WorldWideScience

Sample records for revealing fundamental interactions

  1. Unity of Fundamental Interactions

    CERN Document Server

    Sastry, R R

    2000-01-01

    The vector representation of the linearized gravitational field (the graviton field) or the so called quantum gravitodynamics which describes the motion of masses in a weak gravitational field is employed to understand the unity of the four known interactions. We propose a gauge group SU(3)xSU(2)xU(1)xU(1) for such a unified field theory. In this paper we study the SU(2)xU(1)xU(1) sector of the theory and in analogy to the electroweak mixing angle we define a gravitoweak mixing angle. The unified gauge field theory predicts the existence of three massive vector bosons, the Y+/- and the X^0. and two massless vector bosons, the photon and the graviton (in its vector representation). We determine the mass spectrum of the Y+/- and the X^0 and predict a modification to the fine structure constant under unified field conditions. Furthermore, we briefly discuss the implications of the extended object formulation for the gauge hierarchy problem.

  2. Unified Theory of Fundamental Interactions

    Institute of Scientific and Technical Information of China (English)

    WU Ning

    2003-01-01

    Based on local gauge invariance, four different kinds of fundamental interactions in nature are unified in a theory which has SU(3)C( )SU SU(2)L( )U(1)( )s Gravitational Gauge Group gauge symmetry. In this approach,gravitational field, like electromagnetic field, intermediate gauge field, and gluon field, is represented by gauge potential.Four kinds of fundamental interactions are formulated in the similar manner, and therefore can be unified in a direct or semi-direct product group. The model discussed in this paper is a renormalizable quantum model and can be regarded as an extension of the standard model to gravitational interactions, so it can be used to study quantum effects of gravitational interactions.

  3. Quantum Uncertainty and Fundamental Interactions

    Directory of Open Access Journals (Sweden)

    Tosto S.

    2013-04-01

    Full Text Available The paper proposes a simplified theoretical approach to infer some essential concepts on the fundamental interactions between charged particles and their relative strengths at comparable energies by exploiting the quantum uncertainty only. The worth of the present approach relies on the way of obtaining the results, rather than on the results themselves: concepts today acknowledged as fingerprints of the electroweak and strong interactions appear indeed rooted in the same theoretical frame including also the basic principles of special and general relativity along with the gravity force.

  4. Field Theory of Fundamental Interactions

    Science.gov (United States)

    Wang, Shouhong; Ma, Tian

    2017-01-01

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

  5. Fundamental trends in fluid-structure interaction

    CERN Document Server

    Galdi, Giovanni P

    2010-01-01

    The interaction of a fluid with a solid body is a widespread phenomenon in nature, occurring at different scales and different applied disciplines. Interestingly enough, even though the mathematical theory of the motion of bodies in a liquid is one of the oldest and most classical problems in fluid mechanics, mathematicians have, only very recently, become interested in a systematic study of the basic problems related to fluid-structure interaction, from both analytical and numerical viewpoints. ""Fundamental Trends in Fluid-Structure Interaction"" is a unique collection of important papers wr

  6. Non-Linear Dynamics and Fundamental Interactions

    CERN Document Server

    Khanna, Faqir

    2006-01-01

    The book is directed to researchers and graduate students pursuing an advanced degree. It provides details of techniques directed towards solving problems in non-linear dynamics and chos that are, in general, not amenable to a perturbative treatment. The consideration of fundamental interactions is a prime example where non-perturbative techniques are needed. Extension of these techniques to finite temperature problems is considered. At present these ideas are primarily used in a perturbative context. However, non-perturbative techniques have been considered in some specific cases. Experts in the field on non-linear dynamics and chaos and fundamental interactions elaborate the techniques and provide a critical look at the present status and explore future directions that may be fruitful. The text of the main talks will be very useful to young graduate students who are starting their studies in these areas.

  7. Fundamentals of human-computer interaction

    CERN Document Server

    Monk, Andrew F

    1985-01-01

    Fundamentals of Human-Computer Interaction aims to sensitize the systems designer to the problems faced by the user of an interactive system. The book grew out of a course entitled """"The User Interface: Human Factors for Computer-based Systems"""" which has been run annually at the University of York since 1981. This course has been attended primarily by systems managers from the computer industry. The book is organized into three parts. Part One focuses on the user as processor of information with studies on visual perception; extracting information from printed and electronically presented

  8. Diffusion Equations, Quantum Fields and Fundamental Interactions

    Directory of Open Access Journals (Sweden)

    Tosto S.

    2015-04-01

    Full Text Available The paper concerns an “ab initio” theoretical model based on the space-time quantum uncertainty and aimed to identify the conceptual root common to all four fundamental interactions known in nature. The essential information that identifies unambiguously each kind of interaction is inferred in a straightforward way via simple considerations involving the diffusion laws. The conceptual frame of the model is still that introduced in previous papers, where the basic statements of the relativity and wave mechanics have been contextually obtained as corollaries of the quantum uncertainty.

  9. About strong interaction of fundamental particles

    CERN Document Server

    Sannikov-Proskuryakov, S S

    2002-01-01

    We concentrate upon the main properties of strong interaction of hadrons. It is demonstrated that, due to the unusual character of the field propagator in a fiber (at very small distances) where strong interaction is switched on, a new symmetric Green function is used as a field propagator. As a result, the unitary scattering matrix of strong interaction is represented as a T sub s -time ordered chronological exponent. It is shown that the particle skeleton algebra plays an important role in finding the full interaction Lagrangian. Coupling constants of strong interactions are determined. In Appendix, the radiative corrections to the nucleon mass and the masses of eta, pi, KAPPA mesons transferring the strong interactions are calculated.

  10. Fundamental Elements and Interactions of Nature: A Classical Unification Theory

    Directory of Open Access Journals (Sweden)

    Tianxi Zhang

    2010-04-01

    Full Text Available A classical unification theory that completely unifies all the fundamental interactions of nature is developed. First, the nature is suggested to be composed of the following four fundamental elements: mass, radiation, electric charge, and color charge. All known types of matter or particles are a combination of one or more of the four fundamental elements. Photons are radiation; neutrons have only mass; protons have both mass and electric charge; and quarks contain mass, electric charge, and color charge. The nature fundamental interactions are interactions among these nature fundamental elements. Mass and radiation are two forms of real energy. Electric and color charges are considered as two forms of imaginary energy. All the fundamental interactions of nature are therefore unified as a single interaction between complex energies. The interaction between real energies is the gravitational force, which has three types: mass-mass, mass-radiation, and radiation-radiation interactions. Calculating the work done by the mass-radiation interaction on a photon derives the Einsteinian gravitational redshift. Calculating the work done on a photon by the radiation-radiation interaction derives a radiation redshift, which is much smaller than the gravitational redshift. The interaction between imaginary energies is the electromagnetic (between electric charges, weak (between electric and color charges, and strong (between color charges interactions. In addition, we have four imaginary forces between real and imaginary energies, which are mass-electric charge, radiation-electric charge, mass-color charge, and radiation-color charge interactions. Among the four fundamental elements, there are ten (six real and four imaginary fundamental interactions. This classical unification theory deepens our understanding of the nature fundamental elements and interactions, develops a new concept of imaginary energy for electric and color charges, and provides a

  11. Fundamental Elements and Interactions of Nature: A Classical Unification Theory

    Directory of Open Access Journals (Sweden)

    Zhang T. X.

    2010-04-01

    Full Text Available A classical unification theory that completely unifies all the fundamental interactions of nature is developed. First, the nature is suggested to be composed of the following four fundamental elements: mass, radiation, electric charge, and color charge. All known types of matter or particles are a combination of one or more of the four fundamental elements. Photons are radiation; neutrons have only mass; protons have both mass and electric charge; and quarks contain mass, electric charge, and color charge. The nature fundamental interactions are interactions among these nature fundamental elements. Mass and radiation are two forms of real energy. Electric and color charges are con- sidered as two forms of imaginary energy. All the fundamental interactions of nature are therefore unified as a single interaction between complex energies. The interac- tion between real energies is the gravitational force, which has three types: mass-mass, mass-radiation, and radiation-radiation interactions. Calculating the work done by the mass-radiation interaction on a photon derives the Einsteinian gravitational redshift. Calculating the work done on a photon by the radiation-radiation interaction derives a radiation redshift, which is much smaller than the gravitational redshift. The interaction between imaginary energies is the electromagnetic (between electric charges, weak (between electric and color charges, and strong (between color charges interactions. In addition, we have four imaginary forces between real and imaginary energies, which are mass-electric charge, radiation-electric charge, mass-color charge, and radiation- color charge interactions. Among the four fundamental elements, there are ten (six real and four imaginary fundamental interactions. This classical unification theory deep- ens our understanding of the nature fundamental elements and interactions, develops a new concept of imaginary energy for electric and color charges, and provides a

  12. Fundamental Particles and Interactions. A Wall Chart of Modern Physics.

    Science.gov (United States)

    Achor, William T.; And Others

    1988-01-01

    Discusses a wall chart, "The Standard Model of Fundamental Particles and Interactions," for use in introductory physics courses at either high school or college level. Describes the chart development process, introduction and terminology of particle physics, components of the chart, and suggestions for using the chart, booklet, and…

  13. Constraining the fundamental interactions and couplings with Eoetvoes experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kraiselburd, Lucila, E-mail: lkrai@fcaglp.fcaglp.unlp.edu.ar [Grupo de Gravitacion, Astrofisica y Cosmologia, Facultad de Ciencias Astronomicas y Geofisicas, Universidad Nacional de La Plata, Paseo del Bosque S/N (1900) La Plata (Argentina); Vucetich, Hector, E-mail: vucetich@fcaglp.unlp.edu.ar [Grupo de Gravitacion, Astrofisica y Cosmologia, Facultad de Ciencias Astronomicas y Geofisicas, Universidad Nacional de La Plata, Paseo del Bosque S/N (1900) La Plata (Argentina)

    2012-11-15

    Upper bounds for the violation of the Weak Equivalence Principle (WEP) by the fundamental interactions have been given before. We now recompute the limits on the parameters measuring the strength of the violation with the whole set of high accuracy Eoetvoes experiments. Besides, limits on spatial variation of the fundamental constants {alpha}, sin{sup 2}{theta}{sub W} and v, the vacuum expectation value of the Higgs field, are found in a model independent way. Limits on other parameters in the gauge sector are also found from the structure of the Standard Model.

  14. Extremely high-intensity laser interactions with fundamental quantum systems

    CERN Document Server

    Di Piazza, A; Hatsagortsyan, K Z; Keitel, C H

    2011-01-01

    The field of laser-matter interaction traditionally deals with the response of atoms, molecules and plasmas to an external light wave. However, the recent sustained technological progress is opening the possibility of employing intense laser radiation to prompt or substantially influence physical processes beyond atomic-physics energy scales. Available optical laser intensities exceeding $10^{22}\\;\\text{W/cm$^2$}$ can push the fundamental light-electron interaction to the extreme limit where radiation-reaction effects dominate the electron dynamics, can shed light on the structure of the quantum vacuum and can prime the creation of particles like electrons, muons and pions and the corresponding antiparticles. Also, novel sources of intense coherent high-energy photons and laser-based particle colliders can pave the way to nuclear quantum optics and can even allow for potential discovery of new particles beyond the Standard Model. These are the main topics of the present article, which is devoted to a review o...

  15. Revealing physical interaction networks from statistics of collective dynamics

    Science.gov (United States)

    Nitzan, Mor; Casadiego, Jose; Timme, Marc

    2017-01-01

    Revealing physical interactions in complex systems from observed collective dynamics constitutes a fundamental inverse problem in science. Current reconstruction methods require access to a system’s model or dynamical data at a level of detail often not available. We exploit changes in invariant measures, in particular distributions of sampled states of the system in response to driving signals, and use compressed sensing to reveal physical interaction networks. Dynamical observations following driving suffice to infer physical connectivity even if they are temporally disordered, are acquired at large sampling intervals, and stem from different experiments. Testing various nonlinear dynamic processes emerging on artificial and real network topologies indicates high reconstruction quality for existence as well as type of interactions. These results advance our ability to reveal physical interaction networks in complex synthetic and natural systems. PMID:28246630

  16. Francium sources and traps for fundamental interaction studies

    Science.gov (United States)

    Stancari, G.; Atutov, S. N.; Calabrese, R.; Corradi, L.; Dainelli, A.; de Mauro, C.; Khanbekyan, A.; Mariotti, E.; Minguzzi, P.; Moi, L.; Sanguinetti, S.; Tomassetti, L.; Veronesi, S.

    2007-11-01

    Francium is one of the best candidates for atomic parity nonconservation (APNC) and for the search of permanent electric dipole moments (EDMs). APNC measurements test the weak force between electrons and nucleons at very low momentum transfers. They also represent a unique way to detect weak nucleon-nucleon interactions. EDMs are instead related to the time-reversal symmetry. Preliminary to these fundamental measurements are precision studies in atomic spectroscopy and the development of magneto-optical traps (MOT), which partially compensate for the lack of stable Fr isotopes. At LNL Legnaro, francium is produced by fusion of 100-MeV 18O with 197Au in a thick target, followed by evaporation of neutrons from the compound nucleus. Francium diffuses inside the hot target (1200 K) and is surface ionized for injection at 3 keV in an electrostatic beamline. Typically, we produce 1×106 (210Fr ions)/s for a primary flux of 1.5×1012 particles/s. We have studied Fr yields as a function of primary beam energy, intensity, and target temperature. Information on the efficiency of bulk diffusion, surface desorption and ionization is deduced. The beam then enters a Dryfilm-coated cell, where it is neutralized on a heated yttrium plate. The escape time of neutral Fr (diffusion + desorption) is approximately 20 s at 950 K, as measured with a dedicated setup. In the MOT, we use 6 orthogonal Ti:sapphire laser beams for the main pumping transition and 6 beams from a stabilized diode repumper. Fluorescence from trapped atoms is observed with a cooled CCD camera, in order to reach noise levels from stray light equivalent to approximately 50 atoms. Systematic tests are being done to improve the trapping efficiency. We plan to further develop Fr traps at LNL; in parallel, we will study APNC and EDM techniques and systematics with stable alkalis at Pisa, Siena, and Ferrara.

  17. CHAIRMEN'S PREFACE AND EDITORS' NOTE: Unification of Fundamental Interactions

    Science.gov (United States)

    Brink, Lars; Nilsson, Jan S.; Salomonson, Per; Skagerstam, Bo-Sture

    1987-01-01

    Chairmen's PrefaceIn 1984 we obtained a grant from the Nobel Foundation to organize a Nobel Symposium on "Unification of the Fundamental Interactions". In our proposal which we submitted in the fall of 1983 we stated that we wanted to cover the various attempts to unification such as GUT'S, supergravity, Kaluza-Klein theories and superstrings. What has happened in particle physics since then is already history. With the realization that certain superstring theories could be anomaly free, it became clear that these models could encompass earlier attempts to unification as well as solving the fundamental problem of quantum gravity. The excitement that some of us had felt for some time now spread through most of the particle physics community and this excitement certainly was evident during the Symposium. With the international advisory committee we originally chose a list of around 30 invitees which could best represent the various subjects listed above. When it came to the final planning of the programme essentially all talks dealt with superstrings! We were very fortunate that almost all of the invitees managed to come to the Symposium. From the western world only three were unable to participate, André Neveu, Steven Weinberg and Bruno Zumino. We certainly missed them during the meeting. We were particularly happy that Stephen Hawking managed to take part actively. Our real problem was to get participants from the Soviet Union. Out of eight invitations only one came through. We were very happy to have Renata Kallosh, who really did her utmost to enlighten us about not only her own work but also about recent progress in the USSR, However, we were very sorry that in spite of all our letters, telegrammes and endless attempts to get telephone calls through and despite the good relations between the Swedish and Soviet Academies of Sciences we had to miss Ludwig Faddeev, Valodja Gribov, Andrej Linde, Victor Ogievetsky, Sasha Polyakov, Misha Shifman and Arkadij

  18. Fundamental Interactions in Gasoline Compression Ignition Engines with Fuel Stratification

    Science.gov (United States)

    Wolk, Benjamin Matthew

    Transportation accounted for 28% of the total U.S. energy demand in 2011, with 93% of U.S. transportation energy coming from petroleum. The large impact of the transportation sector on global climate change necessitates more-efficient, cleaner-burning internal combustion engine operating strategies. One such strategy that has received substantial research attention in the last decade is Homogeneous Charge Compression Ignition (HCCI). Although the efficiency and emissions benefits of HCCI are well established, practical limits on the operating range of HCCI engines have inhibited their application in consumer vehicles. One such limit is at high load, where the pressure rise rate in the combustion chamber becomes excessively large. Fuel stratification is a potential strategy for reducing the maximum pressure rise rate in HCCI engines. The aim is to introduce reactivity gradients through fuel stratification to promote sequential auto-ignition rather than a bulk-ignition, as in the homogeneous case. A gasoline-fueled compression ignition engine with fuel stratification is termed a Gasoline Compression Ignition (GCI) engine. Although a reasonable amount of experimental research has been performed for fuel stratification in GCI engines, a clear understanding of how the fundamental in-cylinder processes of fuel spray evaporation, mixing, and heat release contribute to the observed phenomena is lacking. Of particular interest is gasoline's pressure sensitive low-temperature chemistry and how it impacts the sequential auto-ignition of the stratified charge. In order to computationally study GCI with fuel stratification using three-dimensional computational fluid dynamics (CFD) and chemical kinetics, two reduced mechanisms have been developed. The reduced mechanisms were developed from a large, detailed mechanism with about 1400 species for a 4-component gasoline surrogate. The two versions of the reduced mechanism developed in this work are: (1) a 96-species version and (2

  19. Interaction Involvement: A Fundamental Dimension of Interpersonal Communication Competence.

    Science.gov (United States)

    Cegala, Donald J.

    E. Husserl's concept of intentionality provides a conceptual perspective of interpersonal communication that suggests a notion of face-to-face communication called "interaction involvement." Structured along dimensions of awareness and responsiveness, interaction involvement explains interpersonal communication as a transactional relationship…

  20. Advanced man-machine interaction. Fundamentals and implementation

    Energy Technology Data Exchange (ETDEWEB)

    Kraiss, K.F. (ed.) [Aachen Technische Hochschule (Germany). Lehrstuhl fuer Technische Informatik und Computerwissenschaften

    2006-07-01

    Man-machine interaction is the gateway providing access to functions and services, which, due to the ever increasing complexity of smart systems, threatens to become a bottleneck. This book therefore introduces not only advanced interfacing concepts, but also gives insight into the related theoretical background.This refers mainly to the realization of video-based multimodal interaction via gesture, mimics, and speech, but also to interacting with virtual object in virtual environments, cooperating with local or remote robots, and user assistance. While most publications in the field of human factors engineering focus on interface design, this book puts special emphasis on implementation aspects. To this end it is accompanied by software development environments for image processing, classification, and virtual environment implementation. In addition a test data base is included for gestures, head pose, facial expressions, full-body person recognition, and people tracking. These data are used for the examples throughout the book, but are also meant to encourage the reader to start experimentation on his own. Thus the book may serve as a self-contained introduction both for researchers and developers of man-machine interfaces. It may also be used for graduate-level university courses. (orig.)

  1. Revealed Quantum Information in Weak Interaction Processes

    CERN Document Server

    Hiesmayr, B C

    2014-01-01

    We analyze the achievable limits of the quantum information processing of the weak interaction revealed by hyperons with spin. We find that the weak decay process corresponds to an interferometric device with a fixed visibility and fixed phase difference for each hyperon. Nature chooses rather low visibilities expressing a preference to parity conserving or violating processes (except for the decay $\\Sigma^+\\longrightarrow p \\pi^0$). The decay process can be considered as an open quantum channel that carries the information of the hyperon spin to the angular distribution of the momentum of the daughter particles. We find a simple geometrical information theoretic interpretation of this process: two quantization axes are chosen spontaneously with probabilities $\\frac{1\\pm\\alpha}{2}$ where $\\alpha$ is proportional to the visibility times the real part of the phase shift. Differently stated the weak interaction process corresponds to spin measurements with an imperfect Stern-Gerlach apparatus. Equipped with this...

  2. Fundamentals of protein and cell interactions in biomaterials.

    Science.gov (United States)

    Aiyelabegan, Hammed Tanimowo; Sadroddiny, Esmaeil

    2017-04-01

    The extracellular matrix (ECM) is an active and complex microenvironment with outstanding biomechanical, biophysical, and biochemical characteristics, which can indirectly or directly controls cell adhesion, migration, proliferation, and differentiation, as well as partaking in regeneration and homeostasis of organs and tissues. The ECM has captivated a great deal of attention with the rapid progress of tissue engineering (TE) in the field of regenerative medicine (RM). Approaches to TE, RM and cancer therapy center on the necessity to deliver cell signals to direct cell proliferation and differentiation. These "external signals" are induced from cell-cell, and cell-ECM, interactions, as well as from physico-chemical, mechanical stimuli and growth factors. With the advent of new biomaterials such as casein, we gave a general insight into cell-ECM protein interactions in biomaterials and their applications in TE, RM and cancer therapy. An account of the main ECM molecules and cellular receptors with emphasis on integrins and its ligands was given, their effect on the induction of particular signal transduction pathways is also elucidated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. The Weyl Theory of Fundamental Interactions Is CPT violated?

    CERN Document Server

    Soo, C P; Soo, Chopin; Chang, Lay Nam

    1997-01-01

    We compare the conventional description of the interaction of matter with the four known forces in the standard model with an alternative Weyl description in which the chiral coupling is extended to include gravity. The two are indistinguishable at the low energy classical level of equations of motion, but there are subtle differences at the quantum level when nonvanishing torsion and the Adler-Bell-Jackiw anomaly is taken into account. The spin current and energy-momentum of the chiral theory then contain non-Hermitian terms which are not present in the conventional theory. In the chiral alternative, CPT invariance is not automatic because chirality supersedes Hermiticity but full Lorentz invariance holds. New fermion loop processes associated with the theory are discussed together with a perturbative regularization which explicitly maintains the chiral nature and local symmetries of the theory.

  4. Fundamental hydrogen interactions with beryllium : a magnetic fusion perspective.

    Energy Technology Data Exchange (ETDEWEB)

    Wampler, William R. (Sandia National Laboratories, Albuquerque, NM); Felter, Thomas E.; Whaley, Josh A.; Kolasinski, Robert D.; Bartelt, Norman Charles

    2012-03-01

    Increasingly, basic models such as density functional theory and molecular dynamics are being used to simulate different aspects of hydrogen recycling from plasma facing materials. These models provide valuable insight into hydrogen diffusion, trapping, and recombination from surfaces, but their validation relies on knowledge of the detailed behavior of hydrogen at an atomic scale. Despite being the first wall material for ITER, basic single crystal beryllium surfaces have been studied only sparsely from an experimental standpoint. In prior cases researchers used electron spectroscopy to examine surface reconstruction or adsorption kinetics during exposure to a hydrogen atmosphere. While valuable, these approaches lack the ability to directly detect the positioning of hydrogen on the surface. Ion beam techniques, such as low energy ion scattering (LEIS) and direct recoil spectroscopy (DRS), are two of the only experimental approaches capable of providing this information. In this study, we applied both LEIS and DRS to examine how hydrogen binds to the Be(0001) surface. Our measurements were performed using an angle-resolved ion energy spectrometer (ARIES) to probe the surface with low energy ions (500 eV - 3 keV He{sup +} and Ne{sup +}). We were able to obtain a 'scattering maps' of the crystal surface, providing insight on how low energy ions are focused along open surface channels. Once we completed a characterization of the clean surface, we dosed the sample with atomic hydrogen using a heated tungsten capillary. A distinct signal associated with adsorbed hydrogen emerged that was consistent with hydrogen residing between atom rows. To aid in the interpretation of the experimental results, we developed a computational model to simulate ion scattering at grazing incidence. For this purpose, we incorporated a simplified surface model into the Kalypso molecular dynamics code. This approach allowed us to understand how the incident ions interacted with the

  5. The Fundamental Plane of star formation in galaxies revealed by the EAGLE hydrodynamical simulations

    Science.gov (United States)

    Lagos, Claudia del P.; Theuns, Tom; Schaye, Joop; Furlong, Michelle; Bower, Richard G.; Schaller, Matthieu; Crain, Robert A.; Trayford, James W.; Matthee, Jorryt

    2016-07-01

    We investigate correlations between different physical properties of star-forming galaxies in the `Evolution and Assembly of GaLaxies and their Environments' (EAGLE) cosmological hydrodynamical simulation suite over the redshift range 0 ≤ z ≤ 4.5. A principal component analysis reveals that neutral gas fraction (fgas,neutral), stellar mass (Mstellar) and star formation rate (SFR) account for most of the variance seen in the population, with galaxies tracing a two-dimensional, nearly flat, surface in the three-dimensional space of fgas, neutral-Mstellar-SFR with little scatter. The location of this plane varies little with redshift, whereas galaxies themselves move along the plane as their fgas, neutral and SFR drop with redshift. The positions of galaxies along the plane are highly correlated with gas metallicity. The metallicity can therefore be robustly predicted from fgas, neutral, or from the Mstellar and SFR. We argue that the appearance of this `Fundamental Plane of star formation' is a consequence of self-regulation, with the plane's curvature set by the dependence of the SFR on gas density and metallicity. We analyse a large compilation of observations spanning the redshift range 0 ≲ z ≲ 3, and find that such a plane is also present in the data. The properties of the observed Fundamental Plane of star formation are in good agreement with EAGLE's predictions.

  6. Fundamental symmetries and interactions studied with radioactive isotopes in atom traps

    NARCIS (Netherlands)

    Wilschut, H.W.E.M.; Gacsi, Z; Dombradi, Z; Krasznahorkay, A

    2005-01-01

    The structure of certain nuclei and atoms allow one to study fundamental symmetries and interactions. In this review we consider the search for Time-Reversal invariance Violation (TRV). We consider two options: TRV in beta decay or the search for the forbidden Electric Dipole Moment (EDM). In both c

  7. TRI mu P - A new facility to investigate fundamental interactions with optically trapped radioactive atoms

    NARCIS (Netherlands)

    Jungmann, K

    At the Kernfysisch Versneller Instituut (KVI) in Groningen, NL, a new facility (TRImuP) is under development. It aims for producing, slowing down and trapping of radioactive isotopes in order to perform accurate measurements on fundamental symmetries and interactions. A spectrum of radioactive

  8. A Novel Method for Fundamental Interaction Studies with Electrostatic Ion Beam Trap

    CERN Document Server

    Vaintraub, S; Aviv, O; Heber, O; Mardor, I

    2010-01-01

    Trapped radioactive atoms present exciting opportunities for the study of fundamental interactions and symmetries. For example, detecting beta decay in a trap can probe the minute experimental signal that originates from possible tensor or scalar terms in the weak interaction. Such scalar or tensor terms affect, e.g., the angular correlation between a neutrino and an electron in the beta-decay process, thus probing new physics of "beyond-the-standard-model" nature. In particular, this article focuses on a novel use of an innovative ion trapping device, the Electrostatic Ion Beam Trap (EIBT). Such a trap has not been previously considered for Fundamental Interaction studies and exhibits potentially very significant advantages over other schemes. These advantages include improved injection efficiency of the radionuclide under study, an extended field-free region, ion-beam kinematics for better efficiency and ease-of-operation and the potential for a much larger solid angle for the electron and recoiling atom co...

  9. Human-computer interaction handbook fundamentals, evolving technologies and emerging applications

    CERN Document Server

    Sears, Andrew

    2007-01-01

    This second edition of The Human-Computer Interaction Handbook provides an updated, comprehensive overview of the most important research in the field, including insights that are directly applicable throughout the process of developing effective interactive information technologies. It features cutting-edge advances to the scientific knowledge base, as well as visionary perspectives and developments that fundamentally transform the way in which researchers and practitioners view the discipline. As the seminal volume of HCI research and practice, The Human-Computer Interaction Handbook feature

  10. Fundamental gaps with approximate density functionals: The derivative discontinuity revealed from ensemble considerations

    Energy Technology Data Exchange (ETDEWEB)

    Kraisler, Eli; Kronik, Leeor [Department of Materials and Interfaces, Weizmann Institute of Science, Rehovoth 76100 (Israel)

    2014-05-14

    The fundamental gap is a central quantity in the electronic structure of matter. Unfortunately, the fundamental gap is not generally equal to the Kohn-Sham gap of density functional theory (DFT), even in principle. The two gaps differ precisely by the derivative discontinuity, namely, an abrupt change in slope of the exchange-correlation energy as a function of electron number, expected across an integer-electron point. Popular approximate functionals are thought to be devoid of a derivative discontinuity, strongly compromising their performance for prediction of spectroscopic properties. Here we show that, in fact, all exchange-correlation functionals possess a derivative discontinuity, which arises naturally from the application of ensemble considerations within DFT, without any empiricism. This derivative discontinuity can be expressed in closed form using only quantities obtained in the course of a standard DFT calculation of the neutral system. For small, finite systems, addition of this derivative discontinuity indeed results in a greatly improved prediction for the fundamental gap, even when based on the most simple approximate exchange-correlation density functional – the local density approximation (LDA). For solids, the same scheme is exact in principle, but when applied to LDA it results in a vanishing derivative discontinuity correction. This failure is shown to be directly related to the failure of LDA in predicting fundamental gaps from total energy differences in extended systems.

  11. Complex-Dynamical Solution to Many-Body Interaction Problem and Its Applications in Fundamental Physics

    CERN Document Server

    Kirilyuk, Andrei P

    2012-01-01

    We review the recently proposed unreduced, complex-dynamical solution to many-body problem with arbitrary interaction and its application to unified solution of fundamental problems, including foundations of causally complete quantum mechanics, relativity, particle properties and cosmology. We first analyse the universal properties of many-body problem solution without any perturbative reduction and show that the emerging new quality of fundamental dynamic multivaluedness (or redundance) of resulting system configuration leads to universal concept of dynamic complexity, chaoticity and fractality of any real system behaviour. We then consider unified features of this complex dynamics. Applications of that universal description to systems at various complexity levels have been performed and in this paper we review those at the lowest, fundamental complexity levels leading to causal understanding of unified origins of quantum mechanics, relativity (special and general), elementary particles, their intrinsic prop...

  12. Spatial interactions determine temporal feature integration as revealed by unmasking

    Directory of Open Access Journals (Sweden)

    Michael H. Herzog

    2006-01-01

    Full Text Available Feature integration is one of the most fundamental problems in neuroscience. In a recent contribution, we showed that a trailing grating can diminish the masking effects one vernier exerts on another, preceding vernier. Here, we show that this temporal unmasking depends on neural spatial interactions related to the trailing grating. Hence, our paradigm allows us to study the spatio-temporal interactions underlying feature integration.

  13. Fundamental Limits for Light Absorption and Scattering Induced by Cooperative Electromagnetic Interactions

    CERN Document Server

    Hugonin, Jean-Paul; Ben-Abdallah, Philippe

    2015-01-01

    Absorption and scattering of electromagnetic waves by dielectric media are of fundamental importance in many branches of physics. In this Letter we analytically derived the ultimate upper limits for the absorbed and scattered powers by any system of optical resonators in mutual interaction. We show that these bounds depend only on the geometric configuration given an incident field. We give the conditions to fullfill to reach these limits paving so a way for a rational design of optimal metamaterials.

  14. Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification.

    Science.gov (United States)

    Bertazzo, Sergio; Gentleman, Eileen; Cloyd, Kristy L; Chester, Adrian H; Yacoub, Magdi H; Stevens, Molly M

    2013-06-01

    The accumulation of calcified material in cardiovascular tissue is thought to involve cytochemical, extracellular matrix and systemic signals; however, its precise composition and nanoscale architecture remain largely unexplored. Using nano-analytical electron microscopy techniques, we examined valves, aortae and coronary arteries from patients with and without calcific cardiovascular disease and detected spherical calcium phosphate particles, regardless of the presence of calcific lesions. We also examined lesions after sectioning with a focused ion beam and found that the spherical particles are composed of highly crystalline hydroxyapatite that crystallographically and structurally differs from bone mineral. Taken together, these data suggest that mineralized spherical particles may play a fundamental role in calcific lesion formation. Their ubiquitous presence in varied cardiovascular tissues and from patients with a spectrum of diseases further suggests that lesion formation may follow a common process. Indeed, applying materials science techniques to ectopic and orthotopic calcification has great potential to lend critical insights into pathophysiological processes underlying calcific cardiovascular disease.

  15. Human-Computer Interaction Handbook Fundamentals, Evolving Technologies, and Emerging Applications

    CERN Document Server

    Jacko, Julie A

    2012-01-01

    The third edition of a groundbreaking reference, The Human--Computer Interaction Handbook: Fundamentals, Evolving Technologies, and Emerging Applications raises the bar for handbooks in this field. It is the largest, most complete compilation of HCI theories, principles, advances, case studies, and more that exist within a single volume. The book captures the current and emerging sub-disciplines within HCI related to research, development, and practice that continue to advance at an astonishing rate. It features cutting-edge advances to the scientific knowledge base as well as visionary perspe

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

    Energy Technology Data Exchange (ETDEWEB)

    Jack Sculley

    1999-04-27

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Jack Sculley

    1999-04-27

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

  18. Revealing Fundamental Physics from the Daya Bay Neutrino Experiment using Deep Neural Networks

    CERN Document Server

    Racah, Evan; Sadowski, Peter; Bhimji, Wahid; Tull, Craig; Oh, Sang-Yun; Baldi, Pierre; Prabhat,

    2016-01-01

    Experiments in particle physics produce enormous quantities of data that must be analyzed and interpreted by teams of physicists. This analysis is often exploratory, where scientists are unable to enumerate the possible types of signal prior to performing the experiment. Thus, tools for summarizing, clustering, visualizing and classifying high-dimensional data are essential. In this work, we show that meaningful physical content can be revealed by transforming the raw data into a learned high-level representation using deep neural networks, with measurements taken at the Daya Bay Neutrino Experiment as a case study. We further show how convolutional deep neural networks can provide an effective classification filter with greater than 97% accuracy across different classes of physics events, significantly better than other machine learning approaches.

  19. Fundamental x-ray interaction limits in diagnostic imaging detectors: spatial resolution.

    Science.gov (United States)

    Hajdok, G; Battista, J J; Cunningham, I A

    2008-07-01

    The practice of diagnostic x-ray imaging has been transformed with the emergence of digital detector technology. Although digital systems offer many practical advantages over conventional film-based systems, their spatial resolution performance can be a limitation. The authors present a Monte Carlo study to determine fundamental resolution limits caused by x-ray interactions in four converter materials: Amorphous silicon (a-Si), amorphous selenium, cesium iodide, and lead iodide. The "x-ray interaction" modulation transfer function (MTF) was determined for each material and compared in terms of the 50% MTF spatial frequency and Wagner's effective aperture for incident photon energies between 10 and 150 keV and various converter thicknesses. Several conclusions can be drawn from their Monte Carlo study. (i) In low-Z (a-Si) converters, reabsorption of Compton scatter x rays limits spatial resolution with a sharp MTF drop at very low spatial frequencies (x rays plays a dominant role, resulting in a mid-frequency (1-5 cycles/mm) MTF drop. (ii) Coherent scatter plays a minor role in the x-ray interaction MTF. (iii) The spread of energy due to secondary electron (e.g., photoelectrons) transport is significant only at very high spatial frequencies. (iv) Unlike the spread of optical light in phosphors, the spread of absorbed energy from x-ray interactions does not significantly degrade spatial resolution as converter thickness is increased. (v) The effective aperture results reported here represent fundamental spatial resolution limits of the materials tested and serve as target benchmarks for the design and development of future digital x-ray detectors.

  20. The fundamental plane of star formation in galaxies revealed by the EAGLE hydrodynamical simulations

    CERN Document Server

    Lagos, Claudia del P; Schaye, Joop; Furlong, Michelle; Bower, Richard G; Schaller, Matthieu; Crain, Robert A; Trayford, James W; Matthee, Jorryt

    2015-01-01

    We investigate correlations between different physical properties of star-forming galaxies in the "Evolution and Assembly of GaLaxies and their Environments" (EAGLE) cosmological hydrodynamical simulation suite over the redshift range $0\\le z\\le 4.5$. A principal component analysis reveals that neutral gas fraction ($f_{\\rm gas, neutral}$), stellar mass ($M_{\\rm stellar}$) and star formation rate (SFR) account for most of the variance seen in the population, with galaxies tracing a two-dimensional, nearly flat, surface in the three-dimensional space of $f_{\\rm gas, neutral}-M_{\\rm stellar}-\\rm SFR$ with little scatter. The location of this plane varies little with redshift, whereas galaxies themselves move along the plane as their $f_{\\rm gas, neutral}$ and SFR drop with redshift. The positions of galaxies along the plane are highly correlated with gas metallicity. The metallicity can therefore be robustly predicted from $f_{\\rm gas, neutral}$, or from the $M_{\\rm stellar}$ and SFR. We argue that the appearan...

  1. Particles and fundamental interactions supplements, problems and solutions : a deeper insight into particle physics

    CERN Document Server

    Braibant, Sylvie; Spurio, Maurizio

    2012-01-01

    This volume is an exercises and solutions manual that complements  the book "Particles and Fundamental Interactions" by Sylvie Braibant, Giorgio Giacomelli, and Maurizio Spurio.  It aims to give additional intellectual stimulation for students in experimental particle physics. It will be a helpful companion in the preparation of a written examination, but also it provides a means to gaining a deeper understanding of high energy physics. The problems proposed are sometimes true and important research questions, which are described and solved in a step-by-step manner. In addition to the problems and solutions, this book offers fifteen Supplements that give further insight into topical subjects related to particle accelerators, signal and data acquisition systems and computational methods to treat them.

  2. Fundamental fermion interactions via vector bosons of unified SU(2 x SU(4 gauge fields

    Directory of Open Access Journals (Sweden)

    Eckart eMarsch

    2016-02-01

    Full Text Available Employing the fermion unification model based on the intrinsic SU(8 symmetry of a generalized Dirac equation, we discuss the fundamental interactions under the SU(8=SU(2$otimes$SU(4 symmetry group. The physics involved can describe all fermions, the leptons (electron and neutrino, and the coloured up and down quarks of the first generation in the standard model (SM by a complex SU(8 octet of Dirac spinor fields. The fermion interactions are found to be mediated by the unified SU(4 and SU(2 vector gauge boson fields, which include the photon, the gluons, and the bosons $Z$ and $W$ as well known from the SM, but also comprise new ones, namely three coloured $X$ bosons carrying a fractional hypercharge of $pm4/3$ and transmuting leptons into quarks and vice versa. The full covariant derivative of the model is derived and discussed. The Higgs mechanism gives mass to the $Z$ and $W$ bosons, but also permits one to derive the mass of the coloured $X$ boson, for which depending on the choice of the values of the coupling constant, the estimates are 35~GeV or 156~GeV, values that are well within reach of the LHC. The scalar Higgs field can also lend masses to the fermions and fix their physical values for given appropriate coupling constants to that field.

  3. Fundamental fermion interactions via vector bosons of unified SU(2) x SU(4) gauge fields

    Science.gov (United States)

    Marsch, Eckart; Narita, Yasuhito

    2016-02-01

    Employing the fermion unification model based on the intrinsic SU(8) symmetry of a generalized Dirac equation, we discuss the fundamental interactions under the SU(8)=SU(2)⊗SU(4) symmetry group. The physics involved can describe all fermions, the leptons (electron and neutrino), and the coloured up and down quarks of the first generation in the standard model (SM) by a complex SU(8) octet of Dirac spinor fields. The fermion interactions are found to be mediated by the unified SU(4) and SU(2) vector gauge boson fields, which include the photon, the gluons, and the bosons Z and W as well known from the SM, but also comprise new ones, namely three coloured X bosons carrying a fractional hypercharge of ±4/3 and transmuting leptons into quarks and vice versa. The full covariant derivative of the model is derived and discussed. The Higgs mechanism gives mass to the Z and W bosons, but also permits one to derive the mass of the coloured X boson, for which depending on the choice of the values of the coupling constant, the estimates are 35~GeV or 156~GeV, values that are well within reach of the LHC. The scalar Higgs field can also lend masses to the fermions and fix their physical values for given appropriate coupling constants to that field.

  4. Fundamentals of nanoscale polymer-protein interactions and potential contributions to solid-state nanobioarrays.

    Science.gov (United States)

    Hahm, Jong-in

    2014-08-26

    Protein adsorption onto polymer surfaces is a very complex, ubiquitous, and integrated process, impacting essential areas of food processing and packaging, health devices, diagnostic tools, and medical products. The nature of protein-surface interactions is becoming much more complicated with continuous efforts toward miniaturization, especially for the development of highly compact protein detection and diagnostic devices. A large body of literature reports on protein adsorption from the perspective of ensemble-averaged behavior on macroscopic, chemically homogeneous, polymeric surfaces. However, protein-surface interactions governing the nanoscale size regime may not be effectively inferred from their macroscopic and microscopic characteristics. Recently, research efforts have been made to produce periodically arranged, nanoscopic protein patterns on diblock copolymer surfaces solely through self-assembly. Intriguing protein adsorption phenomena are directly probed on the individual biomolecule level for a fundamental understanding of protein adsorption on nanoscale surfaces exhibiting varying degrees of chemical heterogeneity. Insight gained from protein assembly on diblock copolymers can be effectively used to control the surface density, conformation, orientation, and biofunctionality of prebound proteins in highly miniaturized applications, now approaching the nanoscale. This feature article will highlight recent experimental and theoretical advances made on these fronts while focusing on single-biomolecule-level investigations of protein adsorption behavior combined with surface chemical heterogeneity on the length scale commensurate with a single protein. This article will also address advantages and challenges of the self-assembly-driven patterning technology used to produce protein nanoarrays and its implications for ultrahigh density, functional, and quantifiable protein detection in a highly miniaturized format.

  5. TRI{mu}P facility for the study of fundamental interaction and symmetries

    Energy Technology Data Exchange (ETDEWEB)

    Shidling, P.D.; Giri, G.S.; Jungmann, K.; Kruithof, W.L.; Sohani, M.; Hoek, D.J. van der; Versolato, O.O.; Willmann, L.; Wilschut, H.W. [KVI, University of Groningen (Netherlands)

    2009-07-01

    Rare and short lived radioactive isotopes provide unique possibility for the study of fundamental interaction and symmetries. At TRI{mu}P different radioactive isotopes are produced in inverse kinematics mode. Dual magnetic separator is used for separating fast radioactive isotopes of interest from the primary beam. For example, {sup 21}Na are produced with a yield of 10{sup 4}/s/pnA (of primary beam) in the {sup 20}Ne({sup 2}H,n){sup 21}Na reaction. Produced fast radioactive isotopes are converted into low energy ion beams in thermal ionizer. This allows one to collect efficiently and transport the ions into magneto-Optical Trap (MOT) and ions are neutralized in MOT chamber. We will measure {beta}-{nu} energy and angular correlation measurement in {beta} decay for {sup 21}Na. From this measurement, deviation from the weak interaction (V-A type) can be studied. One of the other measurements which are of our particular interest is search of permanent electric dipole moment, and to improve the value for parity non conservation in Ra. Different radium isotopes have been produced in inverse kinematics. {sup 213}Ra has been produced with a typical yield of 10{sup 3} /s/pnA (Pb beam) in {sup 206}Pb({sup 12}C,5n) {sup 213}Ra reaction. A procedure to trap Ra effectively has been successfully developed by the first time trapping of Ba. Details on the facility and new technological approaches for several units of the TRI{mu}P facility are presented.

  6. Longwall roof control through a fundamental understanding of shield-strata interaction

    Energy Technology Data Exchange (ETDEWEB)

    Trueman, R.; Lyman, G.; Cocker, A. [Strata Engineering Australia Pty. Ltd, Charlestown, NSW (Australia)

    2009-02-15

    Real-time and non-real-time software has been developed that encapsulates a fundamental understanding of the interaction between a longwall powered support (shield) and the surrounding strata based on the interpretation of the leg pressure data within each load cycle. A load cycle is the change in support pressure with time from setting the shield against the roof to the next release and movement of the support. It is now possible to automatically identify when a shield has too low a set pressure, and when a shield is faulty and/or has an inadequate capacity for the conditions. The use of this software has the potential to significantly reduce or even eliminate roof control problems on a longwall face with significant benefits to both productivity and safety. By automatically identifying potential causes of roof control problems and offering solutions, the software has the potential to aid longwall automation. A Beta test version of the real-time software has been successfully working at BMA's Broadmeadow Mine in Australia for some time and several Australian mines have benefited from expert off-line analyses using the software. The software can also be used to isolate the many interconnected factors affecting roof control on a longwall face, which will enable their quantification, and is therefore a powerful research tool.

  7. Vowel recognition at fundamental frequencies up to 1 kHz reveals point vowels as acoustic landmarks.

    Science.gov (United States)

    Friedrichs, Daniel; Maurer, Dieter; Rosen, Stuart; Dellwo, Volker

    2017-08-01

    The phonological function of vowels can be maintained at fundamental frequencies (fo) up to 880 Hz [Friedrichs, Maurer, and Dellwo (2015). J. Acoust. Soc. Am. 138, EL36-EL42]. Here, the influence of talker variability and multiple response options on vowel recognition at high fos is assessed. The stimuli (n = 264) consisted of eight isolated vowels (/i y e ø ε a o u/) produced by three female native German talkers at 11 fos within a range of 220-1046 Hz. In a closed-set identification task, 21 listeners were presented excised 700-ms vowel nuclei with quasi-flat fo contours and resonance trajectories. The results show that listeners can identify the point vowels /i a u/ at fos up to almost 1 kHz, with a significant decrease for the vowels /y ε/ and a drop to chance level for the vowels /e ø o/ toward the upper fos. Auditory excitation patterns reveal highly differentiable representations for /i a u/ that can be used as landmarks for vowel category perception at high fos. These results suggest that theories of vowel perception based on overall spectral shape will provide a fuller account of vowel perception than those based solely on formant frequency patterns.

  8. Interactions of subglottal pressure and neuromuscular activation on fundamental frequency and intensity.

    Science.gov (United States)

    Chhetri, Dinesh K; Park, Soo Jin

    2016-05-01

    Fundamental frequency (F0) and intensity sound pressure level (SPL) of voice are controlled by intrinsic laryngeal muscle (ILM) activation and subglottal pressure (Psub). Their interactions were investigated. In an in vivo canine model, the thyroarytenoid (TA), lateral cricoarytenoid/interarytenoid (LCA/IA), and cricothyroid (CT) muscles were independently activated from threshold to maximal contraction by neuromuscular stimulation in various combinations, whereas airflow was increased to phonation onset pressure and beyond. The resultant acoustic output was analyzed for effects of Psub on vibratory stability, F0, and SPL. Muscle activation plots and vocal range profiles by individual ILM activation states were analyzed. Cricothyroid activation increased phonation onset F0, but vibration was less stable in high CT conditions and displayed vibratory mode change. In addition, a decrease in F0 with increased Psub was observed in high CT conditions. Intensity increased with Psub in all conditions, but the slope was greater at high CT, low TA/LCA/IA activations. Lateral cricoarytenoid/interarytenoid activation improved vocal efficiency. To maintain same F0 with increasing SPL (messa di voce), TA activation was decreased and LCA/IA activation was increased. The same F0 and SPL could be achieved with a variety of ILM activation combinations. Cricothyroid is primarily required for increasing F0, whereas TA can increase or decrease F0 and SPL. Lateral cricoarytenoid/interarytenoid activation likely maintains vocal fold adduction during increased Psub and improves vocal efficiency. This study also demonstrates laryngeal motor equivalence, the ability of the larynx to achieve the same target F0 and SPL with multiple combinations of ILM activation. N/A. Laryngoscope, 126:1123-1130, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Fisher's fundamental theorem of inclusive fitness and the change in fitness due to natural selection when conspecifics interact.

    Science.gov (United States)

    Bijma, P

    2010-01-01

    Competition and cooperation is fundamental to evolution by natural selection, both in animals and plants. Here, I investigate the consequences of such interactions for response in fitness due to natural selection. I provide quantitative genetic expressions for heritable variance and response in fitness due to natural selection when conspecifics interact. Results show that interactions among conspecifics generate extra heritable variance in fitness, and that interacting with kin is the key to evolutionary success because it translates the extra heritable variance into response in fitness. This work also unifies Fisher's fundamental theorem of natural selection (FTNS) and Hamilton's inclusive fitness (IF). The FTNS implies that natural selection maximizes fitness, whereas Hamilton proposed maximization of IF. This work shows that the FTNS describes the increase in IF, rather than direct fitness, at a rate equal to the additive genetic variance in fitness. Thus, Hamilton's IF and Fisher's FTNS both describe the maximization of IF.

  10. Fundamental nucleon-nucleon interaction: probing exotic nuclear structure using GEANIE at LANCE/WNR

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, L

    2000-02-25

    The initial goal of this project was to study the in-medium nucleon-nucleon interaction by testing the fundamental theory of nuclear structure, the shell model, for nuclei between {sup 8}Zr and {sup 100}Sn. The shell model predicts that nuclei with ''magic'' (2,8,20,28,40,50, and 82) numbers of protons or neutrons form closed shells in the same fashion as noble gas atoms [may49]. A ''doubly magic'' nucleus with a closed shell of both protons and neutrons has an extremely simple structure and is therefore ideal for studying the nucleon-nucleon interaction. The shell model predicts that doubly magic nuclei will be spherical and that they will have large first-excited-state energies ({approx} 1 to 3 MeV). Although the first four doubly-magic nuclei exhibit this behavior, the N = Z = 40 nucleus, {sup 80}Zr, has a very low first-excited-state energy (290 keV) and appears to be highly deformed. This breakdown is attributed to the small size of the shell gap at N = Z = 40. If this description is accurate, then the N = Z = 50 doubly magic nucleus, {sup 100}Sn, will exhibit ''normal'' closed-shell behavior. The unique insight provided by doubly-magic nuclei from {sup 80}Zr to {sup 100}Sn has made them the focus of tremendous interest in the nuclear structure community. However, doubly-magic nuclei heavier than {sup 56}Ni become increasingly difficult to form due to the coulomb repulsion between the protons which favors the formation of neutron-rich nuclei. The coulomb repulsion creates a ''proton drip-line'' beyond which the addition of any additional bound protons is energetically impossible. The drip line renders the traditional experimental technique used in their formation, the heavy-ion reaction, less than ideal as a method of forming doubly-magic nuclei beyond {sup 80}Zr. The result has been a lack of an new spectroscopic information on doubly magic nuclei in more than a decade [lis87

  11. An Investigation on the Fundamental Interaction between Abeta Peptides and the AT-Rich DNA.

    Science.gov (United States)

    Zhao, Li Na; Zheng, Jie; Chew, Lock Yue; Mu, Yuguang

    2015-07-01

    DNA damage is ubiquitous in all mammalian cells with the occurrence of more than 60,000 times per day per cell. In particular, DNA damage in neurons is found to accumulate with age and has been suggested to interfere with the synthesis of functional proteins. Moreover, recent studies have found through transgenic mice that human amyloid precursor protein causes an increase in DNA double-strand breaks (DSBs) with the effect of a prolongation in DNA repair. It is surmised that amyloid β (Aβ) exacerbates the DNA DSBs in neurons, possibly engendering neuronal dysfunction as a result. However, a good understanding on the holistic interaction mechanisms and the manner in which Aβ intertwines with DNA damage is still in its infancy. In our study, we found that DNA with an AT-rich sequence has a very low binding affinity toward Aβ by means of molecular dynamics simulation. While we have pursued a particular sequence of DNA in this study, other DNA sequences are expected to affect the interaction and binding affinity between DNA and Aβ, and will be pursued in our further research. Nonetheless, we have uncovered favorable interaction between the positively charged side chain of Aβ and the two ends of DNA. The latest experiment reveals that many of the double-stranded breaks in neurons can be fixed via DNA repair mechanisms but not in the case that Aβs are present. It is found that the increased numbers of DSBs prevail in active neurons. Here, on the basis of the favorable interaction between Aβ and the two ends of DNA, we propose the possibility that Aβ prevents DNA repair via binding directly to the break ends of the DNA, which further exacerbates DNA damage. Moreover, we have found that the base pair oxygen of the DNA has a greater preference to form hydrogen bonds than the backbone oxygen with Aβ at the two ends. Thus, we postulate that Aβ could serve to prevent the repair of AT-rich DNA, and it is unlikely to cause its breakage or affect its binding toward

  12. Revealing Fundamental Interactions: the Role of Polarized Positrons and Electrons at the Linear Collider

    Energy Technology Data Exchange (ETDEWEB)

    Moortgat-Pick, G.; /CERN /Durham U., IPPP; Abe, T.; Alexander, G.; Ananthanarayan, B.; Babich, A.A.; Bharadwaj, V.; Barber, D.; Bartl, A.; Brachmann, A.; Chen, S.; Clarke,; Clendenin, J.E.; Dainton, J.; Desch, K.; Diehl, M.; Dobos, B.; Dorland, T.; Eberl, H.; Ellis, John R.; Flottman, K.; Frass, H.; /CERN /Durham U., IPPP /Colorado U. /Tel-Aviv

    2005-07-06

    The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization.

  13. The Role of polarized positrons and electrons in revealing fundamental interactions at the linear collider

    Energy Technology Data Exchange (ETDEWEB)

    Moortgat-Pick, G.; /CERN /Durham U., IPPP; Abe, T.; Alexander, G.; Ananthanarayan, B.; Babich, A.A.; Bharadwaj, V.; Barber, D.; Bartl, A.; Brachmann, A.; Chen, S.; Clarke,; Clendenin, J.E.; Dainton, J.; Desch, K.; Diehl, M.; Dobos, B.; Dorland, T.; Eberl, H.; Ellis, John R.; Flottman, K.; Frass, H.; /CERN /Durham U., IPPP /Colorado U. /Tel-Aviv

    2005-07-01

    The proposed International Linear Collider (ILC) is well-suited for discovering physics beyond the Standard Model and for precisely unraveling the structure of the underlying physics. The physics return can be maximized by the use of polarized beams. This report shows the paramount role of polarized beams and summarizes the benefits obtained from polarizing the positron beam, as well as the electron beam. The physics case for this option is illustrated explicitly by analyzing reference reactions in different physics scenarios. The results show that positron polarization, combined with the clean experimental environment provided by the linear collider, allows to improve strongly the potential of searches for new particles and the identification of their dynamics, which opens the road to resolve shortcomings of the Standard Model. The report also presents an overview of possible designs for polarizing both beams at the ILC, as well as for measuring their polarization.

  14. Fisher's fundamental theorem of inclusive fitness and the change in fitness due to natural selection when conspecifics interact

    NARCIS (Netherlands)

    Bijma, P.

    2010-01-01

    Competition and cooperation is fundamental to evolution by natural selection, both in animals and plants. Here, I investigate the consequences of such interactions for response in fitness due to natural selection. I provide quantitative genetic expressions for heritable variance and response in

  15. Fisher's fundamental theorem of inclusive fitness and the change in fitness due to natural selection when conspecifics interact

    NARCIS (Netherlands)

    Bijma, P.

    2010-01-01

    Competition and cooperation is fundamental to evolution by natural selection, both in animals and plants. Here, I investigate the consequences of such interactions for response in fitness due to natural selection. I provide quantitative genetic expressions for heritable variance and response in fitn

  16. Synthetic protein interactions reveal a functional map of the cell

    Science.gov (United States)

    Berry, Lisa K; Ólafsson, Guðjón; Ledesma-Fernández, Elena; Thorpe, Peter H

    2016-01-01

    To understand the function of eukaryotic cells, it is critical to understand the role of protein-protein interactions and protein localization. Currently, we do not know the importance of global protein localization nor do we understand to what extent the cell is permissive for new protein associations – a key requirement for the evolution of new protein functions. To answer this question, we fused every protein in the yeast Saccharomyces cerevisiae with a partner from each of the major cellular compartments and quantitatively assessed the effects upon growth. This analysis reveals that cells have a remarkable and unanticipated tolerance for forced protein associations, even if these associations lead to a proportion of the protein moving compartments within the cell. Furthermore, the interactions that do perturb growth provide a functional map of spatial protein regulation, identifying key regulatory complexes for the normal homeostasis of eukaryotic cells. DOI: http://dx.doi.org/10.7554/eLife.13053.001 PMID:27098839

  17. Evaluation of Interaction Between Fundamental Landscapes and Sounds in a District via Brain Wave

    Science.gov (United States)

    Okutani, Iwao; Takase, Tatsuo

    Interactions between regional landscape and sound are investigated in terms of subjects’ brain wave properties, i.e., α wave power spectrum and frequency fluctuation index of brain wave. The landscape samples consist of sea, buildings, crowds, trees, flowers, streamlet, vehicular traffic flow and residential area while the sound samples are made up of crowds sound, insect chirpings, rustling sound of leaves, wave sound, stream murmurings, bird chirpings and supersonic. It is revealed that (1) most of the best combinations of landscape and sound include natural landscape and sound whereas the worst combinations are associated with artificial environments, (2) best(worst) combinations determined via fluctuation index are composed of the landscape and sound which are evaluated as bests(worsts) at landscape only or sound only stimulus tests, (3) based on theα wave power spectrum, some of the best combinations include the landscapes and sounds which are evaluated low at the single stimulus tests and also some worst combinations include the stream murmuring sound or wave sound which are highly ranked at the sound only tests, (4) since supersonic appears in many worst combinations, it is likely to bring about unpleasant effects on human psychology.

  18. Fundamental interactions of vortical structures with boundary layers in two-dimensional flows

    DEFF Research Database (Denmark)

    Coutsias, E.A.; Lynov, Jens-Peter

    1991-01-01

    in the vorticity-stream function representation for bounded geometries. Fundamental processes connected to vorticity detachment from the boundary layers caused by the proximity of vortical structures are described. These processes include enstrophy enhancement of the main flow during bursting events, and pinning...

  19. Fundamental properties of molecules on surfaces. Molecular switching and interaction of magnetic molecules with superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Hatter, Nino

    2016-12-14

    In this thesis, we investigate individual molecular switches and metal-organic complexes on surfaces with scanning tunneling microscopy (STM) and spectroscopy (STS) at low temperatures. One focus addresses the switching ability and mechanism of diarylethene on Ag(111). The other focus lies on resolving and tuning magnetic interactions of individual molecules with superconductors. 4,4'-(4,4'-(perfluorocyclopent-1-ene-1,2-diyl)bis (5-methylthiophene-4,2-diyl)dip yridine (PDTE) is a prototypical photochromic switch. We can induce a structural change of individual PDTE molecules on Ag(111) with the STM tip. This change is accompanied by a reduction of the energy gap between the occupied and unoccupied molecular orbitals. Density functional theory (DFT) calculations reveal that the induced switching corresponds to a ring-closing reaction from an open isomer in a flat adsorption configuration to a ring-closed isomer with its methyl groups in a cis configuration. The final product is thermodynamically stabilized by strong dispersion interactions with the surface. A linear dependence of the switching threshold with the tip-sample distance with a minimal threshold of 1.4 V is found, which we assign to a combination of an electric-field induced process and a tunneling-electron contribution. DFT calculations suggest a large activation barrier for a ring-closing reaction from the open flat configuration into the closed cis configuration. The interaction of magnetic molecules with superconductors is studied on manganese phthalocyanine (MnPc) adsorbed on Pb(111). We find triplets of Shiba states inside the superconducting gap. Different adsorption sites of MnPc provide a large variety of exchange coupling strengths, which lead to a collective energy shift of the Shiba triplets. We can assign the splitting of the Shiba states to be an effect of magnetic anisotropy in the system. A quantum phase transition from a ''Kondo screened'' to a &apos

  20. Some fundamental aspects of fault-tree and digraph-matrix relationships for a systems-interaction evaluation procedure

    Energy Technology Data Exchange (ETDEWEB)

    Alesso, H.P.

    1982-02-28

    Recent events, such as Three Mile Island-2, Brown's Ferry-3, and Crystal River-3, have demonstrated that complex accidents can occur as a result of dependent (common-cause/mode) failures. These events are now being called Systems Interactions. A procedure for the identification and evaluation of Systems Interactions is being developed by the NRC. Several national laboratories and utilities have contributed preliminary procedures. As a result, there are several important views of the Systems Interaction problem. This report reviews some fundamental mathematical background of both fault-oriented and success-oriented risk analyses in order to bring out the advantages and disadvantages of each. In addition, it outlines several fault-oriented/dependency analysis approaches and several success-oriented/digraph-matrix approaches. The objective is to obtain a broad perspective of present options for solving the Systems Interaction problem.

  1. Fundamental studies of hydrogen interaction with supported meta and bimetallic catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Bhatia, S.

    1993-12-07

    The thesis is divided into 3 parts: interaction of H with silica supported Ru catalysts (high pressure in situ NMR), in situ NMR study of H interaction with supported Ru-group IB bimetallic catalysts, and in-situ NMR study of H effects on silica-supported Pt, Rh and Ru catalysts.

  2. Electron spin interactions in chemistry and biology fundamentals, methods, reactions mechanisms, magnetic phenomena, structure investigation

    CERN Document Server

    Likhtenshtein, Gertz

    2016-01-01

    This book presents the versatile and pivotal role of electron spin interactions in nature. It provides the background, methodologies and tools for basic areas related to spin interactions, such as spin chemistry and biology, electron transfer, light energy conversion, photochemistry, radical reactions, magneto-chemistry and magneto-biology. The book also includes an overview of designing advanced magnetic materials, optical and spintronic devices and photo catalysts. This monograph appeals to scientists and graduate students working in the areas related to spin interactions physics, biophysics, chemistry and chemical engineering.

  3. Fundamental Interactions for Atom Interferometry with Ultracold Quantum Gases in a Microgravity Environment

    Science.gov (United States)

    D'Incao, Jose P.; Willians, Jason R.

    2015-05-01

    Precision atom interferometers (AI) in space are a key element for several applications of interest to NASA. Our proposal for participating in the Cold Atom Laboratory (CAL) onboard the International Space Station is dedicated to mitigating the leading-order systematics expected to corrupt future high-precision AI-based measurements of fundamental physics in microgravity. One important focus of our proposal is to enhance initial state preparation for dual-species AIs. Our proposed filtering scheme uses Feshbach molecular states to create highly correlated mixtures of heteronuclear atomic gases in both their position and momentum distributions. We will detail our filtering scheme along with the main factors that determine its efficiency. We also show that the atomic and molecular heating and loss rates can be mitigated at the unique temperature and density regimes accessible on CAL. This research is supported by the National Aeronautics and Space Administration.

  4. Fundamental measure theory for lattice fluids with hard-core interactions

    Science.gov (United States)

    Lafuente, Luis; Cuesta, José A.

    2002-11-01

    We present the extension of Rosenfeld's fundamental measure theory to lattice models by constructing a density functional for d-dimensional mixtures of parallel hard hypercubes on a simple hypercubic lattice. The one-dimensional case is exactly solvable and two cases must be distinguished: all the species with the same length parity (additive mixture), and arbitrary length parity (nonadditive mixture). To the best of our knowledge, this is the first time that the latter case has been considered. Based on the one-dimensional exact functional form, we propose the extension to higher dimensions by generalizing the zero-dimensional cavity method to lattice models. This assures the functional will have correct dimensional crossovers to any lower dimension, including the exact zero-dimensional limit. Some applications of the functional to particular systems are also shown.

  5. The Neurobiology of Emotion-Cognition Interactions: Fundamental Questions and Strategies for Future Research

    Directory of Open Access Journals (Sweden)

    Hadas eOkon-Singer

    2015-02-01

    Full Text Available Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular, this research demonstrates that stress, anxiety, and other kinds of emotion can profoundly influence key elements of cognition, including selective attention, working memory, and cognitive control. Often, this influence persists beyond the duration of transient emotional challenges, partially reflecting the slower molecular dynamics of catecholamine and hormonal neurochemistry. In turn, circuits involved in attention, executive control, and working memory contribute to the regulation of emotion. The distinction between the ‘emotional’ and the ‘cognitive’ brain is fuzzy and context-dependent. Indeed, there is compelling evidence that brain territories and psychological processes commonly associated with cognition, such as the dorsolateral prefrontal cortex and working memory, play a central role in emotion. Furthermore, putatively emotional and cognitive regions influence one another via a complex web of connections in ways that jointly contribute to adaptive and maladaptive behavior. This work demonstrates that emotion and cognition are deeply interwoven in the fabric of the brain, suggesting that widely held beliefs about the key constituents of ‘the emotional brain’ and ‘the cognitive brain’ are fundamentally flawed. We conclude by outlining several strategies for enhancing future research. Developing a deeper understanding of the emotional-cognitive brain is important, not just for understanding the mind but also for elucidating the root causes of its disorders.

  6. The neurobiology of emotion–cognition interactions: fundamental questions and strategies for future research

    Science.gov (United States)

    Okon-Singer, Hadas; Hendler, Talma; Pessoa, Luiz; Shackman, Alexander J.

    2015-01-01

    Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular, this research demonstrates that stress, anxiety, and other kinds of emotion can profoundly influence key elements of cognition, including selective attention, working memory, and cognitive control. Often, this influence persists beyond the duration of transient emotional challenges, partially reflecting the slower molecular dynamics of catecholamine and hormonal neurochemistry. In turn, circuits involved in attention, executive control, and working memory contribute to the regulation of emotion. The distinction between the ‘emotional’ and the ‘cognitive’ brain is fuzzy and context-dependent. Indeed, there is compelling evidence that brain territories and psychological processes commonly associated with cognition, such as the dorsolateral prefrontal cortex and working memory, play a central role in emotion. Furthermore, putatively emotional and cognitive regions influence one another via a complex web of connections in ways that jointly contribute to adaptive and maladaptive behavior. This work demonstrates that emotion and cognition are deeply interwoven in the fabric of the brain, suggesting that widely held beliefs about the key constituents of ‘the emotional brain’ and ‘the cognitive brain’ are fundamentally flawed. We conclude by outlining several strategies for enhancing future research. Developing a deeper understanding of the emotional-cognitive brain is important, not just for understanding the mind but also for elucidating the root causes of its disorders. PMID:25774129

  7. Molecular fundamentals of drug interactions in the therapy of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Regulska

    2014-03-01

    Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

  8. A unified conformal model for fundamental interactions without dynamical Higgs field

    CERN Document Server

    Pawlowski, M; Marek Pawlowski; Ryszard Raczka

    1994-01-01

    A Higgsless model for strong, electro-weak and gravitational interactions is proposed. This model is based on the local symmetry group SU(3)xSU(2)xU(1)xC where C is the local conformal symmetry group. The natural minimal conformally invariant form of total lagrangian is postulated. It contains all Standard Model fields and gravitational interaction. Using the unitary gauge and the conformal scale fixing conditions we can eliminate all four real components of the Higgs doublet in this model. However the masses of vector mesons, leptons and quarks are automatically generated and are given by the same formulas as in the conventional Standard Model. The gravitational sector is analyzed and it is shown that the model admits in the classical limit the Einsteinian form of gravitational interactions. No figures.

  9. Fundamental aspects of metallic impurities and impurity interactions in silicon during device processing

    Energy Technology Data Exchange (ETDEWEB)

    Graff, K. [TEMIC, TELEFUNKEN, Heilbronn (Germany)

    1995-08-01

    A review on the behavior of metallic impurities in silicon can be considerably simplified by a restriction on pure, dislocation-free, monocrystalline silicon. In this case interactions between different impurities and between impurities and grown-in lattice defects can be reduced. This restriction is observed in Chapter 1 for discussing the general behavior of metallic impurities in silicon.

  10. From the universe to the elementary particles a first introduction to cosmology and the fundamental interactions

    CERN Document Server

    Ellwanger, Ulrich

    2012-01-01

    In this book, the author leads the reader, step by step and without any advanced mathematics, to a clear understanding of the foundations of modern elementary particle physics and cosmology. He also addresses current and controversial questions on topics such as string theory. The book contains gentle introductions to the theories of special and general relativity, and also classical and quantum field theory. The essential aspects of these concepts are understood with the help of simple calculations; for example, the force of gravity as a consequence of the curvature of the space-time. Also treated are the Big Bang, dark matter and dark energy, as well as the presently known interactions of elementary particles: electrodynamics, the strong and the weak interactions including the Higgs boson. Finally, the book sketches as yet speculative theories: Grand Unification theories, supersymmetry, string theory and the idea of additional dimensions of space-time. Since no higher mathematical or physics expertise is r...

  11. Collaborative Research. Fundamental Science of Low Temperature Plasma-Biological Material Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Graves, David Barry [Univ. California, Berkeley, CA (United States); Oehrlein, Gottlieb [Univ. of Maryland, College Park, MD (United States)

    2014-09-01

    Low temperature plasma (LTP) treatment of biological tissue is a promising path toward sterilization of bacteria due to its versatility and ability to operate under well-controlled and relatively mild conditions. The present collaborative research of an interdisciplinary team of investigators at University of Maryland, College Park (UMD), and University of California, Berkeley (UCB) focused on establishing our knowledge based with regard to low temperature plasma-induced chemical modifications in biomolecules that result in inactivation due to various plasma species, including ions, reactive radicals, and UV/VUV photons. The overall goals of the project were to identify and quantify the mechanisms by which low and atmospheric pressure plasma deactivates endotoxic biomolecules. Additionally, we wanted to understand the mechanism by which atmospheric pressure plasmas (APP) modify surfaces and how these modifications depend on the interaction of APP with the environment. Various low pressure plasma sources, a vacuum beam system and several atmospheric pressure plasma sources were used to accomplish this. In our work we elucidated for the first time the role of ions, VUV photons and radicals in biological deactivation of representative biomolecules, both in a UHV beam system and an inductively coupled, low pressure plasma system, and established the associated atomistic biomolecule changes. While we showed that both ions and VUV photons can be very efficient in deactivation of biomolecules, significant etching and/or deep modification (~200 nm) accompanied these biological effects. One of the most important findings in this work is the significant radical-induced deactivation and surface modification can occur with minimal etching. However, if radical fluxes and corresponding etch rates are relatively high, for example at atmospheric pressure, endotoxic biomolecule film inactivation may require near-complete removal of the film. These findings motivated further work at

  12. Fundamental Study of Interactions Between High-Density Pulsed Plasmas and Materials for Space Propulsion

    Science.gov (United States)

    2012-09-01

    interactions studies (plasma too cold and too “dirty.”) We have built and tested a new, gas -fed, non- ablative, rep-rated capillary plasma source for our...those encountered in space propulsion devices including Pulsed Plasma Thrusters (PPT), Magneto-Plasma Dynamic (MPD) thrusters and capillary plasma...based thrusters . The ongoing research work brings together a team of researchers from the University of Texas at Austin (UT) and the University of

  13. Improving Our Fundamental Understanding of the Role of Aerosol-Cloud Interactions in the Climate System

    Energy Technology Data Exchange (ETDEWEB)

    Seinfeld, John H.; Bretherton, Christopher S.; Carslaw, K. S.; Coe, H.; DeMott, Paul J.; Dunlea, Edward J.; Feingold, G.; Ghan, Steven J.; Guenther, Alex B.; Kahn, Ralph; Kraucunas, Ian P.; Kreidenweis, Sonia M.; Molina, Mario J.; Nenes, Athanasios; Penner, J.; Prather, Kimberly; Ramanathan, Veerabhadran; Ramaswamy, V.; Rasch, Philip J.; Ravishankara, A. R.; Rosenfeld, Daniel; Stephens, Graeme; Wood, R.

    2016-05-24

    The effect of an increase in atmospheric aerosol concentrations on the distribution and radiative properties of Earth’s clouds is the most uncertain component of the overall global radiative forcing from pre-industrial time. General Circulation Models (GCMs) are the tool for predicting future climate, but the treatment of aerosols, clouds, and aerosol-cloud radiative effects carries large uncertainties that directly affect GCM predictions, such as climate sensitivity. Predictions are hampered by the large range of scales of interaction between various components that need to be captured. Observation systems (remote sensing, in situ) are increasingly being used to constrain predictions but significant challenges exist, to some extent because of the large range of scales and the fact that the various measuring systems tend to address different scales. Fine-scale models represent clouds, aerosols, and aerosol-cloud interactions with high fidelity but do not include interactions with the larger scale and are therefore limited from a climatic point of view. We suggest strategies for improving estimates of aerosol-cloud relationships in climate models, for new remote sensing and in situ measurements, and for quantifying and reducing model uncertainty.

  14. Fundamental ecology is fundamental.

    Science.gov (United States)

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

    2015-01-01

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

  15. A Finite-Rate Gas-Surface Interaction Model Informed by Fundamental Computational Chemistry Simulations

    Science.gov (United States)

    2013-03-31

    oxygen interactions with a specific crystalline polymorph of SiO2 (called β- cristobalite ). Computer images of this crystal lattice are shown in Fig...2. The choice of β- cristobalite is motivated by experimental studies from Balat-Pichelin et al. [15,22,23] where silicon-carbide (SiC) surfaces were...conclusion that the measured loss rates correspond to β- cristobalite was based on the fact that for polymorph diagrams of SiO2, β- cristobalite is most stable

  16. Interactive fundamental physics. [Final report], April 15, 1992--November 14, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, E.L.

    1992-11-24

    THE REAL STUFF is an Expanded Media Physics Course aimed at students still in the formative early years of secondary school. Its consists of a working script for an interactive multimedia study unit in basic concepts of physics. The unit begins with a prologue on the Big Bang that sets the stage, and concludes with a lesson on Newton`s first law of motion. The format is interactive, placing the individual student in control of a layered ``hypermedia`` structure that enables him or her to find a level of detail and difficulty that is comfortable and meaningful. The intent is to make physics relevant, intellectually accessible and fun. On-screen presenters and demonstrators will be females and males of various ages, ethnicities and backgrounds, and will include celebrities and physicists of note. A lean, layered design encourages repeated, cumulative study and makes the material useful for self-directed Teaming even by college students. THE REAL STUFF introduces a new science teaching paradigm, a way to teach science that will engage even students who have ``declined`` to be interested in science in the past. Increased participation in science by women, African-Americans and Spanish-speaking students is a particular goal.

  17. Interactive fundamental physics. [THE REAL STUFF: The New Expanded Media Physics Course for secondary school students

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, E.L.

    1992-11-24

    THE REAL STUFF is an Expanded Media Physics Course aimed at students still in the formative early years of secondary school. Its consists of a working script for an interactive multimedia study unit in basic concepts of physics. The unit begins with a prologue on the Big Bang that sets the stage, and concludes with a lesson on Newton's first law of motion. The format is interactive, placing the individual student in control of a layered hypermedia'' structure that enables him or her to find a level of detail and difficulty that is comfortable and meaningful. The intent is to make physics relevant, intellectually accessible and fun. On-screen presenters and demonstrators will be females and males of various ages, ethnicities and backgrounds, and will include celebrities and physicists of note. A lean, layered design encourages repeated, cumulative study and makes the material useful for self-directed Teaming even by college students. THE REAL STUFF introduces a new science teaching paradigm, a way to teach science that will engage even students who have declined'' to be interested in science in the past. Increased participation in science by women, African-Americans and Spanish-speaking students is a particular goal.

  18. Fundamental x-ray interaction limits in diagnostic imaging detectors: frequency-dependent Swank noise.

    Science.gov (United States)

    Hajdok, G; Battista, J J; Cunningham, I A

    2008-07-01

    A frequency-dependent x-ray Swank factor based on the "x-ray interaction" modulation transfer function and normalized noise power spectrum is determined from a Monte Carlo analysis. This factor was calculated in four converter materials: amorphous silicon (a-Si), amorphous selenium (a-Se), cesium iodide (CsI), and lead iodide (PbI2) for incident photon energies between 10 and 150 keV and various converter thicknesses. When scaled by the quantum efficiency, the x-ray Swank factor describes the best possible detective quantum efficiency (DQE) a detector can have. As such, this x-ray interaction DQE provides a target performance benchmark. It is expressed as a function of (Fourier-based) spatial frequency and takes into consideration signal and noise correlations introduced by reabsorption of Compton scatter and photoelectric characteristic emissions. It is shown that the x-ray Swank factor is largely insensitive to converter thickness for quantum efficiency values greater than 0.5. Thus, while most of the tabulated values correspond to thick converters with a quantum efficiency of 0.99, they are appropriate to use for many detectors in current use. A simple expression for the x-ray interaction DQE of digital detectors (including noise aliasing) is derived in terms of the quantum efficiency, x-ray Swank factor, detector element size, and fill factor. Good agreement is shown with DQE curves published by other investigators for each converter material, and the conditions required to achieve this ideal performance are discussed. For high-resolution imaging applications, the x-ray Swank factor indicates: (i) a-Si should only be used at low-energy (e.g., mammography); (ii) a-Se has the most promise for any application below 100 keV; and (iii) while quantum efficiency may be increased at energies just above the K edge in CsI and PbI2, this benefit is offset by a substantial drop in the x-ray Swank factor, particularly at high spatial frequencies.

  19. Geometry of the fundamental interactions on Riemann's legacy to high energy physics and cosmology

    CERN Document Server

    Maia, M D

    2011-01-01

    The Yang-Mills theory of gauge interactions is a prime example of interdisciplinary mathematics and advanced physics. Its historical development is a fascinating window into the ongoing struggle of mankind to understand nature. The discovery of gauge fields and their properties is the most formidable landmark of modern physics. The expression of the gauge field strength as the curvature associated to a given connection, places quantum field theory in the same geometrical footing as the gravitational field of general relativity which is naturally written in geometrical terms. The understanding of such geometrical property may help one day to write a unified field theory starting from symmetry principles. Of course, there are remarkable differences between the standard gauge fields and the gravitational field, which must be understood by mathematicians and physicists before attempting such unification. In particular, it is important to understand why gravitation is not a standard gauge field. This book presents...

  20. Synthetic lethal compound combinations reveal a fundamental connection between wall teichoic acid and peptidoglycan biosyntheses in Staphylococcus aureus

    Science.gov (United States)

    Campbell, Jennifer; Singh, Atul K.; Santa Maria, John P.; Kim, Younghoon; Brown, Stephanie; Swoboda, Jonathan G.; Mylonakis, Eleftherios; Wilkinson, Brian J.; Walker, Suzanne

    2010-01-01

    Methicillin resistance in Staphylococcus aureus depends on the production of mecA, which encodes penicillin-binding protein 2A (PBP2A), an acquired peptidoglycan transpeptidase (TP) with reduced susceptibility to beta-lactam antibiotics. PBP2A crosslinks nascent peptidoglycan when the native TPs are inhibited by beta-lactams. Although mecA expression is essential for beta-lactam resistance, it is not sufficient. Here we show that blocking the expression of wall teichoic acids (WTAs) by inhibiting the first enzyme in the pathway, TarO, sensitizes MRSA strains to beta-lactams even though the beta-lactam-resistant transpeptidase, PBP2A, is still expressed. The dramatic synergy between TarO inhibitors and beta-lactams is noteworthy not simply because strategies to overcome methicillin-resistant S. aureus (MRSA) are desperately needed, but because neither TarO nor the activities of the native TPs are essential in MRSA strains. The “synthetic lethality” of inhibiting TarO and the native TPs suggests a functional connection between ongoing WTA expression and peptidoglycan assembly in S. aureus. Indeed, transmission electron microscopy shows that S. aureus cells blocked in WTA synthesis have extensive defects in septation and cell separation, indicating dysregulated cell wall assembly and degradation. Our studies imply that WTAs play a fundamental role in S. aureus cell division and raise the possibility that synthetic lethal compound combinations may have therapeutic utility for overcoming antibiotic resistant bacterial infections. PMID:20961110

  1. Comparison of fundamental physical properties of the model cells (protocells) and the living cells reveals the need in protophysiology

    Science.gov (United States)

    Matveev, V. V.

    2017-01-01

    A hypothesis is proposed about potassium ponds being the cradles of life enriches the gamut of ideas about the possible conditions of pre-biological evolution on the primeval Earth, but does not bring us closer to solving the real problem of the origin of life. The gist of the matter lies in the mechanism of making a delimitation between two environments - the intracellular environment and the habitat of protocells. Since the sodium-potassium pump (Na+/K+-ATPase) was discovered, no molecular model has been proposed for a predecessor of the modern sodium pump. This has brought into life the idea of the potassium pond, wherein protocells would not need a sodium pump. However, current notions of the operation of living cells come into conflict with even physical laws when trying to use them to explain the origin and functioning of protocells. Thus, habitual explanations of the physical properties of living cells have become inapplicable to explain the corresponding properties of Sidney Fox's microspheres. Likewise, existing approaches to solving the problem of the origin of life do not see the need for the comparative study of living cells and cell models, assemblies of biological and artificial small molecules and macromolecules under physical conditions conducive to the origin of life. The time has come to conduct comprehensive research into the fundamental physical properties of protocells and create a new discipline - protocell physiology or protophysiology - which should bring us much closer to solving the problem of the origin of life.

  2. Cell-material interactions revealed via material techniques of surface patterning.

    Science.gov (United States)

    Yao, Xiang; Peng, Rong; Ding, Jiandong

    2013-10-04

    Cell-material interactions constitute a key fundamental topic in biomaterials study. Various cell cues and matrix cues as well as soluble factors regulate cell behaviors on materials. These factors are coupled with each other as usual, and thus it is very difficult to unambiguously elucidate the role of each regulator. The recently developed material techniques of surface patterning afford unique ways to reveal the underlying science. This paper reviews the pertinent material techniques to fabricate patterns of microscale and nanoscale resolutions, and corresponding cell studies. Some issues are emphasized, such as cell localization on patterned surfaces of chemical contrast, and effects of cell shape, cell size, cell-cell contact, and seeding density on differentiation of stem cells. Material cues to regulate cell adhesion, cell differentiation and other cell events are further summed up. Effects of some physical properties, such as surface topography and matrix stiffness, on cell behaviors are also discussed; nanoscaled features of substrate surfaces to regulate cell fate are summarized as well. The pertinent work sheds new insight into the cell-material interactions, and is stimulating for biomaterial design in regenerative medicine, tissue engineering, and high-throughput detection, diagnosis, and drug screening. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Understanding small biomolecule-biomaterial interactions: a review of fundamental theoretical and experimental approaches for biomolecule interactions with inorganic surfaces.

    Science.gov (United States)

    Costa, Dominique; Garrain, Pierre-Alain; Baaden, Marc

    2013-04-01

    Interactions between biomolecules and inorganic surfaces play an important role in natural environments and in industry, including a wide variety of conditions: marine environment, ship hulls (fouling), water treatment, heat exchange, membrane separation, soils, mineral particles at the earth's surface, hospitals (hygiene), art and buildings (degradation and biocorrosion), paper industry (fouling) and more. To better control the first steps leading to adsorption of a biomolecule on an inorganic surface, it is mandatory to understand the adsorption mechanisms of biomolecules of several sizes at the atomic scale, that is, the nature of the chemical interaction between the biomolecule and the surface and the resulting biomolecule conformations once adsorbed at the surface. This remains a challenging and unsolved problem. Here, we review the state of art in experimental and theoretical approaches. We focus on metallic biomaterial surfaces such as TiO(2) and stainless steel, mentioning some remarkable results on hydroxyapatite. Experimental techniques include atomic force microscopy, surface plasmon resonance, quartz crystal microbalance, X-ray photoelectron spectroscopy, fluorescence microscopy, polarization modulation infrared reflection absorption spectroscopy, sum frequency generation and time of flight secondary ion mass spectroscopy. Theoretical models range from detailed quantum mechanical representations to classical forcefield-based approaches.

  4. The Coriolis Interaction between the nu(9) and nu(7) Fundamental Bands of Methylene Fluoride.

    Science.gov (United States)

    Goh; Tan; Ong; Teo

    2000-06-01

    The infrared spectrum of the nu(7) and nu(9) bands of methylene fluoride-d(2) (CD(2)F(2)) has been recorded with an unapodized resolution of 0.0024 cm(-1) in the frequency range of 940-1030 cm(-1) using the Fourier transform technique. A weak b-type Coriolis interaction term was found to couple these two vibrational states with band centers about 42 cm(-1) apart. By fitting a total of 1031 infrared transitions of both nu(7) and nu(9) with a standard deviation of 0.0011 cm(-1) using a Watson's A-reduced Hamiltonian in the I(r) representation with the inclusion of a b-type Coriolis resonance term, two sets of rovibrational constants for nu(7) = 1 and nu(9) = 1 states up to sextic order were derived. The nu(7) band is C type, while the nu(9) band is A type with band centers at 961.8958 +/- 0.0005 and 1003.7421 +/- 0.0001 cm(-1), respectively. Copyright 2000 Academic Press.

  5. Interaction of Atmospheric-Pressure Air Microplasmas with Amino Acids as Fundamental Processes in Aqueous Solution.

    Directory of Open Access Journals (Sweden)

    Renwu Zhou

    Full Text Available Plasma medicine is a relatively new field that investigates potential applications of cold atmospheric-pressure plasmas in bioengineering, such as for bacterial inactivation and degradation of organic molecules in water. In order to enunciate mechanisms of bacterial inactivation at molecular or atomic levels, we investigated the interaction of atmospheric-pressure air microplasmas with amino acids in aqueous solution by using high-resolution mass spectrometry (HRMS. Results show that the oxidation effect of plasma-induced species on the side chains of the amino acids can be categorized into four types, namely hydroxylation, nitration, dehydrogenation and dimerization. In addition, relative activities of amino acids resulting from plasma treatment come in descending order as follows: sulfur-containing carbon-chain amino acids > aromatic amino acids > five-membered ring amino acids > basic carbon-chain amino acids. Since amino acids are building blocks of proteins vital to the growth and reproduction of bacteria, these results provide an insight into the mechanism of bacterial inactivation by plasma.

  6. Interaction of Atmospheric-Pressure Air Microplasmas with Amino Acids as Fundamental Processes in Aqueous Solution

    Science.gov (United States)

    Zhou, Renwu; Zhou, Rusen; Zhuang, Jinxing; Zong, Zichao; Zhang, Xianhui; Liu, Dongping; Bazaka, Kateryna; Ostrikov, Kostya

    2016-01-01

    Plasma medicine is a relatively new field that investigates potential applications of cold atmospheric-pressure plasmas in bioengineering, such as for bacterial inactivation and degradation of organic molecules in water. In order to enunciate mechanisms of bacterial inactivation at molecular or atomic levels, we investigated the interaction of atmospheric-pressure air microplasmas with amino acids in aqueous solution by using high-resolution mass spectrometry (HRMS). Results show that the oxidation effect of plasma-induced species on the side chains of the amino acids can be categorized into four types, namely hydroxylation, nitration, dehydrogenation and dimerization. In addition, relative activities of amino acids resulting from plasma treatment come in descending order as follows: sulfur-containing carbon-chain amino acids > aromatic amino acids > five-membered ring amino acids > basic carbon-chain amino acids. Since amino acids are building blocks of proteins vital to the growth and reproduction of bacteria, these results provide an insight into the mechanism of bacterial inactivation by plasma. PMID:27183129

  7. Fundamental parameters of the close interacting binary HD170582 and its luminous accretion disc

    CERN Document Server

    Mennickent, R E; Cabezas, M; Cséki, A; G., J Rosales; Niemczura, E; Araya, I; Curé, M

    2015-01-01

    We present a spectroscopic and photometric study of the Double Period Variable HD170582. Based on the study of the ASAS V-band light curve we determine an improved orbital period of 16.87177 $\\pm$ 0.02084 days and a long period of 587 days. We disentangled the light curve into an orbital part, determining ephemerides and revealing orbital ellipsoidal variability with unequal maxima, and a long cycle, showing quasi-sinusoidal changes with amplitude $\\Delta V$= 0.1 mag. Assuming synchronous rotation for the cool stellar component and semi-detached configuration we find a cool evolved star of $M_{2}$ = 1.9 $\\pm$ 0.1 $M_{\\odot}$, $T_{2}$ = 8000 $\\pm$ 100 $K$ and $R_{2}$ = 15.6 $\\pm$ 0.2 $R_{\\odot}$, and an early B-type dwarf of $M_{1}$ = 9.0 $\\pm$ 0.2 $M_{\\odot}$. The B-type star is surrounded by a geometrically and optically thick accretion disc of radial extension 20.8 $\\pm$ 0.3 $R_{\\odot}$ contributing about 35% to the system luminosity at the $V$ band. Two extended regions located at opposite sides of the dis...

  8. Comparison of protein interaction networks reveals species conservation and divergence

    Directory of Open Access Journals (Sweden)

    Teng Maikun

    2006-10-01

    Full Text Available Abstract Background Recent progresses in high-throughput proteomics have provided us with a first chance to characterize protein interaction networks (PINs, but also raised new challenges in interpreting the accumulating data. Results Motivated by the need of analyzing and interpreting the fast-growing data in the field of proteomics, we propose a comparative strategy to carry out global analysis of PINs. We compare two PINs by combining interaction topology and sequence similarity to identify conserved network substructures (CoNSs. Using this approach we perform twenty-one pairwise comparisons among the seven recently available PINs of E.coli, H.pylori, S.cerevisiae, C.elegans, D.melanogaster, M.musculus and H.sapiens. In spite of the incompleteness of data, PIN comparison discloses species conservation at the network level and the identified CoNSs are also functionally conserved and involve in basic cellular functions. We investigate the yeast CoNSs and find that many of them correspond to known complexes. We also find that different species harbor many conserved interaction regions that are topologically identical and these regions can constitute larger interaction regions that are topologically different but similar in framework. Based on the species-to-species difference in CoNSs, we infer potential species divergence. It seems that different species organize orthologs in similar but not necessarily the same topology to achieve similar or the same function. This attributes much to duplication and divergence of genes and their associated interactions. Finally, as the application of CoNSs, we predict 101 protein-protein interactions (PPIs, annotate 339 new protein functions and deduce 170 pairs of orthologs. Conclusion Our result demonstrates that the cross-species comparison strategy we adopt is powerful for the exploration of biological problems from the perspective of networks.

  9. Revealing Significant Learning Moments with Interactive Whiteboards in Mathematics

    Science.gov (United States)

    Bruce, Catherine D.; McPherson, Richard; Sabeti, Farhad Mordy; Flynn, Tara

    2011-01-01

    The aim of this study was to identify when and how the interactive whiteboard (IWB) functioned as a productive tool that impacted student learning in mathematics. Using video data, field notes, and interview transcripts from 1 school year in two optimal case study classrooms, we were able to examine the unique opportunities afforded by the size of…

  10. Metallomics of two microorganisms relevant to heavy metal bioremediation reveal fundamental differences in metal assimilation and utilization

    Energy Technology Data Exchange (ETDEWEB)

    Lancaster, Andrew [Univ. of Georgia, Athens, GA (United States); Menon, Angeli [Univ. of Georgia, Athens, GA (United States); Scott, Israel [Univ. of Georgia, Athens, GA (United States); Poole, Farris [Univ. of Georgia, Athens, GA (United States); Vaccaro, Brian [Univ. of Georgia, Athens, GA (United States); Thorgersen, Michael P. [Univ. of Georgia, Athens, GA (United States); Geller, Jil [Lawrence Berkeley National Laboratory (LBNL); Hazen, Terry C. [Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hurt Jr., Richard Ashley [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Brown, Steven D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Elias, Dwayne A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Adams, Michael W. W. [Univ. of Georgia, Athens, GA (United States)

    2014-03-26

    Although as many as half of all proteins are thought to require a metal cofactor, the metalloproteomes of microorganisms remain relatively unexplored. Microorganisms from different environments are likely to vary greatly in the metals that they assimilate, not just among the metals with well-characterized roles but also those lacking any known function. Herein we investigated the metal utilization of two microorganisms that were isolated from very similar environments and are of interest because of potential roles in the immobilization of heavy metals, such as uranium and chromium. The metals assimilated and their concentrations in the cytoplasm of Desulfovibrio vulgaris strain Hildenborough (DvH) and Enterobacter cloacae strain Hanford (EcH) varied dramatically, with a larger number of metals present in Enterobacter. For example, a total of 9 and 19 metals were assimilated into their cytoplasmic fractions, respectively, and DvH did not assimilate significant amounts of zinc or copper whereas EcH assimilated both. However, bioinformatic analysis of their genome sequences revealed a comparable number of predicted metalloproteins, 813 in DvH and 953 in EcH. These allowed some rationalization of the types of metal assimilated in some cases (Fe, Cu, Mo, W, V) but not in others (Zn, Nd, Ce, Pr, Dy, Hf and Th). It was also shown that U binds an unknown soluble protein in EcH but this incorporation was the result of extracellular U binding to cytoplasmic components after cell lysis.

  11. Metallomics of two microorganisms relevant to heavy metal bioremediation reveal fundamental differences in metal assimilation and utilization.

    Science.gov (United States)

    Lancaster, W Andrew; Menon, Angeli Lal; Scott, Israel; Poole, Farris L; Vaccaro, Brian J; Thorgersen, Michael P; Geller, Jil; Hazen, Terry C; Hurt, Richard A; Brown, Steven D; Elias, Dwayne A; Adams, Michael W W

    2014-05-01

    Although as many as half of all proteins are thought to require a metal cofactor, the metalloproteomes of microorganisms remain relatively unexplored. Microorganisms from different environments are likely to vary greatly in the metals that they assimilate, not just among the metals with well-characterized roles but also those lacking any known function. Herein we investigated the metal utilization of two microorganisms that were isolated from very similar environments and are of interest because of potential roles in the immobilization of heavy metals, such as uranium and chromium. The metals assimilated and their concentrations in the cytoplasm of Desulfovibrio vulgaris strain Hildenborough (DvH) and Enterobacter cloacae strain Hanford (EcH) varied dramatically, with a larger number of metals present in Enterobacter. For example, a total of 9 and 19 metals were assimilated into their cytoplasmic fractions, respectively, and DvH did not assimilate significant amounts of zinc or copper whereas EcH assimilated both. However, bioinformatic analysis of their genome sequences revealed a comparable number of predicted metalloproteins, 813 in DvH and 953 in EcH. These allowed some rationalization of the types of metal assimilated in some cases (Fe, Cu, Mo, W, V) but not in others (Zn, Nd, Ce, Pr, Dy, Hf and Th). It was also shown that U binds an unknown soluble protein in EcH but this incorporation was the result of extracellular U binding to cytoplasmic components after cell lysis.

  12. Fundamentally updating fundamentals.

    Science.gov (United States)

    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.

  13. Galaxy-environment Interactions as Revealed by the Circumgalactic Medium

    Science.gov (United States)

    Burchett, Joseph; Tripp, Todd M.; Wang, Daniel; Willmer, Christopher; Prochaska, Jason X.; Werk, Jessica; Bordoloi, Rongmon; Katz, Neal; Tumlinson, Jason

    2017-01-01

    Galaxies do not live in isolation, and their star formation activity and gas supply are closely tied to the density of the environment in which they reside. The circumgalactic medium (CGM) serves as the point of first contact between a galaxy and its environment and mediates the gas accretion and outflow processes that regulate the galaxy ecosystem. Employing a combination of ultraviolet QSO spectroscopy, optical galaxy surveys, and X-ray imaging and spectroscopy, I will show that the metal-enriched gas and cool, photoionized H I in the CGM gas reflect the galaxy’s large-scale environment from scales of modest groups to clusters. Thus, QSO absorption line spectroscopy provides uniquely sensitive multiphase gas diagnostics of the physical conditions at the sites of galaxy-environment interactions. By shock-heating or stripping the CGM gas, as is indicated by its absorption, these interactions may deplete or deprive the galaxy's gas supply and quench its star formation.

  14. Quantitative Genetic Interactions Reveal Layers of Biological Modularity

    Science.gov (United States)

    Beltrao, Pedro; Cagney, Gerard; Krogan, Nevan J.

    2010-01-01

    In the past, biomedical research has embraced a reductionist approach, primarily focused on characterizing the individual components that comprise a system of interest. Recent technical developments have significantly increased the size and scope of data describing biological systems. At the same time, advances in the field of systems biology have evoked a broader view of how the underlying components are interconnected. In this essay, we discuss how quantitative genetic interaction mapping has enhanced our view of biological systems, allowing a deeper functional interrogation at different biological scales. PMID:20510918

  15. Spectroscopy reveals that ethyl esters interact with proteins in wine.

    Science.gov (United States)

    Di Gaspero, Mattia; Ruzza, Paolo; Hussain, Rohanah; Vincenzi, Simone; Biondi, Barbara; Gazzola, Diana; Siligardi, Giuliano; Curioni, Andrea

    2017-02-15

    Impairment of wine aroma after vinification is frequently associated to bentonite treatments and this can be the result of protein removal, as recently demonstrated for ethyl esters. To evaluate the existence of an interaction between wine proteins and ethyl esters, the effects induced by these fermentative aroma compounds on the secondary structure and stability of VVTL1, a Thaumatin-like protein purified from wine, was analyzed by Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy. The secondary structure of wine VVTL1 was not strongly affected by the presence of selected ethyl esters. In contrast, VVTL1 stability was slightly increased by the addition of ethyl-octanoate, -decanoate and -dodecanoate, but decreased by ethyl-hexanoate. This indicates the existence of an interaction between VVTL1 and at least some aroma compounds produced during fermentation. The data suggest that proteins removal from wine by bentonite can result in indirect removal of at least some aroma compounds associated with them. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Global Geometric Affinity for Revealing High Fidelity Protein Interaction Network

    Science.gov (United States)

    Fang, Yi; Benjamin, William; Sun, Mengtian; Ramani, Karthik

    2011-01-01

    Protein-protein interaction (PPI) network analysis presents an essential role in understanding the functional relationship among proteins in a living biological system. Despite the success of current approaches for understanding the PPI network, the large fraction of missing and spurious PPIs and a low coverage of complete PPI network are the sources of major concern. In this paper, based on the diffusion process, we propose a new concept of global geometric affinity and an accompanying computational scheme to filter the uncertain PPIs, namely, reduce the spurious PPIs and recover the missing PPIs in the network. The main concept defines a diffusion process in which all proteins simultaneously participate to define a similarity metric (global geometric affinity (GGA)) to robustly reflect the internal connectivity among proteins. The robustness of the GGA is attributed to propagating the local connectivity to a global representation of similarity among proteins in a diffusion process. The propagation process is extremely fast as only simple matrix products are required in this computation process and thus our method is geared toward applications in high-throughput PPI networks. Furthermore, we proposed two new approaches that determine the optimal geometric scale of the PPI network and the optimal threshold for assigning the PPI from the GGA matrix. Our approach is tested with three protein-protein interaction networks and performs well with significant random noises of deletions and insertions in true PPIs. Our approach has the potential to benefit biological experiments, to better characterize network data sets, and to drive new discoveries. PMID:21559288

  17. Fundamentals of Filament Interaction

    Science.gov (United States)

    2017-05-19

    provide a 1:1 image of the filament profile onto a CCD camera (The Imaging Source DMK72BUC02). Neutral density filters were used to prevent the...thermal velocity, until their momentum was arrested by collisions with neutral air molecules. This results in a short distance, transient current which...Martin Richardson, 3rd ELI-ALPS User Workshop, Szeged, Hungary November 2015 126 “Photonics and the Changing Energy Scene ”, Martin Richardson

  18. Supramolecular Interactions in Secondary Plant Cell Walls: Effect of Lignin Chemical Composition Revealed with the Molecular Theory of Solvation.

    Science.gov (United States)

    Silveira, Rodrigo L; Stoyanov, Stanislav R; Gusarov, Sergey; Skaf, Munir S; Kovalenko, Andriy

    2015-01-02

    Plant biomass recalcitrance, a major obstacle to achieving sustainable production of second generation biofuels, arises mainly from the amorphous cell-wall matrix containing lignin and hemicellulose assembled into a complex supramolecular network that coats the cellulose fibrils. We employed the statistical-mechanical, 3D reference interaction site model with the Kovalenko-Hirata closure approximation (or 3D-RISM-KH molecular theory of solvation) to reveal the supramolecular interactions in this network and provide molecular-level insight into the effective lignin-lignin and lignin-hemicellulose thermodynamic interactions. We found that such interactions are hydrophobic and entropy-driven, and arise from the expelling of water from the mutual interaction surfaces. The molecular origin of these interactions is carbohydrate-π and π-π stacking forces, whose strengths are dependent on the lignin chemical composition. Methoxy substituents in the phenyl groups of lignin promote substantial entropic stabilization of the ligno-hemicellulosic matrix. Our results provide a detailed molecular view of the fundamental interactions within the secondary plant cell walls that lead to recalcitrance.

  19. Interactions With Robots: The Truths We Reveal About Ourselves.

    Science.gov (United States)

    Broadbent, Elizabeth

    2017-01-03

    In movies, robots are often extremely humanlike. Although these robots are not yet reality, robots are currently being used in healthcare, education, and business. Robots provide benefits such as relieving loneliness and enabling communication. Engineers are trying to build robots that look and behave like humans and thus need comprehensive knowledge not only of technology but also of human cognition, emotion, and behavior. This need is driving engineers to study human behavior toward other humans and toward robots, leading to greater understanding of how humans think, feel, and behave in these contexts, including our tendencies for mindless social behaviors, anthropomorphism, uncanny feelings toward robots, and the formation of emotional attachments. However, in considering the increased use of robots, many people have concerns about deception, privacy, job loss, safety, and the loss of human relationships. Human-robot interaction is a fascinating field and one in which psychologists have much to contribute, both to the development of robots and to the study of human behavior.

  20. Surface Modification of Carbon Nanotubes with Conjugated Polyelectrolytes: Fundamental Interactions and Applications in Composite Materials, Nanofibers, Electronics, and Photovoltaics

    KAUST Repository

    Ezzeddine, Alaa

    2015-10-01

    the composites thermal, mechanical and electrical properties compared to pristine CNTs. Various spectroscopic and microscopic techniques such as UV-vis, fluorescence, TEM, AFM and SEM were used to study and characterize the CPE/CNT complexes. Also, TGA, DSC and DMA were used to study the thermal and mechanical properties of the composite materials. Our current work represents a fundamental study on the non-covalent interactions between CNTs and CPEs on one hand and gives a real life example on the CPE/CNT application in composite materials and electronics.

  1. The Interaction Between Mutual Trust, Mutual Recognition and Fundamental Rights in Private International Law in Relation to the EU’s Aspirations Relating to Contractual Relations

    NARCIS (Netherlands)

    Emaus, J.M.|info:eu-repo/dai/nl/314838635

    2017-01-01

    This contribution aims to provide an analysis of the interrelationship between the principles of mutual trust, mutual recognition and fundamental rights in the field of private international law and to consider the interaction between these principles in relation to the European Union’s aspirations

  2. Genome evolution predicts genetic interactions in protein complexes and reveals cancer drug targets

    NARCIS (Netherlands)

    Lu, X.; Kensche, P.R.; Huynen, M.A.; Notebaart, R.A.

    2013-01-01

    Genetic interactions reveal insights into cellular function and can be used to identify drug targets. Here we construct a new model to predict negative genetic interactions in protein complexes by exploiting the evolutionary history of genes in parallel converging pathways in metabolism. We evaluate

  3. Adding protein context to the human protein-protein interaction network to reveal meaningful interactions.

    Directory of Open Access Journals (Sweden)

    Martin H Schaefer

    Full Text Available Interactions of proteins regulate signaling, catalysis, gene expression and many other cellular functions. Therefore, characterizing the entire human interactome is a key effort in current proteomics research. This challenge is complicated by the dynamic nature of protein-protein interactions (PPIs, which are conditional on the cellular context: both interacting proteins must be expressed in the same cell and localized in the same organelle to meet. Additionally, interactions underlie a delicate control of signaling pathways, e.g. by post-translational modifications of the protein partners - hence, many diseases are caused by the perturbation of these mechanisms. Despite the high degree of cell-state specificity of PPIs, many interactions are measured under artificial conditions (e.g. yeast cells are transfected with human genes in yeast two-hybrid assays or even if detected in a physiological context, this information is missing from the common PPI databases. To overcome these problems, we developed a method that assigns context information to PPIs inferred from various attributes of the interacting proteins: gene expression, functional and disease annotations, and inferred pathways. We demonstrate that context consistency correlates with the experimental reliability of PPIs, which allows us to generate high-confidence tissue- and function-specific subnetworks. We illustrate how these context-filtered networks are enriched in bona fide pathways and disease proteins to prove the ability of context-filters to highlight meaningful interactions with respect to various biological questions. We use this approach to study the lung-specific pathways used by the influenza virus, pointing to IRAK1, BHLHE40 and TOLLIP as potential regulators of influenza virus pathogenicity, and to study the signalling pathways that play a role in Alzheimer's disease, identifying a pathway involving the altered phosphorylation of the Tau protein. Finally, we provide the

  4. Expression and Protein Interaction Analyses Reveal Combinatorial Interactions of LBD Transcription Factors During Arabidopsis Pollen Development.

    Science.gov (United States)

    Kim, Mirim; Kim, Min-Jung; Pandey, Shashank; Kim, Jungmook

    2016-11-01

    LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factor gene family members play key roles in diverse aspects of plant development. LBD10 and LBD27 have been shown to be essential for pollen development in Arabidopsis thaliana. From the previous RNA sequencing (RNA-Seq) data set of Arabidopsis pollen, we identified the mRNAs of LBD22, LBD25 and LBD36 in addition to LBD10 and LBD27 in Arabidopsis pollen. Here we conducted expression and cellular analysis using GFP:GUS (green fluorescent protein:β-glucuronidase) reporter gene and subcellular localization assays using LBD:GFP fusion proteins expressed under the control of their own promoters in Arabidopsis. We found that these LBD proteins display spatially and temporally distinct and overlapping expression patterns during pollen development. Bimolecular fluorescence complementation and GST (glutathione S-transferase) pull-down assays demonstrated that protein-protein interactions occur among the LBDs exhibiting overlapping expression during pollen development. We further showed that LBD10, LBD22, LBD25, LBD27 and LBD36 interact with each other to form heterodimers, which are localized to the nucleus in Arabidopsis protoplasts. Taken together, these results suggest that combinatorial interactions among LBD proteins may be important for their function in pollen development in Arabidopsis.

  5. Fundamentals and Applications of Semiconductor Nanocrystals : A study on the synthesis, optical properties, and interactions of quantum dots

    NARCIS (Netherlands)

    Koole, R.

    2008-01-01

    This thesis focuses on both the fundamental aspects as well as applications of colloidal semiconductor nanocrystals, also called quantum dots (QDs). Due to the unique size-dependent optical and electronic properties of QDs, they hold great promise for a wide range of applications like solar cells, d

  6. Metabolomics Reveals Cryptic Interactive Effects of Species Interactions and Environmental Stress on Nitrogen and Sulfur Metabolism in Seagrass

    DEFF Research Database (Denmark)

    Hasler-Sheetal, Harald; Castorani, Max C. N.; Glud, Ronnie N.

    2016-01-01

    Eutrophication of estuaries and coastal seas is accelerating, increasing light stress on subtidal marine plants and changing their interactions with other species. To date, we have limited understanding of how such variations in environmental and biological stress modify the impact of interactions...... among foundational species and eventually affect ecosystem health. Here, we used metabolomics to assess the impact of light reductions on interactions between the seagrass Zostera marina, an important habitat-forming marine plant, and the abundant and commercially important blue mussel Mytilus edulis....... Plant performance varied with light availability but was unaffected by the presence of mussels. Metabolomic analysis, on the other hand, revealed an interaction between light availability and presence of M. edulis on seagrass metabolism. Under high light, mussels stimulated seagrass nitrogen and energy...

  7. The integrated analysis of metabolic and protein interaction networks reveals novel molecular organizing principles.

    Science.gov (United States)

    Durek, Pawel; Walther, Dirk

    2008-11-25

    The study of biological interaction networks is a central theme of systems biology. Here, we investigate the relationships between two distinct types of interaction networks: the metabolic pathway map and the protein-protein interaction network (PIN). It has long been established that successive enzymatic steps are often catalyzed by physically interacting proteins forming permanent or transient multi-enzymes complexes. Inspecting high-throughput PIN data, it was shown recently that, indeed, enzymes involved in successive reactions are generally more likely to interact than other protein pairs. In our study, we expanded this line of research to include comparisons of the underlying respective network topologies as well as to investigate whether the spatial organization of enzyme interactions correlates with metabolic efficiency. Analyzing yeast data, we detected long-range correlations between shortest paths between proteins in both network types suggesting a mutual correspondence of both network architectures. We discovered that the organizing principles of physical interactions between metabolic enzymes differ from the general PIN of all proteins. While physical interactions between proteins are generally dissortative, enzyme interactions were observed to be assortative. Thus, enzymes frequently interact with other enzymes of similar rather than different degree. Enzymes carrying high flux loads are more likely to physically interact than enzymes with lower metabolic throughput. In particular, enzymes associated with catabolic pathways as well as enzymes involved in the biosynthesis of complex molecules were found to exhibit high degrees of physical clustering. Single proteins were identified that connect major components of the cellular metabolism and may thus be essential for the structural integrity of several biosynthetic systems. Our results reveal topological equivalences between the protein interaction network and the metabolic pathway network. Evolved

  8. Functional Ecological Gene Networks to Reveal the Changes Among Microbial Interactions Under Elevated Carbon Dioxide Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Ye; Zhou, Jizhong; Luo, Feng; He, Zhili; Tu, Qichao; Zhi, Xiaoyang

    2010-05-17

    Biodiversity and its responses to environmental changes is a central issue in ecology, and for society. Almost all microbial biodiversity researches focus on species richness and abundance but ignore the interactions among different microbial species/populations. However, determining the interactions and their relationships to environmental changes in microbial communities is a grand challenge, primarily due to the lack of information on the network structure among different microbial species/populations. Here, a novel random matrix theory (RMT)-based conceptual framework for identifying functional ecological gene networks (fEGNs) is developed with the high throughput functional gene array hybridization data from the grassland microbial communities in a long-term FACE (Free Air CO2 Enrichment) experiment. Both fEGNs under elevated CO2 (eCO2) and ambient CO2 (aCO2) possessed general characteristics of many complex systems such as scale-free, small-world, modular and hierarchical. However, the topological structure of the fEGNs is distinctly different between eCO2 and aCO2, suggesting that eCO2 dramatically altered the interactions among different microbial functional groups/populations. In addition, the changes in network structure were significantly correlated with soil carbon and nitrogen dynamics, and plant productivity, indicating the potential importance of network interactions in ecosystem functioning. Elucidating network interactions in microbial communities and their responses to environmental changes are fundamentally important for research in microbial ecology, systems microbiology, and global change.

  9. Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions.

    Science.gov (United States)

    Lin, Aijing; Liu, Kang K L; Bartsch, Ronny P; Ivanov, Plamen Ch

    2016-05-13

    Within the framework of 'Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

  10. Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

    Science.gov (United States)

    Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

    2016-05-01

    Within the framework of `Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

  11. The Fundamental Planes of E+A galaxies and GALEX UV-excess early-type galaxies: revealing their intimate connection

    Science.gov (United States)

    Choi, Yumi; Goto, Tomotsugu; Yoon, Suk-Jin

    2009-05-01

    Strong Balmer absorption lines and the lack of Hα and [OII] emission lines signify that E+A galaxies are post-starburst systems. Recent studies suggest that E+As may undergo the transition from the `blue cloud' to the `red sequence' and eventually migrate to red-sequence early-type galaxies. An observational validation of this scenario is to identify the intervening galaxy population between E+As and the red sequence. Motivated by recent findings with Galaxy Evolution Explorer (GALEX) that an unexpectedly large fraction of early-type galaxies exhibit ultraviolet (UV) excess (i.e. blue UV - optical colours) as a sign of recent star formation (RSF), we investigate the possible connection of the UV-excess galaxies to E+As. In particular, we examine the Fundamental Plane (FP) scaling relations of the currently largest sample of ~1000 E+As selected from the Sloan Digital Sky Survey (SDSS) and ~20000 morphologically selected SDSS early-type galaxies with GALEX UV data. The FP parameters, combined with stellar population indicators, reveal a certain group of UV-excess early types that bridge between E+As and quiescent red galaxies. The newly identified galaxies are the post-starburst systems characterized by UV-excess but no Hα emission. This is essentially a conceptual generalization of `E+A', in that the Balmer absorption line in the `E+A' definition is replaced with UV - optical colours that are far more sensitive to RSF than the Balmer lines. We refer to these UV-excess galaxies as `E+a' galaxies (named after `E+A'), which stand for elliptical (`E') galaxies with a minority of A-type (`a') young stars. The species are either (1) galaxies that experienced starbursts weaker than those observed in E+As (1 ~ 10 per cent of E+As, `mild E+As') or (2) the products of passively evolved E+As after quenching star formation quite a while ago (~1 Gyr, `old E+As'). We suggest that the latter type of E+a galaxies (i.e. old `E+As') represents the most recent arrival to the red

  12. Fundamentals and Applications of Semiconductor Nanocrystals : A study on the synthesis, optical properties, and interactions of quantum dots

    OpenAIRE

    Koole, R.

    2008-01-01

    This thesis focuses on both the fundamental aspects as well as applications of colloidal semiconductor nanocrystals, also called quantum dots (QDs). Due to the unique size-dependent optical and electronic properties of QDs, they hold great promise for a wide range of applications like solar cells, displays, lasers, or as contrast agent for bio-imaging. The work presented in this thesis can be divided in three sections. In the first part, the synthesis and self-assembly of PbSe nanocrystals of...

  13. Radiology fundamentals

    CERN Document Server

    Singh, Harjit

    2011-01-01

    ""Radiology Fundamentals"" is a concise introduction to the dynamic field of radiology for medical students, non-radiology house staff, physician assistants, nurse practitioners, radiology assistants, and other allied health professionals. The goal of the book is to provide readers with general examples and brief discussions of basic radiographic principles and to serve as a curriculum guide, supplementing a radiology education and providing a solid foundation for further learning. Introductory chapters provide readers with the fundamental scientific concepts underlying the medical use of imag

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

    Science.gov (United States)

    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.

  15. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.

  16. Holistic atlases of functional networks and interactions reveal reciprocal organizational architecture of cortical function.

    Science.gov (United States)

    Lv, Jinglei; Jiang, Xi; Li, Xiang; Zhu, Dajiang; Zhang, Shu; Zhao, Shijie; Chen, Hanbo; Zhang, Tuo; Hu, Xintao; Han, Junwei; Ye, Jieping; Guo, Lei; Liu, Tianming

    2015-04-01

    For decades, it has been largely unknown to what extent multiple functional networks spatially overlap/interact with each other and jointly realize the total cortical function. Here, by developing novel sparse representation of whole-brain fMRI signals and by using the recently publicly released large-scale Human Connectome Project high-quality fMRI data, we show that a number of reproducible and robust functional networks, including both task-evoked and resting state networks, are simultaneously distributed in distant neuroanatomic areas and substantially spatially overlapping with each other, thus forming an initial collection of holistic atlases of functional networks and interactions (HAFNIs). More interestingly, the HAFNIs revealed two distinct patterns of highly overlapped regions and highly specialized regions and exhibited that these two patterns of areas are reciprocally localized, revealing a novel organizational principle of cortical function.

  17. The relation between the fundamental scale controlling high-energy interactions of quarks and the proton mass

    Energy Technology Data Exchange (ETDEWEB)

    Deur, Alexandre [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Brodsky, Stanley J. [SLAC National Accelerator Lab., Menlo Park, CA (United States); de Teramond, Guy F. [Univ. de Costa Rica, San Jose (Costa Rica)

    2015-04-06

    Quantum Chromodynamics (QCD) provides a fundamental description of the physics binding quarks into protons, neutrons, and other hadrons. QCD is well understood at short distances where perturbative calculations are feasible. Establishing an explicit relation between this regime and the large-distance physics of quark confinement has been a long-sought goal. A major challenge is to relate the parameter Λs, which controls the predictions of perturbative QCD (pQCD) at short distances, to the masses of hadrons. Here we show how new theoretical insights into QCD's behavior at large and small distances lead to an analytical relation between hadronic masses and Λs. The resulting prediction, Λs = 0.341 ± 0.024 GeV agrees well with the experimental value 0.339 ± 0.016 GeV. Conversely, the experimental value of Λs can be used to predict the masses of hadrons, a task which had so far only been accomplished through intensive numerical lattice calculations, requiring several phenomenological input parameters.

  18. Joint genetic analysis using variant sets reveals polygenic gene-context interactions.

    Directory of Open Access Journals (Sweden)

    Francesco Paolo Casale

    2017-04-01

    Full Text Available Joint genetic models for multiple traits have helped to enhance association analyses. Most existing multi-trait models have been designed to increase power for detecting associations, whereas the analysis of interactions has received considerably less attention. Here, we propose iSet, a method based on linear mixed models to test for interactions between sets of variants and environmental states or other contexts. Our model generalizes previous interaction tests and in particular provides a test for local differences in the genetic architecture between contexts. We first use simulations to validate iSet before applying the model to the analysis of genotype-environment interactions in an eQTL study. Our model retrieves a larger number of interactions than alternative methods and reveals that up to 20% of cases show context-specific configurations of causal variants. Finally, we apply iSet to test for sub-group specific genetic effects in human lipid levels in a large human cohort, where we identify a gene-sex interaction for C-reactive protein that is missed by alternative methods.

  19. Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex.

    Directory of Open Access Journals (Sweden)

    Mariya M Kucherenko

    Full Text Available The Dystroglycan-Dystrophin (Dg-Dys complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-beta and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought.

  20. Fundamentals of ergonomic exoskeleton robots

    NARCIS (Netherlands)

    Schiele, A.

    2008-01-01

    This thesis is the first to provide the fundamentals of ergonomic exoskeleton design. The fundamental theory as well as technology necessary to analyze and develop ergonomic wearable robots interacting with humans is established and validated by experiments and prototypes. The fundamentals are (1) a

  1. Fundamentals of ergonomic exoskeleton robots

    NARCIS (Netherlands)

    Schiele, A.

    2008-01-01

    This thesis is the first to provide the fundamentals of ergonomic exoskeleton design. The fundamental theory as well as technology necessary to analyze and develop ergonomic wearable robots interacting with humans is established and validated by experiments and prototypes. The fundamentals are (1) a

  2. Fundamental Astronomy

    CERN Document Server

    Karttunen, Hannu; Oja, Heikki; Poutanen, Markku; Donner, Karl Johan

    2007-01-01

    Fundamental Astronomy gives a well-balanced and comprehensive introduction to the topics of classical and modern astronomy. While emphasizing both the astronomical concepts and the underlying physical principles, the text provides a sound basis for more profound studies in the astronomical sciences. The fifth edition of this successful undergraduate textbook has been extensively modernized and extended in the parts dealing with the Milky Way, extragalactic astronomy and cosmology as well as with extrasolar planets and the solar system (as a consequence of recent results from satellite missions and the new definition by the International Astronomical Union of planets, dwarf planets and small solar-system bodies). Furthermore a new chapter on astrobiology has been added. Long considered a standard text for physical science majors, Fundamental Astronomy is also an excellent reference and entrée for dedicated amateur astronomers.

  3. The unification of the fundamental interaction within Maxwell electromagnetism: Model of hydrogen atom. Gravity as the secondary electric force. Calculation of the unified inertia force

    CERN Document Server

    Neslusan, L

    2010-01-01

    Considering two static, electrically charged, elementary particles, we demonstrate a possible way of proving that all known fundamental forces in the nature are the manifestations of the single, unique interaction. We re-define the gauging of integration constants in the Schwarzschild solution of Einstein field equations. We consider the potential energy in this context regardless it is gravitational or electric potential energy. With the newly gauged constants, we sketch how the unique interaction can be described with the help of an appropriate solution of the well-known Maxwell equations. According the solution, there are two zones, in the system of two oppositely charged particles, where the force is oscillating. The first particle can be in a stable, constant distance from the second particle, between the neighbouring regions of repulsion and attraction. In an outer oscillation zone, the corresponding energy levels in the proton-electron systems are identical (on the level of accuracy of values calculate...

  4. Fundamental studies of H{sub 2} interaction with MAl{sub 3} clusters [M = Li, Sc, Ti, Zr

    Energy Technology Data Exchange (ETDEWEB)

    Samolia, Madhu; Dhilip Kumar, T.J., E-mail: dhilip@iitrpr.ac.in

    2014-03-05

    Highlights: • A first-principles calculation on H{sub 2} interaction and saturation on stable MAl{sub 3} clusters [M = Li, Sc, Ti, Zr] is performed. • Transition metals have negative electron charge density while Al atom has positive in MAl{sub 3} from NBO charge analysis. • H{sub 2} undergoes dissociative chemisorption on the M atop site resulting in M–H–Al bridge bond. • H{sub 2} saturation on M atop site results initially chemisorption and then physisorption with 3-centered Kubas interaction. • External electric field applied on TiAl{sub 3}H{sub 4} leads to more polarization, H{sub 2} bond elongation and increased adsorption energy. -- Abstract: Complex metal hydride is a promising hydrogen storage material for automobile applications due to its reversible storage capacity. The presence of transition metal halide is found to improve significantly the kinetics of H{sub 2} adsorption and desorption processes. Experimental studies have indicated the formation of distorted MAl{sub 3} phase where M = Sc, Ti, Zr. In this study, a first-principles density functional study has been performed to investigate the hydrogen interaction and saturation on stable tetrahedral MAl{sub 3} clusters [M = Li, Sc, Ti, and Zr] by employing spin-polarized hybrid and non-local density functionals. On saturation, the first H{sub 2} molecule undergoes chemisorption in the transition metals while further loading results in physisorption with the Kubas-type H{sub 2} interaction. Activation energy barrier for the H{sub 2} dissociation over the cluster is calculated to be ∼0.2 eV for the transition metals. Effect of external electric field on the MAl{sub 3}H{sub 4} cluster with molecular H{sub 2} is studied which leads to polarization of physisorbed H{sub 2} and the cluster. The results offer an explanation for catalysts role in improving the kinetics of H{sub 2} sorption process in complex metal hydrides.

  5. Towards system-level understanding of baculovirus host cell interactions: from molecular fundamental studies to large-scale proteomics approaches

    Directory of Open Access Journals (Sweden)

    Francisca eMonteiro

    2012-11-01

    Full Text Available Baculoviruses are insect viruses extensively exploited as eukaryotic protein expression vectors. Molecular biology studies have provided exciting discoveries on virus-host interactions, but the application of omic high throughput techniques on the baculovirus-insect cell system has been hampered by the lack of host genome sequencing. While a broader, systems level analysis of biological responses to infection is urgently needed, recent advances on proteomic studies have yielded new insights on the impact of infection on the host cell. These works are reviewed and critically assessed in the light of current biological knowledge of the molecular biology of baculoviruses and insect cells.

  6. Systematic Pan-Cancer Analysis Reveals Immune Cell Interactions in the Tumor Microenvironment.

    Science.gov (United States)

    Varn, Frederick S; Wang, Yue; Mullins, David W; Fiering, Steven; Cheng, Chao

    2017-03-15

    With the recent advent of immunotherapy, there is a critical need to understand immune cell interactions in the tumor microenvironment in both pan-cancer and tissue-specific contexts. Multidimensional datasets have enabled systematic approaches to dissect these interactions in large numbers of patients, furthering our understanding of the patient immune response to solid tumors. Using an integrated approach, we inferred the infiltration levels of distinct immune cell subsets in 23 tumor types from The Cancer Genome Atlas. From these quantities, we constructed a coinfiltration network, revealing interactions between cytolytic cells and myeloid cells in the tumor microenvironment. By integrating patient mutation data, we found that while mutation burden was associated with immune infiltration differences between distinct tumor types, additional factors likely explained differences between tumors originating from the same tissue. We concluded this analysis by examining the prognostic value of individual immune cell subsets as well as how coinfiltration of functionally discordant cell types associated with patient survival. In multiple tumor types, we found that the protective effect of CD8(+) T cell infiltration was heavily modulated by coinfiltration of macrophages and other myeloid cell types, suggesting the involvement of myeloid-derived suppressor cells in tumor development. Our findings illustrate complex interactions between different immune cell types in the tumor microenvironment and indicate these interactions play meaningful roles in patient survival. These results demonstrate the importance of personalized immune response profiles when studying the factors underlying tumor immunogenicity and immunotherapy response. Cancer Res; 77(6); 1271-82. ©2017 AACR.

  7. Beyond consensus: statistical free energies reveal hidden interactions in the design of a TPR motif.

    Science.gov (United States)

    Magliery, Thomas J; Regan, Lynne

    2004-10-22

    Consensus design methods have been used successfully to engineer proteins with a particular fold, and moreover to engineer thermostable exemplars of particular folds. Here, we consider how a statistical free energy approach can expand upon current methods of phylogenetic design. As an example, we have analyzed the tetratricopeptide repeat (TPR) motif, using multiple sequence alignment to identify the significance of each position in the TPR. The results provide information above and beyond that revealed by consensus design alone, especially at poorly conserved positions. A particularly striking finding is that certain residues, which TPR-peptide co-crystal structures show are in direct contact with the ligand, display a marked hypervariability. This suggests a novel means of identifying ligand-binding sites, and also implies that TPRs generally function as ligand-binding domains. Using perturbation analysis (or statistical coupling analysis), we examined site-site interactions within the TPR motif. Correlated occurrences of amino acid residues at poorly conserved positions explain how TPRs achieve their near-neutral surface charge distributions, and why a TPR designed from straight consensus has an unusually high net charge. Networks of interacting sites revealed that TPRs fall into two unrecognized families with distinct sets of interactions related to the identity of position 7 (Leu or Lys/Arg). Statistical free energy analysis provides a more complete description of "What makes a TPR a TPR?" than consensus alone, and it suggests general approaches to extend and improve the phylogenetic design of proteins.

  8. Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit.

    Science.gov (United States)

    Ashoori, Maryam; Burns, Catherine M; d'Entremont, Barbara; Momtahan, Kathryn

    2014-01-01

    Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamwork and leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams.

  9. Marketing fundamentals.

    Science.gov (United States)

    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.

  10. Conditional Epistatic Interaction Maps Reveal Global Functional Rewiring of Genome Integrity Pathways in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ashwani Kumar

    2016-01-01

    Full Text Available As antibiotic resistance is increasingly becoming a public health concern, an improved understanding of the bacterial DNA damage response (DDR, which is commonly targeted by antibiotics, could be of tremendous therapeutic value. Although the genetic components of the bacterial DDR have been studied extensively in isolation, how the underlying biological pathways interact functionally remains unclear. Here, we address this by performing systematic, unbiased, quantitative synthetic genetic interaction (GI screens and uncover widespread changes in the GI network of the entire genomic integrity apparatus of Escherichia coli under standard and DNA-damaging growth conditions. The GI patterns of untreated cultures implicated two previously uncharacterized proteins (YhbQ and YqgF as nucleases, whereas reorganization of the GI network after DNA damage revealed DDR roles for both annotated and uncharacterized genes. Analyses of pan-bacterial conservation patterns suggest that DDR mechanisms and functional relationships are near universal, highlighting a modular and highly adaptive genomic stress response.

  11. Vibrational Circular Dichroism (VCD) Reveals Subtle Conformational Aspects and Intermolecular Interactions in the Carnitine Family.

    Science.gov (United States)

    Mazzeo, Giuseppe; Abbate, Sergio; Longhi, Giovanna; Castiglioni, Ettore; Villani, Claudio

    2015-12-01

    Vibrational circular dichroism spectra (VCD) in the mid-IR region and electronic circular dichroism (ECD) spectra for three carnitine derivatives in the form of hydrochloride salts were recorded in deuterated methanol solutions. Density Functional Theory calculations help one to understand the significance of the observed VCD bands. VCD and ECD spectra are informative about the absolute configuration of the molecule, but VCD data reveal also some conformational aspects in the N,N,N-trimethyl moiety and inform us about intermolecular interactions gained from the carbonyl stretching region for the acyl substituted carnitines. © 2015 Wiley Periodicals, Inc.

  12. Intragenic suppressor of Osiaa23 revealed a conserved tryptophan residue crucial for protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Jun Ni

    Full Text Available The Auxin/Indole-3-Acetic Acid (Aux/IAA and Auxin Response Factor (ARF are two important families that play key roles in auxin signal transduction. Both of the families contain a similar carboxyl-terminal domain (Domain III/IV that facilitates interactions between these two families. In spite of the importance of protein-protein interactions among these transcription factors, the mechanisms involved in these interactions are largely unknown. In this study, we isolated six intragenic suppressors of an auxin insensitive mutant, Osiaa23. Among these suppressors, Osiaa23-R5 successfully rescued all the defects of the mutant. Sequence analysis revealed that an amino acid substitution occurred in the Tryptophan (W residue in Domain IV of Osiaa23. Yeast two-hybrid experiments showed that the mutation in Domain IV prevents the protein-protein interactions between Osiaa23 and OsARFs. Phylogenetic analysis revealed that the W residue is conserved in both OsIAAs and OsARFs. Next, we performed site-specific amino acid substitutions within Domain IV of OsARFs, and the conserved W in Domain IV was exchanged by Serine (S. The mutated OsARF(WSs can be released from the inhibition of Osiaa23 and maintain the transcriptional activities. Expression of OsARF(WSs in Osiaa23 mutant rescued different defects of the mutant. Our results suggest a previously unknown importance of Domain IV in both families and provide an indirect way to investigate functions of OsARFs.

  13. Fundamental partial compositeness

    DEFF Research Database (Denmark)

    Sannino, Francesco; Strumia, Alessandro; Tesi, Andrea

    2016-01-01

    We construct renormalizable Standard Model extensions, valid up to the Planck scale, that give a composite Higgs from a new fundamental strong force acting on fermions and scalars. Yukawa interactions of these particles with Standard Model fermions realize the partial compositeness scenario. Unde...

  14. Protein Interaction Networks Reveal Novel Autism Risk Genes within GWAS Statistical Noise

    Science.gov (United States)

    Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M.

    2014-01-01

    Genome-wide association studies (GWAS) for Autism Spectrum Disorder (ASD) thus far met limited success in the identification of common risk variants, consistent with the notion that variants with small individual effects cannot be detected individually in single SNP analysis. To further capture disease risk gene information from ASD association studies, we applied a network-based strategy to the Autism Genome Project (AGP) and the Autism Genetics Resource Exchange GWAS datasets, combining family-based association data with Human Protein-Protein interaction (PPI) data. Our analysis showed that autism-associated proteins at higher than conventional levels of significance (P<0.1) directly interact more than random expectation and are involved in a limited number of interconnected biological processes, indicating that they are functionally related. The functionally coherent networks generated by this approach contain ASD-relevant disease biology, as demonstrated by an improved positive predictive value and sensitivity in retrieving known ASD candidate genes relative to the top associated genes from either GWAS, as well as a higher gene overlap between the two ASD datasets. Analysis of the intersection between the networks obtained from the two ASD GWAS and six unrelated disease datasets identified fourteen genes exclusively present in the ASD networks. These are mostly novel genes involved in abnormal nervous system phenotypes in animal models, and in fundamental biological processes previously implicated in ASD, such as axon guidance, cell adhesion or cytoskeleton organization. Overall, our results highlighted novel susceptibility genes previously hidden within GWAS statistical “noise” that warrant further analysis for causal variants. PMID:25409314

  15. Evolutionarily Conserved Pattern of Interactions in a Protein Revealed by Local Thermal Expansion Properties.

    Science.gov (United States)

    Dellarole, Mariano; Caro, Jose A; Roche, Julien; Fossat, Martin; Barthe, Philippe; García-Moreno E, Bertrand; Royer, Catherine A; Roumestand, Christian

    2015-07-29

    The way in which the network of intramolecular interactions determines the cooperative folding and conformational dynamics of a protein remains poorly understood. High-pressure NMR spectroscopy is uniquely suited to examine this problem because it combines the site-specific resolution of the NMR experiments with the local character of pressure perturbations. Here we report on the temperature dependence of the site-specific volumetric properties of various forms of staphylococcal nuclease (SNase), including three variants with engineered internal cavities, as measured with high-pressure NMR spectroscopy. The strong temperature dependence of pressure-induced unfolding arises from poorly understood differences in thermal expansion between the folded and unfolded states. A significant inverse correlation was observed between the global thermal expansion of the folded proteins and the number of strong intramolecular hydrogen bonds, as determined by the temperature coefficient of the backbone amide chemical shifts. Comparison of the identity of these strong H-bonds with the co-evolution of pairs of residues in the SNase protein family suggests that the architecture of the interactions detected in the NMR experiments could be linked to a functional aspect of the protein. Moreover, the temperature dependence of the residue-specific volume changes of unfolding yielded residue-specific differences in expansivity and revealed how mutations impact intramolecular interaction patterns. These results show that intramolecular interactions in the folded states of proteins impose constraints against thermal expansion and that, hence, knowledge of site-specific thermal expansivity offers insight into the patterns of strong intramolecular interactions and other local determinants of protein stability, cooperativity, and potentially also of function.

  16. Variation of Fundamental Constants

    Science.gov (United States)

    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.

  17. Cross-sensory facilitation reveals neural interactions between visual and tactile motion in humans

    Directory of Open Access Journals (Sweden)

    Monica eGori

    2011-04-01

    Full Text Available Many recent studies show that the human brain integrates information across the different senses and that stimuli of one sensory modality can enhance the perception of other modalities. Here we study the processes that mediate cross-modal facilitation and summation between visual and tactile motion. We find that while summation produced a generic, non-specific improvement of thresholds, probably reflecting higher-order interaction of decision signals, facilitation reveals a strong, direction-specific interaction, which we believe reflects sensory interactions. We measured visual and tactile velocity discrimination thresholds over a wide range of base velocities and conditions. Thresholds for both visual and tactile stimuli showed the characteristic dipper function, with the minimum thresholds occurring at a given pedestal speed. When visual and tactile coherent stimuli were combined (summation condition the thresholds for these multi-sensory stimuli also showed a dipper function with the minimum thresholds occurring in a similar range to that for unisensory signals. However, the improvement of multisensory thresholds was weak and not directionally specific, well predicted by the maximum likelihood estimation model (agreeing with previous research. A different technique (facilitation did, however, reveal direction-specific enhancement. Adding a non-informative pedestal motion stimulus in one sensory modality (vision or touch selectively lowered thresholds in the other, by the same amount as pedestals in the same modality. Facilitation did not occur for neutral stimuli like sounds (that would also have reduced temporal uncertainty, nor for motion in opposite direction, even in blocked trials where the subjects knew that the motion was in the opposite direction showing that the facilitation was not under subject control. Cross-sensory facilitation is strong evidence for functionally relevant cross-sensory integration at early levels of sensory

  18. Yeast mitochondrial protein-protein interactions reveal diverse complexes and disease-relevant functional relationships.

    Science.gov (United States)

    Jin, Ke; Musso, Gabriel; Vlasblom, James; Jessulat, Matthew; Deineko, Viktor; Negroni, Jacopo; Mosca, Roberto; Malty, Ramy; Nguyen-Tran, Diem-Hang; Aoki, Hiroyuki; Minic, Zoran; Freywald, Tanya; Phanse, Sadhna; Xiang, Qian; Freywald, Andrew; Aloy, Patrick; Zhang, Zhaolei; Babu, Mohan

    2015-02-06

    Although detailed, focused, and mechanistic analyses of associations among mitochondrial proteins (MPs) have identified their importance in varied biological processes, a systematic understanding of how MPs function in concert both with one another and with extra-mitochondrial proteins remains incomplete. Consequently, many questions regarding the role of mitochondrial dysfunction in the development of human disease remain unanswered. To address this, we compiled all existing mitochondrial physical interaction data for over 1200 experimentally defined yeast MPs and, through bioinformatic analysis, identified hundreds of heteromeric MP complexes having extensive associations both within and outside the mitochondria. We provide support for these complexes through structure prediction analysis, morphological comparisons of deletion strains, and protein co-immunoprecipitation. The integration of these MP complexes with reported genetic interaction data reveals substantial crosstalk between MPs and non-MPs and identifies novel factors in endoplasmic reticulum-mitochondrial organization, membrane structure, and mitochondrial lipid homeostasis. More than one-third of these MP complexes are conserved in humans, with many containing members linked to clinical pathologies, enabling us to identify genes with putative disease function through guilt-by-association. Although still remaining incomplete, existing mitochondrial interaction data suggests that the relevant molecular machinery is modular, yet highly integrated with non-mitochondrial processes.

  19. Lateral and medial ventral occipitotemporal regions interact during the recognition of images revealed from noise

    Directory of Open Access Journals (Sweden)

    Barbara eNordhjem

    2016-01-01

    Full Text Available Several studies suggest different functional roles for the medial and the lateral ventral sections in object recognition. Texture and surface information is processed in medial regions, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections interact with each other and with early visual cortex to facilitate object recognition. In the current research, we set out to answer this question. In an fMRI study, thirteen subjects viewed and recognized images of objects and animals that were gradually revealed from noise while their brains were being scanned. We applied dynamic causal modeling (DCM – a method to characterize network interactions – to determine the modulatory effect of object recognition on a network comprising the primary visual cortex (V1, the lingual gyrus (LG in medial ventral cortex and the lateral occipital cortex (LO. We found that object recognition modulated the bilateral connectivity between LG and LO. Moreover, the feed-forward connectivity from V1 to LG and LO was modulated, while there was no evidence for feedback from these regions to V1 during object recognition. In particular, the interaction between medial and lateral areas supports a framework in which visual recognition of objects is achieved by networked regions that integrate information on image statistics, scene content and shape – rather than by a single categorically specialized region – within the ventral visual cortex.

  20. Fundamentals of magnetism

    CERN Document Server

    Reis, Mario

    2013-01-01

    The Fundamentals of Magnetism is a truly unique reference text, that explores the study of magnetism and magnetic behavior with a depth that no other book can provide. It covers the most detailed descriptions of the fundamentals of magnetism providing an emphasis on statistical mechanics which is absolutely critical for understanding magnetic behavior. The books covers the classical areas of basic magnetism, including Landau Theory and magnetic interactions, but features a more concise and easy-to-read style. Perfect for upper-level graduate students and industry researchers, The Fu

  1. Conserved BK channel-protein interactions reveal signals relevant to cell death and survival.

    Directory of Open Access Journals (Sweden)

    Bernd Sokolowski

    Full Text Available The large-conductance Ca(2+-activated K(+ (BK channel and its β-subunit underlie tuning in non-mammalian sensory or hair cells, whereas in mammals its function is less clear. To gain insights into species differences and to reveal putative BK functions, we undertook a systems analysis of BK and BK-Associated Proteins (BKAPS in the chicken cochlea and compared these results to other species. We identified 110 putative partners from cytoplasmic and membrane/cytoskeletal fractions, using a combination of coimmunoprecipitation, 2-D gel, and LC-MS/MS. Partners included 14-3-3γ, valosin-containing protein (VCP, stathmin (STMN, cortactin (CTTN, and prohibitin (PHB, of which 16 partners were verified by reciprocal coimmunoprecipitation. Bioinformatics revealed binary partners, the resultant interactome, subcellular localization, and cellular processes. The interactome contained 193 proteins involved in 190 binary interactions in subcellular compartments such as the ER, mitochondria, and nucleus. Comparisons with mice showed shared hub proteins that included N-methyl-D-aspartate receptor (NMDAR and ATP-synthase. Ortholog analyses across six species revealed conserved interactions involving apoptosis, Ca(2+ binding, and trafficking, in chicks, mice, and humans. Functional studies using recombinant BK and RNAi in a heterologous expression system revealed that proteins important to cell death/survival, such as annexinA5, γ-actin, lamin, superoxide dismutase, and VCP, caused a decrease in BK expression. This revelation led to an examination of specific kinases and their effectors relevant to cell viability. Sequence analyses of the BK C-terminus across 10 species showed putative binding sites for 14-3-3, RAC-α serine/threonine-protein kinase 1 (Akt, glycogen synthase kinase-3β (GSK3β and phosphoinositide-dependent kinase-1 (PDK1. Knockdown of 14-3-3 and Akt caused an increase in BK expression, whereas silencing of GSK3β and PDK1 had the opposite

  2. Syndetic model of fundamental interactions

    Directory of Open Access Journals (Sweden)

    Ernest Ma

    2015-02-01

    Full Text Available The standard model of quarks and leptons is extended to connect three outstanding issues in particle physics and astrophysics: (1 the absence of strong CP nonconservation, (2 the existence of dark matter, and (3 the mechanism of nonzero neutrino masses, and that of the first family of quarks and leptons, all in the context of having only one Higgs boson in a renormalizable theory. Some phenomenological implications are discussed.

  3. Historical comparisons reveal altered competitive interactions in a guild of crustose coralline algae.

    Science.gov (United States)

    McCoy, S J; Pfister, C A

    2014-04-01

    As the ocean environment changes over time, a paucity of long-term data sets and historical comparisons limits the exploration of community dynamics over time in natural systems. Here, we used a long-term experimental data set to present evidence for a reversal of competitive dominance within a group of crustose coralline algae (CCA) from the 1980s to present time in the northeast Pacific Ocean. CCA are cosmopolitan species distributed globally, and dominant space holders in intertidal and subtidal systems. Competition experiments showed a markedly lower competitive ability of the previous competitively dominant species and a decreased response of competitive dynamics to grazer presence. Competitive networks obtained from survey data showed concordance between the 1980s and 2013, yet also revealed reductions in interaction strengths across the assemblage. We discuss the potential role of environmental change, including ocean acidification, in altered ecological dynamics in this system.

  4. Genome-wide analysis of the Arabidopsis leaf transcriptome reveals interaction of phosphate and sugar metabolism

    DEFF Research Database (Denmark)

    Muller, Renate; Morant, Marc; Jarmer, Hanne Østergaard

    2007-01-01

    and carbohydrate levels. Transcript profiling revealed the influence of the two factors individually and the interactions between P- and sugar-dependent gene regulation. A large number of gene transcripts changed more than 2-fold: In response to P starvation, 171 genes were induced and 16 repressed, whereas Suc...... incubation resulted in 337 induced and 307 repressed genes. A number of new candidate genes involved in P acquisition were discovered. In addition, several putative transcription factors and signaling proteins of P sensing were disclosed. Several genes previously identified to be sugar responsive were also...... regulated by P starvation and known P-responsive genes were sugar inducible. Nearly 150 genes were synergistically or antagonistically regulated by the two factors. These genes exhibit more prominent or contrasting regulation in response to Suc and P in combination than expected from the effect of the two...

  5. Fundamentals of algebraic topology

    CERN Document Server

    Weintraub, Steven H

    2014-01-01

    This rapid and concise presentation of the essential ideas and results of algebraic topology follows the axiomatic foundations pioneered by Eilenberg and Steenrod. The approach of the book is pragmatic: while most proofs are given, those that are particularly long or technical are omitted, and results are stated in a form that emphasizes practical use over maximal generality. Moreover, to better reveal the logical structure of the subject, the separate roles of algebra and topology are illuminated. Assuming a background in point-set topology, Fundamentals of Algebraic Topology covers the canon of a first-year graduate course in algebraic topology: the fundamental group and covering spaces, homology and cohomology, CW complexes and manifolds, and a short introduction to homotopy theory. Readers wishing to deepen their knowledge of algebraic topology beyond the fundamentals are guided by a short but carefully annotated bibliography.

  6. Amyloid plaque structure and cell surface interactions of β-amyloid fibrils revealed by electron tomography

    Science.gov (United States)

    Han, Shen; Kollmer, Marius; Markx, Daniel; Claus, Stephanie; Walther, Paul; Fändrich, Marcus

    2017-01-01

    The deposition of amyloid fibrils as plaques is a key feature of several neurodegenerative diseases including in particular Alzheimer’s. This disease is characterized, if not provoked, by amyloid aggregates formed from Aβ peptide that deposit inside the brain or are toxic to neuronal cells. We here used scanning transmission electron microscopy (STEM) to determine the fibril network structure and interactions of Aβ fibrils within a cell culture model of Alzheimer’s disease. STEM images taken from the formed Aβ amyloid deposits revealed three main types of fibril network structures, termed amorphous meshwork, fibril bundle and amyloid star. All three were infiltrated by different types of lipid inclusions from small-sized exosome-like structures (50–100 nm diameter) to large-sized extracellular vesicles (up to 300 nm). The fibrils also presented strong interactions with the surrounding cells such that fibril bundles extended into tubular invaginations of the plasma membrane. Amyloid formation in the cell model was previously found to have an intracellular origin and we show here that it functionally destroys the integrity of the intracellular membranes as it leads to lysosomal leakage. These data provide a mechanistic link to explain why intracellular fibril formation is toxic to the cell. PMID:28240273

  7. The Fundamental Planes of E+A galaxies and GALEX UV-excess early-type galaxies: Revealing their intimate connection

    CERN Document Server

    Choi, Yumi; Yoon, Suk-Jin

    2009-01-01

    Strong Balmer absorption lines and the lack of Ha and [OII] emission lines signify that E+As are post-starburst systems. Recent studies suggest that E+As may undergo the transition from the `blue cloud' to the `red sequence' and eventually migrate to red sequence ETGs. An observational validation of this scenario is to identify the intervening galaxy population between E+As and the red-sequence. Motivated by recent findings with GALEX that a large fraction of ETGs exhibit UV-excess as a sign of RSF, we investigate the possible connection of the UV-excess galaxies to E+As. In particular, we examine the FP scaling relations of the largest sample of ~1,000 E+As selected from the SDSS and ~20,000 morphologically-selected SDSS ETGs with GALEX UV data. The FP parameters, combined with stellar population indicators, reveal a certain group of UV-excess ETGs that bridges between E+As and quiescent red galaxies. The newly identified galaxies are the post-starburst systems characterized by UV-excess but no Ha emission. ...

  8. Modelling of Yeast Mating Reveals Robustness Strategies for Cell-Cell Interactions.

    Directory of Open Access Journals (Sweden)

    Weitao Chen

    2016-07-01

    Full Text Available Mating of budding yeast cells is a model system for studying cell-cell interactions. Haploid yeast cells secrete mating pheromones that are sensed by the partner which responds by growing a mating projection toward the source. The two projections meet and fuse to form the diploid. Successful mating relies on precise coordination of dynamic extracellular signals, signaling pathways, and cell shape changes in a noisy background. It remains elusive how cells mate accurately and efficiently in a natural multi-cell environment. Here we present the first stochastic model of multiple mating cells whose morphologies are driven by pheromone gradients and intracellular signals. Our novel computational framework encompassed a moving boundary method for modeling both a-cells and α-cells and their cell shape changes, the extracellular diffusion of mating pheromones dynamically coupled with cell polarization, and both external and internal noise. Quantification of mating efficiency was developed and tested for different model parameters. Computer simulations revealed important robustness strategies for mating in the presence of noise. These strategies included the polarized secretion of pheromone, the presence of the α-factor protease Bar1, and the regulation of sensing sensitivity; all were consistent with data in the literature. In addition, we investigated mating discrimination, the ability of an a-cell to distinguish between α-cells either making or not making α-factor, and mating competition, in which multiple a-cells compete to mate with one α-cell. Our simulations were consistent with previous experimental results. Moreover, we performed a combination of simulations and experiments to estimate the diffusion rate of the pheromone a-factor. In summary, we constructed a framework for simulating yeast mating with multiple cells in a noisy environment, and used this framework to reproduce mating behaviors and to identify strategies for robust cell

  9. Modes of Escherichia coli Dps Interaction with DNA as Revealed by Atomic Force Microscopy.

    Directory of Open Access Journals (Sweden)

    Vladislav V Melekhov

    Full Text Available Multifunctional protein Dps plays an important role in iron assimilation and a crucial role in bacterial genome packaging. Its monomers form dodecameric spherical particles accumulating ~400 molecules of oxidized iron ions within the protein cavity and applying a flexible N-terminal ends of each subunit for interaction with DNA. Deposition of iron is a well-studied process by which cells remove toxic Fe2+ ions from the genetic material and store them in an easily accessible form. However, the mode of interaction with linear DNA remained mysterious and binary complexes with Dps have not been characterized so far. It is widely believed that Dps binds DNA without any sequence or structural preferences but several lines of evidence have demonstrated its ability to differentiate gene expression, which assumes certain specificity. Here we show that Dps has a different affinity for the two DNA fragments taken from the dps gene regulatory region. We found by atomic force microscopy that Dps predominantly occupies thermodynamically unstable ends of linear double-stranded DNA fragments and has high affinity to the central part of the branched DNA molecule self-assembled from three single-stranded oligonucleotides. It was proposed that Dps prefers binding to those regions in DNA that provide more contact pads for the triad of its DNA-binding bundle associated with one vertex of the protein globule. To our knowledge, this is the first study revealed the nucleoid protein with an affinity to branched DNA typical for genomic regions with direct and inverted repeats. As a ubiquitous feature of bacterial and eukaryotic genomes, such structural elements should be of particular care, but the protein system evolutionarily adapted for this function is not yet known, and we suggest Dps as a putative component of this system.

  10. In Vitro Characterization of Thermostable CAM Rubisco Activase Reveals a Rubisco Interacting Surface Loop.

    Science.gov (United States)

    Shivhare, Devendra; Mueller-Cajar, Oliver

    2017-07-01

    To maintain metabolic flux through the Calvin-Benson-Bassham cycle in higher plants, dead-end inhibited complexes of Rubisco must constantly be engaged and remodeled by the molecular chaperone Rubisco activase (Rca). In C3 plants, the thermolability of Rca is responsible for the deactivation of Rubisco and reduction of photosynthesis at moderately elevated temperatures. We reasoned that crassulacean acid metabolism (CAM) plants must possess thermostable Rca to support Calvin-Benson-Bassham cycle flux during the day when stomata are closed. A comparative biochemical characterization of rice (Oryza sativa) and Agave tequilana Rca isoforms demonstrated that the CAM Rca isoforms are approximately10°C more thermostable than the C3 isoforms. Agave Rca also possessed a much higher in vitro biochemical activity, even at low assay temperatures. Mixtures of rice and agave Rca form functional hetero-oligomers in vitro, but only the rice isoforms denature at nonpermissive temperatures. The high thermostability and activity of agave Rca mapped to the N-terminal 244 residues. A Glu-217-Gln amino acid substitution was found to confer high Rca activity to rice Rca Further mutational analysis suggested that Glu-217 restricts the flexibility of the α4-β4 surface loop that interacts with Rubisco via Lys-216. CAM plants thus promise to be a source of highly functional, thermostable Rca candidates for thermal fortification of crop photosynthesis. Careful characterization of their properties will likely reveal further protein-protein interaction motifs to enrich our mechanistic model of Rca function. © 2017 American Society of Plant Biologists. All Rights Reserved.

  11. Complete structure of the bacterial flagellar hook reveals extensive set of stabilizing interactions

    Science.gov (United States)

    Matsunami, Hideyuki; Barker, Clive S.; Yoon, Young-Ho; Wolf, Matthias; Samatey, Fadel A.

    2016-01-01

    The bacterial flagellar hook is a tubular helical structure made by the polymerization of multiple copies of a protein, FlgE. Here we report the structure of the hook from Campylobacter jejuni by cryo-electron microscopy at a resolution of 3.5 Å. On the basis of this structure, we show that the hook is stabilized by intricate inter-molecular interactions between FlgE molecules. Extra domains in FlgE, found only in Campylobacter and in related bacteria, bring more stability and robustness to the hook. Functional experiments suggest that Campylobacter requires an unusually strong hook to swim without its flagella being torn off. This structure reveals details of the quaternary organization of the hook that consists of 11 protofilaments. Previous study of the flagellar filament of Campylobacter by electron microscopy showed its quaternary structure made of seven protofilaments. Therefore, this study puts in evidence the difference between the quaternary structures of a bacterial filament and its hook. PMID:27811912

  12. Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

    Science.gov (United States)

    Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

    2015-11-01

    Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

  13. Whitefly genome expression reveals host-symbiont interaction in amino acid biosynthesis.

    Science.gov (United States)

    Upadhyay, Santosh Kumar; Sharma, Shailesh; Singh, Harpal; Dixit, Sameer; Kumar, Jitesh; Verma, Praveen C; Chandrashekar, K

    2015-01-01

    Whitefly (Bemisia tabaci) complex is a serious insect pest of several crop plants worldwide. It comprises several morphologically indistinguishable species, however very little is known about their genetic divergence and biosynthetic pathways. In the present study, we performed transcriptome sequencing of Asia 1 species of B. tabaci complex and analyzed the interaction of host-symbiont genes in amino acid biosynthetic pathways. We obtained about 83 million reads using Illumina sequencing that assembled into 72716 unitigs. A total of 21129 unitigs were annotated at stringent parameters. Annotated unitigs were mapped to 52847 gene ontology (GO) terms and 131 Kyoto encyclopedia of genes and genomes (KEGG) pathways. Expression analysis of the genes involved in amino acid biosynthesis pathways revealed the complementation between whitefly and its symbiont partner Candidatus Portiera aleyrodidarum. Most of the non-essential amino acids and intermediates of essential amino acid pathways were supplied by the host insect to its symbiont. The symbiont expressed the pathways for the essential amino acids arginine, threonine and tryptophan and the immediate precursors of valine, leucine, isoleucine and phenyl-alanine. High level expression of the amino acid transporters in the whitefly suggested the molecular mechanisms for the exchange of amino acids between the host and the symbiont. Our study provides a comprehensive transcriptome data for Asia 1 species of B. tabaci complex that focusses light on integration of host and symbiont genes in amino acid biosynthesis pathways.

  14. Conversational Interaction in the Scanner: Mentalizing during Language Processing as Revealed by MEG.

    Science.gov (United States)

    Bögels, Sara; Barr, Dale J; Garrod, Simon; Kessler, Klaus

    2015-09-01

    Humans are especially good at taking another's perspective-representing what others might be thinking or experiencing. This "mentalizing" capacity is apparent in everyday human interactions and conversations. We investigated its neural basis using magnetoencephalography. We focused on whether mentalizing was engaged spontaneously and routinely to understand an utterance's meaning or largely on-demand, to restore "common ground" when expectations were violated. Participants conversed with 1 of 2 confederate speakers and established tacit agreements about objects' names. In a subsequent "test" phase, some of these agreements were violated by either the same or a different speaker. Our analysis of the neural processing of test phase utterances revealed recruitment of neural circuits associated with language (temporal cortex), episodic memory (e.g., medial temporal lobe), and mentalizing (temporo-parietal junction and ventromedial prefrontal cortex). Theta oscillations (3-7 Hz) were modulated most prominently, and we observed phase coupling between functionally distinct neural circuits. The episodic memory and language circuits were recruited in anticipation of upcoming referring expressions, suggesting that context-sensitive predictions were spontaneously generated. In contrast, the mentalizing areas were recruited on-demand, as a means for detecting and resolving perceived pragmatic anomalies, with little evidence they were activated to make partner-specific predictions about upcoming linguistic utterances.

  15. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans, E-mail: hans.brandstetter@sbg.ac.at [University of Salzburg, Billrothstrasse 11, 5020 Salzburg (Austria)

    2014-07-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed.

  16. General interaction mode of CIDE:CIDE complex revealed by a mutation study of the Drep2 CIDE domain.

    Science.gov (United States)

    Lee, Seung Mi; Park, Hyun Ho

    2013-04-02

    The CIDE domain is a well known protein-protein interaction module that is initially detected at the apoptotic DNA fragmentation factor (DFF40/45). The interaction mechanism via the CIDE domain is not well understood. To elucidate CIDE domain mediated interactions in the apoptotic DNA fragmentation system, we conducted biochemical and mutational studies and found that the surface of CIDE domains can be divided into an acidic side and a basic side. In addition, a mutagenesis study revealed that the basic surface side of Drep2 CIDE is involved in the interaction with the acidic surface side of Drep1 CIDE and Drep3 CIDE. Our research supports the idea that a charge-charge interaction might be the general interaction mode of the CIDE:CIDE interaction.

  17. Surface Modification of Multiwall Carbon Nanotubes with Cationic Conjugated Polyelectrolytes: Fundamental Interactions and Intercalation into Conductive Poly(methyl-methacrylate) Composites

    KAUST Repository

    Ezzeddine, Alaa

    2015-05-22

    This research investigates the modification and dispersion and of pristine multiwalled carbon nanotubes (MWCNTs) through a simple solution mixing technique based on noncovalent interactions between poly(phenylene ethynylene) based conjugated polyelectrolytes functionalized with cationic imidazolium solubilizing groups (PIM-2 and PIM-4) and MWCNTs. Spectroscopic studies demonstrated the ability of PIMs to strongly interact with and efficiently disperse MWCNTs in different solvents mainly due to π-interactions between the PIMs and MWCNTs. Transmission electron microscopy and atomic force microscopy revealed the coating of the polyelectrolytes on the walls of the nanotubes. Scanning electron microscopy (SEM) studies confirm the homogenous dispersion of PIM modified MWCNTs in poly(methyl methacrylate) (PMMA) matrix. The addition of 1 wt% PIM modified MWCNTs to the matrix has led to a significant decrease in DC resistivity of the composite (13 orders of magnitude). The increase in electrical conductivity and the improvement in thermal and mechanical properties of the membranes containing the PIM modified MWCNTs is ascribed to the formation of MWCNTs networks and cross-linking sites that provided channels for the electrons to move in throughout the matrix and reinforced the interface between MWCNTs and PMMA.

  18. Hyperspectral remote sensing and long term monitoring reveal watershed-estuary ecosystem interactions

    Science.gov (United States)

    Hestir, E. L.; Schoellhamer, D. H.; Santos, M. J.; Greenberg, J. A.; Morgan-King, T.; Khanna, S.; Ustin, S.

    2016-02-01

    Estuarine ecosystems and their biogeochemical processes are extremely vulnerable to climate and environmental changes, and are threatened by sea level rise and upstream activities such as land use/land cover and hydrological changes. Despite the recognized threat to estuaries, most aspects of how change will affect estuaries are not well understood due to the poorly resolved understanding of the complex physical, chemical and biological processes and their interactions in estuarine systems. Remote sensing technologies such as high spectral resolution optical systems enable measurements of key environmental parameters needed to establish baseline conditions and improve modeling efforts. The San Francisco Bay-Delta is a highly modified estuary system in a state of ecological crisis due to the numerous threats to its sustainability. In this study, we used a combination of hyperspectral remote sensing and long-term in situ monitoring records to investigate how water clarity has been responding to extreme climatic events, anthropogenic watershed disturbances, and submerged aquatic vegetation (SAV) invasions. From the long-term turbidity monitoring record, we found that water clarity underwent significant increasing step changes associated with sediment depletion and El Nino-extreme run-off events. Hyperspectral remote sensing data revealed that invasive submerged aquatic pant species have facultative C3 and C4-like photosynthetic pathways that give them a competitive advantage under the changing water clarity conditions of the Bay-Delta system. We postulate that this adaptation facilitated the rapid expansion of SAV following the significant step changes in increasing water clarity caused by watershed disturbances and the 1982-1983 El Nino events. Using SAV maps from hyperspectral remote sensing, we estimate that SAV-water clarity feedbacks were responsible for 20-70% of the increasing water clarity trend in the Bay-Delta. Ongoing and future developments in airborne and

  19. Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Samantha P Tull

    2009-08-01

    only revealed an unsuspected level of regulation in the migration of inflammatory leukocytes, it also contributes to our understanding of the interactions of this bioactive lipid with the inflammatory system. Moreover, it indicates the potential for novel therapeutics that target the inflammatory system with greater affinity and/or specificity than supplementing the diet with n-3-PUFAs.

  20. Variation of fundamental constants

    CERN Document Server

    Flambaum, V V

    2006-01-01

    We present a review of recent works devoted to the variation of the fine structure constant alpha, 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 Feschbach resonance.

  1. A negative genetic interaction map in isogenic cancer cell lines reveals cancer cell vulnerabilities

    National Research Council Canada - National Science Library

    Vizeacoumar, Franco J; Arnold, Roland; Vizeacoumar, Frederick S; Chandrashekhar, Megha; Buzina, Alla; Young, Jordan T F; Kwan, Julian H M; Sayad, Azin; Mero, Patricia; Lawo, Steffen; Tanaka, Hiromasa; Brown, Kevin R; Baryshnikova, Anastasia; Mak, Anthony B; Fedyshyn, Yaroslav; Wang, Yadong; Brito, Glauber C; Kasimer, Dahlia; Makhnevych, Taras; Ketela, Troy; Datti, Alessandro; Babu, Mohan; Emili, Andrew; Pelletier, Laurence; Wrana, Jeff; Wainberg, Zev; Kim, Philip M; Rottapel, Robert; O‧Brien, Catherine A; Andrews, Brenda; Boone, Charles; Moffat, Jason

    ...‐scale sequencing efforts. Using genome‐scale pooled shRNA screening technology, we mapped negative genetic interactions across a set of isogenic cancer cell lines and confirmed hundreds of these interactions in orthogonal co...

  2. Tryptophan probes reveal residue-specific phospholipid interactions of apolipoprotein C-III.

    Science.gov (United States)

    Pfefferkorn, Candace M; Walker, Robert L; He, Yi; Gruschus, James M; Lee, Jennifer C

    2015-11-01

    Apolipoproteins are essential human proteins for lipid metabolism. Together with phospholipids, they constitute lipoproteins, nm to μm sized particles responsible for transporting cholesterol and triglycerides throughout the body. To investigate specific protein-lipid interactions, we produced and characterized three single-Trp containing apolipoprotein C-III (ApoCIII) variants (W42 (W54F/W65F), W54 (W42F/W65F), W65 (W42F/W54F)). Upon binding to phospholipid vesicles, wild-type ApoCIII adopts an α-helical conformation (50% helicity) as determined by circular dichroism spectroscopy with an approximate apparent partition constant of 3×10(4) M(-1). Steady-state and time-resolved fluorescence measurements reveal distinct residue-specific behaviors with W54 experiencing the most hydrophobic environment followed by W42 and W65. Interestingly, time-resolved anisotropy measurements show a converse trend for relative Trp mobility with position 54 being the least immobile. To determine the relative insertion depths of W42, W54, and W65 in the bilayer, fluorescence quenching experiments were performed using three different brominated lipids. W65 had a clear preference for residing near the headgroup while W54 and W42 sample the range of depths ~8-11 Å from the bilayer center. On average, W54 is slightly more embedded than W42. Based on Trp spectral differences between ApoCIII binding to phospholipid vesicles and sodium dodecyl sulfate micelles, we suggest that ApoCIII adopts an alternate helical conformation on the bilayer which could have functional implications.

  3. Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion.

    Science.gov (United States)

    Rosenthal, Sara Brin; Twomey, Colin R; Hartnett, Andrew T; Wu, Hai Shan; Couzin, Iain D

    2015-04-14

    Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

  4. Specific and nonspecific interactions in ultraweak protein−protein associations revealed by solvent paramagnetic relaxation enhancements

    DEFF Research Database (Denmark)

    Johansson, Helle; Jensen, Malene Ringkjøbing; Gesmar, Henrik

    2014-01-01

    Weak and transient protein–protein interactions underlie numerous biological processes. However, the location of the interaction sites of the specific complexes and the effect of transient, non-specific protein–protein interactions often remain elusive. We have investigated the weak selfassociation...

  5. Fundamentals of photonics

    CERN Document Server

    Saleh, Bahaa E A

    2007-01-01

    Now in a new full-color edition, Fundamentals of Photonics, Second Edition is a self-contained and up-to-date introductory-level textbook that thoroughly surveys this rapidly expanding area of engineering and applied physics. Featuring a logical blend of theory and applications, coverage includes detailed accounts of the primary theories of light, including ray optics, wave optics, electromagnetic optics, and photon optics, as well as the interaction of photons and atoms, and semiconductor optics. Presented at increasing levels of complexity, preliminary sections build toward more advan

  6. Neutrons and Fundamental Symmetries

    Energy Technology Data Exchange (ETDEWEB)

    Plaster, Bradley [Univ. of Kentucky, Lexington, KY (United States). Dept. of Physics and Astronomy

    2016-01-11

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

  7. Revealing the Interactional Features of Learning and Teaching Moments in Outdoor Activity

    Science.gov (United States)

    Waters, Jane; Bateman, Amanda

    2015-01-01

    The data considered in this article was generated as part of a doctoral research study entitled: "A sociocultural consideration of child-initiated interaction with teachers in indoor and outdoor spaces" (Waters 2011) where child-initiated, teacher-child interaction in indoor and outdoor spaces were investigated. The purpose of the…

  8. Genome-wide association data reveal a global map of genetic interactions among protein complexes.

    Directory of Open Access Journals (Sweden)

    Gregory Hannum

    2009-12-01

    Full Text Available This work demonstrates how gene association studies can be analyzed to map a global landscape of genetic interactions among protein complexes and pathways. Despite the immense potential of gene association studies, they have been challenging to analyze because most traits are complex, involving the combined effect of mutations at many different genes. Due to lack of statistical power, only the strongest single markers are typically identified. Here, we present an integrative approach that greatly increases power through marker clustering and projection of marker interactions within and across protein complexes. Applied to a recent gene association study in yeast, this approach identifies 2,023 genetic interactions which map to 208 functional interactions among protein complexes. We show that such interactions are analogous to interactions derived through reverse genetic screens and that they provide coverage in areas not yet tested by reverse genetic analysis. This work has the potential to transform gene association studies, by elevating the analysis from the level of individual markers to global maps of genetic interactions. As proof of principle, we use synthetic genetic screens to confirm numerous novel genetic interactions for the INO80 chromatin remodeling complex.

  9. Digital Fourier analysis fundamentals

    CERN Document Server

    Kido, Ken'iti

    2015-01-01

    This textbook is a thorough, accessible introduction to digital Fourier analysis for undergraduate students in the sciences. Beginning with the principles of sine/cosine decomposition, the reader walks through the principles of discrete Fourier analysis before reaching the cornerstone of signal processing: the Fast Fourier Transform. Saturated with clear, coherent illustrations, "Digital Fourier Analysis - Fundamentals" includes practice problems and thorough Appendices for the advanced reader. As a special feature, the book includes interactive applets (available online) that mirror the illustrations.  These user-friendly applets animate concepts interactively, allowing the user to experiment with the underlying mathematics. For example, a real sine signal can be treated as a sum of clockwise and counter-clockwise rotating vectors. The applet illustration included with the book animates the rotating vectors and the resulting sine signal. By changing parameters such as amplitude and frequency, the reader ca...

  10. Fundamental partial compositeness

    CERN Document Server

    Sannino, Francesco

    2016-01-01

    We construct renormalizable Standard Model extensions, valid up to the Planck scale, that give a composite Higgs from a new fundamental strong force acting on fermions and scalars. Yukawa interactions of these particles with Standard Model fermions realize the partial compositeness scenario. Successful models exist because gauge quantum numbers of Standard Model fermions admit a minimal enough 'square root'. Furthermore, right-handed SM fermions have an SU(2)$_R$-like structure, yielding a custodially-protected composite Higgs. Baryon and lepton numbers arise accidentally. Standard Model fermions acquire mass at tree level, while the Higgs potential and flavor violations are generated by quantum corrections. We further discuss accidental symmetries and other dynamical features stemming from the new strongly interacting scalars. If the same phenomenology can be obtained from models without our elementary scalars, they would reappear as composite states.

  11. Biomembrane interactions reveal the mechanism of action of surface-immobilized host defense IDR-1010 peptide.

    Science.gov (United States)

    Gao, Guangzheng; Cheng, John T J; Kindrachuk, Jason; Hancock, Robert E W; Straus, Suzana K; Kizhakkedathu, Jayachandran N

    2012-02-24

    Dissecting the mechanism of action of surface-tethered antimicrobial and immunomodulatory peptides is critical to the design of optimized anti-infection coatings on biomedical devices. To address this, we compared the biomembrane interactions of host defense peptide IDR-1010cys (1) in free form, (2) as a soluble polymer conjugate, and (3) with one end tethered to a solid support with model bacterial and mammalian lipid membranes. Our results show that IDR-1010cys in all three distinct forms interacted with bacterial and mammalian lipid vesicles, but the extent of the interactions as monitored by the induction of secondary structure varied. The enhanced interaction of surface-tethered peptides is well correlated with their very good antimicrobial activities. Our results demonstrate that there may be a difference in the mechanism of action of surface-tethered versus free IDR-1010cys.

  12. Metabolomics of reef benthic interactions reveals a bioactive lipid involved in coral defence.

    Science.gov (United States)

    Quinn, Robert A; Vermeij, Mark J A; Hartmann, Aaron C; Galtier d'Auriac, Ines; Benler, Sean; Haas, Andreas; Quistad, Steven D; Lim, Yan Wei; Little, Mark; Sandin, Stuart; Smith, Jennifer E; Dorrestein, Pieter C; Rohwer, Forest

    2016-04-27

    Holobionts are assemblages of microbial symbionts and their macrobial host. As extant representatives of some of the oldest macro-organisms, corals and algae are important for understanding how holobionts develop and interact with one another. Using untargeted metabolomics, we show that non-self interactions altered the coral metabolome more than self-interactions (i.e. different or same genus, respectively). Platelet activating factor (PAF) and Lyso-PAF, central inflammatory modulators in mammals, were major lipid components of the coral holobionts. When corals were damaged during competitive interactions with algae, PAF increased along with expression of the gene encoding Lyso-PAF acetyltransferase; the protein responsible for converting Lyso-PAF to PAF. This shows that self and non-self recognition among some of the oldest extant holobionts involve bioactive lipids identical to those in highly derived taxa like humans. This further strengthens the hypothesis that major players of the immune response evolved during the pre-Cambrian.

  13. Targeting Bax interaction sites reveals that only homo-oligomerization sites are essential for its activation

    Science.gov (United States)

    Peng, R; Tong, J-S; Li, H; Yue, B; Zou, F; Yu, J; Zhang, L

    2013-01-01

    Bax is a proapoptotic Bcl-2 family member that has a central role in the initiation of mitochondria-dependent apoptosis. However, the mechanism of Bax activation during apoptosis remains unsettled. It is believed that the activation of Bax is mediated by either dissociation from prosurvival Bcl-2 family members, or direct association with BH3-only members. Several interaction sites on Bax that mediate its interactions with other Bcl-2 family members, as well as its proapoptotic activity, have been identified in previous studies by other groups. To rigorously investigate the functional role of these interaction sites, we knocked in their respective mutants using HCT116 colon cancer cells, in which apoptosis induced by several stimuli is strictly Bax-dependent. Bax-mediated apoptosis was intact upon knock-in (KI) of K21E and D33A, which were shown to block the interaction of Bax with BH3-only activators. Apoptosis was partially reduced by KI of D68R, which impairs the interaction of Bax with prosurvival members, and S184V, a constitutively mitochondria-targeting mutant. In contrast, apoptosis was largely suppressed by KI of L70A/D71A, which blocks homo-oligomerization of Bax and its binding to prosurvival Bcl-2 family proteins. Collectively, our results suggest that the activation of endogenous Bax in HCT116 cells is dependent on its homo-oligomerization sites, but not those previously shown to interact with BH3-only activators or prosurvival proteins only. We therefore postulate that critical interaction sites yet to be identified, or mechanisms other than protein-protein interactions, need to be pursued to delineate the mechanism of Bax activation during apoptosis. PMID:23392123

  14. Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

    LENUS (Irish Health Repository)

    Casey, Fergal

    2011-08-22

    Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.

  15. Dynamics of Disagreement: Large-Scale Temporal Network Analysis Reveals Negative Interactions in Online Collaboration

    Science.gov (United States)

    Tsvetkova, Milena; García-Gavilanes, Ruth; Yasseri, Taha

    2016-11-01

    Disagreement and conflict are a fact of social life. However, negative interactions are rarely explicitly declared and recorded and this makes them hard for scientists to study. In an attempt to understand the structural and temporal features of negative interactions in the community, we use complex network methods to analyze patterns in the timing and configuration of reverts of article edits to Wikipedia. We investigate how often and how fast pairs of reverts occur compared to a null model in order to control for patterns that are natural to the content production or are due to the internal rules of Wikipedia. Our results suggest that Wikipedia editors systematically revert the same person, revert back their reverter, and come to defend a reverted editor. We further relate these interactions to the status of the involved editors. Even though the individual reverts might not necessarily be negative social interactions, our analysis points to the existence of certain patterns of negative social dynamics within the community of editors. Some of these patterns have not been previously explored and carry implications for the knowledge collection practice conducted on Wikipedia. Our method can be applied to other large-scale temporal collaboration networks to identify the existence of negative social interactions and other social processes.

  16. Ghost-in-the-Machine reveals human social signals for human–robot interaction

    Science.gov (United States)

    Loth, Sebastian; Jettka, Katharina; Giuliani, Manuel; de Ruiter, Jan P.

    2015-01-01

    We used a new method called “Ghost-in-the-Machine” (GiM) to investigate social interactions with a robotic bartender taking orders for drinks and serving them. Using the GiM paradigm allowed us to identify how human participants recognize the intentions of customers on the basis of the output of the robotic recognizers. Specifically, we measured which recognizer modalities (e.g., speech, the distance to the bar) were relevant at different stages of the interaction. This provided insights into human social behavior necessary for the development of socially competent robots. When initiating the drink-order interaction, the most important recognizers were those based on computer vision. When drink orders were being placed, however, the most important information source was the speech recognition. Interestingly, the participants used only a subset of the available information, focussing only on a few relevant recognizers while ignoring others. This reduced the risk of acting on erroneous sensor data and enabled them to complete service interactions more swiftly than a robot using all available sensor data. We also investigated socially appropriate response strategies. In their responses, the participants preferred to use the same modality as the customer’s requests, e.g., they tended to respond verbally to verbal requests. Also, they added redundancy to their responses, for instance by using echo questions. We argue that incorporating the social strategies discovered with the GiM paradigm in multimodal grammars of human–robot interactions improves the robustness and the ease-of-use of these interactions, and therefore provides a smoother user experience. PMID:26582998

  17. Ghost-in-the-Machine reveals human social signals for human-robot interaction.

    Science.gov (United States)

    Loth, Sebastian; Jettka, Katharina; Giuliani, Manuel; de Ruiter, Jan P

    2015-01-01

    We used a new method called "Ghost-in-the-Machine" (GiM) to investigate social interactions with a robotic bartender taking orders for drinks and serving them. Using the GiM paradigm allowed us to identify how human participants recognize the intentions of customers on the basis of the output of the robotic recognizers. Specifically, we measured which recognizer modalities (e.g., speech, the distance to the bar) were relevant at different stages of the interaction. This provided insights into human social behavior necessary for the development of socially competent robots. When initiating the drink-order interaction, the most important recognizers were those based on computer vision. When drink orders were being placed, however, the most important information source was the speech recognition. Interestingly, the participants used only a subset of the available information, focussing only on a few relevant recognizers while ignoring others. This reduced the risk of acting on erroneous sensor data and enabled them to complete service interactions more swiftly than a robot using all available sensor data. We also investigated socially appropriate response strategies. In their responses, the participants preferred to use the same modality as the customer's requests, e.g., they tended to respond verbally to verbal requests. Also, they added redundancy to their responses, for instance by using echo questions. We argue that incorporating the social strategies discovered with the GiM paradigm in multimodal grammars of human-robot interactions improves the robustness and the ease-of-use of these interactions, and therefore provides a smoother user experience.

  18. Ghost-in-the-Machine Reveals Human Social Signals for Human-Robot Interaction

    Directory of Open Access Journals (Sweden)

    Sebastian eLoth

    2015-11-01

    Full Text Available We used a new method called Ghost-in-the-Machine (GiM to investigate social interactions with a robotic bartender taking orders for drinks and serving them. Using the GiM paradigm allowed us to identify how human participants recognise the intentions of customers on the basis of the output of the robotic recognisers. Specifically, we measured which recogniser modalities (e.g., speech, the distance to the bar were relevant at different stages of the interaction. This provided insights into human social behaviour necessary for the development of socially competent robots. When initiating the drink-order interaction, the most important recognisers were those based on computer vision. When drink orders were being placed, however, the most important information source was the speech recognition. Interestingly, the participants used only a subset of the available information, focussing only on a few relevant recognisers while ignoring others. This reduced the risk of acting on erroneous sensor data and enabled them to complete service interactions more swiftly than a robot using all available sensor data. We also investigated socially appropriate response strategies. In their responses, the participants preferred to use the same modality as the customer’s requests, e.g., they tended to respond verbally to verbal requests. Also, they added redundancy to their responses, for instance by using echo questions. We argue that incorporating the social strategies discovered with the GiM paradigm in multimodal grammars of human-robot interactions improves the robustness and the ease-of-use of these interactions, and therefore provides a smoother user experience.

  19. XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation

    DEFF Research Database (Denmark)

    Mortuza, Gulnahar B.; Cavazza, Tommaso; Garcia-Mayoral, Maria Flor;

    2014-01-01

    chTOG is a conserved microtubule polymerase that catalyses the addition of tubulin dimers to promote microtubule growth. chTOG interacts with TACC3, a member of the transforming acidic coiled-coil (TACC) family. Here we analyse their association using the Xenopus homologues, XTACC3 (TACC3) and XM...

  20. Unraveling the genetics of wheat-necrotrophic pathogen interactions reveals a conundrum

    Science.gov (United States)

    Interactions between wheat and the necrotrophic pathogens Parastagonospora nodorum (Pn) and Pyrenophora tritici-repentis (Ptr), which cause the foliar diseases Septoria nodorum blotch (SNB) and tan spot, respectively, involve host genes that recognize pathogen-produced necrotrophic effectors (NEs) i...

  1. Accidental Interaction between PDZ Domains and Diclofenac Revealed by NMR-Assisted Virtual Screening

    Directory of Open Access Journals (Sweden)

    Kengo Kinoshita

    2013-08-01

    Full Text Available In silico approaches have become indispensable for drug discovery as well as drug repositioning and adverse effect prediction. We have developed the eF-seek program to predict protein–ligand interactions based on the surface structure of proteins using a clique search algorithm. We have also developed a special protein structure prediction pipeline and accumulated predicted 3D models in the Structural Atlas of the Human Genome (SAHG database. Using this database, genome-wide prediction of non-peptide ligands for proteins in the human genome was performed, and a subset of predicted interactions including 14 PDZ domains was then confirmed by NMR titration. Surprisingly, diclofenac, a non-steroidal anti-inflammatory drug, was found to be a non-peptide PDZ domain ligand, which bound to 5 of 15 tested PDZ domains. The critical residues for the PDZ–diclofenac interaction were also determined. Pharmacological implications of the accidental PDZ–diclofenac interaction are further discussed.

  2. Neuron-specific protein interactions of Drosophila CASK-b are revealed by mass spectrometry

    Directory of Open Access Journals (Sweden)

    Konark eMukherjee

    2014-06-01

    Full Text Available Modular scaffolding proteins are designed to have multiple interactors. CASK, a member of the membrane-associated guanylate kinase (MAGUK superfamily, has been shown to have roles in many tissues, including neurons and epithelia. It is likely that the set of proteins it interacts with is different in each of these diverse tissues. In this study we asked if within the Drosophila central nervous system, there were neuron-specific sets of CASK-interacting proteins. A YFP-tagged CASK transgene was expressed in genetically defined subsets of neurons in the Drosophila brain known to be important for CASK function, and proteins present in an anti-GFP immunoprecipitation were identified by mass spectrometry. Each subset of neurons had a distinct set of interacting proteins, suggesting that CASK participates in multiple protein networks and that these networks may be different in different neuronal circuits. One common set of proteins was associated with mitochondria, and we show here that endogenous CASK co-purifies with mitochondria. We also determined CASK posttranslational modifications for one cell type, supporting the idea that this technique can be used to assess cell- and circuit-specific protein modifications as well as protein interaction networks.

  3. Scanning a microhabitat: plant-microbe interactions revealed by confocal laser microscopy

    Directory of Open Access Journals (Sweden)

    Massimiliano eCardinale

    2014-03-01

    Full Text Available No plant or cryptogam exists in nature without microorganisms associated with its tissues. Plants as microbial hosts are puzzles of different microhabitats, each of them colonized by specifically adapted microbiomes. The interactions with such microorganisms have drastic effects on the host fitness. Since the last 20 years, the combination of microscopic tools and molecular approaches contributed to new insights into microbe-host interactions. Particularly, confocal laser scanning microscopy (CLSM facilitated the exploration of microbial habitats and allowed the observation of host-associated microorganisms in situ with an unprecedented accuracy. Here I present an overview of the progresses made in the study of the interactions between microorganisms and plants or plant-like organisms, focusing on the role of CLSM for the understanding of their significance. I critically discuss risks of misinterpretation when procedures of CLSM are not properly optimized. I also review approaches for quantitative and statistical analyses of CLSM images, the combination with other molecular and microscopic methods, and suggest the re-evaluation of natural autofluorescence. In this review, technical aspects were coupled with scientific outcomes, to facilitate the readers in identifying possible CLSM applications in their research or to expand their existing potential. The scope of this review is to highlight the importance of confocal microscopy in the study of plant-microbe interactions and also to be an inspiration for integrating microscopy with molecular techniques in future researches of microbial ecology.

  4. An fMRI Study of Audiovisual Speech Perception Reveals Multisensory Interactions in Auditory Cortex.

    Science.gov (United States)

    Okada, Kayoko; Venezia, Jonathan H; Matchin, William; Saberi, Kourosh; Hickok, Gregory

    2013-01-01

    Research on the neural basis of speech-reading implicates a network of auditory language regions involving inferior frontal cortex, premotor cortex and sites along superior temporal cortex. In audiovisual speech studies, neural activity is consistently reported in posterior superior temporal Sulcus (pSTS) and this site has been implicated in multimodal integration. Traditionally, multisensory interactions are considered high-level processing that engages heteromodal association cortices (such as STS). Recent work, however, challenges this notion and suggests that multisensory interactions may occur in low-level unimodal sensory cortices. While previous audiovisual speech studies demonstrate that high-level multisensory interactions occur in pSTS, what remains unclear is how early in the processing hierarchy these multisensory interactions may occur. The goal of the present fMRI experiment is to investigate how visual speech can influence activity in auditory cortex above and beyond its response to auditory speech. In an audiovisual speech experiment, subjects were presented with auditory speech with and without congruent visual input. Holding the auditory stimulus constant across the experiment, we investigated how the addition of visual speech influences activity in auditory cortex. We demonstrate that congruent visual speech increases the activity in auditory cortex.

  5. Crystal Structure of Prp5p Reveals Interdomain Interactions that Impact Spliceosome Assembly

    Directory of Open Access Journals (Sweden)

    Zhi-Min Zhang

    2013-12-01

    Full Text Available The DEAD-box adenosine triphosphatase (ATPase Prp5p facilitates U2 small nuclear ribonucleoprotein particle (snRNP binding to the intron branch site region during spliceosome assembly. We present crystal structures of S. cerevisiae Prp5p alone and in complex with ADP at 2.12 Å and 1.95 Å resolution. The three-dimensional packing of Prp5p subdomains differs strikingly from that so far observed in other DEAD-box proteins: two RecA-like subdomains adopt an “open state” conformation stabilized by extensive interactions involving sequences that flank the two subdomains. This conformation is distinct from that required for ATP hydrolysis. Consistent with this, Prp5p mutations that destabilize interdomain interactions exhibited increased ATPase activity in vitro and inhibited splicing of suboptimal branch site substrates in vivo, whereas restoration of interdomain interactions reversed these effects. We conclude that the Prp5p open state conformation is biologically relevant and that disruption of the interdomain interaction facilitates a large-scale conformational change of Prp5p during U2 snRNP-branch site recognition.

  6. Hypernetworks Reveal Compound Variables That Capture Cooperative and Competitive Interactions in a Soccer Match

    Directory of Open Access Journals (Sweden)

    João Ramos

    2017-08-01

    Full Text Available The combination of sports sciences theorization and social networks analysis (SNA has offered useful new insights for addressing team behavior. However, SNA typically represents the dynamics of team behavior during a match in dyadic interactions and in a single cumulative snapshot. This study aims to overcome these limitations by using hypernetworks to describe illustrative cases of team behavior dynamics at various other levels of analyses. Hypernetworks simultaneously access cooperative and competitive interactions between teammates and opponents across space and time during a match. Moreover, hypernetworks are not limited to dyadic relations, which are typically represented by edges in other types of networks. In a hypernetwork, n-ary relations (with n > 2 and their properties are represented with hyperedges connecting more than two players simultaneously (the so-called simplex—plural, simplices. Simplices can capture the interactions of sets of players that may include an arbitrary number of teammates and opponents. In this qualitative study, we first used the mathematical formalisms of hypernetworks to represent a multilevel team behavior dynamics, including micro (interactions between players, meso (dynamics of a given critical event, e.g., an attack interaction, and macro (interactions between sets of players levels. Second, we investigated different features that could potentially explain the occurrence of critical events, such as, aggregation or disaggregation of simplices relative to goal proximity. Finally, we applied hypernetworks analysis to soccer games from the English premier league (season 2010–2011 by using two-dimensional player displacement coordinates obtained with a multiple-camera match analysis system provided by STATS (formerly Prozone. Our results show that (i at micro level the most frequently occurring simplices configuration is 1vs.1 (one attacker vs. one defender; (ii at meso level, the dynamics of simplices

  7. Concurrent TMS-fMRI Reveals Interactions between Dorsal and Ventral Attentional Systems

    DEFF Research Database (Denmark)

    Leitao, Joana; Thielscher, Axel; Tuennerhoff, Johannes

    2015-01-01

    Adaptive behavior relies on combining bottom-up sensory inputs with top-down control signals to guide responses in line with current goals and task demands. Over the past decade, accumulating evidence has suggested that the dorsal and ventral frontoparietal attentional systems are recruited...... interactively in this process. This fMRI study used concurrent transcranial magnetic stimulation (TMS) as a causal perturbation approach to investigate the interactions between dorsal and ventral attentional systems and sensory processing areas. In a sustained spatial attention paradigm, human participants......-TMS relative to Sham-TMS increased activation in the parietal cortex regardless of sensory stimulation, confirming the neural effectiveness of TMS stimulation. Visual targets increased activations in the anterior insula, a component of the ventral attentional system responsible for salience detection...

  8. Chemometric analysis reveals links in the formation of fragrant bio-molecules during agarwood (Aquilaria malaccensis) and fungal interactions

    Science.gov (United States)

    Sen, Supriyo; Dehingia, Madhusmita; Talukdar, Narayan Chandra; Khan, Mojibur

    2017-01-01

    Fragrant agarwood, arguably the costliest wood in the world, is formed by plant-fungal interactions in Aquilaria spp. However, very little is known about this fragrant outcome of interaction. Therefore, mimicking the ancient traditions of agarwood production in Assam (Northeast India), a chemometric assessment of the agarwood-fungus interaction was made by chemical profiling (GC-MS) coupled with statistical analysis (principal component, correlation network analysis) across three platforms, viz. callus, juvenile plants and resinous wood-chips with an associated Fusarium. In the study of callus-fungus interaction, increased accumulation of key aroma compounds such as pentatriacontane {fold change (log2FC) = 3.47)}, 17-pentatriacontene (log2FC = 2.95), tetradecane, 2-methyl- (log2FC = 1.10) over callus and activation of pathways related to defense and secondary metabolism indicated links to aroma production. Study on fungal interactions in juvenile plants and resinous wood-chips indicated formation of terpenoid precursors (e.g. farnesol, geranylgeraniol acetate) and agarwood sesquiterpenes (e.g. agarospirol, γ-eudesmol). Correlation network analysis revealed the possible regulation of sesquiterpene biosynthesis involving squalene. Also a direct role of fungus in aroma (e.g. dodecane, 4-methyl-, tetracosane) was highlighted. Appearance of fragrant molecules unknown to agarwood during interaction featured as a new possibility for future research. PMID:28290512

  9. Mutational analysis of Trypanosoma brucei RNA editing ligase reveals regions critical for interaction with KREPA2.

    Directory of Open Access Journals (Sweden)

    Vaibhav Mehta

    Full Text Available The Trypanosoma brucei parasite causes the vector-borne disease African sleeping sickness. Mitochondrial mRNAs of T. brucei undergo posttranscriptional RNA editing to make mature, functional mRNAs. The final step of this process is catalyzed by the essential ligase, T. brucei RNA Editing Ligase 1 (TbREL1 and the closely related T. brucei RNA Editing Ligase 2 (TbREL2. While other ligases such as T7 DNA ligase have both a catalytic and an oligonucleotide/oligosaccharide-binding (OB-fold domain, T. brucei RNA editing ligases contain only the catalytic domain. The OB-fold domain, which is required for interaction with the substrate RNA, is provided in trans by KREPA2 (for TbREL1 and KREPA1 (for TbREL2. KREPA2 enhancement of TbREL1 ligase activity is presumed to occur via an OB-fold-mediated increase in substrate specificity and catalysis. We characterized the interaction between TbREL1 and KREPA2 in vitro using full-length, truncated, and point-mutated ligases. As previously shown, our data indicate strong, specific stimulation of TbREL1 catalytic activity by KREPA2. We narrowed the region of contact to the final 59 C-terminal residues of TbREL1. Specifically, the TbREL1 C-terminal KWKE (441-444 sequence appear to coordinate the KREPA2-mediated enhancement of TbREL1 activities. N-terminal residues F206, T264 and Y275 are crucial for the overall activity of TbREL1, particularly for F206, a mutation of this residue also disrupts KREPA2 interaction. Thus, we have identified the critical TbREL1 regions and amino acids that mediate the KREPA2 interaction.

  10. Lassa Virus Cell Entry Reveals New Aspects of Virus-Host Cell Interaction.

    Science.gov (United States)

    Torriani, Giulia; Galan-Navarro, Clara; Kunz, Stefan

    2017-02-15

    Viral entry represents the first step of every viral infection and is a determinant for the host range and disease potential of a virus. Here, we review the latest developments on cell entry of the highly pathogenic Old World arenavirus Lassa virus, providing novel insights into the complex virus-host cell interaction of this important human pathogen. We will cover new discoveries on the molecular mechanisms of receptor recognition, endocytosis, and the use of late endosomal entry factors.

  11. Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

    OpenAIRE

    Hátylas Azevedo; Carlos Alberto Moreira-Filho

    2015-01-01

    Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed fu...

  12. Analysis of Hsp90 cochaperone interactions reveals a novel mechanism for TPR protein recognition.

    Science.gov (United States)

    Chadli, Ahmed; Bruinsma, Elizabeth S; Stensgard, Bridget; Toft, David

    2008-03-01

    The chaperone Hsp90 is required for the appropriate regulation of numerous key signaling molecules, including the progesterone receptor (PR). Many important cochaperones bind Hsp90 through their tetratricopeptide repeat (TPR) domains. Two such proteins, GCUNC45 and FKBP52, assist PR chaperoning and are thought to interact sequentially with PR-Hsp90 complexes. TPR proteins bind to the C-terminal MEEVD sequence of Hsp90, but GCUNC45 has been shown also to bind to a novel site near the N-terminus. We now show that FKBP52 is also able to bind to this site, and that these two cochaperones act competitively, through Hsp90, to modulate PR activity. The N-terminal site involves noncontiguous amino acids within or near the ATP binding pocket of Hsp90. TPR interactions at this site are thus strongly regulated by nucleotide binding and Hsp90 conformation. We propose an expanded model for client chaperoning in which the coordinated use of TPR recognition sites at both N- and C-terminal ends of Hsp90 enhances its ability to coordinate interactions with multiple TPR partners.

  13. Intermolecular interaction studies of winter flounder antifreeze protein reveal the existence of thermally accessible binding state.

    Science.gov (United States)

    Nguyen, Dat H; Colvin, Michael E; Yeh, Yin; Feeney, Robert E; Fink, William H

    2004-10-05

    The physical nature underlying intermolecular interactions between two rod-like winter flounder antifreeze protein (AFP) molecules and their implication for the mechanism of antifreeze function are examined in this work using molecular dynamics simulations, augmented with free energy calculations employing a continuum solvation model. The energetics for different modes of interactions of two AFP molecules is examined in both vacuum and aqueous phases along with the water distribution in the region encapsulated by two antiparallel AFP backbones. The results show that in a vacuum two AFP molecules intrinsically attract each other in the antiparallel fashion, where their complementary charge side chains face each other directly. In the aqueous environment, this attraction is counteracted by both screening and entropic effects. Therefore, two nearly energetically degenerate states, an aggregated state and a dissociated state, result as a new aspect of intermolecular interaction in the paradigm for the mechanism of action of AFP. The relevance of these findings to the mechanism of function of freezing inhibition in the context of our work on Antarctic cod antifreeze glycoprotein (Nguyen et al., Biophysical Journal, 2002, Vol. 82, pp. 2892-2905) is discussed.

  14. Revealing the role of catechol moieties in the interactions between peptides and inorganic surfaces.

    Science.gov (United States)

    Das, Priyadip; Reches, Meital

    2016-08-18

    Catechol (1,2-dihydroxy benzene) moieties are being widely used today in new adhesive technologies. Understanding their mechanism of action is therefore of high importance for developing their applications in materials science. This paper describes a single-molecule study of the interactions between catechol-related amino acid residues and a well-defined titanium dioxide (TiO2) surface. It is the first quantified measurement of the adhesion of these residues with a well-defined TiO2 surface. Single-molecule force spectroscopy measurements with AFM determined the role of different substitutions of the catechol moiety on the aromatic ring in the adhesion to the surface. These results shed light on the nature of interactions between these residues and inorganic metal oxide surfaces. This information is important for the design and fabrication of catechol-based materials such as hydrogels, coatings, and composites. Specifically, the interaction with TiO2 is important for the development of solar cells.

  15. Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription.

    Science.gov (United States)

    Xu, Zhixiong; Wei, Gang; Chepelev, Iouri; Zhao, Keji; Felsenfeld, Gary

    2011-03-01

    Insulin (INS) synthesis and secretion from pancreatic β-cells are tightly regulated; their deregulation causes diabetes. Here we map INS-associated loci in human pancreatic islets by 4C and 3C techniques and show that the INS gene physically interacts with the SYT8 gene, located over 300 kb away. This interaction is elevated by glucose and accompanied by increases in SYT8 expression. Inactivation of the INS promoter by promoter-targeting siRNA reduces SYT8 gene expression. SYT8-INS interaction and SYT8 transcription are attenuated by CTCF depletion. Furthermore, SYT8 knockdown decreases insulin secretion in islets. These results reveal a nonredundant role for SYT8 in insulin secretion and indicate that the INS promoter acts from a distance to stimulate SYT8 transcription. This suggests a function for the INS promoter in coordinating insulin transcription and secretion through long-range regulation of SYT8 expression in human islets.

  16. Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.

    Science.gov (United States)

    Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E; Levesque, Brié; Pedersen, Stine B; Bartels, Lina; Wapenaar, Hannah; Ye, Fei; Zhang, Mingjie; Bowen, Mark E; Strømgaard, Kristian

    2017-09-15

    The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners. We observed complex effects on affinity. Most notably, phosphorylation at Y397 induced a significant increase in affinity for stargazin, as confirmed by NMR and single molecule FRET. Additionally, we compared the effects of phosphorylation to phosphomimetic mutations, which revealed that phosphomimetics are ineffective substitutes for tyrosine phosphorylation. Our strategy to generate site-specifically phosphorylated PDZ domains provides a detailed understanding of the role of phosphorylation in the regulation of PSD-95 interactions.

  17. Androgen receptor coregulator ARA267-α interacts with death receptor-6 revealed by the yeast two-hybrid

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    ARA267-αis a newly identified androgen receptor coactivator.In order to further elucidate its precise role in cells,using the ARA267- α fragment containing four PHD and one SET conserved domains as bait we revealed an ARA267-α-PHD-SET-interacting protein,death receptor-6(DR6),in the yeast two-hybrid screening.DR6 is the member of TNF receptor family and has a death domain in its intracellular cytoplasmic portion(DR6cp)to mediate the cell apoptosis.The interaction between ARA267-α-PHD-SET and DR6cp was confirmed in vitro and in vivo.Our finding implied that androgen signaling pathway might cross talk with apoptosis signaling pathway through the interaction between ARA267-α and DR6.

  18. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... such as Lorentz and Einstein as well as mathematicians such as Poincare, Minkowski, Hilbert and Weyl contributed to this development. They created the new physical theories and the mathematical disciplines that play such paramount roles in their mathematical formulations. These physicists and mathematicians were...

  19. Virus host protein interaction network analysis reveals that the HEV ORF3 protein may interrupt the blood coagulation process.

    Directory of Open Access Journals (Sweden)

    Yansheng Geng

    Full Text Available Hepatitis E virus (HEV is endemic worldwide and a major cause of acute liver disease in developing countries. However, the molecular mechanisms of liver pathology and clinical disease are not well understood for HEV infection. Open reading frame 3 (ORF3 of HEV encodes a small phosphoprotein, which is assumed to be involved in liver pathology and clinical disease. In this study, the interactions between the HEV ORF3 protein and human proteins were investigated using a stringent, high-throughput yeast two-hybrid (Y2H analysis. Thirty two proteins were shown to interact with genotype 1 ORF3, 28 of which have not been reported previously. These novel interactions were evaluated by coimmunoprecipitation of protein complexes from transfected cells. We found also that the ORF3 proteins of genotype 4 and rabbit HEV interacted with all of the human proteins identified by the genotype 1 ORF3 protein. However, the putative ORF3 protein derived from avian HEV did not interact with the majority of these human proteins. The identified proteins were used to infer an overall interaction map linking the ORF3 protein with components of the host cellular networks. Analysis of this interaction map, based on functional annotation with the Gene Ontology features and KEGG pathways, revealed an enrichment of host proteins involved in complement coagulation, cellular iron ion homeostasis and oxidative stress. Additional canonical pathway analysis highlighted the enriched biological pathways relevant to blood coagulation and hemostasis. Consideration of the clinical manifestations of hepatitis E reported previously and the results of biological analysis from this study suggests that the ORF3 protein is likely to lead to an imbalance of coagulation and fibrinolysis by interacting with host proteins and triggering the corresponding pathological processes. These results suggest critical approaches to further study of the pathogenesis of the HEV ORF3 protein.

  20. Systematic Analysis Reveals Elongation Factor 2 and α-Enolase as Novel Interaction Partners of AKT2.

    Directory of Open Access Journals (Sweden)

    Katharina Bottermann

    Full Text Available AKT2 is one of the three isoforms of the protein kinase AKT being involved in the modulation of cellular metabolism. Since protein-protein interactions are one possibility to convey specificity in signal transduction, we performed AKT2-protein interaction analysis to elucidate their relevance for AKT2-dependent cellular functions. We identified heat shock protein 90 kDa (HSP90, Cdc37, heat shock protein 70 kDa (HSP70, 78 kDa glucose regulated protein (GRP78, tubulin, GAPDH, α-enolase and elongation factor 2 (EF2 as AKT2-interacting proteins by a combination of tandem affinity purification and mass spectrometry in HEK293T cells. Quantitative MS-analysis using stable isotope labeling by amino acids in cell culture (SILAC revealed that only HSP90 and Cdc37 interact stably with AKT2, whereas the other proteins interact with low affinity with AKT2. The interactions of AKT2 with α-enolase and EF2 were further analyzed in order to uncover the functional relevance of these newly discovered binding partners. Despite the interaction of AKT2 and α-enolase, which was additionally validated by proximity ligation assay (PLA, no significant impact of AKT on α-enolase activity was detected in activity measurements. AKT stimulation via insulin and/or inhibition with the ATP-competitive inhibitor CCT128930 did not alter enzymatic activity of α-enolase. Interestingly, the direct interaction of AKT2 and EF2 was found to be dynamically regulated in embryonic rat cardiomyocytes. Treatment with the PI3-kinase inhibitor LY294002 before stimulation with several hormones stabilized the complex, whereas stimulation alone led to complex dissociation which was analyzed in situ with PLA. Taken together, these findings point to new aspects of AKT2-mediated signal transduction in protein synthesis and glucose metabolism.

  1. Resting State fMRI in Mice Reveals Anesthesia Specific Signatures of Brain Functional Networks and Their Interactions

    Science.gov (United States)

    Bukhari, Qasim; Schroeter, Aileen; Cole, David M.; Rudin, Markus

    2017-01-01

    fMRI studies in mice typically require the use of anesthetics. Yet, it is known that anesthesia alters responses to stimuli or functional networks at rest. In this work, we have used Dual Regression analysis Network Modeling to investigate the effects of two commonly used anesthetics, isoflurane and medetomidine, on rs-fMRI derived functional networks, and in particular to what extent anesthesia affected the interaction within and between these networks. Experimental data have been used from a previous study (Grandjean et al., 2014). We applied multivariate ICA analysis and Dual Regression to infer the differences in functional connectivity between isoflurane- and medetomidine-anesthetized mice. Further network analysis was performed to investigate within- and between-network connectivity differences between these anesthetic regimens. The results revealed five major networks in the mouse brain: lateral cortical, associative cortical, default mode, subcortical, and thalamic network. The anesthesia regime had a profound effect both on within- and between-network interactions. Under isoflurane anesthesia predominantly intra- and inter-cortical interactions have been observed, with only minor interactions involving subcortical structures and in particular attenuated cortico-thalamic connectivity. In contrast, medetomidine-anesthetized mice displayed subcortical functional connectivity including interactions between cortical and thalamic ICA components. Combining the two anesthetics at low dose resulted in network interaction that constituted the superposition of the interaction observed for each anesthetic alone. The study demonstrated that network modeling is a promising tool for analyzing the brain functional architecture in mice and comparing alterations therein caused by different physiological or pathological states. Understanding the differential effects of anesthetics on brain networks and their interaction is essential when interpreting fMRI data recorded under

  2. Resting State fMRI in Mice Reveals Anesthesia Specific Signatures of Brain Functional Networks and Their Interactions.

    Science.gov (United States)

    Bukhari, Qasim; Schroeter, Aileen; Cole, David M; Rudin, Markus

    2017-01-01

    fMRI studies in mice typically require the use of anesthetics. Yet, it is known that anesthesia alters responses to stimuli or functional networks at rest. In this work, we have used Dual Regression analysis Network Modeling to investigate the effects of two commonly used anesthetics, isoflurane and medetomidine, on rs-fMRI derived functional networks, and in particular to what extent anesthesia affected the interaction within and between these networks. Experimental data have been used from a previous study (Grandjean et al., 2014). We applied multivariate ICA analysis and Dual Regression to infer the differences in functional connectivity between isoflurane- and medetomidine-anesthetized mice. Further network analysis was performed to investigate within- and between-network connectivity differences between these anesthetic regimens. The results revealed five major networks in the mouse brain: lateral cortical, associative cortical, default mode, subcortical, and thalamic network. The anesthesia regime had a profound effect both on within- and between-network interactions. Under isoflurane anesthesia predominantly intra- and inter-cortical interactions have been observed, with only minor interactions involving subcortical structures and in particular attenuated cortico-thalamic connectivity. In contrast, medetomidine-anesthetized mice displayed subcortical functional connectivity including interactions between cortical and thalamic ICA components. Combining the two anesthetics at low dose resulted in network interaction that constituted the superposition of the interaction observed for each anesthetic alone. The study demonstrated that network modeling is a promising tool for analyzing the brain functional architecture in mice and comparing alterations therein caused by different physiological or pathological states. Understanding the differential effects of anesthetics on brain networks and their interaction is essential when interpreting fMRI data recorded under

  3. Interactions between visual and motor areas during the recognition of plausible actions as revealed by magnetoencephalography.

    Science.gov (United States)

    Pavlidou, Anastasia; Schnitzler, Alfons; Lange, Joachim

    2014-02-01

    Several studies have shown activation of the mirror neuron system (MNS), comprising the temporal, posterior parietal, and sensorimotor areas when observing plausible actions, but far less is known on how these cortical areas interact during the recognition of a plausible action. Here, we recorded neural activity with magnetoencephalography while subjects viewed point-light displays of biologically plausible and scrambled versions of actions. We were interested in modulations of oscillatory activity and, specifically, in coupling of oscillatory activity between visual and motor areas. Both plausible and scrambled actions elicited modulations of θ (5-7 Hz), α (7-13 Hz), β (13-35 Hz), and γ (55-100 Hz) power within visual and motor areas. When comparing between the two actions, we observed sequential and spatially distinct increases of γ (∼65 Hz), β (∼25 Hz), and α (∼11 Hz) power between 0.5 and 1.3 s in parieto-occipital, sensorimotor, and left temporal areas. In addition, significant clusters of γ (∼65 Hz) and α/β (∼15 Hz) power decrease were observed in right temporal and parieto-occipital areas between 1.3 and 2.0 s. We found β-power in sensorimotor areas to be positively correlated on a trial-by-trial basis with parieto-occipital γ and left temporal α-power for the plausible but not for the scrambled condition. These results provide new insights in the neuronal oscillatory activity of the areas involved in the recognition of plausible action movements and their interaction. The power correlations between specific areas underscore the importance of interactions between visual and motor areas of the MNS during the recognition of a plausible action.

  4. The synthetic genetic interaction network reveals small molecules that target specific pathways in Sacchromyces cerevisiae.

    Science.gov (United States)

    Tamble, Craig M; St Onge, Robert P; Giaever, Guri; Nislow, Corey; Williams, Alexander G; Stuart, Joshua M; Lokey, R Scott

    2011-06-01

    High-throughput elucidation of synthetic genetic interactions (SGIs) has contributed to a systems-level understanding of genetic robustness and fault-tolerance encoded in the genome. Pathway targets of various compounds have been predicted by comparing chemical-genetic synthetic interactions to a network of SGIs. We demonstrate that the SGI network can also be used in a powerful reverse pathway-to-drug approach for identifying compounds that target specific pathways of interest. Using the SGI network, the method identifies an indicator gene that may serve as a good candidate for screening a library of compounds. The indicator gene is selected so that compounds found to produce sensitivity in mutants deleted for the indicator gene are likely to abrogate the target pathway. We tested the utility of the SGI network for pathway-to-drug discovery using the DNA damage checkpoint as the target pathway. An analysis of the compendium of synthetic lethal interactions in yeast showed that superoxide dismutase 1 (SOD1) has significant SGI connectivity with a large subset of DNA damage checkpoint and repair (DDCR) genes in Saccharomyces cerevisiae, and minimal SGIs with non-DDCR genes. We screened a sod1Δ strain against three National Cancer Institute (NCI) compound libraries using a soft agar high-throughput halo assay. Fifteen compounds out of ∼3100 screened showed selective toxicity toward sod1Δ relative to the isogenic wild type (wt) strain. One of these, 1A08, caused a transient increase in growth in the presence of sublethal doses of DNA damaging agents, suggesting that 1A08 inhibits DDCR signaling in yeast. Genome-wide screening of 1A08 against the library of viable homozygous deletion mutants further supported DDCR as the relevant targeted pathway of 1A08. When assayed in human HCT-116 colorectal cancer cells, 1A08 caused DNA-damage resistant DNA synthesis and blocked the DNA-damage checkpoint selectively in S-phase.

  5. Interactions of arsenic with calcite surfaces revealed by in situ nanoscale imaging

    Science.gov (United States)

    Renard, François; Putnis, Christine V.; Montes-Hernandez, German; Ruiz-Agudo, Encarnacion; Hovelmann, Jörn; Sarret, Géraldine

    2015-06-01

    Arsenic dissolved in water represents a key environmental and health challenge because several million people are under the threat of contamination. In calcareous environments calcite may play an important role in arsenic solubility and transfer in water. Arsenic-calcite interactions remain controversial, especially for As(III) which was proposed to be either incorporated as such, or as As(V) after oxidation. Here, we provide the first time-lapse in situ study of the evolution of the (10-14) calcite cleavage surface morphology during dissolution and growth in the presence of solutions with various amounts of As(III) or As(V) at room temperature and pH range 6-11 using a flow-through cell connected to an atomic force microscope (AFM). Reaction products were then characterized by Raman spectroscopy. In parallel, co-precipitation experiments with either As(III) or As(V) were performed in batch reactors, and the speciation of arsenic in the resulting solids was studied by X-ray absorption spectroscopy (XAS). For As(V), AFM results showed that it interacts strongly with the calcite surface, and XAS results showed that As(V) was mostly incorporated in the calcite structure. For As(III), AFM results showed much less impact on calcite growth and dissolution and less incorporation was observed. This was confirmed by XAS results that indicate that As(III) was partly oxidized into As(V) before being incorporated into calcite and the resulting calcite contained 36% As(III) and 64% As(V). All these experimental results confirm that As(V) has a much stronger interaction with calcite than As(III) and that calcite may represent an important reservoir for arsenic in various geological environments.

  6. Interactions of arsenic with calcite surfaces revealed by in-situ nanoscale imaging

    Science.gov (United States)

    Renard, Francois; Putnis, Christine; Montes-Hernandez, German; Ruiz-Agudo, Encarnacion; Hövelmann, Jörn; Sarret, Géraldine

    2015-04-01

    Arsenic dissolved in water represents a key environmental and health challenge because several million people are under the threat of contamination. In calcareous environments calcite may play an important role in arsenic solubility and transfer in water. Arsenic-calcite interactions remain controversial, especially for As(III) which was proposed to be either incorporated as such, or as As(V) after oxidation. Here, we provide the first time-lapse in-situ study of calcite dissolution and growth in the presence of solutions with various amounts of As(III) or As(V). This was performed at room temperature and pH range 6-9 using a flow through cell connected to an atomic force microscope (AFM), to study the evolution of the (10-14) calcite cleavage surface morphology. Reaction products were then characterized by Raman spectroscopy. In parallel, co-precipitation experiments with either As(III) or As(V) were performed in batch reactors, and the speciation of arsenic in the resulting solids was studied by X-ray absorption spectroscopy (XAS). For As(V), AFM results showed that it interacts strongly with the calcite surface, and XAS results showed that As(V) was mostly incorporated in the calcite structure. For As(III), AFM results showed much less impact on calcite growth and dissolution and less incorporation was observed. This was confirmed by XAS results that indicate that As(III) was partly oxidized into As(V) before being incorporated into calcite and the resulting calcite contained 36% As(III) and 64% As(V). All these experimental results confirm that As(V) has a much stronger interaction with calcite than As(III) and that calcite may represent an important reservoir for arsenic in various geological environments.

  7. Biomolecular interactions in HCV nucleocapsid-like particles as revealed by vibrational spectroscopy

    Science.gov (United States)

    Rodríguez-Casado, Arantxa; Molina, Marina; Carmona, Pedro

    2007-05-01

    Hepatitis C virus (HCV) occurs in the form of 55-65 nm spherical particles, but the structure of the virion remains to be clarified. Structural studies of HCV have been hampered by the lack of an appropriate cell culture system. However, structural analyses of HCV components can provide an essential framework for understanding of the molecular mechanism of virion assembly. This article reviews the potential of vibrational spectroscopy aimed at the knowledge of HCV structural biology, particularly regarding biomolecular interactions in nucleocapsid-like particles obtained in vitro.

  8. Molecular interaction of zp3 to zp3r reveals a cross-species fertilization mechanism

    Directory of Open Access Journals (Sweden)

    Reni Kurniati

    2017-05-01

    Full Text Available Objective: To evaluate the role of ZP3R in the species-specific fertilization mechanism. Methods: ZP3/ZP3R protein sequences of Mus musculus, Rattus norvegicus, and Cavia porcellus were downloaded from UNIPROT. Percentage of amino acids that was calculated by using the SIAS program. Protein sequences modeled was established by using the Modeller 9.14 program and glycosylation of the ZP3 using GlyProt program. Docking simulation of the ZP3R-ZP3 was performed between the same species and different species with PatchDock program. Results: Comparison of the ZP3R and ZP3 structure between species showed that ZP3 in these three species was more similar than ZP3R. Docking simulations of protein showed that changes in the pattern of the ZP3-ZP3R domain for interaction on cross-species compared to the same species. Changes in the pattern of binding ZP3R-ZP3 made spermegg binding was not functional and could inhibit cross-fertilization. Conclusions: ZP3R-ZP3 interaction is species-specific, and the role of ZP3R is greater than ZP3 in determining the species-specific recognition stage and sperm-egg binding.

  9. Flow Motifs Reveal Limitations of the Static Framework to Represent Human interactions

    CERN Document Server

    Rocha, Luis Enrique Correa

    2013-01-01

    Networks are commonly used to define underlying interaction structures where infections, information, or other quantities may spread. Although the standard approach has been to aggregate all links into a static structure, some studies suggest that the time order in which the links are established may alter the dynamics of spreading. In this paper, we study the impact of the time ordering in the limits of flow on various empirical temporal networks. By using a random walk dynamics, we estimate the flow on links and convert the original undirected network (temporal and static) into a directed flow network. We then introduce the concept of flow motifs and quantify the divergence in the representativity of motifs when using the temporal and static frameworks. We find that the regularity of contacts and persistence of vertices (common in email communication and face-to-face interactions) result on little differences in the limits of flow for both frameworks. On the other hand, in the case of communication within a...

  10. The Symbiosis Interactome: a computational approach reveals novel components, functional interactions and modules in Sinorhizobium meliloti

    Directory of Open Access Journals (Sweden)

    Rodriguez-Llorente Ignacio

    2009-06-01

    Full Text Available Abstract Background Rhizobium-Legume symbiosis is an attractive biological process that has been studied for decades because of its importance in agriculture. However, this system has undergone extensive study and although many of the major factors underpinning the process have been discovered using traditional methods, much remains to be discovered. Results Here we present an analysis of the 'Symbiosis Interactome' using novel computational methods in order to address the complex dynamic interactions between proteins involved in the symbiosis of the model bacteria Sinorhizobium meliloti with its plant hosts. Our study constitutes the first large-scale analysis attempting to reconstruct this complex biological process, and to identify novel proteins involved in establishing symbiosis. We identified 263 novel proteins potentially associated with the Symbiosis Interactome. The topology of the Symbiosis Interactome was used to guide experimental techniques attempting to validate novel proteins involved in different stages of symbiosis. The contribution of a set of novel proteins was tested analyzing the symbiotic properties of several S. meliloti mutants. We found mutants with altered symbiotic phenotypes suggesting novel proteins that provide key complementary roles for symbiosis. Conclusion Our 'systems-based model' represents a novel framework for studying host-microbe interactions, provides a theoretical basis for further experimental validations, and can also be applied to the study of other complex processes such as diseases.

  11. Computational phenotyping of two-person interactions reveals differential neural response to depth-of-thought.

    Directory of Open Access Journals (Sweden)

    Ting Xiang

    Full Text Available Reciprocating exchange with other humans requires individuals to infer the intentions of their partners. Despite the importance of this ability in healthy cognition and its impact in disease, the dimensions employed and computations involved in such inferences are not clear. We used a computational theory-of-mind model to classify styles of interaction in 195 pairs of subjects playing a multi-round economic exchange game. This classification produces an estimate of a subject's depth-of-thought in the game (low, medium, high, a parameter that governs the richness of the models they build of their partner. Subjects in each category showed distinct neural correlates of learning signals associated with different depths-of-thought. The model also detected differences in depth-of-thought between two groups of healthy subjects: one playing patients with psychiatric disease and the other playing healthy controls. The neural response categories identified by this computational characterization of theory-of-mind may yield objective biomarkers useful in the identification and characterization of pathologies that perturb the capacity to model and interact with other humans.

  12. Revealing strong nanocomposite hydrogels reinforced by cellulose nanocrystals: insight into morphologies and interactions.

    Science.gov (United States)

    Yang, Jun; Zhao, Jing-Jing; Xu, Feng; Sun, Run-Cang

    2013-12-26

    Understanding the reinforcement mechanism by dispersing nanoscale particles into a polymer matrix is a critical challenge toward refining control of the composite properties. In this paper, the morphologies and interactions of cellulose nanocrystal/poly(acrylic acid) (CNC/PAA) nanocomposite hydrogels are demystified based on a facile synthetic platform. Two sources of CNCs with different aspect ratios are applied to model the reinforcement process, and the uniaxial tensile measurements indicate that the CNC aspect ratio and the nanocomposite mechanical behaviors are coupled, where the values of aspect ratios and nonpermanent interactions between the fillers and matrix dominate the reinforcement. Dynamic mechanical analysis is performed to examine the nature of the constrained polymer as the semicrystalline fractions, and the results indicate that polymer chain mobility in the vicinity of CNC surfaces is significantly reduced, providing new insight into the origin of the reinforcement mechanism. Rheological analysis and transmission electron microscopy observations show that both stepwise dissociation and polymer chain rearrangements contribute to the viscoelastic behaviors of the nanocomposite hydrogels. The increased modulus of the hydrogels is correlated to the volume of the constrained polymer, where the CNCs impart significant enhancement to the entanglement network. This study of the structure-property relationship deepens the understanding of the filler reinforcement mechanism and provides valuable knowledge for designing high performance nanocomposite hydrogels from cellulose as a raw material.

  13. Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

    Science.gov (United States)

    Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

    2016-10-20

    The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

  14. Modified inoculation and disease assessment methods reveal host specificity in Erwinia tracheiphila-Cucurbitaceae interactions.

    Science.gov (United States)

    Nazareno, Eric S; Dumenyo, C Korsi

    2015-12-01

    We conducted a greenhouse trial to determine specific compatible interactions between Erwinia tracheiphila strains and cucurbit host species. Using a modified inoculation system, E. tracheiphila strains HCa1-5N, UnisCu1-1N, and MISpSq-N were inoculated to cucumber (Cucumis sativus) cv. 'Sweet Burpless', melon (Cucumis melo) cv. 'Athena Hybrid', and squash (Cucubita pepo) cv. 'Early Summer Crookneck'. We observed symptoms and disease progression for 30 days; recorded the number of days to wilting of the inoculated leaf (DWIL), days to wilting of the whole plant (DWWP), and days to death of the plant (DDP). We found significant interactions between host cultivar and pathogen strains, which imply host specificity. Pathogen strains HCa1-5N and UnisCu1-1N isolated from Cucumis species exhibited more virulence in cucumber and melon than in squash, while the reverse was true for strain MISpSq-N, an isolate from Cucurbita spp. Our observations confirm a previous finding that E. tracheiphila strains isolated from Cucumis species were more virulent on Cucumis hosts and those from Cucubita were more virulent on Cucubita hosts. This confirmation helps in better understanding the pathosystem and provides baseline information for the subsequent development of new disease management strategies for bacterial wilt. We also demonstrated the efficiency of our modified inoculation and disease scoring methods.

  15. Adaptation to real motion reveals direction-selective interactions between real and implied motion processing.

    Science.gov (United States)

    Lorteije, Jeannette A M; Kenemans, J Leon; Jellema, Tjeerd; van der Lubbe, Rob H J; Lommers, Marjolein W; van Wezel, Richard J A

    2007-08-01

    Viewing static pictures of running humans evokes neural activity in the dorsal motion-sensitive cortex. To establish whether this response arises from direction-selective neurons that are also involved in real motion processing, we measured the visually evoked potential to implied motion following adaptation to static or moving random dot patterns. The implied motion response was defined as the difference between evoked potentials to pictures with and without implied motion. Interaction between real and implied motion was found as a modulation of this difference response by the preceding motion adaptation. The amplitude of the implied motion response was significantly reduced after adaptation to motion in the same direction as the implied motion, compared to motion in the opposite direction. At 280 msec after stimulus onset, the average difference in amplitude reduction between opposite and same adapted direction was 0.5 muV on an average implied motion amplitude of 2.0 muV. These results indicate that the response to implied motion arises from direction-selective motion-sensitive neurons. This is consistent with interactions between real and implied motion processing at a neuronal level.

  16. Expressed proteins of Herbaspirillum seropedicae in maize (DKB240) roots-bacteria interaction revealed using proteomics.

    Science.gov (United States)

    Ferrari, Cibele Santos; Amaral, Fernanda Plucani; Bueno, Jessica Cavalheiro Ferreira; Scariot, Mirella Christine; Valentim-Neto, Pedro Alexandre; Arisi, Ana Carolina Maisonnave

    2014-11-01

    Several molecular tools have been used to clarify the basis of plant-bacteria interaction; however, the mechanism behind the association is still unclear. In this study, we used a proteomic approach to investigate the root proteome of Zea mays (cv. DKB240) inoculated with Herbaspirillum seropedicae strain SmR1 grown in vitro and harvested 7 days after inoculation. Eighteen differentially accumulated proteins were observed in root samples, ten of which were identified by MALDI-TOF mass spectrometry peptide mass fingerprint. Among the identified proteins, we observed three proteins present exclusively in inoculated root samples and six upregulated proteins and one downregulated protein relative to control. Differentially expressed maize proteins were identified as hypothetical protein ZEAMMB73_483204, hypothetical protein ZEAMMB73_269466, and tubulin beta-7 chain. The following were identified as H. seropedicae proteins: peroxiredoxin protein, EF-Tu elongation factor protein, cation transport ATPase, NADPH:quinone oxidoreductase, dinitrogenase reductase, and type III secretion ATP synthase. Our results presented the first evidence of type III secretion ATP synthase expression during H. seropedicae-maize root interaction.

  17. Scanning STED-FCS reveals spatiotemporal heterogeneity of lipid interaction in the plasma membrane of living cells

    Science.gov (United States)

    Honigmann, Alf; Mueller, Veronika; Ta, Haisen; Schoenle, Andreas; Sezgin, Erdinc; Hell, Stefan W.; Eggeling, Christian

    2014-11-01

    The interaction of lipids and proteins plays an important role in plasma membrane bioactivity, and much can be learned from their diffusion characteristics. Here we present the combination of super-resolution STED microscopy with scanning fluorescence correlation spectroscopy (scanning STED-FCS, sSTED-FCS) to characterize the spatial and temporal heterogeneity of lipid interactions. sSTED-FCS reveals transient molecular interaction hotspots for a fluorescent sphingolipid analogue. The interaction sites are smaller than 80 nm in diameter and lipids are transiently trapped for several milliseconds in these areas. In comparison, newly developed fluorescent phospholipid and cholesterol analogues with improved phase-partitioning properties show more homogenous diffusion, independent of the preference for liquid-ordered or disordered membrane environments. Our results do not support the presence of nanodomains based on lipid-phase separation in the basal membrane of our cultured nonstimulated cells, and show that alternative interactions are responsible for the strong local trapping of our sphingolipid analogue.

  18. Salts of hexamethylenetetramine with organic acids: Enhanced anomeric interactions with a lowering of molecular symmetry revealed by crystal structures

    Science.gov (United States)

    Chandrasekhar, Sosale; Mukherjee, Somnath

    2015-02-01

    The hexamethylenetetramine (HMT) framework displays interesting stereoelectronic interactions of the anomeric type. In the highly symmetrical parent system, the nitrogen centres act as both donors and acceptors. Protonation lowers symmetry and also leads to an enhancement of the anomeric interaction around the protonated centre. X-ray diffraction crystal structures of four derivatives of HMT - with succinic, (DL)-malic, phthalic and 4-hydroxybenzoic acids - reveal significant trends. (The first three form well-defined salts, 4-hydroxybenzoic acid forming a co-crystalline compound.) Each molecular structure is essentially characterised by a major anomeric interaction involving the protonated centre as acceptor. In two cases (succinic and 4-hydroxybenzoic), secondary protonation leads to a weaker anomeric interaction site that apparently competes with the dominant one. Bond length changes indicate that the anomeric interaction decreases as malic > phthalic > succinic > 4-hydroxybenzoic, which correlates with the degree of proton transfer to the nitrogen centre. Along with other bond length and angle changes, the results offer insight into the applicability of the antiperiplanar lone pair hypothesis (ALPH) in a rigid system.

  19. Multifactor dimensionality reduction reveals a three-locus epistatic interaction associated with susceptibility to pulmonary tuberculosis

    DEFF Research Database (Denmark)

    Collins, Ryan L; Hu, Ting; Wejse, Christian;

    2013-01-01

    for this problem. The goal of the present study was to apply MDR to mining high-order epistatic interactions in a population-based genetic study of tuberculosis (TB). Results The study used a previously published data set consisting of 19 candidate single-nucleotide polymorphisms (SNPs) in 321 pulmonary TB cases......Background Identifying high-order genetics associations with non-additive (i.e. epistatic) effects in population-based studies of common human diseases is a computational challenge. Multifactor dimensionality reduction (MDR) is a machine learning method that was designed specifically...... and 347 healthy controls from Guniea-Bissau in Africa. The ReliefF algorithm was applied first to generate a smaller set of the five most informative SNPs. MDR with 10-fold cross-validation was then applied to look at all possible combinations of two, three, four and five SNPs. The MDR model with the best...

  20. Molecular characterization of cancer reveals interactions between ionizing radiation and chemicals on rat mammary carcinogenesis.

    Science.gov (United States)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Doi, Kazutaka; Tani, Shusuke; Ishikawa, Ken-ichi; Yamashita, Satoshi; Ushijima, Toshikazu; Imai, Takashi; Shimada, Yoshiya

    2014-04-01

    Although various mechanisms have been inferred for combinatorial actions of multiple carcinogens, these mechanisms have not been well demonstrated in experimental carcinogenesis models. We evaluated mammary carcinogenesis initiated by combined exposure to various doses of radiation and chemical carcinogens. Female rats at 7 weeks of age were γ-irradiated (0.2-2 Gy) and/or exposed to 1-methyl-1-nitrosourea (MNU) (20 or 40 mg/kg, single intraperitoneal injection) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (40 mg/kg/day by gavage for 10 days) and were observed until 50 weeks of age. The incidence of mammary carcinoma increased steadily as a function of radiation dose in the absence of chemicals; mathematical analysis supported an additive increase when radiation was combined with a chemical carcinogen, irrespective of the chemical species and its dose. Hras mutations were characteristic of carcinomas that developed after chemical carcinogen treatments and were overrepresented in carcinomas induced by the combination of radiation and MNU (but not PhIP), indicating an interaction of radiation and MNU at the level of initiation. The expression profiles of seven classifier genes, previously shown to distinguish two classes of rat mammary carcinomas, categorized almost all examined carcinomas that developed after individual or combined treatments with radiation (1 Gy) and chemicals as belonging to a single class; more comprehensive screening using microarrays and a separate test sample set failed to identify differences in gene expression profiles among these carcinomas. These results suggest that a complex, multilevel interaction underlies the combinatorial action of radiation and chemical carcinogens in the experimental model.

  1. Combining genomic sequencing methods to explore viral diversity and reveal potential virus-host interactions

    Directory of Open Access Journals (Sweden)

    Cheryl-Emiliane Tien Chow

    2015-04-01

    Full Text Available Viral diversity and virus-host interactions in oxygen-starved regions of the ocean, also known as oxygen minimum zones (OMZs, remain relatively unexplored. Microbial community metabolism in OMZs alters nutrient and energy flow through marine food webs, resulting in biological nitrogen loss and greenhouse gas production. Thus, viruses infecting OMZ microbes have the potential to modulate community metabolism with resulting feedback on ecosystem function. Here, we describe viral communities inhabiting oxic surface (10m and oxygen-starved basin (200m waters of Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island, British Columbia using viral metagenomics and complete viral fosmid sequencing on samples collected between April 2007 and April 2010. Of 6459 open reading frames (ORFs predicted across all 34 viral fosmids, 77.6% (n=5010 had no homology to reference viral genomes. These fosmids recruited a higher proportion of viral metagenomic sequences from Saanich Inlet than from nearby northeastern subarctic Pacific Ocean (Line P waters, indicating differences in the viral communities between coastal and open ocean locations. While functional annotations of fosmid ORFs were limited, recruitment to NCBI’s non-redundant ‘nr’ database and publicly available single-cell genomes identified putative viruses infecting marine thaumarchaeal and SUP05 proteobacteria to provide potential host linkages with relevance to coupled biogeochemical cycling processes in OMZ waters. Taken together, these results highlight the power of coupled analyses of multiple sequence data types, such as viral metagenomic and fosmid sequence data with prokaryotic single cell genomes, to chart viral diversity, elucidate genomic and ecological contexts for previously unclassifiable viral sequences, and identify novel host interactions in natural and engineered ecosystems.

  2. Polymorphism of DNA-anionic liposome complexes reveals hierarchy of ion-mediated interactions.

    Science.gov (United States)

    Liang, Hongjun; Harries, Daniel; Wong, Gerard C L

    2005-08-09

    Self-assembled DNA delivery systems based on anionic lipids (ALs) complexed with DNA mediated by divalent cations have been recently introduced as an alternative to cationic lipid-DNA complexes because of their low cytotoxicity. We investigate AL-DNA complexes induced by different cations by using synchrotron small angle x-ray scattering and confocal microscopy to show how different ion-mediated interactions are expressed in the self-assembled structures and phase behavior of AL-DNA complexes. The governing interactions in AL-DNA systems are complex: divalent ions can mediate strong attractions between different combinations of the components (such as DNA-DNA and membrane-membrane). Moreover, divalent cations can coordinate non-electrostatically with lipids and modify the resultant membrane structure. We find that at low membrane charge densities AL-DNA complexes organize into a lamellar structure of alternating DNA and membrane layers crosslinked by ions. At high membrane charge densities, a new phase with no analog in cationic lipid-DNA systems is observed: DNA is expelled from the complex, and a lamellar stack of membranes and intercalated ions is formed. For a subset of the ionic species, high ion concentrations generate an inverted hexagonal phase comprised of DNA strands wrapped by ion-coated lipid tubes. A simple theoretical model that takes into account the electrostatic and membrane elastic contributions to the free energy shows that this transition is consistent with an ion-induced change in the membrane spontaneous curvature, c0. Moreover, the crossover between the lamellar and inverted hexagonal phases occurs at a critical c0 that agrees well with experimental values.

  3. Analysis of virus genomes from glacial environments reveals novel virus groups with unusual host interactions

    Science.gov (United States)

    Bellas, Christopher M.; Anesio, Alexandre M.; Barker, Gary

    2015-01-01

    Microbial communities in glacial ecosystems are diverse, active, and subjected to strong viral pressures and infection rates. In this study we analyse putative virus genomes assembled from three dsDNA viromes from cryoconite hole ecosystems of Svalbard and the Greenland Ice Sheet to assess the potential hosts and functional role viruses play in these habitats. We assembled 208 million reads from the virus-size fraction and developed a procedure to select genuine virus scaffolds from cellular contamination. Our curated virus library contained 546 scaffolds up to 230 Kb in length, 54 of which were circular virus consensus genomes. Analysis of virus marker genes revealed a wide range of viruses had been assembled, including bacteriophages, cyanophages, nucleocytoplasmic large DNA viruses and a virophage, with putative hosts identified as Cyanobacteria, Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Firmicutes, eukaryotic algae and amoebae. Whole genome comparisons revealed the majority of circular genome scaffolds (CGS) formed 12 novel groups, two of which contained multiple phage members with plasmid-like properties, including a group of phage-plasmids possessing plasmid-like partition genes and toxin-antitoxin addiction modules to ensure their replication and a satellite phage-plasmid group. Surprisingly we also assembled a phage that not only encoded plasmid partition genes, but a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas adaptive bacterial immune system. One of the spacers was an exact match for another phage in our virome, indicating that in a novel use of the system, the lysogen was potentially capable of conferring immunity on its bacterial host against other phage. Together these results suggest that highly novel and diverse groups of viruses are present in glacial environments, some of which utilize very unusual life strategies and genes to control their replication and maintain a long-term relationship with their hosts

  4. Size-dependent physicochemical and mechanical interactions in battery paste anodes of Si-microwires revealed by Fast-Fourier-Transform Impedance Spectroscopy

    Science.gov (United States)

    Hansen, Sandra; Quiroga-González, Enrique; Carstensen, Jürgen; Adelung, Rainer; Föll, Helmut

    2017-05-01

    Perfectly aligned silicon microwire arrays show exceptionally high cycling stability with record setting (high) areal capacities of 4.25 mAh cm-2. Those wires have a special, modified length and thickness in order to perform this good. Geometry and sizes are the most important parameters of an anode to obtain batteries with high cycling stability without irreversible losses. The wires are prepared with a unique etching fabrication method, which allows to fabricate wires of very precise sizes. In order to investigate how good randomly oriented silicon wires perform in contrast to the perfect order of the array, the wires are embedded in a paste. This study reveals the fundamental correlation between geometry, mechanics and charge transfer kinetics of silicon electrodes. Using a suitable RC equivalent circuit allows to evaluate data from cyclic voltammetry and simultaneous FFT-Impedance Spectroscopy (FFT-IS), yielding in time-resolved resistances, time constants, and their direct correlation to the phase transformations. The change of the resistances during lithiation and delithiation correlates to kinetics and charge transfer mechanisms. This study demonstrates how the mechanical and physiochemical interactions at the silicon/paste interface inside the paste electrodes lead to void formation around silicon and with it to material loss and capacity fading.

  5. Molecular characterization reveals the complexity of previously overlooked coral-exosymbiont interactions and the implications for coral-guild ecology

    Science.gov (United States)

    Rouzé, H.; Leray, M.; Magalon, H.; Penin, L.; Gélin, P.; Knowlton, N.; Fauvelot, C.

    2017-01-01

    Several obligate associate crabs and shrimps species may co-occur and interact within a single coral host, leading to patterns of associations that can provide essential ecological services. However, knowledge of the dynamics of interactions in this system is limited, partly because identifying species involved in the network remains challenging. In this study, we assessed the diversity of the decapods involved in exosymbiotic assemblages for juvenile and adult Pocillopora damicornis types α and β on reefs of New Caledonia and Reunion Island. This approach revealed complex patterns of association at regional and local scales with a prevalence of assemblages involving crab-shrimp partnerships. Furthermore, the distinction of two lineages in the snapping shrimp Alpheus lottini complex, rarely recognized in ecological studies, reveals a key role for cryptic diversity in structuring communities of mutualists. The existence of partnerships between species that occurred more commonly than expected by chance suggests an increased advantage for the host or a better adaptation of associated species to local environmental conditions. The consideration of cryptic diversity helps to accurately describe the complexity of interaction webs for diverse systems such as coral reefs, as well as the functional roles of dominant associated species for the persistence of coral populations. PMID:28358026

  6. In vivo Host-Pathogen Interaction as Revealed by Global Proteomic Profiling of Zebrafish Larvae

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    Francisco Díaz-Pascual

    2017-07-01

    Full Text Available The outcome of a host-pathogen interaction is determined by the conditions of the host, the pathogen, and the environment. Although numerous proteomic studies of in vitro-grown microbial pathogens have been performed, in vivo proteomic approaches are still rare. In addition, increasing evidence supports that in vitro studies inadequately reflect in vivo conditions. Choosing the proper host is essential to detect the expression of proteins from the pathogen in vivo. Numerous studies have demonstrated the suitability of zebrafish (Danio rerio embryos as a model to in vivo studies of Pseudomonas aeruginosa infection. In most zebrafish-pathogen studies, infection is achieved by microinjection of bacteria into the larvae. However, few reports using static immersion of bacterial pathogens have been published. In this study we infected 3 days post-fertilization (DPF zebrafish larvae with P. aeruginosa PAO1 by immersion and injection and tracked the in vivo immune response by the zebrafish. Additionally, by using non-isotopic (Q-exactive metaproteomics we simultaneously evaluated the proteomic response of the pathogen (P. aeruginosa PAO1 and the host (zebrafish. We found some zebrafish metabolic pathways, such as hypoxia response via HIF activation pathway, were exclusively enriched in the larvae exposed by static immersion. In contrast, we found that inflammation mediated by chemokine and cytokine signaling pathways was exclusively enriched in the larvae exposed by injection, while the integrin signaling pathway and angiogenesis were solely enriched in the larvae exposed by immersion. We also found important virulence factors from P. aeruginosa that were enriched only after exposure by injection, such as the Type-III secretion system and flagella-associated proteins. On the other hand, P. aeruginosa proteins involved in processes like biofilm formation, and cellular responses to antibiotic and starvation were enriched exclusively after exposure by

  7. In vivo Host-Pathogen Interaction as Revealed by Global Proteomic Profiling of Zebrafish Larvae

    Science.gov (United States)

    Díaz-Pascual, Francisco; Ortíz-Severín, Javiera; Varas, Macarena A.; Allende, Miguel L.; Chávez, Francisco P.

    2017-01-01

    The outcome of a host-pathogen interaction is determined by the conditions of the host, the pathogen, and the environment. Although numerous proteomic studies of in vitro-grown microbial pathogens have been performed, in vivo proteomic approaches are still rare. In addition, increasing evidence supports that in vitro studies inadequately reflect in vivo conditions. Choosing the proper host is essential to detect the expression of proteins from the pathogen in vivo. Numerous studies have demonstrated the suitability of zebrafish (Danio rerio) embryos as a model to in vivo studies of Pseudomonas aeruginosa infection. In most zebrafish-pathogen studies, infection is achieved by microinjection of bacteria into the larvae. However, few reports using static immersion of bacterial pathogens have been published. In this study we infected 3 days post-fertilization (DPF) zebrafish larvae with P. aeruginosa PAO1 by immersion and injection and tracked the in vivo immune response by the zebrafish. Additionally, by using non-isotopic (Q-exactive) metaproteomics we simultaneously evaluated the proteomic response of the pathogen (P. aeruginosa PAO1) and the host (zebrafish). We found some zebrafish metabolic pathways, such as hypoxia response via HIF activation pathway, were exclusively enriched in the larvae exposed by static immersion. In contrast, we found that inflammation mediated by chemokine and cytokine signaling pathways was exclusively enriched in the larvae exposed by injection, while the integrin signaling pathway and angiogenesis were solely enriched in the larvae exposed by immersion. We also found important virulence factors from P. aeruginosa that were enriched only after exposure by injection, such as the Type-III secretion system and flagella-associated proteins. On the other hand, P. aeruginosa proteins involved in processes like biofilm formation, and cellular responses to antibiotic and starvation were enriched exclusively after exposure by immersion. We

  8. Amplitude-modulated stimuli reveal auditory-visual interactions in brain activity and brain connectivity.

    Science.gov (United States)

    Laing, Mark; Rees, Adrian; Vuong, Quoc C

    2015-01-01

    The temporal congruence between auditory and visual signals coming from the same source can be a powerful means by which the brain integrates information from different senses. To investigate how the brain uses temporal information to integrate auditory and visual information from continuous yet unfamiliar stimuli, we used amplitude-modulated tones and size-modulated shapes with which we could manipulate the temporal congruence between the sensory signals. These signals were independently modulated at a slow or a fast rate. Participants were presented with auditory-only, visual-only, or auditory-visual (AV) trials in the fMRI scanner. On AV trials, the auditory and visual signal could have the same (AV congruent) or different modulation rates (AV incongruent). Using psychophysiological interaction analyses, we found that auditory regions showed increased functional connectivity predominantly with frontal regions for AV incongruent relative to AV congruent stimuli. We further found that superior temporal regions, shown previously to integrate auditory and visual signals, showed increased connectivity with frontal and parietal regions for the same contrast. Our findings provide evidence that both activity in a network of brain regions and their connectivity are important for AV integration, and help to bridge the gap between transient and familiar AV stimuli used in previous studies.

  9. Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA.

    Science.gov (United States)

    Niewiadomski, Pawel; Zhujiang, Annie; Youssef, Mary; Waschek, James A

    2013-11-01

    Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (cGCPs) and its aberrant activation causes a cerebellar cancer medulloblastoma. Pituitary adenylate cyclase activating polypeptide (PACAP) inhibits Shh-driven proliferation of cGCPs and acts as tumor suppressor in murine medulloblastoma. We show that PACAP blocks canonical Shh signaling by a mechanism that involves activation of protein kinase A (PKA) and inhibition of the translocation of the Shh-dependent transcription factor Gli2 into the primary cilium. PKA is shown to play an essential role in inhibiting gene transcription in the absence of Shh, but global PKA activity levels are found to be a poor predictor of the degree of Shh pathway activation. We propose that the core Shh pathway regulates a small compartmentalized pool of PKA in the vicinity of primary cilia. GPCRs that affect global PKA activity levels, such as the PACAP receptor, cooperate with the canonical Shh signal to regulate Gli protein phosphorylation by PKA. This interaction serves to fine-tune the transcriptional and physiological function of the Shh pathway.

  10. PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila.

    Science.gov (United States)

    Im, Seol Hee; Taghert, Paul H

    2010-06-01

    Daily rhythms of behavior are controlled by a circuit of circadian pacemaking neurons. In Drosophila, 150 pacemakers participate in this network, and recent observations suggest that the network is divisible into M and E oscillators, which normally interact and synchronize. Sixteen oscillator neurons (the small and large lateral neurons [LNvs]) express a neuropeptide called pigment-dispersing factor (PDF) whose signaling is often equated with M oscillator output. Given the significance of PDF signaling to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field. Here we show that GAL4-mediated rescue of pdfr phenotypes using a UAS-PDFR transgene is insufficient to provide complete behavioral rescue. In contrast, we describe a approximately 70-kB PDF receptor (pdfr) transgene that does rescue the entire pdfr circadian behavioral phenotype. The transgene is widely but heterogeneously expressed among pacemakers, and also among a limited number of non-pacemakers. Our results support an important hypothesis: the small LNv cells directly target a subset of the other crucial pacemaker neurons cells. Furthermore, expression of the transgene confirms an autocrine feedback signaling by PDF back to PDF-expressing cells. Finally, the results present an unexpected PDF receptor site: the large LNv cells appear to target a population of non-neuronal cells that resides at the base of the eye. (c) 2009 Wiley-Liss, Inc.

  11. A simple strategy for detecting moving objects during locomotion revealed by animal-robot interactions.

    Science.gov (United States)

    Zabala, Francisco; Polidoro, Peter; Robie, Alice; Branson, Kristin; Perona, Pietro; Dickinson, Michael H

    2012-07-24

    An important role of visual systems is to detect nearby predators, prey, and potential mates, which may be distinguished in part by their motion. When an animal is at rest, an object moving in any direction may easily be detected by motion-sensitive visual circuits. During locomotion, however, this strategy is compromised because the observer must detect a moving object within the pattern of optic flow created by its own motion through the stationary background. However, objects that move creating back-to-front (regressive) motion may be unambiguously distinguished from stationary objects because forward locomotion creates only front-to-back (progressive) optic flow. Thus, moving animals should exhibit an enhanced sensitivity to regressively moving objects. We explicitly tested this hypothesis by constructing a simple fly-sized robot that was programmed to interact with a real fly. Our measurements indicate that whereas walking female flies freeze in response to a regressively moving object, they ignore a progressively moving one. Regressive motion salience also explains observations of behaviors exhibited by pairs of walking flies. Because the assumptions underlying the regressive motion salience hypothesis are general, we suspect that the behavior we have observed in Drosophila may be widespread among eyed, motile organisms.

  12. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners.

    Science.gov (United States)

    Gemperle, Jakub; Hexnerová, Rozálie; Lepšík, Martin; Tesina, Petr; Dibus, Michal; Novotný, Marian; Brábek, Jan; Veverka, Václav; Rosel, Daniel

    2017-08-14

    CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.

  13. Metatranscriptome analysis reveals host-microbiome interactions in traps of carnivorous Genlisea species

    Directory of Open Access Journals (Sweden)

    Hieu X. Cao

    2015-07-01

    Full Text Available In the carnivorous plant genus Genlisea a unique lobster pot trapping mechanism supplements nutrition in nutrient-poor habitats. A wide spectrum of microbes frequently occurs in Genlisea’s leaf-derived traps without clear relevance for Genlisea carnivory. We sequenced the metatranscriptomes of subterrestrial traps versus the aerial chlorophyll-containing leaves of G. nigrocaulis and of G. hispidula. Ribosomal RNA assignment revealed soil-borne microbial diversity in Genlisea traps, with 92 genera of 19 phyla present in more than one sample. Microbes from 16 of these phyla including proteobacteria, green algae, amoebozoa, fungi, ciliates and metazoans, contributed additionally short-lived mRNA to the metatranscriptome. Furthermore, transcripts of 438 members of hydrolases (e.g. proteases, phosphatases, lipases, mainly resembling those of metazoans, ciliates and green algae, were found. Compared to aerial leaves, Genlisea traps displayed a transcriptional up-regulation of endogenous NADH oxidases generating reactive oxygen species as well as of acid phosphatases for prey digestion. A leaf-versus-trap transcriptome comparison reflects that carnivory provides inorganic P- and different forms of N-compounds (ammonium, nitrate, amino acid, oligopeptides and implies the need to protect trap cells against oxidative stress. The analysis elucidates a complex food web inside the Genlisea traps, and suggests ecological relationships between this plant genus and its entrapped microbiome.

  14. Exchange Rates and Fundamentals.

    Science.gov (United States)

    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,…

  15. Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    S Truschel; D Sengupta; A Foote; A Heroux; M Macbeth; A Linstedt

    2011-12-31

    Biogenesis of the ribbon-like membrane network of the mammalian Golgi requires membrane tethering by the conserved GRASP domain in GRASP65 and GRASP55, yet the tethering mechanism is not fully understood. Here, we report the crystal structure of the GRASP55 GRASP domain, which revealed an unusual arrangement of two tandem PDZ folds that more closely resemble prokaryotic PDZ domains. Biochemical and functional data indicated that the interaction between the ligand-binding pocket of PDZ1 and an internal ligand on PDZ2 mediates the GRASP self-interaction, and structural analyses suggest that this occurs via a unique mode of internal PDZ ligand recognition. Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.

  16. Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Truschel, S.T.; Heroux, A.; Sengupta, D.; Foote, A.; Macbeth, M. R.; Linstedt, A. D.

    2011-06-10

    Biogenesis of the ribbon-like membrane network of the mammalian Golgi requires membrane tethering by the conserved GRASP domain in GRASP65 and GRASP55, yet the tethering mechanism is not fully understood. Here, we report the crystal structure of the GRASP55 GRASP domain, which revealed an unusual arrangement of two tandem PDZ folds that more closely resemble prokaryotic PDZ domains. Biochemical and functional data indicated that the interaction between the ligand-binding pocket of PDZ1 and an internal ligand on PDZ2 mediates the GRASP self-interaction, and structural analyses suggest that this occurs via a unique mode of internal PDZ ligand recognition. Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.

  17. Brain-heart interactions reveal consciousness in non-communicating patients.

    Science.gov (United States)

    Raimondo, Federico; Rohaut, Benjamin; Demertzi, Athena; Valente, Melanie; Engemann, Denis; Salti, Moti; Fernandez Slezak, Diego; Naccache, Lionel; Sitt, Jacobo D

    2017-09-11

    Objective We here aimed at characterizing heart-brain interactions in patients with disorders of consciousness. We tested how this information impacts data-driven classification between unresponsive and minimally conscious patients. Methods A cohort of 127 patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS, n=70) and minimally conscious state (MCS, n=57) were presented with the 'Local-Global' auditory oddball paradigm, which distinguishes two levels of processing: short-term deviation of local auditory regularities and global long-term rule violations. In addition to previously validated markers of consciousness extracted from electroencephalograms (EEG), we computed autonomic cardiac markers, such as heart rate and variability (HR, HRV), and cardiac cycle phase-shifts triggered by the processing of the auditory stimuli. Results HR and HRV were similar in patients across groups. The cardiac cycle was not sensitive to the processing of local regularities in either the VS/UWS or MCS patients. In contrast, global regularities induced a phase-shift of the cardiac cycle exclusively in the MCS group. The interval between the auditory stimulation and the following R-peak was significantly shortened in MCS when the auditory rule was violated. When the information of the cardiac cycle modulations and other consciousness-related EEG markers were combined, single-patient classification performance was enhanced compared to classification with solely EEG markers. Interpretation Our work shows a link between residual cognitive processing and the modulation of autonomic somatic markers. These results open a new window to evaluate patients with disorders of consciousness via the embodied paradigm, according to which body-brain functions contribute to a holistic approach to conscious processing. This article is protected by copyright. All rights reserved. © 2017 American Neurological Association.

  18. Field and laboratory studies reveal interacting effects of stream oxygenation and warming on aquatic ectotherms.

    Science.gov (United States)

    Verberk, Wilco C E P; Durance, Isabelle; Vaughan, Ian P; Ormerod, Steve J

    2016-05-01

    Aquatic ecological responses to climatic warming are complicated by interactions between thermal effects and other environmental stressors such as organic pollution and hypoxia. Laboratory experiments have demonstrated how oxygen limitation can set heat tolerance for some aquatic ectotherms, but only at unrealistic lethal temperatures and without field data to assess whether oxygen shortages might also underlie sublethal warming effects. Here, we test whether oxygen availability affects both lethal and nonlethal impacts of warming on two widespread Eurasian mayflies, Ephemera danica, Müller 1764 and Serratella ignita (Poda 1761). Mayfly nymphs are often a dominant component of the invertebrate assemblage in streams, and play a vital role in aquatic and riparian food webs. In the laboratory, lethal impacts of warming were assessed under three oxygen conditions. In the field, effects of oxygen availability on nonlethal impacts of warming were assessed from mayfly occurrence in 42 293 UK stream samples where water temperature and biochemical oxygen demand were measured. Oxygen limitation affected both lethal and sublethal impacts of warming in each species. Hypoxia lowered lethal limits by 5.5 °C (±2.13) and 8.2 °C (±0.62) for E. danica and S. ignita respectively. Field data confirmed the importance of oxygen limitation in warmer waters; poor oxygenation drastically reduced site occupancy, and reductions were especially pronounced under warm water conditions. Consequently, poor oxygenation lowered optimal stream temperatures for both species. The broad concordance shown here between laboratory results and extensive field data suggests that oxygen limitation not only impairs survival at thermal extremes but also restricts species abundance in the field at temperatures well below upper lethal limits. Stream oxygenation could thus control the vulnerability of aquatic ectotherms to global warming. Improving water oxygenation and reducing pollution can provide

  19. Diverse roles and interactions of the SWI/SNF chromatin remodeling complex revealed using global approaches.

    Directory of Open Access Journals (Sweden)

    Ghia M Euskirchen

    2011-03-01

    interactions than previously appreciated.

  20. Perception-memory interactions reveal a computational strategy for perceptual constancy.

    Science.gov (United States)

    Olkkonen, Maria; Saarela, Toni P; Allred, Sarah R

    2016-01-01

    A key challenge for the visual system is to extract constant object properties from incoming sensory information. This information is ambiguous because the same sensory signal can arise from many combinations of object properties and viewing conditions and noisy because of the variability in sensory encoding. The competing accounts for perceptual constancy of surface lightness fall into two classes of model: One derives lightness estimates from border contrasts, and another explicitly infers surface reflectance. To test these accounts, we combined a novel psychophysical task with probabilistic implementations of both models. Observers compared the lightness of two stimuli under a memory demand (a delay between the stimuli), a context change (different surround luminance), or both. Memory biased perceived lightness toward the mean of the whole stimulus ensemble. Context change caused the classical simultaneous lightness contrast effect, in which a target appears lighter against a dark surround and darker against a light surround. These effects were not independent: Combined memory load and context change elicited a bias smaller than predicted assuming an independent combination of biases. Both models explain the memory bias as an effect of prior expectations on perception. Both models also produce a context effect, but only the reflectance model correctly describes the magnitude. The reflectance model, finally, captures the memory-context interaction better than the contrast model, both qualitatively and quantitatively. We conclude that (a) lightness perception is more consistent with reflectance inference than contrast coding and (b) adding a memory demand to a perceptual task both renders it more ecologically valid and helps adjudicate between competing models.

  1. Electron Tomography of Cryofixed, Isometrically Contracting Insect Flight Muscle Reveals Novel Actin-Myosin Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Shenping; Liu, Jun; Reedy, Mary C.; Tregear, Richard T.; Winkler, Hanspeter; Franzini-Armstrong, Clara; Sasaki, Hiroyuki; Lucaveche, Carmen; Goldman, Yale E.; Reedy, Michael K.; Taylor, Kenneth A. (UPENN); (Duke); (MRCLMB); (FSU); (Jikei-Med)

    2010-10-22

    Isometric muscle contraction, where force is generated without muscle shortening, is a molecular traffic jam in which the number of actin-attached motors is maximized and all states of motor action are trapped with consequently high heterogeneity. This heterogeneity is a major limitation to deciphering myosin conformational changes in situ. We used multivariate data analysis to group repeat segments in electron tomograms of isometrically contracting insect flight muscle, mechanically monitored, rapidly frozen, freeze substituted, and thin sectioned. Improved resolution reveals the helical arrangement of F-actin subunits in the thin filament enabling an atomic model to be built into the thin filament density independent of the myosin. Actin-myosin attachments can now be assigned as weak or strong by their motor domain orientation relative to actin. Myosin attachments were quantified everywhere along the thin filament including troponin. Strong binding myosin attachments are found on only four F-actin subunits, the 'target zone', situated exactly midway between successive troponin complexes. They show an axial lever arm range of 77{sup o}/12.9 nm. The lever arm azimuthal range of strong binding attachments has a highly skewed, 127{sup o} range compared with X-ray crystallographic structures. Two types of weak actin attachments are described. One type, found exclusively in the target zone, appears to represent pre-working-stroke intermediates. The other, which contacts tropomyosin rather than actin, is positioned M-ward of the target zone, i.e. the position toward which thin filaments slide during shortening. We present a model for the weak to strong transition in the myosin ATPase cycle that incorporates azimuthal movements of the motor domain on actin. Stress/strain in the S2 domain may explain azimuthal lever arm changes in the strong binding attachments. The results support previous conclusions that the weak attachments preceding force generation are

  2. Electron tomography of cryofixed, isometrically contracting insect flight muscle reveals novel actin-myosin interactions.

    Directory of Open Access Journals (Sweden)

    Shenping Wu

    Full Text Available Isometric muscle contraction, where force is generated without muscle shortening, is a molecular traffic jam in which the number of actin-attached motors is maximized and all states of motor action are trapped with consequently high heterogeneity. This heterogeneity is a major limitation to deciphering myosin conformational changes in situ.We used multivariate data analysis to group repeat segments in electron tomograms of isometrically contracting insect flight muscle, mechanically monitored, rapidly frozen, freeze substituted, and thin sectioned. Improved resolution reveals the helical arrangement of F-actin subunits in the thin filament enabling an atomic model to be built into the thin filament density independent of the myosin. Actin-myosin attachments can now be assigned as weak or strong by their motor domain orientation relative to actin. Myosin attachments were quantified everywhere along the thin filament including troponin. Strong binding myosin attachments are found on only four F-actin subunits, the "target zone", situated exactly midway between successive troponin complexes. They show an axial lever arm range of 77°/12.9 nm. The lever arm azimuthal range of strong binding attachments has a highly skewed, 127° range compared with X-ray crystallographic structures. Two types of weak actin attachments are described. One type, found exclusively in the target zone, appears to represent pre-working-stroke intermediates. The other, which contacts tropomyosin rather than actin, is positioned M-ward of the target zone, i.e. the position toward which thin filaments slide during shortening.We present a model for the weak to strong transition in the myosin ATPase cycle that incorporates azimuthal movements of the motor domain on actin. Stress/strain in the S2 domain may explain azimuthal lever arm changes in the strong binding attachments. The results support previous conclusions that the weak attachments preceding force generation are very

  3. The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

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    Matthias Stein

    Full Text Available BACKGROUND: Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics. CONCLUSIONS/SIGNIFICANCE: We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

  4. Interactions between Casein kinase Iepsilon (CKIepsilon and two substrates from disparate signaling pathways reveal mechanisms for substrate-kinase specificity.

    Directory of Open Access Journals (Sweden)

    Caroline Lund Dahlberg

    Full Text Available BACKGROUND: Members of the Casein Kinase I (CKI family of serine/threonine kinases regulate diverse biological pathways. The seven mammalian CKI isoforms contain a highly conserved kinase domain and divergent amino- and carboxy-termini. Although they share a preferred target recognition sequence and have overlapping expression patterns, individual isoforms often have specific substrates. In an effort to determine how substrates recognize differences between CKI isoforms, we have examined the interaction between CKIepsilon and two substrates from different signaling pathways. METHODOLOGY/PRINCIPAL FINDINGS: CKIepsilon, but not CKIalpha, binds to and phosphorylates two proteins: Period, a transcriptional regulator of the circadian rhythms pathway, and Disheveled, an activator of the planar cell polarity pathway. We use GST-pull-down assays data to show that two key residues in CKIalpha's kinase domain prevent Disheveled and Period from binding. We also show that the unique C-terminus of CKIepsilon does not determine Dishevelled's and Period's preference for CKIepsilon nor is it essential for binding, but instead plays an auxillary role in stabilizing the interactions of CKIepsilon with its substrates. We demonstrate that autophosphorylation of CKIepsilon's C-terminal tail prevents substrate binding, and use mass spectrometry and chemical crosslinking to reveal how a phosphorylation-dependent interaction between the C-terminal tail and the kinase domain prevents substrate phosphorylation and binding. CONCLUSIONS/SIGNIFICANCE: The biochemical interactions between CKIepsilon and Disheveled, Period, and its own C-terminus lead to models that explain CKIepsilon's specificity and regulation.

  5. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    Science.gov (United States)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  6. Stapled peptides in the p53 pathway: computer simulations reveal novel interactions of the staples with the target protein.

    Science.gov (United States)

    Joseph, Thomas Leonard; Lane, David; Verma, Chandra S

    2010-11-15

    Atomistic simulations of a set of stapled peptides derived from the transactivation domain of p53 (designed by Verdine & colleagues, JACS 2007 129:2456) and complexed to MDM2 reveal that the good binders are uniquely characterized by higher helicity and by extensive interactions between the hydrocarbon staples and the MDM2 surface; in contrast the poor binders have reduced helicity and their staples are mostly solvent exposed. Our studies also find that the best binders can also potentially inhibit MDMX with similar affinities, suggesting that such stapled peptides can be evolved for dual inhibition with therapeutic potential.

  7. Analysis of Phosphorylation-dependent Protein Interactions of Adhesion and Degranulation Promoting Adaptor Protein (ADAP) Reveals Novel Interaction Partners Required for Chemokine-directed T cell Migration.

    Science.gov (United States)

    Kuropka, Benno; Witte, Amelie; Sticht, Jana; Waldt, Natalie; Majkut, Paul; Hackenberger, Christian P R; Schraven, Burkhart; Krause, Eberhard; Kliche, Stefanie; Freund, Christian

    2015-11-01

    Stimulation of T cells leads to distinct changes of their adhesive and migratory properties. Signal propagation from activated receptors to integrins depends on scaffolding proteins such as the adhesion and degranulation promoting adaptor protein (ADAP)(1). Here we have comprehensively investigated the phosphotyrosine interactome of ADAP in T cells and define known and novel interaction partners of functional relevance. While most phosphosites reside in unstructured regions of the protein, thereby defining classical SH2 domain interaction sites for master regulators of T cell signaling such as SLP76, Fyn-kinase, and NCK, other binding events depend on structural context. Interaction proteomics using different ADAP constructs comprising most of the known phosphotyrosine motifs as well as the structured domains confirm that a distinct set of proteins is attracted by pY571 of ADAP, including the ζ-chain-associated protein kinase of 70 kDa (ZAP70). The interaction of ADAP and ZAP70 is inducible upon stimulation either of the T cell receptor (TCR) or by chemokine. NMR spectroscopy reveals that the N-terminal SH2 domains within a ZAP70-tandem-SH2 construct is the major site of interaction with phosphorylated ADAP-hSH3(N) and microscale thermophoresis (MST) indicates an intermediate binding affinity (Kd = 2.3 μm). Interestingly, although T cell receptor dependent events such as T cell/antigen presenting cell (APC) conjugate formation and adhesion are not affected by mutation of Y571, migration of T cells along a chemokine gradient is compromised. Thus, although most phospho-sites in ADAP are linked to T cell receptor related functions we have identified a unique phosphotyrosine that is solely required for chemokine induced T cell behavior.

  8. Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-κB-driven transcription.

    Science.gov (United States)

    Mukherjee, Sulakshana P; Behar, Marcelo; Birnbaum, Harry A; Hoffmann, Alexander; Wright, Peter E; Ghosh, Gourisankar

    2013-09-01

    NF-κB plays a vital role in cellular immune and inflammatory response, survival, and proliferation by regulating the transcription of various genes involved in these processes. To activate transcription, RelA (a prominent NF-κB family member) interacts with transcriptional co-activators like CREB-binding protein (CBP) and its paralog p300 in addition to its cognate κB sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is comprised of two components--first, DNA binding domain of RelA interacts with the KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD) of RelA binds to the TAZ1 domain of CBP/p300. A phosphorylation event of a well-conserved RelA(Ser276) is prerequisite for the former interaction to occur and is considered a decisive factor for the overall RelA:CBP/p300 interaction. The role of the latter interaction in the transcription of RelA-activated genes remains unclear. Here we provide the solution structure of the latter component of the RelA:CBP complex by NMR spectroscopy. The structure reveals the folding of RelA-TA2 (a section of TAD) upon binding to TAZ1 through its well-conserved hydrophobic sites in a series of grooves on the TAZ1 surface. The structural analysis coupled with the mechanistic studies by mutational and isothermal calorimetric analyses allowed the design of RelA-mutants that selectively abrogated the two distinct components of the RelA:CBP/p300 interaction. Detailed studies of these RelA mutants using cell-based techniques, mathematical modeling, and genome-wide gene expression analysis showed that a major set of the RelA-activated genes, larger than previously believed, is affected by this interaction. We further show how the RelA:CBP/p300 interaction controls the nuclear response of NF-κB through the negative feedback loop of NF-κB pathway. Additionally, chromatin analyses of RelA target gene promoters showed constitutive recruitment of CBP/p300, thus indicating a possible role of

  9. Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-κB-driven transcription.

    Directory of Open Access Journals (Sweden)

    Sulakshana P Mukherjee

    2013-09-01

    Full Text Available NF-κB plays a vital role in cellular immune and inflammatory response, survival, and proliferation by regulating the transcription of various genes involved in these processes. To activate transcription, RelA (a prominent NF-κB family member interacts with transcriptional co-activators like CREB-binding protein (CBP and its paralog p300 in addition to its cognate κB sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is comprised of two components--first, DNA binding domain of RelA interacts with the KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD of RelA binds to the TAZ1 domain of CBP/p300. A phosphorylation event of a well-conserved RelA(Ser276 is prerequisite for the former interaction to occur and is considered a decisive factor for the overall RelA:CBP/p300 interaction. The role of the latter interaction in the transcription of RelA-activated genes remains unclear. Here we provide the solution structure of the latter component of the RelA:CBP complex by NMR spectroscopy. The structure reveals the folding of RelA-TA2 (a section of TAD upon binding to TAZ1 through its well-conserved hydrophobic sites in a series of grooves on the TAZ1 surface. The structural analysis coupled with the mechanistic studies by mutational and isothermal calorimetric analyses allowed the design of RelA-mutants that selectively abrogated the two distinct components of the RelA:CBP/p300 interaction. Detailed studies of these RelA mutants using cell-based techniques, mathematical modeling, and genome-wide gene expression analysis showed that a major set of the RelA-activated genes, larger than previously believed, is affected by this interaction. We further show how the RelA:CBP/p300 interaction controls the nuclear response of NF-κB through the negative feedback loop of NF-κB pathway. Additionally, chromatin analyses of RelA target gene promoters showed constitutive recruitment of CBP/p300, thus indicating a

  10. How Do Pre-Service Teachers Picture Various Electromagnetic Phenomenon? A Qualitative Study of Pre-Service Teachers' Conceptual Understanding of Fundamental Electromagnetic Interaction

    Science.gov (United States)

    Beer, Christopher P.

    2010-01-01

    This study analyzes the nature of pre-service teachers' conceptual models of various electromagnetic phenomena, specifically electrical current, electrical resistance, and light/matter interactions. This is achieved through the students answering the three questions on electromagnetism using a free response approach including both verbal and…

  11. Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals novel, non-canonical death receptor interactions.

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    Ivana Nemčovičová

    2013-03-01

    Full Text Available The TRAIL (TNF-related apoptosis inducing ligand death receptors (DRs of the tumor necrosis factor receptor superfamily (TNFRSF can promote apoptosis and regulate antiviral immunity by maintaining immune homeostasis during infection. In turn, human cytomegalovirus (HCMV expresses immunomodulatory proteins that down-regulate cell surface expression of TNFRSF members as well as poliovirus receptor-related proteins in an effort to inhibit host immune effector pathways that would lead to viral clearance. The UL141 glycoprotein of human cytomegalovirus inhibits host defenses by blocking cell surface expression of TRAIL DRs (by retention in ER and poliovirus receptor CD155, a nectin-like Ig-fold molecule. Here we show that the immunomodulatory function of HCMV UL141 is associated with its ability to bind diverse proteins, while utilizing at least two distinct binding sites to selectively engage TRAIL DRs or CD155. Binding studies revealed high affinity interaction of UL141 with both TRAIL-R2 and CD155 and low affinity binding to TRAIL-R1. We determined the crystal structure of UL141 bound to TRAIL-R2 at 2.1 Å resolution, which revealed that UL141 forms a homodimer that engages two TRAIL-R2 monomers 90° apart to form a heterotetrameric complex. Our structural and biochemical data reveal that UL141 utilizes its Ig-domain to facilitate non-canonical death receptor interactions while UL141 partially mimics the binding site of TRAIL on TRAIL-R2, which we found to be distinct from that of CD155. Moreover, UL141 also binds to an additional surface patch on TRAIL-R2 that is distinct from the TRAIL binding site. Therefore, the breadth of UL141-mediated effects indicates that HCMV has evolved sophisticated strategies to evade the immune system by modulating multiple effector pathways.

  12. Structure of human cytomegalovirus UL141 binding to TRAIL-R2 reveals novel, non-canonical death receptor interactions.

    Science.gov (United States)

    Nemčovičová, Ivana; Benedict, Chris A; Zajonc, Dirk M

    2013-03-01

    The TRAIL (TNF-related apoptosis inducing ligand) death receptors (DRs) of the tumor necrosis factor receptor superfamily (TNFRSF) can promote apoptosis and regulate antiviral immunity by maintaining immune homeostasis during infection. In turn, human cytomegalovirus (HCMV) expresses immunomodulatory proteins that down-regulate cell surface expression of TNFRSF members as well as poliovirus receptor-related proteins in an effort to inhibit host immune effector pathways that would lead to viral clearance. The UL141 glycoprotein of human cytomegalovirus inhibits host defenses by blocking cell surface expression of TRAIL DRs (by retention in ER) and poliovirus receptor CD155, a nectin-like Ig-fold molecule. Here we show that the immunomodulatory function of HCMV UL141 is associated with its ability to bind diverse proteins, while utilizing at least two distinct binding sites to selectively engage TRAIL DRs or CD155. Binding studies revealed high affinity interaction of UL141 with both TRAIL-R2 and CD155 and low affinity binding to TRAIL-R1. We determined the crystal structure of UL141 bound to TRAIL-R2 at 2.1 Å resolution, which revealed that UL141 forms a homodimer that engages two TRAIL-R2 monomers 90° apart to form a heterotetrameric complex. Our structural and biochemical data reveal that UL141 utilizes its Ig-domain to facilitate non-canonical death receptor interactions while UL141 partially mimics the binding site of TRAIL on TRAIL-R2, which we found to be distinct from that of CD155. Moreover, UL141 also binds to an additional surface patch on TRAIL-R2 that is distinct from the TRAIL binding site. Therefore, the breadth of UL141-mediated effects indicates that HCMV has evolved sophisticated strategies to evade the immune system by modulating multiple effector pathways.

  13. An evolutionary-network model reveals stratified interactions in the V3 loop of the HIV-1 envelope.

    Directory of Open Access Journals (Sweden)

    Art F Y Poon

    2007-11-01

    Full Text Available The third variable loop (V3 of the human immunodeficiency virus type 1 (HIV-1 envelope is a principal determinant of antibody neutralization and progression to AIDS. Although it is undoubtedly an important target for vaccine research, extensive genetic variation in V3 remains an obstacle to the development of an effective vaccine. Comparative methods that exploit the abundance of sequence data can detect interactions between residues of rapidly evolving proteins such as the HIV-1 envelope, revealing biological constraints on their variability. However, previous studies have relied implicitly on two biologically unrealistic assumptions: (1 that founder effects in the evolutionary history of the sequences can be ignored, and; (2 that statistical associations between residues occur exclusively in pairs. We show that comparative methods that neglect the evolutionary history of extant sequences are susceptible to a high rate of false positives (20%-40%. Therefore, we propose a new method to detect interactions that relaxes both of these assumptions. First, we reconstruct the evolutionary history of extant sequences by maximum likelihood, shifting focus from extant sequence variation to the underlying substitution events. Second, we analyze the joint distribution of substitution events among positions in the sequence as a Bayesian graphical model, in which each branch in the phylogeny is a unit of observation. We perform extensive validation of our models using both simulations and a control case of known interactions in HIV-1 protease, and apply this method to detect interactions within V3 from a sample of 1,154 HIV-1 envelope sequences. Our method greatly reduces the number of false positives due to founder effects, while capturing several higher-order interactions among V3 residues. By mapping these interactions to a structural model of the V3 loop, we find that the loop is stratified into distinct evolutionary clusters. We extend our model to

  14. Phosphate/Zinc Interaction Analysis in Two Lettuce Varieties Reveals Contrasting Effects on Biomass, Photosynthesis, and Dynamics of Pi Transport

    Directory of Open Access Journals (Sweden)

    Nadia Bouain

    2014-01-01

    Full Text Available Inorganic phosphate (Pi and Zinc (Zn are essential nutrients for normal plant growth. Interaction between these elements has been observed in many crop plants. Despite its agronomic importance, the biological significance and genetic basis of this interaction remain largely unknown. Here we examined the Pi/Zn interaction in two lettuce (Lactuca sativa varieties, namely, “Paris Island Cos” and “Kordaat.” The effects of variation in Pi and Zn supply were assessed on biomass and photosynthesis for each variety. Paris Island Cos displayed better growth and photosynthesis compared to Kordaat under all the conditions tested. Correlation analysis was performed to determine the interconnectivity between Pi and Zn intracellular contents in both varieties. Paris Island Cos showed a strong negative correlation between the accumulation levels of Pi and Zn in shoots and roots. However, no relation was observed for Kordaat. The increase of Zn concentration in the medium causes a decrease in dynamics of Pi transport in Paris Island Cos, but not in Kordaat plants. Taken together, results revealed a contrasting behavior between the two lettuce varieties in terms of the coregulation of Pi and Zn homeostasis and provided evidence in favor of a genetic basis for the interconnection of these two elements.

  15. Local Environment and Interactions of Liquid and Solid Interfaces Revealed by Spectral Line Shape of Surface Selective Nonlinear Vibrational Probe

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shun-Li; Fu, Li; Chase, Zizwe A.; Gan, Wei; Wang, Hong-Fei

    2016-11-10

    Vibrational spectral lineshape contains important detailed information of molecular vibration and reports its specific interactions and couplings to its local environment. In this work, recently developed sub-1 cm-1 high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) was used to measure the -C≡N stretch vibration in the 4-n-octyl-4’-cyanobiphenyl (8CB) Langmuir or Langmuir-Blodgett (LB) monolayer as a unique vibrational probe, and the spectral lineshape analysis revealed the local environment and interactions at the air/water, air/glass, air/calcium fluoride and air/-quartz interfaces for the first time. The 8CB Langmuir or LB film is uniform and the vibrational spectral lineshape of its -C≡N group has been well characterized, making it a good choice as the surface vibrational probe. Lineshape analysis of the 8CB -C≡N stretch SFG vibrational spectra suggests the coherent vibrational dynamics and the structural and dynamic inhomogeneity of the -C≡N group at each interface are uniquely different. In addition, it is also found that there are significantly different roles for water molecules in the LB films on different substrate surfaces. These results demonstrated the novel capabilities of the surface nonlinear spectroscopy in characterization and in understanding the specific structures and chemical interactions at the liquid and solid interfaces in general.

  16. Revealing the sequence of interactions of PuroA peptide with Candida albicans cells by live-cell imaging

    Science.gov (United States)

    Shagaghi, Nadin; Bhave, Mrinal; Palombo, Enzo A.; Clayton, Andrew H. A.

    2017-03-01

    To determine the mechanism(s) of action of antimicrobial peptides (AMPs) it is desirable to provide details of their interaction kinetics with cellular, sub-cellular and molecular targets. The synthetic peptide, PuroA, displays potent antimicrobial activities which have been attributed to peptide-induced membrane destabilization, or intracellular mechanisms of action (DNA-binding) or both. We used time-lapse fluorescence microscopy and fluorescence lifetime imaging microscopy (FLIM) to directly monitor the localization and interaction kinetics of a FITC- PuroA peptide on single Candida albicans cells in real time. Our results reveal the sequence of events leading to cell death. Within 1 minute, FITC-PuroA was observed to interact with SYTO-labelled nucleic acids, resulting in a noticeable quenching in the fluorescence lifetime of the peptide label at the nucleus of yeast cells, and cell-cycle arrest. A propidium iodide (PI) influx assay confirmed that peptide translocation itself did not disrupt the cell membrane integrity; however, PI entry occurred 25-45 minutes later, which correlated with an increase in fractional fluorescence of pores and an overall loss of cell size. Our results clarify that membrane disruption appears to be the mechanism by which the C. albicans cells are killed and this occurs after FITC-PuroA translocation and binding to intracellular targets.

  17. Revealing the sequence of interactions of PuroA peptide with Candida albicans cells by live-cell imaging

    Science.gov (United States)

    Shagaghi, Nadin; Bhave, Mrinal; Palombo, Enzo A.; Clayton, Andrew H. A.

    2017-01-01

    To determine the mechanism(s) of action of antimicrobial peptides (AMPs) it is desirable to provide details of their interaction kinetics with cellular, sub-cellular and molecular targets. The synthetic peptide, PuroA, displays potent antimicrobial activities which have been attributed to peptide-induced membrane destabilization, or intracellular mechanisms of action (DNA-binding) or both. We used time-lapse fluorescence microscopy and fluorescence lifetime imaging microscopy (FLIM) to directly monitor the localization and interaction kinetics of a FITC- PuroA peptide on single Candida albicans cells in real time. Our results reveal the sequence of events leading to cell death. Within 1 minute, FITC-PuroA was observed to interact with SYTO-labelled nucleic acids, resulting in a noticeable quenching in the fluorescence lifetime of the peptide label at the nucleus of yeast cells, and cell-cycle arrest. A propidium iodide (PI) influx assay confirmed that peptide translocation itself did not disrupt the cell membrane integrity; however, PI entry occurred 25–45 minutes later, which correlated with an increase in fractional fluorescence of pores and an overall loss of cell size. Our results clarify that membrane disruption appears to be the mechanism by which the C. albicans cells are killed and this occurs after FITC-PuroA translocation and binding to intracellular targets. PMID:28252014

  18. Fundamental interactions involving neutrons and neutrinos: reactor-based studies led by Petersburg Nuclear Physics Institute (National Research Centre 'Kurchatov Institute') [PNPI (NRC KI)

    Science.gov (United States)

    Serebrov, A. P.

    2015-11-01

    Neutrons of very low energy ( ˜ 10-7 eV), commonly known as ultracold, are unique in that they can be stored in material and magnetic traps, thus enhancing methodical opportunities to conduct precision experiments and to probe the fundamentals of physics. One of the central problems of physics, of direct relevance to the formation of the Universe, is the violation of time invariance. Experiments searching for the nonzero neutron electric dipole moment serve as a time invariance test, and the use of ultracold neutrons provides very high measurement precision. Precision neutron lifetime measurements using ultracold neutrons are extremely important for checking ideas on the early formation of the Universe. This paper discusses problems that arise in studies using ultracold neutrons. Also discussed are the currently highly topical problem of sterile neutrinos and the search for reactor antineutrino oscillations at distances of 6-12 meters from the reactor core. The field reviewed is being investigated at multiple facilities globally. The present paper mainly concentrates on the results of PNPI-led studies at WWR-M PNPI (Gatchina), ILL (Grenoble), and SM-3 (Dimitrovgrad) reactors, and also covers the results obtained during preparation for research at the PIK reactor which is under construction.

  19. Fundamental mechanisms in flue gas conditioning. Topical report No. 2, Literature review and assembly of theories on the interactions of ash and conditioning agents

    Energy Technology Data Exchange (ETDEWEB)

    Bush, P.V.; Snyder, T.R.

    1992-01-09

    The overall goal of this research project is to formulate a mathematical model of flue gas conditioning. This model will be based on an understanding of why ask properties, such as cohesivity and resistivity, are changed by conditioning. Such a model could serve as a component of the performance models of particulate control devices where flue gas conditioning is used. There are two specific objectives of this research project, which divide the planned research into two main parts. One part of the project is designed to determine how ash particles are modified by interactions with sorbent injection processes and to describe the mechanisms by which these interactions affect fine particle collection. The objective of the other part of the project is to identify the mechanisms by which conditioning agents, including chemically active compounds, modify the key properties of fine fly ash particles.

  20. Interações medicamentosas: fundamentos para a pratica clínica da enfermagem Drugs interactions: fundamental aspects for clinical practice nursing

    Directory of Open Access Journals (Sweden)

    Silvia Regina Secoli

    2001-03-01

    Full Text Available O fenômeno das interações medicamentosas constitui na atualidade um dos temas mais importantes da farmacologia, para a prática clínica dos profissionais da saúde. O uso concomitante de vários medicamentos, enquanto estratégia terapêutica, e o crescente número destes agentes no mercado são alguns dos fatores que contribuem para ampliar os efeitos benéficos da terapia, mas que também possibilitam a interferência mútua de ações farmacológicas podendo resultar em alterações dos efeitos desejados. Este artigo, de revisão, tem por objetivos rever os princípios farmacológicos relacionados aos mecanismos das interações medicamentosas; descrever as classes dos medicamentos interativos, os grupos de pacientes expostos ao risco e sugerir medidas práticas para a equipe de enfermagem, no intuito de prevenir a ocorrência de reações adversas decorrentes de interações fortuitas.Nowadays drugs interactions constitute one the most important subjects of pharmacological for clinical practive of health professionals. The concomitant use of many drugs as therapeutic strategy and the growing number of agents available contribute to enlarge the benefical effects of therapy. Besides, these factors can also permit the mutual interference of pharmacological actions that result in alteractions of therapeutics effects. The aim of this article is to review the principles pharmacological related to the mechanisms of drugs interactions, to describe the types of interactive drugs; the groups of risk patients and to suggest specific nursing interventions aiming the prevention of occurrence of adverse reactions from accidental interactions.

  1. Fundamental neutron physics at LANSCE

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Protein-protein docking and analysis reveal that two homologous bacterial adenylyl cyclase toxins interact with calmodulin differently.

    Science.gov (United States)

    Guo, Qing; Jureller, Justin E; Warren, Julia T; Solomaha, Elena; Florián, Jan; Tang, Wei-Jen

    2008-08-29

    Calmodulin (CaM), a eukaryotic calcium sensor that regulates diverse biological activities, consists of N- and C-terminal globular domains (N-CaM and C-CaM, respectively). CaM serves as the activator of CyaA, a 188-kDa adenylyl cyclase toxin secreted by Bordetella pertussis, which is the etiologic agent for whooping cough. Upon insertion of the N-terminal adenylyl cyclase domain (ACD) of CyaA to its targeted eukaryotic cells, CaM binds to this domain tightly ( approximately 200 pm affinity). This interaction activates the adenylyl cyclase activity of CyaA, leading to a rise in intracellular cAMP levels to disrupt normal cellular signaling. We recently solved the structure of CyaA-ACD in complex with C-CaM to elucidate the mechanism of catalytic activation. However, the structure of the interface between N-CaM and CyaA, the formation of which contributes a 400-fold increase of binding affinity between CyaA and CaM, remains elusive. Here, we used site-directed mutations and molecular dynamic simulations to generate several working models of CaM-bound CyaA-ACD. The validity of these models was evaluated by disulfide bond cross-linking, point mutations, and fluorescence resonance energy transfer experiments. Our study reveals that a beta-hairpin region (amino acids 259-273) of CyaA-ACD likely makes contacts with the second calcium binding motif of the extended CaM. This mode of interaction differs from the interaction of N-CaM with anthrax edema factor, which binds N-CaM via its helical domain. Thus, two structurally conserved, bacterial adenylyl cyclase toxins have evolved to utilize distinct binding surfaces and modes of activation in their interaction with CaM, a highly conserved eukaryotic signaling protein.

  3. Fundamentals of gas dynamics

    CERN Document Server

    Babu, V

    2014-01-01

    Fundamentals of Gas Dynamics, Second Edition isa comprehensively updated new edition and now includes a chapter on the gas dynamics of steam. It covers the fundamental concepts and governing equations of different flows, and includes end of chapter exercises based on the practical applications. A number of useful tables on the thermodynamic properties of steam are also included.Fundamentals of Gas Dynamics, Second Edition begins with an introduction to compressible and incompressible flows before covering the fundamentals of one dimensional flows and normal shock wav

  4. Crystal science fundamentals

    OpenAIRE

    Ramachandran, V.; Halfpenny, PJ; Roberts, KJ

    2017-01-01

    The fundamentals of crystal science notably crystallography, crystal chemistry, crystal defects, crystal morphology and the surface chemistry of crystals are introduced with particular emphasis on organic crystals.

  5. Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions.

    Science.gov (United States)

    Turner, Leslie M; Harr, Bettina

    2014-12-09

    Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.

  6. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

    Science.gov (United States)

    Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

    2016-02-01

    Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  7. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2.

    Science.gov (United States)

    Breitkopf, Susanne B; Yang, Xuemei; Begley, Michael J; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A; Hong, Pengyu; Kontaridis, Maria I; Cantley, Lewis C; Perrimon, Norbert; Asara, John M

    2016-02-03

    Using a series of immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  8. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

    Directory of Open Access Journals (Sweden)

    Rajani Rai

    2015-11-01

    Full Text Available Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR and Classification and Regression Tree Analysis (CRT to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634; FAS (rs2234767; FASL (rs763110; DCC (rs2229080, rs4078288, rs7504990, rs714; PSCA (rs2294008, rs2978974; ADRA2A (rs1801253; ADRB1 (rs1800544; ADRB3 (rs4994; CYP17 (rs2486758 involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634, DCC (rs714, rs2229080, rs4078288 and ADRB3 (rs4994 polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994 to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10 or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10. Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  9. Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae

    Science.gov (United States)

    Tremaine, Mary; Hebert, Alexander S.; Myers, Kevin S.; Sardi, Maria; Dickinson, Quinn; Reed, Jennifer L.; Zhang, Yaoping; Coon, Joshua J.; Hittinger, Chris Todd; Gasch, Audrey P.; Landick, Robert

    2016-01-01

    The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism. PMID:27741250

  10. Fundamentals of Physics

    Science.gov (United States)

    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.

  11. Dependence and Fundamentality

    Directory of Open Access Journals (Sweden)

    Justin Zylstra

    2014-12-01

    Full Text Available I argue that dependence is neither necessary nor sufficient for relative fundamentality. I then introduce the notion of 'likeness in nature' and provide an account of relative fundamentality in terms of it and the notion of dependence. Finally, I discuss some puzzles that arise in Aristotle's Categories, to which the theory developed is applied.

  12. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria.

    Science.gov (United States)

    Hoppins, Suzanne; Collins, Sean R; Cassidy-Stone, Ann; Hummel, Eric; Devay, Rachel M; Lackner, Laura L; Westermann, Benedikt; Schuldiner, Maya; Weissman, Jonathan S; Nunnari, Jodi

    2011-10-17

    To broadly explore mitochondrial structure and function as well as the communication of mitochondria with other cellular pathways, we constructed a quantitative, high-density genetic interaction map (the MITO-MAP) in Saccharomyces cerevisiae. The MITO-MAP provides a comprehensive view of mitochondrial function including insights into the activity of uncharacterized mitochondrial proteins and the functional connection between mitochondria and the ER. The MITO-MAP also reveals a large inner membrane-associated complex, which we term MitOS for mitochondrial organizing structure, comprised of Fcj1/Mitofilin, a conserved inner membrane protein, and five additional components. MitOS physically and functionally interacts with both outer and inner membrane components and localizes to extended structures that wrap around the inner membrane. We show that MitOS acts in concert with ATP synthase dimers to organize the inner membrane and promote normal mitochondrial morphology. We propose that MitOS acts as a conserved mitochondrial skeletal structure that differentiates regions of the inner membrane to establish the normal internal architecture of mitochondria.

  13. Interaction between titanium dioxide nanoparticles and human serum albumin revealed by fluorescence spectroscopy in the absence of photoactivation

    Energy Technology Data Exchange (ETDEWEB)

    Sun Wen [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Du Yingxiang, E-mail: du_yingxiang@126.co [Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, Jiangsu 210009 (China) and Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Chen Jianqiu [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Kou Junping; Yu Boyang [Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 210009 (China)

    2009-08-15

    Titanium dioxide (TiO{sub 2}) nanoparticles (NPs) are widely used as an important kind of biomaterials. The interaction between TiO{sub 2} (P25) at 20 nm in diameter and human serum albumin (HSA) was studied by fluorescence spectroscopy in this work. Under the simulative physiological conditions, fluorescence data revealed the presence of a single class of binding site on HSA and its binding constants (K{sub a}) were 2.18+-0.04x10{sup 4}, 0.87+-0.05x10{sup 4}, 0.68+-0.06x10{sup 4} M{sup -1} at 298, 304 and 310 K, respectively. In addition, according to the Van't Hoff equation, the thermodynamic functions standard enthalpy (DELTAH{sup 0}) and standard entropy (DELTAS{sup 0}) for the reaction were calculated to be -75.18+-0.15 kJ mol{sup -1} and -170.11+-0.38 J mol{sup -1} K{sup -1}. These results indicated that TiO{sub 2} NPs bond to HSA mainly by van der Waals force and hydrogen bonding formation in low dielectric media, and the electrostatic interactions cannot be excluded. Furthermore, the effects of common ions on the binding constant of TiO{sub 2} NPs-HSA complex were discussed.

  14. Exciton Dynamics and Many Body Interactions in Layered Semiconducting Materials Revealed with Non-linear Coherent Spectroscopy

    Science.gov (United States)

    Dey, Prasenjit

    Atomically thin, semiconducting transition metal dichalogenides (TMDs), a special class of layered semiconductors, that can be shaped as a perfect two dimensional material, have garnered a lot of attention owing to their fascinating electronic properties which are achievable at the extreme nanoscale. In contrast to graphene, the most celebrated two-dimensional (2D) material thus far; TMDs exhibit a direct band gap in the monolayer regime. The presence of a non-zero bandgap along with the broken inversion symmetry in the monolayer limit brands semiconducting TMDs as the perfect candidate for future optoelectronic and valleytronics-based device application. These remarkable discoveries demand exploration of different materials that possess similar properties alike TMDs. Recently, III-VI layered semiconducting materials (example: InSe, GaSe etc.) have also emerged as potential materials for optical device based applications as, similar to TMDs, they can be shaped into a perfect two-dimensional form as well as possess a sizable band gap in their nano-regime. The perfect 2D character in layered materials cause enhancement of strong Coulomb interaction. As a result, excitons, a coulomb bound quasiparticle made of electron-hole pair, dominate the optical properties near the bandgap. The basis of development for future optoelectronic-based devices requires accurate characterization of the essential properties of excitons. Two fundamental parameters that characterize the quantum dynamics of excitons are: a) the dephasing rate, gamma, which represents the coherence loss due to the interaction of the excitons with their environment (for example- phonons, impurities, other excitons, etc.) and b) excited state population decay rate arising from radiative and non-radiative relaxation processes. The dephasing rate is representative of the time scale over which excitons can be coherently manipulated, therefore accurately probing the source of exciton decoherence is crucial for

  15. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

    Science.gov (United States)

    Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

    2017-07-11

    Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT

  16. Fundamentals of electronics

    CERN Document Server

    Schubert, Thomas F

    2015-01-01

    This book, Electronic Devices and Circuit Application, is the first of four books of a larger work, Fundamentals of Electronics. It is comprised of four chapters describing the basic operation of each of the four fundamental building blocks of modern electronics: operational amplifiers, semiconductor diodes, bipolar junction transistors, and field effect transistors. Attention is focused on the reader obtaining a clear understanding of each of the devices when it is operated in equilibrium. Ideas fundamental to the study of electronic circuits are also developed in the book at a basic level to

  17. Fundamentals of electrochemical science

    CERN Document Server

    Oldham, Keith

    1993-01-01

    Key Features* Deals comprehensively with the basic science of electrochemistry* Treats electrochemistry as a discipline in its own right and not as a branch of physical or analytical chemistry* Provides a thorough and quantitative description of electrochemical fundamentals

  18. Fundamentals of crystallography

    CERN Document Server

    2011-01-01

    Crystallography is a basic tool for scientists in many diverse disciplines. This text offers a clear description of fundamentals and of modern applications. It supports curricula in crystallography at undergraduate level.

  19. Fundamentals of structural dynamics

    CERN Document Server

    Craig, Roy R

    2006-01-01

    From theory and fundamentals to the latest advances in computational and experimental modal analysis, this is the definitive, updated reference on structural dynamics.This edition updates Professor Craig's classic introduction to structural dynamics, which has been an invaluable resource for practicing engineers and a textbook for undergraduate and graduate courses in vibrations and/or structural dynamics. Along with comprehensive coverage of structural dynamics fundamentals, finite-element-based computational methods, and dynamic testing methods, this Second Edition includes new and e

  20. Masses of Fundamental Particles

    CERN Document Server

    Terazawa, Hidezumi

    2011-01-01

    Not only the masses of fundamental particles including the weak bosons, Higgs scalar, quarks, and leptons, but also the mixing angles of quarks and those of neutrinos are all explained and/or predicted in the unified composite model of quarks and leptons successfully. In addition, both of the two anomalies recently found by the CDF Collaboration are suggested to be taken as evidences for the substructure of the fundamental particles.

  1. Information security fundamentals

    CERN Document Server

    Peltier, Thomas R

    2013-01-01

    Developing an information security program that adheres to the principle of security as a business enabler must be the first step in an enterprise's effort to build an effective security program. Following in the footsteps of its bestselling predecessor, Information Security Fundamentals, Second Edition provides information security professionals with a clear understanding of the fundamentals of security required to address the range of issues they will experience in the field.The book examines the elements of computer security, employee roles and r

  2. Fundamentals of condensed matter physics

    CERN Document Server

    Cohen, Marvin L

    2016-01-01

    Based on an established course and covering the fundamentals, central areas, and contemporary topics of this diverse field, Fundamentals of Condensed Matter Physics is a much-needed textbook for graduate students. The book begins with an introduction to the modern conceptual models of a solid from the points of view of interacting atoms and elementary excitations. It then provides students with a thorough grounding in electronic structure as a starting point to understand many properties of condensed matter systems - electronic, structural, vibrational, thermal, optical, transport, magnetic and superconductivity - and methods to calculate them. Taking readers through the concepts and techniques, the text gives both theoretically and experimentally inclined students the knowledge needed for research and teaching careers in this field. It features 200 illustrations, 40 worked examples and 150 homework problems for students to test their understanding. Solutions to the problems for instructors are available at w...

  3. Fundamentals of estuarine physical oceanography

    CERN Document Server

    Bruner de Miranda, Luiz; Kjerfve, Björn; Castro Filho, Belmiro Mendes de

    2017-01-01

    This book provides an introduction to the complex system functions, variability and human interference in ecosystem between the continent and the ocean. It focuses on circulation, transport and mixing of estuarine and coastal water masses, which is ultimately related to an understanding of the hydrographic and hydrodynamic characteristics (salinity, temperature, density and circulation), mixing processes (advection and diffusion), transport timescales such as the residence time and the exposure time. In the area of physical oceanography, experiments using these water bodies as a natural laboratory and interpreting their circulation and mixing processes using theoretical and semi-theoretical knowledge are of fundamental importance. Small-scale physical models may also be used together with analytical and numerical models. The book highlights the fact that research and theory are interactive, and the results provide the fundamentals for the development of the estuarine research.

  4. Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies

    Energy Technology Data Exchange (ETDEWEB)

    Dusinska, Maria, E-mail: Maria.DUSINSKA@nilu.no [CEE-Health Effects Group, NILU - Norwegian Institute for Air Research, Kjeller (Norway); Staruchova, Marta; Horska, Alexandra [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia); Smolkova, Bozena [Laboratory of Cancer Genetics, Cancer Research Institute of the Slovak Academy of Sciences, Bratislava (Slovakia); Collins, Andrew [Department of Nutrition, Faculty of Medicine, University of Oslo (Norway); Bonassi, Stefano [Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome (Italy); Volkovova, Katarina [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia)

    2012-08-01

    Glutathione S-transferases (GSTs) are members of a multigene family of isoenzymes that are important in the control of oxidative stress and in phase II metabolism. Acting non-enzymically, GSTs can modulate signalling pathways of cell proliferation, cell differentiation and apoptosis. Using a molecular epidemiology approach, we have investigated a potential involvement of GSTs in DNA damage processing, specifically the modulation of DNA repair in a group of 388 healthy adult volunteers; 239 with at least 5 years of occupational exposure to asbestos, stone wool or glass fibre, and 149 reference subjects. We measured DNA damage in lymphocytes using the comet assay (alkaline single cell gel electrophoresis): strand breaks (SBs) and alkali-labile sites, oxidised pyrimidines with endonuclease III, and oxidised purines with formamidopyrimidine DNA glycosylase. We also measured GST activity in erythrocytes, and the capacity for base excision repair (BER) in a lymphocyte extract. Polymorphisms in genes encoding three GST isoenzymes were determined, namely deletion of GSTM1 and GSTT1 and single nucleotide polymorphism Ile105Val in GSTP1. Consumption of vegetables and wine correlated negatively with DNA damage and modulated BER. GST activity correlated with oxidised bases and with BER capacity, and differed depending on polymorphisms in GSTP1, GSTT1 and GSTM1. A significantly lower BER rate was associated with the homozygous GSTT1 deletion in all asbestos site subjects and in the corresponding reference group. Multifactorial analysis revealed effects of sex and exposure in GSTP1 Ile/Val heterozygotes but not in Ile/Ile homozygotes. These variants affected also SBs levels, mainly by interactions of GSTP1 genotype with exposure, with sex, and with smoking habit; and by an interaction between sex and smoking. Our results show that GST polymorphisms and GST activity can apparently influence DNA stability and repair of oxidised bases, suggesting a potential new role for these

  5. Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions.

    Directory of Open Access Journals (Sweden)

    Young-Jun Choi

    2014-05-01

    Full Text Available BACKGROUND: Parasite biology, by its very nature, cannot be understood without integrating it with that of the host, nor can the host response be adequately explained without considering the activity of the parasite. However, due to experimental limitations, molecular studies of parasite-host systems have been predominantly one-sided investigations focusing on either of the partners involved. Here, we conducted a dual RNA-seq time course analysis of filarial worm parasite and host mosquito to better understand the parasite processes underlying development in and interaction with the host tissue, from the establishment of infection to the development of infective-stage larva. METHODOLOGY/PRINCIPAL FINDINGS: Using the Brugia malayi-Aedes aegypti system, we report parasite gene transcription dynamics, which exhibited a highly ordered developmental program consisting of a series of cyclical and state-transitioning temporal patterns. In addition, we contextualized these parasite data in relation to the concurrent dynamics of the host transcriptome. Comparative analyses using uninfected tissues and different host strains revealed the influence of parasite development on host gene transcription as well as the influence of the host environment on parasite gene transcription. We also critically evaluated the life-cycle transcriptome of B. malayi by comparing developmental stages in the mosquito relative to those in the mammalian host, providing insight into gene expression changes underpinning the mosquito-borne parasitic lifestyle of this heteroxenous parasite. CONCLUSIONS/SIGNIFICANCE: The data presented herein provide the research community with information to design wet lab experiments and select candidates for future study to more fully dissect the whole set of molecular interactions of both organisms in this mosquito-filarial worm symbiotic relationship. Furthermore, characterization of the transcriptional program over the complete life cycle of

  6. Differential interaction kinetics of a bipolar structure-specific endonuclease with DNA flaps revealed by single-molecule imaging.

    Directory of Open Access Journals (Sweden)

    Rachid Rezgui

    Full Text Available As DNA repair enzymes are essential for preserving genome integrity, understanding their substrate interaction dynamics and the regulation of their catalytic mechanisms is crucial. Using single-molecule imaging, we investigated the association and dissociation kinetics of the bipolar endonuclease NucS from Pyrococcus abyssi (Pab on 5' and 3'-flap structures under various experimental conditions. We show that association of the PabNucS with ssDNA flaps is largely controlled by diffusion in the NucS-DNA energy landscape and does not require a free 5' or 3' extremity. On the other hand, NucS dissociation is independent of the flap length and thus independent of sliding on the single-stranded portion of the flapped DNA substrates. Our kinetic measurements have revealed previously unnoticed asymmetry in dissociation kinetics from these substrates that is markedly modulated by the replication clamp PCNA. We propose that the replication clamp PCNA enhances the cleavage specificity of NucS proteins by accelerating NucS loading at the ssDNA/dsDNA junctions and by minimizing the nuclease interaction time with its DNA substrate. Our data are also consistent with marked reorganization of ssDNA and nuclease domains occurring during NucS catalysis, and indicate that NucS binds its substrate directly at the ssDNA-dsDNA junction and then threads the ssDNA extremity into the catalytic site. The powerful techniques used here for probing the dynamics of DNA-enzyme binding at the single-molecule have provided new insight regarding substrate specificity of NucS nucleases.

  7. Dual RNA-seq reveals Meloidogyne graminicola transcriptome and candidate effectors during the interaction with rice plants.

    Science.gov (United States)

    Petitot, Anne-Sophie; Dereeper, Alexis; Agbessi, Mawusse; Da Silva, Corinne; Guy, Julie; Ardisson, Morgane; Fernandez, Diana

    2016-08-01

    Root-knot nematodes secrete proteinaceous effectors into plant tissues to facilitate infection by suppressing host defences and reprogramming the host metabolism to their benefit. Meloidogyne graminicola is a major pest of rice (Oryza sativa) in Asia and Latin America, causing important crop losses. The goal of this study was to identify M. graminicola pathogenicity genes expressed during the plant-nematode interaction. Using the dual RNA-sequencing (RNA-seq) strategy, we generated transcriptomic data of M. graminicola samples covering the pre-parasitic J2 stage and five parasitic stages in rice plants, from the parasitic J2 to the adult female. In the absence of a reference genome, a de novo M. graminicola transcriptome of 66 396 contigs was obtained from those reads that were not mapped on the rice genome. Gene expression profiling across the M. graminicola life cycle revealed key genes involved in nematode development and provided insights into the genes putatively associated with parasitism. The development of a 'secreted protein prediction' pipeline revealed a typical set of proteins secreted by nematodes, as well as a large number of cysteine-rich proteins and putative nuclear proteins. Combined with expression data, this pipeline enabled the identification of 15 putative effector genes, including two homologues of well-characterized effectors from cyst nematodes (CLE-like and VAP1) and a metallothionein. The localization of gene expression was assessed by in situ hybridization for a subset of candidates. All of these data represent important molecular resources for the elucidation of M. graminicola biology and for the selection of potential targets for the development of novel control strategies for this nematode species.

  8. Fundamental investigations of catalyst nanoparticles

    DEFF Research Database (Denmark)

    Elkjær, Christian Fink

    fundamental understanding of catalytic processes and our ability to make use of that understanding. This thesis presents fundamental studies of catalyst nanoparticles with particular focus on dynamic processes. Such studies often require atomic-scale characterization, because the catalytic conversion takes...... place on the molecular and atomic level. Transmission electron microscopy (TEM) has the ability to image nanostructures with atomic resolution and reveal the atomic configuration of the important nanoparticle surfaces. In the present work, TEM has been used to study nanoparticles in situ at elevated...... different topics, each related to different aspects of nanoparticle dynamics and catalysis. The first topic is the reduction of a homogeneous solid state precursor to form the catalytically active phase which is metal nanoparticles on an inert support. Here, we have reduced Cu phyllosilicate to Cu on silica...

  9. Fundamentals of Condensed Matter Physics

    Science.gov (United States)

    Cohen, Marvin L.; Louie, Steven G.

    2016-05-01

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

  10. Variation of fundamental constants: theory

    Science.gov (United States)

    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.

  11. Comparative genomic analysis reveals a diverse repertoire of genes involved in prokaryote-eukaryote interactions within the Pseudovibrio genus.

    Directory of Open Access Journals (Sweden)

    Stefano eRomano

    2016-03-01

    Full Text Available Strains of the Pseudovibrio genus have been detected worldwide, mainly as part of bacterial communities associated with marine invertebrates, particularly sponges. This recurrent association has been considered as an indication of a symbiotic relationship between these microbes and their host. Until recently, the availability of only two genomes, belonging to closely related strains, has limited the knowledge on the genomic and physiological features of the genus to a single phylogenetic lineage.Here we present 10 newly sequenced genomes of Pseudovibrio strains isolated from marine sponges from the west coast of Ireland, and including the other two publicly available genomes we performed an extensive comparative genomic analysis. Homogeneity was apparent in terms of both the orthologous genes and the metabolic features shared amongst the 12 strains. At the genomic level, a key physiological difference observed amongst the isolates was the presence only in strain P. axinellae AD2 of genes encoding proteins involved in assimilatory nitrate reduction, which was then proved experimentally. We then focused on studying those systems known to be involved in the interactions with eukaryotic and prokaryotic cells. This analysis revealed that the genus harbors a large diversity of toxin-like proteins, secretion systems and their potential effectors. Their distribution in the genus was not always consistent with the phylogenetic relationship of the strains. Finally, our analyses identified new genomic islands encoding potential toxin-immunity systems, previously unknown in the genus.Our analyses shed new light on the Pseudovibrio genus, indicating a large diversity of both metabolic features and systems for interacting with the host. The diversity in both distribution and abundance of these systems amongst the strains underlines how metabolically and phylogenetically similar bacteria may use different strategies to interact with the host and find a niche

  12. Comparative Genomic Analysis Reveals a Diverse Repertoire of Genes Involved in Prokaryote-Eukaryote Interactions within the Pseudovibrio Genus.

    Science.gov (United States)

    Romano, Stefano; Fernàndez-Guerra, Antonio; Reen, F Jerry; Glöckner, Frank O; Crowley, Susan P; O'Sullivan, Orla; Cotter, Paul D; Adams, Claire; Dobson, Alan D W; O'Gara, Fergal

    2016-01-01

    Strains of the Pseudovibrio genus have been detected worldwide, mainly as part of bacterial communities associated with marine invertebrates, particularly sponges. This recurrent association has been considered as an indication of a symbiotic relationship between these microbes and their host. Until recently, the availability of only two genomes, belonging to closely related strains, has limited the knowledge on the genomic and physiological features of the genus to a single phylogenetic lineage. Here we present 10 newly sequenced genomes of Pseudovibrio strains isolated from marine sponges from the west coast of Ireland, and including the other two publicly available genomes we performed an extensive comparative genomic analysis. Homogeneity was apparent in terms of both the orthologous genes and the metabolic features shared amongst the 12 strains. At the genomic level, a key physiological difference observed amongst the isolates was the presence only in strain P. axinellae AD2 of genes encoding proteins involved in assimilatory nitrate reduction, which was then proved experimentally. We then focused on studying those systems known to be involved in the interactions with eukaryotic and prokaryotic cells. This analysis revealed that the genus harbors a large diversity of toxin-like proteins, secretion systems and their potential effectors. Their distribution in the genus was not always consistent with the phylogenetic relationship of the strains. Finally, our analyses identified new genomic islands encoding potential toxin-immunity systems, previously unknown in the genus. Our analyses shed new light on the Pseudovibrio genus, indicating a large diversity of both metabolic features and systems for interacting with the host. The diversity in both distribution and abundance of these systems amongst the strains underlines how metabolically and phylogenetically similar bacteria may use different strategies to interact with the host and find a niche within its

  13. An autoinhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs.

    Science.gov (United States)

    Pan, Zhu; Zhu, Jinwei; Shang, Yuan; Wei, Zhiyi; Jia, Min; Xia, Caihao; Wen, Wenyu; Wang, Wenning; Zhang, Mingjie

    2013-06-01

    LGN plays essential roles in asymmetric cell divisions via its N-terminal TPR-motif-mediated binding to mInsc and NuMA. This scaffolding activity requires the release of the autoinhibited conformation of LGN by binding of Gα(i) to its C-terminal GoLoco (GL) motifs. The interaction between the GL and TPR motifs of LGN represents a distinct GL/target binding mode with an unknown mechanism. Here, we show that two consecutive GL motifs of LGN form a minimal TPR-motif-binding unit. GL12 and GL34 bind to TPR0-3 and TPR4-7, respectively. The crystal structure of a truncated LGN reveals that GL34 forms a pair of parallel α helices and binds to the concave surface of TPR4-7, thereby preventing LGN from binding to other targets. Importantly, the GLs bind to TPR motifs with a mode distinct from that observed in the GL/Gα(i)·GDP complexes. Our results also indicate that multiple and orphan GL motif proteins likely respond to G proteins with distinct mechanisms.

  14. Structural Snapshots of an Engineered Cystathionine-γ-lyase Reveal the Critical Role of Electrostatic Interactions in the Active Site

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Wupeng; Stone, Everett; Zhang, Yan Jessie

    2017-02-01

    Enzyme therapeutics that can degrade l-methionine (l-Met) are of great interest as numerous malignancies are exquisitely sensitive to l-Met depletion. To exhaust the pool of methionine in human serum, we previously engineered an l-Met-degrading enzyme based on the human cystathionine-γ-lyase scaffold (hCGL-NLV) to circumvent immunogenicity and stability issues observed in the preclinical application of bacterially derived methionine-γ-lyases. To gain further insights into the structure–activity relationships governing the chemistry of the hCGL-NLV lead molecule, we undertook a biophysical characterization campaign that captured crystal structures (2.2 Å) of hCGL-NLV with distinct reaction intermediates, including internal aldimine, substrate-bound, gem-diamine, and external aldimine forms. Curiously, an alternate form of hCGL-NLV that crystallized under higher-salt conditions revealed a locally unfolded active site, correlating with inhibition of activity as a function of ionic strength. Subsequent mutational and kinetic experiments pinpointed that a salt bridge between the phosphate of the essential cofactor pyridoxal 5'-phosphate (PLP) and residue R62 plays an important role in catalyzing β- and γ-eliminations. Our study suggests that solvent ions such as NaCl disrupt electrostatic interactions between R62 and PLP, decreasing catalytic efficiency.

  15. Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Mohan Babu

    2014-02-01

    Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.

  16. Fundamentals of Space Medicine

    Science.gov (United States)

    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

  17. Electronic imaging fundamentals: basic theory.

    Science.gov (United States)

    Vizy, K N

    1983-01-01

    Introduction of the computer into the field of medical imaging, as typified by the extensive use of digital subtraction angiography (DSA), created an important need for a basic understanding of the principles of digital imaging. This paper reviews these fundamental principles, starting with the definition of images and the interaction of these images with television display systems, then continuing with a detailed description of the way in which imaging systems are specified. This work defines the basic terms and concepts that will be used throughout the contents of this issue.

  18. Fundamentals of turbomachines

    CERN Document Server

    Dick, Erik

    2015-01-01

    This book explores the working principles of all kinds of turbomachines. The same theoretical framework is used to analyse the different machine types. Fundamentals are first presented and theoretical concepts are then elaborated for particular machine types, starting with the simplest ones.For each machine type, the author strikes a balance between building basic understanding and exploring knowledge of practical aspects. Readers are invited through challenging exercises to consider how the theory applies to particular cases and how it can be generalised.   The book is primarily meant as a course book. It teaches fundamentals and explores applications. It will appeal to senior undergraduate and graduate students in mechanical engineering and to professional engineers seeking to understand the operation of turbomachines. Readers will gain a fundamental understanding of turbomachines. They will also be able to make a reasoned choice of turbomachine for a particular application and to understand its operation...

  19. Monte Carlo fundamentals

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Supersymmetry and the unification of fundamental interactions.

    Science.gov (United States)

    Fayet, P.

    Les physiciens élaborent progressivement une description unifée des lois de l'Univers, qui fait intervenir des principes de symétrie de plus en plus étendus. La supersymétrie, qui englobe la mécanique quantique et la relativité générale en opérant dans une extension de l'espace-temps ordinaire, appelée le superespace, est-elle l'un de ces principes fondamentaux? Dans cet article, l'auteur explique ce qu'est cette nouvelle symétrie, et comment, pour appliquer celle-ci au monde physique, il a été amené à envisager l'existence de toute une famille de nouvelles particules - comme les photinos, gluinos, squarks et sélectrons - que l'on recherche activement aujourd'hui. On espère parvenir à les détecter grâce aux nouvelles générations d'accélerateurs, et découvrir ainsi un nouveau principe auquel doivent satisfaire toutes les lois physiques, aussi fondamental que la relativité.

  1. Human-computer interaction fundamentals and practice

    CERN Document Server

    Kim, Gerard Jounghyun

    2015-01-01

    Introduction What HCI Is and Why It Is Important Principles of HCI     ""Know Thy User""      Understand the Task      Reduce Memory Load      Strive for Consistency      Remind Users and Refresh Their Memory      Prevent Errors/Reversal of Action      Naturalness SummaryReferences Specific HCI Guidelines Guideline Categories Examples of HCI Guidelines      Visual Display Layout (General HCI Design)      Information Structuring and Navigation (General HCI Design)      Taking User Input (General H

  2. Fundamentals of fluid lubrication

    Science.gov (United States)

    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. Infosec management fundamentals

    CERN Document Server

    Dalziel, Henry

    2015-01-01

    Infosec Management Fundamentals is a concise overview of the Information Security management concepts and techniques, providing a foundational template for both experienced professionals and those new to the industry. This brief volume will also appeal to business executives and managers outside of infosec who want to understand the fundamental concepts of Information Security and how it impacts their business decisions and daily activities. Teaches ISO/IEC 27000 best practices on information security management Discusses risks and controls within the context of an overall information securi

  4. Fundamentals of piping design

    CERN Document Server

    Smith, Peter

    2013-01-01

    Written for the piping engineer and designer in the field, this two-part series helps to fill a void in piping literature,since the Rip Weaver books of the '90s were taken out of print at the advent of the Computer Aid Design(CAD) era. Technology may have changed, however the fundamentals of piping rules still apply in the digitalrepresentation of process piping systems. The Fundamentals of Piping Design is an introduction to the designof piping systems, various processes and the layout of pipe work connecting the major items of equipment forthe new hire, the engineering student and the vetera

  5. Homeschooling and religious fundamentalism

    Directory of Open Access Journals (Sweden)

    Robert KUNZMAN

    2010-10-01

    Full Text Available 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 contemporary culture; suspicion of institutional authority and professional expertise; parental control and centrality of the family; and interweaving of faith and academics. It is important to recognize, however, that fundamentalism exists on a continuum; conservative religious homeschoolers resist liberal democratic values to varying degrees, and efforts to foster dialogue and accommodation with religious homeschoolers can ultimately helpstrengthen the broader civic fabric.

  6. Pragmatic electrical engineering fundamentals

    CERN Document Server

    Eccles, William

    2011-01-01

    Pragmatic Electrical Engineering: Fundamentals introduces the fundamentals of the energy-delivery part of electrical systems. It begins with a study of basic electrical circuits and then focuses on electrical power. Three-phase power systems, transformers, induction motors, and magnetics are the major topics.All of the material in the text is illustrated with completely-worked examples to guide the student to a better understanding of the topics. This short lecture book will be of use at any level of engineering, not just electrical. Its goal is to provide the practicing engineer with a practi

  7. Fundamentals of nonlinear optics

    CERN Document Server

    Powers, Peter E

    2011-01-01

    Peter Powers's rigorous but simple description of a difficult field keeps the reader's attention throughout. … All chapters contain a list of references and large numbers of practice examples to be worked through. … By carefully working through the proposed problems, students will develop a sound understanding of the fundamental principles and applications. … the book serves perfectly for an introductory-level course for second- and third-order nonlinear optical phenomena. The author's writing style is refreshing and original. I expect that Fundamentals of Nonlinear Optics will fast become pop

  8. Fundamentals of continuum mechanics

    CERN Document Server

    Rudnicki, John W

    2014-01-01

    A concise introductory course text on continuum mechanics Fundamentals of Continuum Mechanics focuses on the fundamentals of the subject and provides the background for formulation of numerical methods for large deformations and a wide range of material behaviours. It aims to provide the foundations for further study, not just of these subjects, but also the formulations for much more complex material behaviour and their implementation computationally.  This book is divided into 5 parts, covering mathematical preliminaries, stress, motion and deformation, balance of mass, momentum and energ

  9. Antennas fundamentals, design, measurement

    CERN Document Server

    Long, Maurice

    2009-01-01

    This comprehensive revision (3rd Edition) is a senior undergraduate or first-year graduate level textbook on antenna fundamentals, design, performance analysis, and measurements. In addition to its use as a formal course textbook, the book's pragmatic style and emphasis on the fundamentals make it especially useful to engineering professionals who need to grasp the essence of the subject quickly but without being mired in unnecessary detail. This new edition was prepared for a first year graduate course at Southern Polytechnic State University in Georgia. It provides broad coverage of antenna

  10. Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.

    Science.gov (United States)

    Cory, Seth A; Van Vranken, Jonathan G; Brignole, Edward J; Patra, Shachin; Winge, Dennis R; Drennan, Catherine L; Rutter, Jared; Barondeau, David P

    2017-07-03

    In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters. Here we present crystallographic and electron microscopic structures of the SDA complex coupled to enzyme kinetic and cell-based studies to provide structure-function properties of a mitochondrial cysteine desulfurase. Unlike prokaryotic cysteine desulfurases, the SDA structure adopts an unexpected architecture in which a pair of ISD11 subunits form the dimeric core of the SDA complex, which clarifies the critical role of ISD11 in eukaryotic assemblies. The different quaternary structure results in an incompletely formed substrate channel and solvent-exposed pyridoxal 5'-phosphate cofactor and provides a rationale for the allosteric activator function of FXN in eukaryotic systems. The structure also reveals the 4'-phosphopantetheine-conjugated acyl-group of ACP occupies the hydrophobic core of ISD11, explaining the basis of ACP stabilization. The unexpected architecture for the SDA complex provides a framework for understanding interactions with acceptor proteins for sulfur-containing biosynthetic pathways, elucidating mechanistic details of eukaryotic Fe-S cluster biosynthesis, and clarifying how defects in Fe-S cluster assembly lead to diseases such as Friedreich's ataxia. Moreover, our results support a lock-and-key model in which LYR proteins associate with acyl-ACP as a mechanism for fatty acid biosynthesis to coordinate the expression, Fe-S cofactor maturation, and activity of the respiratory complexes.

  11. Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans.

    Science.gov (United States)

    Ferguson, Jane F; Xue, Chenyi; Hu, Yu; Li, Mingyao; Reilly, Muredach P

    2016-04-01

    Dietary consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against cardiometabolic disease through modulation of systemic and adipose inflammation. However, it is often difficult to detect the subtle effects of n-3 PUFA on inflammatory biomarkers in traditional intervention studies. We aimed to identify novel n-3 PUFA modulated gene expression using unbiased adipose transcriptomics during evoked endotoxemia in a clinical trial of n-3 PUFA supplementation. We analyzed adipose gene expression using RNA sequencing in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) trial of healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=8; 3600mg/day EPA/DHA) for 6weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (lipopolysaccharide 0.6ng/kg i.v.). As expected, supplementation with n-3 PUFA vs. placebo alone had only modest effects on adipose tissue gene expression, e.g., increased expression of immediate early response IER2. In contrast, the transcriptomic response to evoked endotoxemia was significantly modified by n-3 PUFA supplementation, with several genes demonstrating significant n-3 PUFA gene-nutrient interactions, e.g., enhanced transcriptional responses in specific immune genes IER5L, HES1, IL1RN, CCL18, IL1RN, IL7R, IL8, CCL3 and others. These data highlight potential mechanisms whereby n-3 PUFA consumption may enhance the immune response to an inflammatory challenge. In conclusion, unbiased transcriptomics during evoked inflammation reveals novel immune modulating functions of n-3 PUFA nutritional intervention in a dynamic pathophysiological setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Complex interactions of the Eastern and Western Slavic populations with other European groups as revealed by mitochondrial DNA analysis.

    Science.gov (United States)

    Grzybowski, Tomasz; Malyarchuk, Boris A; Derenko, Miroslava V; Perkova, Maria A; Bednarek, Jarosław; Woźniak, Marcin

    2007-06-01

    Mitochondrial DNA sequence variation was examined by the control region sequencing (HVS I and HVS II) and RFLP analysis of haplogroup-diagnostic coding region sites in 570 individuals from four regional populations of Poles and two Russian groups from northwestern part of the country. Additionally, sequences of complete mitochondrial genomes representing K1a1b1a subclade in Polish and Polish Roma populations have been determined. Haplogroup frequency patterns revealed in Poles and Russians are similar to those characteristic of other Europeans. However, there are several features of Slavic mtDNA pools seen on the level of regional populations which are helpful in the understanding of complex interactions of the Eastern and Western Slavic populations with other European groups. One of the most important is the presence of subhaplogroups U5b1b1, D5, Z1 and U8a with simultaneous scarcity of haplogroup K in populations of northwestern Russia suggesting the participation of Finno-Ugrian tribes in the formation of mtDNA pools of Russians from this region. The results of genetic structure analyses suggest that Russians from Velikii Novgorod area (northwestern Russia) and Poles from Suwalszczyzna (northeastern Poland) differ from all remaining Polish and Russian samples. Simultaneously, northwestern Russians and northeastern Poles bear some similarities to Baltic (Latvians) and Finno-Ugrian groups (Estonians) of northeastern Europe, especially on the level of U5 haplogroup frequencies. The occurrence of K1a1b1a subcluster in Poles and Polish Roma is one of the first direct proofs of the presence of Ashkenazi-specific mtDNA lineages in non-Jewish European populations.

  13. Conformational dynamics of abasic DNA upon interactions with AP endonuclease 1 revealed by stopped-flow fluorescence analysis.

    Science.gov (United States)

    Kanazhevskaya, Lyubov Yu; Koval, Vladimir V; Vorobjev, Yury N; Fedorova, Olga S

    2012-02-14

    Apurinic/apyrimidinic (AP) sites are abundant DNA lesions arising from exposure to UV light, ionizing radiation, alkylating agents, and oxygen radicals. In human cells, AP endonuclease 1 (APE1) recognizes this mutagenic lesion and initiates its repair via a specific incision of the phosphodiester backbone 5' to the AP site. We have investigated a detailed mechanism of APE1 functioning using fluorescently labeled DNA substrates. A fluorescent adenine analogue, 2-aminopurine, was introduced into DNA substrates adjacent to the abasic site to serve as an on-site reporter of conformational transitions in DNA during the catalytic cycle. Application of a pre-steady-state stopped-flow technique allows us to observe changes in the fluorescence intensity corresponding to different stages of the process in real time. We also detected an intrinsic Trp fluorescence of the enzyme during interactions with 2-aPu-containing substrates. Our data have revealed a conformational flexibility of the abasic DNA being processed by APE1. Quantitative analysis of fluorescent traces has yielded a minimal kinetic scheme and appropriate rate constants consisting of four steps. The results obtained from stopped-flow data have shown a substantial influence of the 2-aPu base location on completion of certain reaction steps. Using detailed molecular dynamics simulations of the DNA substrates, we have attributed structural distortions of AP-DNA to realization of specific binding, effective locking, and incision of the damaged DNA. The findings allowed us to accurately discern the step that corresponds to insertion of specific APE1 amino acid residues into the abasic DNA void in the course of stabilization of the precatalytic complex.

  14. A Colletotrichum graminicola mutant deficient in the establishment of biotrophy reveals early transcriptional events in the maize anthracnose disease interaction.

    Science.gov (United States)

    Torres, Maria F; Ghaffari, Noushin; Buiate, Ester A S; Moore, Neil; Schwartz, Scott; Johnson, Charles D; Vaillancourt, Lisa J

    2016-03-08

    Colletotrichum graminicola is a hemibiotrophic fungal pathogen that causes maize anthracnose disease. It progresses through three recognizable phases of pathogenic development in planta: melanized appressoria on the host surface prior to penetration; biotrophy, characterized by intracellular colonization of living host cells; and necrotrophy, characterized by host cell death and symptom development. A "Mixed Effects" Generalized Linear Model (GLM) was developed and applied to an existing Illumina transcriptome dataset, substantially increasing the statistical power of the analysis of C. graminicola gene expression during infection and colonization. Additionally, the in planta transcriptome of the wild-type was compared with that of a mutant strain impaired in the establishment of biotrophy, allowing detailed dissection of events occurring specifically during penetration, and during early versus late biotrophy. More than 2000 fungal genes were differentially transcribed during appressorial maturation, penetration, and colonization. Secreted proteins, secondary metabolism genes, and membrane receptors were over-represented among the differentially expressed genes, suggesting that the fungus engages in an intimate and dynamic conversation with the host, beginning prior to penetration. This communication process probably involves reception of plant signals triggering subsequent developmental progress in the fungus, as well as production of signals that induce responses in the host. Later phases of biotrophy were more similar to necrotrophy, with increased production of secreted proteases, inducers of plant cell death, hydrolases, and membrane bound transporters for the uptake and egress of potential toxins, signals, and nutrients. This approach revealed, in unprecedented detail, fungal genes specifically expressed during critical phases of host penetration and biotrophic establishment. Many encoded secreted proteins, secondary metabolism enzymes, and receptors that may

  15. Dynamic membrane interactions of antibacterial and antifungal biomolecules, and amyloid peptides, revealed by solid-state NMR spectroscopy.

    Science.gov (United States)

    Naito, Akira; Matsumori, Nobuaki; Ramamoorthy, Ayyalusamy

    2017-06-06

    A variety of biomolecules acting on the cell membrane folds into a biologically active structure in the membrane environment. It is, therefore, important to determine the structures and dynamics of such biomolecules in a membrane environment. While several biophysical techniques are used to obtain low-resolution information, solid-state NMR spectroscopy is one of the most powerful means for determining the structure and dynamics of membrane bound biomolecules such as antibacterial biomolecules and amyloidogenic proteins; unlike X-ray crystallography and solution NMR spectroscopy, applications of solid-state NMR spectroscopy are not limited by non-crystalline, non-soluble nature or molecular size of membrane-associated biomolecules. This review article focuses on the applications of solid-state NMR techniques to study a few selected antibacterial and amyloid peptides. Solid-state NMR studies revealing the membrane inserted bent α-helical structure associated with the hemolytic activity of bee venom melittin and the chemical shift oscillation analysis used to determine the transmembrane structure (with α-helix and 310-helix in the N- and C-termini, respectively) of antibiotic peptide alamethicin are discussed in detail. Oligomerization of an amyloidogenic islet amyloid polypeptide (IAPP, or also known as amylin) resulting from its aggregation in a membrane environment, molecular interactions of the antifungal natural product amphotericin B with ergosterol in lipid bilayers, and the mechanism of lipid raft formation by sphingomyelin studied using solid state NMR methods are also discussed in this review article. This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Homeschooling and Religious Fundamentalism

    Science.gov (United States)

    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…

  17. Fundamentals of Business Economics

    OpenAIRE

    2013-01-01

    Powerpoint presentations of the 9 theoretical units of the subject: Fundamentals of Business Economics. Business Administration Degree. Faculty of Economics. University of Alicante En el marco de ayudas a preparación de materiales docentes en lengua inglesa, por parte del Servei de Política Llingüística de la Universidad de Alicante

  18. Fundamental Physics Microgravity Sensitivity

    Science.gov (United States)

    Israelsson, Ulf

    1998-01-01

    An introduction followed by a brief discussion about the sensitivity to microgravity environment disturbances for some recent and planned experiments in microgravity fundamental physics will be presented. In particular, correlation between gravity disturbances and the quality of science data sets measured by the Confined Helium Experiment (CHEX) during ground testing and during the November 1997 USMP-4 flight will be described.

  19. Fundamental Metallurgy of Solidification

    DEFF Research Database (Denmark)

    Tiedje, Niels

    2004-01-01

    The text takes the reader through some fundamental aspects of solidification, with focus on understanding the basic physics that govern solidification in casting and welding. It is described how the first solid is formed and which factors affect nucleation. It is described how crystals grow from ...

  20. Fundamentals of convolutional coding

    CERN Document Server

    Johannesson, Rolf

    2015-01-01

    Fundamentals of Convolutional Coding, Second Edition, regarded as a bible of convolutional coding brings you a clear and comprehensive discussion of the basic principles of this field * Two new chapters on low-density parity-check (LDPC) convolutional codes and iterative coding * Viterbi, BCJR, BEAST, list, and sequential decoding of convolutional codes * Distance properties of convolutional codes * Includes a downloadable solutions manual

  1. Fundamentals of soil science

    Science.gov (United States)

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

  2. Fundamentals and Optimal Institutions

    DEFF Research Database (Denmark)

    Gonzalez-Eiras, Martin; Harmon, Nikolaj Arpe; Rossi, Martín

    2016-01-01

    of regulatory institutions such as revenue sharing, salary caps or luxury taxes. We show, theoretically and empirically, that these large differences in adopted institutions can be rationalized as optimal responses to differences in the fundamental characteristics of the sports being played. This provides...

  3. Fundamentals of astrodynamics

    NARCIS (Netherlands)

    Wakker, K.F.

    2015-01-01

    This book deals with the motion of the center of mass of a spacecraft; this discipline is generally called astrodynamics. The book focuses on an analytical treatment of the motion of spacecraft and provides insight into the fundamentals of spacecraft orbit dynamics. A large number of topics are trea

  4. Fundamentals of plasma physics

    CERN Document Server

    Bittencourt, J A

    1986-01-01

    A general introduction designed to present a comprehensive, logical and unified treatment of the fundamentals of plasma physics based on statistical kinetic theory. Its clarity and completeness make it suitable for self-learning and self-paced courses. Problems are included.

  5. Characterization of genome-wide enhancer-promoter interactions reveals co-expression of interacting genes and modes of higher order chromatin organization

    Institute of Scientific and Technical Information of China (English)

    Iouri Chepelev; Gang Wei; Dara Wangsa; Qingsong Tang; Keji Zhao

    2012-01-01

    Recent epigenomic studies have predicted thousands of potential enhancers in the human genome.However,there has not been systematic characterization of target promoters for these potential enhancers.Using H3K4me2 as a mark for active enhancers,we identified genome-wide EP interactions in human CD4+ T cells.Among the 6 520 longdistance chromatin interactions,we identify 2 067 enhancers that interact with 1 619 promoters and enhance their expression.These enhancers exist in accessible chromatin regions and are associated with various histone modifications and polymerase Ⅱ binding.The promoters with interacting enhancers are expressed at higher levels than those without interacting enhancers,and their expression levels are positively correlated with the number of interacting enhancers.Interestingly,interacting promoters are co-expressed in a tissue-specific manner.We also find that chromosomes are organized into multiple levels of interacting domains.Our results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization.The Gene Expression Omnibus accession number for the raw and analyzed chromatin interaction data is GSE32677.

  6. Modeling of fundamental phenomena in welds

    Energy Technology Data Exchange (ETDEWEB)

    Zacharia, T.; Vitek, J.M. [Oak Ridge National Lab., TN (United States); Goldak, J.A. [Carleton Univ., Ottawa, Ontario (Canada); DebRoy, T.A. [Pennsylvania State Univ., University Park, PA (United States); Rappaz, M. [Ecole Polytechnique Federale de Lausanne (Switzerland); Bhadeshia, H.K.D.H. [Cambridge Univ. (United Kingdom)

    1993-12-31

    Recent advances in the mathematical modeling of fundamental phenomena in welds are summarized. State-of-the-art mathematical models, advances in computational techniques, emerging high-performance computers, and experimental validation techniques have provided significant insight into the fundamental factors that control the development of the weldment. The current status and scientific issues in the areas of heat and fluid flow in welds, heat source metal interaction, solidification microstructure, and phase transformations are assessed. Future research areas of major importance for understanding the fundamental phenomena in weld behavior are identified.

  7. Ion beam analysis fundamentals and applications

    CERN Document Server

    Nastasi, Michael; Wang, Yongqiang

    2015-01-01

    Ion Beam Analysis: Fundamentals and Applications explains the basic characteristics of ion beams as applied to the analysis of materials, as well as ion beam analysis (IBA) of art/archaeological objects. It focuses on the fundamentals and applications of ion beam methods of materials characterization.The book explains how ions interact with solids and describes what information can be gained. It starts by covering the fundamentals of ion beam analysis, including kinematics, ion stopping, Rutherford backscattering, channeling, elastic recoil detection, particle induced x-ray emission, and nucle

  8. Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication

    Directory of Open Access Journals (Sweden)

    Bryder David

    2010-02-01

    the stroma. The functional consequences of this were investigated by co-culture experiments revealing that the co-incubation of stromal cells with B cell progenitors altered both the morphology and the gene expression pattern in the stromal cells. Conclusions We believe that this gene expression data analysis method allows for the identification of functionally relevant interactions and therefore could be applied to other data sets to unravel novel communication pathways.

  9. Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci.

    Science.gov (United States)

    Martin, Paul; McGovern, Amanda; Orozco, Gisela; Duffus, Kate; Yarwood, Annie; Schoenfelder, Stefan; Cooper, Nicholas J; Barton, Anne; Wallace, Chris; Fraser, Peter; Worthington, Jane; Eyre, Steve

    2015-11-30

    Genome-wide association studies have been tremendously successful in identifying genetic variants associated with complex diseases. The majority of association signals are intergenic and evidence is accumulating that a high proportion of signals lie in enhancer regions. We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines. Here we report numerous looping interactions and provide evidence that only a minority of interactions are common to both B- and T-cell lines, suggesting interactions may be highly cell-type specific; some disease-associated SNPs do not interact with the nearest gene but with more compelling candidate genes (for example, FOXO1, AZI2) often situated several megabases away; and finally, regions associated with different autoimmune diseases interact with each other and the same promoter suggesting common autoimmune gene targets (for example, PTPRC, DEXI and ZFP36L1).

  10. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer

    National Research Council Canada - National Science Library

    Ihsan, Rakhshan; Chauhan, Pradeep Singh; Mishra, Ashwani Kumar; Yadav, Dhirendra Singh; Kaushal, Mishi; Sharma, Jagannath Dev; Zomawia, Eric; Verma, Yogesh; Kapur, Sujala; Saxena, Sunita

    2011-01-01

    ...) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors...

  11. Multiple Analytical Approaches Reveal Distinct Gene-Environment Interactions in Smokers and Non Smokers in Lung Cancer: e29431

    National Research Council Canada - National Science Library

    Rakhshan Ihsan; Pradeep Singh Chauhan; Ashwani Kumar Mishra; Dhirendra Singh Yadav; Mishi Kaushal; Jagannath Dev Sharma; Eric Zomawia; Yogesh Verma; Sujala Kapur; Sunita Saxena

    2011-01-01

    ...) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors...

  12. Structural and mutational analyses of the interaction between the barley alpha-amylase/subtilisin inhibitor and the subtilisin savinase reveal a novel mode of inhibition.

    Science.gov (United States)

    Micheelsen, Pernille Ollendorff; Vévodová, Jitka; De Maria, Leonardo; Ostergaard, Peter Rahbek; Friis, Esben Peter; Wilson, Keith; Skjøt, Michael

    2008-07-18

    Subtilisins represent a large class of microbial serine proteases. To date, there are three-dimensional structures of proteinaceous inhibitors from three families in complex with subtilisins in the Protein Data Bank. All interact with subtilisin via an exposed loop covering six interacting residues. Here we present the crystal structure of the complex between the Bacillus lentus subtilisin Savinase and the barley alpha-amylase/subtilisin inhibitor (BASI). This is the first reported structure of a cereal Kunitz-P family inhibitor in complex with a subtilisin. Structural analysis revealed that BASI inhibits Savinase in a novel way, as the interacting loop is shorter than loops previously reported. Mutational analysis showed that Thr88 is crucial for the inhibition, as it stabilises the interacting loop through intramolecular interactions with the BASI backbone.

  13. Fundamental stellar parameters

    CERN Document Server

    Wittkowski, M

    2004-01-01

    I present a discussion of fundamental stellar parameters and their observational determination in the context of interferometric measurements with current and future optical/infrared interferometric facilities. Stellar parameters and the importance of their determination for stellar physics are discussed. One of the primary uses of interferometry in the field of stellar physics is the measurement of the intensity profile across the stellar disk, both as a function of position angle and of wavelength. High-precision fundamental stellar parameters are also derived by characterizations of binary and multiple system using interferometric observations. This topic is discussed in detail elsewhere in these proceedings. Comparison of observed spectrally dispersed center-to-limb intensity variations with models of stellar atmospheres and stellar evolution may result in an improved understanding of key phenomena in stellar astrophysics such as the precise evolutionary effects on the main sequence, the evolution of meta...

  14. Fundamentals of nuclear physics

    CERN Document Server

    Takigawa, Noboru

    2017-01-01

    This book introduces the current understanding of the fundamentals of nuclear physics by referring to key experimental data and by providing a theoretical understanding of principal nuclear properties. It primarily covers the structure of nuclei at low excitation in detail. It also examines nuclear forces and decay properties. In addition to fundamentals, the book treats several new research areas such as non-relativistic as well as relativistic Hartree–Fock calculations, the synthesis of super-heavy elements, the quantum chromodynamics phase diagram, and nucleosynthesis in stars, to convey to readers the flavor of current research frontiers in nuclear physics. The authors explain semi-classical arguments and derivation of its formulae. In these ways an intuitive understanding of complex nuclear phenomena is provided. The book is aimed at graduate school students as well as junior and senior undergraduate students and postdoctoral fellows. It is also useful for researchers to update their knowledge of diver...

  15. Fundamentals of differential beamforming

    CERN Document Server

    Benesty, Jacob; Pan, Chao

    2016-01-01

    This book provides a systematic study of the fundamental theory and methods of beamforming with differential microphone arrays (DMAs), or differential beamforming in short. It begins with a brief overview of differential beamforming and some popularly used DMA beampatterns such as the dipole, cardioid, hypercardioid, and supercardioid, before providing essential background knowledge on orthogonal functions and orthogonal polynomials, which form the basis of differential beamforming. From a physical perspective, a DMA of a given order is defined as an array that measures the differential acoustic pressure field of that order; such an array has a beampattern in the form of a polynomial whose degree is equal to the DMA order. Therefore, the fundamental and core problem of differential beamforming boils down to the design of beampatterns with orthogonal polynomials. But certain constraints also have to be considered so that the resulting beamformer does not seriously amplify the sensors’ self noise and the mism...

  16. Fundamentals of Polarized Light

    Science.gov (United States)

    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.

  17. What is Fundamental?

    CERN Multimedia

    2004-01-01

    Discussing what is fundamental in a variety of fields, biologist Richard Dawkins, physicist Gerardus 't Hooft, and mathematician Alain Connes spoke to a packed Main Auditorium at CERN 15 October. Dawkins, Professor of the Public Understanding of Science at Oxford University, explained simply the logic behind Darwinian natural selection, and how it would seem to apply anywhere in the universe that had the right conditions. 't Hooft, winner of the 1999 Physics Nobel Prize, outlined some of the main problems in physics today, and said he thinks physics is so fundamental that even alien scientists from another planet would likely come up with the same basic principles, such as relativity and quantum mechanics. Connes, winner of the 1982 Fields Medal (often called the Nobel Prize of Mathematics), explained how physics is different from mathematics, which he described as a "factory for concepts," unfettered by connection to the physical world. On 16 October, anthropologist Sharon Traweek shared anecdotes from her ...

  18. Fundamental composite electroweak dynamics

    DEFF Research Database (Denmark)

    Arbey, Alexandre; Cacciapaglia, Giacomo; Cai, Haiying

    2017-01-01

    Using the recent joint results from the ATLAS and CMS collaborations on the Higgs boson, we determine the current status of composite electroweak dynamics models based on the expected scalar sector. Our analysis can be used as a minimal template for a wider class of models between the two limiting...... cases of composite Goldstone Higgs and Technicolor-like ones. This is possible due to the existence of a unified description, both at the effective and fundamental Lagrangian levels, of models of composite Higgs dynamics where the Higgs boson itself can emerge, depending on the way the electroweak...... space at the effective Lagrangian level. We show that a wide class of models of fundamental composite electroweak dynamics are still compatible with the present constraints. The results are relevant for the ongoing and future searches at the Large Hadron Collider....

  19. Fundamentals of Stochastic Networks

    CERN Document Server

    Ibe, Oliver C

    2011-01-01

    An interdisciplinary approach to understanding queueing and graphical networks In today's era of interdisciplinary studies and research activities, network models are becoming increasingly important in various areas where they have not regularly been used. Combining techniques from stochastic processes and graph theory to analyze the behavior of networks, Fundamentals of Stochastic Networks provides an interdisciplinary approach by including practical applications of these stochastic networks in various fields of study, from engineering and operations management to communications and the physi

  20. Fundamentals of queueing theory

    CERN Document Server

    Gross, Donald; Thompson, James M; Harris, Carl M

    2013-01-01

    Praise for the Third Edition ""This is one of the best books available. Its excellent organizational structure allows quick reference to specific models and its clear presentation . . . solidifies the understanding of the concepts being presented.""-IIE Transactions on Operations Engineering Thoroughly revised and expanded to reflect the latest developments in the field, Fundamentals of Queueing Theory, Fourth Edition continues to present the basic statistical principles that are necessary to analyze the probabilistic nature of queues. Rather than pre

  1. Fundamentals of Monte Carlo

    Energy Technology Data Exchange (ETDEWEB)

    Wollaber, Allan Benton [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-06-16

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

  2. High voltage engineering fundamentals

    CERN Document Server

    Kuffel, E; Hammond, P

    1984-01-01

    Provides a comprehensive treatment of high voltage engineering fundamentals at the introductory and intermediate levels. It covers: techniques used for generation and measurement of high direct, alternating and surge voltages for general application in industrial testing and selected special examples found in basic research; analytical and numerical calculation of electrostatic fields in simple practical insulation system; basic ionisation and decay processes in gases and breakdown mechanisms of gaseous, liquid and solid dielectrics; partial discharges and modern discharge detectors; and over

  3. Biomedical engineering fundamentals

    CERN Document Server

    Bronzino, Joseph D

    2014-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering.Biomedical Engineering Fundamentals, the first volume of the handbook, presents material from respected scientists with diverse backgrounds in physiological systems, biomechanics, biomaterials, bioelectric phenomena, and neuroengineering. More than three dozen specific topics are examined, including cardia

  4. Fundamentals of neurobiology.

    Science.gov (United States)

    Greg Hall, D

    2011-01-01

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

  5. Fundamentals of Biomechanics

    OpenAIRE

    Duane Knudson

    2007-01-01

    DESCRIPTION This book provides a broad and in-depth theoretical and practical description of the fundamental concepts in understanding biomechanics in the qualitative analysis of human movement. PURPOSE The aim is to bring together up-to-date biomechanical knowledge with expert application knowledge. Extensive referencing for students is also provided. FEATURES This textbook is divided into 12 chapters within four parts, including a lab activities section at the end. The division is as follow...

  6. Fundamentals of linear algebra

    CERN Document Server

    Dash, Rajani Ballav

    2008-01-01

    FUNDAMENTALS OF LINEAR ALGEBRA is a comprehensive Text Book, which can be used by students and teachers of All Indian Universities. The Text has easy, understandable form and covers all topics of UGC Curriculum. There are lots of worked out examples which helps the students in solving the problems without anybody's help. The Problem sets have been designed keeping in view of the questions asked in different examinations.

  7. Value of Fundamental Science

    Science.gov (United States)

    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?

  8. The Transcriptome of Compatible and Incompatible Interactions of Potato (Solanum tuberosum) with Phytophthora infestans Revealed by DeepSAGE Analysis

    DEFF Research Database (Denmark)

    Gyetvai, Gabor; Sønderkær, Mads; Göbel, Ulrike

    2012-01-01

    -assissted selection or by transgenic approaches. Specific P. infestans races having the Avr1 effector gene trigger a hypersensitive resistance response in potato plants carrying the R1 resistance gene (incompatible interaction) and cause disease in plants lacking R1 (compatible interaction). The transcriptomes...

  9. Virtual screening and experimental validation reveal novel small-molecule inhibitors of 14-3-3 protein-protein interactions.

    Science.gov (United States)

    Thiel, Philipp; Röglin, Lars; Meissner, Nicole; Hennig, Sven; Kohlbacher, Oliver; Ottmann, Christian

    2013-10-04

    We report first non-covalent and exclusively extracellular inhibitors of 14-3-3 protein-protein interactions identified by virtual screening. Optimization by crystal structure analysis and in vitro binding assays yielded compounds capable of disrupting the interaction of 14-3-3σ with aminopeptidase N in a cellular assay.

  10. Current status and future perspectives of electron interactions with molecules, clusters, surfaces, and interfaces [Workshop on Fundamental challenges in electron-driven chemistry; Workshop on Electron-driven processes: Scientific challenges and technological opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Kurt H.; McCurdy, C. William; Orlando, Thomas M.; Rescigno, Thomas N.

    2000-09-01

    This report is based largely on presentations and discussions at two workshops and contributions from workshop participants. The workshop on Fundamental Challenges in Electron-Driven Chemistry was held in Berkeley, October 9-10, 1998, and addressed questions regarding theory, computation, and simulation. The workshop on Electron-Driven Processes: Scientific Challenges and Technological Opportunities was held at Stevens Institute of Technology, March 16-17, 2000, and focused largely on experiments. Electron-molecule and electron-atom collisions initiate and drive almost all the relevant chemical processes associated with radiation chemistry, environmental chemistry, stability of waste repositories, plasma-enhanced chemical vapor deposition, plasma processing of materials for microelectronic devices and other applications, and novel light sources for research purposes (e.g. excimer lamps in the extreme ultraviolet) and in everyday lighting applications. The life sciences are a rapidly advancing field where the important role of electron-driven processes is only now beginning to be recognized. Many of the applications of electron-initiated chemical processes require results in the near term. A large-scale, multidisciplinary and collaborative effort should be mounted to solve these problems in a timely way so that their solution will have the needed impact on the urgent questions of understanding the physico-chemical processes initiated and driven by electron interactions.

  11. Complex structure of cytochrome c-cytochrome c oxidase reveals a novel protein-protein interaction mode.

    Science.gov (United States)

    Shimada, Satoru; Shinzawa-Itoh, Kyoko; Baba, Junpei; Aoe, Shimpei; Shimada, Atsuhiro; Yamashita, Eiki; Kang, Jiyoung; Tateno, Masaru; Yoshikawa, Shinya; Tsukihara, Tomitake

    2017-02-01

    Mitochondrial cytochrome c oxidase (CcO) transfers electrons from cytochrome c (Cyt.c) to O2 to generate H2O, a process coupled to proton pumping. To elucidate the mechanism of electron transfer, we determined the structure of the mammalian Cyt.c-CcO complex at 2.0-Å resolution and identified an electron transfer pathway from Cyt.c to CcO. The specific interaction between Cyt.c and CcO is stabilized by a few electrostatic interactions between side chains within a small contact surface area. Between the two proteins are three water layers with a long inter-molecular span, one of which lies between the other two layers without significant direct interaction with either protein. Cyt.c undergoes large structural fluctuations, using the interacting regions with CcO as a fulcrum. These features of the protein-protein interaction at the docking interface represent the first known example of a new class of protein-protein interaction, which we term "soft and specific". This interaction is likely to contribute to the rapid association/dissociation of the Cyt.c-CcO complex, which facilitates the sequential supply of four electrons for the O2 reduction reaction.

  12. Revealing the interactions between pentagon-octagon-pentagon defect graphene and organic donor/acceptor molecules: a theoretical study.

    Science.gov (United States)

    Li, Jie-Wei; Liu, Yu-Yu; Xie, Ling-Hai; Shang, Jing-Zhi; Qian, Yan; Yi, Ming-Dong; Yu, Ting; Huang, Wei

    2015-02-21

    Defect engineering and the non-covalent interaction strategy allow for dramatically tuning the optoelectronic features of graphene. Herein, we theoretically investigated the intrinsic mechanism of non-covalent interactions between pentagon-octagon-pentagon (5-8-5) defect graphene (DG) and absorbed molecules, tetrathiafulvalene (TTF), perfluoronaphthalene (FNa), tetracyanoquinodimethane (TCNQ) and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), through geometry, distance, interaction energy, Mulliken charge distribution, terahertz frequency vibration, visualization of the interactions, charge density difference, electronic transition behaviour, band structure and density of state. All the calculations were performed using density functional theory including a dispersion correction (DFT-D). The calculated results indicate that the cyano- (CN) group (electron withdraw group) in TCNQ and F4TCNQ, rather than the F group, gain the electron from DG effectively and exhibit much stronger interactions via wavefunction overlap with DG, leading to a short non-covalent interaction distance, a large interaction energy and a red-shift of out-of-plane terahertz frequency vibration, changing the bands near the Fermi level and enhancing the infrared (IR) light absorption significantly. The enhancement of such IR absorbance offering a broader absorption (from 300 to 1200 nm) will benefit light harvesting in potential applications of solar energy conversion.

  13. Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions

    DEFF Research Database (Denmark)

    Zhu, Xuefeng; Wirén, Marianna; Sinha, Indranil

    2006-01-01

    to investigate genome-wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display similar binding patterns, and interactions with promoters and upstream activating sequences correlate with increased transcription activity. Unexpectedly, Mediator also interacts...... with the downstream coding region of many genes. These interactions display a negative bias for positions closer to the 5' ends of open reading frames (ORFs) and appear functionally important, because downregulation of transcription in a temperature-sensitive med17 mutant strain correlates with increased Mediator...

  14. Brain transcriptome-wide screen for HIV-1 Nef protein interaction partners reveals various membrane-associated proteins.

    Directory of Open Access Journals (Sweden)

    Ellen C Kammula

    Full Text Available HIV-1 Nef protein contributes essentially to the pathology of AIDS by a variety of protein-protein-interactions within the host cell. The versatile functionality of Nef is partially attributed to different conformational states and posttranslational modifications, such as myristoylation. Up to now, many interaction partners of Nef have been identified using classical yeast two-hybrid screens. Such screens rely on transcriptional activation of reporter genes in the nucleus to detect interactions. Thus, the identification of Nef interaction partners that are integral membrane proteins, membrane-associated proteins or other proteins that do not translocate into the nucleus is hampered. In the present study, a split-ubiquitin based yeast two-hybrid screen was used to identify novel membrane-localized interaction partners of Nef. More than 80% of the hereby identified interaction partners of Nef are transmembrane proteins. The identified hits are GPM6B, GPM6A, BAP31, TSPAN7, CYB5B, CD320/TCblR, VSIG4, PMEPA1, OCIAD1, ITGB1, CHN1, PH4, CLDN10, HSPA9, APR-3, PEBP1 and B3GNT, which are involved in diverse cellular processes like signaling, apoptosis, neurogenesis, cell adhesion and protein trafficking or quality control. For a subfraction of the hereby identified proteins we present data supporting their direct interaction with HIV-1 Nef. We discuss the results with respect to many phenotypes observed in HIV infected cells and patients. The identified Nef interaction partners may help to further elucidate the molecular basis of HIV-related diseases.

  15. Brain transcriptome-wide screen for HIV-1 Nef protein interaction partners reveals various membrane-associated proteins.

    Science.gov (United States)

    Kammula, Ellen C; Mötter, Jessica; Gorgels, Alexandra; Jonas, Esther; Hoffmann, Silke; Willbold, Dieter

    2012-01-01

    HIV-1 Nef protein contributes essentially to the pathology of AIDS by a variety of protein-protein-interactions within the host cell. The versatile functionality of Nef is partially attributed to different conformational states and posttranslational modifications, such as myristoylation. Up to now, many interaction partners of Nef have been identified using classical yeast two-hybrid screens. Such screens rely on transcriptional activation of reporter genes in the nucleus to detect interactions. Thus, the identification of Nef interaction partners that are integral membrane proteins, membrane-associated proteins or other proteins that do not translocate into the nucleus is hampered. In the present study, a split-ubiquitin based yeast two-hybrid screen was used to identify novel membrane-localized interaction partners of Nef. More than 80% of the hereby identified interaction partners of Nef are transmembrane proteins. The identified hits are GPM6B, GPM6A, BAP31, TSPAN7, CYB5B, CD320/TCblR, VSIG4, PMEPA1, OCIAD1, ITGB1, CHN1, PH4, CLDN10, HSPA9, APR-3, PEBP1 and B3GNT, which are involved in diverse cellular processes like signaling, apoptosis, neurogenesis, cell adhesion and protein trafficking or quality control. For a subfraction of the hereby identified proteins we present data supporting their direct interaction with HIV-1 Nef. We discuss the results with respect to many phenotypes observed in HIV infected cells and patients. The identified Nef interaction partners may help to further elucidate the molecular basis of HIV-related diseases.

  16. The transcriptome of compatible and incompatible interactions of potato (Solanum tuberosum with Phytophthora infestans revealed by DeepSAGE analysis.

    Directory of Open Access Journals (Sweden)

    Gabor Gyetvai

    Full Text Available Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum. Understanding the molecular basis of resistance and susceptibility to late blight is therefore highly relevant for developing resistant cultivars, either by marker-assissted selection or by transgenic approaches. Specific P. infestans races having the Avr1 effector gene trigger a hypersensitive resistance response in potato plants carrying the R1 resistance gene (incompatible interaction and cause disease in plants lacking R1 (compatible interaction. The transcriptomes of the compatible and incompatible interaction were captured by DeepSAGE analysis of 44 biological samples comprising five genotypes, differing only by the presence or absence of the R1 transgene, three infection time points and three biological replicates. 30,859 unique 21 base pair sequence tags were obtained, one third of which did not match any known potato transcript sequence. Two third of the tags were expressed at low frequency (<10 tag counts/million. 20,470 unitags matched to approximately twelve thousand potato transcribed genes. Tag frequencies were compared between compatible and incompatible interactions over the infection time course and between compatible and incompatible genotypes. Transcriptional changes were more numerous in compatible than in incompatible interactions. In contrast to incompatible interactions, transcriptional changes in the compatible interaction were observed predominantly for multigene families encoding defense response genes and genes functional in photosynthesis and CO(2 fixation. Numerous transcriptional differences were also observed between near isogenic genotypes prior to infection with P. infestans. Our DeepSAGE transcriptome analysis uncovered novel candidate genes for plant host pathogen interactions, examples of which are discussed with respect to possible function.

  17. FUNDAMENTALS OF BIOMECHANICS

    Directory of Open Access Journals (Sweden)

    Duane Knudson

    2007-09-01

    Full Text Available DESCRIPTION This book provides a broad and in-depth theoretical and practical description of the fundamental concepts in understanding biomechanics in the qualitative analysis of human movement. PURPOSE The aim is to bring together up-to-date biomechanical knowledge with expert application knowledge. Extensive referencing for students is also provided. FEATURES This textbook is divided into 12 chapters within four parts, including a lab activities section at the end. The division is as follows: Part 1 Introduction: 1.Introduction to biomechanics of human movement; 2.Fundamentals of biomechanics and qualitative analysis; Part 2 Biological/Structural Bases: 3.Anatomical description and its limitations; 4.Mechanics of the musculoskeletal system; Part 3 Mechanical Bases: 5.Linear and angular kinematics; 6.Linear kinetics; 7.Angular kinetics; 8.Fluid mechanics; Part 4 Application of Biomechanics in Qualitative Analysis :9.Applying biomechanics in physical education; 10.Applying biomechanics in coaching; 11.Applying biomechanics in strength and conditioning; 12.Applying biomechanics in sports medicine and rehabilitation. AUDIENCE This is an important reading for both student and educators in the medicine, sport and exercise-related fields. For the researcher and lecturer it would be a helpful guide to plan and prepare more detailed experimental designs or lecture and/or laboratory classes in exercise and sport biomechanics. ASSESSMENT The text provides a constructive fundamental resource for biomechanics, exercise and sport-related students, teachers and researchers as well as anyone interested in understanding motion. It is also very useful since being clearly written and presenting several ways of examples of the application of biomechanics to help teach and apply biomechanical variables and concepts, including sport-related ones

  18. Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci

    Science.gov (United States)

    Martin, Paul; McGovern, Amanda; Orozco, Gisela; Duffus, Kate; Yarwood, Annie; Schoenfelder, Stefan; Cooper, Nicholas J.; Barton, Anne; Wallace, Chris; Fraser, Peter; Worthington, Jane; Eyre, Steve

    2015-01-01

    Genome-wide association studies have been tremendously successful in identifying genetic variants associated with complex diseases. The majority of association signals are intergenic and evidence is accumulating that a high proportion of signals lie in enhancer regions. We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines. Here we report numerous looping interactions and provide evidence that only a minority of interactions are common to both B- and T-cell lines, suggesting interactions may be highly cell-type specific; some disease-associated SNPs do not interact with the nearest gene but with more compelling candidate genes (for example, FOXO1, AZI2) often situated several megabases away; and finally, regions associated with different autoimmune diseases interact with each other and the same promoter suggesting common autoimmune gene targets (for example, PTPRC, DEXI and ZFP36L1). PMID:26616563

  19. Information security fundamentals

    CERN Document Server

    Blackley, John A; Peltier, Justin

    2004-01-01

    Effective security rules and procedures do not exist for their own sake-they are put in place to protect critical assets, thereby supporting overall business objectives. Recognizing security as a business enabler is the first step in building a successful program.Information Security Fundamentals allows future security professionals to gain a solid understanding of the foundations of the field and the entire range of issues that practitioners must address. This book enables students to understand the key elements that comprise a successful information security program and eventually apply thes

  20. El grupo fundamental

    Directory of Open Access Journals (Sweden)

    Carlos A. Robles Corbalá

    2015-12-01

    Full Text Available En este artículo se aborda un problema clásico para poder detectar si dos espacios topológicos son homeomorfos o no. Para lo cual a cada espacio topológico se le asocia un grupo algebraico, de tal suerte que si los espacios son homeomorfos, entonces los grupos asociados serán isomorfos. Se presenta una construcción del grupo fundamental de un espacio topológico y se enfoca en demostrar que efectivamente es un grupo.

  1. Fundamentals of calculus

    CERN Document Server

    Morris, Carla C

    2015-01-01

    Fundamentals of Calculus encourages students to use power, quotient, and product rules for solutions as well as stresses the importance of modeling skills.  In addition to core integral and differential calculus coverage, the book features finite calculus, which lends itself to modeling and spreadsheets.  Specifically, finite calculus is applied to marginal economic analysis, finance, growth, and decay.  Includes: Linear Equations and FunctionsThe DerivativeUsing the Derivative Exponential and Logarithmic Functions Techniques of DifferentiationIntegral CalculusIntegration TechniquesFunctions

  2. Fundamentals of engineering electromagnetism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nam; Yoon, Youngro; Jun, Sukhee; Jun, Hoin

    2004-08-15

    It indicates fundamentals of engineering electromagnetism. It mentions electromagnetic field model of introduction and International system of units and universal constant, Vector analysis with summary and orthogonal coordinate systems, electrostatic field on Coulomb's law and Gauss's law, electrostatic energy and strength, steady state current with Ohm's law and Joule's law and calculation of resistance, crystallite field with Vector's electrostatic potential, Biot-Savart law and application and Magnetic Dipole, time-Savart and Maxwell equation with potential function and Faraday law of electromagnetic induction, plane electromagnetic wave, transmission line, a wave guide and cavity resonator and antenna arrangement.

  3. Fundamentals of attosecond optics

    CERN Document Server

    Chang, Zenghu

    2011-01-01

    Attosecond optical pulse generation, along with the related process of high-order harmonic generation, is redefining ultrafast physics and chemistry. A practical understanding of attosecond optics requires significant background information and foundational theory to make full use of these cutting-edge lasers and advance the technology toward the next generation of ultrafast lasers. Fundamentals of Attosecond Optics provides the first focused introduction to the field. The author presents the underlying concepts and techniques required to enter the field, as well as recent research advances th

  4. Fundamentals of microwave photonics

    CERN Document Server

    Urick, V J; McKinney , Jason D

    2015-01-01

    A comprehensive resource to designing andconstructing analog photonic links capable of high RFperformanceFundamentals of Microwave Photonics provides acomprehensive description of analog optical links from basicprinciples to applications.  The book is organized into fourparts. The first begins with a historical perspective of microwavephotonics, listing the advantages of fiber optic links anddelineating analog vs. digital links. The second section coversbasic principles associated with microwave photonics in both the RFand optical domains.  The third focuses on analog modulationformats-starti

  5. Mathematical analysis fundamentals

    CERN Document Server

    Bashirov, Agamirza

    2014-01-01

    The author's goal is a rigorous presentation of the fundamentals of analysis, starting from elementary level and moving to the advanced coursework. The curriculum of all mathematics (pure or applied) and physics programs include a compulsory course in mathematical analysis. This book will serve as can serve a main textbook of such (one semester) courses. The book can also serve as additional reading for such courses as real analysis, functional analysis, harmonic analysis etc. For non-math major students requiring math beyond calculus, this is a more friendly approach than many math-centric o

  6. Fundamentals of Project Management

    CERN Document Server

    Heagney, Joseph

    2011-01-01

    With sales of more than 160,000 copies, Fundamentals of Project Management has helped generations of project managers navigate the ins and outs of every aspect of this complex discipline. Using a simple step-by-step approach, the book is the perfect introduction to project management tools, techniques, and concepts. Readers will learn how to: ò Develop a mission statement, vision, goals, and objectives ò Plan the project ò Create the work breakdown structure ò Produce a workable schedule ò Understand earned value analysis ò Manage a project team ò Control and evaluate progress at every stage.

  7. Fundamental concepts of mathematics

    CERN Document Server

    Goodstein, R L

    Fundamental Concepts of Mathematics, 2nd Edition provides an account of some basic concepts in modern mathematics. The book is primarily intended for mathematics teachers and lay people who wants to improve their skills in mathematics. Among the concepts and problems presented in the book include the determination of which integral polynomials have integral solutions; sentence logic and informal set theory; and why four colors is enough to color a map. Unlike in the first edition, the second edition provides detailed solutions to exercises contained in the text. Mathematics teachers and people

  8. Fundamentals of semiconductor devices

    CERN Document Server

    Lindmayer, Joseph

    1965-01-01

    Semiconductor properties ; semiconductor junctions or diodes ; transistor fundamentals ; inhomogeneous impurity distributions, drift or graded-base transistors ; high-frequency properties of transistors ; band structure of semiconductors ; high current densities and mechanisms of carrier transport ; transistor transient response and recombination processes ; surfaces, field-effect transistors, and composite junctions ; additional semiconductor characteristics ; additional semiconductor devices and microcircuits ; more metal, insulator, and semiconductor combinations for devices ; four-pole parameters and configuration rotation ; four-poles of combined networks and devices ; equivalent circuits ; the error function and its properties ; Fermi-Dirac statistics ; useful physical constants.

  9. Fundamental of biomedical engineering

    CERN Document Server

    Sawhney, GS

    2007-01-01

    About the Book: A well set out textbook explains the fundamentals of biomedical engineering in the areas of biomechanics, biofluid flow, biomaterials, bioinstrumentation and use of computing in biomedical engineering. All these subjects form a basic part of an engineer''s education. The text is admirably suited to meet the needs of the students of mechanical engineering, opting for the elective of Biomedical Engineering. Coverage of bioinstrumentation, biomaterials and computing for biomedical engineers can meet the needs of the students of Electronic & Communication, Electronic & Instrumenta

  10. Fundamentals of Cavitation

    CERN Document Server

    Franc, Jean-Pierre

    2005-01-01

    The present book is aimed at providing a comprehensive presentation of cavitation phenomena in liquid flows. It is further backed up by the experience, both experimental and theoretical, of the authors whose expertise has been internationally recognized. A special effort is made to place the various methods of investigation in strong relation with the fundamental physics of cavitation, enabling the reader to treat specific problems independently. Furthermore, it is hoped that a better knowledge of the cavitation phenomenon will allow engineers to create systems using it positively. Examples in the literature show the feasibility of this approach.

  11. Nanomachines fundamentals and applications

    CERN Document Server

    Wang, Joseph

    2013-01-01

    This first-hand account by one of the pioneers of nanobiotechnology brings together a wealth of valuable material in a single source. It allows fascinating insights into motion at the nanoscale, showing how the proven principles of biological nanomotors are being transferred to artificial nanodevices.As such, the author provides engineers and scientists with the fundamental knowledge surrounding the design and operation of biological and synthetic nanomotors and the latest advances in nanomachines. He addresses such topics as nanoscale propulsions, natural biomotors, molecular-scale machin

  12. Electronic circuits fundamentals & applications

    CERN Document Server

    Tooley, Mike

    2015-01-01

    Electronics explained in one volume, using both theoretical and practical applications.New chapter on Raspberry PiCompanion website contains free electronic tools to aid learning for students and a question bank for lecturersPractical investigations and questions within each chapter help reinforce learning Mike Tooley provides all the information required to get to grips with the fundamentals of electronics, detailing the underpinning knowledge necessary to appreciate the operation of a wide range of electronic circuits, including amplifiers, logic circuits, power supplies and oscillators. The

  13. The MOND Fundamental Plane

    CERN Document Server

    Cardone, V F; Diaferio, A; Tortora, C; Molinaro, R

    2010-01-01

    Modified Newtonian Dynamics (MOND) has been shown to be able to fit spiral galaxy rotation curves as well as giving a theoretical foundation for empirically determined scaling relations, such as the Tully - Fisher law, without the need for a dark matter halo. As a complementary analysis, one should investigate whether MOND can also reproduce the dynamics of early - type galaxies (ETGs) without dark matter. As a first step, we here show that MOND can indeed fit the observed central velocity dispersion $\\sigma_0$ of a large sample of ETGs assuming a simple MOND interpolating functions and constant anisotropy. We also show that, under some assumptions on the luminosity dependence of the Sersic n parameter and the stellar M/L ratio, MOND predicts a fundamental plane for ETGs : a log - linear relation among the effective radius $R_{eff}$, $\\sigma_0$ and the mean effective intensity $\\langle I_e \\rangle$. However, we predict a tilt between the observed and the MOND fundamental planes.

  14. Testing Our Fundamental Assumptions

    Science.gov (United States)

    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

  15. Fundamentals of Space Systems

    Science.gov (United States)

    Pisacane, Vincent L.

    2005-06-01

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

  16. Analysis of a summary network of co-infection in humans reveals that parasites interact most via shared resources.

    Science.gov (United States)

    Griffiths, Emily C; Pedersen, Amy B; Fenton, Andy; Petchey, Owen L

    2014-05-07

    Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show co-infected humans to have worse health than those with single infections. However, we have little understanding of how co-infecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of co-infecting parasites tend to interact. The network had three levels comprising parasites, the resources they consume and the immune responses they elicit, connected by potential, observed and experimentally proved links. Pairs of parasite species had most potential to interact indirectly through shared resources, rather than through immune responses or other parasites. In addition, the network comprised 10 tightly knit groups, eight of which were associated with particular body parts, and seven of which were dominated by parasite-resource links. Reported co-infection in humans is therefore structured by physical location within the body, with bottom-up, resource-mediated processes most often influencing how, where and which co-infecting parasites interact. The many indirect interactions show how treating an infection could affect other infections in co-infected patients, but the compartmentalized structure of the network will limit how far these indirect effects are likely to spread.

  17. Genomic and proteomic analyses of Prdm5 reveal interactions with insulator binding proteins in embryonic stem cells

    DEFF Research Database (Denmark)

    Galli, Giorgio Giacomo; Carrara, Matteo; Francavilla, Chiara

    2013-01-01

    find that Prdm5 is highly expressed in mouse embryonic stem cells (mES) and exploit this cellular system to characterize molecular functions of Prdm5. By combining proteomics and next generation sequencing technologies we identify Prdm5 interaction partners and genomic occupancy. We demonstrate that......, despite Prdm5 is dispensable for mES cell maintenance, it directly targets genomic regions involved in early embryonic development and affects the expression of a subset of developmental regulators during cell differentiation. Importantly, Prdm5 interacts with Ctcf, Cohesin and TFIIIC and co...

  18. Different foraging preferences of hummingbirds on artificial and natural flowers reveal mechanisms structuring plant-pollinator interactions.

    Science.gov (United States)

    Maglianesi, María A; Böhning-Gaese, Katrin; Schleuning, Matthias

    2015-05-01

    In plant-pollinator networks, the floral morphology of food plants is an important determinant of the interaction niche of pollinators. Studies on foraging preferences of pollinators combining experimental and observational approaches may help to understand the mechanisms behind patterns of interactions and niche partitioning within pollinator communities. In this study, we tested whether morphological floral traits were associated with foraging preferences of hummingbirds for artificial and natural flower types in Costa Rica. We performed field experiments with artificial feeders, differing in length and curvature of flower types, to quantify the hummingbirds' interaction niche under unlimited nectar resources. To quantify the interaction niche under real-world conditions of limited nectar resources, we measured foraging preferences of hummingbirds for a total of 34 plant species. Artificial feeders were visited by Eupherusa nigriventris and Phaethornis guy in the pre-montane forest, and Lampornis calolaemus in the lower montane forest. Under experimental conditions, all three hummingbird species overlapped their interaction niches and showed a preference for the short artificial flower type over the long-straight and the long-curved flower types. Under natural conditions, the two co-occurring hummingbird species preferred to feed on plant species with floral traits corresponding to their bill morphology. The short-billed hummingbird E. nigriventris preferred to feed on short and straight flowers, whereas the long- and curved-billed P. guy preferred long and curved natural flowers. The medium-size billed species L. calolaemus preferred to feed on flowers of medium length and did not show preferences for plant species with specific corolla curvature. Our results show that floral morphological traits constrain access by short-billed hummingbird species to nectar resources. Morphological constraints, therefore, represent one important mechanism structuring trophic

  19. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik;

    2010-01-01

    the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies...

  20. Meta-analysis reveals complex marine biological responses to the interactive effects of ocean acidification and warming

    Science.gov (United States)

    Harvey, Ben P; Gwynn-Jones, Dylan; Moore, Pippa J

    2013-01-01

    Ocean acidification and warming are considered two of the greatest threats to marine biodiversity, yet the combined effect of these stressors on marine organisms remains largely unclear. Using a meta-analytical approach, we assessed the biological responses of marine organisms to the effects of ocean acidification and warming in isolation and combination. As expected biological responses varied across taxonomic groups, life-history stages, and trophic levels, but importantly, combining stressors generally exhibited a stronger biological (either positive or negative) effect. Using a subset of orthogonal studies, we show that four of five of the biological responses measured (calcification, photosynthesis, reproduction, and survival, but not growth) interacted synergistically when warming and acidification were combined. The observed synergisms between interacting stressors suggest that care must be made in making inferences from single-stressor studies. Our findings clearly have implications for the development of adaptive management strategies particularly given that the frequency of stressors interacting in marine systems will be likely to intensify in the future. There is now an urgent need to move toward more robust, holistic, and ecologically realistic climate change experiments that incorporate interactions. Without them accurate predictions about the likely deleterious impacts to marine biodiversity and ecosystem functioning over the next century will not be possible. PMID:23610641

  1. Process-based species pools reveal the hidden signature of biotic interactions amid the influence of temperature filtering

    DEFF Research Database (Denmark)

    Lessard, Jean-Philippe; Weinstein, Ben G.; Borregaard, Michael Krabbe

    2016-01-01

    A persistent challenge in ecology is to tease apart the in-fluence of multiple processes acting simultaneously and interacting in complex ways to shape the structure of species assemblages. We implement a heuristic approach that relies on explicitly defining spe-cies pools and permits assessment ...

  2. High-resolution profiling of stationary-phase survival reveals yeast longevity factors and their genetic interactions.

    Directory of Open Access Journals (Sweden)

    Erika Garay

    2014-02-01

    Full Text Available Lifespan is influenced by a large number of conserved proteins and gene-regulatory pathways. Here, we introduce a strategy for systematically finding such longevity factors in Saccharomyces cerevisiae and scoring the genetic interactions (epistasis among these factors. Specifically, we developed an automated competition-based assay for chronological lifespan, defined as stationary-phase survival of yeast populations, and used it to phenotype over 5,600 single- or double-gene knockouts at unprecedented quantitative resolution. We found that 14% of the viable yeast mutant strains were affected in their stationary-phase survival; the extent of true-positive chronological lifespan factors was estimated by accounting for the effects of culture aeration and adaptive regrowth. We show that lifespan extension by dietary restriction depends on the Swr1 histone-exchange complex and that a functional link between autophagy and the lipid-homeostasis factor Arv1 has an impact on cellular lifespan. Importantly, we describe the first genetic interaction network based on aging phenotypes, which successfully recapitulated the core-autophagy machinery and confirmed a role of the human tumor suppressor PTEN homologue in yeast lifespan and phosphatidylinositol phosphate metabolism. Our quantitative analysis of longevity factors and their genetic interactions provides insights into the gene-network interactions of aging cells.

  3. High-resolution profiling of stationary-phase survival reveals yeast longevity factors and their genetic interactions.

    Science.gov (United States)

    Garay, Erika; Campos, Sergio E; González de la Cruz, Jorge; Gaspar, Ana P; Jinich, Adrian; Deluna, Alexander

    2014-02-01

    Lifespan is influenced by a large number of conserved proteins and gene-regulatory pathways. Here, we introduce a strategy for systematically finding such longevity factors in Saccharomyces cerevisiae and scoring the genetic interactions (epistasis) among these factors. Specifically, we developed an automated competition-based assay for chronological lifespan, defined as stationary-phase survival of yeast populations, and used it to phenotype over 5,600 single- or double-gene knockouts at unprecedented quantitative resolution. We found that 14% of the viable yeast mutant strains were affected in their stationary-phase survival; the extent of true-positive chronological lifespan factors was estimated by accounting for the effects of culture aeration and adaptive regrowth. We show that lifespan extension by dietary restriction depends on the Swr1 histone-exchange complex and that a functional link between autophagy and the lipid-homeostasis factor Arv1 has an impact on cellular lifespan. Importantly, we describe the first genetic interaction network based on aging phenotypes, which successfully recapitulated the core-autophagy machinery and confirmed a role of the human tumor suppressor PTEN homologue in yeast lifespan and phosphatidylinositol phosphate metabolism. Our quantitative analysis of longevity factors and their genetic interactions provides insights into the gene-network interactions of aging cells.

  4. The geometric framework for nutrition reveals interactions between protein and carbohydrate during larval growth in honey bees

    Science.gov (United States)

    In holometabolous insects, larval nutrition affects adult body size, a life history trait with a profound influence on performance and fitness. Individual nutritional components of larval diet are often complex and may interact with one another, necessitating the use of a geometric framework for und...

  5. Genome-Wide Analysis of PDZ Domain Binding Reveals Inherent Functional Overlap within the PDZ Interaction Network

    NARCIS (Netherlands)

    Te Veldhuis, A.J.W.; Sakalis, P.A.; Fowler, D.A.; Bagowski, C.P.

    2011-01-01

    Binding selectivity and cross-reactivity within one of the largest and most abundant interaction domain families, the PDZ family, has long been enigmatic. The complete human PDZ domain complement (the PDZome) consists of 267 domains and we applied here a Bayesian selectivity model to predict hundred

  6. Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes.

    Directory of Open Access Journals (Sweden)

    Greta E Weiss

    2015-02-01

    Full Text Available During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite's life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1 an early heparin-blockable interaction which weakly deforms the erythrocyte, 2 EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite's actin-myosin motor, 3 a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4 an AMA1-RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine.

  7. A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions.

    Directory of Open Access Journals (Sweden)

    Jessica B Hostetler

    2015-12-01

    Full Text Available A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC, and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion.We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further suggesting that the proteins

  8. Fundamentals of quantum mechanics

    CERN Document Server

    House, J E

    2017-01-01

    Fundamentals of Quantum Mechanics, Third Edition is a clear and detailed introduction to quantum mechanics and its applications in chemistry and physics. All required math is clearly explained, including intermediate steps in derivations, and concise review of the math is included in the text at appropriate points. Most of the elementary quantum mechanical models-including particles in boxes, rigid rotor, harmonic oscillator, barrier penetration, hydrogen atom-are clearly and completely presented. Applications of these models to selected “real world” topics are also included. This new edition includes many new topics such as band theory and heat capacity of solids, spectroscopy of molecules and complexes (including applications to ligand field theory), and small molecules of astrophysical interest.

  9. Lasers Fundamentals and Applications

    CERN Document Server

    Thyagarajan, K

    2010-01-01

    Lasers: Fundamentals and Applications, serves as a vital textbook to accompany undergraduate and graduate courses on lasers and their applications. Ever since their invention in 1960, lasers have assumed tremendous importance in the fields of science, engineering and technology because of their diverse uses in basic research and countless technological applications. This book provides a coherent presentation of the basic physics behind the way lasers work, and presents some of their most important applications in vivid detail. After reading this book, students will understand how to apply the concepts found within to practical, tangible situations. This textbook includes worked-out examples and exercises to enhance understanding, and the preface shows lecturers how to most beneficially match the textbook with their course curricula. The book includes several recent Nobel Lectures, which will further expose students to the emerging applications and excitement of working with lasers. Students who study lasers, ...

  10. Fundamentals of Structural Engineering

    CERN Document Server

    Connor, Jerome J

    2013-01-01

    Fundamentals of Structural Engineering provides a balanced, seamless treatment of both classic, analytic methods and contemporary, computer-based techniques for conceptualizing and designing a structure. The book’s principle goal is to foster an intuitive understanding of structural behavior based on problem solving experience for students of civil engineering and architecture who have been exposed to the basic concepts of engineering mechanics and mechanics of materials. Making it distinct from many other undergraduate textbooks, the authors of this text recognize the notion that engineers reason about behavior using simple models and intuition they acquire through problem solving. The approach adopted in this text develops this type of intuition  by presenting extensive, realistic problems and case studies together with computer simulation, which allows rapid exploration of  how a structure responds to changes in geometry and physical parameters. This book also: Emphasizes problem-based understanding of...

  11. Fundamentals of sustainable neighbourhoods

    CERN Document Server

    Friedman, Avi

    2015-01-01

    This book introduces architects, engineers, builders, and urban planners to a range of design principles of sustainable communities and illustrates them with outstanding case studies. Drawing on the author’s experience as well as local and international case studies, Fundamentals of Sustainable Neighbourhoods presents planning concepts that minimize developments' carbon footprint through compact communities, adaptable and expandable dwellings, adaptable landscapes, and smaller-sized yet quality-designed housing. This book also: Examines in-depth global strategies for minimizing the residential carbon footprint, including district heating, passive solar gain, net-zero residences, as well as preserving the communities' natural assets Reconsiders conceptual approaches in building design and urban planning to promote a better connection between communities and nature Demonstrates practical applications of green architecture Focuses on innovative living spaces in urban environments

  12. Fundamentals of phosphors

    CERN Document Server

    Yen, William M; Yamamoto, Hajime

    2006-01-01

    Drawing from the second edition of the best-selling Handbook of Phosphors, Fundamentals of Phosphors covers the principles and mechanisms of luminescence in detail and surveys the primary phosphor materials as well as their optical properties. The book addresses cutting-edge developments in phosphor science and technology including oxynitride phosphors and the impact of lanthanide level location on phosphor performance.Beginning with an explanation of the physics underlying luminescence mechanisms in solids, the book goes on to interpret various luminescence phenomena in inorganic and organic materials. This includes the interpretation of the luminescence of recently developed low-dimensional systems, such as quantum wells and dots. The book also discusses the excitation mechanisms by cathode-ray and ionizing radiation and by electric fields to produce electroluminescence. The book classifies phosphor materials according to the type of luminescence centers employed or the class of host materials used and inte...

  13. Superconductivity fundamentals and applications

    CERN Document Server

    Buckel, Werner

    2004-01-01

    This is the second English edition of what has become one of the definitive works on superconductivity in German -- currently in its sixth edition. Comprehensive and easy to understand, this introductory text is written especially with the non-specialist in mind. The authors, both long-term experts in this field, present the fundamental considerations without the need for extensive mathematics, describing the various phenomena connected with the superconducting state, with liberal insertion of experimental facts and examples for modern applications. While all fields of superconducting phenomena are dealt with in detail, this new edition pays particular attention to the groundbreaking discovery of magnesium diboride and the current developments in this field. In addition, a new chapter provides an overview of the elements, alloys and compounds where superconductivity has been observed in experiments, together with their major characteristics. The chapter on technical applications has been considerably expanded...

  14. Fundamentals of Fire Phenomena

    DEFF Research Database (Denmark)

    Quintiere, James

    discipline. It covers thermo chemistry including mixtures and chemical reactions; Introduces combustion to the fire protection student; Discusses premixed flames and spontaneous ignition; Presents conservation laws for control volumes, including the effects of fire; Describes the theoretical bases...... analyses. Fire phenomena encompass everything about the scientific principles behind fire behaviour. Combining the principles of chemistry, physics, heat and mass transfer, and fluid dynamics necessary to understand the fundamentals of fire phenomena, this book integrates the subject into a clear...... for empirical aspects of the subject of fire; Analyses ignition of liquids and the importance of evaporation including heat and mass transfer; Features the stages of fire in compartments, and the role of scale modelling in fire. The book is written by Prof. James G. Quintiere from University of Maryland...

  15. Automotive electronics design fundamentals

    CERN Document Server

    Zaman, Najamuz

    2015-01-01

    This book explains the topology behind automotive electronics architectures and examines how they can be profoundly augmented with embedded controllers. These controllers serve as the core building blocks of today’s vehicle electronics. Rather than simply teaching electrical basics, this unique resource focuses on the fundamental concepts of vehicle electronics architecture, and details the wide variety of Electronic Control Modules (ECMs) that enable the increasingly sophisticated "bells & whistles" of modern designs.  A must-have for automotive design engineers, technicians working in automotive electronics repair centers and students taking automotive electronics courses, this guide bridges the gap between academic instruction and industry practice with clear, concise advice on how to design and optimize automotive electronics with embedded controllers.

  16. Fundamentals of Fire Phenomena

    DEFF Research Database (Denmark)

    Quintiere, James

    Understanding fire dynamics and combustion is essential in fire safety engineering and in fire science curricula. Engineers and students involved in fire protection, safety and investigation need to know and predict how fire behaves to be able to implement adequate safety measures and hazard...... analyses. Fire phenomena encompass everything about the scientific principles behind fire behaviour. Combining the principles of chemistry, physics, heat and mass transfer, and fluid dynamics necessary to understand the fundamentals of fire phenomena, this book integrates the subject into a clear...... discipline. It covers thermo chemistry including mixtures and chemical reactions; Introduces combustion to the fire protection student; Discusses premixed flames and spontaneous ignition; Presents conservation laws for control volumes, including the effects of fire; Describes the theoretical bases...

  17. Comprehensive binary interaction mapping of SH2 domains via fluorescence polarization reveals novel functional diversification of ErbB receptors.

    Directory of Open Access Journals (Sweden)

    Ronald J Hause

    Full Text Available First-generation interaction maps of Src homology 2 (SH2 domains with receptor tyrosine kinase (RTK phosphosites have previously been generated using protein microarray (PM technologies. Here, we developed a large-scale fluorescence polarization (FP methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry

  18. Distortion/interaction analysis reveals the origins of selectivities in iridium-catalyzed C-H borylation of substituted arenes and 5-membered heterocycles

    OpenAIRE

    Green, AG; Liu, P.; Merlic, CA; Houk, KN

    2014-01-01

    The iridium-catalyzed borylation of mono- and disubstituted arenes and heteroarenes has been studied with density functional theory. The distortion/interaction model was employed to understand the origins of selectivities in these reactions. Computations revealed that the transition states for C-H oxidative addition are very late, resembling the aryl iridium hydride intermediate with a fully formed Ir-C bond. Consequently, the regioselectivity is mainly controlled by differences in the intera...

  19. Quantitative secretome analysis reveals the interactions between epithelia and tumor cells by in vitro modulating colon cancer microenvironment.

    Science.gov (United States)

    Zeng, Xiao; Yang, Pengbo; Chen, Bing; Jin, Xuewen; Liu, Yuling; Zhao, Xia; Liang, Shufang

    2013-08-26

    In tumor microenvironment, interactions among multiple cell types are critical for cancer progression. Secreted proteins are responsible for crosstalk among these cells within tumor microenvironment. To elucidate the interactions of tumor and epithelia, we co-cultured colon cancer cell line HT29 with normal human colon mucosal epithelial cell line NCM460 to mimic tumor microenvironment in vitro and investigated the differential expression pattern of secretome. A quantitative proteomics approach based on stable isotope labeling by amino acids in cell culture (SILAC) and LC-mass spectrometry was used for secretome analysis. Totally 45 proteins were altered over 2-fold in co-cultured cellular supernatants between equal amounts of NCM460 and HT29 cells, compared with mono-cultured conditions. These differential secreted proteins involve in multiple tumor-associated biological functions. The secretion level and acting pattern of acrogranin, IGFBP6 and vimentin were changed along with different co-cultured cell number ratios between NCM460 and HT29 cells, simulating early, middle or advanced stage of colon cancer. Therefore, a quantitative secretome profiling based on a co-culture system can track secreted protein changes and their associated biological roles between tumor and epithelia, which gives a new insight on communications between tumor and epithelia as well as cancer biotherapy by inhibiting cell interactions. Tumor microenvironment is a complex system and comprised of cancer cells and host stromal cells. The growth and progression of tumor have been recognized were affected by multidirectional interactions of secreted proteins (secretome), which were produced by the cells within tumor microenvironment. Focus on general secreted molecules of living cells via proteomic tools, is promising for investigating cell communication. Stable isotope labeling by amino acids in cell culture (SILAC) is a metabolic labeling strategy for quantitative analysis, which is gaining

  20. Formation of arenicin-1 microdomains in bilayers and their specific lipid interaction revealed by Z-scan FCS.

    Science.gov (United States)

    Macháň, Radek; Hof, Martin; Chernovets, Tatsiana; Zhmak, Maxim N; Ovchinnikova, Tatiana V; Sýkora, Jan

    2011-04-01

    Z-scan fluorescence correlation spectroscopy (FCS) is employed to characterize the interaction between arenicin-1 and supported lipid bilayers (SLBs) of different compositions. Lipid analogue C8-BODIPY 500/510C5-HPC and ATTO 465 labelled arenicin-1 are used to detect changes in lipid and peptide diffusion upon addition of unlabelled arenicin-1 to SLBs. Arenicin-1 decreases lipid mobility in negatively charged SLBs. According to diffusion law analysis, microdomains of significantly lower lipid mobility are formed. The analysis of peptide FCS data confirms the presence of microdomains for anionic SLBs. No indications of microdomain formation are detected in SLBs composed purely of zwitterionic lipids. Additionally, our FCS results imply that arenicin-1 exists in the form of oligomers and/or aggregates when interacting with membranes of both compositions.

  1. Trypanosoma cruzi: gene expression surveyed by proteomic analysis reveals interaction between different genotypes in mixed in vitro cultures.

    Directory of Open Access Journals (Sweden)

    Alexandre Machin

    Full Text Available We have analyzed the comportment in in vitro culture of 2 different genotypes of Trypanosoma cruzi, the agent of Chagas disease, pertaining to 2 major genetic subdivisions (near-clades of this parasite. One of the stocks was a fast-growing one, highly virulent in mice, while the other one was slow-growing, mildly virulent in mice. The working hypothesis was that mixtures of genotypes interact, a pattern that has been observed by us in empirical experimental studies. Genotype mixtures were followed every 7 days and characterized by the DIGE technology of proteomic analysis. Proteic spots of interest were characterized by the SAMESPOT software. Patterns were compared to those of pure genotypes that were also evaluated every 7 days. One hundred and three spots exhibited changes in time by comparison with T = 0. The major part of these spots (58% exhibited an under-expression pattern by comparison with the pure genotypes. 32% of the spots were over-expressed; 10% of spots were not different from those of pure genotypes. Interestingly, interaction started a few minutes after the mixtures were performed. We have retained 43 different proteins that clearly exhibited either under- or over-expression. Proteins showing interaction were characterized by mass spectrometry (MALDI-TOF. Close to 50% of them were either tubulins or heat shock proteins. This study confirms that mixed genotypes of T. cruzi interact at the molecular level. This is of great interest because mixtures of genotypes are very frequent in Chagas natural cycles, both in insect vectors and in mammalian hosts, and may play an important role in the transmission and severity of Chagas disease. The methodology proposed here is potentially applicable to any micropathogen, including fungi, bacteria and viruses. It should be of great interest in the case of bacteria, for which the epidemiological and clinical consequences of mixed infections could be underestimated.

  2. Factors affecting the interactions between beta-lactoglobulin and fatty acids as revealed in molecular dynamics simulations

    Science.gov (United States)

    Yi, Changhong; Wambo, Thierry O.

    2015-01-01

    Beta-lactoglobulin (BLG), a bovine dairy protein, is a promiscuously interacting protein that can bind multiple hydrophobic ligands. Fatty acids (FAs), common hydrophobic molecules bound to BLG, are important sources of fuel for life because they yield large quantities of ATP when metabolized. The binding affinity increases with the length of the ligands, indicating the importance of the van der Waals (vdW) interactions between the hydrocarbon tail and the hydrophobic calyx of BLG. An exception to this rule is caprylic acid (OCA) which is two-carbon shorter but has a stronger binding affinity than capric acid. Theoretical calculations in the current literature are not accurate enough to shed light on the underlying physics of this exception. The computed affinity values are greater for longer fatty acids without respect for the caprylic exception and those values are generally several orders of magnitude away from the experimental data. In this work, we used hybrid steered molecular dynamics to accurately compute the binding free energies between BLG and the five saturated FAs of 8 to 16 carbon atoms. The computed binding free energies agree well with experimental data not only in rank but also in absolute values. We gained insights into the exceptional behavior of caprylic acid in the computed values of entropy and electrostatic interactions. We found that the electrostatic interaction between the carboxyl group of caprylic acid and the two amino groups of K60/69 in BLG is much stronger than the vdW force between OCA’s hydrophobic tail and the BLG calyx. This pulls OCA to the top of the beta barrel where it is easier to fluctuate, giving rise to greater entropy of OCA at the binding site. PMID:26272099

  3. The geometric framework for nutrition reveals interactions between protein and carbohydrate during larval growth in honey bees

    Directory of Open Access Journals (Sweden)

    Bryan R. Helm

    2017-06-01

    Full Text Available In holometabolous insects, larval nutrition affects adult body size, a life history trait with a profound influence on performance and fitness. Individual nutritional components of larval diets are often complex and may interact with one another, necessitating the use of a geometric framework for elucidating nutritional effects. In the honey bee, Apis mellifera, nurse bees provision food to developing larvae, directly moderating growth rates and caste development. However, the eusocial nature of honey bees makes nutritional studies challenging, because diet components cannot be systematically manipulated in the hive. Using in vitro rearing, we investigated the roles and interactions between carbohydrate and protein content on larval survival, growth, and development in A. mellifera. We applied a geometric framework to determine how these two nutritional components interact across nine artificial diets. Honey bees successfully completed larval development under a wide range of protein and carbohydrate contents, with the medium protein (∼5% diet having the highest survival. Protein and carbohydrate both had significant and non-linear effects on growth rate, with the highest growth rates observed on a medium-protein, low-carbohydrate diet. Diet composition did not have a statistically significant effect on development time. These results confirm previous findings that protein and carbohydrate content affect the growth of A. mellifera larvae. However, this study identified an interaction between carbohydrate and protein content that indicates a low-protein, high-carb diet has a negative effect on larval growth and survival. These results imply that worker recruitment in the hive would decline under low protein conditions, even when nectar abundance or honey stores are sufficient.

  4. Transcription profile of soybean-root-knot nematode interaction reveals a key role of phythormones in the resistance reaction

    OpenAIRE

    Beneventi, Magda Aparecida; da Silva, Orzenil Bonfim; SÁ,MARIA EUGÊNIA LISEI DE; Firmino, Alexandre Augusto Pereira; de Amorim, Regina Maria Santos; Albuquerque, Érika Valéria Saliba; da Silva, Maria Cristina Mattar; da Silva, Joseane Padilha; Campos,Magnólia de Araújo; Lopes,Marcus José Conceição; Togawa, Roberto Coiti; Pappas, Georgios Joanis; Grossi–de–Sa, Maria Fatima

    2013-01-01

    Background Root-knot nematodes (RKN– Meloidogyne genus) present extensive challenges to soybean crop. The soybean line (PI 595099) is known to be resistant against specific strains and races of nematode species, thus its differential gene expression analysis can lead to a comprehensive gene expression profiling in the incompatible soybean-RKN interaction. Even though many disease resistance genes have been studied, little has been reported about phytohormone crosstalk on modulation of ROS sig...

  5. Interaction Network among Escherichia coli Membrane Proteins Involved in Cell Division as Revealed by Bacterial Two-Hybrid Analysis

    OpenAIRE

    Karimova, Gouzel; Dautin, Nathalie; Ladant, Daniel

    2005-01-01

    Formation of the Escherichia coli division septum is catalyzed by a number of essential proteins (named Fts) that assemble into a ring-like structure at the future division site. Several of these Fts proteins are intrinsic transmembrane proteins whose functions are largely unknown. Although these proteins appear to be recruited to the division site in a hierarchical order, the molecular interactions underlying the assembly of the cell division machinery remain mostly unspecified. In the prese...

  6. Information physics fundamentals of nanophotonics.

    Science.gov (United States)

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

    2013-05-01

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

  7. Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies.

    Science.gov (United States)

    Furuita, Kyoko; Jee, JunGoo; Fukada, Harumi; Mishima, Masaki; Kojima, Chojiro

    2010-04-23

    Oxysterol-binding protein (OSBP), a cytosolic receptor of cholesterol and oxysterols, is recruited to the endoplasmic reticulum by binding to the cytoplasmic major sperm protein (MSP) domain of integral endoplasmic reticulum protein VAMP-associated protein-A (VAP-A), a process essential for the stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. To delineate the interaction mechanism between VAP-A and OSBP, we determined the complex structure between the VAP-A MSP domain (VAP-A(MSP)) and the OSBP fragment containing a VAP-A binding motif FFAT (OSBP(F)) by NMR. This solution structure explained that five of six conserved residues in the FFAT motif are required for the stable complex formation, and three of five, including three critical intermolecular electrostatic interactions, were not explained before. By combining NMR relaxation and titration, isothermal titration calorimetry, and mutagenesis experiments with structural information, we further elucidated the detailed roles of the FFAT motif and underlying motions of VAP-A(MSP), OSBP(F), and the complex. Our results show that OSBP(F) is disordered in the free state, and VAP-A(MSP) and OSBP(F) form a final complex by means of intermediates, where electrostatic interactions through acidic residues, including an acid patch preceding the FFAT motif, probably play a collective role. Additionally, we report that the mutation that causes the familial motor neuron disease decreases the stability of the MSP domain.

  8. Electrostatic Interaction between Oxysterol-binding Protein and VAMP-associated Protein A Revealed by NMR and Mutagenesis Studies*

    Science.gov (United States)

    Furuita, Kyoko; Jee, JunGoo; Fukada, Harumi; Mishima, Masaki; Kojima, Chojiro

    2010-01-01

    Oxysterol-binding protein (OSBP), a cytosolic receptor of cholesterol and oxysterols, is recruited to the endoplasmic reticulum by binding to the cytoplasmic major sperm protein (MSP) domain of integral endoplasmic reticulum protein VAMP-associated protein-A (VAP-A), a process essential for the stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. To delineate the interaction mechanism between VAP-A and OSBP, we determined the complex structure between the VAP-A MSP domain (VAP-AMSP) and the OSBP fragment containing a VAP-A binding motif FFAT (OSBPF) by NMR. This solution structure explained that five of six conserved residues in the FFAT motif are required for the stable complex formation, and three of five, including three critical intermolecular electrostatic interactions, were not explained before. By combining NMR relaxation and titration, isothermal titration calorimetry, and mutagenesis experiments with structural information, we further elucidated the detailed roles of the FFAT motif and underlying motions of VAP-AMSP, OSBPF, and the complex. Our results show that OSBPF is disordered in the free state, and VAP-AMSP and OSBPF form a final complex by means of intermediates, where electrostatic interactions through acidic residues, including an acid patch preceding the FFAT motif, probably play a collective role. Additionally, we report that the mutation that causes the familial motor neuron disease decreases the stability of the MSP domain. PMID:20178991

  9. What is special about expertise? Visual expertise reveals the interactive nature of real-world object recognition.

    Science.gov (United States)

    Harel, Assaf

    2016-03-01

    Ever since Diamond and Carey (1986. J. Exp. Psychol.: Gen., vol. 115, pp. 107-117) seminal work, the main model for studying expertise in visual object recognition ("visual expertise") has been face perception. The underlying assumption was that since faces may be considered the ultimate domain of visual expertise, any face-processing signature might actually be a general characteristic of visual expertise. However, while humans are clearly experts in face recognition, visual expertise is not restricted to faces and can be observed in a variety of domains. This raises the question of whether face recognition is in fact the right model to study visual expertise, and if not, what are the common cognitive and neural characteristics of visual expertise. The current perspective article addresses this question by revisiting past and recent neuroimaging and behavioural works on visual expertise. The view of visual expertise that emerges from these works is that expertise is a unique phenomenon, with distinctive neural and cognitive characteristics. Specifically, visual expertise is a controlled, interactive process that develops from the reciprocal interactions between the visual system and multiple top-down factors, including semantic knowledge, top-down attentional control, and task relevance. These interactions enable the ability to flexibly access domain-specific information at multiple scales and levels guided by multiple recognition goals. Extensive visual experience with a given object category culminates in the recruitment of these multiple systems, and is reflected in widespread neural activity, extending well beyond visual cortex, to include higher-level cortical areas.

  10. A DNA-Centric Protein Interaction Map of Ultraconserved Elements Reveals Contribution of Transcription Factor Binding Hubs to Conservation

    Directory of Open Access Journals (Sweden)

    Tar Viturawong

    2013-10-01

    Full Text Available Ultraconserved elements (UCEs have been the subject of great interest because of their extreme sequence identity and their seemingly cryptic and largely uncharacterized functions. Although in vivo studies of UCE sequences have demonstrated regulatory activity, protein interactors at UCEs have not been systematically identified. Here, we combined high-throughput affinity purification, high-resolution mass spectrometry, and SILAC quantification to map intrinsic protein interactions for 193 UCE sequences. The interactome contains over 400 proteins, including transcription factors with known developmental roles. We demonstrate based on our data that UCEs consist of strongly conserved overlapping binding sites. We also generated a fine-resolution interactome of a UCE, confirming the hub-like nature of the element. The intrinsic interactions mapped here are reflected in open chromatin, as indicated by comparison with existing ChIP data. Our study argues for a strong contribution of protein-DNA interactions to UCE conservation and provides a basis for further functional characterization of UCEs.

  11. Two dimensional VOPBA reveals laminin receptor (LAMR1 interaction with dengue virus serotypes 1, 2 and 3

    Directory of Open Access Journals (Sweden)

    Cardosa Mary

    2005-03-01

    Full Text Available Abstract Background The search for the dengue virus receptor has generated many candidates often identified only by molecular mass. The wide host range of the viruses in vitro combined with multiple approaches to identifying the receptor(s has led to the notion that many receptors or attachment proteins may be involved and that the different dengue virus serotypes may utilize different receptors on the same cells as well as on different cell types. Results In this study we used sequential extraction of PS Clone D cell monolayers with the detergent β-octylglucopyranoside followed by sodium deoxycholate to prepare a cell membrane-rich fraction. We then used 2 dimensional (2D gel electrophoresis to separate the membrane proteins and applied a modified virus overlay protein binding assay (VOPBA to show that dengue virus serotypes 1, 2 and 3 all interact with the 37 kDa/67 kDa laminin receptor (LAMR1, a common non-integrin surface protein on many cell types. Conclusion At least 3 of the 4 dengue serotypes interact with the 37 kDa/67 kDa laminin receptor, LAMR1, which may be a common player in dengue virus-cell surface interaction.

  12. Citizen science data reveal ecological, historical and evolutionary factors shaping interactions between woody hosts and wood-inhabiting fungi.

    Science.gov (United States)

    Heilmann-Clausen, Jacob; Maruyama, Pietro K; Bruun, Hans Henrik; Dimitrov, Dimitar; Laessøe, Thomas; Frøslev, Tobias Guldberg; Dalsgaard, Bo

    2016-12-01

    Woody plants host diverse communities of associated organisms, including wood-inhabiting fungi. In this group, host effects on species richness and interaction network structure are not well understood, especially not at large geographical scales. We investigated ecological, historical and evolutionary determinants of fungal species richness and network modularity, that is, subcommunity structure, across woody hosts in Denmark, using a citizen science data set comprising > 80 000 records of > 1000 fungal species on 91 genera of woody plants. Fungal species richness was positively related to host size, wood pH, and the number of species in the host genus, with limited influence of host frequency and host history, that is, time since host establishment in the area. Modularity patterns were unaffected by host history, but largely reflected host phylogeny. Notably, fungal communities differed substantially between angiosperm and gymnosperm hosts. Host traits and evolutionary history appear to be more important than host frequency and recent history in structuring interactions between hosts and wood-inhabiting fungi. High wood acidity appears to act as a stress factor reducing fungal species richness, while large host size, providing increased niche diversity, enhances it. In some fungal groups that are known to interact with live host cells in the establishment phase, host selectivity is common, causing a modular community structure. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  13. Specific interactions between arbuscular mycorrhizal fungi and plant growth-promoting bacteria--as revealed by different combinations

    Energy Technology Data Exchange (ETDEWEB)

    Jaderlund, Lotta; Arthurson, Veronica; Granhall, Ulf; Jansson, Janet K.

    2008-05-15

    The interactions between two plant growth promoting rhizobacteria (PGPR), Pseudomonas fluorescens SBW25 and Paenibacillus brasilensis PB177, two arbuscular mycorrhizal (AM) fungi (Glomus mosseae and G. intraradices) and one pathogenic fungus (Microdochium nivale) were investigated on winter wheat (Triticum aestivum cultivar Tarso) in a greenhouse trial. PB177, but not SBW25, had strong inhibitory effects on M. nivale in dual culture plate assays. The results from the greenhouse experiment show very specific interactions; e.g. the two AM fungi react differently when interacting with the same bacteria on plants. G. intraradices (single inoculation or together with SBW25) increased plant dry weight on M. nivale infested plants, suggesting that the pathogenic fungus is counteracted by G. intraradices, but PB177 inhibited this positive effect. This is an example of two completely different reactions between the same AM fungus and two species of bacteria, previously known to enhance plant growth and inhibit pathogens. When searching for plant growth promoting microorganisms it is therefore important to test for the most suitable combination of plant, bacteria and fungi in order to get satisfactory plant growth benefits.

  14. Multiple Pairwise Analysis of Non-homologous Centromere Coupling Reveals Preferential Chromosome Size-Dependent Interactions and a Role for Bouquet Formation in Establishing the Interaction Pattern.

    Science.gov (United States)

    Lefrançois, Philippe; Rockmill, Beth; Xie, Pingxing; Roeder, G Shirleen; Snyder, Michael

    2016-10-01

    During meiosis, chromosomes undergo a homology search in order to locate their homolog to form stable pairs and exchange genetic material. Early in prophase, chromosomes associate in mostly non-homologous pairs, tethered only at their centromeres. This phenomenon, conserved through higher eukaryotes, is termed centromere coupling in budding yeast. Both initiation of recombination and the presence of homologs are dispensable for centromere coupling (occurring in spo11 mutants and haploids induced to undergo meiosis) but the presence of the synaptonemal complex (SC) protein Zip1 is required. The nature and mechanism of coupling have yet to be elucidated. Here we present the first pairwise analysis of centromere coupling in an effort to uncover underlying rules that may exist within these non-homologous interactions. We designed a novel chromosome conformation capture (3C)-based assay to detect all possible interactions between non-homologous yeast centromeres during early meiosis. Using this variant of 3C-qPCR, we found a size-dependent interaction pattern, in which chromosomes assort preferentially with chromosomes of similar sizes, in haploid and diploid spo11 cells, but not in a coupling-defective mutant (spo11 zip1 haploid and diploid yeast). This pattern is also observed in wild-type diploids early in meiosis but disappears as meiosis progresses and homologous chromosomes pair. We found no evidence to support the notion that ancestral centromere homology plays a role in pattern establishment in S. cerevisiae post-genome duplication. Moreover, we found a role for the meiotic bouquet in establishing the size dependence of centromere coupling, as abolishing bouquet (using the bouquet-defective spo11 ndj1 mutant) reduces it. Coupling in spo11 ndj1 rather follows telomere clustering preferences. We propose that a chromosome size preference for centromere coupling helps establish efficient homolog recognition.

  15. The unique architecture and function of cellulose-interacting proteins in oomycetes revealed by genomic and structural analyses

    Directory of Open Access Journals (Sweden)

    Larroque Mathieu

    2012-11-01

    Full Text Available Abstract Background Oomycetes are fungal-like microorganisms evolutionary distinct from true fungi, belonging to the Stramenopile lineage and comprising major plant pathogens. Both oomycetes and fungi express proteins able to interact with cellulose, a major component of plant and oomycete cell walls, through the presence of carbohydrate-binding module belonging to the family 1 (CBM1. Fungal CBM1-containing proteins were implicated in cellulose degradation whereas in oomycetes, the Cellulose Binding Elicitor Lectin (CBEL, a well-characterized CBM1-protein from Phytophthora parasitica, was implicated in cell wall integrity, adhesion to cellulosic substrates and induction of plant immunity. Results To extend our knowledge on CBM1-containing proteins in oomycetes, we have conducted a comprehensive analysis on 60 fungi and 7 oomycetes genomes leading to the identification of 518 CBM1-containing proteins. In plant-interacting microorganisms, the larger number of CBM1-protein coding genes is expressed by necrotroph and hemibiotrophic pathogens, whereas a strong reduction of these genes is observed in symbionts and biotrophs. In fungi, more than 70% of CBM1-containing proteins correspond to enzymatic proteins in which CBM1 is associated with a catalytic unit involved in cellulose degradation. In oomycetes more than 90% of proteins are similar to CBEL in which CBM1 is associated with a non-catalytic PAN/Apple domain, known to interact with specific carbohydrates or proteins. Distinct Stramenopile genomes like diatoms and brown algae are devoid of CBM1 coding genes. A CBM1-PAN/Apple association 3D structural modeling was built allowing the identification of amino acid residues interacting with cellulose and suggesting the putative interaction of the PAN/Apple domain with another type of glucan. By Surface Plasmon Resonance experiments, we showed that CBEL binds to glycoproteins through galactose or N-acetyl-galactosamine motifs. Conclusions This study

  16. Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer.

    Directory of Open Access Journals (Sweden)

    Rakhshan Ihsan

    Full Text Available Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR, classification and regression tree (CART and multifactor dimensionality reduction (MDR, was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11-2.59,p = 0.01, whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25-0.65,p<0.001 and OR = 0.51;95%CI = 0.33-0.78,p = 0.002 respectively. In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His, SULT1A1 213GG (Arg/Arg or AA (His/His and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33-10.55,p = 0.006, whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15-7.51,p = 0.01. MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His with testing balance accuracy (TBA of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with

  17. Fundamentals of klystron testing

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, J.W. Jr.

    1978-08-01

    Fundamentals of klystron testing is a text primarily intended for the indoctrination of new klystron group test stand operators. It should significantly reduce the familiarization time of a new operator, making him an asset to the group sooner than has been experienced in the past. The new employee must appreciate the mission of SLAC before he can rightfully be expected to make a meaningful contribution to the group's effort. Thus, the introductory section acquaints the reader with basic concepts of accelerators in general, then briefly describes major physical aspects of the Stanford Linear Accelerator. Only then is his attention directed to the klystron, with its auxiliary systems, and the rudiments of klystron tube performance checks. It is presumed that the reader is acquainted with basic principles of electronics and scientific notation. However, to preserve the integrity of an indoctrination guide, tedious technical discussions and mathematical analysis have been studiously avoided. It is hoped that the new operator will continue to use the text for reference long after his indoctrination period is completed. Even the more experienced operator should find that particular sections will refresh his understanding of basic principles of klystron testing.

  18. GRBs and Fundamental Physics

    Science.gov (United States)

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

    2016-12-01

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

  19. Fundamental Limits of Cooperation

    CERN Document Server

    Lozano, Angel; Andrews, Jeffrey G

    2012-01-01

    Cooperation is viewed as a key ingredient for interference management in wireless systems. This paper shows that cooperation has fundamental limitations. The main result is that even full cooperation between transmitters cannot in general change an interference-limited network to a noise-limited network. The key idea is that there exists a spectral efficiency upper bound that is independent of the transmit power. First, a spectral efficiency upper bound is established for systems that rely on pilot-assisted channel estimation; in this framework, cooperation is shown to be possible only within clusters of limited size, which are subject to out-of-cluster interference whose power scales with that of the in-cluster signals. Second, an upper bound is also shown to exist when cooperation is through noncoherent communication; thus, the spectral efficiency limitation is not a by-product of the reliance on pilot-assisted channel estimation. Consequently, existing literature that routinely assumes the high-power spect...

  20. Revisiting energy efficiency fundamentals

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Lombard, L.; Velazquez, D. [Grupo de Termotecnia, Escuela Superior de Ingenieros, Universidad de Sevilla, Camino de los Descubrimientos s/n, 41092 Seville (Spain); Ortiz, J. [Building Research Establishment (BRE), Garston, Watford, WD25 9XX (United Kingdom)

    2013-05-15

    Energy efficiency is a central target for energy policy and a keystone to mitigate climate change and to achieve a sustainable development. Although great efforts have been carried out during the last four decades to investigate the issue, focusing into measuring energy efficiency, understanding its trends and impacts on energy consumption and to design effective energy efficiency policies, many energy efficiency-related concepts, some methodological problems for the construction of energy efficiency indicators (EEI) and even some of the energy efficiency potential gains are often ignored or misunderstood, causing no little confusion and controversy not only for laymen but even for specialists. This paper aims to revisit, analyse and discuss some efficiency fundamental topics that could improve understanding and critical judgement of efficiency stakeholders and that could help in avoiding unfounded judgements and misleading statements. Firstly, we address the problem of measuring energy efficiency both in qualitative and quantitative terms. Secondly, main methodological problems standing in the way of the construction of EEI are discussed, and a sequence of actions is proposed to tackle them in an ordered fashion. Finally, two key topics are discussed in detail: the links between energy efficiency and energy savings, and the border between energy efficiency improvement and renewable sources promotion.

  1. Fundamental enabling issues in nanotechnology :

    Energy Technology Data Exchange (ETDEWEB)

    Floro, Jerrold Anthony [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Foiles, Stephen Martin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hearne, Sean Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoyt, Jeffrey John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Seel, Steven Craig [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Webb III, Edmund Blackburn [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Morales, Alfredo Martin [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Zimmerman, Jonathan A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    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

  2. Analysis of whitefly transcriptional responses to Beauveria bassiana infection reveals new insights into insect-fungus interactions.

    Science.gov (United States)

    Xia, Jun; Zhang, Chang-Rong; Zhang, Shan; Li, Fang-Fang; Feng, Ming-Guang; Wang, Xiao-Wei; Liu, Shu-Sheng

    2013-01-01

    The fungal pathogen, Beauveria bassiana, is an efficient biocontrol agent against a variety of agricultural pests. A thorough understanding of the basic principles of insect-fungus interactions may enable the genetic modification of Beauveria bassiana to enhance its virulence. However, the molecular mechanism of insect response to Beauveria bassiana infection is poorly understood, let alone the identification of fungal virulent factors involved in pathogenesis. Here, next generation sequencing technology was applied to examine the expression of whitefly (Bemisia tabaci) genes in response to the infection of Beauveria bassiana. Results showed that, compared to control, 654 and 1,681genes were differentially expressed at 48 hours and 72 hours post-infected whiteflies, respectively. Functional and enrichment analyses indicated that the DNA damage stimulus response and drug metabolism were important anti-fungi strategies of the whitefly. Mitogen-activated protein kinase (MAPK) pathway was also likely involved in the whitefly defense responses. Furthermore, the notable suppression of general metabolism and ion transport genes observed in 72 hours post-infected B. tabaci might be manipulated by fungal secreted effectors. By mapping the sequencing tags to B. bassiana genome, we also identified a number of differentially expressed fungal genes between the early and late infection stages. These genes are generally associated with fungal cell wall synthesis and energy metabolism. The expression of fungal cell wall protein genes might play an important role in fungal pathogenesis and the dramatically up-regulated enzymes of carbon metabolism indicate the increasing usage of energy during the fungal infection. To our knowledge, this is the first report on the molecular mechanism of fungus-whitefly interactions. Our results provide a road map for future investigations on insect-pathogen interactions and genetically modifying the fungus to enhance its efficiency in whitefly

  3. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility

    Energy Technology Data Exchange (ETDEWEB)

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E.; Schief, William R.; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D. (UWASH); (NIH); (Tulane); (DFCI)

    2010-04-15

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded {beta}-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate - and structurally plastic - layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated {beta}-sandwich and providing for conformational diversity used in immune evasion. A 'layered' gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a {beta}-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  4. IF-combined smRNA FISH reveals interaction of MCPIP1 protein with IER3 mRNA

    OpenAIRE

    Jakub Kochan; Mateusz Wawro; Aneta Kasza

    2016-01-01

    ABSTRACT MCPIP1 and IER3 are recently described proteins essential for maintenance of immune homeostasis. IER3 is involved in the regulation of apoptosis and differentiation and has been shown lately to protect activated T cells and macrophages from apoptosis. MCPIP1 is an RNase critical for controlling inflammation-related mRNAs. MCPIP1 interacts with and degrades a set of stem-loop-containing mRNAs (including IL-6). Our results demonstrate the involvement of MCPIP1 in the regulation of IER3...

  5. Interaction indole-3-acetic acid IAA with lectin Canavalia maritima seeds reveal new function of lectins in plant physiology

    Energy Technology Data Exchange (ETDEWEB)

    Silva Filho, J.C.; Santi-Gadelha, T.; Gadelha, C.A.A.; Delatorre, P. [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil); Teixeira, C.S.; Rocha, B.A.M.; Nobrega, R.B.; Alencar, K.L.L.; Cavada, B.S. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil)

    2012-07-01

    Full text: Lectins are a class of proteins of non-immune origin characterized by its capability in interacts specifically and reversibly to mono and oligosaccharides. In plant several possible roles have been suggested including their function in seed maturation, cell wall assembly, defense mechanisms, or rhizobial nodulation of legume roots. Nearly all application and proposed of the plant lectins are based on their specific carbohydrate binding. However, it has been reported that lectins from legumes, might interact with other molecules, such as non proteic amino acids and hydrophobic compounds. This study show the first the crystal structure based on molecular replacement of the Canavalia maritima (CML) complexed with IAA correlated with possible role in plant development. Purified CML was dissolved in 20 mMTrisHCl pH 7.6 containing 5 mM IAA, the suitable co-crystals from CML-IAA complex grew in condition 4 of screen I (0.1 M TrisHCl pH 8.5 and 2.0 M ammonium sulfate). This crystal belong to the orthorhombic space group I222 with unit-cell parameters a = 67.1 ; b = 70.7 , c = 97.7 , The structure was refined at 2.1 of resolution to a final R factor of 20.63 % and an R free of 22.54 %. To check the relative position of the IAA molecule in relation to the biological assemble of the CML, the tetrameric structure was generate by crystallographic symmetry. IAA molecules are positioned in the central cavity. The IAA is stabilized by interacting through hydrogen bounds and Van der Waals forces with the amino acids residues Ser 108 and Asn131, and two water molecules. The hydrophilic interactions occur between IAA and side chains of Ser 108, Asn131 and water molecules 26 and 31 by H-bonds. The OG oxygen from Ser108 display H-bonds with O2 and O3 oxygen atoms from IAA, 3.1 and 2.8 respectively. The tetrameric structure of CML complexed with IAA revels which this protein can act during the seedling in plant development. (author)

  6. Plasmonics fundamentals and applications

    CERN Document Server

    Maier, Stefan Alexander

    2007-01-01

    Considered a major field of photonics, plasmonics offers the potential to confine and guide light below the diffraction limit and promises a new generation of highly miniaturized photonic devices. This book combines a comprehensive introduction with an extensive overview of the current state of the art. Coverage includes plasmon waveguides, cavities for field-enhancement, nonlinear processes and the emerging field of active plasmonics studying interactions of surface plasmons with active media.

  7. Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis

    Science.gov (United States)

    Shakeel, Shabih; Westerhuis, Brenda M.; Domanska, Ausra; Koning, Roman I.; Matadeen, Rishi; Koster, Abraham J.; Bakker, Arjen Q.; Beaumont, Tim; Wolthers, Katja C.; Butcher, Sarah J.

    2016-07-01

    The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-Å resolution structure of HPeV3 on its own and at 15 Å resolution in complex with human monoclonal antibody Fabs demonstrates the expected picornavirus capsid structure with three distinct features. First, 25% of the HPeV3 RNA genome in 60 sites is highly ordered as confirmed by asymmetric reconstruction, and interacts with conserved regions of the capsid proteins VP1 and VP3. Second, the VP0 N terminus stabilizes the capsid inner surface, in contrast to other picornaviruses where on expulsion as VP4, it forms an RNA translocation channel. Last, VP1's hydrophobic pocket, the binding site for the antipicornaviral drug, pleconaril, is blocked and thus inappropriate for antiviral development. Together, these results suggest a direction for development of neutralizing antibodies, antiviral drugs based on targeting the RNA-protein interactions and dissection of virus assembly on the basis of RNA nucleation.

  8. Interaction of gold and silver nanoparticles with human plasma: Analysis of protein corona reveals specific binding patterns.

    Science.gov (United States)

    Lai, Wenjia; Wang, Qingsong; Li, Lumeng; Hu, Zhiyuan; Chen, Jiankui; Fang, Qiaojun

    2017-04-01

    Determining how nanomaterials interact with plasma will assist in understanding their effects on the biological system. This work presents a systematic study of the protein corona formed from human plasma on 20nm silver and gold nanoparticles with three different surface modifications, including positive and negative surface charges. The results show that all nanoparticles, even those with positive surface modifications, acquire negative charges after interacting with plasma. Approximately 300 proteins are identified on the coronas, while 99 are commonly found on each nanomaterial. The 20 most abundant proteins account for over 80% of the total proteins abundance. Remarkably, the surface charge and core of the nanoparticles, as well as the isoelectric point of the plasma proteins, are found to play significant roles in determining the nanoparticle coronas. Albumin and globulins are present at levels of less than 2% on these nanoparticle coronas. Fibrinogen, which presents in the plasma but not in the serum, preferably binds to negatively charged gold nanoparticles. These observations demonstrate the specific plasma protein binding pattern of silver and gold nanoparticles, as well as the importance of the surface charge and core in determining the protein corona compositions. The potential downstream biological impacts of the corona proteins were also investigated.

  9. Physiologically-Relevant Modes of Membrane Interactions by the Human Antimicrobial Peptide, LL-37, Revealed by SFG Experiments

    Science.gov (United States)

    Ding, Bei; Soblosky, Lauren; Nguyen, Khoi; Geng, Junqing; Yu, Xinglong; Ramamoorthy, Ayyalusamy; Chen, Zhan

    2013-05-01

    Antimicrobial peptides (AMPs) could become the next generation antibiotic compounds which can overcome bacterial resistance by disrupting cell membranes and it is essential to determine the factors underlying its mechanism of action. Although high-resolution NMR and other biological studies have provided valuable insights, it has been a major challenge to follow the AMP-membrane interactions at physiologically-relevant low peptide concentrations. In this study, we demonstrate a novel approach to overcome this major limitation by performing Sum Frequency Generation (SFG) vibrational spectroscopic experiments on lipid bilayers containing an AMP, LL-37. Our results demonstrate the power of SFG to study non-linear helical peptides and also infer that lipid-peptide interaction and the peptide orientation depend on the lipid membrane composition. The observed SFG signal changes capture the aggregating process of LL-37 on membrane. In addition, our SFG results on cholesterol-containing lipid bilayers indicate the inhibition effect of cholesterol on peptide-induced membrane permeation process.

  10. Genome-wide analysis of PDZ domain binding reveals inherent functional overlap within the PDZ interaction network.

    Directory of Open Access Journals (Sweden)

    Aartjan J W te Velthuis

    Full Text Available Binding selectivity and cross-reactivity within one of the largest and most abundant interaction domain families, the PDZ family, has long been enigmatic. The complete human PDZ domain complement (the PDZome consists of 267 domains and we applied here a Bayesian selectivity model to predict hundreds of human PDZ domain interactions, using target sequences of 22,997 non-redundant proteins. Subsequent analysis of these binding scores shows that PDZs can be divided into two genome-wide clusters that coincide well with the division between canonical class 1 and 2 PDZs. Within the class 1 PDZs we observed binding overlap at unprecedented levels, mediated by two residues at positions 1 and 5 of the second α-helix of the binding pocket. Eight PDZ domains were subsequently selected for experimental binding studies and to verify the basics of our predictions. Overall, the PDZ domain class 1 cross-reactivity identified here implies that auxiliary mechanisms must be in place to overcome this inherent functional overlap and to minimize cross-selectivity within the living cell. Indeed, when we superimpose PDZ domain binding affinities with gene ontologies, network topology data and the domain position within a PDZ superfamily protein, functional overlap is minimized and PDZ domains position optimally in the binding space. We therefore propose that PDZ domain selectivity is achieved through cellular context rather than inherent binding specificity.

  11. External Heavy-Atom Effect via Orbital Interactions Revealed by Single-Crystal X-ray Diffraction.

    Science.gov (United States)

    Sun, Xingxing; Zhang, Baicheng; Li, Xinyang; Trindle, Carl O; Zhang, Guoqing

    2016-07-28

    Enhanced spin-orbit coupling through external heavy-atom effect (EHE) has been routinely used to induce room-temperature phosphorescence (RTP) for purely organic molecular materials. Therefore, understanding the nature of EHE, i.e., the specific orbital interactions between the external heavy atom and the luminophore, is of essential importance in molecular design. For organic systems, halogens (e.g., Cl, Br, and I) are the most commonly seen heavy atoms serving to realize the EHE-related RTP. In this report, we conduct an investigation on how heavy-atom perturbers and aromatic luminophores interact on the basis of data obtained from crystallography. We synthesized two classes of molecular systems including N-haloalkyl-substituted carbazoles and quinolinium halides, where the luminescent molecules are considered as "base" or "acid" relative to the heavy-atom perturbers, respectively. We propose that electron donation from a π molecular orbital (MO) of the carbazole to the σ* MO of the C-X bond (π/σ*) and n electron donation to a π* MO of the quinolinium moiety (n/π*) are responsible for the EHE (RTP) in the solid state, respectively.

  12. Crystal Structures of the Helicobacter pylori MTAN Enzyme Reveal Specific Interactions between S-Adenosylhomocysteine and the 5'-Alkylthio Binding Subsite

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Vidhi [Univ. of Toledo, OH (United States); Ronning, Donald R. [Univ. of Toledo, OH (United States)

    2012-11-13

    The bacterial 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) enzyme is a multifunctional enzyme that catalyzes the hydrolysis of the N-ribosidic bond of at least four different adenosine-based metabolites: S-adenosylhomocysteine (SAH), 5'-methylthioadenosine (MTA), 5'-deoxyadenosine (5'-DOA), and 6-amino-6-deoxyfutalosine. These activities place the enzyme at the hub of seven fundamental bacterial metabolic pathways: S-adenosylmethionine (SAM) utilization, polyamine biosynthesis, the purine salvage pathway, the methionine salvage pathway, the SAM radical pathways, autoinducer-2 biosynthesis, and menaquinone biosynthesis. The last pathway makes MTAN essential for Helicobacter pylori viability. Although structures of various bacterial and plant MTANs have been described, the interactions between the homocysteine moiety of SAH and the 5'-alkylthiol binding site of MTAN have never been resolved. We have determined crystal structures of an inactive mutant form of H. pylori MTAN bound to MTA and SAH to 1.63 and 1.20 Å, respectively. The active form of MTAN was also crystallized in the presence of SAH, allowing the determination of the structure of a ternary enzyme–product complex resolved at 1.50 Å. These structures identify interactions between the homocysteine moiety and the 5'-alkylthiol binding site of the enzyme. This information can be leveraged for the development of species-specific MTAN inhibitors that prevent the growth of H. pylori.

  13. Genome and metagenome analyses reveal adaptive evolution of the host and interaction with the gut microbiota in the goose

    Science.gov (United States)

    Gao, Guangliang; Zhao, Xianzhi; Li, Qin; He, Chuan; Zhao, Wenjing; Liu, Shuyun; Ding, Jinmei; Ye, Weixing; Wang, Jun; Chen, Ye; Wang, Haiwei; Li, Jing; Luo, Yi; Su, Jian; Huang, Yong; Liu, Zuohua; Dai, Ronghua; Shi, Yixiang; Meng, He; Wang, Qigui

    2016-01-01

    The goose is an economically important waterfowl that exhibits unique characteristics and abilities, such as liver fat deposition and fibre digestion. Here, we report de novo whole-genome assemblies for the goose and swan goose and describe the evolutionary relationships among 7 bird species, including domestic and wild geese, which diverged approximately 3.4~6.3 million years ago (Mya). In contrast to chickens as a proximal species, the expanded and rapidly evolving genes found in the goose genome are mainly involved in metabolism, including energy, amino acid and carbohydrate metabolism. Further integrated analysis of the host genome and gut metagenome indicated that the most widely shared functional enrichment of genes occurs for functions such as glycolysis/gluconeogenesis, starch and sucrose metabolism, propanoate metabolism and the citrate cycle. We speculate that the unique physiological abilities of geese benefit from the adaptive evolution of the host genome and symbiotic interactions with gut microbes. PMID:27608918

  14. The interaction of asbestos and iron in lung tissue revealed by synchrotron-based scanning X-ray microscopy

    Science.gov (United States)

    Pascolo, Lorella; Gianoncelli, Alessandra; Schneider, Giulia; Salomé, Murielle; Schneider, Manuela; Calligaro, Carla; Kiskinova, Maya; Melato, Mauro; Rizzardi, Clara

    2013-01-01

    Asbestos is a potent carcinogen associated with malignant mesothelioma and lung cancer but its carcinogenic mechanisms are still poorly understood. Asbestos toxicity is ascribed to its particular physico-chemical characteristics, and one of them is the presence of and ability to adsorb iron, which may cause an alteration of iron homeostasis in the tissue. This observational study reports a combination of advanced synchrotron-based X-ray imaging and micro-spectroscopic methods that provide correlative morphological and chemical information for shedding light on iron mobilization features during asbestos permanence in lung tissue. The results show that the processes responsible for the unusual distribution of iron at different stages of interaction with the fibres also involve calcium, phosphorus and magnesium. It has been confirmed that the dominant iron form present in asbestos bodies is ferritin, while the concurrent presence of haematite suggests alteration of iron chemistry during asbestos body permanence. PMID:23350030

  15. Toroidal Interaction and Propeller Chirality of Hexaarylbenzenes. Dynamic Domino Inversion Revealed by Combined Experimental and Theoretical Circular Dichroism Studies.

    Science.gov (United States)

    Kosaka, Tomoyo; Inoue, Yoshihisa; Mori, Tadashi

    2016-03-01

    Hexaarylbenzenes (HABs) have greatly attracted much attention due to their unique propeller-shaped structure and potential application in materials science, such as liquid crystals, molecular capsules/rotors, redox materials, nonlinear optical materials, as well as molecular wires. Less attention has however been paid to their propeller chirality. By introducing small point-chiral group(s) at the periphery of HABs, propeller chirality was effectively induced, provoking strong Cotton effects in the circular dichroism (CD) spectrum. Temperature and solvent polarity manipulate the dynamics of propeller inversion in solution. As such, whizzing toroids become more substantial in polar solvents and at an elevated temperature, where radial aromatic rings (propeller blades) prefer orthogonal alignment against the central benzene ring (C6 core), maximizing toroidal interactions.

  16. Association studies in Populus tomentosa reveal the genetic interactions of Pto-MIR156c and its targets in wood formation

    Directory of Open Access Journals (Sweden)

    Mingyang Quan

    2016-08-01

    Full Text Available MicroRNAs (miRNAs regulate gene expression in many biological processes, but the significance of the interaction between a miRNA and its targets in perennial trees remains largely unknown. Here, we employed transcript profiling and association studies in Populus tomentosa (Pto to decipher the effect of genetic variation and interactions between Pto-miR156c and its potential targets (Pto-SPL15, Pto-SPL20, and Pto-SPL25 in 435 unrelated individuals from a natural population of P. tomentosa. Single-SNP (single-nucleotide polymorphism based association studies with analysis of the underlying additive and dominant effects identified 69 significant associations (P 0.05 from Pto-MIR156c and its three potential targets, with six wood and growth traits, revealing their common roles in wood formation. Epistasis analysis uncovered 129 significant SNP-SNP associations with ten traits, indicating the potential genetic interactions of Pto-MIR156c and its three putative targets. Interestingly, expression analysis in stem (phloem, cambium, and xylem revealed that Pto-miR156c expression showed strong negative correlations with Pto-SPL20 (r = -0.90, P < 0.01 and Pto-SPL25 (r = -0.65, P < 0.01, and a positive correlation with Pto-SPL15 (r = 0.40, P < 0.01, which also indicated the putative interactions of Pto-miR156c and its potential targets and their common roles in wood formation. Thus, our study provided an alternative approach to decipher the interaction between miRNAs and their targets and to dissect the genetic architecture of complex traits in trees.

  17. Proteomic analysis of ACTN4-interacting proteins reveals it's a putative involvement in mRNA metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Khotin, Mikhail, E-mail: h_mg@mail.ru [Department of Cell Cultures, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, 194064 St. Petersburg (Russian Federation); Turoverova, Lidia [Department of Cell Cultures, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, 194064 St. Petersburg (Russian Federation); Aksenova, Vasilisa [Department of Cell Cultures, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, 194064 St. Petersburg (Russian Federation); Department of Genetics, St. Petersburg State University, Universitetskaya nab., 7/9, 199034 St. Petersburg (Russian Federation); Barlev, Nikolai [Department of Cell Cultures, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, 194064 St. Petersburg (Russian Federation); Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN (United Kingdom); Borutinskaite, Veronika Viktorija [Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Department of Developmental Biology, Institute of Biochemistry, LT-08662 Vilnius (Lithuania); Vener, Alexander [Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Bajenova, Olga [Department of Genetics, St. Petersburg State University, Universitetskaya nab., 7/9, 199034 St. Petersburg (Russian Federation); Magnusson, Karl-Eric [Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Pinaev, George P. [Department of Cell Cultures, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, 194064 St. Petersburg (Russian Federation); Tentler, Dmitri, E-mail: dtentler@mail.cytspb.rssi.ru [Department of Cell Cultures, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, 194064 St. Petersburg (Russian Federation)

    2010-06-25

    Alpha-actinin 4 (ACTN4) is an actin-binding protein. In the cytoplasm, ACTN4 participates in structural organisation of the cytoskeleton via cross-linking of actin filaments. Nuclear localisation of ACTN4 has also been reported, but no clear role in the nucleus has been established. In this report, we describe the identification of proteins associated with ACTN4 in the nucleus. A combination of two-dimensional gel electrophoresis (2D-GE) and MALDI-TOF mass-spectrometry revealed a large number of ACTN4-bound proteins that are involved in various aspects of mRNA processing and transport. The association of ACTN4 with different ribonucleoproteins suggests that a major function of nuclear ACTN4 may be regulation of mRNA metabolism and signaling.

  18. Transcriptome–metabolome wide association study (TMWAS of maneb and paraquat neurotoxicity reveals network level interactions in toxicologic mechanism

    Directory of Open Access Journals (Sweden)

    James R. Roede

    2014-01-01

    Full Text Available A combination of the herbicide paraquat (PQ and fungicide maneb (MB has been linked to Parkinson's disease. Previous studies show that this involves an additive toxicity with at least two different mechanisms. However, detailed understanding of mixtures is often difficult to elucidate because of the multiple ways by which toxic agents can interact. In the present study, we used a combination of transcriptomics and metabolomics to investigate mechanisms of toxicity of PQ and MB in a neuroblastoma cell line. Conditions were studied with concentrations of PQ and MB that each individually caused 20% cell death and together caused 50% cell death. Transcriptomic and metabolomic samples were collected at time points prior to significant cell death. Statistical and bioinformatic methods were applied to the resulting 30,869 transcripts and 1358 metabolites. Results showed that MB significantly changed more transcripts and metabolites than PQ, and combined PQ + MB impacted more than MB alone. Transcriptome–metabolome-wide association study (TMWAS showed that significantly changed transcripts and metabolites mapped to two network substructures, one associating with significant effects of MB and the other included features significantly associated with PQ + MB. The latter contained 4 clusters of genes and associated metabolites, with one containing genes for two cation transporters and a cation transporter regulatory protein also recognized as a pro-apoptotic protein. Other clusters included stress response genes and transporters linked to cytoprotective mechanisms. MB also had a significant network structure linked to cell proliferation. Together, the results show that the toxicologic mechanism of the combined neurotoxicity of PQ and MB involves network level interactions and that TMWAS provides an effective approach to investigate such complex mechanisms.

  19. Distinct Enzyme-Substrate Interactions Revealed by Two Dimensional Kinetic Comparison between Dehaloperoxidase-Hemoglobin and Horseradish Peroxidase.

    Science.gov (United States)

    Zhao, Jing; Lu, Chang; Franzen, Stefan

    2015-10-08

    The time-resolved kinetics of substrate oxidation and cosubstrate H2O2 reduction by dehaloperoxidase-hemoglobin (DHP) on a seconds-to-minutes time scale was analyzed for peroxidase substrates 2,4,6-tribromophenol (2,4,6-TBP), 2,4,6-trichlorophenol (2,4,6-TCP), and ABTS. Substrates 2,4,6-TBP and 2,4,6-TCP show substrate inhibition at high concentration due to the internal binding at the distal pocket of DHP, whereas ABTS does not show substrate inhibition at any concentration. The data are consistent with an external binding site for the substrates with an internal substrate inhibitor binding site for 2,4,6-TBP and 2,4,6-TCP. We have also compared the kinetic behavior of horseradish peroxidase (HRP) in terms of kcat, Km(AH2) and Km(H2O2) using the same kinetic scheme. Unlike DHP, HRP does not exhibit any measurable substrate inhibition, consistent with substrate binding at the edge of heme near the protein surface at all substrate concentrations. The binding of substrates and their interactions with the heme iron were further compared between DHP and HRP using a competitive fluoride binding experiment, which provides a method for quantitative measurement of internal association constants associated with substrate inhibition. These experiments show the regulatory role of an internal substrate binding site in DHP from both a kinetic and competitive ligand binding perspective. The interaction of DHP with substrates as a result of internal binding actually stabilizes that protein and permits DHP to function under conditions that denature HRP. As a consequence, DHP is a tortoise, a slow but steady enzyme that wins the evolutionary race against the HRP-type of peroxidase, which is a hare, initially rapid, but flawed for this application because of the protein denaturation under the conditions of the experiment.

  20. Single-molecule visualization of Saccharomyces cerevisiae leading-strand synthesis reveals dynamic interaction between MTC and the replisome.

    Science.gov (United States)

    Lewis, Jacob S; Spenkelink, Lisanne M; Schauer, Grant D; Hill, Flynn R; Georgescu, Roxanna E; O'Donnell, Michael E; van Oijen, Antoine M

    2017-09-18

    The replisome, the multiprotein system responsible for genome duplication, is a highly dynamic complex displaying a large number of different enzyme activities. Recently, the Saccharomyces cerevisiae minimal replication reaction has been successfully reconstituted in vitro. This provided an opportunity to uncover the enzymatic activities of many of the components in a eukaryotic system. Their dynamic behavior and interactions in the context of the replisome, however, remain unclear. We use a tethered-bead assay to provide real-time visualization of leading-strand synthesis by the S. cerevisiae replisome at the single-molecule level. The minimal reconstituted leading-strand replisome requires 24 proteins, forming the CMG helicase, the Pol ε DNA polymerase, the RFC clamp loader, the PCNA sliding clamp, and the RPA single-stranded DNA binding protein. We observe rates and product lengths similar to those obtained from ensemble biochemical experiments. At the single-molecule level, we probe the behavior of two components of the replication progression complex and characterize their interaction with active leading-strand replisomes. The Minichromosome maintenance protein 10 (Mcm10), an important player in CMG activation, increases the number of productive replication events in our assay. Furthermore, we show that the fork protection complex Mrc1-Tof1-Csm3 (MTC) enhances the rate of the leading-strand replisome threefold. The introduction of periods of fast replication by MTC leads to an average rate enhancement of a factor of 2, similar to observations in cellular studies. We observe that the MTC complex acts in a dynamic fashion with the moving replisome, leading to alternating phases of slow and fast replication.

  1. AFM force spectroscopy reveals how subtle structural differences affect the interaction strength between Candida albicans and DC-SIGN.

    Science.gov (United States)

    te Riet, Joost; Reinieren-Beeren, Inge; Figdor, Carl G; Cambi, Alessandra

    2015-11-01

    The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, such as the C-type lectin dendritic cell-specific intracellular cell adhesion molecule-3 (ICAM-3)-grabbing non-integrin (DC-SIGN), because a detailed characterization at the structural level is lacking. DC-SIGN recognizes specific Candida-associated molecular patterns, that is, mannan structures present in the cell wall of Candida. The molecular recognition mechanism is however poorly understood. We postulated that small differences in mannan-branching may result in considerable differences in the binding affinity. Here, we exploit atomic force microscope-based dynamic force spectroscopy with single Candida cells to gain better insight in the carbohydrate recognition capacity of DC-SIGN. We demonstrate that slight differences in the N-mannan structure of Candida, that is, the absence or presence of a phosphomannan side chain, results in differences in the recognition by DC-SIGN as follows: (i) it contributes to the compliance of the outer cell wall of Candida, and (ii) its presence results in a higher binding energy of 1.6 kB T. The single-bond affinity of tetrameric DC-SIGN for wild-type C. albicans is ~10.7 kB T and a dissociation constant kD of 23 μM, which is relatively strong compared with other carbohydrate-protein interactions described in the literature. In conclusion, this study shows that DC-SIGN specifically recognizes mannan patterns on C. albicans with high affinity. Knowledge on the binding pocket of DC-SIGN and its pathogenic ligands will lead to a better understanding of how fungal-associated carbohydrate structures are recognized by receptors of the immune system and can ultimately contribute to the development of new anti-fungal drugs.

  2. Continuous flow atomic force microscopy imaging reveals fluidity and time-dependent interactions of antimicrobial dendrimer with model lipid membranes.

    Science.gov (United States)

    Lind, Tania Kjellerup; Zielińska, Paulina; Wacklin, Hanna Pauliina; Urbańczyk-Lipkowska, Zofia; Cárdenas, Marité

    2014-01-28

    In this paper, an amphiphilic peptide dendrimer with potential applications against multi-resistant bacteria such as Staphylococcus aureus was synthesized and studied on model cell membranes. The combination of quartz crystal microbalance and atomic force microscopy imaging during continuous flow allowed for in situ monitoring of the very initial interaction processes and membrane transformations on longer time scales. We used three different membrane compositions of low and high melting temperature phospholipids to vary the membrane properties from a single fluid phase to a pure gel phase, while crossing the phase coexistence boundaries at room temperature. The interaction mechanism of the dendrimer was found to be time-dependent and to vary remarkably with the fluidity and coexistence of liquid-solid phases in the membrane. Spherical micelle-like dendrimer-lipid aggregates were formed in the fluid-phase bilayer and led to partial solubilization of the membrane, while in gel-phase membranes, the dendrimers caused areas of local depressions followed by redeposition of flexible lipid patches. Domain coexistence led to a sequence of events initiated by the formation of a ribbon-like network and followed by membrane solubilization via spherical aggregates from the edges of bilayer patches. Our results show that the dendrimer molecules were able to destroy the membrane integrity through different mechanisms depending on the lipid phase and morphology and shed light on their antimicrobial activity. These findings could have an impact on the efficacy of the dendrimers since lipid membranes in certain bacteria have transition temperatures very close to the host body temperature.

  3. Functional interactions within the parahippocampal region revealed by voltage-sensitive dye imaging in the isolated guinea pig brain.

    Science.gov (United States)

    Biella, Gerardo; Spaiardi, Paolo; Toselli, Mauro; de Curtis, Marco; Gnatkovsky, Vadym

    2010-02-01

    The massive transfer of information from the neocortex to the entorhinal cortex (and vice versa) is hindered by a powerful inhibitory control generated in the perirhinal cortex. In vivo and in vitro experiments performed in rodents and cats support this conclusion, further extended in the present study to the analysis of the interaction between the entorhinal cortex and other parahippocampal areas, such as the postrhinal and the retrosplenial cortices. The experiments were performed in the in vitro isolated guinea pig brain by a combined approach based on electrophysiological recordings and fast imaging of optical signals generated by voltage-sensitive dyes applied to the entire brain by arterial perfusion. Local stimuli delivered in different portions of the perirhinal, postrhinal, and retrosplenial cortex evoked local responses that did not propagate to the entorhinal cortex. Neither high- and low-frequency-patterned stimulation nor paired associative stimuli facilitated the propagation of activity to the entorhinal region. Similar stimulations performed during cholinergic neuromodulation with carbachol were also ineffective in overcoming the inhibitory network that controls propagation to the entorhinal cortex. The pharmacological inactivation of GABAergic transmission by local application of bicuculline (1 mM) in area 36 of the perirhinal cortex facilitated the longitudinal (rostrocaudal) propagation of activity into the perirhinal/postrhinal cortices but did not cause propagation into the entorhinal cortex. Bicuculline injection in both area 35 and medial entorhinal cortex released the inhibitory control and allowed the propagation of the neural activity to the entorhinal cortex. These results demonstrate that, as for the perirhinal-entorhinal reciprocal interactions, also the connections between the postrhinal/retrosplenial cortices and the entorhinal region are subject to a powerful inhibitory control.

  4. Global gene expression analysis of the zoonotic parasite Trichinella spiralis revealed novel genes in host parasite interaction.

    Directory of Open Access Journals (Sweden)

    Xiaolei Liu

    Full Text Available BACKGROUND: Trichinellosis is a typical food-borne zoonotic disease which is epidemic worldwide and the nematode Trichinella spiralis is the main pathogen. The life cycle of T. spiralis contains three developmental stages, i.e. adult worms, new borne larva (new borne L1 larva and muscular larva (infective L1 larva. Stage-specific gene expression in the parasites has been investigated with various immunological and cDNA cloning approaches, whereas the genome-wide transcriptome and expression features of the parasite have been largely unknown. The availability of the genome sequence information of T. spiralis has made it possible to deeply dissect parasite biology in association with global gene expression and pathogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we analyzed the global gene expression patterns in the three developmental stages of T. spiralis using digital gene expression (DGE analysis. Almost 15 million sequence tags were generated with the Illumina RNA-seq technology, producing expression data for more than 9,000 genes, covering 65% of the genome. The transcriptome analysis revealed thousands of differentially expressed genes within the genome, and importantly, a panel of genes encoding functional proteins associated with parasite invasion and immuno-modulation were identified. More than 45% of the genes were found to be transcribed from both strands, indicating the importance of RNA-mediated gene regulation in the development of the parasite. Further, based on gene ontological analysis, over 3000 genes were functionally categorized and biological pathways in the three life cycle stage were elucidated. CONCLUSIONS AND SIGNIFICANCE: The global transcriptome of T. spiralis in three developmental stages has been profiled, and most gene activity in the genome was found to be developmentally regulated. Many metabolic and biological pathways have been revealed. The findings of the differential expression of several protein

  5. All-atom molecular dynamics simulations reveal significant differences in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc1 complexes.

    Science.gov (United States)

    Kokhan, Oleksandr; Shinkarev, Vladimir P

    2011-02-02

    Antimycin A is the most frequently used specific and powerful inhibitor of the mitochondrial respiratory chain. We used all-atom molecular dynamics (MD) simulations to study the dynamic aspects of the interaction of antimycin A with the Q(i) site of the bacterial and bovine bc(1) complexes embedded in a membrane. The MD simulations revealed considerable conformational flexibility of antimycin and significant mobility of antimycin, as a whole, inside the Q(i) pocket. We conclude that many of the differences in antimycin binding observed in high-resolution x-ray structures may have a dynamic origin and result from fluctuations of protein and antimycin between multiple conformational states of similar energy separated by low activation barriers, as well as from the mobility of antimycin within the Q(i) pocket. The MD simulations also revealed a significant difference in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc(1) complexes. The strong hydrogen bond between antimycin and conserved Asp-228 (bovine numeration) was observed to be frequently broken in the bacterial bc(1) complex and only rarely in the bovine bc(1) complex. In addition, the distances between antimycin and conserved His-201 and Lys-227 were consistently larger in the bacterial bc(1) complex. The observed differences could be responsible for a weaker interaction of antimycin with the bacterial bc(1) complex.

  6. Maximum Entropy Fundamentals

    Directory of Open Access Journals (Sweden)

    F. Topsøe

    2001-09-01

    Full Text Available Abstract: 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

  7. Computer modeling reveals that modifications of the histone tail charges define salt-dependent interaction of the nucleosome core particles.

    Science.gov (United States)

    Yang, Ye; Lyubartsev, Alexander P; Korolev, Nikolay; Nordenskiöld, Lars

    2009-03-18

    Coarse-grained Langevin molecular dynamics computer simulations were conducted for systems that mimic solutions of nucleosome core particles (NCPs). The NCP was modeled as a negatively charged spherical particle representing the complex of DNA and the globular part of the histones combined with attached strings of connected charged beads modeling the histone tails. The size, charge, and distribution of the tails relative to the core were built to match real NCPs. Three models of NCPs were constructed to represent different extents of covalent modification on the histone tails: (nonmodified) recombinant (rNCP), acetylated (aNCP), and acetylated and phosphorylated (paNCP). The simulation cell contained 10 NCPs in a dielectric continuum with explicit mobile counterions and added salt. The NCP-NCP interaction is decisively dependent on the modification state of the histone tails and on salt conditions. Increasing the monovalent salt concentration (KCl) from salt-free to physiological concentration leads to NCP aggregation in solution for rNCP, whereas NCP associates are observed only occasionally in the system of aNCPs. In the presence of divalent salt (Mg(2+)), rNCPs form dense stable aggregates, whereas aNCPs form aggregates less frequently. Aggregates are formed via histone-tail bridging and accumulation of counterions in the regions of NCP-NCP contacts. The paNCPs do not show NCP-NCP interaction upon addition of KCl or in the presence of Mg(2+). Simulations for systems with a gradual substitution of K(+) for Mg(2+), to mimic the Mg(2+) titration of an NCP solution, were performed. The rNCP system showed stronger aggregation that occurred at lower concentrations of added Mg(2+), compared to the aNCP system. Additional molecular dynamics simulations performed with a single NCP in the simulation cell showed that detachment of the tails from the NCP core was modest under a wide range of salt concentrations. This implies that salt-induced tail dissociation of the

  8. The emergence of the dimensions and fundamental forces in the universe, an information-theoretical approach for the expaining of the quantity ratios of the fundamental interactions. 2. rev. and enl. ed.; Die Entstehung der Dimensionen und Grundkraefte im Universum, ein informationstheoretischer Ansatz zur Erklaerung der Groessenverhaeltnisse der Fundamentalen Wechselwirkungen

    Energy Technology Data Exchange (ETDEWEB)

    Ganter, Bernd

    2013-06-01

    After a description of the four fundamental inteactions and the connection of information with energy the principle of the fast maximation together with the Ganter tableau is described. Then as example the derivation of the value of the fine-structure constant from the Ganter tableau is described. Thereafter the extension of the Ganter tableau, further properties of the Ganter tableau, and the persuasion of the Ganter tableau are considered. (HSI)

  9. Characterization of Kbot21 Reveals Novel Side Chain Interactions of Scorpion Toxins Inhibiting Voltage-Gated Potassium Channels.

    Science.gov (United States)

    ElFessi-Magouri, Rym; Peigneur, Steve; Othman, Houcemeddine; Srairi-Abid, Najet; ElAyeb, Mohamed; Tytgat, Jan; Kharrat, Riadh

    2015-01-01

    Scorpion toxins are important pharmacological tools for probing the physiological roles of ion channels which are involved in many physiological processes and as such have significant therapeutic potential. The discovery of new scorpion toxins with different specificities and affinities is needed to further characterize the physiology of ion channels. In this regard, a new short polypeptide called Kbot21 has been purified to homogeneity from the venom of Buthus occitanus tunetanus scorpion. Kbot21 is structurally related to BmBKTx1 from the venom of the Asian scorpion Buthus martensii Karsch. These two toxins differ by only two residues at position 13 (R /V) and 24 (D/N).Despite their very similar sequences, Kbot21 and BmBKTx1 differ in their electrophysiological activities. Kbot21 targets KV channel subtypes whereas BmBKTx1 is active on both big conductance (BK) and small conductance (SK) Ca2+-activated K+ channel subtypes, but has no effects on Kv channel subtypes. The docking model of Kbot21 with the Kv1.2 channel shows that the D24 and R13 side-chain of Kbot21 are critical for its interaction with KV channels.

  10. A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions

    KAUST Repository

    Fan, Qihui

    2017-07-10

    A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tuneable biochemical gradients that mimics the tumour microenvironment of mammary glands was constructed for the investigation on the interactions between invasive breast cancer cells and stromal cells. The hollow microchambers in collagen provide a very similar 3-D environment to that in vivo that regulates collective cellular dynamics and behaviour, while the microfluidic channels surrounding the collagen microchamber arrays allow one to impose complex concentration gradients of specific biological molecules or drugs. We found that breast epithelial cells (MCF-10A) seeded in the microchambers formed lumen-like structures similar to those in epithelial layers. When MCF-10A cells were co-cultured with invasive breast cancer cells (MDA-MB-231), the formation of lumen-like structures in the microchambers was inhibited, indicating the capability of cancer cells to disrupt the structures formed by surrounding cells for further invasion and metastasis. Subsequent mechanism studies showed that down regulation of E-cad expression due to MMPs produced by the cancer cells plays a dominant role in determining the cellular behaviour. Our microfluidic system offers a robust platform for high throughput studies that aim to understand combinatorial effects of multiple biochemical and microenvironmental factors.

  11. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  12. Mutational Analysis Reveals a Noncontractile but Interactive Role of Actin and Profilin in Viral RNA-Dependent RNA Synthesis▿

    Science.gov (United States)

    Harpen, Mary; Barik, Tiasha; Musiyenko, Alla; Barik, Sailen

    2009-01-01

    As obligatory parasites, viruses co-opt a variety of cellular functions for robust replication. The expression of the nonsegmented negative-strand RNA genome of respiratory syncytial virus (RSV), a significant pediatric pathogen, absolutely requires actin and is stimulated by the actin-regulatory protein profilin. As actin is a major contractile protein, it was important to determine whether the known functional domains of actin and profilin were important for their ability to activate RSV transcription. Analyses of recombinant mutants in a reconstituted RSV transcription system suggested that the divalent-cation-binding domain of actin is critically needed for binding to the RSV genome template and for the activation of viral RNA synthesis. In contrast, the nucleotide-binding domain and the N-terminal acidic domain were needed neither for template binding nor for transcription. Specific surface residues of actin, required for actin-actin contact during filamentation, were also nonessential for viral transcription. Unlike actin, profilin did not directly bind to the viral template but was recruited by actin. Mutation of the interactive residues of actin or profilin, resulting in the loss of actin-profilin binding, also abolished profilin's ability to stimulate viral transcription. Together, these results suggest that actin acts as a classical transcription factor for the virus by divalent-cation-dependent binding to the viral template and that profilin acts as a transcriptional cofactor, in part by associating with actin. This essential viral role of actin is independent of its contractile cellular role. PMID:19710142

  13. Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method.

    Directory of Open Access Journals (Sweden)

    Martin Meier-Schellersheim

    2006-07-01

    Full Text Available The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential activation/deactivation of membrane-bound and cytosolic components. As such, it provides particularly interesting challenges for a combined computational and experimental analysis. We developed a novel detailed molecular signaling model that, when used to simulate the response to the attractant cyclic adenosine monophosphate (cAMP, made nontrivial predictions about Dictyostelium chemosensing. These predictions, including the unexpected existence of spatially asymmetrical, multiphasic, cyclic adenosine monophosphate-induced PTEN translocation and phosphatidylinositol-(3,4,5P3 generation, were experimentally verified by quantitative single-cell microscopy leading us to propose significant modifications to the current standard model for chemoattractant-induced biochemical polarization in this organism. Key to this successful modeling effort was the use of "Simmune," a new software package that supports the facile development and testing of detailed computational representations of cellular behavior. An intuitive interface allows user definition of complex signaling networks based on the definition of specific molecular binding site interactions and the subcellular localization of molecules. It automatically translates such inputs into spatially resolved simulations and dynamic graphical representations of the resulting signaling network that can be explored in a manner that closely parallels wet lab experimental procedures. These features of Simmune were critical to the model development and analysis presented here and are likely to be useful in the computational investigation of many aspects of cell biology.

  14. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Ryo Sato

    2017-01-01

    Full Text Available Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  15. Genetic and transgenic perturbations of carbon reserve production in Arabidopsis seeds reveal metabolic interactions of biochemical pathways.

    Science.gov (United States)

    Lin, Yun; Ulanov, Alexander V; Lozovaya, Vera; Widholm, Jack; Zhang, Guirong; Guo, Jinhua; Goodman, Howard M

    2006-12-01

    The biosynthesis of seed oil and starch both depend on the supply of carbon from the maternal plant. The biochemical interactions between these two pathways are not fully understood. In the Arabidopsis mutant shrunken seed 1 (sse1)/pex16, a reduced rate of fatty acid synthesis leads to starch accumulation. To further understand the metabolic impact of the decrease in oil synthesis, we compared soluble metabolites in sse1 and wild type (WT) seeds. Sugars, sugar phosphates, alcohols, pyruvate, and many other organic acids accumulated in sse1 seeds as a likely consequence of the reduced carbon demand for lipid synthesis. The enlarged pool size of hexose-P, the metabolites at the crossroad of sugar metabolism, glycolysis, and starch synthesis, was likely a direct cause of the increased flow into starch. Downstream of glycolysis, more carbon entered the TCA cycle as an alternative to the fatty acid pathway, causing the total amount of TCA cycle intermediates to rise while moving the steady state of the cycle away from fumarate. To convert the excess carbon metabolites into starch, we introduced the Escherichia coli starch synthetic enzyme ADP-glucose pyrophosphorylase (AGPase) into sse1 seeds. Expression of AGPase enhanced net starch biosynthesis in the mutant, resulting in starch levels that reached 37% of seed weight. However, further increases above this level were not achieved and most of the carbon intermediates remained high in comparison with the WT, indicating that additional mechanisms limit starch deposition in Arabidopsis seeds.

  16. Single-cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks involved In the Central Circadian Clock

    Directory of Open Access Journals (Sweden)

    James Park

    2016-10-01

    Full Text Available Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN. Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we developed a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies towards understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.

  17. Large-scale screening of transcription factor-promoter interactions in spruce reveals a transcriptional network involved in vascular development.

    Science.gov (United States)

    Duval, Isabelle; Lachance, Denis; Giguère, Isabelle; Bomal, Claude; Morency, Marie-Josée; Pelletier, Gervais; Boyle, Brian; MacKay, John J; Séguin, Armand

    2014-06-01

    This research aimed to investigate the role of diverse transcription factors (TFs) and to delineate gene regulatory networks directly in conifers at a relatively high-throughput level. The approach integrated sequence analyses, transcript profiling, and development of a conifer-specific activation assay. Transcript accumulation profiles of 102 TFs and potential target genes were clustered to identify groups of coordinately expressed genes. Several different patterns of transcript accumulation were observed by profiling in nine different organs and tissues: 27 genes were preferential to secondary xylem both in stems and roots, and other genes were preferential to phelloderm and periderm or were more ubiquitous. A robust system has been established as a screening approach to define which TFs have the ability to regulate a given promoter in planta. Trans-activation or repression effects were observed in 30% of TF-candidate gene promoter combinations. As a proof of concept, phylogenetic analysis and expression and trans-activation data were used to demonstrate that two spruce NAC-domain proteins most likely play key roles in secondary vascular growth as observed in other plant species. This study tested many TFs from diverse families in a conifer tree species, which broadens the knowledge of promoter-TF interactions in wood development and enables comparisons of gene regulatory networks found in angiosperms and gymnosperms.

  18. Characterization of Kbot21 Reveals Novel Side Chain Interactions of Scorpion Toxins Inhibiting Voltage-Gated Potassium Channels.

    Directory of Open Access Journals (Sweden)

    Rym ElFessi-Magouri

    Full Text Available Scorpion toxins are important pharmacological tools for probing the physiological roles of ion channels which are involved in many physiological processes and as such have significant therapeutic potential. The discovery of new scorpion toxins with different specificities and affinities is needed to further characterize the physiology of ion channels. In this regard, a new short polypeptide called Kbot21 has been purified to homogeneity from the venom of Buthus occitanus tunetanus scorpion. Kbot21 is structurally related to BmBKTx1 from the venom of the Asian scorpion Buthus martensii Karsch. These two toxins differ by only two residues at position 13 (R /V and 24 (D/N.Despite their very similar sequences, Kbot21 and BmBKTx1 differ in their electrophysiological activities. Kbot21 targets KV channel subtypes whereas BmBKTx1 is active on both big conductance (BK and small conductance (SK Ca2+-activated K+ channel subtypes, but has no effects on Kv channel subtypes. The docking model of Kbot21 with the Kv1.2 channel shows that the D24 and R13 side-chain of Kbot21 are critical for its interaction with KV channels.

  19. Quantitative Trait Locus Analysis of Seed Germination and Seedling Vigor in Brassica rapa Reveals QTL Hotspots and Epistatic Interactions.

    Science.gov (United States)

    Basnet, Ram K; Duwal, Anita; Tiwari, Dev N; Xiao, Dong; Monakhos, Sokrat; Bucher, Johan; Visser, Richard G F; Groot, Steven P C; Bonnema, Guusje; Maliepaard, Chris

    2015-01-01

    The genetic basis of seed germination and seedling vigor is largely unknown in Brassica species. We performed a study to evaluate the genetic basis of these important traits in a B. rapa doubled haploid population from a cross of a yellow-seeded oil-type yellow sarson and a black-seeded vegetable-type pak choi. We identified 26 QTL regions across all 10 linkage groups for traits related to seed weight, seed germination and seedling vigor under non-stress and salt stress conditions illustrating the polygenic nature of these traits. QTLs for multiple traits co-localized and we identified eight hotspots for quantitative trait loci (QTL) of seed weight, seed germination, and root and shoot lengths. A QTL hotspot for seed germination on A02 mapped at the B. rapa Flowering Locus C (BrFLC2). Another hotspot on A05 with salt stress specific QTLs co-located with the B. rapa Fatty acid desaturase 2 (BrFAD2) locus. Epistatic interactions were observed between QTL hotspots for seed germination on A02 and A10 and with a salt tolerance QTL on A05. These results contribute to the understanding of the genetics of seed quality and seeding vigor in B. rapa and can offer tools for Brassica breeding.

  20. Genetic Interactions Reveal that Specific Defects of Chloroplast Translation are Associated with the Suppression of var2-Mediated Leaf Variegation

    Institute of Scientific and Technical Information of China (English)

    Xiayan Liu; Mengdi Zheng; Rui Wang; Ruijuan Wang; Lijun An; Steve R. Rodermel; Fei Yu

    2013-01-01

    Arabidopsis thaliana L. yellow variegated (var2) mutant is defective in a chloroplast FtsH family metalloprotease, AtFtsH2/VAR2, and displays an intriguing green and white leaf variegation. This unique var2-mediated leaf variegation offers a simple yet powerful tool for dissecting the genetic regulation of chloroplast development. Here, we report the isolation and characterization of a new var2 suppressor gene, SUPPRESSOR OF VARIEGATION8 (SVR8), which encodes a putative chloroplast ribosomal large subunit protein, L24. Mutations in SVR8 suppress var2 leaf variegation at ambient temperature and partially suppress the cold-induced chlorosis phenotype of var2. Loss of SVR8 causes unique chloroplast rRNA processing defects, particularly the 23S-4.5S dicistronic precursor. The recovery of the major abnormal processing site in svr8 23S-4.5S precursor indicate that it does not lie in the same position where SVR8/L24 binds on the ribosome. Surprisingly, we found that the loss of a chloroplast ribosomal small subunit protein, S21, results in aberrant chloroplast rRNA processing but not suppression of var2 variegation. These findings suggest that the disruption of specific aspects of chloroplast translation, rather than a general impairment in chloroplast translation, suppress var2 variegation and the existence of complex genetic interactions in chloroplast development.

  1. A delicate balance of magmatic-tectonic interaction at Kilauea Volcano, Hawai`i, revealed from slow slip events

    Science.gov (United States)

    Montgomery-Brown, Emily; Poland, Michael; Miklius, Asta

    2015-01-01

    Eleven slow slip events (SSEs) have occurred on the southern flank of Kilauea Volcano, Hawai’i, since 1997 through 2014. We analyze this series of SSEs in the context of Kilauea’s magma system to assess whether or not there are interactions between these tectonic events and eruptive/intrusive activity. Over time, SSEs have increased in magnitude and become more regular, with interevent times averaging 2.44 ± 0.15 years since 2003. Two notable SSEs that impacted both the flank and the magmatic system occurred in 2007, when an intrusion and small eruption on the East Rift Zone were part of a feedback with a SSE and 2012, when slow slip induced 2.5 cm of East Rift Zone opening (but without any change in eruptive activity). A summit inflation event and surge in East Rift Zone lava effusion was associated with a SSE in 2005, but the inferred triggering relation is not clear due to a poorly constrained slip onset time. Our results demonstrate that slow slip along Kilauea’s décollement has the potential to trigger and be triggered by activity within the volcano’s magma system. Since only three of the SSEs have been associated with changes in magmatic activity within the summit and rift zones, both the décollement and magma system must be close to failure for triggering to occur.

  2. Functional interaction between S1 and S4 segments in voltage-gated sodium channels revealed by human channelopathies.

    Science.gov (United States)

    Amarouch, Mohamed-Yassine; Kasimova, Marina A; Tarek, Mounir; Abriel, Hugues

    2014-01-01

    The p.I141V mutation of the voltage-gated sodium channel is associated with several clinical hyper-excitability phenotypes. To understand the structural bases of the p.I141V biophysical alterations, molecular dynamics simulations were performed. These simulations predicted that the p.I141V substitution induces the formation of a hydrogen bond between the Y168 residue of the S2 segment and the R225 residue of the S4 segment. We generated a p.I141V-Y168F double mutant for both the Nav1.4 and Nav1.5 channels. The double mutants demonstrated the abolition of the functional effects of the p.I141V mutation, consistent with the formation of a specific interaction between Y168-S2 and R225-S4. The single p.Y168F mutation, however, positively shifted the activation curve, suggesting a compensatory role of these residues on the stability of the voltage-sensing domain.

  3. Determinants of the direction illusion: motion speed and dichoptic presentation interact to reveal systematic individual differences in sign.

    Science.gov (United States)

    Chen, Tony T; Maloney, Ryan T; Clifford, Colin W G

    2014-07-17

    When two fields of dots with different directions of movement are presented in tandem, the perceived direction of one is biased by the presence of the other. Although this ‘‘direction illusion’’ typically involves repulsion, with an exaggeration of the perceived angular difference in direction between the dot fields, attraction effects, where the perceived difference is reduced, have also been found under certain presentation conditions. Earlier literature has been inconsistent, and there is debate surrounding the nature of the interactions that facilitate the direction illusion, as well as whether they occur at a local or global stage of the motion processing hierarchy. Here we measured the operating characteristics of the direction illusion by parametrically varying inducer contrast and coherence while examining the effects of stimulus speed and dichoptic presentation. It was found that the magnitude and sign of the direction illusion differed substantially from earlier research. Furthermore, there appeared to be significant interindividual variability, with dichoptic presentation producing an attractive rather than repulsive direction illusion in some participants.

  4. Fluorescence mapping of mitochondrial TIM23 complex reveals a water-facing, substrate-interacting helix surface.

    Science.gov (United States)

    Alder, Nathan N; Jensen, Robert E; Johnson, Arthur E

    2008-08-08

    Protein translocation across the mitochondrial inner membrane is mediated by the TIM23 complex. While its central component, Tim23, is believed to form a protein-conducting channel, the regions of this subunit that face the imported protein are unknown. To examine Tim23 structure and environment in intact membranes at high resolution, various derivatives, each with a single, environment-sensitive fluorescent probe positioned at a specific site, were assembled into functional TIM23 complexes in active mitochondria and analyzed by multiple spectral techniques. Probes placed sequentially throughout a transmembrane region that was identified by crosslinking as part of the protein-conducting channel revealed an alpha helix in an amphipathic environment. Probes on the aqueous-facing helical surface specifically underwent spectral changes during protein import, and their accessibility to hydrophilic quenching agents is considered in terms of channel gating. This approach has therefore provided an unprecedented view of a translocon channel structure in an intact, fully operational, membrane-embedded complex.

  5. An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions.

    Science.gov (United States)

    Arvey, Aaron; Tempera, Italo; Tsai, Kevin; Chen, Horng-Shen; Tikhmyanova, Nadezhda; Klichinsky, Michael; Leslie, Christina; Lieberman, Paul M

    2012-08-16

    Epstein-Barr virus (EBV), which is associated with multiple human tumors, persists as a minichromosome in the nucleus of B lymphocytes and induces malignancies through incompletely understood mechanisms. Here, we present a large-scale functional genomic analysis of EBV. Our experimentally generated nucleosome positioning maps and viral protein binding data were integrated with over 700 publicly available high-throughput sequencing data sets for human lymphoblastoid cell lines mapped to the EBV genome. We found that viral lytic genes are coexpressed with cellular cancer-associated pathways, suggesting that the lytic cycle may play an unexpected role in virus-mediated oncogenesis. Host regulators of viral oncogene expression and chromosome structure were identified and validated, revealing a role for the B cell-specific protein Pax5 in viral gene regulation and the cohesin complex in regulating higher order chromatin structure. Our findings provide a deeper understanding of latent viral persistence in oncogenesis and establish a valuable viral genomics resource for future exploration.

  6. Crystal structure of TAZ-TEAD complex reveals a distinct interaction mode from that of YAP-TEAD complex.

    Science.gov (United States)

    Kaan, Hung Yi Kristal; Chan, Siew Wee; Tan, Siew Kim Joyce; Guo, Fusheng; Lim, Chun Jye; Hong, Wanjin; Song, Haiwei

    2017-05-17

    The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the transcription of growth-promoting genes. Herein, we report the crystal structure of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to the published YAP-TEAD structure. The second is a unique binding mode, whereby two molecules of TAZ bind to and bridge two molecules of TEAD4. We validated the latter using cross-linking and multi-angle light scattering. Using siRNA, we showed that TAZ knockdown leads to a decrease in TEAD4 dimerization. Lastly, results from luciferase assays, using YAP/TAZ transfected or knockdown cells, give support to the non-redundancy of YAP/TAZ co-activators in regulating gene expression in the Hippo pathway.

  7. Proteomics Analysis Reveals Distinct Corona Composition on Magnetic Nanoparticles with Different Surface Coatings: Implications for Interactions with Primary Human Macrophages.

    Science.gov (United States)

    Vogt, Carmen; Pernemalm, Maria; Kohonen, Pekka; Laurent, Sophie; Hultenby, Kjell; Vahter, Marie; Lehtiö, Janne; Toprak, Muhammet S; Fadeel, Bengt

    2015-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising contrast agents for magnetic resonance imaging. The influence of different surface coatings on the biocompatibility of SPIONs has been addressed, but the potential impact of the so-called corona of adsorbed proteins on the surface of SPIONs on their biological behavior is less well studied. Here, we determined the composition of the plasma protein corona on silica-coated versus dextran-coated SPIONs using mass spectrometry-based proteomics approaches. Notably, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs.

  8. Proteomics Analysis Reveals Distinct Corona Composition on Magnetic Nanoparticles with Different Surface Coatings: Implications for Interactions with Primary Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Carmen Vogt

    Full Text Available Superparamagnetic iron oxide nanoparticles (SPIONs have emerged as promising contrast agents for magnetic resonance imaging. The influence of different surface coatings on the biocompatibility of SPIONs has been addressed, but the potential impact of the so-called corona of adsorbed proteins on the surface of SPIONs on their biological behavior is less well studied. Here, we determined the composition of the plasma protein corona on silica-coated versus dextran-coated SPIONs using mass spectrometry-based proteomics approaches. Notably, gene ontology (GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway analysis revealed distinct protein corona compositions for the two different SPIONs. Relaxivity of silica-coated SPIONs was modulated by the presence of a protein corona. Moreover, the viability of primary human monocyte-derived macrophages was influenced by the protein corona on silica-coated, but not dextran-coated SPIONs, and the protein corona promoted cellular uptake of silica-coated SPIONs, but did not affect internalization of dextran-coated SPIONs.

  9. Fundamentals of neuromechanics

    CERN Document Server

    Valero-Cuevas, Francisco J

    2016-01-01

    This book provides a conceptual and computational framework to study how the nervous system exploits the anatomical properties of limbs to produce mechanical function. The study of the neural control of limbs has historically emphasized the use of optimization to find solutions to the muscle redundancy problem. That is, how does the nervous system select a specific muscle coordination pattern when the many muscles of a limb allow for multiple solutions? I revisit this problem from the emerging perspective of neuromechanics that emphasizes finding and implementing families of feasible solutions, instead of a single and unique optimal solution. Those families of feasible solutions emerge naturally from the interactions among the feasible neural commands, anatomy of the limb, and constraints of the task. Such alternative perspective to the neural control of limb function is not only biologically plausible, but sheds light on the most central tenets and debates in the fields of neural control, robotics, rehabilit...

  10. Hyperbolic metamaterials: fundamentals and applications.

    Science.gov (United States)

    Shekhar, Prashant; Atkinson, Jonathan; Jacob, Zubin

    2014-01-01

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

  11. Mapping temporal dynamics in social interactions with unified structural equation modeling: A description and demonstration revealing time-dependent sex differences in play behavior.

    Science.gov (United States)

    Beltz, Adriene M; Beekman, Charles; Molenaar, Peter C M; Buss, Kristin A

    2013-07-01

    Developmental science is rich with observations of social interactions, but few available methodological and statistical approaches take full advantage of the information provided by these data. The authors propose implementation of the unified structural equation model (uSEM), a network analysis technique, for observational data coded repeatedly across time; uSEM captures the temporal dynamics underlying changes in behavior at the individual level by revealing the ways in which a single person influences - concurrently and in the future - other people. To demonstrate the utility of uSEM, the authors applied it to ratings of positive affect and vigor of activity during children's unstructured laboratory play with unfamiliar, same-sex peers. Results revealed the time-dependent nature of sex differences in play behavior. For girls more than boys, positive affect was dependent upon peers' prior positive affect. For boys more than girls, vigor of activity was dependent upon peers' current vigor of activity.

  12. Integrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue.

    Science.gov (United States)

    Kirby, Tyler J; Walton, R Grace; Finlin, Brian; Zhu, Beibei; Unal, Resat; Rasouli, Neda; Peterson, Charlotte A; Kern, Philip A

    2016-02-01

    Adipose tissue has profound effects on whole-body insulin sensitivity. However, the underlying biological processes are quite complex and likely multifactorial. For instance, the adipose transcriptome is posttranscriptionally modulated by microRNAs, but the relationship between microRNAs and insulin sensitivity in humans remains to be determined. To this end, we utilized an integrative mRNA-microRNA microarray approach to identify putative molecular interactions that regulate the transcriptome in subcutaneous adipose tissue of insulin-sensitive (IS) and insulin-resistant (IR) individuals. Using the NanoString nCounter Human v1 microRNA Expression Assay, we show that 17 microRNAs are differentially expressed in IR vs. IS. Of these, 16 microRNAs (94%) are downregulated in IR vs. IS, including miR-26b, miR-30b, and miR-145. Using Agilent Human Whole Genome arrays, we identified genes that were predicted targets of miR-26b, miR-30b, and miR-145 and were upregulated in IR subjects. This analysis produced ADAM22, MYO5A, LOX, and GM2A as predicted gene targets of these microRNAs. We then validated that miR-145 and miR-30b regulate these mRNAs in differentiated human adipose stem cells. We suggest that use of bioinformatic integration of mRNA and microRNA arrays yields verifiable mRNA-microRNA pairs that are associated with insulin resistance and can be validated in vitro. Copyright © 2016 the American Physiological Society.

  13. Fluid flow and water-rock interaction across the active Nankai Trough subduction zone forearc revealed by boron isotope geochemistry

    Science.gov (United States)

    Hüpers, Andre; Kasemann, Simone A.; Kopf, Achim J.; Meixner, Anette; Toki, Tomohiro; Shinjo, Ryuichi; Wheat, C. Geoffrey; You, Chen-Feng

    2016-11-01

    Compositional changes, dehydration reactions and fluid flow in subducted sediments influence seismogenesis and arc magmatism in subduction zones. To identify fluid flow and water-rock interaction processes in the western Nankai Trough subduction zone (SW Japan) we analyzed boron concentration and boron isotope composition (δ11B) of pore fluids sampled across the subduction zone forearc from depths of up to ∼922 m below seafloor during four Integrated Ocean Drilling Program (IODP) Expeditions. The major structural regimes that were sampled by coring include: (1) sedimentary inputs, (2) the frontal thrust zone, (3) the megasplay fault zone, and (4) the forearc basin. From mass balance consideration we find that consumption of boron (B) by ash alteration and desorption of B from the solid phase, mediated by organic matter degradation, produces a net decrease in B concentrations with depth down to ∼120 μM and variable δ11B values in the range of ∼+20‰ and +49‰. Interstitial water in sediments on the incoming oceanic plate are influenced by more efficient mobilization of exchangeable B from the solid phase due to higher temperatures and alteration of the oceanic crust that acts as a sink for 10B. At the tip of the megasplay fault zone, elevated B concentration and B isotopic composition suggest that underthrust coarse-grained slope sediments provide a pathway for fluids out of the upper (balance considerations suggest a shallower fluid source depth compared to pore fluids sampled previously near the décollement zone along the central portion of the Nankai margin.

  14. Lanthanide–lanthanide and lanthanide–defect interactions in co-doped ceria revealed by luminescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Avram, Daniel; Gheorghe, Cristina [National Institute for Laser, Plasma and Radiation Physics, P.O. Box MG-36, RO 76900 Bucharest-Magurele (Romania); Rotaru, Codruta; Cojocaru, Bogdan; Florea, Mihaela; Parvulescu, Vasile [University of Bucharest, Department of Chemical Technology and Catalysis, 4–12 Regina Elisabeta Bvd., Bucharest (Romania); Tiseanu, Carmen, E-mail: tiseanuc@yahoo.com [National Institute for Laser, Plasma and Radiation Physics, P.O. Box MG-36, RO 76900 Bucharest-Magurele (Romania)

    2014-12-15

    Highlights: • (Sm, Nd) and (Sm, Eu) co-doped CeO{sub 2} are investigated by luminescence spectroscopy. • Local structure at Sm sites is not changed by Nd or Eu co-dopant. • Sm is not involved in non-radiative energy transfer to Nd or Eu co-dopant. • The excitation mode of perturbed Eu centre is modified by Sm co-dopant. - Abstract: Here, we present a first study on the local structure properties, lanthanide–lanthanide and lanthanide–defect interactions in lanthanide (Sm{sup 3+}/Nd{sup 3+} and Sm{sup 3+}/Eu{sup 3+}) co-doped CeO{sub 2} nanoparticles by use of luminescence spectroscopy. By comparing the emission/excitation spectra and decays measured with the single doped and co-doped ceria, it is established that the local structure at Sm{sup 3+} sites is not affected by the presence of the Nd{sup 3+} or Eu{sup 3+} co-dopant irrespective of concentration. The results suggest that the excess of oxygen vacancies generated by the co-dopant is not associated with Sm{sup 3+}, being more probably associated with the Nd{sup 3+}/Eu{sup 3+} or/and Ce{sup 4+} cations. It is also observed that Sm{sup 3+} is not involved in significant non-radiative energy transfer to Nd{sup 3+} or Eu{sup 3+} while the relative strong shortening of Nd{sup 3+} luminescence decay with concentration is most probably related to cross-relaxation in Nd{sup 3+}–Nd{sup 3+} pairs.

  15. Gating Competence of Constitutively Open CLC-0 Mutants Revealed by the Interaction with a Small Organic Inhibitor

    Science.gov (United States)

    Traverso, Sonia; Elia, Laura; Pusch, Michael

    2003-01-01

    Opening of CLC chloride channels is coupled to the translocation of the permeant anion. From the recent structure determination of bacterial CLC proteins in the closed and open configuration, a glutamate residue was hypothesized to form part of the Cl−-sensitive gate. The negatively charged side-chain of the glutamate was suggested to occlude the permeation pathway in the closed state, while opening of a single protopore of the double-pore channel would reflect mainly a movement of this side-chain toward the extracellular pore vestibule, with little rearrangement of the rest of the channel. Here we show that mutating this critical residue (Glu166) in the prototype Torpedo CLC-0 to alanine, serine, or lysine leads to constitutively open channels, whereas a mutation to aspartate strongly slowed down opening. Furthermore, we investigated the interaction of the small organic channel blocker p-chlorophenoxy-acetic acid (CPA) with the mutants E166A and E166S. Both mutants were strongly inhibited by CPA at negative voltages with a >200-fold larger affinity than for wild-type CLC-0 (apparent KD at −140 mV ∼4 μM). A three-state linear model with an open state, a low-affinity and a high-affinity CPA-bound state can quantitatively describe steady-state and kinetic properties of the CPA block. The parameters of the model and additional mutagenesis suggest that the high-affinity CPA-bound state is similar to the closed configuration of the protopore gate of wild-type CLC-0. In the E166A mutant the glutamate side chain that occludes the permeation pathway is absent. Thus, if gating consists only in movement of this side-chain the mutant E166A should not be able to assume a closed conformation. It may thus be that fast gating in CLC-0 is more complex than anticipated from the bacterial structures. PMID:12913089

  16. Genome sequence reveals that Pseudomonas fluorescens F113 possesses a large and diverse array of systems for rhizosphere function and host interaction

    OpenAIRE

    2013-01-01

    Redondo-Nieto et al.: Genome sequence reveals that Pseudomonas fluorescens F113 possesses a large and diverse array of systems for rhizosphere function and host interaction. BMC Genomics 2013 14:54.The electronic version of this article is the complete one and can be found online at http://www.biomedcentral.com/1471-2164/14/54 Background: Pseudomonas fluorescens F113 is a plant growth-promoting rhizobacterium (PGPR) isolated from the sugar-beet rhizosphere. This bacterium has been extensiv...

  17. Communication technology update and fundamentals

    CERN Document Server

    Grant, August E

    2010-01-01

    New communication technologies are being introduced at an astonishing rate. Making sense of these technologies is increasingly difficult. Communication Technology Update and Fundamentals is the single best source for the latest developments, trends, and issues in communication technology. Featuring the fundamental framework along with the history and background of communication technologies, Communication Technology Update and Fundamentals, 12th edition helps you stay ahead of these ever-changing and emerging technologies.As always, every chapter ha

  18. Dietary soyasaponin supplementation to pea protein concentrate reveals nutrigenomic interactions underlying enteropathy in Atlantic salmon (Salmo salar

    Directory of Open Access Journals (Sweden)

    Kortner Trond M

    2012-07-01

    Full Text Available Abstract Background Use of plant ingredients in aquaculture feeds is impeded by high contents of antinutritional factors such as saponins, which may cause various pharmacological and biological effects. In this study, transcriptome changes were analyzed using a 21 k oligonucleotide microarray and qPCR in the distal intestine of Atlantic salmon fed diets based on five plant protein sources combined with soybean saponins. Results Diets with corn gluten, sunflower, rapeseed or horsebean produced minor effects while the combination of saponins with pea protein concentrate caused enteritis and major transcriptome changes. Acute inflammation was characterised by up-regulation of cytokines, NFkB and TNFalpha related genes and regulators of T-cell function, while the IFN-axis was suppressed. Induction of lectins, complement, metalloproteinases and the respiratory burst complex parallelled a down-regulation of genes for free radical scavengers and iron binding proteins. Marked down-regulation of xenobiotic metabolism was also observed, possibly increasing vulnerability of the intestinal tissue. A hallmark of metabolic changes was dramatic down-regulation of lipid, bile and steroid metabolism. Impairment of digestion was further suggested by expression changes of nutrient transporters and regulators of water balance (e.g. aquaporin, guanylin. On the other hand, microarray profiling revealed activation of multiple mucosal defence processes. Annexin-1, with important anti-inflammatory and gastroprotective properties, was markedly up-regulated. Furthermore, augmented synthesis of polyamines needed for cellular proliferation (up-regulation of arginase and ornithine decarboxylase and increased mucus production (down-regulation of glycan turnover and goblet cell hyperplasia could participate in mucosal healing and restoration of normal tissue function. Conclusion The current study promoted understanding of salmon intestinal pathology and establishment of a

  19. Creating Shared Value. A Fundamental Critique

    OpenAIRE

    Beschorner, Thomas; Hajduk, Thomas

    2017-01-01

    This article offers a fundamental critique of Michael Porter’s and Marc Kramer’s “Creating Shared Value” (CSV) concept. First, the authors summarise the positive and negative criticism which CSV has received since 2011. They then show that CSV falls short of a modern understanding of corporate responsibility which is centred on more adequate ideas about the relationship between business and society. The article concludes with critical comments on the role of scholars in their interaction with...

  20. Head-head interactions of resting myosin crossbridges in intact frog skeletal muscles, revealed by synchrotron x-ray fiber diffraction.

    Directory of Open Access Journals (Sweden)

    Kanji Oshima

    Full Text Available The intensities of the myosin-based layer lines in the x-ray diffraction patterns from live resting frog skeletal muscles with full thick-thin filament overlap from which partial lattice sampling effects had been removed were analyzed to elucidate the configurations of myosin crossbridges around the thick filament backbone to nanometer resolution. The repeat of myosin binding protein C (C-protein molecules on the thick filaments was determined to be 45.33 nm, slightly longer than that of myosin crossbridges. With the inclusion of structural information for C-proteins and a pre-powerstroke head shape, modeling in terms of a mixed population of regular and perturbed regions of myosin crown repeats along the filament revealed that the myosin filament had azimuthal perturbations of crossbridges in addition to axial perturbations in the perturbed region, producing pseudo-six-fold rotational symmetry in the structure projected down the filament axis. Myosin crossbridges had a different organization about the filament axis in each of the regular and perturbed regions. In the regular region that lacks C-proteins, there were inter-molecular interactions between the myosin heads in axially adjacent crown levels. In the perturbed region that contains C-proteins, in addition to inter-molecular interactions between the myosin heads in the closest adjacent crown levels, there were also intra-molecular interactions between the paired heads on the same crown level. Common features of the interactions in both regions were interactions between a portion of the 50-kDa-domain and part of the converter domain of the myosin heads, similar to those found in the phosphorylation-regulated invertebrate myosin. These interactions are primarily electrostatic and the converter domain is responsible for the head-head interactions. Thus multiple head-head interactions of myosin crossbridges also characterize the switched-off state and have an important role in the regulation

  1. Fundamental concepts in Particle Physics course

    CERN Document Server

    CERN. Geneva HR-RFA

    2006-01-01

    The course will provide an introduction to some of the basic theoretical techniques used to describe the fundamental particles and their interactions. Of central importance to our understanding of these forces are the underlying symmetries of nature and I will review the nature of these symmetries and how they are used to build a predictive theory. I discuss how the combination of quantum mechanics and relativity leads to the quantum field theory (QFT) description of the states of matter and their interactions. The Feynman rules used to determine the QFT predictions for experimentally measurable processes are derived and applied to the calculation of decay widths and cross sections.

  2. Graphene nanophotonics: From fundamentals to applications

    DEFF Research Database (Denmark)

    Xiao, Sanshui

    With unique possibilities for controlling light in nanoscale devices, graphene has opened new perspectives to the nanophotonics community with potential applications in metamaterials, modulators, photodetectors, and sensors. Following a brief introduction of graphene, I will address some...... fundamentals, such as excitation of graphene plasmon polartions [1], pushing graphene plasmons to low wavelengths, and investigating of graphene plasmon-phonon interactions [2] and light-matter interactions in graphene-metal hybrid structures [3]. Then I will discuss graphene-based optical modulators......, particularly focusing on graphene-silicon platforms for electro-absorption modulating [4]....

  3. Interaction structure of the complex between neuroprotective factor humanin and Alzheimer's β-amyloid peptide revealed by affinity mass spectrometry and molecular modeling.

    Science.gov (United States)

    Maftei, Madalina; Tian, Xiaodan; Manea, Marilena; Exner, Thomas E; Schwanzar, Daniel; von Arnim, Christine A F; Przybylski, Michael

    2012-06-01

    Humanin (HN) is a linear 24-aa peptide recently detected in human Alzheimer's disease (AD) brain. HN specifically inhibits neuronal cell death in vitro induced by ß-amyloid (Aß) peptides and by amyloid precursor protein and its gene mutations in familial AD, thereby representing a potential therapeutic lead structure for AD; however, its molecular mechanism of action is not well understood. We report here the identification of the binding epitopes between HN and Aß(1-40) and characterization of the interaction structure through a molecular modeling study. Wild-type HN and HN-sequence mutations were synthesized by SPPS and the HPLC-purified peptides characterized by MALDI-MS. The interaction epitopes between HN and Aß(1-40) were identified by affinity-MS using proteolytic epitope excision and extraction, followed by elution and mass spectrometric characterization of the affinity-bound peptides. The affinity-MS analyses revealed HN(5-15) as the epitope sequence of HN, whereas Aß(17-28) was identified as the Aß interaction epitope. The epitopes and binding sites were ascertained by ELISA of the complex of HN peptides with immobilized Aß(1-40) and by ELISA with Aß(1-40) and Aß-partial sequences as ligands to immobilized HN. The specificity and affinity of the HN-Aß interaction were characterized by direct ESI-MS of the HN-Aß(1-40) complex and by bioaffinity analysis using a surface acoustic wave biosensor, providing a K(D) of the complex of 610 nm. A molecular dynamics simulation of the HN-Aß(1-40) complex was consistent with the binding specificity and shielding effects of the HN and Aß interaction epitopes. These results indicate a specific strong association of HN and Aß(1-40) polypeptide and provide a molecular basis for understanding the neuroprotective function of HN.

  4. A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding

    Directory of Open Access Journals (Sweden)

    Omi Shizue

    2010-11-01

    Full Text Available Abstract Background Proteins may evolve through the recruitment and modification of discrete domains, and in many cases, protein action can be dissected at the domain level. PDZ domains are found in many important structural and signaling complexes, and are generally thought to interact with their protein partners through a C-terminal consensus sequence. We undertook a comprehensive search for protein partners of all individual PDZ domains in C. elegans to characterize their function and mode of interaction. Results Coupling high-throughput yeast two-hybrid screens with extensive validation by co-affinity purification, we defined a domain-orientated interactome map. This integrates PDZ domain proteins in numerous cell-signaling pathways and shows that PDZ domain proteins are implicated in an unexpectedly wide range of cellular processes. Importantly, we uncovered a high frequency of non-canonical interactions, not involving the C-terminus of the protein partner, which were directly confirmed in most cases. We completed our study with the generation of a yeast array representing the entire set of PDZ domains from C. elegans and provide a proof-of-principle for its application to the discovery of PDZ domain targets for any protein or peptide of interest. Conclusions We provide an extensive domain-centered dataset, together with a clone resource, that will help future functional study of PDZ domains. Through this unbiased approach, we revealed frequent non-canonical interactions between PDZ domains and their protein partners that will require a re-evaluation of this domain's molecular function. [The protein interactions from this publication have been submitted to the IMEx (http://www.imexconsortium.org consortium through IntAct (PMID: 19850723 and assigned the identifier IM-14654

  5. A novel immuno-competitive capture mass spectrometry strategy for protein-protein interaction profiling reveals that LATS kinases regulate HCV replication through NS5A phosphorylation.

    Science.gov (United States)

    Meistermann, Hélène; Gao, Junjun; Golling, Sabrina; Lamerz, Jens; Le Pogam, Sophie; Tzouros, Manuel; Sankabathula, Sailaja; Gruenbaum, Lore; Nájera, Isabel; Langen, Hanno; Klumpp, Klaus; Augustin, Angélique

    2014-11-01

    Mapping protein-protein interactions is essential to fully characterize the biological function of a protein and improve our understanding of diseases. Affinity purification coupled to mass spectrometry (AP-MS) using selective antibodies against a target protein has been commonly applied to study protein complexes. However, one major limitation is a lack of specificity as a substantial part of the proposed binders is due to nonspecific interactions. Here, we describe an innovative immuno-competitive capture mass spectrometry (ICC-MS) method to allow systematic investigation of protein-protein interactions. ICC-MS markedly increases the specificity of classical immunoprecipitation (IP) by introducing a competition step between free and capturing antibody prior to IP. Instead of comparing only one experimental sample with a control, the methodology generates a 12-concentration antibody competition profile. Label-free quantitation followed by a robust statistical analysis of the data is then used to extract the cellular interactome of a protein of interest and to filter out background proteins. We applied this new approach to specifically map the interactome of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) in a cellular HCV replication system and uncovered eight new NS5A-interacting protein candidates along with two previously validated binding partners. Follow-up biological validation experiments revealed that large tumor suppressor homolog 1 and 2 (LATS1 and LATS2, respectively), two closely related human protein kinases, are novel host kinases responsible for NS5A phosphorylation at a highly conserved position required for optimal HCV genome replication. These results are the first illustration of the value of ICC-MS for the analysis of endogenous protein complexes to identify biologically relevant protein-protein interactions with high specificity.

  6. Fundamentals and Techniques of Nonimaging

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-10

    other system parameter permits the construction of whole new classes of devices with greatly expanded capabilities compared to conventional approaches. These ''tailored edge-ray'' designs have dramatically broadened the range of geometries in which nonimaging optics can provide a significant performance improvement. Considerable progress continues to be made in furthering the incorporation of nonimaging secondaries into practical high concentration and ultra-high concentration solar collector systems. In parallel with the continuing development of nonimaging geometrical optics, our group has been working to develop an understanding of certain fundamental physical optics concepts in the same context. In particular, our study of the behavior of classical radiance in nonimaging systems, has revealed some fundamentally important new understandings that we have pursued both theoretically and experimentally. The field is still relatively new and is rapidly gaining widespread recognition because it fuels many industrial applications. Because of this, during the final years of the project, our group at Chicago has been working more closely with a team of industrial scientists from Science Applications International Corporation (SAIC) at first informally, and later more formally, beginning in 1998, under a formal program initiated by the Department of Energy and incrementally funded through this existing grant. This collaboration has been very fruitful and has led to new conceptual breakthroughs which have provided the foundation for further exciting growth. Many of these concepts are described in some detail in the report.

  7. Laser-fundamentals and applications

    Energy Technology Data Exchange (ETDEWEB)

    Schinagl, W.

    1982-09-01

    The survey article gives an introduction to laser technology. Fundamentals and physical aspects are discussed at large. After a brief historical review and a discussion of the physical fundamentals, important types of laser, characteristics of laser radiation and its applications in medicine are discussed.

  8. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  9. RNA synthesis by the brome mosaic virus RNA-dependent RNA polymerase in human cells reveals requirements for de novo initiation and protein-protein interaction.

    Science.gov (United States)

    Subba-Reddy, Chennareddy V; Tragesser, Brady; Xu, Zhili; Stein, Barry; Ranjith-Kumar, C T; Kao, C Cheng

    2012-04-01

    Brome mosaic virus (BMV) is a model positive-strand RNA virus whose replication has been studied in a number of surrogate hosts. In transiently transfected human cells, the BMV polymerase 2a activated signaling by the innate immune receptor RIG-I, which recognizes de novo-initiated non-self-RNAs. Active-site mutations in 2a abolished RIG-I activation, and coexpression of the BMV 1a protein stimulated 2a activity. Mutations previously shown to abolish 1a and 2a interaction prevented the 1a-dependent enhancement of 2a activity. New insights into 1a-2a interaction include the findings that helicase active site of 1a is required to enhance 2a polymerase activity and that negatively charged amino acid residues between positions 110 and 120 of 2a contribute to interaction with the 1a helicase-like domain but not to the intrinsic polymerase activity. Confocal fluorescence microscopy revealed that the BMV 1a and 2a colocalized to perinuclear region in human cells. However, no perinuclear spherule-like structures were detected in human cells by immunoelectron microscopy. Sequencing of the RNAs coimmunoprecipitated with RIG-I revealed that the 2a-synthesized short RNAs are derived from the message used to translate 2a. That is, 2a exhibits a strong cis preference for BMV RNA2. Strikingly, the 2a RNA products had initiation sequences (5'-GUAAA-3') identical to those from the 5' sequence of the BMV genomic RNA2 and RNA3. These results show that the BMV 2a polymerase does not require other BMV proteins to initiate RNA synthesis but that the 1a helicase domain, and likely helicase activity, can affect RNA synthesis by 2a.

  10. The Fundamental Scale of Descriptions

    CERN Document Server

    Febres, Gerardo

    2014-01-01

    The complexity of a system description is a function of the entropy of its symbolic description. Prior to computing the entropy of the system description, an observation scale has to be assumed. In natural language texts, typical scales are binary, characters, and words. However, considering languages as structures built around certain preconceived set of symbols, like words or characters, is only a presumption. This study depicts the notion of the Description Fundamental Scale as a set of symbols which serves to analyze the essence a language structure. The concept of Fundamental Scale is tested using English and MIDI music texts by means of an algorithm developed to search for a set of symbols, which minimizes the system observed entropy, and therefore best expresses the fundamental scale of the language employed. Test results show that it is possible to find the Fundamental Scale of some languages. The concept of Fundamental Scale, and the method for its determination, emerges as an interesting tool to fac...

  11. A yeast two-hybrid screen reveals a strong interaction between the Legionella chaperonin Hsp60 and the host cell small heat shock protein Hsp10.

    Science.gov (United States)

    Nasrallah, Gheyath K

    2015-06-01

    L. pneumophila is an intracellular bacterium that replicates inside a membrane-bound vacuole called Legionella-containing vacuole (LCV), where it plentifully liberates its HtpB chaperonin. From LCV, HtpB reaches the host cell cytoplasm, where it interacts with SAMDC, a cytoplasmic protein required for synthesis of host polyamines that are important for intracellular growth of L. pneumophila. Additionally, cytoplasmic expression of HtpB in S. cerevisiae induces pseudohyphal growth, and in mammalian cells recruits mitochondria to LCV, and modifies actin microfilaments organization. This led us to hypothesize here that HtpB recruits a protein(s) from eukaryotic cells that is involved in the emergence of the aforementioned phenotypes. To identify this protein, a commercially available HeLa cDNA library was screened using a yeast two-hybrid system. Approximately 5×10(6) yeast clones carrying HeLa cDNA library plasmid were screened. Twenty-one positive clones were identified. DNA sequence analysis revealed that all of these positive clones encoded the mammalian small heat shock protein Hsp10. Based on the fact that chaperonions are required to interact with co-chaperonins to function properly in protein folding, we believe that HtpB recruits the host cell Hsp10 to appropriately interact with SAMDC and to induce the multifunction phenotypes deemed important in L. pneumophila pathogenesis.

  12. Interrogation of the protein-protein interactions between human BRCA2 BRC repeats and RAD51 reveals atomistic determinants of affinity.

    Directory of Open Access Journals (Sweden)

    Daniel J Cole

    2011-07-01

    Full Text Available The breast cancer suppressor BRCA2 controls the recombinase RAD51 in the reactions that mediate homologous DNA recombination, an essential cellular process required for the error-free repair of DNA double-stranded breaks. The primary mode of interaction between BRCA2 and RAD51 is through the BRC repeats, which are ∼35 residue peptide motifs that interact directly with RAD51 in vitro. Human BRCA2, like its mammalian orthologues, contains 8 BRC repeats whose sequence and spacing are evolutionarily conserved. Despite their sequence conservation, there is evidence that the different human BRC repeats have distinct capacities to bind RAD51. A previously published crystal structure reports the structural basis of the interaction between human BRC4 and the catalytic core domain of RAD51. However, no structural information is available regarding the binding of the remaining seven BRC repeats to RAD51, nor is it known why the BRC repeats show marked variation in binding affinity to RAD51 despite only subtle sequence variation. To address these issues, we have performed fluorescence polarisation assays to indirectly measure relative binding affinity, and applied computational simulations to interrogate the behaviour of the eight human BRC-RAD51 complexes, as well as a suite of BRC cancer-associated mutations. Our computational approaches encompass a range of techniques designed to link sequence variation with binding free energy. They include MM-PBSA and thermodynamic integration, which are based on classical force fields, and a recently developed approach to computing binding free energies from large-scale quantum mechanical first principles calculations with the linear-scaling density functional code onetep. Our findings not only reveal how sequence variation in the BRC repeats directly affects affinity with RAD51 and provide significant new insights into the control of RAD51 by human BRCA2, but also exemplify a palette of computational and

  13. Fundamental principles of heat transfer

    CERN Document Server

    Whitaker, Stephen

    1977-01-01

    Fundamental Principles of Heat Transfer introduces the fundamental concepts of heat transfer: conduction, convection, and radiation. It presents theoretical developments and example and design problems and illustrates the practical applications of fundamental principles. The chapters in this book cover various topics such as one-dimensional and transient heat conduction, energy and turbulent transport, forced convection, thermal radiation, and radiant energy exchange. There are example problems and solutions at the end of every chapter dealing with design problems. This book is a valuable int

  14. Fundamentals of technology project management

    CERN Document Server

    Garton, Colleen

    2012-01-01

    Designed to provide software engineers, students, and IT professionals with an understanding of the fundamentals of project management in the technology/IT field, this book serves as a practical introduction to the subject. Updated with information on how Fundamentals of Project Management integrates with and complements Project Management Institute''s Project Management Body of Knowledge, this collection explains fundamental methodologies and techniques while also discussing new technology, tools, and virtual work environments. Examples and case studies are based on technology projects, and t

  15. Tumor-stroma interaction: Revealing fibroblast-secreted exosomes as potent regulators of Wnt-planar cell polarity signaling in cancer metastasis.

    Science.gov (United States)

    Luga, Valbona; Wrana, Jeffrey L

    2013-12-01

    Cancer-associated fibroblasts (CAF) regulate tumor progression, but their role in cancer metastasis remains largely unexplored. Exosomes are secreted microvesicles that are emerging as potent mediators of cell-cell communication that are of particular importance in tumor-stroma interactions. The Wnt-planar cell polarity (PCP) pathway is the primary regulator of convergent extension cell movements during vertebrate development, but the role of this signaling pathway in cancer cell migration and metastasis has been unclear. Recently, we revealed that fibroblasts secrete exosomes that promote breast cancer cell (BCC) protrusive activity, motility, and metastasis by activating autocrine Wnt-PCP signaling in BCCs. Moreover, we showed that Wnt ligands produced by BCCs tether to fibroblast exosomes upon trafficking of exosomes in BCCs. These findings have several implications that motivate promising future research in the fields of tumor-stroma communication, exosome function, and Wnt-PCP signaling in cancer metastasis.

  16. Fundamental approach to discrete mathematics

    CERN Document Server

    Acharjya, DP

    2005-01-01

    Salient Features Mathematical logic, fundamental concepts, proofs and mathematical induction (Chapter 1) Set theory, fundamental concepts, theorems, proofs, Venn diagrams, product of sets, application of set theory and fundamental products (Chapter 2) An introduction to binary relations and concepts, graphs, arrow diagrams, relation matrix, composition of relations, types of relation, partial order relations, total order relation, closure of relations, poset, equivalence classes and partitions. (Chapter 3) An introduction to functions and basic concepts, graphs, composition of functions, floor and ceiling function, characteristic function, remainder function, signum function and introduction to hash function. (Chapter 4) The algebraic structure includes group theory and ring theory. Group theory includes group, subgroups, cyclic group, cosets, homomorphism, introduction to codes and group codes and error correction for block code. The ring theory includes general definition, fundamental concepts, integra...

  17. Clinical fundamentals for radiation oncologists.

    Science.gov (United States)

    Yang, Jack

    2011-11-01

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

  18. Quantum mechanics I the fundamentals

    CERN Document Server

    Rajasekar, S

    2015-01-01

    Quantum Mechanics I: The Fundamentals provides a graduate-level account of the behavior of matter and energy at the molecular, atomic, nuclear, and sub-nuclear levels. It covers basic concepts, mathematical formalism, and applications to physically important systems.

  19. Fundamentals of modern unsteady aerodynamics

    CERN Document Server

    Gülçat, Ülgen

    2010-01-01

    This introduction to the principles of unsteady aerodynamics covers all the core concepts, provides readers with a review of the fundamental physics, terminology and basic equations, and covers hot new topics such as the use of flapping wings for propulsion.

  20. Structure-function studies of DNA binding domain of response regulator KdpE reveals equal affinity interactions at DNA half-sites.

    Directory of Open Access Journals (Sweden)

    Anoop Narayanan

    Full Text Available Expression of KdpFABC, a K(+ pump that restores osmotic balance, is controlled by binding of the response regulator KdpE to a specific DNA sequence (kdpFABC(BS via the winged helix-turn-helix type DNA binding domain (KdpE(DBD. Exploration of E. coli KdpE(DBD and kdpFABC(BS interaction resulted in the identification of two conserved, AT-rich 6 bp direct repeats that form half-sites. Despite binding to these half-sites, KdpE(DBD was incapable of promoting gene expression in vivo. Structure-function studies guided by our 2.5 Å X-ray structure of KdpE(DBD revealed the importance of residues R193 and R200 in the α-8 DNA recognition helix and T215 in the wing region for DNA binding. Mutation of these residues renders KdpE incapable of inducing expression of the kdpFABC operon. Detailed biophysical analysis of interactions using analytical ultracentrifugation revealed a 2∶1 stoichiometry of protein to DNA with dissociation constants of 200±100 and 350±100 nM at half-sites. Inactivation of one half-site does not influence binding at the other, indicating that KdpE(DBD binds independently to the half-sites with approximately equal affinity and no discernable cooperativity. To our knowledge, these data are the first to describe in quantitative terms the binding at half-sites under equilibrium conditions for a member of the ubiquitous OmpR/PhoB family of proteins.