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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. Gauge unification of fundamental forces

    NASA Astrophysics Data System (ADS)

    Salam, Abdus

    The following sections are included: * I. Fundamental Particles, Fundamental Forces, and Gauge Unification * II. The Emergence of Spontaneously Broken SU(2)×U(1) Gauge Theory * III. The Present and Its Problems * IV. Direct Extrapolation from the Electroweak to the Electronuclear * A. The three ideas * B. Tests of electronuclear grand unification * V. Elementarity: Unification with Gravity and Nature of Charge * A. The quest for elementarity, prequarks (preons and pre-preons * B. Post-Planck physics, supergravity, and Einstein's dreams * C. Extended supergravity, SU(8) preons, and composite gauge fields * Appendix A: Examples of Grand Unifying Groups * Appendix B: Does the Grand Plateau really exist * References

  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. 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.

  7. Fundamentals of force feedback and application to a surgery simulator.

    PubMed

    Maass, Heiko; Chantier, Benjamin B A; Cakmak, Hueseyin K; Trantakis, Christos; Kuehnapfel, Uwe G

    2003-01-01

    Force feedback increases the effectiveness of virtual-reality surgery training systems. An overview of the fundamentals of applying force feedback is presented. An impedance control technique and data processing methods for stability preservation are illustrated. A flexible interface for general force-feedback applications has been developed. This interface is capable of controlling several different force-feedback hardware systems, including the SensAble PHANTOM, the Laparoscopic Impulse Engines from Immersion, and the VS-One virtual endoscopic surgery trainer. The findings are evaluated using the main simulation system, KISMET, and the modeling tools KISMO and VESUV. Within the scope of a cooperative project called HapticIO (funded by the German Ministry of Education and Research [BMBF]), new haptic devices have been designed for virtual neuroendoscopy and laparoscopy. The concept and implementations presented in this paper have been found to be flexible, stable and suitable for universal use. The impedance method, combined with the open-loop feed-forward control technique, is well suited and appropriate for the task.

  8. Atomic force microscopy measurements of intermolecular binding forces.

    PubMed

    Misevic, Gradimir N; Karamanos, Yannis; Misevic, Nikola J

    2009-01-01

    Atomic force microscopy (AFM) measurements of intermolecular binding strength between a single pair of complementary cell adhesion molecules in physiological solutions provided the first quantitative evidence for their cohesive function. This novel AFM-based nanobiotechnology opens a molecular mechanic approach for studying structure- to function-related properties of any type of individual biological macromolecules. The presented example of Porifera cell adhesion glyconectin proteoglycans showed that homotypic carbohydrate to carbohydrate interactions between two primordial proteoglycans can hold the weight of 1,600 cells. Thus, glyconectin type carbohydrates, as the most peripheral cell surface molecules of sponges (today's simplest living Metazoa), are proposed to be the primary cell adhesive molecules essential for the evolution of the multicellularity.

  9. 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.

  10. Molecular forces for the binding and condensation of DNA molecules.

    PubMed Central

    Cai, Xian-E; Yang, Jie

    2002-01-01

    Atomic force microscopy has been used to investigate the binding between a double-stranded DNA and bilayers of cationic lipids and zwitterionic lipids in low ionic-strength solutions. The binding of a DNA molecule to freshly cleaved mica surface in solution has also been measured. The binding of DNA molecules to cationic lipid bilayers has a minimal strength of approximately 45 pN. On zwitterionic lipid bilayers and mica surface, the minimal binding strength is approximately twice that value. The binding also has a dynamic nature, with only a certain percentage of recorded force curves containing the binding characteristics. Divalent Mg(2+) ions enhance the binding by increasing that percentage without any effect on the binding strength. We have also observed a long-range attraction between DNA molecules and cationic lipid bilayers with a strength much larger than the minimum force and a range well over 50 nm, possibly related to the driving force responsible for the two-dimensional condensation of DNA. PMID:11751322

  11. 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

  12. Binding Forces of Streptococcus mutans P1 Adhesin

    PubMed Central

    Sullan, Ruby May A.; Li, James K.; Crowley, Paula J.; Brady, L. Jeannine; Dufrêne, Yves F.

    2015-01-01

    Streptococcus mutans is a Gram-positive oral bacterium that is a primary etiological agent associated with human dental caries. In the oral cavity, S. mutans adheres to immobilized salivary agglutinin (SAG) contained within the salivary pellicle on the tooth surface. Binding to SAG is mediated by cell surface P1, a multifunctional adhesin that is also capable of interacting with extracellular matrix proteins. This may be of particular importance outside of the oral cavity as S. mutans has been associated with infective endocarditis and detected in atherosclerotic plaque. Despite the biomedical importance of P1, its binding mechanisms are not completely understood. In this work, we use atomic force microscopy-based single-molecule and single-cell force spectroscopy to quantify the nanoscale forces driving P1-mediated adhesion. Single-molecule experiments show that full-length P1, as well as fragments containing only the P1 globular head or C-terminal region, binds to SAG with relatively weak forces (~50 pN). In contrast, single-cell analyses reveal that adhesion of a single S. mutans cell to SAG is mediated by strong (~500 pN) and long-range (up to 6000 nm) forces. This is likely due to the binding of multiple P1 adhesins to self-associated gp340 glycoproteins. Such a cooperative, long-range character of the S. mutans–SAG interaction would therefore dramatically increase the strength and duration of cell adhesion. We also demonstrate, at single-molecule and single-cell levels, the interaction of P1 with fibronectin and collagen, as well as with hydrophobic, but not hydrophilic, substrates. The binding mechanism (strong forces, cooperativity, broad specificity) of P1 provides a molecular basis for its multifunctional adhesion properties. Our methodology represents a valuable approach to probe the binding forces of bacterial adhesins and offers a tractable methodology to assess anti-adhesion therapy. PMID:25671413

  13. 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.

  14. Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors.

    PubMed

    Mosayebi, Majid; Louis, Ard A; Doye, Jonathan P K; Ouldridge, Thomas E

    2015-12-22

    The rupture of double-stranded DNA under stress is a key process in biophysics and nanotechnology. In this article, we consider the shear-induced rupture of short DNA duplexes, a system that has been given new importance by recently designed force sensors and nanotechnological devices. We argue that rupture must be understood as an activated process, where the duplex state is metastable and the strands will separate in a finite time that depends on the duplex length and the force applied. Thus, the critical shearing force required to rupture a duplex depends strongly on the time scale of observation. We use simple models of DNA to show that this approach naturally captures the observed dependence of the force required to rupture a duplex within a given time on duplex length. In particular, this critical force is zero for the shortest duplexes, before rising sharply and then plateauing in the long length limit. The prevailing approach, based on identifying when the presence of each additional base pair within the duplex is thermodynamically unfavorable rather than allowing for metastability, does not predict a time-scale-dependent critical force and does not naturally incorporate a critical force of zero for the shortest duplexes. We demonstrate that our findings have important consequences for the behavior of a new force-sensing nanodevice, which operates in a mixed mode that interpolates between shearing and unzipping. At a fixed time scale and duplex length, the critical force exhibits a sigmoidal dependence on the fraction of the duplex that is subject to shearing.

  15. The Fundamental Role of Flexibility on the Strength of Molecular Binding

    PubMed Central

    Douglas, Jack F.; Gilson, Michael K.

    2012-01-01

    Non-covalent molecular association underlies a diverse set of biologically and technologically relevant phenomena, including the action of drugs on their biomolecular targets and self- and supra-molecular assembly processes. Computer models employed to model binding frequently use interaction potentials with atomistic detail while neglecting the thermal molecular motions of the binding species. However, errors introduced by this simplification and, more broadly, the thermodynamic consequences of molecular flexibility on binding, are little understood. Here, we isolate the fundamental relationship of molecular flexibility to binding thermodynamics via simulations of simplified molecules with a wide range of flexibilities but the same interaction potential. Disregarding molecular motion is found to generate large errors in binding entropy, enthalpy and free energy, even for molecules that are nearly rigid. Indeed, small decreases in rigidity markedly reduce affinity for highly rigid molecules. Remarkably, precisely the opposite occurs for more flexible molecules, for which increasing flexibility leads to stronger binding affinity. We also find that differences in flexibility suffice to generate binding specificity: for example, a planar surface selectively binds rigid over flexible molecules. Intriguingly, varying molecular flexibility while keeping interaction potentials constant leads to near-linear enthalpy-entropy compensation over a wide range of flexibilities, with the unexpected twist that increasing flexibility produces opposite changes in entropy and enthalpy for molecules in the flexible versus the rigid regime. Molecular flexibility is thus a crucial determinant of binding affinity and specificity and variations in flexibility can lead to strong yet non-intuitive consequences. PMID:22707976

  16. 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.

  17. 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

    2016-05-01

    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

  18. An ab initio quartic force field and the fundamental frequencies of o-benzyne

    NASA Astrophysics Data System (ADS)

    Bludský, Ota; Pirko, Vladimír; Kobayashi, Rika; Jørgensen, Poul

    1994-10-01

    The ab initio SCF, MCSCF and MP2 molecular energies, gradients and Hessians have been evaluated at 33 points for the ground electronic state of the o-benzyne molecule. The corresponding potential energy surfaces have been fitted to obtain a quartic force field from which the fundamental frequencies have been determined using second-order perturbation theory. Theoretical predictions reproduce the majority of the experimental data to a degree of agreement which allows a complete assignment of all the fundamental frequencies of o-benzyne.

  19. 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

  20. Improvements in fundamental performance of liquid-environment atomic force microscopy with true atomic resolution

    NASA Astrophysics Data System (ADS)

    Miyata, Kazuki; Miyazawa, Keisuke; Akrami, Seyed Mohammad Reza; Fukuma, Takeshi

    2015-08-01

    Recently, there have been significant advancements in liquid-environment atomic force microscopy (AFM) with true atomic resolution. The technical advancements are followed by a rapid expansion of its application area. Examples include subnanometer-scale imaging of biological systems and three-dimensional measurements of water distributions (i.e., hydration structures) and fluctuating surface structures. However, to continue this progress, we should improve the fundamental performance of liquid-environment dynamic-mode AFM. The present AFM technique does not allow real-time imaging of atomic-scale dynamic phenomena at a solid-liquid interface. This has hindered atomic-level understanding of crystal growth and dissolution, catalytic reactions and metal corrosion processes. Improvement in force sensitivity is required not only for such a high-speed imaging but also for various surface property measurements using a high-resolution AFM technique. In this review, we summarize recent works on the improvements in the force sensitivity and operation speed of atomic-resolution dynamic-mode AFM for liquid-environment applications.

  1. 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.

  2. Spatial analysis and quantification of the thermodynamic driving forces in protein-ligand binding: binding site variability.

    PubMed

    Raman, E Prabhu; MacKerell, Alexander D

    2015-02-25

    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 provide an unprecedented level of detail into the mechanisms of binding. Direct protein-ligand interaction energies play a significant role in both nonpolar 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. It is notable to have 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

  3. 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. PMID:27359243

  4. 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.

  5. 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.

  6. 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

  7. 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

    2016-01-01

    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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

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

    PubMed

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

    2015-08-13

    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 nonoptimal 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.

  14. An integrated methodology for data processing in dynamic force spectroscopy of ligand-receptor binding.

    PubMed

    Odorico, M; Teulon, J-M; Berthoumieu, O; Chen, S-w W; Parot, P; Pellequer, J-L

    2007-10-01

    Dynamic force spectroscopy (DFS), using atomic force microscopy (AFM), is a powerful tool to study ligand-receptor binding. The interaction mode of two binding partners is investigated by exploring stochastic behaviors of bond rupture events. However, to define a rupture event from force-distance measurements is not conclusive or unique in literature. To reveal the influence of event identification methods, we have developed an efficient protocol to manage tremendous amount of data by implementing different choices of peak selection from the force-distance curve. This data processing software simplifies routinely experimental procedures such as cantilever spring constant and force-distance curve calibrations, statistical treatments of data, and analysis distributions of rupture events. In the present work, we took available experimental data from a complex between a chelate metal compound and a monoclonal antibody as a study system.

  15. 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

  16. 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.

  17. Protonated nitrous oxide, NNOH+: fundamental vibrational frequencies and spectroscopic constants from quartic force fields.

    PubMed

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

    2013-08-28

    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(J) quartic distortion constants agree with experiment to within 3%. The known gas phase O-H stretch of NNOH(+) is 3330.91 cm(-1), and the vibrational configuration interaction computed result is 3330.9 cm(-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 interstellar medium and the laboratory. PMID:24007003

  18. 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…

  19. 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

  20. Dynamic force spectroscopy of the Helicobacter pylori BabA-Lewis b binding.

    PubMed

    Björnham, Oscar; Bugaytsova, Jeanna; Borén, Thomas; Schedin, Staffan

    2009-07-01

    The binding strength of the Helicobacter pylori adhesin-receptor complex BabA-ABO/Lewis b has been analyzed by means of dynamic force spectroscopy. High-resolution measurements of rupture forces were performed in situ on single bacterial cells, expressing the high-affinity binding BabA adhesin, by the use of force measuring optical tweezers. The resulting force spectra revealed the mechanical properties of a single BabA-Leb bond. It was found that the bond is dominated by one single energy barrier and that it is a slip-bond. The bond length and thermal off-rate were assessed to be 0.86+/-0.07 nm and 0.015+/-0.006 s(-1), respectively.

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

    PubMed Central

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

    2015-01-01

    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 predicteddual binding modes across multiple bacterial species, our approach opens up newpossibilities for understanding assembly and catalytic properties of a broadrange of multi-enzyme complexes. DOI: http://dx.doi.org/10.7554/eLife.10319.001 PMID:26519733

  2. Three-Dimensional Self Assembly of Semiconducting Colloidal Nanocrystals: From Fundamental Forces to Collective Optical Properties.

    PubMed

    Abécassis, Benjamin

    2016-03-01

    Self-assembly of colloidal nanoparticles into higher order superstructures is becoming an important topic in current research in nanoscience. More and more research efforts are being dedicated to the controlled processing of nanoparticle dispersions to yield complex architectures from these simple building blocks. This is due to the fact that collective effects can emerge from an assembly of organized nanoparticles. Semiconducting colloidal nanocrystals such as quantum dots are promising materials for a wide range of applications in optoelectronic photovoltaics. The fundamental interactions that dictate the self-assembly of semiconducting colloidal nanocrystals in apolar solvents are reviewed with a focus on 3D structures and basic shapes (spheres, rods, and platelets). Emergent collective properties and the effect of the self-assembly on the optical properties of the particles are also discussed.

  3. 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

  4. 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.

  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. PMID:23706043

  6. Binding activity of patterned concanavalin A studied by atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Lebed, Kateryna; Pyka-Fosciak, Grazyna; Raczkowska, Joanna; Lekka, Malgorzata; Styczen, Jan

    2005-05-01

    The mode of protein immobilization plays a crucial role in the preparation of protein microarrays used for a wide spectrum of applications in analytical biochemistry. The microcontact printing technique was used to form a protein pattern using concanavalin A (Con A) since Con A belongs to a group of proteins widely used in analytical assays due to their selectivity as regards different kinds of carbohydrates. Atomic force microscopy was used to image surface topography, delivering information about the quality of the protein pattern. The force spectroscopy mode was used to verify the functional activity of deposited proteins via determination of the forces of interaction between Con A and carboxypeptidase Y bearing carbohydrate structure recognized by Con A. The calculated binding force between Con A and CaY was 105 ± 2 pN and it was compared with that measured for Con A deposited directly from the protein solution. The similarity of the value obtained for the interaction force was independent of the mode of protein deposition, thereby verifying that the microcontact printing technique did not influence the carbohydrate binding activity of Con A. The correlation between the surface topography of patterned samples and adhesion maps obtained showed the possible use of AFM for studying the chemical properties of different regions of the micropatterns produced.

  7. 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)

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

    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.

  10. 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

  11. 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

  12. 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…

  13. Forces and Dynamics of Glucose and Inhibitor Binding to Sodium Glucose Co-transporter SGLT1 Studied by Single Molecule Force Spectroscopy*

    PubMed Central

    Neundlinger, Isabel; Puntheeranurak, Theeraporn; Wildling, Linda; Rankl, Christian; Wang, Lai-Xi; Gruber, Hermann J.; Kinne, Rolf K. H.; Hinterdorfer, Peter

    2014-01-01

    Single molecule force spectroscopy was employed to investigate the dynamics of the sodium glucose co-transporter (SGLT1) upon substrate and inhibitor binding on the single molecule level. CHO cells stably expressing rbSGLT1 were probed by using atomic force microscopy tips carrying either thioglucose, 2′-aminoethyl β-d-glucopyranoside, or aminophlorizin. Poly(ethylene glycol) (PEG) chains of different length and varying end groups were used as tether. Experiments were performed at 10, 25 and 37 °C to address different conformational states of SGLT1. Unbinding forces between ligands and SGLT1 were recorded at different loading rates by changing the retraction velocity, yielding binding probability, width of energy barrier of the binding pocket, and the kinetic off rate constant of the binding reaction. With increasing temperature, width of energy barrier and average life time increased for the interaction of SGLT1 with thioglucose (coupled via acrylamide to a long PEG) but decreased for aminophlorizin binding. The former indicates that in the membrane-bound SGLT1 the pathway to sugar translocation involves several steps with different temperature sensitivity. The latter suggests that also the aglucon binding sites for transport inhibitors have specific, temperature-sensitive conformations. PMID:24962566

  14. Atomic force microscopy measurements reveal multiple bonds between Helicobacter pylori blood group antigen binding adhesin and Lewis b ligand.

    PubMed

    Parreira, P; Shi, Q; Magalhaes, A; Reis, C A; Bugaytsova, J; Borén, T; Leckband, D; Martins, M C L

    2014-12-01

    The strength of binding between the Helicobacter pylori blood group antigen-binding adhesin (BabA) and its cognate glycan receptor, the Lewis b blood group antigen (Le(b)), was measured by means of atomic force microscopy. High-resolution measurements of rupture forces between single receptor-ligand pairs were performed between the purified BabA and immobilized Le(b) structures on self-assembled monolayers. Dynamic force spectroscopy revealed two similar but statistically different bond populations. These findings suggest that the BabA may form different adhesive attachments to the gastric mucosa in ways that enhance the efficiency and stability of bacterial adhesion.

  15. 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

  16. Characterization of Folic Acid and Poly(amidoamine) Dendrimer Interactions with Folate Binding Protein: A Force-Pulling Study

    PubMed Central

    Leroueil, Pascale R.; DiMaggio, Stassi; Leistra, Abigail N.; Blanchette, Craig D.; Orme, Christine; Sinniah, Kumar; Orr, Bradford G.; Holl, Mark M. Banaszak

    2016-01-01

    Atomic force microscopy force-pulling experiments have been used to measure the binding forces between folic acid (FA) conjugated poly(amidoamine) (PAMAM) dendrimers and folate binding protein (FBP). The generation 5 (G5) PAMAM conjugates contained an average of 2.7, 4.7, and 7.2 FA per dendrimer. The most probable rupture force was measured to be 83, 201, and 189 pN for G5-FA2.7, G5-FA4.7, and G5-FA7.2, respectively. Folic acid blocking experiments for G5-FA7.2 reduced the frequency of successful binding events and increased the magnitude of the average rupture force to 274 pN. The force data is interpreted as arising from a network of van der Waals and electrostatic interactions that form between FBP and G5 PAMAM dendrimer resulting in a binding strength far greater than that expected for an interaction between FA and FBP alone. PMID:26256755

  17. Characterization of Folic Acid and Poly(amidoamine) Dendrimer Interactions with Folate Binding Protein: A Force-Pulling Study.

    PubMed

    Leroueil, Pascale R; DiMaggio, Stassi; Leistra, Abigail N; Blanchette, Craig D; Orme, Christine; Sinniah, Kumar; Orr, Bradford G; Banaszak Holl, Mark M

    2015-09-01

    Atomic force microscopy force-pulling experiments have been used to measure the binding forces between folic acid (FA) conjugated poly(amidoamine) (PAMAM) dendrimers and folate binding protein (FBP). The generation 5 (G5) PAMAM conjugates contained an average of 2.7, 4.7, and 7.2 FA per dendrimer. The most probable rupture force was measured to be 83, 201, and 189 pN for G5-FA2.7, G5-FA4.7, and G5-FA7.2, respectively. Folic acid blocking experiments for G5-FA7.2 reduced the frequency of successful binding events and increased the magnitude of the average rupture force to 274 pN. The force data are interpreted as arising from a network of van der Waals and electrostatic interactions that form between FBP and G5 PAMAM dendrimer, resulting in a binding strength far greater than that expected for an interaction between FA and FBP alone.

  18. 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

  19. 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. PMID:27007455

  20. Modeling Cu(II) Binding to Peptides Using the Extensible Systematic Force Field

    PubMed Central

    Ryvkin, Faina; Greenaway, Frederick T.

    2010-01-01

    The utility of the extensible systematic force field (ESFF) was tested for copper(II) binding to a 34-amino-acid Cu(II) peptide, which includes five histidine residues and is the putative copper-binding site of lysyl oxidase. To improve computational efficiency, distance geometry calculations were used to constrain all combinations of three histidine ligands to be within bonding distance of the copper and the best results were utilized as starting structures for the ESFF computations. All likely copper geometries were modeled, but the results showed only a small dependence on the geometrical model in that all resulted in a distorted square pyramidal geometry about the copper, some of the imidazole rings were poorly oriented for ligation to the Cu(II), and the copper-nitrogen bond distances were too long. The results suggest that ESFF should be used with caution for Cu(II) complexes where the copper-ligand bonds have significant covalency and when the ligands are not geometrically constrained to be planar. PMID:20300581

  1. Mapping the Nucleotide Binding Site of Uncoupling Protein 1 Using Atomic Force Microscopy

    PubMed Central

    2013-01-01

    A tight regulation of proton transport in the inner mitochondrial membrane is crucial for physiological processes such as ATP synthesis, heat production, or regulation of the reactive oxygen species as proposed for the uncoupling protein family members (UCP). Specific regulation of proton transport is thus becoming increasingly important in the therapy of obesity and inflammatory, neurodegenerative, and ischemic diseases. We and other research groups have shown previously that UCP1- and UCP2-mediated proton transport is inhibited by purine nucleotides. Several hypotheses have been proposed to explain the inhibitory effect of ATP, although structural details are still lacking. Moreover, the unresolved mystery is how UCP operates in vivo despite the permanent presence of high (millimolar) concentrations of ATP in mitochondria. Here we use the topographic and recognition (TREC) mode of an atomic force microscope to visualize UCP1 reconstituted into lipid bilayers and to analyze the ATP–protein interaction at a single molecule level. The comparison of recognition patterns obtained with anti-UCP1 antibody and ATP led to the conclusion that the ATP binding site can be accessed from both sides of the membrane. Using cantilever tips with different cross-linker lengths, we determined the location of the nucleotide binding site inside the membrane with 1 Å precision. Together with the recently published NMR structure of a UCP family member (Berardi et al. Nature, 2011, 476, 109–113), our data provide a valuable insight into the mechanism of the nucleotide binding and pave the way for new pharmacological approaches against the diseases mentioned above. PMID:23414455

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

    PubMed

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

    2012-08-01

    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/Mg(2+) 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

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

    PubMed

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

    2013-06-18

    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 intermolecular force measurement of 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 1 μm/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 nonpolar attraction between multiple aligned ion pairs and hydrophobic residues. Also, we tested the Jarzynski's equality and demonstrated, as expected, that nonequilibrium 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.

  4. 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.

  5. 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.

  6. 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)

  7. The Effects of Force Inhibition by Sodium Vanadate on Cross-Bridge Binding, Force Redevelopment, and Ca2+ Activation in Cardiac Muscle

    SciTech Connect

    Martyn,D.; Smith, L.; Kreutziger, K.; Xu, S.; Yu, L.; Regnie, M.

    2007-01-01

    Strongly bound, force generating myosin crossbridges play an important role as allosteric activators of cardiac thin filaments. Sodium vanadate (Vi) is a phosphate analog that inhibits force by preventing crossbridge transition into force producing states. This study characterizes the mechanical state of crossbridges with bound Vi as a tool to examine the contribution of crossbridges to cardiac contractile activation. The K{sub i} of force inhibition by Vi was {approx} 40 {mu}M. Sinusoidal stiffness was inhibited with Vi, although to a lesser extent than force. We used chord stiffness measurements to monitor Vi induced changes in crossbridge attachment/detachment kinetics at saturating [Ca{sup 2+}]. Vi decreased chord stiffness at the fastest rates of stretch, while at slow rates chord stiffness actually increased. This suggests a shift in crossbridge population towards low force states with very slow attachment/detachment kinetics. Low angle X-ray diffraction measurements indicate that with Vi crossbridge mass shifted away from thin filaments, implying decreased crossbridge-thin filament interaction. The combined X-ray and mechanical data suggest at least two crossbridge populations with Vi; one characteristic of normal cycling crossbridges, and a population of weak-binding crossbridges with bound Vi and slow attachment/detachment kinetics. The Ca{sup 2+}-sensitivity of force (pCa{sub 50}) and force redevelopment kinetics (k{sub TR}) were measured to study the effects of Vi on contractile activation. When maximal force was inhibited by 40% with Vi pCa{sub 50} decreased, but greater force inhibition at higher [Vi] did not further alter pCa{sub 50}. In contrast, the Ca{sup 2+}-sensitivity of k{sub TR} was unaffected by Vi. Interestingly, when force was inhibited by Vi k{sub TR} increased at sub-maximal levels of CaS{sup 2+}-activated force. Additionally, kTR is faster at saturating Ca{sup 2+} at [Vi] that inhibit force by more than {approx}70%. The effects of Vi on

  8. Prediction of SAMPL3 host-guest binding affinities: evaluating the accuracy of generalized force-fields.

    PubMed

    Muddana, Hari S; Gilson, Michael K

    2012-05-01

    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.

  9. 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.

  10. 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.

  11. 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.

  12. Evaluation of adhesion force and binding affinity of phytohemagglutinin erythroagglutinating to EGF receptor on human lung cancer cells.

    PubMed

    Kuo, W-T; Dong, G-C; Yao, C-H; Huang, J-Y; Lin, F-H

    2013-01-01

    PHA-E is a natural product extracted from red kidney beans, and it has been reported to induce cell apoptosis by blocking EGFR in lung cancer cells. Because EGF is the major in vivo competitor to PHA-E in clinical application, PHA-E must be proved that has better affinity to EGFR than EGF. This study would focus on how PHA-E tightly bind to EGFR and the results would compare with EGF. The adhesion force, measured by AFM, between EGFR and PHA-E was 207.14±74.42 pN that was higher than EGF (183.65±86.93 pN). The equilibrium dissociation constant of PHA-E and EGF to EGFR was 2.4 10(-9)±1.4 10(-9) and 7.3 10(-8)±2.7 10(-8), respectively, that could evaluate binding affinity. The result showed that binding affinity of PHA-E to EGFR was one order higher than EGF to EGFR. In the results of flow cytometer and confocal microscope, we found binding efficiency of EGF to EGFR was decrease as the concentration of PHA-E increased. In the analysis of Western blot, treatment of A-549 cells with PHA-E resulted in a dose-dependent decrease in EGFR phosphorylation. In conclusion, we found that PHA-E had better adhesion force and binding affinity to EGFR than that of the EGF. The interaction between PHA-E and EGFR could block EGF binding and then inhibit EGFR phosphorylation. PHA-E could be developed into a new target molecule for lung cancer treatment that could be immobilized on the drug carrier to guide therapeutic particles to the tumor site. PMID:23394551

  13. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

    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.

  15. 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

    2016-01-01

    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

  16. 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

    2016-01-01

    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.

  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. PMID:22331426

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. ...

  20. 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. PMID:26575767

  1. 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.

  2. 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

  3. 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. PMID:24370945

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

    NASA Astrophysics Data System (ADS)

    Yang, Changwon; Jang, Soonmin; Pak, Youngshang

    2011-12-01

    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 Sr2+ (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.

  5. 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.

  6. 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.

  7. 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

  8. Mechanisms for optical binding

    NASA Astrophysics Data System (ADS)

    Andrews, David L.; Davila Romero, Luciana C.

    2009-08-01

    The phenomenon of optical binding is now experimentally very well established. With a recognition of the facility to collect and organize particles held in an optical trap, the related term 'optical matter' has also been gaining currency, highlighting possibilities for a significant interplay between optically induced inter-particle forces and other interactions such as chemical bonding and dispersion forces. Optical binding itself has a variety of interpretations. With some of these explanations being more prominent than others, and their applicability to some extent depending on the nature of the particles involved, a listing of these has to include the following: collective scattering, laser-dressed Casimir forces, virtual photon coupling, optically induced dipole resonance, and plasmon resonance coupling. It is the purpose of this paper to review and to establish the extent of fundamental linkages between these theoretical descriptions, recognizing the value that each has in relating the phenomenon of optical binding to the broader context of other, closely related physical measurements.

  9. Protein-specific force field derived from the fragment molecular orbital method can improve protein-ligand binding interactions.

    PubMed

    Chang, Le; Ishikawa, Takeshi; Kuwata, Kazuo; Takada, Shoji

    2013-05-30

    Accurate computational estimate of the protein-ligand binding affinity is of central importance in rational drug design. To improve accuracy of the molecular mechanics (MM) force field (FF) for protein-ligand simulations, we use a protein-specific FF derived by the fragment molecular orbital (FMO) method and by the restrained electrostatic potential (RESP) method. Applying this FMO-RESP method to two proteins, dodecin, and lysozyme, we found that protein-specific partial charges tend to differ more significantly from the standard AMBER charges for isolated charged atoms. We did not see the dependence of partial charges on the secondary structure. Computing the binding affinities of dodecin with five ligands by MM PBSA protocol with the FMO-RESP charge set as well as with the standard AMBER charges, we found that the former gives better correlation with experimental affinities than the latter. While, for lysozyme with five ligands, both charge sets gave similar and relatively accurate estimates of binding affinities.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Mapping site-specific endonuclease binding to DNA by direct imaging with atomic force microscopy (AFM)

    NASA Astrophysics Data System (ADS)

    Allison, David P.; Thundat, Thomas G.; Modrich, P.; Isfort, R. J.; Doktycz, Mitchel J.; Kerper, P. S.; Warmack, R. J.

    1995-04-01

    Physical mapping of DNA can be accomplished by direct AFM imaging of site specific proteins bound to DNA molecules. Using Gln-111, a mutant of EcoRI endonuclease with a specific affinity for EcoRI sites 1000 times greater than wild type enzyme but with cleavage rate constants reduced by a factor of 104, we demonstrate site-specific mapping by direct AFM imaging. Images are presented showing specific-site binding of Gln-111 to plasmids having either one (pBS+) or two (pMP32) EcoRI sites. Identification of the Gln-111/DNA complex is greatly enhanced by biotinylation of the complex followed by reaction with streptavidin gold prior to imaging. Image enhancement coupled with improvements in our preparation techniques for imaging large DNA molecules, such as lambda DNA (47 kb), has the potential to contribute to direct AFM restriction mapping of cosmid-sized genomic DNAs.

  15. Measurement of membrane binding between recoverin, a calcium-myristoyl switch protein, and lipid bilayers by AFM-based force spectroscopy.

    PubMed Central

    Desmeules, Philippe; Grandbois, Michel; Bondarenko, Vladimir A; Yamazaki, Akio; Salesse, Christian

    2002-01-01

    Myristoyl switch is a feature of several peripheral membrane proteins involved in signal transduction pathways. This unique molecular property is best illustrated by the "Ca(2+)-myristoyl switch" of recoverin, which is a Ca(2+)-binding protein present in retinal rod cells of vertebrates. In this transduction pathway, the Ca(2+)-myristoyl switch acts as a calcium sensor involved in cell recovery from photoactivation. Ca(2+) binding by recoverin induces the extrusion of its myristoyl group to the solvent, which leads to its translocation from cytosol to rod disk membranes. Force spectroscopy, based on atomic force microscope (AFM) technology, was used to determine the extent of membrane binding of recoverin in the absence and presence of calcium, and to quantify this force of binding. An adhesion force of 48 +/- 5 pN was measured between recoverin and supported phospholipid bilayers in the presence of Ca(2+). However, no binding was observed in the absence of Ca(2+). Experiments with nonmyristoylated recoverin confirmed these observations. Our results are consistent with previously measured extraction forces of lipids from membranes. PMID:12023256

  16. Binding preference of carbon nanotube over proline-rich motif ligand on SH3-domain: a comparison with different force fields.

    PubMed

    Shi, Biyun; Zuo, Guanghong; Xiu, Peng; Zhou, Ruhong

    2013-04-01

    With the widespread applications of nanomaterials such as carbon nanotubes, there is a growing concern on the biosafety of these engineered nanoparticles, in particular their interactions with proteins. In molecular simulations of nanoparticle-protein interactions, the choice of empirical parameters (force fields) plays a decisive role, and thus is of great importance and should be examined carefully before wider applications. Here we compare three commonly used force fields, CHARMM, OPLSAA, and AMBER in study of the competitive binding of a single wall carbon nanotube (SWCNT) with a native proline-rich motif (PRM) ligand on its target protein SH3 domain, a ubiquitous protein-protein interaction mediator involved in signaling and regulatory pathways. We find that the SWCNT displays a general preference over the PRM in binding with SH3 domain in all the three force fields examined, although the degree of preference can be somewhat different, with the AMBER force field showing the highest preference. The SWCNT prevents the ligand from reaching its native binding pocket by (i) occupying the binding pocket directly, and (ii) binding with the ligand itself and then being trapped together onto some off-sites. The π-π stacking interactions between the SWCNT and aromatic residues are found to play a significant role in its binding to the SH3 domain in all the three force fields. Further analyses show that even the SWCNT-ligand binding can also be relatively more stable than the native ligand-protein binding, indicating a serious potential disruption to the protein SH3 function.

  17. Probing force-induced unfolding intermediates of a single staphylococcal nuclease molecule and the effect of ligand binding

    SciTech Connect

    Ishii, Takaaki Murayama, Yoshihiro; Katano, Atsuto; Maki, Kosuke; Kuwajima, Kunihiro; Sano, Masaki

    2008-10-31

    Single-molecule manipulation techniques have given experimental access to unfolding intermediates of proteins that are inaccessible in conventional experiments. A detailed characterization of the intermediates is a challenging problem that provides new possibilities for directly probing the energy landscape of proteins. We investigated single-molecule mechanical unfolding of a small globular protein, staphylococcal nuclease (SNase), using atomic force microscopy. The unfolding trajectories of the protein displayed sub-molecular and stochastic behavior with typical lengths corresponding to the size of the unfolded substructures. Our results support the view that the single protein unfolds along multiple pathways as suggested in recent theoretical studies. Moreover, we found the drastic change, caused by the ligand and inhibitor bindings, in the mechanical unfolding dynamics.

  18. Force-induced globule-coil transition in laminin binding protein and its role for viral-cell membrane fusion.

    PubMed

    Zaitsev, Boris N; Benedetti, Fabrizio; Mikhaylov, Andrey G; Korneev, Denis V; Sekatskii, Sergey K; Karakouz, Tanya; Belavin, Pavel A; Netesova, Nina A; Protopopova, Elena V; Konovalova, Svetlana N; Dietler, Giovanni; Loktev, Valery B

    2014-12-01

    The specific interactions of the pairs laminin binding protein (LBP)-purified tick-borne encephalitis viral surface protein E and certain recombinant fragments of this protein, as well as West Nile viral surface protein E and certain recombinant fragments of that protein, are studied by combined methods of single-molecule dynamic force spectroscopy (SMDFS), enzyme immunoassay and optical surface waves-based biosensor measurements. The experiments were performed at neutral pH (7.4) and acid pH (5.3) conditions. The data obtained confirm the role of LBP as a cell receptor for two typical viral species of the Flavivirus genus. A comparison of these data with similar data obtained for another cell receptor of this family, namely human αVβ3 integrin, reveals that both these receptors are very important. Studying the specific interaction between the cell receptors in question and specially prepared monoclonal antibodies against them, we could show that both interaction sites involved in the process of virus-cell interaction remain intact at pH 5.3. At the same time, for these acid conditions characteristic for an endosome during flavivirus-cell membrane fusion, SMDFS data reveal the existence of a force-induced (effective already for forces as small as 30-70 pN) sharp globule-coil transition for LBP and LBP-fragments of protein E complexes. We argue that this conformational transformation, being an analog of abrupt first-order phase transition and having similarity with the famous Rayleigh hydrodynamic instability, might be indispensable for the flavivirus-cell membrane fusion process. PMID:25319621

  19. 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.

  20. 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.

  1. Contact mechanics modeling of pull-off measurements: effect of solvent, probe radius, and chemical binding probability on the detection of single-bond rupture forces by atomic force microscopy.

    PubMed

    Skulason, Hjalti; Frisbie, C Daniel

    2002-07-01

    Pull-off forces for chemically modified atomic force microscopy tips in contact with flat substrates coated with receptor molecules are calculated using a Johnson, Kendall, and Roberts contact mechanics model. The expression for the work of adhesion is modified to account for the formation of discrete numbers of chemical bonds (nBonds) between the tip and substrate. The model predicts that the pull-off force scales as nBonds(1/2), which differs from a common assumption that the pull-off force scales linearly with nBonds. Periodic peak progressions are observed in histograms generated from hundreds of computed pull-off forces. The histogram periodicity is the signature of discrete chemical interactions between the tip and substrate and allows estimation of single-bond rupture forces. The effects of solvent, probe tip radius, and chemical binding probability on the detection of single-bond forces are examined systematically. A dimensionless parameter, the effective force resolution, is introduced that serves as a quantitative predictor for determining when periodicity in force histograms can occur. The output of model is compared to recent experimental results involving tips and substrates modified with self-assembled monolayers. An advantage of this contact mechanics approach is that it allows straightforward estimation of solvent effects on pull-off forces.

  2. Patch clamp and atomic force microscopy demonstrate TATA-binding protein (TBP) interactions with the nuclear pore complex.

    PubMed

    Bustamante, J O; Liepins, A; Prendergast, R A; Hanover, J A; Oberleithner, H

    1995-08-01

    The universal TATA-binding protein, TBP, is an essential component of the multiprotein complex known as transcription factor IID (TFIID). This complex, which consists of TBP and TBP-associated factors (TAFs), is essential for RNA polymerase II-mediated transcription. The molecular size of human TBP (37.7 kD) is close to the passive diffusion limit along the transport channel of the nuclear pore complex (NPC). Therefore, the possibility exists that NPCs restrict TBP translocation to the nuclear interior. Here we show for the first time, with patch-clamp and atomic force microscopy (AFM), that NPCs regulate TBP movement into the nucleus and that TBP (10(-15)-10(-10)M) is capable of modifying NPC structure and function. The translocation of TBP was ATP-dependent and could be detected as a transient plugging of the NPC channels, with a concomitant transient reduction in single NPC channel conductance, gamma, to a negligible value. NPC unplugging was accompanied by permanent channel opening at concentrations greater than 250 pM. AFM images demonstrated that the TBP molecules attached to and accumulated on the NPC cytosolic side. NPC channel activity could be recorded for more than 48 hr. These observations suggest that three novel functions of TBP are: to stabilize NPC, to force the NPC channels into an open state, and to increase the number of functional channels. Since TBP is a major component of transcription, our observations are relevant to the understanding of the gene expression mechanisms underlying normal and pathological cell structure and function. PMID:8568841

  3. 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 Central

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

    1995-01-01

    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. Images FIGURE 1 PMID:7647245

  4. 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.

  5. Probing the molecular forces involved in binding of selected volatile flavour compounds to salt-extracted pea proteins.

    PubMed

    Wang, Kun; Arntfield, Susan D

    2016-11-15

    Molecular interactions between heterologous classes of flavour compounds with salt-extracted pea protein isolates (PPIs) were determined using various bond disrupting agents followed by GC/MS analysis. Flavour bound by proteins decreased in the order: dibutyl disulfide>octanal>hexyl acetate>2-octanone=benzaldehyde. Benzaldehyde, 2-octanone and hexyl acetate interacted non-covalently with PPIs, whereas octanal bound PPIs via covalent and non-covalent forces. Dibutyl disulfide reacted with PPIs covalently, as its retention was not diminished by urea and guanidine hydrochloride. Using propylene glycol, H-bonding and ionic interactions were implicated for hexyl acetate, benzaldehyde, and 2-octanone. A protein-destabilising salt (Cl3CCOONa) reduced bindings for 2-octanone, hexyl acetate, and benzaldehyde; however, retention for octanal and dibutyl disulfide increased. Conversely, a protein-stabilising salt (Na2SO4) enhanced retention for benzaldehyde, 2-octanone, hexyl acetate and octanal. Formation of a volatile flavour by-product, 1-butanethiol, from dibutyl disulfide when PPIs were treated with dithiothreitol indicated occurrence of sulfhydryl-disulfide interchange reactions. PMID:27283627

  6. 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

  7. Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

    PubMed

    Sugimoto, Yumi; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

    2008-09-11

    Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine.

  8. An essential serotype recognition pocket on phage P22 tailspike protein forces Salmonella enterica serovar Paratyphi A O-antigen fragments to bind as nonsolution conformers.

    PubMed

    Andres, Dorothee; Gohlke, Ulrich; Broeker, Nina K; Schulze, Stefan; Rabsch, Wolfgang; Heinemann, Udo; Barbirz, Stefanie; Seckler, Robert

    2013-04-01

    Bacteriophage P22 recognizes O-antigen polysaccharides of Salmonella enterica subsp. enterica (S.) with its tailspike protein (TSP). In the serovars S. Typhimurium, S. Enteritidis, and S. Paratyphi A, the tetrasaccharide repeat units of the respective O-antigens consist of an identical main chain trisaccharide but different 3,6-dideoxyhexose substituents. Here, the epimers abequose, tyvelose and paratose determine the specific serotype. P22 TSP recognizes O-antigen octasaccharides in an extended binding site with a single 3,6-dideoxyhexose binding pocket. We have isolated S. Paratyphi A octasaccharides which were not available previously and determined the crystal structure of their complex with P22 TSP. We discuss our data together with crystal structures of complexes with S. Typhimurium and S. Enteritidis octasaccharides determined earlier. Isothermal titration calorimetry showed that S. Paratyphi A octasaccharide binds P22 TSP less tightly, with a difference in binding free energy of ∼7 kJ mol(-1) at 20°C compared with S. Typhimurium and S. Enteritidis octasaccharides. Individual protein-carbohydrate contacts were probed by amino acid replacements showing that the dideoxyhexose pocket contributes to binding of all three serotypes. However, S. Paratyphi A octasaccharides bind in a conformation with an energetically unfavorable ϕ/ψ glycosidic bond angle combination. In contrast, octasaccharides from the other serotypes bind as solution-like conformers. Two water molecules are conserved in all P22 TSP complexes with octasaccharides of different serotypes. They line the dideoxyhexose binding pocket and force the S. Paratyphi A octasaccharides to bind as nonsolution conformers. This emphasizes the role of solvent as part of carbohydrate binding sites.

  9. Molecular dynamics simulations reveal fundamental role of water as factor determining affinity of binding of beta-blocker nebivolol to beta(2)-adrenergic receptor.

    PubMed

    Kaszuba, Karol; Róg, Tomasz; Bryl, Krzysztof; Vattulainen, Ilpo; Karttunen, Mikko

    2010-07-01

    The beta-adrenergic antagonists (beta-blockers) constitute a class of drugs that have well-established roles in treatments of various cardiovascular diseases. Despite a 50 year history, there are two clinically important subtypes of beta-adrenergic receptors (betaARs) called beta(1)AR and beta(2)AR that still are promising drug targets. Our study maps the interactions between nebivolol-one of the most efficient beta-blocking agents-and the beta(2)-adrenergic receptor by simulating two optical isomers of nebivolol: ssss-nebivolol and srrr-nebivolol. The srrr-configuration binds preferentially to beta(1)AR and beta(2)AR. The ssss-form has much lower binding affinity to both of them. Our work indicates that water is a very important component of the binding site of the beta(2)AR receptor. We found that the higher stereoselectivity of the srrr-configuration is due to interactions with water molecules, which extensively hydrate the binding site of beta(2)AR. By lowering the energy of binding, water enhanced the affinity of the srrr-form to beta(2)AR. We also address the problem of beta(1)AR/beta(2)AR selectivity. At higher concentrations, all beta-blocking agents lose their specificity and bind nonselectively, causing many adverse effects. Our simulations indicate that PHE194, TYR308, and ILE309 of the beta(2)AR and the corresponding residues of the beta(1)AR receptor may be important determinants of beta(1)AR versus beta(2)AR selectivity.

  10. Transgene integration into the human AAVS1 locus enhances myosin II-dependent contractile force by reducing expression of myosin binding subunit 85.

    PubMed

    Mizutani, Takeomi; Li, Rui; Haga, Hisashi; Kawabata, Kazushige

    2015-09-18

    The adeno-associated virus site 1 (AAVS1) locus in the human genome is a strong candidate for gene therapy by insertion of an exogenous gene into the locus. The AAVS1 locus includes the coding region for myosin binding subunit 85 (MBS85). Although the function of MBS85 is not well understood, myosin II-dependent contractile force may be affected by altered expression of MBS85. The effect of altered expression of MBS85 on cellular contractile force should be examined prior to the application of gene therapy. In this study, we show that transgene integration into AAVS1 and consequent reduction of MBS85 expression changes myosin II-dependent cellular contractile force. We established a human fibroblast cell line with exogenous DNA knocked-in to AAVS1 (KI cells) using the CRISPR/Cas9 genome editing system. Western blotting analysis showed that KI cells had significantly reduced MBS85 expression. KI cells also showed greater cellular contractile force than control cells. The increased contractile force was associated with phosphorylation of the myosin II regulatory light chain (MRLC). Transfection of KI cells with an MBS85 expression plasmid restored cellular contractile force and phosphorylation of MRLC to the levels in control cells. These data suggest that transgene integration into the human AAVS1 locus induces an increase in cellular contractile force and thus should be considered as a gene therapy to effect changes in cellular contractile force.

  11. 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.

  12. 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

  13. 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. PMID:11401791

  14. 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

  15. A fundamental relationship between hydrophobic properties and biological activity for the duocarmycin class of DNA-alkylating antitumor drugs: hydrophobic-binding-driven bonding.

    PubMed

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

    2013-09-12

    Two systematic series of increasingly hydrophilic derivatives of duocarmycin SA that feature the incorporation of ethylene glycol units (n = 1-5) into the methoxy substituents of the trimethoxyindole subunit are described. 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. Linear relationships of cLogP with -log IC50 for cell growth inhibition and -log AE (AE = cell-free DNA alkylation efficiency) were observed, with the cLogP values spanning the productive range of 2.5-0.49 and the -log IC50 values spanning the range of 11.2-6.4, representing IC50 values that vary by a factor of 10(5) (0.008 to 370 nM). The results quantify the fundamental role played by the hydrophobic character of the compound 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.

  16. 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

    2011-11-01

    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.

  17. 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.

  18. 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

  19. A physical reference state unifies the structure-derived potential of mean force for protein folding and binding.

    PubMed

    Liu, Song; Zhang, Chi; Zhou, Hongyi; Zhou, Yaoqi

    2004-07-01

    Extracting knowledge-based statistical potential from known structures of proteins is proved to be a simple, effective method to obtain an approximate free-energy function. However, the different compositions of amino acid residues at the core, the surface, and the binding interface of proteins prohibited the establishment of a unified statistical potential for folding and binding despite the fact that the physical basis of the interaction (water-mediated interaction between amino acids) is the same. Recently, a physical state of ideal gas, rather than a statistically averaged state, has been used as the reference state for extracting the net interaction energy between amino acid residues of monomeric proteins. Here, we find that this monomer-based potential is more accurate than an existing all-atom knowledge-based potential trained with interfacial structures of dimers in distinguishing native complex structures from docking decoys (100% success rate vs. 52% in 21 dimer/trimer decoy sets). It is also more accurate than a recently developed semiphysical empirical free-energy functional enhanced by an orientation-dependent hydrogen-bonding potential in distinguishing native state from Rosetta docking decoys (94% success rate vs. 74% in 31 antibody-antigen and other complexes based on Z score). In addition, the monomer potential achieved a 93% success rate in distinguishing true dimeric interfaces from artificial crystal interfaces. More importantly, without additional parameters, the potential provides an accurate prediction of binding free energy of protein-peptide and protein-protein complexes (a correlation coefficient of 0.87 and a root-mean-square deviation of 1.76 kcal/mol with 69 experimental data points). This work marks a significant step toward a unified knowledge-based potential that quantitatively captures the common physical principle underlying folding and binding. A Web server for academic users, established for the prediction of binding free energy

  20. 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. PMID

  1. 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.

  2. 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.

  3. 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.

  4. The contribution of cardiac myosin binding protein-c Ser282 phosphorylation to the rate of force generation and in vivo cardiac contractility

    PubMed Central

    Gresham, Kenneth S; Mamidi, Ranganath; Stelzer, Julian E

    2014-01-01

    Cardiac myosin binding protein-C phosphorylation plays an important role in modulating cardiac muscle function and accelerating contraction. It has been proposed that Ser282 phosphorylation may serve as a critical molecular switch that regulates the phosphorylation of neighbouring Ser273 and Ser302 residues, and thereby govern myofilament contractile acceleration in response to protein kinase A (PKA). Therefore, to determine the regulatory roles of Ser282 we generated a transgenic (TG) mouse model expressing cardiac myosin binding protein-C with a non-phosphorylatable Ser282 (i.e. serine to alanine substitution, TGS282A). Myofibrils isolated from TGS282A hearts displayed robust PKA-mediated phosphorylation of Ser273 and Ser302, and the increase in phosphorylation was identical to TG wild-type (TGWT) controls. No signs of pathological cardiac hypertrophy were detected in TGS282A hearts by either histological examination of cardiac sections or echocardiography. Baseline fractional shortening, ejection fraction, isovolumic relaxation time, rate of pressure development and rate of relaxation (τ) were unaltered in TGS282A mice. However, the increase in cardiac contractility as well as the acceleration of pressure development observed in response to β-adrenergic stimulation was attenuated in TGS282A mice. In agreement with our in vivo data, in vitro force measurements revealed that PKA-mediated acceleration of cross-bridge kinetics in TGS282A myocardium was significantly attenuated compared to TGWT myocardium. Taken together, our data suggest that while Ser282 phosphorylation does not regulate the phosphorylation of neighbouring Ser residues and basal cardiac function, full acceleration of cross-bridge kinetics and left ventricular pressure development cannot be achieved in its absence. PMID:24951619

  5. 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

  6. One Force

    NASA Astrophysics Data System (ADS)

    Kotas, Ronald R.

    2002-04-01

    There is only one entity that can extend force and couple through space; and it should be apparent that Electromagnetism is that entity. In the cases of the nuclear strong force and the nuclear weak force, this is the same fundamental Electromagnetism manifesting itself in two different ways in the nucleus. It remains the same basic Electromagnetism. On the other hand, General Relativity fails to produce force at a distance, fails the Cavendish experiment, and does not allow an apple to fall to the ground. The result shows there is only Electromagnetism that functions through physical nature providing gravity, actions in the nucleus, as well as all other physical actions universally, including Gravity and Gravitation. There are many direct proofs of this, the same proofs as in NUCLEAR QUANTUM GRAVITATION. In contrast, General Relativity plainly relies on fallacy abstract and incoherent proofs; proofs which have now been mostly disproved. In the past it was deemed necessary by some to have an "ether" to propagate Electromagnetic waves. The fallacy concept of time space needs "space distortions" in order to cause gravity. However, Electromagnetic gravity does not have this problem. Clearly there is only ONE FORCE that causes Gravity, Electromagnetism, the Nuclear Strong Force, and the Nuclear Weak Force, and that ONE FORCE is Electromagnetism.

  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. 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,…

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity.

    PubMed

    Elosegui-Artola, Alberto; Oria, Roger; Chen, Yunfeng; Kosmalska, Anita; Pérez-González, Carlos; Castro, Natalia; Zhu, Cheng; Trepat, Xavier; Roca-Cusachs, Pere

    2016-05-01

    Cell function depends on tissue rigidity, which cells probe by applying and transmitting forces to their extracellular matrix, and then transducing them into biochemical signals. Here we show that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. We demonstrate that force transmission is regulated by a dynamic clutch mechanism, which unveils its fundamental biphasic force/rigidity relationship on talin depletion. Force transduction is triggered by talin unfolding above a stiffness threshold. Below this threshold, integrins unbind and release force before talin can unfold. Above the threshold, talin unfolds and binds to vinculin, leading to adhesion growth and YAP nuclear translocation. Matrix density, myosin contractility, integrin ligation and talin mechanical stability differently and nonlinearly regulate both force transmission and the transduction threshold. In all cases, coupling of talin unfolding dynamics to a theoretical clutch model quantitatively predicts cell response. PMID:27065098

  16. On some fundamental concepts of galactic dynamics

    NASA Astrophysics Data System (ADS)

    Ossipkov, L. P.

    2013-10-01

    We discuss the following fundamental concepts of galactic dynamics: (a) regular (smoothed) and irregular (random) forces, (b) truncation of the impact parameter, (c) the invariance of the Maxwellian velocity distribution, and (d) the Jeans theorem. Dedicated to Felix Alexandrovich Tsitsin (1931-2005)

  17. 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.

  18. Variation of Fundamental Constants

    NASA Astrophysics Data System (ADS)

    Flambaum, V. V.

    2006-11-01

    Theories unifying gravity with other interactions suggest temporal and spatial variation of the fundamental ``constants'' in expanding Universe. The spatial variation can explain a fine tuning of the fundamental constants which allows humans (and any life) to appear. We appeared in the area of the Universe where the values of the fundamental constants are consistent with our existence. We present a review of recent works devoted to the variation of the fine structure constant α, strong interaction and fundamental masses. There are some hints for the variation in quasar absorption spectra. Big Bang nucleosynthesis, and Oklo natural nuclear reactor data. A very promising method to search for the variation of the fundamental constants consists in comparison of different atomic clocks. Huge enhancement of the variation effects happens in transition between accidentally degenerate atomic and molecular energy levels. A new idea is to build a ``nuclear'' clock based on the ultraviolet transition between very low excited state and ground state in Thorium nucleus. This may allow to improve sensitivity to the variation up to 10 orders of magnitude! Huge enhancement of the variation effects is also possible in cold atomic and molecular collisions near Feshbach resonance.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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…

  5. 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.…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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.

  12. 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.

  13. 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?

  14. 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.

    PubMed

    Desgranges, Caroline; Delhommelle, Jerome

    2016-03-28

    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. PMID:27036464

  15. 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.

  16. Isolation of ZnO-binding 12-mer peptides and determination of their binding epitopes by NMR spectroscopy.

    PubMed

    Rothenstein, Dirk; Claasen, Birgit; Omiecienski, Beatrice; Lammel, Patricia; Bill, Joachim

    2012-08-01

    Inorganic-binding peptides are in the focus of research fields such as materials science, nanotechnology, and biotechnology. Applications concern surface functionalization by the specific coupling to inorganic target substrates, the binding of soluble molecules for sensing applications, or biomineralization approaches for the controlled formation of inorganic materials. The specific molecular recognition of inorganic surfaces by peptides is of major importance for such applications. Zinc oxide (ZnO) is an important semiconductor material which is applied in various devices. In this study the molecular fundamentals for a ZnO-binding epitope was determined. 12-mer peptides, which specifically bind to the zinc- or/and the oxygen-terminated sides of single-crystalline ZnO (0001) and (000-1) substrates, were selected from a random peptide library using the phage display technique. For two ZnO-binding peptides the mandatory amino acid residues, which are of crucial importance for the specific binding were determined with a label-free nuclear magnetic resonance (NMR) approach. NMR spectroscopy allows the identification of pH dependent interaction sites on the atomic level of 12-mer peptides and ZnO nanoparticles. Here, ionic and polar interaction forces were determined. For the oxygen-terminated side the consensus peptide-binding sequence (HSXXH) was predicted in silico and confirmed by the NMR approach. PMID:22720657

  17. 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.

  18. Fundamental "Uncertainty" in Science

    NASA Astrophysics Data System (ADS)

    Reichl, Linda E.

    The conference on "Uncertainty and Surprise" was concerned with our fundamental inability to predict future events. How can we restructure organizations to effectively function in an uncertain environment? One concern is that many large complex organizations are built on mechanical models, but mechanical models cannot always respond well to "surprises." An underlying assumption a bout mechanical models is that, if we give them enough information about the world, they will know the future accurately enough that there will be few or no surprises. The assumption is that the future is basically predictable and deterministic.

  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. 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. 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

  2. Entropic force between biomembranes

    NASA Astrophysics Data System (ADS)

    Li, Long; Song, Fan

    2016-08-01

    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.

  3. 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

  4. Fundamentals of electrokinetics

    NASA Astrophysics Data System (ADS)

    Kozak, M. W.

    The study of electrokinetics is a very mature field. Experimental studies date from the early 1800s, and acceptable theoretical analyses have existed since the early 1900s. The use of electrokinetics in practical field problems is more recent, but it is still quite mature. Most developments in the fundamental understanding of electrokinetics are in the colloid science literature. A significant and increasing divergence between the theoretical understanding of electrokinetics found in the colloid science literature and the theoretical analyses used in interpreting applied experimental studies in soil science and waste remediation has developed. The soil science literature has to date restricted itself to the use of very early theories, with their associated limitations. The purpose of this contribution is to review fundamental aspects of electrokinetic phenomena from a colloid science viewpoint. It is hoped that a bridge can be built between the two branches of the literature, from which both will benefit. Attention is paid to special topics such as the effects of overlapping double layers, applications in unsaturated soils, the influence of dispersivity, and the differences between electrokinetic theory and conductivity theory.

  5. Imaging G protein–coupled receptors while quantifying their ligand-binding free-energy landscape

    PubMed Central

    Zhang, Cheng; Spoerri, Patrizia M; Coughlin, Shaun R; Kobilka, Brian K; Müller, Daniel J

    2016-01-01

    Imaging native membrane receptors and testing how they interact with ligands is of fundamental interest in the life sciences but has proven remarkably difficult to accomplish. Here, we introduce an approach that uses force-distance curve–based atomic force microscopy to simultaneously image single native G protein–coupled receptors in membranes and quantify their dynamic binding strength to native and synthetic ligands. We measured kinetic and thermodynamic parameters for individual protease-activated receptor-1 (PAR1) molecules in the absence and presence of antagonists, and these measurements enabled us to describe PAR1’s ligand-binding free-energy landscape with high accuracy. Our nanoscopic method opens an avenue to directly image and characterize ligand binding of native membrane receptors. PMID:26167642

  6. Fundamentals of Geophysics

    NASA Astrophysics Data System (ADS)

    Lowrie, William

    1997-10-01

    This unique textbook presents a comprehensive overview of the fundamental principles of geophysics. Unlike most geophysics textbooks, it combines both the applied and theoretical aspects to the subject. The author explains complex geophysical concepts using abundant diagrams, a simplified mathematical treatment, and easy-to-follow equations. After placing the Earth in the context of the solar system, he describes each major branch of geophysics: gravitation, seismology, dating, thermal and electrical properties, geomagnetism, paleomagnetism and geodynamics. Each chapter begins with a summary of the basic physical principles, and a brief account of each topic's historical evolution. The book will satisfy the needs of intermediate-level earth science students from a variety of backgrounds, while at the same time preparing geophysics majors for continued study at a higher level.

  7. 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.

  8. Fundamentals in Nuclear Physics

    NASA Astrophysics Data System (ADS)

    Basdevant, Jean-Louis, Rich, James, Spiro, Michael

    This course on nuclear physics leads the reader to the exploration of the field from nuclei to astrophysical issues. Much nuclear phenomenology can be understood from simple arguments such as those based on the Pauli principle and the Coulomb barrier. This book is concerned with extrapolating from such arguments and illustrating nuclear systematics with experimental data. Starting with the basic concepts in nuclear physics, nuclear models, and reactions, the book covers nuclear decays and the fundamental electro-weak interactions, radioactivity, and nuclear energy. After the discussions of fission and fusion leading into nuclear astrophysics, there is a presentation of the latest ideas about cosmology. As a primer this course will lay the foundations for more specialized subjects. This book emerged from a series of topical courses the authors delivered at the Ecole Polytechnique and will be useful for graduate students and for scientists in a variety of fields.

  9. 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.

  10. 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

  11. Overlay accuracy fundamentals

    NASA Astrophysics Data System (ADS)

    Kandel, Daniel; Levinski, Vladimir; Sapiens, Noam; Cohen, Guy; Amit, Eran; Klein, Dana; Vakshtein, Irina

    2012-03-01

    Currently, the performance of overlay metrology is evaluated mainly based on random error contributions such as precision and TIS variability. With the expected shrinkage of the overlay metrology budget to < 0.5nm, it becomes crucial to include also systematic error contributions which affect the accuracy of the metrology. Here we discuss fundamental aspects of overlay accuracy and a methodology to improve accuracy significantly. We identify overlay mark imperfections and their interaction with the metrology technology, as the main source of overlay inaccuracy. The most important type of mark imperfection is mark asymmetry. Overlay mark asymmetry leads to a geometrical ambiguity in the definition of overlay, which can be ~1nm or less. It is shown theoretically and in simulations that the metrology may enhance the effect of overlay mark asymmetry significantly and lead to metrology inaccuracy ~10nm, much larger than the geometrical ambiguity. The analysis is carried out for two different overlay metrology technologies: Imaging overlay and DBO (1st order diffraction based overlay). It is demonstrated that the sensitivity of DBO to overlay mark asymmetry is larger than the sensitivity of imaging overlay. Finally, we show that a recently developed measurement quality metric serves as a valuable tool for improving overlay metrology accuracy. Simulation results demonstrate that the accuracy of imaging overlay can be improved significantly by recipe setup optimized using the quality metric. We conclude that imaging overlay metrology, complemented by appropriate use of measurement quality metric, results in optimal overlay accuracy.

  12. Fundamentals of Atmospheric Radiation

    NASA Astrophysics Data System (ADS)

    Bohren, Craig F.; Clothiaux, Eugene E.

    2006-02-01

    This textbook fills a gap in the literature for teaching material suitable for students of atmospheric science and courses on atmospheric radiation. It covers the fundamentals of emission, absorption, and scattering of electromagnetic radiation from ultraviolet to infrared and beyond. Much of the book applies to planetary atmosphere. The authors are physicists and teach at the largest meteorology department of the US at Penn State. Craig T. Bohren has taught the atmospheric radiation course there for the past 20 years with no book. Eugene Clothiaux has taken over and added to the course notes. Problems given in the text come from students, colleagues, and correspondents. The design of the figures especially for this book is meant to ease comprehension. Discussions have a graded approach with a thorough treatment of subjects, such as single scattering by particles, at different levels of complexity. The discussion of the multiple scattering theory begins with piles of plates. This simple theory introduces concepts in more advanced theories, i.e. optical thickness, single-scattering albedo, asymmetry parameter. The more complicated theory, the two-stream theory, then takes the reader beyond the pile-of-plates theory. Ideal for advanced undergraduate and graduate students of atmospheric science.

  13. Orthogonal non-covalent binding forces in solid state supramolecular herringbone-shaped "interlocked dimers". Pseudopolymorphism in [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) complex.

    PubMed

    Pérez, José; Espinosa, Arturo; Galiana, J Miguel; Pérez, Eduardo; Serrano, J Luis; Aranda, Miguel A G; Insausti, Maite

    2009-11-21

    The crystal structures of [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) (1) and two different solvatomorphs of it, [(ppy)Pd(mu-pz)](2) x 1/2 CH(2)Cl(2) (2) and [(ppy)Pd(mu-pz)](2) x 1/2 CHCl(3) (3) have been elucidated by powder (1 and 2) and single crystal (3) X-ray diffraction. In all of them two molecules fit together following a very similar pattern forming a "dimer". All neutral dinuclear square-planar complexes having mu-pz or related bridges and planar aromatic ligands completing the coordination spheres found in the CSD show a similar arrangement to those observed in compounds 1-3, consisting of "interlocked dimers" following a herringbone-like pattern. A DFT study reveals the simultaneous action of pi,pi- and T-stacking interactions occurring as two sets of orthogonally oriented binding forces, as well as anagostic bonds overlapped with the latter.

  14. A density functional tight binding/force field approach to the interaction of molecules with rare gas clusters: Application to (C{sub 6}H{sub 6}){sup +/0}Ar{sub n} clusters

    SciTech Connect

    Iftner, Christophe; Simon, Aude; Korchagina, Kseniia; Rapacioli, Mathias; Spiegelman, Fernand

    2014-01-21

    We propose in the present paper a SCC-DFTB/FF (Self-Consistent-Charge Density Functional based Tight Binding/Force-Field) scheme adapted to the investigation of molecules trapped in rare gas environments. With respect to usual FF descriptions, the model involves the interaction of quantum electrons in a molecule with rare gas atoms in an anisotropic scheme. It includes polarization and dispersion contributions and can be used for both neutral and charged species. Parameters for this model are determined for hydrocarbon-argon complexes and the model is validated for small hydrocarbons. With the future aim of studying polycyclic aromatic hydrocarbons in Ar matrices, extensive benchmark calculations are performed on (C{sub 6}H{sub 6}){sup +/0}Ar{sub n} clusters against DFT and CCSD(T) calculations for the smaller sizes, and more generally against other experimental and theoretical data. Results on the structures and energetics (isomer ordering and energy separation, cohesion energy per Ar atom) are presented in detail for n = 1–8, 13, 20, 27, and 30, for both neutrals and cations. We confirm that the clustering of Ar atoms leads to a monotonous decrease of the ionization potential of benzene for n ⩽ 20, in line with previous experimental and FF data.

  15. 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

  16. 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

  17. 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

  18. Maximum Entropy Fundamentals

    NASA Astrophysics Data System (ADS)

    Harremoeës, P.; Topsøe, F.

    2001-09-01

    In its modern formulation, the Maximum Entropy Principle was promoted by E.T. Jaynes, starting in the mid-fifties. The principle dictates that one should look for a distribution, consistent with available information, which maximizes the entropy. However, this principle focuses only on distributions and it appears advantageous to bring information theoretical thinking more prominently into play by also focusing on the "observer" and on coding. This view was brought forward by the second named author in the late seventies and is the view we will follow-up on here. It leads to the consideration of a certain game, the Code Length Game and, via standard game theoretical thinking, to a principle of Game Theoretical Equilibrium. This principle is more basic than the Maximum Entropy Principle in the sense that the search for one type of optimal strategies in the Code Length Game translates directly into the search for distributions with maximum entropy. In the present paper we offer a self-contained and comprehensive treatment of fundamentals of both principles mentioned, based on a study of the Code Length Game. Though new concepts and results are presented, the reading should be instructional and accessible to a rather wide audience, at least if certain mathematical details are left aside at a rst reading. The most frequently studied instance of entropy maximization pertains to the Mean Energy Model which involves a moment constraint related to a given function, here taken to represent "energy". This type of application is very well known from the literature with hundreds of applications pertaining to several different elds and will also here serve as important illustration of the theory. But our approach reaches further, especially regarding the study of continuity properties of the entropy function, and this leads to new results which allow a discussion of models with so-called entropy loss. These results have tempted us to speculate over the development of natural

  19. 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.

  20. Forces in yeast flocculation.

    PubMed

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

    2015-02-01

    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.

  1. 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.

  2. Against Fundamentalism, for Democracy: Towards a Pedagogy of Tolerance in Higher Education

    ERIC Educational Resources Information Center

    Badley, Graham

    2005-01-01

    Fundamentalism and democracy are presented as opposing forces in a world in conflict. Fundamentalism is described both as a threat to democracy itself and also to supposedly democratic institutions such as the university. First, fundamentalism is defined in its various guises: Christian, Islamic and economic. Each of these forms is pernicious in…

  3. 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

  4. Nuclear forces

    SciTech Connect

    Machleidt, R.

    2013-06-10

    These lectures present an introduction into the theory of nuclear forces. We focus mainly on the modern approach, in which the forces between nucleons emerge from low-energy QCD via chiral effective field theory.

  5. 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…

  6. 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.

  7. 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.

  8. 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.

  9. Forces Driving Chaperone Action.

    PubMed

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

    2016-07-14

    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

  10. Van der Waals Forces

    NASA Astrophysics Data System (ADS)

    Parsegian, V. Adrian

    2006-03-01

    This should prove to be the definitive work explaining van der Waals forces, how to calculate them and take account of their impact under any circumstances and conditions. These weak intermolecular forces are of truly pervasive impact, and biologists, chemists, physicists and engineers will profit greatly from the thorough grounding in these fundamental forces that this book offers. Parsegian has organized his book at three successive levels of mathematical sophistication, to satisfy the needs and interests of readers at all levels of preparation. The Prelude and Level 1 are intended to give everyone an overview in words and pictures of the modern theory of van der Waals forces. Level 2 gives the formulae and a wide range of algorithms to let readers compute the van der Waals forces under virtually any physical or physiological conditions. Level 3 offers a rigorous basic formulation of the theory. Author is among the most highly respected biophysicists Van der Waals forces are significant for a wide range of questions and problems in the life sciences, chemistry, physics, and engineering, ranging up to the macro level No other book that develops the subject vigorously, and this book also makes the subject intuitively accessible to students who had not previously been mathematically sophisticated enough to calculate them

  11. 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.

  12. Mechanical force analysis of peptide interactions using atomic force microscopy.

    PubMed

    Nakamura, Chikashi; Takeda, Seiji; Kageshima, Masami; Ito, Miyuki; Sugimoto, Naoki; Sekizawa, Kazuko; Miyake, Jun

    2004-01-01

    Some peptides have previously been reported to bind low molecular weight chemicals. One such peptide with the amino acid sequence His-Ala-Ser-Tyr-Ser was selectively screened from a phage library and bound to a cationic porphyrin, 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphine (TMpyP), with a binding constant of 10(5) M(-1) (J. Kawakami, T. Kitano, and N. Sugimoto, Chemical Communications, 1999, pp. 1765-1766). The proposed binding was due to pi-electron stacking from two aromatic amino acids of histidine and tyrosine. In this study, the weak interactions between TMpyP and the peptide were further investigated by force curve analysis using atomic force microscopy (AFM). The mechanical force required to unbind the peptide-porphyrin complex was measured by vertical movement of the AFM tip. Peptide self-assembled monolayers were formed on both a gold-coated mica substrate and a gold-coated AFM tip. The TMpyPs could bind between the two peptide layers when the peptide-immobilized AFM tip contacted the peptide-immobilized substrate in solution containing TMpyP. In the retracting process a force that ruptured the interaction between TMpyPs and peptides was observed. The unbinding force values correlated to the concentration of TMpyP. A detection limit of 100 ng/mL porphyrin was obtained for the force measurement, and was similar to surface plasmon resonance sensor detection limits. Furthermore, we calculated the product of the observed force and the length of the molecular elongation to determine the work required to unbind the complexes. The obtained values of unbinding work were in a reasonable range compared to the binding energy of porphyrin-peptide.

  13. 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…

  14. 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.

  15. 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.

  16. 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.

  17. Fundamental Practices of Curriculum Development.

    ERIC Educational Resources Information Center

    Usova, George M.; Gibson, Marcia

    Designed to give guidance to those involved in the curriculum development process within the Shipyard Training Modernization Program (STMP), this guide provides an understanding of the fundamental practices followed in the curriculum development process. It also demonstrates incorrect and correct approaches to the development of the curriculum…

  18. 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)

  19. 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)

  20. 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…

  1. 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

  2. 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 cultural…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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.

  8. 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.

  9. Big Bang nucleosynthesis as a probe of varying fundamental ``constants''

    NASA Astrophysics Data System (ADS)

    Dent, Thomas; Stern, Steffen; Wetterich, Christof

    2007-11-01

    We analyze the effect of variation of fundamental couplings and mass scales on primordial nucleosynthesis in a systematic way. The first step establishes the response of primordial element abundances to the variation of a large number of nuclear physics parameters, including nuclear binding energies. We find a strong influence of the n-p mass difference, of the nucleon mass and of A = 3,4,7 binding energies. A second step relates the nuclear parameters to the parameters of the Standard Model of particle physics. The deuterium, and, above all, 7Li abundances depend strongly on the average light quark mass. We calculate the behaviour of abundances when variations of fundamental parameters obey relations arising from grand unification. We also discuss the possibility of a substantial shift in the lithium abundance while the deuterium and 4He abundances are only weakly affected.

  10. Primordial nucleosynthesis as a probe of fundamental physics parameters

    NASA Astrophysics Data System (ADS)

    Dent, Thomas; Stern, Steffen; Wetterich, Christof

    2007-09-01

    We analyze the effect of variation of fundamental couplings and mass scales on primordial nucleosynthesis in a systematic way. The first step establishes the response of primordial element abundances to the variation of a large number of nuclear physics parameters, including nuclear binding energies. We find a strong influence of the n-p mass difference (for the He4 abundance), of the nucleon mass (for deuterium), and of A=3, 4, 7 binding energies (for He3, Li6, and Li7). A second step relates the nuclear parameters to the parameters of the standard model of particle physics. The deuterium, and, above all, Li7 abundances depend strongly on the average light quark mass m^≡(mu+md)/2. We calculate the behavior of abundances when variations of fundamental parameters obey relations arising from grand unification. We also discuss the possibility of a substantial shift in the lithium abundance while the deuterium and He4 abundances are only weakly affected.

  11. 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.

  12. Variation of fundamental constants: theory

    NASA Astrophysics Data System (ADS)

    Flambaum, Victor

    2008-05-01

    Theories unifying gravity with other interactions suggest temporal and spatial variation of the fundamental ``constants'' in expanding Universe. There are some hints for the variation of different fundamental constants in quasar absorption spectra and Big Bang nucleosynthesis data. A large number of publications (including atomic clocks) report limits on the variations. We want to study the variation of the main dimensionless parameters of the Standard Model: 1. Fine structure constant alpha (combination of speed of light, electron charge and Plank constant). 2. Ratio of the strong interaction scale (LambdaQCD) to a fundamental mass like electron mass or quark mass which are proportional to Higgs vacuum expectation value. The proton mass is propotional to LambdaQCD, therefore, the proton-to-electron mass ratio comes into this second category. We performed necessary atomic, nuclear and QCD calculations needed to study variation of the fundamental constants using the Big Bang Nucleosynthsis, quasar spectra, Oklo natural nuclear reactor and atomic clock data. The relative effects of the variation may be enhanced in transitions between narrow close levels in atoms, molecules and nuclei. If one will study an enhanced effect, the relative value of systematic effects (which are not enhanced) may be much smaller. Note also that the absolute magnitude of the variation effects in nuclei (e.g. in very narrow 7 eV transition in 229Th) may be 5 orders of magnitude larger than in atoms. A different possibility of enhancement comes from the inversion transitions in molecules where splitting between the levels is due to the quantum tunneling amplitude which has strong, exponential dependence on the electron to proton mass ratio. Our study of NH3 quasar spectra has already given the best limit on the variation of electron to proton mass ratio.

  13. Vacuum force

    NASA Astrophysics Data System (ADS)

    Han, Yongquan

    2015-03-01

    To study on vacuum force, we must clear what is vacuum, vacuum is a space do not have any air and also ray. There is not exist an absolute the vacuum of space. The vacuum of space is relative, so that the vacuum force is relative. There is a certain that vacuum vacuum space exists. In fact, the vacuum space is relative, if the two spaces compared to the existence of relative vacuum, there must exist a vacuum force, and the direction of the vacuum force point to the vacuum region. Any object rotates and radiates. Rotate bend radiate- centripetal, gravity produced, relative gravity; non gravity is the vacuum force. Gravity is centripetal, is a trend that the objects who attracted wants to Centripetal, or have been do Centripetal movement. Any object moves, so gravity makes the object curve movement, that is to say, the radiation range curve movement must be in the gravitational objects, gravity must be existed in non vacuum region, and make the object who is in the region of do curve movement (for example: The earth moves around the sun), or final attracted in the form gravitational objects, and keep relatively static with attract object. (for example: objects on the earth moves but can't reach the first cosmic speed).

  14. Frontiers of Fundamental Physics 14

    NASA Astrophysics Data System (ADS)

    The 14th annual international symposium "Frontiers of Fundamental Physics" (FFP14) was organized by the OCEVU Labex. It was held in Marseille, on the Saint-Charles Campus of Aix Marseille University (AMU) and had over 280 participants coming from all over the world. FFP Symposium began in India in 1997 and it became itinerant in 2004, through Europe, Canada and Australia. It covers topics in fundamental physics with the objective to enable scholars working in related areas to meet on a single platform and exchange ideas. In addition to highlighting the progress in these areas, the symposium invites the top researchers to reflect on the educational aspects of our discipline. Moreover, the scientific concepts are also discussed through philosophical and epistemological viewpoints. Several eminent scientists, such as the laureates of prestigious awards (Nobel Prize, Fields Medal,…), have already participated in these meetings. The FFP14 Symposium developed around seven main themes, namely: Astroparticle Physics, Cosmology, High Energy Physics, Quantum Gravity, Mathematical Physics, Physics Education, Epistemology and Philosophy. The morning was devoted to the plenary session, with talks for a broad audience of physicists in its first half (9:00-10:30), and more specialized in its second half (11:00-12:30); this part was held in three amphitheaters. The parallel session of the Symposium took place during the afternoon (14:30-18:30) with seven thematic conferences and an additional conference on open topics named "Frontiers of Fundamental Physics". These eight conferences were organized around the contributions of participants, in addition to the ones of invited speakers. Altogether, there were some 250 contributions to the symposium (talks and posters). The plenary talks were webcasted live and recorded. The slides of the talks and the videos of the plenary talks are available from the Symposium web site: http://ffp14.cpt.univ-mrs.fr/

  15. An entropic understanding of Coulomb force

    NASA Astrophysics Data System (ADS)

    Cho, Jin-Ho; Kim, Hyosung

    2012-02-01

    Exploiting Verlinde's proposal on the entropic understanding of Newton's law, we show that Coulomb force could also be understood as an entropically emergent force (rather than as a fundamental force). We apply Kaluza-Klein idea to Verlinde's formalism to obtain Coulomb interaction in the lower dimensions. The kinematics concerning the Kaluza-Klein momenta separates the interaction due to the momentum flow from the gravitational interaction. The momentum-charge conversion relation results in the precise form of Coulomb interaction.

  16. 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..

  17. 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.

  18. 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.

  19. 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.

  20. Involvement of the 5-HT(1A) receptor in the anti-immobility effects of fluvoxamine in the forced swimming test and mouse strain differences in 5-HT(1A) receptor binding.

    PubMed

    Sugimoto, Yumi; Furutani, Sachiko; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

    2010-03-10

    We previously demonstrated the presence of strain differences in baseline immobility time and sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in five strains of mice (ICR, ddY, C57BL, DBA/2 and BALB/c mice). Furthermore, variations in serotonin (5-HT) transporter binding in the brain were strongly related to strain differences in baseline immobility and sensitivity to fluvoxamine. In the present study, we examined the involvement of the 5-HT(1A) receptor in anti-immobility effects in DBA/2 mice, which show high sensitivity to fluvoxamine. The anti-immobility effects of fluvoxamine in DBA/2 mice were inhibited by the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT(1B) receptor antagonist 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide (GR55562), the 5-HT(2) receptor antagonist 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT(3) receptor antagonist ondansetron and the 5-HT(4) receptor antagonist 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not influence the anti-immobility effects of fluvoxamine in DBA/2 mice. These results suggest that fluvoxamine-induced antidepressant-like effects in DBA/2 mice are mediated by the 5-HT(1A) receptor. We analyzed 5-HT(1A) receptor binding in the brains of five strains of mice. Strain differences in 5-HT(1A) receptor binding were observed. 5-HT(1A) receptor binding in brain was not correlated with baseline immobility time in the five strains of mice examined. These results suggest that, although the anti-immobility effects of fluvoxamine in DBA/2 mice are mediated by the 5-HT(1A) receptor, strain differences in 5-HT(1A) receptor binding are not related to variation in immobility time and responses to fluvoxamine.

  1. Molecular Force Spectroscopy on Cells

    NASA Astrophysics Data System (ADS)

    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.

  2. 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

  3. 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.

  4. 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.

  5. Fundamental reaction pathways during coprocessing

    SciTech Connect

    Stock, L.M.; Gatsis, J.G.

    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.

  6. 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. PMID:24477692

  7. Holographic viscosity of fundamental matter.

    PubMed

    Mateos, David; Myers, Robert C; Thomson, Rowan M

    2007-03-01

    A holographic dual of a finite-temperature SU(Nc) gauge theory with a small number of flavors Nf or =1/4pi. Given the known results for the entropy density, the contribution of the fundamental matter eta fund is therefore enhanced at strong 't Hooft coupling lambda; for example, eta fund approximately lambda NcNfT3 in four dimensions. Other transport coefficients are analogously enhanced. These results hold with or without a baryon number chemical potential. PMID:17358523

  8. [INFORMATION, A FUNDAMENTAL PATIENT RIGHT?].

    PubMed

    Mémeteau, Gérard

    2015-03-01

    Although expressed before the "Lambert" case, which has led us to think about refusal and assent in the context of internal rights, conventional rights--and in the context of the patient's bed!--these simple remarks present the patient's right to medical information as a so-called fundamental right. But it can only be understood with a view to a treatment or other medical act; otherwise it has no reason to be and is only an academic exercise, however exciting, but not much use by itself. What if we reversed the terms of the problem: the right of the doctor to information? (The beautiful thesis of Ph. Gaston, Paris 8, 2 December 2014).

  9. 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.

  10. 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

  11. 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

  12. Fundamental issues in questionnaire design.

    PubMed

    Murray, P

    1999-07-01

    The questionnaire is probably the most common form of data collection tool used in nursing research. There is a misconception that anyone with a clear grasp of English and a modicum of common sense can design an effective questionnaire. Contrary to such common belief, this article will demonstrate that questionnaire design is a complex and time consuming process, but a necessary labour to ensure valid and reliable data is collected. In addition, meticulous construction is more likely to yield data that can be utilized in the pursuit of objective, quantitative and generalizable truths, upon which practice and policy decisions can be formulated. This article examines a myriad of fundamental issues surrounding questionnaire design, which encompass question wording, question order, presentation, administration and data collection, amongst other issues.

  13. Fundamentals of air quality systems

    SciTech Connect

    Noll, K.E.

    1999-08-01

    The book uses numerous examples to demonstrate how basic design concepts can be applied to the control of air emissions from industrial sources. It focuses on the design of air pollution control devices for the removal of gases and particles from industrial sources, and provides detailed, specific design methods for each major air pollution control system. Individual chapters provide design methods that include both theory and practice with emphasis on the practical aspect by providing numerous examples that demonstrate how air pollution control devices are designed. Contents include air pollution laws, air pollution control devices; physical properties of air, gas laws, energy concepts, pressure; motion of airborne particles, filter and water drop collection efficiency; fundamentals of particulate emission control; cyclones; fabric filters; wet scrubbers; electrostatic precipitators; control of volatile organic compounds; adsorption; incineration; absorption; control of gaseous emissions from motor vehicles; practice problems (with solutions) for the P.E. examination in environmental engineering. Design applications are featured throughout.

  14. 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.

  15. Fundamental enabling issues in nanotechnology :

    SciTech Connect

    Floro, Jerrold Anthony; Foiles, Stephen Martin; Hearne, Sean Joseph; Hoyt, Jeffrey John; Seel, Steven Craig; Webb, 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  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. 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.

  3. 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.

  4. Fluorescence lifetimes: fundamentals and interpretations.

    PubMed

    Noomnarm, Ulai; Clegg, Robert M

    2009-01-01

    Fluorescence measurements have been an established mainstay of photosynthesis experiments for many decades. Because in the photosynthesis literature the basics of excited states and their fates are not usually described, we have presented here an easily understandable text for biology students in the style of a chapter in a text book. In this review we give an educational overview of fundamental physical principles of fluorescence, with emphasis on the temporal response of emission. Escape from the excited state of a molecule is a dynamic event, and the fluorescence emission is in direct kinetic competition with several other pathways of de-excitation. It is essentially through a kinetic competition between all the pathways of de-excitation that we gain information about the fluorescent sample on the molecular scale. A simple probability allegory is presented that illustrates the basic ideas that are important for understanding and interpreting most fluorescence experiments. We also briefly point out challenges that confront the experimenter when interpreting time-resolved fluorescence responses.

  5. 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.

  6. 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.

  7. 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.

  8. 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. PMID:27143175

  9. 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

  10. Fundamental Mechanisms of Interface Roughness

    SciTech Connect

    Randall L. Headrick

    2009-01-06

    Publication quality results were obtained for several experiments and materials systems including: (i) Patterning and smoothening of sapphire surfaces by energetic Ar+ ions. Grazing Incidence Small Angle X-ray Scattering (GISAXS) experiments were performed in the system at the National Synchrotron Light Source (NSLS) X21 beamline. Ar+ ions in the energy range from 300 eV to 1000 eV were used to produce ripples on the surfaces of single-crystal sapphire. It was found that the ripple wavelength varies strongly with the angle of incidence of the ions, which increase significantly as the angle from normal is varied from 55° to 35°. A smooth region was found for ion incidence less than 35° away from normal incidence. In this region a strong smoothening mechanism with strength proportional to the second derivative of the height of the surface was found to be responsible for the effect. The discovery of this phase transition between stable and unstable regimes as the angle of incidence is varied has also stimulated new work by other groups in the field. (ii) Growth of Ge quantum dots on Si(100) and (111). We discovered the formation of quantum wires on 4° misoriented Si(111) using real-time GISAXS during the deposition of Ge. The results represent the first time-resolved GISAXS study of Ge quantum dot formation. (iii) Sputter deposition of amorphous thin films and multilayers composed of WSi2 and Si. Our in-situ GISAXS experiments reveal fundamental roughening and smoothing phenomena on surfaces during film deposition. The main results of this work is that the WSi2 layers actually become smoother during deposition due to the smoothening effect of energetic particles in the sputter deposition process.

  11. Receptor-binding sites: bioinformatic approaches.

    PubMed

    Flower, Darren R

    2006-01-01

    It is increasingly clear that both transient and long-lasting interactions between biomacromolecules and their molecular partners are the most fundamental of all biological mechanisms and lie at the conceptual heart of protein function. In particular, the protein-binding site is the most fascinating and important mechanistic arbiter of protein function. In this review, I examine the nature of protein-binding sites found in both ligand-binding receptors and substrate-binding enzymes. I highlight two important concepts underlying the identification and analysis of binding sites. The first is based on knowledge: when one knows the location of a binding site in one protein, one can "inherit" the site from one protein to another. The second approach involves the a priori prediction of a binding site from a sequence or a structure. The full and complete analysis of binding sites will necessarily involve the full range of informatic techniques ranging from sequence-based bioinformatic analysis through structural bioinformatics to computational chemistry and molecular physics. Integration of both diverse experimental and diverse theoretical approaches is thus a mandatory requirement in the evaluation of binding sites and the binding events that occur within them. PMID:16671408

  12. 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

  13. 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.

  14. 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.

  15. Exotic nuclei and nuclear forces

    NASA Astrophysics Data System (ADS)

    Otsuka, Takaharu

    2013-01-01

    I overview new aspects of the structure of exotic nuclei as compared to stable nuclei, focusing on several characteristic effects of nuclear forces. The shell structure of nuclei has been proposed by Mayer and Jensen, and has been considered to be kept valid basically for all nuclei, with well-known magic numbers, 2, 8, 20, 28, 50, …. Nuclear forces were shown, very recently, to change this paradigm. It will be presented that the evolution of shell structure occurs in various ways as more neutrons and/or protons are added, and I will present basic points of this shell evolution in terms of the monopole interaction of nuclear forces. I will discuss three types of nuclear forces. The first one is the tensor force. The tensor force is one of the most fundamental nuclear forces, but its first-order effect on the shell structure has been clarified only recently in studies on exotic nuclei. The tensor force can change the spin-orbit splitting depending on the occupation of specific orbits. This results in changes of the shell structure in many nuclei, and consequently some of Mayer-Jensen's magic numbers are lost and new ones emerge, in certain nuclei. This mechanism can be understood in an intuitive way, meaning that the effect is general and robust. The second type of nuclear forces is central force. I will show a general but unknown property of the central force in the shell-model Hamiltonian that can describe nuclear properties in a good agreement with experiment. I will then demonstrate how it can be incorporated into a simple model of the central force, and will discuss how this force works in the shell evolution. Actually, by combining this central force with the tensor force, one can understand and foresee how the same proton-neutron interaction drives the shell evolution, for examples such as Sn/Sb isotopes, N = 20 nuclei and Ni/Cu isotopes. The distribution of single-particle strength is discussed also in comparison to (e,e‧p) experiment on 48Ca. The shell

  16. 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.

  17. Molecular Self-Assembly Driven by London Dispersion Forces

    SciTech Connect

    Li, Guo; Cooper, Valentino R; Cho, Jun-Hyung; Du, Shixuan; Gao, Hongjun; Zhang, Zhenyu

    2011-01-01

    The nature and strength of intermolecular interactions are crucial to a variety of kinetic and dynamic processes at surfaces. Whereas strong chemisorption bonds are known to facilitate molecular binding, the importance of the weaker yet ubiquitous van der Waals (vdW) interactions remains elusive in most cases. Here we use first-principles calculations combined with kinetic Monte Carlo simulations to unambiguously demonstrate the vital role that vdW interactions play in molecular self-assembly, using styrene nanowire growth on silicon as a prototypical example. We find that, only when the London dispersion forces are included, accounting for the attractive parts of vdW interactions, can the effective intermolecular interaction be reversed from being repulsive to attractive. Such attractive interactions, in turn, ensure the preferred growth of long wires under physically realistic conditions as observed experimentally. We further propose a cooperative scheme, invoking the application of an electric field and the selective creation of Si dangling bonds, to drastically improve the ordered arrangement of the molecular structures. The present study represents a significant step forward in the fundamental understanding and precise control of molecular self-assembly guided by London dispersion forces.

  18. 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.

  19. 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.

  20. New Quasar Studies Keep Fundamental Physical Constant Constant

    NASA Astrophysics Data System (ADS)

    2004-03-01

    Very Large Telescope sets stringent limit on possible variation of the fine-structure constant over cosmological time Summary Detecting or constraining the possible time variations of fundamental physical constants is an important step toward a complete understanding of basic physics and hence the world in which we live. A step in which astrophysics proves most useful. Previous astronomical measurements of the fine structure constant - the dimensionless number that determines the strength of interactions between charged particles and electromagnetic fields - suggested that this particular constant is increasing very slightly with time. If confirmed, this would have very profound implications for our understanding of fundamental physics. New studies, conducted using the UVES spectrograph on Kueyen, one of the 8.2-m telescopes of ESO's Very Large Telescope array at Paranal (Chile), secured new data with unprecedented quality. These data, combined with a very careful analysis, have provided the strongest astronomical constraints to date on the possible variation of the fine structure constant. They show that, contrary to previous claims, no evidence exist for assuming a time variation of this fundamental constant. PR Photo 07/04: Relative Changes with Redshift of the Fine Structure Constant (VLT/UVES) A fine constant To explain the Universe and to represent it mathematically, scientists rely on so-called fundamental constants or fixed numbers. The fundamental laws of physics, as we presently understand them, depend on about 25 such constants. Well-known examples are the gravitational constant, which defines the strength of the force acting between two bodies, such as the Earth and the Moon, and the speed of light. One of these constants is the so-called "fine structure constant", alpha = 1/137.03599958, a combination of electrical charge of the electron, the Planck constant and the speed of light. The fine structure constant describes how electromagnetic forces hold

  1. Analyzing binding data.

    PubMed

    Motulsky, Harvey J; Neubig, Richard R

    2010-07-01

    Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments.

  2. 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

  3. 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.

  4. Investigating the Fundamental Theorem of Calculus

    ERIC Educational Resources Information Center

    Johnson, Heather L.

    2010-01-01

    The fundamental theorem of calculus, in its simplified complexity, connects differential and integral calculus. The power of the theorem comes not merely from recognizing it as a mathematical fact but from using it as a systematic tool. As a high school calculus teacher, the author developed and taught lessons on this fundamental theorem that were…

  5. Fundamentals of fossil simulator instructor training

    SciTech Connect

    Not Available

    1984-01-01

    This single-volume, looseleaf text introduces the beginning instructor to fundamental instructor training principles, and then shows how to apply those principles to fossil simulator training. Topics include the fundamentals of classroom instruction, the learning process, course development, and the specifics of simulator training program development.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  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. 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…

  13. 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.

  14. 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.

  15. Fundamental design concepts in multi-lane smart electromechanical actuators

    NASA Astrophysics Data System (ADS)

    Annaz, Fawaz Yahya

    2005-12-01

    The most fundamental concept in designing multi-lane smart electromechanical actuation systems, besides meeting performance requirements, is the realization of high integrity. The essential requirements for realizing high integrity (and in any safety-critical system) are hardware redundancy and intelligent monitoring. To correctly detect, identify, isolate and replace redundant components, an intelligent fault detection and fault isolation scheme is required. The effectiveness of any fault detection and fault isolation system is assessed by examining promptness of detection, sensitivity, missed fault detection, the rate of false alarms, and incorrect fault identification. These terms are very much dependent on the threshold values of the monitoring devices imbedded in the system. The main aim of this paper is to provide fundamental consolidation designs and monitoring schemes in different architectures. It will address single-type and two-type summing architectures and highlight feedback sensor integration and monitoring strategies in the former, and explore the suitability of different threshold setting methodologies such as a simulation-graphical based Monte Carlo method, decision theory and analysis of variance. The paper will also address other fundamentals that are essential at the design stage, such as control surface load estimation, force fight (between mismatch lanes) reduction through lane equalization, and threshold setting concepts (scheduled and unscheduled) in a multi-mode operation system. The analysis is based on a four-lane actuation system capable of driving aerodynamic and inertial loads (with two lanes failed) of an aileron control surface similar to that of the Sea Harrier.

  16. Molecular dynamics simulations of calcium binding in gramicidin A

    NASA Astrophysics Data System (ADS)

    Baştuğ, Turgut; Kuyucak, Serdar

    2006-06-01

    An important issue in molecular dynamics (MD) simulations of biomolecules is whether membrane proteins can be described using nonpolarizable force fields. To shed further light into this question, we study calcium ion binding and blocking of the gramicidin A channel which has not been investigated in MD simulations before. Potential of mean force calculations for calcium and potassium ions using a nonpolarizable force field reveal that calcium binding to the channel is much weaker compared to potassium, and hence calcium block of potassium current cannot be described. Inclusion of polarization interaction in force fields may help to rectify this problem.

  17. 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.

  18. 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.

  19. The estimation of affinity constants for the binding of model peptides to DNA by equilibrium dialysis.

    PubMed Central

    Standke, K C; Brunnert, H

    1975-01-01

    The binding of lysine model peptides of the type Lys-X-Lys, Lys-X-X-Lys and Lys-X-X-X-Lys (X = different aliphatic and aromatic amino acids) has been studied by equilibrium dialysis. It was shown that the strong electrostatic binding forces generated by protonated amino groups of lysine can be distinguished from the weak forces stemming from neutral and aromatic spacer amino acids. The overall binding strength of the lysine model peptides is modified by these weak binding forces and the apparent binding constants are influenced more by the hydrophobic character of the spacer amino acid side chains than by the chainlength of the spacers. PMID:1187347

  20. Analysis of affinities between specific biological ligands using atomic force microscopy.

    PubMed

    Hu, Xiao; Dinu, Cerasela Zoica

    2015-12-21

    In the cell, protein-ligand recognition involves association and dissociation processes controlled by the affinity of the two binding partners and chemical harvesting of adenosine triphosphate energy. Fundamental knowledge of selected recognition events is currently translated in a synthetic environment for biosensors, immunoassays and diagnosis applications, or for pharmaceutical development. However, in order to advance such fields, one needs to determine the lifetime and binding efficiency of the two partners, as well as the complex energy landscape parameters. We employed contact mode atomic force microscopy to evaluate the association and dissociation events between streptavidin protein and its anti-streptavidin antibody ligand currently used for nucleotide array, ELISA, and flow cytometry applications, just to name a few. Using biotin as the control, our analysis helped characterize and differentiate multi- or single bonds of different strengths as well as associated energy landscapes to determine the protein-ligand structural arrangement at nanointerfaces and how these depend on the specificity of the ligand-recognition reaction. Our results suggest that understanding the importance of the rupture forces between a protein and its ligand could serve as the first step to protect on-off switches for biomedical research applications where specificity and selectivity are foremost sought. PMID:26525901

  1. Feasibility of measuring antigen-antibody interaction forces using a scanning force microscope.

    PubMed

    Stuart, J K; Hlady, V

    1999-08-31

    The molecular affinity scanning force microscopy (MASFM) described in this study was developed in an effort to test the possibility of antigen-antibody binding measurement using force-separation distance profiles. The MASFM configuration was comprised of a spherical glass bead as an MASFM probe, to which the fluorescein antigen has been covalently attached, and a silicon dioxide-based substrate, to which the antifluorescyl IgG antibody was covalently bound. The bead was glued to the tip of a commercial SFM cantilever. Adhesion forces have been measured between two different specific antigen-antibody pairs and between nonspecific surfaces bearing only glycidoxypropylsilane immobilization chemistry. In force-separation (F-s) measurements, nonspecific forces displayed relatively few force discontinuities and mean adhesion forces lower than those found for specific antigen-antibody measurements. Force-separation profiles measured between specific antigen-antibody pairs showed many discontinuities and had higher mean forces. Positive controls revealed that the mean forces were slightly reduced by the addition of free ligand. The magnitude of mean forces did not correlate with the respective activation enthalpies of the proteins, as would be expected. At lower force values the force histograms for the specific pairs and for positive controls were indistinguishable. None of the force-separation data sets could fit a Poisson discrete-force model. This statistical analysis showed a large relative contribution from nonspecific interactions. It is concluded that the use of the large sphere as an SFM probe is counterproductive: while the large sphere does sample a larger number of specific interactions during each measurement, it also samples at the same time a large proportion of nonspecific forces. The presence of the nonspecific force contributions is likely due to the deformation of the polymerized GPS spacer layer which is thought to be delaminated from the surface upon

  2. Force-Mediated Kinetics of Single P-Selectin/Ligand Complexes Observed by Atomic Force Microscopy

    NASA Astrophysics Data System (ADS)

    Fritz, Jurgen; Katopodis, Andreas G.; Kolbinger, Frank; Anselmetti, Dario

    1998-10-01

    Leukocytes roll along the endothelium of postcapillary venules in response to inflammatory signals. Rolling under the hydrodynamic drag forces of blood flow is mediated by the interaction between selectins and their ligands across the leukocyte and endothelial cell surfaces. Here we present force-spectroscopy experiments on single complexes of P-selectin and P-selectin glycoprotein ligand-1 by atomic force microscopy to determine the intrinsic molecular properties of this dynamic adhesion process. By modeling intermolecular and intramolecular forces as well as the adhesion probability in atomic force microscopy experiments we gain information on rupture forces, elasticity, and kinetics of the P-selectin/P-selectin glycoprotein ligand-1 interaction. The complexes are able to withstand forces up to 165 pN and show a chain-like elasticity with a molecular spring constant of 5.3 pN nm-1 and a persistence length of 0.35 nm. The dissociation constant (off-rate) varies over three orders of magnitude from 0.02 s-1 under zero force up to 15 s-1 under external applied forces. Rupture force and lifetime of the complexes are not constant, but directly depend on the applied force per unit time, which is a product of the intrinsic molecular elasticity and the external pulling velocity. The high strength of binding combined with force-dependent rate constants and high molecular elasticity are tailored to support physiological leukocyte rolling.

  3. A second Las17 monomeric actin-binding motif functions in Arp2/3-dependent actin polymerization during endocytosis.

    PubMed

    Feliciano, Daniel; Tolsma, Thomas O; Farrell, Kristen B; Aradi, Al; Di Pietro, Santiago M

    2015-04-01

    During clathrin-mediated endocytosis (CME), actin assembly provides force to drive vesicle internalization. Members of the Wiskott-Aldrich syndrome protein (WASP) family play a fundamental role stimulating actin assembly. WASP family proteins contain a WH2 motif that binds globular actin (G-actin) and a central-acidic motif that binds the Arp2/3 complex, thus promoting the formation of branched actin filaments. Yeast WASP (Las17) is the strongest of five factors promoting Arp2/3-dependent actin polymerization during CME. It was suggested that this strong activity may be caused by a putative second G-actin-binding motif in Las17. Here, we describe the in vitro and in vivo characterization of such Las17 G-actin-binding motif (LGM) and its dependence on a group of conserved arginine residues. Using the yeast two-hybrid system, GST-pulldown, fluorescence polarization and pyrene-actin polymerization assays, we show that LGM binds G-actin and is necessary for normal Arp2/3-mediated actin polymerization in vitro. Live-cell fluorescence microscopy experiments demonstrate that LGM is required for normal dynamics of actin polymerization during CME. Further, LGM is necessary for normal dynamics of endocytic machinery components that are recruited at early, intermediate and late stages of endocytosis, as well as for optimal endocytosis of native CME cargo. Both in vitro and in vivo experiments show that LGM has relatively lower potency compared to the previously known Las17 G-actin-binding motif, WH2. These results establish a second G-actin-binding motif in Las17 and advance our knowledge on the mechanism of actin assembly during CME.

  4. The swim force as a body force

    NASA Astrophysics Data System (ADS)

    Yan, Wen; Brady, John

    2015-11-01

    Net (as opposed to random) motion of active matter results from an average swim (or propulsive) force. It is shown that the average swim force acts like a body force - an internal body force [Yan and Brady, Soft Matter, DOI:10.1039/C5SM01318F]. As a result, the particle-pressure exerted on a container wall is the sum of the swim pressure [Takatori et al., Phys. Rev. Lett., 2014, 113, 028103] and the `weight' of the active particles. A continuum mechanical description is possible when variations occur on scales larger than the run length of the active particles and gives a Boltzmann-like distribution from a balance of the swim force and the swim pressure. Active particles may also display `action at a distance' and accumulate adjacent to (or be depleted from) a boundary without any external forces. In the momentum balance for the suspension - the mixture of active particles plus fluid - only external body forces appear.

  5. Bonds that strengthen under force

    NASA Astrophysics Data System (ADS)

    Vogel, Viola

    2006-03-01

    While the adhesive strength of most receptor-ligand interactions is exponentially reduced if strained, some receptor-ligand complexes exist that strengthen under force which is the hallmark of catch bonds. Although the existence of catch bonds was theoretically predicted, the first experimental demonstrations of their existence were given only recently, i.e. for the bacterial adhesin FimH that is located at the tip of type I fimbriae of E. coli and for p-selectin. In a major collaborative effort, we studied the structural origin by which the FimH-mannose bond is switched by force to a high binding state. Mutational studies were thereby combined with steered molecular dynamic simulations to decipher how force might affect protein conformation. Force-activation of FimH leads to a complex `stick-and-roll' bacterial adhesion behavior in which E. coli preferentially rolls over mannosylated surfaces at low shear but increasingly sticks firmly as the shear is increased. Interesting similarities are further seen if comparing the structural mechanisms by which liganded FimH and liganded integrins are switched to a high binding state. This comparison was made possible by docking fibronectin's 10^th type III module (fnIII10) to αVβ3 integrin. αVβ3 can switch from the ``closed'' αVβ3 integrin headpiece to the ``open'' conformation by opening the hinge angle between the βA domain and the hybrid domain of the β-integrin. The ``open'' state has been implicated by many experimental laboratories to correspond to the activated state of integrins. W. E. Thomas, E. Trintchina, M. Forero, V. Vogel, E. Sokurenko, Bacterial adhesion to target cells enhanced by shear-force, Cell, 109 (2002) 913. W. E. Thomas, L. M. Nilsson, M. Forero, E. V. Sokurenko, V. Vogel, Shear-dependent `stick-and-roll' adhesion of type 1 fimbriated Escherichia coli, Molecular Microbiology 53 (2004) 1545. W. Thomas, M. Forero, O. Yakovenko, L. Nilsson, P. Vicini, E. Sokurenko, V. Vogel, Catch Bond Model

  6. Carbohydrate-binding modules from a thermostable Rhodothermus marinus xylanase: cloning, expression and binding studies.

    PubMed Central

    Abou Hachem, M; Nordberg Karlsson, E; Bartonek-Roxâ, E; Raghothama, S; Simpson, P J; Gilbert, H J; Williamson, M P; Holst, O

    2000-01-01

    The two N-terminally repeated carbohydrate-binding modules (CBM4-1 and CBM4-2) encoded by xyn10A from Rhodothermus marinus were produced in Escherichia coli and purified by affinity chromatography. Binding assays to insoluble polysaccharides showed binding to insoluble xylan and to phosphoric-acid-swollen cellulose but not to Avicel or crystalline cellulose. Binding to insoluble substrates was significantly enhanced by the presence of Na(+) and Ca(2+) ions. The binding affinities for soluble polysaccharides were tested by affinity electrophoresis; strong binding occurred with different xylans and beta-glucan. CBM4-2 displayed a somewhat higher binding affinity than CBM4-1 for both soluble and insoluble substrates but both had similar specificities. Binding to short oligosaccharides was measured by NMR; both modules bound with similar affinities. The binding of the modules was shown to be dominated by enthalpic forces. The binding modules did not contribute with any significant synergistic effects on xylan hydrolysis when incubated with a Xyn10A catalytic module. This is the first report of family 4 CBMs with affinity for both insoluble xylan and amorphous cellulose. PMID:10600638

  7. Heterogeneity and Specificity of Nanoscale Adhesion Forces Measured between Self-Assembled Monolayers and Lignocellulosic Substrates: A Chemical Force Microscopy Study.

    PubMed

    Arslan, Baran; Ju, Xiaohui; Zhang, Xiao; Abu-Lail, Nehal I

    2015-09-22

    Lack of fundamental understanding of cellulase interactions with different plant cell wall components during cellulose saccharification hinders progress toward achieving an economic production of biofuels from renewable plant biomass. Here, chemical force microscopy (CFM) was utilized to quantify the interactions between two surfaces that model either hydrophilic or hydrophobic functional groups of cellulases and a set of lignocellulosic substrates prepared through Kraft, sulfite, or organosolv pulping with defined chemical composition. The measured forces were then decoupled into specific and nonspecific components using the Poisson statistical approach. Heterogeneities in the distributions of forces as a function of the pretreatment method were mapped. Our results showed that hydrophobic domains and chemical moieties involved in hydrogen bonding and polar interactions were homogeneously distributed on all substrates but with distribution densities that varied with the type of the pretreatment method used to prepare substrates. In addition, we showed that increasing surface lignin coverage increased the heterogeneity of the substrates. When forces were decoupled, our results indicated that xylan reduced the strength of hydrogen bonding between the hydrophilic model surface and substrates. Permanent dipole-dipole interactions dominated the adhesion of the hydrophilic model surface to lignosulfonates, whereas hydrophobic interactions facilitated the adhesion of the hydrophobic model surface to Kraft lignin. We further showed that the structure of lignin determines the type of forces that dominate lignocellulosic interactions with other surfaces. Our findings suggest that nonproductive binding of cellulases to lignocellulosic biomass can be reduced by altering the hydrophobicity and/or chemical moieties involved in the polar interactions and by utilizing organosolv as a pretreatment method. PMID:26339982

  8. Heterogeneity and Specificity of Nanoscale Adhesion Forces Measured between Self-Assembled Monolayers and Lignocellulosic Substrates: A Chemical Force Microscopy Study.

    PubMed

    Arslan, Baran; Ju, Xiaohui; Zhang, Xiao; Abu-Lail, Nehal I

    2015-09-22

    Lack of fundamental understanding of cellulase interactions with different plant cell wall components during cellulose saccharification hinders progress toward achieving an economic production of biofuels from renewable plant biomass. Here, chemical force microscopy (CFM) was utilized to quantify the interactions between two surfaces that model either hydrophilic or hydrophobic functional groups of cellulases and a set of lignocellulosic substrates prepared through Kraft, sulfite, or organosolv pulping with defined chemical composition. The measured forces were then decoupled into specific and nonspecific components using the Poisson statistical approach. Heterogeneities in the distributions of forces as a function of the pretreatment method were mapped. Our results showed that hydrophobic domains and chemical moieties involved in hydrogen bonding and polar interactions were homogeneously distributed on all substrates but with distribution densities that varied with the type of the pretreatment method used to prepare substrates. In addition, we showed that increasing surface lignin coverage increased the heterogeneity of the substrates. When forces were decoupled, our results indicated that xylan reduced the strength of hydrogen bonding between the hydrophilic model surface and substrates. Permanent dipole-dipole interactions dominated the adhesion of the hydrophilic model surface to lignosulfonates, whereas hydrophobic interactions facilitated the adhesion of the hydrophobic model surface to Kraft lignin. We further showed that the structure of lignin determines the type of forces that dominate lignocellulosic interactions with other surfaces. Our findings suggest that nonproductive binding of cellulases to lignocellulosic biomass can be reduced by altering the hydrophobicity and/or chemical moieties involved in the polar interactions and by utilizing organosolv as a pretreatment method.

  9. 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.

  10. Fuzzy logic algorithm to extract specific interaction forces from atomic force microscopy data

    NASA Astrophysics Data System (ADS)

    Kasas, Sandor; Riederer, Beat M.; Catsicas, Stefan; Cappella, Brunero; Dietler, Giovanni

    2000-05-01

    The atomic force microscope is not only a very convenient tool for studying the topography of different samples, but it can also be used to measure specific binding forces between molecules. For this purpose, one type of molecule is attached to the tip and the other one to the substrate. Approaching the tip to the substrate allows the molecules to bind together. Retracting the tip breaks the newly formed bond. The rupture of a specific bond appears in the force-distance curves as a spike from which the binding force can be deduced. In this article we present an algorithm to automatically process force-distance curves in order to obtain bond strength histograms. The algorithm is based on a fuzzy logic approach that permits an evaluation of "quality" for every event and makes the detection procedure much faster compared to a manual selection. In this article, the software has been applied to measure the binding strength between tubuline and microtubuline associated proteins.

  11. Calcium binding characteristics and structural changes of phosvitin.

    PubMed

    Zhang, Xiaowei; Geng, Fang; Huang, Xi; Ma, Meihu

    2016-06-01

    Phosvitin is a unique highly phosphorylated protein that plays a role in the regulation of calcification. We conducted a comprehensive study of the chemical, thermodynamic and structural aspects of the interaction of phosvitin with calcium ions using a calcium ion selective electrode (ISE), isothermal titration calorimetry (ITC), circular dichroism spectrum (CD) and fluorescence spectroscopy, respectively. The results showed that under neutral and alkaline conditions, distinct high affinity and low affinity binding modes existed in the interaction between phosvitin and calcium. The high affinity association constant was approximately 10(4)mol(-1), while the binding sites contained nearly 30mol of calcium per mole of phosvitin. This reaction was driven by enthalpy. The unordered and β-turn conformations of phosvitin increased, while the β-sheet conformation decreased. The main interaction forces were electrostatic force, hydrogen bonds or van der Waals force. The low affinity association constant and binding sites were not constant, as many calcium ions were sequestered by phosvitin. The binding reaction was driven by entropy, and the β-sheet conformation of phosvitin increased while the unordered conformation decreased. The main interaction force was hydrophobic force. However, under acidic conditions, the interaction between phosvitin and calcium was an entropy-driven endothermic reaction, and the main interaction force was weak hydrophobic force. This calcium-binding characteristic of phosvitin may play a specific role in its biological function. PMID:26953964

  12. Molecular Mechanotransduction: how forces trigger cytoskeletal dynamics

    NASA Astrophysics Data System (ADS)

    Ehrlicher, Allen

    2012-02-01

    Mechanical stresses elicit cellular reactions mediated by chemical signals. Defective responses to forces underlie human medical disorders, such as cardiac failure and pulmonary injury. Despite detailed knowledge of the cytoskeleton's structure, the specific molecular switches that convert mechanical stimuli into chemical signals have remained elusive. Here we identify the actin-binding protein, filamin A (FLNa) as a central mechanotransduction element of the cytoskeleton by using Fluorescence Loss After photoConversion (FLAC), a novel high-speed alternative to FRAP. We reconstituted a minimal system consisting of actin filaments, FLNa and two FLNa-binding partners: the cytoplasmic tail of ß-integrin, and FilGAP. Integrins form an essential mechanical linkage between extracellular and intracellular environments, with ß integrin tails connecting to the actin cytoskeleton by binding directly to filamin. FilGAP is a FLNa-binding GTPase-activating protein specific for Rac, which in vivo regulates cell spreading and bleb formation. We demonstrate that both externally-imposed bulk shear and myosin II driven forces differentially regulate the binding of integrin and FilGAP to FLNa. Consistent with structural predictions, strain increases ß-integrin binding to FLNa, whereas it causes FilGAP to dissociate from FLNa, providing a direct and specific molecular basis for cellular mechanotransduction. These results identify the first molecular mechanotransduction element within the actin cytoskeleton, revealing that mechanical strain of key proteins regulates the binding of signaling molecules. Moreover, GAP activity has been shown to switch cell movement from mesenchymal to amoeboid motility, suggesting that mechanical forces directly impact the invasiveness of cancer.

  13. Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive.

    PubMed

    Beauchamp, Kyle A; Behr, Julie M; Rustenburg, Ariën S; Bayly, Christopher I; Kroenlein, Kenneth; Chodera, John D

    2015-10-01

    Atomistic molecular simulations are a powerful way to make quantitative predictions, but the accuracy of these predictions depends entirely on the quality of the force field employed. Although experimental measurements of fundamental physical properties offer a straightforward approach for evaluating force field quality, the bulk of this information has been tied up in formats that are not machine-readable. Compiling benchmark data sets of physical properties from non-machine-readable sources requires substantial human effort and is prone to the accumulation of human errors, hindering the development of reproducible benchmarks of force-field accuracy. Here, we examine the feasibility of benchmarking atomistic force fields against the NIST ThermoML data archive of physicochemical measurements, which aggregates thousands of experimental measurements in a portable, machine-readable, self-annotating IUPAC-standard format. As a proof of concept, we present a detailed benchmark of the generalized Amber small-molecule force field (GAFF) using the AM1-BCC charge model against experimental measurements (specifically, bulk liquid densities and static dielectric constants at ambient pressure) automatically extracted from the archive and discuss the extent of data available for use in larger scale (or continuously performed) benchmarks. The results of even this limited initial benchmark highlight a general problem with fixed-charge force fields in the representation low-dielectric environments, such as those seen in binding cavities or biological membranes.

  14. Periodicity in bimodal atomic force microscopy

    SciTech Connect

    Lai, Chia-Yun; Santos, Sergio Chiesa, Matteo; Barcons, Victor

    2015-07-28

    Periodicity is fundamental for quantification and the application of conservation principles of many important systems. Here, we discuss periodicity in the context of bimodal atomic force microscopy (AFM). The relationship between the excited frequencies is shown to affect and control both experimental observables and the main expressions quantified via these observables, i.e., virial and energy transfer expressions, which form the basis of the bimodal AFM theory. The presence of a fundamental frequency further simplifies the theory and leads to close form solutions. Predictions are verified via numerical integration of the equation of motion and experimentally on a mica surface.

  15. Recent Progress in Molecular Recognition Imaging Using Atomic Force Microscopy.

    PubMed

    Senapati, Subhadip; Lindsay, Stuart

    2016-03-15

    Atomic force microscopy (AFM) is an extremely powerful tool in the field of bionanotechnology because of its ability to image single molecules and make measurements of molecular interaction forces with piconewton sensitivity. It works in aqueous media, enabling studies of molecular phenomenon taking place under physiological conditions. Samples can be imaged in their near-native state without any further modifications such as staining or tagging. The combination of AFM imaging with the force measurement added a new feature to the AFM technique, that is, molecular recognition imaging. Molecular recognition imaging enables mapping of specific interactions between two molecules (one attached to the AFM tip and the other to the imaging substrate) by generating simultaneous topography and recognition images (TREC). Since its discovery, the recognition imaging technique has been successfully applied to different systems such as antibody-protein, aptamer-protein, peptide-protein, chromatin, antigen-antibody, cells, and so forth. Because the technique is based on specific binding between the ligand and receptor, it has the ability to detect a particular protein in a mixture of proteins or monitor a biological phenomenon in the native physiological state. One key step for recognition imaging technique is the functionalization of the AFM tips (generally, silicon, silicon nitrides, gold, etc.). Several different functionalization methods have been reported in the literature depending on the molecules of interest and the material of the tip. Polyethylene glycol is routinely used to provide flexibility needed for proper binding as a part of the linker that carries the affinity molecule. Recently, a heterofunctional triarm linker has been synthesized and successfully attached with two different affinity molecules. This novel linker, when attached to AFM tip, helped to detect two different proteins simultaneously from a mixture of proteins using a so-called "two

  16. Nanonet Force Microscopy for Measuring Cell Forces.

    PubMed

    Sheets, Kevin; Wang, Ji; Zhao, Wei; Kapania, Rakesh; Nain, Amrinder S

    2016-07-12

    The influence of physical forces exerted by or felt by cells on cell shape, migration, and cytoskeleton arrangement is now widely acknowledged and hypothesized to occur due to modulation of cellular inside-out forces in response to changes in the external fibrous environment (outside-in). Our previous work using the non-electrospinning Spinneret-based Tunable Engineered Parameters' suspended fibers has revealed that cells are able to sense and respond to changes in fiber curvature and structural stiffness as evidenced by alterations to focal adhesion cluster lengths. Here, we present the development and application of a suspended nanonet platform for measuring C2C12 mouse myoblast forces attached to fibers of three diameters (250, 400, and 800 nm) representing a wide range of structural stiffness (3-50 nN/μm). The nanonet force microscopy platform measures cell adhesion forces in response to symmetric and asymmetric external perturbation in single and cyclic modes. We find that contractility-based, inside-out forces are evenly distributed at the edges of the cell, and that forces are dependent on fiber structural stiffness. Additionally, external perturbation in symmetric and asymmetric modes biases cell-fiber failure location without affecting the outside-in forces of cell-fiber adhesion. We then extend the platform to measure forces of (1) cell-cell junctions, (2) single cells undergoing cyclic perturbation in the presence of drugs, and (3) cancerous single-cells transitioning from a blebbing to a pseudopodial morphology. PMID:27410747

  17. 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. PMID:27022923

  18. 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.

  19. 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.

  20. Nucleosynthesis and the variation of fundamental couplings

    SciTech Connect

    Mueller, Christian M.; Schaefer, Gregor; Wetterich, Christof

    2004-10-15

    We determine the influence of a variation of the fundamental 'constants' on the predicted helium abundance in Big Bang Nucleosynthesis. The analytic estimate is performed in two parts: the first step determines the dependence of the helium abundance on the nuclear physics parameters, while the second step relates those parameters to the fundamental couplings of particle physics. This procedure can incorporate in a flexible way the time variation of several couplings within a grand unified theory while keeping the nuclear physics computation separate from any GUT model dependence.

  1. 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.

  2. Fundamental ethical principles in health care.

    PubMed

    Thompson, I E

    1987-12-01

    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.

  3. Fundamentals of Pharmacogenetics in Personalized, Precision Medicine.

    PubMed

    Valdes, Roland; Yin, DeLu Tyler

    2016-09-01

    This article introduces fundamental principles of pharmacogenetics as applied to personalized and precision medicine. Pharmacogenetics establishes relationships between pharmacology and genetics by connecting phenotypes and genotypes in predicting the response of therapeutics in individual patients. We describe differences between precision and personalized medicine and relate principles of pharmacokinetics and pharmacodynamics to applications in laboratory medicine. We also review basic principles of pharmacogenetics, including its evolution, how it enables the practice of personalized therapeutics, and the role of the clinical laboratory. These fundamentals are a segue for understanding specific clinical applications of pharmacogenetics described in subsequent articles in this issue.

  4. 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.

  5. Dark Energy: A Crisis for Fundamental Physics

    SciTech Connect

    Stubbs, Christopher

    2010-04-12

    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.

  6. 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.

  7. Fundamentals of Pharmacogenetics in Personalized, Precision Medicine.

    PubMed

    Valdes, Roland; Yin, DeLu Tyler

    2016-09-01

    This article introduces fundamental principles of pharmacogenetics as applied to personalized and precision medicine. Pharmacogenetics establishes relationships between pharmacology and genetics by connecting phenotypes and genotypes in predicting the response of therapeutics in individual patients. We describe differences between precision and personalized medicine and relate principles of pharmacokinetics and pharmacodynamics to applications in laboratory medicine. We also review basic principles of pharmacogenetics, including its evolution, how it enables the practice of personalized therapeutics, and the role of the clinical laboratory. These fundamentals are a segue for understanding specific clinical applications of pharmacogenetics described in subsequent articles in this issue. PMID:27514461

  8. 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.

  9. Charles Augustin Coulomb and the fundamental law of electrostatics

    NASA Astrophysics Data System (ADS)

    Falconer, Isobel

    2004-10-01

    In his famous experiment on the inverse square law of electrostatics, Coulomb neither defined electric charge nor gave reliable measurements of the force-distance relation. Yet the experiment has often been viewed as the basis of the fundamental law of electrostatics. This paper discusses Coulomb's life, showing the context within which he was working, how he arrived at the experiment, and the use he made of it. Physics in France in the late 18th century was undergoing a transformation from a science of holistic observation and explanations to one of universal laws and exact measurement. Coulomb was both a subject of, and an important contributor to, this change, and these two aspects are evident in his approach to the experiment and to the later uptake of his results. The reaction in the rest of Europe was initially less favourable, and the ultimate fame of Coulomb's experiment was dependent on the triumph of French mathematical physics in the 19th century.

  10. Confocal reference free traction force microscopy

    PubMed Central

    Bergert, Martin; Lendenmann, Tobias; Zündel, Manuel; Ehret, Alexander E.; Panozzo, Daniele; Richner, Patrizia; Kim, David K.; Kress, Stephan J. P.; Norris, David J.; Sorkine-Hornung, Olga; Mazza, Edoardo; Poulikakos, Dimos; Ferrari, Aldo

    2016-01-01

    The mechanical wiring between cells and their surroundings is fundamental to the regulation of complex biological processes during tissue development, repair or pathology. Traction force microscopy (TFM) enables determination of the actuating forces. Despite progress, important limitations with intrusion effects in low resolution 2D pillar-based methods or disruptive intermediate steps of cell removal and substrate relaxation in high-resolution continuum TFM methods need to be overcome. Here we introduce a novel method allowing a one-shot (live) acquisition of continuous in- and out-of-plane traction fields with high sensitivity. The method is based on electrohydrodynamic nanodrip-printing of quantum dots into confocal monocrystalline arrays, rendering individually identifiable point light sources on compliant substrates. We demonstrate the undisrupted reference-free acquisition and quantification of high-resolution continuous force fields, and the simultaneous capability of this method to correlatively overlap traction forces with spatial localization of proteins revealed using immunofluorescence methods. PMID:27681958

  11. Photoelectron Spectroscopy and Theoretical Studies of Anion-pi Interactions: Binding Strength and Anion Specificity

    SciTech Connect

    Zhang, Jian; Zhou, Bin; Sun, Zhenrong; Wang, Xue B.

    2015-01-01

    Proposed in theory and confirmed to exist, anion–π interactions have been recognized as new and important non-covalent binding forces. Despite extensive theoretical studies, numerous crystal structural identifications, and a plethora of solution phase investigations, intrinsic anion–π interaction strengths that are free from complications of condensed phases’ environments, have not been directly measured in the gas phase. Herein we present a joint photoelectron spectroscopic and theoretical study on this subject, in which tetraoxacalix[2]arene[2]triazine 1, an electron-deficient and cavity self-tunable macrocyclic was used as a charge-neutral molecular host to probe its interactions with a series of anions with distinctly different shapes and charge states (spherical halides Cl⁻, Br⁻, I⁻, linear thiocyanate SCN⁻, trigonal planar nitrate NO₃⁻, pyramidic iodate IO₃⁻, and tetrahedral sulfate SO₄²⁻). The binding energies of the resultant gaseous 1:1 complexes (1•Cl⁻,1•Br⁻, 1•I⁻, 1•SCN⁻, 1•NO₃⁻, 1•IO₃⁻ and 1•SO₄²⁻) were directly measured experimentally, exhibiting substantial non-covalent interactions with pronounced anion specific effects. The binding strengths of Cl⁻, NO₃⁻, IO₃⁻ with 1 are found to be strongest among all singly charged anions, amounting to ca. 30 kcal/mol, but only about 40% of that between 1 and SO₄²⁻. Quantum chemical calculations reveal that all anions reside in the center of the cavity of 1 with anion–π binding motif in the complexes’ optimized structures, where 1 is seen to be able to self-regulate its cavity structure to accommodate anions of different geometries and three-dimensional shapes. Electron density surface and natural bond orbital charge distribution analysis further support anion–π binding formation. The calculated binding energies of the anions and 1 nicely reproduce the experimentally estimated electron binding energy increase. This work

  12. Extreme impact and cavitation forces of a biological hammer: strike forces of the peacock mantis shrimp Odontodactylus scyllarus.

    PubMed

    Patek, S N; Caldwell, R L

    2005-10-01

    Mantis shrimp are renowned for their unusual method of breaking shells with brief, powerful strikes of their raptorial appendages. Due to the extreme speeds of these strikes underwater, cavitation occurs between their appendages and hard-shelled prey. Here we examine the magnitude and relative contribution of the impact and cavitation forces generated by the peacock mantis shrimp Odontodactylus scyllarus. We present the surprising finding that each strike generates two brief, high-amplitude force peaks, typically 390-480 micros apart. Based on high-speed imaging, force measurements and acoustic analyses, it is evident that the first force peak is caused by the limb's impact and the second force peak is due to the collapse of cavitation bubbles. Peak limb impact forces range from 400 to 1501 N and peak cavitation forces reach 504 N. Despite their small size, O. scyllarus can generate impact forces thousands of times their body weight. Furthermore, on average, cavitation peak forces are 50% of the limb's impact force, although cavitation forces may exceed the limb impact forces by up to 280%. The rapid succession of high peak forces used by mantis shrimp suggests that mantis shrimp use a potent combination of cavitation forces and extraordinarily high impact forces to fracture shells. The stomatopod's hammer is fundamentally different from typical shell-crushing mechanisms such as fish jaws and lobster claws, and may have played an important and as yet unexamined role in the evolution of shell form. PMID:16169943

  13. 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 of single…

  14. Getting a Better Grasp on Flu Fundamentals

    MedlinePlus

    ... a Better Grasp on Flu Fundamentals Inside Life Science View All Articles | Inside Life Science Home Page Getting a Better Grasp on Flu ... Seasonal Flu Patterns? Forecasting Flu This Inside Life Science article also appears on LiveScience . Learn about related ...

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. The Case for Fundamentals of Oral Communication

    ERIC Educational Resources Information Center

    Emanuel, Richard

    2005-01-01

    Dozens of studies support the fact that communication skills are essential for success in a number of areas. After citing a sampling of these studies, a survey of the communication course offerings in Alabama's 2-year-college system reveals that most students are required to take only one communication course-either Fundamentals of Oral…

  20. Measurement and Fundamental Processes in Quantum Mechanics

    NASA Astrophysics Data System (ADS)

    Jaeger, Gregg

    2015-07-01

    In the standard mathematical formulation of quantum mechanics, measurement is an additional, exceptional fundamental process rather than an often complex, but ordinary process which happens also to serve a particular epistemic function: during a measurement of one of its properties which is not already determined by a preceding measurement, a measured system, even if closed, is taken to change its state discontinuously rather than continuously as is usual. Many, including Bell, have been concerned about the fundamental role thus given to measurement in the foundation of the theory. Others, including the early Bohr and Schwinger, have suggested that quantum mechanics naturally incorporates the unavoidable uncontrollable disturbance of physical state that accompanies any local measurement without the need for an exceptional fundamental process or a special measurement theory. Disturbance is unanalyzable for Bohr, but for Schwinger it is due to physical interactions' being borne by fundamental particles having discrete properties and behavior which is beyond physical control. Here, Schwinger's approach is distinguished from more well known treatments of measurement, with the conclusion that, unlike most, it does not suffer under Bell's critique of quantum measurement. Finally, Schwinger's critique of measurement theory is explicated as a call for a deeper investigation of measurement processes that requires the use of a theory of quantum fields.

  1. 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;…

  2. 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…

  3. 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…

  4. A Fundamental Breakdown. Part II: Manipulative Skills

    ERIC Educational Resources Information Center

    Townsend, J. Scott; Mohr, Derek J.

    2005-01-01

    In the May, 2005, issue of "TEPE," the "Research to Practice" section initiated a two-part series focused on assessing fundamental locomotor and manipulative skills. The series was generated in response to research by Pappa, Evanggelinou, & Karabourniotis (2005), recommending that curricular programming in physical education at the elementary…

  5. 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.

  6. 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)

  7. 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)

  8. 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).

  9. 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.

  10. 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,…

  11. Why quarks cannot be fundamental particles

    NASA Astrophysics Data System (ADS)

    Kalman, C. S.

    2005-05-01

    Many reasons why quarks should be considered composite particles are found in the book Preons by D'Souza and Kalman. One reason not found in the book is that all the quarks except for the u quark decay. The electron and the electron neutrino do not decay. A model of fundamental particles based upon the weak charge is presented.

  12. 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…

  13. 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…

  14. Reversing: A Fundamental Idea in Computer Science

    ERIC Educational Resources Information Center

    Armoni, Michal; Ginat, David

    2008-01-01

    Reversing is the notion of thinking or working in reverse. Computer science textbooks and tutors recognize it primarily in the form of recursion. However, recursion is only one form of reversing. Reversing appears in the computer science curriculum in many other forms, at various intellectual levels, in a variety of fundamental courses. As such,…

  15. 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…

  16. Time-resolved force distribution analysis

    PubMed Central

    2013-01-01

    Background Biomolecules or other complex macromolecules undergo conformational transitions upon exposure to an external perturbation such as ligand binding or mechanical force. To follow fluctuations in pairwise forces between atoms or residues during such conformational changes as observed in Molecular Dynamics (MD) simulations, we developed Time-Resolved Force Distribution Analysis (TRFDA). Results The implementation focuses on computational efficiency and low-memory usage and, along with the wide range of output options, makes possible time series analysis of pairwise forces variation in long MD simulations and for large molecular systems. It also provides an exact decomposition of pairwise forces resulting from 3- and 4-body potentials and a unified treatment of pairwise forces between atoms or residues. As a proof of concept, we present a stress analysis during unfolding of ubiquitin in a force-clamp MD simulation. Conclusions TRFDA can be used, among others, in tracking signal propagation at atomic level, for characterizing dynamical intermolecular interactions (e.g. protein-ligand during flexible docking), in development of force fields and for following stress distribution during conformational changes. PMID:24499624

  17. Universal spin-momentum locked optical forces

    NASA Astrophysics Data System (ADS)

    Kalhor, Farid; Thundat, Thomas; Jacob, Zubin

    2016-02-01

    Evanescent electromagnetic waves possess spin-momentum locking, where the direction of propagation (momentum) is locked to the inherent polarization of the wave (transverse spin). We study the optical forces arising from this universal phenomenon and show that the fundamental origin of recently reported non-trivial optical chiral forces is spin-momentum locking. For evanescent waves, we show that the direction of energy flow, the direction of decay, and the direction of spin follow a right hand rule for three different cases of total internal reflection, surface plasmon polaritons, and HE11 mode of an optical fiber. Furthermore, we explain how the recently reported phenomena of lateral optical force on chiral and achiral particles are caused by the transverse spin of the evanescent field and the spin-momentum locking phenomenon. Finally, we propose an experiment to identify the unique lateral forces arising from the transverse spin in the optical fiber and point to fundamental differences of the spin density from the well-known orbital angular momentum of light. Our work presents a unified view on spin-momentum locking and how it affects optical forces on chiral and achiral particles.

  18. Analyzing radioligand binding data.

    PubMed

    Motulsky, Harvey; Neubig, Richard

    2002-08-01

    Radioligand binding experiments are easy to perform, and provide useful data in many fields. They can be used to study receptor regulation, discover new drugs by screening for compounds that compete with high affinity for radioligand binding to a particular receptor, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling, via measurements of agonist binding and its regulation by ions, nucleotides, and other allosteric modulators. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  19. Influenza virus binds its host cell using multiple dynamic interactions

    PubMed Central

    Sieben, Christian; Kappel, Christian; Zhu, Rong; Wozniak, Anna; Rankl, Christian; Hinterdorfer, Peter; Grubmüller, Helmut; Herrmann, Andreas

    2012-01-01

    Influenza virus belongs to a wide range of enveloped viruses. The major spike protein hemagglutinin binds sialic acid residues of glycoproteins and glycolipids with dissociation constants in the millimolar range [Sauter NK, et al. (1992) Biochemistry 31:9609–9621], indicating a multivalent binding mode. Here, we characterized the attachment of influenza virus to host cell receptors using three independent approaches. Optical tweezers and atomic force microscopy-based single-molecule force spectroscopy revealed very low interaction forces. Further, the observation of sequential unbinding events strongly suggests a multivalent binding mode between virus and cell membrane. Molecular dynamics simulations reveal a variety of unbinding pathways that indicate a highly dynamic interaction between HA and its receptor, allowing rationalization of influenza virus–cell binding quantitatively at the molecular level. PMID:22869709

  20. Genome-wide transcription factor binding: beyond direct target regulation.

    PubMed

    MacQuarrie, Kyle L; Fong, Abraham P; Morse, Randall H; Tapscott, Stephen J

    2011-04-01

    The binding of transcription factors to specific DNA target sequences is the fundamental basis of gene regulatory networks. Chromatin immunoprecipitation combined with DNA tiling arrays or high-throughput sequencing (ChIP-chip and ChIP-seq, respectively) has been used in many recent studies that detail the binding sites of various transcription factors. Surprisingly, data from a variety of model organisms and tissues have demonstrated that transcription factors vary greatly in their number of genomic binding sites, and that binding events can significantly exceed the number of known or possible direct gene targets. Thus, current understanding of transcription factor function must expand to encompass what role, if any, binding might have outside of direct transcriptional target regulation. In this review, we discuss the biological significance of genome-wide binding of transcription factors and present models that can account for this phenomenon.

  1. Electron binding energies using perturbative delta-SCF method

    NASA Astrophysics Data System (ADS)

    Bhusal, Shusil; Baruah, Tunna; Zope, Rajendra

    The knowledge of fundamental and optical gaps is of significant importance for organic photovoltaics. The electron binding energies estimated from the Kohn-Sham eigenvalues are significantly underestimated. Here, we use our recently outlined perturbative delta-SCF approach to compute the electron binding energies of a number of aromatic organic molecules commonly used in organic photovoltaics. Further, the electron affinities are also computed for the C60, C70 and PCBM. The results show that the perturbative delta-SCF provide adequate description of valence electron binding energies. We also applied the method to compute the core binding energies and the core-valence excited states. While the method can successfully predict the core-valence excited states the results on the core-binding energies are mixed. The strategies for improvement of the core binding energies will be discussed.

  2. Biomolecular interactions measured by atomic force microscopy.

    PubMed

    Willemsen, O H; Snel, M M; Cambi, A; Greve, J; De Grooth, B G; Figdor, C G

    2000-12-01

    Atomic force microscopy (AFM) is nowadays frequently applied to determine interaction forces between biological molecules. Starting with the detection of the first discrete unbinding forces between ligands and receptors by AFM only several years ago, measurements have become more and more quantitative. At the same time, theories have been developed to describe and understand the dynamics of the unbinding process and experimental techniques have been refined to verify this theory. In addition, the detection of molecular recognition forces has been exploited to map and image the location of binding sites. In this review we discuss the important contributions that have led to the development of this field. In addition, we emphasize the potential of chemically well-defined surface modification techniques to further improve reproducible measurements by AFM. This increased reproducibility will pave the way for a better understanding of molecular interactions in cell biology.

  3. The Cytoskeleton and Force Response Mechanisms

    NASA Technical Reports Server (NTRS)

    Allen, Philip Goodwin

    2003-01-01

    The long term aim of this project was to define the mechanisms by which cells sense and respond to the physical forces experienced at 1g and missing in microgravity. Identification and characterization of the elements of the cells force response mechanism could provide pathways and molecules to serve as targets for pharmacological intervention to mitigate the pathologic effects of microgravity. Mechanical forces experienced by the organism can be transmitted to cells through molecules that allow cells to bind to the extracellular matrix and through other types of molecules which bind cells to each other. These molecules are coupled in large complexes of proteins to structural elements such as the actin cytoskeleton that give the cell the ability to sense, resist and respond to force. Application of small forces to tissue culture cells causes local elevation of intracellular calcium through stretch activated ion channels, increased tyrosine phosphorylation and a restructuring of the actin cytoskeleton. Using collagen coated iron oxide beads and strong magnets, we can apply different levels of force to cells in culture. We have found that force application causes the cells to polymerize actin at the site of mechanical deformation and unexpectedly, to depolymerize actin across the rest of the cell. Observations of GFP- actin expressing cells demonstrate that actin accumulates at the site of deformation within the first five minutes of force application and is maintained for many tens of minutes after force is removed. Consistent with the reinforcement of the cytoskeletal structures underlying the integrin-bead interaction, force also alters the motion of bound magnetic beads. This effect is seen following the removal of the magnetic field, and is only partially ablated by actin disruption with cytochalsin B. While actin is polymerizing locally at the site of force application, force also stimulates a global reduction in actin filament content within the cells. We have

  4. Foundations of Physical Theory, I: Force and Energy. Physical Processes in Terrestrial and Aquatic Ecosystems, Fundamentals.

    ERIC Educational Resources Information Center

    Pearson, Nolan E.

    This module is part of a series designed to be used by life science students for instruction in the application of physical theory to ecosystem operation. Most modules contain computer programs which are built around a particular application of a physical process. This module is one of two units on the foundations of physical theory and the…

  5. Proximity effect: insight into the fundamental forces governing chemical reactivity of aromatic systems.

    PubMed

    Vidhani, Dinesh V; Krafft, Marie E

    2015-03-26

    The analysis of different layers of proximity effect in ortho-substituted aromatic compounds, using a DFT-level study, is reported. Polar and steric components of the proximity effect have been partitioned by applying multivariate regression analysis to an unusual six-electron heteroelectrocyclic reaction of the ortho-substituted nitrosostyrenes. The two pathways, 1,5- and 1,6-cyclizations, emanating from these substrates result into zwitterionic five-membered and neutral six-membered rings, respectively. The substituents at position 1, which are adjacent to the polar nitroso group, influenced the barrier primarily through electronic effect. Furthermore, a mechanistic shift from the 1,5 to 1,6 pathway, for certain substrates, is explained by the electronic repulsion. In contrast to position 1, the substituents on position 4 stereoelectronically interacted with a bulkier alkene moiety. Furthermore, unlike position 1, the position-4-substituted substrates are predicted to give only 1,5 products. A comparison of the two ortho positions with position 2, which is meta to the nitroso and para to the alkene, revealed an intriguing relationship between various electronic factors.

  6. The architecture of neutrophil extracellular traps investigated by atomic force microscopy.

    PubMed

    Pires, Ricardo H; Felix, Stephan B; Delcea, Mihaela

    2016-08-01

    Neutrophils are immune cells that engage in a suicidal pathway leading to the release of partially decondensed chromatin, or neutrophil extracellular traps (NETs). NETs behave as a double edged sword; they can bind to pathogens thereby ensnaring them and limiting their spread during infection; however, they may bind to host circulating materials and trigger thrombotic events, and are associated with autoimmune disorders. Despite the fundamental role of NETs as part of an immune system response, there is currently a very poor understanding of how their nanoscale properties are reflected in their macroscopic impact. In this work, using a combination of fluorescence and atomic force microscopy, we show that NETs appear as a branching filament network that results in a substantially organized porous structure with openings with 0.03 ± 0.04 μm(2) on average and thus in the size range of small pathogens. Topological profiles typically up to 3 ± 1 nm in height are compatible with a "beads on a string" model of nucleosome chromatin. Typical branch lengths of 153 ± 103 nm appearing as rigid rods and height profiles of naked DNA in NETs of 1.2 ± 0.5 nm are indicative of extensive DNA supercoiling throughout NETs. The presence of DNA duplexes could also be inferred from force spectroscopy and the occurrence of force plateaus that ranged from ∼65 pN to 300 pN. Proteolytic digestion of NETs resulted in widespread disassembly of the network structure and considerable loss of mechanical properties. Our results suggest that the underlying structure of NETs is considerably organized and that part of its protein content plays an important role in maintaining its mesh architecture. We anticipate that NETs may work as microscopic mechanical sieves with elastic properties that stem from their DNA-protein composition, which is able to segregate particles also as a result of their size. Such a behavior may explain their participation in capturing pathogens and their association

  7. Atomic Force Microscopy of Biochemically Tagged DNA

    NASA Astrophysics Data System (ADS)

    Murray, Matthew N.; Hansma, Helen G.; Bezanilla, Magdalena; Sano, Takeshi; Ogletree, D. Frank; Kolbe, William; Smith, Casandra L.; Cantor, Charles R.; Spengler, Sylvia; Hansma, Paul K.; Salmeron, Miquel

    1993-05-01

    Small fragments of DNA of known length were made with the polymerase chain reaction. These fragments had biotin molecules covalently attached at their ends. They were subsequently labeled with a chimeric protein fusion between streptavidin and two immunoglobulin G-binding domains of staphyloccocal protein A. This tetrameric species was expected to bind up to four DNA molecules via their attached biotin moieties. The DNA-protein complex was deposited on mica and imaged with an atomic force microscope. The images revealed the protein chimera at the expected location at the ends of the strands of DNA as well as the expected dimers, trimers, and tetramers of DNA bound to a single protein.

  8. Force propagation and force generation in cells.

    PubMed

    Jonas, Oliver; Duschl, Claus

    2010-09-01

    Determining how forces are produced by and propagated through the cytoskeleton (CSK) of the cell is of great interest as dynamic processes of the CSK are intimately correlated with many molecular signaling pathways. We are presenting a novel approach for integrating measurements on cell elasticity, transcellular force propagation, and cellular force generation to obtain a comprehensive description of dynamic and mechanical properties of the CSK under force loading. This approach uses a combination of scanning force microscopy (SFM) and Total Internal Reflection Fluorescence (TIRF) microscopy. We apply well-defined loading schemes onto the apical cell membrane of fibroblasts using the SFM and simultaneously use TIRF microscopy to image the topography of the basal cell membrane. The locally distinct changes of shape and depth of the cytoskeletal imprints onto the basal membrane are interpreted as results of force propagation through the cytoplasm. This observation provides evidence for the tensegrity model and demonstrates the usefulness of our approach that does not depend on potentially disturbing marker compounds. We confirm that the actin network greatly determines cell stiffness and represents the substrate that mediates force transduction through the cytoplasm of the cell. The latter is an essential feature of tensegrity. Most importantly, our new finding that, both intact actin and microtubule networks are required for enabling the cell to produce work, can only be understood within the framework of the tensegrity model. We also provide, for the first time, a direct measurement of the cell's mechanical power output under compression at two femtowatts. PMID:20607861

  9. Binding energies of hypernuclei and hypernuclear interactions

    SciTech Connect

    Bodmer, A.R. |; Murali, S.; Usmani, Q.N.

    1996-05-01

    In part 1 the effect of nuclear core dynamics on the binding energies of {Lambda} hypernuclei is discussed in the framework of variational correlated wave functions. In particular, the authors discuss a new rearrangement energy contribution and its effect on the core polarization. In part 2 they consider the interpretation of the {Lambda} single-particle energy in terms of basic {Lambda}-nuclear interactions using a local density approximation based on a Fermi hypernetted chain calculation of the A binding to nuclear matter. To account for the data strongly repulsive 3-body {Lambda}NN forces are required. Also in this framework they discuss core polarization for medium and heavier hypernuclei.

  10. The Aerodynamic Forces on Airship Hulls

    NASA Technical Reports Server (NTRS)

    Munk, M. M.

    1979-01-01

    The new method for making computations in connection with the study of rigid airships, which was used in the investigation of Navy's ZR-1 by the special subcommittee of the National Advisory Committee for Aeronautics appointed for this purpose is presented. The general theory of the air forces on airship hulls of the type mentioned is described and an attempt was made to develop the results from the very fundamentals of mechanics.

  11. Fundamental deformation processes controlling nanoscale friction and wear

    NASA Astrophysics Data System (ADS)

    Gotsmann, Bernd

    2010-03-01

    Thermally activated processes are often responsible for the kinetics of deformation and can control tribological performance. In this contribution two such processes are discussed in combination with nanoscale tribology experiments using atomic force microscopy (AFM). The first process describes single asperity wear as an atom-by-atom loss process driven by frictional shear stresses an interface. The wear rate is described by a thermally activated bond breaking process in which the energy barrier is reduced by the frictional shear stress. This leads to dramatic deviations from Archard's wear law which is commonly used to described macroscopic wear. Experimental confirmation of an atom-by-atom wear process is given by AFM wear experiments using different material combinations of tips sliding on surfaces [1]. The second process relates fundamental rearranging processes in polymers to friction. As an example, data of sliding friction between a silicon tip and a highly cross-linked polyaryletherketone film using friction force microscopy are presented. Energy dissipation into so-called molecular relaxations (alpha and beta relaxations) is identified as distinctive maxima of the friction force as a function of temperature between 150 and 500 K. A strong shift of such peak temperatures as a function of applied load is observed. Again, a model with an Arrhenius activation modulated by the applied shear stress describes experimental results quantitatively. The effect of the stress-shifted relaxation on friction-versus-load experiments is discussed [2]. Both processes will be discussed in the context of technological applications. [4pt] [1] B. Gotsmann and M. A. Lantz, Phys. Rev. Lett. 101, 125501 (2008) [0pt] [2] L. Jansen et al. Phys. Rev. Lett. 102, 236101 (2009)

  12. The Study of Biomolecule-Substrate Interactions by Single Molecule Force Spectroscopy and Brownian Dynamics Simulations

    NASA Astrophysics Data System (ADS)

    Cook, Sara Iliafar

    Hybrids of biomolecules and nanomaterials have been identified as promising candidates in the development of novel therapeutics and electronic devices. Single stranded DNA (ssDNA)-bound Single-walled carbon nanotubes (SWCNTs) are of particular interest as they may be the key to solving the challenges that face the carbon nanotube separation technology and because of their potential application in bio-nanomedicine. The ability of ssDNA to form a stable hybrid with CNTs has been attributed to the structure and amphiphilic nature of this macromolecule, enabling the dispersion, sorting and patterned placement of nanotubes. Considering the significant role of ssDNA-CNTs in future technologies and the potential toxicity of such nanomaterials in biological systems, it is essential to gain a quantitative and fundamental understanding on the interactions that allow, weaken or prevent the formation of these hybrids. In this dissertation, we use both experimental and theoretical methods to systematically investigate the major characteristics of these interactions. The free energy of binding of ssDNA homopolymers to solvated carbon nanotubes is one of the key characteristics that determine the stability of such dispersions. We used single molecule force spectroscopy (SMFS), first on graphite and next on single walled carbon nanotubes, to probe and directly quantify the binding strength of ssDNA homopolymer oligomers to these substrates. The force resisting removal of DNA molecules from these surfaces shows characteristic steady-state force plateaus which were distinguishable for each DNA sequence. The free energy of binding per nucleotide for these oligomers on graphite were ranked as T >= A > G >= C (11.3 +/- 0.8 kT, 9.9 +/- 0.4 kT, 8.3 +/- 0.2 kT, and 7.5 +/- 0.8 kT, respectively). On SWCNTs, these interactions decreased in the following order: A > G > T > C, and their magnitude was much larger than on graphite (38.1 +/- 0.2; 33.9 +/- 0.1; 23.3 +/- 0.1; 17.1 +/- 0.1 k

  13. Aerodynamic Lifting Force.

    ERIC Educational Resources Information Center

    Weltner, Klaus

    1990-01-01

    Describes some experiments showing both qualitatively and quantitatively that aerodynamic lift is a reaction force. Demonstrates reaction forces caused by the acceleration of an airstream and the deflection of an airstream. Provides pictures of demonstration apparatus and mathematical expressions. (YP)

  14. Fundamental Physics for Probing and Imaging

    NASA Astrophysics Data System (ADS)

    Allison, Wade

    2006-12-01

    This book addresses the question 'What is physics for?' Physics has provided many answers for mankind by extending his ability to see. Modern technology has enabled the power of physics to see into objects to be used in archaeology, medicine including therapy, geophysics, forensics and other spheres important to the good of society. The book looks at the fundamental physics of the various methods and how they are used by technology. These methods are magnetic resonance, ionising radiation and sound. By taking a broad view over the whole field it encourages comparisons, but also addresses questions of risk and benefit to society from a fundamental viewpoint. This textbook has developed from a course given to third year students at Oxford and is written so that it can be used coherently as a basis for shortened courses by omitting a number of chapters.

  15. Protein Binding Pocket Dynamics.

    PubMed

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C

    2016-05-17

    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

  16. Protein Binding Pocket Dynamics.

    PubMed

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C

    2016-05-17

    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

  17. DOE fundamentals handbook: Material science. Volume 1

    SciTech Connect

    Not Available

    1993-01-01

    The Mechanical Science Handbook was developed to assist nuclear facility operating contractors in providing operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of mechanical components and mechanical science. The handbook includes information on diesel engines, heat exchangers, pumps, valves, and miscellaneous mechanical components. This information will provide personnel with a foundation for understanding the construction and operation of mechanical components that are associated with various DOE nuclear facility operations and maintenance.

  18. [Reduction of biology to fundamental physics].

    PubMed

    Okhonin, V A

    2001-01-01

    It was shown that, while interpreting life as a physical phenomenon, fundamental physics allows for the following alternatives: relativity of animate and inanimate upon canonical transformations; the impossibility of the change from animate to inanimate state of isolated systems; the abandonment of attempts to reduce biology to the physics of isolated systems. The possibility of reducing biology to phenomenological physics was considered. A number of equations for the general phenomenological dynamics of density matrix was proposed.

  19. Baryogenesis and its implications to fundamental physics

    SciTech Connect

    Yoshimura, M.

    2008-08-08

    In this talk I shall explain some basic concepts of baryogenesis and leptogenesis theory, and a new idea of experimental method of verification of fundamental ingredients of leptogenesis theory; the Majorana nature and the absolute magnitude of neutrino masses. Both of these are important to the quest of physics beyond the standard theory, and have far reaching implications irrespective of any particular medel of leptogenesis. If this new method works ideally, there is even a further possibility of detecting relic neutrinos.

  20. Fundamental plasma emission involving ion sound waves

    NASA Technical Reports Server (NTRS)

    Cairns, Iver H.

    1987-01-01

    The theory for fundamental plasma emission by the three-wave processes L + or - S to T (where L, S and T denote Langmuir, ion sound and transverse waves, respectively) is developed. Kinematic constraints on the characteristics and growth lengths of waves participating in the wave processes are identified. In addition the rates, path-integrated wave temperatures, and limits on the brightness temperature of the radiation are derived.

  1. DOE fundamentals handbook: Material science. Volume 1

    SciTech Connect

    Not Available

    1993-01-01

    This handbook was developed to assist nuclear facility operating contractors in providing operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of the structure and properties of metals. This volume contains the two modules: structure of metals (bonding, common lattic types, grain structure/boundary, polymorphis, alloys, imperfections in metals) and properties of metals (stress, strain, Young modulus, stress-strain relation, physical properties, working of metals, corrosion, hydrogen embrittlement, tritium/material compatibility).

  2. DOE fundamentals handbook: Mechanical science. Volume 2

    SciTech Connect

    Not Available

    1993-01-01

    The Mechanical Science Handbook was developed to assist nuclear facility operating contractors in providing operators, maintenance personnel, and the technical staff with the necessary fundamentals training to ensure a basic understanding of mechanical components and mechanical science. The handbook includes information diesel engines, heat exchangers, pumps, valves, and miscellaneous mechanical components. This information will provide personnel with a foundation for understanding the construction and operation of mechanical components that are associated with various DOE nuclear facility operations and maintenance.

  3. Microprocessor controlled force actuator

    NASA Technical Reports Server (NTRS)

    Zimmerman, D. C.; Inman, D. J.; Horner, G. C.

    1986-01-01

    The mechanical and electrical design of a prototype force actuator for vibration control of large space structures (LSS) is described. The force actuator is an electromagnetic system that produces a force by reacting against a proof-mass. The actuator has two colocated sensors, a digital microcontroller, and a power amplifier. The total weight of actuator is .998 kg. The actuator has a steady state force output of approximately 2.75 N from approximately 2 Hz to well beyond 1000 Hz.

  4. Fluid force transducer

    DOEpatents

    Jendrzejczyk, Joseph A.

    1982-01-01

    An electrical fluid force transducer for measuring the magnitude and direction of fluid forces caused by lateral fluid flow, includes a movable sleeve which is deflectable in response to the movement of fluid, and a rod fixed to the sleeve to translate forces applied to the sleeve to strain gauges attached to the rod, the strain gauges being connected in a bridge circuit arrangement enabling generation of a signal output indicative of the magnitude and direction of the force applied to the sleeve.

  5. Fundamental Processes in Plasmas. Final report

    SciTech Connect

    O'Neil, Thomas M.; Driscoll, C. Fred

    2009-11-30

    This research focuses on fundamental processes in plasmas, and emphasizes problems for which precise experimental tests of theory can be obtained. Experiments are performed on non-neutral plasmas, utilizing three electron traps and one ion trap with a broad range of operating regimes and diagnostics. Theory is focused on fundamental plasma and fluid processes underlying collisional transport and fluid turbulence, using both analytic techniques and medium-scale numerical simulations. The simplicity of these systems allows a depth of understanding and a precision of comparison between theory and experiment which is rarely possible for neutral plasmas in complex geometry. The recent work has focused on three areas in basic plasma physics. First, experiments and theory have probed fundamental characteristics of plasma waves: from the low-amplitude thermal regime, to inviscid damping and fluid echoes, to cold fluid waves in cryogenic ion plasmas. Second, the wide-ranging effects of dissipative separatrices have been studied experimentally and theoretically, finding novel wave damping and coupling effects and important plasma transport effects. Finally, correlated systems have been investigated experimentally and theoretically: UCSD experients have now measured the Salpeter correlation enhancement, and theory work has characterized the 'guiding center atoms of antihydrogen created at CERN.

  6. Fundamentals of Physics, Extended 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! Fundamentals of Physics, 7th Edition and the Extended Version, 7th Edition offer a solid understanding of fundamental physics concepts, helping readers apply this conceptual understanding to quantitative problem solving, in a breezy, easy-to-understand style. A unique combination of authoritative content and stimulating applications. * Numerous improvements in the text, based on feedback from the many users of the sixth edition (both instructors and students) * Several thousand end-of-chapter problems have been rewritten to streamline both the presentations and answers * 'Chapter Puzzlers' open each chapter with an intriguing application or question that is explained or answered in the chapter * Problem-solving tactics are provided to help beginning Physics students solve problems and avoid common error * The first section in every chapter introduces the subject of the chapter by asking and answering, "What is Physics?" as the question pertains to the chapter * Numerous supplements available to aid teachers and students The extended edition provides coverage of developments in Physics in the last 100 years, including: Einstein and Relativity, Bohr and others and Quantum Theory, and the more recent theoretical developments like String Theory.

  7. Translation Against An Applied Force.

    NASA Astrophysics Data System (ADS)

    Skinner, Gary M.; Seol, Yeonee; Visscher, Koen

    2008-02-01

    Ribosome structure and mechanism are largely conserved among all known forms of life. Therefore, the motions associated with translation may be among the most ancient and fundamental in biology. However, the molecular mechanism of translocation, the coordinated movement of tRNAs and associated mRNA on the ribosome, has eluded scientists and remains obscure. Single-molecule experiments using optical tweezers and fluorescence microscope are starting to shed new light on these questions. For example, we have observed that moderate forces reverse direction of motion and ribosomes seem to slip backward into the 5' direction along a poly(U) message. Although the detailed molecular mechanism for ribosome slippage is not fully understood, these observations raise interesting biological questions about e.g. -1 frameshifting. Is the -1 frameshift essential for HIV-1 replication a result of tension in the message? Single-molecule experiments open the way towards quantitative modeling of ribosome motion and related phenomena such as -1 frameshifting.

  8. Forces in General Relativity

    ERIC Educational Resources Information Center

    Ridgely, Charles T.

    2010-01-01

    Many textbooks dealing with general relativity do not demonstrate the derivation of forces in enough detail. The analyses presented herein demonstrate straightforward methods for computing forces by way of general relativity. Covariant divergence of the stress-energy-momentum tensor is used to derive a general expression of the force experienced…

  9. Turkish Students' Force Meanings

    ERIC Educational Resources Information Center

    Menekse, Muhsin; Clark, Douglas B.; Ozdemir, Gokhan; D'angelo, Cynthia; Scheligh, Sharon

    2009-01-01

    What are Turkish pre, elementary, middle, and high school students' force ideas? And, how do Turkish students' non-normative force ideas differ or be similar to the well-known force misconceptions reported in the literature? Students have false and persistent beliefs about the physical world and they struggle with challenging misconceptions based…

  10. Debunking Coriolis Force Myths

    ERIC Educational Resources Information Center

    Shakur, Asif

    2014-01-01

    Much has been written and debated about the Coriolis force. Unfortunately, this has done little to demystify the paradoxes surrounding this fictitious force invoked by an observer in a rotating frame of reference. It is the purpose of this article to make another valiant attempt to slay the dragon of the Coriolis force! This will be done without…

  11. Crossflow force transducer. [LMFBR

    SciTech Connect

    Mulcahy, T M

    1982-05-01

    A force transducer for measuring lift and drag coefficients for a circular cylinder in turbulent water flow is presented. In addition to describing the actual design and construction of the strain-gauged force- ring based transducer, requirements for obtained valid fluid force test data are discussed, and pertinent flow test experience is related.

  12. Prebending the estrogen response element destabilizes binding of the estrogen receptor DNA binding domain.

    PubMed Central

    Kim, J; de Haan, G; Nardulli, A M; Shapiro, D J

    1997-01-01

    Binding of many eukaryotic transcription regulatory proteins to their DNA recognition sequences results in conformational changes in DNA. To test the effect of altering DNA topology by prebending a transcription factor binding site, we examined the interaction of the estrogen receptor (ER) DNA binding domain (DBD) with prebent estrogen response elements (EREs). When the ERE in minicircle DNA was prebent toward the major groove, which is in the same direction as the ER-induced DNA bend, there was no significant effect on ER DBD binding relative to the linear counterparts. However, when the ERE was bent toward the minor groove, in a direction that opposes the ER-induced DNA bend, there was a four- to eightfold reduction in ER DBD binding. Since reduced binding was also observed with the ERE in nicked circles, the reduction in binding was not due to torsional force induced by binding of ER DBD to the prebent ERE in covalently closed minicircles. To determine the mechanism responsible for reduced binding to the prebent ERE, we examined the effect of prebending the ERE on the association and dissociation of the ER DBD. Binding of the ER DBD to ERE-containing minicircles was rapid when the EREs were prebent toward either the major or minor groove of the DNA (k(on) of 9.9 x 10(6) to 1.7 x 10(7) M(-1) s(-1)). Prebending the ERE toward the minor groove resulted in an increase in k(off) of four- to fivefold. Increased dissociation of the ER DBD from the ERE is, therefore, the major factor responsible for reduced binding of the ER DBD to an ERE prebent toward the minor groove. These data provide the first direct demonstration that the interaction of a eukaryotic transcription factor with its recognition sequence can be strongly influenced by altering DNA topology through prebending the DNA. PMID:9154816

  13. A Streptavidin Binding Site Mutation Yields an Unexpected Result: An Ionized Asp128 Residue Is Not Essential for Strong Biotin Binding.

    PubMed

    Baugh, Loren; Le Trong, Isolde; Stayton, Patrick S; Stenkamp, Ronald E; Lybrand, Terry P

    2016-09-20

    We report a detailed study of a point mutation of the crucial binding site residue, D128, in the biotin-streptavidin complex. The conservative substitution, D128N, preserves the detailed structure observed for the wild-type complex but has an only minimal impact on biotin binding, even though previous experimental and computational studies suggested that a charged D128 residue was crucial for high-affinity binding. These results show clearly that the fundamental basis for streptavidin's extremely strong biotin binding affinity is more complex than assumed and illustrate some of the challenges that may arise when analyzing extremely strong ligand-protein binding interactions. PMID:27603565

  14. Analyzing radioligand binding data.

    PubMed

    Motulsky, H; Neubig, R

    2001-05-01

    A radioligand is a radioactively labeled drug that can associate with a receptor, transporter, enzyme, or any protein of interest. Measuring the rate and extent of binding provides information on the number of binding sites, and their affinity and accessibility for various drugs. Radioligand binding experiments are easy to perform, and provide useful data in many fields. For example, radioligand binding studies are used to study receptor regulation, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  15. PREFACE New developments in nanopore research—from fundamentals to applications New developments in nanopore research—from fundamentals to applications

    NASA Astrophysics Data System (ADS)

    Albrecht, Tim; Edel, Joshua B.; Winterhalter, Mathias

    2010-11-01

    Biological and solid-state nanopores are an exciting field of research, which has seen a rapid development over the last 10 to 20 years. Activities in this area range from theoretical and experimental work on the underlying fundamental (bio)physics to applications in single-molecule biosensing. And while the prospect of DNA sequencing continues to be a major driving force, other applications with potentially similar impact begin to emerge, for example the detection of small molecules, proteins, protein/protein and protein/DNA complexes, and RNA to name just a few. It has also become apparent that both classes of nanopore devices have intrinsic advantages and disadvantages; hybrid structures combining the better of the two worlds would be a logical consequence and are beginning to appear in the literature. Many other highly innovative ideas and concepts continue to emerge and the number of nanopore-related publications has increased drastically over recent years. We found that more than 100 research groups worldwide are active in this area; several commercial settings are in the process of translating fundamental research into real-life applications. We therefore felt that now is the right time to showcase these new developments in a special issue: to inspire researchers active in the field, to liberate inherent synergies, and not least, to demonstrate to the outside world the current state-of-the-art and future opportunities. The title 'New developments in nanopore research—from fundamentals to applications' in some way reflects these ambitions and, even though not everyone invited was able to contribute, we were able to assemble 34 high-quality research papers from all over the world. We would like to acknowledge and thank all the contributors for their submissions, which made this special issue possible in the first place. Moreover, we would like to thank the staff at IOP Publishing for helping us with the administrative aspects and for coordinating the

  16. Fundamental Physics Explored with High Intensity Laser

    NASA Astrophysics Data System (ADS)

    Tajima, T.; Homma, K.

    2012-10-01

    Over the last century the method of particle acceleration to high energies has become the prime approach to explore the fundamental nature of matter in laboratory. It appears that the latest search of the contemporary accelerator based on the colliders shows a sign of saturation (or at least a slow-down) in increasing its energy and other necessary parameters to extend this frontier. We suggest two pronged approach enabled by the recent progress in high intensity lasers. First we envision the laser-driven plasma accelerator may be able to extend the reach of the collider. For this approach to bear fruit, we need to develop the technology of high averaged power laser in addition to the high intensity. For this we mention that the latest research effort of ICAN is an encouraging sign. In addition to this, we now introduce the concept of the noncollider paradigm in exploring fundamental physics with high intensity (and large energy) lasers. One of the examples we mention is the laser wakefield acceleration (LWFA) far beyond TeV without large luminosity. If we relax or do not require the large luminosity necessary for colliders, but solely in ultrahigh energy frontier, we are still capable of exploring such a fundamental issue. Given such a high energetic particle source and high-intensity laser fields simultaneously, we expect to be able to access new aspects on the matter and the vacuum structure from fundamental physical point of views. LWFA naturally exploits the nonlinear optical effects in the plasma when it becomes of relativistic intensity. Normally nonlinear optical effects are discussed based upon polarization susceptibility of matter to external fields. We suggest application of this concept even to the vacuum structure as a new kind of order parameter to discuss vacuum-originating phenomena at semimacroscopic scales. This viewpoint unifies the following observables with the unprecedented experimental environment we envision; the dispersion relation of

  17. Evolving nucleotide binding surfaces

    NASA Technical Reports Server (NTRS)

    Kieber-Emmons, T.; Rein, R.

    1981-01-01

    An analysis is presented of the stability and nature of binding of a nucleotide to several known dehydrogenases. The employed approach includes calculation of hydrophobic stabilization of the binding motif and its intermolecular interaction with the ligand. The evolutionary changes of the binding motif are studied by calculating the Euclidean deviation of the respective dehydrogenases. Attention is given to the possible structural elements involved in the origin of nucleotide recognition by non-coded primordial polypeptides.

  18. Electrostatically biased binding of kinesin to microtubules.

    PubMed

    Grant, Barry J; Gheorghe, Dana M; Zheng, Wenjun; Alonso, Maria; Huber, Gary; Dlugosz, Maciej; McCammon, J Andrew; Cross, Robert A

    2011-11-01

    The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules. PMID:22140358

  19. Electrostatically Biased Binding of Kinesin to Microtubules

    PubMed Central

    Zheng, Wenjun; Alonso, Maria; Huber, Gary; Dlugosz, Maciej; McCammon, J. Andrew; Cross, Robert A.

    2011-01-01

    The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules. PMID:22140358

  20. Molecular design of substrate binding sites

    SciTech Connect

    Shelnutt, J.A.; Hobbs, J.D.

    1991-12-31

    Computer-aided molecular design methods were used to tailor binding sites for small substrate molecules, including CO{sub 2} and methane. The goal is to design a cavity, adjacent to a catalytic metal center, into which the substrate will selectively bind through only non-bonding interactions with the groups lining the binding pocket. Porphyrins are used as a basic molecular structure, with various substituents added to construct the binding pocket. The conformations of these highly-substituted porphyrins are predicted using molecular mechanics calculations with a force field that gives accurate predictions for metalloporhyrins. Dynamics and energy-minimization calculations of substrate molecules bound to the cavity indicate high substrate binding affinity. The size, shape and charge-distribution of groups surrounding the cavity provide molecular selectivity. Specifically, calculated binding energies of methane, benzene, dichloromethane, CO{sub 2} and chloroform vary by about 10 kcal/mol for metal octaethyl-tetraphenylporphyrins (OETPPs) with chloroform, dichloromethane, and CO{sub 2} having the lowest. Significantly, a solvent molecule is found in the cavity in the X-ray structures of Co- and CuOETPP crystals obtained from dichloromethane. 5 refs., 3 figs., 3 tabs.

  1. Molecular design of substrate binding sites

    SciTech Connect

    Shelnutt, J.A.; Hobbs, J.D.

    1991-01-01

    Computer-aided molecular design methods were used to tailor binding sites for small substrate molecules, including CO{sub 2} and methane. The goal is to design a cavity, adjacent to a catalytic metal center, into which the substrate will selectively bind through only non-bonding interactions with the groups lining the binding pocket. Porphyrins are used as a basic molecular structure, with various substituents added to construct the binding pocket. The conformations of these highly-substituted porphyrins are predicted using molecular mechanics calculations with a force field that gives accurate predictions for metalloporhyrins. Dynamics and energy-minimization calculations of substrate molecules bound to the cavity indicate high substrate binding affinity. The size, shape and charge-distribution of groups surrounding the cavity provide molecular selectivity. Specifically, calculated binding energies of methane, benzene, dichloromethane, CO{sub 2} and chloroform vary by about 10 kcal/mol for metal octaethyl-tetraphenylporphyrins (OETPPs) with chloroform, dichloromethane, and CO{sub 2} having the lowest. Significantly, a solvent molecule is found in the cavity in the X-ray structures of Co- and CuOETPP crystals obtained from dichloromethane. 5 refs., 3 figs., 3 tabs.

  2. Fundamental Physics Program and the NASA Mission

    NASA Technical Reports Server (NTRS)

    Trinh, Eugene

    2003-01-01

    The accomplishments of Physics, the increasing power of its instruments, and its expanding reach into other sciences have generated an unprecedented set of scientific opportunities. The committee has identified six such Grand Challenges listed below in no particular order: Developing quantum technologies. Creating new materials. Understanding complex systems. Unifying the forces of Nature. Exploring the universe Applying Physics to Biology.

  3. Efficacy of climate forcings

    NASA Astrophysics Data System (ADS)

    Hansen, J.; Sato, M.; Ruedy, R.; Nazarenko, L.; Lacis, A.; Schmidt, G. A.; Russell, G.; Aleinov, I.; Bauer, M.; Bauer, S.; Bell, N.; Cairns, B.; Canuto, V.; Chandler, M.; Cheng, Y.; Del Genio, A.; Faluvegi, G.; Fleming, E.; Friend, A.; Hall, T.; Jackman, C.; Kelley, M.; Kiang, N.; Koch, D.; Lean, J.; Lerner, J.; Lo, K.; Menon, S.; Miller, R.; Minnis, P.; Novakov, T.; Oinas, V.; Perlwitz, Ja.; Perlwitz, Ju.; Rind, D.; Romanou, A.; Shindell, D.; Stone, P.; Sun, S.; Tausnev, N.; Thresher, D.; Wielicki, B.; Wong, T.; Yao, M.; Zhang, S.

    2005-09-01

    We use a global climate model to compare the effectiveness of many climate forcing agents for producing climate change. We find a substantial range in the "efficacy" of different forcings, where the efficacy is the global temperature response per unit forcing relative to the response to CO2 forcing. Anthropogenic CH4 has efficacy ˜110%, which increases to ˜145% when its indirect effects on stratospheric H2O and tropospheric O3 are included, yielding an effective climate forcing of ˜0.8 W/m2 for the period 1750-2000 and making CH4 the largest anthropogenic climate forcing other than CO2. Black carbon (BC) aerosols from biomass burning have a calculated efficacy ˜58%, while fossil fuel BC has an efficacy ˜78%. Accounting for forcing efficacies and for indirect effects via snow albedo and cloud changes, we find that fossil fuel soot, defined as BC + OC (organic carbon), has a net positive forcing while biomass burning BC + OC has a negative forcing. We show that replacement of the traditional instantaneous and adjusted forcings, Fi and Fa, with an easily computed alternative, Fs, yields a better predictor of climate change, i.e., its efficacies are closer to unity. Fs is inferred from flux and temperature changes in a fixed-ocean model run. There is remarkable congruence in the spatial distribution of climate change, normalized to the same forcing Fs, for most climate forcing agents, suggesting that the global forcing has more relevance to regional climate change than may have been anticipated. Increasing greenhouse gases intensify the Hadley circulation in our model, increasing rainfall in the Intertropical Convergence Zone (ITCZ), Eastern United States, and East Asia, while intensifying dry conditions in the subtropics including the Southwest United States, the Mediterranean region, the Middle East, and an expanding Sahel. These features survive in model simulations that use all estimated forcings for the period 1880-2000. Responses to localized forcings, such

  4. Cell adhesion force microscopy

    PubMed Central

    Sagvolden, G.; Giaever, I.; Pettersen, E. O.; Feder, J.

    1999-01-01

    The adhesion forces of cervical carcinoma cells in tissue culture were measured by using the manipulation force microscope, a novel atomic force microscope. The forces were studied as a function of time and temperature for cells cultured on hydrophilic and hydrophobic polystyrene substrates with preadsorbed proteins. The cells attached faster and stronger at 37°C than at 23°C and better on hydrophilic than on hydrophobic substrates, even though proteins adsorb much better to the hydrophobic substrates. Because cell adhesion serves to control several stages in the cell cycle, we anticipate that the manipulation force microscope can help clarify some cell-adhesion related issues. PMID:9892657

  5. Forces in molecules.

    PubMed

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another?

  6. Forces in molecules.

    PubMed

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another? PMID:17328425

  7. Force-Measuring Clamps

    NASA Technical Reports Server (NTRS)

    Nunnelee, Mark

    2003-01-01

    Force-measuring clamps have been invented to facilitate and simplify the task of measuring the forces or pressures applied to clamped parts. There is a critical need to measure clamping forces or pressures in some applications for example, while bonding sensors to substrates or while clamping any sensitive or delicate parts. Many manufacturers of adhesives and sensors recommend clamping at specific pressures while bonding sensors or during adhesive bonding between parts in general. In the absence of a force-measuring clamp, measurement of clamping force can be cumbersome at best because of the need for additional load sensors and load-indicating equipment. One prior method of measuring clamping force involved the use of load washers or miniature load cells in combination with external power sources and load-indicating equipment. Calibrated spring clamps have also been used. Load washers and miniature load cells constitute additional clamped parts in load paths and can add to the destabilizing effects of loading mechanisms. Spring clamps can lose calibration quickly through weakening of the springs and are limited to the maximum forces that the springs can apply. The basic principle of a force-measuring clamp can be implemented on a clamp of almost any size and can enable measurement of a force of almost any magnitude. No external equipment is needed because the component(s) for transducing the clamping force and the circuitry for supplying power, conditioning the output of the transducers, and displaying the measurement value are all housed on the clamp. In other words, a force-measuring clamp is a complete force-application and force-measurement system all in one package. The advantage of unitary packaging of such a system is that it becomes possible to apply the desired clamping force or pressure with precision and ease.

  8. Force Limited Vibration Testing

    NASA Technical Reports Server (NTRS)

    Scharton, Terry; Chang, Kurng Y.

    2005-01-01

    This slide presentation reviews the concept and applications of Force Limited Vibration Testing. The goal of vibration testing of aerospace hardware is to identify problems that would result in flight failures. The commonly used aerospace vibration tests uses artificially high shaker forces and responses at the resonance frequencies of the test item. It has become common to limit the acceleration responses in the test to those predicted for the flight. This requires an analysis of the acceleration response, and requires placing accelerometers on the test item. With the advent of piezoelectric gages it has become possible to improve vibration testing. The basic equations have are reviewed. Force limits are analogous and complementary to the acceleration specifications used in conventional vibration testing. Just as the acceleration specification is the frequency spectrum envelope of the in-flight acceleration at the interface between the test item and flight mounting structure, the force limit is the envelope of the in-flight force at the interface . In force limited vibration tests, both the acceleration and force specifications are needed, and the force specification is generally based on and proportional to the acceleration specification. Therefore, force limiting does not compensate for errors in the development of the acceleration specification, e.g., too much conservatism or the lack thereof. These errors will carry over into the force specification. Since in-flight vibratory force data are scarce, force limits are often derived from coupled system analyses and impedance information obtained from measurements or finite element models (FEM). Fortunately, data on the interface forces between systems and components are now available from system acoustic and vibration tests of development test models and from a few flight experiments. Semi-empirical methods of predicting force limits are currently being developed on the basis of the limited flight and system test

  9. 32 CFR 2001.16 - Fundamental classification guidance review.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Fundamental classification guidance review. 2001... INFORMATION Classification § 2001.16 Fundamental classification guidance review. (a) Performance of fundamental classification guidance reviews. An initial fundamental classification guidance review shall...

  10. Giant vacuum forces via transmission lines

    PubMed Central

    Shahmoon, Ephraim; Mazets, Igor; Kurizki, Gershon

    2014-01-01

    Quantum electromagnetic fluctuations induce forces between neutral particles, known as the van der Waals and Casimir interactions. These fundamental forces, mediated by virtual photons from the vacuum, play an important role in basic physics and chemistry and in emerging technologies involving, e.g., microelectromechanical systems or quantum information processing. Here we show that these interactions can be enhanced by many orders of magnitude upon changing the character of the mediating vacuum modes. By considering two polarizable particles in the vicinity of any standard electric transmission line, along which photons can propagate in one dimension, we find a much stronger and longer-range interaction than in free space. This enhancement may have profound implications on many-particle and bulk systems and impact the quantum technologies mentioned above. The predicted giant vacuum force is estimated to be measurable in a coplanar waveguide line. PMID:25002503

  11. Model for a fundamental theory with supersymmetry

    NASA Astrophysics Data System (ADS)

    Yokoo, Seiichiro

    Physics in the year 2006 is tightly constrained by experiment, observation, and mathematical consistency. The Standard Model provides a remarkably precise description of particle physics, and general relativity is quite successful in describing gravitational phenomena. At the same time, it is clear that a more fundamental theory is needed for several distinct reasons. Here we consider a new approach, which begins with the unusually ambitious point of view that a truly fundamental theory should aspire to explaining the origins of Lorentz invariance, gravity, gauge fields and their symmetry, supersymmetry, fermionic fields, bosonic fields, quantum mechanics and spacetime. The present dissertation is organized so that it starts with the most conventional ideas for extending the Standard Model and ends with a microscopic statistical picture, which is actually the logical starting point of the theory, but which is also the most remote excursion from conventional physics. One motivation for the present work is the fact that a Euclidean path integral in quantum physics is equivalent to a partition function in statistical physics. This suggests that the most fundamental description of nature may be statistical. This dissertation may be regarded as an attempt to see how far one can go with this premise in explaining the observed phenomena, starting with the simplest statistical picture imaginable. It may be that nature is richer than the model assumed here, but the present results are quite suggestive, because, with a set of assumptions that are not unreasonable, one recovers the phenomena listed above. At the end, the present theory leads back to conventional physics, except that Lorentz invariance and supersymmetry are violated at extremely high energy. To be more specific, one obtains local Lorentz invariance (at low energy compared to the Planck scale), an SO( N) unified gauge theory (with N = 10 as the simplest possibility), supersymmetry of Standard Model fermions and

  12. [Relation between fundamental and realized ecological niche].

    PubMed

    Severtsov, A S

    2012-01-01

    Since species are formed in course of evolutionary process, their ecological niches are formed in the evolutionary process, too. Species exist in a state of evolutionary stasis diring hundreds of thousands and millions years. Stasis in sustained mainly by counterbalance of vectors of directional selection. Niche can be viewed as a multidimensional structure. Multitude of environmental factors acts upon every population, which cause elimination and, by that, selection for adaptation to each eliminating factor. Different directions of these vectors of selection lead to their counteractions; selection in one direction is interfered by selection in an opposite direction. The counterbalance of vectors of selection interferes with progressive evolution thus supporting stasis. During species existence in a stasis condition it endures a whole set of various deterioration of environment. Such deteriorations lead to imbalance of selective processes. Unbalanced vectors of selection form adaptations to extreme conditions of existence. Such adaptations are superfluous as for usual conditions; but they define fitness borders and, by that, borders of a fundamental niche. Realized niche, as well as fundamental one, is a multidimensional structure. Each population occupies a subniche of the specific realized niche. Thus, it occupies habitats where conditions are as close to an ecological optimum as can be admitted by the conditions in the given part of the areal. The sum of all subniches of populations--the specific realized niche--coincides with a part of fundamental niche because only the part of adaptive possibilities of a species sufficient for existence in the given environment is used. Interspecific competition, even when it is capable to restrict consumption of limiting resources, is not the reason of the realized niche limitation. Restriction of one or two of niche parameters does not influece all others parameters of its multidimensional space.

  13. 146 Kepler-Lamost targets fundamental parameters

    NASA Astrophysics Data System (ADS)

    Wu, Yaqian

    2015-08-01

    Accurate stellar fundamental parameters with high precision are important for distinguishing stellar populationand star study.Turn-off stars are in the relatively vital stellar evolution state. Studying turn-off stars can help us to have a more comprehensive understand of the stellar physics.With the help of observation provided by Lamost project, we obtain atmospheric parameters of 146 turn-off stars from LSP3 pipeline. Combined with stellar pulsation data from Kepler, we can get asteroseismic characteristic of stars,such as Δν and νmax.In this paper,we constructed a grid of evolutionary models, with the mass range from 0.8 to 2.5 M⊙ and metallicities Zini = 0.0085, 0.0105, 0.0130, 0.0165, 0.0200, 0.0250, 0.0300, 0.0400 (i.e.[Fe/H] from -0.3 to 0.4dex).All evolutionary tracks were started in the pre-main sequence birth line and ended at the base of Red Giant Branch.Based on the stellar model grid we constructed,as well as Kepler-Lamost observations, we obtained fundamental parameters of 146 around turn-off stars, and found that 112 targets lied in turn-off state or in the Main Sequence,15 targets are subgiant stars and 7 targets have evolved to the red giants stage.Then we use pulsation code(JIG) of Guenther to extract theorical individual frequencies and calculate theorical Δν.Meanwhile we obtained more precise fundamental parameters of these stars.

  14. Fundamentals of air pollution. Third edition

    SciTech Connect

    Boubel, R.W.; Fox, D.L.; Turner, D.B.; Stern, A.C.

    1994-12-31

    This book presents an overview of air pollution. In Part I, the history of air pollution and the basic concepts involved with air pollution such as sources, scales, definitions are covered. Part II describes how airborne pollutants damage materials, vegetation, animals, and humans. Six fundamental aspects of air pollution are included in the text: The Elements of Air Pollution; The Effects of Air Pollution; Measurement and Monitoring of Air Pollution; Meterology of Air Pollution; regulatory Control of Air Pollution; and Engineering Control of Air Pollution.

  15. Fundamental investigation of duct/ESP phenomena

    SciTech Connect

    Brown, C.A. ); Durham, M.D. ); Sowa, W.A. . Combustion Lab.); Himes, R.M. ); Mahaffey, W.A. )

    1991-10-21

    Radian Corporation was contracted to investigate duct injection and ESP phenomena in a 1.7 MW pilot plant constructed for this test program. This study was an attempt to resolve problems found in previous studies and answer remaining questions for the technology using an approach which concentrates on the fundamental mechanisms of the process. The goal of the study was to obtain a better understanding of the basic physical and chemical phenomena that control: (1) the desulfurization of flue gas by calcium-based reagent, and (2) the coupling of an existing ESP particulate collection device to the duct injection process. Process economics are being studied by others. (VC)

  16. Development of Fundamental Technologies for Micro Bioreactors

    NASA Astrophysics Data System (ADS)

    Sato, Kiichi; Kitamori, Takehiko

    This chapter reviews the development of fundamental technologies required for microchip-based bioreactors utilizing living mammalian cells and pressure driven flow. The most important factor in the bioreactor is the cell culture. For proper cell culturing, continuous medium supply from a microfluidic channel and appropriate modification of the channel surface to accommodate cell attachment is required. Moreover, the medium flow rate should be chosen carefully, because shear stress affects cell activity. The techniques presented here could be applied to the development of micro bioreactors such as microlivers, pigment production by plant cells, and artificial insemination.

  17. Fundamental studies of passivity and passivity breakdown

    SciTech Connect

    Macdonald, D.D.; Urquidi-Macdonald, M.; Song, H.; Biaggio-Rocha, S.; Searson, P.

    1991-11-01

    This report summarizes the findings of our fundamental research program on passivity and passivity breakdown. During the past three and one half years in this program (including the three year incrementally-funded grant prior to the present grant), we developed and experimentally tested various physical models for the growth and breakdown of passive films on metal surfaces. These models belong to a general class termed point defects models'' (PDMs), in which the growth and breakdown of passive films are described in terms of the movement of anion and cation vacancies.

  18. Fundamental science of nanometer-size clusters

    SciTech Connect

    Wilcoxon, J.P.; Newcomer, P.P.; Samara, G.A.; Venturini, E.L.; Williamson, R.L.

    1995-10-01

    This research has produced a variety of monodisperse, nanometer-size clusters (nanoclusters for short), characterized their size and crystal structure and developed a scientific understanding of the size dependence of their physical properties. Of specific interest were the influence of quantum electronic confinement on the optical properties, magnetic properties, and dielectric properties. These properties were chosen both for their potential practical impact on various applications identified in the National Critical Technologies list (e.g., catalysis, information storage, sensors, environmental remediation, ...) as well as for their importance to the fundamental science of clusters. An Executive Summary provides a description of the major highlights.

  19. Antennas in matter: Fundamentals, theory, and applications

    NASA Technical Reports Server (NTRS)

    King, R. W. P.; Smith, G. S.; Owens, M.; Wu, T. T.

    1981-01-01

    The volume provides an introduction to antennas and probes embedded within or near material bodies such as the earth, the ocean, or a living organism. After a fundamental analysis of insulated and bare antennas, an advanced treatment of antennas in various media is presented, including a detailed study of the electromagnetic equations in homogeneous isotropic media, the complete theory of the bare dipole in a general medium, and a rigorous analysis of the insulated antenna as well as bare and insulated loop antennas. Finally, experimental models and measuring techniques related to antennas and probes in a general dissipative or dielectric medium are examined.

  20. Fundamental Limits of Spatial Resolution in PET

    PubMed Central

    Moses, William W.

    2010-01-01

    The fundamental limits of spatial resolution in positron emission tomography (PET) have been understood for many years. The physical size of the detector element usually plays the dominant role in determining resolution, but the combined contributions from acollinearity, positron range, penetration into the detector ring, and decoding errors in the detector modules often combine to be of similar size. In addition, the sampling geometry and statistical noise further degrade the effective resolution. This paper describes quantitatively describes these effects, discusses potential methods for reducing the magnitude of these effects, and computes the ultimately achievable spatial resolution for clinical and pre-clinical PET cameras. PMID:21804677

  1. Fundamental Structure of Matter and Strong Interaction

    SciTech Connect

    Jian-Ping Chen

    2011-11-01

    More than 99% of the visible matter in the universe are the protons and neutrons. Their internal structure is mostly governed by the strong interaction. Understanding their internal structure in terms of fundamental degrees-of-freedom is one of the most important subjects in modern physics. Worldwide efforts in the last few decades have lead to numerous surprises and discoveries, but major challenges still remain. An overview of the progress will be presented with a focus on the recent studies of the proton and neutron's electromagnetic and spin structure. Future perspectives will be discussed.

  2. Fundamental bioprocessing research for coal applications

    SciTech Connect

    Kaufman, E.N.

    1996-06-01

    The purpose of this program is to gain a fundamental understanding and sound scientific technical basis for evaluating the potential roles of innovative bioprocessing concepts for the utilization and conversion of coal. The aim is to explore the numerous ways in which advanced biological processes and techniques can open new opportunities for coal utilization or can replace more conventional techniques by use of milder conditions with less energy consumption or loss. There are several roles where biotechnology is likely to be important in coal utilization and conversion. These include potential bioprocessing systems such.

  3. Fundamental constraints on two-time physics

    NASA Astrophysics Data System (ADS)

    Piceno, E.; Rosado, A.; Sadurní, E.

    2016-10-01

    We show that generalizations of classical and quantum dynamics with two times lead to a fundamentally constrained evolution. At the level of classical physics, Newton's second law is extended and exactly integrated in a (1 + 2) -dimensional space, leading to effective single-time evolution for any initial condition. The cases 2 + 2 and 3 + 2 are also analyzed. In the domain of quantum mechanics, we follow strictly the hypothesis of probability conservation by extending the Heisenberg picture to unitary evolution with two times. As a result, the observability of two temporal axes is constrained by a generalized uncertainty relation involving level spacings, total duration of the effect and Planck's constant.

  4. A "fundamental theorem" of biomedical informatics.

    PubMed

    Friedman, Charles P

    2009-01-01

    This paper proposes, in words and pictures, a "fundamental theorem" to help clarify what informatics is and what it is not. In words, the theorem stipulates that a person working in partnership with an information resource is "better" than that same person unassisted. The theorem is applicable to health care, research, education, and administrative activities. Three corollaries to the theorem illustrate that informatics is more about people than technology; that in order for the theorem to hold, resources must be informative in addition to being correct; and that the theorem can fail to hold for reasons explained by understanding the interaction between the person and the resource.

  5. Critical Casimir forces for colloidal assembly.

    PubMed

    Nguyen, V D; Dang, M T; Nguyen, T A; Schall, P

    2016-02-01

    Critical Casimir forces attract increasing interest due to their opportunities for reversible particle assembly in soft matter and nano science. These forces provide a thermodynamic analogue of the celebrated quantum mechanical Casimir force that arises from the confinement of vacuum fluctuations of the electromagnetic field. In its thermodynamic analogue, solvent fluctuations, confined between suspended particles, give rise to an attractive or repulsive force between the particles. Due to its unique temperature dependence, this effect allows in situ control of reversible assembly. Both the force magnitude and range vary with the solvent correlation length in a universal manner, adjusting with temperature from fractions of the thermal energy, k B T, and nanometre range to several ten kT and micrometer length scale. Combined with recent breakthroughs in the synthesis of complex particles, critical Casimir forces promise the design and assembly of complex colloidal structures, for fundamental studies of equilibrium and out-of-equilibrium phase behaviour. This review highlights recent developments in this evolving field, with special emphasis on the dynamic interaction control to assemble colloidal structures, in and out of equilibrium. PMID:26750980

  6. Critical Casimir forces for colloidal assembly

    NASA Astrophysics Data System (ADS)

    Nguyen, V. D.; Dang, M. T.; Nguyen, T. A.; Schall, P.

    2016-02-01

    Critical Casimir forces attract increasing interest due to their opportunities for reversible particle assembly in soft matter and nano science. These forces provide a thermodynamic analogue of the celebrated quantum mechanical Casimir force that arises from the confinement of vacuum fluctuations of the electromagnetic field. In its thermodynamic analogue, solvent fluctuations, confined between suspended particles, give rise to an attractive or repulsive force between the particles. Due to its unique temperature dependence, this effect allows in situ control of reversible assembly. Both the force magnitude and range vary with the solvent correlation length in a universal manner, adjusting with temperature from fractions of the thermal energy, k B T, and nanometre range to several ten kT and micrometer length scale. Combined with recent breakthroughs in the synthesis of complex particles, critical Casimir forces promise the design and assembly of complex colloidal structures, for fundamental studies of equilibrium and out-of-equilibrium phase behaviour. This review highlights recent developments in this evolving field, with special emphasis on the dynamic interaction control to assemble colloidal structures, in and out of equilibrium.

  7. Casimir force measurements from silicon carbide surfaces

    NASA Astrophysics Data System (ADS)

    Sedighi, M.; Svetovoy, V. B.; Palasantzas, G.

    2016-02-01

    Using an atomic force microscope we performed measurements of the Casimir force between a gold- coated (Au) microsphere and doped silicon carbide (SiC) samples. The last of these is a promising material for devices operating under severe environments. The roughness of the interacting surfaces was measured to obtain information for the minimum separation distance upon contact. Ellipsometry data for both systems were used to extract optical properties needed for the calculation of the Casimir force via the Lifshitz theory and for comparison to the experiment. Special attention is devoted to the separation of the electrostatic contribution to the measured total force. Our measurements demonstrate large contact potential V0(≈0.67 V ) , and a relatively small density of charges trapped in SiC. Knowledge of both Casimir and electrostatic forces between interacting materials is not only important from the fundamental point of view, but also for device applications involving actuating components at separations of less than 200 nm where surface forces play dominant role.

  8. The Distribution of Active Force Generators Controls Mitotic Spindle Position

    NASA Astrophysics Data System (ADS)

    Grill, Stephan W.; Howard, Jonathon; Schäffer, Erik; Stelzer, Ernst H. K.; Hyman, Anthony A.

    2003-07-01

    During unequal cell divisions a mitotic spindle is eccentrically positioned before cell cleavage. To determine the basis of the net force imbalance that causes spindle displacement in one-cell Caenorhabditis elegans embryos, we fragmented centrosomes with an ultraviolet laser. Analysis of the mean and variance of fragment speeds suggests that the force imbalance is due to a larger number of force generators pulling on astral microtubules of the posterior aster relative to the anterior aster. Moreover, activation of heterotrimeric guanine nucleotide-binding protein (G protein) α subunits is required to generate these astral forces.

  9. Melanin-binding radiopharmaceuticals

    SciTech Connect

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  10. Fundamental Dynamics of Black Hole Physics

    NASA Astrophysics Data System (ADS)

    Haramein, Nassim

    2002-04-01

    The dynamics of rotating, charged black holes, obeying the Kerr-Newman metric is presented. These dynamical high-density, gravitationally collapsing, black hole systems for stellar, galactic, intergalactic and cosmogenesis appear to obey similar constraints on their mass, apparent density and radius. Under these extreme conditions, the gravitational force becomes "balanced" with the larger coupling constant of the electromagnetic force. Thus, the gravitational attraction forms dynamic pseudo equilibrium with the plasma dynamics surrounding the black holes. Thermodynamic-type processes occupy a role in energy transfer between gravitational attraction and electro-dynamic repulsion. Solving the modified Einstein-Maxwell's equations under high magnetic field conditions, with additional thermodynamic conditions, leads to a good description of the processes occurring externally, near and in the event horizons of the Kerr-Newman geometry and leads to a unification possibility. Reference; N. Haramein, Bull. Amer. Phys. Soc. AB06, 1154(2001)

  11. The fundamentals of adaptive grid movement

    NASA Technical Reports Server (NTRS)

    Eiseman, Peter R.

    1990-01-01

    Basic grid point movement schemes are studied. The schemes are referred to as adaptive grids. Weight functions and equidistribution in one dimension are treated. The specification of coefficients in the linear weight, attraction to a given grid or a curve, and evolutionary forces are considered. Curve by curve and finite volume methods are described. The temporal coupling of partial differential equations solvers and grid generators was discussed.

  12. Coulomb force as an entropic force

    SciTech Connect

    Wang Tower

    2010-05-15

    Motivated by Verlinde's theory of entropic gravity, we give a tentative explanation to the Coulomb's law with an entropic force. When trying to do this, we find the equipartition rule should be extended to charges and the concept of temperature should be reinterpreted. If one accepts the holographic principle as well as our generalizations and reinterpretations, then Coulomb's law, the Poisson equation, and the Maxwell equations can be derived smoothly. Our attempt can be regarded as a new way to unify the electromagnetic force with gravity, from the entropic origin. Possibly some of our postulates are related to the D-brane picture of black hole thermodynamics.

  13. Coulomb force as an entropic force

    NASA Astrophysics Data System (ADS)

    Wang, Tower

    2010-05-01

    Motivated by Verlinde’s theory of entropic gravity, we give a tentative explanation to the Coulomb’s law with an entropic force. When trying to do this, we find the equipartition rule should be extended to charges and the concept of temperature should be reinterpreted. If one accepts the holographic principle as well as our generalizations and reinterpretations, then Coulomb’s law, the Poisson equation, and the Maxwell equations can be derived smoothly. Our attempt can be regarded as a new way to unify the electromagnetic force with gravity, from the entropic origin. Possibly some of our postulates are related to the D-brane picture of black hole thermodynamics.

  14. Microbial Cellulose Utilization: Fundamentals and Biotechnology

    PubMed Central

    Lynd, Lee R.; Weimer, Paul J.; van Zyl, Willem H.; Pretorius, Isak S.

    2002-01-01

    Fundamental features of microbial cellulose utilization are examined at successively higher levels of aggregation encompassing the structure and composition of cellulosic biomass, taxonomic diversity, cellulase enzyme systems, molecular biology of cellulase enzymes, physiology of cellulolytic microorganisms, ecological aspects of cellulase-degrading communities, and rate-limiting factors in nature. The methodological basis for studying microbial cellulose utilization is considered relative to quantification of cells and enzymes in the presence of solid substrates as well as apparatus and analysis for cellulose-grown continuous cultures. Quantitative description of cellulose hydrolysis is addressed with respect to adsorption of cellulase enzymes, rates of enzymatic hydrolysis, bioenergetics of microbial cellulose utilization, kinetics of microbial cellulose utilization, and contrasting features compared to soluble substrate kinetics. A biological perspective on processing cellulosic biomass is presented, including features of pretreated substrates and alternative process configurations. Organism development is considered for “consolidated bioprocessing” (CBP), in which the production of cellulolytic enzymes, hydrolysis of biomass, and fermentation of resulting sugars to desired products occur in one step. Two organism development strategies for CBP are examined: (i) improve product yield and tolerance in microorganisms able to utilize cellulose, or (ii) express a heterologous system for cellulose hydrolysis and utilization in microorganisms that exhibit high product yield and tolerance. A concluding discussion identifies unresolved issues pertaining to microbial cellulose utilization, suggests approaches by which such issues might be resolved, and contrasts a microbially oriented cellulose hydrolysis paradigm to the more conventional enzymatically oriented paradigm in both fundamental and applied contexts. PMID:12209002

  15. Microbial cellulose utilization: fundamentals and biotechnology.

    PubMed

    Lynd, Lee R; Weimer, Paul J; van Zyl, Willem H; Pretorius, Isak S

    2002-09-01

    Fundamental features of microbial cellulose utilization are examined at successively higher levels of aggregation encompassing the structure and composition of cellulosic biomass, taxonomic diversity, cellulase enzyme systems, molecular biology of cellulase enzymes, physiology of cellulolytic microorganisms, ecological aspects of cellulase-degrading communities, and rate-limiting factors in nature. The methodological basis for studying microbial cellulose utilization is considered relative to quantification of cells and enzymes in the presence of solid substrates as well as apparatus and analysis for cellulose-grown continuous cultures. Quantitative description of cellulose hydrolysis is addressed with respect to adsorption of cellulase enzymes, rates of enzymatic hydrolysis, bioenergetics of microbial cellulose utilization, kinetics of microbial cellulose utilization, and contrasting features compared to soluble substrate kinetics. A biological perspective on processing cellulosic biomass is presented, including features of pretreated substrates and alternative process configurations. Organism development is considered for "consolidated bioprocessing" (CBP), in which the production of cellulolytic enzymes, hydrolysis of biomass, and fermentation of resulting sugars to desired products occur in one step. Two organism development strategies for CBP are examined: (i) improve product yield and tolerance in microorganisms able to utilize cellulose, or (ii) express a heterologous system for cellulose hydrolysis and utilization in microorganisms that exhibit high product yield and tolerance. A concluding discussion identifies unresolved issues pertaining to microbial cellulose utilization, suggests approaches by which such issues might be resolved, and contrasts a microbially oriented cellulose hydrolysis paradigm to the more conventional enzymatically oriented paradigm in both fundamental and applied contexts.

  16. Fundamental studies of supported bimetallic catalysts by NMR spectroscopy

    SciTech Connect

    Savargaonkar, N.

    1996-10-17

    Various hydrogenation reactions on transition metals are important commercially whereas certain hydrogenolysis reactions are useful from fundamental point of view. Understanding the hydrogen mobility and kinetics of adsorption-desorption of hydrogen is important in understanding the mechanisms of such reactions involving hydrogen. The kinetics of hydrogen chemisorption was studied by means of selective excitation NMR on silica supported Pt, Rh and Pt-Rh catalysts. The activation energy of hydrogen desorption was found to be lower on silica supported Pt catalysts as compared to Rh and Pt-Rh catalysts. It was found that the rates of hydrogen adsorption and desorption on Pt-Rh catalyst were similar to those on Rh catalyst and much higher as compared to Pt catalyst. The Ru-Ag bimetallic system is much simpler to study than the Pt-Rh system and serves as a model system to characterize more complicated systems such as the K/Ru system. Ag was found to decrease the amounts of adsorbed hydrogen and the hydrogen-to-ruthenium stoichiometry. Ag reduced the populations of states with low and intermediate binding energies of hydrogen on silica supported Ru catalyst. The rates of hydrogen adsorption and desorption were also lower on silica supported Ru-Ag catalyst as compared to Ru catalyst. This report contains introductory information, the literature review, general conclusions, and four appendices. An additional four chapters and one appendix have been processed separately for inclusion on the data base.

  17. Nanoparticles for Biomedical Imaging: Fundamentals of Clinical Translation

    PubMed Central

    Choi, Hak Soo; Frangioni, John V.

    2010-01-01

    Because of their large size compared to small molecules, and their multi-functionality, nanoparticles (NPs) hold promise as biomedical imaging, diagnostic, and theragnostic agents. However, the key to their success hinges on a detailed understanding of their behavior after administration into the body. NP biodistribution, target binding, and clearance are a complex function of their physicochemical properties in serum, which include hydrodynamic diameter, solubility, stability, shape and flexibility, surface charge, composition, and formulation. Moreover, many materials used to construct NPs have real or potential toxicity, or may interfere with other medical tests. In this review, we discuss the design considerations that mediate NP behavior in the body and the fundamental principles that govern clinical translation. By analyzing those nanomaterials that have already received regulatory approval, most of which are actually therapeutic agents, we attempt to predict which types of NPs hold potential as diagnostic agents for biomedical imaging. Finally, using quantum dots as an example, we provide a framework for deciding whether an NP-based agent is the best choice for a particular clinical application. PMID:21084027

  18. Quantum Fictitious Forces

    NASA Astrophysics Data System (ADS)

    Białynicki-Birula, I.; Cirone, M. A.; Dahl, J. P.; Seligman, T. H.; Straub, F.; Schleich, W. P.

    2003-09-01

    We present Heisenberg's equation of motion for the radial variable of a free non-relativistic particle in D dimensions. The resulting radial force consists of three contributions: (i) the quantum fictitious force which is either attractive or repulsive depending on the number of dimensions, (ii) a singular quantum force located at the origin, and (iii) the centrifugal force associated with non-vanishing angular momentum. Moreover, we use Heisenberg's uncertainty relation to introduce a lower bound for the kinetic energy of an ensemble of neutral particles. This bound is quadratic in the number of atoms and can be traced back to the repulsive quantum fictitious potential. All three forces arise for a free particle: “Force without force”.

  19. Relativistic Linear Restoring Force

    ERIC Educational Resources Information Center

    Clark, D.; Franklin, J.; Mann, N.

    2012-01-01

    We consider two different forms for a relativistic version of a linear restoring force. The pair comes from taking Hooke's law to be the force appearing on the right-hand side of the relativistic expressions: d"p"/d"t" or d"p"/d["tau"]. Either formulation recovers Hooke's law in the non-relativistic limit. In addition to these two forces, we…

  20. Debunking Coriolis Force Myths

    NASA Astrophysics Data System (ADS)

    Shakur, Asif

    2014-11-01

    Much has been written and debated about the Coriolis force.1-8 Unfortunately, this has done little to demystify the paradoxes surrounding this fictitious force invoked by an observer in a rotating frame of reference. It is the purpose of this article to make another valiant attempt to slay the dragon of the Coriolis force! This will be done without unleashing the usual mathematical apparatus, which we believe is more of a hindrance than a help.

  1. Opposites attract: a theorem about the Casimir Force.

    PubMed

    Kenneth, Oded; Klich, Israel

    2006-10-20

    We consider the Casimir interaction between (nonmagnetic) dielectric bodies or conductors. Our main result is a proof that the Casimir force between two bodies related by reflection is always attractive, independent of the exact form of the bodies or dielectric properties. Apart from being a fundamental property of fields, the theorem and its corollaries also rule out a class of suggestions to obtain repulsive forces, such as the two hemisphere repulsion suggestion and its relatives.

  2. Electrodynamic force law controversy.

    PubMed

    Graneau, P; Graneau, N

    2001-05-01

    Cavalleri et al. [Phys. Rev. E 52, 2505 (1998); Eur. J. Phys. 17, 205 (1996)] have attempted to resolve the electrodynamic force law controversy. This attempt to prove the validity of either the Ampère or Lorentz force law by theory and experiment has revealed only that the two are equivalent when predicting the force on part of a circuit due to the current in the complete circuit. However, in our analysis of internal stresses, only Ampère's force law agrees with experiment. PMID:11415053

  3. Fundamental Complex Plasma Research on Ground and under Microgravity Conditions

    NASA Astrophysics Data System (ADS)

    Thomas, Hubertus; Fortov, Vladimir; Thoma, Markus; Pustylnik, Mikhail; Lipaev, Andrey; Morfill, Gregor; Molotkov, Vladimir; Usachev, Alexander; Nosenko, Vladimir; Fink, Martin; Petrov, Oleg; Rubin-Zuzic, Milenko

    2016-07-01

    Complex (dusty) plasma is plasma containing small solid particles in the sub-mm range. Those "dust" particles are highly charged due to the collection of electrons and ions and they interact electrostatically. Depending on the charge, density, and kinetic temperature of the particles, the interaction may be strong leading to collective effects and the emergence of liquid or solid behavior. In that sense complex plasmas are perfect model systems for the investigation of fundamental processes in classical condensed matter physics since their constituent mesoscopic particles are individually observable and can be regarded as classically interacting "proxy atoms". The term "complex plasmas" is widely used in the literature to distinguish dusty plasmas composed of a weakly ionized gas and charged microparticles specially "designed" for investigations in classical condensed matter, from naturally occurring systems. Gravity influences the complex plasma, the microparticles sediment and stable systems can only be achieved through counteracting gravity with other volume forces, e.g. electric or thermophoretic force. This allows producing two-dimensional - monolayer - systems, or three-dimensional systems under stress. Only under weightlessness conditions, large and homogeneous 3D systems can be formed. Although phenomena in classical condensed matter physics are in the forefront of complex plasma research the basic know-how gained from experiments, theory and numerical simulations can be of importance for the understanding of naturally occurring dusty plasmas in space. Thus, in this presentation I will show recent work on complex plasmas from the ground and first results from the PK-4 facility onboard the International Space Station ISS. Acknowledgements: We would like to acknowledge the joint ESA-ROSCOSMOS Experiment «Plasma Kristall-4» onboard the International Space Station ISS. This work is partly supported by DLR grant 50WM1441/ 50WM1442 and by the Russian Science

  4. A Newtonian interpretation of configurational forces on dislocations and cracks

    NASA Astrophysics Data System (ADS)

    Ballarini, Roberto; Royer-Carfagni, Gianni

    2016-10-01

    Configurational forces are fundamental concepts in the description of the motion of dislocations, cracks and other defects that introduce singularities within the solid state. They are defined by considering variations in energies associated with the movement of such defects, and are therefore different from the classical forces that enter the balance laws of classical Newtonian mechanics. Here, it is demonstrated how a configurational force can be viewed as the resultant of the (Newtonian) contact forces acting on the perturbed shape of an object of substance equivalent to the defect, and evaluated in the limit of the shape being restored to the primitive configuration. The expressions for the configurational forces on the paradigmatic examples of cracks and dislocations are in agreement with those determined using classical variational arguments. This finding opens a new prospective in the use of configurational forces by permitting their physical and intuitive visualization.

  5. Investigating the Binding of Peptides to Graphene Surfaces for Biosensing Applications

    NASA Astrophysics Data System (ADS)

    Garley, Amanda; Saikia, Nabanita; Barr, Stephen; Leuty, Gary; Berry, Rajiv; Heinz, Hendrik

    The Air Force Research Lab is focused on developing highly selective and sensitive graphene-based sensors functionalized with peptides for biomolecule detection. To achieve this there is a need to model interfacial binding interactions between the organic and inorganic components to complement ongoing experimental investigations. It is important to characterize the binding behavior of individual amino acids, with the goal of predicting binding of large peptides. Since polarization is important in graphene systems, a new force field which includes polarizability is used. This allows for an in depth exploration of pi-pi interactions, electrostatics and van der Waals forces involved with binding. The binding strength is determined via enthalpy and free energy calculations. Additionally, structural quantities are computed, such as how aromatic rings align with the graphene surface and the arrangement of various residue substituents in relation to the surface and water layers. Computational results are useful in guiding experimental methods focused on rapidly screening optimal peptide sequence for binding.

  6. Crude oil prices: Speculation versus fundamentals

    NASA Astrophysics Data System (ADS)

    Kolodziej, Marek Krzysztof

    Beginning in 2004, the price of crude oil fluctuates rapidly over a wide range. Large and rapid price increases have recessionary consequences and dampen long-term infrastructural investment. I investigate whether price changes are driven by market fundamentals or speculation. With regard to market fundamentals, I revisit econometric evidence for the importance of demand shocks, as proxied by dry maritime cargo rates, on oil prices. When I eliminate transportation costs from both sides of the equation, disaggregate OPEC and non-OPEC production, and allow for more than one cointegrating relation, I find that previous specifications are inconsistent with arguments that demand shocks play an important role. Instead, results confirm the importance of OPEC supply shocks. I investigate two channels by which speculation may affect oil prices; the direct effect of trader behavior and changes in oil from a commodity to a financial asset. With regard to trader behavior, I find evidence that trader positions are required to explain the spread between spot and futures prices of crude oil on the New York Mercantile Exchange. The inclusion of trader positions clarifies the process of equilibrium error correction, such that there is bidirectional causality between prices and trader positions. This creates the possibility of speculative bubbles. With regard to oil as a commodity and/or financial asset, I use a Kalman Filter model to estimate the time-varying partial correlation between returns to investments in equity and oil markets. This correlation changes from negative to positive at the onset of the 2008 financial crisis. The low interest rates used to rescue the economy depress convenience yields, which reduces the benefits of holding oil as a commodity. Instead, oil becomes a financial asset (on net) as the oil market changed from contango to backwardation. Contradicting simple political narratives, my research suggests that both market fundamentals and speculation drive

  7. Fundamentals of Physics, Part 1 (Chapters 1-11)

    NASA Astrophysics Data System (ADS)

    Halliday, David; Resnick, Robert; Walker, Jearl

    2003-12-01

    . 10-8 Torque. 10-9 Newton's Second Law for Rotation. 10-10 Work and Rotational Kinetic Energy. Review & Summary. Questions. Problems. Chapter 11.Rolling, Torque, and Angular Momentum. When a jet-powered car became supersonic in setting the land-speed record, what was the danger to the wheels? 11-1 What Is Physics? 11-2 Rolling as Translation and Rotation Combined. 11-3 The Kinetic Energy of Rolling. 11-4 The Forces of Rolling. 11-5 The Yo-Yo. 11-6 Torque Revisited. 11-7 Angular Momentum. 11-8 Newton's Second Law in Angular Form. 11-9 The Angular Momentum of a System of Particles. 11-10 The Angular Momentum of a Rigid Body Rotating About a Fixed Axis. 11-11 Conservation of Angular Momentum. 11-12 Precession of a Gyroscope. Review & Summary. Questions. Problems. Appendix A: The International System of Units (SI). Appendix B: Some Fundamental Constants of Physics. Appendix C: Some Astronomical Data. Appendix D: Conversion Factors. Appendix E: Mathematical Formulas. Appendix F: Properties of the Elements. Appendix G: Periodic Table of the Elements. Answers to Checkpoints and Odd-Numbered Questions and Problems. Index.

  8. Climate forcings and feedbacks

    NASA Technical Reports Server (NTRS)

    Hansen, James

    1993-01-01

    Global temperature has increased significantly during the past century. Understanding the causes of observed global temperature change is impossible in the absence of adequate monitoring of changes in global climate forcings and radiative feedbacks. Climate forcings are changes imposed on the planet's energy balance, such as change of incoming sunlight or a human-induced change of surface properties due to deforestation. Radiative feedbacks are radiative changes induced by climate change, such as alteration of cloud properties or the extent of sea ice. Monitoring of global climate forcings and feedbacks, if sufficiently precise and long-term, can provide a very strong constraint on interpretation of observed temperature change. Such monitoring is essential to eliminate uncertainties about the relative importance of various climate change mechanisms including tropospheric sulfate aerosols from burning of coal and oil smoke from slash and burn agriculture, changes of solar irradiance changes of several greenhouse gases, and many other mechanisms. The considerable variability of observed temperature, together with evidence that a substantial portion of this variability is unforced indicates that observations of climate forcings and feedbacks must be continued for decades. Since the climate system responds to the time integral of the forcing, a further requirement is that the observations be carried out continuously. However, precise observations of forcings and feedbacks will also be able to provide valuable conclusions on shorter time scales. For example, knowledge of the climate forcing by increasing CFC's relative to the forcing by changing ozone is important to policymakers, as is information on the forcing by CO2 relative to the forcing by sulfate aerosols. It will also be possible to obtain valuable tests of climate models on short time scales, if there is precise monitoring of all forcings and feedbacks during and after events such as a large volcanic eruption

  9. Loudness predicts prominence: Fundamental frequency lends little

    NASA Astrophysics Data System (ADS)

    Kochanski, G.; Grabe, E.; Coleman, J.; Rosner, B.

    2005-08-01

    We explored a database covering seven dialects of British and Irish English and three different styles of speech to find acoustic correlates of prominence. We built classifiers, trained the classifiers on human prominence/nonprominence judgments, and then evaluated how well they behaved. The classifiers operate on 452 ms windows centered on syllables, using different acoustic measures. By comparing the performance of classifiers based on different measures, we can learn how prominence is expressed in speech. Contrary to textbooks and common assumption, fundamental frequency (f0) played a minor role in distinguishing prominent syllables from the rest of the utterance. Instead, speakers primarily marked prominence with patterns of loudness and duration. Two other acoustic measures that we examined also played a minor role, comparable to f0. All dialects and speaking styles studied here share a common definition of prominence. The result is robust to differences in labeling practice and the dialect of the labeler.

  10. Fundamental Considerations Of Gas Core Reactor Systems

    NASA Astrophysics Data System (ADS)

    Bussard, Robert W.

    1988-04-01

    Fundamental physics and engineering limitations on gas core reactors (GCR) have been found from coupled effects of reactor neutronics with oscillatory core fuel gas flows and with overall gas dynamics. These show allowable regimes for system operation as natural re-sults of the basiciphysics of the system. Cylindrical BeO-moderated systems, such as the acoustic GCR (AGCR ), are found to be well-suited for pressure wave oscillation at 100-Hz frequencies. These result in stable oscillations of core gas electrical conductivity which may be used for direct alternating current electric power production in magnetohydrodynamic (MHD) convertors. In contrast, single-cavity axial-flow spherical GCR (SGCR2) systems are inherently limited by core flow and fission energy-generation fluctuation phenomena (to continuous wave operation with mixed flows that cannot sustain high internal core gas tempera-ture gradients. Resulting low mixed-mean temperatures place upper limits on system MHD electrical performance.

  11. [Fundamental ophthalmology: the role of electrophysiological studies].

    PubMed

    Zueva, M V

    2014-01-01

    Studying of functional aspects of eye disease pathogenesis by electrophysiological methods is widely demanded in fundamental ophthalmology. Introduction of modern methods of functional assessment into experimental and clinical projects significantly broadens knowledge of normal and pathological functioning of the visual system and is the basis for further development of new strategies of pathogenetic treatment, diagnostics and expert evaluation. Some problems of ophthalmology, including those that concern age-related macular degeneration, glaucoma, diabetic retinopathy, and other diseases, are considered in the context of how much electrophysiology contributes to their solution. The role of functional examinations of the retina in studying pathophysiology of neurodegenerative brain diseases, such as Alzheimer's and Parkinson's, is also discussed. PMID:25715550

  12. Fundamental Constants and Tests with Simple Atoms

    NASA Astrophysics Data System (ADS)

    Tan, Joseph

    2015-05-01

    Precise measurements with simple atoms provide stringent tests of physical laws, improving the accuracy of fundamental constants--a set of which will be selected to fully define the proposed New International System of Units. This talk focuses on the atomic constants (namely, the Rydberg constant, the fine-structure constant, and the proton charge radius), discussing the impact of the proton radius obtained from the Lamb-shift measurements in muonic hydrogen. Significant discrepancies persist despite years of careful examination: the slightly smaller proton radius obtained from muonic hydrogen requires the Rydberg constant and the fine-structure constant to have values that disagree significantly with the CODATA recommendations. After giving a general overview, I will discuss our effort to produce one-electron ions in Rydberg states, to enable a different test of theory and measurement of the Rydberg constant.

  13. The fundamental non-critical string

    NASA Astrophysics Data System (ADS)

    Lugo, Adrián R.; Sturla, Mauricio B.

    2006-06-01

    We obtain the (super) gravity solution in arbitrary space-time dimension less than ten, that gives a low energy description of a fundamental string embedded in a non-critical vacuum, product of d-dimensional Minkowski space-time and a cigar-like geometry with scale r0. This solution, one of the few known examples of objects doubly localized, both at the origin of the transverse space as well as at the tip of the cigar, is determined by its charge Q under the Kalb-Ramond gauge field B, and presumably preserves, for even d, 2 d/2 supercharges. Moreover, we show that the solution is reliable at least in a region far away from both origins, as it is the case with the well known branes of critical string theory.

  14. Fundamental physics of infrared detector materials

    NASA Astrophysics Data System (ADS)

    Kinch, Michael A.

    2001-06-01

    The fundamental parameters of IR photon detection are discussed relevant to the meaningful comparison of a wide range of proposed IR detecting materials systems. The thermal generation rate of the IR material is seen to be the key parameter that enables this comparison. The simple materials physics of (1) intrinsic direct bandgap semiconductors, (2) extrinsic semiconductors, (3) quantum well devices, including types I, II, and III superlattices, (4) Si Schottky barriers, are examined with regard to the potential performance of these materials as IR detectors, utilizing the thermal generation rate as a differentiator. The possibility of room temperature photon detection over the whole IR spectral range is discussed, and comparison made with uncooled thermal detection.

  15. Fundamental physics of infrared detector materials

    NASA Astrophysics Data System (ADS)

    Kinch, Michael A.

    2000-06-01

    The fundamental parameters of IR photon detection are discussed relevant to the meaningful comparison of a wide range of proposed IR detecting materials systems. The thermal generation rate of the IR material is seen to be the key parameter that enables this comparison. The simple materials physics of 1) intrinsic direct bandgap semiconductors; 2) extrinsic semiconductors; 3) quantum well devices, including types I, II, and III superlattices; 4) Si Schottky barriers; and 5) high temperature superconductors, will be examined with regard to the potential performance of these materials as IR detectors, utilizing the thermal generation rate as a differentiator. The possibility of room temperature photon detection over the whole IR spectral range is discussed, and comparisons made with uncooled thermal detection.

  16. Future fundamental combustion research for aeropropulsion systems

    NASA Technical Reports Server (NTRS)

    Mularz, E. J.

    1985-01-01

    Physical fluid mechanics, heat transfer, and chemical kinetic processes which occur in the combustion chamber of aeropropulsion systems were investigated. With the component requirements becoming more severe for future engines, the current design methodology needs the new tools to obtain the optimum configuration in a reasonable design and development cycle. Research efforts in the last few years were encouraging but to achieve these benefits research is required into the fundamental aerothermodynamic processes of combustion. It is recommended that research continues in the areas of flame stabilization, combustor aerodynamics, heat transfer, multiphase flow and atomization, turbulent reacting flows, and chemical kinetics. Associated with each of these engineering sciences is the need for research into computational methods to accurately describe and predict these complex physical processes. Research needs in each of these areas are highlighted.

  17. Fundamental Fluidization Research Project. Environmental Assessment

    SciTech Connect

    Not Available

    1994-01-01

    Morgantown Energy Technology Center proposes to conduct fundamental research on fluidization technology by designing, constructing, and operating a 2-foot diameter, 50-foot high, pressurized fluidized-bed unit. The anticipated result of the proposed project would be a better, understanding of fluidization phenomena under pressurized and high velocity conditions. This improved understanding would, provide a sound basis for design and scale-up of pressurized circulating fluidized-bed combustion (PCFBC) processes for fossil energy applications. Based on the analysis in the EA, DOE has determined that the proposed action is not a major, Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, the preparation of an Environmental Impact Statement is not required and the Department is issuing this FONSI.

  18. Sperm preservation: Fundamental cryobiology and practical implications

    SciTech Connect

    Watson, P.F. ); Critser, J.K. ); Mazur, P. )

    1992-01-01

    Human spermatozoa were first frozen successfully almost 40 years ago. While developments in packaging and storing have occurred in the intervening period, there is still little known specifically about how spermatozoa are adversely affected by freezing and thawing. This is largely due to the fact that sufficient cells survive the challenge to give a reasonable expectation of fertilization, but the shift to the exclusive use of cryopreserved semen for donor insemination, occasioned by the awareness of the risks particularly of AIDS transmission, has resulted in a renewed critical interest in the process of cryopreservation. This review will cover the more significant contributions over the past few years, and develop an argument for a sustained fundamental approach to sperm cryobiology.

  19. Sperm preservation: Fundamental cryobiology and practical implications

    SciTech Connect

    Watson, P.F.; Critser, J.K.; Mazur, P.

    1992-07-01

    Human spermatozoa were first frozen successfully almost 40 years ago. While developments in packaging and storing have occurred in the intervening period, there is still little known specifically about how spermatozoa are adversely affected by freezing and thawing. This is largely due to the fact that sufficient cells survive the challenge to give a reasonable expectation of fertilization, but the shift to the exclusive use of cryopreserved semen for donor insemination, occasioned by the awareness of the risks particularly of AIDS transmission, has resulted in a renewed critical interest in the process of cryopreservation. This review will cover the more significant contributions over the past few years, and develop an argument for a sustained fundamental approach to sperm cryobiology.

  20. Fundamental aspects of quantum Brownian motion

    SciTech Connect

    Haenggi, Peter; Ingold, Gert-Ludwig

    2005-06-01

    With this work we elaborate on the physics of quantum noise in thermal equilibrium and in stationary nonequilibrium. Starting out from the celebrated quantum fluctuation-dissipation theorem we discuss some important consequences that must hold for open, dissipative quantum systems in thermal equilibrium. The issue of quantum dissipation is exemplified with the fundamental problem of a damped harmonic quantum oscillator. The role of quantum fluctuations is discussed in the context of both, the nonlinear generalized quantum Langevin equation and the path integral approach. We discuss the consequences of the time-reversal symmetry for an open dissipative quantum dynamics and, furthermore, point to a series of subtleties and possible pitfalls. The path integral methodology is applied to the decay of metastable states assisted by quantum Brownian noise.

  1. Two Fundamental Principles of Nature's Interactions

    NASA Astrophysics Data System (ADS)

    Ma, Tian; Wang, Shouhong

    2014-03-01

    In this talk, we present two fundamental principles of nature's interactions, the principle of interaction dynamics (PID) and the principle of representation invariance (PRI). Intuitively, PID takes the variation of the action functional under energy-momentum conservation constraint. PID offers a completely different and natural way of introducing Higgs fields. PRI requires that physical laws be independent of representations of the gauge groups. These two principles give rise to a unified field model for four interactions, which can be naturally decoupled to study individual interactions. With these two principles, we are able to derive 1) a unified theory for dark matter and dark energy, 2) layered strong and weak interaction potentials, and 3) the energy levels of subatomic particles. Supported in part by NSF, ONR and Chinese NSF.

  2. Constraining fundamental physics with future CMB experiments

    SciTech Connect

    Galli, Silvia; Martinelli, Matteo; Melchiorri, Alessandro; Pagano, Luca; Sherwin, Blake D.; Spergel, David N.

    2010-12-15

    The Planck experiment will soon provide a very accurate measurement of cosmic microwave background anisotropies. This will let cosmologists determine most of the cosmological parameters with unprecedented accuracy. Future experiments will improve and complement the Planck data with better angular resolution and better polarization sensitivity. This unexplored region of the CMB power spectrum contains information on many parameters of interest, including neutrino mass, the number of relativistic particles at recombination, the primordial helium abundance, and the injection of additional ionizing photons by dark matter self-annihilation. We review the imprint of each parameter on the CMB and forecast the constraints achievable by future experiments by performing a Monte Carlo analysis on synthetic realizations of simulated data. We find that next generation satellite missions such as CMBPol could provide valuable constraints with a precision close to that expected in current and near future laboratory experiments. Finally, we discuss the implications of this intersection between cosmology and fundamental physics.

  3. k-strings as fundamental strings

    NASA Astrophysics Data System (ADS)

    Giataganas, Dimitrios

    2015-05-01

    It has been noticed that the k-string observables can be expressed in terms of the fundamental string ones. We identify a sufficient condition for a generic gravity dual background which when satisfied the mapping can be done. The condition is naturally related to a preserved quantity under the T-dualities acting on the Dp-brane describing the high representation Wilson loops. We also find the explicit relation between the observables of the heavy k-quark and the single quark states. As an application to our generic study and motivated by the fact that the anisotropic theories satisfy our condition, we compute the width of the k-string in these theories to find that the logarithmic broadening is still present, but the total result is affected by the anisotropy of the space.

  4. Fundamentals of natural computing: an overview

    NASA Astrophysics Data System (ADS)

    de Castro, Leandro Nunes

    2007-03-01

    Natural computing is a terminology introduced to encompass three classes of methods: (1) those that take inspiration from nature for the development of novel problem-solving techniques; (2) those that are based on the use of computers to synthesize natural phenomena; and (3) those that employ natural materials (e.g., molecules) to compute. The main fields of research that compose these three branches are the artificial neural networks, evolutionary algorithms, swarm intelligence, artificial immune systems, fractal geometry, artificial life, DNA computing, and quantum computing, among others. This paper provides an overview of the fundamentals of natural computing, particularly the fields listed above, emphasizing the biological motivation, some design principles, their scope of applications, current research trends and open problems. The presentation is concluded with a discussion about natural computing, and when it should be used.

  5. Fundamentals of tribology at the atomic level

    NASA Technical Reports Server (NTRS)

    Ferrante, John; Pepper, Stephen V.

    1989-01-01

    Tribology, the science and engineering of solid surfaces in moving contact, is a field that encompasses many disciplines: solid state physics, chemistry, materials science, and mechanical engineering. In spite of the practical importance and maturity of the field, the fundamental understanding of basic phenomena has only recently been attacked. An attempt to define some of these problems and indicate some profitable directions for future research is presented. There are three broad classifications: (1) fluid properties (compression, rheology, additives and particulates); (2) material properties of the solids (deformation, defect formation and energy loss mechanisms); and (3) interfacial properties (adhesion, friction chemical reactions, and boundary films). Research in the categories has traditionally been approached by considering macroscopic material properties. Recent activity has shown that some issues can be approached at the atomic level: the atoms in the materials can be manipulated both experimentally and theoretically, and can produce results related to macroscopic phenomena.

  6. Photoacoustic tomography: fundamentals, advances and prospects

    PubMed Central

    Yao, Junjie; Wang, Lihong V.

    2011-01-01

    Optical microscopy has been contributing to the development of life science for more than three centuries. However, due to strong optical scattering in tissue, its in vivo imaging ability has been restricted to studies at superficial depths. Advances in photoacoustic tomography (PAT) now allow multiscale imaging at depths from sub-millimeter to several centimeters, with spatial resolutions from sub-micrometer to sub-millimeter. Because of this high scalability and its unique optical absorption contrast, PAT is capable of performing anatomical, functional, molecular and fluid-dynamic imaging at various system levels, and is playing an increasingly important role in fundamental biological research and clinical practice. This Review discusses recent technical progress in PAT and presents corresponding applications. It ends with a discussion of several prospects and their technical challenges. PMID:22025335

  7. Fundamentals and applications of gas hydrates.

    PubMed

    Koh, Carolyn A; Sloan, E Dendy; Sum, Amadeu K; Wu, David T

    2011-01-01

    Fundamental understanding of gas hydrate formation and decomposition processes is critical in many energy and environmental areas and has special importance in flow assurance for the oil and gas industry. These areas represent the core of gas hydrate applications, which, albeit widely studied, are still developing as growing fields of research. Discovering the molecular pathways and chemical and physical concepts underlying gas hydrate formation potentially can lead us beyond flowline blockage prevention strategies toward advancing new technological solutions for fuel storage and transportation, safely producing a new energy resource from natural deposits of gas hydrates in oceanic and arctic sediments, and potentially facilitating effective desalination of seawater. The state of the art in gas hydrate research is leading us to new understanding of formation and dissociation phenomena that focuses on measurement and modeling of time-dependent properties of gas hydrates on the basis of their well-established thermodynamic properties.

  8. Magnetic skyrmions: from fundamental to applications

    NASA Astrophysics Data System (ADS)

    Finocchio, Giovanni; Büttner, Felix; Tomasello, Riccardo; Carpentieri, Mario; Kläui, Mathias

    2016-10-01

    In this topical review, we will discuss recent advances in the field of skyrmionics (fundamental and applied aspects) mainly focusing on skyrmions that can be realized in thin film structures where an ultrathin ferromagnetic layer (<1 nm) is coupled to materials with large spin-orbit coupling. We review the basic topological nature of the skyrmion spin structure that can entail a stabilization due to the chiral exchange interaction present in many multilayer systems with structural inversion asymmetry. The static spin structures and the dynamics of the skyrmions are also discussed. In particular, we show that skyrmions can be displaced with high reliability and efficiency as needed for the use in devices. We discuss major possible applications, such as memory, microwave oscillators and logic, and combinations of these, making skyrmions very promising candidates for future low power IT devices.

  9. Fundamentals of Digital Engineering: Designing for Reliability

    NASA Technical Reports Server (NTRS)

    Katz, R.; Day, John H. (Technical Monitor)

    2001-01-01

    The concept of designing for reliability will be introduced along with a brief overview of reliability, redundancy and traditional methods of fault tolerance is presented, as applied to current logic devices. The fundamentals of advanced circuit design and analysis techniques will be the primary focus. The introduction will cover the definitions of key device parameters and how analysis is used to prove circuit correctness. Basic design techniques such as synchronous vs asynchronous design, metastable state resolution time/arbiter design, and finite state machine structure/implementation will be reviewed. Advanced topics will be explored such as skew-tolerant circuit design, the use of triple-modular redundancy and circuit hazards, device transients and preventative circuit design, lock-up states in finite state machines generated by logic synthesizers, device transient characteristics, radiation mitigation techniques. worst-case analysis, the use of timing analyzer and simulators, and others. Case studies and lessons learned from spaceflight designs will be given as examples

  10. Fundamentals of ergonomics in theory and practice.

    PubMed

    Wilson, J R

    2000-12-01

    In this paper ergonomics is defined as a discipline in its own right, as the theoretical and fundamental understanding of human behaviour and performance in purposeful interacting socio-technical systems, and the application of that understanding to design of interactions in the context of real settings. This definition is justified in the financial, technicat, legal, organisational, social, political and professional contexts in which ergonomists work. On the basis of the history of ergonomics and contemporary contributions, it is proposed that it is one of the modern sciences, drawing as much from the field as from the laboratory, and including elements of an art and a craft as well. Justification for the new definition is provided by examining the interacting systems which are prevalent in the modern world and which are the domain best understood through the holistic approach of ergonomics. Finally a number of challenges for ergonomics are identified. PMID:11132041

  11. Fundamentals and applications of gas hydrates.

    PubMed

    Koh, Carolyn A; Sloan, E Dendy; Sum, Amadeu K; Wu, David T

    2011-01-01

    Fundamental understanding of gas hydrate formation and decomposition processes is critical in many energy and environmental areas and has special importance in flow assurance for the oil and gas industry. These areas represent the core of gas hydrate applications, which, albeit widely studied, are still developing as growing fields of research. Discovering the molecular pathways and chemical and physical concepts underlying gas hydrate formation potentially can lead us beyond flowline blockage prevention strategies toward advancing new technological solutions for fuel storage and transportation, safely producing a new energy resource from natural deposits of gas hydrates in oceanic and arctic sediments, and potentially facilitating effective desalination of seawater. The state of the art in gas hydrate research is leading us to new understanding of formation and dissociation phenomena that focuses on measurement and modeling of time-dependent properties of gas hydrates on the basis of their well-established thermodynamic properties. PMID:22432618

  12. Fundamentals of bipolar high-frequency surgery.

    PubMed

    Reidenbach, H D

    1993-04-01

    In endoscopic surgery a very precise surgical dissection technique and an efficient hemostasis are of decisive importance. The bipolar technique may be regarded as a method which satisfies both requirements, especially regarding a high safety standard in application. In this context the biophysical and technical fundamentals of this method, which have been known in principle for a long time, are described with regard to the special demands of a newly developed field of modern surgery. After classification of this method into a general and a quasi-bipolar mode, various technological solutions of specific bipolar probes, in a strict and in a generalized sense, are characterized in terms of indication. Experimental results obtained with different bipolar instruments and probes are given. The application of modern microprocessor-controlled high-frequency surgery equipment and, wherever necessary, the integration of additional ancillary technology into the specialized bipolar instruments may result in most useful and efficient tools of a key technology in endoscopic surgery.

  13. The search for the hydrophobic force law.

    PubMed

    Hammer, Malte U; Anderson, Travers H; Chaimovich, Aviel; Shell, M Scott; Israelachvili, Jacob

    2010-01-01

    After nearly 30 years of research on the hydrophobic interaction, the search for the hydrophobic force law is still continuing. Indeed, there are more questions than answers, and the experimental data are often quite different for nominally similar conditions, as well as, apparently, for nano-, micro-, and macroscopic surfaces. This has led to the conclusion that the experimentally observed force-distance relationships are either a combination of different 'fundamental' interactions, or that the hydrophobic force-law, if there is one, is complex--depending on numerous parameters. The only unexpectedly strong attractive force measured in all experiments so far has a range of D approximately 100-200 angstroms, increasing roughly exponentially down to approximately 10-20 angstroms and then more steeply down to adhesive contact at D = 0 or, for power-law potentials, effectively at D approximately 2 angstroms. The measured forces in this regime (100-200 angstroms) and especially the adhesive forces are much stronger, and have a different distance-dependence from the continuum VDW force (Lifshitz theory) for non-conducting dielectric media. We suggest a three-regime force-law for the forces observed between hydrophobic surfaces: In the first, from 100-200 angstroms to thousands of angstroms, the dominating force is created by complementary electrostatic domains or patches on the apposing surfaces and/or bridging vapour cavities; a 'pure' but still not well-understood 'long-range hydrophobic force' dominates the second regime from approximately 150 to approximately 15 angstroms, possibly due to an enhanced Hamaker constant associated with the 'proton-hopping' polarizability of water; while below approximately 10-15 anstroms to contact there is another 'pure short-range hydrophobic force' related to water structuring effects associated with surface-induced changes in the orientation and/or density of water molecules and H-bonds at the water-hydrophobic interface. We

  14. Universal aspects of adhesion and atomic force microscopy

    NASA Technical Reports Server (NTRS)

    Banerjea, Amitava; Smith, John R.; Ferrante, John

    1990-01-01

    Adhesive energies are computed for flat and atomically sharp tips as a function of the normal distance to the substrate. The dependence of binding energies on tip shape is investigated. The magnitudes of the binding energies for the atomic force microscope are found to depend sensitively on tip material, tip shape and the sample site being probed. The form of the energy-distance curve, however, is universal and independent of these variables, including tip shape.

  15. Fundamental Space Biology 2010-2020

    NASA Astrophysics Data System (ADS)

    Tomko, David; Souza, Kenneth; Quincy, Charles; Sun, Sidney

    The goal of NASA's Fundamental Space Biology (FSB) is to strive for U.S. excellence in the whole range of Space Biology -Cell and Molecular, Microbiology, Plant and Animal Biology, Developmental Biology. NASA plans to solicit and conduct research that will contribute to our basic knowledge of the effect of space on living systems. NASA will issue recurring FSB NASA Research Announcements (NRAs) to more fully engage the space biology community. In doing so, FSB research will optimize ISS utilization, develop and demonstrate technology and hard-ware that will enable new science, and contribute to the base of knowledge that will facilitate human countermeasure development. New research capabilities for whole animal and plant bi-ology will be added, and will be optimized by providing state-of-the-art automated technology and analytic techniques wherever possible to maximize scientific return and optimize animal use. Ground-based research to develop and test hypotheses for flight experiments, including hy-pergravity and hypogravity simulations will be an integral FSB activity. Flight experiments will use the most appropriate platform to achieve science results -e.g., ISS, free flyers, sub-orbital flights, and NASA will work with its international partners and other U.S. agencies to achieve these objectives. FSB's highest priority for the near future is the development of mammalian fundamental research capabilities. Another high priority is the development of hardware for studying multiple generations of large plants. Current research in cell and molecular biology will be expanded to include new analytical capabilities. By taking these steps, NASA hopes to energize the Space Biology user community and advance our knowledge of the effect of gravity on living systems.

  16. Cation charge dependence of the forces driving DNA assembly.

    PubMed

    DeRouchey, Jason; Parsegian, V Adrian; Rau, Donald C

    2010-10-20

    Understanding the strength and specificity of interactions among biologically important macromolecules that control cellular functions requires quantitative knowledge of intermolecular forces. Controlled DNA condensation and assembly are particularly critical for biology, with separate repulsive and attractive intermolecular forces determining the extent of DNA compaction. How these forces depend on the charge of the condensing ion has not been determined, but such knowledge is fundamental for understanding the basis of DNA-DNA interactions. Here, we measure DNA force-distance curves for a homologous set of arginine peptides. All forces are well fit as the sum of two exponentials with 2.4- and 4.8-Å decay lengths. The shorter-decay-length force is always repulsive, with an amplitude that varies slightly with length or charge. The longer-decay-length force varies strongly with cation charge, changing from repulsion with Arg¹ to attraction with Arg². Force curves for a series of homologous polyamines and the heterogeneous protein protamine are quite similar, demonstrating the universality of these forces for DNA assembly. Repulsive amplitudes of the shorter-decay-length force are species-dependent but nearly independent of charge within each species. A striking observation was that the attractive force amplitudes for all samples collapse to a single curve, varying linearly with the inverse of the cation charge.

  17. Polarizable force fields.

    PubMed

    Antila, Hanne S; Salonen, Emppu

    2013-01-01

    This chapter provides an overview of the most common methods for including an explicit description of electronic polarization in molecular mechanics force fields: the induced point dipole, shell, and fluctuating charge models. The importance of including polarization effects in biomolecular simulations is discussed, and some of the most important achievements in the development of polarizable biomolecular force fields to date are highlighted.

  18. Force Concept Inventory.

    ERIC Educational Resources Information Center

    Hestenes, David; And Others

    1992-01-01

    Reports the rationale, design, validation, and uses of the "Force Concept Inventory," an instrument to assess the students' beliefs on force. Includes results and implications of two studies that compared the inventory with the "Mechanics Baseline." Includes a copy of the instrument. (MDH)

  19. SCM-Forcing Data

    DOE Data Explorer

    Xie, Shaocheng; Tang,Shuaiqi; Zhang,Yunyan; Zhang,Minghua

    2016-07-01

    Single-Column Model (SCM) Forcing Data are derived from the ARM facility observational data using the constrained variational analysis approach (Zhang and Lin 1997 and Zhang et al., 2001). The resulting products include both the large-scale forcing terms and the evaluation fields, which can be used for driving the SCMs and Cloud Resolving Models (CRMs) and validating model simulations.

  20. The relative entropy is fundamental to adaptive resolution simulations

    NASA Astrophysics Data System (ADS)

    Kreis, Karsten; Potestio, Raffaello

    2016-07-01

    Adaptive resolution techniques are powerful methods for the efficient simulation of soft matter systems in which they simultaneously employ atomistic and coarse-grained (CG) force fields. In such simulations, two regions with different resolutions are coupled with each other via a hybrid transition region, and particles change their description on the fly when crossing this boundary. Here we show that the relative entropy, which provides a fundamental basis for many approaches in systematic coarse-graining, is also an effective instrument for the understanding of adaptive resolution simulation methodologies. We demonstrate that the use of coarse-grained potentials which minimize the relative entropy with respect to the atomistic system can help achieve a smoother transition between the different regions within the adaptive setup. Furthermore, we derive a quantitative relation between the width of the hybrid region and the seamlessness of the coupling. Our results do not only shed light on the what and how of adaptive resolution techniques but will also help setting up such simulations in an optimal manner.

  1. Eigenpairs of a coupled rectangular cavity and its fundamental properties.

    PubMed

    Tanaka, Nobuo; Takara, Yusuke; Iwamoto, Hiroyuki

    2012-03-01

    This paper deals with the eigenvalue problem of a coupled rectangular cavity comprising five rigid walls and one flexible panel frequently employed in much literature. It is the purpose of this paper to derive explicitly the eigenpairs of the coupled cavity, which are yet to be found. First, the coupling orthogonality conditions the eigenpairs need to satisfy are derived, thereby enabling the verification of the eigenpairs newly sought or already existent. Using the coupling orthogonality conditions, the modal equation of the coupled cavity system is then obtained, permitting one to deal with a forced response of the coupled cavity. It is shown that the eigenfunctions governing the dynamics of the sound field are expressed as the infinite sum of degenerate eigenfunctions. The characteristic matrix equation is then derived, specifying the eigenpairs of the coupled cavity. In order to investigate the fundamental properties of the eigenpairs derived, a numerical analysis is conducted, revealing the presence of evanescent modes in addition to the conventional standing wave modes. Finally, an experiment is carried out, verifying the validity of the eigenpairs derived in the article.

  2. Plasmon assisted optical trapping: fundamentals and biomedical applications

    NASA Astrophysics Data System (ADS)

    Serafetinides, Alexandros A.; Makropoulou, Mersini; Tsigaridas, Georgios N.; Gousetis, Anastasios

    2015-01-01

    The field of optical trapping has dramatically grown due to implementation in various arenas including physics, biology, medicine and nanotechnology. Certainly, optical tweezers are an invaluable tool to manipulate a variation of particles, such as small dielectric spheres, cells, bacteria, chromosomes and even genes, by highly focused laser beams through microscope. As the main disadvantage of the conventional optical trapping systems is the diffraction limit of the incident light, plasmon assisted nanotrapping is reported as a suitable technique for trapping sub-wavelength metallic or dielectric particles. In this work, firstly, we report briefly on the basic theory of plasmon excitation, focusing on the interaction of nanoscale metallic structures with laser light. Secondly, experimental and numerical simulation results are also presented, demonstrating enhancement of the trapping efficiency of glass or SiO2 substrates, coated with Au and Ag nanostructures, with or without nanoparticles. The optical forces were calculated by measuring the particle's escape velocity calibration method. Finally, representative applications of plasmon assisted optical trapping are reviewed, from cancer therapeutics to fundamental biology and cell nanosurgery.

  3. A Postulation of a Concept in Fundamental Physics

    NASA Astrophysics Data System (ADS)

    Goradia, Shantilal

    2006-10-01

    I am postulating that all fermions have a quantum mouth (Planck size) that radiates a flux density of gravitons as a function of the mass of the particle. Nucleons are not hard balls like light bulbs radiating photons challenging Newtonian concepts of centers and surfaces. The hardball analogy is implicit in coupling constants that compare strong force relative to gravity. The radiating mouth is not localized at the center like a hypothetical point size filament of a light bulb with a hard surface. A point invokes mass of zero volume. It is too precise, inconsistent and illogical. Nothing can be localized with more accuracy that Planck length. Substituting the hard glass bulb surface with flexible plastic surface would clearly make the interacting mouths of particles approach each other as close as possible, but no less than the quantum limit of Planck length. Therefore, surface distance in Newtonian gravity would be a close approximation at particle scale and fits Feynman's road map [1]. My postulation reflected by Fig. 2 of gr-qc/0507130 explains observations of increasing values of coupling constants resulting from decreasing values of Planck length (See physics/0210040 v1). Since Planck length is the fundamental unit of length of nature, its variation can impact our observation of the universe and the evolutionary process.

  4. Fundamental scaling properties of electro-mechanical switches

    NASA Astrophysics Data System (ADS)

    Knoll, A. W.; Grogg, D.; Despont, M.; Duerig, U.

    2012-12-01

    We discuss the fundamental processes including electron conduction and adhesion of metallic contacts pertaining to the scaling of the performance metrics of nano-electro-mechanical switches. In particular, we show that under most circumstances, the switching energy is governed by the force that is needed in order to break the electrical contact when opening the switch. For an optimally designed parallel plate capacitor switch, the energy consumption does not depend on the actuation voltage. However, stray capacitances degrade the energy efficiency if a high operating voltage is chosen. The limit is of the order of 1 V for an aggressively scaled Si device, for which an overall switching energy of the order of 150 eV, a footprint area of 2500 nm2 and a switching time of 200 ps are predicted. The scaling analysis also stipulates that materials with a low free electron density and high effective mass should be used for the electrical contact, which is counter-intuitive, as such materials are known to be poor conductors on the macroscopic scale.

  5. Metallochaperones: bind and deliver

    SciTech Connect

    Rosenzweig, A.C.

    2010-03-08

    Metallochaperones deliver metal ions directly to target proteins via specific protein-protein interactions. Recent research has led to a molecular picture of how some metallochaperones bind metal ions, recognize their partner proteins, and accomplish metal ion transfer.

  6. Lorentz force velocimetry.

    PubMed

    Thess, A; Votyakov, E V; Kolesnikov, Y

    2006-04-28

    We describe a noncontact technique for velocity measurement in electrically conducting fluids. The technique, which we term Lorentz force velocimetry (LFV), is based on exposing the fluid to a magnetic field and measuring the drag force acting upon the magnetic field lines. Two series of measurements are reported, one in which the force is determined through the angular velocity of a rotary magnet system and one in which the force on a fixed magnet system is measured directly. Both experiments confirm that the measured signal is a linear function of the flow velocity. We then derive the scaling law that relates the force on a localized distribution of magnetized material to the velocity of an electrically conducting fluid. This law shows that LFV, if properly designed, has a wide range of potential applications in metallurgy, semiconductor crystal growth, and glass manufacturing. PMID:16712237

  7. Conservative entropic forces

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    2011-10-01

    Entropic forces have recently attracted considerable attention as ways to reformulate, retrodict, and perhaps even "explain" classical Newtonian gravity from a rather specific thermodynamic perspective. In this article I point out that if one wishes to reformulate classical Newtonian gravity in terms of an entropic force, then the fact that Newtonian gravity is described by a conservative force places significant constraints on the form of the entropy and temperature functions. (These constraints also apply to entropic reinterpretations of electromagnetism, and indeed to any conservative force derivable from a potential.) The constraints I will establish are sufficient to present real and significant problems for any reasonable variant of Verlinde's entropic gravity proposal, though for technical reasons the constraints established herein do not directly impact on either Jacobson'sor Padmanabhan's versions of entropic gravity. In an attempt to resolve these issues, I will extend the usual notion of entropic force to multiple heat baths with multiple "temperatures" and multiple "entropies".

  8. How to deal with multiple binding poses in alchemical relative protein-ligand binding free energy calculations.

    PubMed

    Kaus, Joseph W; Harder, Edward; Lin, Teng; Abel, Robert; McCammon, J Andrew; Wang, Lingle

    2015-06-01

    Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enhanced sampling methods. In this paper, we apply a previously developed method that provides a corrected binding free energy for ligands with multiple binding modes by combining the free energy results from multiple alchemical FEP calculations starting from all enumerated poses, and the results are compared with Glide docking and MM-GBSA calculations. From these calculations, the dominant ligand binding mode can also be predicted. We apply this method to a series of ligands that bind to c-Jun N-terminal kinase-1 (JNK1) and obtain improved free energy results. The dominant ligand binding modes predicted by this method agree with the available crystallography, while both Glide docking and MM-GBSA calculations incorrectly predict the binding modes for some ligands. The method also helps separate the force field error from the ligand sampling error, such that deviations in the predicted binding free energy from the experimental values likely indicate possible inaccuracies in the force field. An error in the force field for a subset of the ligands studied was identified using this method, and improved free energy results were obtained by correcting the partial charges assigned to the

  9. Dynamic force spectroscopy of parallel individual mucin1-antibody bonds

    SciTech Connect

    Sulchek, T A; Friddle, R W; Langry, K; Lau, E; Albrecht, H; Ratto, T; DeNardo, S; Colvin, M E; Noy, A

    2005-05-02

    We used atomic force microscopy (AFM) to measure the binding forces between Mucin1 (MUC1) peptide and a single chain antibody fragment (scFv) selected from a scFv library screened against MUC1. This binding interaction is central to the design of the molecules for targeted delivery of radioimmunotherapeutic agents for prostate and breast cancer treatment. Our experiments separated the specific binding interaction from non-specific interactions by tethering the antibody and MUC1 molecules to the AFM tip and sample surface with flexible polymer spacers. Rupture force magnitude and elastic characteristics of the spacers allowed identification of the bond rupture events corresponding to different number of interacting proteins. We used dynamic force spectroscopy to estimate the intermolecular potential widths and equivalent thermodynamic off rates for mono-, bi-, and tri-valent interactions. Measured interaction potential parameters agree with the results of molecular docking simulation. Our results demonstrate that an increase of the interaction valency leads to a precipitous decline in the dissociation rate. Binding forces measured for mono and multivalent interactions match the predictions of a Markovian model for the strength of multiple uncorrelated bonds in parallel configuration. Our approach is promising for comparison of the specific effects of molecular modifications as well as for determination of the best configuration of antibody-based multivalent targeting agents.

  10. Astronomers Gain Clues About Fundamental Physics

    NASA Astrophysics Data System (ADS)

    2005-12-01

    An international team of astronomers has looked at something very big -- a distant galaxy -- to study the behavior of things very small -- atoms and molecules -- to gain vital clues about the fundamental nature of our entire Universe. The team used the National Science Foundation's Robert C. Byrd Green Bank Telescope (GBT) to test whether the laws of nature have changed over vast spans of cosmic time. The Green Bank Telescope The Robert C. Byrd Green Bank Telescope CREDIT: NRAO/AUI/NSF (Click on image for GBT gallery) "The fundamental constants of physics are expected to remain fixed across space and time; that's why they're called constants! Now, however, new theoretical models for the basic structure of matter indicate that they may change. We're testing these predictions." said Nissim Kanekar, an astronomer at the National Radio Astronomy Observatory (NRAO), in Socorro, New Mexico. So far, the scientists' measurements show no change in the constants. "We've put the most stringent limits yet on some changes in these constants, but that's not the end of the story," said Christopher Carilli, another NRAO astronomer. "This is the exciting frontier where astronomy meets particle physics," Carilli explained. The research can help answer fundamental questions about whether the basic components of matter are tiny particles or tiny vibrating strings, how many dimensions the Universe has, and the nature of "dark energy." The astronomers were looking for changes in two quantities: the ratio of the masses of the electron and the proton, and a number physicists call the fine structure constant, a combination of the electron charge, the speed of light and the Planck constant. These values, considered fundamental physical constants, once were "taken as time independent, with values given once and forever" said German particle physicist Christof Wetterich. However, Wetterich explained, "the viewpoint of modern particle theory has changed in recent years," with ideas such as

  11. Fundamental Characterization Studies of Advanced Photocatalytic Materials

    NASA Astrophysics Data System (ADS)

    Phivilay, Somphonh Peter

    Solar powered photocatalytic water splitting has been proposed as a method for the production of sustainable, non-carbon hydrogen fuel. Although much technological progress has been achieved in recent years in the discovery of advanced photocatalytic materials, the progress in the fundamental scientific understanding of such novel, complex mixed oxide and oxynitride photocatalysts has significantly lagged. One of the major reasons for this slow scientific progress is the limited number of reported surface characterization studies of the complex bulk mixed oxide and oxynitride photocatalyst systems. Although photocatalytic splitting of water by bulk mixed oxide and oxynitride materials involves both bulk (generation of excited electrons and holes) and surface phenomena (reaction of H2O with excited electrons and holes at the surface), the photocatalysis community has almost completely ignored the surface characteristics of such complex bulk photocatalysts and correlates the photocatalytic properties with bulk properties. Some of the most promising photocatalyst systems (NaTaO3, GaN, (Ga1-xZnx)(N1-xOx) and TaON) were investigated to establish fundamental bulk/surface structure photoactivity relationships. The bulk molecular and electronic structures of the photocatalysts were determined with Raman and UV-vis spectroscopy. Photoluminescence (PL) and transient PL spectroscopy were provided insight into how recombination of photogenerated electrons is related to the photocatalysis activity. The chemical states and atomic compositions of the surface region of the photocatalysts were determined with high resolution X-ray photoelectron spectroscopy (˜1-3 nm) and high sensitivity-low energy ion scattering spectroscopy (˜0.3 nm). The new insights obtained from surface characterization clarified the role of La and Ni promoters species for the NaTaO3 photocatalyst system. The La2O3 additive was found to be a structural promoter that stabilizes small NaTaO3 nanoparticles (NPs

  12. Role of silver ions in destabilization of intermolecular adhesion forces measured by atomic force microscopy in Staphylococcus epidermidis biofilms.

    PubMed

    Chaw, K C; Manimaran, M; Tay, Francis E H

    2005-12-01

    In this paper, we report on the potential use of atomic force microscopy (AFM) as a tool to measure the intermolecular forces in biofilm structures and to study the effect of silver ions on sessile Staphylococcus epidermidis cell viability and stability. We propose a strategy of destabilizing the biofilm matrix by reducing the intermolecular forces within the extracellular polymeric substances (EPSs) using a low concentration (50 ppb) of silver ions. Our AFM studies on the intermolecular forces within the EPSs of S. epidermidis RP62A and S.epidermidis 1457 biofilms suggest that the silver ions can destabilize the biofilm matrix by binding to electron donor groups of the biological molecules. This leads to reductions in the number of binding sites for hydrogen bonds and electrostatic and hydrophobic interactions and, hence, the destabilization of the biofilm structure.

  13. Fundamental Physics in Space: the French Contribution

    NASA Astrophysics Data System (ADS)

    Leon-Hirtz, S.

    2002-01-01

    Relativity and quantum physics provide the framework for contemporary physics in which the relations between matter, space and time have been radically rethought during the past century. Physicists however cannot be satisfied with these two distinct theories and they are seeking to unify them and thereby quantify the gravitational field. The key of this research lies in the highly precise study of the gravitational laws. Space environment, allowing large distance experiments and isolation from terrestrial noise, is the ideal place for carrying out very precise experiments on gravitation and is highly suitable for seeking new interactions that could show up in low-energy conditions. Since 1993 when the scientific community gave its first recommandations, CNES has been working out with french research laboratories on a variety of advanced technical instrumentations needed to fulfill such space experiments, especially in the fields of electrostatic microaccelerometers, cold atom clocks and cold atom inertial sensors, optical datation, optical interferometry and drag-free control. A number of Fundamental Physics projects are now under progress, in the frame of the national programme and the participation to the ESA programme, such as : -the MICROSCOPE microsatellite project aimed at testing the Equivalence Principle between inertial mass and gravitational mass at a high level of precision, which is the fourth CNES scientific project based on the MYRIADE microsatellite series, -the PHARAO cold-atom clock which is the heart of the ACES (Atomic Clock Ensemble in Space) european project located on an external pallett of the International Space Station, together with a swiss H- MASER and a micro-wave link making comparison with ground clocks, aimed at relativistic tests and measurement of universal constants, -the T2L2 optical link allowing to compare ultra-stable and ultra-precise clocks, -contribution to the AMS spectrometer aimed at the search for cosmic antimatter, on

  14. Fiber mass, count and breaking force from Stelometer test

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A fundamental understanding of the relationship among cotton fiber mass, count, and breaking force is important, as bundle fiber tenacity, elongation, and linear density can be calculated from these three parameters. In this study, the Stelometer instrument was employed, mostly because it is the tra...

  15. The mettle of moral fundamentalism: a reply to Robert Baker.

    PubMed

    Beauchamp, Tom L

    1998-12-01

    This article is a reply to Robert Baker's attempt to rebut moral fundamentalism, while grounding international bioethics in a form of contractarianism. Baker is mistaken in several of his interpretations of the alleged moral fundamentalism and findings of the Advisory Committee on Human Radiation Experiments. He also misunderstands moral fundamentalism generally and wrongly categorizes it as morally bankrupt. His negotiated contract model is, in the final analysis, itself a form of the moral fundamentalism he declares bankrupt.

  16. Discrete electron forces in a nanoparticle-tunnel junction system

    NASA Astrophysics Data System (ADS)

    Suganuma, Y.; Trudeau, P.-E.; Dhirani, A.-A.; Leathem, B.; Shieh, B.

    2003-06-01

    According to the "orthodox" model for single electron tunneling, sudden changes in current-voltage characteristics of nanoparticle (NP)-tunnel junction (TJ) systems ["Coulomb blockade" (CB) and "Coulomb staircase" (CS) phenomena] arise fundamentally due to charge quantization. We have embedded NPs (˜2.5 nm in diameter) in the TJ of a hybrid scanning tunneling-atomic force microscope and have simultaneously measured current and forces generated in the system. We discuss an application to micromechanical switching actuated by single electrons. We also show that CB and CS phenomena are in fact associated with steplike changes in force, directly confirming the discrete charge nature of the phenomena.

  17. Traceable periodic force calibration

    NASA Astrophysics Data System (ADS)

    Schlegel, Ch; Kieckenap, G.; Glöckner, B.; Buß, A.; Kumme, R.

    2012-06-01

    A procedure for dynamic force calibration using sinusoidal excitations of force transducers is described. The method is based on a sinusoidal excitation of force transducers equipped with an additional top mass excited with an electrodynamic shaker system. The acting dynamic force can in this way be determined according to Newton's law as mass times acceleration, whereby the acceleration is measured on the surface of the top mass with the aid of laser interferometers. The dynamic sensitivity, which is the ratio of the electrical output signal of the force transducer and the acting dynamic force, is the main point of interest of such a dynamic calibration. In addition to the sensitivity, the parameter stiffness and damping of the transducer can also be determined. The first part of the paper outlines a mathematical model to describe the dynamic behaviour of a transducer. This is followed by a presentation of the traceability of the measured quantities involved and their uncertainties. The paper finishes with an example calibration of a 25 kN strain gauge force transducer.

  18. Turbomachinery rotor forces

    NASA Technical Reports Server (NTRS)

    Arndt, Norbert

    1988-01-01

    The fluid-induced forces, both steady and unsteady, acting upon an impeller of a centrifugal pump, and impeller blade-diffuser vane interaction in centrifugal pumps with vaned radial diffusers were evaluated experimentally and theoretically. Knowledge of the steady and unsteady forces, and the associated rotordynamic coefficients are required to effectively model the rotor dynamics of the High Pressure Fuel Turbopump (HPFTP) of the Space Shuttle Main Engine (SSME). These forces and rotordynamic coefficients were investigated using different impellers in combination with volutes and vaned diffusers, and axial inducers. These rotor forces are global. Local forces and pressures are also important in impeller-diffuser interaction, for they may cause cavitation damage and even vane failures. Thus, in a separate investigation, impeller wake, and impeller blade and diffuser vane pressure measurements were made. The nature of the rotordynamic forces is discussed, the experimental facility is described, and the measurements of unsteady forces and pressure are reported together with a brief and incomplete attempt to calculate these flows.

  19. OOTW Force Design Tools

    SciTech Connect

    Bell, R.E.; Hartley, D.S.III; Packard, S.L.

    1999-05-01

    This report documents refined requirements for tools to aid the process of force design in Operations Other Than War (OOTWs). It recommends actions for the creation of one tool and work on other tools relating to mission planning. It also identifies the governmental agencies and commands with interests in each tool, from whom should come the user advisory groups overseeing the respective tool development activities. The understanding of OOTWs and their analytical support requirements has matured to the point where action can be taken in three areas: force design, collaborative analysis, and impact analysis. While the nature of the action and the length of time before complete results can be expected depends on the area, in each case the action should begin immediately. Force design for OOTWs is not a technically difficult process. Like force design for combat operations, it is a process of matching the capabilities of forces against the specified and implied tasks of the operation, considering the constraints of logistics, transport and force availabilities. However, there is a critical difference that restricts the usefulness of combat force design tools for OOTWs: the combat tools are built to infer non-combat capability requirements from combat capability requirements and cannot reverse the direction of the inference, as is required for OOTWs. Recently, OOTWs have played a larger role in force assessment, system effectiveness and tradeoff analysis, and concept and doctrine development and analysis. In the first Quadrennial Defense Review (QDR), each of the Services created its own OOTW force design tool. Unfortunately, the tools address different parts of the problem and do not coordinate the use of competing capabilities. These tools satisfied the immediate requirements of the QDR, but do not provide a long-term cost-effective solution.

  20. Manual discrimination of force

    NASA Technical Reports Server (NTRS)

    Pang, Xiao-Dong; Tan, HONG-Z.; Durlach, Nathaniel I.

    1991-01-01

    Optimal design of human-machine interfaces for teleoperators and virtual-environment systems which involve the tactual and kinesthetic modalities requires knowledge of the human's resolving power in these modalities. The resolution of the interface should be appropriately matched to that of the human operator. We report some preliminary results on the ability of the human hand to distinguish small differences in force under a variety of conditions. Experiments were conducted on force discrimination with the thumb pushing an interface that exerts a constant force over the pushing distance and the index finger pressing against a fixed support. The dependence of the sensitivity index d' on force increment can be fit by a straight line through the origin and the just-noticeable difference (JND) in force can thus be described by the inverse of the slope of this line. The receiver operating characteristic (ROC) was measured by varying the a priori probabilities of the two alternatives, reference force and reference force plus an increment, in one-interval, two-alternative, forced-choice experiments. When plotted on normal deviate coordinates, the ROC's were roughly straight lines of unit slope, thus supporting the assumption of equal-variance normal distributions and the use of the conventional d' measure. The JND was roughly 6-8 percent for reference force ranging from 2.5 to 10 newtons, pushing distance from 5 to 30 mm, and initial finger-span from 45 to 125 mm. Also, the JND remained the same when the subjects were instructed to change the average speed of pushing from 23 to 153 mm/sec. The pushing was terminated by reaching either a wall or a well, and the JND's were essentially the same in both cases.

  1. Characterization of the pre-force-generation state in the actomyosin cross-bridge cycle

    PubMed Central

    Sun, Mingxuan; Rose, Michael B.; Ananthanarayanan, Shobana K.; Jacobs, Donald J.; Yengo, Christopher M.

    2008-01-01

    Myosin is an actin-based motor protein that generates force by cycling between actin-attached (strong binding: ADP or rigor) and actin-detached (weak binding: ATP or ADP·Pi) states during its ATPase cycle. However, it remains unclear what specific conformational changes in the actin binding site take place on binding to actin, and how these structural changes lead to product release and the production of force and motion. We studied the dynamics of the actin binding region of myosin V by using fluorescence resonance energy transfer (FRET) to monitor conformational changes in the upper-50-kDa domain of the actin binding cleft in the weak and strong actin binding states. Steady-state and lifetime data monitoring the FRET signal suggest that the cleft is in a more open conformation in the weak actin binding states. Transient kinetic experiments suggest that a rapid conformational change occurs, which is consistent with cleft closure before actin-activated phosphate release. Our results have identified a pre-force-generation actomyosin ADP·Pi state, and suggest force generation may occur from a state not yet seen by crystallography in which the actin binding cleft and the nucleotide binding pocket are closed. Computational modeling uncovers dramatic changes in the rigidity of the upper-50-kDa domain in different nucleotide states, which suggests that the intrinsic flexibility of this domain allows myosin motors to accomplish simultaneous tight nucleotide binding (closed nucleotide binding pocket) and high-affinity actin binding (closed actin binding cleft). PMID:18552179

  2. Designing ligands to bind proteins.

    PubMed

    Whitesides, George M; Krishnamurthy, Vijay M

    2005-11-01

    The ability to design drugs (so-called 'rational drug design') has been one of the long-term objectives of chemistry for 50 years. It is an exceptionally difficult problem, and many of its parts lie outside the expertise of chemistry. The much more limited problem - how to design tight-binding ligands (rational ligand design) - would seem to be one that chemistry could solve, but has also proved remarkably recalcitrant. The question is 'Why is it so difficult?' and the answer is 'We still don't entirely know'. This perspective discusses some of the technical issues - potential functions, protein plasticity, enthalpy/entropy compensation, and others - that contribute, and suggests areas where fundamental understanding of protein-ligand interactions falls short of what is needed. It surveys recent technological developments (in particular, isothermal titration calorimetry) that will, hopefully, make now the time for serious progress in this area. It concludes with the calorimetric examination of the association of a series of systematically varied ligands with a model protein. The counterintuitive thermodynamic results observed serve to illustrate that, even in relatively simple systems, understanding protein-ligand association is challenging.

  3. 43 CFR 4180.1 - Fundamentals of rangeland health.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Fundamentals of rangeland health. 4180.1... Fundamentals of Rangeland Health and Standards and Guidelines for Grazing Administration § 4180.1 Fundamentals of rangeland health. Standards and guidelines developed or revised by a Bureau of Land...

  4. 43 CFR 4180.1 - Fundamentals of rangeland health.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Fundamentals of rangeland health. 4180.1... Fundamentals of Rangeland Health and Standards and Guidelines for Grazing Administration § 4180.1 Fundamentals of rangeland health. Standards and guidelines developed or revised by a Bureau of Land...

  5. 43 CFR 4180.1 - Fundamentals of rangeland health.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Fundamentals of rangeland health. 4180.1... Fundamentals of Rangeland Health and Standards and Guidelines for Grazing Administration § 4180.1 Fundamentals of rangeland health. Standards and guidelines developed or revised by a Bureau of Land...

  6. 33 CFR 86.03 - Limits of fundamental frequencies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Limits of fundamental frequencies... of fundamental frequencies. To ensure a wide variety of whistle characteristics, the fundamental frequency of a whistle shall be between the following limits: (a) 70-200 Hz, for a vessel 200 meters or...

  7. 33 CFR 86.03 - Limits of fundamental frequencies.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Limits of fundamental frequencies... of fundamental frequencies. To ensure a wide variety of whistle characteristics, the fundamental frequency of a whistle shall be between the following limits: (a) 70-200 Hz, for a vessel 200 meters or...

  8. 33 CFR 86.03 - Limits of fundamental frequencies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Limits of fundamental frequencies... of fundamental frequencies. To ensure a wide variety of whistle characteristics, the fundamental frequency of a whistle shall be between the following limits: (a) 70-200 Hz, for a vessel 200 meters or...

  9. 47 CFR 36.2 - Fundamental principles underlying procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-kilometers is the basic fundamental allocation factor for interexchange circuit plant and exchange trunk... 47 Telecommunication 2 2010-10-01 2010-10-01 false Fundamental principles underlying procedures... Fundamental principles underlying procedures. (a) The following general principles underlie the...

  10. Mechanochemical regulations of RPA's binding to ssDNA.

    PubMed

    Chen, Jin; Le, Shimin; Basu, Anindita; Chazin, Walter J; Yan, Jie

    2015-01-01

    Replication protein A (RPA) is a ubiquitous eukaryotic single-stranded DNA (ssDNA) binding protein that serves to protect ssDNA from degradation and annealing, and as a template for recruitment of many downstream factors in virtually all DNA transactions in cell. During many of these transactions, DNA is tethered and is likely subject to force. Previous studies of RPA's binding behavior on ssDNA were conducted in the absence of force; therefore the RPA-ssDNA conformations regulated by force remain unclear. Here, using a combination of atomic force microscopy imaging and mechanical manipulation of single ssDNA tethers, we show that force mediates a switch of the RPA bound ssDNA from amorphous aggregation to a much more regular extended conformation. Further, we found an interesting non-monotonic dependence of the binding affinity on monovalent salt concentration in the presence of force. In addition, we discovered that zinc in micromolar concentrations drives ssDNA to a unique, highly stiff and more compact state. These results provide new mechanochemical insights into the influences and the mechanisms of action of RPA on large single ssDNA. PMID:25787788

  11. Mechanochemical regulations of RPA's binding to ssDNA

    NASA Astrophysics Data System (ADS)

    Chen, Jin; Le, Shimin; Basu, Anindita; Chazin, Walter J.; Yan, Jie

    2015-03-01

    Replication protein A (RPA) is a ubiquitous eukaryotic single-stranded DNA (ssDNA) binding protein that serves to protect ssDNA from degradation and annealing, and as a template for recruitment of many downstream factors in virtually all DNA transactions in cell. During many of these transactions, DNA is tethered and is likely subject to force. Previous studies of RPA's binding behavior on ssDNA were conducted in the absence of force; therefore the RPA-ssDNA conformations regulated by force remain unclear. Here, using a combination of atomic force microscopy imaging and mechanical manipulation of single ssDNA tethers, we show that force mediates a switch of the RPA bound ssDNA from amorphous aggregation to a much more regular extended conformation. Further, we found an interesting non-monotonic dependence of the binding affinity on monovalent salt concentration in the presence of force. In addition, we discovered that zinc in micromolar concentrations drives ssDNA to a unique, highly stiff and more compact state. These results provide new mechanochemical insights into the influences and the mechanisms of action of RPA on large single ssDNA.

  12. Characterization of the Binding Properties of Molecularly Imprinted Polymers.

    PubMed

    Ansell, Richard J

    2015-01-01

    The defining characteristic of the binding sites of any particular molecularly imprinted material is heterogeneity: that is, they are not all identical. Nonetheless, it is useful to study their fundamental binding properties, and to obtain average properties. In particular, it has been instructive to compare the binding properties of imprinted and non-imprinted materials. This chapter begins by considering the origins of this site heterogeneity. Next, the properties of interest of imprinted binding sites are described in brief: affinity, selectivity, and kinetics. The binding/adsorption isotherm, the graph of concentration of analyte bound to a MIP versus concentration of free analyte at equilibrium, over a range of total concentrations, is described in some detail. Following this, the techniques for studying the imprinted sites are described (batch-binding assays, radioligand binding assays, zonal chromatography, frontal chromatography, calorimetry, and others). Thereafter, the parameters that influence affinity, selectivity and kinetics are discussed (solvent, modifiers of organic solvents, pH of aqueous solvents, temperature). Finally, mathematical attempts to fit the adsorption isotherms for imprinted materials, so as to obtain information about the range of binding affinities characterizing the imprinted sites, are summarized. PMID:25796622

  13. Dilatonic Entropic Force

    NASA Astrophysics Data System (ADS)

    Sakalli, I.

    2011-08-01

    We show in detail that the entropic force of the static spherically symmetric spacetimes with unusual asymptotics can be calculated through the Verlinde's arguments. We introduce three different holographic screen candidates, which are first employed thoroughly by Myung and Kim [Phys. Rev. D 81, 105012 (2010)] for Schwarzschild black hole solutions, in order to identify the entropic force arising between a charged dilaton black hole and a test particle. The significance of the dilaton parameter on the entropic force is highlighted, and shown graphically.

  14. Dielectric elastomers: generator mode fundamentals and applications

    NASA Astrophysics Data System (ADS)

    Pelrine, Ron; Kornbluh, Roy D.; Eckerle, Joseph; Jeuck, Philip; Oh, Seajin; Pei, Qibing; Stanford, Scott

    2001-07-01

    Dielectric elastomers have shown great promise as actuator materials. Their advantages in converting mechanical to electrical energy in a generator mode are less well known. If a low voltage charge is placed on a stretched elastomer prior to contraction, the contraction works against the electrostatic field pressure and raises the voltage of the charge, thus generating electrical energy. This paper discusses the fundamentals of dielectric elastomer generators, experimental verification of the phenomenon, practical issues, and potential applications. Acrylic elastomers have demonstrated an estimated 0.4 J/g specific energy density, greater than that of piezoelectric materials. Much higher energy densities, over 1 J/g, are predicted. Conversion efficiency can also be high, theoretically up to 80-90%; the paper discusses the operating conditions and materials required for high efficiency. Practical considerations may limit the specific outputs and efficiencies of dielectric elastomeric generators, tradeoffs between electronics and generator material performance are discussed. Lastly, the paper describes work on potential applications such as an ongoing effort to develop a boot generator based on dielectric elastomers, as well as other applications such as conventional power generators, backpack generators, and wave power applications.

  15. Two-voice fundamental frequency estimation

    NASA Astrophysics Data System (ADS)

    de Cheveigné, Alain

    2002-05-01

    An algorithm is presented that estimates the fundamental frequencies of two concurrent voices or instruments. The algorithm models each voice as a periodic function of time, and jointly estimates both periods by cancellation according to a previously proposed method [de Cheveigné and Kawahara, Speech Commun. 27, 175-185 (1999)]. The new algorithm improves on the old in several respects; it allows an unrestricted search range, effectively avoids harmonic and subharmonic errors, is more accurate (it uses two-dimensional parabolic interpolation), and is computationally less costly. It remains subject to unavoidable errors when periods are in certain simple ratios and the task is inherently ambiguous. The algorithm is evaluated on a small database including speech, singing voice, and instrumental sounds. It can be extended in several ways; to decide the number of voices, to handle amplitude variations, and to estimate more than two voices (at the expense of increased processing cost and decreased reliability). It makes no use of instrument models, learned or otherwise, although it could usefully be combined with such models. [Work supported by the Cognitique programme of the French Ministry of Research and Technology.

  16. Electrochemical metallization memories—fundamentals, applications, prospects

    NASA Astrophysics Data System (ADS)

    Valov, Ilia; Waser, Rainer; Jameson, John R.; Kozicki, Michael N.

    2011-06-01

    This review focuses on electrochemical metallization memory cells (ECM), highlighting their advantages as the next generation memories. In a brief introduction, the basic switching mechanism of ECM cells is described and the historical development is sketched. In a second part, the full spectra of materials and material combinations used for memory device prototypes and for dedicated studies are presented. In a third part, the specific thermodynamics and kinetics of nanosized electrochemical cells are described. The overlapping of the space charge layers is found to be most relevant for the cell properties at rest. The major factors determining the functionality of the ECM cells are the electrode reaction and the transport kinetics. Depending on electrode and/or electrolyte material electron transfer, electro-crystallization or slow diffusion under strong electric fields can be rate determining. In the fourth part, the major device characteristics of ECM cells are explained. Emphasis is placed on switching speed, forming and SET/RESET voltage, RON to ROFF ratio, endurance and retention, and scaling potentials. In the last part, circuit design aspects of ECM arrays are discussed, including the pros and cons of active and passive arrays. In the case of passive arrays, the fundamental sneak path problem is described and as well as a possible solution by two anti-serial (complementary) interconnected resistive switches per cell. Furthermore, the prospects of ECM with regard to further scalability and the ability for multi-bit data storage are addressed.

  17. Ultralight porous metals: From fundamentals to applications

    NASA Astrophysics Data System (ADS)

    Tianjian, Lu

    2002-10-01

    Over the past few years a number of low cost metallic foams have been produced and used as the core of sandwich panels and net shaped parts. The main aim is to develop lightweight structures which are stiff, strong, able to absorb large amount of energy and cheap for application in the transport and construction industries. For example, the firewall between the engine and passenger compartment of an automobile must have adequate mechanical strength, good energy and sound absorbing properties, and adequate fire retardance. Metal foams provide all of these features, and are under serious consideration for this applications by a number of automobile manufacturers (e.g., BMW and Audi). Additional specialized applications for foam-cored sandwich panels range from heat sinks for electronic devices to crash barriers for automobiles, from the construction panels in lifts on aircraft carriers to the luggage containers of aircraft, from sound proofing walls along railway tracks and highways to acoustic absorbers in lean premixed combustion chambers. But there is a problem. Before metallic foams can find a widespread application, their basic properties must be measured, and ideally modeled as a function of microstructural details, in order to be included in a design. This work aims at reviewing the recent progress and presenting some new results on fundamental research regarding the micromechanical origins of the mechanical, thermal, and acoustic properties of metallic foams.

  18. A Study of Fundamental Shock Noise Mechanisms

    NASA Technical Reports Server (NTRS)

    Meadows, Kristine R.

    1997-01-01

    This paper investigates two mechanisms fundamental to sound generation in shocked flows: shock motion and shock deformation. Shock motion is modeled numerically by examining the interaction of a sound wave with a shock. This numerical approach is validated by comparison with results obtained by linear theory for a small-disturbance case. Analysis of the perturbation energy with Myers' energy corollary demonstrates that acoustic energy is generated by the interaction of acoustic disturbances with shocks. This analysis suggests that shock motion generates acoustic and entropy disturbance energy. Shock deformation is modeled numerically by examining the interaction of a vortex ring with a shock. These numerical simulations demonstrate the generation of both an acoustic wave and contact surfaces. The acoustic wave spreads cylindrically. The sound intensity is highly directional and the sound pressure increases with increasing shock strength. The numerically determined relationship between the sound pressure and the Mach number is found to be consistent with experimental observations of shock noise. This consistency implies that a dominant physical process in the generation of shock noise is modeled in this study.

  19. Fundamental Considerations for Biobank Legacy Planning.

    PubMed

    Matzke, Lise Anne Marie; Fombonne, Benjamin; Watson, Peter Hamilton; Moore, Helen Marie

    2016-04-01

    Biobanking in its various forms is an activity involving the collection of biospecimens and associated data and their storage for differing lengths of time before use. In some cases, biospecimens are immediately used, but in others, they are stored typically for the term of a specified project or in perpetuity until the materials are used up or declared to be of little scientific value. Legacy planning involves preparing for the phase that follows either biobank closure or a significant change at an operational level. In the case of a classical finite collection, this may be brought about by the completion of the initial scientific goals of a project, a loss of funding, or loss of or change in leadership. Ultimately, this may require making a decision about when and where to transfer materials or whether to destroy them. Because biobanking in its entirety is a complex endeavour, legacy planning touches on biobank operations as well as ethical, legal, financial, and governance parameters. Given the expense and time that goes into setting up and maintaining biobanks, coupled with the ethical imperative to appropriately utilize precious resources donated to research, legacy planning is an activity that every biobanking entity should think about. This article describes some of the fundamental considerations for preparing and executing a legacy plan, and we envisage that this article will facilitate dialogue to help inform best practices and policy development in the future. PMID:26890981

  20. Fundamentals of free flux flow: proposed studies

    NASA Astrophysics Data System (ADS)

    Alexander, J. A.; Gafarov, O.; Gapud, A. A.; Wu, J. Z.

    2013-03-01

    Although much is known about free flux flow (FFF) in superconductors - in which pinning is insignificant compared to interactions between quantized vortices - there still remain questions concerning fundamental dynamics. Building on our previous work in correlating FFF with vortex core size (PRB 80, 134524), we propose three new studies examining more deeply the normal state in the vortex core and interactions between vortices. A correlation between scattering inside cores and the viscosity of FFF has not been explicitly determined; this may be investigated by probing the effect of scattering centers created by proton irradiation. Using results of previous irradiation work, one could control the extent of normal state scattering while monitoring effects on FFF. Questions also exist concerning vortex motion in channels with widths approaching that of individual vortices - as determined solely by inter-vortex interactions. Studies have suggested that flux flow through constrictions could imitate ``jamming'' in the collective motion of grains: Under certain conditions, it is possible for grains to form a barrier, blocking flow. More than just qualitatively comparing flux flow and granular flow to find evidence of jamming, we propose a new experiment for quantitatively modeling flux jamming by realizing the flux flow equivalent of granular jamming in a ``hopper''. In the same way, we also propose a FFF equivalent of another granular-flow phenomenon, ``non-Newtonian'' fluids, where rapid shear causes jamming. Funded by NSF-RUI grant, DMR-0907038.