; Fletcher, Raymond C.

    2005-09-01

    Fundamentals of Structural Geology provides a new framework for the investigation of geological structures by integrating field mapping and mechanical analysis. Assuming a basic knowledge of physical geology, introductory calculus and physics, it emphasizes the observational data, modern mapping technology, principles of continuum mechanics, and the mathematical and computational skills, necessary to quantitatively map, describe, model, and explain deformation in Earth's lithosphere. By starting from the fundamental conservation laws of mass and momentum, the constitutive laws of material behavior, and the kinematic relationships for strain and rate of deformation, the authors demonstrate the relevance of solid and fluid mechanics to structural geology. This book offers a modern quantitative approach to structural geology for advanced students and researchers in structural geology and tectonics. It is supported by a website hosting images from the book, additional colour images, student exercises and MATLAB scripts. Solutions to the exercises are available to instructors. The book integrates field mapping using modern technology with the analysis of structures based on a complete mechanics MATLAB is used to visualize physical fields and analytical results and MATLAB scripts can be downloaded from the website to recreate textbook graphics and enable students to explore their choice of parameters and boundary conditions The supplementary website hosts color images of outcrop photographs used in the text, supplementary color images, and images of textbook figures for classroom presentations The textbook website also includes student exercises designed to instill the fundamental relationships, and to encourage the visualization of the evolution of geological structures; solutions are available to instructors

  16. Value of Fundamental Science

    NASA Astrophysics Data System (ADS)

    Burov, Alexey

    Fundamental science is a hard, long-term human adventure that has required high devotion and social support, especially significant in our epoch of Mega-science. The measure of this devotion and this support expresses the real value of the fundamental science in public opinion. Why does fundamental science have value? What determines its strength and what endangers it? The dominant answer is that the value of science arises out of curiosity and is supported by the technological progress. Is this really a good, astute answer? When trying to attract public support, we talk about the ``mystery of the universe''. Why do these words sound so attractive? What is implied by and what is incompatible with them? More than two centuries ago, Immanuel Kant asserted an inseparable entanglement between ethics and metaphysics. Thus, we may ask: which metaphysics supports the value of scientific cognition, and which does not? Should we continue to neglect the dependence of value of pure science on metaphysics? If not, how can this issue be addressed in the public outreach? Is the public alienated by one or another message coming from the face of science? What does it mean to be politically correct in this sort of discussion?

  17. Quantum electrodynamics and fundamental constants

    NASA Astrophysics Data System (ADS)

    Wundt, Benedikt Johannes Wilhelm

    The unprecedented precision achieved both in the experimental measurements as well as in the theoretical description of atomic bound states make them an ideal study object for fundamental physics and the determination of fundamental constants. This requires a careful study of the effects from quantum electrodynamics (QED) on the interaction between the electron and the nucleus. The two theoretical approaches for the evaluation of QED corrections are presented and discussed. Due to the presence of two energy scales from the binding potential and the radiation field, an overlapping parameter has to be used in both approaches in order to separate the energy scales. The different choices for the overlapping parameter in the two methods are further illustrated in a model example. With the nonrelativistic theory, relativistic corrections in order ( Zalpha)2 to the two-photon decay rate of ionic states are calculated, as well as the leading radiative corrections of alpha( Zalpha)2ln[(Zalpha)-2 ]. It is shown that the corrections is gauge-invariant under a "hybrid" gauge transformation between Coulomb and Yennie gauge. Furthermore, QED corrections for Rydberg states in one-electron ions are investigated. The smallness of the corrections and the absence of nuclear size corrections enable very accurate theoretical predictions. Measuring transition frequencies and comparing them to the theoretical predictions, QED theory can be tested more precisely. In turn, this could yield a more accurate value for the Rydberg constant. Using a transition in a nucleus with a well determined mass, acting as a reference, a comparison to transition in other nuclei can even allow to determined nuclear masses. Finally, in order to avoid an additional uncertainty in nuclei with non zero nuclear spin, QED self-energy corrections to the hyperfine structure up to order alpha(Zalpha)2Delta EHFS are determined for highly excited Rydberg states.

  18. Force-clamp laser trapping of rapidly interacting molecules

    NASA Astrophysics Data System (ADS)

    Capitanio, Marco; Monico, Carina; Vanzi, Francesco; Pavone, Francesco S.

    2013-06-01

    Forces play a fundamental role in a wide array of biological processes, regulating enzymatic activity, kinetics of molecular bonds, and molecular motors mechanics. Single molecule force spectroscopy techniques have enabled the investigation of such processes, but they are inadequate to probe short-lived (millisecond and sub-millisecond) molecular complexes. We developed an ultrafast force-clamp spectroscopy technique that uses a dual trap configuration to apply constant loads to a single intermittently interacting biological polymer and a binding protein. Our system displays a delay of only ˜10 μs between formation of the molecular bond and application of the force and is capable of detecting interactions as short as 100 μs. The force-clamp configuration in which our assay operates allows direct measurements of load-dependence of lifetimes of single molecular bonds. Moreover, conformational changes of single proteins and molecular motors can be recorded with sub-nanometer accuracy and few tens of microseconds of temporal resolution. We demonstrate our technique on molecular motors, using myosin II from fast skeletal muscle and on protein-DNA interaction, specifically on Lactose repressor (LacI). The apparatus is stabilized to less than 1 nm with both passive and active stabilization, allowing resolving specific binding regions along the actin filament and DNA molecule. Our technique extends single-molecule force-clamp spectroscopy to molecular complexes that have been inaccessible up to now, opening new perspectives for the investigation of the effects of forces on biological processes.

  19. Fundamental experiments in velocimetry

    SciTech Connect

    Briggs, Matthew Ellsworth; Hull, Larry; Shinas, Michael

    2009-01-01

    One can understand what velocimetry does and does not measure by understanding a few fundamental experiments. Photon Doppler Velocimetry (PDV) is an interferometer that will produce fringe shifts when the length of one of the legs changes, so we might expect the fringes to change whenever the distance from the probe to the target changes. However, by making PDV measurements of tilted moving surfaces, we have shown that fringe shifts from diffuse surfaces are actually measured only from the changes caused by the component of velocity along the beam. This is an important simplification in the interpretation of PDV results, arising because surface roughness randomizes the scattered phases.

  20. Fundamental research data base

    NASA Technical Reports Server (NTRS)

    1983-01-01

    A fundamental research data base was created on a single 9-track 1600 BPI tape containing ground truth, image, and Badhwar profile feature data for 17 North Dakota, South Dakota, and Minnesota agricultural sites. Each site is 5x6 nm in area. Image data has been provided for a minimum of four acquisition dates for each site. All four images have been registered to one another. A list of the order of the files on tape and the dates of acquisition is provided.

  1. Electrostatic Forces as Dominant Interactions Between Proteins and Polyanions: an ESI MS Study of Fibroblast Growth Factor Binding to Heparin Oligomers

    NASA Astrophysics Data System (ADS)

    Minsky, Burcu Baykal; Dubin, Paul L.; Kaltashov, Igor A.

    2017-04-01

    The interactions between fibroblast growth factors (FGFs) and their receptors (FGFRs) are facilitated by heparan sulfate (HS) and heparin (Hp), highly sulfated biological polyelectrolytes. The molecular basis of FGF interactions with these polyelectrolytes is highly complex due to the structural heterogeneity of HS/Hp, and many details still remain elusive, especially the significance of charge density and minimal chain length of HS/Hp in growth factor recognition and multimerization. In this work, we use electrospray ionization mass spectrometry (ESI MS) to investigate the association of relatively homogeneous oligoheparins (octamer, dp8, and decamer, dp10) with acidic fibroblast growth factor (FGF-1). This growth factor forms 1:1, 2:1, and 3:1 protein/heparinoid complexes with both dp8 and dp10, and the fraction of bound protein is highly dependent on protein/heparinoid molar ratio. Multimeric complexes are preferentially formed on the highly sulfated Hp oligomers. Although a variety of oligomers appear to be binding-competent, there is a strong correlation between the affinity and the overall level of sulfation (the highest charge density polyanions binding FGF most strongly via multivalent interactions). These results show that the interactions between FGF-1 and Hp oligomers are primarily directed by electrostatics, and also demonstrate the power of ESI MS as a tool to study multiple binding equilibria between proteins and structurally heterogeneous polyanions.

  2. Electrostatic Forces as Dominant Interactions Between Proteins and Polyanions: an ESI MS Study of Fibroblast Growth Factor Binding to Heparin Oligomers.

    PubMed

    Minsky, Burcu Baykal; Dubin, Paul L; Kaltashov, Igor A

    2017-04-01

    The interactions between fibroblast growth factors (FGFs) and their receptors (FGFRs) are facilitated by heparan sulfate (HS) and heparin (Hp), highly sulfated biological polyelectrolytes. The molecular basis of FGF interactions with these polyelectrolytes is highly complex due to the structural heterogeneity of HS/Hp, and many details still remain elusive, especially the significance of charge density and minimal chain length of HS/Hp in growth factor recognition and multimerization. In this work, we use electrospray ionization mass spectrometry (ESI MS) to investigate the association of relatively homogeneous oligoheparins (octamer, dp8, and decamer, dp10) with acidic fibroblast growth factor (FGF-1). This growth factor forms 1:1, 2:1, and 3:1 protein/heparinoid complexes with both dp8 and dp10, and the fraction of bound protein is highly dependent on protein/heparinoid molar ratio. Multimeric complexes are preferentially formed on the highly sulfated Hp oligomers. Although a variety of oligomers appear to be binding-competent, there is a strong correlation between the affinity and the overall level of sulfation (the highest charge density polyanions binding FGF most strongly via multivalent interactions). These results show that the interactions between FGF-1 and Hp oligomers are primarily directed by electrostatics, and also demonstrate the power of ESI MS as a tool to study multiple binding equilibria between proteins and structurally heterogeneous polyanions. Graphical Abstract ᅟ.

  3. Electrostatic Forces as Dominant Interactions Between Proteins and Polyanions: an ESI MS Study of Fibroblast Growth Factor Binding to Heparin Oligomers

    NASA Astrophysics Data System (ADS)

    Minsky, Burcu Baykal; Dubin, Paul L.; Kaltashov, Igor A.

    2017-02-01

    The interactions between fibroblast growth factors (FGFs) and their receptors (FGFRs) are facilitated by heparan sulfate (HS) and heparin (Hp), highly sulfated biological polyelectrolytes. The molecular basis of FGF interactions with these polyelectrolytes is highly complex due to the structural heterogeneity of HS/Hp, and many details still remain elusive, especially the significance of charge density and minimal chain length of HS/Hp in growth factor recognition and multimerization. In this work, we use electrospray ionization mass spectrometry (ESI MS) to investigate the association of relatively homogeneous oligoheparins (octamer, dp8, and decamer, dp10) with acidic fibroblast growth factor (FGF-1). This growth factor forms 1:1, 2:1, and 3:1 protein/heparinoid complexes with both dp8 and dp10, and the fraction of bound protein is highly dependent on protein/heparinoid molar ratio. Multimeric complexes are preferentially formed on the highly sulfated Hp oligomers. Although a variety of oligomers appear to be binding-competent, there is a strong correlation between the affinity and the overall level of sulfation (the highest charge density polyanions binding FGF most strongly via multivalent interactions). These results show that the interactions between FGF-1 and Hp oligomers are primarily directed by electrostatics, and also demonstrate the power of ESI MS as a tool to study multiple binding equilibria between proteins and structurally heterogeneous polyanions.

  4. Testing Our Fundamental Assumptions

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Science is all about testing the things we take for granted including some of the most fundamental aspects of how we understand our universe. Is the speed of light in a vacuum the same for all photons regardless of their energy? Is the rest mass of a photon actually zero? A series of recent studies explore the possibility of using transient astrophysical sources for tests!Explaining Different Arrival TimesArtists illustration of a gamma-ray burst, another extragalactic transient, in a star-forming region. [NASA/Swift/Mary Pat Hrybyk-Keith and John Jones]Suppose you observe a distant transient astrophysical source like a gamma-ray burst, or a flare from an active nucleus and two photons of different energies arrive at your telescope at different times. This difference in arrival times could be due to several different factors, depending on how deeply you want to question some of our fundamental assumptions about physics:Intrinsic delayThe photons may simply have been emitted at two different times by the astrophysical source.Delay due to Lorentz invariance violationPerhaps the assumption that all massless particles (even two photons with different energies) move at the exact same velocity in a vacuum is incorrect.Special-relativistic delayMaybe there is a universal speed for massless particles, but the assumption that photons have zero rest mass is wrong. This, too, would cause photon velocities to be energy-dependent.Delay due to gravitational potentialPerhaps our understanding of the gravitational potential that the photons experience as they travel is incorrect, also causing different flight times for photons of different energies. This would mean that Einsteins equivalence principle, a fundamental tenet of general relativity (GR), is incorrect.If we now turn this problem around, then by measuring the arrival time delay between photons of different energies from various astrophysical sources the further away, the better we can provide constraints on these

  5. Fundamentals of Space Systems

    NASA Astrophysics Data System (ADS)

    Pisacane, Vincent L.

    2005-06-01

    Fundamentals of Space Systems was developed to satisfy two objectives: the first is to provide a text suitable for use in an advanced undergraduate or beginning graduate course in both space systems engineering and space system design. The second is to be a primer and reference book for space professionals wishing to broaden their capabilities to develop, manage the development, or operate space systems. The authors of the individual chapters are practicing engineers that have had extensive experience in developing sophisticated experimental and operational spacecraft systems in addition to having experience teaching the subject material. The text presents the fundamentals of all the subsystems of a spacecraft missions and includes illustrative examples drawn from actual experience to enhance the learning experience. It included a chapter on each of the relevant major disciplines and subsystems including space systems engineering, space environment, astrodynamics, propulsion and flight mechanics, attitude determination and control, power systems, thermal control, configuration management and structures, communications, command and telemetry, data processing, embedded flight software, survuvability and reliability, integration and test, mission operations, and the initial conceptual design of a typical small spacecraft mission.

  6. The social epidemiologic concept of fundamental cause.

    PubMed

    Ward, Andrew

    2007-01-01

    The goal of research in social epidemiology is not simply conceptual clarification or theoretical understanding, but more importantly it is to contribute to, and enhance the health of populations (and so, too, the people who constitute those populations). Undoubtedly, understanding how various individual risk factors such as smoking and obesity affect the health of people does contribute to this goal. However, what is distinctive of much on-going work in social epidemiology is the view that analyses making use of individual-level variables is not enough. In the spirit of Durkheim and Weber, S. Leonard Syme makes this point by writing that just "as bad water and food may be harmful to our health, unhealthful forces in our society may be detrimental to our capacity to make choices and to form opinions" conducive to health and well-being. Advocates of upstream (distal) causes of adverse health outcomes propose to identify the most important of these "unhealthful forces" as the fundamental causes of adverse health outcomes. However, without a clear, theoretically precise and well-grounded understanding of the characteristics of fundamental causes, there is little hope in applying the statistical tools of the health sciences to hypotheses about fundamental causes, their outcomes, and policies intended to enhance the health of populations. This paper begins the process of characterizing the social epidemiological concept of fundamental cause in a theoretically respectable and robust way.

  7. Structural Properties of MgSiO3 Perovskite, Twin Walls and Their Binding to Oxygen Vacancies at High Pressures from Force Field Simulations

    NASA Astrophysics Data System (ADS)

    Goncalves-Ferreira, L.; Redfern, S. A.; Artacho, E.

    2007-12-01

    Aiming to understand possible origins of seismic wave attenuation and variations in the quality factor (Q) of minerals at the Earth's interior, it has been accepted that the friction in the motion of twin domain walls under applied stress leads to a reduction in Q [1]. To interpret this behaviour one must first appreciate the influence of pressure on wall motion and dynamics. Experimental observations of twin wall motion at high pressure are difficult at present. For this reason, we have undertaken a computational study of wall structure and dynamics in MgSiO3 perovskite, in the absence or presence of defects, as a function of pressure between 0 and 140 GPa. This work is based on previous studies on CaTiO3 perovskite [2,3] (symmetry Pbnm) with 7800 atoms and orthorhombic periodic boundary conditions. It has been geometrically adapted to lower mantle's MgSiO3 perovskite. The system comprises two (100) ferroelastic twin walls separated by 34.2 Å, relaxed within a variable supercell of 26x10x6 unit cells, with the rigid ion set of interatomic potentials with partial ionic charges employed by Alfredsson et al., 2005 [4]. The degree of distortion in the system is manifest in the octahedral tilting angles along each of the crystallographic directions. The octahedral tilting orientations close to the walls are well described by the behaviour of two order parameters: the main one, defining the wall, goes as α tanh(2(x - x')/w) , where α = 11.14° is the bulk value for the tilt, and w = 11.11 Å is the wall width. The secondary order parameters describe a slight breather at the wall. As wall dynamics are influenced by the presence of oxygen vacancies, we have calculated their binding energies to the described twin walls as a function of pressure. We find that this binding strongly depends on the vacancy disposition. For a vacancy between Si atoms in an axis perpendicular to the wall the binding energy is 1.09 eV at zero pressure. For vacancies along Si-Si axes parallel

  8. Chemical Force Spectroscopy Evidence Supporting the Layer-by-Layer Model of Organic Matter Binding to Iron (oxy)Hydroxide Mineral Surfaces.

    PubMed

    Chassé, Alexander W; Ohno, Tsutomu; Higgins, Steven R; Amirbahman, Aria; Yildirim, Nadir; Parr, Thomas B

    2015-08-18

    The adsorption of dissolved organic matter (DOM) to metal (oxy)hydroxide mineral surfaces is a critical step for C sequestration in soils. Although equilibrium studies have described some of the factors controlling this process, the molecular-scale description of the adsorption process has been more limited. Chemical force spectroscopy revealed differing adhesion strengths of DOM extracted from three soils and a reference peat soil material to an iron (oxy)hydroxide mineral surface. The DOM was characterized using ultrahigh-resolution negative ion mode electrospray ionization Fourier Transform ion cyclotron resonance mass spectrometry. The results indicate that carboxyl-rich aromatic and N-containing aliphatic molecules of DOM are correlated with high adhesion forces. Increasing molecular mass was shown to decrease the adhesion force between the mineral surface and the DOM. Kendrick mass defect analysis suggests that mechanisms involving two carboxyl groups result in the most stable bond to the mineral surface. We conceptualize these results using a layer-by-layer "onion" model of organic matter stabilization on soil mineral surfaces.

  9. Binding Strength and Dynamics of Invariant Natural Killer Cell T Cell Receptor/CD1d-Glycosphingolipid Interaction on Living Cells by Single Molecule Force Spectroscopy*

    PubMed Central

    Bozna, Bianca L.; Polzella, Paolo; Rankl, Christian; Zhu, Rong; Salio, Mariolina; Shepherd, Dawn; Duman, Memed; Cerundolo, Vincenzo; Hinterdorfer, Peter

    2011-01-01

    Invariant natural killer T (iNKT) cells are a population of T lymphocytes that play an important role in regulating immunity to infection and tumors by recognizing endogenous and exogenous CD1d-bound lipid molecules. Using soluble iNKT T cell receptor (TCR) molecules, we applied single molecule force spectroscopy for the investigation of the iNKT TCR affinity for human CD1d molecules loaded with glycolipids differing in the length of the phytosphingosine chain using either recombinant CD1d molecules or lipid-pulsed THP1 cells. In both settings, the dissociation of the iNKT TCR from human CD1d molecules loaded with the lipid containing the longer phytosphingosine chain required higher unbinding forces compared with the shorter phytosphingosine lipid. Our findings are discussed in the context of previous results obtained by surface plasmon resonance measurements. We present new insights into the energy landscape and the kinetic rate constants of the iNKT TCR/human CD1d-glycosphingolipid interaction and emphasize the unique potential of single molecule force spectroscopy on living cells. PMID:21454514

  10. Binding strength and dynamics of invariant natural killer cell T cell receptor/CD1d-glycosphingolipid interaction on living cells by single molecule force spectroscopy.

    PubMed

    Bozna, Bianca L; Polzella, Paolo; Rankl, Christian; Zhu, Rong; Salio, Mariolina; Shepherd, Dawn; Duman, Memed; Cerundolo, Vincenzo; Hinterdorfer, Peter

    2011-05-06

    Invariant natural killer T (iNKT) cells are a population of T lymphocytes that play an important role in regulating immunity to infection and tumors by recognizing endogenous and exogenous CD1d-bound lipid molecules. Using soluble iNKT T cell receptor (TCR) molecules, we applied single molecule force spectroscopy for the investigation of the iNKT TCR affinity for human CD1d molecules loaded with glycolipids differing in the length of the phytosphingosine chain using either recombinant CD1d molecules or lipid-pulsed THP1 cells. In both settings, the dissociation of the iNKT TCR from human CD1d molecules loaded with the lipid containing the longer phytosphingosine chain required higher unbinding forces compared with the shorter phytosphingosine lipid. Our findings are discussed in the context of previous results obtained by surface plasmon resonance measurements. We present new insights into the energy landscape and the kinetic rate constants of the iNKT TCR/human CD1d-glycosphingolipid interaction and emphasize the unique potential of single molecule force spectroscopy on living cells.

  11. Fundamentals of gel dosimeters

    NASA Astrophysics Data System (ADS)

    McAuley, K. B.; Nasr, A. T.

    2013-06-01

    Fundamental chemical and physical phenomena that occur in Fricke gel dosimeters, polymer gel dosimeters, micelle gel dosimeters and genipin gel dosimeters are discussed. Fricke gel dosimeters are effective even though their radiation sensitivity depends on oxygen concentration. Oxygen contamination can cause severe problems in polymer gel dosimeters, even when THPC is used. Oxygen leakage must be prevented between manufacturing and irradiation of polymer gels, and internal calibration methods should be used so that contamination problems can be detected. Micelle gel dosimeters are promising due to their favourable diffusion properties. The introduction of micelles to gel dosimetry may open up new areas of dosimetry research wherein a range of water-insoluble radiochromic materials can be explored as reporter molecules.

  12. Wall of fundamental constants

    SciTech Connect

    Olive, Keith A.; Peloso, Marco; Uzan, Jean-Philippe

    2011-02-15

    We consider the signatures of a domain wall produced in the spontaneous symmetry breaking involving a dilatonlike scalar field coupled to electromagnetism. Domains on either side of the wall exhibit slight differences in their respective values of the fine-structure constant, {alpha}. If such a wall is present within our Hubble volume, absorption spectra at large redshifts may or may not provide a variation in {alpha} relative to the terrestrial value, depending on our relative position with respect to the wall. This wall could resolve the contradiction between claims of a variation of {alpha} based on Keck/Hires data and of the constancy of {alpha} based on Very Large Telescope data. We derive the properties of the wall and the parameters of the underlying microscopic model required to reproduce the possible spatial variation of {alpha}. We discuss the constraints on the existence of the low-energy domain wall and describe its observational implications concerning the variation of the fundamental constants.

  13. Fundamentals of zoological scaling

    NASA Astrophysics Data System (ADS)

    Lin, Herbert

    1982-01-01

    Most introductory physics courses emphasize highly idealized problems with unique well-defined answers. Though many textbooks complement these problems with estimation problems, few books present anything more than an elementary discussion of scaling. This paper presents some fundamentals of scaling in the zoological domain—a domain complex by any standard, but one also well suited to illustrate the power of very simple physical ideas. We consider the following animal characteristics: skeletal weight, speed of running, height and range of jumping, food consumption, heart rate, lifetime, locomotive efficiency, frequency of wing flapping, and maximum sizes of animals that fly and hover. These relationships are compared to zoological data and everyday experience, and match reasonably well.

  14. Nuclei and Fundamental Symmetries

    NASA Astrophysics Data System (ADS)

    Haxton, Wick

    2016-09-01

    Nuclei provide marvelous laboratories for testing fundamental interactions, often enhancing weak processes through accidental degeneracies among states, and providing selection rules that can be exploited to isolate selected interactions. I will give an overview of current work, including the use of parity violation to probe unknown aspects of the hadronic weak interaction; nuclear electric dipole moment searches that may shed light on new sources of CP violation; and tests of lepton number violation made possible by the fact that many nuclei can only decay by rare second-order weak interactions. I will point to opportunities in both theory and experiment to advance the field. Based upon work supported in part by the US Department of Energy, Office of Science, Office of Nuclear Physics and SciDAC under Awards DE-SC00046548 (Berkeley), DE-AC02-05CH11231 (LBNL), and KB0301052 (LBNL).

  15. Mapping the force-field of a hydrogen bonded assembly

    NASA Astrophysics Data System (ADS)

    Moriarty, Philip

    2014-03-01

    Hydrogen-bonding underpins the structure, properties, and dynamics of a vast array of systems spanning a wide variety of scientific fields. From the striking complexity of the phase diagram of H2O and the elegance of base pair interactions in DNA, to the directionality inherent in supramolecular self-assembly at surfaces, hydrogen bonds play an essential role in directing intermolecular forces. Yet fundamental aspects of the H-bond, including the magnitude of the force and binding energy, force constant, and decay length associated with the interaction, have been vigorously debated for many decades. I will discuss how dynamic force microscopy (DFM) using a qPlus sensor can quantitatively map the tip-sample force-field for naphthalene tetracarboxylic diimide (NTCDI) molecules hydrogen-bonded in 2D assemblies. A comparison of experimental images and force spectra with their simulated counterparts from density functional theory calculations shows that image contrast due to intermolecular hydrogen bonds arises fundamentally from charge density depletion due to strong tip-sample interactions. Interpretation of DFM images of hydrogen bonds therefore necessitates detailed consideration of the coupled tip-molecule system: analyses based on intermolecular charge density in the absence of the tip fail to capture the essential physical chemistry underpinning the imaging mechanism.

  16. Finite-difference analysis of plasmon-induced forces of metal nano-clusters by the Lorentz force formulation.

    PubMed

    Fujii, Masafumi

    2010-12-20

    We analyze light-induced forces on metal nano-spheres by using the three-dimensional finite-difference time-domain method with the Lorentz force formulation. Convergent analysis of the force on metal nano-particle clusters has been achieved by integrating the Lorentz and the Coulomb forces over the volume of the metal particles. Comparison to the Mie theory of radiation pressure on metal spheres under a plane wave illumination has verified rigorously the accuracy of the numerical method. We also analyze separate two metal spheres in close proximity and the results of the induced forces are compared to those in previous publications. The present method allows analysis of forces on various irregular structures; we apply the method to touching metal spheres, forming a simple cluster with a slight deformation at the contact point, to analyze the forces induced by the plasmonic resonance of the clusters. We show that the fundamental resonance modes, which newly appear in an infrared range when spheres are touching, exhibit strong binding forces within the clusters. Based on the numerical analyses we identify the resonance modes and evaluate quantitatively the infrared-induced forces on metal nano-sphere clusters.

  17. Fundamental frequency from classical molecular dynamics.

    PubMed

    Yamada, Tomonori; Aida, Misako

    2015-02-07

    We give a theoretical validation for calculating fundamental frequencies of a molecule from classical molecular dynamics (MD) when its anharmonicity is small enough to be treated by perturbation theory. We specifically give concrete answers to the following questions: (1) What is the appropriate initial condition of classical MD to calculate the fundamental frequency? (2) From that condition, how accurately can we extract fundamental frequencies of a molecule? (3) What is the benefit of using ab initio MD for frequency calculations? Our analytical approaches to those questions are classical and quantum normal form theories. As numerical examples we perform two types of MD to calculate fundamental frequencies of H2O with MP2/aug-cc-pVTZ: one is based on the quartic force field and the other one is direct ab initio MD, where the potential energies and the gradients are calculated on the fly. From those calculations, we show comparisons of the frequencies from MD with the post vibrational self-consistent field calculations, second- and fourth-order perturbation theories, and experiments. We also apply direct ab initio MD to frequency calculations of C-H vibrational modes of tetracene and naphthalene. We conclude that MD can give the same accuracy in fundamental frequency calculation as second-order perturbation theory but the computational cost is lower for large molecules.

  18. Fundamental Physics within Complex Plasmas

    NASA Astrophysics Data System (ADS)

    Douglass, Angela Michelle

    In this work, both experimental and numerical methods are used to investigate several of the fundamental processes and assumptions commonly found in an earth-based radio-frequency (RF) complex plasma discharge. First the manner in which the dust particle charge varies with the particle's height above the powered electrode is investigated. Knowledge of the dust particle charge is required to understand nearly all complex plasma experiments since it affects the dust particle's levitation height and particle-particle interactions. A fluid model which includes effects due to ion flow and electron depletion (which are significant dust charging effects within the sheath where the particles levitate) is employed to determine the plasma parameters required to calculate the dust particle charge. Second, the levitation limits of the dust particles and the structure of the sheath are investigated. The CASPER GEC RF reference cell is used to perform two experiments: one to measure the dust levitation height as a function of applied RF voltage and one to determine the electric force profile. The fluid model is then used to interpret the experimental results. This study provides a better understanding of the sheath structure, particle behavior within the sheath, and provides a new, in situ experimental method for locating the approximate height of the sheath edge in any dusty plasma system. Finally, both molecular dynamics (MD) simulations and an experiment are employed to determine the physical processes that a complex plasma system goes through as it rapidly transitions from a liquid to solid state.

  19. Binding Energy and Enzymatic Catalysis.

    ERIC Educational Resources Information Center

    Hansen, David E.; Raines, Ronald T.

    1990-01-01

    Discussed is the fundamental role that the favorable free energy of binding of the rate-determining transition state plays in catalysis. The principle that all of the catalytic factors discussed are realized by the use of this binding energy is reviewed. (CW)

  20. Binding Energy and Enzymatic Catalysis.

    ERIC Educational Resources Information Center

    Hansen, David E.; Raines, Ronald T.

    1990-01-01

    Discussed is the fundamental role that the favorable free energy of binding of the rate-determining transition state plays in catalysis. The principle that all of the catalytic factors discussed are realized by the use of this binding energy is reviewed. (CW)

  1. No fifth force?

    NASA Astrophysics Data System (ADS)

    Maggs, William Ward

    Hopes that geophysicists might be able to document a fifth force of nature have diminished, as new measurements and analyses of earlier geodetic experiments have yielded no solid evidence of a non-Newtonian component of gravity.Modern physics recognizes four fundamental forces with distinct spheres of influence: The strong and weak nuclear forces operate over the range of one atom, while gravity and electromagnetism have an infinite range. Gravity measurements over a few centimeters in laboratories and over millions of kilometers in space continue to buttress Issac Newton's conclusion that the gravitational force between two objects decreases as the square of the distance between them.

  2. GRBs and Fundamental Physics

    NASA Astrophysics Data System (ADS)

    Petitjean, Patrick; Wang, F. Y.; Wu, X. F.; Wei, J. J.

    2016-12-01

    Gamma-ray bursts (GRBs) are short and intense flashes at the cosmological distances, which are the most luminous explosions in the Universe. The high luminosities of GRBs make them detectable out to the edge of the visible universe. So, they are unique tools to probe the properties of high-redshift universe: including the cosmic expansion and dark energy, star formation rate, the reionization epoch and the metal evolution of the Universe. First, they can be used to constrain the history of cosmic acceleration and the evolution of dark energy in a redshift range hardly achievable by other cosmological probes. Second, long GRBs are believed to be formed by collapse of massive stars. So they can be used to derive the high-redshift star formation rate, which can not be probed by current observations. Moreover, the use of GRBs as cosmological tools could unveil the reionization history and metal evolution of the Universe, the intergalactic medium (IGM) properties and the nature of first stars in the early universe. But beyond that, the GRB high-energy photons can be applied to constrain Lorentz invariance violation (LIV) and to test Einstein's Equivalence Principle (EEP). In this paper, we review the progress on the GRB cosmology and fundamental physics probed by GRBs.

  3. Evaluation of the grand-canonical partition function using expanded Wang-Landau simulations. IV. Performance of many-body force fields and tight-binding schemes for the fluid phases of silicon

    NASA Astrophysics Data System (ADS)

    Desgranges, Caroline; Delhommelle, Jerome

    2016-03-01

    We extend Expanded Wang-Landau (EWL) simulations beyond classical systems and develop the EWL method for systems modeled with a tight-binding Hamiltonian. We then apply the method to determine the partition function and thus all thermodynamic properties, including the Gibbs free energy and entropy, of the fluid phases of Si. We compare the results from quantum many-body (QMB) tight binding models, which explicitly calculate the overlap between the atomic orbitals of neighboring atoms, to those obtained with classical many-body (CMB) force fields, which allow to recover the tetrahedral organization in condensed phases of Si through, e.g., a repulsive 3-body term that favors the ideal tetrahedral angle. Along the vapor-liquid coexistence, between 3000 K and 6000 K, the densities for the two coexisting phases are found to vary significantly (by 5 orders of magnitude for the vapor and by up to 25% for the liquid) and to provide a stringent test of the models. Transitions from vapor to liquid are predicted to occur for chemical potentials that are 10%-15% higher for CMB models than for QMB models, and a ranking of the force fields is provided by comparing the predictions for the vapor pressure to the experimental data. QMB models also reveal the formation of a gap in the electronic density of states of the coexisting liquid at high temperatures. Subjecting Si to a nanoscopic confinement has a dramatic effect on the phase diagram with, e.g. at 6000 K, a decrease in liquid densities by about 50% for both CMB and QMB models and an increase in vapor densities between 90% (CMB) and 170% (QMB). The results presented here provide a full picture of the impact of the strategy (CMB or QMB) chosen to model many-body effects on the thermodynamic properties of the fluid phases of Si.

  4. Fundamentals of Space Medicine

    NASA Astrophysics Data System (ADS)

    Clément, G.

    2003-10-01

    As of today, a total of more than 240 human space flights have been completed, involving about 450 astronauts from various countries, for a combined total presence in space of more than 70 years. The seventh long-duration expedition crew is currently in residence aboard the International Space Station, continuing a permanent presence in space that began in October 2000. During that time, investigations have been conducted on both humans and animal models to study the bone demineralization and muscle deconditioning, space motion sickness, the causes and possible treatment of postflight orthostatic intolerance, the changes in immune function, crew and crew-ground interactions, and the medical issues of living in a space environment, such as the effects of radiation or the risk of developing kidney stones. Some results of these investigations have led to fundamental discoveries about the adaptation of the human body to the space environment. Gilles Clément has been active in this research. This book presents in a readable text the findings from the life science experiments conducted during and after space missions. Topics discussed in this book include: adaptation of sensory-motor, cardiovascular, bone and muscle systems to the microgravity of spaceflight; psychological and sociological issues of living in a confined, isolated and stressful environment; operational space medicine, such as crew selection, training and in-flight health monitoring, countermeasures and support; results of space biology experiments on individual cells, plants, and animal models; and the impact of long-duration missions such as the human mission to Mars. The author also provides a detailed description of how to fly a space experiment, based on his own experience with research projects conducted onboard Salyut-7, Mir, Spacelab, and the Space Shuttle. Now is the time to look at the future of human spaceflight and what comes next. The future human exploration of Mars captures the imagination

  5. Fundamentals of Space Medicine

    NASA Astrophysics Data System (ADS)

    Clément, Gilles

    2005-03-01

    A total of more than 240 human space flights have been completed to date, involving about 450 astronauts from various countries, for a combined total presence in space of more than 70 years. The seventh long-duration expedition crew is currently in residence aboard the International Space Station, continuing a permanent presence in space that began in October 2000. During that time, investigations have been conducted on both humans and animal models to study the bone demineralization and muscle deconditioning, space motion sickness, the causes and possible treatment of postflight orthostatic intolerance, the changes in immune function, crew and crew-ground interactions, and the medical issues of living in a space environment, such as the effects of radiation or the risk of developing kidney stones. Some results of these investigations have led to fundamental discoveries about the adaptation of the human body to the space environment. Gilles Clément has been active in this research. This readable text presents the findings from the life science experiments conducted during and after space missions. Topics discussed in this book include: adaptation of sensory-motor, cardio-vascular, bone, and muscle systems to the microgravity of spaceflight; psychological and sociological issues of living in a confined, isolated, and stressful environment; operational space medicine, such as crew selection, training and in-flight health monitoring, countermeasures and support; results of space biology experiments on individual cells, plants, and animal models; and the impact of long-duration missions such as the human mission to Mars. The author also provides a detailed description of how to fly a space experiment, based on his own experience with research projects conducted onboard Salyut-7, Mir, Spacelab, and the Space Shuttle. Now is the time to look at the future of human spaceflight and what comes next. The future human exploration of Mars captures the imagination of both the

  6. Fundamentals of phosphate transfer.

    PubMed

    Kirby, Anthony J; Nome, Faruk

    2015-07-21

    Historically, the chemistry of phosphate transfer-a class of reactions fundamental to the chemistry of Life-has been discussed almost exclusively in terms of the nucleophile and the leaving group. Reactivity always depends significantly on both factors; but recent results for reactions of phosphate triesters have shown that it can also depend strongly on the nature of the nonleaving or "spectator" groups. The extreme stabilities of fully ionised mono- and dialkyl phosphate esters can be seen as extensions of the same effect, with one or two triester OR groups replaced by O(-). Our chosen lead reaction is hydrolysis-phosphate transfer to water: because water is the medium in which biological chemistry takes place; because the half-life of a system in water is an accepted basic index of stability; and because the typical mechanisms of hydrolysis, with solvent H2O providing specific molecules to act as nucleophiles and as general acids or bases, are models for reactions involving better nucleophiles and stronger general species catalysts. Not least those available in enzyme active sites. Alkyl monoester dianions compete with alkyl diester monoanions for the slowest estimated rates of spontaneous hydrolysis. High stability at physiological pH is a vital factor in the biological roles of organic phosphates, but a significant limitation for experimental investigations. Almost all kinetic measurements of phosphate transfer reactions involving mono- and diesters have been followed by UV-visible spectroscopy using activated systems, conveniently compounds with good leaving groups. (A "good leaving group" OR* is electron-withdrawing, and can be displaced to generate an anion R*O(-) in water near pH 7.) Reactivities at normal temperatures of P-O-alkyl derivatives-better models for typical biological substrates-have typically had to be estimated: by extended extrapolation from linear free energy relationships, or from rate measurements at high temperatures. Calculation is free

  7. Binding kinetics of mutant p53R175H with wild type p53 and p63: A Surface Plasmon Resonance and Atomic Force Spectroscopy study.

    PubMed

    Moscetti, Ilaria; Bizzarri, Anna Rita; Cannistraro, Salvatore

    2017-09-01

    The oncogenic mutant p53R175H, one of the most frequently occurring in human cancers and usually associated with poor prognosis and chemo resistance, can exert a dominant negative effect over p53 family members, namely wild type p53, p63 and p73, inhibiting their oncosuppressive function. Novel anticancer strategies based on drugs able to prevent the formation of complexes between p53R175H and the p53 family members call for a deeper knowledge on the molecular mechanisms of their interaction. To this aim, p53R175H/p63 and p53R175H/p53 complexes were investigated in vitro by using Surface Plasmon Resonance and Atomic Force Spectroscopy, two emerging and complementary techniques able to provide interaction kinetic information, in near physiological conditions and without any labelling. Both approaches show that p53R175H forms a very specific and highly stable bimolecular complex with both p63 and p53; with these interactions being characterized by a very high affinity with equilibrium dissociation constant, KD, of about 10(-9)M. These kinetics results, discussed also in connection with those previously reported for the interaction of p53R175H with p73, could inspire the design of suitable anticancer drugs able to antagonize the interaction of p53R175H with the p53 family members, by restoring then their anti-tumour function. Copyright © 2017. Published by Elsevier B.V.

  8. Assessment of DNA binding to human Rad51 protein by using quartz crystal microbalance and atomic force microscopy: effects of ADP and BRC4-28 peptide inhibitor.

    PubMed

    Esnault, Charles; Renodon-Cornière, Axelle; Takahashi, Masayuki; Casse, Nathalie; Delorme, Nicolas; Louarn, Guy; Fleury, Fabrice; Pilard, Jean-François; Chénais, Benoît

    2014-12-01

    The interaction of human Rad51 protein (HsRad51) with single-stranded deoxyribonucleic acid (ssDNA) was investigated by using quartz crystal microbalance (QCM) monitoring and atomic force microscopy (AFM) visualization. Gold surfaces for QCM and AFM were modified by electrografting of the in situ generated aryldiazonium salt from the sulfanilic acid to obtain the organic layer Au-ArSO3 H. The Au-ArSO3 H layer was activated by using a solution of PCl5 in CH2 Cl2 to give a Au-ArSO2 Cl layer. The modified surface was then used to immobilize long ssDNA molecules. The results obtained showed that the presence of adenosine diphosphate promotes the protein autoassociation rather than nucleation around DNA. In addition, when the BRC4-28 peptide inhibitor was used, both QCM and AFM confirmed the inhibitory effect of BRC4-28 toward HsRad51 autoassociation. Altogether these results show the suitability of this modified surface to investigate the kinetics and structure of DNA-protein interactions and for the screening of inhibitors.

  9. Plasma Sail Concept Fundamentals

    NASA Technical Reports Server (NTRS)

    Khazanov, G. V.; Delamere, P.; Kabin, K.; Linde, T. J.

    2004-01-01

    The mini-magnetospheric plasma propulsion (M2P2) device, originally proposed by Winglee et al., predicts that a 15-km standoff distance (or 20-km cross-sectional dimension) of the magnetic bubble will provide for sufficient momentum transfer from the solar wind to accelerate a spacecraft to unprecedented speeds of 50 C80 km/s after an acceleration period of 3 mo. Such velocities will enable travel out of the solar system in period of 7 yr almost an order of magnitude improvement over present chemical-based propulsion systems. However, for the parameters of the simulation of Winglee et al., a fluid model for the interaction of M2P2 with the solar wind is not valid. It is assumed in the magnetohydrodynamic (MHD) fluid model, normally applied to planetary magnetospheres, that the characteristic scale size is much greater than the Larmor radius and ion skin depth of the solar wind. In the case of M2P2, the size of the magnetic bubble is actually less than or comparable to the scale of these characteristic parameters. Therefore, a kinetic approach, which addresses the small-scale physical mechanisms, must be used. A two-component approach to determining a preliminary estimate of the momentum transfer to the plasma sail has been adopted. The first component is a self-consistent MHD simulation of the small-scale expansion phase of the magnetic bubble. The fluid treatment is valid to roughly 5 km from the source and the steady-state MHD solution at the 5 km boundary was then used as initial conditions for the hybrid simulation. The hybrid simulations showed that the forces delivered to the innermost regions of the plasma sail are considerably ( 10 times) smaller than the MHD counterpart, are dominated by the magnetic field pressure gradient, and are directed primarily in the transverse direction.

  10. Is there any fundamental difference between ionic, covalent, and others types of bond? A canonical perspective on the question.

    PubMed

    Walton, Jay R; Rivera-Rivera, Luis A; Lucchese, Robert R; Bevan, John W

    2017-06-21

    The concept of chemical bonding is normally presented and simplified through two models: the covalent bond and the ionic bond. Expansion of the ideal covalent and ionic models leads chemists to the concepts of electronegativity and polarizability, and thus to the classification of polar and non-polar bonds. In addition, the intermolecular interactions are normally viewed as physical phenomena without direct correlation to the chemical bond in any simplistic model. Contrary to these traditional concepts of chemical bonding, recently developed canonical approaches demonstrate a unified perspective on the nature of binding in pairwise interatomic interactions. This new canonical model, which is a force-based approach with a basis in fundamental molecular quantum mechanics, confirms much earlier assertions that in fact there are no fundamental distinctions among covalent bonds, ionic bonds, and intermolecular interactions including the hydrogen bond, the halogen bond, and van der Waals interactions.

  11. On Correlation Effect of the Van-der-Waals and Intramolecular Forces for the Nucleotide Chain - Metallic Nanoparticles - Carbon Nanotube Binding.

    PubMed

    Khusenov, M A; Dushanov, E B; Kholmurodov, Kh T; Zaki, M M; Sweilam, N H

    2016-01-01

    The tertiary system of nucleotide chain (NC) - gold nanoparticles (NPs) - carbon nanotube (CNT) represents a great interest in the modern research and application of the bio-nano-technologies. The application aspects include, for example, the development of electronic mobile diagnostic facilities, nanorobotic design for a drug delivery inside living cell, and so on. The small NC chain represents an important stage in the understanding of the interaction mechanism of a full DNA or RNA molecule with NP and CNT. In this regard, one has to mention the development of the DNA-CNT devices for the purposes of diagnostic applications in the chemical or drug delivery. For the NC-NP-CNT system, we have built up a series of the molecular dynamics (MD) models with different NC-NP configurations and performed their MD analysis. The entire system (the NC chain, gold NPs and CNT) was allowed to interact with each other by the only VdW forces. The Lennard-Jones short-ranged interaction was assumed between the NC, NP and CNT. For the CNT a many body Tersoff potential having a quantum-chemistry nature was used. So far, the so-called hybrid MD approach was realized, where the quantum-chemistry potential in combination with a classical trajectory calculation applied . The peculiarities of the NC-NP interaction and bond formation inside of a CNT matrix were investigated along with the structural and dynamical behavior. The correlation effects between the weak Van der Waals (VdW) forces and intramolecular vibrations were enlighten for the molecular system consisting of a small nucleotide chain (NC), gold nanoparticles (NPs) and carbon nanotube (CNT) using molecular dynamics (MD) simulation method. The NC intermolecular motions were estimated from MD data thereby building the distance distributions, the angular and dihedral (torsional) bond energy graphs versus simulation time at different temperatures from T=100 K up to 300 K. The MD simulation results have shown that depending on the

  12. On Correlation Effect of the Van-der-Waals and Intramolecular Forces for the Nucleotide Chain - Metallic Nanoparticles - Carbon Nanotube Binding

    PubMed Central

    Khusenov, M.A.; Dushanov, E.B.; Kholmurodov, Kh.T; Zaki, M.M.; Sweilam, N.H.

    2016-01-01

    Background: The tertiary system of nucleotide chain (NC) - gold nanoparticles (NPs) - carbon nanotube (CNT) represents a great interest in the modern research and application of the bio-nano-technologies. The application aspects include, for example, the development of electronic mobile diagnostic facilities, nanorobotic design for a drug delivery inside living cell, and so on. The small NC chain represents an important stage in the understanding of the interaction mechanism of a full DNA or RNA molecule with NP and CNT. In this regard, one has to mention the development of the DNA-CNT devices for the purposes of diagnostic applications in the chemical or drug delivery. Methods: For the NC-NP-CNT system, we have built up a series of the molecular dynamics (MD) models with different NC-NP configurations and performed their MD analysis. The entire system (the NC chain, gold NPs and CNT) was allowed to interact with each other by the only VdW forces. The Lennard-Jones short-ranged interaction was assumed between the NC, NP and CNT. For the CNT a many body Tersoff potential having a quantum-chemistry nature was used. So far, the so-called hybrid MD approach was realized, where the quantum-chemistry potential in combination with a classical trajectory calculation applied . Results: The peculiarities of the NC-NP interaction and bond formation inside of a CNT matrix were investigated along with the structural and dynamical behavior. The correlation effects between the weak Van der Waals (VdW) forces and intramolecular vibrations were enlighten for the molecular system consisting of a small nucleotide chain (NC), gold nanoparticles (NPs) and carbon nanotube (CNT) using molecular dynamics (MD) simulation method. Conclusion: The NC intermolecular motions were estimated from MD data thereby building the distance distributions, the angular and dihedral (torsional) bond energy graphs versus simulation time at different temperatures from T=100 K up to 300 K. The MD simulation

  13. Liposculpture 4. Fundamentals of good liposculpture technique.

    PubMed

    Fischer, G

    1992-03-01

    The fundamentals for good liposculpture are discussed. Horizontal tunneling is to be avoided because the more horizontally the tunnel is angled, the more likely the overlying skin will drape in folds, resulting in poor cosmesis. Superficial tunneling (less than 1 cm) is to be avoided. The author believes that it is important to maintain the adhesive forces and lymphatics of the superficial layer of fat because it leads to more even healing and remodelling postoperatively. Liposuction within 3 cm of the subgluteal fold should be avoided because it can lead to ptosis of the buttocks postoperatively.

  14. Entropic force between biomembranes

    NASA Astrophysics Data System (ADS)

    Li, Long; Song, Fan

    2016-10-01

    Undulation force, an entropic force, stems from thermally excited fluctuations, and plays a key role in the essential interactions between neighboring surfaces of objects. Although the characteristics of the undulation force have been widely studied theoretically and experimentally, the distance dependence of the force, which constitutes its most fundamental characteristic, remains poorly understood. In this paper, first, we obtain a novel expression for the undulation force by employing elasticity and statistical mechanics and prove it to be in good agreement with existing experimental results. Second, we clearly demonstrate that the two representative forms of the undulation force proposed by Helfrich and Freund were respectively the upper and lower bounds of the present expression when the separation between membranes is sufficiently small, which was intrinsically different from the existing results where Helfrich's and Freund's forms of the undulation force were only suitable for the intermediate and small separations. The investigations show that only in a sufficiently small separation does Helfrich's result stand for the undulation force with a large wave number and Freund's result express the force with a small wave number. Finally, a critical acting distance of the undulation force, beyond which the entropic force will rapidly decay approaching zero, is presented.

  15. An Evaluation of Fundamental Schools.

    ERIC Educational Resources Information Center

    Weber, Larry J.; And Others

    1984-01-01

    When compared with regular schools in the same district, fundamental school students performed as well as or better than regular school students; fundamental schools rated better on learning climate, discipline, and suspensions; and there were no differences in student self-concept. (Author/BW)

  16. Fundamental mechanisms of micromachine reliability

    SciTech Connect

    DE BOER,MAARTEN P.; SNIEGOWSKI,JEFFRY J.; KNAPP,JAMES A.; REDMOND,JAMES M.; MICHALSKE,TERRY A.; MAYER,THOMAS K.

    2000-01-01

    Due to extreme surface to volume ratios, adhesion and friction are critical properties for reliability of Microelectromechanical Systems (MEMS), but are not well understood. In this LDRD the authors established test structures, metrology and numerical modeling to conduct studies on adhesion and friction in MEMS. They then concentrated on measuring the effect of environment on MEMS adhesion. Polycrystalline silicon (polysilicon) is the primary material of interest in MEMS because of its integrated circuit process compatibility, low stress, high strength and conformal deposition nature. A plethora of useful micromachined device concepts have been demonstrated using Sandia National Laboratories' sophisticated in-house capabilities. One drawback to polysilicon is that in air the surface oxidizes, is high energy and is hydrophilic (i.e., it wets easily). This can lead to catastrophic failure because surface forces can cause MEMS parts that are brought into contact to adhere rather than perform their intended function. A fundamental concern is how environmental constituents such as water will affect adhesion energies in MEMS. The authors first demonstrated an accurate method to measure adhesion as reported in Chapter 1. In Chapter 2 through 5, they then studied the effect of water on adhesion depending on the surface condition (hydrophilic or hydrophobic). As described in Chapter 2, they find that adhesion energy of hydrophilic MEMS surfaces is high and increases exponentially with relative humidity (RH). Surface roughness is the controlling mechanism for this relationship. Adhesion can be reduced by several orders of magnitude by silane coupling agents applied via solution processing. They decrease the surface energy and render the surface hydrophobic (i.e. does not wet easily). However, only a molecular monolayer coats the surface. In Chapters 3-5 the authors map out the extent to which the monolayer reduces adhesion versus RH. They find that adhesion is independent of

  17. Nanofluids mediating surface forces.

    PubMed

    Pilkington, Georgia A; Briscoe, Wuge H

    2012-11-01

    Fluids containing nanostructures, known as nanofluids, are increasingly found in a wide array of applications due to their unique physical properties as compared with their base fluids and larger colloidal suspensions. With several tuneable parameters such as the size, shape and surface chemistry of nanostructures, as well as numerous base fluids available, nanofluids also offer a new paradigm for mediating surface forces. Other properties such as local surface plasmon resonance and size dependent magnetism of nanostructures also present novel mechanisms for imparting tuneable surface interactions. However, our fundamental understanding, experimentally and theoretically, of how these parameters might affect surface forces remains incomplete. Here we review recent results on equilibrium and dynamic surface forces between macroscopic surfaces in nanofluids, highlighting the overriding trends in the correlation between the physical parameters that characterise nanofluids and the surface forces they mediate. We also discuss the challenges that confront existing surface force knowledge as a result of this new paradigm.

  18. Fundamental Investigations of the Tribological Properties of Biological Interfaces

    DTIC Science & Technology

    2005-10-01

    Final Technical Report Air Force Contract # F49620-02-1-0346 Fundamental Investigations of the Tribological Properties of Biological Interfaces For... tribological systems lubricated by aqueous solutions. The proposed experimental program will be aimed at measuring interfacial forces over a range of...structure) in determining the adsorption, load- bearing , and frictional properties of self-assembling waterborne organic coatings. It will also examine

  19. Ablative Thermal Protection System Fundamentals

    NASA Technical Reports Server (NTRS)

    Beck, Robin A. S.

    2013-01-01

    This is the presentation for a short course on the fundamentals of ablative thermal protection systems. It covers the definition of ablation, description of ablative materials, how they work, how to analyze them and how to model them.

  20. Clinical fundamentals for radiation oncologists.

    PubMed

    Yang, Jack

    2011-11-01

    Clinical fundamentals for radiation oncologists. Hasan Murshed. Medical Physics Publishing, Madison, WI, 2011. 680 pp. (soft cover), Price: $90.00. 978-1-930524-43-9. © 2011 American Association of Physicists in Medicine.

  1. Fundamental principles of particle detectors

    SciTech Connect

    Fernow, R.C.

    1988-01-01

    This paper goes through the fundamental physics of particles-matter interactions which is necessary for the detection of these particles with detectors. A listing of 41 concepts and detector principles are given. 14 refs., 11 figs.

  2. Chiral discrimination in optical binding

    NASA Astrophysics Data System (ADS)

    Forbes, Kayn A.; Andrews, David L.

    2015-05-01

    The laser-induced intermolecular force that exists between two or more particles in the presence of an electromagnetic field is commonly termed "optical binding." Distinct from the single-particle forces that are at play in optical trapping at the molecular level, the phenomenon of optical binding is a manifestation of the coupling between optically induced dipole moments in neutral particles. In other, more widely known areas of optics, there are many examples of chiral discrimination—signifying the different response a chiral material has to the handedness of an optical input. In the present analysis, extending previous work on chiral discrimination in optical binding, a mechanism is identified using a quantum electrodynamical approach. It is shown that the optical binding force between a pair of chiral molecules can be significantly discriminatory in nature, depending upon both the handedness of the interacting particles and the polarization of the incident light, and it is typically several orders of magnitude larger than previously reported.

  3. Defining the fundamentals of care.

    PubMed

    Kitson, Alison; Conroy, Tiffany; Wengstrom, Yvonne; Profetto-McGrath, Joanne; Robertson-Malt, Suzi

    2010-08-01

    A three-stage process is being undertaken to investigate the fundamentals of care. Stage One (reported here) involves the use of a met a-narrative review methodology to undertake a thematic analysis, categorization and synthesis of selected contents extracted from seminal texts relating to nursing practice. Stage Two will involve a search for evidence to inform the fundamentals of care and a refinement of the review method. Stage Three will extend the reviews of the elements defined as fundamentals of care. This introductory paper covers the following aspects: the conceptual basis upon which nursing care is delivered; how the fundamentals of care have been defined in the literature and in practice; an argument that physiological aspects of care, self-care elements and aspects of the environment of care are central to the conceptual refinement of the term fundamentals of care; and that efforts to systematize such information will enhance overall care delivery through improvements in patient safety and quality initiatives in health systems.

  4. Astrophysical probes of fundamental physics

    NASA Astrophysics Data System (ADS)

    Martins, C. J. A. P.

    2009-10-01

    I review the motivation for varying fundamental couplings and discuss how these measurements can be used to constrain fundamental physics scenarios that would otherwise be inaccessible to experiment. I highlight the current controversial evidence for varying couplings and present some new results. Finally I focus on the relation between varying couplings and dark energy, and explain how varying coupling measurements might be used to probe the nature of dark energy, with some advantages over standard methods. In particular I discuss what can be achieved with future spectrographs such as ESPRESSO and CODEX.

  5. Graphene oxide: from fundamentals to applications

    NASA Astrophysics Data System (ADS)

    Perrozzi, F.; Prezioso, S.; Ottaviano, L.

    2015-01-01

    In this review, we discuss the fundamental characterization of graphene oxide (GO) and its future application perspectives. Morphology is discussed through optical microscopy, fluorescence microscopy, scanning electron microscopy, and atomic force microscopy studies. Chemical, structural, and vibrational properties are discussed through x-ray photoemission spectroscopy and Raman spectroscopy studies. Two easy characterization strategies, based on the correlation between x-ray photoemission spectroscopy and contact angle/optical contrast measurements are reported. Sensing and nano-biotechnology applications are discussed with focus on practical gas sensing and optical sensing, on the one hand, and on the toxicity issue of GO, on the other hand. Synthesis and post-synthesis treatments are also discussed, these latter with emphasis on lithography.

  6. Museum Techniques in Fundamental Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    Some museum techniques and methods can be used in fundamental educational programs without elaborate buildings or equipment; exhibitions should be based on valid presumptions and should take into account the "common sense" beliefs of people for whom the exhibit is designed. They can be used profitably in the economic development of local…

  7. Fundamentals of the Slide Library.

    ERIC Educational Resources Information Center

    Boerner, Susan Zee

    This paper is an introduction to the fundamentals of the art (including architecture) slide library, with some emphasis on basic procedures of the science slide library. Information in this paper is particularly relevant to the college, university, and museum slide library. Topics addressed include: (1) history of the slide library; (2) duties of…

  8. Light as a Fundamental Particle

    ERIC Educational Resources Information Center

    Weinberg, Steven

    1975-01-01

    Presents two arguments concerning the role of the photon. One states that the photon is just another particle distinguished by a particular value of charge, spin, mass, lifetime, and interaction properties. The second states that the photon plays a fundamental role with a deep relation to ultimate formulas of physics. (GS)

  9. Fundamentals of Welding. Teacher Edition.

    ERIC Educational Resources Information Center

    Fortney, Clarence; And Others

    These instructional materials assist teachers in improving instruction on the fundamentals of welding. The following introductory information is included: use of this publication; competency profile; instructional/task analysis; related academic and workplace skills list; tools, materials, and equipment list; and 27 references. Seven units of…

  10. Status of Fundamental Physics Program

    NASA Technical Reports Server (NTRS)

    Lee, Mark C.

    2003-01-01

    Update of the Fundamental Physics Program. JEM/EF Slip. 2 years delay. Reduced budget. Community support and advocacy led by Professor Nick Bigelow. Reprogramming led by Fred O Callaghan/JPL team. LTMPF M1 mission (DYNAMX and SUMO). PARCS. Carrier re baselined on JEM/EF.

  11. Environmental Law: Fundamentals for Schools.

    ERIC Educational Resources Information Center

    Day, David R.

    This booklet outlines the environmental problems most likely to arise in schools. An overview provides a fundamental analysis of environmental issues rather than comprehensive analysis and advice. The text examines the concerns that surround superfund cleanups, focusing on the legal framework, and furnishes some practical pointers, such as what to…

  12. Brake Fundamentals. Automotive Articulation Project.

    ERIC Educational Resources Information Center

    Cunningham, Larry; And Others

    Designed for secondary and postsecondary auto mechanics programs, this curriculum guide contains learning exercises in seven areas: (1) brake fundamentals; (2) brake lines, fluid, and hoses; (3) drum brakes; (4) disc brake system and service; (5) master cylinder, power boost, and control valves; (6) parking brakes; and (7) trouble shooting. Each…

  13. Fundamentals of Environmental Education. Report.

    ERIC Educational Resources Information Center

    1976

    An outline of fundamental definitions, relationships, and human responsibilities related to environment provides a basis from which a variety of materials, programs, and activities can be developed. The outline can be used in elementary, secondary, higher education, or adult education programs. The framework is based on principles of the science…

  14. Programs for Fundamentals of Chemistry.

    ERIC Educational Resources Information Center

    Gallardo, Julio; Delgado, Steven

    This document provides computer programs, written in BASIC PLUS, for presenting fundamental or remedial college chemistry students with chemical problems in a computer assisted instructional program. Programs include instructions, a sample run, and 14 separate practice sessions covering: mathematical operations, using decimals, solving…

  15. Chronometric cosmology and fundamental fermions

    PubMed Central

    Segal, I. E.

    1982-01-01

    It is proposed that the fundamental fermions of nature are modeled by fields on the chronometric cosmos that are not precisely spinors but become such only in the nonchronometric limit. The imbedding of the scale-extended Poincaré group in the linearizer of the Minkowskian conformal group defines such fields, by induction. PMID:16593266

  16. Fundamentals of Environmental Education. Report.

    ERIC Educational Resources Information Center

    1976

    An outline of fundamental definitions, relationships, and human responsibilities related to environment provides a basis from which a variety of materials, programs, and activities can be developed. The outline can be used in elementary, secondary, higher education, or adult education programs. The framework is based on principles of the science…

  17. Light as a Fundamental Particle

    ERIC Educational Resources Information Center

    Weinberg, Steven

    1975-01-01

    Presents two arguments concerning the role of the photon. One states that the photon is just another particle distinguished by a particular value of charge, spin, mass, lifetime, and interaction properties. The second states that the photon plays a fundamental role with a deep relation to ultimate formulas of physics. (GS)

  18. Fundamentals of Welding. Teacher Edition.

    ERIC Educational Resources Information Center

    Fortney, Clarence; And Others

    These instructional materials assist teachers in improving instruction on the fundamentals of welding. The following introductory information is included: use of this publication; competency profile; instructional/task analysis; related academic and workplace skills list; tools, materials, and equipment list; and 27 references. Seven units of…

  19. Brake Fundamentals. Automotive Articulation Project.

    ERIC Educational Resources Information Center

    Cunningham, Larry; And Others

    Designed for secondary and postsecondary auto mechanics programs, this curriculum guide contains learning exercises in seven areas: (1) brake fundamentals; (2) brake lines, fluid, and hoses; (3) drum brakes; (4) disc brake system and service; (5) master cylinder, power boost, and control valves; (6) parking brakes; and (7) trouble shooting. Each…

  20. Fundamentals of Microelectronics Processing (VLSI).

    ERIC Educational Resources Information Center

    Takoudis, Christos G.

    1987-01-01

    Describes a 15-week course in the fundamentals of microelectronics processing in chemical engineering, which emphasizes the use of very large scale integration (VLSI). Provides a listing of the topics covered in the course outline, along with a sample of some of the final projects done by students. (TW)

  1. Lighting Fundamentals. Monograph Number 13.

    ERIC Educational Resources Information Center

    Locatis, Craig N.; Gerlach, Vernon S.

    Using an accompanying, specified film that consists of 10-second pictures separated by blanks, the learner can, with the 203-step, self-correcting questions and answers provided in this program, come to understand the fundamentals of lighting in photography. The learner should, by the end of the program, be able to describe and identify the…

  2. Fundamentals of Microelectronics Processing (VLSI).

    ERIC Educational Resources Information Center

    Takoudis, Christos G.

    1987-01-01

    Describes a 15-week course in the fundamentals of microelectronics processing in chemical engineering, which emphasizes the use of very large scale integration (VLSI). Provides a listing of the topics covered in the course outline, along with a sample of some of the final projects done by students. (TW)

  3. FUNdamental Movement in Early Childhood.

    ERIC Educational Resources Information Center

    Campbell, Linley

    2001-01-01

    Noting that the development of fundamental movement skills is basic to children's motor development, this booklet provides a guide for early childhood educators in planning movement experiences for children between 4 and 8 years. The booklet introduces a wide variety of appropriate practices to promote movement skill acquisition and increased…

  4. Fundamental Limits to Nonlinear Energy Harvesting

    NASA Astrophysics Data System (ADS)

    Haji Hosseinloo, Ashkan; Turitsyn, Konstantin

    2015-12-01

    Linear and nonlinear vibration energy harvesting has been the focus of considerable research in recent years. However, fundamental limits on the harvestable energy of a harvester subjected to an arbitrary excitation force and different constraints is not yet fully understood. Understanding these limits is not only essential for an assessment of the technology potential, but it also provides a broader perspective on the current harvesting mechanisms and guidance in their improvement. Here, we derive the fundamental limits on the output power of an ideal energy harvester for arbitrary excitation waveforms and build on the current analysis framework for the simple computation of this limit for more sophisticated setups. We show that the optimal harvester maximizes the harvested energy through a mechanical analog of a buy-low-sell-high strategy. We also propose a nonresonant passive latch-assisted harvester to realize this strategy for an effective harvesting. It is shown that the proposed harvester harvests energy more effectively than its linear and bistable counterparts over a wider range of excitation frequencies and amplitudes. The buy-low-sell-high strategy also reveals why the conventional bistable harvester works well at low-frequency excitation.

  5. Lateral optical binding between two colloidal particles

    PubMed Central

    Wei, Ming-Tzo; Ng, Jack; Chan, C. T.; Ou-Yang, H. Daniel

    2016-01-01

    An optical binding force between two nearby colloidal particles trapped by two coherent laser beams is measured by phase-sensitive detection. The binding force is long-range and spatially oscillatory. For identical linearly-polarized incident beams, the oscillation period is equal to the optical wavelength. For mutually perpendicular polarizations, a new force appears with half-wavelength periodicity, caused by double inter-particle scattering. This force is observable only with cross-polarized incident beams, for which the stronger single-scattering forces are forbidden by parity. PMID:27982052

  6. The Fundamental Manifold of Spheroids

    NASA Astrophysics Data System (ADS)

    Zaritsky, Dennis; Gonzalez, Anthony H.; Zabludoff, Ann I.

    2006-02-01

    We present a unifying empirical description of the structural and kinematic properties of all spheroids embedded in dark matter halos. We find that the intracluster stellar spheroidal components of galaxy clusters, which we call cluster spheroids (CSphs) and which are typically 100 times the size of normal elliptical galaxies, lie on a ``fundamental plane'' as tight as that defined by elliptical galaxies (rms in effective radius of ~0.07) but having a different slope. The slope, as measured by the coefficient of the logσ term, declines significantly and systematically between the fundamental planes of ellipticals, brightest cluster galaxies (BCGs), and CSphs. We attribute this decline primarily to a continuous change in Me/Le, the mass-to-light ratio within the effective radius re, with spheroid scale. The magnitude of the slope change requires that it arise principally from differences in the relative distributions of luminous and dark matter, rather than from stellar population differences such as in age and metallicity. By expressing the Me/Le term as a function of σ in the simple derivation of the fundamental plane and requiring the behavior of that term to mimic the observed nonlinear relationship between logMe/Le and logσ, we simultaneously fit a two-dimensional manifold to the measured properties of dwarf elliptical and elliptical galaxies, BCGs, and CSphs. The combined data have an rms scatter in logre of 0.114 (0.099 for the combination of ellipticals, BCGs, and CSphs), which is modestly larger than each fundamental plane has alone, but which includes the scatter introduced by merging different studies done in different filters by different investigators. This ``fundamental manifold'' fits the structural and kinematic properties of spheroids that span a factor of 100 in σ and 1000 in re. While our mathematical form is neither unique nor derived from physical principles, the tightness of the fit leaves little room for improvement by other unification

  7. Binding Procurement

    NASA Technical Reports Server (NTRS)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

    This viewgraph presentation reviews the use of the binding procurement process in purchasing Aerospace Flight Battery Systems. NASA Engineering and Safety Center (NESC) requested NASA Aerospace Flight Battery Systems Working Group to develop a set of guideline requirements document for Binding Procurement Contracts.

  8. Forces in yeast flocculation

    NASA Astrophysics Data System (ADS)

    El-Kirat-Chatel, Sofiane; Beaussart, Audrey; Vincent, Stéphane P.; Abellán Flos, Marta; Hols, Pascal; Lipke, Peter N.; Dufrêne, Yves F.

    2015-01-01

    In the baker's yeast Saccharomyces cerevisiae, cell-cell adhesion (``flocculation'') is conferred by a family of lectin-like proteins known as the flocculin (Flo) proteins. Knowledge of the adhesive and mechanical properties of flocculins is important for understanding the mechanisms of yeast adhesion, and may help controlling yeast behaviour in biotechnology. We use single-molecule and single-cell atomic force microscopy (AFM) to explore the nanoscale forces engaged in yeast flocculation, focusing on the role of Flo1 as a prototype of flocculins. Using AFM tips labelled with mannose, we detect single flocculins on Flo1-expressing cells, showing they are widely exposed on the cell surface. When subjected to force, individual Flo1 proteins display two distinct force responses, i.e. weak lectin binding forces and strong unfolding forces reflecting the force-induced extension of hydrophobic tandem repeats. We demonstrate that cell-cell adhesion bonds also involve multiple weak lectin interactions together with strong unfolding forces, both associated with Flo1 molecules. Single-molecule and single-cell data correlate with microscale cell adhesion behaviour, suggesting strongly that Flo1 mechanics is critical for yeast flocculation. These results favour a model in which not only weak lectin-sugar interactions are involved in yeast flocculation but also strong hydrophobic interactions resulting from protein unfolding.

  9. Force As A Momentum Current

    SciTech Connect

    Munera, Hector A.

    2010-07-28

    Advantages of a neo-Cartesian approach to classical mechanics are noted. If conservation of linear momentum is the fundamental principle, Newton's three laws become theorems. A minor paradox in static Newtonian mechanics is identified, and solved by reinterpreting force as a current of momentum. Contact force plays the role of a mere midwife in the exchange of momentum; however, force cannot be eliminated from physics because it provides the numerical value for momentum current. In this sense, in a neo-Cartesian formulation of mechanics the concept of force becomes strengthened rather than weakened.

  10. Force As A Momentum Current

    NASA Astrophysics Data System (ADS)

    Múnera, Héctor A.

    2010-07-01

    Advantages of a neo-Cartesian approach to classical mechanics are noted. If conservation of linear momentum is the fundamental principle, Newton's three laws become theorems. A minor paradox in static Newtonian mechanics is identified, and solved by reinterpreting force as a current of momentum. Contact force plays the role of a mere midwife in the exchange of momentum; however, force cannot be eliminated from physics because it provides the numerical value for momentum current. In this sense, in a neo-Cartesian formulation of mechanics the concept of force becomes strengthened rather than weakened.

  11. Quantifying forces in cell biology.

    PubMed

    Roca-Cusachs, Pere; Conte, Vito; Trepat, Xavier

    2017-07-01

    Cells exert, sense, and respond to physical forces through an astounding diversity of mechanisms. Here we review recently developed tools to quantify the forces generated by cells. We first review technologies based on sensors of known or assumed mechanical properties, and discuss their applicability and limitations. We then proceed to draw an analogy between these human-made sensors and force sensing in the cell. As mechanics is increasingly revealed to play a fundamental role in cell function we envisage that tools to quantify physical forces may soon become widely applied in life-sciences laboratories.

  12. Microphotonic Forces from Superfluid Flow

    NASA Astrophysics Data System (ADS)

    McAuslan, D. L.; Harris, G. I.; Baker, C.; Sachkou, Y.; He, X.; Sheridan, E.; Bowen, W. P.

    2016-04-01

    In cavity optomechanics, radiation pressure and photothermal forces are widely utilized to cool and control micromechanical motion, with applications ranging from precision sensing and quantum information to fundamental science. Here, we realize an alternative approach to optical forcing based on superfluid flow and evaporation in response to optical heating. We demonstrate optical forcing of the motion of a cryogenic microtoroidal resonator at a level of 1.46 nN, roughly 1 order of magnitude larger than the radiation pressure force. We use this force to feedback cool the motion of a microtoroid mechanical mode to 137 mK. The photoconvective forces we demonstrate here provide a new tool for high bandwidth control of mechanical motion in cryogenic conditions, while the ability to apply forces remotely, combined with the persistence of flow in superfluids, offers the prospect for new applications.

  13. Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations

    PubMed Central

    Yu, Zhe; Ma, Yu-chi; Ai, Jing; Chen, Dan-qi; Zhao, Dong-mei; Wang, Xin; Chen, Yue-lei; Geng, Mei-yu; Xiong, Bing; Cheng, Mao-sheng; Shen, Jing-kang

    2013-01-01

    Aim: To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Methods: Based on the prototype model inhibitor 1, four ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Results: Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich π–π interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. Conclusion: The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met. PMID:24056705

  14. Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations.

    PubMed

    Yu, Zhe; Ma, Yu-chi; Ai, Jing; Chen, Dan-qi; Zhao, Dong-mei; Wang, Xin; Chen, Yue-lei; Geng, Mei-yu; Xiong, Bing; Cheng, Mao-sheng; Shen, Jing-Kang

    2013-11-01

    To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Based on the prototype model inhibitor 1, four ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich π-π interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met.

  15. Astrophysical Probes of Fundamental Physics

    NASA Astrophysics Data System (ADS)

    Martins, C. J. A. P.

    I review the theoretical motivation for varying fundamental couplings and discuss how these measurements can be used to constrain a number of fundamental physics scenarios that would otherwise be inacessible to experiment. As a case study I will focus on the relation between varying couplings and dark energy, and explain how varying coupling measurements can be used to probe the nature of dark energy, with important advantages over the standard methods. Assuming that the current observational evidence for varying α. and μ is correct, a several-sigma detection of dynamical dark energy is feasible within a few years, using currently operational ground-based facilities. With forthcoming instruments like CODEX, a high-accuracy reconstruction of the equation of state may be possible all the way up to redshift z ˜ 4.

  16. Fundamental neutron physics at LANSCE

    SciTech Connect

    Greene, G.

    1995-10-01

    Modern neutron sources and science share a common origin in mid-20th-century scientific investigations concerned with the study of the fundamental interactions between elementary particles. Since the time of that common origin, neutron science and the study of elementary particles have evolved into quite disparate disciplines. The neutron became recognized as a powerful tool for studying condensed matter with modern neutron sources being primarily used (and justified) as tools for neutron scattering and materials science research. The study of elementary particles has, of course, led to the development of rather different tools and is now dominated by activities performed at extremely high energies. Notwithstanding this trend, the study of fundamental interactions using neutrons has continued and remains a vigorous activity at many contemporary neutron sources. This research, like neutron scattering research, has benefited enormously by the development of modern high-flux neutron facilities. Future sources, particularly high-power spallation sources, offer exciting possibilities for continuing this research.

  17. Microplasmas: from applications to fundamentals

    NASA Astrophysics Data System (ADS)

    Nguon, Olivier; Huang, Sisi; Gauthier, Mario; Karanassios, Vassili

    2014-05-01

    Microplasmas are receiving increasing attention in the scientific literature and in recent conferences. Yet, few analytical applications of microplasmas for elemental analysis using liquid samples have been described in the literature. To address this, we describe two applications: one involves the determination of Zn in microsamples of the metallo-enzyme Super Oxide Dismutase. The other involves determination of Pd-concentration in microsamples of Pd nanocatalysts. These applications demonstrate the potential of microplasmas and point to the need for future fundamental studies.

  18. CP, T and fundamental interactions

    NASA Astrophysics Data System (ADS)

    Frère, Jean-Marie

    2012-03-01

    We discuss the importance of the CP (simultaneous particle-antiparticle and left-right permutation) and T (time reversal) symmetries in the context of fundamental interactions. We show that they may provide clues to go beyond the 4-D gauge interactions. We insist on the fact that T violation is not associated to a degradation (like in entropy), but simply characterised by different trajectories.

  19. Binding manners

    NASA Astrophysics Data System (ADS)

    2012-08-01

    Claudia Turro from The Ohio State University talks Nature Chemistry through the different binding modes small metal complexes can adopt when interacting with DNA -- and why elucidating them in detail matters.

  20. Forces Driving Chaperone Action

    PubMed Central

    Koldewey, Philipp; Stull, Frederick; Horowitz, Scott; Martin, Raoul; Bardwell, James C. A.

    2016-01-01

    SUMMARY It is still unclear what molecular forces drive chaperone-mediated protein folding. Here, we obtain a detailed mechanistic understanding of the forces that dictate the four key steps of chaperone-client interaction: initial binding, complex stabilization, folding, and release. Contrary to the common belief that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7. Short-range hydrophobic interactions follow, which serve to stabilize the complex. Hydrophobic collapse of the client protein then drives its folding. By burying hydrophobic residues in its core, the client’s affinity to Spy decreases, which causes client release. By allowing the client to fold itself, Spy circumvents the need for client-specific folding instructions. This mechanism might help explain how chaperones can facilitate the folding of various unrelated proteins. PMID:27293188

  1. Quantifying Coulombic and solvent polarization-mediated forces between DNA helices.

    PubMed

    He, Zhaojian; Chen, Shi-Jie

    2013-06-20

    One of the fundamental problems in nucleic acids biophysics is to predict the different forces that stabilize nucleic acid tertiary folds. Here we provide a quantitative estimation and analysis for the forces between DNA helices in an ionic solution. Using the generalized Born model and the improved atomistic tightly binding ions model, we evaluate ion correlation and solvent polarization effects in interhelix interactions. The results suggest that hydration, Coulomb correlation and ion entropy act together to cause the repulsion and attraction between nucleic acid helices in Mg(2+) and Mn(2+) solutions, respectively. The theoretical predictions are consistent with experimental findings. Detailed analysis further suggests that solvent polarization and ion correlation both are crucial for the interhelix interactions. The theory presented here may provide a useful framework for systematic and quantitative predictions of the forces in nucleic acids folding.

  2. Labor Force

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2012

    2012-01-01

    The labor force is the number of people ages 16 or older who are either working or looking for work. It does not include active-duty military personnel or the institutionalized population, such as prison inmates. Determining the size of the labor force is a way of determining how big the economy can get. The size of the labor force depends on two…

  3. Fundamental molecular differences between alcohol dehydrogenase classes.

    PubMed Central

    Danielsson, O; Atrian, S; Luque, T; Hjelmqvist, L; Gonzàlez-Duarte, R; Jörnvall, H

    1994-01-01

    Two types of alcohol dehydrogenase in separate protein families are the "medium-chain" zinc enzymes (including the classical liver and yeast forms) and the "short-chain" enzymes (including the insect form). Although the medium-chain family has been characterized in prokaryotes and many eukaryotes (fungi, plants, cephalopods, and vertebrates), insects have seemed to possess only the short-chain enzyme. We have now also characterized a medium-chain alcohol dehydrogenase in Drosophila. The enzyme is identical to insect octanol dehydrogenase. It is a typical class III alcohol dehydrogenase, similar to the corresponding human form (70% residue identity), with mostly the same residues involved in substrate and coenzyme interactions. Changes that do occur are conservative, but Phe-51 is of functional interest in relation to decreased coenzyme binding and increased overall activity. Extra residues versus the human enzyme near position 250 affect the coenzyme-binding domain. Enzymatic properties are similar--i.e., very low activity toward ethanol (Km beyond measurement) and high selectivity for formaldehyde/glutathione (S-hydroxymethylglutathione; kcat/Km = 160,000 min-1.mM-1). Between the present class III and the ethanol-active class I enzymes, however, patterns of variability differ greatly, highlighting fundamentally separate molecular properties of these two alcohol dehydrogenases, with class III resembling enzymes in general and class I showing high variation. The gene coding for the Drosophila class III enzyme produces an mRNA of about 1.36 kb that is present at all developmental stages of the fly, compatible with the constitutive nature of the vertebrate enzyme. Taken together, the results bridge a previously apparent gap in the distribution of medium-chain alcohol dehydrogenases and establish a strictly conserved class III enzyme, consistent with an important role for this enzyme in cellular metabolism. Images PMID:8197167

  4. Fundamental Characteristics of Breather Hydrodynamics

    NASA Astrophysics Data System (ADS)

    Chabchoub, Amin

    2014-05-01

    The formation of oceanic rogue waves can be explained by the modulation instability of deep-water Stokes waves. In particular, being doubly-localized and amplifying the background wave amplitude by a factor of three or higher, the class of Peregrine-type breather solutions of the nonlinear Schrödinger equation (NLS) are considered to be appropriate models to describe extreme ocean wave dynamics. Here, we present an experimental validation of fundamental properties of the NLS within the context of Peregrine breather dynamics and we discuss the long-term behavior of such in time and space localized structures.

  5. Solid Lubrication Fundamentals and Applications

    NASA Technical Reports Server (NTRS)

    Miyoshi, Kazuhisa

    2001-01-01

    Solid Lubrication Fundamentals and Applications description of the adhesion, friction, abrasion, and wear behavior of solid film lubricants and related tribological materials, including diamond and diamond-like solid films. The book details the properties of solid surfaces, clean surfaces, and contaminated surfaces as well as discussing the structures and mechanical properties of natural and synthetic diamonds; chemical-vapor-deposited diamond film; surface design and engineering toward wear-resistant, self-lubricating diamond films and coatings. The author provides selection and design criteria as well as applications for synthetic and natural coatings in the commercial, industrial and aerospace industries..

  6. Thermodynamics fundamentals of energy conversion

    NASA Astrophysics Data System (ADS)

    Dan, Nicolae

    The work reported in the chapters 1-5 focuses on the fundamentals of heat transfer, fluid dynamics, thermodynamics and electrical phenomena related to the conversion of one form of energy to another. Chapter 6 is a re-examination of the fundamental heat transfer problem of how to connect a finite-size heat generating volume to a concentrated sink. Chapter 1 extends to electrical machines the combined thermodynamics and heat transfer optimization approach that has been developed for heat engines. The conversion efficiency at maximum power is 1/2. When, as in specific applications, the operating temperature of windings must not exceed a specified level, the power output is lower and efficiency higher. Chapter 2 addresses the fundamental problem of determining the optimal history (regime of operation) of a battery so that the work output is maximum. Chapters 3 and 4 report the energy conversion aspects of an expanding mixture of hot particles, steam and liquid water. At the elemental level, steam annuli develop around the spherical drops as time increases. At the mixture level, the density decreases while the pressure and velocity increases. Chapter 4 describes numerically, based on the finite element method, the time evolution of the expanding mixture of hot spherical particles, steam and water. The fluid particles are moved in time in a Lagrangian manner to simulate the change of the domain configuration. Chapter 5 describes the process of thermal interaction between the molten material and water. In the second part of the chapter the model accounts for the irreversibility due to the flow of the mixture through the cracks of the mixing vessel. The approach presented in this chapter is based on exergy analysis and represents a departure from the line of inquiry that was followed in chapters 3-4. Chapter 6 shows that the geometry of the heat flow path between a volume and one point can be optimized in two fundamentally different ways. In the "growth" method the

  7. Reconstruction of fundamental SUSY parameters

    SciTech Connect

    P. M. Zerwas et al.

    2003-09-25

    We summarize methods and expected accuracies in determining the basic low-energy SUSY parameters from experiments at future e{sup +}e{sup -} linear colliders in the TeV energy range, combined with results from LHC. In a second step we demonstrate how, based on this set of parameters, the fundamental supersymmetric theory can be reconstructed at high scales near the grand unification or Planck scale. These analyses have been carried out for minimal supergravity [confronted with GMSB for comparison], and for a string effective theory.

  8. Solid Lubrication Fundamentals and Applications

    NASA Technical Reports Server (NTRS)

    Miyoshi, Kazuhisa

    2001-01-01

    Solid Lubrication Fundamentals and Applications description of the adhesion, friction, abrasion, and wear behavior of solid film lubricants and related tribological materials, including diamond and diamond-like solid films. The book details the properties of solid surfaces, clean surfaces, and contaminated surfaces as well as discussing the structures and mechanical properties of natural and synthetic diamonds; chemical-vapor-deposited diamond film; surface design and engineering toward wear-resistant, self-lubricating diamond films and coatings. The author provides selection and design criteria as well as applications for synthetic and natural coatings in the commercial, industrial and aerospace industries..

  9. Spectroscopic study of binding of chlorogenic acid with the surface of ZnO nanoparticles

    NASA Astrophysics Data System (ADS)

    Belay, Abebe; Kim, Hyung Kook; Hwang, Yoon-Hwae

    2017-09-01

    Understanding the interaction properties of biological materials with ZnO NPs is fundamental interest in the field of biotechnological applications as well as in the formation of optoelectronic devices. In this research, the binding of ZnO NPs and chlorogenic acid (CGA) were investigated using fluorescence quenching, UV-Vis absorption spectroscopy, Fourier transform infrared (FTIR), Raman spectroscopy, scanning electron microscopy (TEM), and dynamic light scattering (DLS) techniques. The study results indicated the fluorescence quenching between ZnO NPs and CGA rationalized in terms of static quenching mechanism or the formation of nonfluorescent CGA-ZnO. From fluorescence quenching spectral analysis the binding constant ( K a ), number of binding sites ( n), and thermodynamic properties, were determined. The quenching constants ( K sv) and binding constant ( K a ), decrease with increasing the temperature and their binding sites n are 2. The thermodynamic parameters determined using Van't Hoff equation indicated binding occurs spontaneously involving the hydrogen bond and van der Walls forces played the major role in the reaction of ZnO NPs with CGA. The Raman, SEM, DLS, and Zeta potential measurements were also indicated the differences in the structure, morphology and sizes of CGA, ZnO NPs, and their corresponding CGA-ZnO due to adsorption of CGA on the surface of ZnO NPs

  10. [From fundamental research to clinical development: a review of orthodontics].

    PubMed

    Zhao, Zhi-he; Bai, Ding

    2011-11-01

    In recent years, new approaches to the diagnosis and treatment of malocclusion have emerged. The diagnostic and therapeutic techniques of orthodontics have evolved from two dimensions to five dimensions with the development of computer technology, auto-machining and imaging. Furthermore, interdisciplinary study has become the driving force for the advancement of fundamental research in orthodontics. The mechanisms of malocclusion and orthodontic tooth movement have been extensively studied to the details at the level of cells and molecules.

  11. Field Theory of Fundamental Interactions

    NASA Astrophysics Data System (ADS)

    Wang, Shouhong; Ma, Tian

    2017-01-01

    First, we present two basic principles, the principle of interaction dynamics (PID) and the principle of representation invariance (PRI). Intuitively, PID takes the variation of the action under energy-momentum conservation constraint. We show that the PID is the requirement of the presence of dark matter and dark energy, the Higgs field and the quark confinement. PRI requires that the SU(N) gauge theory be independent of representations of SU(N). It is clear that PRI is the logic requirement of any gauge theory. With PRI, we demonstrate that the coupling constants for the strong and the weak interactions are the main sources of these two interactions, reminiscent of the electric charge. Second, we emphasize that symmetry principles-the principle of general relativity and the principle of Lorentz invariance and gauge invariance-together with the simplicity of laws of nature, dictate the actions for the four fundamental interactions. Finally, we show that the PID and the PRI, together with the symmetry principles give rise to a unified field model for the fundamental interactions, which is consistent with current experimental observations and offers some new physical predictions. The research is supported in part by the National Science Foundation (NSF) grant DMS-1515024, and by the Office of Naval Research (ONR) grant N00014-15-1-2662.

  12. Fundamental tribological properties of ceramics

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.; Miyoshi, K.

    1985-01-01

    When a ceramic is brought into contact with itself, another ceramic, or a metal, strong bond forces can develop between the materials. Adhesion between a ceramic and itself or another solid are discussed from a theoretical consideration of the nature of the surfaces and experimentally by relating bond forces to the interface resulting from solid state contact. Elastic, plastic, and fracture behavior of ceramics in solid-state contact are discussed as they relate to friction and wear. The contact load necessary to initiate fracture in ceramics is shown to be appreciably reduced with tangential motion. Both friction and wear of ceramics are anisotropic and relate to crystal structure as with metals. Both free energy of oxide formation and the d valence bond character of metals are related to the friction and wear characteristics for metals in contact with ceramics. Lubrication is found to increase the critical load necessary to initiate fracture of ceramics with sliding or rubbing contact.

  13. Fundamentals of small animal orthodontics.

    PubMed

    Surgeon, Thoulton W

    2005-07-01

    The basic principles and concepts that govern the discipline of orthodontics are explored. The movement of teeth is mediated primarily through the periodontal ligament. When the periodontal ligament is stretched, bone apposition occurs. Conversely, in areas of compression, bone resorption occurs. The subject tooth moves in the direction of the force. The orthodontist must be cognizant of the prevailing ethical guidelines and the functional needs of the patient.

  14. Interpreting the widespread nonlinear force spectra of intermolecular bonds

    PubMed Central

    Friddle, Raymond W.; Noy, Aleksandr; De Yoreo, James J.

    2012-01-01

    Single molecule force spectroscopy probes the strength, lifetime, and energetic details of intermolecular interactions in a simple experiment. A growing number of these studies have reported distinctly nonlinear trends in rupture force with loading rate that are typically explained in conventional models by invoking complex escape pathways. Recent analyses suggested that these trends should be expected even for simple barriers based on the basic assumptions of bond rupture dynamics and thus may represent the norm rather than the exception. Here we explore how these nonlinear trends reflect the two fundamental regimes of bond rupture: (i) a near-equilibrium regime, produced either by bond reforming in the case of a single bond or by asynchronized rupture of multiple individual bonds, and (ii) a kinetic regime produced by fast, non-equilibrium bond rupture. We analyze both single- and multi-bonded cases, describe the full evolution of the system as it transitions between near- and far-from-equilibrium loading regimes, and show that both interpretations produce essentially identical force spectra. Data from 10 different molecular systems show that this model provides a comprehensive description of force spectra for a diverse suite of bonds over experimentally relevant loading rates, removes the inconsistencies of previous interpretations of transition state distances, and gives ready access to both kinetic and thermodynamic information about the interaction. These results imply that single-molecule binding free energies for a vast number of bonds have already been measured. PMID:22869712

  15. Force cycles and force chains.

    PubMed

    Tordesillas, Antoinette; Walker, David M; Lin, Qun

    2010-01-01

    We examine the coevolution of N cycles and force chains as part of a broader study which is designed to quantitatively characterize the role of the laterally supporting contact network to the evolution of force chains. Here, we elucidate the rheological function of these coexisting structures, especially in the lead up to failure. In analogy to force chains, we introduce the concept of force cycles: N cycles whose contacts each bear above average force. We examine their evolution around force chains in a discrete element simulation of a dense granular material under quasistatic biaxial loading. Three-force cycles are shown to be stabilizing structures that inhibit relative particle rotations and provide strong lateral support to force chains. These exhibit distinct behavior from other cycles. Their population decreases rapidly during the initial stages of the strain-hardening regime-a trend that is suddenly interrupted and reversed upon commencement of force chain buckling prior to peak shear stress. Results suggest that the three-force cycles are called upon for reinforcements to ward off failure via shear banding. Ultimately though, the resistance to buckling proves futile; buckling wins under the combined effects of dilatation and increasing compressive load. The sudden increase in three-force cycles may thus be viewed as an indicator of imminent failure via shear bands.

  16. Fundamental Travel Demand Model Example

    NASA Technical Reports Server (NTRS)

    Hanssen, Joel

    2010-01-01

    Instances of transportation models are abundant and detailed "how to" instruction is available in the form of transportation software help documentation. The purpose of this paper is to look at the fundamental inputs required to build a transportation model by developing an example passenger travel demand model. The example model reduces the scale to a manageable size for the purpose of illustrating the data collection and analysis required before the first step of the model begins. This aspect of the model development would not reasonably be discussed in software help documentation (it is assumed the model developer comes prepared). Recommendations are derived from the example passenger travel demand model to suggest future work regarding the data collection and analysis required for a freight travel demand model.

  17. Cognition is … Fundamentally Cultural

    PubMed Central

    Bender, Andrea; Beller, Sieghard

    2013-01-01

    A prevailing concept of cognition in psychology is inspired by the computer metaphor. Its focus on mental states that are generated and altered by information input, processing, storage and transmission invites a disregard for the cultural dimension of cognition, based on three (implicit) assumptions: cognition is internal, processing can be distinguished from content, and processing is independent of cultural background. Arguing against each of these assumptions, we point out how culture may affect cognitive processes in various ways, drawing on instances from numerical cognition, ethnobiological reasoning, and theory of mind. Given the pervasive cultural modulation of cognition—on all of Marr’s levels of description—we conclude that cognition is indeed fundamentally cultural, and that consideration of its cultural dimension is essential for a comprehensive understanding. PMID:25379225

  18. Astronomical reach of fundamental physics.

    PubMed

    Burrows, Adam S; Ostriker, Jeremiah P

    2014-02-18

    Using basic physical arguments, we derive by dimensional and physical analysis the characteristic masses and sizes of important objects in the universe in terms of just a few fundamental constants. This exercise illustrates the unifying power of physics and the profound connections between the small and the large in the cosmos we inhabit. We focus on the minimum and maximum masses of normal stars, the corresponding quantities for neutron stars, the maximum mass of a rocky planet, the maximum mass of a white dwarf, and the mass of a typical galaxy. To zeroth order, we show that all these masses can be expressed in terms of either the Planck mass or the Chandrasekar mass, in combination with various dimensionless quantities. With these examples, we expose the deep interrelationships imposed by nature between disparate realms of the universe and the amazing consequences of the unifying character of physical law.

  19. Fundamental concepts of quantum chaos

    NASA Astrophysics Data System (ADS)

    Robnik, M.

    2016-09-01

    We review the fundamental concepts of quantum chaos in Hamiltonian systems. The quantum evolution of bound systems does not possess the sensitive dependence on initial conditions, and thus no chaotic behaviour occurs, whereas the study of the stationary solutions of the Schrödinger equation in the quantum phase space (Wigner functions) reveals precise analogy of the structure of the classical phase portrait. We analyze the regular eigenstates associated with invariant tori in the classical phase space, and the chaotic eigenstates associated with the classically chaotic regions, and the corresponding energy spectra. The effects of quantum localization of the chaotic eigenstates are treated phenomenologically, resulting in Brody-like level statistics, which can be found also at very high-lying levels, while the coupling between the regular and the irregular eigenstates due to tunneling, and of the corresponding levels, manifests itself only in low-lying levels.

  20. Fundamental reaction pathways during coprocessing

    SciTech Connect

    Stock, L.M.; Gatsis, J.G. . Dept. of Chemistry)

    1992-12-01

    The objective of this research was to investigate the fundamental reaction pathways in coal petroleum residuum coprocessing. Once the reaction pathways are defined, further efforts can be directed at improving those aspects of the chemistry of coprocessing that are responsible for the desired results such as high oil yields, low dihydrogen consumption, and mild reaction conditions. We decided to carry out this investigation by looking at four basic aspects of coprocessing: (1) the effect of fossil fuel materials on promoting reactions essential to coprocessing such as hydrogen atom transfer, carbon-carbon bond scission, and hydrodemethylation; (2) the effect of varied mild conditions on the coprocessing reactions; (3) determination of dihydrogen uptake and utilization under severe conditions as a function of the coal or petroleum residuum employed; and (4) the effect of varied dihydrogen pressure, temperature, and residence time on the uptake and utilization of dihydrogen and on the distribution of the coprocessed products. Accomplishments are described.

  1. Astronomical reach of fundamental physics

    NASA Astrophysics Data System (ADS)

    Burrows, Adam S.; Ostriker, Jeremiah P.

    2014-02-01

    Using basic physical arguments, we derive by dimensional and physical analysis the characteristic masses and sizes of important objects in the universe in terms of just a few fundamental constants. This exercise illustrates the unifying power of physics and the profound connections between the small and the large in the cosmos we inhabit. We focus on the minimum and maximum masses of normal stars, the corresponding quantities for neutron stars, the maximum mass of a rocky planet, the maximum mass of a white dwarf, and the mass of a typical galaxy. To zeroth order, we show that all these masses can be expressed in terms of either the Planck mass or the Chandrasekar mass, in combination with various dimensionless quantities. With these examples, we expose the deep interrelationships imposed by nature between disparate realms of the universe and the amazing consequences of the unifying character of physical law.

  2. Quantum repeaters: fundamental and future

    NASA Astrophysics Data System (ADS)

    Li, Yue; Hua, Sha; Liu, Yu; Ye, Jun; Zhou, Quan

    2007-04-01

    An overview of the Quantum Repeater techniques based on Entanglement Distillation and Swapping is provided. Beginning with a brief history and the basic concepts of the quantum repeaters, the article primarily focuses on the communication model based on the quantum repeater techniques, which mainly consists of two fundamental modules --- the Entanglement Distillation module and the Swapping module. The realizations of Entanglement Distillation are discussed, including the Bernstein's Procrustean method, the Entanglement Concentration and the CNOT-purification method, etc. The schemes of implementing Swapping, which include the Swapping based on Bell-state measurement and the Swapping in Cavity QED, are also introduced. Then a comparison between these realizations and evaluations on them are presented. At last, the article discusses the experimental schemes of quantum repeaters at present, documents some remaining problems and emerging trends in this field.

  3. Fundamental base closure environmental principles

    SciTech Connect

    Yim, R.A.

    1994-12-31

    Military base closures present a paradox. The rate, scale and timing of military base closures is historically unique. However, each base itself typically does not present unique problems. Thus, the challenge is to design innovative solutions to base redevelopment and remediation issues, while simultaneously adopting common, streamlined or pre-approved strategies to shared problems. The author presents six environmental principles that are fundamental to base closure. They are: remediation not clean up; remediation will impact reuse; reuse will impact remediation; remediation and reuse must be coordinated; environmental contamination must be evaluated as any other initial physical constraint on development, not as an overlay after plans are created; and remediation will impact development, financing and marketability.

  4. Cognition is … Fundamentally Cultural.

    PubMed

    Bender, Andrea; Beller, Sieghard

    2013-03-01

    A prevailing concept of cognition in psychology is inspired by the computer metaphor. Its focus on mental states that are generated and altered by information input, processing, storage and transmission invites a disregard for the cultural dimension of cognition, based on three (implicit) assumptions: cognition is internal, processing can be distinguished from content, and processing is independent of cultural background. Arguing against each of these assumptions, we point out how culture may affect cognitive processes in various ways, drawing on instances from numerical cognition, ethnobiological reasoning, and theory of mind. Given the pervasive cultural modulation of cognition-on all of Marr's levels of description-we conclude that cognition is indeed fundamentally cultural, and that consideration of its cultural dimension is essential for a comprehensive understanding.

  5. Fundamentals of Neurogastroenterology: Basic Science.

    PubMed

    Vanner, Stephen; Greenwood-Van Meerveld, Beverley; Mawe, Gary; Shea-Donohue, Terez; Verdu, Elena F; Wood, Jackie; Grundy, David

    2016-02-18

    This review examines the fundamentals of neurogastroenterology that may underlie the pathophysiology of functional GI disorders (FGIDs). It was prepared by an invited committee of international experts and represents an abbreviated version of their consensus document that will be published in its entirety in the forthcoming book and online version entitled ROME IV. It emphasizes recent advances in our understanding of the enteric nervous system, sensory physiology underlying pain, and stress signaling pathways. There is also a focus on neuroimmmune signaling and intestinal barrier function, given the recent evidence implicating the microbiome, diet, and mucosal immune activation in FGIDs. Together, these advances provide a host of exciting new targets to identify and treat FGIDs and new areas for future research into their pathophysiology. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Fundamentals of Condensed Matter Physics

    NASA Astrophysics Data System (ADS)

    Cohen, Marvin L.; Louie, Steven G.

    2016-05-01

    Part I. Basic Concepts: Electrons and Phonons: 1. Concept of a solid: qualitative introduction and overview; 2. Electrons in crystals; 3. Electronic energy bands; 4. Lattice vibrations and phonons; Part II. Electron Intercations, Dynamics and Responses: 5. Electron dynamics in crystals; 6. Many-electron interactions: the interacting electron gas and beyond; 7. Density functional theory; 8. The dielectric function for solids; Part III. Optical and Transport Phenomena: 9. Electronic transitions and optical properties of solids; 10. Electron-phonon interactions; 11. Dynamics of crystal electrons in a magnetic field; 12. Fundamentals of transport phenomena in solids; Part IV. Superconductivity, Magnetism, and Lower Dimensional Systems: 13. Using many-body techniques; 14. Superconductivity; 15. Magnetism; 16. Reduced-dimensional systems and nanostructures; Index.

  7. Astronomical reach of fundamental physics

    PubMed Central

    Burrows, Adam S.; Ostriker, Jeremiah P.

    2014-01-01

    Using basic physical arguments, we derive by dimensional and physical analysis the characteristic masses and sizes of important objects in the universe in terms of just a few fundamental constants. This exercise illustrates the unifying power of physics and the profound connections between the small and the large in the cosmos we inhabit. We focus on the minimum and maximum masses of normal stars, the corresponding quantities for neutron stars, the maximum mass of a rocky planet, the maximum mass of a white dwarf, and the mass of a typical galaxy. To zeroth order, we show that all these masses can be expressed in terms of either the Planck mass or the Chandrasekar mass, in combination with various dimensionless quantities. With these examples, we expose the deep interrelationships imposed by nature between disparate realms of the universe and the amazing consequences of the unifying character of physical law. PMID:24477692

  8. Fundamental enabling issues in nanotechnology :

    SciTech Connect

    Floro, Jerrold Anthony; Foiles, Stephen Martin; Hearne, Sean Joseph; Hoyt, Jeffrey John; Seel, Steven Craig; Webb III, Edmund Blackburn; Morales, Alfredo Martin; Zimmerman, Jonathan A.

    2007-10-01

    To effectively integrate nanotechnology into functional devices, fundamental aspects of material behavior at the nanometer scale must be understood. Stresses generated during thin film growth strongly influence component lifetime and performance; stress has also been proposed as a mechanism for stabilizing supported nanoscale structures. Yet the intrinsic connections between the evolving morphology of supported nanostructures and stress generation are still a matter of debate. This report presents results from a combined experiment and modeling approach to study stress evolution during thin film growth. Fully atomistic simulations are presented predicting stress generation mechanisms and magnitudes during all growth stages, from island nucleation to coalescence and film thickening. Simulations are validated by electrodeposition growth experiments, which establish the dependence of microstructure and growth stresses on process conditions and deposition geometry. Sandia is one of the few facilities with the resources to combine experiments and modeling/theory in this close a fashion. Experiments predicted an ongoing coalescence process that generates signficant tensile stress. Data from deposition experiments also supports the existence of a kinetically limited compressive stress generation mechanism. Atomistic simulations explored island coalescence and deposition onto surfaces intersected by grain boundary structures to permit investigation of stress evolution during later growth stages, e.g. continual island coalescence and adatom incorporation into grain boundaries. The predictive capabilities of simulation permit direct determination of fundamental processes active in stress generation at the nanometer scale while connecting those processes, via new theory, to continuum models for much larger island and film structures. Our combined experiment and simulation results reveal the necessary materials science to tailor stress, and therefore performance, in

  9. Rare Isotopes and Fundamental Symmetries

    NASA Astrophysics Data System (ADS)

    Brown, B. Alex; Engel, Jonathan; Haxton, Wick; Ramsey-Musolf, Michael; Romalis, Michael; Savard, Guy

    2009-01-01

    Experiments searching for new interactions in nuclear beta decay / Klaus P. Jungmann -- The beta-neutrino correlation in sodium-21 and other nuclei / P. A. Vetter ... [et al.] -- Nuclear structure and fundamental symmetries/ B. Alex Brown -- Schiff moments and nuclear structure / J. Engel -- Superallowed nuclear beta decay: recent results and their impact on V[symbol] / J. C. Hardy and I. S. Towner -- New calculation of the isospin-symmetry breaking correlation to superallowed Fermi beta decay / I. S. Towner and J. C. Hardy -- Precise measurement of the [symbol]H to [symbol]He mass difference / D. E. Pinegar ... [et al.] -- Limits on scalar currents from the 0+ to 0+ decay of [symbol]Ar and isospin breaking in [symbol]Cl and [symbol]Cl / A. Garcia -- Nuclear constraints on the weak nucleon-nucleon interaction / W. C. Haxton -- Atomic PNC theory: current status and future prospects / M. S. Safronova -- Parity-violating nucleon-nucleon interactions: what can we learn from nuclear anapole moments? / B. Desplanques -- Proposed experiment for the measurement of the anapole moment in francium / A. Perez Galvan ... [et al.] -- The Radon-EDM experiment / Tim Chupp for the Radon-EDM collaboration -- The lead radius Eexperiment (PREX) and parity violating measurements of neutron densities / C. J. Horowitz -- Nuclear structure aspects of Schiff moment and search for collective enhancements / Naftali Auerbach and Vladimir Zelevinsky -- The interpretation of atomic electric dipole moments: Schiff theorem and its corrections / C. -P. Liu -- T-violation and the search for a permanent electric dipole moment of the mercury atom / M. D. Swallows ... [et al.] -- The new concept for FRIB and its potential for fundamental interactions studies / Guy Savard -- Collinear laser spectroscopy and polarized exotic nuclei at NSCL / K. Minamisono -- Environmental dependence of masses and coupling constants / M. Pospelov.

  10. Fundamental Physics and Precision Measurements

    NASA Astrophysics Data System (ADS)

    Hänsch, T. W.

    2006-11-01

    "Very high precision physics has always appealed to me. The steady improvement in technologies that afford higher and higher precision has been a regular source of excitement and challenge during my career. In science, as in most things, whenever one looks at something more closely, new aspects almost always come into play …" With these word from the book "How the Laser happened", Charles H. Townes expresses a passion for precision that is now shared by many scientists. Masers and lasers have become indispensible tools for precision measurements. During the past few years, the advent of femtosecond laser frequency comb synthesizers has revolutionized the art of directly comparing optical and microwave frequencies. Inspired by the needs of precision laser spectroscopy of the simple hydrogen atom, such frequency combs are now enabling ultra-precise spectroscopy over wide spectral ranges. Recent laboratory experiments are already setting stringent limits for possible slow variations of fundamental constants. Laser frequency combs also provide the long missing clockwork for optical atomic clocks that may ultimately reach a precision of parts in 1018 and beyond. Such tools will open intriguing new opportunities for fundamental experiments including new tests of special and general relativity. In the future, frequency comb techniques may be extended into the extreme ultraviolet and soft xray regime, opening a vast new spectral territory to precision measurements. Frequency combs have also become a key tool for the emerging new field of attosecond science, since they can control the electric field of ultrashort laser pulses on an unprecedented time scale. The biggest surprise in these endeavours would be if we found no surprise.

  11. Natural convection: Fundamentals and applications

    NASA Astrophysics Data System (ADS)

    Kakac, S.; Aung, W.; Viskanta, R.

    Among the topics discussed are: stability solutions for laminar external boundary region flows; natural convection in plane layers and cavities with volumetric energy sources; and turbulence modelling equations. Consideration is also given to: natural convection in enclosures containing tube bundles; natural limiting behaviors in porous media cavity flows; numerical solutions in laminar and turbulent natural convection; and heat transfer in the critical region of binary mixtures. Additional topics discussed include: natural convective cooling of electronic equipment; natural convection suppression in solar collectors; and laser induced buoyancy and forced convection in vertical tubes.

  12. Fundamentals of soft robot locomotion

    PubMed Central

    2017-01-01

    Soft robotics and its related technologies enable robot abilities in several robotics domains including, but not exclusively related to, manipulation, manufacturing, human–robot interaction and locomotion. Although field applications have emerged for soft manipulation and human–robot interaction, mobile soft robots appear to remain in the research stage, involving the somehow conflictual goals of having a deformable body and exerting forces on the environment to achieve locomotion. This paper aims to provide a reference guide for researchers approaching mobile soft robotics, to describe the underlying principles of soft robot locomotion with its pros and cons, and to envisage applications and further developments for mobile soft robotics. PMID:28539483

  13. From self-assembly fundamental knowledge to nanomedicine developments.

    PubMed

    Monduzzi, Maura; Lampis, Sandrina; Murgia, Sergio; Salis, Andrea

    2014-03-01

    This review highlights the key role of NMR techniques in demonstrating the molecular aspects of the self-assembly of surfactant molecules that nowadays constitute the basic knowledge which modern nanoscience relies on. The aim is to provide a tutorial overview. The story of a rigorous scientific approach to understand self-assembly in surfactant systems and biological membranes starts in the early seventies when the progresses of SAXRD and NMR technological facilities allowed to demonstrate the existence of ordered soft matter, and the validity of Tanford approach concerning self-assembly at a molecular level. Particularly, NMR quadrupolar splittings, NMR chemical shift anisotropy, and NMR relaxation of dipolar and quadrupolar nuclei in micellar solutions, microemulsions, and liquid crystals proved the existence of an ordered polar-apolar interface, on the NMR time scale. NMR data, rationalized in terms of the two-step model of relaxation, allowed to quantify the dynamic aspects of the supramolecular aggregates in different soft matter systems. In addition, NMR techniques allowed to obtain important information on counterion binding as well as on size of the aggregate through molecular self-diffusion. Indeed NMR self-diffusion proved without any doubt the existence of bicontinuous microemulsions and bicontinuous cubic liquid crystals, suggested by pioneering and brilliant interpretation of SAXRD investigations. Moreover, NMR self-diffusion played a fundamental role in the understanding of microemulsion and emulsion nanostructures, phase transitions in phase diagrams, and particularly percolation phenomena in microemulsions. Since the nineties, globalization of the knowledge along with many other technical facilities such as electron microscopy, particularly cryo-EM, produced huge progresses in surfactant and colloid science. Actually we refer to nanoscience: bottom up/top down strategies allow to build nanodevices with applications spanning from ICT to food

  14. Space-Based Research in Fundamental Physics and Quantum Technologies

    NASA Astrophysics Data System (ADS)

    Turyshev, Slava G.; Israelsson, Ulf E.; Shao, Michael; Yu, Nan; Kusenko, Alexander; Wright, Edward L.; Everitt, C. W. Francis; Kasevich, Mark; Lipa, John A.; Mester, John C.; Reasenberg, Robert D.; Walsworth, Ronald L.; Ashby, Neil; Gould, Harvey; Paik, Ho Jung

    Space offers unique experimental conditions and a wide range of opportunities to explore the foundations of modern physics with an accuracy far beyond that of ground-based experiments. Space-based experiments today can uniquely address important questions related to the fundamental laws of Nature. In particular, high-accuracy physics experiments in space can test relativistic gravity and probe the physics beyond the Standard Model; they can perform direct detection of gravitational waves and are naturally suited for investigations in precision cosmology and astroparticle physics. In addition, atomic physics has recently shown substantial progress in the development of optical clocks and atom interferometers. If placed in space, these instruments could turn into powerful high-resolution quantum sensors greatly benefiting fundamental physics. We discuss the current status of space-based research in fundamental physics, its discovery potential, and its importance for modern science. We offer a set of recommendations to be considered by the upcoming National Academy of Sciences' Decadal Survey in Astronomy and Astrophysics. In our opinion, the Decadal Survey should include space-based research in fundamental physics as one of its focus areas. We recommend establishing an Astronomy and Astrophysics Advisory Committee's interagency "Fundamental Physics Task Force" to assess the status of both ground- and space-based efforts in the field, to identify the most important objectives, and to suggest the best ways to organize the work of several federal agencies involved. We also recommend establishing a new NASA-led interagency program in fundamental physics that will consolidate new technologies, prepare key instruments for future space missions, and build a strong scientific and engineering community. Our goal is to expand NASA's science objectives in space by including "laboratory research in fundamental physics" as an element in the agency's ongoing space research efforts.

  15. Was Fundamental Education Another Form Of Colonialism?

    NASA Astrophysics Data System (ADS)

    Watras, Joseph

    2007-01-01

    A description of the work of Pedro Tamesis Orata provides an opportunity to investigate the conflicts that can occur when educators seek to reduce poverty while trying to respect indigenous cultures. A native of the Philippines, Orata completed his doctoral studies at the Ohio State University in 1927. During US President Franklin Roosevelt's New Deal, he accepted the position of school principal for the US Bureau of Indian Affairs. After World War II, he directed the spread of fundamental education through the United Nations Educational, Scientific and Cultural Organization (UNESCO). In his final years, he returned to the Philippines where he began a movement to spread what were called self-help high schools. In these activities, Orata taught people to follow John Dewey's five steps of thinking while working to improve their standards of living. In the 1970s, educators, such as Paulo Freire, complained that problem-solving methods, similar to those Orata favored, reinforced the oppressive aspects of formerly colonial societies. While Freire may have been overly critical, conflicts among cultural orientations appear to be unavoidable. The hope behind this investigation is that the difficulties can be reduced when people understand the different forces that persist.

  16. How vinculin regulates force transmission.

    PubMed

    Dumbauld, David W; Lee, Ted T; Singh, Ankur; Scrimgeour, Jan; Gersbach, Charles A; Zamir, Evan A; Fu, Jianping; Chen, Christopher S; Curtis, Jennifer E; Craig, Susan W; García, Andrés J

    2013-06-11

    Focal adhesions mediate force transfer between ECM-integrin complexes and the cytoskeleton. Although vinculin has been implicated in force transmission, few direct measurements have been made, and there is little mechanistic insight. Using vinculin-null cells expressing vinculin mutants, we demonstrate that vinculin is not required for transmission of adhesive and traction forces but is necessary for myosin contractility-dependent adhesion strength and traction force and for the coupling of cell area and traction force. Adhesion strength and traction forces depend differentially on vinculin head (V(H)) and tail domains. V(H) enhances adhesion strength by increasing ECM-bound integrin-talin complexes, independently from interactions with vinculin tail ligands and contractility. A full-length, autoinhibition-deficient mutant (T12) increases adhesion strength compared with VH, implying roles for both vinculin activation and the actin-binding tail. In contrast to adhesion strength, vinculin-dependent traction forces absolutely require a full-length and activated molecule; V(H) has no effect. Physical linkage of the head and tail domains is required for maximal force responses. Residence times of vinculin in focal adhesions, but not T12 or V(H), correlate with applied force, supporting a mechanosensitive model for vinculin activation in which forces stabilize vinculin's active conformation to promote force transfer.

  17. How Do Fundamental Christians Deal with Depression?

    ERIC Educational Resources Information Center

    Spinney, Douglas Harvey

    1991-01-01

    Provides explanation of developmental dynamics in experience of fundamental Christians that provoke reactive depression. Describes depressant retardant defenses against depression that have been observed in Christian fundamental subculture. Suggests four counseling strategies for helping fundamentalists. (Author/ABL)

  18. Fundamentals and Techniques of Nonimaging

    SciTech Connect

    O'Gallagher, J. J.; Winston, R.

    2003-07-10

    This is the final report describing a long term basic research program in nonimaging optics that has led to major advances in important areas, including solar energy, fiber optics, illumination techniques, light detectors, and a great many other applications. The term ''nonimaging optics'' refers to the optics of extended sources in systems for which image forming is not important, but effective and efficient collection, concentration, transport, and distribution of light energy is. Although some of the most widely known developments of the early concepts have been in the field of solar energy, a broad variety of other uses have emerged. Most important, under the auspices of this program in fundamental research in nonimaging optics established at the University of Chicago with support from the Office of Basic Energy Sciences at the Department of Energy, the field has become very dynamic, with new ideas and concepts continuing to develop, while applications of the early concepts continue to be pursued. While the subject began as part of classical geometrical optics, it has been extended subsequently to the wave optics domain. Particularly relevant to potential new research directions are recent developments in the formalism of statistical and wave optics, which may be important in understanding energy transport on the nanoscale. Nonimaging optics permits the design of optical systems that achieve the maximum possible concentration allowed by physical conservation laws. The earliest designs were constructed by optimizing the collection of the extreme rays from a source to the desired target: the so-called ''edge-ray'' principle. Later, new concentrator types were generated by placing reflectors along the flow lines of the ''vector flux'' emanating from lambertian emitters in various geometries. A few years ago, a new development occurred with the discovery that making the design edge-ray a functional of some other system parameter permits the construction of whole

  19. Labor Force

    ERIC Educational Resources Information Center

    Occupational Outlook Quarterly, 2010

    2010-01-01

    The labor force is the number of people aged 16 or older who are either working or looking for work. It does not include active-duty military personnel or institutionalized people, such as prison inmates. Quantifying this total supply of labor is a way of determining how big the economy can get. Labor force participation rates vary significantly…

  20. Ultra-fast optical manipulation of single proteins binding to the actin cytoskeleton

    NASA Astrophysics Data System (ADS)

    Capitanio, Marco; Gardini, Lucia; Pavone, Francesco Saverio

    2014-02-01

    In the last decade, forces and mechanical stresses acting on biological systems are emerging as regulatory factors essential for cell life. Emerging evidences indicate that factors such as applied forces or the rigidity of the extracellular matrix (ECM) determine the shape and function of cells and organisms1. Classically, the regulation of biological systems is described through a series of biochemical signals and enzymatic reactions, which direct the processes and cell fate. However, mechanotransduction, i.e. the conversion of mechanical forces into biochemical and biomolecular signals, is at the basis of many biological processes fundamental for the development and differentiation of cells, for their correct function and for the development of pathologies. We recently developed an in vitro system that allows the investigation of force-dependence of the interaction of proteins binding the actin cytoskeleton, at the single molecule level. Our system displays a delay of only ~10 μs between formation of the molecular bond and application of the force and is capable of detecting interactions as short as 100 μs. Our assay allows direct measurements of load-dependence of lifetimes of single molecular bonds and conformational changes of single proteins and molecular motors. We demonstrate our technique on molecular motors, using myosin II from fast skeletal muscle and on protein-DNA interaction, specifically on Lactose repressor (LacI). The apparatus is stabilized to less than 1 nm with both passive and active stabilization, allowing resolving specific binding regions along the actin filament and DNA molecule. Our technique extends single-molecule force-clamp spectroscopy to molecular complexes that have been inaccessible up to now, opening new perspectives for the investigation of the effects of forces on biological processes.

  1. Future Fundamental Combustion Research for Aeropropulsion Systems.

    DTIC Science & Technology

    1985-01-01

    AD-MISS 771 FUTURE FUNDAMENTAL COMBUSTION RESEARCH FOR I AEROPROPULSION SYSTEMS(U) NATIONAL AERONAUTICS AND I SPACE ADMINISTRATION CLEVELAND OH LEWIS... Future Fundamental Combustion Research for Aeropropulsion Systems u. Edward J. Mularz V Propulsion Laboratory A VSCOM Research and Technology Laboratories... FUTURE FUNDAMENTAL COMBUSTION RESEARCH FOR AEROPROPULSION SYSTEMS Edward J. Mularz

  2. Fundamental Scaling Laws in Nanophotonics.

    PubMed

    Liu, Ke; Sun, Shuai; Majumdar, Arka; Sorger, Volker J

    2016-11-21

    The success of information technology has clearly demonstrated that miniaturization often leads to unprecedented performance, and unanticipated applications. This hypothesis of "smaller-is-better" has motivated optical engineers to build various nanophotonic devices, although an understanding leading to fundamental scaling behavior for this new class of devices is missing. Here we analyze scaling laws for optoelectronic devices operating at micro and nanometer length-scale. We show that optoelectronic device performance scales non-monotonically with device length due to the various device tradeoffs, and analyze how both optical and electrical constrains influence device power consumption and operating speed. Specifically, we investigate the direct influence of scaling on the performance of four classes of photonic devices, namely laser sources, electro-optic modulators, photodetectors, and all-optical switches based on three types of optical resonators; microring, Fabry-Perot cavity, and plasmonic metal nanoparticle. Results show that while microrings and Fabry-Perot cavities can outperform plasmonic cavities at larger length-scales, they stop working when the device length drops below 100 nanometers, due to insufficient functionality such as feedback (laser), index-modulation (modulator), absorption (detector) or field density (optical switch). Our results provide a detailed understanding of the limits of nanophotonics, towards establishing an opto-electronics roadmap, akin to the International Technology Roadmap for Semiconductors.

  3. Fundamental Scaling Laws in Nanophotonics

    NASA Astrophysics Data System (ADS)

    Liu, Ke; Sun, Shuai; Majumdar, Arka; Sorger, Volker J.

    2016-11-01

    The success of information technology has clearly demonstrated that miniaturization often leads to unprecedented performance, and unanticipated applications. This hypothesis of “smaller-is-better” has motivated optical engineers to build various nanophotonic devices, although an understanding leading to fundamental scaling behavior for this new class of devices is missing. Here we analyze scaling laws for optoelectronic devices operating at micro and nanometer length-scale. We show that optoelectronic device performance scales non-monotonically with device length due to the various device tradeoffs, and analyze how both optical and electrical constrains influence device power consumption and operating speed. Specifically, we investigate the direct influence of scaling on the performance of four classes of photonic devices, namely laser sources, electro-optic modulators, photodetectors, and all-optical switches based on three types of optical resonators; microring, Fabry-Perot cavity, and plasmonic metal nanoparticle. Results show that while microrings and Fabry-Perot cavities can outperform plasmonic cavities at larger length-scales, they stop working when the device length drops below 100 nanometers, due to insufficient functionality such as feedback (laser), index-modulation (modulator), absorption (detector) or field density (optical switch). Our results provide a detailed understanding of the limits of nanophotonics, towards establishing an opto-electronics roadmap, akin to the International Technology Roadmap for Semiconductors.

  4. Information physics fundamentals of nanophotonics.

    PubMed

    Naruse, Makoto; Tate, Naoya; Aono, Masashi; Ohtsu, Motoichi

    2013-05-01

    Nanophotonics has been extensively studied with the aim of unveiling and exploiting light-matter interactions that occur at a scale below the diffraction limit of light, and recent progress made in experimental technologies--both in nanomaterial fabrication and characterization--is driving further advancements in the field. From the viewpoint of information, on the other hand, novel architectures, design and analysis principles, and even novel computing paradigms should be considered so that we can fully benefit from the potential of nanophotonics. This paper examines the information physics aspects of nanophotonics. More specifically, we present some fundamental and emergent information properties that stem from optical excitation transfer mediated by optical near-field interactions and the hierarchical properties inherent in optical near-fields. We theoretically and experimentally investigate aspects such as unidirectional signal transfer, energy efficiency and networking effects, among others, and we present their basic theoretical formalisms and describe demonstrations of practical applications. A stochastic analysis of light-assisted material formation is also presented, where an information-based approach provides a deeper understanding of the phenomena involved, such as self-organization. Furthermore, the spatio-temporal dynamics of optical excitation transfer and its inherent stochastic attributes are utilized for solution searching, paving the way to a novel computing paradigm that exploits coherent and dissipative processes in nanophotonics.

  5. Levitated Optomechanics for Fundamental Physics

    NASA Astrophysics Data System (ADS)

    Rashid, Muddassar; Bateman, James; Vovrosh, Jamie; Hempston, David; Ulbricht, Hendrik

    2015-05-01

    Optomechanics with levitated nano- and microparticles is believed to form a platform for testing fundamental principles of quantum physics, as well as find applications in sensing. We will report on a new scheme to trap nanoparticles, which is based on a parabolic mirror with a numerical aperture of 1. Combined with achromatic focussing, the setup is a cheap and readily straightforward solution to trapping nanoparticles for further study. Here, we report on the latest progress made in experimentation with levitated nanoparticles; these include the trapping of 100 nm nanodiamonds (with NV-centres) down to 1 mbar as well as the trapping of 50 nm Silica spheres down to 10?4 mbar without any form of feedback cooling. We will also report on the progress to implement feedback stabilisation of the centre of mass motion of the trapped particle using digital electronics. Finally, we argue that such a stabilised particle trap can be the particle source for a nanoparticle matterwave interferometer. We will present our Talbot interferometer scheme, which holds promise to test the quantum superposition principle in the new mass range of 106 amu. EPSRC, John Templeton Foundation.

  6. Fundamental theory of crystal decomposition

    NASA Astrophysics Data System (ADS)

    Kunz, A. B.

    1991-05-01

    Lattice defects in or on crystalline materials, determine many technologically important properties. Reliable computerized simulation of such defects are of potential value, and may be expected to contribute to a fundamental understanding of the physical processes that determine the structure and properties of these materials. In the case of point defects, it is attractive to use quantum mechanics to describe the region of the crystal in proximity to the defect, perhaps embedding this region in an external potential determined by some auxiliary principle. The hope here is that the structural response of the lattice to the point defect may then be described by some method which is simpler than the quantum mechanical method used to describe the point defect itself. In the present case, the development is begun for the case of non-metals. In many studies performed prior to the present for such systems, the use of a classical shell model, based upon point charges, and masses, interacting by simple parameterized potentials has been successful in correlating perfect lattice equilibrium data with the ground state properties of defects in these systems. Therefore, the study was begun by choosing to think of the embedding lattice in terms of the classical shell model. It was found that it is possible to retain the functional form of the shell model, but determine all needed parameters from the quantum mechanical calculation, and to augment this functional form with appropriate angular potentials as well.

  7. Fundamental Scaling Laws in Nanophotonics

    PubMed Central

    Liu, Ke; Sun, Shuai; Majumdar, Arka; Sorger, Volker J.

    2016-01-01

    The success of information technology has clearly demonstrated that miniaturization often leads to unprecedented performance, and unanticipated applications. This hypothesis of “smaller-is-better” has motivated optical engineers to build various nanophotonic devices, although an understanding leading to fundamental scaling behavior for this new class of devices is missing. Here we analyze scaling laws for optoelectronic devices operating at micro and nanometer length-scale. We show that optoelectronic device performance scales non-monotonically with device length due to the various device tradeoffs, and analyze how both optical and electrical constrains influence device power consumption and operating speed. Specifically, we investigate the direct influence of scaling on the performance of four classes of photonic devices, namely laser sources, electro-optic modulators, photodetectors, and all-optical switches based on three types of optical resonators; microring, Fabry-Perot cavity, and plasmonic metal nanoparticle. Results show that while microrings and Fabry-Perot cavities can outperform plasmonic cavities at larger length-scales, they stop working when the device length drops below 100 nanometers, due to insufficient functionality such as feedback (laser), index-modulation (modulator), absorption (detector) or field density (optical switch). Our results provide a detailed understanding of the limits of nanophotonics, towards establishing an opto-electronics roadmap, akin to the International Technology Roadmap for Semiconductors. PMID:27869159

  8. Gas cell neutralizers (Fundamental principles)

    SciTech Connect

    Fuehrer, B.

    1985-06-01

    Neutralizing an ion-beam of the size and energy levels involved in the neutral-particle-beam program represents a considerable extension of the state-of-the-art of neutralizer technology. Many different mediums (e.g., solid, liquid, gas, plasma, photons) can be used to strip the hydrogen ion of its extra electron. A large, multidisciplinary R and D effort will no doubt be required to sort out all of the ''pros and cons'' of these various techniques. The purpose of this particular presentation is to discuss some basic configurations and fundamental principles of the gas type of neutralizer cell. Particular emphasis is placed on the ''Gasdynamic Free-Jet'' neutralizer since this configuration has the potential of being much shorter than other type of gas cells (in the beam direction) and it could operate in nearly a continuous mode (CW) if necessary. These were important considerations in the ATSU design which is discussed in some detail in the second presentation entitled ''ATSU Point Design''.

  9. Do goldfish miss the fundamental?

    NASA Astrophysics Data System (ADS)

    Fay, Richard R.

    2003-10-01

    The perception of harmonic complexes was studied in goldfish using classical respiratory conditioning and a stimulus generalization paradigm. Groups of animals were initially conditioned to several harmonic complexes with a fundamental frequency (f0) of 100 Hz. ln some cases the f0 component was present, and in other cases, the f0 component was absent. After conditioning, animals were tested for generalization to novel harmonic complexes having different f0's, some with f0 present and some with f0 absent. Generalization gradients always peaked at 100 Hz, indicating that the pitch value of the conditioning complexes was consistent with the f0, whether or not f0 was present in the conditioning or test complexes. Thus, goldfish do not miss the fundmental with respect to a pitch-like perceptual dimension. However, generalization gradients tended to have different skirt slopes for the f0-present and f0-absent conditioning and test stimuli. This suggests that goldfish distinguish between f0 present/absent stimuli, probably on the basis of a timbre-like perceptual dimension. These and other results demonstrate that goldfish respond to complex sounds as if they possessed perceptual dimensions similar to pitch and timbre as defined for human and other vertebrate listeners. [Work supported by NIH/NIDCD.

  10. Fundamental studies of fusion plasmas

    SciTech Connect

    Aamodt, R.E.; Catto, P.J.; D'Ippolito, D.A.; Myra, J.R.; Russell, D.A.

    1992-05-26

    The major portion of this program is devoted to critical ICH phenomena. The topics include edge physics, fast wave propagation, ICH induced high frequency instabilities, and a preliminary antenna design for Ignitor. This research was strongly coordinated with the world's experimental and design teams at JET, Culham, ORNL, and Ignitor. The results have been widely publicized at both general scientific meetings and topical workshops including the speciality workshop on ICRF design and physics sponsored by Lodestar in April 1992. The combination of theory, empirical modeling, and engineering design in this program makes this research particularly important for the design of future devices and for the understanding and performance projections of present tokamak devices. Additionally, the development of a diagnostic of runaway electrons on TEXT has proven particularly useful for the fundamental understanding of energetic electron confinement. This work has led to a better quantitative basis for quasilinear theory and the role of magnetic vs. electrostatic field fluctuations on electron transport. An APS invited talk was given on this subject and collaboration with PPPL personnel was also initiated. Ongoing research on these topics will continue for the remainder fo the contract period and the strong collaborations are expected to continue, enhancing both the relevance of the work and its immediate impact on areas needing critical understanding.

  11. Hyperbolic metamaterials: fundamentals and applications.

    PubMed

    Shekhar, Prashant; Atkinson, Jonathan; Jacob, Zubin

    2014-01-01

    Metamaterials are nano-engineered media with designed properties beyond those available in nature with applications in all aspects of materials science. In particular, metamaterials have shown promise for next generation optical materials with electromagnetic responses that cannot be obtained from conventional media. We review the fundamental properties of metamaterials with hyperbolic dispersion and present the various applications where such media offer potential for transformative impact. These artificial materials support unique bulk electromagnetic states which can tailor light-matter interaction at the nanoscale. We present a unified view of practical approaches to achieve hyperbolic dispersion using thin film and nanowire structures. We also review current research in the field of hyperbolic metamaterials such as sub-wavelength imaging and broadband photonic density of states engineering. The review introduces the concepts central to the theory of hyperbolic media as well as nanofabrication and characterization details essential to experimentalists. Finally, we outline the challenges in the area and offer a set of directions for future work.

  12. Fundamental approach to dipmeter analysis

    SciTech Connect

    Enderlin, M.B.; Hansen, D.K.T.

    1988-01-01

    Historically, in dipmeter analysis, depositional patterns are delineated for environmental, structural, and stratigraphic interpretations. The proposed method is a fundamental approach using raw data measurements from the dipmeter sonde to help the geologist describe subsurface structures on a stratigraphic scale. Raw data are available at the well site, require no post-processing, are cost effective, easy to use, require only a basic understanding of sedimentary features and can be combined with computed results. A case study illustrates the reconstruction of sedimentary features from a raw data log recorded by a six-arm dipmeter. The dipmeter is a wireline tool with a series of evenly spaced, focused electrodes applied to the circumference of the borehole wall. The raw data are presented as curves representing the electrode response and tool orientation. In outcrop, the geologist usually can see an entire sedimentary feature in a large perspective, that is, with the surrounding landscape. Therefore, a large range of features can be resolved. However, in the borehole environment the perspective is reduced to the borehole diameter, thus reducing the range of recognizable features. In this study, a table was assembled that identifies the features distinguished by the proposed method as a function of borehole diameter.

  13. Fundamentals of soft robot locomotion.

    PubMed

    Calisti, M; Picardi, G; Laschi, C

    2017-05-01

    Soft robotics and its related technologies enable robot abilities in several robotics domains including, but not exclusively related to, manipulation, manufacturing, human-robot interaction and locomotion. Although field applications have emerged for soft manipulation and human-robot interaction, mobile soft robots appear to remain in the research stage, involving the somehow conflictual goals of having a deformable body and exerting forces on the environment to achieve locomotion. This paper aims to provide a reference guide for researchers approaching mobile soft robotics, to describe the underlying principles of soft robot locomotion with its pros and cons, and to envisage applications and further developments for mobile soft robotics. © 2017 The Author(s).

  14. Force sensor

    DOEpatents

    Grahn, Allen R.

    1993-01-01

    A force sensor and related method for determining force components. The force sensor includes a deformable medium having a contact surface against which a force can be applied, a signal generator for generating signals that travel through the deformable medium to the contact surface, a signal receptor for receiving the signal reflected from the contact surface, a generation controller, a reception controller, and a force determination apparatus. The signal generator has one or more signal generation regions for generating the signals. The generation controller selects and activates the signal generation regions. The signal receptor has one or more signal reception regions for receiving signals and for generating detections signals in response thereto. The reception controller selects signal reception regions and detects the detection signals. The force determination apparatus measures signal transit time by timing activation and detection and, optionally, determines force components for selected cross-field intersections. The timer which times by activation and detection can be any means for measuring signal transit time. A cross-field intersection is defined by the overlap of a signal generation region and a signal reception region.

  15. Force sensor

    DOEpatents

    Grahn, A.R.

    1993-05-11

    A force sensor and related method for determining force components is described. The force sensor includes a deformable medium having a contact surface against which a force can be applied, a signal generator for generating signals that travel through the deformable medium to the contact surface, a signal receptor for receiving the signal reflected from the contact surface, a generation controller, a reception controller, and a force determination apparatus. The signal generator has one or more signal generation regions for generating the signals. The generation controller selects and activates the signal generation regions. The signal receptor has one or more signal reception regions for receiving signals and for generating detections signals in response thereto. The reception controller selects signal reception regions and detects the detection signals. The force determination apparatus measures signal transit time by timing activation and detection and, optionally, determines force components for selected cross-field intersections. The timer which times by activation and detection can be any means for measuring signal transit time. A cross-field intersection is defined by the overlap of a signal generation region and a signal reception region.

  16. Analytic, non-perturbative, gauge-invariant quantum chromodynamics: Nucleon scattering and binding potentials

    SciTech Connect

    Fried, H.M.; Gabellini, Y.; Grandou, T.; Sheu, Y.-M.

    2013-11-15

    Removal of the quenched approximation in the mechanism which produced an analytic estimate of quark-binding potentials, along with a reasonable conjecture of the color structure of the nucleon formed by such a binding potential, is shown to generate an effective nucleon scattering and binding potential. The mass-scale factor on the order of the pion mass, previously introduced to define the transverse imprecision of quark coordinates, is again used, while the strength of the potential is proportional to the square of a renormalized quantum chromodynamics (QCD) coupling constant. The potential so derived does not include corrections due to spin, angular momentum, nucleon structure, and electroweak interactions; rather, it is qualitative in nature, showing how Nuclear Physics can arise from fundamental QCD. -- Highlights: •Nucleon–nucleon forces are derived qualitatively from basic realistic quantum chromodynamics. •An effective nucleon binding is obtained from the simplest unquenched approximation. •A model deuteron binding energy of −2.2 MeV follows with α{sub s,R}=12.5.

  17. A force-based protein biochip

    NASA Astrophysics Data System (ADS)

    Blank, K.; Mai, T.; Gilbert, I.; Schiffmann, S.; Rankl, J.; Zivin, R.; Tackney, C.; Nicolaus, T.; Spinnler, K.; Oesterhelt, F.; Benoit, M.; Clausen-Schaumann, H.; Gaub, H. E.

    2003-09-01

    A parallel assay for the quantification of single-molecule binding forces was developed based on differential unbinding force measurements where ligand-receptor interactions are compared with the unzipping forces of DNA hybrids. Using the DNA zippers as molecular force sensors, the efficient discrimination between specific and nonspecific interactions was demonstrated for small molecules binding to specific receptors, as well as for protein-protein interactions on protein arrays. Finally, an antibody sandwich assay with different capture antibodies on one chip surface and with the detection antibodies linked to a congruent surface via the DNA zippers was used to capture and quantify a recombinant hepatitis C antigen from solution. In this case, the DNA zippers enable not only discrimination between specific and nonspecific binding, but also allow for the local application of detection antibodies, thereby eliminating false-positive results caused by cross-reactive antibodies and nonspecific binding.

  18. BOOK REVIEWS: Quantum Mechanics: Fundamentals

    NASA Astrophysics Data System (ADS)

    Whitaker, A.

    2004-02-01

    mechanics, which is assumed, but to examine whether it gives a consistent account of measurement. The conclusion is that after a measurement, interference terms are ‘effectively’ absent; the set of ‘one-to-one correlations between states of the apparatus and the object’ has the same form as that of everyday statistics and is thus a probability distribution. This probability distribution refers to potentialities, only one of which is actually realized in any one trial. Opinions may differ on whether their treatment is any less vulnerable to criticisms such as those of Bell. To sum up, Gottfried and Yan’s book contains a vast amount of knowledge and understanding. As well as explaining the way in which quantum theory works, it attempts to illuminate fundamental aspects of the theory. A typical example is the ‘fable’ elaborated in Gottfried’s article in Nature cited above, that if Newton were shown Maxwell’s equations and the Lorentz force law, he could deduce the meaning of E and B, but if Maxwell were shown Schrödinger’s equation, he could not deduce the meaning of Psi. For use with a well-constructed course (and, of course, this is the avowed purpose of the book; a useful range of problems is provided for each chapter), or for the relative expert getting to grips with particular aspects of the subject or aiming for a deeper understanding, the book is certainly ideal. It might be suggested, though, that, even compared to the first edition, the isolated learner might find the wide range of topics, and the very large number of mathematical and conceptual techniques, introduced in necessarily limited space, somewhat overwhelming. The second book under consideration, that of Schwabl, contains ‘Advanced’ elements of quantum theory; it is designed for a course following on from one for which Gottfried and Yan, or Schwabl’s own `Quantum Mechanics' might be recommended. It is the second edition in English, and is a translation of the third German edition

  19. Chronometric Geodesy and Fundamental Physics

    NASA Astrophysics Data System (ADS)

    Delva, P.; Puchades, N.; Lodewyck, J.

    2016-12-01

    Atomic clocks are today essential for several daily life applications, such as the building of the International Atomic Time (TAI) or Global Navigation Satellite Systems (GNSS). With the new generation of optical clocks, they reach such accuracy and stability that they are now considered in practical applications for the measurement of gravitational potential differences, thanks to the Einstein effect, or gravitational redshift. Several projects explored the possibilities of using clocks in geodesy or geophysical applications and research. This context offers a fantastic opportunity to use atomic clocks to test fundamental physics. In this talk I will present two such studies for testing the gravitational redshift and Lorentz invariance.The first project is the "Galileo gravitational Redshift test with Eccentric sATellites" (GREAT), funded by the European Space Agency (ESA). Here we use the on-board atomic clocks of the Galileo satellites 5 and 6 to look for violations of general relativity theory. These two satellites were launched on August, 30th 2014 and, because of a technical problem, the launcher brought them on an elliptic orbit. An elliptic orbit induces a periodic modulation of the gravitational redshift while the good stability of recent GNSS clocks allows to test this periodic modulation to a very good level of accuracy. The Galileo 5 and 6 satellites, with their large eccentricity and on-board H-maser clocks, are hence perfect candidates to perform this test.In the second study we propose a test of special relativity theory using a network of distant optical lattice clocks located in France, Germany and Great-Britain. By exploiting the difference between the velocities of each clock in the inertial geocentric frame, due to their different positions on the surface of the Earth, we can test the time dilation effect. The connection between these clocks, achieved with phase-compensated optical fibers, allows for an unprecedented level of statistical

  20. Astronomia Motivadora no Ensino Fundamental

    NASA Astrophysics Data System (ADS)

    Melo, J.; Voelzke, M. R.

    2008-09-01

    O objetivo principal deste trabalho é procurar desenvolver o interesse dos alunos pelas ciências através da Astronomia. Uma pesquisa com perguntas sobre Astronomia foi realizada junto a 161 alunos do Ensino Fundamental, com o intuito de descobrir conhecimentos prévios dos alunos sobre o assunto. Constatou-se, por exemplo, que 29,3% da 6ª série responderam corretamente o que é eclipse, 30,0% da 8ª série acertaram o que a Astronomia estuda, enquanto 42,3% dos alunos da 5ª série souberam definir o Sol. Pretende-se ampliar as turmas participantes e trabalhar, principalmente de forma prática com: dimensões e escalas no Sistema Solar, construção de luneta, questões como dia e noite, estações do ano e eclipses. Busca-se abordar, também, outros conteúdos de Física tais como a óptica na construção da luneta, e a mecânica no trabalho com escalas e medidas, e ao utilizar uma luminária para representar o Sol na questão do eclipse, e de outras disciplinas como a Matemática na transformação de unidades, regras de três; Artes na modelagem ou desenho dos planetas; a própria História com relação à busca pela origem do universo, e a Informática que possibilita a busca mais rápida por informações, além de permitir simulações e visualizações de imagens importantes. Acredita-se que a Astronomia é importante no processo ensino aprendizagem, pois permite a discussão de temas curiosos como, por exemplo, a origem do universo, viagens espaciais a existência ou não de vida em outros planetas, além de temas atuais como as novas tecnologias.

  1. T cell activation requires force generation

    PubMed Central

    Hu, Kenneth H.

    2016-01-01

    Triggering of the T cell receptor (TCR) integrates both binding kinetics and mechanical forces. To understand the contribution of the T cell cytoskeleton to these forces, we triggered T cells using a novel application of atomic force microscopy (AFM). We presented antigenic stimulation using the AFM cantilever while simultaneously imaging with optical microscopy and measuring forces on the cantilever. T cells respond forcefully to antigen after calcium flux. All forces and calcium responses were abrogated upon treatment with an F-actin inhibitor. When we emulated the forces of the T cell using the AFM cantilever, even these actin-inhibited T cells became activated. Purely mechanical stimulation was not sufficient; the exogenous forces had to couple through the TCR. These studies suggest a mechanical–chemical feedback loop in which TCR-triggered T cells generate forceful contacts with antigen-presenting cells to improve access to antigen. PMID:27241914

  2. Investigation of fundamental limits to beam brightness available from photoinjectors

    SciTech Connect

    Bazarov, Ivan

    2015-07-09

    The goal of this project was investigation of fundamental limits to beam brightness available from photoinjectors. This basic research in accelerator physics spanned over 5 years aiming to extend the fundamental understanding of high average current, low emittance sources of relativistic electrons based on photoemission guns, a necessary prerequisite for a new generation of coherent X-ray synchrotron radiation facilities based on continuous duty superconducting linacs. The program focused on two areas critical to making advances in the electron source performance: 1) the physics of photocathodes for the production of low emittance electrons and 2) control of space charge forces in the immediate vicinity to the cathode via 3D laser pulse shaping.

  3. Forced Snaking

    NASA Astrophysics Data System (ADS)

    Ponedel, Benjamin; Knobloch, Edgar

    2016-11-01

    We study spatial localization in the real subcritical Ginzburg-Landau equation ut =m0 u +m1 cos2/π l x u +uxx +d | u | 2 u -| u | 4 u with spatially periodic forcing. When d > 0 and m1 = 0 this equation exhibits bistability between the trivial state u = 0 and a homogeneous nontrivial state u =u0 with stationary localized structures which accumulate at the Maxwell point m0 = - 3d2 / 16 . When spatial forcing is included its wavelength is imprinted on u0 creating conditions favorable to front pinning and hence spatial localization. We use numerical continuation to show that under appropriate conditions such forcing generates a sequence of localized states organized within a snakes-and-ladders structure centered on the Maxwell point, and refer to this phenomenon as forced snaking. We determine the stability properties of these states and show that longer lengthscale forcing leads to stationary trains consisting of a finite number of strongly localized, weakly interacting pulses exhibiting foliated snaking.

  4. Implementing fundamental care in clinical practice.

    PubMed

    Feo, Rebecca; Conroy, Tiffany; Alderman, Jan; Kitson, Alison

    2017-04-05

    Modern healthcare environments are becoming increasingly complex. Delivering high-quality fundamental care in these environments is challenging for nurses and has been the focus of recent media, policy, academic and public scrutiny. Much of this attention arises from evidence that fundamental care is being neglected or delivered inadequately. There are an increasing number of standards and approaches to the delivery of fundamental care, which may result in confusion and additional documentation for nurses to complete. This article provides nurses with an approach to reframe their thinking about fundamental care, to ensure they meet patients' care needs and deliver holistic, person-centred care.

  5. Proposed experiment to test fundamentally binary theories

    NASA Astrophysics Data System (ADS)

    Kleinmann, Matthias; Vértesi, Tamás; Cabello, Adán

    2017-09-01

    Fundamentally binary theories are nonsignaling theories in which measurements of many outcomes are constructed by selecting from binary measurements. They constitute a sensible alternative to quantum theory and have never been directly falsified by any experiment. Here we show that fundamentally binary theories are experimentally testable with current technology. For that, we identify a feasible Bell-type experiment on pairs of entangled qutrits. In addition, we prove that, for any n , quantum n -ary correlations are not fundamentally (n -1 ) -ary. For that, we introduce a family of inequalities that hold for fundamentally (n -1 ) -ary theories but are violated by quantum n -ary correlations.

  6. Molecular force spectroscopy on cells.

    PubMed

    Liu, Baoyu; Chen, Wei; Zhu, Cheng

    2015-04-01

    Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

  7. Intermolecular forces.

    PubMed

    Buckingham, A D

    1975-11-06

    The nature of molecular interactions is examined. Intermolecular forces are divided into long-range and short-range components; the former operate at distances where the effects of electron exchange are negligible and decrease as an inverse power of the separation. The long-range interactions may be subdividied into electrostatic, induction and dispersion contributions, where the electrostatic component is the interaction of the permanent charge distributions and the others originate in the fluctuations in the distributions. Typical magnitudes of the various contributions are given. The forces between macroscopic bodies are briefly considered, as are the effects of a medium. Some of the manifestations of molecular interactions are discussed.

  8. Fundamental Mistuning Model for Probabilistic Analysis Studied Experimentally

    NASA Technical Reports Server (NTRS)

    Griffin, Jerry H.

    2005-01-01

    The Fundamental Mistuning Model (FMM) is a reduced-order model for efficiently calculating the forced response of a mistuned bladed disk. FMM ID is a companion program that determines the mistuning in a particular rotor. Together, these methods provide a way to acquire mistuning data in a population of bladed disks and then simulate the forced response of the fleet. This process was tested experimentally at the NASA Glenn Research Center, and the simulated results were compared with laboratory measurements of a "fleet" of test rotors. The method was shown to work quite well. It was found that the accuracy of the results depends on two factors: (1) the quality of the statistical model used to characterize mistuning and (2) how sensitive the system is to errors in the statistical modeling.

  9. An Analysis of Islamic Fundamentalism and Its Future Role in the Muslim World.

    DTIC Science & Technology

    1988-04-01

    must contain the name(s) of the report’s author(s). - If format modification is necessary to 5better serve the user’s needs , adjustments may be made to...PROGRAM PROJECT TASK WORK UNIT ELEMENT NO. NO. NO CCESSION NO. 11. TITLE (Include Security Clasification ) AN ANALYSIS OF ISLAMIC FUNDAMENTALISM AND...and social policies. As the forces of fundamentalism increase and are neither understood nor dealt with *correctly, many established governments

  10. Fundamental Skills in Science: Measurement. ERIC Digest.

    ERIC Educational Resources Information Center

    Haury, David L.

    This ERIC Digest concerns the fundamental science process skills of measurement. One only has to glance around the home or workplace to realize that measurement is fundamental to everyday life. International tests and student scores on measurement, measurement and curriculum standards, student difficulties and misconceptions, the challenge to…

  11. Individual differences in fundamental social motives.

    PubMed

    Neel, Rebecca; Kenrick, Douglas T; White, Andrew Edward; Neuberg, Steven L

    2016-06-01

    Motivation has long been recognized as an important component of how people both differ from, and are similar to, each other. The current research applies the biologically grounded fundamental social motives framework, which assumes that human motivational systems are functionally shaped to manage the major costs and benefits of social life, to understand individual differences in social motives. Using the Fundamental Social Motives Inventory, we explore the relations among the different fundamental social motives of Self-Protection, Disease Avoidance, Affiliation, Status, Mate Seeking, Mate Retention, and Kin Care; the relationships of the fundamental social motives to other individual difference and personality measures including the Big Five personality traits; the extent to which fundamental social motives are linked to recent life experiences; and the extent to which life history variables (e.g., age, sex, childhood environment) predict individual differences in the fundamental social motives. Results suggest that the fundamental social motives are a powerful lens through which to examine individual differences: They are grounded in theory, have explanatory value beyond that of the Big Five personality traits, and vary meaningfully with a number of life history variables. A fundamental social motives approach provides a generative framework for considering the meaning and implications of individual differences in social motivation. (PsycINFO Database Record

  12. Fundamentals of Physics, Problem Supplement No. 1

    NASA Astrophysics Data System (ADS)

    Halliday, David; Resnick, Robert; Walker, Jearl

    2000-05-01

    No other book on the market today can match the success of Halliday, Resnick and Walker's Fundamentals of Physics! In a breezy, easy-to-understand style the book offers a solid understanding of fundamental physics concepts, and helps readers apply this conceptual understanding to quantitative problem solving.

  13. Fundamentals of Physics, Student's Solutions Manual

    NASA Astrophysics Data System (ADS)

    Halliday, David; Resnick, Robert; Walker, Jearl

    2000-07-01

    No other book on the market today can match the success of Halliday, Resnick and Walker's Fundamentals of Physics! In a breezy, easy-to-understand style the book offers a solid understanding of fundamental physics concepts, and helps readers apply this conceptual understanding to quantitative problem solving.

  14. Fundamentals of Physics, 7th Edition

    NASA Astrophysics Data System (ADS)

    Halliday, David; Resnick, Robert; Walker, Jearl

    2004-05-01

    No other book on the market today can match the 30-year success of Halliday, Resnick and Walker's Fundamentals of Physics! In a breezy, easy-to-understand style the book offers a solid understanding of fundamental physics concepts, and helps readers apply this conceptual understanding to quantitative problem solving. This book offers a unique combination of authoritative content and stimulating applications.

  15. Fundamental optics: On-chip Casimir effect

    NASA Astrophysics Data System (ADS)

    Milton, Kimball A.

    2017-02-01

    Measurement of the forces that arise from quantum vacuum fluctuations between closely spaced surfaces typically requires large apparatus, making applications difficult. Now, an experiment on a silicon chip to measure the Casimir force has been realized.

  16. Fundamentals of wetting and spreading with emphasis on soldering

    SciTech Connect

    Yost, F.G.

    1991-01-01

    Soldering is often referred to as a mature technology whose fundamentals were established long ago. Yet a multitude of soldering problems persist, not the least of which are related to the wetting and spreading of solder. The Buff-Goodrich approach to thermodynamics of capillarity is utilized in a review of basic wetting principles. These thermodynamics allow a very compact formulation of capillary phenomena which is used to calculate various meniscus shapes and wetting forces. These shapes and forces lend themselves to experimental techniques, such as the sessile drop and the Wilhelmy plate, for measuring useful surface and interfacial energies. The familiar equations of Young, Wilhelmy, and Neumann are all derived with this approach. The force-energy duality of surface energy is discussed and the force method is developed and used to derive the Herring relations for anisotropic surfaces. The importance of contact angle hysteresis which results from surface roughness and chemical inhomogeneity is presented and Young's equation is modified to reflect these ever present effects. Finally, an analysis of wetting with simultaneous metallurigical reaction is given and used to discuss solder wetting phenomena. 60 refs., 13 figs.

  17. Fundamentals of Physics, Part 1 Revised Printing

    NASA Astrophysics Data System (ADS)

    Cummings, Karen; Halliday, David; Resnick, Robert; Walker, Jearl

    2001-08-01

    Measurement. Motion Along a Straight Line. Forces and Motion Along a Line. Vectors. Forces and Motion in Two Dimensions. Combined Forces. Translational Momentum. Extended Systems. Kinetic Energy and Work. Potential Energy and the Conservation of Energy. Rotation. Complex Rotations. Exercises and Problems. Special Problems. Appendices. Answers to Reading Exercises. Photo Credits. Index.

  18. Canonical Force Distributions in Pairwise Interatomic Interactions from the Perspective of the Hellmann-Feynman Theorem.

    PubMed

    Walton, Jay R; Rivera-Rivera, Luis A; Lucchese, Robert R; Bevan, John W

    2016-05-26

    Force-based canonical approaches have recently given a unified but different viewpoint on the nature of bonding in pairwise interatomic interactions. Differing molecular categories (covalent, ionic, van der Waals, hydrogen, and halogen bonding) of representative interatomic interactions with binding energies ranging from 1.01 to 1072.03 kJ/mol have been modeled canonically giving a rigorous semiempirical verification to high accuracy. However, the fundamental physical basis expected to provide the inherent characteristics of these canonical transformations has not yet been elucidated. Subsequently, it was shown through direct numerical differentiation of these potentials that their associated force curves have canonical shapes. However, this approach to analyzing force results in inherent loss of accuracy coming from numerical differentiation of the potentials. We now show that this serious obstruction can be avoided by directly demonstrating the canonical nature of force distributions from the perspective of the Hellmann-Feynman theorem. This requires only differentiation of explicitly known Coulombic potentials, and we discuss how this approach to canonical forces can be used to further explain the nature of chemical bonding in pairwise interatomic interactions. All parameter values used in the canonical transformation are determined through explicit physical based algorithms, and it does not require direct consideration of electron correlation effects.

  19. Fundamental solutions in a half space of two-dimensional hexagonal quasicrystal and their applications

    SciTech Connect

    Wang, T.; Li, X. Y.; Zhang, X.; Müller, R.

    2015-04-21

    Fundamental phonon-phason field in a half-infinite space of two-dimensional hexagonal quasicrystal is derived, on the basis of general solutions in terms of quasi-harmonic functions, by virtue of the trial-and-error technique. Extended Boussinesq and Cerruti problems are studied. Appropriate potential functions are assumed and corresponding fundamental solutions are explicitly derived in terms of elementary functions. The boundary integral equations governing the contact and crack problems are constructed from the present fundament solutions. The obtained analytical solutions can serve as guidelines for future indentation tests via scanning probe microscopy and atomic force microscopy methods.

  20. The FP4026 Research Database on the fundamental period of RC infilled frame structures.

    PubMed

    Asteris, Panagiotis G

    2016-12-01

    The fundamental period of vibration appears to be one of the most critical parameters for the seismic design of buildings because it strongly affects the destructive impact of the seismic forces. In this article, important research data (entitled FP4026 Research Database (Fundamental Period-4026 cases of infilled frames) based on a detailed and in-depth analytical research on the fundamental period of reinforced concrete structures is presented. In particular, the values of the fundamental period which have been analytically determined are presented, taking into account the majority of the involved parameters. This database can be extremely valuable for the development of new code proposals for the estimation of the fundamental period of reinforced concrete structures fully or partially infilled with masonry walls.

  1. Differential force balances during levitation

    NASA Astrophysics Data System (ADS)

    Todd, Paul

    The simplest arithmetic of inertial, buoyant, magnetic and electrokinetic levitation is explored in the context of a model living system with “acceleration-sensitive structures” in which motion, if allowed, produces a biological effect. The simple model is a finite-sized object enclosed within another finite-sized object suspended in an outer fluid (liquid or vapor) medium. The inner object has density and electrical and magnetic properties quantitatively different from those of the outer object and the medium. In inertial levitation (“weightlessness”) inertial accelerations are balanced, and the forces due to them are canceled in accordance with Newton’s third law. In the presence of inertial acceleration (gravity, centrifugal) motionlessness depends on a balance between the levitating force and the inertial force. If the inner and outer objects differ in density one or the other will be subjected to an unbalanced force when one object is levitated by any other force (buoyant, magnetic, electrokinetic). The requirements for motionlessness of the internal object in the presence of a levitating force are equality of density in the case of buoyant levitation, equality of magnetic susceptibility in the case of magnetic levitation, and equality of zeta potential and dielectric constant in the case of electrokinetic levitation. Examples of internal “acceleration-sensitive structures” are cellular organelles and the organs of advanced plants and animals. For these structures fundamental physical data are important in the interpretation of the effects of forces used for levitation.

  2. Loss of Desmoglein Binding Is Not Sufficient for Keratinocyte Dissociation in Pemphigus.

    PubMed

    Vielmuth, Franziska; Waschke, Jens; Spindler, Volker

    2015-12-01

    Pemphigus vulgaris (PV) is a severe autoimmune disease in which autoantibodies against the desmosomal cell adhesion molecules desmoglein (Dsg) 1 and Dsg3 cause intraepidermal blister formation. Mechanistically, the fundamental question is still unresolved whether loss of cell cohesion is a result of (1) direct inhibition of Dsg interaction by autoantibodies or (2) intracellular signaling events, which are altered in response to antibody binding and finally cause desmosome destabilization. We used atomic force microscopy (AFM) to perform Dsg3 adhesion measurements on living keratinocytes to investigate the contributions of direct inhibition and signaling to loss of cell cohesion after autoantibody treatment. Dsg3 binding was rapidly blocked following antibody exposure under conditions where no depletion of surface Dsg3 was detectable, demonstrating direct inhibition of Dsg3 interaction. Inhibition of p38MAPK, a central signaling molecule in PV pathogenesis, abrogated loss of cell cohesion, but had a minor effect on loss of Dsg3 binding. Similarly, the cholesterol-depleting agent methyl-β-cyclodextrin (β-MCD) fully blocked cell dissociation, but did not restore Dsg3 interactions or prevent the activation of p38MAPK. These results demonstrate that inhibition of Dsg3 binding is not sufficient to cause loss of cell cohesion, but rather alters signaling events which, in lipid raft-dependent manner, induce cell dissociation.

  3. Energy profile of nanobody-GFP complex under force

    NASA Astrophysics Data System (ADS)

    Klamecka, Kamila; Severin, Philip M.; Milles, Lukas F.; Gaub, Hermann E.; Leonhardt, Heinrich

    2015-10-01

    Nanobodies (Nbs)—the smallest known fully functional and naturally occuring antigen-binding fragments—have attracted a lot of attention throughout the last two decades. Exploring their potential beyond the current use requires more detailed characterization of their binding forces as those cannot be directly derived from the binding affinities. Here we used atomic force microscope to measure rupture force of the Nb-green fluorescent protein (GFP) complex in various pulling geometries and derived the energy profile characterizing the interaction along the direction of the pulling force. We found that—despite identical epitopes—the Nb binds stronger (41-56 pN) to enhanced GFP than to wild-type GFP (28-45 pN). Measured forces make the Nb-GFP pair a potent reference for investigating molecular forces in living systems both in and ex vivo.

  4. Bacterial adhesion force quantification by fluidic force microscopy

    NASA Astrophysics Data System (ADS)

    Potthoff, Eva; Ossola, Dario; Zambelli, Tomaso; Vorholt, Julia A.

    2015-02-01

    Quantification of detachment forces between bacteria and substrates facilitates the understanding of the bacterial adhesion process that affects cell physiology and survival. Here, we present a method that allows for serial, single bacterial cell force spectroscopy by combining the force control of atomic force microscopy with microfluidics. Reversible bacterial cell immobilization under physiological conditions on the pyramidal tip of a microchanneled cantilever is achieved by underpressure. Using the fluidic force microscopy technology (FluidFM), we achieve immobilization forces greater than those of state-of-the-art cell-cantilever binding as demonstrated by the detachment of Escherichia coli from polydopamine with recorded forces between 4 and 8 nN for many cells. The contact time and setpoint dependence of the adhesion forces of E. coli and Streptococcus pyogenes, as well as the sequential detachment of bacteria out of a chain, are shown, revealing distinct force patterns in the detachment curves. This study demonstrates the potential of the FluidFM technology for quantitative bacterial adhesion measurements of cell-substrate and cell-cell interactions that are relevant in biofilms and infection biology.Quantification of detachment forces between bacteria and substrates facilitates the understanding of the bacterial adhesion process that affects cell physiology and survival. Here, we present a method that allows for serial, single bacterial cell force spectroscopy by combining the force control of atomic force microscopy with microfluidics. Reversible bacterial cell immobilization under physiological conditions on the pyramidal tip of a microchanneled cantilever is achieved by underpressure. Using the fluidic force microscopy technology (FluidFM), we achieve immobilization forces greater than those of state-of-the-art cell-cantilever binding as demonstrated by the detachment of Escherichia coli from polydopamine with recorded forces between 4 and 8 nN for many

  5. Force decomposition in robot force control

    NASA Technical Reports Server (NTRS)

    Murphy, Steve H.; Wen, John T.

    1991-01-01

    The unit inconsistency in force decomposition has motivated an investigation into the force control problem in multiple-arm manipulation. Based on physical considerations, it is argued that the force that should be controlled is the internal force at the specified frame in the payload. This force contains contributions due to both applied forces from the arms and the inertial force from the payload and the arms. A least-squares scheme free of unit inconsistency for finding this internal force is presented. The force control issue is analyzed, and an integral force feedback controller is proposed.

  6. Strategic forces

    SciTech Connect

    Not Available

    1990-10-01

    The Air Force now plans to retain the Minuteman II and III missile force through fiscal year 2008. Introduced about 25 years ago, these missiles have served as a nuclear deterrence for longer than initially envisioned. Over the extended lives of the systems, questions have arisen over their continued reliability and operational effectiveness, particularly the Minuteman II system. Limited flight testing, due to a shortage of test missiles, and reduced reliability caused by age-related deterioration of guidance computers and propulsion motors are two factors undermining confidence in the Minuteman II. GAO believes that the Minuteman II could be retired before 1998 as presently contemplated under an assumption of a Strategic Arms Reduction Talks agreement. An alternative would be to reinstate the Air Force's plans to replace deteriorated missile components and acquire the assets needed to resume flight testing at rates necessary to restore and sustain confidence in the system's performance through fiscal year 2008. However, on the basis of current test schedules, GAO is concerned that components to test the missile's warheads will be depleted by about 1999.

  7. Ion-pair binding: is binding both binding better?

    PubMed

    Roelens, Stefano; Vacca, Alberto; Francesconi, Oscar; Venturi, Chiara

    2009-08-17

    It is often tempting to explain chemical phenomena on the basis of intuitive principles, but this practice can frequently lead to biased analysis of data and incorrect conclusions. One such intuitive principle is brought into play in the binding of salts by synthetic receptors. Following the heuristic concept that "binding both is binding better", it is widely believed that ditopic receptors capable of binding both ionic partners of a salt are more effective than monotopic receptors because of a cooperative effect. Using a newly designed ditopic receptor and a generalized binding descriptor, we show here that, when the problem is correctly formulated and the appropriate algorithm is derived, the cooperativity principle is neither general nor predictable, and that competition between ion binding and ion pairing may even lead to inhibition rather than enhancement of the binding of an ion to a ditopic receptor.

  8. Modeling of fundamental phenomena in welds

    SciTech Connect

    Zacharia, T.; Vitek, J.M.; Goldak, J.A.; DebRoy, T.A.; Rappaz, M.; Bhadeshia, H.K.D.H.

    1993-12-31

    Recent advances in the mathematical modeling of fundamental phenomena in welds are summarized. State-of-the-art mathematical models, advances in computational techniques, emerging high-performance computers, and experimental validation techniques have provided significant insight into the fundamental factors that control the development of the weldment. The current status and scientific issues in the areas of heat and fluid flow in welds, heat source metal interaction, solidification microstructure, and phase transformations are assessed. Future research areas of major importance for understanding the fundamental phenomena in weld behavior are identified.

  9. Fundamentals of preparative and nonlinear chromatography

    SciTech Connect

    Guiochon, Georges A; Felinger, Attila; Katti, Anita; Shirazi, Dean G

    2006-02-01

    The second edition of Fundamentals of Preparative and Nonlinear Chromatography is devoted to the fundamentals of a new process of purification or extraction of chemicals or proteins widely used in the pharmaceutical industry and in preparative chromatography. This process permits the preparation of extremely pure compounds satisfying the requests of the US Food and Drug Administration. The book describes the fundamentals of thermodynamics, mass transfer kinetics, and flow through porous media that are relevant to chromatography. It presents the models used in chromatography and their solutions, discusses the applications made, describes the different processes used, their numerous applications, and the methods of optimization of the experimental conditions of this process.

  10. Rotor-Liquid-Fundament System's Oscillation

    NASA Astrophysics Data System (ADS)

    Kydyrbekuly, A.

    The work is devoted to research of oscillation and sustainability of stationary twirl of vertical flexible static dynamically out-of-balance rotor with cavity partly filled with liquid and set on relative frame fundament. The accounting of such factors like oscillation of fundament, liquid oscillation, influence of asymmetry of installation of a rotor on a shaft, anisotropism of shaft support and fundament, static and dynamic out-of-balance of a rotor, an external friction, an internal friction of a shaft, allows to settle an invoice more precisely kinematic and dynamic characteristics of system.

  11. Representation of Ion–Protein Interactions Using the Drude Polarizable Force-Field

    PubMed Central

    2016-01-01

    Small metal ions play critical roles in numerous biological processes. Of particular interest is how metalloenzymes are allosterically regulated by the binding of specific ions. Understanding how ion binding affects these biological processes requires atomic models that accurately treat the microscopic interactions with the protein ligands. Theoretical approaches at different levels of sophistication can contribute to a deeper understanding of these systems, although computational models must strike a balance between accuracy and efficiency in order to enable long molecular dynamics simulations. In this study, we present a systematic effort to optimize the parameters of a polarizable force field based on classical Drude oscillators to accurately represent the interactions between ions (K+, Na+, Ca2+, and Cl–) and coordinating amino-acid residues for a set of 30 biologically important proteins. By combining ab initio calculations and experimental thermodynamic data, we derive a polarizable force field that is consistent with a wide range of properties, including the geometries and interaction energies of gas-phase ion/protein-like model compound clusters, and the experimental solvation free-energies of the cations in liquids. The resulting models display significant improvements relative to the fixed-atomic-charge additive CHARMM C36 force field, particularly in their ability to reproduce the many-body electrostatic nonadditivity effects estimated from ab initio calculations. The analysis clarifies the fundamental limitations of the pairwise additivity assumption inherent in classical fixed-charge force fields, and shows its dramatic failures in the case of Ca2+ binding sites. These optimized polarizable models, amenable to computationally efficient large-scale MD simulations, set a firm foundation and offer a powerful avenue to study the roles of the ions in soluble and membrane transport proteins. PMID:25578354

  12. The binding interactions of imidacloprid with earthworm fibrinolytic enzyme

    NASA Astrophysics Data System (ADS)

    Wang, Yan-Qing; Zhang, Hong-Mei; Chen, Tao

    2014-08-01

    In this paper, several studies were conducted to elucidate the binding mechanism of earthworm fibrinolytic enzyme (EFE) with imidocloprid (IMI) by using theoretical calculation, fluorescence, UV-vis, circular dichroism spectroscopy and an enzymatic inhibition assay. The spectral data showed that the binding interactions existed between IMI and EFE. The binding constants, binding site, thermodynamic parameters and binding forces were analyzed in detail. The results indicate a single class of binding sites for IMI in EFE and that this binding interaction is a spontaneous process with the estimated enthalpy and entropy changes being 2.195 kJ mol-1 and 94.480 J mol-1 K-1, respectively. A single class of binding site existed for IMI in EFE. The tertiary or secondary structure of EFE was partly destroyed by IMI. The visualized binding details were also exhibited by the theoretical calculation and the results indicated that the interaction between IMI and Phe (Tyr, or Trp) or EFE occurred. Combining the experimental data with the theoretical calculation data, we showed that the binding forces between IMI and EFE were mainly hydrophobic force accompanied by hydrogen binding, and π-π stacking. In addition, IMI did not obviously influence the activity of EFE. In a word, the above analysis offered insights into the binding mechanism of IMI with EFE and could provide some important information for the molecular toxicity of IMI for earthworms.

  13. Force measurement enabling precise analysis by dynamic force spectroscopy.

    PubMed

    Taninaka, Atsushi; Hirano, Yuuichi; Takeuchi, Osamu; Shigekawa, Hidemi

    2012-01-01

    Dynamic force spectroscopy (DFS) makes it possible to investigate specific interactions between two molecules such as ligand-receptor pairs at the single-molecule level. In the DFS method based on the Bell-Evans model, the unbinding force applied to a molecular bond is increased at a constant rate, and the force required to rupture the molecular bond is measured. By analyzing the relationship between the modal rupture force and the logarithm of the loading rate, microscopic potential barrier landscapes and the lifetimes of bonds can be obtained. However, the results obtained, for example, in the case of streptavidin/biotin complexes, have differed among previous studies and some results have been inconsistent with theoretical predictions. In this study, using an atomic force microscopy technique that enables the precise analysis of molecular interactions on the basis of DFS, we investigated the effect of the sampling rate on DFS analysis. The shape of rupture force histograms, for example, was significantly deformed at a sampling rate of 1 kHz in comparison with that of histograms obtained at 100 kHz, indicating the fundamental importance of ensuring suitable experimental conditions for further advances in the DFS method.

  14. Accounting Fundamentals for Non-Accountants

    EPA Pesticide Factsheets

    The purpose of this module is to provide an introduction and overview of accounting fundamentals for non-accountants. The module also covers important topics such as communication, internal controls, documentation and recordkeeping.

  15. Fundamentals of Indoor Air Quality in Buildings

    EPA Pesticide Factsheets

    This module provides the fundamentals to understanding indoor air quality. It provides a rudimentary framework for understanding how indoor and outdoor sources of pollution affect the indoor air quality of buildings.

  16. Strategic Information Resources Management: Fundamental Practices.

    ERIC Educational Resources Information Center

    Caudle, Sharon L.

    1996-01-01

    Discusses six fundamental information resources management (IRM) practices in successful organizations that can improve government service delivery performance. Highlights include directing changes, integrating IRM decision making into a strategic management process, performance management, maintaining an investment philosophy, using business…

  17. Language Policy and Planning: Fundamental Issues.

    ERIC Educational Resources Information Center

    Kaplan, Robert B.

    1994-01-01

    Fundamental issues in language policy and planning are discussed: language death, language survival, language change, language revival, language shift and expansion, language contact and pidginization or creolization, and literacy development. (Contains 21 references.) (LB)

  18. Instructor Special Report: RIF (Reading Is FUNdamental)

    ERIC Educational Resources Information Center

    Instructor, 1976

    1976-01-01

    At a time when innovative programs of the sixties are quickly falling out of the picture, Reading Is FUNdamental, after ten years and five million free paperbacks, continues to expand and show results. (Editor)

  19. The structure of binding curves and practical identifiability of equilibrium ligand-binding parameters

    PubMed Central

    Middendorf, Thomas R.

    2017-01-01

    A critical but often overlooked question in the study of ligands binding to proteins is whether the parameters obtained from analyzing binding data are practically identifiable (PI), i.e., whether the estimates obtained from fitting models to noisy data are accurate and unique. Here we report a general approach to assess and understand binding parameter identifiability, which provides a toolkit to assist experimentalists in the design of binding studies and in the analysis of binding data. The partial fraction (PF) expansion technique is used to decompose binding curves for proteins with n ligand-binding sites exactly and uniquely into n components, each of which has the form of a one-site binding curve. The association constants of the PF component curves, being the roots of an n-th order polynomial, may be real or complex. We demonstrate a fundamental connection between binding parameter identifiability and the nature of these one-site association constants: all binding parameters are identifiable if the constants are all real and distinct; otherwise, at least some of the parameters are not identifiable. The theory is used to construct identifiability maps from which the practical identifiability of binding parameters for any two-, three-, or four-site binding curve can be assessed. Instructions for extending the method to generate identifiability maps for proteins with more than four binding sites are also given. Further analysis of the identifiability maps leads to the simple rule that the maximum number of structurally identifiable binding parameters (shown in the previous paper to be equal to n) will also be PI only if the binding curve line shape contains n resolved components. PMID:27993951

  20. Does logic moderate the fundamental attribution error?

    PubMed

    Stalder, D R

    2000-06-01

    The fundamental attribution error was investigated from an individual difference perspective. Mathematicians were compared with nonmathematicians (Exp. 1; n: 84), and undergraduates who scored high on a test of logical reasoning ability were compared with those who scored low (Exp. 2; n: 62). The mathematicians and those participants scoring higher on logic appeared less prone to the fundamental attribution error, primarily using a measure of confidence in attributions.

  1. Force spectroscopy of DNA: there is still a lot to learn

    NASA Astrophysics Data System (ADS)

    Paik, D. H.; Perkins, Thomas T.

    2012-10-01

    Single-molecule studies of the mechanical properties of individual double-stranded DNA have excited interest across many scientific disciplines because of DNA's fundamental role in biology and DNA's remarkable overstretching transition at higher forces. Here, we discuss a recent result on the overstretching transition of DNA and on the dynamics of dye molecules intercalating into DNA under tension. Overstretching DNA is mechanical transition whereby DNA's extension increases by 70% at 65 pN. Notwithstanding more than a decade of experimental and theoretical studies, there remains significant debate on the nature of overstretched DNA. We developed a topologically closed but torsionally unconstrained DNA assay that contains no nicks or free ends. DNA in this assay exhibited the canonical overstretching transition at 65 pN but without hysteresis upon retraction. Controlled introduction of a nick led to hysteresis in the force extension curve. Moreover, the degree of hysteresis increased with the number of nicks. In the second study, we isolated the effects of binding and intercalation of a DNA staining dye, by combining single molecule force spectroscopy with simple buffer exchange. We showed that force-enhanced intercalation can occur from a reservoir of bound dye that was not bis-intercalated, yet remained out of equilibrium with free dye for long periods (<5 min for YOPRO and <2 hr for YOYO). Our work highlights that binding/unbinding and intercalation/de-intercalation are distinct processes that can occur on very different time scales. Taken together, these works highlight ongoing discoveries based on a twenty year old technique, force spectroscopy of single DNA molecules.

  2. Fundamental Reaction Mechanism for Cocaine Hydrolysis in Human Butyrylcholinesterase

    PubMed Central

    Zhan, Chang-Guo; Zheng, Fang; Landry, Donald W.

    2010-01-01

    Butyrylcholinesterase (BChE)-cocaine binding and the fundamental pathway for BChE-catalyzed hydrolysis of cocaine have been studied by molecular modelling, molecular dynamics (MD) simulations, and ab initio calculations. Modelling and simulations indicate that the structures of the prereactive BChE-substrate complexes for (−)-cocaine and (+)-cocaine are all similar to that of the corresponding prereactive BChE-butyrylcholine (BCh) complex. The overall binding of BChE with (−)-cocaine and (+)-cocaine is also similar to that proposed with butyrylthiocholine and succinyldithiocholine, i.e. (−)-cocaine/(+)-cocaine first slides down the substrate-binding gorge to bind to Trp-82 and stands vertically in the gorge between Asp-70 and Trp-82 (non-prereactive complex) and then rotates to a position in the catalytic site within a favorable distance for nucleophilic attack and hydrolysis by Ser-198 (prereactive complex). In the prereactive complex, cocaine lies horizontally at the bottom of the gorge. The fundamental catalytic hydrolysis pathway, consisting of acylation and deacylation stages similar to those for ester hydrolysis by other serine hydrolases, was proposed based on the simulated prereactive complex and confirmed theoretically by ab initio reaction coordinate calculations. Both the acylation and deacylation follow a double-proton-transfer mechanism. The calculated energetic results show that within the chemical reaction process the highest energy barrier and Gibbs free energy barrier are all associated with the first step of deacylation. The calculated ratio of the rate constant (kcat) for the catalytic hydrolysis to that (k0) for the spontaneous hydrolysis is ~ 9.0 × 107. The estimated kcat/k0 value of ~ 9.0 × 107 is in excellent agreement with the experimentally-derived kcat/k0 value of ~ 7.2 × 107 for (+)-cocaine, whereas it is ~ 2000 times larger than the experimentally-derived kcat/k0 value of ~ 4.4 × 104 for (−)-cocaine. All of the results

  3. Compulsory Bible Reading in Arkansas and the Culture of Southern Fundamentalism.

    ERIC Educational Resources Information Center

    Bolton, S. Charles; Ledbetter, Cal Jr.

    1983-01-01

    Arkansas passed a law requiring Bible reading in public schools in 1930, two years after passing an antievolution act. Votes on both measures, which were the result of initiatives, are compared to explain the forces that produced them. The source of support of fundamentalism is traditional southern religious attitudes. (Author/IS)

  4. FUNDAMENTAL DIFFERENCES BETWEEN NATURAL ANTIBODIES AND POLYREACTIVE IMMUNOGLOBULINS.

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A problem of similarity and differences between so-called polyreactive immunoglobulins (PRIGs) and natural antibodies (NAbs), capable of cross-reacting with some structurally dissimilar antigens, has been considered. The analysis of mechanisms of an unspecific interaction between PRIGs or NAbs and antigens evidences for the fact that essential differences exist between these substances. These differences permit classifying the abovementioned substances as different types of immunoglobulin molecules. The major difference between PRIGs and NAbs may include both the mechanisms of the above mentioned immunoglobulin molecules binding to antigens and their interaction affinity, as well as an absolutely different influence of some low-molecular substances on the efficiency of the interaction with antigens. Relying on the obtained data it can be assumed that, since PRIGs and NAbs have fundamental differences, they may perform not only similar but also different functions of the immune system.

  5. Producing the deuteron in stars: anthropic limits on fundamental constants

    NASA Astrophysics Data System (ADS)

    Barnes, Luke A.; Lewis, Geraint F.

    2017-07-01

    Stellar nucleosynthesis proceeds via the deuteron (D), but only a small change in the fundamental constants of nature is required to unbind it. Here, we investigate the effect of altering the binding energy of the deuteron on proton burning in stars. We find that the most definitive boundary in parameter space that divides probably life-permitting universes from probably life-prohibiting ones is between a bound and unbound deuteron. Due to neutrino losses, a ball of gas will undergo rapid cooling or stabilization by electron degeneracy pressure before it can form a stable, nuclear reaction-sustaining star. We also consider a less-bound deuteron, which changes the energetics of the pp and pep reactions. The transition to endothermic pp and pep reactions, and the resulting beta-decay instability of the deuteron, do not seem to present catastrophic problems for life.

  6. A Fundamental Equation of State for Ethanol

    NASA Astrophysics Data System (ADS)

    Schroeder, J. A.; Penoncello, S. G.; Schroeder, J. S.

    2014-12-01

    The existing fundamental equation for ethanol demonstrates undesirable behavior in several areas and especially in the critical region. In addition, new experimental data have become available in the open literature since the publication of the current correlation. The development of a new fundamental equation for ethanol, in the form of Helmholtz energy as a function of temperature and density, is presented. New, nonlinear fitting techniques, along with the new experimental data, are shown to improve the behavior of the fundamental equation. Ancillary equations are developed, including equations for vapor pressure, saturated liquid density, saturated vapor density, and ideal gas heat capacity. Both the fundamental and ancillary equations are compared to experimental data. The fundamental equation can compute densities to within ±0.2%, heat capacities to within ±1%-2%, and speed of sound to within ±1%. Values of the vapor pressure and saturated vapor densities are represented to within ±1% at temperatures of 300 K and above, while saturated liquid densities are represented to within ±0.3% at temperatures of 200 K and above. The uncertainty of all properties is higher in the critical region and near the triple point. The equation is valid for pressures up to 280 MPa and temperatures from 160 to 650 K.

  7. Coriolis Force

    NASA Astrophysics Data System (ADS)

    Marciuc, Daly; Solschi, Viorel

    2017-04-01

    Understanding the Coriolis effect is essential for explaining the movement of air masses and ocean currents. The lesson we propose aims to familiarize students with the manifestation of the Coriolis effect. Students are guided to build, using the GeoGebra software, a simulation of the motion of a body, related to a rotating reference system. The mathematical expression of the Coriolis force is deduced, for particular cases, and the Foucault's pendulum is presented and explained. Students have the opportunity to deepen the subject, by developing materials related to topics such as: • Global Wind Pattern • Ocean Currents • Coriolis Effect in Long Range Shooting • Finding the latitude with a Foucault Pendulum

  8. Comparison of the depth profiles of water and water-binding substances in the stratum corneum determined in vivo by Raman spectroscopy between the cheek and volar forearm skin: effects of age, seasonal changes and artificial forced hydration.

    PubMed

    Egawa, M; Tagami, H

    2008-02-01

    Dermatologists and cosmetic scientists are becoming increasingly interested in stratum corneum (SC) hydration because the SC plays an important role in keeping the skin surface soft and smooth. However, conventional in vivo noninvasive methods do not provide direct information about the depth profiles of water content or SC components that hold water. To study the depth profiles of water and SC components in vivo by Raman spectroscopy, and to analyse the changes due to age, anatomical location, season and water application. In vivo Raman spectra of the skin of the cheek and the volar forearm were obtained from 50 healthy Japanese volunteers of different ages (age range 22-76 years) with a confocal Raman spectrometer. The depth-dependent profiles of water and of SC water-binding components were calculated from the respective Raman spectra. The depth profile of the SC water content was observed in a pattern ranging from around 30% (water/wet tissue) at the outermost layer of the SC to about 70% at the deeper living layer. Although the water content at a depth of 10-30 microm in the forearm skin tended to be lower in older subjects than in younger subjects, no such difference was found in the much thinner SC of the cheek. Moreover, there was no seasonal difference in depth profile of water content from the mid part of the SC to an 80-microm depth from the skin surface both in the cheek and in the forearm. The water content of all the evaluated SC components showed a gradual decrease from the surface to deeper portions. The mean amounts of lactate in the forearm skin and cholesterol in the cheek skin were significantly higher in younger subjects than in older subjects. In contrast, the levels of free amino acids and trans-urocanic acid were higher in the forearm skin of older subjects than in younger subjects. The relative amounts of urea and lactate were the highest in summer, when that of trans-urocanic acid was the lowest. Prolonged water application on the forearm

  9. The role of nonlinear dynamics in quantitative atomic force microscopy.

    PubMed

    Platz, Daniel; Forchheimer, Daniel; Tholén, Erik A; Haviland, David B

    2012-07-05

    Various methods of force measurement with the atomic force microscope are compared for their ability to accurately determine the tip-surface force from analysis of the nonlinear cantilever motion. It is explained how intermodulation, or the frequency mixing of multiple drive tones by the nonlinear tip-surface force, can be used to concentrate the nonlinear motion in a narrow band of frequency near the cantilever's fundamental resonance, where accuracy and sensitivity of force measurement are greatest. Two different methods for reconstructing tip-surface forces from intermodulation spectra are explained. The reconstruction of both conservative and dissipative tip-surface interactions from intermodulation spectra are demonstrated on simulated data.

  10. Natural transition from rate to force control of a manipulator

    NASA Technical Reports Server (NTRS)

    Harrison, F. W.; Soloway, Don; Williams, Robert L.; Hogge, Edward F.

    1992-01-01

    A method for teleoperator control which offers advantages over previous techniques is demonstrated. In the new method, a fundamental variable exchanged between the master and slave is the rate of change in position and force. An inherent capability of the control scheme is demonstrated for transition between control methods based on environmental constraints in a manner natural to the operator. Specifically, rate control of a manipulator makes the transition to force-force control when a force-reflecting hand controller is used with a local force accommodation algorithm running on the remote manipulator. The transition from rate to force occurs when contact is made with the environment.

  11. Ratiometric Tension Probes for Mapping Receptor Forces and Clustering at Intermembrane Junctions.

    PubMed

    Ma, Victor Pui-Yan; Liu, Yang; Blanchfield, Lori; Su, Hanquan; Evavold, Brian D; Salaita, Khalid

    2016-07-13

    Short-range communication between cells is required for the survival of multicellular organisms. One mechanism of chemical signaling between adjacent cells employs surface displayed ligands and receptors that only bind when two cells make physical contact. Ligand-receptor complexes that form at the cell-cell junction and physically bridge two cells likely experience mechanical forces. A fundamental challenge in this area pertains to mapping the mechanical forces experienced by ligand-receptor complexes within such a fluid intermembrane junction. Herein, we describe the development of ratiometric tension probes for direct imaging of receptor tension, clustering, and lateral transport within a model cell-cell junction. These probes employ two fluorescent reporters that quantify both the ligand density and the ligand tension and thus generate a tension signal independent of clustering. As a proof-of-concept, we applied the ratiometric tension probes to map the forces experienced by the T-cell receptor (TCR) during activation and showed the first direct evidence that the TCR-ligand complex experiences sustained pN forces within a fluid membrane junction. We envision that the ratiometric tension probes will be broadly useful for investigating mechanotransduction in juxtacrine signaling pathways.

  12. Fundamental Interventions: How Clinicians Can Address the Fundamental Causes of Disease.

    PubMed

    Reich, Adam D; Hansen, Helena B; Link, Bruce G

    2016-06-01

    In order to enhance the "structural competency" of medicine-the capability of clinicians to address social and institutional determinants of their patients' health-physicians need a theoretical lens to see how social conditions influence health and how they might address them. We consider one such theoretical lens, fundamental cause theory, and propose how it might contribute to a more structurally competent medical profession. We first describe fundamental cause theory and how it makes the social causes of disease and health visible. We then outline the sorts of "fundamental interventions" that physicians might make in order to address the fundamental causes.

  13. Improtance of fundamental study in hydrometallurgy

    NASA Astrophysics Data System (ADS)

    Majima, Hiroshi

    1995-02-01

    Recent developments in modeling and optimization studies using computer technology have had a remarkable effect on all areas of extractive metallurgy. However, a lack of fundamental data regarding, for instance, activities, diffusion coefficients, limiting current densities, etc. obstructs the reliable use of this method. In studying hydrometallurgy, I recognized the importance of fundamental analysis and continued such works throughout my university life. For example, activities of water and solutes of the solution systems H2SO4-Mx(SO4)y-H2O and HCl-MClx-H2O were determined, and the results were employed to analyze the dissolution mechanism of metal oxides as well as metal sulfides in those solutions. In this article, fundamental studies mainly made in my laboratory to understand hydrometallurgical phenomena will be discussed.

  14. Sensors, Volume 1, Fundamentals and General Aspects

    NASA Astrophysics Data System (ADS)

    Grandke, Thomas; Ko, Wen H.

    1996-12-01

    'Sensors' is the first self-contained series to deal with the whole area of sensors. It describes general aspects, technical and physical fundamentals, construction, function, applications and developments of the various types of sensors. This volume deals with the fundamentals and common principles of sensors and covers the wide areas of principles, technologies, signal processing, and applications. Contents include: Sensor Fundamentals, e.g. Sensor Parameters, Modeling, Design and Packaging; Basic Sensor Technologies, e.g. Thin and Thick Films, Integrated Magnetic Sensors, Optical Fibres and Intergrated Optics, Ceramics and Oxides; Sensor Interfaces, e.g. Signal Processing, Multisensor Signal Processing, Smart Sensors, Interface Systems; Sensor Applications, e.g. Automotive: On-board Sensors, Traffic Surveillance and Control, Home Appliances, Environmental Monitoring, etc. This volume is an indispensable reference work and text book for both specialits and newcomers, researchers and developers.

  15. The Fundamental Neutron Physics Facilities at NIST.

    PubMed

    Nico, J S; Arif, M; Dewey, M S; Gentile, T R; Gilliam, D M; Huffman, P R; Jacobson, D L; Thompson, A K

    2005-01-01

    The program in fundamental neutron physics at the National Institute of Standards and Technology (NIST) began nearly two decades ago. The Neutron Interactions and Dosimetry Group currently maintains four neutron beam lines dedicated to studies of fundamental neutron interactions. The neutrons are provided by the NIST Center for Neutron Research, a national user facility for studies that include condensed matter physics, materials science, nuclear chemistry, and biological science. The beam lines for fundamental physics experiments include a high-intensity polychromatic beam, a 0.496 nm monochromatic beam, a 0.89 nm monochromatic beam, and a neutron interferometer and optics facility. This paper discusses some of the parameters of the beam lines along with brief presentations of some of the experiments performed at the facilities.

  16. Fundamental cosmology from precision spectroscopy: Varying couplings

    NASA Astrophysics Data System (ADS)

    Leite, A. C. O.; Martins, C. J. A. P.; Pedrosa, P. O. J.; Nunes, N. J.

    2014-09-01

    The observational evidence for the acceleration of the Universe demonstrates that canonical theories of cosmology and particle physics are incomplete, if not incorrect, and that new physics is out there, waiting to be discovered. Forthcoming high-resolution ultrastable spectrographs will play a crucial role in this quest for new physics, by enabling a new generation of precision consistency tests. Here we focus on astrophysical tests of the stability of nature's fundamental couplings, and by using principal component analysis techniques further calibrated by existing VLT data we discuss how the improvements that can be expected with ESPRESSO and ELT-HIRES will impact on fundamental cosmology. In particular we show that a 20 to 30 night program on ELT-HIRES will allow it to play a leading role in fundamental cosmology.

  17. The perception of fundamental frequency declination.

    PubMed

    Pierrehumbert, J

    1979-08-01

    A series of experiments was carried out to investigate how fundamental frequency declination is perceived by speakers of English. Using linear predictor coded speech, nonsense sentences were constructed in which fundamental frequency on the last stressed syllable had been systematically varied. Listeners were asked to judge which stressed syllable was higher in pitch. Their judgments were found to reflect normalization for expected declination; in general, when two stressed syllables sounded equal in pitch, the second was actually lower. The pattern of normalization reflected certain major features of production patterns: A greater correction for declination was made for wide pitch range stimuli than for narrow pitch range stimuli. The slope of expected declination was less for longer stimuli than for shorter ones. Lastly, amplitude was found to have a significant effect on judgments, suggesting that the amplitude downdrift which normally accompanies fundamental frequency declination may have an important role in the perception of phrasing.

  18. Fundamental understanding of matter: an engineering viewpoint

    SciTech Connect

    Cullingford, H.S.; Cort, G.E.

    1980-01-01

    Fundamental understanding of matter is a continuous process that should produce physical data for use by engineers and scientists in their work. Lack of fundamental property data in any engineering endeavor cannot be mitigated by theoretical work that is not confirmed by physical experiments. An engineering viewpoint will be presented to justify the need for understanding of matter. Examples will be given in the energy engineering field to outline the importance of further understanding of material and fluid properties and behavior. Cases will be cited to show the effects of various data bases in energy, mass, and momentum transfer. The status of fundamental data sources will be discussed in terms of data centers, new areas of engineering, and the progress in measurement techniques. Conclusions and recommendations will be outlined to improve the current situation faced by engineers in carrying out their work. 4 figures.

  19. Fundamental Vocabulary Selection Based on Word Familiarity

    NASA Astrophysics Data System (ADS)

    Sato, Hiroshi; Kasahara, Kaname; Kanasugi, Tomoko; Amano, Shigeaki

    This paper proposes a new method for selecting fundamental vocabulary. We are presently constructing the Fundamental Vocabulary Knowledge-base of Japanese that contains integrated information on syntax, semantics and pragmatics, for the purposes of advanced natural language processing. This database mainly consists of a lexicon and a treebank: Lexeed (a Japanese Semantic Lexicon) and the Hinoki Treebank. Fundamental vocabulary selection is the first step in the construction of Lexeed. The vocabulary should include sufficient words to describe general concepts for self-expandability, and should not be prohibitively large to construct and maintain. There are two conventional methods for selecting fundamental vocabulary. The first is intuition-based selection by experts. This is the traditional method for making dictionaries. A weak point of this method is that the selection strongly depends on personal intuition. The second is corpus-based selection. This method is superior in objectivity to intuition-based selection, however, it is difficult to compile a sufficiently balanced corpora. We propose a psychologically-motivated selection method that adopts word familiarity as the selection criterion. Word familiarity is a rating that represents the familiarity of a word as a real number ranging from 1 (least familiar) to 7 (most familiar). We determined the word familiarity ratings statistically based on psychological experiments over 32 subjects. We selected about 30,000 words as the fundamental vocabulary, based on a minimum word familiarity threshold of 5. We also evaluated the vocabulary by comparing its word coverage with conventional intuition-based and corpus-based selection over dictionary definition sentences and novels, and demonstrated the superior coverage of our lexicon. Based on this, we conclude that the proposed method is superior to conventional methods for fundamental vocabulary selection.

  20. Dark Energy: A Crisis for Fundamental Physics

    ScienceCinema

    Stubbs, Christopher [Harvard University, Cambridge, Massachusetts, USA

    2016-07-12

    Astrophysical observations provide robust evidence that our current picture of fundamental physics is incomplete. The discovery in 1998 that the expansion of the Universe is accelerating (apparently due to gravitational repulsion between regions of empty space!) presents us with a profound challenge, at the interface between gravity and quantum mechanics. This "Dark Energy" problem is arguably the most pressing open question in modern fundamental physics. The first talk will describe why the Dark Energy problem constitutes a crisis, with wide-reaching ramifications. One consequence is that we should probe our understanding of gravity at all accessible scales, and the second talk will present experiments and observations that are exploring this issue.

  1. DOE Fundamentals Handbook: Mathematics, Volume 2

    SciTech Connect

    Not Available

    1992-06-01

    The Mathematics Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of mathematics and its application to facility operation. The handbook includes a review of introductory mathematics and the concepts and functional use of algebra, geometry, trigonometry, and calculus. Word problems, equations, calculations, and practical exercises that require the use of each of the mathematical concepts are also presented. This information will provide personnel with a foundation for understanding and performing basic mathematical calculations that are associated with various DOE nuclear facility operations.

  2. DOE Fundamentals Handbook: Mathematics, Volume 1

    SciTech Connect

    Not Available

    1992-06-01

    The Mathematics Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of mathematics and its application to facility operation. The handbook includes a review of introductory mathematics and the concepts and functional use of algebra, geometry, trigonometry, and calculus. Word problems, equations, calculations, and practical exercises that require the use of each of the mathematical concepts are also presented. This information will provide personnel with a foundation for understanding and performing basic mathematical calculations that are associated with various DOE nuclear facility operations.

  3. Fundamental ethical principles in health care.

    PubMed

    Thompson, I E

    1987-12-05

    In an attempt to clarify which requirements of morality are logically primary to the ethics of health care, two questions are examined: is there sufficient common ground among the medical, nursing, paramedical, chaplaincy, and social work professions to justify looking for ethical principles common to health care? Do sufficient logical grounds or consensus among health workers and the public exist to speak of "fundamental ethical principles in health care"? While respect for persons, justice, and beneficence are fundamental principles in a formal sense, how we view these principles in practice will depend on our particular culture and experience and the kinds of metaethical criteria we use for applying these principles.

  4. DOE Fundamentals Handbook: Electrical Science, Volume 1

    SciTech Connect

    Not Available

    1992-06-01

    The Electrical Science Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of electrical theory, terminology, and application. The handbook includes information on alternating current (AC) and direct current (DC) theory, circuits, motors, and generators; AC power and reactive components; batteries; AC and DC voltage regulators; transformers; and electrical test instruments and measuring devices. This information will provide personnel with a foundation for understanding the basic operation of various types of DOE nuclear facility electrical equipment.

  5. DOE Fundamentals Handbook: Electrical Science, Volume 2

    SciTech Connect

    Not Available

    1992-06-01

    The Electrical Science Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding terminology, and application. The handbook includes information on alternating current (AC) and direct current (DC) theory, circuits, motors, and generators; AC power and reactive components; batteries; AC and DC voltage regulators; transformers; and electrical test instruments and measuring devices. This information will provide personnel with a foundation for understanding the basic operation of various types of DOE nuclear facility electrical equipment.

  6. DOE Fundamentals Handbook: Electrical Science, Volume 4

    SciTech Connect

    Not Available

    1992-06-01

    The Electrical Science Fundamentals Handbook was developed to assist nuclear facility operating contractors provide operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of electrical theory, terminology, and application. The handbook includes information on alternating current (AC) and direct current (DC) theory, circuits, motors, and generators; AC power and reactive transformers; and electrical test components; batteries; AC and DC voltage regulators; instruments and measuring devices. This information will provide personnel with a foundation for understanding the basic operation of various types of DOE nuclear facility electrical equipment.

  7. Friction Force: From Mechanics to Thermodynamics

    ERIC Educational Resources Information Center

    Ferrari, Christian; Gruber, Christian

    2010-01-01

    We study some mechanical problems in which a friction force is acting on a system. Using the fundamental concepts of state, time evolution and energy conservation, we explain how to extend Newtonian mechanics to thermodynamics. We arrive at the two laws of thermodynamics and then apply them to investigate the time evolution and heat transfer of…

  8. Friction Force: From Mechanics to Thermodynamics

    ERIC Educational Resources Information Center

    Ferrari, Christian; Gruber, Christian

    2010-01-01

    We study some mechanical problems in which a friction force is acting on a system. Using the fundamental concepts of state, time evolution and energy conservation, we explain how to extend Newtonian mechanics to thermodynamics. We arrive at the two laws of thermodynamics and then apply them to investigate the time evolution and heat transfer of…

  9. Summary remarks: Fundamental physics with the cosmic microwave background radiation

    NASA Astrophysics Data System (ADS)

    Partridge, Bruce

    2006-12-01

    This article is less a summary of the meeting, vibrant as it was, than a reflection on the present state of CMB studies. We are at an interesting juncture: in the week before the Irvine meeting, the rich results of the WMAP 3-year study were released, and the next goals in CMB studies have been examined in some detail by a recent multi-agency Task Force. I will look at the value of theory and phenomenology to the field, and the increasing importance of CMB studies to fundamental physics. Then I'll move to challenges facing us over the next decade or so. These include coping with foreground emission, polarized and unpolarized, and readjusting the sociology of our field as experiments grow more complex and costly.

  10. Forces driving epithelial wound healing

    NASA Astrophysics Data System (ADS)

    Brugués, Agustí; Anon, Ester; Conte, Vito; Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2014-09-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and `purse-string’ contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate.

  11. Forces driving epithelial wound healing

    PubMed Central

    Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2015-01-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and “purse-string” contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate. PMID:27340423

  12. The influence of fundamental frequency on perceived duration in spectrally comparable sounds.

    PubMed

    Dawson, Caitlin; Aalto, Daniel; Simko, Juraj; Vainio, Martti

    2017-01-01

    The perceived duration of a sound is affected by its fundamental frequency and intensity: higher sounds are judged to be longer, as are sounds with greater intensity. Since increasing intensity lengthens the perceived duration of the auditory object, and increasing the fundamental frequency increases the sound's perceived loudness (up to ca. 3 kHz), frequency modulation of duration could be potentially explained by a confounding effect where the primary cause of the modulation would be variations in intensity. Here, a series of experiments are described that were designed to disentangle the contributions of fundamental frequency, intensity, and duration to perceived loudness and duration. In two forced-choice tasks, participants judged duration and intensity differences between two sounds varying simultaneously in intensity, fundamental frequency, fundamental frequency gliding range, and duration. The results suggest that fundamental frequency and intensity each have an impact on duration judgments, while frequency gliding range did not influence the present results. We also demonstrate that the modulation of perceived duration by sound fundamental frequency cannot be fully explained by the confounding relationship between frequency and intensity.

  13. The role of DNA-binding specificity in the evolution of bacterial regulatory networks

    PubMed Central

    Lozada-Chávez, Irma; Angarica, Vladimir Espinosa; Collado-Vides, Julio; Contreras-Moreira, Bruno

    2008-01-01

    Understanding the mechanisms by which transcriptional regulatory networks (TRNs) change through evolution is a fundamental problem. Here we analyze this question using data from Escherichia coli and Bacillus subtilis, finding that paralogy relationships are insufficient to explain the global or local role observed for transcription factors (TFs) within regulatory networks. Our results provide a picture in which DNA-binding specificity, a molecular property that can be measured in different ways, is a predictor of the role of transcription factors. In particular, we observe that global regulators consistently display low binding specificities, while displaying comparatively higher expression values in microarray experiments. In addition, in this work we find a strong negative correlation between binding specificity and the number of co-regulators which help coordinate genetic expression at a genomic scale. A close look at several orthologous TFs, including FNR, a regulator found to be global in E. coli and local in B. subtilis, confirms the diagnostic value of specificity in order to understand their regulatory function, and also highlights the importance of evaluating the metabolic and ecological relevance of effectors as another variable in the evolutionary equation of regulatory networks. Finally, a general model is presented that integrates some evolutionary forces and molecular properties, aiming to explain how regulons grow and shrink, as bacteria tune their regulation to increase adaptation. PMID:18466918

  14. Fundamentals of Energy Technology. Energy Technology Series.

    ERIC Educational Resources Information Center

    Center for Occupational Research and Development, Inc., Waco, TX.

    This course in fundamentals of energy technology is one of 16 courses in the Energy Technology Series developed for an Energy Conservation-and-Use Technology curriculum. Intended for use in two-year postsecondary technical institutions to prepare technicians for employment, the courses are also useful in industry for updating employees in…

  15. Fundamental Movement Skills: An Important Focus

    ERIC Educational Resources Information Center

    Barnett, Lisa M.; Stodden, David; Cohen, Kristen E.; Smith, Jordan J.; Lubans, David Revalds; Lenoir, Matthieu; Iivonen, Susanna; Miller, Andrew D.; Laukkanen, Arto; Dudley, Dean; Lander, Natalie J.; Brown, Helen; Morgan, Philip J.

    2016-01-01

    Purpose: Recent international conference presentations have critiqued the promotion of fundamental movement skills (FMS) as a primary pedagogical focus. Presenters have called for a debate about the importance of, and rationale for teaching FMS, and this letter is a response to that call. The authors of this letter are academics who actively…

  16. Fundamental Movement Skill Proficiency amongst Adolescent Youth

    ERIC Educational Resources Information Center

    O' Brien, Wesley; Belton, Sarahjane; Issartel, Johann

    2016-01-01

    Background: Literature suggests that physical education programmes ought to provide intense instruction towards basic movement skills needed to enjoy a variety of physical activities. Fundamental movement skills (FMS) are basic observable patterns of behaviour present from childhood to adulthood (e.g. run, skip and kick). Recent evidence indicates…

  17. Fundamentals of Electric Circuits. Laboratory Manual.

    ERIC Educational Resources Information Center

    Wentworth Inst., Boston, MA.

    This laboratory manual consists of three major sections. The first section deals with Direct Current (DC) fundamentals, and is divided into 17 phases leading towards the design and analysis of a DC ammeter and a DC voltmeter. Each phase consists of facts and problems to be learned in the phase, preliminary discussion, laboratory operation…

  18. Fundamental and Gradient Differences in Language Development

    ERIC Educational Resources Information Center

    Herschensohn, Julia

    2009-01-01

    This article reexamines Bley-Vroman's original (1990) and evolved fundamental difference hypothesis that argues that differences in path and endstate of first language acquisition and adult foreign language learning result from differences in the acquisition procedure (i.e., language faculty and cognitive strategies, respectively). The evolved…

  19. A Fundamental Theorem on Particle Acceleration

    SciTech Connect

    Xie, Ming

    2003-05-01

    A fundamental theorem on particle acceleration is derived from the reciprocity principle of electromagnetism and a rigorous proof of the theorem is presented. The theorem establishes a relation between acceleration and radiation, which is particularly useful for insightful understanding of and practical calculation about the first order acceleration in which energy gain of the accelerated particle is linearly proportional to the accelerating field.

  20. Fundamental problems in provable security and cryptography.

    PubMed

    Dent, Alexander W

    2006-12-15

    This paper examines methods for formally proving the security of cryptographic schemes. We show that, despite many years of active research and dozens of significant results, there are fundamental problems which have yet to be solved. We also present a new approach to one of the more controversial aspects of provable security, the random oracle model.

  1. Fundamental Concepts Bridging Education and the Brain

    ERIC Educational Resources Information Center

    Masson, Steve; Foisy, Lorie-Marlène Brault

    2014-01-01

    Although a number of papers have already discussed the relevance of brain research for education, the fundamental concepts and discoveries connecting education and the brain have not been systematically reviewed yet. In this paper, four of these concepts are presented and evidence concerning each one is reviewed. First, the concept of…

  2. Prequantum Classical Statistical Field Theory: Fundamentals

    SciTech Connect

    Khrennikov, Andrei

    2011-03-28

    We present fundamentals of a prequantum model with hidden variables of the classical field type. In some sense this is the comeback of classical wave mechanics. Our approach also can be considered as incorporation of quantum mechanics into classical signal theory. All quantum averages (including correlations of entangled systems) can be represented as classical signal averages and correlations.

  3. Fundamentals of Library Science. Library Science 424.

    ERIC Educational Resources Information Center

    Foster, Donald L.

    An introductory letter, a list of general instructions on how to proceed with a correspondence course, a syllabus, and an examination request form are presented for a correspondence course in the fundamentals of library science offered by the University of New Mexico's Division of Continuing Education and Community Services. The course is a survey…

  4. Fundamentals of Library Science. Library Science 424.

    ERIC Educational Resources Information Center

    Foster, Donald L.

    An introductory letter, a list of general instructions on how to proceed with a correspondence course, a syllabus, and an examination request form are presented for a correspondence course in the fundamentals of library science offered by the University of New Mexico's Division of Continuing Education and Community Services. The course is a survey…

  5. Fundamental and Gradient Differences in Language Development

    ERIC Educational Resources Information Center

    Herschensohn, Julia

    2009-01-01

    This article reexamines Bley-Vroman's original (1990) and evolved fundamental difference hypothesis that argues that differences in path and endstate of first language acquisition and adult foreign language learning result from differences in the acquisition procedure (i.e., language faculty and cognitive strategies, respectively). The evolved…

  6. The Failed Feminist Challenge to "Fundamental Epistemology"

    ERIC Educational Resources Information Center

    Pinnick, Cassandra L.

    2005-01-01

    Despite volumes written in the name of the new and fundamental feminist project in philosophy of science, and conclusions drawn on the strength of the hypothesis that the feminist project will boost progress toward cognitive aims associated with science and rationality (and, one might add, policy decisions enacted in the name of these aims), the…

  7. Man's Size in Terms of Fundamental Constants.

    ERIC Educational Resources Information Center

    Press, William H.

    1980-01-01

    Reviews calculations that derive an order of magnitude expression for the size of man in terms of fundamental constants, assuming that man satifies these three properties: he is made of complicated molecules; he requires an atmosphere which is not hydrogen and helium; he is as large as possible. (CS)

  8. Fundamental Movement Skills and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Staples, Kerri L.; Reid, Greg

    2010-01-01

    Delays and deficits may both contribute to atypical development of movement skills by children with ASD. Fundamental movement skills of 25 children with autism spectrum disorders (ASD) (ages 9-12 years) were compared to three typically developing groups using the "Test of Gross Motor Development" ("TGMD-2"). The group matched on chronological age…

  9. Retention of Electronic Fundamentals: Differences Among Topics.

    ERIC Educational Resources Information Center

    Johnson, Kirk A.

    Criterion-referenced tests were used to measure the learning and retention of a sample of material taught by means of programed instruction in the Avionics Fundamentals Course, Class A. It was found that the students knew about 30 percent of the material before reading the programs, that mastery rose to a very high level on the immediate posttest,…

  10. Man's Size in Terms of Fundamental Constants.

    ERIC Educational Resources Information Center

    Press, William H.

    1980-01-01

    Reviews calculations that derive an order of magnitude expression for the size of man in terms of fundamental constants, assuming that man satifies these three properties: he is made of complicated molecules; he requires an atmosphere which is not hydrogen and helium; he is as large as possible. (CS)

  11. Mathematical Literacy--It's Become Fundamental

    ERIC Educational Resources Information Center

    McCrone, Sharon Soucy; Dossey, John A.

    2007-01-01

    The rising tide of numbers and statistics in daily life signals a need for a fundamental broadening of the concept of literacy: mathematical literacy assuming a coequal role in the curriculum alongside language-based literacy. Mathematical literacy is not about studying higher levels of formal mathematics, but about making math relevant and…

  12. Solar Energy: Solar System Design Fundamentals.

    ERIC Educational Resources Information Center

    Knapp, Henry H., III

    This module on solar system design fundamentals is one of six in a series intended for use as supplements to currently available materials on solar energy and energy conservation. Together with the recommended texts and references (sources are identified), these modules provide an effective introduction to energy conservation and solar energy…

  13. Biological and cognitive underpinnings of religious fundamentalism.

    PubMed

    Zhong, Wanting; Cristofori, Irene; Bulbulia, Joseph; Krueger, Frank; Grafman, Jordan

    2017-04-06

    Beliefs profoundly affect people's lives, but their cognitive and neural pathways are poorly understood. Although previous research has identified the ventromedial prefrontal cortex (vmPFC) as critical to representing religious beliefs, the means by which vmPFC enables religious belief is uncertain. We hypothesized that the vmPFC represents diverse religious beliefs and that a vmPFC lesion would be associated with religious fundamentalism, or the narrowing of religious beliefs. To test this prediction, we assessed religious adherence with a widely-used religious fundamentalism scale in a large sample of 119 patients with penetrating traumatic brain injury (pTBI). If the vmPFC is crucial to modulating diverse personal religious beliefs, we predicted that pTBI patients with lesions to the vmPFC would exhibit greater fundamentalism, and that this would be modulated by cognitive flexibility and trait openness. Instead, we found that participants with dorsolateral prefrontal cortex (dlPFC) lesions have fundamentalist beliefs similar to patients with vmPFC lesions and that the effect of a dlPFC lesion on fundamentalism was significantly mediated by decreased cognitive flexibility and openness. These findings indicate that cognitive flexibility and openness are necessary for flexible and adaptive religious commitment, and that such diversity of religious thought is dependent on dlPFC functionality.

  14. Euler and the Fundamental Theorem of Algebra.

    ERIC Educational Resources Information Center

    Duham, William

    1991-01-01

    The complexity of the proof of the Fundamental Theorem of Algebra makes it inaccessible to lower level students. Described are more understandable attempts of proving the theorem and a historical account of Euler's efforts that relates the progression of the mathematical process used and indicates some of the pitfalls encountered. (MDH)

  15. Fundamental Theorems of Algebra for the Perplexes

    ERIC Educational Resources Information Center

    Poodiak, Robert; LeClair, Kevin

    2009-01-01

    The fundamental theorem of algebra for the complex numbers states that a polynomial of degree n has n roots, counting multiplicity. This paper explores the "perplex number system" (also called the "hyperbolic number system" and the "spacetime number system") In this system (which has extra roots of +1 besides the usual [plus or minus]1 of the…

  16. Fundamental Movement Skills: An Important Focus

    ERIC Educational Resources Information Center

    Barnett, Lisa M.; Stodden, David; Cohen, Kristen E.; Smith, Jordan J.; Lubans, David Revalds; Lenoir, Matthieu; Iivonen, Susanna; Miller, Andrew D.; Laukkanen, Arto; Dudley, Dean; Lander, Natalie J.; Brown, Helen; Morgan, Philip J.

    2016-01-01

    Purpose: Recent international conference presentations have critiqued the promotion of fundamental movement skills (FMS) as a primary pedagogical focus. Presenters have called for a debate about the importance of, and rationale for teaching FMS, and this letter is a response to that call. The authors of this letter are academics who actively…

  17. Course Objectives: Electronic Fundamentals, EL16.

    ERIC Educational Resources Information Center

    Wilson, David H.

    The general objective, recommended text, and specific objectives of a course titled "Electronic Fundamentals," as offered at St. Lawrence College of Applied Arts and Technology, are provided. The general objective of the course is "to acquire an understanding of diodes, transistors, and tubes, and so be able to analyze the operation…

  18. Fundamentals of Athletic Training. Second Edition.

    ERIC Educational Resources Information Center

    Behling, Fred L.; And Others

    This book provides an authoritative reference on the fundamentals of athletic training for people with varied backgrounds but a common interest in the health and education of the high school athlete. The book is designed especially for the novice athletic trainer. Section 1 of the book concerns the organization and administration of athletic…

  19. Fundamental Ideas: Rethinking Computer Science Education.

    ERIC Educational Resources Information Center

    Schwill, Andreas

    1997-01-01

    Describes a way to teach computer science based on J.S. Bruner's psychological framework. This educational philosophy has been integrated into two German federal state schools. One way to cope with the rapid developments in computer science is to teach the fundamental ideas, principles, methods, and ways of thinking to K-12 students, (PEN)

  20. Radio and Television Repairer Fundamentals. Student's Manual.

    ERIC Educational Resources Information Center

    Maul, Chuck

    This self-contained student manual on fundamentals of radio and television repair is designed to help trade and industrial students relate work experience on the job to information studied at school. Designed for individualized instruction under the supervision of a coordinator or instructor, the manual has 9 sections, each containing 2 to 10…

  1. Fundamental Movement Skill Proficiency amongst Adolescent Youth

    ERIC Educational Resources Information Center

    O' Brien, Wesley; Belton, Sarahjane; Issartel, Johann

    2016-01-01

    Background: Literature suggests that physical education programmes ought to provide intense instruction towards basic movement skills needed to enjoy a variety of physical activities. Fundamental movement skills (FMS) are basic observable patterns of behaviour present from childhood to adulthood (e.g. run, skip and kick). Recent evidence indicates…

  2. Fundamental Theorems of Algebra for the Perplexes

    ERIC Educational Resources Information Center

    Poodiak, Robert; LeClair, Kevin

    2009-01-01

    The fundamental theorem of algebra for the complex numbers states that a polynomial of degree n has n roots, counting multiplicity. This paper explores the "perplex number system" (also called the "hyperbolic number system" and the "spacetime number system") In this system (which has extra roots of +1 besides the usual [plus or minus]1 of the…

  3. Fundamentalism or Pluralism: Iranian Youth's Orientation

    ERIC Educational Resources Information Center

    Pasha, Nourollah; Ahmad, Zaid

    2014-01-01

    Islamic fundamentalism is an extreme perception of Islam that views "the 'Other' as the enemy demonized" against the "West", which also views the Muslim "enemy within". In contrast, pluralism perceives 'others' as different people, with different values from us. While the fundamentalist seeks to engage in war with the…

  4. Mathematical Literacy--It's Become Fundamental

    ERIC Educational Resources Information Center

    McCrone, Sharon Soucy; Dossey, John A.

    2007-01-01

    The rising tide of numbers and statistics in daily life signals a need for a fundamental broadening of the concept of literacy: mathematical literacy assuming a coequal role in the curriculum alongside language-based literacy. Mathematical literacy is not about studying higher levels of formal mathematics, but about making math relevant and…

  5. Drafting Fundamentals. Drafting Module 1. Instructor's Guide.

    ERIC Educational Resources Information Center

    Missouri Univ., Columbia. Instructional Materials Lab.

    This Missouri Vocational Instruction Management System instructor's drafting guide has been keyed to the drafting competency profile developed by state industry and education professionals. The guide contains a cross-reference table of instructional materials. Ten units cover drafting fundamentals: (1) introduction to drafting; (2) general safety;…

  6. [Reading Is Fundamental: Pamphlets and Newsletters].

    ERIC Educational Resources Information Center

    Smithsonian Institution, Washington, DC.

    These pamphlets and newsletters are products of the Reading Is Fundamental (RIF) program, which provides free and inexpensive books to children through a variety of community organizations throughout the country. The newsletter appears monthly and contains reports on specific programs, trends in the national program, RIF involvement with other…

  7. Uncovering Racial Bias in Nursing Fundamentals Textbooks.

    ERIC Educational Resources Information Center

    Byrne, Michelle M.

    2001-01-01

    The portrayal of African Americans in nursing fundamentals textbooks was analyzed, resulting in 11 themes in the areas of history, culture, and physical assessment. Few African American leaders were included, and racial bias and stereotyping were apparent. Differences were often discussed using Eurocentric norms, and language tended to minimize…

  8. An Epistemological View on Fundamental Stochastic Ideas

    ERIC Educational Resources Information Center

    Heitele, Dietger

    1975-01-01

    Arguing that the teaching of stochastic processes should reflect the experience and reality of the student, the author urges concentration on fundamental ideas. The development of intuition should be encouraged, and to this end continuity in teaching and a spiralled curriculum are important. (SD)

  9. Forgotten Fundamentals of the Energy Crisis.

    ERIC Educational Resources Information Center

    Bartlett, Albert A.

    1980-01-01

    Examines what is believed to be the forgotten fundamental of the energy crisis, the elementary arithmetic of growth. The arithmetic is applied to what is known about the reserves of fossil fuels. A large number of erroneous pronouncements from public figures and news media are collected here. (SA)

  10. Workshop on Fundamental Science using Pulsed Power

    SciTech Connect

    Wootton, Alan

    2016-02-20

    The project objective was to fund travel to a workshop organized by the Institute for High Energy Density Science (IHEDS) at the University of Texas at Austin. In so doing the intent was to a) Grow the national academic High Energy Density Science (HEDS) community, b) Expand high impact, discovery driven fundamental HEDS, and c) Facilitate user-oriented research

  11. Fundamental Concepts Bridging Education and the Brain

    ERIC Educational Resources Information Center

    Masson, Steve; Foisy, Lorie-Marlène Brault

    2014-01-01

    Although a number of papers have already discussed the relevance of brain research for education, the fundamental concepts and discoveries connecting education and the brain have not been systematically reviewed yet. In this paper, four of these concepts are presented and evidence concerning each one is reviewed. First, the concept of…

  12. Fundamental studies on passivity and passivity breakdown

    SciTech Connect

    Macdonald, D.D.; Urquidi-Macdonald, M.

    1993-06-01

    Using photoelectrochemical impedance and admittance spectroscopies, a fundamental and quantitative understanding of the mechanisms for the growth and breakdown of passive films on metal and alloy surfaces in contact with aqueous environments is being developed. A point defect model has been extended to explain the breakdown of passive films, leading to pitting and crack growth and thus development of damage due to localized corrosion.

  13. The equivalent fundamental-mode source

    SciTech Connect

    Spriggs, G.D.; Busch, R.D.; Sakurai, Takeshi; Okajima, Shigeaki

    1997-02-01

    In 1960, Hansen analyzed the problem of assembling fissionable material in the presence of a weak neutron source. Using point kinetics, he defined the weak source condition and analyzed the consequences of delayed initiation during ramp reactivity additions. Although not clearly stated in Hansen`s work, the neutron source strength that appears in the weak source condition corresponds to the equivalent fundamental-mode source. In this work, we describe the concept of an equivalent fundamental-mode source and we derive a deterministic expression for a factor, g*, that converts any arbitrary source distribution to an equivalent fundamental-mode source. We also demonstrate a simplified method for calculating g* in subcritical systems. And finally, we present a new experimental method that can be employed to measure the equivalent fundamental-mode source strength in a multiplying assembly. We demonstrate the method on the zero-power, XIX-1 assembly at the Fast Critical Assembly (FCA) Facility, Japan Atomic Energy Research Institute (JAERI).

  14. Radio and Television Repairer Fundamentals. Student's Manual.

    ERIC Educational Resources Information Center

    Maul, Chuck

    This self-contained student manual on fundamentals of radio and television repair is designed to help trade and industrial students relate work experience on the job to information studied at school. Designed for individualized instruction under the supervision of a coordinator or instructor, the manual has 9 sections, each containing 2 to 10…

  15. Quantitative modeling of forces in electromagnetic tweezers.

    PubMed

    Bijamov, Alex; Shubitidze, Fridon; Oliver, Piercen M; Vezenov, Dmitri V

    2010-11-15

    This paper discusses numerical simulations of the magnetic field produced by an electromagnet for generation of forces on superparamagnetic microspheres used in manipulation of single molecules or cells. Single molecule force spectroscopy based on magnetic tweezers can be used in applications that require parallel readout of biopolymer stretching or biomolecular binding. The magnetic tweezers exert forces on the surface-immobilized macromolecule by pulling a magnetic bead attached to the free end of the molecule in the direction of the field gradient. In a typical force spectroscopy experiment, the pulling forces can range between subpiconewton to tens of piconewtons. In order to effectively provide such forces, an understanding of the source of the magnetic field is required as the first step in the design of force spectroscopy systems. In this study, we use a numerical technique, the method of auxiliary sources, to investigate the influence of electromagnet geometry and material parameters of the magnetic core on the magnetic forces pulling the target beads in the area of interest. The close proximity of the area of interest to the magnet body results in deviations from intuitive relations between magnet size and pulling force, as well as in the force decay with distance. We discuss the benefits and drawbacks of various geometric modifications affecting the magnitude and spatial distribution of forces achievable with an electromagnet.

  16. Fundamental surprise in the application of airpower.

    DTIC Science & Technology

    2017-05-25

    deep into enemy held terrain, or a tool to drastically shift the balance of force presented at the decisive point. The enemy’s perspective...freedom of maneuver, a way of seeing deep into enemy held terrain, or a tool to drastically shift the balance of force presented at the decisive point...The outcome of the Six-Day War and the role airpower played in achieving a decisive victory altered the balance of power in the Middle East. This

  17. DNA Origami Seesaws as Comparative Binding Assay

    PubMed Central

    Nickels, Philipp C.; Høiberg, Hans C.; Simmel, Stephanie S.; Holzmeister, Phil; Tinnefeld, Philip

    2016-01-01

    Abstract The application of commonly used force spectroscopy in biological systems is often limited by the need for an invasive tether connecting the molecules of interest to a bead or cantilever tip. Here we present a DNA origami‐based prototype in a comparative binding assay. It has the advantage of in situ readout without any physical connection to the macroscopic world. The seesaw‐like structure has a lever that is able to move freely relative to its base. Binding partners on each side force the structure into discrete and distinguishable conformations. Model experiments with competing DNA hybridisation reactions yielded a drastic shift towards the conformation with the stronger binding interaction. With reference DNA duplexes of tuneable length on one side, this device can be used to measure ligand interactions in comparative assays. PMID:27038073

  18. Talin mediated force transmission and mechanosensing

    NASA Astrophysics Data System (ADS)

    Yan, Jie; Yao, Mingxi; Goult, Benjamin; Sheetz, Michael

    Cells adhere to extracellular matrix (ECM) through focal adhesion. Talin is a cytoplasmic adapter protein that links the actin cytoskeleton to focal adhesion, playing a central role in regulation of cell spreading and migration. Talin's functions depend on the binding of talin rod domains to a cytoplasmic protein vinculin in a force dependent manner. By stretching full-length talin rod using magnetic tweezers, we have determined the force-dependent unfolding and refolding rates of subdomains in talin rod. Kinetics simulations based on these rates have revealed that talin rod can serve as a force buffer, capable of maintaining tension in talin in a range of 5-10 pN over a wide range of extension change of talin rod from 50 nm to 400 nm. Further, this level of force is found able to expose the cryptic vinculin-binding sites, promoting subsequent binding of the head domain of vinculin with a nano Molar affinity. Such a force-sensitive interaction between talin rod and vinculin is described by a force-dependent dissociation constant derived based on the mechanical stability of the talin rod domains. Together, these results provide important insights into the mechanosensing at focal adhesion that is crucial for cells to sense and respond to their microenvironments. The research is supported by the National Research Foundation of Singapore through Mechanobiology Institute and NRF Investigatorship to YJ.

  19. Mechanical force characterization in manipulating live cells with optical tweezers.

    PubMed

    Wu, Yanhua; Sun, Dong; Huang, Wenhao

    2011-02-24

    Laser trapping with optical tweezers is a noninvasive manipulation technique and has received increasing attentions in biological applications. Understanding forces exerted on live cells is essential to cell biomechanical characterizations. Traditional numerical or experimental force measurement assumes live cells as ideal objects, ignoring their complicated inner structures and rough membranes. In this paper, we propose a new experimental method to calibrate the trapping and drag forces acted on live cells. Binding a micro polystyrene sphere to a live cell and moving the mixture with optical tweezers, we can obtain the drag force on the cell by subtracting the drag force on the sphere from the total drag force on the mixture, under the condition of extremely low Reynolds number. The trapping force on the cell is then obtained from the drag force when the cell is in force equilibrium state. Experiments on numerous live cells demonstrate the effectiveness of the proposed force calibration approach.

  20. Coupling mechanical forces to electrical signaling: molecular motors and the intracellular transport of ion channels.

    PubMed

    Barry, Joshua; Gu, Chen

    2013-04-01

    Proper localization of various ion channels is fundamental to neuronal functions, including postsynaptic potential plasticity, dendritic integration, action potential initiation and propagation, and neurotransmitter release. Microtubule-based forward transport mediated by kinesin motors plays a key role in placing ion channel proteins to correct subcellular compartments. PDZ- and coiled-coil-domain proteins function as adaptor proteins linking ionotropic glutamate and GABA receptors to various kinesin motors, respectively. Recent studies show that several voltage-gated ion channel/transporter proteins directly bind to kinesins during forward transport. Three major regulatory mechanisms underlying intracellular transport of ion channels are also revealed. These studies contribute to understanding how mechanical forces are coupled to electrical signaling and illuminating pathogenic mechanisms in neurodegenerative diseases.