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Sample records for folding model

  1. Vocal Fold Collision Modeling

    DEFF Research Database (Denmark)

    Granados, Alba; Brunskog, Jonas; Misztal, M. K.

    2015-01-01

    When vocal folds vibrate at normal speaking frequencies, collisions occurs. The numerics and formulations behind a position-based continuum model of contact is an active field of research in the contact mechanics community. In this paper, a frictionless three-dimensional finite element model...

  2. Mechanical Models of Fault-Related Folding

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, A. M.

    2003-01-09

    The subject of the proposed research is fault-related folding and ground deformation. The results are relevant to oil-producing structures throughout the world, to understanding of damage that has been observed along and near earthquake ruptures, and to earthquake-producing structures in California and other tectonically-active areas. The objectives of the proposed research were to provide both a unified, mechanical infrastructure for studies of fault-related foldings and to present the results in computer programs that have graphical users interfaces (GUIs) so that structural geologists and geophysicists can model a wide variety of fault-related folds (FaRFs).

  3. Folding models for elastic and inelastic scattering

    International Nuclear Information System (INIS)

    Satchler, G.R.

    1982-01-01

    The most widely used models are the optical model potential (OMP) for elastic scattering, and its generalization to non-spherical shapes, the deformed optical model potential (DOMP) for inelastic scattering. These models are simple and phenomenological; their parameters are adjusted so as to reproduce empirical data. Nonetheless, there are certain, not always well-defined, constraints to be imposed. The potential shapes and their parameter values must be reasonable and should vary in a smooth and systematic way with the masses of the colliding nuclei and their energy. One way of satisfying these constraints, without going back to a much more fundamental theory, is through the use of folding models. The basic justification for using potentials of the Woods-Saxon shape for nucleon-nucleus scattering, for example, is our knowledge that a nuclear density distribution is more-or-less constant in the nuclear interior with a diffuse surface. When this is folded with a short-range nucleon-nucleon interaction, the result is a similar shape with a more diffuse surface. Folding procedures allow us to incorporate many aspects of nuclear structure (although the nuclear size is one of the most important), as well as theoretical ideas about the effective interaction of two nucleons within nuclear matter. It also provides us with a means of linking information obtained from nuclear (hadronic) interactions with that from other sources, as well as correlating that from the use of different hadronic probes. Folding model potentials, single-folded potentials, and the double-folding model including applications to heavy-ion scattering are discussed

  4. SDEM modelling of fault-propagation folding

    DEFF Research Database (Denmark)

    Clausen, O.R.; Egholm, D.L.; Poulsen, Jane Bang

    2009-01-01

    and variations in Mohr-Coulomb parameters including internal friction. Using SDEM modelling, we have mapped the propagation of the tip-line of the fault, as well as the evolution of the fold geometry across sedimentary layers of contrasting rheological parameters, as a function of the increased offset......Understanding the dynamics and kinematics of fault-propagation-folding is important for evaluating the associated hydrocarbon play, for accomplishing reliable section balancing (structural reconstruction), and for assessing seismic hazards. Accordingly, the deformation style of fault-propagation...... a precise indication of when faults develop and hence also the sequential evolution of secondary faults. Here we focus on the generation of a fault -propagated fold with a reverse sense of motion at the master fault, and varying only the dip of the master fault and the mechanical behaviour of the deformed...

  5. Protein Folding: Search for Basic Physical Models

    Directory of Open Access Journals (Sweden)

    Ivan Y. Torshin

    2003-01-01

    Full Text Available How a unique three-dimensional structure is rapidly formed from the linear sequence of a polypeptide is one of the important questions in contemporary science. Apart from biological context of in vivo protein folding (which has been studied only for a few proteins, the roles of the fundamental physical forces in the in vitro folding remain largely unstudied. Despite a degree of success in using descriptions based on statistical and/or thermodynamic approaches, few of the current models explicitly include more basic physical forces (such as electrostatics and Van Der Waals forces. Moreover, the present-day models rarely take into account that the protein folding is, essentially, a rapid process that produces a highly specific architecture. This review considers several physical models that may provide more direct links between sequence and tertiary structure in terms of the physical forces. In particular, elaboration of such simple models is likely to produce extremely effective computational techniques with value for modern genomics.

  6. Folding model analysis of alpha radioactivity

    International Nuclear Information System (INIS)

    Basu, D N

    2003-01-01

    Radioactive decay of nuclei via emission of α-particles has been studied theoretically in the framework of a superasymmetric fission model using the double folding (DF) procedure for obtaining the α-nucleus interaction potential. The DF nuclear potential has been obtained by folding in the density distribution functions of the α nucleus and the daughter nucleus with a realistic effective interaction. The M3Y effective interaction has been used for calculating the nuclear interaction potential which has been supplemented by a zero-range pseudo-potential for exchange along with the density dependence. The nuclear microscopic α-nucleus potential thus obtained has been used along with the Coulomb interaction potential to calculate the action integral within the WKB approximation. This subsequently yields calculations for the half-lives of α decays of nuclei. The density dependence and the exchange effects have not been found to be very significant. These calculations provide reasonable estimates for the lifetimes of α-radioactivity of nuclei

  7. A Rat Excised Larynx Model of Vocal Fold Scar

    Science.gov (United States)

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  8. Approximate self-similarity in models of geological folding

    NARCIS (Netherlands)

    Budd, C.J.; Peletier, M.A.

    2000-01-01

    We propose a model for the folding of rock under the compression of tectonic plates. This models an elastic rock layer imbedded in a viscous foundation by a fourth-order parabolic equation with a nonlinear constraint. The large-time behavior of solutions of this problem is examined and found to be

  9. Visualization of protein folding funnels in lattice models.

    Directory of Open Access Journals (Sweden)

    Antonio B Oliveira

    Full Text Available Protein folding occurs in a very high dimensional phase space with an exponentially large number of states, and according to the energy landscape theory it exhibits a topology resembling a funnel. In this statistical approach, the folding mechanism is unveiled by describing the local minima in an effective one-dimensional representation. Other approaches based on potential energy landscapes address the hierarchical structure of local energy minima through disconnectivity graphs. In this paper, we introduce a metric to describe the distance between any two conformations, which also allows us to go beyond the one-dimensional representation and visualize the folding funnel in 2D and 3D. In this way it is possible to assess the folding process in detail, e.g., by identifying the connectivity between conformations and establishing the paths to reach the native state, in addition to regions where trapping may occur. Unlike the disconnectivity maps method, which is based on the kinetic connections between states, our methodology is based on structural similarities inferred from the new metric. The method was developed in a 27-mer protein lattice model, folded into a 3×3×3 cube. Five sequences were studied and distinct funnels were generated in an analysis restricted to conformations from the transition-state to the native configuration. Consistent with the expected results from the energy landscape theory, folding routes can be visualized to probe different regions of the phase space, as well as determine the difficulty in folding of the distinct sequences. Changes in the landscape due to mutations were visualized, with the comparison between wild and mutated local minima in a single map, which serves to identify different trapping regions. The extension of this approach to more realistic models and its use in combination with other approaches are discussed.

  10. Measurement of flow separation in a human vocal folds model

    Czech Academy of Sciences Publication Activity Database

    Šidlof, Petr; Doaré, O.; Cadot, O.; Chaigne, A.

    2011-01-01

    Roč. 51, č. 1 (2011), s. 123-136 ISSN 0723-4864 R&D Projects: GA AV ČR KJB200760801 Institutional research plan: CEZ:AV0Z20760514 Keywords : vocal folds * flow separation * physical model Subject RIV: BI - Acoustics Impact factor: 1.735, year: 2011 http://www.springerlink.com/content/t81114611760jp23/

  11. Mechanical Modeling and Computer Simulation of Protein Folding

    Science.gov (United States)

    Prigozhin, Maxim B.; Scott, Gregory E.; Denos, Sharlene

    2014-01-01

    In this activity, science education and modern technology are bridged to teach students at the high school and undergraduate levels about protein folding and to strengthen their model building skills. Students are guided from a textbook picture of a protein as a rigid crystal structure to a more realistic view: proteins are highly dynamic…

  12. Glottal aerodynamics in compliant, life-sized vocal fold models

    Science.gov (United States)

    McPhail, Michael; Dowell, Grant; Krane, Michael

    2013-11-01

    This talk presents high-speed PIV measurements in compliant, life-sized models of the vocal folds. A clearer understanding of the fluid-structure interaction of voiced speech, how it produces sound, and how it varies with pathology is required to improve clinical diagnosis and treatment of vocal disorders. Physical models of the vocal folds can answer questions regarding the fundamental physics of speech, as well as the ability of clinical measures to detect the presence and extent of disorder. Flow fields were recorded in the supraglottal region of the models to estimate terms in the equations of fluid motion, and their relative importance. Experiments were conducted over a range of driving pressures with flow rates, given by a ball flowmeter, and subglottal pressures, given by a micro-manometer, reported for each case. Imaging of vocal fold motion, vector fields showing glottal jet behavior, and terms estimated by control volume analysis will be presented. The use of these results for a comparison with clinical measures, and for the estimation of aeroacoustic source strengths will be discussed. Acknowledge support from NIH R01 DC005642.

  13. On the single-mass model of the vocal folds

    International Nuclear Information System (INIS)

    Howe, M S; McGowan, R S

    2010-01-01

    An analysis is made of the fluid-structure interactions necessary to support self-sustained oscillations of a single-mass mechanical model of the vocal folds subject to a nominally steady subglottal overpressure. The single-mass model of Fant and Flanagan is re-examined and an analytical representation of vortex shedding during 'voiced speech' is proposed that promotes cooperative, periodic excitation of the folds by the glottal flow. Positive feedback that sustains glottal oscillations is shown to occur during glottal contraction, when the flow separates from the 'trailing edge' of the glottis producing a low-pressure 'suction' force that tends to pull the folds together. Details are worked out for flow that can be regarded as locally two-dimensional in the glottal region. Predictions of free-streamline theory are used to model the effects of quasi-static variations in the separation point on the glottal wall. Numerical predictions are presented to illustrate the waveform of the sound radiated towards the mouth from the glottis. The theory is easily modified to include feedback on the glottal flow of standing acoustic waves, both in the vocal tract beyond the glottis and in the subglottal region. (invited paper)

  14. Developing guinea pig brain as a model for cortical folding.

    Science.gov (United States)

    Hatakeyama, Jun; Sato, Haruka; Shimamura, Kenji

    2017-05-01

    The cerebral cortex in mammals, the neocortex specifically, is highly diverse among species with respect to its size and morphology, likely reflecting the immense adaptiveness of this lineage. In particular, the pattern and number of convoluted ridges and fissures, called gyri and sulci, respectively, on the surface of the cortex are variable among species and even individuals. However, little is known about the mechanism of cortical folding, although there have been several hypotheses proposed. Recent studies on embryonic neurogenesis revealed the differences in cortical progenitors as a critical factor of the process of gyrification. Here, we investigated the gyrification processes using developing guinea pig brains that form a simple but fundamental pattern of gyri. In addition, we established an electroporation-mediated gene transfer method for guinea pig embryos. We introduce the guinea pig brain as a useful model system to understand the mechanisms and basic principle of cortical folding. © 2017 Japanese Society of Developmental Biologists.

  15. Separable potential approach in the folding model. Pt. 2

    International Nuclear Information System (INIS)

    Lee, C.L.; Robson, D.

    1982-01-01

    A microscopic folding formalism using a separable potential approach is applied to the elastic scattering of the n-α system. Starting with a separable nucleon-nucleon (NN) potential model, a sum of separable nucleon-nucleus potentials is obtained. A simple structure of the α-particle is assumed and the Tabakin, the Doleschall and the Strobel NN potentials are considered. These phenomenological interactions are of Yukawa or gaussian form with variable parameters for each partial wave. Spin-orbit and tensor forces are included. The resulting potentials developed from our folding calculations give approximately the same ssub(1/2) phase shifts for the n-α elastic scattering. However, in the psub(1/2) and psub(3/2) phase-shift analysis, an effective interaction derived from the NN potential is necessary to reproduce the resonances. One free energy independent parameter is introduced in our approximate G-matrix concept to give a good fit for the phase shifts. Single-nucleon knockout exchange (SNKE) is considered throughout. (orig.)

  16. Folded Sheet Versus Transparent Sheet Models for Human Symmetry Judgments

    Directory of Open Access Journals (Sweden)

    Jacques Ninio

    2011-07-01

    Full Text Available As a contribution to the mysteries of human symmetry perception, reaction time data were collected on the detection of symmetry or repetition violations, in the context of short term visual memory studies. The histograms for reaction time distributions are rather narrow in the case of symmetry judgments. Their analysis was performed in terms of a simple kinetic model of a mental process in two steps, a slow one for the construction of the representation of the images to be compared, and a fast one, in the 50 ms range, for the decision. There was no need for an additional ‘mental rotation’ step. Symmetry seems to facilitate the construction step. I also present here original stimuli showing a color equalization effect across a symmetry axis, and its counterpart in periodic patterns. According to a “folded sheet model”, when a shape is perceived, the brain automatically constructs a mirror-image representation of the shape. Based in part on the reaction time analysis, I present here an alternative “transparent sheet” model in which the brain constructs a single representation, which can be accessed from two sides, thus generating simultaneously a pattern and its mirror-symmetric partner. Filtering processes, implied by current models of symmetry perception could intervene at an early stage, by nucleating the propagation of similar perceptual groupings in the two symmetric images.

  17. Denatured state is critical in determining the properties of model proteins designed on different folds

    DEFF Research Database (Denmark)

    Amatori, Andrea; Ferkinghoff-Borg, Jesper; Tiana, Guido

    2008-01-01

    The thermodynamics of proteins designed on three common folds (SH3, chymotrypsin inhibitor 2 [CI2], and protein G) is studied with a simplified C alpha, model and compared with the thermodynamics of proteins designed on random-generated folds. The model allows to design sequences to fold within a...

  18. Modeling Vocal Fold Intravascular Flow using Synthetic Replicas

    Science.gov (United States)

    Terry, Aaron D.; Ricks, Matthew T.; Thomson, Scott L.

    2017-11-01

    Vocal fold vibration that is induced by air flowing from the lungs is believed to decrease blood flow through the vocal folds. This is important due to the critical role of blood flow in maintaining tissue health. However, the precise mechanical relationships between vocal fold vibration and blood perfusion remain understudied. A platform for studying liquid perfusion in a synthetic, life-size, self-oscillating vocal fold replica has recently been developed. The replicas are fabricated using molded silicone with material properties comparable to those of human vocal fold tissues and that include embedded microchannels through which liquid is perfused. The replicas are mounted on an air flow supply tube to initiate flow-induced vibration. A liquid reservoir is attached to the microchannel to cause liquid to perfuse through replica in the anterior-posterior direction. As replica vibration is initiated and amplitude increases, perfusion flow rate decreases. In this presentation, the replica design will be presented, along with data quantifying the relationships between parameters such as replica vibration amplitude, stiffness, microchannel diameter, and perfusion flow rate. This work was supported by Grant NIDCD R01DC005788 from the National Institutes of Health.

  19. Modeling the Biomechanical Influence of Epilaryngeal Stricture on the Vocal Folds: A Low-Dimensional Model of Vocal-Ventricular Fold Coupling

    Science.gov (United States)

    Moisik, Scott R.; Esling, John H.

    2014-01-01

    Purpose: Physiological and phonetic studies suggest that, at moderate levels of epilaryngeal stricture, the ventricular folds impinge upon the vocal folds and influence their dynamical behavior, which is thought to be responsible for constricted laryngeal sounds. In this work, the authors examine this hypothesis through biomechanical modeling.…

  20. Self-organized critical model for protein folding

    Science.gov (United States)

    Moret, M. A.

    2011-09-01

    The major factor that drives a protein toward collapse and folding is the hydrophobic effect. At the folding process a hydrophobic core is shielded by the solvent-accessible surface area of the protein. We study the fractal behavior of 5526 protein structures present in the Brookhaven Protein Data Bank. Power laws of protein mass, volume and solvent-accessible surface area are measured independently. The present findings indicate that self-organized criticality is an alternative explanation for the protein folding. Also we note that the protein packing is an independent and constant value because the self-similar behavior of the volumes and protein masses have the same fractal dimension. This power law guarantees that a protein is a complex system. From the analyzed data, q-Gaussian distributions seem to fit well this class of systems.

  1. Double folding model including the Pauli exclusion principle

    International Nuclear Information System (INIS)

    Gridnev, K.A.; Soubbotin, V.B.; Oertzen, W. von; Bohlen, H.G.; Vinas, X.

    2002-01-01

    A new method to incorporate the Pauli principle into the double folding approach to the heavy ion potential is proposed. It is shown that in order to take into account the Pauli blocking a redefinition of the density matrices of the free isolated nuclei must be one. A solution to the self-consistent incorporation of the Pauli-blocking effects in the mean-field nucleus-nucleus potential is obtained in the Thomas-Fermi approximation [ru

  2. Modeling the Pathophysiology of Phonotraumatic Vocal Hyperfunction with a Triangular Glottal Model of the Vocal Folds

    Science.gov (United States)

    Galindo, Gabriel E.; Peterson, Sean D.; Erath, Byron D.; Castro, Christian; Hillman, Robert E.; Zañartu, Matías

    2017-01-01

    Purpose: Our goal was to test prevailing assumptions about the underlying biomechanical and aeroacoustic mechanisms associated with phonotraumatic lesions of the vocal folds using a numerical lumped-element model of voice production. Method: A numerical model with a triangular glottis, posterior glottal opening, and arytenoid posturing is…

  3. Double-folding model including the Pauli exclusion principle

    International Nuclear Information System (INIS)

    Gridnev, K.A.; Soubbotin, V.B.; Oertzen, W. von; Bohlen, H.G.; Vinas, X.

    2002-01-01

    A new method for incorporating the Pauli exclusion principle into the double-folding approach to the heavy-ion potential is proposed. The description of the exchange terms at the level of the semiclassical one-body density matrix is used. It is shown that, in order to take into account Pauli blocking properly, the density matrices of free isolated nuclei must be redefined. A solution to the self-consistent incorporation of Pauli blocking effects in the mean-field nucleus-nucleus potential is obtained in the Thomas-Fermi approximation

  4. Protein folding simulations: from coarse-grained model to all-atom model.

    Science.gov (United States)

    Zhang, Jian; Li, Wenfei; Wang, Jun; Qin, Meng; Wu, Lei; Yan, Zhiqiang; Xu, Weixin; Zuo, Guanghong; Wang, Wei

    2009-06-01

    Protein folding is an important and challenging problem in molecular biology. During the last two decades, molecular dynamics (MD) simulation has proved to be a paramount tool and was widely used to study protein structures, folding kinetics and thermodynamics, and structure-stability-function relationship. It was also used to help engineering and designing new proteins, and to answer even more general questions such as the minimal number of amino acid or the evolution principle of protein families. Nowadays, the MD simulation is still undergoing rapid developments. The first trend is to toward developing new coarse-grained models and studying larger and more complex molecular systems such as protein-protein complex and their assembling process, amyloid related aggregations, and structure and motion of chaperons, motors, channels and virus capsides; the second trend is toward building high resolution models and explore more detailed and accurate pictures of protein folding and the associated processes, such as the coordination bond or disulfide bond involved folding, the polarization, charge transfer and protonate/deprotonate process involved in metal coupled folding, and the ion permeation and its coupling with the kinetics of channels. On these new territories, MD simulations have given many promising results and will continue to offer exciting views. Here, we review several new subjects investigated by using MD simulations as well as the corresponding developments of appropriate protein models. These include but are not limited to the attempt to go beyond the topology based Gō-like model and characterize the energetic factors in protein structures and dynamics, the study of the thermodynamics and kinetics of disulfide bond involved protein folding, the modeling of the interactions between chaperonin and the encapsulated protein and the protein folding under this circumstance, the effort to clarify the important yet still elusive folding mechanism of protein BBL

  5. Computational Modeling of Proteins based on Cellular Automata: A Method of HP Folding Approximation.

    Science.gov (United States)

    Madain, Alia; Abu Dalhoum, Abdel Latif; Sleit, Azzam

    2018-06-01

    The design of a protein folding approximation algorithm is not straightforward even when a simplified model is used. The folding problem is a combinatorial problem, where approximation and heuristic algorithms are usually used to find near optimal folds of proteins primary structures. Approximation algorithms provide guarantees on the distance to the optimal solution. The folding approximation approach proposed here depends on two-dimensional cellular automata to fold proteins presented in a well-studied simplified model called the hydrophobic-hydrophilic model. Cellular automata are discrete computational models that rely on local rules to produce some overall global behavior. One-third and one-fourth approximation algorithms choose a subset of the hydrophobic amino acids to form H-H contacts. Those algorithms start with finding a point to fold the protein sequence into two sides where one side ignores H's at even positions and the other side ignores H's at odd positions. In addition, blocks or groups of amino acids fold the same way according to a predefined normal form. We intend to improve approximation algorithms by considering all hydrophobic amino acids and folding based on the local neighborhood instead of using normal forms. The CA does not assume a fixed folding point. The proposed approach guarantees one half approximation minus the H-H endpoints. This lower bound guaranteed applies to short sequences only. This is proved as the core and the folds of the protein will have two identical sides for all short sequences.

  6. Nuclear interaction potential in a folded-Yukawa model with diffuse densities

    International Nuclear Information System (INIS)

    Randrup, J.

    1975-09-01

    The folded-Yukawa model for the nuclear interaction potential is generalized to diffuse density distributions which are generated by folding a Yukawa function into sharp generating distributions. The effect of a finite density diffuseness or of a finite interaction range is studied. The Proximity Formula corresponding to the generalized model is derived and numerical comparison is made with the exact results. (8 figures)

  7. Modeling and imaging of the vocal fold vibration for voice health

    DEFF Research Database (Denmark)

    Granados, Alba

    Identication of abnormalities on the vocal fold by means of dierent diagnostic methods is a key step to determine the cause or causes of a voice disorder, and subsequently give an adequate treatment. To this end, clinical investigations benet from accurate mathematical models for prediction......, analysis and inference. This thesis deals with biomechanical models of the vocal fold, specially of the collision, and laryngeal videoendoscopic analysis procedures suitable for the inference of the underlying vocal fold characteristics. The rst part of this research is devoted to frictionless contact...... modeling during asymmetric vocal fold vibration. The prediction problem is numerically addressed with a self-sustained three-dimensional nite element model of the vocal fold with position-based contact constraints. A novel contact detection mechanism is shown to successfully detect collision in asymmetric...

  8. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Yongping Yue

    2016-01-01

    Full Text Available Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin gene in the heart at 50-fold and 100-fold of the normal levels. In the line with 50-fold overexpression, minidystrophin showed sarcolemmal localization and electrocardiogram abnormalities were corrected. However, in the line with 100-fold overexpression, we not only detected sarcolemmal minidystrophin expression but also observed accumulation of minidystrophin vesicles in the sarcoplasm. Excessive minidystrophin expression did not correct tachycardia, a characteristic feature of Duchenne muscular dystrophy. Importantly, several electrocardiogram parameters (QT interval, QRS duration and the cardiomyopathy index became worse than that of mdx mice. Our data suggests that the mouse heart can tolerate 50-fold minidystrophin overexpression, but 100-fold overexpression leads to cardiac toxicity.

  9. Scattering of long folded strings and mixed correlators in the two-matrix model

    International Nuclear Information System (INIS)

    Bourgine, J.-E.; Hosomichi, K.; Kostov, I.; Matsuo, Y.

    2008-01-01

    We study the interactions of Maldacena's long folded strings in two-dimensional string theory. We find the amplitude for a state containing two long folded strings to come and go back to infinity. We calculate this amplitude both in the worldsheet theory and in the dual matrix model, the matrix quantum mechanics. The matrix model description allows to evaluate the amplitudes involving any number of long strings, which are given by the mixed trace correlators in an effective two-matrix model

  10. A numerical strategy for finite element modeling of frictionless asymmetric vocal fold collision.

    Science.gov (United States)

    Granados, Alba; Misztal, Marek Krzysztof; Brunskog, Jonas; Visseq, Vincent; Erleben, Kenny

    2017-02-01

    Analysis of voice pathologies may require vocal fold models that include relevant features such as vocal fold asymmetric collision. The present study numerically addresses the problem of frictionless asymmetric collision in a self-sustained three-dimensional continuum model of the vocal folds. Theoretical background and numerical analysis of the finite-element position-based contact model are presented, along with validation. A novel contact detection mechanism capable to detect collision in asymmetric oscillations is developed. The effect of inexact contact constraint enforcement on vocal fold dynamics is examined by different variational methods for inequality constrained minimization problems, namely, the Lagrange multiplier method and the penalty method. In contrast to the penalty solution, which is related to classical spring-like contact forces, numerical examples show that the parameter-independent Lagrange multiplier solution is more robust and accurate in the estimation of dynamical and mechanical features at vocal fold contact. Furthermore, special attention is paid to the temporal integration schemes in relation to the contact problem, the results suggesting an advantage of highly diffusive schemes. Finally, vocal fold contact enforcement is shown to affect asymmetric oscillations. The present model may be adapted to existing vocal fold models, which may contribute to a better understanding of the effect of the nonlinear contact phenomenon on phonation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Calculation of real optical model potential for heavy ions in the framework of the folding model

    International Nuclear Information System (INIS)

    Goncharov, S.A.; Timofeyuk, N.K.; Kazacha, G.S.

    1987-01-01

    The code for calculation of a real optical model potential in the framework of the folding model is realized. The program of numerical Fourier-Bessel transformation based on Filon's integration rule is used. The accuracy of numerical calculations is ∼ 10 -4 for a distance interval up to a bout (2.5-3) times the size of nuclei. The potentials are calculated for interactions of 3,4 He with nuclei from 9 Be to 27 Al with different effective NN-interactions and densities obtained from electron scattering data. Calculated potentials are similar to phenomenological potentials in Woods-Saxon form. With calculated potentials the available elastic scattering data for the considered nuclei in the energy interval 18-56 MeV are analysed. The needed renormalizations for folding potentials are < or approx. 20%

  12. Model-unrestricted scattering potentials for light ions and their interpretation in the folding model

    International Nuclear Information System (INIS)

    Ermer, M.; Clement, H.; Frank, G.; Grabmayr, P.; Heberle, N.; Wagner, G.J.

    1989-01-01

    High-quality data for elastic proton, deuteron and α-particle scattering on 40 Ca and 208 Pb at 26-30 MeV/N have been analyzed in terms of the model-unrestricted Fourier-Bessel concept. While extracted scattering potentials show substantial deviations from Woods-Saxon shapes, their real central parts are well described by folding calculations using a common effective nucleon-nucleon interaction with a weak density dependence. (orig.)

  13. The IntFOLD server: an integrated web resource for protein fold recognition, 3D model quality assessment, intrinsic disorder prediction, domain prediction and ligand binding site prediction.

    Science.gov (United States)

    Roche, Daniel B; Buenavista, Maria T; Tetchner, Stuart J; McGuffin, Liam J

    2011-07-01

    The IntFOLD server is a novel independent server that integrates several cutting edge methods for the prediction of structure and function from sequence. Our guiding principles behind the server development were as follows: (i) to provide a simple unified resource that makes our prediction software accessible to all and (ii) to produce integrated output for predictions that can be easily interpreted. The output for predictions is presented as a simple table that summarizes all results graphically via plots and annotated 3D models. The raw machine readable data files for each set of predictions are also provided for developers, which comply with the Critical Assessment of Methods for Protein Structure Prediction (CASP) data standards. The server comprises an integrated suite of five novel methods: nFOLD4, for tertiary structure prediction; ModFOLD 3.0, for model quality assessment; DISOclust 2.0, for disorder prediction; DomFOLD 2.0 for domain prediction; and FunFOLD 1.0, for ligand binding site prediction. Predictions from the IntFOLD server were found to be competitive in several categories in the recent CASP9 experiment. The IntFOLD server is available at the following web site: http://www.reading.ac.uk/bioinf/IntFOLD/.

  14. Fold catastrophe model of dynamic pillar failure in asymmetric mining

    Energy Technology Data Exchange (ETDEWEB)

    Yue Pan; Ai-wu Li; Yun-song Qi [Qingdao Technological University, Qingdao (China). College of Civil Engineering

    2009-01-15

    A rock burst disaster not only destroys the pit facilities and results in economic loss but it also threatens the life of the miners. Pillar rock burst has a higher frequency of occurrence in the pit compared to other kinds of rock burst. Understanding the cause, magnitude and prevention of pillar rock burst is a significant undertaking. Equations describing the bending moment and displacement of the rock beam in asymmetric mining have been deduced for simplified asymmetric beam-pillar systems. Using the symbolic operation software MAPLE 9.5 a catastrophe model of the dynamic failure of an asymmetric rock-beam pillar system has been established. The differential form of the total potential function deduced from the law of conservation of energy was used for this deduction. The critical conditions and the initial and final positions of the pillar during failure have been given in analytical form. The amount of elastic energy released by the rock beam at the instant of failure is determined as well. A diagrammatic form showing the pillar failure was plotted using MATLAB software. This graph contains a wealth of information and is important for understanding the behavior during each deformation phase of the rock-beam pillar system. The graphic also aids in distinguishing the equivalent stiffness of the rock beam in different directions. 11 refs., 8 figs.

  15. Performance of a reduced-order FSI model for flow-induced vocal fold vibration

    Science.gov (United States)

    Luo, Haoxiang; Chang, Siyuan; Chen, Ye; Rousseau, Bernard; PhonoSim Team

    2017-11-01

    Vocal fold vibration during speech production involves a three-dimensional unsteady glottal jet flow and three-dimensional nonlinear tissue mechanics. A full 3D fluid-structure interaction (FSI) model is computationally expensive even though it provides most accurate information about the system. On the other hand, an efficient reduced-order FSI model is useful for fast simulation and analysis of the vocal fold dynamics, which can be applied in procedures such as optimization and parameter estimation. In this work, we study performance of a reduced-order model as compared with the corresponding full 3D model in terms of its accuracy in predicting the vibration frequency and deformation mode. In the reduced-order model, we use a 1D flow model coupled with a 3D tissue model that is the same as in the full 3D model. Two different hyperelastic tissue behaviors are assumed. In addition, the vocal fold thickness and subglottal pressure are varied for systematic comparison. The result shows that the reduced-order model provides consistent predictions as the full 3D model across different tissue material assumptions and subglottal pressures. However, the vocal fold thickness has most effect on the model accuracy, especially when the vocal fold is thin.

  16. FoldEco: A Model for Proteostasis in E. coli

    Directory of Open Access Journals (Sweden)

    Evan T. Powers

    2012-03-01

    Full Text Available To gain insight into the interplay of processes and species that maintain a correctly folded, functional proteome, we have developed a computational model called FoldEco. FoldEco models the cellular proteostasis network of the E. coli cytoplasm, including protein synthesis, degradation, aggregation, chaperone systems, and the folding characteristics of protein clients. We focused on E. coli because much of the needed input information—including mechanisms, rate parameters, and equilibrium coefficients—is available, largely from in vitro experiments; however, FoldEco will shed light on proteostasis in other organisms. FoldEco can generate hypotheses to guide the design of new experiments. Hypothesis generation leads to system-wide questions and shows how to convert these questions to experimentally measurable quantities, such as changes in protein concentrations with chaperone or protease levels, which can then be used to improve our current understanding of proteostasis and refine the model. A web version of FoldEco is available at http://foldeco.scripps.edu.

  17. Kinematic evolution of fold and thrust belts. Insights from experimental modeling

    International Nuclear Information System (INIS)

    Ueta, Keiichi

    2011-01-01

    Physical experiments were performed to gain a better understanding on the kinematic evolution of fold and thrust belts. The present study focuses on deformation of sedimentary cover caused by thrust and reverse movements along the basement fault. Our physical models comprise dry quartz sand representing brittle sedimentary rock and viscous silicone polymer representing overpressured mudstone. Computerized X-ray tomography was applied to the experiments to analyze the kinematic evolution of fold and thrust belts. In the sand models, the width of deformation zone above thrust was wider than that above reverse fault, because back thrust developed on the hanging wall of reverse fault. Within the physical models composed of dry sand and silicone polymer, minor folds and thrusts with minor displacement developed on the footwall of the major monoclinal flexure. These results compare well with the geometry and kinematic evolution of the fold and thrust belts in Japan. (author)

  18. Orogen-transverse tectonic window in the Eastern Himalayan fold belt: A superposed buckling model

    Science.gov (United States)

    Bose, Santanu; Mandal, Nibir; Acharyya, S. K.; Ghosh, Subhajit; Saha, Puspendu

    2014-09-01

    The Eastern Lesser Himalayan fold-thrust belt is punctuated by a row of orogen-transverse domal tectonic windows. To evaluate their origin, a variety of thrust-stack models have been proposed, assuming that the crustal shortening occurred dominantly by brittle deformations. However, the Rangit Window (RW) in the Darjeeling-Sikkim Himalaya (DSH) shows unequivocal structural imprints of ductile deformations of multiple episodes. Based on new structural maps, coupled with outcrop-scale field observations, we recognize at least four major episodes of folding in the litho-tectonic units of DSH. The last episode has produced regionally orogen-transverse upright folds (F4), the interference of which with the third-generation (F3) orogen-parallel folds has shaped the large-scale structural patterns in DSH. We propose a new genetic model for the RW, invoking the mechanics of superposed buckling in the mechanically stratified litho-tectonic systems. We substantiate this superposed buckling model with results obtained from analogue experiments. The model explains contrasting F3-F4 interferences in the Lesser Himalayan Sequence (LHS). The lower-order (terrain-scale) folds have undergone superposed buckling in Mode 1, producing large-scale domes and basins, whereas the RW occurs as a relatively higher-order dome nested in the first-order Tista Dome. The Gondwana and the Proterozoic rocks within the RW underwent superposed buckling in Modes 3 and 4, leading to Type 2 fold interferences, as evident from their structural patterns.

  19. An optical flow-based state-space model of the vocal folds

    DEFF Research Database (Denmark)

    Granados, Alba; Brunskog, Jonas

    2017-01-01

    High-speed movies of the vocal fold vibration are valuable data to reveal vocal fold features for voice pathology diagnosis. This work presents a suitable Bayesian model and a purely theoretical discussion for further development of a framework for continuum biomechanical features estimation. A l...... to capture different deformation patterns between the computed optical flow and the finite element deformation, controlled by the choice of the model tissue parameters........ A linear and Gaussian nonstationary state-space model is proposed and thoroughly discussed. The evolution model is based on a self-sustained three-dimensional finite element model of the vocal folds, and the observation model involves a dense optical flow algorithm. The results show that the method is able...

  20. An optical flow-based state-space model of the vocal folds.

    Science.gov (United States)

    Granados, Alba; Brunskog, Jonas

    2017-06-01

    High-speed movies of the vocal fold vibration are valuable data to reveal vocal fold features for voice pathology diagnosis. This work presents a suitable Bayesian model and a purely theoretical discussion for further development of a framework for continuum biomechanical features estimation. A linear and Gaussian nonstationary state-space model is proposed and thoroughly discussed. The evolution model is based on a self-sustained three-dimensional finite element model of the vocal folds, and the observation model involves a dense optical flow algorithm. The results show that the method is able to capture different deformation patterns between the computed optical flow and the finite element deformation, controlled by the choice of the model tissue parameters.

  1. Prevention of vocal fold scarring by local application of basic fibroblast growth factor in a rat vocal fold injury model.

    Science.gov (United States)

    Suzuki, Ryo; Kawai, Yoshitaka; Tsuji, Takuya; Hiwatashi, Nao; Kishimoto, Yo; Tateya, Ichiro; Nakamura, Tatsuo; Hirano, Shigeru

    2017-02-01

    Vocal fold scarring, which causes severe hoarseness, is intractable. The optimal treatment for vocal fold scarring has not been established; therefore, prevention of scarring is important. The aim of this study was to clarify the effectiveness of basic fibroblast growth factor (bFGF) for prevention of postsurgical vocal fold scarring. Prospective animal experiments with controls. The vocal folds of Sprague-Dawley rats were injured unilaterally or bilaterally after local application of a 10 μL solution of bFGF. Larynges ware harvested for histological and immunohistochemical examination 2 months postoperation and for quantitative real-time polymerase chain reaction (qRT-PCR) analysis 1 week postoperation. Histological examination showed significantly increased hyaluronic acid and decreased deposition of dense collagen in the bFGF-treated group at 100 ng/10 μL compared with the sham-treated group. Immunohistochemical examination showed significantly decreased collagen type III deposition in the bFGF-treated group at 100 ng/10 μL compared with the sham-treated group. qRT-PCR revealed that hyaluronan synthase 2 (Has2), Has3, and hepatocyte growth factor were upregulated in bFGF-treated groups compared with sham-treated group. The current results suggest that local application of bFGF at the time of injury has the potential to prevent vocal fold scarring. Preventive injection of bFGF could be applied at the time of phonomicrosurgery to avoid postoperative scar formation. N/A. Laryngoscope, 2016 127:E67-E74, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  2. Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures

    International Nuclear Information System (INIS)

    Lammert, Heiko; Noel, Jeffrey K.; Haglund, Ellinor; Onuchic, José N.; Schug, Alexander

    2015-01-01

    The diversity in a set of protein nuclear magnetic resonance (NMR) structures provides an estimate of native state fluctuations that can be used to refine and enrich structure-based protein models (SBMs). Dynamics are an essential part of a protein’s functional native state. The dynamics in the native state are controlled by the same funneled energy landscape that guides the entire folding process. SBMs apply the principle of minimal frustration, drawn from energy landscape theory, to construct a funneled folding landscape for a given protein using only information from the native structure. On an energy landscape smoothed by evolution towards minimal frustration, geometrical constraints, imposed by the native structure, control the folding mechanism and shape the native dynamics revealed by the model. Native-state fluctuations can alternatively be estimated directly from the diversity in the set of NMR structures for a protein. Based on this information, we identify a highly flexible loop in the ribosomal protein S6 and modify the contact map in a SBM to accommodate the inferred dynamics. By taking into account the probable native state dynamics, the experimental transition state is recovered in the model, and the correct order of folding events is restored. Our study highlights how the shared energy landscape connects folding and function by showing that a better description of the native basin improves the prediction of the folding mechanism

  3. Distinct Element Method modelling of fold-related fractures in a multilayer sequence

    Science.gov (United States)

    Kaserer, Klemens; Schöpfer, Martin P. J.; Grasemann, Bernhard

    2017-04-01

    Natural fractures have a significant impact on the performance of hydrocarbon systems/reservoirs. In a multilayer sequence, both the fracture density within the individual layers and the type of fracture intersection with bedding contacts are key parameters controlling fluid pathways. In the present study the influence of layer stacking and interlayer friction on fracture density and connectivity within a folded sequence is systematically investigated using 2D Distinct Element Method modelling. Our numerical approach permits forward modelling of both fracture nucleation/propagation/arrest and (contemporaneous) frictional slip along bedding planes in a robust and mechanically sound manner. Folding of the multilayer sequence is achieved by enforcing constant curvature folding by means of a velocity boundary condition at the model base, while a constant overburden pressure is maintained at the model top. The modelling reveals that with high bedding plane friction the multilayer stack behaves mechanically as a single layer so that the neutral surface develops in centre of the sequence and fracture spacing is controlled by the total thickness of the folded sequence. In contrast, low bedding plane friction leads to decoupling of the individual layers (flexural slip folding) so that a neutral surface develops in the centre of each layer and fracture spacing is controlled by the thickness of the individual layers. The low interfacial friction models illustrate that stepping of fractures across bedding planes is a common process, which can however have two contrasting origins: The mechanical properties of the interface cause fracture stepping during fracture propagation. Originally through-going fractures are later offset by interfacial slip during folding. A combination of these two different origins may lead to (apparently) inconsistent fracture offsets across bedding planes within a flexural slip fold.

  4. A Corner-Point-Grid-Based Voxelization Method for Complex Geological Structure Model with Folds

    Science.gov (United States)

    Chen, Qiyu; Mariethoz, Gregoire; Liu, Gang

    2017-04-01

    3D voxelization is the foundation of geological property modeling, and is also an effective approach to realize the 3D visualization of the heterogeneous attributes in geological structures. The corner-point grid is a representative data model among all voxel models, and is a structured grid type that is widely applied at present. When carrying out subdivision for complex geological structure model with folds, we should fully consider its structural morphology and bedding features to make the generated voxels keep its original morphology. And on the basis of which, they can depict the detailed bedding features and the spatial heterogeneity of the internal attributes. In order to solve the shortage of the existing technologies, this work puts forward a corner-point-grid-based voxelization method for complex geological structure model with folds. We have realized the fast conversion from the 3D geological structure model to the fine voxel model according to the rule of isocline in Ramsay's fold classification. In addition, the voxel model conforms to the spatial features of folds, pinch-out and other complex geological structures, and the voxels of the laminas inside a fold accords with the result of geological sedimentation and tectonic movement. This will provide a carrier and model foundation for the subsequent attribute assignment as well as the quantitative analysis and evaluation based on the spatial voxels. Ultimately, we use examples and the contrastive analysis between the examples and the Ramsay's description of isoclines to discuss the effectiveness and advantages of the method proposed in this work when dealing with the voxelization of 3D geologic structural model with folds based on corner-point grids.

  5. Roles of beta-turns in protein folding: from peptide models to protein engineering.

    Science.gov (United States)

    Marcelino, Anna Marie C; Gierasch, Lila M

    2008-05-01

    Reverse turns are a major class of protein secondary structure; they represent sites of chain reversal and thus sites where the globular character of a protein is created. It has been speculated for many years that turns may nucleate the formation of structure in protein folding, as their propensity to occur will favor the approximation of their flanking regions and their general tendency to be hydrophilic will favor their disposition at the solvent-accessible surface. Reverse turns are local features, and it is therefore not surprising that their structural properties have been extensively studied using peptide models. In this article, we review research on peptide models of turns to test the hypothesis that the propensities of turns to form in short peptides will relate to the roles of corresponding sequences in protein folding. Turns with significant stability as isolated entities should actively promote the folding of a protein, and by contrast, turn sequences that merely allow the chain to adopt conformations required for chain reversal are predicted to be passive in the folding mechanism. We discuss results of protein engineering studies of the roles of turn residues in folding mechanisms. Factors that correlate with the importance of turns in folding indeed include their intrinsic stability, as well as their topological context and their participation in hydrophobic networks within the protein's structure.

  6. Frequency Response of Synthetic Vocal Fold Models with Linear and Nonlinear Material Properties

    Science.gov (United States)

    Shaw, Stephanie M.; Thomson, Scott L.; Dromey, Christopher; Smith, Simeon

    2012-01-01

    Purpose: The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency (F[subscript 0]) during anterior-posterior stretching. Method: Three materially linear and 3 materially nonlinear models were…

  7. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  8. Correlation of phonatory behavior with vocal fold structure, observed in a physical model

    Science.gov (United States)

    Krane, Michael; Walters, Gage; McPhail, Michael

    2017-11-01

    The effect of vocal fold shape and internal structure on phonation was studied experimentally using a physical model of the human airway. Model folds used a ``M5'' or a swept ellipse coronal cross-section shape. Models were molded in either 2 or three layers. Two-layer models included a more stiff ``body'' layer and a much softer ``cover'' layer, while the 3-layer models also incorporated an additional, thin, ``ligament/conus'' layer stiffer than the body layer. The elliptical section models were all molded in 3 such layers. Measurements of transglottal pressure, volume flow, mouth sound pressure, and high-speed imaging of vocal fold vibration were performed. These show that models with the ``ligament'' layer experienced much attenuated vertical deformation, that glottal closure was more likely, and that phonation was much easier to initiate. These findings suggest that the combination of the vocal ligament and the conus elasticus stabilize the vocal fold for efficient phonation by limiting vertical deformation, while allowing transverse deformations to occur. Acknowledge support from NIH DC R01005642-11.

  9. Coupled channel folding model description of α scattering from 9Be

    International Nuclear Information System (INIS)

    Roy, S.; Chatterjee, J.M.; Majumdar, H.; Datta, S.K.; Banerjee, S.R.; Chintalapudi, S.N.

    1995-01-01

    Alpha scattering from 9 Be at E α = 65 MeV is described in the coupled channel framework with phenomenological as well as folded potentials. The multipole components of the deformed density of 9 Be are derived from Nilsson model wave functions. Reasonably good agreements are obtained for the angular distributions of 3/2 - (g.s.) and 5/2 - (2.43 MeV) states of the ground state band with folded potentials. The deformation predicted by the model corroborates with that derived from the phenomenological analysis with potentials of different geometries

  10. Coupled channel folding model description of {alpha} scattering from {sup 9}Be

    Energy Technology Data Exchange (ETDEWEB)

    Roy, S.; Chatterjee, J.M.; Majumdar, H. [Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Calcutta 700064 (India); Datta, S.K. [Nuclear Science Centre, P.O.10502, New Delhi 110067 (India); Banerjee, S.R. [Variable Energy Cyclotron Centre, 1/AF Bidhannagar, Calcutta 700064 (India); Chintalapudi, S.N. [Inter-University Consortium, Department of Atomic Energy Facilities, Bidhannagar, Calcutta 700064 (India)

    1995-09-01

    Alpha scattering from {sup 9}Be at {ital E}{sub {alpha}}= 65 MeV is described in the coupled channel framework with phenomenological as well as folded potentials. The multipole components of the deformed density of {sup 9}Be are derived from Nilsson model wave functions. Reasonably good agreements are obtained for the angular distributions of 3/2{sup {minus}}(g.s.) and 5/2{sup {minus}}(2.43 MeV) states of the ground state band with folded potentials. The deformation predicted by the model corroborates with that derived from the phenomenological analysis with potentials of different geometries.

  11. Ab initio folding of mixed-fold FSD-EY protein using formula-based polarizable hydrogen bond (PHB) charge model

    Science.gov (United States)

    Zhang, Dawei; Lazim, Raudah; Mun Yip, Yew

    2017-09-01

    We conducted an all-atom ab initio folding of FSD-EY, a protein with a ββα configuration using non-polarizable (AMBER) and polarizable force fields (PHB designed by Gao et al.) in implicit solvent. The effect of reducing the polarization effect integrated into the force field by the PHB model, termed the PHB0.7 was also examined in the folding of FSD-EY. This model incorporates into the force field 70% of the original polarization effect to minimize the likelihood of over-stabilizing the backbone hydrogen bonds. Precise folding of the β-sheet of FSD-EY was further achieved by relaxing the REMD structure obtained in explicit water.

  12. Three-Dimensional Flow Separation Induced by a Model Vocal Fold Polyp

    Science.gov (United States)

    Stewart, Kelley C.; Erath, Byron D.; Plesniak, Michael W.

    2012-11-01

    The fluid-structure energy exchange process for normal speech has been studied extensively, but it is not well understood for pathological conditions. Polyps and nodules, which are geometric abnormalities that form on the medial surface of the vocal folds, can disrupt vocal fold dynamics and thus can have devastating consequences on a patient's ability to communicate. A recent in-vitro investigation of a model polyp in a driven vocal fold apparatus demonstrated that such a geometric abnormality considerably disrupts the glottal jet behavior and that this flow field adjustment was a likely reason for the severe degradation of the vocal quality in patients. Understanding of the formation and propagation of vortical structures from a geometric protuberance, and their subsequent impact on the aerodynamic loadings that drive vocal fold dynamic, is a critical component in advancing the treatment of this pathological condition. The present investigation concerns the three-dimensional flow separation induced by a wall-mounted prolate hemispheroid with a 2:1 aspect ratio in cross flow, i.e. a model vocal fold polyp. Unsteady three-dimensional flow separation and its impact of the wall pressure loading are examined using skin friction line visualization and wall pressure measurements. Supported by the National Science Foundation, Grant No. CBET-1236351 and GW Center for Biomimetics and Bioinspired Engineering (COBRE).

  13. Time-resolved transglottal pressure measurements in a scaled up vocal fold model

    Science.gov (United States)

    Ringenberg, Hunter; Krane, Michael; Rogers, Dylan; Misfeldt, Mitchel; Wei, Timothy

    2016-11-01

    Experimental measurements of flow through a scaled up dynamic human vocal fold model are presented. The simplified 10x scale vocal fold model from Krane, et al. (2007) was used to examine fundamental features of vocal fold oscillatory motion. Of particular interest was the temporal variation of transglottal pressure multiplied by the volume flow rate through the glottis throughout an oscillation cycle. Experiments were dynamically scaled to examine a range of frequencies, 100 - 200 Hz, corresponding to the male and female voice. By using water as the working fluid, very high resolution, both spatial and temporal resolution, was achieved. Time resolved movies of flow through symmetrically oscillating vocal folds will be presented. Both individual realizations as well as phase-averaged data will be shown. Key features, such as randomness and development time of the Coanda effect, vortex shedding, and volume flow rate data have been presented in previous APS-DFD meetings. This talk will focus more on the relation between the flow and aeroacoustics associated with vocal fold oscillations. Supported by the NIH.

  14. Heterotic line bundle models on elliptically fibered Calabi-Yau three-folds

    Science.gov (United States)

    Braun, Andreas P.; Brodie, Callum R.; Lukas, Andre

    2018-04-01

    We analyze heterotic line bundle models on elliptically fibered Calabi-Yau three-folds over weak Fano bases. In order to facilitate Wilson line breaking to the standard model group, we focus on elliptically fibered three-folds with a second section and a freely-acting involution. Specifically, we consider toric weak Fano surfaces as base manifolds and identify six such manifolds with the required properties. The requisite mathematical tools for the construction of line bundle models on these spaces, including the calculation of line bundle cohomology, are developed. A computer scan leads to more than 400 line bundle models with the right number of families and an SU(5) GUT group which could descend to standard-like models after taking the ℤ2 quotient. A common and surprising feature of these models is the presence of a large number of vector-like states.

  15. Finite Element Modelling of Bends and Creases during Folding Ultra Thin Stainless Steel Foils

    NARCIS (Netherlands)

    Datta, K.; Akagi, H.; Geijselaers, Hubertus J.M.; Huetink, Han

    2003-01-01

    Finite Element Modelling of an ultra thin foil of SUS 304 stainless steel is carried out. These foils are 20 mm and below in thickness. The development of stresses and strains during folding of these foils is studied. The objective of this study is to induce qualities of paper in the foils of

  16. A numerical strategy for finite element modeling of frictionless asymmetric vocal fold collision

    DEFF Research Database (Denmark)

    Granados, Alba; Misztal, Marek Krzysztof; Brunskog, Jonas

    2016-01-01

    . Theoretical background and numerical analysis of the finite-element position-based contact model are presented, along with validation. A novel contact detection mechanism capable to detect collision in asymmetric oscillations is developed. The effect of inexact contact constraint enforcement on vocal fold...

  17. Cross-tropopause Transport In Tropopause Folds: Mechanisms and Sensitivity To Model Resolution

    Science.gov (United States)

    Gray, S. L.

    The rate and processes of transfer of mass and chemical species between the strato- sphere and troposphere (stratosphere-troposphere exchange) are currently uncertain. In the midlatitudes exchange appears to be dominated by processes associated with tropopause folds and cut-off lows. The development of a tropopause fold is a reversible process and thus irreversible processes must occur for the permanent transfer of ma- terial across the tropopause boundary. Proposed processes include turbulent mixing, quasi-isentropic mixing, convectively breaking gravity waves, deep convection and radiative heating. Numerical models run at typical climate or regional-scale resolutions are unable to re- solve the fine-scale features observed in tropopause folds. It is hypothesised that both the rate of exchange and its partitioning into different processes, as derived from nu- merical model simulations, are sensitive to model resolution. This hypothesis is tested through simulations of a tropopause folding event associated with a vigorous surface cold front which tracked across the British Isles. Climate to high-mesoscale resolution simulations incorporating passive tracers are performed using the mesoscale version of the Met Office Unified Model. The mechanism by which the parametrized convec- tion leads to exchange is the subject of further examination.

  18. Folding model analysis of the nucleus–nucleus scattering based on ...

    Indian Academy of Sciences (India)

    ... Lecture Workshops · Refresher Courses · Symposia · Live Streaming. Home; Journals; Pramana – Journal of Physics; Volume 87; Issue 6. Folding model analysis of the nucleus–nucleus scattering based on Jacobi coordinates. F PAKDEL A A RAJABI L NICKHAH. Regular Volume 87 Issue 6 December 2016 Article ID 90 ...

  19. Characteristics of phonation onset in a two-layer vocal fold model.

    Science.gov (United States)

    Zhang, Zhaoyan

    2009-02-01

    Characteristics of phonation onset were investigated in a two-layer body-cover continuum model of the vocal folds as a function of the biomechanical and geometric properties of the vocal folds. The analysis showed that an increase in either the body or cover stiffness generally increased the phonation threshold pressure and phonation onset frequency, although the effectiveness of varying body or cover stiffness as a pitch control mechanism varied depending on the body-cover stiffness ratio. Increasing body-cover stiffness ratio reduced the vibration amplitude of the body layer, and the vocal fold motion was gradually restricted to the medial surface, resulting in more effective flow modulation and higher sound production efficiency. The fluid-structure interaction induced synchronization of more than one group of eigenmodes so that two or more eigenmodes may be simultaneously destabilized toward phonation onset. At certain conditions, a slight change in vocal fold stiffness or geometry may cause phonation onset to occur as eigenmode synchronization due to a different pair of eigenmodes, leading to sudden changes in phonation onset frequency, vocal fold vibration pattern, and sound production efficiency. Although observed in a linear stability analysis, a similar mechanism may also play a role in register changes at finite-amplitude oscillations.

  20. Modeling programmable deformation of self-folding all-polymer structures with temperature-sensitive hydrogels

    International Nuclear Information System (INIS)

    Guo, Wei; Zhou, Jinxiong; Li, Meie

    2013-01-01

    Combination of soft active hydrogels with hard passive polymers gives rise to all-polymer composites. The hydrogel is sensitive to external stimuli while the passive polymer is inert. Utilizing the different behaviors of two materials subject to environmental variation, for example temperature, results in self-folding soft machines. We report our efforts to model the programmable deformation of self-folding structures with temperature-sensitive hydrogels. The self-folding structures are realized either by constructing a bilayer structure or by incorporating hydrogels as hinges. The methodology and the results may aid the design, control and fabrication of 3D complex structures from 2D simple configurations through self-assembly. (paper)

  1. A mixed-effects model approach for the statistical analysis of vocal fold viscoelastic shear properties.

    Science.gov (United States)

    Xu, Chet C; Chan, Roger W; Sun, Han; Zhan, Xiaowei

    2017-11-01

    A mixed-effects model approach was introduced in this study for the statistical analysis of rheological data of vocal fold tissues, in order to account for the data correlation caused by multiple measurements of each tissue sample across the test frequency range. Such data correlation had often been overlooked in previous studies in the past decades. The viscoelastic shear properties of the vocal fold lamina propria of two commonly used laryngeal research animal species (i.e. rabbit, porcine) were measured by a linear, controlled-strain simple-shear rheometer. Along with published canine and human rheological data, the vocal fold viscoelastic shear moduli of these animal species were compared to those of human over a frequency range of 1-250Hz using the mixed-effects models. Our results indicated that tissues of the rabbit, canine and porcine vocal fold lamina propria were significantly stiffer and more viscous than those of human. Mixed-effects models were shown to be able to more accurately analyze rheological data generated from repeated measurements. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Generic framework for mining cellular automata models on protein-folding simulations.

    Science.gov (United States)

    Diaz, N; Tischer, I

    2016-05-13

    Cellular automata model identification is an important way of building simplified simulation models. In this study, we describe a generic architectural framework to ease the development process of new metaheuristic-based algorithms for cellular automata model identification in protein-folding trajectories. Our framework was developed by a methodology based on design patterns that allow an improved experience for new algorithms development. The usefulness of the proposed framework is demonstrated by the implementation of four algorithms, able to obtain extremely precise cellular automata models of the protein-folding process with a protein contact map representation. Dynamic rules obtained by the proposed approach are discussed, and future use for the new tool is outlined.

  3. Influence of Embedded Fibers and an Epithelium Layer on the Glottal Closure Pattern in a Physical Vocal Fold Model

    Science.gov (United States)

    Xuan, Yue; Zhang, Zhaoyan

    2014-01-01

    Purpose: The purpose of this study was to explore the possible structural and material property features that may facilitate complete glottal closure in an otherwise isotropic physical vocal fold model. Method: Seven vocal fold models with different structural features were used in this study. An isotropic model was used as the baseline model, and…

  4. Three-dimensional laryngeal flow fields induced by a model vocal fold polyp

    Energy Technology Data Exchange (ETDEWEB)

    Erath, Byron D., E-mail: erath@gwu.edu [Department of Mechanical and Aerospace Engineering, George Washington University, 801 22nd Street NW, 739 Phillips Hall, Washington, DC 20052 (United States); Plesniak, Michael W., E-mail: plesniak@gwu.edu [Department of Mechanical and Aerospace Engineering, George Washington University, 801 22nd Street NW, 739 Phillips Hall, Washington, DC 20052 (United States)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Pathological speech with a unilateral polyp is modeled in a scaled-up flow facility. Black-Right-Pointing-Pointer Vortex shedding from the polyp disrupts normal flow behavior. Black-Right-Pointing-Pointer Hairpin vortices create spatial velocity asymmetries in the glottal flow. - Abstract: Pathological laryngeal flow fields are investigated in a dynamically-driven, scaled-up model of the vocal folds. Disruption of the flow field due to the presence of a geometric protuberance, representative of a sessile unilateral polyp, is investigated in both the streamwise and transverse flow directions using phase-averaged particle image velocimetry. It is shown that the protuberance disrupts the normal flow behavior of the glottal jet throughout the phonatory cycle. During the divergent portions of the glottal cycle, the flow is characterized by the formation of hairpin vortices downstream of the protuberance. The protuberance also introduces significant velocity gradients in the anterior-posterior direction, which cover {approx}30 - 40% of the vocal fold length. It is proposed that the disruption of the normal velocity behavior owing to the presence of a polyp will adversely impact the aerodynamic loadings that drive vocal fold motion, contributing to the temporal and spatial vocal fold asymmetries that are clinically-observed in patients with unilateral polyps.

  5. Three-dimensional laryngeal flow fields induced by a model vocal fold polyp

    International Nuclear Information System (INIS)

    Erath, Byron D.; Plesniak, Michael W.

    2012-01-01

    Highlights: ► Pathological speech with a unilateral polyp is modeled in a scaled-up flow facility. ► Vortex shedding from the polyp disrupts normal flow behavior. ► Hairpin vortices create spatial velocity asymmetries in the glottal flow. - Abstract: Pathological laryngeal flow fields are investigated in a dynamically-driven, scaled-up model of the vocal folds. Disruption of the flow field due to the presence of a geometric protuberance, representative of a sessile unilateral polyp, is investigated in both the streamwise and transverse flow directions using phase-averaged particle image velocimetry. It is shown that the protuberance disrupts the normal flow behavior of the glottal jet throughout the phonatory cycle. During the divergent portions of the glottal cycle, the flow is characterized by the formation of hairpin vortices downstream of the protuberance. The protuberance also introduces significant velocity gradients in the anterior-posterior direction, which cover ∼30 − 40% of the vocal fold length. It is proposed that the disruption of the normal velocity behavior owing to the presence of a polyp will adversely impact the aerodynamic loadings that drive vocal fold motion, contributing to the temporal and spatial vocal fold asymmetries that are clinically-observed in patients with unilateral polyps.

  6. A kinetic model of trp-cage folding from multiple biased molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Fabrizio Marinelli

    2009-08-01

    Full Text Available Trp-cage is a designed 20-residue polypeptide that, in spite of its size, shares several features with larger globular proteins.Although the system has been intensively investigated experimentally and theoretically, its folding mechanism is not yet fully understood. Indeed, some experiments suggest a two-state behavior, while others point to the presence of intermediates. In this work we show that the results of a bias-exchange metadynamics simulation can be used for constructing a detailed thermodynamic and kinetic model of the system. The model, although constructed from a biased simulation, has a quality similar to those extracted from the analysis of long unbiased molecular dynamics trajectories. This is demonstrated by a careful benchmark of the approach on a smaller system, the solvated Ace-Ala3-Nme peptide. For theTrp-cage folding, the model predicts that the relaxation time of 3100 ns observed experimentally is due to the presence of a compact molten globule-like conformation. This state has an occupancy of only 3% at 300 K, but acts as a kinetic trap.Instead, non-compact structures relax to the folded state on the sub-microsecond timescale. The model also predicts the presence of a state at Calpha-RMSD of 4.4 A from the NMR structure in which the Trp strongly interacts with Pro12. This state can explain the abnormal temperature dependence of the Pro12-delta3 and Gly11-alpha3 chemical shifts. The structures of the two most stable misfolded intermediates are in agreement with NMR experiments on the unfolded protein. Our work shows that, using biased molecular dynamics trajectories, it is possible to construct a model describing in detail the Trp-cage folding kinetics and thermodynamics in agreement with experimental data.

  7. Multimodal imaging of vocal fold scarring in a rabbit model by multiphoton microscopy

    Science.gov (United States)

    Kazarine, Alexei; Bouhabel, Sarah; Douillette, Annie H.; Kost, Karen; Li-Jessen, Nicole Y. K.; Mongeau, Luc; Wiseman, Paul W.

    2017-02-01

    Vocal fold scarring as a result of injury or disease can lead to voice disorders which can significantly affect the quality of life. During the scarring process, the normally elastic tissue of the vocal fold lamina propria is replaced by a much stiffer collagen-based fibrotic tissue, which impacts the fold's ability to vibrate. Surgical removal of this tissue is often ineffective and can result in further scarring. Injectable biomaterials, a form of tissue engineering, have been proposed as a potential solution to reduce existing scars or prevent scarring altogether. In order to properly evaluate the effectiveness of these new materials, multiphoton microscopy emerges as an effective tool due to its intrinsic multiple label free contrast mechanisms that highlight extracellular matrix elements. In this study, we evaluate the spatial distribution of collagen and elastin fibers in a rabbit model using second harmonic generation (SHG), third harmonic generation (THG) and two photon autofluorescence (TPAF) applied to unlabeled tissue sections. In comparison to traditional methods that rely on histological staining or immunohistochemistry, SHG, THG and TPAF provide a more reliable detection of these native proteins. The evaluation of collagen levels allows us to follow the extent of scarring, while the presence of elastin fibers is thought to be indicative of the level of healing of the injured fold. Using these imaging modalities, we characterize the outcome of injectable biomaterial treatments in order to direct future treatments for tissue engineering.

  8. The parametrization of Coulomb barrier heights and positions using the double folding model

    International Nuclear Information System (INIS)

    Qu, W.W.; Zhang, G.L.; Le, X.Y.

    2011-01-01

    The Coulomb barrier heights and positions are systematically shown with mass numbers and charge radii of the interacting nuclei. The nuclear potential is calculated by using the double folding model with the density-dependence nucleon-nucleon interaction (CDM3Y6). The pocket formulas are obtained for the Coulomb barrier heights and positions by analyzing several hundreds of heavy-ion systems with mass numbers from light nuclei to heavy nuclei. The parameterized formulas can reproduce the calculated barrier heights and positions by using the double folding model within the accuracy of ±1%. Moreover, the results are agreeable with the experimental data. The relation between the barrier height and the barrier position is also studied.

  9. Cluster folding-model for quasi-elastic scattering of 23Na from 208Pb

    International Nuclear Information System (INIS)

    Kabir, A.; Johnson, R.C.; Tostevin, M.H.

    1991-01-01

    A cluster model of 23 Na is used to calculate the 23 Na-target interaction potentials by folding the cluster wavefunction with the cluster-target interaction potentials. Coupled channels calculations are carried out for the quasi-elastic scattering of polarized 23 Na from 208 Pb at 170 MeV and compared with recent experiments. Qualitative agreement with experiment is obtained when the interaction is adjusted by a single overall normalization constant. (author)

  10. A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma.

    Science.gov (United States)

    Kwag, Hye Rin; Serbo, Janna V; Korangath, Preethi; Sukumar, Saraswati; Romer, Lewis H; Gracias, David H

    2016-04-01

    A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma.

  11. Folding-type coupling potentials in the context of the generalized rotation-vibration model

    Science.gov (United States)

    Chamon, L. C.; Morales Botero, D. F.

    2018-03-01

    The generalized rotation-vibration model was proposed in previous works to describe the structure of heavy nuclei. The model was successfully tested in the description of experimental results related to the electron-nucleus elastic and inelastic scattering. In the present work, we consider heavy-ion collisions and assume this model to calculate folding-type coupling potentials for inelastic states, through the corresponding transition densities. As an example, the method is applied to coupled-channel data analyses for the α + 70,72,74,76Ge systems.

  12. How to fold a spin chain: Integrable boundaries of the Heisenberg XXX and Inozemtsev hyperbolic models

    Science.gov (United States)

    De La Rosa Gomez, Alejandro; MacKay, Niall; Regelskis, Vidas

    2017-04-01

    We present a general method of folding an integrable spin chain, defined on a line, to obtain an integrable open spin chain, defined on a half-line. We illustrate our method through two fundamental models with sl2 Lie algebra symmetry: the Heisenberg XXX and the Inozemtsev hyperbolic spin chains. We obtain new long-range boundary Hamiltonians and demonstrate that they exhibit Yangian symmetries, thus ensuring integrability of the models we obtain. The method presented provides a ;bottom-up; approach for constructing integrable boundaries and can be applied to any spin chain model.

  13. The ModFOLD4 server for the quality assessment of 3D protein models

    OpenAIRE

    McGuffin, Liam J.; Buenavista, Maria T.; Roche, Daniel B.

    2013-01-01

    Once you have generated a 3D model of a protein,\\ud how do you know whether it bears any resemblance\\ud to the actual structure? To determine the usefulness\\ud of 3D models of proteins, they must be assessed in\\ud terms of their quality by methods that predict their\\ud similarity to the native structure. The ModFOLD4\\ud server is the latest version of our leading independent\\ud server for the estimation of both the global and\\ud local (per-residue) quality of 3D protein models. The\\ud server ...

  14. Study of elastic scattering of polarized proton with 6He by folding model

    International Nuclear Information System (INIS)

    Iseri, Y.; Tanifuji, M.; Ishikawa, S.; Hiyama, E.; Yamamoto, Y.

    2005-01-01

    Experimental data of the elastic scattering of 6 He with polarized proton target has been analyzed using a simple folding model. As we regard 6 He as three bodies consisting of 4 He+n+n, the potential between the proton and 6 He is obtained by folding the two potentials, one between a proton and 4 He and another between a proton and a neutron, with the density distribution of 6 He. Calculated results of both the differential cross section and the vector analyzing power reproduce the experimental data satisfactorily. It is shown that the vector analyzing power of the p- 6 He scattering is mainly due to the spin orbit interaction between the proton and 4 He. (S. Funahashi)

  15. Folding paper swans, modeling lives: the ritual of Filipina eldercare in Israel.

    Science.gov (United States)

    Mazuz, Keren

    2013-06-01

    This article examines the practices of folding paper swans by Filipina migrants employed as live-in caregivers for elderly, dying patients in Israel. These practices create a microsystem model of adjustment through precise, small-scale, and repetitive movements. This microsystem synchronizes a tripartite process: the swan's process of construction, the patient's process of decay, and the caregiver's process of self-creation. In the short term, the microsystem is sustained, but in the long term, the microsystem contains within it the seeds of its own self-destruction, as the patient eventually dies, the caregiver is reassigned to another patient or deported, and the swans are gifted. Therefore, the swan folding expands both medical anthropology understanding of caregiving as a ritual and the phenomenology of global caregivers who use immediately accessible materials-paper and glue-as an imaginative tool for ordering their daily experiences as dislocated and marginalized workers. © 2013 by the American Anthropological Association.

  16. ModFOLD6: an accurate web server for the global and local quality estimation of 3D protein models.

    Science.gov (United States)

    Maghrabi, Ali H A; McGuffin, Liam J

    2017-07-03

    Methods that reliably estimate the likely similarity between the predicted and native structures of proteins have become essential for driving the acceptance and adoption of three-dimensional protein models by life scientists. ModFOLD6 is the latest version of our leading resource for Estimates of Model Accuracy (EMA), which uses a pioneering hybrid quasi-single model approach. The ModFOLD6 server integrates scores from three pure-single model methods and three quasi-single model methods using a neural network to estimate local quality scores. Additionally, the server provides three options for producing global score estimates, depending on the requirements of the user: (i) ModFOLD6_rank, which is optimized for ranking/selection, (ii) ModFOLD6_cor, which is optimized for correlations of predicted and observed scores and (iii) ModFOLD6 global for balanced performance. The ModFOLD6 methods rank among the top few for EMA, according to independent blind testing by the CASP12 assessors. The ModFOLD6 server is also continuously automatically evaluated as part of the CAMEO project, where significant performance gains have been observed compared to our previous server and other publicly available servers. The ModFOLD6 server is freely available at: http://www.reading.ac.uk/bioinf/ModFOLD/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. FRankenstein becomes a cyborg: the automatic recombination and realignment of fold recognition models in CASP6.

    Science.gov (United States)

    Kosinski, Jan; Gajda, Michal J; Cymerman, Iwona A; Kurowski, Michal A; Pawlowski, Marcin; Boniecki, Michal; Obarska, Agnieszka; Papaj, Grzegorz; Sroczynska-Obuchowicz, Paulina; Tkaczuk, Karolina L; Sniezynska, Paulina; Sasin, Joanna M; Augustyn, Anna; Bujnicki, Janusz M; Feder, Marcin

    2005-01-01

    In the course of CASP6, we generated models for all targets using a new version of the "FRankenstein's monster approach." Previously (in CASP5) we were able to build many very accurate full-atom models by selection and recombination of well-folded fragments obtained from crude fold recognition (FR) results, followed by optimization of the sequence-structure fit and assessment of alternative alignments on the structural level. This procedure was however very arduous, as most of the steps required extensive visual and manual input from the human modeler. Now, we have automated the most tedious steps, such as superposition of alternative models, extraction of best-scoring fragments, and construction of a hybrid "monster" structure, as well as generation of alternative alignments in the regions that remain poorly scored in the refined hybrid model. We have also included the ROSETTA method to construct those parts of the target for which no reasonable structures were generated by FR methods (such as long insertions and terminal extensions). The analysis of successes and failures of the current version of the FRankenstein approach in modeling of CASP6 targets reveals that the considerably streamlined and automated method performs almost as well as the initial, mostly manual version, which suggests that it may be a useful tool for accurate protein structure prediction even in the hands of nonexperts. 2005 Wiley-Liss, Inc.

  18. Altered vocal fold kinematics in synthetic self-oscillating models that employ adipose tissue as a lateral boundary condition.

    Science.gov (United States)

    Saidi, Hiba; Erath, Byron D.

    2015-11-01

    The vocal folds play a major role in human communication by initiating voiced sound production. During voiced speech, the vocal folds are set into sustained vibrations. Synthetic self-oscillating vocal fold models are regularly employed to gain insight into flow-structure interactions governing the phonation process. Commonly, a fixed boundary condition is applied to the lateral, anterior, and posterior sides of the synthetic vocal fold models. However, physiological observations reveal the presence of adipose tissue on the lateral surface between the thyroid cartilage and the vocal folds. The goal of this study is to investigate the influence of including this substrate layer of adipose tissue on the dynamics of phonation. For a more realistic representation of the human vocal folds, synthetic multi-layer vocal fold models have been fabricated and tested while including a soft lateral layer representative of adipose tissue. Phonation parameters have been collected and are compared to those of the standard vocal fold models. Results show that vocal fold kinematics are affected by adding the adipose tissue layer as a new boundary condition.

  19. Modeling and experimental verification of a fan-folded vibration energy harvester for leadless pacemakers

    Science.gov (United States)

    Ansari, M. H.; Karami, M. Amin

    2016-03-01

    This paper studies energy harvesting from heartbeat vibrations for powering leadless pacemakers. Unlike traditional pacemakers, leadless pacemakers are implanted inside the heart and the pacemaker is in direct contact with the myocardium. A leadless pacemaker is in the shape of a cylinder. Thus, in order to utilize the available 3-dimensional space for the energy harvester, we choose a fan-folded 3D energy harvester. The proposed device consists of several piezoelectric beams stacked on top of each other. The volume of the energy harvester is 1 cm3 and its dimensions are 2 cm × 0.5 cm × 1 cm. Although high natural frequency is generally a major concern with micro-scale energy harvesters, by utilizing the fan-folded geometry and adding tip mass and link mass to the configuration, we reduced the natural frequency to the desired range. This fan-folded design makes it possible to generate more than 10 μ W of power per cubic centimeter. The proposed device is compatible with Magnetic Resonance Imaging. Although the proposed device is a linear energy harvester, it is relatively insensitive to the heart rate. The natural frequencies and the mode shapes of the device are calculated analytically. The accuracy of the analytical model is verified by experimental investigations. We use a closed loop shaker system to precisely replicate heartbeat vibrations in vitro.

  20. Communication: Role of explicit water models in the helix folding/unfolding processes

    Science.gov (United States)

    Palazzesi, Ferruccio; Salvalaglio, Matteo; Barducci, Alessandro; Parrinello, Michele

    2016-09-01

    In the last years, it has become evident that computer simulations can assume a relevant role in modelling protein dynamical motions for their ability to provide a full atomistic image of the processes under investigation. The ability of the current protein force-fields in reproducing the correct thermodynamics and kinetics systems behaviour is thus an essential ingredient to improve our understanding of many relevant biological functionalities. In this work, employing the last developments of the metadynamics framework, we compare the ability of state-of-the-art all-atom empirical functions and water models to consistently reproduce the folding and unfolding of a helix turn motif in a model peptide. This theoretical study puts in evidence that the choice of the water models can influence the thermodynamic and the kinetics of the system under investigation, and for this reason cannot be considered trivial.

  1. A Self-Assisting Protein Folding Model for Teaching Structural Molecular Biology.

    Science.gov (United States)

    Davenport, Jodi; Pique, Michael; Getzoff, Elizabeth; Huntoon, Jon; Gardner, Adam; Olson, Arthur

    2017-04-04

    Structural molecular biology is now becoming part of high school science curriculum thus posing a challenge for teachers who need to convey three-dimensional (3D) structures with conventional text and pictures. In many cases even interactive computer graphics does not go far enough to address these challenges. We have developed a flexible model of the polypeptide backbone using 3D printing technology. With this model we have produced a polypeptide assembly kit to create an idealized model of the Triosephosphate isomerase mutase enzyme (TIM), which forms a structure known as TIM barrel. This kit has been used in a laboratory practical where students perform a step-by-step investigation into the nature of protein folding, starting with the handedness of amino acids to the formation of secondary and tertiary structure. Based on the classroom evidence we collected, we conclude that these models are valuable and inexpensive resource for teaching structural molecular biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Folding model analysis of Λ binding energies and three-body ΛNN force

    International Nuclear Information System (INIS)

    Mian, M.; Rahman Khan, M.Z.

    1988-02-01

    Working within the framework of the folding model, we analyze the Λ binding energy data of light hypernuclei with effective two-body ΛN plus three-body ΛNN interaction. The two-body density for the core nucleus required for evaluating the three-body force contribution is obtained in terms of the centre of mass pair correlation. It is found that except for Λ 5 He the data are fairly well explained. The three-body force seems to account for the density dependence of the effective two-body ΛN interaction proposed earlier. (author). 13 refs, 2 tabs

  3. A model in which heat shock protein 90 targets protein-folding clefts: rationale for a new approach to neuroprotective treatment of protein folding diseases.

    Science.gov (United States)

    Pratt, William B; Morishima, Yoshihiro; Gestwicki, Jason E; Lieberman, Andrew P; Osawa, Yoichi

    2014-11-01

    In an EBM Minireview published in 2010, we proposed that the heat shock protein (Hsp)90/Hsp70-based chaperone machinery played a major role in determining the selection of proteins that have undergone oxidative or other toxic damage for ubiquitination and proteasomal degradation. The proposal was based on a model in which the Hsp90 chaperone machinery regulates signaling by modulating ligand-binding clefts. The model provides a framework for thinking about the development of neuroprotective therapies for protein-folding diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and the polyglutamine expansion disorders, such as Huntington's disease (HD) and spinal and bulbar muscular atrophy (SBMA). Major aberrant proteins that misfold and accumulate in these diseases are "client" proteins of the abundant and ubiquitous stress chaperone Hsp90. These Hsp90 client proteins include tau (AD), α-synuclein (PD), huntingtin (HD), and the expanded glutamine androgen receptor (polyQ AR) (SBMA). In this Minireview, we update our model in which Hsp90 acts on protein-folding clefts and show how it forms a rational basis for developing drugs that promote the targeted elimination of these aberrant proteins. © 2014 by the Society for Experimental Biology and Medicine.

  4. Use of the peritracheal fold in the dog tracheal transplantation model.

    Science.gov (United States)

    Gannon, P J; Costantino, P D; Lueg, E A; Chaplin, J M; Brandwein, M S; Passalaqua, P J; Fliegelman, L J; Laitman, J T; Marquez, S; Urken, M L

    1999-09-01

    To investigate the technical aspects of the canine model of human tracheal transplantation for potential application to reconstruction of extremely long tracheal defects (> 10 cm). In phase 1, long tracheal segments were skeletonized and pedicled with the thyroid glands, cranial thyroid arteries and veins, and internal jugular vein branches. The segments were elevated completely, attached to the vascular pedicle only, and replaced with primary tracheal anastomoses. In phase 2, long segments were elevated along with a diffuse soft tissue "blanket" that envelops the trachea and thyroid glands. Because this study was designed to primarily address, in situ, tracheal perfusion territories of a cranially located vascular pedicle, microvascular anastomoses were not conducted. Two small-bodied beagles (10-15 kg) and 5 large-bodied mixed-breed dogs (20-30 kg) were humanely killed 2 to 41 days after surgery, and anatomic and histological analyses were conducted. Unlike that of humans, the thyroid gland complex of dogs is not intimately associated with the trachea but is conjoined with a peritracheal soft tissue "fold." Within this fold, blood is transmitted to the trachea via a diffuse, segmental vascular plexus. In phase 1, pronounced tracheal necrosis occurred within 2 to 5 days. In phase 2, extremely long tracheal segments (10-12 cm), based only on a cranially located pedicle, were still viable at 2 to 6 weeks. Preservation of the "peritracheal fold" in the dog model of tracheal transplantation is critical to the onset and maintenance of vascular perfusion in a long tracheal segment. Furthermore, the use of large-bodied dogs is necessary to provide for a usable venous efflux component.

  5. Spherical aberration correction with an in-lens N-fold symmetric line currents model.

    Science.gov (United States)

    Hoque, Shahedul; Ito, Hiroyuki; Nishi, Ryuji

    2018-04-01

    In our previous works, we have proposed N-SYLC (N-fold symmetric line currents) models for aberration correction. In this paper, we propose "in-lens N-SYLC" model, where N-SYLC overlaps rotationally symmetric lens. Such overlap is possible because N-SYLC is free of magnetic materials. We analytically prove that, if certain parameters of the model are optimized, an in-lens 3-SYLC (N = 3) doublet can correct 3rd order spherical aberration. By computer simulation, we show that the required excitation current for correction is less than 0.25 AT for beam energy 5 keV, and the beam size after correction is smaller than 1 nm at the corrector image plane for initial slope less than 4 mrad. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. A replica exchange Monte Carlo algorithm for protein folding in the HP model

    Directory of Open Access Journals (Sweden)

    Shmygelska Alena

    2007-09-01

    Full Text Available Abstract Background The ab initio protein folding problem consists of predicting protein tertiary structure from a given amino acid sequence by minimizing an energy function; it is one of the most important and challenging problems in biochemistry, molecular biology and biophysics. The ab initio protein folding problem is computationally challenging and has been shown to be NP MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFneVtcqqGqbauaaa@3961@-hard even when conformations are restricted to a lattice. In this work, we implement and evaluate the replica exchange Monte Carlo (REMC method, which has already been applied very successfully to more complex protein models and other optimization problems with complex energy landscapes, in combination with the highly effective pull move neighbourhood in two widely studied Hydrophobic Polar (HP lattice models. Results We demonstrate that REMC is highly effective for solving instances of the square (2D and cubic (3D HP protein folding problem. When using the pull move neighbourhood, REMC outperforms current state-of-the-art algorithms for most benchmark instances. Additionally, we show that this new algorithm provides a larger ensemble of ground-state structures than the existing state-of-the-art methods. Furthermore, it scales well with sequence length, and it finds significantly better conformations on long biological sequences and sequences with a provably unique ground-state structure, which is believed to be a characteristic of real proteins. We also present evidence that our REMC algorithm can fold sequences which exhibit significant interaction between termini in the hydrophobic core relatively easily. Conclusion We demonstrate that REMC utilizing the pull move

  7. Assessing groundwater availability in a folded carbonate aquifer through the development of a numerical model

    Science.gov (United States)

    Di Salvo, Cristina; Romano, Emanuele; Guyennon, Nicolas; Bruna Petrangeli, Anna; Preziosi, Elisabetta

    2015-04-01

    The study of aquifer systems from a quantitative point of view is fundamental for adopting water management plans aiming at preserving water resources and reducing environmental risks related to groundwater level and discharge changes. This is also what the European Union Water Framework Directive (WFD, 2000/60/EC) states, holding the development of numerical models as a key aspect for groundwater management. The objective of this research is to i) define a methodology for modeling a complex hydrogeological structure in a structurally folded carbonate area and ii) estimate the concurrent effects of exploitation and climate changes on groundwater availability through the implementation of a 3D groundwater flow model. This study concerns the Monte Coscerno karst aquifer located in the Apennine chain in Central Italy in the Nera River Valley.This aquifer, is planned to be exploited in the near future for water supply. Negative trends of precipitation in Central Italy have been reported in relation to global climate changes, which are expected to affect the availability of recharge to carbonate aquifers throughout the region . A great concern is the combined impact of climate change and groundwater exploitation, hence scenarios are needed taking into account the effect of possible temperature and precipitation trends on recharge rates. Following a previous experience with model conceptualization and long-term simulation of groundwater flow, an integrated three-dimensional groundwater model has been developed for the Monte Coscerno aquifer. In a previous paper (Preziosi et al 2014) the spatial distribution of recharge to this aquifer was estimated through the Thornthwaite Mather model at a daily time step using as inputs past precipitation and temperature values (1951-2013) as well as soil and landscape properties. In this paper the numerical model development is described. On the basis of well logs from private consulting companies and literature cross sections the

  8. Factors controlling the evolution of the Perdido Fold Belt, northwestern Gulf of Mexico, determined from numerical models

    Science.gov (United States)

    Gradmann, Sofie; Beaumont, Christopher; Albertz, Markus

    2009-04-01

    The Perdido Fold Belt (PFB) is a prominent salt-cored deep water structure in the northwestern Gulf of Mexico. It is characterized by symmetric, kink-banded folds of a ˜4.5 km thick prekinematic layer and its vicinity to the extensive Sigsbee Salt Canopy. We use 2-D finite element numerical models to study the evolution of the PFB as a gravity-driven fold belt both in a local context and in the context of the larger-scale passive margin, influenced by adjacent allochthonous salt structures. We show that parameters such as overburden strength, salt geometry, or salt viscosity determine timing, extent, and location of the modeled fold belt. Simplified models of the Gulf of Mexico show that toe-of-slope folding is a viable mechanism to develop diapirs in the deep salt basin and to delay folding of the distal overburden. In this scenario, the PFB likely represents the terminal folding of a much larger, diachronously formed fold belt system.

  9. The Efficacy of Fibroblast Growth Factor for the Treatment of Chronic Vocal Fold Scarring: From Animal Model to Clinical Application.

    Science.gov (United States)

    Ban, Myung Jin; Park, Jae Hong; Kim, Jae Wook; Park, Ki Nam; Lee, Jae Yong; Kim, Hee Kyung; Lee, Seung Won

    2017-12-01

    This study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition. FGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post-injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection. FGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (Pvocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring.

  10. Thermodynamics of protein folding using a modified Wako-Saitô-Muñoz-Eaton model.

    Science.gov (United States)

    Tsai, Min-Yeh; Yuan, Jian-Min; Teranishi, Yoshiaki; Lin, Sheng Hsien

    2012-09-01

    Herein, we propose a modified version of the Wako-Saitô-Muñoz-Eaton (WSME) model. The proposed model introduces an empirical temperature parameter for the hypothetical structural units (i.e., foldons) in proteins to include site-dependent thermodynamic behavior. The thermodynamics for both our proposed model and the original WSME model were investigated. For a system with beta-hairpin topology, a mathematical treatment (contact-pair treatment) to facilitate the calculation of its partition function was developed. The results show that the proposed model provides better insight into the site-dependent thermodynamic behavior of the system, compared with the original WSME model. From this site-dependent point of view, the relationship between probe-dependent experimental results and model's thermodynamic predictions can be explained. The model allows for suggesting a general principle to identify foldon behavior. We also find that the backbone hydrogen bonds may play a role of structural constraints in modulating the cooperative system. Thus, our study may contribute to the understanding of the fundamental principles for the thermodynamics of protein folding.

  11. Three-dimensional biomechanical properties of human vocal folds: Parameter optimization of a numerical model to match in vitro dynamics

    Science.gov (United States)

    Yang, Anxiong; Berry, David A.; Kaltenbacher, Manfred; Döllinger, Michael

    2012-01-01

    The human voice signal originates from the vibrations of the two vocal folds within the larynx. The interactions of several intrinsic laryngeal muscles adduct and shape the vocal folds to facilitate vibration in response to airflow. Three-dimensional vocal fold dynamics are extracted from in vitro hemilarynx experiments and fitted by a numerical three-dimensional-multi-mass-model (3DM) using an optimization procedure. In this work, the 3DM dynamics are optimized over 24 experimental data sets to estimate biomechanical vocal fold properties during phonation. Accuracy of the optimization is verified by low normalized error (0.13 ± 0.02), high correlation (83% ± 2%), and reproducible subglottal pressure values. The optimized, 3DM parameters yielded biomechanical variations in tissue properties along the vocal fold surface, including variations in both the local mass and stiffness of vocal folds. That is, both mass and stiffness increased along the superior-to-inferior direction. These variations were statistically analyzed under different experimental conditions (e.g., an increase in tension as a function of vocal fold elongation and an increase in stiffness and a decrease in mass as a function of glottal airflow). The study showed that physiologically relevant vocal fold tissue properties, which cannot be directly measured during in vivo human phonation, can be captured using this 3D-modeling technique. PMID:22352511

  12. Theoretical models for designing a 220-GHz folded waveguide backward wave oscillator

    International Nuclear Information System (INIS)

    Cai Jin-Chi; Chen Huai-Bi; Hu Lin-Lin; Ma Guo-Wu; Chen Hong-Bin; Jin Xiao

    2015-01-01

    In this paper, the basic equations of beam-wave interaction for designing the 220 GHz folded waveguide (FW) backward wave oscillator (BWO) are described. On the whole, these equations are mainly classified into small signal model (SSM), large signal model (LSM), and simplified small signal model (SSSM). Using these linear and nonlinear one-dimensional (1D) models, the oscillation characteristics of the FW BWO of a given configuration of slow wave structure (SWS) can be calculated by numerical iteration algorithm, which is more time efficient than three-dimensional (3D) particle-in-cell (PIC) simulation. The SSSM expressed by analytical formulas is innovatively derived for determining the initial values of the FW SWS conveniently. The dispersion characteristics of the FW are obtained by equivalent circuit analysis. The space charge effect, the end reflection effect, the lossy wall effect, and the relativistic effect are all considered in our models to offer more accurate results. The design process of the FW BWO tube with output power of watt scale in a frequency range between 215 GHz and 225 GHz based on these 1D models is demonstrated. The 3D PIC method is adopted to verify the theoretical design results, which shows that they are in good agreement with each other. (paper)

  13. Investigation of the three-dimensional lattice HP protein folding model using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Fábio L. Custódio

    2004-01-01

    Full Text Available An approach to the hydrophobic-polar (HP protein folding model was developed using a genetic algorithm (GA to find the optimal structures on a 3D cubic lattice. A modification was introduced to the scoring system of the original model to improve the model's capacity to generate more natural-like structures. The modification was based on the assumption that it may be preferable for a hydrophobic monomer to have a polar neighbor than to be in direct contact with the polar solvent. The compactness and the segregation criteria were used to compare structures created by the original HP model and by the modified one. An islands' algorithm, a new selection scheme and multiple-points crossover were used to improve the performance of the algorithm. Ten sequences, seven with length 27 and three with length 64 were analyzed. Our results suggest that the modified model has a greater tendency to form globular structures. This might be preferable, since the original HP model does not take into account the positioning of long polar segments. The algorithm was implemented in the form of a program with a graphical user interface that might have a didactical potential in the study of GA and on the understanding of hydrophobic core formation.

  14. Rf modeling and design of a folded waveguide launcher for the Alcator C-Mod tokamak

    International Nuclear Information System (INIS)

    Bigelow, T.S.; Fogelman, C.F.; Baity, F.W.; Carter, M.D.; Hoffman, D.J.; Ryan, P.M.; Yugo, J.J.; Golovato, S.N.; Bonoli, P.

    1993-01-01

    The folded waveguide (FWG) launcher is being investigated as an improved antenna configuration for plasma heating in the ion cyclotron range of frequencies (ICRF). A development FWG launcher was successfully tested at Oak Ridge National Laboratory (ORNL) with a low-density plasma load and found to have significantly greater power density capability than current strap-type antennas operating in similar plasmas. To further test the concept on a high density tokamak plasma, a collaboration has been set up between ORNL and Massachusetts Institute of Technology (MIT) to develop and test an 80-MHz, 2-MW FWG on the Alcator C-Mod tokamak at MIT. The radio frequency (rf) electromagnetic modeling techniques and laboratory measurements used in the design of this antenna are described in this paper. A companion paper describes the mechanical design of the FWG

  15. Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model.

    Science.gov (United States)

    Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho; Bless, Diane M

    2016-03-01

    Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring.

  16. The influence of material anisotropy on vibration at onset in a three-dimensional vocal fold model

    Science.gov (United States)

    Zhang, Zhaoyan

    2014-01-01

    Although vocal folds are known to be anisotropic, the influence of material anisotropy on vocal fold vibration remains largely unknown. Using a linear stability analysis, phonation onset characteristics were investigated in a three-dimensional anisotropic vocal fold model. The results showed that isotropic models had a tendency to vibrate in a swing-like motion, with vibration primarily along the superior-inferior direction. Anterior-posterior (AP) out-of-phase motion was also observed and large vocal fold vibration was confined to the middle third region along the AP length. In contrast, increasing anisotropy or increasing AP-transverse stiffness ratio suppressed this swing-like motion and allowed the vocal fold to vibrate in a more wave-like motion with strong medial-lateral motion over the entire medial surface. Increasing anisotropy also suppressed the AP out-of-phase motion, allowing the vocal fold to vibrate in phase along the entire AP length. Results also showed that such improvement in vibration pattern was the most effective with large anisotropy in the cover layer alone. These numerical predictions were consistent with previous experimental observations using self-oscillating physical models. It was further hypothesized that these differences may facilitate complete glottal closure in finite-amplitude vibration of anisotropic models as observed in recent experiments. PMID:24606284

  17. Expression of tenascin-C in a rat vocal fold injury model and its regulation of fibroblasts.

    Science.gov (United States)

    Li, Juan; Liu, Yiqiong; Wang, Yiming; Xu, Wen

    2018-03-23

    Tenascin-C (Tnc) is an extracellular matrix (ECM) glycoprotein that plays a vital role in wound healing and fibrotic disease. Tnc is highly upregulated soon after vocal fold injury, but its function in the vocal fold has not yet been defined. In this study, we investigated Tnc expression in a rat vocal fold injury model in vivo and its roles in fibroblasts in vitro. In vivo and in vitro. Tnc mRNA and protein expression levels were quantified on days 3, 7, 14, 28, and 56 after vocal fold injury in Sprague-Dawley rats. In vitro, immunocytochemistry, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed in primary rat vocal fold fibroblasts following Tnc or transforming growth factor (TGF)-β1 stimulation to investigate the phenotypic effects. Tnc mRNA and protein expression was upregulated dramatically on days 3 and 7 after injury, and significant differences were observed by qRT-PCR (P vocal fold fibroblasts. Following incubation with Tnc for 72 hours, α-smooth muscle actin, collagen I, and fibronectin expression was significantly upregulated (P vocal fold fibroblast migration, transdifferentiation, and ECM protein synthesis in vitro. Tnc was induced by TGF-β1 in a SMAD3-dependent manner. Transient expression of Tnc is likely to promote regeneration, but its potential role in fibrosis requires further study. NA Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Protein folding optimization based on 3D off-lattice model via an improved artificial bee colony algorithm.

    Science.gov (United States)

    Li, Bai; Lin, Mu; Liu, Qiao; Li, Ya; Zhou, Changjun

    2015-10-01

    Protein folding is a fundamental topic in molecular biology. Conventional experimental techniques for protein structure identification or protein folding recognition require strict laboratory requirements and heavy operating burdens, which have largely limited their applications. Alternatively, computer-aided techniques have been developed to optimize protein structures or to predict the protein folding process. In this paper, we utilize a 3D off-lattice model to describe the original protein folding scheme as a simplified energy-optimal numerical problem, where all types of amino acid residues are binarized into hydrophobic and hydrophilic ones. We apply a balance-evolution artificial bee colony (BE-ABC) algorithm as the minimization solver, which is featured by the adaptive adjustment of search intensity to cater for the varying needs during the entire optimization process. In this work, we establish a benchmark case set with 13 real protein sequences from the Protein Data Bank database and evaluate the convergence performance of BE-ABC algorithm through strict comparisons with several state-of-the-art ABC variants in short-term numerical experiments. Besides that, our obtained best-so-far protein structures are compared to the ones in comprehensive previous literature. This study also provides preliminary insights into how artificial intelligence techniques can be applied to reveal the dynamics of protein folding. Graphical Abstract Protein folding optimization using 3D off-lattice model and advanced optimization techniques.

  19. A cervid vocal fold model suggests greater glottal efficiency in calling at high frequencies.

    Directory of Open Access Journals (Sweden)

    Ingo R Titze

    2010-08-01

    Full Text Available Male Rocky Mountain elk (Cervus elaphus nelsoni produce loud and high fundamental frequency bugles during the mating season, in contrast to the male European Red Deer (Cervus elaphus scoticus who produces loud and low fundamental frequency roaring calls. A critical step in understanding vocal communication is to relate sound complexity to anatomy and physiology in a causal manner. Experimentation at the sound source, often difficult in vivo in mammals, is simulated here by a finite element model of the larynx and a wave propagation model of the vocal tract, both based on the morphology and biomechanics of the elk. The model can produce a wide range of fundamental frequencies. Low fundamental frequencies require low vocal fold strain, but large lung pressure and large glottal flow if sound intensity level is to exceed 70 dB at 10 m distance. A high-frequency bugle requires both large muscular effort (to strain the vocal ligament and high lung pressure (to overcome phonation threshold pressure, but at least 10 dB more intensity level can be achieved. Glottal efficiency, the ration of radiated sound power to aerodynamic power at the glottis, is higher in elk, suggesting an advantage of high-pitched signaling. This advantage is based on two aspects; first, the lower airflow required for aerodynamic power and, second, an acoustic radiation advantage at higher frequencies. Both signal types are used by the respective males during the mating season and probably serve as honest signals. The two signal types relate differently to physical qualities of the sender. The low-frequency sound (Red Deer call relates to overall body size via a strong relationship between acoustic parameters and the size of vocal organs and body size. The high-frequency bugle may signal muscular strength and endurance, via a 'vocalizing at the edge' mechanism, for which efficiency is critical.

  20. Multimodality pH imaging in a mouse dorsal skin fold window chamber model

    Science.gov (United States)

    Leung, Hui Min; Schafer, Rachel; Pagel, Mark M.; Robey, Ian F.; Gmitro, Arthur F.

    2013-03-01

    Upregulate levels of expression and activity of membrane H+ ion pumps in cancer cells drives the extracellular pH (pHe,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pHe could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pHe in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described. A custom-made plastic window chamber structure was developed that is compatible with both imaging optical and MR imaging modalities and provides a model system for continuous study of the same tissue microenvironment on multiple imaging platforms over a 3-week period. For optical imaging of pHe, SNARF-1 carboxylic acid is injected intravenously into a SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence signal captured on a confocal microscope reveals the pHe of the tissue visible within the window chamber. This imaging method was used in a preliminary study to evaluate sodium bicarbonate as a potential drug treatment to reverse tissue acidosis. For MR imaging of pHe the chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST®, a FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm chemical shift provides a means to estimate the local pHe.

  1. Airflow visualization in a model of human glottis near the self-oscillating vocal folds model

    Czech Academy of Sciences Publication Activity Database

    Horáček, Jaromír; Uruba, Václav; Radolf, Vojtěch; Veselý, Jan; Bula, Vítězslav

    2011-01-01

    Roč. 5, č. 1 (2011), s. 21-28 ISSN 1802-680X R&D Projects: GA ČR GA101/08/1155 Institutional research plan: CEZ:AV0Z20760514 Keywords : biomechanics of human voice * voice production modelling * PIV measurement of streamline patterns Subject RIV: BI - Acoustics

  2. Double folding model of nucleus-nucleus potential: formulae, iteration method and computer code

    International Nuclear Information System (INIS)

    Luk'yanov, K.V.

    2008-01-01

    Method of construction of the nucleus-nucleus double folding potential is described. Iteration procedure for the corresponding integral equation is presented. Computer code and numerical results are presented

  3. Implementation of a 3d numerical model of a folded multilayer carbonate aquifer

    Science.gov (United States)

    Di Salvo, Cristina; Guyennon, Nicolas; Romano, Emanuele; Bruna Petrangeli, Anna; Preziosi, Elisabetta

    2016-04-01

    The main objective of this research is to present a case study of the numerical model implementation of a complex carbonate, structurally folded aquifer, with a finite difference, porous equivalent model. The case study aquifer (which extends over 235 km2 in the Apennine chain, Central Italy) provides a long term average of 3.5 m3/s of good quality groundwater to the surface river network, sustaining the minimum vital flow, and it is planned to be exploited in the next years for public water supply. In the downstream part of the river in the study area, a "Site of Community Importance" include the Nera River for its valuable aquatic fauna. However, the possible negative effects of the foreseen exploitation on groundwater dependent ecosystems are a great concern and model grounded scenarios are needed. This multilayer aquifer was conceptualized as five hydrostratigraphic units: three main aquifers (the uppermost unconfined, the central and the deepest partly confined), are separated by two locally discontinuous aquitards. The Nera river cuts through the two upper aquifers and acts as the main natural sink for groundwater. An equivalent porous medium approach was chosen. The complex tectonic structure of the aquifer requires several steps in defining the conceptual model; the presence of strongly dipping layers with very heterogeneous hydraulic conductivity, results in different thicknesses of saturated portions. Aquifers can have both unconfined or confined zones; drying and rewetting must be allowed when considering recharge/discharge cycles. All these characteristics can be included in the conceptual and numerical model; however, being the number of flow and head target scarce, the over-parametrization of the model must be avoided. Following the principle of parsimony, three steady state numerical models were developed, starting from a simple model, and then adding complexity: 2D (single layer), QUASI -3D (with leackage term simulating flow through aquitards) and

  4. Space-time evolution of a growth fold (Betic Cordillera, Spain). Evidences from 3D geometrical modelling

    Science.gov (United States)

    Martin-Rojas, Ivan; Alfaro, Pedro; Estévez, Antonio

    2014-05-01

    We present a study that encompasses several software tools (iGIS©, ArcGIS©, Autocad©, etc.) and data (geological mapping, high resolution digital topographic data, high resolution aerial photographs, etc.) to create a detailed 3D geometric model of an active fault propagation growth fold. This 3D model clearly shows structural features of the analysed fold, as well as growth relationships and sedimentary patterns. The results obtained permit us to discuss the kinematics and structural evolution of the fold and the fault in time and space. The study fault propagation fold is the Crevillente syncline. This fold represents the northern limit of the Bajo Segura Basin, an intermontane basin in the Eastern Betic Cordillera (SE Spain) developed from upper Miocene on. 3D features of the Crevillente syncline, including growth pattern, indicate that limb rotation and, consequently, fault activity was higher during Messinian than during Tortonian; consequently, fault activity was also higher. From Pliocene on our data point that limb rotation and fault activity steadies or probably decreases. This in time evolution of the Crevillente syncline is not the same all along the structure; actually the 3D geometric model indicates that observed lateral heterogeneity is related to along strike variation of fault displacement.

  5. Simultaneous temporally resolved DPIV and pressure measurements of symmetric oscillations in a scaled-up vocal fold model

    Science.gov (United States)

    Ringenberg, Hunter; Rogers, Dylan; Wei, Nathaniel; Krane, Michael; Wei, Timothy

    2017-11-01

    The objective of this study is to apply experimental data to theoretical framework of Krane (2013) in which the principal aeroacoustic source is expressed in terms of vocal fold drag, glottal jet dynamic head, and glottal exit volume flow, reconciling formal theoretical aeroacoustic descriptions of phonation with more traditional lumped-element descriptions. These quantities appear in the integral equations of motion for phonatory flow. In this way time resolved velocity field measurements can be used to compute time-resolved estimates of the relevant terms in the integral equations of motion, including phonation aeroacoustic source strength. A simplified 10x scale vocal fold model from Krane, et al. (2007) was used to examine symmetric, i.e. `healthy', oscillatory motion of the vocal folds. By using water as the working fluid, very high spatial and temporal resolution was achieved. Temporal variation of transglottal pressure was simultaneously measured with flow on the vocal fold model mid-height. Experiments were dynamically scaled to examine a range of frequencies corresponding to male and female voice. The simultaneity of the pressure and flow provides new insights into the aeroacoustics associated with vocal fold oscillations. Supported by NIH Grant No. 2R01 DC005642-11.

  6. Use of integrated analogue and numerical modelling to predict tridimensional fracture intensity in fault-related-folds.

    Science.gov (United States)

    Pizzati, Mattia; Cavozzi, Cristian; Magistroni, Corrado; Storti, Fabrizio

    2016-04-01

    Fracture density pattern predictions with low uncertainty is a fundamental issue for constraining fluid flow pathways in thrust-related anticlines in the frontal parts of thrust-and-fold belts and accretionary prisms, which can also provide plays for hydrocarbon exploration and development. Among the drivers that concur to determine the distribution of fractures in fold-and-thrust-belts, the complex kinematic pathways of folded structures play a key role. In areas with scarce and not reliable underground information, analogue modelling can provide effective support for developing and validating reliable hypotheses on structural architectures and their evolution. In this contribution, we propose a working method that combines analogue and numerical modelling. We deformed a sand-silicone multilayer to eventually produce a non-cylindrical thrust-related anticline at the wedge toe, which was our test geological structure at the reservoir scale. We cut 60 serial cross-sections through the central part of the deformed model to analyze faults and folds geometry using dedicated software (3D Move). The cross-sections were also used to reconstruct the 3D geometry of reference surfaces that compose the mechanical stratigraphy thanks to the use of the software GoCad. From the 3D model of the experimental anticline, by using 3D Move it was possible to calculate the cumulative stress and strain underwent by the deformed reference layers at the end of the deformation and also in incremental steps of fold growth. Based on these model outputs it was also possible to predict the orientation of three main fractures sets (joints and conjugate shear fractures) and their occurrence and density on model surfaces. The next step was the upscaling of the fracture network to the entire digital model volume, to create DFNs.

  7. Finite element modeling of the vocal folds with deformable interface tracking

    DEFF Research Database (Denmark)

    Granados Corsellas, Alba; Brunskog, Jonas; Misztal, Marek Krzysztof

    2014-01-01

    Continuous and prolonged use of the sp eaking voice may lead to functional sp eech disorders that are not apparent for voice clinicians from high-sp eed imaging of the vo cal folds' vibration. However, it is hyp othesized that time dep endent tissue prop erties provide some insight into the injury...... pro cess. To infer material parameters via an inverse optimization problem from recorded deformation, a self sustained theoretical mo del of the vo cal folds is needed. With this purp ose, a transversely isotropic three-dimensional nite element mo del is prop osed and investigated. Sp ecial attention...

  8. Relation of Structural and Vibratory Kinematics of the Vocal Folds to Two Acoustic Measures of Breathy Voice Based on Computational Modeling

    Science.gov (United States)

    Samlan, Robin A.; Story, Brad H.

    2011-01-01

    Purpose: To relate vocal fold structure and kinematics to 2 acoustic measures: cepstral peak prominence (CPP) and the amplitude of the first harmonic relative to the second (H1-H2). Method: The authors used a computational, kinematic model of the medial surfaces of the vocal folds to specify features of vocal fold structure and vibration in a…

  9. Examining diseased states in a scaled-up vocal fold model using simultaneous temporally resolved DPIV and pressure measurements

    Science.gov (United States)

    Rogers, Dylan; Wei, Nathaniel; Ringenber, Hunter; Krane, Michael; Wei, Timothy

    2017-11-01

    This study builds on the parallel presentation of Ringenberg, et al. (APS-DFD 2017) involving simultaneous, temporally and spatially resolved flow and pressure measurements in a scaled-up vocal fold model. In this talk, data from experiments replicating characteristics of diseased vocal folds are presented. This begins with vocal folds that do not fully close and continues with asymmetric oscillations. Data are compared to symmetric, i.e. `healthy', oscillatory motions presented in the companion talk. Having pressure and flow data for individual as well as phase averaged oscillations for these diseased cases highlights the potential for aeroacoustic analysis in this complex system. Supported by NIH Grant No. 2R01 DC005642-11.

  10. Geometry of human vocal folds and glottal channel for mathematical and biomechanical modeling of voice production

    Czech Academy of Sciences Publication Activity Database

    Šidlof, Petr; Švec, J. G.; Horáček, Jaromír; Veselý, Jan; Klepáček, I.; Havlík, R.

    2008-01-01

    Roč. 41, - (2008), s. 985-995 ISSN 0021-9290 R&D Projects: GA AV ČR IAA2076401 Institutional research plan: CEZ:AV0Z20760514 Keywords : vocal fold geometry * glottal channel shape * quantitative description Subject RIV: BI - Acoustics Impact factor: 2.784, year: 2008

  11. Self-similar voiding solutions for a single layered model of folding rocks

    NARCIS (Netherlands)

    Dodwell, T.J.; Peletier, M.A.; Budd, C.J.; Hunt, G.W.

    2011-01-01

    In this paper we derive an obstacle problem with a free boundary to describe the formation of voids at areas of intense geological folding. An elastic layer is forced by overburden pressure against a V-shaped rigid obstacle. Energy minimization leads to representation as a non-linear fourth-order

  12. Numerical Simulation of Interaction of Fluid Flow and Elastic Structure Modelling Vocal Fold

    Czech Academy of Sciences Publication Activity Database

    Valášek, J.; Sváček, P.; Horáček, Jaromír

    2016-01-01

    Roč. 821, č. 2016 (2016), s. 693-700 ISSN 1660-9336 R&D Projects: GA ČR(CZ) GAP101/11/0207 Institutional support: RVO:61388998 Keywords : finite element method * 2D Navier-Stokes equations * vocal folds * aeroelasticity Subject RIV: BI - Acoustics

  13. The human vocal fold layers. Their delineation inside vocal fold as a background to create 3D digital and synthetic glottal model

    Czech Academy of Sciences Publication Activity Database

    Klepáček, I.; Jirák, D.; Dušková-Smrčková, Miroslava; Janoušková, Olga; Vampola, T.

    2016-01-01

    Roč. 30, č. 5 (2016), s. 529-537 ISSN 0892-1997 R&D Projects: GA ČR(CZ) GAP101/12/1306 Institutional support: RVO:61389013 Keywords : human vocal fold * vocal ligamentous complex * lamina propria Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.381, year: 2016

  14. Combination of Markov state models and kinetic networks for the analysis of molecular dynamics simulations of peptide folding.

    Science.gov (United States)

    Radford, Isolde H; Fersht, Alan R; Settanni, Giovanni

    2011-06-09

    Atomistic molecular dynamics simulations of the TZ1 beta-hairpin peptide have been carried out using an implicit model for the solvent. The trajectories have been analyzed using a Markov state model defined on the projections along two significant observables and a kinetic network approach. The Markov state model allowed for an unbiased identification of the metastable states of the system, and provided the basis for commitment probability calculations performed on the kinetic network. The kinetic network analysis served to extract the main transition state for folding of the peptide and to validate the results from the Markov state analysis. The combination of the two techniques allowed for a consistent and concise characterization of the dynamics of the peptide. The slowest relaxation process identified is the exchange between variably folded and denatured species, and the second slowest process is the exchange between two different subsets of the denatured state which could not be otherwise identified by simple inspection of the projected trajectory. The third slowest process is the exchange between a fully native and a partially folded intermediate state characterized by a native turn with a proximal backbone H-bond, and frayed side-chain packing and termini. The transition state for the main folding reaction is similar to the intermediate state, although a more native like side-chain packing is observed.

  15. Structurally and functionally characterized in vitro model of rabbit vocal fold epithelium.

    Science.gov (United States)

    Mizuta, Masanobu; Kurita, Takashi; Kimball, Emily E; Rousseau, Bernard

    2017-06-01

    In this paper, we describe a method for primary culture of a well differentiated electrically tight rabbit vocal fold epithelial cell multilayer and the measurement of transepithelial electrical resistance (TEER) for the evaluation of epithelial barrier function in vitro. Rabbit larynges were harvested and enzymatically treated to isolate vocal fold epithelial cells and to establish primary culture. Vocal fold epithelial cells were co-cultured with mitomycin C-treated feeder cells on collagen-coated plates. After 10-14 days in primary culture, cells were passaged and cultured until they achieved 70-90% confluence on collagen-coated plates. Epithelial cells were then passaged onto collagen-coated cell culture inserts using 4.5cm 2 membrane filters (1.0μm pore size) with 10% fetal bovine serum or 30μg/mL bovine pituitary extract to investigate the effects of growth-promoting additives on TEER. Additional experiments were performed to investigate optimal seeding density (1.1, 2.2, 4.4, or 8.9×10 5 cells/cm 2 ), the effect of co-culture with feeder cells, and the effect of passage number on epithelial barrier function. Characterization of in vitro cultures was performed using hematoxylin and eosin staining and immunostaining for vocal fold epithelial cell markers and tight junctions. Results revealed higher TEER in cells supplemented with fetal bovine serum compared to bovine pituitary extract. TEER was highest in cells passaged at a seeding density of 2.2×10 4 cells/cm 2 , and TEER was higher in cells at passage two than passage three. Ultrastructural experiments revealed a well-differentiated epithelial cell multilayer, expressing the epithelial cell markers CK13, CK14 and the tight junction proteins occludin and ZO-1. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. A first-principles model of early evolution: emergence of gene families, species, and preferred protein folds.

    Directory of Open Access Journals (Sweden)

    Konstantin B Zeldovich

    2007-07-01

    Full Text Available In this work we develop a microscopic physical model of early evolution where phenotype--organism life expectancy--is directly related to genotype--the stability of its proteins in their native conformations-which can be determined exactly in the model. Simulating the model on a computer, we consistently observe the "Big Bang" scenario whereby exponential population growth ensues as soon as favorable sequence-structure combinations (precursors of stable proteins are discovered. Upon that, random diversity of the structural space abruptly collapses into a small set of preferred proteins. We observe that protein folds remain stable and abundant in the population at timescales much greater than mutation or organism lifetime, and the distribution of the lifetimes of dominant folds in a population approximately follows a power law. The separation of evolutionary timescales between discovery of new folds and generation of new sequences gives rise to emergence of protein families and superfamilies whose sizes are power-law distributed, closely matching the same distributions for real proteins. On the population level we observe emergence of species--subpopulations that carry similar genomes. Further, we present a simple theory that relates stability of evolving proteins to the sizes of emerging genomes. Together, these results provide a microscopic first-principles picture of how first-gene families developed in the course of early evolution.

  17. Parallel CFD simulation of flow in a 3D model of vibrating human vocal folds

    Czech Academy of Sciences Publication Activity Database

    Šidlof, Petr; Horáček, Jaromír; Řidký, V.

    2013-01-01

    Roč. 80, č. 1 (2013), s. 290-300 ISSN 0045-7930 R&D Projects: GA ČR(CZ) GAP101/11/0207 Institutional research plan: CEZ:AV0Z20760514 Keywords : numerical simulation * vocal folds * glottal airflow * inite volume method * parallel CFD Subject RIV: BI - Acoustics Impact factor: 1.532, year: 2013 http://www.sciencedirect.com/science?_ob=ArticleListURL&_method=list&_ArticleListID=-268060849&_sort=r&_st=13&view=c&_acct=C000034318&_version=1&_urlVersion=0&_userid=640952&md5=7c5b5539857ee9a02af5e690585b3126&searchtype=a

  18. Folding 19 proteins to their native state and stability of large proteins from a coarse-grained model.

    Science.gov (United States)

    Kapoor, Abhijeet; Travesset, Alex

    2014-03-01

    We develop an intermediate resolution model, where the backbone is modeled with atomic resolution but the side chain with a single bead, by extending our previous model (Proteins (2013) DOI: 10.1002/prot.24269) to properly include proline, preproline residues and backbone rigidity. Starting from random configurations, the model properly folds 19 proteins (including a mutant 2A3D sequence) into native states containing β sheet, α helix, and mixed α/β. As a further test, the stability of H-RAS (a 169 residue protein, critical in many signaling pathways) is investigated: The protein is stable, with excellent agreement with experimental B-factors. Despite that proteins containing only α helices fold to their native state at lower backbone rigidity, and other limitations, which we discuss thoroughly, the model provides a reliable description of the dynamics as compared with all atom simulations, but does not constrain secondary structures as it is typically the case in more coarse-grained models. Further implications are described. Copyright © 2013 Wiley Periodicals, Inc.

  19. Group theoretical classification of broken symmetry states of the two-fold degenerate Hubbard model on a triangular lattice

    International Nuclear Information System (INIS)

    Masago, Akira; Suzuki, Naoshi

    2001-01-01

    By a group theoretical procedure we derive the possible spontaneously broken-symmetry states for the two-fold degenerate Hubbard model on a two-dimensional triangular lattice. For ordering wave vectors corresponding to the points Γ and K in the first BZ we find 22 states which include 16 collinear and six non-collinear states. The collinear states include the usual SDW and CDW states which appear also in the single-band Hubbard model. The non-collinear states include exotic ordering states of orbitals and spins as well as the triangular arrangement of spins

  20. Polyphase tertiary fold-and-thrust tectonics in the Belluno Dolomites: new mapping, kinematic analysis, and 3D modelling

    Science.gov (United States)

    Chistolini, Filippo; Bistacchi, Andrea; Massironi, Matteo; Consonni, Davide; Cortinovis, Silvia

    2014-05-01

    performed a dip-domain analysis that allowed to categorize the different fold limbs and reduce the uncertainty in the reconstruction of the fault network topology in map view. This enabled us to reconstruct a high-quality, low-uncertainty 3D structural and geological model, which unambiguously proves that deformations with a top-to-WSW Dinaric transport direction propagate farther to the west than previously supposed in this part of the Southern Alps. Our new structural reconstruction of the Vajont valley have also clarified the structural control on the 1963 catastrophic landslide (which caused over 2000 losses). Besides being a challenging natural laboratory for testing analysis and modelling methodologies to be used when reconstructing in 3D this kind of complex interference structures, the Vajont area also provides useful clues on the still-enigmatic structures in the frontal part of the Friuli-Venetian Southern Alps, buried in the Venetian Plain foredeep. These include active seismogenic thrust-faults and, at the same time, represent a growing interest for the oil industry.

  1. An extended Kalman filter approach to non-stationary Bayesian estimation of reduced-order vocal fold model parameters.

    Science.gov (United States)

    Hadwin, Paul J; Peterson, Sean D

    2017-04-01

    The Bayesian framework for parameter inference provides a basis from which subject-specific reduced-order vocal fold models can be generated. Previously, it has been shown that a particle filter technique is capable of producing estimates and associated credibility intervals of time-varying reduced-order vocal fold model parameters. However, the particle filter approach is difficult to implement and has a high computational cost, which can be barriers to clinical adoption. This work presents an alternative estimation strategy based upon Kalman filtering aimed at reducing the computational cost of subject-specific model development. The robustness of this approach to Gaussian and non-Gaussian noise is discussed. The extended Kalman filter (EKF) approach is found to perform very well in comparison with the particle filter technique at dramatically lower computational cost. Based upon the test cases explored, the EKF is comparable in terms of accuracy to the particle filter technique when greater than 6000 particles are employed; if less particles are employed, the EKF actually performs better. For comparable levels of accuracy, the solution time is reduced by 2 orders of magnitude when employing the EKF. By virtue of the approximations used in the EKF, however, the credibility intervals tend to be slightly underpredicted.

  2. Identifying Conformational-Selection and Induced-Fit Aspects in the Binding-Induced Folding of PMI from Markov State Modeling of Atomistic Simulations.

    Science.gov (United States)

    Paul, Fabian; Noé, Frank; Weikl, Thomas R

    2018-03-27

    Unstructured proteins and peptides typically fold during binding to ligand proteins. A challenging problem is to identify the mechanism and kinetics of these binding-induced folding processes in experiments and atomistic simulations. In this Article, we present a detailed picture for the folding of the inhibitor peptide PMI into a helix during binding to the oncoprotein fragment 25-109 Mdm2 obtained from atomistic, explicit-water simulations and Markov state modeling. We find that binding-induced folding of PMI is highly parallel and can occur along a multitude of pathways. Some pathways are induced-fit-like with binding occurring prior to PMI helix formation, while other pathways are conformational-selection-like with binding after helix formation. On the majority of pathways, however, binding is intricately coupled to folding, without clear temporal ordering. A central feature of these pathways is PMI motion on the Mdm2 surface, along the binding groove of Mdm2 or over the rim of this groove. The native binding groove of Mdm2 thus appears as an asymmetric funnel for PMI binding. Overall, binding-induced folding of PMI does not fit into the classical picture of induced fit or conformational selection that implies a clear temporal ordering of binding and folding events. We argue that this holds in general for binding-induced folding processes because binding and folding events in these processes likely occur on similar time scales and do exhibit the time-scale separation required for temporal ordering.

  3. A Three Dimension Model to Demonstrate Head and Tail Fold Formation in Mammalian Embryos

    Science.gov (United States)

    Bressler, Robert S.

    1977-01-01

    Many students have difficulty visualizing the delineation of the embryonic body from the flat germ disc. An easily-constructed model is described that has been used successfully to convey the dynamics of embryological events at Mount Sinai School of Medicine. (LBH)

  4. Impact stress in a self-oscillating model of human vocal folds

    Czech Academy of Sciences Publication Activity Database

    Horáček, Jaromír; Bula, Vítězslav; Radolf, Vojtěch; Šidlof, Petr

    2016-01-01

    Roč. 4, č. 3 (2016), s. 183-190 ISSN 2321-3558 R&D Projects: GA ČR(CZ) GAP101/12/1306 Institutional support: RVO:61388998 Keywords : fluid-structure interaction * flutter * biomechanics of voice modeling * phonation * aeroelasticity Subject RIV: BI - Acoustics Impact factor: 0.259, year: 2016 http://www.tvi-in.com/Journals/journaldetail.aspx?Id=2016062811045074383592dcc719793

  5. Diffusion maps, clustering and fuzzy Markov modeling in peptide folding transitions

    International Nuclear Information System (INIS)

    Nedialkova, Lilia V.; Amat, Miguel A.; Kevrekidis, Ioannis G.; Hummer, Gerhard

    2014-01-01

    Using the helix-coil transitions of alanine pentapeptide as an illustrative example, we demonstrate the use of diffusion maps in the analysis of molecular dynamics simulation trajectories. Diffusion maps and other nonlinear data-mining techniques provide powerful tools to visualize the distribution of structures in conformation space. The resulting low-dimensional representations help in partitioning conformation space, and in constructing Markov state models that capture the conformational dynamics. In an initial step, we use diffusion maps to reduce the dimensionality of the conformational dynamics of Ala5. The resulting pretreated data are then used in a clustering step. The identified clusters show excellent overlap with clusters obtained previously by using the backbone dihedral angles as input, with small—but nontrivial—differences reflecting torsional degrees of freedom ignored in the earlier approach. We then construct a Markov state model describing the conformational dynamics in terms of a discrete-time random walk between the clusters. We show that by combining fuzzy C-means clustering with a transition-based assignment of states, we can construct robust Markov state models. This state-assignment procedure suppresses short-time memory effects that result from the non-Markovianity of the dynamics projected onto the space of clusters. In a comparison with previous work, we demonstrate how manifold learning techniques may complement and enhance informed intuition commonly used to construct reduced descriptions of the dynamics in molecular conformation space

  6. Diffusion maps, clustering and fuzzy Markov modeling in peptide folding transitions

    Energy Technology Data Exchange (ETDEWEB)

    Nedialkova, Lilia V.; Amat, Miguel A. [Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544 (United States); Kevrekidis, Ioannis G., E-mail: yannis@princeton.edu, E-mail: gerhard.hummer@biophys.mpg.de [Department of Chemical and Biological Engineering and Program in Applied and Computational Mathematics, Princeton University, Princeton, New Jersey 08544 (United States); Hummer, Gerhard, E-mail: yannis@princeton.edu, E-mail: gerhard.hummer@biophys.mpg.de [Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main (Germany)

    2014-09-21

    Using the helix-coil transitions of alanine pentapeptide as an illustrative example, we demonstrate the use of diffusion maps in the analysis of molecular dynamics simulation trajectories. Diffusion maps and other nonlinear data-mining techniques provide powerful tools to visualize the distribution of structures in conformation space. The resulting low-dimensional representations help in partitioning conformation space, and in constructing Markov state models that capture the conformational dynamics. In an initial step, we use diffusion maps to reduce the dimensionality of the conformational dynamics of Ala5. The resulting pretreated data are then used in a clustering step. The identified clusters show excellent overlap with clusters obtained previously by using the backbone dihedral angles as input, with small—but nontrivial—differences reflecting torsional degrees of freedom ignored in the earlier approach. We then construct a Markov state model describing the conformational dynamics in terms of a discrete-time random walk between the clusters. We show that by combining fuzzy C-means clustering with a transition-based assignment of states, we can construct robust Markov state models. This state-assignment procedure suppresses short-time memory effects that result from the non-Markovianity of the dynamics projected onto the space of clusters. In a comparison with previous work, we demonstrate how manifold learning techniques may complement and enhance informed intuition commonly used to construct reduced descriptions of the dynamics in molecular conformation space.

  7. Numerical seismic modelling of fault-fold structures in a mountainous setting

    Energy Technology Data Exchange (ETDEWEB)

    Kirtland Grech, M.G.; Lawton, D.C.; Spratt, D.A. (Calgary Univ., AB (Canada))

    1999-01-01

    Experiments were conducted to determine the performance of different prestack migration algorithms in complex structural areas, particularly in the presence of rugged topography and thrust faults that result in severe lateral and vertical velocity changes, using a series of numerical seismic models. The numerical model used was based on a cross section through the Rocky Mountains Front Ranges of Western Canada and is 33 km wide and 11 km deep. The best migrated section was obtained with FD shot migration in depth and from topography, using the known velocity model. This result was superior to Kirchhoff depth migration from topography and from a flat datum. As the velocities departed from their true value, the deeper events were most affected, because of the accumulation of velocity errors with depth. The small-scale features of Target A, in the shallower part of the section, could still be interpreted even when the velocities were inaccurate. In the presence of velocity errors, the different structures could still be interpreted, but were at the wrong depth and had the wrong structural shape and size. Layers that were of the order of 1 km in width and 500 km in thickness, such as Layer 4, were the most poorly imaged and focussed, both with time migration and with depth migration. Fault planes were not imaged in the absence of a velocity contrast across them, making some FW cutoffs difficult to interpret. 2 refs.

  8. Numerical seismic modelling of fault-fold structures in a mountainous setting

    Energy Technology Data Exchange (ETDEWEB)

    Kirtland Grech, M.G.; Lawton, D.C.; Spratt, D.A. [Calgary Univ., AB (Canada)

    1999-11-01

    Experiments were conducted to determine the performance of different prestack migration algorithms in complex structural areas, particularly in the presence of rugged topography and thrust faults that result in severe lateral and vertical velocity changes, using a series of numerical seismic models. The numerical model used was based on a cross section through the Rocky Mountains Front Ranges of Western Canada and is 33 km wide and 11 km deep. The best migrated section was obtained with FD shot migration in depth and from topography, using the known velocity model. This result was superior to Kirchhoff depth migration from topography and from a flat datum. As the velocities departed from their true value, the deeper events were most affected, because of the accumulation of velocity errors with depth. The small-scale features of Target A, in the shallower part of the section, could still be interpreted even when the velocities were inaccurate. In the presence of velocity errors, the different structures could still be interpreted, but were at the wrong depth and had the wrong structural shape and size. Layers that were of the order of 1 km in width and 500 km in thickness, such as Layer 4, were the most poorly imaged and focussed, both with time migration and with depth migration. Fault planes were not imaged in the absence of a velocity contrast across them, making some FW cutoffs difficult to interpret. 2 refs.

  9. New insights into chromatin folding and dynamics from multi-scale modeling

    Science.gov (United States)

    Olson, Wilma

    The dynamic organization of chromatin plays an essential role in the regulation of gene expression and in other fundamental cellular processes. The underlying physical basis of these activities lies in the sequential positioning, chemical composition, and intermolecular interactions of the nucleosomes-the familiar assemblies of roughly 150 DNA base pairs and eight histone proteins-found on chromatin fibers. We have developed a mesoscale model of short nucleosomal arrays and a computational framework that make it possible to incorporate detailed structural features of DNA and histones in simulations of short chromatin constructs with 3-25 evenly spaced nucleosomes. The correspondence between the predicted and observed effects of nucleosome composition, spacing, and numbers on long-range communication between regulatory proteins bound to the ends of designed nucleosome arrays lends credence to the model and to the molecular insights gleaned from the simulated structures. We have extracted effective nucleosome-nucleosome potentials from the mesoscale simulations and introduced the potentials in a larger scale computational treatment of regularly repeating chromatin fibers. Our results reveal a remarkable influence of nucleosome spacing on chromatin flexibility. Small changes in the length of the DNA fragments linking successive nucleosomes introduce marked changes in the local interactions of the nucleosomes and in the spatial configurations of the fiber as a whole. The changes in nucleosome positioning influence the statistical properties of longer chromatin constructs with 100-10,000 nucleosomes. We are investigating the extent to which the `local' interactions of regularly spaced nucleosomes contribute to the corresponding interactions in chains with mixed spacings as a step toward the treatment of fibers with nucleosomes positioned at the sites mapped at base-pair resolution on genomic sequences. Support of the work by USPHS R01 GM 34809 is gratefully acknowledged.

  10. The Complexity of Folding Self-Folding Origami

    Directory of Open Access Journals (Sweden)

    Menachem Stern

    2017-12-01

    Full Text Available Why is it difficult to refold a previously folded sheet of paper? We show that even crease patterns with only one designed folding motion inevitably contain an exponential number of “distractor” folding branches accessible from a bifurcation at the flat state. Consequently, refolding a sheet requires finding the ground state in a glassy energy landscape with an exponential number of other attractors of higher energy, much like in models of protein folding (Levinthal’s paradox and other NP-hard satisfiability (SAT problems. As in these problems, we find that refolding a sheet requires actuation at multiple carefully chosen creases. We show that seeding successful folding in this way can be understood in terms of subpatterns that fold when cut out (“folding islands”. Besides providing guidelines for the placement of active hinges in origami applications, our results point to fundamental limits on the programmability of energy landscapes in sheets.

  11. The Complexity of Folding Self-Folding Origami

    Science.gov (United States)

    Stern, Menachem; Pinson, Matthew B.; Murugan, Arvind

    2017-10-01

    Why is it difficult to refold a previously folded sheet of paper? We show that even crease patterns with only one designed folding motion inevitably contain an exponential number of "distractor" folding branches accessible from a bifurcation at the flat state. Consequently, refolding a sheet requires finding the ground state in a glassy energy landscape with an exponential number of other attractors of higher energy, much like in models of protein folding (Levinthal's paradox) and other NP-hard satisfiability (SAT) problems. As in these problems, we find that refolding a sheet requires actuation at multiple carefully chosen creases. We show that seeding successful folding in this way can be understood in terms of subpatterns that fold when cut out ("folding islands"). Besides providing guidelines for the placement of active hinges in origami applications, our results point to fundamental limits on the programmability of energy landscapes in sheets.

  12. Reflex vocal fold adduction in the porcine model: the effects of stimuli delivered to various sensory nerves.

    Science.gov (United States)

    Woo, Jeong-Soo; Hundal, Jagdeep S; Sasaki, Clarence T; Abdelmessih, Mikhail W; Kelleher, Stephen P

    2008-10-01

    The aim of this study was to identify a panel of sensory nerves capable of eliciting an evoked glottic closure reflex (GCR) and to quantify the glottic closing force (GCF) of these responses in a porcine model. In 5 pigs, the internal branch of the superior laryngeal nerve (iSLN) and the trigeminal, pharyngeal plexus, glossopharyngeal, radial, and intercostal nerves were surgically isolated and electrically stimulated. During stimulation of each nerve, the GCR was detected by laryngeal electromyography and the GCF was measured with a pressure transducer. The only nerve that elicited the GCR in the 5 pigs was the iSLN. The average GCF was 288.9 mm Hg. This study demonstrates that the only afferent nerve that elicits the GCR in pigs is the iSLN, and that it should remain the focus of research for the rehabilitation of patients with absent or defective reflex vocal fold adduction.

  13. A Summary of Coupled, Uncoupled, and Hybrid Tectonic Models for the Yakima Fold Belt--Topical Report

    Energy Technology Data Exchange (ETDEWEB)

    Chamness, Michele A.; Winsor, Kelsey; Unwin, Stephen D.

    2012-08-01

    This document is one in a series of topical reports compiled by the Pacific Northwest National Laboratory to summarize technical information on selected topics important to the performance of a probabilistic seismic hazard analysis of the Hanford Site. The purpose of this report is to summarize the range of opinions and supporting information expressed by the expert community regarding whether a coupled or uncoupled model, or a combination of both, best represents structures in the Yakima Fold Belt. This issue was assessed to have a high level of contention with up to moderate potential for impact on the hazard estimate. This report defines the alternative conceptual models relevant to this technical issue and the arguments and data that support those models. It provides a brief description of the technical issue and principal uncertainties; a general overview on the nature of the technical issue, along with alternative conceptual models, supporting arguments and information, and uncertainties; and finally, suggests some possible approaches for reducing uncertainties regarding this issue.

  14. Modelling "reality" in tectonics: Simulation of the mechanical evolution of the Jura Mountains-Molasse Basin system, and routes to forward-inverse modelling of fold thrust belts.

    Science.gov (United States)

    Hindle, David; Kley, Jonas

    2016-04-01

    The ultimate validation of any numerical model of any geological process comes when it can accurately forward model a case study from the geological record. However, as the example of the Jura-Molasse fold thrust belt demonstrates, geological information on even the most basic aspects of the present day state of such systems is highly incomplete and usually known only with large uncertainties. Fold thrust-belts are studied and understood by geologists in an iterative process of constructing their subsurface geometries and structures (folds, faults, bedding etc) based on limited subsurface information from boreholes, tunnels or seismic data where available, and surface information on outcrops of different layers and their dips. This data is usually processed through geometric models which involve conservation of line length of different beds over the length of an entire cross section. Constructing such sections is the art of cross section balancing. A balanced cross section can be easily restored to its pre-deformation state, assuming (usually) originally horizontal bedding to remove the effects of folding and faulting. Such a pre-deformation state can then form an initial condition for a forward mechanical model of the section. A mechanical model introduces new parameters into the system such as rock elasticity, cohesion, and frictional properties. However, a forward mechanical model can also potentially show the continuous evolution of a fold thrust belt, including dynamic quantities like stress. Moreover, a forward mechanical model, if correct in most aspects, should match in its final state, the present day geological cross section it is simulating. However, when attempting to achieve a match between geometric and mechanical models, it becomes clear that many more aspects of the geodynamic history of a fold thrust belt have to be taken into account. Erosion of the uppermost layers of an evolving thrust belt is the most obvious one of these. This can potentially

  15. RNA folding: structure prediction, folding kinetics and ion electrostatics.

    Science.gov (United States)

    Tan, Zhijie; Zhang, Wenbing; Shi, Yazhou; Wang, Fenghua

    2015-01-01

    Beyond the "traditional" functions such as gene storage, transport and protein synthesis, recent discoveries reveal that RNAs have important "new" biological functions including the RNA silence and gene regulation of riboswitch. Such functions of noncoding RNAs are strongly coupled to the RNA structures and proper structure change, which naturally leads to the RNA folding problem including structure prediction and folding kinetics. Due to the polyanionic nature of RNAs, RNA folding structure, stability and kinetics are strongly coupled to the ion condition of solution. The main focus of this chapter is to review the recent progress in the three major aspects in RNA folding problem: structure prediction, folding kinetics and ion electrostatics. This chapter will introduce both the recent experimental and theoretical progress, while emphasize the theoretical modelling on the three aspects in RNA folding.

  16. Vocal Fold Paralysis

    Science.gov (United States)

    ... here Home » Health Info » Voice, Speech, and Language Vocal Fold Paralysis On this page: What is vocal fold ... Where can I get additional information? What is vocal fold paralysis? Structures involved in speech and voice production ...

  17. Discrete gauge groups in F-theory models on genus-one fibered Calabi-Yau 4-folds without section

    International Nuclear Information System (INIS)

    Kimura, Yusuke

    2017-01-01

    We determine the discrete gauge symmetries that arise in F-theory compactifications on examples of genus-one fibered Calabi-Yau 4-folds without a section. We construct genus-one fibered Calabi-Yau 4-folds using Fano manifolds, cyclic 3-fold covers of Fano 4-folds, and Segre embeddings of products of projective spaces. Discrete ℤ 5 , ℤ 4 , ℤ 3 and ℤ 2 symmetries arise in these constructions. We introduce a general method to obtain multisections for several constructions of genus-one fibered Calabi-Yau manifolds. The pullbacks of hyperplane classes under certain projections represent multisections to these genus-one fibrations. We determine the degrees of these multisections by computing the intersection numbers with fiber classes. As a result, we deduce the discrete gauge symmetries that arise in F-theory compactifications. This method applies to various Calabi-Yau genus-one fibrations.

  18. Flips for 3-folds and 4-folds

    CERN Document Server

    Corti, Alessio

    2007-01-01

    This edited collection of chapters, authored by leading experts, provides a complete and essentially self-contained construction of 3-fold and 4-fold klt flips. A large part of the text is a digest of Shokurov's work in the field and a concise, complete and pedagogical proof of the existence of 3-fold flips is presented. The text includes a ten page glossary and is accessible to students and researchers in algebraic geometry.

  19. Physics of protein folding

    Science.gov (United States)

    Finkelstein, A. V.; Galzitskaya, O. V.

    2004-04-01

    Protein physics is grounded on three fundamental experimental facts: protein, this long heteropolymer, has a well defined compact three-dimensional structure; this structure can spontaneously arise from the unfolded protein chain in appropriate environment; and this structure is separated from the unfolded state of the chain by the “all-or-none” phase transition, which ensures robustness of protein structure and therefore of its action. The aim of this review is to consider modern understanding of physical principles of self-organization of protein structures and to overview such important features of this process, as finding out the unique protein structure among zillions alternatives, nucleation of the folding process and metastable folding intermediates. Towards this end we will consider the main experimental facts and simple, mostly phenomenological theoretical models. We will concentrate on relatively small (single-domain) water-soluble globular proteins (whose structure and especially folding are much better studied and understood than those of large or membrane and fibrous proteins) and consider kinetic and structural aspects of transition of initially unfolded protein chains into their final solid (“native”) 3D structures.

  20. Observation of a tropopause fold by MARA VHF wind-profiler radar and ozonesonde at Wasa, Antarctica: comparison with ECMWF analysis and a WRF model simulation

    Directory of Open Access Journals (Sweden)

    M. Mihalikova

    2012-09-01

    Full Text Available Tropopause folds are one of the mechanisms of stratosphere–troposphere exchange, which can bring ozone rich stratospheric air to low altitudes in the extra-tropical regions. They have been widely studied at northern mid- or high latitudes, but so far almost no studies have been made at mid- or high southern latitudes. The Moveable Atmospheric Radar for Antarctica (MARA, a 54.5 MHz wind-profiler radar, has operated at the Swedish summer station Wasa, Antarctica (73° S, 13.5° W during austral summer seasons from 2007 to 2011 and has observed on several occasions signatures similar to those caused by tropopause folds at comparable Arctic latitudes. Here a case study is presented of one of these events when an ozonesonde successfully sampled the fold. Analysis from European Center for Medium Range Weather Forecasting (ECMWF is used to study the circumstances surrounding the event, and as boundary conditions for a mesoscale simulation using the Weather Research and Forecasting (WRF model. The fold is well resolved by the WRF simulation, and occurs on the poleward side of the polar jet stream. However, MARA resolves fine-scale layering associated with the fold better than the WRF simulation.

  1. Depletion of the chromatin looping proteins CTCF and cohesin causes chromatin compaction: insight into chromatin folding by polymer modelling

    NARCIS (Netherlands)

    Tark-Dame, M.; Jerabek, H.; Manders, E.M.M.; Heermann, D.W.; van Driel, R.

    2014-01-01

    Folding of the chromosomal fibre in interphase nuclei is an important element in the regulation of gene expression. For instance, physical contacts between promoters and enhancers are a key element in cell-type-specific transcription. We know remarkably little about the principles that control

  2. Influence of pre-existing basement faults on the structural evolution of the Zagros Simply Folded belt: 3D numerical modelling

    Science.gov (United States)

    Ruh, Jonas B.; Gerya, Taras

    2015-04-01

    The Simply Folded Belt of the Zagros orogen is characterized by elongated fold trains symptomatically defining the geomorphology along this mountain range. The Zagros orogen results from the collision of the Arabian and the Eurasian plates. The Simply Folded Belt is located southwest of the Zagros suture zone. An up to 2 km thick salt horizon below the sedimentary sequence enables mechanical and structural detachment from the underlying Arabian basement. Nevertheless, deformation within the basement influences the structural evolution of the Simply Folded Belt. It has been shown that thrusts in form of reactivated normal faults can trigger out-of-sequence deformation within the sedimentary stratigraphy. Furthermore, deeply rooted strike-slip faults, such as the Kazerun faults between the Fars zone in the southeast and the Dezful embayment and the Izeh zone, are largely dispersing into the overlying stratigraphy, strongly influencing the tectonic evolution and mechanical behaviour. The aim of this study is to reveal the influence of basement thrusts and strike-slip faults on the structural evolution of the Simply Folded Belt depending on the occurrence of intercrustal weak horizons (Hormuz salt) and the rheology and thermal structure of the basement. Therefore, we present high-resolution 3D thermo-mechnical models with pre-existing, inversively reactivated normal faults or strike-slip faults within the basement. Numerical models are based on finite difference, marker-in-cell technique with (power-law) visco-plastic rheology accounting for brittle deformation. Preliminary results show that deep tectonic structures present in the basement may have crucial effects on the morphology and evolution of a fold-and-thrust belt above a major detachment horizon.

  3. Covering folded shapes

    Directory of Open Access Journals (Sweden)

    Oswin Aichholzer

    2014-05-01

    Full Text Available Can folding a piece of paper flat make it larger? We explore whether a shape S must be scaled to cover a flat-folded copy of itself. We consider both single folds and arbitrary folds (continuous piecewise isometries \\(S\\to\\mathbb{R}^2\\. The underlying problem is motivated by computational origami, and is related to other covering and fixturing problems, such as Lebesgue's universal cover problem and force closure grasps. In addition to considering special shapes (squares, equilateral triangles, polygons and disks, we give upper and lower bounds on scale factors for single folds of convex objects and arbitrary folds of simply connected objects.

  4. Efficient molecular mechanics simulations of the folding, orientation, and assembly of peptides in lipid bilayers using an implicit atomic solvation model

    Science.gov (United States)

    Bordner, Andrew J.; Zorman, Barry; Abagyan, Ruben

    2011-10-01

    Membrane proteins comprise a significant fraction of the proteomes of sequenced organisms and are the targets of approximately half of marketed drugs. However, in spite of their prevalence and biomedical importance, relatively few experimental structures are available due to technical challenges. Computational simulations can potentially address this deficit by providing structural models of membrane proteins. Solvation within the spatially heterogeneous membrane/solvent environment provides a major component of the energetics driving protein folding and association within the membrane. We have developed an implicit solvation model for membranes that is both computationally efficient and accurate enough to enable molecular mechanics predictions for the folding and association of peptides within the membrane. We derived the new atomic solvation model parameters using an unbiased fitting procedure to experimental data and have applied it to diverse problems in order to test its accuracy and to gain insight into membrane protein folding. First, we predicted the positions and orientations of peptides and complexes within the lipid bilayer and compared the simulation results with solid-state NMR structures. Additionally, we performed folding simulations for a series of host-guest peptides with varying propensities to form alpha helices in a hydrophobic environment and compared the structures with experimental measurements. We were also able to successfully predict the structures of amphipathic peptides as well as the structures for dimeric complexes of short hexapeptides that have experimentally characterized propensities to form beta sheets within the membrane. Finally, we compared calculated relative transfer energies with data from experiments measuring the effects of mutations on the free energies of translocon-mediated insertion of proteins into lipid bilayers and of combined folding and membrane insertion of a beta barrel protein.

  5. Fault-related-folding structure and reflection seismic sections. Construction of earth model using balanced cross section; Danso ga kaizaisuru shukyoku kozo no keitai to jishin tansa danmen. 1. Balanced cross section wo mochiita chika model no kochiku

    Energy Technology Data Exchange (ETDEWEB)

    Matsuoka, T; Tamagawa, T [Japan Petroleum Exploration Corp., Tokyo (Japan); Tsukui, R [Japan National Oil Corp., Tokyo (Japan). Technology Research Center

    1997-05-27

    Pre-stacking depth migration treatment is studied for the estimation of the fold configuration from seismic survey cross sections. The estimation of a velocity structure is necessary for the execution of such treatment, and the utilization of structural-geological knowledge is required for its interpretation. The concept of balanced cross section in relation to the fault-bend fold constructs a stratum structure model under conditions that the deformation during fold and fault formation is a planar strain, that there is no change in volume due to deformation, and that a fold is a parallel fold. In addition to the above geometric and kinetic approach, there is another fold formation process simulation model using a Newtonian fluid for study from the viewpoint of dynamics. This simulation stands on the presumption that the boundary contains a ramp that had been in presence before fold formation and that an incompressible viscous matter is mounted on the top surface. The viscous matter flows and deforms for the formation of an anticline on the ramp. Such enables the reproduction of a fault-bend fold formation process, and helpful discussion may be furthered on the dynamic aspect of this simulation. 5 refs., 4 figs.

  6. Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chunhua [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States); Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Su, Jiguo, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [College of Science, Yanshan University, Qinhuangdao 066004 (China); Zhang, Yang, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States)

    2016-07-07

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

  7. Folding model analysis of 58Ni + 64Ni elastic and inelastic scattering at Elab=203.8 and 219.2 MeV

    International Nuclear Information System (INIS)

    Ruiz, J.A.; Ferrero, J.L.; Bilwes, B.; Bilwes, R.

    1992-01-01

    Angular distributions of elastic scattering of 58 Ni by 64 Ni and inelastic scattering leading to the first 2 + state in 58 Ni or in 64 Ni were measured at E lab =203.8 and 219.2 MeV. The data were analyzed in the frame of the folding model. A renormalization N of the folding potential consistently lower than unity (N∼0.65) is needed to reproduce the elastic scattering data. Coupled-channel calculations including the main inelastic channels explain partly this discrepancy. They reproduce the elastic and inelastic scattering data with a renormalization of N∼0.8 at both energies. Interference between Coulomb and nuclear excitation is shown to play an important role in the repulsive character of the polarization potential. (author) 38 refs.; 6 figs.; 1 tab

  8. Fold-recognition and comparative modeling of human α2,3-sialyltransferases reveal their sequence and structural similarities to CstII from Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Balaji Petety V

    2006-04-01

    Full Text Available Abstract Background The 3-D structure of none of the eukaryotic sialyltransferases (SiaTs has been determined so far. Sequence alignment algorithms such as BLAST and PSI-BLAST could not detect a homolog of these enzymes from the protein databank. SiaTs, thus, belong to the hard/medium target category in the CASP experiments. The objective of the current work is to model the 3-D structures of human SiaTs which transfer the sialic acid in α2,3-linkage viz., ST3Gal I, II, III, IV, V, and VI, using fold-recognition and comparative modeling methods. The pair-wise sequence similarity among these six enzymes ranges from 41 to 63%. Results Unlike the sequence similarity servers, fold-recognition servers identified CstII, a α2,3/8 dual-activity SiaT from Campylobacter jejuni as the homolog of all the six ST3Gals; the level of sequence similarity between CstII and ST3Gals is only 15–20% and the similarity is restricted to well-characterized motif regions of ST3Gals. Deriving template-target sequence alignments for the entire ST3Gal sequence was not straightforward: the fold-recognition servers could not find a template for the region preceding the L-motif and that between the L- and S-motifs. Multiple structural templates were identified to model these regions and template identification-modeling-evaluation had to be performed iteratively to choose the most appropriate templates. The modeled structures have acceptable stereochemical properties and are also able to provide qualitative rationalizations for some of the site-directed mutagenesis results reported in literature. Apart from the predicted models, an unexpected but valuable finding from this study is the sequential and structural relatedness of family GT42 and family GT29 SiaTs. Conclusion The modeled 3-D structures can be used for docking and other modeling studies and for the rational identification of residues to be mutated to impart desired properties such as altered stability, substrate

  9. The four-fold way

    International Nuclear Information System (INIS)

    Terazawa, H.

    1986-01-01

    The four-fold way is proposed in a minimal composite model of quarks and leptons. Various new pictures and consequences are presented and discussed. They include 1) generation, 2) quark-lepton mass spectrum, 3) quark mixing, 4) supersymmetry, 5) effective gauge theory. (author)

  10. RNA secondary structures in a polymer-zeta model how foldings should be shaped for sparsification to establish a linear speedup

    DEFF Research Database (Denmark)

    Jin, Emma Yu; Nebel, M. E.

    2016-01-01

    that the corresponding conditional probabilities behave according to a polymer-zeta probability model. We show that even if some of the structural parameters exhibit an almost realistic behavior on average, the expected shape of a folding in that model must be assumed to highly differ from those observed in nature. More...... sparsification) may reduce the runtime to n2 on average, assuming that nucleotides of distance d form a hydrogen bond (i.e. are paired) with probability (Formula Presented.) for some constants b > 0, c > 1. The latter is called the polymer-zeta model and plays a crucial role in speeding up the above mentioned...... algorithm. In this paper we discuss the application of the polymer-zeta property for the analysis of sparsification, showing that it must be applied conditionally on first and last positions to pair. Afterwards, we will investigate the combinatorics of RNA secondary structures assuming...

  11. Fold and Fit: Space Conserving Shape Editing

    KAUST Repository

    Ibrahim, Mohamed

    2017-09-01

    We present a framework that folds man-made objects in a structure-aware manner for space-conserving storage and transportation. Given a segmented 3D mesh of a man-made object, our framework jointly optimizes for joint locations, the folding order, and folding angles for each part of the model, enabling it to transform into a spatially efficient configuration while keeping its original functionality as intact as possible. That is, if a model is supposed to withstand several forces in its initial state to serve its functionality, our framework places the joints between the parts of the model such that the model can withstand forces with magnitudes that are comparable to the magnitudes applied on the unedited model. Furthermore, if the folded shape is not compact, our framework proposes further segmentation of the model to improve its compactness in its folded state.

  12. NoFold: RNA structure clustering without folding or alignment.

    Science.gov (United States)

    Middleton, Sarah A; Kim, Junhyong

    2014-11-01

    Structures that recur across multiple different transcripts, called structure motifs, often perform a similar function-for example, recruiting a specific RNA-binding protein that then regulates translation, splicing, or subcellular localization. Identifying common motifs between coregulated transcripts may therefore yield significant insight into their binding partners and mechanism of regulation. However, as most methods for clustering structures are based on folding individual sequences or doing many pairwise alignments, this results in a tradeoff between speed and accuracy that can be problematic for large-scale data sets. Here we describe a novel method for comparing and characterizing RNA secondary structures that does not require folding or pairwise alignment of the input sequences. Our method uses the idea of constructing a distance function between two objects by their respective distances to a collection of empirical examples or models, which in our case consists of 1973 Rfam family covariance models. Using this as a basis for measuring structural similarity, we developed a clustering pipeline called NoFold to automatically identify and annotate structure motifs within large sequence data sets. We demonstrate that NoFold can simultaneously identify multiple structure motifs with an average sensitivity of 0.80 and precision of 0.98 and generally exceeds the performance of existing methods. We also perform a cross-validation analysis of the entire set of Rfam families, achieving an average sensitivity of 0.57. We apply NoFold to identify motifs enriched in dendritically localized transcripts and report 213 enriched motifs, including both known and novel structures. © 2014 Middleton and Kim; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  13. Swelling pressure induced phase-volume transition in hybrid biopolymer gels caused by unfolding of folded crosslinks: A model

    Czech Academy of Sciences Publication Activity Database

    Dušek, Karel; Dušková, Miroslava; Ilavský, Michal; Steward, R.; Kopeček, J.

    2003-01-01

    Roč. 4, č. 6 (2003), s. 1818-1826 ISSN 1525-7797 R&D Projects: GA AV ČR KSK4050111 Keywords : thermodynamic model * swelling transitions * hybrid gels Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.824, year: 2003

  14. Coherent structures in the flow inside a model of the human vocal tract with self-oscillating vocal folds

    Czech Academy of Sciences Publication Activity Database

    Horáček, Jaromír; Šidlof, Petr; Uruba, Václav; Veselý, Jan; Radolf, Vojtěch; Bula, Vítězslav

    2010-01-01

    Roč. 55, č. 4 (2010), s. 327-343 ISSN 0001-7043 R&D Projects: GA ČR GA101/08/1155 Institutional research plan: CEZ:AV0Z20760514 Keywords : biomechanics of voice * voice production modeling * PIV method * coherent structures Subject RIV: BI - Acoustics

  15. Combining structural modeling with ensemble machine learning to accurately predict protein fold stability and binding affinity effects upon mutation.

    Directory of Open Access Journals (Sweden)

    Niklas Berliner

    Full Text Available Advances in sequencing have led to a rapid accumulation of mutations, some of which are associated with diseases. However, to draw mechanistic conclusions, a biochemical understanding of these mutations is necessary. For coding mutations, accurate prediction of significant changes in either the stability of proteins or their affinity to their binding partners is required. Traditional methods have used semi-empirical force fields, while newer methods employ machine learning of sequence and structural features. Here, we show how combining both of these approaches leads to a marked boost in accuracy. We introduce ELASPIC, a novel ensemble machine learning approach that is able to predict stability effects upon mutation in both, domain cores and domain-domain interfaces. We combine semi-empirical energy terms, sequence conservation, and a wide variety of molecular details with a Stochastic Gradient Boosting of Decision Trees (SGB-DT algorithm. The accuracy of our predictions surpasses existing methods by a considerable margin, achieving correlation coefficients of 0.77 for stability, and 0.75 for affinity predictions. Notably, we integrated homology modeling to enable proteome-wide prediction and show that accurate prediction on modeled structures is possible. Lastly, ELASPIC showed significant differences between various types of disease-associated mutations, as well as between disease and common neutral mutations. Unlike pure sequence-based prediction methods that try to predict phenotypic effects of mutations, our predictions unravel the molecular details governing the protein instability, and help us better understand the molecular causes of diseases.

  16. From Holonomy of the Ising Model Form Factors to n-Fold Integrals and the Theory of Elliptic Curves

    Directory of Open Access Journals (Sweden)

    Salah Boukraa

    2007-10-01

    Full Text Available We recall the form factors $f^(j_{N,N}$ corresponding to the $lambda$-extension $C(N,N; lambda$ of the two-point diagonal correlation function of the Ising model on the square lattice and their associated linear differential equations which exhibit both a "Russian-doll" nesting, and a decomposition of the linear differential operators as a direct sum of operators (equivalent to symmetric powers of the differential operator of the complete elliptic integral $E$. The scaling limit of these differential operators breaks the direct sum structure but not the "Russian doll" structure, the "scaled" linear differential operators being no longer Fuchsian. We then introduce some multiple integrals of the Ising class expected to have the same singularities as the singularities of the $n$-particle contributions $chi^{(n}$ to the susceptibility of the square lattice Ising model. We find the Fuchsian linear differential equations satisfied by these multiple integrals for $n = 1, 2, 3, 4$ and, only modulo a prime, for $n = 5$ and 6, thus providing a large set of (possible new singularities of the $chi^{(n}$. We get the location of these singularities by solving the Landau conditions. We discuss the mathematical, as well as physical, interpretation of these new singularities. Among the singularities found, we underline the fact that the quadratic polynomial condition $1 + 3w + 4w^2 = 0$, that occurs in the linear differential equation of $chi^{(3}$, actually corresponds to the occurrence of complex multiplication for elliptic curves. The interpretation of complex multiplication for elliptic curves as complex fixed points of generators of the exact renormalization group is sketched. The other singularities occurring in our multiple integrals are not related to complex multiplication situations, suggesting a geometric interpretation in terms of more general (motivic mathematical structures beyond the theory of elliptic curves. The scaling limit of the (lattice

  17. Quantification of Porcine Vocal Fold Geometry.

    Science.gov (United States)

    Stevens, Kimberly A; Thomson, Scott L; Jetté, Marie E; Thibeault, Susan L

    2016-07-01

    The aim of this study was to quantify porcine vocal fold medial surface geometry and three-dimensional geometric distortion induced by freezing the larynx, especially in the region of the vocal folds. The medial surface geometries of five excised porcine larynges were quantified and reported. Five porcine larynges were imaged in a micro-CT scanner, frozen, and rescanned. Segmentations and three-dimensional reconstructions were used to quantify and characterize geometric features. Comparisons were made with geometry data previously obtained using canine and human vocal folds as well as geometries of selected synthetic vocal fold models. Freezing induced an overall expansion of approximately 5% in the transverse plane and comparable levels of nonuniform distortion in sagittal and coronal planes. The medial surface of the porcine vocal folds was found to compare reasonably well with other geometries, although the compared geometries exhibited a notable discrepancy with one set of published human female vocal fold geometry. Porcine vocal folds are qualitatively geometrically similar to data available for canine and human vocal folds, as well as commonly used models. Freezing of tissue in the larynx causes distortion of around 5%. The data can provide direction in estimating uncertainty due to bulk distortion of tissue caused by freezing, as well as quantitative geometric data that can be directly used in developing vocal fold models. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  18. Evaluating realized seed dispersal across fragmented tropical landscapes: a two-fold approach using parentage analysis and the neighbourhood model.

    Science.gov (United States)

    Ismail, Sascha A; Ghazoul, Jaboury; Ravikanth, Gudasalamani; Kushalappa, Cheppudira G; Uma Shaanker, Ramanan; Kettle, Chris J

    2017-05-01

    Despite the importance of seed dispersal for survival of plant species in fragmented landscapes, data on seed dispersal at landscape scales remain sparse. Effective seed dispersal among fragments determines recolonization and plant species persistence in such landscapes. We present the first large-scale (216-km 2 ) direct estimates of realized seed dispersal of a high-value timber tree (Dysoxylum malabaricum) across an agro-forest landscape in the Western Ghats, India. Based upon an exhaustive inventory of adult trees and a sample of 488 seedlings all genotyped at 10 microsatellite loci, we estimated realized seed dispersal using parentage analysis and the neighbourhood model. Our estimates found that most realized seed dispersal was within 200 m, which is insufficient to effectively bridge the distances between forest patches. We conclude that using mobility of putative animal dispersers can be misleading when estimating tropical tree species vulnerability to habitat fragmentation. This raises serious concerns about the potential of many tropical trees to recolonize isolated forest patches where high-value tree species have already been removed. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  19. Folding worlds between pages

    CERN Multimedia

    Meier, Matthias

    2010-01-01

    "We all remember pop-up books form our childhood. As fascinated as we were back then, we probably never imagined how much engineering know-how went into these books. Pop-up engineer Anton Radevsky has even managed to fold a 27-kilometre particle accelerator into a book" (4 pages)

  20. Folds and Etudes

    Science.gov (United States)

    Bean, Robert

    2007-01-01

    In this article, the author talks about "Folds" and "Etudes" which are images derived from anonymous typing exercises that he found in a used copy of "Touch Typing Made Simple". "Etudes" refers to the musical tradition of studies for a solo instrument, which is a typewriter. Typing exercises are repetitive attempts to type words and phrases…

  1. Folding model study of the charge-exchange scattering to the isobaric analog state and implication for the nuclear symmetry energy

    International Nuclear Information System (INIS)

    Khoa, Dao T.; Thang, Dang Ngoc; Loc, Bui Minh

    2014-01-01

    The Fermi transition (ΔL = ΔS = 0 and ΔT = 1) between the nuclear isobaric analog states (IAS), induced by the charge-exchange (p, n) or ( 3 He, t) reaction, can be considered as ''elastic'' scattering of proton or 3 He by the isovector term of the optical potential (OP) that flips the projectile isospin. The accurately measured (p, n) or ( 3 He, t) scattering cross section to the IAS can be used, therefore, to probe the isospin dependence of the proton or 3 He optical potential. Within the folding model, the isovector part of the OP is determined exclusively by the neutron-proton difference in the nuclear densities and the isospin dependence of the effective nucleon-nucleon (NN) interaction. Because the isovector coupling explicitly links the isovector part of the proton or 3 He optical potential to the cross section of the charge-exchange (p, n) or ( 3 He, t) scattering to the IAS, the isospin dependence of the effective (in-medium) NN interaction can be well tested in the folding model analysis of these charge-exchange reactions. On the other hand, the same isospin- and density-dependent NN interaction can also be used in a Hartree-Fock calculation of asymmetric nuclear matter, to estimate the nuclear matter energy and its asymmetry part (the nuclear symmetry energy). As a result, the fine-tuning of the isospin dependence of the effective NN interaction against the measured (p, n) or ( 3 He, t) cross sections should allow us to make some realistic prediction of the nuclear symmetry energy and its density dependence. (orig.)

  2. Folding model study of the charge-exchange scattering to the isobaric analog state and implication for the nuclear symmetry energy

    Energy Technology Data Exchange (ETDEWEB)

    Khoa, Dao T.; Thang, Dang Ngoc [VINATOM, Institute for Nuclear Science and Technique, Hanoi (Viet Nam); Loc, Bui Minh [VINATOM, Institute for Nuclear Science and Technique, Hanoi (Viet Nam); University of Pedagogy, Ho Chi Minh City (Viet Nam)

    2014-02-15

    The Fermi transition (ΔL = ΔS = 0 and ΔT = 1) between the nuclear isobaric analog states (IAS), induced by the charge-exchange (p, n) or ({sup 3}He, t) reaction, can be considered as ''elastic'' scattering of proton or {sup 3}He by the isovector term of the optical potential (OP) that flips the projectile isospin. The accurately measured (p, n) or ({sup 3}He, t) scattering cross section to the IAS can be used, therefore, to probe the isospin dependence of the proton or {sup 3}He optical potential. Within the folding model, the isovector part of the OP is determined exclusively by the neutron-proton difference in the nuclear densities and the isospin dependence of the effective nucleon-nucleon (NN) interaction. Because the isovector coupling explicitly links the isovector part of the proton or {sup 3}He optical potential to the cross section of the charge-exchange (p, n) or ({sup 3}He, t) scattering to the IAS, the isospin dependence of the effective (in-medium) NN interaction can be well tested in the folding model analysis of these charge-exchange reactions. On the other hand, the same isospin- and density-dependent NN interaction can also be used in a Hartree-Fock calculation of asymmetric nuclear matter, to estimate the nuclear matter energy and its asymmetry part (the nuclear symmetry energy). As a result, the fine-tuning of the isospin dependence of the effective NN interaction against the measured (p, n) or ({sup 3}He, t) cross sections should allow us to make some realistic prediction of the nuclear symmetry energy and its density dependence. (orig.)

  3. Approaching climate-adaptive facades with foldings

    DEFF Research Database (Denmark)

    Sack-Nielsen, Torsten

    2014-01-01

    envelopes based on folding principles such as origami. Three major aspects cover the project’s interest in this topic: Shape, kinetics and the application of new multi-functional materials form the interdisciplinary framework of this research. Shape// Initially small paper sketch models demonstrate folding...

  4. Kinematics of large scale asymmetric folds and associated smaller ...

    Indian Academy of Sciences (India)

    The present work reiterates the importance of analysis of ... these models is the assumption that the folds are passive folds ... applicability of these models is thus limited in the case of ...... with contrasted rheological properties, a theory for the.

  5. Real-Time Agent-Based Modeling Simulation with in-situ Visualization of Complex Biological Systems: A Case Study on Vocal Fold Inflammation and Healing.

    Science.gov (United States)

    Seekhao, Nuttiiya; Shung, Caroline; JaJa, Joseph; Mongeau, Luc; Li-Jessen, Nicole Y K

    2016-05-01

    We present an efficient and scalable scheme for implementing agent-based modeling (ABM) simulation with In Situ visualization of large complex systems on heterogeneous computing platforms. The scheme is designed to make optimal use of the resources available on a heterogeneous platform consisting of a multicore CPU and a GPU, resulting in minimal to no resource idle time. Furthermore, the scheme was implemented under a client-server paradigm that enables remote users to visualize and analyze simulation data as it is being generated at each time step of the model. Performance of a simulation case study of vocal fold inflammation and wound healing with 3.8 million agents shows 35× and 7× speedup in execution time over single-core and multi-core CPU respectively. Each iteration of the model took less than 200 ms to simulate, visualize and send the results to the client. This enables users to monitor the simulation in real-time and modify its course as needed.

  6. 3D Reservoir Modeling of Semutang Gas Field: A lonely Gas field in Chittagong-Tripura Fold Belt, with Integrated Well Log, 2D Seismic Reflectivity and Attributes.

    Science.gov (United States)

    Salehin, Z.; Woobaidullah, A. S. M.; Snigdha, S. S.

    2015-12-01

    Bengal Basin with its prolific gas rich province provides needed energy to Bangladesh. Present energy situation demands more Hydrocarbon explorations. Only 'Semutang' is discovered in the high amplitude structures, where rest of are in the gentle to moderate structures of western part of Chittagong-Tripura Fold Belt. But it has some major thrust faults which have strongly breached the reservoir zone. The major objectives of this research are interpretation of gas horizons and faults, then to perform velocity model, structural and property modeling to obtain reservoir properties. It is needed to properly identify the faults and reservoir heterogeneities. 3D modeling is widely used to reveal the subsurface structure in faulted zone where planning and development drilling is major challenge. Thirteen 2D seismic and six well logs have been used to identify six gas bearing horizons and a network of faults and to map the structure at reservoir level. Variance attributes were used to identify faults. Velocity model is performed for domain conversion. Synthetics were prepared from two wells where sonic and density logs are available. Well to seismic tie at reservoir zone shows good match with Direct Hydrocarbon Indicator on seismic section. Vsh, porosity, water saturation and permeability have been calculated and various cross plots among porosity logs have been shown. Structural modeling is used to make zone and layering accordance with minimum sand thickness. Fault model shows the possible fault network, those liable for several dry wells. Facies model have been constrained with Sequential Indicator Simulation method to show the facies distribution along the depth surfaces. Petrophysical models have been prepared with Sequential Gaussian Simulation to estimate petrophysical parameters away from the existing wells to other parts of the field and to observe heterogeneities in reservoir. Average porosity map for each gas zone were constructed. The outcomes of the research

  7. The folding mechanism and key metastable state identification of the PrP127-147 monomer studied by molecular dynamics simulations and Markov state model analysis.

    Science.gov (United States)

    Zhou, Shuangyan; Wang, Qianqian; Wang, Yuwei; Yao, Xiaojun; Han, Wei; Liu, Huanxiang

    2017-05-10

    The structural transition of prion proteins from a native α-helix (PrP C ) to a misfolded β-sheet-rich conformation (PrP Sc ) is believed to be the main cause of a number of prion diseases in humans and animals. Understanding the molecular basis of misfolding and aggregation of prion proteins will be valuable for unveiling the etiology of prion diseases. However, due to the limitation of conventional experimental techniques and the heterogeneous property of oligomers, little is known about the molecular architecture of misfolded PrP Sc and the mechanism of structural transition from PrP C to PrP Sc . The prion fragment 127-147 (PrP127-147) has been reported to be a critical region for PrP Sc formation in Gerstmann-Straussler-Scheinker (GSS) syndrome and thus has been used as a model for the study of prion aggregation. In the present study, we employ molecular dynamics (MD) simulation techniques to study the conformational change of this fragment that could be relevant to the PrP C -PrP Sc transition. Employing extensive replica exchange molecular dynamics (REMD) and conventional MD simulations, we sample a huge number of conformations of PrP127-147. Using the Markov state model (MSM), we identify the metastable conformational states of this fragment and the kinetic network of transitions between the states. The resulting MSM reveals that disordered random-coiled conformations are the dominant structures. A key metastable folded state with typical extended β-sheet structures is identified with Pro137 being located in a turn region, consistent with a previous experimental report. Conformational analysis reveals that intrapeptide hydrophobic interaction and two key residue interactions, including Arg136-His140 and Pro137-His140, contribute a lot to the formation of ordered extended β-sheet states. However, network pathway analysis from the most populated disordered state indicates that the formation of extended β-sheet states is quite slow (at the millisecond

  8. Geometric U-folds in four dimensions

    Science.gov (United States)

    Lazaroiu, C. I.; Shahbazi, C. S.

    2018-01-01

    We describe a general construction of geometric U-folds compatible with a non-trivial extension of the global formulation of four-dimensional extended supergravity on a differentiable spin manifold. The topology of geometric U-folds depends on certain flat fiber bundles which encode how supergravity fields are globally glued together. We show that smooth non-trivial U-folds of this type can exist only in theories where both the scalar and space-time manifolds have non-trivial fundamental group and in addition the scalar map of the solution is homotopically non-trivial. Consistency with string theory requires smooth geometric U-folds to be glued using subgroups of the effective discrete U-duality group, implying that the fundamental group of the scalar manifold of such solutions must be a subgroup of the latter. We construct simple examples of geometric U-folds in a generalization of the axion-dilaton model of \

  9. Muscular anatomy of the human ventricular folds.

    Science.gov (United States)

    Moon, Jerald; Alipour, Fariborz

    2013-09-01

    Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds. The ventricular folds contained anteriorly coursing thyroarytenoid and ventricularis muscle fibers that were in the lower half of the ventricular fold posteriorly, and some ventricularis muscle was evident in the upper and lateral portions of the fold more anteriorly. Very little muscle tissue was observed in the medial half of the fold, and the anterior half of the ventricular fold was largely devoid of any muscle tissue. All 4 larynges contained muscle bundles that coursed superiorly and medially through the upper half of the fold, toward the lateral margin of the epiglottis. Although variability of expression was evident, a well-defined thyroarytenoid muscle was readily apparent lateral to the arytenoid cartilage in all specimens.

  10. Frustration in Condensed Matter and Protein Folding

    Science.gov (United States)

    Li, Z.; Tanner, S.; Conroy, B.; Owens, F.; Tran, M. M.; Boekema, C.

    2014-03-01

    By means of computer modeling, we are studying frustration in condensed matter and protein folding, including the influence of temperature and Thomson-figure formation. Frustration is due to competing interactions in a disordered state. The key issue is how the particles interact to reach the lowest frustration. The relaxation for frustration is mostly a power function (randomly assigned pattern) or an exponential function (regular patterns like Thomson figures). For the atomic Thomson model, frustration is predicted to decrease with the formation of Thomson figures at zero kelvin. We attempt to apply our frustration modeling to protein folding and dynamics. We investigate the homogeneous protein frustration that would cause the speed of the protein folding to increase. Increase of protein frustration (where frustration and hydrophobicity interplay with protein folding) may lead to a protein mutation. Research is supported by WiSE@SJSU and AFC San Jose.

  11. Folding model analyses of 12C-12C and 16O-16O elastic scattering using the density-dependent LOCV-averaged effective interaction

    Science.gov (United States)

    Rahmat, M.; Modarres, M.

    2018-03-01

    The averaged effective two-body interaction (AEI), which can be generated through the lowest order constrained variational (LOCV) method for symmetric nuclear matter (SNM) with the input [Reid68, Ann. Phys. 50, 411 (1968), 10.1016/0003-4916(68)90126-7] nucleon-nucleon potential, is used as the effective nucleon-nucleon potential in the folding model to describe the heavy-ion (HI) elastic scattering cross sections. The elastic scattering cross sections of 12C-12C and 16O-16O systems are calculated in the above framework. The results are compared with the corresponding calculations coming from the fitting procedures with the input finite range D D M 3 Y 1 -Reid potential and the available experimental data at different incident energies. It is shown that a reasonable description of the elastic 12C-12C and 16O-16O scattering data at the low and medium energies can be obtained by using the above LOCV AEI, without any need to define a parametrized density-dependent function in the effective nucleon-nucleon potential, which is formally considered in the typical D D M 3 Y 1 -Reid interactions.

  12. Simulation Modeling Method and Experimental Investigation on the Uniflow Scavenging System of an Opposed-Piston Folded-Cranktrain Diesel Engine

    Directory of Open Access Journals (Sweden)

    Fukang Ma

    2017-05-01

    Full Text Available The scavenging process for opposed-piston folded-cranktrain (OPFC diesel engines can be described by the time evolution of the in-cylinder and exhaust chamber residual gas rates. The relation curve of in-cylinder and exhaust chamber residual gas rate is called scavenging profile, which is calculated through the changes of in-cylinder and exhaust chamber gas compositions determined by computational fluid dynamics (CFD simulation. The scavenging profile is used to calculate the scavenging process by mono-dimensional (1D simulation. The tracer gas method (TGM is employed to validate the accuracy of the scavenging profile. At the same time, the gas exchange performance under different intake and exhaust state parameters was examined based on the TGM. The results show that the scavenging process from 1D simulation and experiment match well, which means the scavenging model obtained by CFD simulation performs well and validation of its effectiveness by TGM is possible. The difference between intake and exhaust pressure has a significant positive effect on the gas exchange performance and trapped gas mass, but the pressure difference has little effect on the scavenging efficiency and the trapped air mass if the delivery ratio exceeds 1.4.

  13. Fault-related-folding structures and reflection seismic sections. Study by seismic modeling and balanced cross section; Danso ga kaizaisuru shukyoku kozo no keitai to jishin tansa danmen. 2. Seismic modeling oyobi balanced cross section ni yoru study

    Energy Technology Data Exchange (ETDEWEB)

    Tamagawa, T; Matsuoka, T [Japan Petroleum Exploration Corp., Tokyo (Japan); Tsukui, R [Japan National Oil Corp., Tokyo (Japan). Technology Research Center

    1997-05-27

    It occasionally happens that there exists a part where reflection near the thrust is not clearly observed in a thrust zone seismic survey cross section. For the effective interpretation of such an occurrence, the use of geological structures as well as the reflected pattern is effective. When the velocity structures for a fold structure having a listric fault caused anticline (unidirectionally inclined with a backlimb, without a forelimb) and for a fault propagation fold are involved, a wrong interpretation may be made since they look alike in reflection wave pattern despite their difference in geological structure. In the concept of balanced cross section, a check is performed, when the stratum after deformation is recovered to the time of deposition, as to whether the geologic stratum area is conserved without excess or shortage. An excess or shortage occurs if there is an error in the model, and this shows that the fault surface or fold structure is not correctly reflected. Positive application of geological knowledge is required in the processing and interpreting of data from a seismic survey. 6 refs., 6 figs.

  14. Effects of gravity in folding

    Science.gov (United States)

    Minkel, Donald Howe

    Effects of gravity on buckle folding are studied using a Newtonian fluid finite element model of a single layer embedded between two thicker less viscous layers. The methods allow arbitrary density jumps, surface tension coefficients, resistance to slip at the interfaces, and tracking of fold growth to a large amplitudes. When density increases downward in two equal jumps, a layer buckles less and thickens more than with uniform density. When density increases upward in two equal jumps, it buckles more and thickens less. A low density layer with periodic thickness variations buckles more, sometimes explosively. Thickness variations form, even if not present initially. These effects are greater with; smaller viscosities, larger density jump, larger length scale, and slower shortening rate. They also depend on wavelength and amplitude, and these dependencies are described in detail. The model is applied to the explosive growth of the salt anticlines of the Paradox Basin, Colorado and Utah. There, shale (higher density) overlies salt (lower density). Methods for simulating realistic earth surface erosion and deposition conditions are introduced. Growth rates increase both with ease of slip at the salt-shale interface, and when earth surface relief stays low due to erosion and deposition. Model anticlines grow explosively, attaining growth rates and amplitudes close to those of the field examples. Fastest growing wavelengths are the same as seen in the field. It is concluded that a combination of partial-slip at the salt-shale interface, with reasonable earth surface conditions, promotes sufficiently fast buckling of the salt-shale interface due to density inversion alone. Neither basement faulting, nor tectonic shortening is required to account for the observed structures. Of fundamental importance is the strong tendency of gravity to promote buckling in low density layers with thickness variations. These develop, even if not present initially. folds

  15. Non-cylindrical fold growth in the Zagros fold and thrust belt (Kurdistan, NE-Iraq)

    Science.gov (United States)

    Bartl, Nikolaus; Bretis, Bernhard; Grasemann, Bernhard; Lockhart, Duncan

    2010-05-01

    The Zagros mountains extends over 1800 km from Kurdistan in N-Iraq to the Strait of Hormuz in Iran and is one of the world most promising regions for the future hydrocarbon exploration. The Zagros Mountains started to form as a result of the collision between the Eurasian and Arabian Plates, whose convergence began in the Late Cretaceous as part of the Alpine-Himalayan orogenic system. Geodetic and seismological data document that both plates are still converging and that the fold and thrust belt of the Zagros is actively growing. Extensive hydrocarbon exploration mainly focuses on the antiforms of this fold and thrust belt and therefore the growth history of the folds is of great importance. This work investigates by means of structural field work and quantitative geomorphological techniques the progressive fold growth of the Permam, Bana Bawi- and Safeen- Anticlines located in the NE of the city of Erbil in the Kurdistan region of Northern Iraq. This part of the Zagros fold and thrust belt belongs to the so-called Simply Folded Belt, which is dominated by gentle to open folding. Faults or fault related folds have only minor importance. The mechanical anisotropy of the formations consisting of a succession of relatively competent (massive dolomite and limestone) and incompetent (claystone and siltstone) sediments essentially controls the deformation pattern with open to gentle parallel folding of the competent layers and flexural flow folding of the incompetent layers. The characteristic wavelength of the fold trains is around 10 km. Due to faster erosion of the softer rock layers in the folded sequence, the more competent lithologies form sharp ridges with steeply sloping sides along the eroded flanks of the anticlines. Using an ASTER digital elevation model in combination with geological field data we quantified 250 drainage basins along the different limbs of the subcylindrical Permam, Bana Bawi- and Safeen- Anticlines. Geomorphological indices of the drainage

  16. Vocal fold injection medialization laryngoplasty.

    Science.gov (United States)

    Modi, Vikash K

    2012-01-01

    Unilateral vocal fold paralysis (UVFP) can cause glottic insufficiency that can result in hoarseness, chronic cough, dysphagia, and/or aspiration. In rare circumstances, UVFP can cause airway obstruction necessitating a tracheostomy. The treatment options for UVFP include observation, speech therapy, vocal fold injection medialization laryngoplasty, thyroplasty, and laryngeal reinnervation. In this chapter, the author will discuss the technique of vocal fold injection for medialization of a UVFP. Copyright © 2012 S. Karger AG, Basel.

  17. The review on tessellation origami inspired folded structure

    Science.gov (United States)

    Chu, Chai Chen; Keong, Choong Kok

    2017-10-01

    Existence of folds enhances the load carrying capacity of a folded structure which makes it suitable to be used for application where large open space is required such as large span roof structures and façade. Folded structure is closely related to origami especially the tessellation origami. Tessellation origami provides a folded configuration with facetted surface as a result from repeated folding pattern. Besides that, tessellation origami has flexible folding mechanism that produced a variety of 3-dimensional folded configurations. Despite the direct relationship between fold in origami and folded structure, the idea of origami inspired folded structure is not properly reviewed in the relevant engineering field. Hence, this paper aims to present the current studies from related discipline which has direct relation with application of tessellation origami in folded structure. First, tessellation origami is properly introduced and defined. Then, the review covers the topic on the origami tessellation design suitable for folded structure, its modeling and simulation method, and existing studies and applications of origami as folded structure is presented. The paper also includes the discussion on the current issues related to each topic.

  18. Solvent Effects on Protein Folding/Unfolding

    Science.gov (United States)

    García, A. E.; Hillson, N.; Onuchic, J. N.

    Pressure effects on the hydrophobic potential of mean force led Hummer et al. to postulate a model for pressure denaturation of proteins in which denaturation occurs by means of water penetration into the protein interior, rather than by exposing the protein hydrophobic core to the solvent --- commonly used to describe temperature denaturation. We study the effects of pressure in protein folding/unfolding kinetics in an off-lattice minimalist model of a protein in which pressure effects have been incorporated by means of the pair-wise potential of mean force of hydrophobic groups in water. We show that pressure slows down the kinetics of folding by decreasing the reconfigurational diffusion coefficient and moves the location of the folding transition state.

  19. Bifurcation of self-folded polygonal bilayers

    Science.gov (United States)

    Abdullah, Arif M.; Braun, Paul V.; Hsia, K. Jimmy

    2017-09-01

    Motivated by the self-assembly of natural systems, researchers have investigated the stimulus-responsive curving of thin-shell structures, which is also known as self-folding. Self-folding strategies not only offer possibilities to realize complicated shapes but also promise actuation at small length scales. Biaxial mismatch strain driven self-folding bilayers demonstrate bifurcation of equilibrium shapes (from quasi-axisymmetric doubly curved to approximately singly curved) during their stimulus-responsive morphing behavior. Being a structurally instable, bifurcation could be used to tune the self-folding behavior, and hence, a detailed understanding of this phenomenon is appealing from both fundamental and practical perspectives. In this work, we investigated the bifurcation behavior of self-folding bilayer polygons. For the mechanistic understanding, we developed finite element models of planar bilayers (consisting of a stimulus-responsive and a passive layer of material) that transform into 3D curved configurations. Our experiments with cross-linked Polydimethylsiloxane samples that change shapes in organic solvents confirmed our model predictions. Finally, we explored a design scheme to generate gripper-like architectures by avoiding the bifurcation of stimulus-responsive bilayers. Our research contributes to the broad field of self-assembly as the findings could motivate functional devices across multiple disciplines such as robotics, artificial muscles, therapeutic cargos, and reconfigurable biomedical devices.

  20. How old is your fold?

    NARCIS (Netherlands)

    Winstanley, Henry F.; Abeln, Sanne; Deane, Charlotte M.

    Motivation: At present there exists no age estimate for the different protein structures found in nature. It has become clear from occurrence studies that different folds arose at different points in evolutionary time. An estimation of the age of different folds would be a starting point for many

  1. Teaching computers to fold proteins

    DEFF Research Database (Denmark)

    Winther, Ole; Krogh, Anders Stærmose

    2004-01-01

    A new general algorithm for optimization of potential functions for protein folding is introduced. It is based upon gradient optimization of the thermodynamic stability of native folds of a training set of proteins with known structure. The iterative update rule contains two thermodynamic averages...

  2. Periodic folding of viscous sheets

    Science.gov (United States)

    Ribe, Neil M.

    2003-09-01

    The periodic folding of a sheet of viscous fluid falling upon a rigid surface is a common fluid mechanical instability that occurs in contexts ranging from food processing to geophysics. Asymptotic thin-layer equations for the combined stretching-bending deformation of a two-dimensional sheet are solved numerically to determine the folding frequency as a function of the sheet’s initial thickness, the pouring speed, the height of fall, and the fluid properties. As the buoyancy increases, the system bifurcates from “forced” folding driven kinematically by fluid extrusion to “free” folding in which viscous resistance to bending is balanced by buoyancy. The systematics of the numerically predicted folding frequency are in good agreement with laboratory experiments.

  3. Factors that affect coseismic folds in an overburden layer

    Science.gov (United States)

    Zeng, Shaogang; Cai, Yongen

    2018-03-01

    Coseismic folds induced by blind thrust faults have been observed in many earthquake zones, and they have received widespread attention from geologists and geophysicists. Numerous studies have been conducted regarding fold kinematics; however, few have studied fold dynamics quantitatively. In this paper, we establish a conceptual model with a thrust fault zone and tectonic stress load to study the factors that affect coseismic folds and their formation mechanisms using the finite element method. The numerical results show that the fault dip angle is a key factor that controls folding. The greater the dip angle is, the steeper the fold slope. The second most important factor is the overburden thickness. The thicker the overburden is, the more gradual the fold. In this case, folds are difficult to identify in field surveys. Therefore, if a fold can be easily identified with the naked eye, the overburden is likely shallow. The least important factors are the mechanical parameters of the overburden. The larger the Young's modulus of the overburden is, the smaller the displacement of the fold and the fold slope. Strong horizontal compression and vertical extension in the overburden near the fault zone are the main mechanisms that form coseismic folds.

  4. A new class of compact high sensitive tiltmeter based on the UNISA folded pendulum mechanical architecture

    Science.gov (United States)

    Barone, Fabrizio; Giordano, Gerardo

    2018-02-01

    We present the Extended Folded Pendulum Model (EFPM), a model developed for a quantitative description of the dynamical behavior of a folded pendulum generically oriented in space. This model, based on the Tait-Bryan angular reference system, highlights the relationship between the folded pendulum orientation in the gravitational field and its natural resonance frequency. Tis model validated by tests performed with a monolithic UNISA Folded Pendulum, highlights a new technique of implementation of folded pendulum based tiltmeters.

  5. Curved Folded Plate Timber Structures

    OpenAIRE

    Buri, Hans Ulrich; Stotz, Ivo; Weinand, Yves

    2011-01-01

    This work investigates the development of a Curved Origami Prototype made with timber panels. In the last fifteen years the timber industry has developed new, large size, timber panels. Composition and dimensions of these panels and the possibility of milling them with Computer Numerical Controlled machines shows great potential for folded plate structures. To generate the form of these structures we were inspired by Origami, the Japanese art of paper folding. Common paper tessellations are c...

  6. No-recoil approximation to the knock-on exchange potential in the double folding model for heavy-ion collisions

    International Nuclear Information System (INIS)

    Hagino, K.; Takehi, T.; Takigawa, N.

    2006-01-01

    We propose the no-recoil approximation, which is valid for heavy systems, for a double folding nucleus-nucleus potential. With this approximation, the nonlocal knock-on exchange contribution becomes a local form. We discuss the applicability of this approximation for elastic scattering of the 6 Li + 40 Ca system. We find that, for this and heavier systems , the no-recoil approximation works as good as another widely used local approximation that employs a local plane wave for the relative motion between the colliding nuclei. We also compare the results of the no-recoil calculations with those of the zero-range approximation often used to handle the knock-on exchange effect

  7. PREFACE Protein folding: lessons learned and new frontiers Protein folding: lessons learned and new frontiers

    Science.gov (United States)

    Pappu, Rohit V.; Nussinov, Ruth

    2009-03-01

    In appropriate physiological milieux proteins spontaneously fold into their functional three-dimensional structures. The amino acid sequences of functional proteins contain all the information necessary to specify the folds. This remarkable observation has spawned research aimed at answering two major questions. (1) Of all the conceivable structures that a protein can adopt, why is the ensemble of native-like structures the most favorable? (2) What are the paths by which proteins manage to robustly and reproducibly fold into their native structures? Anfinsen's thermodynamic hypothesis has guided the pursuit of answers to the first question whereas Levinthal's paradox has influenced the development of models for protein folding dynamics. Decades of work have led to significant advances in the folding problem. Mean-field models have been developed to capture our current, coarse grain understanding of the driving forces for protein folding. These models are being used to predict three-dimensional protein structures from sequence and stability profiles as a function of thermodynamic and chemical perturbations. Impressive strides have also been made in the field of protein design, also known as the inverse folding problem, thereby testing our understanding of the determinants of the fold specificities of different sequences. Early work on protein folding pathways focused on the specific sequence of events that could lead to a simplification of the search process. However, unifying principles proved to be elusive. Proteins that show reversible two-state folding-unfolding transitions turned out to be a gift of natural selection. Focusing on these simple systems helped researchers to uncover general principles regarding the origins of cooperativity in protein folding thermodynamics and kinetics. On the theoretical front, concepts borrowed from polymer physics and the physics of spin glasses led to the development of a framework based on energy landscape theories. These

  8. The influence of thyroarytenoid and cricothyroid muscle activation on vocal fold stiffness and eigenfrequencies

    OpenAIRE

    Yin, Jun; Zhang, Zhaoyan

    2013-01-01

    The influence of the thyroarytenoid (TA) and cricothyroid (CT) muscle activation on vocal fold stiffness and eigenfrequencies was investigated in a muscularly controlled continuum model of the vocal folds. Unlike the general understanding that vocal fold fundamental frequency was determined by vocal fold tension, this study showed that vocal fold eigenfrequencies were primarily determined by vocal fold stiffness. This study further showed that, with reference to the resting state of zero stra...

  9. Repairing the vibratory vocal fold.

    Science.gov (United States)

    Long, Jennifer L

    2018-01-01

    A vibratory vocal fold replacement would introduce a new treatment paradigm for structural vocal fold diseases such as scarring and lamina propria loss. This work implants a tissue-engineered replacement for vocal fold lamina propria and epithelium in rabbits and compares histology and function to injured controls and orthotopic transplants. Hypotheses were that the cell-based implant would engraft and control the wound response, reducing fibrosis and restoring vibration. Translational research. Rabbit adipose-derived mesenchymal stem cells (ASC) were embedded within a three-dimensional fibrin gel, forming the cell-based outer vocal fold replacement (COVR). Sixteen rabbits underwent unilateral resection of vocal fold epithelium and lamina propria, as well as reconstruction with one of three treatments: fibrin glue alone with healing by secondary intention, replantation of autologous resected vocal fold cover, or COVR implantation. After 4 weeks, larynges were examined histologically and with phonation. Fifteen rabbits survived. All tissues incorporated well after implantation. After 1 month, both graft types improved histology and vibration relative to injured controls. Extracellular matrix (ECM) of the replanted mucosa was disrupted, and ECM of the COVR implants remained immature. Immune reaction was evident when male cells were implanted into female rabbits. Best histologic and short-term vibratory outcomes were achieved with COVR implants containing male cells implanted into male rabbits. Vocal fold cover replacement with a stem cell-based tissue-engineered construct is feasible and beneficial in acute rabbit implantation. Wound-modifying behavior of the COVR implant is judged to be an important factor in preventing fibrosis. NA. Laryngoscope, 128:153-159, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Folding Membrane Proteins by Deep Transfer Learning

    KAUST Repository

    Wang, Sheng

    2017-08-29

    Computational elucidation of membrane protein (MP) structures is challenging partially due to lack of sufficient solved structures for homology modeling. Here, we describe a high-throughput deep transfer learning method that first predicts MP contacts by learning from non-MPs and then predicts 3D structure models using the predicted contacts as distance restraints. Tested on 510 non-redundant MPs, our method has contact prediction accuracy at least 0.18 better than existing methods, predicts correct folds for 218 MPs, and generates 3D models with root-mean-square deviation (RMSD) less than 4 and 5 Å for 57 and 108 MPs, respectively. A rigorous blind test in the continuous automated model evaluation project shows that our method predicted high-resolution 3D models for two recent test MPs of 210 residues with RMSD ∼2 Å. We estimated that our method could predict correct folds for 1,345–1,871 reviewed human multi-pass MPs including a few hundred new folds, which shall facilitate the discovery of drugs targeting at MPs.

  11. Comparing the Folding and Misfolding Energy Landscapes of Phosphoglycerate Kinase

    OpenAIRE

    Agocs, Gergely; Szabo, Bence T.; Koehler, Gottfried; Osvath, Szabolcs

    2012-01-01

    Partitioning of polypeptides between protein folding and amyloid formation is of outstanding pathophysiological importance. Using yeast phosphoglycerate kinase as model, here we identify the features of the energy landscape that decide the fate of the protein: folding or amyloidogenesis. Structure formation was initiated from the acid-unfolded state, and monitored by fluorescence from 10 ms to 20 days. Solvent conditions were gradually shifted between folding and amyloidogenesis, and the prop...

  12. Ligand-promoted protein folding by biased kinetic partitioning.

    Science.gov (United States)

    Hingorani, Karan S; Metcalf, Matthew C; Deming, Derrick T; Garman, Scott C; Powers, Evan T; Gierasch, Lila M

    2017-04-01

    Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems.

  13. Iterative Controller Tuning for Process with Fold Bifurcations

    DEFF Research Database (Denmark)

    Huusom, Jakob Kjøbsted; Poulsen, Niels Kjølstad; Jørgensen, Sten Bay

    2007-01-01

    Processes involving fold bifurcation are notoriously difficult to control in the vicinity of the fold where most often optimal productivity is achieved . In cases with limited process insight a model based control synthesis is not possible. This paper uses a data driven approach with an improved...... version of iterative feedback tuning to optimizing a closed loop performance criterion, as a systematic tool for tuning process with fold bifurcations....

  14. Objective Quantification of Pre-and Postphonosurgery Vocal Fold Vibratory Characteristics Using High-Speed Videoendoscopy and a Harmonic Waveform Model

    Science.gov (United States)

    Ikuma, Takeshi; Kunduk, Melda; McWhorter, Andrew J.

    2014-01-01

    Purpose: The model-based quantitative analysis of high-speed videoendoscopy (HSV) data at a low frame rate of 2,000 frames per second was assessed for its clinical adequacy. Stepwise regression was employed to evaluate the HSV parameters using harmonic models and their relationships to the Voice Handicap Index (VHI). Also, the model-based HSV…

  15. On the relationship between input parameters in two-mass vocal-fold model with acoustical coupling an signal parameters of the glottal flow

    NARCIS (Netherlands)

    van Hirtum, Annemie; Lopez, Ines; Hirschberg, Abraham; Pelorson, Xavier

    2003-01-01

    In this paper the sensitivity of the two-mass model with acoustical coupling to the model input-parameters is assessed. The model-output or the glottal volume air flow is characterised by signal-parameters in the time-domain. The influence of changing input-parameters on the signal-parameters is

  16. On the relationship between input parameters in the two-mass vocal-fold model with acoustical coupling and signal parameters of the glottal flow

    NARCIS (Netherlands)

    Hirtum, van A.; Lopez Arteaga, I.; Hirschberg, A.; Pelorson, X.

    2003-01-01

    In this paper the sensitivity of the two-mass model with acoustical coupling to the model input-parameters is assessed. The model-output or the glottal volume air flow is characterised by signal-parameters in the time-domain. The influence of changing input-parameters on the signal-parameters is

  17. Folding pathways explored with artificial potential functions

    International Nuclear Information System (INIS)

    Ulutaş, B; Bozma, I; Haliloglu, T

    2009-01-01

    This paper considers the generation of trajectories to a given protein conformation and presents a novel approach based on artificial potential functions—originally proposed for multi-robot navigation. The artificial potential function corresponds to a simplified energy model, but with the novelty that—motivated by work on robotic navigation—a nonlinear compositional scheme of constructing the energy model is adapted instead of an additive formulation. The artificial potential naturally gives rise to a dynamic system for the protein structure that ensures collision-free motion to an equilibrium point. In cases where the equilibrium point is the native conformation, the motion trajectory corresponds to the folding pathway. This framework is used to investigate folding in a variety of protein structures, and the results are compared with those of other approaches including experimental studies

  18. Competition between folding and glycosylation in the endoplasmic reticulum

    DEFF Research Database (Denmark)

    Holst, B; Bruun, A W; Kielland-Brandt, Morten

    1996-01-01

    Using carboxypeptidase Y in Saccharomyces cerevisiae as a model system, the in vivo relationship between protein folding and N-glycosylation was studied. Seven new sites for N-glycosylation were introduced at positions buried in the folded protein structure. The level of glycosylation of such new...... acceptor sites. In some cases, all the newly synthesized mutant protein was modified at the novel site while in others no modification took place. In the most interesting category of mutants, the level of glycosylation was dependent on the conditions for folding. This shows that folding and glycosylation...

  19. Thermodynamics of protein folding: a random matrix formulation.

    Science.gov (United States)

    Shukla, Pragya

    2010-10-20

    The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters, e.g. the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon molecules. Our study, based on random matrix modeling of the interactions, shows, however, that the evolution of the statistical measures, e.g. Gibbs free energy, heat capacity, and entropy, is single parametric. The information can explain the selection of specific folding pathways from an infinite number of possible ways as well as other folding characteristics observed in computer simulation studies. © 2010 IOP Publishing Ltd

  20. Wrinkles, folds, and plasticity in granular rafts

    Science.gov (United States)

    Jambon-Puillet, Etienne; Josserand, Christophe; Protière, Suzie

    2017-09-01

    We investigate the mechanical response of a compressed monolayer of large and dense particles at a liquid-fluid interface: a granular raft. Upon compression, rafts first wrinkle; then, as the confinement increases, the deformation localizes in a unique fold. This characteristic buckling pattern is usually associated with floating elastic sheets, and as a result, particle laden interfaces are often modeled as such. Here, we push this analogy to its limits by comparing quantitative measurements of the raft morphology to a theoretical continuous elastic model of the interface. We show that, although powerful to describe the wrinkle wavelength, the wrinkle-to-fold transition, and the fold shape, this elastic description does not capture the finer details of the experiment. We describe an unpredicted secondary wavelength, a compression discrepancy with the model, and a hysteretic behavior during compression cycles, all of which are a signature of the intrinsic discrete and frictional nature of granular rafts. It suggests also that these composite materials exhibit both plastic transition and jamming dynamics.

  1. The influence of thyroarytenoid and cricothyroid muscle activation on vocal fold stiffness and eigenfrequencies

    Science.gov (United States)

    Yin, Jun; Zhang, Zhaoyan

    2013-01-01

    The influence of the thyroarytenoid (TA) and cricothyroid (CT) muscle activation on vocal fold stiffness and eigenfrequencies was investigated in a muscularly controlled continuum model of the vocal folds. Unlike the general understanding that vocal fold fundamental frequency was determined by vocal fold tension, this study showed that vocal fold eigenfrequencies were primarily determined by vocal fold stiffness. This study further showed that, with reference to the resting state of zero strain, vocal fold stiffness in both body and cover layers increased with either vocal fold elongation or shortening. As a result, whether vocal fold eigenfrequencies increased or decreased with CT/TA activation depended on how the CT/TA interaction influenced vocal fold deformation. For conditions of strong CT activation and thus an elongated vocal fold, increasing TA contraction reduced the degree of vocal fold elongation and thus reduced vocal fold eigenfrequencies. For conditions of no CT activation and thus a resting or slightly shortened vocal fold, increasing TA contraction increased the degree of vocal fold shortening and thus increased vocal fold eigenfrequencies. In the transition region of a slightly elongated vocal fold, increasing TA contraction first decreased and then increased vocal fold eigenfrequencies. PMID:23654401

  2. Dynamics in thin folded polymer films

    Science.gov (United States)

    Croll, Andrew; Rozairo, Damith

    Origami and Kirigami inspired structures depend on a complex interplay between geometry and material properties. While clearly important to the overall function, very little attention has focused on how extreme curvatures and singularities in real materials influence the overall dynamic behaviour of folded structures. In this work we use a set of three polymer thin films in order to closely examine the interaction of material and geometry. Specifically, we use polydimethylsiloxane (PDMS), polystyrene (PS) and polycarbonate (PC) thin films which we subject to loading in several model geometries of varying complexity. Depending on the material, vastly different responses are noted in our experiments; D-cones can annihilate, cut or lead to a crumpling cascade when pushed through a film. Remarkably, order can be generated with additional perturbation. Finally, the role of adhesion in complex folded structures can be addressed. AFOSR under the Young Investigator Program (FA9550-15-1-0168).

  3. New insight in the structural features of haloadaptation in α-amylases from halophilic Archaea following homology modeling strategy: folded and stable conformation maintained through low hydrophobicity and highly negative charged surface

    Science.gov (United States)

    Zorgani, Mohamed Amine; Patron, Kevin; Desvaux, Mickaël

    2014-07-01

    Proteins from halophilic archaea, which live in extreme saline conditions, have evolved to remain folded, active and stable at very high ionic strengths. Understanding the mechanism of haloadaptation is the first step toward engineering of halostable biomolecules. Amylases are one of the main enzymes used in industry. Yet, no three-dimensional structure has been experimentally resolved for α-amylases from halophilic archaea. In this study, homology structure modeling of α-amylases from the halophilic archaea Haloarcula marismortui, Haloarcula hispanica, and Halalkalicoccus jeotgali were performed. The resulting models were subjected to energy minimization, evaluation, and structural analysis. Calculations of the amino acid composition, salt bridges and hydrophobic interactions were also performed and compared to a set of non-halophilic counterparts. It clearly appeared that haloarchaeal α-amylases exhibited lower propensities for helix formation and higher propensities for coil-forming regions. Furthermore, they could maintain a folded and stable conformation in high salt concentration through highly negative charged surface with over representation of acidic residues, especially Asp, and low hydrophobicity with increase of salt bridges and decrease in hydrophobic interactions on the protein surface. This study sheds some light on the stability of α-amylases from halophilic archaea and provides strong basis not only to understand haloadaptation mechanisms of proteins in microorganisms from hypersalines environments but also for biotechnological applications.

  4. Deformation and kinematics of the central Kirthar Fold Belt, Pakistan

    Science.gov (United States)

    Hinsch, Ralph; Hagedorn, Peter; Asmar, Chloé; Nasim, Muhammad; Aamir Rasheed, Muhammad; Kiely, James M.

    2017-04-01

    The Kirthar Fold Belt is part of the lateral mountain belts in Pakistan linking the Himalaya orogeny with the Makran accretionary wedge. This region is deforming very oblique/nearly parallel to the regional plate motion vector. The study area is situated between the prominent Chaman strike-slip fault in the West and the un-deformed foreland (Kirthar Foredeep/Middle Indus Basin) in the East. The Kirthar Fold Belt is subdivided into several crustal blocks/units based on structural orientation and deformation style (e.g. Kallat, Khuzdar, frontal Kirthar). This study uses newly acquired and depth-migrated 2D seismic lines, surface geology observations and Google Earth assessments to construct three balanced cross sections for the frontal part of the fold belt. Further work was done in order to insure the coherency of the built cross-sections by taking a closer look at the regional context inferred from published data, simple analogue modelling, and constructed regional sketch sections. The Khuzdar area and the frontal Kirthar Fold Belt are dominated by folding. Large thrusts with major stratigraphic repetitions are not observed. Furthermore, strike-slip faults in the Khuzdar area are scarce and not observed in the frontal Kirthar Fold Belt. The regional structural elevation rises from the foreland across the Kirthar Fold Belt towards the hinterland (Khuzdar area). These observations indicate that basement-involved deformation is present at depth. The domination of folding indicates a weak decollement below the folds (soft-linked deformation). The fold pattern in the Khuzdar area is complex, whereas the large folds of the central Kirthar Fold Belt trend SSW-NNE to N-S and are best described as large detachment folds that have been slightly uplifted by basement involved transpressive deformation underneath. Towards the foreland, the deformation is apparently more hard-linked and involves fault-propagation folding and a small triangle zone in Cretaceous sediments

  5. Mimicking the action of folding chaperones by Hamiltonian replica-exchange molecular dynamics simulations : Application in the refinement of de novo models

    NARCIS (Netherlands)

    Fan, Hao; Periole, Xavier; Mark, Alan E.

    The efficiency of using a variant of Hamiltonian replica-exchange molecular dynamics (Chaperone H-replica-exchange molecular dynamics [CH-REMD]) for the refinement of protein structural models generated de novo is investigated. In CH-REMD, the interaction between the protein and its environment,

  6. The use of paleo-thermo-barometers and coupled thermal, fluid flow and pore fluid pressure modelling for hydrocarbon and reservoir prediction in fold and thrust belts

    NARCIS (Netherlands)

    Roure, F.; Andriessen, P.A.M.; Callot, J.P.; Ferket, H.; Gonzales, E.; Guilhaumou, N.; Hardebol, N.J.; Lacombe, O.; Malandain, J.; Mougin, P.; Muska, K.; Ortuno, S.; Sassi, W.; Swennen, R.; Vilasi, N.

    2010-01-01

    Basin modelling tools are now more efficient to reconstruct palinspastic structural cross sections and compute the history of temperature, pore-fluid pressure and fluid flow circulations in complex structural settings. In many cases and especially in areas where limited erosion occurred, the use of

  7. Current Understanding and Future Directions for Vocal Fold Mechanobiology

    Science.gov (United States)

    Li, Nicole Y.K.; Heris, Hossein K.; Mongeau, Luc

    2013-01-01

    The vocal folds, which are located in the larynx, are the main organ of voice production for human communication. The vocal folds are under continuous biomechanical stress similar to other mechanically active organs, such as the heart, lungs, tendons and muscles. During speech and singing, the vocal folds oscillate at frequencies ranging from 20 Hz to 3 kHz with amplitudes of a few millimeters. The biomechanical stress associated with accumulated phonation is believed to alter vocal fold cell activity and tissue structure in many ways. Excessive phonatory stress can damage tissue structure and induce a cell-mediated inflammatory response, resulting in a pathological vocal fold lesion. On the other hand, phonatory stress is one major factor in the maturation of the vocal folds into a specialized tri-layer structure. One specific form of vocal fold oscillation, which involves low impact and large amplitude excursion, is prescribed therapeutically for patients with mild vocal fold injuries. Although biomechanical forces affect vocal fold physiology and pathology, there is little understanding of how mechanical forces regulate these processes at the cellular and molecular level. Research into vocal fold mechanobiology has burgeoned over the past several years. Vocal fold bioreactors are being developed in several laboratories to provide a biomimic environment that allows the systematic manipulation of physical and biological factors on the cells of interest in vitro. Computer models have been used to simulate the integrated response of cells and proteins as a function of phonation stress. The purpose of this paper is to review current research on the mechanobiology of the vocal folds as it relates to growth, pathogenesis and treatment as well as to propose specific research directions that will advance our understanding of this subject. PMID:24812638

  8. Force generation by titin folding.

    Science.gov (United States)

    Mártonfalvi, Zsolt; Bianco, Pasquale; Naftz, Katalin; Ferenczy, György G; Kellermayer, Miklós

    2017-07-01

    Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent folding mechanisms, here we manipulated skeletal-muscle titin molecules with high-resolution optical tweezers. In force-clamp mode, after quenching the force (force trace contained rapid fluctuations and a gradual increase of average force, indicating that titin can develop force via dynamic transitions between its structural states en route to the native conformation. In 4 M urea, which destabilizes H-bonds hence the consolidated native domain structure, the net force increase disappeared but the fluctuations persisted. Thus, whereas net force generation is caused by the ensemble folding of the elastically-coupled domains, force fluctuations arise due to a dynamic equilibrium between unfolded and molten-globule states. Monte-Carlo simulations incorporating a compact molten-globule intermediate in the folding landscape recovered all features of our nanomechanics results. The ensemble molten-globule dynamics delivers significant added contractility that may assist sarcomere mechanics, and it may reduce the dissipative energy loss associated with titin unfolding/refolding during muscle contraction/relaxation cycles. © 2017 The Protein Society.

  9. Quantification of fold growth of frontal antiforms in the Zagros fold and thrust belt (Kurdistan, NE Iraq)

    Science.gov (United States)

    Bretis, Bernhard; Bartl, Nikolaus; Graseman, Bernhard; Lockhart, Duncan

    2010-05-01

    The Zagros fold and thrust belt is a seismically active orogen, where actual kinematic models based on GPS networks suggest a north-south shortening between Arabian and Eurasian in the order of 1.5-2.5 cm/yr. Most of this deformation is partitioned in south-southwest oriented folding and thrusting with northwest-southeast to north-south trending dextral strike slip faults. The Zagros fold and thrust belt is of great economic interest because it has been estimated that this area contains about 15% of the global recoverable hydrocarbons. Whereas the SE parts of the Zagros have been investigated by detailed geological studies, the NW extent being part of the Republic of Iraq have experienced considerably less attention. In this study we combine field work and remote sensing techniques in order to investigate the interaction of erosion and fold growth in the area NE of Erbil (Kurdistan, Iraq). In particular we focus on the interaction of the transient development of drainage patterns along growing antiforms, which directly reflects the kinematics of progressive fold growth. Detailed geomorphological studies of the Bana Bawi-, Permam- and Safeen fold trains show that these anticlines have not developed from subcylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification. This fold segments with length between 5 and 25 km have been detected by mapping ancient and modern river courses that initially cut the nose of growing folds and eventually got defeated leaving behind a wind gap. Fold segments, propagating in different directions force rivers to join resulting in steep gorges, which dissect the merging fold noses. Along rapidly lateral growing folds (e.g. at the SE end of the Bana Bawi Anticline) we observed "curved wind gaps", a new type of abandoned river course, where form of the wind gap mimics a formed nose of a growing antiform. The inherited curved segments of uplifted curved river courses strongly

  10. Synovial folds in equine articular process joints

    DEFF Research Database (Denmark)

    Thomsen, Line Nymann; Berg, Lise Charlotte; Markussen, Bo

    2013-01-01

    Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses.......Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses....

  11. Araguaia fold belt, new geochronological data

    International Nuclear Information System (INIS)

    Lafon, J.M.; Macambira, J.B.; Macambira, M.J.B.; Moura, C.A.V.; Souza, A.C.C.

    1990-01-01

    The northern part of the Araguaia Fold Belt (AFB) outcrops in a N-S direction for about 400 km in the state of Tocantins. Dome-like structures occur in this fold belt also in a N-S direction. Both deformation and metamorphism increase from the West to the East. The basement of the AFB consist of Colmeia complex and Cantao gneiss, which crop out mainly in the core of the dome-like structures. The supracrustals rocks of the fold belt belongs to the Baixo Araguaia supergroup which is divided into the lower Estrondo group and the upper Tocantins group. Preliminary Sm-Nd data from the Colmeia complex (Grota Rica dome) gave Archean model ages of 2.8 Ga (TNd sub(DM)) while Rb-Sr data in the same rocks give an age of 2530 ± 200 Ma. In the others dome-like structures, the Rb-Sr systematics gave ages for the Colmeia a complex of 2239 ± 47 Ma (Colmeia structure) and 1972 ± 46 Ma (Lontra structure). These younger ages are believed to represent partial to total isotopic resetting of the Rb-Sr system during the Transamazonian Event. The Rb-Sr studies of the Cantao gneiss gave an age of 1774 ± 31 Ma. (author)

  12. Origami-Inspired Folding of Thick, Rigid Panels

    Science.gov (United States)

    Trease, Brian P.; Thomson, Mark W.; Sigel, Deborah A.; Walkemeyer, Phillip E.; Zirbel, Shannon; Howell, Larry; Lang, Robert

    2014-01-01

    To achieve power of 250 kW or greater, a large compression ratio of stowed-to-deployed area is needed. Origami folding patterns were used to inspire the folding of a solar array to achieve synchronous deployment; however, origami models are generally created for near-zero-thickness material. Panel thickness is one of the main challenges of origami-inspired design. Three origami-inspired folding techniques (flasher, square twist, and map fold) were created with rigid panels and hinges. Hinge components are added to the model to enable folding of thick, rigid materials. Origami models are created assuming zero (or near zero) thickness. When a material with finite thickness is used, the panels are required to bend around an increasingly thick fold as they move away from the center of the model. The two approaches for dealing with material thickness are to use membrane hinges to connect the panels, or to add panel hinges, or hinges of the same thickness, at an appropriate width to enable folding.

  13. In vivo measurement of vocal fold surface resistance.

    Science.gov (United States)

    Mizuta, Masanobu; Kurita, Takashi; Dillon, Neal P; Kimball, Emily E; Garrett, C Gaelyn; Sivasankar, M Preeti; Webster, Robert J; Rousseau, Bernard

    2017-10-01

    A custom-designed probe was developed to measure vocal fold surface resistance in vivo. The purpose of this study was to demonstrate proof of concept of using vocal fold surface resistance as a proxy of functional tissue integrity after acute phonotrauma using an animal model. Prospective animal study. New Zealand White breeder rabbits received 120 minutes of airflow without vocal fold approximation (control) or 120 minutes of raised intensity phonation (experimental). The probe was inserted via laryngoscope and placed on the left vocal fold under endoscopic visualization. Vocal fold surface resistance of the middle one-third of the vocal fold was measured after 0 (baseline), 60, and 120 minutes of phonation. After the phonation procedure, the larynx was harvested and prepared for transmission electron microscopy. In the control group, vocal fold surface resistance values remained stable across time points. In the experimental group, surface resistance (X% ± Y% relative to baseline) was significantly decreased after 120 minutes of raised intensity phonation. This was associated with structural changes using transmission electron microscopy, which revealed damage to the vocal fold epithelium after phonotrauma, including disruption of the epithelium and basement membrane, dilated paracellular spaces, and alterations to epithelial microprojections. In contrast, control vocal fold specimens showed well-preserved stratified squamous epithelia. These data demonstrate the feasibility of measuring vocal fold surface resistance in vivo as a means of evaluating functional vocal fold epithelial barrier integrity. Device prototypes are in development for additional testing, validation, and for clinical applications in laryngology. NA Laryngoscope, 127:E364-E370, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Double folded Yukawa interaction potential between two heavy ions

    International Nuclear Information System (INIS)

    Bulgac, A.; Carstoiu, F.; Dumitrescu, O.

    1980-02-01

    A simple semi-analytical formula for the heavy ion interaction potential within the double-folding model approximation is obtained. The folded interaction is assumed to be expressed in Yukawa terms or the derivatives of them. The densities used can be both experimental or theoretical (of simple ''step-wise'', ''Fermi-Saxon-Woods'' or complicated ''shell model'' structure) densities. A way of inserting the exchange terms is discussed. Numerical calculations for some colliding partners are reported. (author)

  15. Measured and modeled evidence for a two-fold increase in water use efficiency at an old-growth forest site in the Pacific Northwest

    Science.gov (United States)

    Jiang, Y.; Rastogi, B.; Kim, J. B.; Voelker, S.; Meinzer, F. C.; Still, C. J.

    2017-12-01

    Water use efficiency (WUE), the ratio of carbon uptake to transpiration, has been widely recognized as an important measure of carbon and water cycling in plants, and is used to track forest ecosystem responses to climate change and rising atmospheric CO2concentrations. In this study we used eddy covariance measurement data and Ecosystem Demography model (ED2) simulations to explore the patterns and physiological and biophysical controls of WUE at Wind River Experimental Forest, an old-growth coniferous forest in the Pacific Northwest. We characterized how observed and simulated WUE vary between wet and dry years, and explored the drivers of the differences in WUE between the wet and dry years. Through this explorative process, we evaluated the utility of various ways that WUE have been computed in literature. Measurement-based and simulated WUE at the old-growth forest increased over twofold from 1998 to 2015. The primary driver of this trend is a decreasing trend in evapotranspiration (ET). There were significant inter-annual variations. For example, during drought years, higher air temperature drove increases in early season ET, thereby depleting soil water and decreasing GPP. Lower GPP in turn resulted in lower WUE. This mechanism might drive changes in future carbon and water budgets under warming climate. Our evaluation of multiple WUE metrics demonstrates that each metric has a distinct sensitivity to climate anomalies, but also indicates a robust increasing trend of WUE. Statistical (multiple linear regression) and machine learning (Random Forest) analyses of flux measurements indicated that atmospheric CO2 concentration, air temperature and radiation were the most important predictors of WUE at monthly, daily and half-hourly time scale, respectively. In contrast, WUE mechanism was stable across all time scales in ED2 simulations: vapor pressure deficit was consistently the most important predictor of WUE at the monthly, daily and half-hourly time scales.

  16. Vocal fold contact patterns based on normal modes of vibration.

    Science.gov (United States)

    Smith, Simeon L; Titze, Ingo R

    2018-05-17

    The fluid-structure interaction and energy transfer from respiratory airflow to self-sustained vocal fold oscillation continues to be a topic of interest in vocal fold research. Vocal fold vibration is driven by pressures on the vocal fold surface, which are determined by the shape of the glottis and the contact between vocal folds. Characterization of three-dimensional glottal shapes and contact patterns can lead to increased understanding of normal and abnormal physiology of the voice, as well as to development of improved vocal fold models, but a large inventory of shapes has not been directly studied previously. This study aimed to take an initial step toward characterizing vocal fold contact patterns systematically. Vocal fold motion and contact was modeled based on normal mode vibration, as it has been shown that vocal fold vibration can be almost entirely described by only the few lowest order vibrational modes. Symmetric and asymmetric combinations of the four lowest normal modes of vibration were superimposed on left and right vocal fold medial surfaces, for each of three prephonatory glottal configurations, according to a surface wave approach. Contact patterns were generated from the interaction of modal shapes at 16 normalized phases during the vibratory cycle. Eight major contact patterns were identified and characterized by the shape of the flow channel, with the following descriptors assigned: convergent, divergent, convergent-divergent, uniform, split, merged, island, and multichannel. Each of the contact patterns and its variation are described, and future work and applications are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Understanding ensemble protein folding at atomic detail

    International Nuclear Information System (INIS)

    Wallin, Stefan; Shakhnovich, Eugene I

    2008-01-01

    Although far from routine, simulating the folding of specific short protein chains on the computer, at a detailed atomic level, is starting to become a reality. This remarkable progress, which has been made over the last decade or so, allows a fundamental aspect of the protein folding process to be addressed, namely its statistical nature. In order to make quantitative comparisons with experimental kinetic data a complete ensemble view of folding must be achieved, with key observables averaged over the large number of microscopically different folding trajectories available to a protein chain. Here we review recent advances in atomic-level protein folding simulations and the new insight provided by them into the protein folding process. An important element in understanding ensemble folding kinetics are methods for analyzing many separate folding trajectories, and we discuss techniques developed to condense the large amount of information contained in an ensemble of trajectories into a manageable picture of the folding process. (topical review)

  18. Glycoprotein folding and quality-control mechanisms in protein-folding diseases

    Directory of Open Access Journals (Sweden)

    Sean P. Ferris

    2014-03-01

    Full Text Available Biosynthesis of proteins – from translation to folding to export – encompasses a complex set of events that are exquisitely regulated and scrutinized to ensure the functional quality of the end products. Cells have evolved to capitalize on multiple post-translational modifications in addition to primary structure to indicate the folding status of nascent polypeptides to the chaperones and other proteins that assist in their folding and export. These modifications can also, in the case of irreversibly misfolded candidates, signal the need for dislocation and degradation. The current Review focuses on the glycoprotein quality-control (GQC system that utilizes protein N-glycosylation and N-glycan trimming to direct nascent glycopolypeptides through the folding, export and dislocation pathways in the endoplasmic reticulum (ER. A diverse set of pathological conditions rooted in defective as well as over-vigilant ER quality-control systems have been identified, underlining its importance in human health and disease. We describe the GQC pathways and highlight disease and animal models that have been instrumental in clarifying our current understanding of these processes.

  19. Protein folding and wring resonances

    DEFF Research Database (Denmark)

    Bohr, Jakob; Bohr, Henrik; Brunak, Søren

    1997-01-01

    The polypeptide chain of a protein is shown to obey topological contraints which enable long range excitations in the form of wring modes of the protein backbone. Wring modes of proteins of specific lengths can therefore resonate with molecular modes present in the cell. It is suggested that prot......The polypeptide chain of a protein is shown to obey topological contraints which enable long range excitations in the form of wring modes of the protein backbone. Wring modes of proteins of specific lengths can therefore resonate with molecular modes present in the cell. It is suggested...... that protein folding takes place when the amplitude of a wring excitation becomes so large that it is energetically favorable to bend the protein backbone. The condition under which such structural transformations can occur is found, and it is shown that both cold and hot denaturation (the unfolding...

  20. Radiation Fibrosis of the Vocal Fold: From Man to Mouse

    Science.gov (United States)

    Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

    2013-01-01

    Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis. PMID:23242839

  1. Impact of hydrodynamic interactions on protein folding rates depends on temperature

    Science.gov (United States)

    Zegarra, Fabio C.; Homouz, Dirar; Eliaz, Yossi; Gasic, Andrei G.; Cheung, Margaret S.

    2018-03-01

    We investigated the impact of hydrodynamic interactions (HI) on protein folding using a coarse-grained model. The extent of the impact of hydrodynamic interactions, whether it accelerates, retards, or has no effect on protein folding, has been controversial. Together with a theoretical framework of the energy landscape theory (ELT) for protein folding that describes the dynamics of the collective motion with a single reaction coordinate across a folding barrier, we compared the kinetic effects of HI on the folding rates of two protein models that use a chain of single beads with distinctive topologies: a 64-residue α /β chymotrypsin inhibitor 2 (CI2) protein, and a 57-residue β -barrel α -spectrin Src-homology 3 domain (SH3) protein. When comparing the protein folding kinetics simulated with Brownian dynamics in the presence of HI to that in the absence of HI, we find that the effect of HI on protein folding appears to have a "crossover" behavior about the folding temperature. This means that at a temperature greater than the folding temperature, the enhanced friction from the hydrodynamic solvents between the beads in an unfolded configuration results in lowered folding rate; conversely, at a temperature lower than the folding temperature, HI accelerates folding by the backflow of solvent toward the folded configuration of a protein. Additionally, the extent of acceleration depends on the topology of a protein: for a protein like CI2, where its folding nucleus is rather diffuse in a transition state, HI channels the formation of contacts by favoring a major folding pathway in a complex free energy landscape, thus accelerating folding. For a protein like SH3, where its folding nucleus is already specific and less diffuse, HI matters less at a temperature lower than the folding temperature. Our findings provide further theoretical insight to protein folding kinetic experiments and simulations.

  2. Nanoscale Dewetting Transition in Protein Complex Folding

    Science.gov (United States)

    Hua, Lan; Huang, Xuhui; Liu, Pu; Zhou, Ruhong; Berne, Bruce J.

    2011-01-01

    In a previous study, a surprising drying transition was observed to take place inside the nanoscale hydrophobic channel in the tetramer of the protein melittin. The goal of this paper is to determine if there are other protein complexes capable of displaying a dewetting transition during their final stage of folding. We searched the entire protein data bank (PDB) for all possible candidates, including protein tetramers, dimers, and two-domain proteins, and then performed the molecular dynamics (MD) simulations on the top candidates identified by a simple hydrophobic scoring function based on aligned hydrophobic surface areas. Our large scale MD simulations found several more proteins, including three tetramers, six dimers, and two two-domain proteins, which display a nanoscale dewetting transition in their final stage of folding. Even though the scoring function alone is not sufficient (i.e., a high score is necessary but not sufficient) in identifying the dewetting candidates, it does provide useful insights into the features of complex interfaces needed for dewetting. All top candidates have two features in common: (1) large aligned (matched) hydrophobic areas between two corresponding surfaces, and (2) large connected hydrophobic areas on the same surface. We have also studied the effect on dewetting of different water models and different treatments of the long-range electrostatic interactions (cutoff vs PME), and found the dewetting phenomena is fairly robust. This work presents a few proteins other than melittin tetramer for further experimental studies of the role of dewetting in the end stages of protein folding. PMID:17608515

  3. Dynamics of Folds in the Plane

    Science.gov (United States)

    Krylov, Nikolai A.; Rogers, Edwin L.

    2011-01-01

    Take a strip of paper and fold a crease intersecting the long edges, creating two angles. Choose one edge and consider the angle with the crease. Fold the opposite edge along the crease, creating a new crease that bisects the angle. Fold again, this time using the newly created crease and the initial edge, creating a new angle along the chosen…

  4. A novel folding blade of wind turbine rotor for effective power control

    International Nuclear Information System (INIS)

    Xie, Wei; Zeng, Pan; Lei, Liping

    2015-01-01

    Highlights: • A novel folding blade for wind turbine power control is proposed. • Wind tunnel experiments were conducted to analyze folding blade validity. • Folding blade is valid to control wind turbine power output. • Compared to pitch control, thrust was reduced by fold control in power regulation. • Optimum fold angles were found for wind turbine start up and aerodynamic brake. - Abstract: A concept of novel folding blade of horizontal axis wind turbine is proposed in current study. The folding blade comprises a stall regulated root blade section and a folding tip blade section with the fold axis inclined relative to blade span. By folding blade, lift force generated on the tip blade section changes and the moment arm also shortens, which leads to variations of power output. The blade folding actuation mechanism with servo motor and worm-gear reducer was designed. Wind turbine rotor control scheme and servo system with double feedback loops for blade fold angle control were proposed. In this study, a small folding blade model was tested in a wind tunnel to analyze its performance. The blade model performance was estimated in terms of rotation torque coefficient and thrust coefficient. Wind tunnel experiments were also conducted for pitch control using the same blade model in order to make a direct comparison. The power control, start up and aerodynamic brake performance of the folding blade were analyzed. According to the wind tunnel experiment results, fold angle magnitude significantly affected blade aerodynamic performance and the thrust characteristic together with the rotation torque characteristic of folding blade were revealed. The experiment results demonstrated that the folding blade was valid to control power output and had advantages in reducing thrust with maximum reduction of 51.1% compared to pitch control. Optimum fold angles of 55° and 90° were also found for start up and aerodynamic brake, respectively

  5. Unraveling metamaterial properties in zigzag-base folded sheets.

    Science.gov (United States)

    Eidini, Maryam; Paulino, Glaucio H

    2015-09-01

    Creating complex spatial objects from a flat sheet of material using origami folding techniques has attracted attention in science and engineering. In the present work, we use the geometric properties of partially folded zigzag strips to better describe the kinematics of known zigzag/herringbone-base folded sheet metamaterials such as Miura-ori. Inspired by the kinematics of a one-degree of freedom zigzag strip, we introduce a class of cellular folded mechanical metamaterials comprising different scales of zigzag strips. This class of patterns combines origami folding techniques with kirigami. Using analytical and numerical models, we study the key mechanical properties of the folded materials. We show that our class of patterns, by expanding on the design space of Miura-ori, is appropriate for a wide range of applications from mechanical metamaterials to deployable structures at small and large scales. We further show that, depending on the geometry, these materials exhibit either negative or positive in-plane Poisson's ratios. By introducing a class of zigzag-base materials in the current study, we unify the concept of in-plane Poisson's ratio for similar materials in the literature and extend it to the class of zigzag-base folded sheet materials.

  6. Anatomy and Histology of an Epicanthal Fold.

    Science.gov (United States)

    Park, Jae Woo; Hwang, Kun

    2016-06-01

    The aim of this study is to elucidate the precise anatomical and histological detail of the epicanthal fold.Thirty-two hemifaces of 16 Korean adult cadavers were used in this study (30 hemifaces with an epicanthal fold, 2 without an epicanthal fold). In 2 patients who had an epicanthoplasty, the epicanthal folds were sampled.In a dissection, the periorbital skin and subcutaneous tissues were removed and the epicanthal fold was observed in relation to each part of the orbicularis oculi muscle. Specimens including the epicanthal fold were embeddedin in paraffin, sectioned at 10 um, and stained with Hematoxylin-Eosin. The horizontal section in the level of the paplebral fissure was made and the prepared slides were observed under a light microscope.In the specimens without an epicanthal fold, no connection between the upper preseptal muscle and the lower preseptal muscle was found. In the specimens with an epicanthal fold, a connection of the upper preseptal muscle to the lower preseptal muscle was observed. It was present in all 15 hemifaces (100%). There was no connection between the pretarsal muscles. In a horizontal section, the epicanthal fold was composed of 3 compartments: an outer skin lining, a core structure, and an innerskin lining. The core structure was mainly composed of muscular fibers and fibrotic tissue and they were intermingled.Surgeons should be aware of the anatomical details of an epicanthal fold. In removing or reconstructing an epicanthal fold, the fibromuscular core band should also be removed or reconstructed.

  7. Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

    Directory of Open Access Journals (Sweden)

    Angelou Valerie

    2016-01-01

    Full Text Available Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group. We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments.

  8. Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

    Science.gov (United States)

    Vassiliki, Kalodimou; Irini, Messini; Nikolaos, Psychalakis; Karampela, Eleftheria; Apostolos, Papalois

    2016-01-01

    Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid. Study Design. Animal experiment. Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months. Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC. Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments. PMID:26933440

  9. Folding two dimensional crystals by swift heavy ion irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ochedowski, Oliver; Bukowska, Hanna [Fakultät für Physik and CENIDE, Universität Duisburg-Essen, D-47048 Duisburg (Germany); Freire Soler, Victor M. [Fakultät für Physik and CENIDE, Universität Duisburg-Essen, D-47048 Duisburg (Germany); Departament de Fisica Aplicada i Optica, Universitat de Barcelona, E08028 Barcelona (Spain); Brökers, Lara [Fakultät für Physik and CENIDE, Universität Duisburg-Essen, D-47048 Duisburg (Germany); Ban-d' Etat, Brigitte; Lebius, Henning [CIMAP (CEA-CNRS-ENSICAEN-UCBN), 14070 Caen Cedex 5 (France); Schleberger, Marika, E-mail: marika.schleberger@uni-due.de [Fakultät für Physik and CENIDE, Universität Duisburg-Essen, D-47048 Duisburg (Germany)

    2014-12-01

    Ion irradiation of graphene, the showcase model of two dimensional crystals, has been successfully applied to induce various modifications in the graphene crystal. One of these modifications is the formation of origami like foldings in graphene which are created by swift heavy ion irradiation under glancing incidence angle. These foldings can be applied to locally alter the physical properties of graphene like mechanical strength or chemical reactivity. In this work we show that the formation of foldings in two dimensional crystals is not restricted to graphene but can be applied for other materials like MoS{sub 2} and hexagonal BN as well. Further we show that chemical vapour deposited graphene forms foldings after swift heavy ion irradiation while chemical vapour deposited MoS{sub 2} does not.

  10. Folding two dimensional crystals by swift heavy ion irradiation

    International Nuclear Information System (INIS)

    Ochedowski, Oliver; Bukowska, Hanna; Freire Soler, Victor M.; Brökers, Lara; Ban-d'Etat, Brigitte; Lebius, Henning; Schleberger, Marika

    2014-01-01

    Ion irradiation of graphene, the showcase model of two dimensional crystals, has been successfully applied to induce various modifications in the graphene crystal. One of these modifications is the formation of origami like foldings in graphene which are created by swift heavy ion irradiation under glancing incidence angle. These foldings can be applied to locally alter the physical properties of graphene like mechanical strength or chemical reactivity. In this work we show that the formation of foldings in two dimensional crystals is not restricted to graphene but can be applied for other materials like MoS 2 and hexagonal BN as well. Further we show that chemical vapour deposited graphene forms foldings after swift heavy ion irradiation while chemical vapour deposited MoS 2 does not

  11. Some physical approaches to protein folding

    Science.gov (United States)

    Bascle, J.; Garel, T.; Orland, H.

    1993-02-01

    To understand how a protein folds is a problem which has important biological implications. In this article, we would like to present a physics-oriented point of view, which is twofold. First of all, we introduce simple statistical mechanics models which display, in the thermodynamic limit, folding and related transitions. These models can be divided into (i) crude spin glass-like models (with their Mattis analogs), where one may look for possible correlations between the chain self-interactions and the folded structure, (ii) glass-like models, where one emphasizes the geometrical competition between one- or two-dimensional local order (mimicking α helix or β sheet structures), and the requirement of global compactness. Both models are too simple to predict the spatial organization of a realistic protein, but are useful for the physicist and should have some feedback in other glassy systems (glasses, collapsed polymers .... ). These remarks lead us to the second physical approach, namely a new Monte-Carlo method, where one grows the protein atom-by-atom (or residue-by-residue), using a standard form (CHARMM .... ) for the total energy. A detailed comparison with other Monte-Carlo schemes, or Molecular Dynamics calculations, is then possible; we will sketch such a comparison for poly-alanines. Our twofold approach illustrates some of the difficulties one encounters in the protein folding problem, in particular those associated with the existence of a large number of metastable states. Le repliement des protéines est un problème qui a de nombreuses implications biologiques. Dans cet article, nous présentons, de deux façons différentes, un point de vue de physicien. Nous introduisons tout d'abord des modèles simples de mécanique statistique qui exhibent, à la limite thermodynamique, des transitions de repliement. Ces modèles peuvent être divisés en (i) verres de spin (éventuellement à la Mattis), où l'on peut chercher des corrélations entre les

  12. RNAslider: a faster engine for consecutive windows folding and its application to the analysis of genomic folding asymmetry.

    Science.gov (United States)

    Horesh, Yair; Wexler, Ydo; Lebenthal, Ilana; Ziv-Ukelson, Michal; Unger, Ron

    2009-03-04

    Scanning large genomes with a sliding window in search of locally stable RNA structures is a well motivated problem in bioinformatics. Given a predefined window size L and an RNA sequence S of size N (L free energy (MFE) for the folding of each of the L-sized substrings of S. The consecutive windows folding problem can be naively solved in O(NL3) by applying any of the classical cubic-time RNA folding algorithms to each of the N-L windows of size L. Recently an O(NL2) solution for this problem has been described. Here, we describe and implement an O(NLpsi(L)) engine for the consecutive windows folding problem, where psi(L) is shown to converge to O(1) under the assumption of a standard probabilistic polymer folding model, yielding an O(L) speedup which is experimentally confirmed. Using this tool, we note an intriguing directionality (5'-3' vs. 3'-5') folding bias, i.e. that the minimal free energy (MFE) of folding is higher in the native direction of the DNA than in the reverse direction of various genomic regions in several organisms including regions of the genomes that do not encode proteins or ncRNA. This bias largely emerges from the genomic dinucleotide bias which affects the MFE, however we see some variations in the folding bias in the different genomic regions when normalized to the dinucleotide bias. We also present results from calculating the MFE landscape of a mouse chromosome 1, characterizing the MFE of the long ncRNA molecules that reside in this chromosome. The efficient consecutive windows folding engine described in this paper allows for genome wide scans for ncRNA molecules as well as large-scale statistics. This is implemented here as a software tool, called RNAslider, and applied to the scanning of long chromosomes, leading to the observation of features that are visible only on a large scale.

  13. Asymmetric hindwing foldings in rove beetles.

    Science.gov (United States)

    Saito, Kazuya; Yamamoto, Shuhei; Maruyama, Munetoshi; Okabe, Yoji

    2014-11-18

    Foldable wings of insects are the ultimate deployable structures and have attracted the interest of aerospace engineering scientists as well as entomologists. Rove beetles are known to fold their wings in the most sophisticated ways that have right-left asymmetric patterns. However, the specific folding process and the reason for this asymmetry remain unclear. This study reveals how these asymmetric patterns emerge as a result of the folding process of rove beetles. A high-speed camera was used to reveal the details of the wing-folding movement. The results show that these characteristic asymmetrical patterns emerge as a result of simultaneous folding of overlapped wings. The revealed folding mechanisms can achieve not only highly compact wing storage but also immediate deployment. In addition, the right and left crease patterns are interchangeable, and thus each wing internalizes two crease patterns and can be folded in two different ways. This two-way folding gives freedom of choice for the folding direction to a rove beetle. The use of asymmetric patterns and the capability of two-way folding are unique features not found in artificial structures. These features have great potential to extend the design possibilities for all deployable structures, from space structures to articles of daily use.

  14. Kinetic partitioning mechanism of HDV ribozyme folding

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiawen; Gong, Sha; Wang, Yujie; Zhang, Wenbing, E-mail: wbzhang@whu.edu.cn [Department of Physics, Wuhan University, Wuhan, Hubei 430072 (China)

    2014-01-14

    RNA folding kinetics is directly tied to RNA biological functions. We introduce here a new approach for predicting the folding kinetics of RNA secondary structure with pseudoknots. This approach is based on our previous established helix-based method for predicting the folding kinetics of RNA secondary structure. In this approach, the transition rates for an elementary step: (1) formation, (2) disruption of a helix stem, and (3) helix formation with concomitant partial melting of an incompatible helix, are calculated with the free energy landscape. The folding kinetics of the Hepatitis delta virus (HDV) ribozyme and the mutated sequences are studied with this method. The folding pathways are identified by recursive searching the states with high net flux-in(out) population starting from the native state. The theory results are in good agreement with that of the experiments. The results indicate that the bi-phasic folding kinetics for the wt HDV sequence is ascribed to the kinetic partitioning mechanism: Part of the population will quickly fold to the native state along the fast pathway, while another part of the population will fold along the slow pathway, in which the population is trapped in a non-native state. Single mutation not only changes the folding rate but also the folding pathway.

  15. Vocal Fold Vibratory Changes Following Surgical Intervention.

    Science.gov (United States)

    Chen, Wenli; Woo, Peak; Murry, Thomas

    2016-03-01

    High-speed videoendoscopy (HSV) captures direct cycle-to-cycle visualization of vocal fold movement in real time. This ultrafast recording rate is capable of visualizing the vibratory motion of the vocal folds in severely disordered phonation and provides a direct method for examining vibratory changes after vocal fold surgery. The purpose of this study was to examine the vibratory motion before and after surgical intervention. HSV was captured from two subjects with identifiable midvocal fold benign lesions and six subjects with highly aperiodic vocal fold vibration before and after phonosurgery. Digital kymography (DKG) was used to extract high-speed kymographic vocal fold images sampled at the midmembranous, anterior 1/3, and posterior 1/3 region. Spectral analysis was subsequently applied to the DKG to quantify the cycle-to-cycle movements of the left and the right vocal fold, expressed as a spectrum. Before intervention, the vibratory spectrum consisted of decreased and flat-like spectral peaks with robust power asymmetry. After intervention, increases in spectral power and decreases in power symmetry were noted. Spectral power increases were most remarkable in the midmembranous region of the vocal fold. Surgical modification resulted in improved lateral excursion of the vocal folds, vibratory function, and perceptual measures of Voice Handicap Index-10. These changes in vibratory behavior trended toward normal vocal fold vibration. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  16. A folded plate clamped along one side only

    Science.gov (United States)

    Nazarov, Serguei A.; Slutskij, Andrey S.

    2017-12-01

    An asymptotic model of a folded thin elastic plate is posed on two plane domains and contains transmission conditions at the common line segment of their boundaries. These conditions become non-local and inhomogeneous if only one side of the plate is fixed. Solvability and smoothness results and error estimates for the model are derived. xml:lang="fr"

  17. The nature of folded states of globular proteins.

    Science.gov (United States)

    Honeycutt, J D; Thirumalai, D

    1992-06-01

    We suggest, using dynamical simulations of a simple heteropolymer modelling the alpha-carbon sequence in a protein, that generically the folded states of globular proteins correspond to statistically well-defined metastable states. This hypothesis, called the metastability hypothesis, states that there are several free energy minima separated by barriers of various heights such that the folded conformations of a polypeptide chain in each of the minima have similar structural characteristics but have different energies from one another. The calculated structural characteristics, such as bond angle and dihedral angle distribution functions, are assumed to arise from only those configurations belonging to a given minimum. The validity of this hypothesis is illustrated by simulations of a continuum model of a heteropolymer whose low temperature state is a well-defined beta-barrel structure. The simulations were done using a molecular dynamics algorithm (referred to as the "noisy" molecular dynamics method) containing both friction and noise terms. It is shown that for this model there are several distinct metastable minima in which the structural features are similar. Several new methods of analyzing fluctuations in structures belonging to two distinct minima are introduced. The most notable one is a dynamic measure of compactness that can in principle provide the time required for maximal compactness to be achieved. The analysis shows that for a given metastable state in which the protein has a well-defined folded structure the transition to a state of higher compactness occurs very slowly, lending credence to the notion that the system encounters a late barrier in the process of folding to the most compact structure. The examination of the fluctuations in the structures near the unfolding----folding transition temperature indicates that the transition state for the unfolding to folding process occurs closer to the folded state.

  18. Adaptive Origami for Efficiently Folded Structures

    Science.gov (United States)

    2016-02-01

    heating. Although a large fold angle at a high temperature is desirable in order to extrapolate the origami geometry toward closure, more emphasis is...AFRL-RQ-WP-TR-2016-0020 ADAPTIVE ORIGAMI FOR EFFICIENTLY FOLDED STRUCTURES James J. Joo and Greg Reich Design and Analysis Branch... ORIGAMI FOR EFFICIENTLY FOLDED STRUCTURES 5a. CONTRACT NUMBER In-house 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) James J

  19. Vocal fold paralysis secondary to phonotrauma.

    Science.gov (United States)

    Klein, Travis A L; Gaziano, Joy E; Ridley, Marion B

    2014-01-01

    A unique case of acute onset vocal fold paralysis secondary to phonotrauma is presented. The cause was forceful vocalization by a drill instructor on a firearm range. Imaging studies revealed extensive intralaryngeal and retropharyngeal hemorrhage. Laryngoscopy showed a complete left vocal fold paralysis. Relative voice rest was recommended, and the patient regained normal vocal fold mobility and function after approximately 12 weeks. Copyright © 2014 The Voice Foundation. All rights reserved.

  20. Spherical images and inextensible curved folding

    Science.gov (United States)

    Seffen, Keith A.

    2018-02-01

    In their study, Duncan and Duncan [Proc. R. Soc. London A 383, 191 (1982), 10.1098/rspa.1982.0126] calculate the shape of an inextensible surface folded in two about a general curve. They find the analytical relationships between pairs of generators linked across the fold curve, the shape of the original path, and the fold angle variation along it. They present two special cases of generator layouts for which the fold angle is uniform or the folded curve remains planar, for simplifying practical folding in sheet-metal processes. We verify their special cases by a graphical treatment according to a method of Gauss. We replace the fold curve by a piecewise linear path, which connects vertices of intersecting pairs of hinge lines. Inspired by the d-cone analysis by Farmer and Calladine [Int. J. Mech. Sci. 47, 509 (2005), 10.1016/j.ijmecsci.2005.02.013], we construct the spherical images for developable folding of successive vertices: the operating conditions of the special cases in Duncan and Duncan are then revealed straightforwardly by the geometric relationships between the images. Our approach may be used to synthesize folding patterns for novel deployable and shape-changing surfaces without need of complex calculation.

  1. A folding algorithm for extended RNA secondary structures.

    Science.gov (United States)

    Höner zu Siederdissen, Christian; Bernhart, Stephan H; Stadler, Peter F; Hofacker, Ivo L

    2011-07-01

    RNA secondary structure contains many non-canonical base pairs of different pair families. Successful prediction of these structural features leads to improved secondary structures with applications in tertiary structure prediction and simultaneous folding and alignment. We present a theoretical model capturing both RNA pair families and extended secondary structure motifs with shared nucleotides using 2-diagrams. We accompany this model with a number of programs for parameter optimization and structure prediction. All sources (optimization routines, RNA folding, RNA evaluation, extended secondary structure visualization) are published under the GPLv3 and available at www.tbi.univie.ac.at/software/rnawolf/.

  2. Guiding the folding pathway of DNA origami.

    Science.gov (United States)

    Dunn, Katherine E; Dannenberg, Frits; Ouldridge, Thomas E; Kwiatkowska, Marta; Turberfield, Andrew J; Bath, Jonathan

    2015-09-03

    DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short 'staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its

  3. RNA folding kinetics using Monte Carlo and Gillespie algorithms.

    Science.gov (United States)

    Clote, Peter; Bayegan, Amir H

    2018-04-01

    RNA secondary structure folding kinetics is known to be important for the biological function of certain processes, such as the hok/sok system in E. coli. Although linear algebra provides an exact computational solution of secondary structure folding kinetics with respect to the Turner energy model for tiny ([Formula: see text]20 nt) RNA sequences, the folding kinetics for larger sequences can only be approximated by binning structures into macrostates in a coarse-grained model, or by repeatedly simulating secondary structure folding with either the Monte Carlo algorithm or the Gillespie algorithm. Here we investigate the relation between the Monte Carlo algorithm and the Gillespie algorithm. We prove that asymptotically, the expected time for a K-step trajectory of the Monte Carlo algorithm is equal to [Formula: see text] times that of the Gillespie algorithm, where [Formula: see text] denotes the Boltzmann expected network degree. If the network is regular (i.e. every node has the same degree), then the mean first passage time (MFPT) computed by the Monte Carlo algorithm is equal to MFPT computed by the Gillespie algorithm multiplied by [Formula: see text]; however, this is not true for non-regular networks. In particular, RNA secondary structure folding kinetics, as computed by the Monte Carlo algorithm, is not equal to the folding kinetics, as computed by the Gillespie algorithm, although the mean first passage times are roughly correlated. Simulation software for RNA secondary structure folding according to the Monte Carlo and Gillespie algorithms is publicly available, as is our software to compute the expected degree of the network of secondary structures of a given RNA sequence-see http://bioinformatics.bc.edu/clote/RNAexpNumNbors .

  4. Intermediates and the folding of proteins L and G

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Scott; Head-Gordon, Teresa

    2003-07-01

    We use a minimalist protein model, in combination with a sequence design strategy, to determine differences in primary structure for proteins L and G that are responsible for the two proteins folding through distinctly different folding mechanisms. We find that the folding of proteins L and G are consistent with a nucleation-condensation mechanism, each of which is described as helix-assisted {beta}-1 and {beta}-2 hairpin formation, respectively. We determine that the model for protein G exhibits an early intermediate that precedes the rate-limiting barrier of folding and which draws together misaligned secondary structure elements that are stabilized by hydrophobic core contacts involving the third {beta}-strand, and presages the later transition state in which the correct strand alignment of these same secondary structure elements is restored. Finally the validity of the targeted intermediate ensemble for protein G was analyzed by fitting the kinetic data to a two-step first order reversible reaction, proving that protein G folding involves an on-pathway early intermediate, and should be populated and therefore observable by experiment.

  5. Monadic Maps and Folds for Arbitrary Datatypes

    NARCIS (Netherlands)

    Fokkinga, M.M.

    Each datatype constructor comes equiped not only with a so-called map and fold (catamorphism), as is widely known, but, under some condition, also with a kind of map and fold that are related to an arbitrary given monad. This result follows from the preservation of initiality under lifting

  6. Fold and Fit: Space Conserving Shape Editing

    KAUST Repository

    Ibrahim, Mohamed; Yan, Dong-Ming

    2017-01-01

    We present a framework that folds man-made objects in a structure-aware manner for space-conserving storage and transportation. Given a segmented 3D mesh of a man-made object, our framework jointly optimizes for joint locations, the folding order

  7. Merging monads and folds for functional programming

    NARCIS (Netherlands)

    Meijer, E.; Jeuring, J.T.

    1995-01-01

    These notes discuss the simultaneous use of generalised fold operators and monads to structure functional programs. Generalised fold operators structure programs after the decomposition of the value they consume. Monads structure programs after the computation of the value they produce. Our programs

  8. Theoretical study of the folded waveguide

    International Nuclear Information System (INIS)

    Chen, G.L.; Owens, T.L.; Whealton, J.H.

    1988-01-01

    We have applied a three-dimensional (3-D) algorithm for solving Maxwell's equations to the analysis of foleded waveguides used for fusion plasma heating at the ion cyclotron resonance frequency. A rigorous analysis of the magnetic field structure in the folded waveguide is presented. The results are compared to experimenntal measurements. Optimum conditions for the folded waveguide are discussed. 6 refs., 10 figs

  9. Experimental investigation into the mechanism of folding

    NARCIS (Netherlands)

    Kuenen, Ph.H.; Sitter, de L.U.

    1938-01-01

    The investigation of geological structures due to folding led de Sitter to form an opinion on the mechanical problems involved (Bibl. 7). His principal contention is that in simple cases the relative movements of particles with respect to eachother during deformation leading to a fold, have been

  10. A comparison of RNA folding measures

    Directory of Open Access Journals (Sweden)

    Gardner Paul P

    2005-10-01

    Full Text Available Abstract Background In the last few decades there has been a great deal of discussion concerning whether or not noncoding RNA sequences (ncRNAs fold in a more well-defined manner than random sequences. In this paper, we investigate several existing measures for how well an RNA sequence folds, and compare the behaviour of these measures over a large range of Rfam ncRNA families. Such measures can be useful in, for example, identifying novel ncRNAs, and indicating the presence of alternate RNA foldings. Results Our analysis shows that ncRNAs, but not mRNAs, in general have lower minimal free energy (MFE than random sequences with the same dinucleotide frequency. Moreover, even when the MFE is significant, many ncRNAs appear to not have a unique fold, but rather several alternative folds, at least when folded in silico. Furthermore, we find that the six investigated measures are correlated to varying degrees. Conclusion Due to the correlations between the different measures we find that it is sufficient to use only two of them in RNA folding studies, one to test if the sequence in question has lower energy than a random sequence with the same dinucleotide frequency (the Z-score and the other to see if the sequence has a unique fold (the average base-pair distance, D.

  11. Graph-representation of oxidative folding pathways

    Directory of Open Access Journals (Sweden)

    Kaján László

    2005-01-01

    Full Text Available Abstract Background The process of oxidative folding combines the formation of native disulfide bond with conformational folding resulting in the native three-dimensional fold. Oxidative folding pathways can be described in terms of disulfide intermediate species (DIS which can also be isolated and characterized. Each DIS corresponds to a family of folding states (conformations that the given DIS can adopt in three dimensions. Results The oxidative folding space can be represented as a network of DIS states interconnected by disulfide interchange reactions that can either create/abolish or rearrange disulfide bridges. We propose a simple 3D representation wherein the states having the same number of disulfide bridges are placed on separate planes. In this representation, the shuffling transitions are within the planes, and the redox edges connect adjacent planes. In a number of experimentally studied cases (bovine pancreatic trypsin inhibitor, insulin-like growth factor and epidermal growth factor, the observed intermediates appear as part of contiguous oxidative folding pathways. Conclusions Such networks can be used to visualize folding pathways in terms of the experimentally observed intermediates. A simple visualization template written for the Tulip package http://www.tulip-software.org/ can be obtained from V.A.

  12. [Clinical analysis of vocal fold firbrous mass].

    Science.gov (United States)

    Chen, Hao; Sun, Jing Wu; Wan, Guang Lun; Hu, Yan Ming

    2018-03-01

    To explore the character of laryngoscopy finding, voice, and therapy of vocal fold fibrous mass. Clinical data, morphology, voice character, surgery and pathology of 15 cases with vocal fold fibrous mass were analyzed. The morbidity of vocal fold fibrous mass might be related to overuse of voice and laryngopharyngeal reflex. Laryngoscopy revealed shuttle line appearance, smoothness and decreased mucosal wave of vocal fold. These patients were invalid for voice training and might be improved by surgery, but recovery is slow. The morbidity of vocal fold fibrous mass might be related to overuse of voice and laryngopharyngeal reflex. Conservative treatment is ineffective for this disease, and surgery might improve. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  13. Sarcoidosis Presenting as Bilateral Vocal Fold Immobility.

    Science.gov (United States)

    Hintze, Justin M; Gnagi, Sharon H; Lott, David G

    2018-05-01

    Bilateral true vocal fold paralysis is rarely attributable to inflammatory diseases. Sarcoidosis is a rare but important etiology of bilateral true vocal fold paralysis by compressive lymphadenopathy, granulomatous infiltration, and neural involvement. We describe the first reported case of sarcoidosis presenting as bilateral vocal fold immobility caused by direct fixation by granulomatous infiltration severe enough to necessitate tracheostomy insertion. In addition, we discuss the presentation, the pathophysiology, and the treatment of this disease with a review of the literature of previously reported cases of sarcoidosis-related vocal fold immobility. Sarcoidosis should therefore be an important consideration for the otolaryngologist's differential diagnosis of true vocal fold immobility. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  14. Microvascular lesions of the true vocal fold.

    Science.gov (United States)

    Postma, G N; Courey, M S; Ossoff, R H

    1998-06-01

    Microvascular lesions, also called varices or capillary ectasias, in contrast to vocal fold polyps with telangiectatic vessels, are relatively small lesions arising from the microcirculation of the vocal fold. Varices are most commonly seen in female professional vocalists and may be secondary to repetitive trauma, hormonal variations, or repeated inflammation. Microvascular lesions may either be asymptomatic or cause frank dysphonia by interrupting the normal vibratory pattern, mass, or closure of the vocal folds. They may also lead to vocal fold hemorrhage, scarring, or polyp formation. Laryngovideostroboscopy is the key in determining the functional significance of vocal fold varices. Management of patients with a varix includes medical therapy, speech therapy, and occasionally surgical vaporization. Indications for surgery are recurrent hemorrhage, enlargement of the varix, development of a mass in conjunction with the varix or hemorrhage, and unacceptable dysphonia after maximal medical and speech therapy due to a functionally significant varix.

  15. Delayed Collapse of Wooden Folding Stairs

    Science.gov (United States)

    Krentowski, Janusz; Chyzy, Tadeusz

    2017-10-01

    During operation of folding stairs, a fastener joining the ladder hanger with the frame was torn off. A person using the stairs sustained serious injury. In several dozen other locations similar accidents were observed. As a result of inspections, some threaded parts of the screws were found in the gaps between the wooden elements of the stairs’ flaps. In the construction a hatch made of wooden strips is attached to an external frame by means of metal hangers. Laboratory strength tests were conducted on three samples made of wooden elements identical to the ones used in the damaged stairs. Due to complex load distribution mechanism acting on the base of the structure, a three-dimensional FEM model was created. An original software was used for calculations. Five computational model variants were considered. As a result of the numerical analyses, it was unquestionably shown that faulty connections were the cause of the destruction of the stairs. The weakest link in the load transmission chain were found to have been the screws connecting the hatch board with the hangers.

  16. Energy Landscapes of Folding Chromosomes

    Science.gov (United States)

    Zhang, Bin

    The genome, the blueprint of life, contains nearly all the information needed to build and maintain an entire organism. A comprehensive understanding of the genome is of paramount interest to human health and will advance progress in many areas, including life sciences, medicine, and biotechnology. The overarching goal of my research is to understand the structure-dynamics-function relationships of the human genome. In this talk, I will be presenting our efforts in moving towards that goal, with a particular emphasis on studying the three-dimensional organization, the structure of the genome with multi-scale approaches. Specifically, I will discuss the reconstruction of genome structures at both interphase and metaphase by making use of data from chromosome conformation capture experiments. Computationally modeling of chromatin fiber at atomistic level from first principles will also be presented as our effort for studying the genome structure from bottom up.

  17. Solitons and protein folding: An In Silico experiment

    International Nuclear Information System (INIS)

    Ilieva, N.; Dai, J.; Sieradzan, A.; Niemi, A.

    2015-01-01

    Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen’s dogma states that the native 3D shape of a protein is completely determined by protein’s amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolved problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix–loop–helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics

  18. Solitons and protein folding: An In Silico experiment

    Energy Technology Data Exchange (ETDEWEB)

    Ilieva, N., E-mail: nevena.ilieva@parallel.bas.bg [Institute of Information and Communication Technologies, Bulgarian Aacademy of Sciences, Sofia (Bulgaria); Dai, J., E-mail: daijing491@gmail.com [School of Physics, Beijing Institute of Technology, Beijing (China); Sieradzan, A., E-mail: adams86@wp.pl [Faculty of Chemistry, University of Gdańsk, Gdańsk (Poland); Niemi, A., E-mail: Antti.Niemi@physics.uu.se [Department of Physics and Astronomy, Uppsala University, Uppsala (Sweden); LMPT–CNRS, Université de Tours, Tours (France)

    2015-10-28

    Protein folding [1] is the process of formation of a functional 3D structure from a random coil — the shape in which amino-acid chains leave the ribosome. Anfinsen’s dogma states that the native 3D shape of a protein is completely determined by protein’s amino acid sequence. Despite the progress in understanding the process rate and the success in folding prediction for some small proteins, with presently available physics-based methods it is not yet possible to reliably deduce the shape of a biologically active protein from its amino acid sequence. The protein-folding problem endures as one of the most important unresolved problems in science; it addresses the origin of life itself. Furthermore, a wrong fold is a common cause for a protein to lose its function or even endanger the living organism. Soliton solutions of a generalized discrete non-linear Schrödinger equation (GDNLSE) obtained from the energy function in terms of bond and torsion angles κ and τ provide a constructive theoretical framework for describing protein folds and folding patterns [2]. Here we study the dynamics of this process by means of molecular-dynamics simulations. The soliton manifestation is the pattern helix–loop–helix in the secondary structure of the protein, which explains the importance of understanding loop formation in helical proteins. We performed in silico experiments for unfolding one subunit of the core structure of gp41 from the HIV envelope glycoprotein (PDB ID: 1AIK [3]) by molecular-dynamics simulations with the MD package GROMACS. We analyzed 80 ns trajectories, obtained with one united-atom and two different all-atom force fields, to justify the side-chain orientation quantification scheme adopted in the studies and to eliminate force-field based artifacts. Our results are compatible with the soliton model of protein folding and provide first insight into soliton-formation dynamics.

  19. Folding and insertion thermodynamics of the transmembrane WALP peptide

    NARCIS (Netherlands)

    Bereau, T.; Bennett, W.F.D.; Pfaendtner, J.; Deserno, M.; Karttunen, M.E.J.

    2015-01-01

    The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)$_n$(L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural

  20. Folding and insertion thermodynamics of the transmembrane WALP peptide

    NARCIS (Netherlands)

    Bereau, T.; Bennett, W.F.D. Drew; Pfaendtner, J.; Deserno, M.; Karttunen, M.

    2015-01-01

    The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)n (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural

  1. Stretched versus compressed exponential kinetics in α-helix folding

    International Nuclear Information System (INIS)

    Hamm, Peter; Helbing, Jan; Bredenbeck, Jens

    2006-01-01

    In a recent paper (J. Bredenbeck, J. Helbing, J.R. Kumita, G.A. Woolley, P. Hamm, α-helix formation in a photoswitchable peptide tracked from picoseconds to microseconds by time resolved IR spectroscopy, Proc. Natl. Acad. Sci USA 102 (2005) 2379), we have investigated the folding of a photo-switchable α-helix with a kinetics that could be fit by a stretched exponential function exp(-(t/τ) β ). The stretching factor β became smaller as the temperature was lowered, a result which has been interpreted in terms of activated diffusion on a rugged energy surface. In the present paper, we discuss under which conditions diffusion problems occur with stretched exponential kinetics (β 1). We show that diffusion problems do have a strong tendency to yield stretched exponential kinetics, yet, that there are conditions (strong perturbation from equilibrium, performing the experiment in the folding direction) under which compressed exponential kinetics would be expected instead. We discuss the kinetics on free energy surfaces predicted by simple initiation-propagation models (zipper models) of α-helix folding, as well as by folding funnel models. We show that our recent experiment has been performed under condition for which models with strong downhill driving force, such as the zipper model, would predict compressed, rather than stretched exponential kinetics, in disagreement with the experimental observation. We therefore propose that the free energy surface along a reaction coordinate that governs the folding kinetics must be relatively flat and has a shape similar to a 1D golf course. We discuss how this conclusion can be unified with the thermodynamically well established zipper model by introducing an additional kinetic reaction coordinate

  2. Coarsely resolved topography along protein folding pathways

    Science.gov (United States)

    Fernández, Ariel; Kostov, Konstantin S.; Berry, R. Stephen

    2000-03-01

    The kinetic data from the coarse representation of polypeptide torsional dynamics described in the preceding paper [Fernandez and Berry, J. Chem. Phys. 112, 5212 (2000), preceding paper] is inverted by using detailed balance to obtain a topographic description of the potential-energy surface (PES) along the dominant folding pathway of the bovine pancreatic trypsin inhibitor (BPTI). The topography is represented as a sequence of minima and effective saddle points. The dominant folding pathway displays an overall monotonic decrease in energy with a large number of staircaselike steps, a clear signature of a good structure-seeker. The diversity and availability of alternative folding pathways is analyzed in terms of the Shannon entropy σ(t) associated with the time-dependent probability distribution over the kinetic ensemble of contact patterns. Several stages in the folding process are evident. Initially misfolded states form and dismantle revealing no definite pattern in the topography and exhibiting high Shannon entropy. Passage down a sequence of staircase steps then leads to the formation of a nativelike intermediate, for which σ(t) is much lower and fairly constant. Finally, the structure of the intermediate is refined to produce the native state of BPTI. We also examine how different levels of tolerance to mismatches of side chain contacts influence the folding kinetics, the topography of the dominant folding pathway, and the Shannon entropy. This analysis yields upper and lower bounds of the frustration tolerance required for the expeditious and robust folding of BPTI.

  3. Recovery of Vocal Fold Epithelium after Acute Phonotrauma.

    Science.gov (United States)

    Rousseau, Bernard; Kojima, Tsuyoshi; Novaleski, Carolyn K; Kimball, Emily E; Valenzuela, Carla V; Mizuta, Masanobu; Daniero, James J; Garrett, C Gaelyn; Sivasankar, M Preeti

    2017-01-01

    We investigated the timeline of tissue repair of vocal fold epithelium after acute vibration exposure using an in vivo rabbit model. Sixty-five New Zealand white breeder rabbits were randomized to 120 min of modal- or raised-intensity phonation. After the larynges were harvested at 0, 4, 8, and 24 h, and at 3 and 7 days, the vocal fold tissue was evaluated using electron microscopy and quantitative real-time polymerase chain reaction. There was an immediate decrease in the microprojection depth and height following raised-intensity phonation, paired with upregulation of cyclooxygenase-2. This initial 24-h period was also characterized by the significant downregulation of junction proteins. Interleukin 1β and transforming growth factor β1 were upregulated for 3 and 7 days, respectively, followed by an increase in epithelial cell surface depth at 3 and 7 days. These data appear to demonstrate a shift from inflammatory response to the initiation of a restorative process in the vocal fold epithelium between 24 h and 3 days. Despite the initial damage from raised-intensity phonation, the vocal fold epithelium demonstrates a remarkable capacity for the expeditious recovery of structural changes from transient episodes of acute phonotrauma. While structurally intact, the return of functional barrier integrity may be delayed by repeated episodes of phonotrauma and may also play an important role in the pathophysiology of vocal fold lesions. © 2017 S. Karger AG, Basel.

  4. Probabilistic analysis for identifying the driving force of protein folding

    Science.gov (United States)

    Tokunaga, Yoshihiko; Yamamori, Yu; Matubayasi, Nobuyuki

    2018-03-01

    Toward identifying the driving force of protein folding, energetics was analyzed in water for Trp-cage (20 residues), protein G (56 residues), and ubiquitin (76 residues) at their native (folded) and heat-denatured (unfolded) states. All-atom molecular dynamics simulation was conducted, and the hydration effect was quantified by the solvation free energy. The free-energy calculation was done by employing the solution theory in the energy representation, and it was seen that the sum of the protein intramolecular (structural) energy and the solvation free energy is more favorable for a folded structure than for an unfolded one generated by heat. Probabilistic arguments were then developed to determine which of the electrostatic, van der Waals, and excluded-volume components of the interactions in the protein-water system governs the relative stabilities between the folded and unfolded structures. It was found that the electrostatic interaction does not correspond to the preference order of the two structures. The van der Waals and excluded-volume components were shown, on the other hand, to provide the right order of preference at probabilities of almost unity, and it is argued that a useful modeling of protein folding is possible on the basis of the excluded-volume effect.

  5. Peptide folding in the presence of interacting protein crowders

    Energy Technology Data Exchange (ETDEWEB)

    Bille, Anna, E-mail: anna.bille@thep.lu.se; Irbäck, Anders, E-mail: anders@thep.lu.se [Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund (Sweden); Mohanty, Sandipan, E-mail: s.mohanty@fz-juelich.de [Jülich Supercomputing Centre, Institute for Advanced Simulation, Forschungszentrum Jülich, D-52425 Jülich (Germany)

    2016-05-07

    Using Monte Carlo methods, we explore and compare the effects of two protein crowders, BPTI and GB1, on the folding thermodynamics of two peptides, the compact helical trp-cage and the β-hairpin-forming GB1m3. The thermally highly stable crowder proteins are modeled using a fixed backbone and rotatable side-chains, whereas the peptides are free to fold and unfold. In the simulations, the crowder proteins tend to distort the trp-cage fold, while having a stabilizing effect on GB1m3. The extent of the effects on a given peptide depends on the crowder type. Due to a sticky patch on its surface, BPTI causes larger changes than GB1 in the melting properties of the peptides. The observed effects on the peptides stem largely from attractive and specific interactions with the crowder surfaces, and differ from those seen in reference simulations with purely steric crowder particles.

  6. Melody discrimination and protein fold classification

    Directory of Open Access Journals (Sweden)

    Robert P. Bywater

    2016-10-01

    Full Text Available One of the greatest challenges in theoretical biophysics and bioinformatics is the identification of protein folds from sequence data. This can be regarded as a pattern recognition problem. In this paper we report the use of a melody generation software where the inputs are derived from calculations of evolutionary information, secondary structure, flexibility, hydropathy and solvent accessibility from multiple sequence alignment data. The melodies so generated are derived from the sequence, and by inference, of the fold, in ways that give each fold a sound representation that may facilitate analysis, recognition, or comparison with other sequences.

  7. A bidirectional shape memory alloy folding actuator

    International Nuclear Information System (INIS)

    Paik, Jamie K; Wood, Robert J

    2012-01-01

    This paper presents a low-profile bidirectional folding actuator based on annealed shape memory alloy sheets applicable for meso- and microscale systems. Despite the advantages of shape memory alloys—high strain, silent operation, and mechanical simplicity—their application is often limited to unidirectional operation. We present a bidirectional folding actuator that produces two opposing 180° motions. A laser-patterned nickel alloy (Inconel 600) heater localizes actuation to the folding sections. The actuator has a thin ( < 1 mm) profile, making it appropriate for use in robotic origami. Various design parameters and fabrication variants are described and experimentally explored in the actuator prototype. (paper)

  8. Folded Plate Structures as Building Envelopes

    DEFF Research Database (Denmark)

    Falk, Andreas; Buelow, Peter von; Kirkegaard, Poul Henning

    2012-01-01

    This paper treats applications of cross-laminated timber (CLT) in structural systems for folded façade solutions. Previous work on CLT-based systems for folded roofs has shown a widening range of structural possibilities to develop timber-based shells. Geometric and material properties play...... CLT-based systems, which are studied and analysed by using a combination of digital tools for structural and environmental design and analysis. The results show gainful, rational properties of folded systems and beneficial effects from an integration of architectural and environmental performance...... criteria in the design of CLT-based façades....

  9. RNAslider: a faster engine for consecutive windows folding and its application to the analysis of genomic folding asymmetry

    Directory of Open Access Journals (Sweden)

    Ziv-Ukelson Michal

    2009-03-01

    Full Text Available Abstract Background Scanning large genomes with a sliding window in search of locally stable RNA structures is a well motivated problem in bioinformatics. Given a predefined window size L and an RNA sequence S of size N (L 3 by applying any of the classical cubic-time RNA folding algorithms to each of the N-L windows of size L. Recently an O(NL2 solution for this problem has been described. Results Here, we describe and implement an O(NLψ(L engine for the consecutive windows folding problem, where ψ(L is shown to converge to O(1 under the assumption of a standard probabilistic polymer folding model, yielding an O(L speedup which is experimentally confirmed. Using this tool, we note an intriguing directionality (5'-3' vs. 3'-5' folding bias, i.e. that the minimal free energy (MFE of folding is higher in the native direction of the DNA than in the reverse direction of various genomic regions in several organisms including regions of the genomes that do not encode proteins or ncRNA. This bias largely emerges from the genomic dinucleotide bias which affects the MFE, however we see some variations in the folding bias in the different genomic regions when normalized to the dinucleotide bias. We also present results from calculating the MFE landscape of a mouse chromosome 1, characterizing the MFE of the long ncRNA molecules that reside in this chromosome. Conclusion The efficient consecutive windows folding engine described in this paper allows for genome wide scans for ncRNA molecules as well as large-scale statistics. This is implemented here as a software tool, called RNAslider, and applied to the scanning of long chromosomes, leading to the observation of features that are visible only on a large scale.

  10. Folding very short peptides using molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Bosco K Ho

    2006-04-01

    Full Text Available Peptides often have conformational preferences. We simulated 133 peptide 8-mer fragments from six different proteins, sampled by replica-exchange molecular dynamics using Amber7 with a GB/SA (generalized-Born/solvent-accessible electrostatic approximation to water implicit solvent. We found that 85 of the peptides have no preferred structure, while 48 of them converge to a preferred structure. In 85% of the converged cases (41 peptides, the structures found by the simulations bear some resemblance to their native structures, based on a coarse-grained backbone description. In particular, all seven of the beta hairpins in the native structures contain a fragment in the turn that is highly structured. In the eight cases where the bioinformatics-based I-sites library picks out native-like structures, the present simulations are largely in agreement. Such physics-based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments.

  11. Topology Explains Why Automobile Sunshades Fold Oddly

    Science.gov (United States)

    Feist, Curtis; Naimi, Ramin

    2009-01-01

    Automobile sunshades always fold into an "odd" number of loops. The explanation why involves elementary topology (braid theory and linking number, both explained in detail here with definitions and examples), and an elementary fact from algebra about symmetric group.

  12. Reinke Edema: Watch For Vocal Fold Cysts.

    Science.gov (United States)

    Tüzüner, Arzu; Demirci, Sule; Yavanoglu, Ahmet; Kurkcuoglu, Melih; Arslan, Necmi

    2015-06-01

    Reinke edema is one of the common cause of dysphonia middle-aged population, and severe thickening of vocal folds require surgical treatment. Smoking plays a major role on etiology. Vocal fold cysts are also benign lesions and vocal trauma blamed for acquired cysts. We would like to present 3 cases with vocal fold cyst related with Reinke edema. First case had a subepidermal epidermoid cyst with Reinke edema, which could be easily observed before surgery during laryngostroboscopy. Second case had a mucous retention cyst into the edematous Reinke tissue, which was detected during surgical intervention, and third case had a epidermoid cyst that occurred 2 months after before microlaryngeal operation regarding Reinke edema reduction. These 3 cases revealed that surgical management of Reinke edema needs a careful dissection and close follow-up after surgery for presence of vocal fold cysts.

  13. Origami: Paper Folding--The Algorithmic Way.

    Science.gov (United States)

    Heukerott, Pamela Beth

    1988-01-01

    Describes origami, the oriental art of paper folding as an activity to teach upper elementary students concepts and skills in geometry involving polygons, angles, measurement, symmetry, and congruence. (PK)

  14. Self-folding miniature elastic electric devices

    International Nuclear Information System (INIS)

    Miyashita, Shuhei; Meeker, Laura; Rus, Daniela; Tolley, Michael T; Wood, Robert J

    2014-01-01

    Printing functional materials represents a considerable impact on the access to manufacturing technology. In this paper we present a methodology and validation of print-and-self-fold miniature electric devices. Polyvinyl chloride laminated sheets based on metalized polyester film show reliable self-folding processes under a heat application, and it configures 3D electric devices. We exemplify this technique by fabricating fundamental electric devices, namely a resistor, capacitor, and inductor. Namely, we show the development of a self-folded stretchable resistor, variable resistor, capacitive strain sensor, and an actuation mechanism consisting of a folded contractible solenoid coil. Because of their pre-defined kinematic design, these devices feature elasticity, making them suitable as sensors and actuators in flexible circuits. Finally, an RLC circuit obtained from the integration of developed devices is demonstrated, in which the coil based actuator is controlled by reading a capacitive strain sensor. (paper)

  15. Benign Lesions of The Vocal Fold

    Directory of Open Access Journals (Sweden)

    Ozgur Surmelioglu

    2013-02-01

    Full Text Available Benign lesions of vocal folds are common disorders. Fifty percent of patients who have sound complaints are found to have these lesions after endoscopic and stroboscopic examinations. Benign vocal fold diseases are primarily caused by vibratory trauma. However they may also occur as a result of viral infections and congenital causes. These lesions are often presented with the complaints of dysphonia. [Archives Medical Review Journal 2013; 22(1.000: 86-95

  16. Folding of non-Euclidean curved shells

    Science.gov (United States)

    Bende, Nakul; Evans, Arthur; Innes-Gold, Sarah; Marin, Luis; Cohen, Itai; Santangelo, Christian; Hayward, Ryan

    2015-03-01

    Origami-based folding of 2D sheets has been of recent interest for a variety of applications ranging from deployable structures to self-folding robots. Though folding of planar sheets follows well-established principles, folding of curved shells involves an added level of complexity due to the inherent influence of curvature on mechanics. In this study, we use principles from differential geometry and thin shell mechanics to establish fundamental rules that govern folding of prototypical creased shells. In particular, we show how the normal curvature of a crease line controls whether the deformation is smooth or discontinuous, and investigate the influence of shell thickness and boundary conditions. We show that snap-folding of shells provides a route to rapid actuation on time-scales dictated by the speed of sound. The simple geometric design principles developed can be applied at any length-scale, offering potential for bio-inspired soft actuators for tunable optics, microfluidics, and robotics. This work was funded by the National Science Foundation through EFRI ODISSEI-1240441 with additional support to S.I.-G. through the UMass MRSEC DMR-0820506 REU program.

  17. Vocal fold hemorrhage: factors predicting recurrence.

    Science.gov (United States)

    Lennon, Christen J; Murry, Thomas; Sulica, Lucian

    2014-01-01

    Vocal fold hemorrhage is an acute phonotraumatic injury treated with voice rest; recurrence is a generally accepted indication for surgical intervention. This study aims to identify factors predictive of recurrence based on outcomes of a large clinical series. Retrospective cohort. Retrospective review of cases of vocal fold hemorrhage presenting to a university laryngology service. Demographic information was compiled. Videostroboscopic exams were evaluated for hemorrhage extent, presence of varix, mucosal lesion, and/or vocal fold paresis. Vocal fold hemorrhage recurrence was the main outcome measure. Follow-up telephone survey was used to complement clinical data. Forty-seven instances of vocal fold hemorrhage were evaluated (25M:22F; 32 professional voice users). Twelve of the 47 (26%) patients experienced recurrence. Only the presence of varix demonstrated significant association with recurrence (P = 0.0089) on multivariate logistic regression. Vocal fold hemorrhage recurred in approximately 26% of patients. Varix was a predictor of recurrence, with 48% of those with varix experiencing recurrence. Monitoring, behavioral management and/or surgical intervention may be indicated to treat patients with such characteristics. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Kinematics, structural mechanics, and design of origami structures with smooth folds

    Science.gov (United States)

    Peraza Hernandez, Edwin Alexander

    Origami provides novel approaches to the fabrication, assembly, and functionality of engineering structures in various fields such as aerospace, robotics, etc. With the increase in complexity of the geometry and materials for origami structures that provide engineering utility, computational models and design methods for such structures have become essential. Currently available models and design methods for origami structures are generally limited to the idealization of the folds as creases of zeroth-order geometric continuity. Such an idealization is not proper for origami structures having non-negligible thickness or maximum curvature at the folds restricted by material limitations. Thus, for general structures, creased folds of merely zeroth-order geometric continuity are not appropriate representations of structural response and a new approach is needed. The first contribution of this dissertation is a model for the kinematics of origami structures having realistic folds of non-zero surface area and exhibiting higher-order geometric continuity, here termed smooth folds. The geometry of the smooth folds and the constraints on their associated kinematic variables are presented. A numerical implementation of the model allowing for kinematic simulation of structures having arbitrary fold patterns is also described. Examples illustrating the capability of the model to capture realistic structural folding response are provided. Subsequently, a method for solving the origami design problem of determining the geometry of a single planar sheet and its pattern of smooth folds that morphs into a given three-dimensional goal shape, discretized as a polygonal mesh, is presented. The design parameterization of the planar sheet and the constraints that allow for a valid pattern of smooth folds and approximation of the goal shape in a known folded configuration are presented. Various testing examples considering goal shapes of diverse geometries are provided. Afterwards, a

  19. The mechanics of fault-bend folding and tear-fault systems in the Niger Delta

    Science.gov (United States)

    Benesh, Nathan Philip

    This dissertation investigates the mechanics of fault-bend folding using the discrete element method (DEM) and explores the nature of tear-fault systems in the deep-water Niger Delta fold-and-thrust belt. In Chapter 1, we employ the DEM to investigate the development of growth structures in anticlinal fault-bend folds. This work was inspired by observations that growth strata in active folds show a pronounced upward decrease in bed dip, in contrast to traditional kinematic fault-bend fold models. Our analysis shows that the modeled folds grow largely by parallel folding as specified by the kinematic theory; however, the process of folding over a broad axial surface zone yields a component of fold growth by limb rotation that is consistent with the patterns observed in natural folds. This result has important implications for how growth structures can he used to constrain slip and paleo-earthquake ages on active blind-thrust faults. In Chapter 2, we expand our DEM study to investigate the development of a wider range of fault-bend folds. We examine the influence of mechanical stratigraphy and quantitatively compare our models with the relationships between fold and fault shape prescribed by the kinematic theory. While the synclinal fault-bend models closely match the kinematic theory, the modeled anticlinal fault-bend folds show robust behavior that is distinct from the kinematic theory. Specifically, we observe that modeled structures maintain a linear relationship between fold shape (gamma) and fault-horizon cutoff angle (theta), rather than expressing the non-linear relationship with two distinct modes of anticlinal folding that is prescribed by the kinematic theory. These observations lead to a revised quantitative relationship for fault-bend folds that can serve as a useful interpretation tool. Finally, in Chapter 3, we examine the 3D relationships of tear- and thrust-fault systems in the western, deep-water Niger Delta. Using 3D seismic reflection data and new

  20. Experimental investigation of protein folding and misfolding.

    Science.gov (United States)

    Dobson, Christopher M

    2004-09-01

    Newly synthesised proteins need to fold, often to intricate and close-packed structures, in order to function. The underlying mechanism by which this complex process takes place both in vitro and in vivo is now becoming understood, at least in general terms, as a result of the application of a wide range of biophysical and computational methods used in combination with the techniques of biochemistry and protein engineering. It is increasingly apparent, however, that folding is not only crucial for generating biological activity, but that it is also coupled to a wide range of processes within the cell, ranging from the trafficking of proteins to specific organelles to the regulation of cell growth and differentiation. Not surprisingly, therefore, the failure of proteins to fold appropriately, or to remain correctly folded, is associated with a large number of cellular malfunctions that give rise to disease. Misfolding, and its consequences such as aggregation, can be investigated by extending the types of techniques used to study the normal folding process. Application of these techniques is enabling the development of a unified description of the interconversion and regulation of the different conformational states available to proteins in living systems. Such a description proves a generic basis for understanding the fundamental links between protein misfolding and its associated clinical disorders, such as Alzheimer's disease and Type II diabetes, and for exploring novel therapeutic strategies directed at their prevention and treatment on a rational basis.

  1. Kinetics and Thermodynamics of Membrane Protein Folding

    Directory of Open Access Journals (Sweden)

    Ernesto A. Roman

    2014-03-01

    Full Text Available Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparison, advances in the membrane protein folding field lag far behind. Although membrane proteins constitute about a third of the proteins encoded in known genomes, stability studies on membrane proteins have been impaired due to experimental limitations. Furthermore, no systematic experimental strategies are available for folding these biomolecules in vitro. Common denaturing agents such as chaotropes usually do not work on helical membrane proteins, and ionic detergents have been successful denaturants only in few cases. Refolding a membrane protein seems to be a craftsman work, which is relatively straightforward for transmembrane β-barrel proteins but challenging for α-helical membrane proteins. Additional complexities emerge in multidomain membrane proteins, data interpretation being one of the most critical. In this review, we will describe some recent efforts in understanding the folding mechanism of membrane proteins that have been reversibly refolded allowing both thermodynamic and kinetic analysis. This information will be discussed in the context of current paradigms in the protein folding field.

  2. Measurement of stress in vocal folds during phonation using spatiotemporal synchronization

    International Nuclear Information System (INIS)

    Tao, Chao; Jiang, Jack J.; Zhang, Yu

    2007-01-01

    A method based on spatiotemporal synchronization is proposed to measure stress distribution in the vocal folds. It is theoretically proved that a measurement system can be synchronized with a vocal fold vibration system by coupling their surface dynamic variables. Therefore, the stress in the vocal folds is predicted by the synchronized continuous model. Numerical experiments are employed to verify this method. The influences of the different coupling variables and the parameter mismatches on stress measurement are also investigated

  3. Measurement of stress in vocal folds during phonation using spatiotemporal synchronization

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Chao [Department of Surgery, Division of Otolaryngology Head and Neck Surgery, University of Wisconsin Medical School, Madison, WI 53792-7375 (United States); Jiang, Jack J. [Department of Surgery, Division of Otolaryngology Head and Neck Surgery, University of Wisconsin Medical School, Madison, WI 53792-7375 (United States)]. E-mail: jiang@surgery.wisc.edu; Zhang, Yu [Department of Surgery, Division of Otolaryngology Head and Neck Surgery, University of Wisconsin Medical School, Madison, WI 53792-7375 (United States)

    2007-02-19

    A method based on spatiotemporal synchronization is proposed to measure stress distribution in the vocal folds. It is theoretically proved that a measurement system can be synchronized with a vocal fold vibration system by coupling their surface dynamic variables. Therefore, the stress in the vocal folds is predicted by the synchronized continuous model. Numerical experiments are employed to verify this method. The influences of the different coupling variables and the parameter mismatches on stress measurement are also investigated.

  4. The distribution of deformation in parallel fault-related folds with migrating axial surfaces: comparison between fault-propagation and fault-bend folding

    Science.gov (United States)

    Salvini, Francesco; Storti, Fabrizio

    2001-01-01

    In fault-related folds that form by axial surface migration, rocks undergo deformation as they pass through axial surfaces. The distribution and intensity of deformation in these structures has been impacted by the history of axial surface migration. Upon fold initiation, unique dip panels develop, each with a characteristic deformation intensity, depending on their history. During fold growth, rocks that pass through axial surfaces are transported between dip panels and accumulate additional deformation. By tracking the pattern of axial surface migration in model folds, we predict the distribution of relative deformation intensity in simple-step, parallel fault-bend and fault-propagation anticlines. In both cases the deformation is partitioned into unique domains we call deformation panels. For a given rheology of the folded multilayer, deformation intensity will be homogeneously distributed in each deformation panel. Fold limbs are always deformed. The flat crests of fault-propagation anticlines are always undeformed. Two asymmetric deformation panels develop in fault-propagation folds above ramp angles exceeding 29°. For lower ramp angles, an additional, more intensely-deformed panel develops at the transition between the crest and the forelimb. Deformation in the flat crests of fault-bend anticlines occurs when fault displacement exceeds the length of the footwall ramp, but is never found immediately hinterland of the crest to forelimb transition. In environments dominated by brittle deformation, our models may serve as a first-order approximation of the distribution of fractures in fault-related folds.

  5. The Risk of Vocal Fold Atrophy after Serial Corticosteroid Injections of the Vocal Fold.

    Science.gov (United States)

    Shi, Lucy L; Giraldez-Rodriguez, Laureano A; Johns, Michael M

    2016-11-01

    The aim of this study was to illustrate the risk of vocal fold atrophy in patients who receive serial subepithelial steroid injections for vocal fold scar. This study is a retrospective case report of two patients who underwent a series of weekly subepithelial infusions of 10 mg/mL dexamethasone for benign vocal fold lesion. Shortly after the procedures, both patients developed a weak and breathy voice. The first patient was a 53-year-old man with radiation-induced vocal fold stiffness. Six injections were performed unilaterally, and 1 week later, he developed unilateral vocal fold atrophy with new glottal insufficiency. The second patient was a 67-year-old woman with severe vocal fold inflammation related to laryngitis and calcinosis, Raynaud's phenomenon, esophagean dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. Five injections were performed bilaterally, and 1 week later, she developed bilateral vocal fold atrophy with a large midline glottal gap during phonation. In both cases, the steroid-induced vocal atrophy resolved spontaneously after 4 months. Serial subepithelial steroid infusions of the vocal folds, although safe in the majority of patients, carry the risk of causing temporary vocal fold atrophy when given at short intervals. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  6. Improvement of a Vocal Fold Imaging System

    Energy Technology Data Exchange (ETDEWEB)

    Krauter, K. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-02-01

    Medical professionals can better serve their patients through continual update of their imaging tools. A wide range of pathologies and disease may afflict human vocal cords or, as they’re also known, vocal folds. These diseases can affect human speech hampering the ability of the patient to communicate. Vocal folds must be opened for breathing and the closed to produce speech. Currently methodologies to image markers of potential pathologies are difficult to use and often fail to detect early signs of disease. These current methodologies rely on a strobe light and slower frame rate camera in an attempt to obtain images as the vocal folds travel over the full extent of their motion.

  7. Analysis of high-fold gamma data

    International Nuclear Information System (INIS)

    Radford, D. C.; Cromaz, M.; Beyer, C. J.

    1999-01-01

    Historically, γ-γ and γ-γ-γ coincidence spectra were utilized to build nuclear level schemes. With the development of large detector arrays, it has became possible to analyze higher fold coincidence data sets. This paper briefly reports on software to analyze 4-fold coincidence data sets that allows creation of 4-fold histograms (hypercubes) of at least 1024 channels per side (corresponding to a 43 gigachannel data space) that will fit onto a few gigabytes of disk space, and extraction of triple-gated spectra in a few seconds. Future detector arrays may have even much higher efficiencies, and detect as many as 15 or 20 γ rays simultaneously; such data will require very different algorithms for storage and analysis. Difficulties inherent in the analysis of such data are discussed, and two possible new solutions are presented, namely adaptive list-mode systems and 'list-list-mode' storage

  8. Extreme Mechanics: Self-Folding Origami

    Science.gov (United States)

    Santangelo, Christian D.

    2017-03-01

    Origami has emerged as a tool for designing three-dimensional structures from flat films. Because they can be fabricated by lithographic or roll-to-roll processing techniques, they have great potential for the manufacture of complicated geometries and devices. This article discusses the mechanics of origami and kirigami with a view toward understanding how to design self-folding origami structures. Whether an origami structure can be made to fold autonomously depends strongly on the geometry and kinematics of the origami fold pattern. This article collects some of the results on origami rigidity into a single framework, and discusses how these aspects affect the foldability of origami. Despite recent progress, most problems in origami and origami design remain completely open.

  9. In vitro folding of inclusion body proteins.

    Science.gov (United States)

    Rudolph, R; Lilie, H

    1996-01-01

    Insoluble, inactive inclusion bodies are frequently formed upon recombinant protein production in transformed microorganisms. These inclusion bodies, which contain the recombinant protein in an highly enriched form, can be isolated by solid/liquid separation. After solubilization, native proteins can be generated from the inactive material by using in vitro folding techniques. New folding procedures have been developed for efficient in vitro reconstitution of complex hydrophobic, multidomain, oligomeric, or highly disulfide-bonded proteins. These protocols take into account process parameters such as protein concentration, catalysis of disulfide bond formation, temperature, pH, and ionic strength, as well as specific solvent ingredients that reduce unproductive side reactions. Modification of the protein sequence has been exploited to improve in vitro folding.

  10. Exact folded-band chaotic oscillator.

    Science.gov (United States)

    Corron, Ned J; Blakely, Jonathan N

    2012-06-01

    An exactly solvable chaotic oscillator with folded-band dynamics is shown. The oscillator is a hybrid dynamical system containing a linear ordinary differential equation and a nonlinear switching condition. Bounded oscillations are provably chaotic, and successive waveform maxima yield a one-dimensional piecewise-linear return map with segments of both positive and negative slopes. Continuous-time dynamics exhibit a folded-band topology similar to Rössler's oscillator. An exact solution is written as a linear convolution of a fixed basis pulse and a discrete binary sequence, from which an equivalent symbolic dynamics is obtained. The folded-band topology is shown to be dependent on the symbol grammar.

  11. Heterochiral Knottin Protein: Folding and Solution Structure.

    Science.gov (United States)

    Mong, Surin K; Cochran, Frank V; Yu, Hongtao; Graziano, Zachary; Lin, Yu-Shan; Cochran, Jennifer R; Pentelute, Bradley L

    2017-10-31

    Homochirality is a general feature of biological macromolecules, and Nature includes few examples of heterochiral proteins. Herein, we report on the design, chemical synthesis, and structural characterization of heterochiral proteins possessing loops of amino acids of chirality opposite to that of the rest of a protein scaffold. Using the protein Ecballium elaterium trypsin inhibitor II, we discover that selective β-alanine substitution favors the efficient folding of our heterochiral constructs. Solution nuclear magnetic resonance spectroscopy of one such heterochiral protein reveals a homogeneous global fold. Additionally, steered molecular dynamics simulation indicate β-alanine reduces the free energy required to fold the protein. We also find these heterochiral proteins to be more resistant to proteolysis than homochiral l-proteins. This work informs the design of heterochiral protein architectures containing stretches of both d- and l-amino acids.

  12. Vascular lesions of the vocal fold.

    Science.gov (United States)

    Gökcan, Kürşat Mustafa; Dursun, Gürsel

    2009-04-01

    The aim of the study was to present symptoms, laryngological findings, clinical course, management modalities, and consequences of vascular lesions of vocal fold. This study examined 162 patients, the majority professional voice users, with vascular lesions regarding their presenting symptoms, laryngological findings, clinical courses and treatment results. The most common complaint was sudden hoarseness with hemorrhagic polyp. Microlaryngoscopic surgery was performed in 108 cases and the main indication of surgery was the presence of vocal fold mass or development of vocal polyp during clinical course. Cold microsurgery was utilized for removal of vocal fold masses and feeding vessels cauterized using low power, pulsed CO(2) laser. Acoustic analysis of patients revealed a significant improvement of jitter, shimmer and harmonics/noise ratio values after treatment. Depending on our clinical findings, we propose treatment algorithm where voice rest and behavioral therapy is the integral part and indications of surgery are individualized for each patient.

  13. Natural triple beta-stranded fibrous folds.

    Science.gov (United States)

    Mitraki, Anna; Papanikolopoulou, Katerina; Van Raaij, Mark J

    2006-01-01

    A distinctive family of beta-structured folds has recently been described for fibrous proteins from viruses. Virus fibers are usually involved in specific host-cell recognition. They are asymmetric homotrimeric proteins consisting of an N-terminal virus-binding tail, a central shaft or stalk domain, and a C-terminal globular receptor-binding domain. Often they are entirely or nearly entirely composed of beta-structure. Apart from their biological relevance and possible gene therapy applications, their shape, stability, and rigidity suggest they may be useful as blueprints for biomechanical design. Folding and unfolding studies suggest their globular C-terminal domain may fold first, followed by a "zipping-up" of the shaft domains. The C-terminal domains appear to be important for registration because peptides corresponding to shaft domains alone aggregate into nonnative fibers and/or amyloid structures. C-terminal domains can be exchanged between different fibers and the resulting chimeric proteins are useful as a way to solve structures of unknown parts of the shaft domains. The following natural triple beta-stranded fibrous folds have been discovered by X-ray crystallography: the triple beta-spiral, triple beta-helix, and T4 short tail fiber fold. All have a central longitudinal hydrophobic core and extensive intermonomer polar and nonpolar interactions. Now that a reasonable body of structural and folding knowledge has been assembled about these fibrous proteins, the next challenge and opportunity is to start using this information in medical and industrial applications such as gene therapy and nanotechnology.

  14. Laryngeal ultrasound and pediatric vocal fold nodules.

    Science.gov (United States)

    Ongkasuwan, Julina; Devore, Danielle; Hollas, Sarah; Jones, Jeremy; Tran, Brandon

    2017-03-01

    The term vocal fold nodules refers to bilateral thickening of the membranous folds with minimal impairment of the vibratory properties of the mucosa. Nodules are thought to be related to repetitive mechanical stress, associated with voice use patterns. Diagnosis is typically made in the office via either rigid or flexible laryngeal stroboscopy. Depending on the individual child, obtaining an optimal view of the larynx can be difficult if not impossible. Recent advances in high-frequency ultrasonography allows for transcervical examination of laryngeal structures. The goal of this project was to determine if laryngeal ultrasound (LUS) can be used to identify vocal fold nodules in dysphonic children. Prospective case-control study in which the patient acted as his or her own control. Forty-six pediatric patients were recruited for participation in this study; the mean age was 4.8 years. Twenty-three did not have any vocal fold lesions and 23 had a diagnosis of vocal fold nodules on laryngeal stroboscopy. Recorded LUSs were reviewed by two pediatric radiologists who were blinded to the nodule status. There was substantial inter-rater agreement (κ = 0.70, 95% confidence interval [CI]: 0.50-0.89) between the two radiologists regarding the presence of nodules. There was also substantial agreement (κ = 0.87, 95% CI: 0.72-1) between LUS and laryngeal stroboscopy. Sensitivity of LUS was 100% (95% CI: 85%-100%) and specificity was 87% (95% CI: 66%-97%). LUS can be used to identify vocal fold nodules in children with substantial agreement with laryngeal stroboscopy. 3b Laryngoscope, 127:676-678, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Periodic and stochastic thermal modulation of protein folding kinetics.

    Science.gov (United States)

    Platkov, Max; Gruebele, Martin

    2014-07-21

    Chemical reactions are usually observed either by relaxation of a bulk sample after applying a sudden external perturbation, or by intrinsic fluctuations of a few molecules. Here we show that the two ideas can be combined to measure protein folding kinetics, either by periodic thermal modulation, or by creating artificial thermal noise that greatly exceeds natural thermal fluctuations. We study the folding reaction of the enzyme phosphoglycerate kinase driven by periodic temperature waveforms. As the temperature waveform unfolds and refolds the protein, its fluorescence color changes due to FRET (Förster resonant Energy Transfer) of two donor/acceptor fluorophores labeling the protein. We adapt a simple model of periodically driven kinetics that nicely fits the data at all temperatures and driving frequencies: The phase shifts of the periodic donor and acceptor fluorescence signals as a function of driving frequency reveal reaction rates. We also drive the reaction with stochastic temperature waveforms that produce thermal fluctuations much greater than natural fluctuations in the bulk. Such artificial thermal noise allows the recovery of weak underlying signals due to protein folding kinetics. This opens up the possibility for future detection of a stochastic resonance for protein folding subject to noise with controllable amplitude.

  16. Biosimulation of inflammation and healing in surgically injured vocal folds.

    Science.gov (United States)

    Li, Nicole Y K; Vodovotz, Yoram; Hebda, Patricia A; Abbott, Katherine Verdolini

    2010-06-01

    The pathogenesis of vocal fold scarring is complex and remains to be deciphered. The current study is part of research endeavors aimed at applying systems biology approaches to address the complex biological processes involved in the pathogenesis of vocal fold scarring and other lesions affecting the larynx. We developed a computational agent-based model (ABM) to quantitatively characterize multiple cellular and molecular interactions involved in inflammation and healing in vocal fold mucosa after surgical trauma. The ABM was calibrated with empirical data on inflammatory mediators (eg, tumor necrosis factor) and extracellular matrix components (eg, hyaluronan) from published studies on surgical vocal fold injury in the rat population. The simulation results reproduced and predicted trajectories seen in the empirical data from the animals. Moreover, the ABM studies suggested that hyaluronan fragments might be the clinical surrogate of tissue damage, a key variable that in these simulations both is enhanced by and further induces inflammation. A relatively simple ABM such as the one reported in this study can provide new understanding of laryngeal wound healing and generate working hypotheses for further wet-lab studies.

  17. Stretching and folding mechanism in foams

    International Nuclear Information System (INIS)

    Tufaile, Alberto; Pedrosa Biscaia Tufaile, Adriana

    2008-01-01

    We have described the stretching and folding of foams in a vertical Hele-Shaw cell containing air and a surfactant solution, from a sequence of upside-down flips. Besides the fractal dimension of the foam, we have observed the logistic growth for the soap film length. The stretching and folding mechanism is present during the foam formation, and this mechanism is observed even after the foam has reached its respective maximum fractal dimension. Observing the motion of bubbles inside the foam, large bubbles present power spectrum associated with random walk motion in both directions, while the small bubbles are scattered like balls in a Galton board

  18. Assessment of thyroplasty for vocal fold paralysis

    DEFF Research Database (Denmark)

    Grøntved, Ågot Møller; Faber, Christian; Jakobsen, John

    2009-01-01

    INTRODUCTION: Thyroplasty with silicone rubber implantation is a surgical procedure for treatment of patients with vocal fold paralysis. The aim of the present study was to evaluate the outcome of the operation and to monitor which of the analyses were the more beneficial. MATERIAL AND METHODS...... because it offers a quantitative measure of the voice capacity and intensity, which are the major problems experienced by patients with vocal fold paralysis. Used together, these tools are highly instrumental in guiding the patient's choice of surgery or no surgery. Udgivelsesdato: 2009-Jan-12...

  19. Stretching and folding mechanism in foams

    Energy Technology Data Exchange (ETDEWEB)

    Tufaile, Alberto [Escola de Artes, Ciencias e Humanidades, Soft Matter Laboratory, Universidade de Sao Paulo, 03828-000 Sao Paulo, SP (Brazil)], E-mail: tufaile@usp.br; Pedrosa Biscaia Tufaile, Adriana [Escola de Artes, Ciencias e Humanidades, Soft Matter Laboratory, Universidade de Sao Paulo, 03828-000 Sao Paulo, SP (Brazil)

    2008-10-13

    We have described the stretching and folding of foams in a vertical Hele-Shaw cell containing air and a surfactant solution, from a sequence of upside-down flips. Besides the fractal dimension of the foam, we have observed the logistic growth for the soap film length. The stretching and folding mechanism is present during the foam formation, and this mechanism is observed even after the foam has reached its respective maximum fractal dimension. Observing the motion of bubbles inside the foam, large bubbles present power spectrum associated with random walk motion in both directions, while the small bubbles are scattered like balls in a Galton board.

  20. Nucleation phenomena in protein folding: the modulating role of protein sequence

    International Nuclear Information System (INIS)

    Travasso, Rui D M; FaIsca, Patricia F N; Gama, Margarida M Telo da

    2007-01-01

    For the vast majority of naturally occurring, small, single-domain proteins, folding is often described as a two-state process that lacks detectable intermediates. This observation has often been rationalized on the basis of a nucleation mechanism for protein folding whose basic premise is the idea that, after completion of a specific set of contacts forming the so-called folding nucleus, the native state is achieved promptly. Here we propose a methodology to identify folding nuclei in small lattice polymers and apply it to the study of protein molecules with a chain length of N = 48. To investigate the extent to which protein topology is a robust determinant of the nucleation mechanism, we compare the nucleation scenario of a native-centric model with that of a sequence-specific model sharing the same native fold. To evaluate the impact of the sequence's finer details in the nucleation mechanism, we consider the folding of two non-homologous sequences. We conclude that, in a sequence-specific model, the folding nucleus is, to some extent, formed by the most stable contacts in the protein and that the less stable linkages in the folding nucleus are solely determined by the fold's topology. We have also found that, independently of the protein sequence, the folding nucleus performs the same 'topological' function. This unifying feature of the nucleation mechanism results from the residues forming the folding nucleus being distributed along the protein chain in a similar and well-defined manner that is determined by the fold's topological features

  1. Transient intermediates are populated in the folding pathways of single-domain two-state folding protein L

    Science.gov (United States)

    Maity, Hiranmay; Reddy, Govardhan

    2018-04-01

    Small single-domain globular proteins, which are believed to be dominantly two-state folders, played an important role in elucidating various aspects of the protein folding mechanism. However, recent single molecule fluorescence resonance energy transfer experiments [H. Y. Aviram et al. J. Chem. Phys. 148, 123303 (2018)] on a single-domain two-state folding protein L showed evidence for the population of an intermediate state and it was suggested that in this state, a β-hairpin present near the C-terminal of the native protein state is unfolded. We performed molecular dynamics simulations using a coarse-grained self-organized-polymer model with side chains to study the folding pathways of protein L. In agreement with the experiments, an intermediate is populated in the simulation folding pathways where the C-terminal β-hairpin detaches from the rest of the protein structure. The lifetime of this intermediate structure increased with the decrease in temperature. In low temperature conditions, we also observed a second intermediate state, which is globular with a significant fraction of the native-like tertiary contacts satisfying the features of a dry molten globule.

  2. Folding of multidomain proteins: biophysical consequences of tethering even in apparently independent folding.

    Science.gov (United States)

    Arviv, Oshrit; Levy, Yaakov

    2012-12-01

    Most eukaryotic and a substantial fraction of prokaryotic proteins are composed of more than one domain. The tethering of these evolutionary, structural, and functional units raises, among others, questions regarding the folding process of conjugated domains. Studying the folding of multidomain proteins in silico enables one to identify and isolate the tethering-induced biophysical determinants that govern crosstalks generated between neighboring domains. For this purpose, we carried out coarse-grained and atomistic molecular dynamics simulations of two two-domain constructs from the immunoglobulin-like β-sandwich fold. Each of these was experimentally shown to behave as the "sum of its parts," that is, the thermodynamic and kinetic folding behavior of the constituent domains of these constructs seems to occur independently, with the folding of each domain uncoupled from the folding of its partner in the two-domain construct. We show that the properties of the individual domains can be significantly affected by conjugation to another domain. The tethering may be accompanied by stabilizing as well as destabilizing factors whose magnitude depends on the size of the interface, the length, and the flexibility of the linker, and the relative stability of the domains. Accordingly, the folding of a multidomain protein should not be viewed as the sum of the folding patterns of each of its parts, but rather, it involves abrogating several effects that lead to this outcome. An imbalance between these effects may result in either stabilization or destabilization owing to the tethering. Copyright © 2012 Wiley Periodicals, Inc.

  3. A comparison of RNA folding measures

    DEFF Research Database (Denmark)

    Freyhult, E.; Gardner, P. P.; Moulton, V.

    2005-01-01

    the behaviour of these measures over a large range of Rfam ncRNA families. Such measures can be useful in, for example, identifying novel ncRNAs, and indicating the presence of alternate RNA foldings. Results Our analysis shows that ncRNAs, but not mRNAs, in general have lower minimal free energy (MFE) than....... Conclusion Due to the correlations between the different measures we find that it is sufficient to use only two of them in RNA folding studies, one to test if the sequence in question has lower energy than a random sequence with the same dinucleotide frequency (the Z-score) and the other to see......Background In the last few decades there has been a great deal of discussion concerning whether or not noncoding RNA sequences (ncRNAs) fold in a more well-defined manner than random sequences. In this paper, we investigate several existing measures for how well an RNA sequence folds, and compare...

  4. Mapping the universe of RNA tetraloop folds

    DEFF Research Database (Denmark)

    Bottaro, Sandro; Lindorff-Larsen, Kresten

    2017-01-01

    We report a map of RNA tetraloop conformations constructed by calculating pairwise distances among all experimentally determined four-nucleotide hairpin loops. Tetraloops with similar structures are clustered together and, as expected, the two largest clusters are the canonical GNRA and UNCG fold...

  5. Fold in Origami and Unfold Math

    Science.gov (United States)

    Georgeson, Joseph

    2011-01-01

    Students enjoy origami and like making everything from paper cranes to footballs out of small, colorful squares of paper. They can invent their own shapes and are intrigued by the polyhedrons that they can construct. Paper folding is fun, but where is the math? Unless teachers develop lessons that address mathematical objectives, origami could be…

  6. Self-folding graphene-polymer bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Tao [Institute of Microelectronics, Tsinghua University, Beijing 100084 (China); Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Yoon, ChangKyu [Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Jin, Qianru [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Li, Mingen [Department of Physics, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Liu, Zewen [Institute of Microelectronics, Tsinghua University, Beijing 100084 (China); Gracias, David H., E-mail: dgracias@jhu.edu [Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States)

    2015-05-18

    In order to incorporate the extraordinary intrinsic thermal, electrical, mechanical, and optical properties of graphene with three dimensional (3D) flexible substrates, we introduce a solvent-driven self-folding approach using graphene-polymer bilayers. A polymer (SU-8) film was spin coated atop chemically vapor deposited graphene films on wafer substrates and graphene-polymer bilayers were patterned with or without metal electrodes using photolithography, thin film deposition, and etching. After patterning, the bilayers were released from the substrates and they self-folded to form fully integrated, curved, and folded structures. In contrast to planar graphene sensors on rigid substrates, we assembled curved and folded sensors that are flexible and they feature smaller form factors due to their 3D geometry and large surface areas due to their multiple rolled architectures. We believe that this approach could be used to assemble a range of high performance 3D electronic and optical devices of relevance to sensing, diagnostics, wearables, and energy harvesting.

  7. Targeted transtracheal stimulation for vocal fold closure.

    Science.gov (United States)

    Hadley, Aaron J; Thompson, Paul; Kolb, Ilya; Hahn, Elizabeth C; Tyler, Dustin J

    2014-06-01

    Paralysis of the structures in the head and neck due to stroke or other neurological disorder often causes dysphagia (difficulty in swallowing). Patients with dysphagia have a significantly higher incidence of aspiration pneumonia and death. The recurrent laryngeal nerve (RLN), which innervates the intrinsic laryngeal muscles that control the vocal folds, travels superiorly in parallel to the trachea in the tracheoesophageal groove. This study tests the hypothesis that functional electrical stimulation (FES) applied via transtracheal electrodes can produce controlled vocal fold adduction. Bipolar electrodes were placed at 15° intervals around the interior mucosal surface of the canine trachea, and current was applied to the tissue while electromyography (EMG) from the intrinsic laryngeal muscles and vocal fold movement visualization via laryngoscopy were recorded. The lowest EMG thresholds were found at an average location of 100° to the left of the ventral midsagittal line and 128° to the right. A rotatable pair of bipolar electrodes spaced 230° apart were able to stimulate bilaterally both RLNs in every subject. Laryngoscopy showed complete glottal closure with transtracheal stimulation in six of the eight subjects, and this closure was maintained under simultaneous FES-induced laryngeal elevation. Transtracheal stimulation is an effective tool for minimally invasive application of FES to induce vocal fold adduction, providing an alternative mechanism to study airway protection.

  8. Amylose folding under the influence of lipids

    NARCIS (Netherlands)

    Lopez, Cesar A.; de Vries, Alex H.; Marrink, Siewert J.

    2012-01-01

    The molecular dynamics simulation technique was used to study the folding and complexation process of a short amylose fragment in the presence of lipids. In aqueous solution, the amylose chain remains as an extended left-handed helix. After the addition of lipids in the system, however, we observe

  9. MARATHON DESPITE UNILATERAL VOCAL FOLD PARALYSIS

    Directory of Open Access Journals (Sweden)

    Matthias Echternach

    2008-06-01

    Full Text Available The principal symptoms of unilateral vocal fold paralysis are hoarseness and difficulty in swallowing. Dyspnea is comparatively rare (Laccourreye et al., 2003. The extent to which unilateral vocal fold paralysis may lead to respiratory problems at all - in contrast to bilateral vocal fold paralysis- has not yet well been determined. On the one hand, inspiration is impaired with unilateral vocal fold paralysis; on the other hand, neither the position of the vocal fold paralysis nor the degree of breathiness correlates with respiratory parameters (Cantarella et al., 2003; 2005. The question of what respiratory stress a patient with a vocal fold paresis can endure has not yet been dealt with.A 43 year-old female patient was suffering from recurrent unspecific respiratory complaints for four months after physical activity. During training for a marathon, she experienced no difficulty in breathing. These unspecific respiratory complaints occurred only after athletic activity and persisted for hours. The patient observed neither an increased coughing nor a stridor. Her voice remained unaltered during the attacks, nor were there any signs of a symptomatic gastroesophageal reflux or infectious disease. A cardio-pulmonary and a radiological examination by means of an X-ray of the thorax also revealed no pathological phenomena. As antiallergic and antiobstructive therapy remained unsuccessful, a laryngological examination was performed in order to exclude a vocal cord dysfunction.Surprisingly enough, the laryngostroboscopy showed, as an initial description, a vocal fold paralysis of the left vocal fold in median position (Figure 1. The anamnestic background for the cause was unclear. The only clue was a thoracotomy on the left side due to a pleuritis in childhood. A subsequent laryngoscopic examination had never been performed. Good mucosa waves and amplitudes were shown bilateral with complete glottal closure. Neither in the acoustic analysis, nor in the

  10. Towards a systematic classification of protein folds

    DEFF Research Database (Denmark)

    Lindgård, Per-Anker; Bohr, Henrik

    1997-01-01

    structures are given a unique name, which simultaneously represent a linear string of physical coupling constants describing hinge spin interactions. We have defined a metric and a precise distance measure between the fold classes. An automated procedure is constructed in which any protein structure...

  11. Vocal fold submucosal infusion technique in phonomicrosurgery.

    Science.gov (United States)

    Kass, E S; Hillman, R E; Zeitels, S M

    1996-05-01

    Phonomicrosurgery is optimized by maximally preserving the vocal fold's layered microstructure (laminae propriae). The technique of submucosal infusion of saline and epinephrine into the superficial lamina propria (SLP) was examined to delineate how, when, and why it was helpful toward this surgical goal. A retrospective review revealed that the submucosal infusion technique was used to enhance the surgery in 75 of 152 vocal fold procedures that were performed over the last 2 years. The vocal fold epithelium was noted to be adherent to the vocal ligament in 29 of the 75 cases: 19 from previous surgical scarring, 4 from cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1 from radiotherapy. The submucosal infusion technique was most helpful when the vocal fold epithelium required resection and/or when extensive dissection in the SLP was necessary. The infusion enhanced the surgery by vasoconstriction of the microvasculature in the SLP, which improved visualization during cold-instrument tangential dissection. Improved visualization facilitated maximal preservation of the SLP, which is necessary for optimal pliability of the overlying epithelium. The infusion also improved the placement of incisions at the perimeter of benign, premalignant, and malignant lesions, and thereby helped preserve epithelium uninvolved by the disorder.

  12. Predicting protein folding pathways at the mesoscopic level based on native interactions between secondary structure elements

    Directory of Open Access Journals (Sweden)

    Sze Sing-Hoi

    2008-07-01

    Full Text Available Abstract Background Since experimental determination of protein folding pathways remains difficult, computational techniques are often used to simulate protein folding. Most current techniques to predict protein folding pathways are computationally intensive and are suitable only for small proteins. Results By assuming that the native structure of a protein is known and representing each intermediate conformation as a collection of fully folded structures in which each of them contains a set of interacting secondary structure elements, we show that it is possible to significantly reduce the conformation space while still being able to predict the most energetically favorable folding pathway of large proteins with hundreds of residues at the mesoscopic level, including the pig muscle phosphoglycerate kinase with 416 residues. The model is detailed enough to distinguish between different folding pathways of structurally very similar proteins, including the streptococcal protein G and the peptostreptococcal protein L. The model is also able to recognize the differences between the folding pathways of protein G and its two structurally similar variants NuG1 and NuG2, which are even harder to distinguish. We show that this strategy can produce accurate predictions on many other proteins with experimentally determined intermediate folding states. Conclusion Our technique is efficient enough to predict folding pathways for both large and small proteins at the mesoscopic level. Such a strategy is often the only feasible choice for large proteins. A software program implementing this strategy (SSFold is available at http://faculty.cs.tamu.edu/shsze/ssfold.

  13. Folding and Fracturing of Rocks: the background

    Science.gov (United States)

    Ramsay, John G.

    2017-04-01

    This book was generated by structural geology teaching classes at Imperial College. I was appointed lecturer during 1957 and worked together with Dr Gilbert Wilson teaching basic structural geology at B.Sc level. I became convinced that the subject, being essentially based on geometric field observations, required a firm mathematical basis for its future development. In particular it seemed to me to require a very sound understanding of stress and strain. My field experience suggested that a knowledge of two- and three-demensional strain was critical in understanding natural tectonic processes. I found a rich confirmation for this in early publications of deformed fossils, oolitic limestones and spotted slates made by several geologists around the beginning of the 20th century (Sorby, Philips, Haughton, Harker) often using surprisingly sophisticated mathematical methods. These methods were discussed and elaborated in Folding and Fracturing of Rocks in a practical way. The geometric features of folds were related to folding mechanisms and the fold related small scale structures such as cleavage, schistosity and lineation explained in terms of rock strain. My work in the Scottish Highlands had shown just how repeated fold superposition could produce very complex geometric features, while further work in other localities suggested that such geometric complications are common in many orogenic zones. From the development of structural geological studies over the past decades it seems that the readers of this book have found many of the ideas set out are still of practical application. The mapping of these outcrop-scale structures should be emphasised in all field studies because they can be seen as ''fingerprints'' of regional scale tectonic processes. My own understanding of structural geology has been inspired by field work and I am of the opinion that future progress in understanding will be likewise based on careful observation and measurement of the features of

  14. ETIOLOGICAL FACTORS FOR VOCAL FOLD POLYP FORMATION

    Directory of Open Access Journals (Sweden)

    DAŠA GLUVAJIĆ

    2016-05-01

    Full Text Available Background: Vocal fold polyp is one of the most common causes for hoarseness. Many different etiological factors contribute to vocal fold polyp formation. The aim of the study was to find out whether the etiological factors for polyp formation have changed in the last 30 years.Methods: Eighty-one patients with unilateral vocal fold polyp were included in the study. A control group was composed of 50 volunteers without voice problems who matched the patients by age and gender. The data about etiological factors and the findings of phoniatric examination were obtained from the patients' medical documentation and from the questionnaires for the control group. The incidence of etiological factors was compared between the two groups. The program SPSS, Version 18 was used for statistical analysis.Results: The most frequent etiological factors were occupational voice load, GER, allergy and smoking. In 79% of patients 2 – 6 contemporary acting risk factors were found. Occupational voice load (p=0,018 and GER (p=0,004 were significantly more frequent in the patients than in the controls. The other factors did not significantly influence the polyp formation.Conclusions: There are several factors involved simultaneously in the formation of vocal fold polyps both nowadays and 30 years ago. Some of the most common factors remain the same (voice load, smoking, others are new (GER, allergy, which is probably due to the different lifestyle and working conditions than 30 years ago. Occupational voice load and GER were significantly more frequently present in the patients with polyp than in the control group. Regarding the given results it is important to instruct workers with professional vocal load about etiological factors for vocal fold polyp formation.

  15. Inverse folding of RNA pseudoknot structures

    Directory of Open Access Journals (Sweden)

    Li Linda YM

    2010-06-01

    Full Text Available Abstract Background RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures. Results In this paper we present the inverse folding algorithm Inv. We give a detailed analysis of Inv, including pseudocodes. We show that Inv allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. Inv is freely available at http://www.combinatorics.cn/cbpc/inv.html. Conclusions The algorithm Inv extends inverse folding capabilities to RNA pseudoknot structures. In comparison with RNAinverse it uses new ideas, for instance by considering sets of competing structures. As a result, Inv is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions.

  16. Influence of Left-Right Asymmetries on Voice Quality in Simulated Paramedian Vocal Fold Paralysis

    Science.gov (United States)

    Samlan, Robin A.; Story, Brad H.

    2017-01-01

    Purpose: The purpose of this study was to determine the vocal fold structural and vibratory symmetries that are important to vocal function and voice quality in a simulated paramedian vocal fold paralysis. Method: A computational kinematic speech production model was used to simulate an exemplar "voice" on the basis of asymmetric…

  17. Entropic formulation for the protein folding process: Hydrophobic stability correlates with folding rates

    Science.gov (United States)

    Dal Molin, J. P.; Caliri, A.

    2018-01-01

    Here we focus on the conformational search for the native structure when it is ruled by the hydrophobic effect and steric specificities coming from amino acids. Our main tool of investigation is a 3D lattice model provided by a ten-letter alphabet, the stereochemical model. This minimalist model was conceived for Monte Carlo (MC) simulations when one keeps in mind the kinetic behavior of protein-like chains in solution. We have three central goals here. The first one is to characterize the folding time (τ) by two distinct sampling methods, so we present two sets of 103 MC simulations for a fast protein-like sequence. The resulting sets of characteristic folding times, τ and τq were obtained by the application of the standard Metropolis algorithm (MA), as well as by an enhanced algorithm (Mq A). The finding for τq shows two things: (i) the chain-solvent hydrophobic interactions {hk } plus a set of inter-residues steric constraints {ci,j } are able to emulate the conformational search for the native structure. For each one of the 103MC performed simulations, the target is always found within a finite time window; (ii) the ratio τq / τ ≅ 1 / 10 suggests that the effect of local thermal fluctuations, encompassed by the Tsallis weight, provides to the chain an innate efficiency to escape from energetic and steric traps. We performed additional MC simulations with variations of our design rule to attest this first result, both algorithms the MA and the Mq A were applied to a restricted set of targets, a physical insight is provided. Our second finding was obtained by a set of 600 independent MC simulations, only performed with the Mq A applied to an extended set of 200 representative targets, our native structures. The results show how structural patterns should modulate τq, which cover four orders of magnitude; this finding is our second goal. The third, and last result, was obtained with a special kind of simulation performed with the purpose to explore a

  18. Protein fold recognition using geometric kernel data fusion.

    Science.gov (United States)

    Zakeri, Pooya; Jeuris, Ben; Vandebril, Raf; Moreau, Yves

    2014-07-01

    Various approaches based on features extracted from protein sequences and often machine learning methods have been used in the prediction of protein folds. Finding an efficient technique for integrating these different protein features has received increasing attention. In particular, kernel methods are an interesting class of techniques for integrating heterogeneous data. Various methods have been proposed to fuse multiple kernels. Most techniques for multiple kernel learning focus on learning a convex linear combination of base kernels. In addition to the limitation of linear combinations, working with such approaches could cause a loss of potentially useful information. We design several techniques to combine kernel matrices by taking more involved, geometry inspired means of these matrices instead of convex linear combinations. We consider various sequence-based protein features including information extracted directly from position-specific scoring matrices and local sequence alignment. We evaluate our methods for classification on the SCOP PDB-40D benchmark dataset for protein fold recognition. The best overall accuracy on the protein fold recognition test set obtained by our methods is ∼ 86.7%. This is an improvement over the results of the best existing approach. Moreover, our computational model has been developed by incorporating the functional domain composition of proteins through a hybridization model. It is observed that by using our proposed hybridization model, the protein fold recognition accuracy is further improved to 89.30%. Furthermore, we investigate the performance of our approach on the protein remote homology detection problem by fusing multiple string kernels. The MATLAB code used for our proposed geometric kernel fusion frameworks are publicly available at http://people.cs.kuleuven.be/∼raf.vandebril/homepage/software/geomean.php?menu=5/. © The Author 2014. Published by Oxford University Press.

  19. Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

    A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

  20. Improving protein fold recognition by extracting fold-specific features from predicted residue-residue contacts.

    Science.gov (United States)

    Zhu, Jianwei; Zhang, Haicang; Li, Shuai Cheng; Wang, Chao; Kong, Lupeng; Sun, Shiwei; Zheng, Wei-Mou; Bu, Dongbo

    2017-12-01

    Accurate recognition of protein fold types is a key step for template-based prediction of protein structures. The existing approaches to fold recognition mainly exploit the features derived from alignments of query protein against templates. These approaches have been shown to be successful for fold recognition at family level, but usually failed at superfamily/fold levels. To overcome this limitation, one of the key points is to explore more structurally informative features of proteins. Although residue-residue contacts carry abundant structural information, how to thoroughly exploit these information for fold recognition still remains a challenge. In this study, we present an approach (called DeepFR) to improve fold recognition at superfamily/fold levels. The basic idea of our approach is to extract fold-specific features from predicted residue-residue contacts of proteins using deep convolutional neural network (DCNN) technique. Based on these fold-specific features, we calculated similarity between query protein and templates, and then assigned query protein with fold type of the most similar template. DCNN has showed excellent performance in image feature extraction and image recognition; the rational underlying the application of DCNN for fold recognition is that contact likelihood maps are essentially analogy to images, as they both display compositional hierarchy. Experimental results on the LINDAHL dataset suggest that even using the extracted fold-specific features alone, our approach achieved success rate comparable to the state-of-the-art approaches. When further combining these features with traditional alignment-related features, the success rate of our approach increased to 92.3%, 82.5% and 78.8% at family, superfamily and fold levels, respectively, which is about 18% higher than the state-of-the-art approach at fold level, 6% higher at superfamily level and 1% higher at family level. An independent assessment on SCOP_TEST dataset showed consistent

  1. Fractal Folding and Medium Viscoelasticity Contribute Jointly to Chromosome Dynamics

    Science.gov (United States)

    Polovnikov, K. E.; Gherardi, M.; Cosentino-Lagomarsino, M.; Tamm, M. V.

    2018-02-01

    Chromosomes are key players of cell physiology, their dynamics provides valuable information about its physical organization. In both prokaryotes and eukaryotes, the short-time motion of chromosomal loci has been described with a Rouse model in a simple or viscoelastic medium. However, little emphasis has been put on the influence of the folded organization of chromosomes on the local dynamics. Clearly, stress propagation, and thus dynamics, must be affected by such organization, but a theory allowing us to extract such information from data, e.g., on two-point correlations, is lacking. Here, we describe a theoretical framework able to answer this general polymer dynamics question. We provide a scaling analysis of the stress-propagation time between two loci at a given arclength distance along the chromosomal coordinate. The results suggest a precise way to assess folding information from the dynamical coupling of chromosome segments. Additionally, we realize this framework in a specific model of a polymer whose long-range interactions are designed to make it fold in a fractal way and immersed in a medium characterized by subdiffusive fractional Langevin motion with a tunable scaling exponent. This allows us to derive explicit analytical expressions for the correlation functions.

  2. Neuromuscular compensation mechanisms in vocal fold paralysis and paresis.

    Science.gov (United States)

    Dewan, Karuna; Vahabzadeh-Hagh, Andrew; Soofer, Donna; Chhetri, Dinesh K

    2017-07-01

    Vocal fold paresis and paralysis are common conditions. Treatment options include augmentation laryngoplasty and voice therapy. The optimal management for this condition is unclear. The objective of this study was to assess possible neuromuscular compensation mechanisms that could potentially be used in the treatment of vocal fold paresis and paralysis. In vivo canine model. In an in vivo canine model, we examined three conditions: 1) unilateral right recurrent laryngeal nerve (RLN) paresis and paralysis, 2) unilateral superior laryngeal nerve (SLN) paralysis, and 3) unilateral vagal nerve paresis and paralysis. Phonatory acoustics and aerodynamics were measured in each of these conditions. Effective compensation was defined as improved acoustic and aerodynamic profile. The most effective compensation for all conditions was increasing RLN activation and decreasing glottal gap. Increasing RLN activation increased the percentage of possible phonatory conditions that achieved phonation onset. SLN activation generally led to decreased number of total phonation onset conditions within each category. Differential effects of SLN (cricothyroid [CT] muscle) activation were seen. Ipsilateral SLN activation could compensate for RLN paralysis; normal CT compensated well in unilateral SLN paralysis; and in vagal paresis/paralysis, contralateral SLN and RLN displayed antagonistic relationships. Methods to improve glottal closure should be the primary treatment for large glottal gaps. Neuromuscular compensation is possible for paresis. This study provides insights into possible compensatory mechanisms in vocal fold paresis and paralysis. NA Laryngoscope, 127:1633-1638, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Folding and insertion thermodynamics of the transmembrane WALP peptide

    Energy Technology Data Exchange (ETDEWEB)

    Bereau, Tristan, E-mail: bereau@mpip-mainz.mpg.de [Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz (Germany); Bennett, W. F. Drew [Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Pfaendtner, Jim [Department of Chemical Engineering, University of Washington, Seattle, Washington 98195 (United States); Deserno, Markus [Department of Physics, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Karttunen, Mikko [Department of Mathematics and Computer Science & Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, MetaForum, 5600 MB Eindhoven (Netherlands)

    2015-12-28

    The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA){sub n} (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide’s insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum—in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.

  4. Folding and insertion thermodynamics of the transmembrane WALP peptide

    International Nuclear Information System (INIS)

    Bereau, Tristan; Bennett, W. F. Drew; Pfaendtner, Jim; Deserno, Markus; Karttunen, Mikko

    2015-01-01

    The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA) n (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide’s insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum—in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence

  5. Ca-Dependent Folding of Human Calumenin

    Science.gov (United States)

    Mazzorana, Marco; Hussain, Rohanah; Sorensen, Thomas

    2016-01-01

    Human calumenin (hCALU) is a six EF-hand protein belonging to the CREC family. As other members of the family, it is localized in the secretory pathway and regulates the activity of SERCA2a and of the ryanodine receptor in the endoplasmic reticulum (ER). We have studied the effects of Ca2+ binding to the protein and found it to attain a more compact structure upon ion binding. Circular Dichroism (CD) measurements suggest a major rearrangement of the protein secondary structure, which reversibly switches from disordered at low Ca2+ concentrations to predominantly alpha-helical when Ca2+ is added. SAXS experiments confirm the transition from an unfolded to a compact structure, which matches the structural prediction of a trilobal fold. Overall our experiments suggest that calumenin is a Ca2+ sensor, which folds into a compact structure, capable of interacting with its molecular partners, when Ca2+ concentration within the ER reaches the millimolar range. PMID:26991433

  6. Self-folding micropatterned polymeric containers.

    Science.gov (United States)

    Azam, Anum; Laflin, Kate E; Jamal, Mustapha; Fernandes, Rohan; Gracias, David H

    2011-02-01

    We demonstrate self-folding of precisely patterned, optically transparent, all-polymeric containers and describe their utility in mammalian cell and microorganism encapsulation and culture. The polyhedral containers, with SU-8 faces and biodegradable polycaprolactone (PCL) hinges, spontaneously assembled on heating. Self-folding was driven by a minimization of surface area of the liquefying PCL hinges within lithographically patterned two-dimensional (2D) templates. The strategy allowed for the fabrication of containers with variable polyhedral shapes, sizes and precisely defined porosities in all three dimensions. We provide proof-of-concept for the use of these polymeric containers as encapsulants for beads, chemicals, mammalian cells and bacteria. We also compare accelerated hinge degradation rates in alkaline solutions of varying pH. These optically transparent containers resemble three-dimensional (3D) micro-Petri dishes and can be utilized to sustain, monitor and deliver living biological components.

  7. Folded membrane dialyzer with mechanically sealed edges

    Energy Technology Data Exchange (ETDEWEB)

    Markley, F.W.

    A semipermeable membrane is folded in accordion fashion to form a stack of pleats and the edges are sealed so as to isolate the opposite surfaces of the membrane. The stack is contained within a case that provides ports for flow of blood in contact with one surface of the membrane through channels formed by the pleats and also provides ports for flow of a dialysate through channels formed by the pleats in contact with the other surface of the membrane. The serpentine side edges of the membrane are sealed by a solidified plastic material, whereas effective mechanical means are provided to seal the end edges of the folded membrane. The mechanical means include a clamping strip which biases case sealing flanges into a sealed relationship with end portions of the membrane near the end edges, which portions extend from the stack and between the sealing flanges.

  8. Image Analysis for Nail-fold Capillaroscopy

    OpenAIRE

    Vucic, Vladimir

    2015-01-01

    Detection of diseases in an early stage is very important since it can make the treatment of patients easier, safer and more ecient. For the detection of rheumatic diseases, and even prediction of tendencies towards such diseases, capillaroscopy is becoming an increasingly recognized method. Nail-fold capillaroscopy is a non-invasive imaging technique that is used for analysis of microcirculation abnormalities that may lead todisease like systematic sclerosis, Reynauds phenomenon and others. ...

  9. Coherent topological phenomena in protein folding

    DEFF Research Database (Denmark)

    Bohr, Henrik; Brunak, Søren; Bohr, Jakob

    1997-01-01

    A theory is presented for coherent topological phenomena in protein dynamics with implications for protein folding and stability. We discuss the relationship to the writhing number used in knot diagrams of DNA. The winding state defines a long-range order along the backbone of a protein with long......-range excitations, `wring' modes, that play an important role in protein denaturation and stability. Energy can be pumped into these excitations, either thermally or by an external force....

  10. A Particle Swarm Optimization-Based Approach with Local Search for Predicting Protein Folding.

    Science.gov (United States)

    Yang, Cheng-Hong; Lin, Yu-Shiun; Chuang, Li-Yeh; Chang, Hsueh-Wei

    2017-10-01

    The hydrophobic-polar (HP) model is commonly used for predicting protein folding structures and hydrophobic interactions. This study developed a particle swarm optimization (PSO)-based algorithm combined with local search algorithms; specifically, the high exploration PSO (HEPSO) algorithm (which can execute global search processes) was combined with three local search algorithms (hill-climbing algorithm, greedy algorithm, and Tabu table), yielding the proposed HE-L-PSO algorithm. By using 20 known protein structures, we evaluated the performance of the HE-L-PSO algorithm in predicting protein folding in the HP model. The proposed HE-L-PSO algorithm exhibited favorable performance in predicting both short and long amino acid sequences with high reproducibility and stability, compared with seven reported algorithms. The HE-L-PSO algorithm yielded optimal solutions for all predicted protein folding structures. All HE-L-PSO-predicted protein folding structures possessed a hydrophobic core that is similar to normal protein folding.

  11. Energetic frustrations in protein folding at residue resolution: a homologous simulation study of Im9 proteins.

    Directory of Open Access Journals (Sweden)

    Yunxiang Sun

    Full Text Available Energetic frustration is becoming an important topic for understanding the mechanisms of protein folding, which is a long-standing big biological problem usually investigated by the free energy landscape theory. Despite the significant advances in probing the effects of folding frustrations on the overall features of protein folding pathways and folding intermediates, detailed characterizations of folding frustrations at an atomic or residue level are still lacking. In addition, how and to what extent folding frustrations interact with protein topology in determining folding mechanisms remains unclear. In this paper, we tried to understand energetic frustrations in the context of protein topology structures or native-contact networks by comparing the energetic frustrations of five homologous Im9 alpha-helix proteins that share very similar topology structures but have a single hydrophilic-to-hydrophobic mutual mutation. The folding simulations were performed using a coarse-grained Gō-like model, while non-native hydrophobic interactions were introduced as energetic frustrations using a Lennard-Jones potential function. Energetic frustrations were then examined at residue level based on φ-value analyses of the transition state ensemble structures and mapped back to native-contact networks. Our calculations show that energetic frustrations have highly heterogeneous influences on the folding of the four helices of the examined structures depending on the local environment of the frustration centers. Also, the closer the introduced frustration is to the center of the native-contact network, the larger the changes in the protein folding. Our findings add a new dimension to the understanding of protein folding the topology determination in that energetic frustrations works closely with native-contact networks to affect the protein folding.

  12. Evolution of a protein folding nucleus.

    Science.gov (United States)

    Xia, Xue; Longo, Liam M; Sutherland, Mason A; Blaber, Michael

    2016-07-01

    The folding nucleus (FN) is a cryptic element within protein primary structure that enables an efficient folding pathway and is the postulated heritable element in the evolution of protein architecture; however, almost nothing is known regarding how the FN structurally changes as complex protein architecture evolves from simpler peptide motifs. We report characterization of the FN of a designed purely symmetric β-trefoil protein by ϕ-value analysis. We compare the structure and folding properties of key foldable intermediates along the evolutionary trajectory of the β-trefoil. The results show structural acquisition of the FN during gene fusion events, incorporating novel turn structure created by gene fusion. Furthermore, the FN is adjusted by circular permutation in response to destabilizing functional mutation. FN plasticity by way of circular permutation is made possible by the intrinsic C3 cyclic symmetry of the β-trefoil architecture, identifying a possible selective advantage that helps explain the prevalence of cyclic structural symmetry in the proteome. © 2015 The Protein Society.

  13. Hierarchical Diagnosis of Vocal Fold Disorders

    Science.gov (United States)

    Nikkhah-Bahrami, Mansour; Ahmadi-Noubari, Hossein; Seyed Aghazadeh, Babak; Khadivi Heris, Hossein

    This paper explores the use of hierarchical structure for diagnosis of vocal fold disorders. The hierarchical structure is initially used to train different second-level classifiers. At the first level normal and pathological signals have been distinguished. Next, pathological signals have been classified into neurogenic and organic vocal fold disorders. At the final level, vocal fold nodules have been distinguished from polyps in organic disorders category. For feature selection at each level of hierarchy, the reconstructed signal at each wavelet packet decomposition sub-band in 5 levels of decomposition with mother wavelet of (db10) is used to extract the nonlinear features of self-similarity and approximate entropy. Also, wavelet packet coefficients are used to measure energy and Shannon entropy features at different spectral sub-bands. Davies-Bouldin criterion has been employed to find the most discriminant features. Finally, support vector machines have been adopted as classifiers at each level of hierarchy resulting in the diagnosis accuracy of 92%.

  14. Thermostability in endoglucanases is fold-specific

    Science.gov (United States)

    2011-01-01

    Background Endoglucanases are usually considered to be synergistically involved in the initial stages of cellulose breakdown-an essential step in the bioprocessing of lignocellulosic plant materials into bioethanol. Despite their economic importance, we currently lack a basic understanding of how some endoglucanases can sustain their ability to function at elevated temperatures required for bioprocessing, while others cannot. In this study, we present a detailed comparative analysis of both thermophilic and mesophilic endoglucanases in order to gain insights into origins of thermostability. We analyzed the sequences and structures for sets of endoglucanase proteins drawn from the Carbohydrate-Active enZymes (CAZy) database. Results Our results demonstrate that thermophilic endoglucanases and their mesophilic counterparts differ significantly in their amino acid compositions. Strikingly, these compositional differences are specific to protein folds and enzyme families, and lead to differences in intramolecular interactions in a fold-dependent fashion. Conclusions Here, we provide fold-specific guidelines to control thermostability in endoglucanases that will aid in making production of biofuels from plant biomass more efficient. PMID:21291533

  15. Thermostability in endoglucanases is fold-specific

    Directory of Open Access Journals (Sweden)

    Wolt Jeffrey D

    2011-02-01

    Full Text Available Abstract Background Endoglucanases are usually considered to be synergistically involved in the initial stages of cellulose breakdown-an essential step in the bioprocessing of lignocellulosic plant materials into bioethanol. Despite their economic importance, we currently lack a basic understanding of how some endoglucanases can sustain their ability to function at elevated temperatures required for bioprocessing, while others cannot. In this study, we present a detailed comparative analysis of both thermophilic and mesophilic endoglucanases in order to gain insights into origins of thermostability. We analyzed the sequences and structures for sets of endoglucanase proteins drawn from the Carbohydrate-Active enZymes (CAZy database. Results Our results demonstrate that thermophilic endoglucanases and their mesophilic counterparts differ significantly in their amino acid compositions. Strikingly, these compositional differences are specific to protein folds and enzyme families, and lead to differences in intramolecular interactions in a fold-dependent fashion. Conclusions Here, we provide fold-specific guidelines to control thermostability in endoglucanases that will aid in making production of biofuels from plant biomass more efficient.

  16. BiP clustering facilitates protein folding in the endoplasmic reticulum.

    Directory of Open Access Journals (Sweden)

    Marc Griesemer

    2014-07-01

    Full Text Available The chaperone BiP participates in several regulatory processes within the endoplasmic reticulum (ER: translocation, protein folding, and ER-associated degradation. To facilitate protein folding, a cooperative mechanism known as entropic pulling has been proposed to demonstrate the molecular-level understanding of how multiple BiP molecules bind to nascent and unfolded proteins. Recently, experimental evidence revealed the spatial heterogeneity of BiP within the nuclear and peripheral ER of S. cerevisiae (commonly referred to as 'clusters'. Here, we developed a model to evaluate the potential advantages of accounting for multiple BiP molecules binding to peptides, while proposing that BiP's spatial heterogeneity may enhance protein folding and maturation. Scenarios were simulated to gauge the effectiveness of binding multiple chaperone molecules to peptides. Using two metrics: folding efficiency and chaperone cost, we determined that the single binding site model achieves a higher efficiency than models characterized by multiple binding sites, in the absence of cooperativity. Due to entropic pulling, however, multiple chaperones perform in concert to facilitate the resolubilization and ultimate yield of folded proteins. As a result of cooperativity, multiple binding site models used fewer BiP molecules and maintained a higher folding efficiency than the single binding site model. These insilico investigations reveal that clusters of BiP molecules bound to unfolded proteins may enhance folding efficiency through cooperative action via entropic pulling.

  17. Functional results after external vocal fold medialization thyroplasty with the titanium vocal fold medialization implant.

    Science.gov (United States)

    Schneider, Berit; Denk, Doris-Maria; Bigenzahn, Wolfgang

    2003-04-01

    A persistent insufficiency of glottal closure is mostly a consequence of a unilateral vocal fold movement impairment. It can also be caused by vocal fold atrophy or scarring processes with regular bilateral respiratory vocal fold function. Because of consequential voice, breathing, and swallowing impairments, a functional surgical treatment is required. The goal of the study was to outline the functional results after medialization thyroplasty with the titanium vocal fold medialization implant according to Friedrich. In the period of 1999 to 2001, an external vocal fold medialization using the titanium implant was performed on 28 patients (12 women and 16 men). The patients were in the age range of 19 to 84 years. Twenty-two patients had a paralysis of the left-side vocal fold, and six patients, of the right-side vocal fold. Detailed functional examinations were executed on all patients before and after the surgery: perceptive voice sound analysis according to the "roughness, breathiness, and hoarseness" method, judgment of the s/z ratio and voice dysfunction index, voice range profile measurements, videostroboscopy, and pulmonary function tests. In case of dysphagia/aspiration, videofluoroscopy of swallowing was also performed. The respective data were statistically analyzed (paired t test, Wilcoxon-test). All patients reported on improvement of voice, swallowing, and breathing functions postoperatively. Videostroboscopy revealed an almost complete glottal closure after surgery in all of the patients. All voice-related parameters showed a significant improvement. An increase of the laryngeal resistance by the medialization procedure could be excluded by analysis of the pulmonary function test. The results confirm the external medialization of the vocal folds as an adequate method in the therapy of voice, swallowing, and breathing impairment attributable to an insufficient glottal closure. The titanium implant offers, apart from good tissue tolerability, the

  18. FOLD-EM: automated fold recognition in medium- and low-resolution (4-15 Å) electron density maps.

    Science.gov (United States)

    Saha, Mitul; Morais, Marc C

    2012-12-15

    Owing to the size and complexity of large multi-component biological assemblies, the most tractable approach to determining their atomic structure is often to fit high-resolution radiographic or nuclear magnetic resonance structures of isolated components into lower resolution electron density maps of the larger assembly obtained using cryo-electron microscopy (cryo-EM). This hybrid approach to structure determination requires that an atomic resolution structure of each component, or a suitable homolog, is available. If neither is available, then the amount of structural information regarding that component is limited by the resolution of the cryo-EM map. However, even if a suitable homolog cannot be identified using sequence analysis, a search for structural homologs should still be performed because structural homology often persists throughout evolution even when sequence homology is undetectable, As macromolecules can often be described as a collection of independently folded domains, one way of searching for structural homologs would be to systematically fit representative domain structures from a protein domain database into the medium/low resolution cryo-EM map and return the best fits. Taken together, the best fitting non-overlapping structures would constitute a 'mosaic' backbone model of the assembly that could aid map interpretation and illuminate biological function. Using the computational principles of the Scale-Invariant Feature Transform (SIFT), we have developed FOLD-EM-a computational tool that can identify folded macromolecular domains in medium to low resolution (4-15 Å) electron density maps and return a model of the constituent polypeptides in a fully automated fashion. As a by-product, FOLD-EM can also do flexible multi-domain fitting that may provide insight into conformational changes that occur in macromolecular assemblies.

  19. Glass ionomer application for vocal fold augmentation: Histopathological analysis on rabbit vocal fold.

    Science.gov (United States)

    Demirci, Sule; Tuzuner, Arzu; Callıoglu, Elif Ersoy; Yumusak, Nihat; Arslan, Necmi; Baltacı, Bülent

    2016-04-01

    The aim of this study was to investigate the use of glass ionomer cement (GIC) as an injection material for vocal fold augmentation and to evaluate the biocompatibility of the material. Ten adult New Zealand rabbits were used. Under general anesthesia, 0.1-cc GIC was injected to one vocal fold and the augmentation of vocal fold was observed. No injection was applied to the opposite side, which was accepted as the control group. The animals were sacrificed after 3 months and the laryngeal specimens were histopathologically evaluated. The injected and the noninjected control vocal folds were analyzed. The GIC particles were observed in histological sections on the injected side, and no foreign body giant cells, granulomatous inflammation, necrosis, or marked chronic inflammation were detected around the glass ionomer particles. Mild inflammatory reactions were noticed in only two specimens. The noninjected sides of vocal folds were completely normal. The findings of this study suggest that GIC is biocompatible and may be further investigated as an alternative injection material for augmentation of the vocal fold. Further studies are required to examine the viscoelastic properties of GIC and the long-term effects in experimental studies. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Interferences of Silica Nanoparticles in Green Fluorescent Protein Folding Processes.

    Science.gov (United States)

    Klein, Géraldine; Devineau, Stéphanie; Aude, Jean Christophe; Boulard, Yves; Pasquier, Hélène; Labarre, Jean; Pin, Serge; Renault, Jean Philippe

    2016-01-12

    We investigated the relationship between unfolded proteins, silica nanoparticles and chaperonin to determine whether unfolded proteins could stick to silica surfaces and how this process could impair heat shock protein activity. The HSP60 catalyzed green fluorescent protein (GFP) folding was used as a model system. The adsorption isotherms and adsorption kinetics of denatured GFP were measured, showing that denaturation increases GFP affinity for silica surfaces. This affinity is maintained even if the surfaces are covered by a protein corona and allows silica NPs to interfere directly with GFP folding by trapping it in its unstructured state. We determined also the adsorption isotherms of HSP60 and its chaperonin activity once adsorbed, showing that SiO2 NP can interfere also indirectly with protein folding through chaperonin trapping and inhibition. This inhibition is specifically efficient when NPs are covered first with a layer of unfolded proteins. These results highlight for the first time the antichaperonin activity of silica NPs and ask new questions about the toxicity of such misfolded proteins/nanoparticles assembly toward cells.

  1. Equilibrium amide hydrogen exchange and protein folding kinetics

    International Nuclear Information System (INIS)

    Bai Yawen

    1999-01-01

    The classical Linderstrom-Lang hydrogen exchange (HX) model is extended to describe the relationship between the HX behaviors (EX1 and EX2) and protein folding kinetics for the amide protons that can only exchange by global unfolding in a three-state system including native (N), intermediate (I), and unfolded (U) states. For these slowly exchanging amide protons, it is shown that the existence of an intermediate (I) has no effect on the HX behavior in an off-pathway three-state system (I↔U↔N). On the other hand, in an on-pathway three-state system (U↔I↔N), the existence of a stable folding intermediate has profound effect on the HX behavior. It is shown that fast refolding from the unfolded state to the stable intermediate state alone does not guarantee EX2 behavior. The rate of refolding from the intermediate state to the native state also plays a crucial role in determining whether EX1 or EX2 behavior should occur. This is mainly due to the fact that only amide protons in the native state are observed in the hydrogen exchange experiment. These new concepts suggest that caution needs to be taken if one tries to derive the kinetic events of protein folding from equilibrium hydrogen exchange experiments

  2. Oral and vocal fold diadochokinesis in dysphonic women.

    Science.gov (United States)

    Louzada, Talita; Beraldinelle, Roberta; Berretin-Felix, Giédre; Brasolotto, Alcione Ghedini

    2011-01-01

    The evaluation of oral and vocal fold diadochokinesis (DDK) in individuals with voice disorders may contribute to the understanding of factors that affect the balanced vocal production. Scientific studies that make use of this assessment tool support the knowledge advance of this area, reflecting the development of more appropriate therapeutic planning. To compare the results of oral and vocal fold DDK in dysphonic women and in women without vocal disorders. For this study, 28 voice recordings of women from 19 to 54 years old, diagnosed with dysphonia and submitted to a voice assessment from speech pathologist and otorhinolaryngologist, were used. The control group included 30 nondysphonic women evaluated in prior research from normal adults. The analysis parameters like number and duration of emissions, as well as the regularity of the repetition of syllables "pa", "ta", "ka" and the vowels "a" and "i," were provided by the Advanced Motor Speech Profile program (MSP) Model-5141, version-2.5.2 (KayPentax). The DDK sequence "pataka" was analyzed quantitatively through the Sound Forge 7.0 program, as well as manually with the audio-visual help of sound waves. Average values of oral and vocal fold DDK dysphonic and nondysphonic women were compared using the "t Student" test and were considered significant when pwomen (CvP=10.42%, 12.79%, 12.05%; JittP=2.05%, 6.05%, 3.63%) compared to the control group (CvP=8.86%; 10.95%, 11.20%; JittP=1.82%, 2.98%, 3.15%). Although the results do not indicate any difficulties in oral and laryngeal motor control in the dysphonic group, the largest instability in vocal fold DDK in the experimental group should be considered, and studies of this ability in individuals with communication disorders must be intensified.

  3. Incremental fold tests of remagnetized carbonate rocks

    Science.gov (United States)

    Van Der Voo, R.; van der Pluijm, B.

    2017-12-01

    Many unmetamorphosed carbonates all over the world are demonstrably remagnetized, with the age of the secondary magnetizations typically close to that of the nearest orogeny in space and time. This observation did not become compelling until the mid-1980's, when the incremental fold test revealed the Appalachian carbonates to carry a syn-deformational remanence of likely Permian age (Scotese et al., 1982, Phys. Earth Planet. Int., v. 30, p. 385-395; Cederquist et al., 2006, Tectonophysics v. 422, p. 41-54). Since that time scores of Appalachian and Rocky Mountain carbonate rocks have added results to the growing database of paleopoles representing remagnetizations. Late Paleozoic remagnetizations form a cloud of results surrounding the reference poles of the Laurentian APWP. Remagnetizations in other locales and with inferred ages coeval with regional orogenies (e.g., Taconic, Sevier/Laramide, Variscan, Indosinian) are also ubiquitous. To be able to transform this cornucopia into valuable anchor-points on the APWP would be highly desirable. This may indeed become feasible, as will be explained next. Recent studies of faulted and folded carbonate-shale sequences have shown that this deformation enhances the illitization of smectite (Haines & van der Pluijm, 2008, Jour. Struct. Geol., v. 30, p. 525-538; Fitz-Diaz et al., 2014, International Geol. Review, v. 56, p. 734-755). 39Ar-40Ar dating of the authigenic illite (neutralizing any detrital illite contribution by taking the intercept of a mixing line) yields, therefore, the age of the deformation. We know that this date is also the age of the syndeformational remanence; thus we have the age of the corresponding paleopole. Results so far are obtained for the Canadian and U.S. Rocky Mountains and for the Spanish Cantabrian carbonates (Tohver et al., 2008, Earth Planet. Sci. Lett., v. 274, p. 524-530) and make good sense in accord with geological knowledge. Incremental fold tests are the tools used for this

  4. Synovial folds in the knee joint

    International Nuclear Information System (INIS)

    Schaefer, H.

    1987-01-01

    Stimulated by arthroscopic insight into central abnormalities of the knee joint and by the large number of unexplained case of 'anterior knee pain', we have studied the synovia in more than 2000 contrast examinations of the joint. Surprisingly, and contrary to the views expressed in the literature, the clinically significant plica parapatellaris medialis was seen as frequently during pneumo-arthrography as during more complex procedures. Abnormalities in the synovial fold emerged as a discreet disease identified as the 'medial shelf syndrome' and should be included in the differential diagnosis of causes of pain round the lower end of the femur and patella. (orig.) [de

  5. Axons Pull on the Brain, But Tension Does Not Drive Cortical Folding

    Science.gov (United States)

    Xu, Gang; Knutsen, Andrew K.; Dikranian, Krikor; Kroenke, Christopher D.; Bayly, Philip V.; Taber, Larry A.

    2011-01-01

    During human brain development, the cerebral cortex undergoes substantial folding, leading to its characteristic highly convoluted form. Folding is necessary to accommodate the expansion of the cerbral cortex; abnormal cortical folding is linked to various neurological disorders, including schizophrenia, epilepsy, autism and mental retardation. Although this process requires mechanical forces, the specific force-generating mechanisms that drive folding remain unclear. The two most widely accepted hypotheses are (1) folding is caused by differential growth of the cortex and (2) folding is caused by mechanical tension generated in axons. Direct evidence supporting either theory, however, is lacking. Here we show that axons are indeed under considerable tension in the developing ferret brain, but the patterns of tissue stress are not consistent with a causal role for axonal tension. In particular, microdissection assays reveal that significant tension exists along axons aligned circumferentially in subcortical white matter tracts, as well as those aligned radially inside developing gyri (outward folds). Contrary to previous speculation, however, axonal tension is not directed across developing gyri, suggesting that axon tension does not drive folding. On the other hand, using computational (finite element) models, we show that differential cortical growth accompanied by remodeling of the subplate leads to outward folds and stress fields that are consistent with our microdissection experiments, supporting a mechanism involving differential growth. Local perturbations, such as temporal differences in the initiation of cortical growth, can ensure consistent folding patterns. This study shows that a combination of experimental and computational mechanics can be used to evaluate competing hypotheses of morphogenesis, and illuminate the biomechanics of cortical folding. PMID:20590291

  6. Self-folding origami: shape memory composites activated by uniform heating

    International Nuclear Information System (INIS)

    Tolley, Michael T; Felton, Samuel M; Aukes, Daniel; Wood, Robert J; Miyashita, Shuhei; Rus, Daniela

    2014-01-01

    Self-folding is an approach used frequently in nature for the efficient fabrication of structures, but is seldom used in engineered systems. Here, self-folding origami are presented, which consist of shape memory composites that are activated with uniform heating in an oven. These composites are rapidly fabricated using inexpensive materials and tools. The folding mechanism based on the in-plane contraction of a sheet of shape memory polymer is modeled, and parameters for the design of composites that self-fold into target shapes are characterized. Four self-folding shapes are demonstrated: a cube, an icosahedron, a flower, and a Miura pattern; each of which is activated in an oven in less than 4 min. Self-sealing is also investigated using hot melt adhesive, and the resulting structures are found to bear up to twice the load of unsealed structures. (paper)

  7. Functional analysis of propeptide as an intramolecular chaperone for in vivo folding of subtilisin nattokinase.

    Science.gov (United States)

    Jia, Yan; Liu, Hui; Bao, Wei; Weng, Meizhi; Chen, Wei; Cai, Yongjun; Zheng, Zhongliang; Zou, Guolin

    2010-12-01

    Here, we show that during in vivo folding of the precursor, the propeptide of subtilisin nattokinase functions as an intramolecular chaperone (IMC) that organises the in vivo folding of the subtilisin domain. Two residues belonging to β-strands formed by conserved regions of the IMC are crucial for the folding of the subtilisin domain through direct interactions. An identical protease can fold into different conformations in vivo due to the action of a mutated IMC, resulting in different kinetic parameters. Some interfacial changes involving conserved regions, even those induced by the subtilisin domain, blocked subtilisin folding and altered its conformation. Insight into the interaction between the subtilisin and IMC domains is provided by a three-dimensional structural model. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Numerical approximations of flow induced vibrations of vocal folds

    Directory of Open Access Journals (Sweden)

    Sváček Petr

    2017-01-01

    Full Text Available The paper focus on mathematical modelling of incompressible fluid flow interacting with vibrations of an elastic vocal fold. The flow in moving domain is modelled by the incompressible Navier-Stokes equations written in the Arbitrary Lagrangian-Eulerian (ALE form. The channel geometry is an approximation of the human glottal region. The flow model is coupled with a simplified structure model. The problem is mathematically described and the resulting fluid-structure interaction problem is discretized by a stabilized finite element method. A strong coupling algorithm is applied for solution of the coupled fluid-structure problem. The choice of boundary conditions is discussed, particularly the choice of different artificial inlet/outlet boundary conditions is described in details. The numerical results are shown.

  9. Numerical approximations of flow induced vibrations of vocal folds

    Science.gov (United States)

    Sváček, Petr

    The paper focus on mathematical modelling of incompressible fluid flow interacting with vibrations of an elastic vocal fold. The flow in moving domain is modelled by the incompressible Navier-Stokes equations written in the Arbitrary Lagrangian-Eulerian (ALE) form. The channel geometry is an approximation of the human glottal region. The flow model is coupled with a simplified structure model. The problem is mathematically described and the resulting fluid-structure interaction problem is discretized by a stabilized finite element method. A strong coupling algorithm is applied for solution of the coupled fluid-structure problem. The choice of boundary conditions is discussed, particularly the choice of different artificial inlet/outlet boundary conditions is described in details. The numerical results are shown.

  10. Mapping the kinetic barriers of a Large RNA molecule's folding landscape.

    Directory of Open Access Journals (Sweden)

    Jörg C Schlatterer

    Full Text Available The folding of linear polymers into discrete three-dimensional structures is often required for biological function. The formation of long-lived intermediates is a hallmark of the folding of large RNA molecules due to the ruggedness of their energy landscapes. The precise thermodynamic nature of the barriers (whether enthalpic or entropic that leads to intermediate formation is still poorly characterized in large structured RNA molecules. A classic approach to analyzing kinetic barriers are temperature dependent studies analyzed with Eyring's transition state theory. We applied Eyring's theory to time-resolved hydroxyl radical (•OH footprinting kinetics progress curves collected at eight temperature from 21.5 °C to 51 °C to characterize the thermodynamic nature of folding intermediate formation for the Mg(2+-mediated folding of the Tetrahymena thermophila group I ribozyme. A common kinetic model configuration describes this RNA folding reaction over the entire temperature range studied consisting of primary (fast transitions to misfolded intermediates followed by much slower secondary transitions, consistent with previous studies. Eyring analysis reveals that the primary transitions are moderate in magnitude and primarily enthalpic in nature. In contrast, the secondary transitions are daunting in magnitude and entropic in nature. The entropic character of the secondary transitions is consistent with structural rearrangement of the intermediate species to the final folded form. This segregation of kinetic control reveals distinctly different molecular mechanisms during the two stages of RNA folding and documents the importance of entropic barriers to defining rugged RNA folding landscapes.

  11. Free energy landscape and multiple folding pathways of an H-type RNA pseudoknot.

    Directory of Open Access Journals (Sweden)

    Yunqiang Bian

    Full Text Available How RNA sequences fold to specific tertiary structures is one of the key problems for understanding their dynamics and functions. Here, we study the folding process of an H-type RNA pseudoknot by performing a large-scale all-atom MD simulation and bias-exchange metadynamics. The folding free energy landscapes are obtained and several folding intermediates are identified. It is suggested that the folding occurs via multiple mechanisms, including a step-wise mechanism starting either from the first helix or the second, and a cooperative mechanism with both helices forming simultaneously. Despite of the multiple mechanism nature, the ensemble folding kinetics estimated from a Markov state model is single-exponential. It is also found that the correlation between folding and binding of metal ions is significant, and the bound ions mediate long-range interactions in the intermediate structures. Non-native interactions are found to be dominant in the unfolded state and also present in some intermediates, possibly hinder the folding process of the RNA.

  12. Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c

    Directory of Open Access Journals (Sweden)

    David S. Kliger

    2009-04-01

    Full Text Available Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-angle X-ray scattering and amide hydrogen exchange studies on the t £ 1 ms timescale reveals a picture of cytochrome c folding that starts with the ~ 1-ms conformational diffusion dynamics of the unfolded chains. A fractional population of the unfolded chains collapses on the 1 – 100 ms timescale to a compact intermediate IC containing some native-like secondary structure. Although the existence and nature of IC as a discrete folding intermediate remains controversial, there is extensive high time-resolution kinetic evidence for the rapid formation of IC as a true intermediate, i.e., a metastable state separated from the unfolded state by a discrete free energy barrier. Final folding to the native state takes place on millisecond and longer timescales, depending on the presence of kinetic traps such as heme misligation and proline mis-isomerization. The high folding rates observed in equilibrium molten globule models suggest that IC may be a productive folding intermediate. Whether it is an obligatory step on the pathway to the high free energy barrier associated with millisecond timescale folding to the native state, however, remains to be determined.

  13. PyFolding: Open-Source Graphing, Simulation, and Analysis of the Biophysical Properties of Proteins.

    Science.gov (United States)

    Lowe, Alan R; Perez-Riba, Albert; Itzhaki, Laura S; Main, Ewan R G

    2018-02-06

    For many years, curve-fitting software has been heavily utilized to fit simple models to various types of biophysical data. Although such software packages are easy to use for simple functions, they are often expensive and present substantial impediments to applying more complex models or for the analysis of large data sets. One field that is reliant on such data analysis is the thermodynamics and kinetics of protein folding. Over the past decade, increasingly sophisticated analytical models have been generated, but without simple tools to enable routine analysis. Consequently, users have needed to generate their own tools or otherwise find willing collaborators. Here we present PyFolding, a free, open-source, and extensible Python framework for graphing, analysis, and simulation of the biophysical properties of proteins. To demonstrate the utility of PyFolding, we have used it to analyze and model experimental protein folding and thermodynamic data. Examples include: 1) multiphase kinetic folding fitted to linked equations, 2) global fitting of multiple data sets, and 3) analysis of repeat protein thermodynamics with Ising model variants. Moreover, we demonstrate how PyFolding is easily extensible to novel functionality beyond applications in protein folding via the addition of new models. Example scripts to perform these and other operations are supplied with the software, and we encourage users to contribute notebooks and models to create a community resource. Finally, we show that PyFolding can be used in conjunction with Jupyter notebooks as an easy way to share methods and analysis for publication and among research teams. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Gauge Theory and Calibrated Geometry for Calabi-Yau 4-folds

    Science.gov (United States)

    Cao, Yalong

    This thesis is devoted to the study of gauge theory and calibrated geometry for Calabi-Yau 4-folds. More specifically, our study is along the following five directions. 1. We develop Donaldson-Thomas type theory on Calabi-Yau 4-folds. Let X be a compact complex Calabi-Yau 4-fold. We define Donaldson-Thomas type deformation invariants (DT4 invariants) by studying moduli spaces of solutions to the Donaldson- Thomas equations on X. We also study sheaves counting problems on local Calabi-Yau 4-folds. We relate DT4 invariants of KY to the Donaldson-Thomas invariants of the associated Fano 3-fold Y. When the Calabi-Yau 4-fold is toric, we adapt the virtual localization formula to define the corresponding equivariant DT4 invariants. We also discuss the non-commutative version of DT4 invariants for quivers with relations. Finally, we compute DT4 invariants for certain Calabi-Yau 4-folds when moduli spaces are smooth and find a DT 4/GW correspondence for X. Examples of wall-crossing phenomenon in DT4 theory are also given. 2. Given a complex 4-fold X with an (Calabi-Yau 3-fold) anti-canonical divisor Y, we study relative Donaldson-Thomas invariants for this pair, which are elements in the Donaldson-Thomas cohomologies of Y. We also discuss gluing formulas which relate relative invariants and DT4 invariants for Calabi-Yau 4-folds. 3. We study orientability issues of moduli spaces from gauge theories on Calabi-Yau manifolds. Our results generalize and strengthen those for Donaldson-Thomas theory on Calabi-Yau manifolds of dimensions 3 and 4. We also prove a corresponding result in the relative situation which is relevant to the gluing formula in DT theory. 4. Motivated by Strominger-Yau-Zaslow's mirror symmetry proposal and Kontsevich's homological mirror symmetry conjecture, we study mirror phenomena (in A-model) of certain results from Donaldson-Thomas theory for Calabi-Yau 4-folds. More precisely, we study calibrated geometry in the sense of Harvey-Lawson and Lagrangian

  15. Folding and fracturing of rock adjacent to salt diapirs

    Science.gov (United States)

    Rowan, Mark G.

    2017-04-01

    When John Ramsay wrote his groundbreaking book in 1967, deformation around salt diapirs was not something he covered. At the time, most geologists considered diapirs to form due to density inversion, rising through thick overlying strata due to buoyancy. In doing so, salt was thought to shove aside the younger rocks, shearing and fracturing them in drag folds and supposedly producing "salt gouge". Even after it was realized that the majority of diapirs spend most of their history growing at or just beneath the surface, the relative rise of salt and sinking of minibasins were (and are) still thought by many to be accommodated in part by shear and fracturing of rocks in a collar zone around the salt. There are two arguments against this model. The first is mechanical: whereas halite behaves as a viscous fluid, even young sediment deforms as a brittle material with layer anisotropy. Thus, the salt-sediment interface is the outer margin of an intrasalt shear zone caused by viscous drag against the diapir margin. The velocity of salt flow decreases dramatically toward the edge of the diapir, so that the outermost salt effectively doesn't move. Hence, no shear or fracturing is expected in surrounding strata. The second and more important argument is that empirical field data do not support the idea of drag folds and associated deformation. Certainly, strata are typically folded and thinned adjacent to diapirs. However, stratal upturn is generated by monoclinal drape folding of the diapir roof over the edge of the rising salt, and thinning is caused by deposition onto the bathymetric highs formed by the diapirs, often supplemented by roof erosion and slumping. Halokinetic sequences observed in numerous salt basins (e.g., Paradox Basin, La Popa Basin, Spanish Pyrenees, Sivas Basin, Zagros Mountains, Kuqa Basin) contain no diapir-parallel shear zones and minimal thinning and fracturing caused by diapir rise. Even megaflaps, in which strata extend for kilometers up the sides

  16. Three-Dimensional Growth of Flexural Slip Fault-Bend and Fault-Propagation Folds and Their Geomorphic Expression

    Directory of Open Access Journals (Sweden)

    Asdrúbal Bernal

    2018-03-01

    Full Text Available The three-dimensional growth of fault-related folds is known to be an important process during the development of compressive mountain belts. However, comparatively little is known concerning the manner in which fold growth is expressed in topographic relief and local drainage networks. Here we report results from a coupled kinematic and surface process model of fault-related folding. We consider flexural slip fault-bend and fault-propagation folds that grow in both the transport and strike directions, linked to a surface process model that includes bedrock channel development and hillslope diffusion. We investigate various modes of fold growth under identical surface process conditions and critically analyse their geomorphic expression. Fold growth results in the development of steep forelimbs and gentler, wider backlimbs resulting in asymmetric drainage basin development (smaller basins on forelimbs, larger basins on backlimbs. However, topographies developed above fault-propagation folds are more symmetric than those developed above fault-bend folds as a result of their different forelimb kinematics. In addition, the surface expression of fault-bend and fault-propagation folds depends both on the slip distribution along the fault and on the style of fold growth. When along-strike plunge is a result of slip events with gently decreasing slip towards the fault tips (with or without lateral propagation, large plunge-panel drainage networks are developed at the expense of backpanel (transport-opposing and forepanel (transport-facing drainage basins. In contrast, if the fold grows as a result of slip events with similar displacements along strike, plunge-panel drainage networks are poorly developed (or are transient features of early fold growth and restricted to lateral fold terminations, particularly when the number of propagation events is small. The absence of large-scale plunge-panel drainage networks in natural examples suggests that the

  17. Biomechanical simulation of vocal fold dynamics in adults based on laryngeal high-speed videoendoscopy.

    Directory of Open Access Journals (Sweden)

    Michael Döllinger

    Full Text Available Human voice is generated in the larynx by the two oscillating vocal folds. Owing to the limited space and accessibility of the larynx, endoscopic investigation of the actual phonatory process in detail is challenging. Hence the biomechanics of the human phonatory process are still not yet fully understood. Therefore, we adapt a mathematical model of the vocal folds towards vocal fold oscillations to quantify gender and age related differences expressed by computed biomechanical model parameters.The vocal fold dynamics are visualized by laryngeal high-speed videoendoscopy (4000 fps. A total of 33 healthy young subjects (16 females, 17 males and 11 elderly subjects (5 females, 6 males were recorded. A numerical two-mass model is adapted to the recorded vocal fold oscillations by varying model masses, stiffness and subglottal pressure. For adapting the model towards the recorded vocal fold dynamics, three different optimization algorithms (Nelder-Mead, Particle Swarm Optimization and Simulated Bee Colony in combination with three cost functions were considered for applicability. Gender differences and age-related kinematic differences reflected by the model parameters were analyzed.The biomechanical model in combination with numerical optimization techniques allowed phonatory behavior to be simulated and laryngeal parameters involved to be quantified. All three optimization algorithms showed promising results. However, only one cost function seems to be suitable for this optimization task. The gained model parameters reflect the phonatory biomechanics for men and women well and show quantitative age- and gender-specific differences. The model parameters for younger females and males showed lower subglottal pressures, lower stiffness and higher masses than the corresponding elderly groups. Females exhibited higher subglottal pressures, smaller oscillation masses and larger stiffness than the corresponding similar aged male groups. Optimizing

  18. Biomechanical simulation of vocal fold dynamics in adults based on laryngeal high-speed videoendoscopy.

    Science.gov (United States)

    Döllinger, Michael; Gómez, Pablo; Patel, Rita R; Alexiou, Christoph; Bohr, Christopher; Schützenberger, Anne

    2017-01-01

    Human voice is generated in the larynx by the two oscillating vocal folds. Owing to the limited space and accessibility of the larynx, endoscopic investigation of the actual phonatory process in detail is challenging. Hence the biomechanics of the human phonatory process are still not yet fully understood. Therefore, we adapt a mathematical model of the vocal folds towards vocal fold oscillations to quantify gender and age related differences expressed by computed biomechanical model parameters. The vocal fold dynamics are visualized by laryngeal high-speed videoendoscopy (4000 fps). A total of 33 healthy young subjects (16 females, 17 males) and 11 elderly subjects (5 females, 6 males) were recorded. A numerical two-mass model is adapted to the recorded vocal fold oscillations by varying model masses, stiffness and subglottal pressure. For adapting the model towards the recorded vocal fold dynamics, three different optimization algorithms (Nelder-Mead, Particle Swarm Optimization and Simulated Bee Colony) in combination with three cost functions were considered for applicability. Gender differences and age-related kinematic differences reflected by the model parameters were analyzed. The biomechanical model in combination with numerical optimization techniques allowed phonatory behavior to be simulated and laryngeal parameters involved to be quantified. All three optimization algorithms showed promising results. However, only one cost function seems to be suitable for this optimization task. The gained model parameters reflect the phonatory biomechanics for men and women well and show quantitative age- and gender-specific differences. The model parameters for younger females and males showed lower subglottal pressures, lower stiffness and higher masses than the corresponding elderly groups. Females exhibited higher subglottal pressures, smaller oscillation masses and larger stiffness than the corresponding similar aged male groups. Optimizing numerical models

  19. SVM-Fold: a tool for discriminative multi-class protein fold and superfamily recognition.

    Science.gov (United States)

    Melvin, Iain; Ie, Eugene; Kuang, Rui; Weston, Jason; Stafford, William Noble; Leslie, Christina

    2007-05-22

    Predicting a protein's structural class from its amino acid sequence is a fundamental problem in computational biology. Much recent work has focused on developing new representations for protein sequences, called string kernels, for use with support vector machine (SVM) classifiers. However, while some of these approaches exhibit state-of-the-art performance at the binary protein classification problem, i.e. discriminating between a particular protein class and all other classes, few of these studies have addressed the real problem of multi-class superfamily or fold recognition. Moreover, there are only limited software tools and systems for SVM-based protein classification available to the bioinformatics community. We present a new multi-class SVM-based protein fold and superfamily recognition system and web server called SVM-Fold, which can be found at http://svm-fold.c2b2.columbia.edu. Our system uses an efficient implementation of a state-of-the-art string kernel for sequence profiles, called the profile kernel, where the underlying feature representation is a histogram of inexact matching k-mer frequencies. We also employ a novel machine learning approach to solve the difficult multi-class problem of classifying a sequence of amino acids into one of many known protein structural classes. Binary one-vs-the-rest SVM classifiers that are trained to recognize individual structural classes yield prediction scores that are not comparable, so that standard "one-vs-all" classification fails to perform well. Moreover, SVMs for classes at different levels of the protein structural hierarchy may make useful predictions, but one-vs-all does not try to combine these multiple predictions. To deal with these problems, our method learns relative weights between one-vs-the-rest classifiers and encodes information about the protein structural hierarchy for multi-class prediction. In large-scale benchmark results based on the SCOP database, our code weighting approach

  20. Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Chang, Joseph; Yung, Katherine C

    2014-11-01

    This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.

  1. Structural analysis of sheath folds in the Sylacauga Marble Group, Talladega slate belt, southern Appalachians

    Science.gov (United States)

    Mies, J.W.

    1993-01-01

    Remnant blocks of marble from the Moretti-Harrah dimension-stone quarry provide excellent exposure of meter-scale sheath folds. Tubular structures with elliptical cross-sections (4 ???Ryz ??? 5) are the most common expression of the folds. The tubes are elongate subparallel to stretching lineation and are defined by centimeter-scale layers of schist. Eccentrically nested elliptical patterns and opposing asymmetry of folds ('S' and 'Z') are consistent with the sheath-fold interpretation. Sheath folds are locally numerous in the Moretti-Harrah quarry but are not widely distributed in the Sylacauga Marble Group; reconnaissance in neighboring quarries provided no additional observations. The presence of sheath folds in part of the Talladega slate belt indicates a local history of plastic, non-coaxial deformation. Such a history of deformation is substantiated by petrographic study of an extracted hinge from the Moretti-Harrah quarry. The sheath folds are modeled as due to passive amplification of initial structures during simple shear, using both analytic geometry and graphic simulation. As indicated by these models, relatively large shear strains (y ??? 9) and longitudinal initial structures are required. The shear strain presumably relates to NW-directed displacement of overlying crystalline rocks during late Paleozoic orogeny. ?? 1993.

  2. Improving decoy databases for protein folding algorithms

    KAUST Repository

    Lindsey, Aaron

    2014-01-01

    Copyright © 2014 ACM. Predicting protein structures and simulating protein folding are two of the most important problems in computational biology today. Simulation methods rely on a scoring function to distinguish the native structure (the most energetically stable) from non-native structures. Decoy databases are collections of non-native structures used to test and verify these functions. We present a method to evaluate and improve the quality of decoy databases by adding novel structures and removing redundant structures. We test our approach on 17 different decoy databases of varying size and type and show significant improvement across a variety of metrics. We also test our improved databases on a popular modern scoring function and show that they contain a greater number of native-like structures than the original databases, thereby producing a more rigorous database for testing scoring functions.

  3. Folded tandem ion accelerator facility at BARC

    International Nuclear Information System (INIS)

    Agarwal, Arun; Padmakumar, Sapna; Subrahmanyam, N.B.V.; Singh, V.P.; Bhatt, J.P.; Ware, Shailaja V.; Pol, S.S; Basu, A.; Singh, S.K.; Krishnagopal, S.; Bhagwat, P.V.

    2017-01-01

    The 5.5 MV single stage Van de Graaff (VDG) accelerator was in continuous operation at Nuclear Physics Division (NPD), Bhabha Atomic Research Centre (BARC) since its inception in 1962. During 1993-96, VDG accelerator was converted to a Folded Tandem Ion Accelerator (FOTIA). The scientists and engineers of NPD, IADD (then a part of NPD) along with several other divisions of BARC joined hands together in designing, fabrication, installation and commissioning of the FOTIA for the maximum terminal voltage of 6 MV. After experiencing the first accelerated ion beam on the target from FOTIA during April 2000, different ion species were accelerated and tested. Now this accelerator FOTIA is in continuous use for different kind of experiments

  4. Electrotransfection of Polyamine Folded DNA Origami Structures.

    Science.gov (United States)

    Chopra, Aradhana; Krishnan, Swati; Simmel, Friedrich C

    2016-10-12

    DNA origami structures are artificial molecular nanostructures in which DNA double helices are forced into a closely packed configuration by a multitude of DNA strand crossovers. We show that three different types of origami structures (a flat sheet, a hollow tube, and a compact origami block) can be formed in magnesium-free buffer solutions containing low (origami folding is proportional to the DNA concentration. At excessive amounts, the structures aggregate and precipitate. In contrast to origami structures formed in conventional buffers, the resulting structures are stable in the presence of high electric field pulses, such as those commonly used for electrotransfection experiments. We demonstrate that spermidine-stabilized structures are stable in cell lysate and can be delivered into mammalian cells via electroporation.

  5. Improving Protein Fold Recognition by Deep Learning Networks

    Science.gov (United States)

    Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

    2015-12-01

    For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl’s benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

  6. Improving Protein Fold Recognition by Deep Learning Networks.

    Science.gov (United States)

    Jo, Taeho; Hou, Jie; Eickholt, Jesse; Cheng, Jianlin

    2015-12-04

    For accurate recognition of protein folds, a deep learning network method (DN-Fold) was developed to predict if a given query-template protein pair belongs to the same structural fold. The input used stemmed from the protein sequence and structural features extracted from the protein pair. We evaluated the performance of DN-Fold along with 18 different methods on Lindahl's benchmark dataset and on a large benchmark set extracted from SCOP 1.75 consisting of about one million protein pairs, at three different levels of fold recognition (i.e., protein family, superfamily, and fold) depending on the evolutionary distance between protein sequences. The correct recognition rate of ensembled DN-Fold for Top 1 predictions is 84.5%, 61.5%, and 33.6% and for Top 5 is 91.2%, 76.5%, and 60.7% at family, superfamily, and fold levels, respectively. We also evaluated the performance of single DN-Fold (DN-FoldS), which showed the comparable results at the level of family and superfamily, compared to ensemble DN-Fold. Finally, we extended the binary classification problem of fold recognition to real-value regression task, which also show a promising performance. DN-Fold is freely available through a web server at http://iris.rnet.missouri.edu/dnfold.

  7. An overlapping region between the two terminal folding units of the outer surface protein A (OspA) controls its folding behavior.

    Science.gov (United States)

    Makabe, Koki; Nakamura, Takashi; Dhar, Debanjan; Ikura, Teikichi; Koide, Shohei; Kuwajima, Kunihiro

    2018-04-27

    Although many naturally occurring proteins consist of multiple domains, most studies on protein folding to date deal with single-domain proteins or isolated domains of multi-domain proteins. Studies of multi-domain protein folding are required for further advancing our understanding of protein folding mechanisms. Borrelia outer surface protein A (OspA) is a β-rich two-domain protein, in which two globular domains are connected by a rigid and stable single-layer β-sheet. Thus, OspA is particularly suited as a model system for studying the interplays of domains in protein folding. Here, we studied the equilibria and kinetics of the urea-induced folding-unfolding reactions of OspA probed with tryptophan fluorescence and ultraviolet circular dichroism. Global analysis of the experimental data revealed compelling lines of evidence for accumulation of an on-pathway intermediate during kinetic refolding and for the identity between the kinetic intermediate and a previously described equilibrium unfolding intermediate. The results suggest that the intermediate has the fully native structure in the N-terminal domain and the single layer β-sheet, with the C-terminal domain still unfolded. The observation of the productive on-pathway folding intermediate clearly indicates substantial interactions between the two domains mediated by the single-layer β-sheet. We propose that a rigid and stable intervening region between two domains creates an overlap between two folding units and can energetically couple their folding reactions. Copyright © 2018. Published by Elsevier Ltd.

  8. Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments

    DEFF Research Database (Denmark)

    Seemann, Ernst Stefan; Gorodkin, Jan; Backofen, Rolf

    2008-01-01

    Computational methods for determining the secondary structure of RNA sequences from given alignments are currently either based on thermodynamic folding, compensatory base pair substitutions or both. However, there is currently no approach that combines both sources of information in a single...... the corresponding probability of being single stranded. Furthermore, we found that structurally conserved RNA motifs are mostly supported by folding energies. Other problems (e.g. RNA-folding kinetics) may also benefit from employing the principles of the model we introduce. Our implementation, PETfold, was tested...

  9. Detecting protein folding by thermal fluctuations of microcantilevers.

    Directory of Open Access Journals (Sweden)

    Romina Muñoz

    Full Text Available The accurate characterization of proteins in both their native and denatured states is essential to effectively understand protein function, folding and stability. As a proof of concept, a micro rheological method is applied, based on the characterization of thermal fluctuations of a micro cantilever immersed in a bovine serum albumin solution, to assess changes in the viscosity associated with modifications in the protein's structure under the denaturant effect of urea. Through modeling the power spectrum density of the cantilever's fluctuations over a broad frequency band, it is possible to implement a fitting procedure to accurately determine the viscosity of the fluid, even at low volumes. Increases in viscosity during the denaturant process are identified using the assumption that the protein is a hard sphere, with a hydrodynamic radius that increases during unfolding. This is modeled accordingly through the Einstein-Batchelor formula. The Einstein-Batchelor formula estimates are verified through dynamic light scattering, which measures the hydrodynamic radius of proteins. Thus, this methodology is proven to be suitable for the study of protein folding in samples of small size at vanishing shear stresses.

  10. Crosstalk properties of 36-fold segmented symmetric hexagonal HPGe detectors

    International Nuclear Information System (INIS)

    Bruyneel, Bart; Reiter, Peter; Wiens, Andreas; Eberth, Juergen; Hess, Herbert; Pascovici, Gheorghe; Warr, Nigel; Weisshaar, Dirk

    2009-01-01

    Crosstalk properties of three 36-fold segmented, symmetric, large volume, HPGe detectors from the AGATA Collaboration were deduced from coincidence measurements performed with digitized segment and core signals after interaction of γ rays with energies of 1.33 MeV. The mean energy values measured by the core signal fluctuate for γ-ray interactions with energy deposited in two segments. A regular pattern is observed depending on the hit segment combinations. The core energy shifts deviate 0.03-0.06% from the average energy calibration. The segment-sum energy is reduced with respect to the core energy as a function of the decoupling capacitance and the segment multiplicity. The deviation of the segment-sum energies from multiplicity two events fluctuates within an interval of less than 0.1% depending on the different segment combinations. The energy shifts caused by crosstalk for the core and segment signals are comparable for all three detectors. A linear electronic model of the detector and preamplifier assembly was developed to evaluate the results. The fold-dependent energy shifts of the segment-sum energies are reproduced. The model yields a constant shift in all segments, proportional to the core signal. The measured crosstalk pattern and its intensity variation in the segments agree well with the calculated values. The regular variation observed in the core energies cannot be directly related to crosstalk and may be caused by other effects like electron trapping.

  11. Fracture zones constrained by neutral surfaces in a fault-related fold: Insights from the Kelasu tectonic zone, Kuqa Depression

    Science.gov (United States)

    Sun, Shuai; Hou, Guiting; Zheng, Chunfang

    2017-11-01

    Stress variation associated with folding is one of the controlling factors in the development of tectonic fractures, however, little attention has been paid to the influence of neutral surfaces during folding on fracture distribution in a fault-related fold. In this study, we take the Cretaceous Bashijiqike Formation in the Kuqa Depression as an example and analyze the distribution of tectonic fractures in fault-related folds by core observation and logging data analysis. Three fracture zones are identified in a fault-related fold: a tensile zone, a transition zone and a compressive zone, which may be constrained by two neutral surfaces of fold. Well correlation reveals that the tensile zone and the transition zone reach the maximum thickness at the fold hinge and get thinner in the fold limbs. A 2D viscoelastic stress field model of a fault-related fold was constructed to further investigate the mechanism of fracturing. Statistical and numerical analysis reveal that the tensile zone and the transition zone become thicker with decreasing interlimb angle. Stress variation associated with folding is the first level of control over the general pattern of fracture distribution while faulting is a secondary control over the development of local fractures in a fault-related fold.

  12. RNAiFold: a web server for RNA inverse folding and molecular design.

    Science.gov (United States)

    Garcia-Martin, Juan Antonio; Clote, Peter; Dotu, Ivan

    2013-07-01

    Synthetic biology and nanotechnology are poised to make revolutionary contributions to the 21st century. In this article, we describe a new web server to support in silico RNA molecular design. Given an input target RNA secondary structure, together with optional constraints, such as requiring GC-content to lie within a certain range, requiring the number of strong (GC), weak (AU) and wobble (GU) base pairs to lie in a certain range, the RNAiFold web server determines one or more RNA sequences, whose minimum free-energy secondary structure is the target structure. RNAiFold provides access to two servers: RNA-CPdesign, which applies constraint programming, and RNA-LNSdesign, which applies the large neighborhood search heuristic; hence, it is suitable for larger input structures. Both servers can also solve the RNA inverse hybridization problem, i.e. given a representation of the desired hybridization structure, RNAiFold returns two sequences, whose minimum free-energy hybridization is the input target structure. The web server is publicly accessible at http://bioinformatics.bc.edu/clotelab/RNAiFold, which provides access to two specialized servers: RNA-CPdesign and RNA-LNSdesign. Source code for the underlying algorithms, implemented in COMET and supported on linux, can be downloaded at the server website.

  13. Effect of Vocal Fold Medialization on Dysphagia in Patients with Unilateral Vocal Fold Immobility.

    Science.gov (United States)

    Cates, Daniel J; Venkatesan, Naren N; Strong, Brandon; Kuhn, Maggie A; Belafsky, Peter C

    2016-09-01

    The effect of vocal fold medialization (VFM) on vocal improvement in persons with unilateral vocal fold immobility (UVFI) is well established. The effect of VFM on the symptom of dysphagia is uncertain. The purpose of this study is to evaluate dysphagia symptoms in patients with UVFI pre- and post-VFM. Case series with chart review. Academic tertiary care medical center. The charts of 44 persons with UVFI who underwent VFM between June 1, 2013, and December 31, 2014, were abstracted from a prospectively maintained database at the University of California, Davis, Voice and Swallowing Center. Patient demographics, indications, and type of surgical procedure were recorded. Self-reported swallowing impairment was assessed with the validated 10-item Eating Assessment Tool (EAT-10) before and after surgery. A paired samples t test was used to compare pre- and postmedialization EAT-10 scores. Forty-four patients met criteria and underwent either vocal fold injection (73%) or thyroplasty (27%). Etiologies of vocal fold paralysis were iatrogenic (55%), idiopathic (29%), benign or malignant neoplastic (9%), traumatic (5%), or related to the late effects of radiation (2%). EAT-10 (mean ± SD) scores improved from 12.2 ± 11.1 to 7.7 ± 7.2 after medialization (P dysphagia and report significant improvement in swallowing symptoms following VFM. The symptomatic improvement appears to be durable over time. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  14. Self-folding origami at any energy scale

    Science.gov (United States)

    Pinson, Matthew B.; Stern, Menachem; Carruthers Ferrero, Alexandra; Witten, Thomas A.; Chen, Elizabeth; Murugan, Arvind

    2017-05-01

    Programmable stiff sheets with a single low-energy folding motion have been sought in fields ranging from the ancient art of origami to modern meta-materials research. Despite such attention, only two extreme classes of crease patterns are usually studied; special Miura-Ori-based zero-energy patterns, in which crease folding requires no sheet bending, and random patterns with high-energy folding, in which the sheet bends as much as creases fold. We present a physical approach that allows systematic exploration of the entire space of crease patterns as a function of the folding energy. Consequently, we uncover statistical results in origami, finding the entropy of crease patterns of given folding energy. Notably, we identify three classes of Mountain-Valley choices that have widely varying `typical' folding energies. Our work opens up a wealth of experimentally relevant self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or any special symmetry in space.

  15. Phonosurgery of vocal fold polyps, cysts and nodules is beneficial

    DEFF Research Database (Denmark)

    Jensen, Jane Bjerg; Rasmussen, Niels

    2013-01-01

    This study reports our experience with microscopic phonosurgery (PS) of benign lesions of the vocal folds.......This study reports our experience with microscopic phonosurgery (PS) of benign lesions of the vocal folds....

  16. Diagnostic and therapeutic pitfalls in benign vocal fold diseases

    Science.gov (United States)

    Bohlender, Jörg

    2013-01-01

    More than half of patients presenting with hoarseness show benign vocal fold changes. The clinician should be familiar with the anatomy, physiology and functional aspects of voice disorders and also the modern diagnostic and therapeutic possibilities in order to ensure an optimal and patient specific management. This review article focuses on the diagnostic and therapeutic limitations and difficulties of treatment of benign vocal fold tumors, the management and prevention of scarred vocal folds and the issue of unilateral vocal fold paresis. PMID:24403969

  17. Chloroplast Chaperonin: An Intricate Protein Folding Machine for Photosynthesis

    Directory of Open Access Journals (Sweden)

    Qian Zhao

    2018-01-01

    Full Text Available Group I chaperonins are large cylindrical-shaped nano-machines that function as a central hub in the protein quality control system in the bacterial cytosol, mitochondria and chloroplasts. In chloroplasts, proteins newly synthesized by chloroplast ribosomes, unfolded by diverse stresses, or translocated from the cytosol run the risk of aberrant folding and aggregation. The chloroplast chaperonin system assists these proteins in folding into their native states. A widely known protein folded by chloroplast chaperonin is the large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco, an enzyme responsible for the fixation of inorganic CO2 into organic carbohydrates during photosynthesis. Chloroplast chaperonin was initially identified as a Rubisco-binding protein. All photosynthetic eucaryotes genomes encode multiple chaperonin genes which can be divided into α and β subtypes. Unlike the homo-oligomeric chaperonins from bacteria and mitochondria, chloroplast chaperonins are more complex and exists as intricate hetero-oligomers containing both subtypes. The Group I chaperonin requires proper interaction with a detachable lid-like co-chaperonin in the presence of ATP and Mg2+ for substrate encapsulation and conformational transition. Besides the typical Cpn10-like co-chaperonin, a unique co-chaperonin consisting of two tandem Cpn10-like domains joined head-to-tail exists in chloroplasts. Since chloroplasts were proposed as sensors to various environmental stresses, this diversified chloroplast chaperonin system has the potential to adapt to complex conditions by accommodating specific substrates or through regulation at both the transcriptional and post-translational levels. In this review, we discuss recent progress on the unique structure and function of the chloroplast chaperonin system based on model organisms Chlamydomonas reinhardtii and Arabidopsis thaliana. Knowledge of the chloroplast chaperonin system may ultimately lead

  18. A digitally assisted, signal folding neural recording amplifier.

    Science.gov (United States)

    Chen, Yi; Basu, Arindam; Liu, Lei; Zou, Xiaodan; Rajkumar, Ramamoorthy; Dawe, Gavin Stewart; Je, Minkyu

    2014-08-01

    A novel signal folding and reconstruction scheme for neural recording applications that exploits the 1/f(n) characteristics of neural signals is described in this paper. The amplified output is 'folded' into a predefined range of voltages by using comparison and reset circuits along with the core amplifier. After this output signal is digitized and transmitted, a reconstruction algorithm can be applied in the digital domain to recover the amplified signal from the folded waveform. This scheme enables the use of an analog-to-digital convertor with less number of bits for the same effective dynamic range. It also reduces the transmission data rate of the recording chip. Both of these features allow power and area savings at the system level. Other advantages of the proposed topology are increased reliability due to the removal of pseudo-resistors, lower harmonic distortion and low-voltage operation. An analysis of the reconstruction error introduced by this scheme is presented along with a behavioral model to provide a quick estimate of the post reconstruction dynamic range. Measurement results from two different core amplifier designs in 65 nm and 180 nm CMOS processes are presented to prove the generality of the proposed scheme in the neural recording applications. Operating from a 1 V power supply, the amplifier in 180 nm CMOS has a gain of 54.2 dB, bandwidth of 5.7 kHz, input referred noise of 3.8 μVrms and power dissipation of 2.52 μW leading to a NEF of 3.1 in spike band. It exhibits a dynamic range of 66 dB and maximum SNDR of 43 dB in LFP band. It also reduces system level power (by reducing the number of bits in the ADC by 2) as well as data rate to 80% of a conventional design. In vivo measurements validate the ability of this amplifier to simultaneously record spike and LFP signals.

  19. Epithelial Folding Driven by Apical or Basal-Lateral Modulation: Geometric Features, Mechanical Inference, and Boundary Effects.

    Science.gov (United States)

    Wen, Fu-Lai; Wang, Yu-Chiun; Shibata, Tatsuo

    2017-06-20

    During embryonic development, epithelial sheets fold into complex structures required for tissue and organ functions. Although substantial efforts have been devoted to identifying molecular mechanisms underlying epithelial folding, far less is understood about how forces deform individual cells to sculpt the overall sheet morphology. Here we describe a simple and general theoretical model for the autonomous folding of monolayered epithelial sheets. We show that active modulation of intracellular mechanics along the basal-lateral as well as the apical surfaces is capable of inducing fold formation in the absence of buckling instability. Apical modulation sculpts epithelia into shallow and V-shaped folds, whereas basal-lateral modulation generates deep and U-shaped folds. These characteristic tissue shapes remain unchanged when subject to mechanical perturbations from the surroundings, illustrating that the autonomous folding is robust against environmental variabilities. At the cellular scale, how cells change shape depends on their initial aspect ratios and the modulation mechanisms. Such cell deformation characteristics are verified via experimental measurements for a canonical folding process driven by apical modulation, indicating that our theory could be used to infer the underlying folding mechanisms based on experimental data. The mechanical principles revealed in our model could potentially guide future studies on epithelial folding in diverse systems. Copyright © 2017. Published by Elsevier Inc.

  20. Fold distributions at clover, crystal and segment levels for segmented clover detectors

    International Nuclear Information System (INIS)

    Kshetri, R; Bhattacharya, P

    2014-01-01

    Fold distributions at clover, crystal and segment levels have been extracted for an array of segmented clover detectors for various gamma energies. A simple analysis of the results based on a model independant approach has been presented. For the first time, the clover fold distribution of an array and associated array addback factor have been extracted. We have calculated the percentages of the number of crystals and segments that fire for a full energy peak event

  1. Numerical solution of fluid-structure interaction represented by human vocal folds in airflow

    Directory of Open Access Journals (Sweden)

    Valášek J.

    2016-01-01

    Full Text Available The paper deals with the human vocal folds vibration excited by the fluid flow. The vocal fold is modelled as an elastic body assuming small displacements and therefore linear elasticity theory is used. The viscous incompressible fluid flow is considered. For purpose of numerical solution the arbitrary Lagrangian-Euler method (ALE is used. The whole problem is solved by the finite element method (FEM based solver. Results of numerical experiments with different boundary conditions are presented.

  2. Numerical solution of fluid-structure interaction represented by human vocal folds in airflow

    Science.gov (United States)

    Valášek, J.; Sváček, P.; Horáček, J.

    2016-03-01

    The paper deals with the human vocal folds vibration excited by the fluid flow. The vocal fold is modelled as an elastic body assuming small displacements and therefore linear elasticity theory is used. The viscous incompressible fluid flow is considered. For purpose of numerical solution the arbitrary Lagrangian-Euler method (ALE) is used. The whole problem is solved by the finite element method (FEM) based solver. Results of numerical experiments with different boundary conditions are presented.

  3. Folds in multilayered rocks of Proterozoic age, Rajasthan, India

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    Johnson and Johnson 2002 etc) shows that the fold shape modification may be brought about by buckling and flattening operating simultaneously throughout the development of fold. In the present paper a series of F1 folds devel- oped in slates with interlayered alternations with quartzite of Proterozoic age and unaffected ...

  4. Nomenclature proposal to describe vocal fold motion impairment

    NARCIS (Netherlands)

    Rosen, Clark A.; Mau, Ted; Remacle, Marc; Hess, Markus; Eckel, Hans E.; Young, VyVy N.; Hantzakos, Anastasios; Yung, Katherine C.; Dikkers, Frederik G.

    2016-01-01

    The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold

  5. Nomenclature proposal to describe vocal fold motion impairment

    NARCIS (Netherlands)

    Rosen, Clark A.; Mau, Ted; Remacle, Marc; Hess, Markus; Eckel, Hans E.; Young, VyVy N.; Hantzakos, Anastasios; Yung, Katherine C.; Dikkers, Frederik G.

    The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold

  6. Technique to achieve the symmetry of the new inframammary fold

    Science.gov (United States)

    Pozzi, Marcello; Zoccali, Giovanni; Buccheri, Ernesto Maria; de Vita, Roy

    2014-01-01

    Summary The literature outlines several surgical techniques to restore inframmammary fold definition, but symmetry of the fold is often left to irreproducible procedures. We report our personal technique to restore the symmetry of the inframmammary fold during multistep breast reconstruction. PMID:25078934

  7. Effects of knot type in the folding of topologically complex lattice proteins

    Science.gov (United States)

    Soler, Miguel A.; Nunes, Ana; Faísca, Patrícia F. N.

    2014-07-01

    The folding properties of a protein whose native structure contains a 52 knot are investigated by means of extensive Monte Carlo simulations of a simple lattice model and compared with those of a 31 knot. A 52 knot embedded in the native structure enhances the kinetic stability of the carrier lattice protein in a way that is clearly more pronounced than in the case of the 31 knot. However, this happens at the expense of a severe loss in folding efficiency, an observation that is consistent with the relative abundance of 31 and 52 knots in the Protein Data Bank. The folding mechanism of the 52 knot shares with that of the 31 knot the occurrence of a threading movement of the chain terminus that lays closer to the knotted core. However, co-concomitant knotting and folding in the 52 knot occurs with negligible probability, in sharp contrast to what is observed for the 31 knot. The study of several single point mutations highlights the importance in the folding of knotted proteins of the so-called structural mutations (i.e., energetic perturbations of native interactions between residues that are critical for knotting but not for folding). On the other hand, the present study predicts that mutations that perturb the folding transition state may significantly enhance the kinetic stability of knotted proteins provided they involve residues located within the knotted core.

  8. Transferable coarse-grained potential for de novo protein folding and design.

    Directory of Open Access Journals (Sweden)

    Ivan Coluzza

    Full Text Available Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here we provide evidence of how a novel parametrization of the Caterpillar model may be used for both quantitative protein design and folding. With computer simulations it is shown that, for a large set of real protein structures, the model produces designed sequences with similar physical properties to the corresponding natural occurring sequences. The designed sequences require further experimental testing. For an independent set of proteins, previously used as benchmark, the correct folded structure of both the designed and the natural sequences is also demonstrated. The equilibrium folding properties are characterized by free energy calculations. The resulting free energy profiles not only are consistent among natural and designed proteins, but also show a remarkable precision when the folded structures are compared to the experimentally determined ones. Ultimately, the updated Caterpillar model is unique in the combination of its fundamental three features: its simplicity, its ability to produce natural foldable designed sequences, and its structure prediction precision. It is also remarkable that low frustration sequences can be obtained with such a simple and universal design procedure, and that the folding of natural proteins shows funnelled free energy landscapes without the need of any potentials based on the native structure.

  9. Folding in and out: passive morphing in flapping wings.

    Science.gov (United States)

    Stowers, Amanda K; Lentink, David

    2015-03-25

    We present a new mechanism for passive wing morphing of flapping wings inspired by bat and bird wing morphology. The mechanism consists of an unactuated hand wing connected to the arm wing with a wrist joint. Flapping motion generates centrifugal accelerations in the hand wing, forcing it to unfold passively. Using a robotic model in hover, we made kinematic measurements of unfolding kinematics as functions of the non-dimensional wingspan fold ratio (2-2.5) and flapping frequency (5-17 Hz) using stereo high-speed cameras. We find that the wings unfold passively within one to two flaps and remain unfolded with only small amplitude oscillations. To better understand the passive dynamics, we constructed a computer model of the unfolding process based on rigid body dynamics, contact models, and aerodynamic correlations. This model predicts the measured passive unfolding within about one flap and shows that unfolding is driven by centrifugal acceleration induced by flapping. The simulations also predict that relative unfolding time only weakly depends on flapping frequency and can be reduced to less than half a wingbeat by increasing flapping amplitude. Subsequent dimensional analysis shows that the time required to unfold passively is of the same order of magnitude as the flapping period. This suggests that centrifugal acceleration can drive passive unfolding within approximately one wingbeat in small and large wings. Finally, we show experimentally that passive unfolding wings can withstand impact with a branch, by first folding and then unfolding passively. This mechanism enables flapping robots to squeeze through clutter without sophisticated control. Passive unfolding also provides a new avenue in morphing wing design that makes future flapping morphing wings possibly more energy efficient and light-weight. Simultaneously these results point to possible inertia driven, and therefore metabolically efficient, control strategies in bats and birds to morph or recover

  10. Oral and vocal fold diadochokinesis in dysphonic women

    Directory of Open Access Journals (Sweden)

    Talita Louzada

    2011-12-01

    Full Text Available The evaluation of oral and vocal fold diadochokinesis (DDK in individuals with voice disorders may contribute to the understanding of factors that affect the balanced vocal production. Scientific studies that make use of this assessment tool support the knowledge advance of this area, reflecting the development of more appropriate therapeutic planning. Objective: To compare the results of oral and vocal fold DDK in dysphonic women and in women without vocal disorders. Material and methods: For this study, 28 voice recordings of women from 19 to 54 years old, diagnosed with dysphonia and submitted to a voice assessment from speech pathologist and otorhinolaryngologist, were used. The control group included 30 nondysphonic women evaluated in prior research from normal adults. The analysis parameters like number and duration of emissions, as well as the regularity of the repetition of syllables "pa", "ta", "ka" and the vowels "a" and "i," were provided by the Advanced Motor Speech Profile program (MSP Model-5141, version-2.5.2 (KayPentax. The DDK sequence "pataka" was analyzed quantitatively through the Sound Forge 7.0 program, as well as manually with the audio-visual help of sound waves. Average values of oral and vocal fold DDK dysphonic and nondysphonic women were compared using the "t Student" test and were considered significant when p<0.05. Results: The findings showed no significant differences between populations; however, the coefficient of variation of period (CvP and jitter of period (JittP average of the "ka," "a" and "i" emissions, respectively, were higher in dysphonic women (CvP=10.42%, 12.79%, 12.05%; JittP=2.05%, 6.05%, 3.63% compared to the control group (CvP=8.86%; 10.95%, 11.20%; JittP=1.82%, 2.98%, 3.15%. Conclusion: Although the results do not indicate any difficulties in oral and laryngeal motor control in the dysphonic group, the largest instability in vocal fold DDK in the experimental group should be considered, and

  11. Folding and unfolding phylogenetic trees and networks.

    Science.gov (United States)

    Huber, Katharina T; Moulton, Vincent; Steel, Mike; Wu, Taoyang

    2016-12-01

    Phylogenetic networks are rooted, labelled directed acyclic graphswhich are commonly used to represent reticulate evolution. There is a close relationship between phylogenetic networks and multi-labelled trees (MUL-trees). Indeed, any phylogenetic network N can be "unfolded" to obtain a MUL-tree U(N) and, conversely, a MUL-tree T can in certain circumstances be "folded" to obtain aphylogenetic network F(T) that exhibits T. In this paper, we study properties of the operations U and F in more detail. In particular, we introduce the class of stable networks, phylogenetic networks N for which F(U(N)) is isomorphic to N, characterise such networks, and show that they are related to the well-known class of tree-sibling networks. We also explore how the concept of displaying a tree in a network N can be related to displaying the tree in the MUL-tree U(N). To do this, we develop aphylogenetic analogue of graph fibrations. This allows us to view U(N) as the analogue of the universal cover of a digraph, and to establish a close connection between displaying trees in U(N) and reconciling phylogenetic trees with networks.

  12. Structural basis of the 9-fold symmetry of centrioles.

    Science.gov (United States)

    Kitagawa, Daiju; Vakonakis, Ioannis; Olieric, Natacha; Hilbert, Manuel; Keller, Debora; Olieric, Vincent; Bortfeld, Miriam; Erat, Michèle C; Flückiger, Isabelle; Gönczy, Pierre; Steinmetz, Michel O

    2011-02-04

    The centriole, and the related basal body, is an ancient organelle characterized by a universal 9-fold radial symmetry and is critical for generating cilia, flagella, and centrosomes. The mechanisms directing centriole formation are incompletely understood and represent a fundamental open question in biology. Here, we demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization is essential for centriole formation in C. elegans and human cells. We further generate a structural model of the related protein Bld12p from C. reinhardtii, in which nine homodimers assemble into a ring from which nine coiled-coil rods radiate outward. Moreover, we demonstrate that recombinant Bld12p self-assembles into structures akin to the central hub of the cartwheel, which serves as a scaffold for centriole formation. Overall, our findings establish a structural basis for the universal 9-fold symmetry of centrioles. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Folding and Function of Proteorhodopsins in Photoenergy Transducing Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Spudich, John L. [University of Texas Medical School, Houston, TX (United States). Health Science Center, Dept. of Biochemistry and Molecular Biology

    2012-08-10

    The overall research objectives are to develop proteorhodopsin (PR) proteins as a model system for α-helical membrane protein insertion and folding, and to advance understanding of the diversity and mechanisms of PRs, a large family of photoenergy transducers (~4000 identified) abundant in the world’s oceans. Specific aims are: (1) To develop a high-efficiency genetic selection procedure for light-driven proton-pumping in E. coli cells. Such a procedure would provide a positive selection method for proper folding and function of PRs in the E. coli membrane. (2) Characterize flash-induced absorption changes and photocurrents in PR variants in organisms from various environments, and their expression level and function when expressed in E. coli. Subaims are to: (a) elucidate the relationship of the transport mechanism to mechanisms of other microbial rhodopsins, some of which like PRs function as ion transporters and some of which use light energy to activate signaling pathways (sensory rhodopsins); and (b) identify important residues and chemical events in light-driven proton transport by PRs. In addition to their importance to the energy of the biosphere PRs have attracted interest for their potential for use in making photoenergy-transducing membranes for bioengineering applications.

  14. Mechanics of the scrolling and folding of graphene

    Science.gov (United States)

    Li, Hao; Li, Ming; Kang, Zhan

    2018-06-01

    The competition between the out-of-plane rigidity and the van der Waals interaction leads to the scrolled and folded structural configurations of graphene. These configuration changes, as compared with the initially planar geometry, significantly affect the electronic, optical and mechanical properties of graphene, promising exciting applications in graphene-nanoelectronics. We propose a finite-deformation theoretical model, in which no presumed assumptions on the geometries of deformed configurations are required. Both the predicted deformed profiles and the critical conditions show great agreements with molecular dynamics simulations results when compared with existing studies with simple geometrical assumptions. Moreover, MD simulations are performed to explore the morphology transitions between different configurations. It is observed that the folded configuration is energetically favorable for a short graphene sheet, while a long graphene sheet tends to scroll. Of particular interest, we observe the morphology transition from a Fermat scroll to the Archimedean scroll for the bi-scrolled graphene. These findings are useful for understanding the stability of graphene and may provide guidance to the design of programmable graphene-nanoelectronics.

  15. Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.

    Science.gov (United States)

    Sun, Jian; Zhang, Qing; Schlick, Tamar

    2005-06-07

    Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.

  16. Mechanics of the scrolling and folding of graphene.

    Science.gov (United States)

    Li, Hao; Li, Ming; Kang, Zhan

    2018-06-15

    The competition between the out-of-plane rigidity and the van der Waals interaction leads to the scrolled and folded structural configurations of graphene. These configuration changes, as compared with the initially planar geometry, significantly affect the electronic, optical and mechanical properties of graphene, promising exciting applications in graphene-nanoelectronics. We propose a finite-deformation theoretical model, in which no presumed assumptions on the geometries of deformed configurations are required. Both the predicted deformed profiles and the critical conditions show great agreements with molecular dynamics simulations results when compared with existing studies with simple geometrical assumptions. Moreover, MD simulations are performed to explore the morphology transitions between different configurations. It is observed that the folded configuration is energetically favorable for a short graphene sheet, while a long graphene sheet tends to scroll. Of particular interest, we observe the morphology transition from a Fermat scroll to the Archimedean scroll for the bi-scrolled graphene. These findings are useful for understanding the stability of graphene and may provide guidance to the design of programmable graphene-nanoelectronics.

  17. The pathophysiology of the nodular and micronodular small bowel fold

    International Nuclear Information System (INIS)

    Olmsted, W.W.; Ros, P.R.; Moser, R.P.; Shekita, K.M.; Lichtenstein, J.E.

    1986-01-01

    The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is at the limit of resolution of current roentgenographic technique. When the villi are enlarged, they appear radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor,inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold

  18. Pathophysiology of the nodular and micronodular small bowel fold

    International Nuclear Information System (INIS)

    Olmstead, W.W.; Ros, P.R.; Moser, R.P.; Shekitka, K.M.; Lichtenstein, J.E.; Buck, J.L.

    1987-01-01

    The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is just at the resolution of current roentgenographic technique. When the villi are enlarged, they can be seen radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor, inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold

  19. Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

    Science.gov (United States)

    Suzuki, Ryo; Katsuno, Tatsuya; Kishimoto, Yo; Nakamura, Ryosuke; Mizuta, Masanobu; Suehiro, Atsushi; Yamashita, Masaru; Nakamura, Tatsuo; Tateya, Ichiro; Omori, Koichi

    2018-04-01

    The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Animal experiments with controls. Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. NA. Laryngoscope, 128:E150-E156, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Protein Folding Free Energy Landscape along the Committor - the Optimal Folding Coordinate.

    Science.gov (United States)

    Krivov, Sergei V

    2018-06-06

    Recent advances in simulation and experiment have led to dramatic increases in the quantity and complexity of produced data, which makes the development of automated analysis tools very important. A powerful approach to analyze dynamics contained in such data sets is to describe/approximate it by diffusion on a free energy landscape - free energy as a function of reaction coordinates (RC). For the description to be quantitatively accurate, RCs should be chosen in an optimal way. Recent theoretical results show that such an optimal RC exists; however, determining it for practical systems is a very difficult unsolved problem. Here we describe a solution to this problem. We describe an adaptive nonparametric approach to accurately determine the optimal RC (the committor) for an equilibrium trajectory of a realistic system. In contrast to alternative approaches, which require a functional form with many parameters to approximate an RC and thus extensive expertise with the system, the suggested approach is nonparametric and can approximate any RC with high accuracy without system specific information. To avoid overfitting for a realistically sampled system, the approach performs RC optimization in an adaptive manner by focusing optimization on less optimized spatiotemporal regions of the RC. The power of the approach is illustrated on a long equilibrium atomistic folding simulation of HP35 protein. We have determined the optimal folding RC - the committor, which was confirmed by passing a stringent committor validation test. It allowed us to determine a first quantitatively accurate protein folding free energy landscape. We have confirmed the recent theoretical results that diffusion on such a free energy profile can be used to compute exactly the equilibrium flux, the mean first passage times, and the mean transition path times between any two points on the profile. We have shown that the mean squared displacement along the optimal RC grows linear with time as for

  1. Design and simulation of origami structures with smooth folds.

    Science.gov (United States)

    Peraza Hernandez, E A; Hartl, D J; Lagoudas, D C

    2017-04-01

    Origami has enabled new approaches to the fabrication and functionality of multiple structures. Current methods for origami design are restricted to the idealization of folds as creases of zeroth-order geometric continuity. Such an idealization is not proper for origami structures of non-negligible fold thickness or maximum curvature at the folds restricted by material limitations. For such structures, folds are not properly represented as creases but rather as bent regions of higher-order geometric continuity. Such fold regions of arbitrary order of continuity are termed as smooth folds . This paper presents a method for solving the following origami design problem: given a goal shape represented as a polygonal mesh (termed as the goal mesh ), find the geometry of a single planar sheet, its pattern of smooth folds, and the history of folding motion allowing the sheet to approximate the goal mesh. The parametrization of the planar sheet and the constraints that allow for a valid pattern of smooth folds are presented. The method is tested against various goal meshes having diverse geometries. The results show that every determined sheet approximates its corresponding goal mesh in a known folded configuration having fold angles obtained from the geometry of the goal mesh.

  2. Single-Chain Folding of Synthetic Polymers: A Critical Update.

    Science.gov (United States)

    Altintas, Ozcan; Barner-Kowollik, Christopher

    2015-11-23

    The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Protein folding: Over half a century lasting quest. Comment on "There and back again: Two views on the protein folding puzzle" by Alexei V. Finkelstein et al.

    Science.gov (United States)

    Krokhotin, Andrey; Dokholyan, Nikolay V.

    2017-07-01

    Most proteins fold into unique three-dimensional (3D) structures that determine their biological functions, such as catalytic activity or macromolecular binding. Misfolded proteins can pose a threat through aberrant interactions with other proteins leading to a number of diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis [1,2]. What does determine 3D structure of proteins? The first clue to this question came more than fifty years ago when Anfinsen demonstrated that unfolded proteins can spontaneously fold to their native 3D structures [3,4]. Anfinsen's experiments lead to the conclusion that proteins fold to unique native structure corresponding to the stable and kinetically accessible free energy minimum, and protein native structure is solely determined by its amino acid sequence. The question of how exactly proteins find their free energy minimum proved to be a difficult problem. One of the puzzles, initially pointed out by Levinthal, was an inconsistency between observed protein folding times and theoretical estimates. A self-avoiding polymer model of a globular protein of 100-residues length on a cubic lattice can sample at least 1047 states. Based on the assumption that conformational sampling occurs at the highest vibrational mode of proteins (∼picoseconds), predicted folding time by searching among all the possible conformations leads to ∼1027 years (much larger than the age of the universe) [5]. In contrast, observed protein folding time range from microseconds to minutes. Due to tremendous theoretical progress in protein folding field that has been achieved in past decades, the source of this inconsistency is currently understood that is thoroughly described in the review by Finkelstein et al. [6].

  4. Finite element analysis of electroactive polymer and magnetoactive elastomer based actuation for origami folding

    Science.gov (United States)

    Zhang, Wei; Ahmed, Saad; Masters, Sarah; Ounaies, Zoubeida; Frecker, Mary

    2017-10-01

    The incorporation of smart materials such as electroactive polymers and magnetoactive elastomers in origami structures can result in active folding using external electric and magnetic stimuli, showing promise in many origami-inspired engineering applications. In this study, 3D finite element analysis (FEA) models are developed using COMSOL Multiphysics software for three configurations that incorporate a combination of active and passive material layers, namely: (1) a single-notch unimorph folding configuration actuated using only external electric field, (2) a double-notch unimorph folding configuration actuated using only external electric field, and (3) a bifold configuration which is actuated using multi-field (electric and magnetic) stimuli. The objectives of the study are to verify the effectiveness of the FEA models to simulate folding behavior and to investigate the influence of geometric parameters on folding quality. Equivalent mechanical pressure and surface stress are used as external loads in the FEA to simulate electric and magnetic fields, respectively. Compared quantitatively with experimental data, FEA captured the folding performance of electric actuation well for notched configurations and magnetic actuation for a bifold structure, but underestimated electric actuation for the bifold structure. By investigating the impact of geometric parameters and locations to place smart materials, FEA can be used in design, avoiding trial-and-error iterations of experiments.

  5. Analysis of the free-energy surface of proteins from reversible folding simulations.

    Directory of Open Access Journals (Sweden)

    Lucy R Allen

    2009-07-01

    Full Text Available Computer generated trajectories can, in principle, reveal the folding pathways of a protein at atomic resolution and possibly suggest general and simple rules for predicting the folded structure of a given sequence. While such reversible folding trajectories can only be determined ab initio using all-atom transferable force-fields for a few small proteins, they can be determined for a large number of proteins using coarse-grained and structure-based force-fields, in which a known folded structure is by construction the absolute energy and free-energy minimum. Here we use a model of the fast folding helical lambda-repressor protein to generate trajectories in which native and non-native states are in equilibrium and transitions are accurately sampled. Yet, representation of the free-energy surface, which underlies the thermodynamic and dynamic properties of the protein model, from such a trajectory remains a challenge. Projections over one or a small number of arbitrarily chosen progress variables often hide the most important features of such surfaces. The results unequivocally show that an unprojected representation of the free-energy surface provides important and unbiased information and allows a simple and meaningful description of many-dimensional, heterogeneous trajectories, providing new insight into the possible mechanisms of fast-folding proteins.

  6. CASP10-BCL::Fold efficiently samples topologies of large proteins.

    Science.gov (United States)

    Heinze, Sten; Putnam, Daniel K; Fischer, Axel W; Kohlmann, Tim; Weiner, Brian E; Meiler, Jens

    2015-03-01

    During CASP10 in summer 2012, we tested BCL::Fold for prediction of free modeling (FM) and template-based modeling (TBM) targets. BCL::Fold assembles the tertiary structure of a protein from predicted secondary structure elements (SSEs) omitting more flexible loop regions early on. This approach enables the sampling of conformational space for larger proteins with more complex topologies. In preparation of CASP11, we analyzed the quality of CASP10 models throughout the prediction pipeline to understand BCL::Fold's ability to sample the native topology, identify native-like models by scoring and/or clustering approaches, and our ability to add loop regions and side chains to initial SSE-only models. The standout observation is that BCL::Fold sampled topologies with a GDT_TS score > 33% for 12 of 18 and with a topology score > 0.8 for 11 of 18 test cases de novo. Despite the sampling success of BCL::Fold, significant challenges still exist in clustering and loop generation stages of the pipeline. The clustering approach employed for model selection often failed to identify the most native-like assembly of SSEs for further refinement and submission. It was also observed that for some β-strand proteins model refinement failed as β-strands were not properly aligned to form hydrogen bonds removing otherwise accurate models from the pool. Further, BCL::Fold samples frequently non-natural topologies that require loop regions to pass through the center of the protein. © 2015 Wiley Periodicals, Inc.

  7. Folding Dynamics of the Trp-Cage Miniprotein: Evidence for a Native-Like Intermediate from Combined Time-Resolved Vibrational Spectroscopy and Molecular Dynamics Simulations

    NARCIS (Netherlands)

    Meuzelaar, H.; Marino, K.A.; Huerta-Viga, A.; Panman, M.R.; Smeenk, L.E.J.; Kettelarij, A.J.; van Maarseveen, J.H.; Timmerman, P.; Bolhuis, P.G.; Woutersen, S.

    2013-01-01

    Trp-cage is a synthetic 20-residue miniprotein which folds rapidly and spontaneously to a well-defined globular structure more typical of larger proteins. Due to its small size and fast folding, it is an ideal model system for experimental and theoretical investigations of protein folding

  8. What determines the structures of native folds of proteins?

    International Nuclear Information System (INIS)

    Trovato, Antonio; Hoang, Trinh X; Banavar, Jayanth R; Maritan, Amos; Seno, Flavio

    2005-01-01

    We review a simple physical model (Hoang et al 2004 Proc. Natl Acad. Sci. USA 101 7960, Banavar et al 2004 Phys. Rev. E at press) which captures the essential physico-chemical ingredients that determine protein structure, such as the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by hydrogen bonds, sterics, and hydrophobicity. Within this framework, marginally compact conformations resembling the native state folds of proteins emerge as competing minima in the free energy landscape. Here we demonstrate that a hydrophobic-polar (HP) sequence composed of regularly repeated patterns has as its ground state a β-helical structure remarkably similar to a known architecture in the Protein Data Bank

  9. Accurately controlled sequential self-folding structures by polystyrene film

    Science.gov (United States)

    Deng, Dongping; Yang, Yang; Chen, Yong; Lan, Xing; Tice, Jesse

    2017-08-01

    Four-dimensional (4D) printing overcomes the traditional fabrication limitations by designing heterogeneous materials to enable the printed structures evolve over time (the fourth dimension) under external stimuli. Here, we present a simple 4D printing of self-folding structures that can be sequentially and accurately folded. When heated above their glass transition temperature pre-strained polystyrene films shrink along the XY plane. In our process silver ink traces printed on the film are used to provide heat stimuli by conducting current to trigger the self-folding behavior. The parameters affecting the folding process are studied and discussed. Sequential folding and accurately controlled folding angles are achieved by using printed ink traces and angle lock design. Theoretical analyses are done to guide the design of the folding processes. Programmable structures such as a lock and a three-dimensional antenna are achieved to test the feasibility and potential applications of this method. These self-folding structures change their shapes after fabrication under controlled stimuli (electric current) and have potential applications in the fields of electronics, consumer devices, and robotics. Our design and fabrication method provides an easy way by using silver ink printed on polystyrene films to 4D print self-folding structures for electrically induced sequential folding with angular control.

  10. Vocal fold paresis - a debilitating and underdiagnosed condition.

    Science.gov (United States)

    Harris, G; O'Meara, C; Pemberton, C; Rough, J; Darveniza, P; Tisch, S; Cole, I

    2017-07-01

    To review the clinical signs of vocal fold paresis on laryngeal videostroboscopy, to quantify its impact on patients' quality of life and to confirm the benefit of laryngeal electromyography in its diagnosis. Twenty-nine vocal fold paresis patients were referred for laryngeal electromyography. Voice Handicap Index 10 results were compared to 43 patients diagnosed with vocal fold paralysis. Laryngeal videostroboscopy analysis was conducted to determine side of paresis. Blinded laryngeal electromyography confirmed vocal fold paresis in 92.6 per cent of cases, with vocal fold lag being the most common diagnostic sign. The laryngology team accurately predicted side of paresis in 76 per cent of cases. Total Voice Handicap Index 10 responses were not significantly different between vocal fold paralysis and vocal fold paresis groups (26.08 ± 0.21 and 22.93 ± 0.17, respectively). Vocal fold paresis has a significant impact on quality of life. This study shows that laryngeal electromyography is an important diagnostic tool. Patients with persisting dysphonia and apparently normal vocal fold movement, who fail to respond to appropriate speech therapy, should be investigated for a diagnosis of vocal fold paresis.

  11. Quantitative electromyographic characteristics of idiopathic unilateral vocal fold paralysis.

    Science.gov (United States)

    Chang, Wei-Han; Fang, Tuan-Jen; Li, Hsueh-Yu; Jaw, Fu-Shan; Wong, Alice M K; Pei, Yu-Cheng

    2016-11-01

    Unilateral vocal fold paralysis with no preceding causes is diagnosed as idiopathic unilateral vocal fold paralysis. However, comprehensive guidelines for evaluating the defining characteristics of idiopathic unilateral vocal fold paralysis are still lacking. In the present study, we hypothesized that idiopathic unilateral vocal fold paralysis may have different clinical and neurologic characteristics from unilateral vocal fold paralysis caused by surgical trauma. Retrospective, case series study. Patients with unilateral vocal fold paralysis were evaluated using quantitative laryngeal electromyography, videolaryngostroboscopy, voice acoustic analysis, the Voice Outcome Survey, and the Short Form-36 Health Survey quality-of-life questionnaire. Patients with idiopathic and iatrogenic vocal fold paralysis were compared. A total of 124 patients were recruited. Of those, 17 with no definite identified causes after evaluation and follow-up were assigned to the idiopathic group. The remaining 107 patients with surgery-induced vocal fold paralysis were assigned to the iatrogenic group. Patients in the idiopathic group had higher recruitment of the thyroarytenoid-lateral cricoarytenoid muscle complex and better quality of life compared with the iatrogenic group. Idiopathic unilateral vocal fold paralysis has a distinct clinical presentation, with relatively minor denervation changes in the involved laryngeal muscles, and less impact on quality of life compared with iatrogenic vocal fold paralysis. 4. Laryngoscope, 126:E362-E368, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Polymer collapse, protein folding, and the percolation threshold.

    Science.gov (United States)

    Meirovitch, Hagai

    2002-01-15

    We study the transition of polymers in the dilute regime from a swollen shape at high temperatures to their low-temperature structures. The polymers are modeled by a single self-avoiding walk (SAW) on a lattice for which l of the monomers (the H monomers) are self-attracting, i.e., if two nonbonded H monomers become nearest neighbors on the lattice they gain energy of interaction (epsilon = -/epsilon/); the second type of monomers, denoted P, are neutral. This HP model was suggested by Lau and Dill (Macromolecules 1989, 22, 3986-3997) to study protein folding, where H and P are the hydrophobic and polar amino acid residues, respectively. The model is simulated on the square and simple cubic (SC) lattices using the scanning method. We show that the ground state and the sharpness of the transition depend on the lattice, the fraction g of the H monomers, as well as on their arrangement along the chain. In particular, if the H monomers are distributed at random and g is larger than the site percolation threshold of the lattice, a collapsed transition is very likely to occur. This conclusion, drawn for the lattice models, is also applicable to proteins where an effective lattice with coordination number between that of the SC lattice and the body centered cubic lattice is defined. Thus, the average fraction of hydrophobic amino acid residues in globular proteins is found to be close to the percolation threshold of the effective lattice.

  13. Cation-induced folding of alginate-bearing bilayer gels: an unusual example of spontaneous folding along the long axis.

    Science.gov (United States)

    Athas, Jasmin C; Nguyen, Catherine P; Kummar, Shailaa; Raghavan, Srinivasa R

    2018-04-04

    The spontaneous folding of flat gel films into tubes is an interesting example of self-assembly. Typically, a rectangular film folds along its short axis when forming a tube; folding along the long axis has been seen only in rare instances when the film is constrained. Here, we report a case where the same free-swelling gel film folds along either its long or short axis depending on the concentration of a solute. Our gels are sandwiches (bilayers) of two layers: a passive layer of cross-linked N,N'-dimethylyacrylamide (DMAA) and an active layer of cross-linked DMAA that also contains chains of the biopolymer alginate. Multivalent cations like Ca2+ and Cu2+ induce these bilayer gels to fold into tubes. The folding occurs instantly when a flat film of the gel is introduced into a solution of these cations. The likely cause for folding is that the active layer stiffens and shrinks (because the alginate chains in it get cross-linked by the cations) whereas the passive layer is unaffected. The resulting mismatch in swelling degree between the two layers creates internal stresses that drive folding. Cations that are incapable of cross-linking alginate, such as Na+ and Mg2+, do not induce gel folding. Moreover, the striking aspect is the direction of folding. When the Ca2+ concentration is high (100 mM or higher), the gels fold along their long axis, whereas when the Ca2+ concentration is low (40 to 80 mM), the gels fold along their short axis. We hypothesize that the folding axis is dictated by the inhomogeneous nature of alginate-cation cross-linking, i.e., that the edges get cross-linked before the faces of the gel. At high Ca2+ concentration, the stiffer edges constrain the folding; in turn, the gel folds such that the longer edges are deformed less, which explains the folding along the long axis. At low Ca2+ concentration, the edges and the faces of the gel are more similar in their degree of cross-linking; therefore, the gel folds along its short axis. An analogy

  14. Mechanical versus kinematical shortening reconstructions of the Zagros High Folded Zone (Kurdistan region of Iraq)

    Science.gov (United States)

    Frehner, Marcel; Reif, Daniel; Grasemann, Bernhard

    2012-06-01

    This paper compares kinematical and mechanical techniques for the palinspastic reconstruction of folded cross sections in collision orogens. The studied area and the reconstructed NE-SW trending, 55.5 km long cross section is located in the High Folded Zone of the Zagros fold-and-thrust belt in the Kurdistan region of Iraq. The present-day geometry of the cross section has been constructed from field as well as remote sensing data. In a first step, the structures and the stratigraphy are simplified and summarized in eight units trying to identify the main geometric and mechanical parameters. In a second step, the shortening is kinematically estimated using the dip domain method to 11%-15%. Then the same cross section is used in a numerical finite element model to perform dynamical unfolding simulations taking various rheological parameters into account. The main factor allowing for an efficient dynamic unfolding is the presence of interfacial slip conditions between the mechanically strong units. Other factors, such as Newtonian versus power law viscous rheology or the presence of a basement, affect the numerical simulations much less strongly. If interfacial slip is accounted for, fold amplitudes are reduced efficiently during the dynamical unfolding simulations, while welded layer interfaces lead to unrealistic shortening estimates. It is suggested that interfacial slip and decoupling of the deformation along detachment horizons is an important mechanical parameter that controlled the folding processes in the Zagros High Folded Zone.

  15. Birefringence Optical Feedback with a Folded Cavity in HeNe Laser

    International Nuclear Information System (INIS)

    Wu Yun; Tan Yi-Dong

    2013-01-01

    The birefringence optical feedback with a folded cavity in HeNe laser is investigated. A theory model based on the equivalent cavity of the Fabry—Perot interferometer is presented. The phase difference between the two intensities in birefringence feedback is twice the retardation of the wave plate. The phase difference is invariable when the length of the feedback cavity changes. With the adoption of a cube corner prism (CCP) to form a folded cavity, the fringe frequency is doubled, and the resolution of the displacement sensor based on birefringence optical feedback with a folded cavity is improved. A resistance chain of 5-fold subdivision and 4-fold logic subdivision is used as further subdivision. The resolution of λ/80 is obtained eventually; for 632.8 nm HeNe laser it is 7.91 nm. The displacement sensor based on birefringence optical feedback with a folded cavity is simple and of high resolution, large measurement range, low cost, and is of great application potential in industry

  16. Strange temperature dependence of the folding rate of a 16-residue β-hairpin

    International Nuclear Information System (INIS)

    Xu Yao; Wang Ting; Gai Feng

    2006-01-01

    The folding/unfolding kinetics of a 16-residue β-hairpin that undergoes cold denaturation at ambient temperatures were investigated by time-resolved infrared spectroscopy coupled with the laser-induced temperature jump (T-jump) initiation method. We found that the relaxation kinetics of this β-hairpin following a T-jump, obtained by probing the amide I' band of the peptide backbone, show strange temperature dependence. At temperatures below approximately 35 deg. C where this β-hairpin mainly exhibits cold denaturation, the T-jump induced relaxation rate is ∼5 μs -1 , whereas at temperatures where heat denaturation takes place, the relaxation rate increases to ∼1 μs -1 . These results cannot be readily explained by a two-state folding model that has been used to describe the folding thermodynamics of this β-hairpin. In addition, these results suggest that the folding free energy barrier separating the cold-denatured state from the folded state is different from that separating the heat-denatured state from the folded state, coinciding with the idea that the mechanism leading to cold denaturation is different from that leading to heat denaturation

  17. The role of atomic level steric effects and attractive forces in protein folding.

    Science.gov (United States)

    Lammert, Heiko; Wolynes, Peter G; Onuchic, José N

    2012-02-01

    Protein folding into tertiary structures is controlled by an interplay of attractive contact interactions and steric effects. We investigate the balance between these contributions using structure-based models using an all-atom representation of the structure combined with a coarse-grained contact potential. Tertiary contact interactions between atoms are collected into a single broad attractive well between the C(β) atoms between each residue pair in a native contact. Through the width of these contact potentials we control their tolerance for deviations from the ideal structure and the spatial range of attractive interactions. In the compact native state dominant packing constraints limit the effects of a coarse-grained contact potential. During folding, however, the broad attractive potentials allow an early collapse that starts before the native local structure is completely adopted. As a consequence the folding transition is broadened and the free energy barrier is decreased. Eventually two-state folding behavior is lost completely for systems with very broad attractive potentials. The stabilization of native-like residue interactions in non-perfect geometries early in the folding process frequently leads to structural traps. Global mirror images are a notable example. These traps are penalized by the details of the repulsive interactions only after further collapse. Successful folding to the native state requires simultaneous guidance from both attractive and repulsive interactions. Copyright © 2011 Wiley Periodicals, Inc.

  18. Heat capacity changes in RNA folding: application of perturbation theory to hammerhead ribozyme cold denaturation.

    Science.gov (United States)

    Mikulecky, Peter J; Feig, Andrew L

    2004-01-01

    In proteins, empirical correlations have shown that changes in heat capacity (DeltaC(P)) scale linearly with the hydrophobic surface area buried upon folding. The influence of DeltaC(P) on RNA folding has been widely overlooked and is poorly understood. In addition to considerations of solvent reorganization, electrostatic effects might contribute to DeltaC(P)s of folding in polyanionic species such as RNAs. Here, we employ a perturbation method based on electrostatic theory to probe the hot and cold denaturation behavior of the hammerhead ribozyme. This treatment avoids much of the error associated with imposing two-state folding models on non-two-state systems. Ribozyme stability is perturbed across a matrix of solvent conditions by varying the concentration of NaCl and methanol co-solvent. Temperature-dependent unfolding is then monitored by circular dichroism spectroscopy. The resulting array of unfolding transitions can be used to calculate a DeltaC(P) of folding that accurately predicts the observed cold denaturation temperature. We confirm the accuracy of the calculated DeltaC(P) by using isothermal titration calorimetry, and also demonstrate a methanol-dependence of the DeltaC(P). We weigh the strengths and limitations of this method for determining DeltaC(P) values. Finally, we discuss the data in light of the physical origins of the DeltaC(P)s for RNA folding and consider their impact on biological function.

  19. The Ventricular-Fold Dynamics in Human Phonation

    OpenAIRE

    Bailly , Lucie; Henrich Bernardoni , Nathalie; Müller , Frank; Rohlfs , Anna-Katharina; Hess , Markus

    2014-01-01

    International audience; Purpose: In this study, the authors aimed (a) to provide a classification of the ventricular-fold dynamics during voicing, (b) to study the aerodynamic impact of these motions on vocal-fold vibrations, and (c) to assess whether ventricularfold oscillations could be sustained by aerodynamic coupling with the vocal folds. Method: A 72-sample database of vocal gestures accompanying different acoustical events comprised highspeed cinematographic, audio, and electroglottogr...

  20. Cenozoic structural evolution, thermal history, and erosion of the Ukrainian Carpathians fold-thrust belt

    Science.gov (United States)

    Nakapelyukh, Mykhaylo; Bubniak, Ihor; Bubniak, Andriy; Jonckheere, Raymond; Ratschbacher, Lothar

    2018-01-01

    The Carpathians are part of the Alpine-Carpathian-Dinaridic orogen surrounding the Pannonian basin. Their Ukrainian part constitutes an ancient subduction-accretion complex that evolved into a foreland fold-thrust belt with a shortening history that was perpendicular to the orogenic strike. Herein, we constrain the evolution of the Ukrainian part of the Carpathian fold-thrust belt by apatite fission-track dating of sedimentary and volcanic samples and cross-section balancing and restoration. The apatite fission-track ages are uniform in the inner―southwestern part of the fold-thrust belt, implying post-shortening erosion since 12-10 Ma. The ages in the leading and trailing edges record provenance, i.e., sources in the Trans-European suture zone and the Inner Carpathians, respectively, and show that these parts of the fold-thrust were not heated to more than 100 °C. Syn-orogenic strata show sediment recycling: in the interior of the fold-thrust belt―the most thickened and most deeply eroded nappes―the apatite ages were reset, eroded, and redeposited in the syn-orogenic strata closer to the fore- and hinterland; the lag times are only a few million years. Two balanced cross sections, one constructed for this study and based on field and subsurface data, reveal an architecture characterized by nappe stacks separated by high-displacement thrusts; they record 340-390 km shortening. A kinematic forward model highlights the fold-thrust belt evolution from the pre-contractional configuration over the intermediate geometries during folding and thrusting and the post-shortening, erosional-unloading configuration at 12-10 Ma to the present-day geometry. Average shortening rates between 32-20 Ma and 20-12 Ma amounted to 13 and 21 km/Ma, respectively, implying a two-phased deformation of the Ukrainian fold-thrust belt.

  1. Double folding model analysis of elastic scattering of halo nucleus ...

    Indian Academy of Sciences (India)

    carried out which provide valuable insight for improving our understanding of nuclear reactions. One of the interesting aspects is to understand the effect of the halo structure, on elastic scattering cross-sections at near-Coulomb barrier energies in reactions induced by neutron halo nuclei and weakly bound radioactive ...

  2. Fractal Globule as a model of DNA folding in eukaryotes

    Science.gov (United States)

    Imakaev, Maksim; Mirny, Leonid

    2012-02-01

    A recent study (Lieberman-Aiden et al., Science, 2009) observed that the structure of the genome, on the scale of a few megabases, is consistent with a fractal globule. The fractal globule is a quasi-equilibrium state of a polymer after a rapid collapse. First proposed theoretically in 1988, this structure had never been simulated. Fractal globule was seen as a state, in which each subchain is compact, and doesn't mix with other subchains due to their mutual unentanglement (topological constraints). We use GPU-assisted dynamics to create fractal globules of different sizes and observe their dynamics. Our simulations confirm that a polymer after rapid collapse has compact subchains. We measure the scaling of looping probability of a subchain with it's length, and observe the remarkably robust inverse proportionality. Dynamic simulation of the equilibration of this state show that it exhibits Rose type subdiffusion. Due to diffusion, fractal globule quickly degrades to a quasi-equilibrium state, in which subchains of a polymer are mixed, but topologically unentangled. We propose that separation of spatial and topological equilibration of a polymer chain might have implications in different fields of physics.

  3. Folding System for the Clothes by a Robot and Tools

    OpenAIRE

    大澤, 文明; 関, 啓明; 神谷, 好承

    2004-01-01

    The works of a home robot has the laundering. The purpose of this study is to find a means of folding of the clothes and store the clothes in a drawer by a home robot. Because the shape of cloth tends to change in various ways depending on the situation, it is difficult for robot hands to fold the clothes. In this paper, we propose a realistic folding system for the clothes by a robot and tools. The function of a tool is folding the clothes in half by inserting the clothes using two plates. T...

  4. Specific features of vocal fold paralysis in functional computed tomography

    International Nuclear Information System (INIS)

    Laskowska, K.; Mackiewicz-Nartowicz, H.; Serafin, Z.; Nawrocka, E.

    2008-01-01

    Vocal fold paralysis is usually recognized in laryngological examination, and detailed vocal fold function may be established based on laryngovideostroboscopy. Additional imaging should exclude any morphological causes of the paresis, which should be treated pharmacologically or surgically. The aim of this paper was to analyze the computed tomography (CT) images of the larynx in patients with unilateral vocal fold paralysis. CT examinations of the larynx were performed in 10 patients with clinically defined unilateral vocal fold paralysis. The examinations consisted of unenhanced acquisition and enhanced 3-phased acquisition: during free breathing, Valsalva maneuver, and phonation. The analysis included the following morphologic features of the paresis.the deepened epiglottic vallecula, the deepened piriform recess, the thickened and medially positioned aryepiglottic fold, the widened laryngeal pouch, the anteriorly positioned arytenoid cartilage, the thickened vocal fold, and the filled infraglottic space in frontal CT reconstruction. CT images were compared to laryngovideostroboscopy. The most common symptoms of vocal cord paralysis in CT were the deepened epiglottic vallecula and piriform recess, the widened laryngeal pouch with the filled infraglottic space, and the thickened aryepiglottic fold. Regarding the efficiency of the paralysis determination, the three functional techniques of CT larynx imaging used did not differ significantly, and laryngovideostroboscopy demonstrated its advantage over CT. CT of the larynx is a supplementary examination in the diagnosis of vocal fold paralysis, which may enable topographic analysis of the fold dysfunction. The knowledge of morphological CT features of the paralysis may help to prevent false-positive diagnosis of laryngeal cancer. (author)

  5. Using enzyme folding to explore the mechanism of therapeutic touch: a feasibility study.

    Science.gov (United States)

    Strickland, Mallory L; Boylan, Helen M

    2010-07-01

    The goal of this research is to design a novel model using protein folding to study Therapeutic Touch, a noncontact form of energy manipulation healing. Presented is a feasibility study suggesting that the denaturation path of ribonuclease A may be a useful model to study the energy exchange underlying therapeutic touch. The folding of ribonuclease A serves as a controlled energy-requiring system in which energy manipulation can be measured by the degree of folding achieved. A kinetic assay and fluorescence spectroscopy are used to assess the enzyme-folding state. The data suggest that the kinetic assay is a useful means of assessing the degree of refolding, and specifically, the enzyme function. However, fluorescence spectroscopy was not shown to be an effective measurement of enzyme structure for the purposes of this work. More research is needed to assess the underlying mechanism of therapeutic touch to complement the existing studies. An enzyme-folding model may provide a useful means of studying the energy exchange in therapeutic touch.

  6. Cache and energy efficient algorithms for Nussinov's RNA Folding.

    Science.gov (United States)

    Zhao, Chunchun; Sahni, Sartaj

    2017-12-06

    An RNA folding/RNA secondary structure prediction algorithm determines the non-nested/pseudoknot-free structure by maximizing the number of complementary base pairs and minimizing the energy. Several implementations of Nussinov's classical RNA folding algorithm have been proposed. Our focus is to obtain run time and energy efficiency by reducing the number of cache misses. Three cache-efficient algorithms, ByRow, ByRowSegment and ByBox, for Nussinov's RNA folding are developed. Using a simple LRU cache model, we show that the Classical algorithm of Nussinov has the highest number of cache misses followed by the algorithms Transpose (Li et al.), ByRow, ByRowSegment, and ByBox (in this order). Extensive experiments conducted on four computational platforms-Xeon E5, AMD Athlon 64 X2, Intel I7 and PowerPC A2-using two programming languages-C and Java-show that our cache efficient algorithms are also efficient in terms of run time and energy. Our benchmarking shows that, depending on the computational platform and programming language, either ByRow or ByBox give best run time and energy performance. The C version of these algorithms reduce run time by as much as 97.2% and energy consumption by as much as 88.8% relative to Classical and by as much as 56.3% and 57.8% relative to Transpose. The Java versions reduce run time by as much as 98.3% relative to Classical and by as much as 75.2% relative to Transpose. Transpose achieves run time and energy efficiency at the expense of memory as it takes twice the memory required by Classical. The memory required by ByRow, ByRowSegment, and ByBox is the same as that of Classical. As a result, using the same amount of memory, the algorithms proposed by us can solve problems up to 40% larger than those solvable by Transpose.

  7. Arytenoid and posterior vocal fold surgery for bilateral vocal fold immobility.

    Science.gov (United States)

    Young, VyVy N; Rosen, Clark A

    2011-12-01

    Many procedures exist to address the airway restriction often seen with bilateral vocal fold immobility. We review the most recent studies involving arytenoid and/or posterior vocal fold surgery to provide an update on the issues related to these procedures. Specific focus is placed on selection of the surgical approach and operative side, use of adjunctive therapies, and outcome measures including decannulation rate, revision and complication rate, and postoperative results. Ten studies were identified between 2004 and 2011. Modifications to the orginal transverse cordotomy and medial arytenoidectomy techniques continue to be investigated to seek improvement in dyspnea symptoms with minimal decline in voice and/or swallowing function. Decannulation rates for these approaches are high. Postoperative dysphagia appears to be less commonly observed but requires continued study. The use of mitomycin-C in these procedures has been poorly studied to date. Both transverse cordotomy and medial arytenoidectomy procedures result in high success rates. However, many questions related to these procedures remain unanswered, particularly with respect to preoperative and postoperative evaluations of voice quality, swallowing function, and pulmonary status. There is need for rigorous prospective clinical studies to address these many issues further.

  8. Endo-extralaryngeal Laterofixation of the Vocal Folds in Patients with Bilateral Vocal Fold Immobility.

    Science.gov (United States)

    Wiegand, Susanne; Teymoortash, Afshin; Hanschmann, Holger

    2017-01-01

    Bilateral vocal fold paralysis can result in shortness of breath and severe dyspnea which can be life-threatening. Thirty-five patients with bilateral vocal fold paralysis who underwent endo-extralaryngeal laterofixation according to Lichtenberger were retrospectively analyzed regarding etiology, symptoms, treatment and complications. In 27 patients, laterofixation of the vocal cord alone was performed. Eight patients underwent laterofixation and additional posterior chordectomy of the opposite vocal cord according to Dennis and Kashima. The time of intervention ranged from 1 day to 38 years after the onset of bilateral vocal cord immobility. The intraoperative course was uneventful in all patients. None of the patients had postoperative aspiration. Postoperative voice function was acceptable in all patients. Complications of suture laterofixation were laryngeal edema, formation of fibrin, and malposition of the suture. Laterofixation of the vocal cords according to Lichtenberger is a safe and easy method that can be used as a first-stage treatment of vocal cord paralysis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Morphotectonic aspects of active folding in Zagros Mountains (Fin, SE of Iran)

    Science.gov (United States)

    Roustaei, M.; Abbasi, M.

    2008-05-01

    Active deformation in Iran, structural province of Zagros is a result of the convergence between the Arabian & Eurasian plates. The Zagros Mountains in southern Iran are one of the seismically active region & is introduced as fold-thrust belt trending NW-SE within the Arabian plate. Fin lies in Hormozgan province; the south of Iran. The vastness is surrounded by central Iran in the north, High Zagros in the North West and west, Folded Zagros in the east, Makran in the south east and Persian Gulf in the south. The study area is determined by complex structures, alternation of folding, salt diapers and faulting. The surface geology mainly comprises Neogene; Marls, Conglomerate, Sandstones (Mishan, Aghajari, Bakhtiyari formations), old fans and alluvium as syncline that Shur River cuts its north limb and passes from the middle of core .The older formations( Ghachsaran, Rzak and Guri member) folded into prominent anticlines. The fold axes mostly follow the parallel trends .Folds trending are NW-SE (Tashkend anticline), NE-SW (Khur anticline), E-W (Guniz & Handun anticline) and the trend of axes Baz fold in the main part is E-W. Hormoz salt also outcrops in the cores of many whaleback anticlines. Thus, anticlines may be cored with evaporates, even though no salt is currently exposed at the surface. Reason of selecting this area as an example referred to active seismcity. Release of energy is gradually in every events, this seismic character cusses that there was not earthquake with high magnitude in the area but it can not be a role. Answer to the question concerning relationship between folding of the crust layer and faulting at depth is more difficult. There is 2 terms to describe this relationship; "detachment folds" and" forced folds". In this paper, we try to analysis of different satellite imagery; Aster, spot and digital elevation model with high resolution (10 m) in order to detect geomorphic indicators which can help us to find a relationship between faulting

  10. Folding Membrane Proteins by Deep Transfer Learning

    KAUST Repository

    Wang, Sheng; Li, Zhen; Yu, Yizhou; Xu, Jinbo

    2017-01-01

    contacts by learning from non-MPs and then predicts 3D structure models using the predicted contacts as distance restraints. Tested on 510 non-redundant MPs, our method has contact prediction accuracy at least 0.18 better than existing methods, predicts

  11. Why and how does native topology dictate the folding speed of a protein?

    Science.gov (United States)

    Rustad, Mark; Ghosh, Kingshuk

    2012-11-01

    Since the pioneering work of Plaxco, Simons, and Baker, it is now well known that the rates of protein folding strongly correlate with the average sequence separation (absolute contact order (ACO)) of native contacts. In spite of multitude of papers, our understanding to the basis of the relation between folding speed and ACO is still lacking. We model the transition state as a Gaussian polymer chain decorated with weak springs between native contacts while the unfolded state is modeled as a Gaussian chain only. Using these hamiltonians, our perturbative calculation explicitly shows folding speed and ACO are linearly related when only the first order term in the series is considered. However, to the second order, we notice the existence of two new topological metrics, termed COC1 and COC2 (COC stands for contact order correction). These additional correction terms are needed to properly account for the entropy loss due to overlapping (nested or linked) loops that are not well described by simple addition of entropies in ACO. COC1 and COC2 are related to fluctuations and correlations among different sequence separations. The new metric combining ACO, COC1, and COC2 improves folding speed dependence on native topology when applied to three different databases: (i) two-state proteins with only α/β and β proteins, (ii) two-state proteins (α/β, β and purely helical proteins all combined), and (iii) master set (multi-state and two-state) folding proteins. Furthermore, the first principle calculation provides us direct physical insights to the meaning of the fit parameters. The coefficient of ACO, for example, is related to the average strength of the contacts, while the constant term is related to the protein folding speed limit. With the new scaling law, our estimate of the folding speed limit is in close agreement with the widely accepted value of 1 μs observed in proteins and RNA. Analyzing an exhaustive set (7367) of monomeric proteins from protein data bank

  12. Incidence of vocal fold immobility in patients with dysphagia.

    Science.gov (United States)

    Leder, Steven B; Ross, Douglas A

    2005-01-01

    This study prospectively investigated the incidence of vocal fold immobility, unilateral and bilateral, and its influence on aspiration status in a referred population of 1452 patients for a dysphagia evaluation from a large, urban, tertiary-care, teaching hospital. Main outcome measures included overall incidence of vocal fold immobility and aspiration status, with specific emphasis on age, etiology, and side of vocal fold immobility, i.e., right, left, or bilateral. Overall incidence of vocal fold immobility was 5.6% (81 of 1452 patients), including 47 males (mean age 55.7 yr) and 34 females (mean age 59.7 yr). In the subgroup of patients with vocal fold immobility, 31% (25 of 81) exhibited unilateral right, 60% (49 of 81) unilateral left, and 9% (7 of 81) bilateral impairment. Overall incidence of aspiration was found to be 29% (426 of 1452) of all patients referred for a swallow evaluation. Aspiration was observed in 44% (36 of 81) of patients presenting with vocal fold immobility, i.e., 44% (11 of 25) unilateral right, 43% (21 of 49) unilateral left, and 57% (4 of 7) bilateral vocal fold immobility. Left vocal fold immobility occurred most frequently due to surgical trauma. A liquid bolus was aspirated more often than a puree bolus. Side of vocal fold immobility and age were not factors that increased incidence of aspiration. In conclusion, vocal fold immobility, with an incidence of 5.6%, is not an uncommon finding in patients referred for a dysphagia evaluation in the acute-care setting, and vocal fold immobility, when present, was associated with a 15% increased incidence of aspiration when compared with a population already being evaluated for dysphagia.

  13. Prolonged phonation impairs the integrity and barrier function of porcine vocal fold epithelium: a preliminary study.

    Science.gov (United States)

    Zhang, Chi; Paddock, Kieran; Chou, Adriana; Scholp, Austin; Gong, Ting; Jiang, Jack J

    2018-04-18

    Voice abuse is known to be a common risk factor of voice disorders and prolonged; high-intensity phonation has been shown to damage the vocal fold epithelium. We aim to evaluate the effects of phonation on the integrity and barrier function of vocal fold epithelium using a porcine laryngeal model. Ex vivo porcine larynges were phonated at low intensity or high intensity for 15, 30, or 60 min within 4 h after harvest. Vocal fold epithelium was visualized using transmission electron microscopy (TEM). The barrier function of vocal fold epithelium was evaluated by measuring the permeability to model molecules, fluorescein (376 Da), and fluorescein isothiocyanate (FITC)-dextrans of 4000 and 10,000 Da (FD4, FD10), in a Franz diffusing cell. Cell death and dilated intercellular space after phonation were observed using TEM. Thickness of vocal fold epithelium was significantly reduced after low-intensity phonation for 30 and 60 min and high-intensity phonation for 15, 30, and 60 min. Epithelial permeability to fluorescein was significantly increased after low-intensity phonation for 30 and 60 min, and high-intensity phonation. Permeability to FD4 was significantly increased after high-intensity phonation for 30 and 60 min. Phonation did not alter the permeability to FD10 significantly. Long-duration phonation destroys the integrity and barrier function of vocal fold epithelium. These effects likely make vocal folds more vulnerable to other environmental irritants, such as tobacco smoke, reflux components, allergens, and inhaled pollutants. Destroyed barrier function may be an important factor in the pathogenesis of voice lesions related to voice abuse.

  14. TurboFold: Iterative probabilistic estimation of secondary structures for multiple RNA sequences

    Directory of Open Access Journals (Sweden)

    Sharma Gaurav

    2011-04-01

    Full Text Available Abstract Background The prediction of secondary structure, i.e. the set of canonical base pairs between nucleotides, is a first step in developing an understanding of the function of an RNA sequence. The most accurate computational methods predict conserved structures for a set of homologous RNA sequences. These methods usually suffer from high computational complexity. In this paper, TurboFold, a novel and efficient method for secondary structure prediction for multiple RNA sequences, is presented. Results TurboFold takes, as input, a set of homologous RNA sequences and outputs estimates of the base pairing probabilities for each sequence. The base pairing probabilities for a sequence are estimated by combining intrinsic information, derived from the sequence itself via the nearest neighbor thermodynamic model, with extrinsic information, derived from the other sequences in the input set. For a given sequence, the extrinsic information is computed by using pairwise-sequence-alignment-based probabilities for co-incidence with each of the other sequences, along with estimated base pairing probabilities, from the previous iteration, for the other sequences. The extrinsic information is introduced as free energy modifications for base pairing in a partition function computation based on the nearest neighbor thermodynamic model. This process yields updated estimates of base pairing probability. The updated base pairing probabilities in turn are used to recompute extrinsic information, resulting in the overall iterative estimation procedure that defines TurboFold. TurboFold is benchmarked on a number of ncRNA datasets and compared against alternative secondary structure prediction methods. The iterative procedure in TurboFold is shown to improve estimates of base pairing probability with each iteration, though only small gains are obtained beyond three iterations. Secondary structures composed of base pairs with estimated probabilities higher than a

  15. Conformational dynamics of a protein in the folded and the unfolded state

    Energy Technology Data Exchange (ETDEWEB)

    Fitter, Joerg

    2003-08-01

    In a quasielastic neutron scattering experiment, the picosecond dynamics of {alpha}-amylase was investigated for the folded and the unfolded state of the protein. In order to ensure a reasonable interpretation of the internal protein dynamics, the protein was measured in D{sub 2}O-buffer solution. The much higher structural flexibility of the pH induced unfolded state as compared to the native folded state was quantified using a simple analytical model, describing a local diffusion inside a sphere. In terms of this model the conformational volume, which is explored mainly by confined protein side-chain movements, is parameterized by the radius of a sphere (folded state, r=1.2 A; unfolded state, 1.8 A). Differences in conformational dynamics between the folded and the unfolded state of a protein are of fundamental interest in the field of protein science, because they are assumed to play an important role for the thermodynamics of folding/unfolding transition and for protein stability.

  16. Tissue Engineering-based Therapeutic Strategies for Vocal Fold Repair and Regeneration

    Science.gov (United States)

    Li, Linqing; Stiadle, Jeanna M.; Lau, Hang K.; Zerdoum, Aidan B.; Jia, Xinqiao; L.Thibeault, Susan; Kiick, Kristi L.

    2016-01-01

    Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice. PMID:27619243

  17. Status report on the folded tandem ion accelerator at BARC

    Indian Academy of Sciences (India)

    Folded tandem ion accelerator; charged particle beams; voltage stability; Rutherford backscattering; ion optics; beam lines. Abstract. The folded tandem ion accelerator (FOTIA) facility set up at BARC has become operational. At present, it is used for elemental analysis studies using the Rutherford backscattering technique.

  18. The effect of surface electrical stimulation on vocal fold position.

    Science.gov (United States)

    Humbert, Ianessa A; Poletto, Christopher J; Saxon, Keith G; Kearney, Pamela R; Ludlow, Christy L

    2008-01-01

    Closure of the true and false vocal folds is a normal part of airway protection during swallowing. Individuals with reduced or delayed true vocal fold closure can be at risk for aspiration and may benefit from intervention to ameliorate the problem. Surface electrical stimulation is currently used during therapy for dysphagia, despite limited knowledge of its physiological effects. Prospective single effects study. The immediate physiological effect of surface stimulation on true vocal fold angle was examined at rest in 27 healthy adults using 10 different electrode placements on the submental and neck regions. Fiberoptic nasolaryngoscopic recordings during passive inspiration were used to measure change in true vocal fold angle with stimulation. Vocal fold angles changed only to a small extent during two electrode placements (P vocal fold abduction was 2.4 degrees; while horizontal placements of electrodes in the submental region produced a mean adduction of 2.8 degrees (P = .03). Surface electrical stimulation to the submental and neck regions does not produce immediate true vocal fold adduction adequate for airway protection during swallowing, and one position may produce a slight increase in true vocal fold opening.

  19. Cotranslational protein folding reveals the selective use of ...

    Indian Academy of Sciences (India)

    to fold properly by decelerating the translation rate at these sites. Thus the cotranslational protein folding is believed to be true for many proteins and is an important selection factor for the selective codon usage to optimize proper gene expres- sion and function (Komar 2009). A web server CS and S has been created by ...

  20. Vocal Fold Mucus Aggregation in Persons with Voice Disorders

    Science.gov (United States)

    Bonilha, Heather Shaw; White, Lisa; Kuckhahn, Kelsey; Gerlach, Terri Treman; Deliyski, Dimitar D.

    2012-01-01

    Mucus aggregation on the vocal folds is a common finding from laryngeal endoscopy. Patients with voice disorders report the presence of mucus aggregation. Patients also report that mucus aggregation causes them to clear their throat, a behavior believed to be harmful to vocal fold mucosa. Even though clinicians and patients report and discuss…

  1. Surfing the free energy landscape of flavodoxin folding

    NARCIS (Netherlands)

    Bollen, Y.J.M.

    2004-01-01

    The research described in this thesis has been carried out to obtain a better understanding of the fundamental rules describing protein folding. Protein folding is the process in which a linear chain of amino acids contracts to a compact state in which it is active. Flavodoxin from Azotobacter

  2. New variants of known folds: do they bring new biology?

    International Nuclear Information System (INIS)

    Koonin, Eugene V.

    2010-01-01

    New distinct versions of known protein folds provide a powerful means of protein-function prediction that complements sequence and genomic context analysis. New distinct versions of known protein folds provide a powerful means of protein-function prediction that complements sequence and genomic context analysis. These structures do not supplant direct biochemical experiments, but are indispensable for the complete characterization of proteins

  3. Acute vocal fold hemorrhage caught on video during office exam.

    Science.gov (United States)

    Carroll, Thomas L; Smith, Libby J

    2009-03-01

    This article presents a unique video of a laryngeal exam during which a vocal fold hemorrhage occurs. This patient had likely been suffering from intermittent vocal fold hemorrhages for the last decade due to a persistent vascular lesion and an underlying chronic cough.

  4. Transiently disordered tails accelerate folding of globular proteins.

    Science.gov (United States)

    Mallik, Saurav; Ray, Tanaya; Kundu, Sudip

    2017-07-01

    Numerous biological proteins exhibit intrinsic disorder at their termini, which are associated with multifarious functional roles. Here, we show the surprising result that an increased percentage of terminal short transiently disordered regions with enhanced flexibility (TstDREF) is associated with accelerated folding rates of globular proteins. Evolutionary conservation of predicted disorder at TstDREFs and drastic alteration of folding rates upon point-mutations suggest critical regulatory role(s) of TstDREFs in shaping the folding kinetics. TstDREFs are associated with long-range intramolecular interactions and the percentage of native secondary structural elements physically contacted by TstDREFs exhibit another surprising positive correlation with folding kinetics. These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing. © 2017 Federation of European Biochemical Societies.

  5. Method of generating ploynucleotides encoding enhanced folding variants

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

    2017-05-02

    The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

  6. Folding propensity of intrinsically disordered proteins by osmotic stress

    International Nuclear Information System (INIS)

    Mansouri, Amanda L.; Grese, Laura N.; Rowe, Erica L.

    2016-01-01

    Proteins imparted with intrinsic disorder conduct a range of essential cellular functions. To better understand the folding and hydration properties of intrinsically disordered proteins (IDPs), we used osmotic stress to induce conformational changes in nuclear co-activator binding domain (NCBD) and activator for thyroid hormone and retinoid receptor (ACTR). Osmotic stress was applied by the addition of small and polymeric osmolytes, where we discovered that water contributions to NCBD folding always exceeded those for ACTR. Both NCBD and ACTR were found to gain a-helical structure with increasing osmotic stress, consistent with their folding upon NCBD/ACTR complex formation. Using small-angle neutron scattering (SANS), we further characterized NCBD structural changes with the osmolyte ethylene glycol. Here a large reduction in overall size initially occurred before substantial secondary structural change. In conclusion, by focusing on folding propensity, and linked hydration changes, we uncover new insights that may be important for how IDP folding contributes to binding.

  7. Folding of polymer chains with short-range binormal interactions

    International Nuclear Information System (INIS)

    Craig, A; Terentjev, E M

    2006-01-01

    We study the structure of chains which have anisotropic short-range contact interactions that depend on the alignment of the binormal vectors of chain segments. This represents a crude model of hydrogen bonding or 'stacking' interactions out of the plane of curvature. The polymers are treated as ribbon-like semi-flexible chains, where the plane of the ribbon is determined by the local binormal. We show that with dipole-dipole interactions between the binormals of contacting chain segments, mean-field theory predicts a first-order transition to a binormally aligned state. We describe the onset of this transition as a function of the temperature-dependent parameters that govern the chain stiffness and the strength of the binormal interaction, as well as the binormal alignment's coupling to chain collapse. We also examine a metastable state governing the folding kinetics. Finally, we discuss the possible mesoscopic structure of the aligned phase, and application of our model to secondary structure motifs like β-sheets and α-helices, as well as composite structures like β-(amyloid) fibrils

  8. Fluvial-Deltaic Strata as a High-Resolution Recorder of Fold Growth and Fault Slip

    Science.gov (United States)

    Anastasio, D. J.; Kodama, K. P.; Pazzaglia, F. P.

    2008-12-01

    Fluvial-deltaic systems characterize the depositional record of most wedge-top and foreland basins, where the synorogenic stratigraphy responds to interactions between sediment supply driven by tectonic uplift, climate modulated sea level change and erosion rate variability, and fold growth patterns driven by unsteady fault slip. We integrate kinematic models of fault-related folds with growth strata and fluvial terrace records to determine incremental rates of shortening, rock uplift, limb tilting, and fault slip with 104-105 year temporal resolution in the Pyrenees and Apennines. At Pico del Aguila anticline, a transverse dècollement fold along the south Pyrenean mountain front, formation-scale synorogenic deposition and clastic facies patterns in prodeltaic and slope facies reflect tectonic forcing of sediment supply, sea level variability controlling delta front position, and climate modulated changes in terrestrial runoff. Growth geometries record a pinned anticline and migrating syncline hinges during folding above the emerging Guarga thrust sheet. Lithologic and anhysteretic remanent magnetization (ARM) data series from the Eocene Arguis Fm. show cyclicity at Milankovitch frequencies allowing detailed reconstruction of unsteady fold growth. Multiple variations in limb tilting rates from roof ramp and basal dècollement. Along the northern Apennine mountain front, the age and geometry of strath terraces preserved across the Salsomaggiore anticline records the Pleistocene-Recent kinematics of the underlying fault-propagation fold as occurring with a fixed anticline hinge, a rolling syncline hinge, and along-strike variations in uplift and forelimb tilting. The uplifted intersection of terrace deposits documents syncline axial surface migration and underlying fault-tip propagation at a rate of ~1.4 cm/yr since the Middle Pleistocene. Because this record of fault slip coincides with the well-known large amplitude oscillations in global climate that contribute

  9. Vfold: a web server for RNA structure and folding thermodynamics prediction.

    Science.gov (United States)

    Xu, Xiaojun; Zhao, Peinan; Chen, Shi-Jie

    2014-01-01

    The ever increasing discovery of non-coding RNAs leads to unprecedented demand for the accurate modeling of RNA folding, including the predictions of two-dimensional (base pair) and three-dimensional all-atom structures and folding stabilities. Accurate modeling of RNA structure and stability has far-reaching impact on our understanding of RNA functions in human health and our ability to design RNA-based therapeutic strategies. The Vfold server offers a web interface to predict (a) RNA two-dimensional structure from the nucleotide sequence, (b) three-dimensional structure from the two-dimensional structure and the sequence, and (c) folding thermodynamics (heat capacity melting curve) from the sequence. To predict the two-dimensional structure (base pairs), the server generates an ensemble of structures, including loop structures with the different intra-loop mismatches, and evaluates the free energies using the experimental parameters for the base stacks and the loop entropy parameters given by a coarse-grained RNA folding model (the Vfold model) for the loops. To predict the three-dimensional structure, the server assembles the motif scaffolds using structure templates extracted from the known PDB structures and refines the structure using all-atom energy minimization. The Vfold-based web server provides a user friendly tool for the prediction of RNA structure and stability. The web server and the source codes are freely accessible for public use at "http://rna.physics.missouri.edu".

  10. How do horizontal, frictional discontinuities affect reverse fault-propagation folding?

    Science.gov (United States)

    Bonanno, Emanuele; Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Seno, Silvio

    2017-09-01

    The development of new reverse faults and related folds is strongly controlled by the mechanical characteristics of the host rocks. In this study we analyze the impact of a specific kind of anisotropy, i.e. thin mechanical and frictional discontinuities, in affecting the development of reverse faults and of the associated folds using physical scaled models. We perform analog modeling introducing one or two initially horizontal, thin discontinuities above an initially blind fault dipping at 30° in one case, and 45° in another, and then compare the results with those obtained from a fully isotropic model. The experimental results show that the occurrence of thin discontinuities affects both the development and the propagation of new faults and the shape of the associated folds. New faults 1) accelerate or decelerate their propagation depending on the location of the tips with respect to the discontinuities, 2) cross the discontinuities at a characteristic angle (∼90°), and 3) produce folds with different shapes, resulting not only from the dip of the new faults but also from their non-linear propagation history. Our results may have direct impact on future kinematic models, especially those aimed to reconstruct the tectonic history of faults that developed in layered rocks or in regions affected by pre-existing faults.

  11. Partially folded intermediates during trypsinogen denaturation

    Directory of Open Access Journals (Sweden)

    Martins N.F.

    1999-01-01

    Full Text Available The equilibrium unfolding of bovine trypsinogen was studied by circular dichroism, differential spectra and size exclusion HPLC. The change in free energy of denaturation was = 6.99 ± 1.40 kcal/mol for guanidine hydrochloride and = 6.37 ± 0.57 kcal/mol for urea. Satisfactory fits of equilibrium unfolding transitions required a three-state model involving an intermediate in addition to the native and unfolded forms. Size exclusion HPLC allowed the detection of an intermediate population of trypsinogen whose Stokes radii varied from 24.1 ± 0.4 Å to 26.0 ± 0.3 Å for 1.5 M and 2.5 M guanidine hydrochloride, respectively. During urea denaturation, the range of Stokes radii varied from 23.9 ± 0.3 Å to 25.7 ± 0.6 Å for 4.0 M and 6.0 M urea, respectively. Maximal intrinsic fluorescence was observed at about 3.8 M urea with 8-aniline-1-naphthalene sulfonate (ANS binding. These experimental data indicate that the unfolding of bovine trypsinogen is not a simple transition and suggest that the equilibrium intermediate population comprises one intermediate that may be characterized as a molten globule. To obtain further insight by studying intermediates representing different stages of unfolding, we hope to gain a better understanding of the complex interrelations between protein conformation and energetics.

  12. The role of the mesenchyme in cranial neural fold elevation

    International Nuclear Information System (INIS)

    Morris-Wiman, J.A.

    1988-01-01

    It has been previously postulated that the expansion of an hyaluronate-rich extracellular matrix in the fold mesenchyme is responsible for neural fold elevation. In this study we provide evidence that such expansions may play an important role in cranial neural fold elevation by pushing the folds towards the dorsal midline to assist in their elevation. For mesenchymal expansion to result in fold elevation, hyaluronate (HA) and mesenchymal cells must be non-randomly distributed within the mesenchyme. Patterns of mesenchymal cell distribution and cell proliferation were analyzed using the computer-assisted method of smoothed spatial averaging. The distribution of Alcian blue-stained and 3 H-glucosamine-labelled HA was also analyzed during cranial neural fold elevation using established image processing techniques. Analysis of the distribution of 3 H-thymidine-labelled mesenchymal cells indicated that differential mitotic activity was not responsible for decreased mesenchymal cell density. Likewise, analysis of distribution patterns of 3 H-glucosamine-labelled HA indicated that decreased HA concentration was not produced by regional differences in HA synthesis. These results suggest that decreases in mesenchymal cell density and HA concentration that occur during neural fold elevation are produced by mesenchymal expansion

  13. Fluorescence of Alexa fluor dye tracks protein folding.

    Directory of Open Access Journals (Sweden)

    Simon Lindhoud

    Full Text Available Fluorescence spectroscopy is an important tool for the characterization of protein folding. Often, a protein is labeled with appropriate fluorescent donor and acceptor probes and folding-induced changes in Förster Resonance Energy Transfer (FRET are monitored. However, conformational changes of the protein potentially affect fluorescence properties of both probes, thereby profoundly complicating interpretation of FRET data. In this study, we assess the effects protein folding has on fluorescence properties of Alexa Fluor 488 (A488, which is commonly used as FRET donor. Here, A488 is covalently attached to Cys69 of apoflavodoxin from Azotobacter vinelandii. Although coupling of A488 slightly destabilizes apoflavodoxin, the three-state folding of this protein, which involves a molten globule intermediate, is unaffected. Upon folding of apoflavodoxin, fluorescence emission intensity of A488 changes significantly. To illuminate the molecular sources of this alteration, we applied steady state and time-resolved fluorescence techniques. The results obtained show that tryptophans cause folding-induced changes in quenching of Alexa dye. Compared to unfolded protein, static quenching of A488 is increased in the molten globule. Upon populating the native state both static and dynamic quenching of A488 decrease considerably. We show that fluorescence quenching of Alexa Fluor dyes is a sensitive reporter of conformational changes during protein folding.

  14. The impact of intraglottal vortices on vocal fold dynamics

    Science.gov (United States)

    Erath, Byron; Pirnia, Alireza; Peterson, Sean

    2016-11-01

    During voiced speech a critical pressure is produced in the lungs that separates the vocal folds and creates a passage (the glottis) for airflow. As air passes through the vocal folds the resulting aerodynamic loading, coupled with the tissue properties of the vocal folds, produces self-sustained oscillations. Throughout each cycle a complex flow field develops, characterized by a plethora of viscous flow phenomena. Air passing through the glottis creates a jet, with periodically-shed vortices developing due to flow separation and the Kelvin-Helmholtz instability in the shear layer. These vortices have been hypothesized to be a crucial mechanism for producing vocal fold vibrations. In this study the effect of vortices on the vocal fold dynamics is investigated experimentally by passing a vortex ring over a flexible beam with the same non-dimensional mechanical properties as the vocal folds. Synchronized particle image velocimetry data are acquired in tandem with the beam dynamics. The resulting impact of the vortex ring loading on vocal fold dynamics is discussed in detail. This work was supported by the National Science Foundation Grant CBET #1511761.

  15. Idiopathic unilateral vocal-fold paralysis in the adult.

    Science.gov (United States)

    Rubin, F; Villeneuve, A; Alciato, L; Slaïm, L; Bonfils, P; Laccourreye, O

    2018-02-02

    To analyze the characteristics of adult idiopathic unilateral vocal-fold paralysis. Retrospective study of diagnostic problems, clinical data and recovery in an inception cohort of 100 adult patients with idiopathic unilateral vocal-fold paralysis (Group A) and comparison with a cohort of 211 patients with isolated non-idiopathic non-traumatic unilateral vocal-fold paralysis (Group B). Diagnostic problems were noted in 24% of cases in Group A: eight patients with concomitant common upper aerodigestive tract infection, five patients with a concomitant condition liable to induce immunodepression and 11 patients in whom a malignant tumor occurred along the path of the ipsilateral vagus and inferior laryngeal nerves or in the ipsilateral paralyzed larynx. There was no recovery of vocal-fold motion beyond 51 months after onset of paralysis. The 5-year actuarial estimate for recovery differed significantly (Pvocal-fold paralysis. In non-traumatic vocal-fold paralysis in adult patients, without recovery of vocal-fold motion, a minimum three years' regular follow-up is recommended. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Endoscopic Anatomy of the Tensor Fold and Anterior Attic.

    Science.gov (United States)

    Li, Bin; Doan, Phi; Gruhl, Robert R; Rubini, Alessia; Marchioni, Daniele; Fina, Manuela

    2018-02-01

    Objectives The objectives of the study were to (1) study the anatomical variations of the tensor fold and its anatomic relation with transverse crest, supratubal recess, and anterior epitympanic space and (2) explore the most appropriate endoscopic surgical approach to each type of the tensor fold variants. Study Design Cadaver dissection study. Setting Temporal bone dissection laboratory. Subjects and Methods Twenty-eight human temporal bones (26 preserved and 2 fresh) were dissected through an endoscopic transcanal approach between September 2016 and June 2017. The anatomical variations of the tensor fold, transverse crest, supratubal recess, and anterior epitympanic space were studied before and after removing ossicles. Results Three different tensor fold orientations were observed: vertical (type A, 11/28, 39.3%) with attachment to the transverse crest, oblique (type B, 13/28, 46.4%) with attachment to the anterior tegmen tympani, and horizontal (type C, 4/28, 14.3%) with attachment to the tensor tympani canal. The tensor fold was a complete membrane in 20 of 28 (71.4%) specimens, preventing direct ventilation between the supratubal recess and anterior epitympanic space. We identified 3 surgical endoscopic approaches, which allowed visualization of the tensor fold without removing the ossicles. Conclusions The orientation of the tensor fold is the determining structure that dictates the conformation and limits of the epitympanic space. We propose a classification of the tensor fold based on 3 anatomical variants. We also describe 3 different minimally invasive endoscopic approaches to identify the orientation of the tensor fold while maintaining ossicular chain continuity.

  17. A nomenclature paradigm for benign midmembranous vocal fold lesions.

    Science.gov (United States)

    Rosen, Clark A; Gartner-Schmidt, Jackie; Hathaway, Bridget; Simpson, C Blake; Postma, Gregory N; Courey, Mark; Sataloff, Robert T

    2012-06-01

    There is a significant lack of uniform agreement regarding nomenclature for benign vocal fold lesions (BVFLs). This confusion results in difficulty for clinicians communicating with their patients and with each other. In addition, BVFL research and comparison of treatment methods are hampered by the lack of a detailed and uniform BVFL nomenclature. Clinical consensus conferences were held to develop an initial BVFL nomenclature paradigm. Perceptual video analysis was performed to validate the stroboscopy component of the paradigm. The culmination of the consensus conferences and the video-perceptual analysis was used to evaluate the BVFL nomenclature paradigm using a retrospective review of patients with BVFL. An initial BVFL nomenclature paradigm was proposed utilizing detailed definitions relating to vocal fold lesion morphology, stroboscopy, response to voice therapy and intraoperative findings. Video-perceptual analysis of stroboscopy demonstrated that the proposed binary stroboscopy system used in the BVFL nomenclature paradigm was valid and widely applicable. Retrospective review of 45 patients with BVFL followed to the conclusion of treatment demonstrated that slight modifications of the initial BVFL nomenclature paradigm were required. With the modified BVFL nomenclature paradigm, 96% of the patients fit into the predicted pattern and definitions of the BVFL nomenclature system. This study has validated a multidimensional BVFL nomenclature paradigm. This vocal fold nomenclature paradigm includes nine distinct vocal fold lesions: vocal fold nodules, vocal fold polyp, pseudocyst, vocal fold cyst (subepithelial or ligament), nonspecific vocal fold lesion, vocal fold fibrous mass (subepithelial or ligament), and reactive lesion. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  18. Autologous orbicularis muscle for filling facial folds-an experimental and clinical study.

    Science.gov (United States)

    Schellini, Silvana Artioli; Hirai, Flavio Eduardo; Hoyama, Erika; Mattos, Maila Karina; Chaves, Fernando Rodrigo; Pellizon, Claudia Helena; Padovani, Carlos Roberto

    2009-01-01

    To present a technique for filling facial folds by using autologous orbicularis oculi muscle, based on an experimental model. two studies are presented: (1) an experimental study using 15 albino guinea-pigs from which a strip of the sural triceps muscle was removed and implanted in the subcutaneous tissue of the dorsal area. The animals were sacrificed 7, 30 and 60 days after the implantation, and the material was histologically evaluated. And (2) an interventional prospective clinical trial carried out on 20 patients referred to blepharoplasty surgery. They received autologous preseptal orbicularis muscle for filling facial folds. The results where evaluated by patients satisfaction and clinical exam. the sural tricep muscle, when implanted in the subcutaneous tissue, resulted in fibrosis. The patients whom received autologous orbicularis muscle implanted for filling facial folds showed that the procedure can be successfully carried out. autologous preseptal orbicularis muscle is a good material for filling facial folds. Cicatricial tissue will be formed on its implantation site, filling the tissue gap that forms the folds on the skin.

  19. Destiny of autologous bone marrow-derived stromal cells implanted in the vocal fold.

    Science.gov (United States)

    Kanemaru, Shin-ichi; Nakamura, Tatsuo; Yamashita, Masaru; Magrufov, Akhmar; Kita, Tomoko; Tamaki, Hisanobu; Tamura, Yoshihiro; Iguchi, Fuku-ichiro; Kim, Tae Soo; Kishimoto, Masanao; Omori, Koichi; Ito, Juichi

    2005-12-01

    The aim of this study was to investigate the destiny of implanted autologous bone marrow-derived stromal cells (BSCs) containing mesenchymal stem cells. We previously reported the successful regeneration of an injured vocal fold through implantation of BSCs in a canine model. However, the fate of the implanted BSCs was not examined. In this study, implanted BSCs were traced in order to determine the type of tissues resulting at the injected site of the vocal fold. After harvest of bone marrow from the femurs of green fluorescent transgenic mice, adherent cells were cultured and selectively amplified. By means of a fluorescence-activated cell sorter, it was confirmed that some cells were strongly positive for mesenchymal stem cell markers, including CD29, CD44, CD49e, and Sca-1. These cells were then injected into the injured vocal fold of a nude rat. Immunohistologic examination of the resected vocal folds was performed 8 weeks after treatment. The implanted cells were alive in the host tissues and showed positive expression for keratin and desmin, markers for epithelial tissue and muscle, respectively. The implanted BSCs differentiated into more than one tissue type in vivo. Cell-based tissue engineering using BSCs may improve the quality of the healing process in vocal fold injuries.

  20. Modulation of the maladaptive stress response to manage diseases of protein folding.

    Directory of Open Access Journals (Sweden)

    Daniela Martino Roth

    2014-11-01

    Full Text Available Diseases of protein folding arise because of the inability of an altered peptide sequence to properly engage protein homeostasis components that direct protein folding and function. To identify global principles of misfolding disease pathology we examined the impact of the local folding environment in alpha-1-antitrypsin deficiency (AATD, Niemann-Pick type C1 disease (NPC1, Alzheimer's disease (AD, and cystic fibrosis (CF. Using distinct models, including patient-derived cell lines and primary epithelium, mouse brain tissue, and Caenorhabditis elegans, we found that chronic expression of misfolded proteins not only triggers the sustained activation of the heat shock response (HSR pathway, but that this sustained activation is maladaptive. In diseased cells, maladaptation alters protein structure-function relationships, impacts protein folding in the cytosol, and further exacerbates the disease state. We show that down-regulation of this maladaptive stress response (MSR, through silencing of HSF1, the master regulator of the HSR, restores cellular protein folding and improves the disease phenotype. We propose that restoration of a more physiological proteostatic environment will strongly impact the management and progression of loss-of-function and gain-of-toxic-function phenotypes common in human disease.

  1. Right- and left-handed three-helix proteins. I. Experimental and simulation analysis of differences in folding and structure.

    Science.gov (United States)

    Glyakina, Anna V; Pereyaslavets, Leonid B; Galzitskaya, Oxana V

    2013-09-01

    Despite the large number of publications on three-helix protein folding, there is no study devoted to the influence of handedness on the rate of three-helix protein folding. From the experimental studies, we make a conclusion that the left-handed three-helix proteins fold faster than the right-handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three-helix proteins (four right-handed and four left-handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary-structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left-handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right-handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three-helix proteins (238 right- and 94 left-handed). From our analysis, we found that the left-handed three-helix proteins have some less-dense packing that should result in faster folding for some proteins as compared to the case of right-handed proteins. Copyright © 2013 Wiley Periodicals, Inc.

  2. Effects of thermo-mechanical behavior and hinge geometry on folding response of shape memory polymer sheets

    Science.gov (United States)

    Mailen, Russell W.; Dickey, Michael D.; Genzer, Jan; Zikry, Mohammed

    2017-11-01

    Shape memory polymer (SMP) sheets patterned with black ink hinges change shape in response to external stimuli, such as absorbed thermal energy from an infrared (IR) light. The geometry of these hinges, including size, orientation, and location, and the applied thermal loads significantly influence the final folded shape of the sheet, but these variables have not been fully investigated. We perform a systematic study on SMP sheets to fundamentally understand the effects of single and double hinge geometries, hinge orientation and spacing, initial temperature, heat flux intensity, and pattern width on the folding behavior. We have developed thermo-viscoelastic finite element models to characterize and quantify the stresses, strains, and temperatures as they relate to SMP shape changes. Our predictions indicate that hinge orientation can be used to reduce the total bending angle, which is the angle traversed by the folding face of the sheet. Two parallel hinges increase the total bending angle, and heat conduction between the hinges affects the transient folding response. IR intensity and initial temperatures can also influence the transient folding behavior. These results can provide guidelines to optimize the transient folding response and the three-dimensional folded structure obtained from self-folding polymer origami sheets that can be applied for myriad applications.

  3. Small Intestinal Submucosa Implantation for the Possible Treatment of Vocal Fold Scar, Sulcus, and Superficial Lamina Propria Atrophy.

    Science.gov (United States)

    Pitman, Michael J; Cabin, Jonathan A; Iacob, Codrin E

    2016-02-01

    Evaluate the histologic effects of grafting porcine-derived small intestinal submucosa (SIS) into the vocal fold superficial lamina propria (SLP) layer for the potential treatment of vocal fold scar, sulcus and superficial lamina propria atrophy. Small intestinal submucosa was implanted into the right vocal fold SLP of 6 mongrel dogs. The left vocal fold served as a sham surgical control. At 2, 4, and 6 weeks postoperative, bilateral vocal fold specimens were evaluated histologically. At 2 and 4 weeks, respectively, SIS-implanted vocal folds demonstrated moderate and mild inflammation and acute and chronic inflammation. At 6 weeks, inflammation was minimal and chronic. The 6-week specimens showed copious amounts of newly generated hyaluronic acid (HA) within the graft. There was no reactive fibrosis at 6 weeks. In the canine model, SIS appears safe for SLP grafting. Inflammation is similar to that of sham surgery. Small intestinal submucosa results in newly generated HA without concomitant fibrosis. Small intestinal submucosa has potential to be used in treatment of disorders with SLP, including vocal fold scar, sulcus, and atrophy. Studies evaluating the effect of SIS implantation on vocal fold function, as well as the ultimate fate of the graft, are required. © The Author(s) 2015.

  4. Recoverable and Programmable Collapse from Folding Pressurized Origami Cellular Solids.

    Science.gov (United States)

    Li, S; Fang, H; Wang, K W

    2016-09-09

    We report a unique collapse mechanism by exploiting the negative stiffness observed in the folding of an origami solid, which consists of pressurized cells made by stacking origami sheets. Such a collapse mechanism is recoverable, since it only involves rigid folding of the origami sheets and it is programmable by pressure control and the custom design of the crease pattern. The collapse mechanism features many attractive characteristics for applications such as energy absorption. The reported results also suggest a new branch of origami study focused on its nonlinear mechanics associated with folding.

  5. Water dynamics clue to key residues in protein folding

    International Nuclear Information System (INIS)

    Gao, Meng; Zhu, Huaiqiu; Yao, Xin-Qiu; She, Zhen-Su

    2010-01-01

    A computational method independent of experimental protein structure information is proposed to recognize key residues in protein folding, from the study of hydration water dynamics. Based on all-atom molecular dynamics simulation, two key residues are recognized with distinct water dynamical behavior in a folding process of the Trp-cage protein. The identified key residues are shown to play an essential role in both 3D structure and hydrophobic-induced collapse. With observations on hydration water dynamics around key residues, a dynamical pathway of folding can be interpreted.

  6. Microwave-enhanced folding and denaturation of globular proteins

    DEFF Research Database (Denmark)

    Bohr, Henrik; Bohr, Jakob

    2000-01-01

    It is shown that microwave irradiation can affect the kinetics of the folding process of some globular proteins, especially beta-lactoglobulin. At low temperature the folding from the cold denatured phase of the protein is enhanced, while at a higher temperature the denaturation of the protein from...... its folded state is enhanced. In the latter case, a negative temperature gradient is needed for the denaturation process, suggesting that the effects of the microwaves are nonthermal. This supports the notion that coherent topological excitations can exist in proteins. The application of microwaves...

  7. Protein folding and the organization of the protein topology universe

    DEFF Research Database (Denmark)

    Lindorff-Larsen,, Kresten; Røgen, Peter; Paci, Emanuele

    2005-01-01

    residues and, in addition, that the topology of the transition state is closer to that of the native state than to that of any other fold in the protein universe. Here, we review the evidence for these conclusions and suggest a molecular mechanism that rationalizes these findings by presenting a view...... of protein folds that is based on the topological features of the polypeptide backbone, rather than the conventional view that depends on the arrangement of different types of secondary-structure elements. By linking the folding process to the organization of the protein structure universe, we propose...

  8. Adjustable thermal resistor by reversibly folding a graphene sheet.

    Science.gov (United States)

    Song, Qichen; An, Meng; Chen, Xiandong; Peng, Zhan; Zang, Jianfeng; Yang, Nuo

    2016-08-11

    Phononic (thermal) devices such as thermal diodes, thermal transistors, thermal logic gates, and thermal memories have been studied intensively. However, tunable thermal resistors have not been demonstrated yet. Here, we propose an instantaneously adjustable thermal resistor based on folded graphene. Through theoretical analysis and molecular dynamics simulations, we study the phonon-folding scattering effect and the dependence of thermal resistivity on the length between two folds and the overall length. Furthermore, we discuss the possibility of realizing instantaneously adjustable thermal resistors in experiment. Our studies bring new insights into designing thermal resistors and understanding the thermal modulation of 2D materials by adjusting basic structure parameters.

  9. Sex Hormone Receptor Expression in the Human Vocal Fold Subunits.

    Science.gov (United States)

    Kirgezen, Tolga; Sunter, Ahmet Volkan; Yigit, Ozgur; Huq, Gulben Erdem

    2017-07-01

    The study aimed to evaluate the existence of sex hormone receptors in the subunits of vocal fold. This is a cadaver study. The androgen, estrogen, and progesterone receptors were examined in the epithelium (EP), superficial layer of the lamina propria (SLP), vocal ligament (VL), and macula flava (MF) of the vocal folds from 42 human cadavers (21 male, 21 female) by immunohistochemical methods. Their staining ratios were scored and statistically compared. The androgen receptor score was significantly higher for the MF than for the EP and SLP (P vocal fold, mostly in the MF and VLs. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  10. Miniaturization of Multiple-Layer Folded Patch Antennas

    DEFF Research Database (Denmark)

    Zhang, Jiaying; Breinbjerg, Olav

    2009-01-01

    A new folded patch antenna with multiple layers was developed in this paper, by folding the patch in a proper way, and a highly miniaturized antenna can be realized. The multiple layer patch with 4-layer and 6-layer are designed and evaluated at 2.4 GHz, 915 MHz, and 415 MHz respectively. Then a 4...... layer patch is fabricated and measured to validate the design method. The theoretical analysis, design and simulations, fabrications, as well as the measurements are presented in this paper. All the results show that the folded patch antenna is a good candidate in making a highly miniaturized compact...

  11. Endoscopic vocal fold injection using a 25-gauge butterfly needle.

    Science.gov (United States)

    Buchanan, M A; Riffat, F; Palme, C E

    2016-04-01

    To describe a useful technique for infiltrating a bulking agent using a butterfly needle, as part of a transoral endoscopic vocal fold medialisation procedure. This paper describes the procedure of grasping the needle with phonosurgery forceps and administering the injectate to the vocal fold through careful application of the syringe plunger via a length of rubber tubing from outside the mouth. This procedure is performed routinely in our institution without complication. The advantages of this technique are discussed. This is a safe and easy method of injecting into a vocal fold.

  12. Computational simulations of vocal fold vibration: Bernoulli versus Navier-Stokes.

    Science.gov (United States)

    Decker, Gifford Z; Thomson, Scott L

    2007-05-01

    The use of the mechanical energy (ME) equation for fluid flow, an extension of the Bernoulli equation, to predict the aerodynamic loading on a two-dimensional finite element vocal fold model is examined. Three steady, one-dimensional ME flow models, incorporating different methods of flow separation point prediction, were compared. For two models, determination of the flow separation point was based on fixed ratios of the glottal area at separation to the minimum glottal area; for the third model, the separation point determination was based on fluid mechanics boundary layer theory. Results of flow rate, separation point, and intraglottal pressure distribution were compared with those of an unsteady, two-dimensional, finite element Navier-Stokes model. Cases were considered with a rigid glottal profile as well as with a vibrating vocal fold. For small glottal widths, the three ME flow models yielded good predictions of flow rate and intraglottal pressure distribution, but poor predictions of separation location. For larger orifice widths, the ME models were poor predictors of flow rate and intraglottal pressure, but they satisfactorily predicted separation location. For the vibrating vocal fold case, all models resulted in similar predictions of mean intraglottal pressure, maximum orifice area, and vibration frequency, but vastly different predictions of separation location and maximum flow rate.

  13. Interaction of β-sheet folds with a gold surface.

    Directory of Open Access Journals (Sweden)

    Martin Hoefling

    Full Text Available The adsorption of proteins on inorganic surfaces is of fundamental biological importance. Further, biomedical and nanotechnological applications increasingly use interfaces between inorganic material and polypeptides. Yet, the underlying adsorption mechanism of polypeptides on surfaces is not well understood and experimentally difficult to analyze. Therefore, we investigate here the interactions of polypeptides with a gold(111 surface using computational molecular dynamics (MD simulations with a polarizable gold model in explicit water. Our focus in this paper is the investigation of the interaction of polypeptides with β-sheet folds. First, we concentrate on a β-sheet forming model peptide. Second, we investigate the interactions of two domains with high β-sheet content of the biologically important extracellular matrix protein fibronectin (FN. We find that adsorption occurs in a stepwise mechanism both for the model peptide and the protein. The positively charged amino acid Arg facilitates the initial contact formation between protein and gold surface. Our results suggest that an effective gold-binding surface patch is overall uncharged, but contains Arg for contact initiation. The polypeptides do not unfold on the gold surface within the simulation time. However, for the two FN domains, the relative domain-domain orientation changes. The observation of a very fast and strong adsorption indicates that in a biological matrix, no bare gold surfaces will be present. Hence, the bioactivity of gold surfaces (like bare gold nanoparticles will critically depend on the history of particle administration and the proteins present during initial contact between gold and biological material. Further, gold particles may act as seeds for protein aggregation. Structural re-organization and protein aggregation are potentially of immunological importance.

  14. Sparse RNA folding revisited: space-efficient minimum free energy structure prediction.

    Science.gov (United States)

    Will, Sebastian; Jabbari, Hosna

    2016-01-01

    RNA secondary structure prediction by energy minimization is the central computational tool for the analysis of structural non-coding RNAs and their interactions. Sparsification has been successfully applied to improve the time efficiency of various structure prediction algorithms while guaranteeing the same result; however, for many such folding problems, space efficiency is of even greater concern, particularly for long RNA sequences. So far, space-efficient sparsified RNA folding with fold reconstruction was solved only for simple base-pair-based pseudo-energy models. Here, we revisit the problem of space-efficient free energy minimization. Whereas the space-efficient minimization of the free energy has been sketched before, the reconstruction of the optimum structure has not even been discussed. We show that this reconstruction is not possible in trivial extension of the method for simple energy models. Then, we present the time- and space-efficient sparsified free energy minimization algorithm SparseMFEFold that guarantees MFE structure prediction. In particular, this novel algorithm provides efficient fold reconstruction based on dynamically garbage-collected trace arrows. The complexity of our algorithm depends on two parameters, the number of candidates Z and the number of trace arrows T; both are bounded by [Formula: see text], but are typically much smaller. The time complexity of RNA folding is reduced from [Formula: see text] to [Formula: see text]; the space complexity, from [Formula: see text] to [Formula: see text]. Our empirical results show more than 80 % space savings over RNAfold [Vienna RNA package] on the long RNAs from the RNA STRAND database (≥2500 bases). The presented technique is intentionally generalizable to complex prediction algorithms; due to their high space demands, algorithms like pseudoknot prediction and RNA-RNA-interaction prediction are expected to profit even stronger than "standard" MFE folding. SparseMFEFold is free

  15. Microsecond simulations of the folding/unfolding thermodynamics of the Trp-cage mini protein

    Science.gov (United States)

    Day, Ryan; Paschek, Dietmar; Garcia, Angel E.

    2012-01-01

    We study the unbiased folding/unfolding thermodynamics of the Trp-cage miniprotein using detailed molecular dynamics simulations of an all-atom model of the protein in explicit solvent, using the Amberff99SB force field. Replica-exchange molecular dynamics (REMD) simulations are used to sample the protein ensembles over a broad range of temperatures covering the folded and unfolded states, and at two densities. The obtained ensembles are shown to reach equilibrium in the 1 μs per replica timescale. The total simulation time employed in the calculations exceeds 100 μs. Ensemble averages of the fraction folded, pressure, and energy differences between the folded and unfolded states as a function of temperature are used to model the free energy of the folding transition, ΔG(P,T), over the whole region of temperature and pressures sampled in the simulations. The ΔG(P,T) diagram describes an ellipse over the range of temperatures and pressures sampled, predicting that the system can undergo pressure induced unfolding and cold denaturation at low temperatures and high pressures, and unfolding at low pressures and high temperatures. The calculated free energy function exhibits remarkably good agreement with the experimental folding transition temperature (Tf = 321 K), free energy and specific heat changes. However, changes in enthalpy and entropy are significantly different than the experimental values. We speculate that these differences may be due to the simplicity of the semi-empirical force field used in the simulations and that more elaborate force fields may be required to describe appropriately the thermodynamics of proteins. PMID:20408169

  16. Do mesoscale faults in a young fold belt indicate regional or local stress?

    Science.gov (United States)

    Kokado, Akihiro; Yamaji, Atsushi; Sato, Katsushi

    2017-04-01

    The result of paleostress analyses of mesoscale faults is usually thought of as evidence of a regional stress. On the other hand, the recent advancement of the trishear modeling has enabled us to predict the deformation field around fault-propagation folds without the difficulty of assuming paleo mechanical properties of rocks and sediments. We combined the analysis of observed mesoscale faults and the trishear modeling to understand the significance of regional and local stresses for the formation of mesoscale faults. To this end, we conducted the 2D trishear inverse modeling with a curved thrust fault to predict the subsurface structure and strain field of an anticline, which has a more or less horizontal axis and shows a map-scale plane strain perpendicular to the axis, in the active fold belt of Niigata region, central Japan. The anticline is thought to have been formed by fault-propagation folding under WNW-ESE regional compression. Based on the attitudes of strata and the positions of key tephra beds in Lower Pleistocene soft sediments cropping out at the surface, we obtained (1) a fault-propagation fold with the fault tip at a depth of ca. 4 km as the optimal subsurface structure, and (2) the temporal variation of deformation field during the folding. We assumed that mesoscale faults were activated along the direction of maximum shear strain on the faults to test whether the fault-slip data collected at the surface were consistent with the deformation in some stage(s) of folding. The Wallace-Bott hypothesis was used to estimate the consistence of faults with the regional stress. As a result, the folding and the regional stress explained 27 and 33 of 45 observed faults, respectively, with the 11 faults being consistent with the both. Both the folding and regional one were inconsistent with the remaining 17 faults, which could be explained by transfer faulting and/or the gravitational spreading of the growing anticline. The lesson we learnt from this work was

  17. Sex differences in thickness, and folding developments throughout the cortex.

    Science.gov (United States)

    Mutlu, A Kadir; Schneider, Maude; Debbané, Martin; Badoud, Deborah; Eliez, Stephan; Schaer, Marie

    2013-11-15

    While significant differences in male and female brain structures have commonly been reported, only a few studies have focused on the sex differences in the way the cortex matures over time. Here, we investigated cortical thickness maturation between the age of 6 to 30 years, using 209 longitudinally-acquired brain MRI scans. Significant sex differences in the trajectories of cortical thickness change with age were evidenced using non-linear mixed effects models. Similar statistical analyses were computed to quantify the differences between cortical gyrification changes with age in males and females. During adolescence, we observed a statistically significant higher rate of cortical thinning in females compared to males in the right temporal regions, the left temporoparietal junction and the left orbitofrontal cortex. This finding is interpreted as a faster maturation of the social brain areas in females. Concomitantly, statistically significant sex differences in cortical folding changes with age were observed only in one cluster of the right prefrontal regions, suggesting that the mechanisms underlying cortical thickness and gyrification changes with age are quite distinct. Sexual dimorphism in the developmental course of the cortical maturation may be associated with the different age of onset and clinical presentation of many psychiatric disorders between males and females. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Botulinum toxin in the treatment of vocal fold nodules.

    Science.gov (United States)

    Allen, Jacqui E; Belafsky, Peter C

    2009-12-01

    Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

  19. New Analysis and Theory of Deployable Folded Structures, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — A recently developed mathematical folding theory has great value for deployable space structures and in situ manufacture of large beams, panels and cylinders. The...

  20. RNA inverse folding using Monte Carlo tree search.

    Science.gov (United States)

    Yang, Xiufeng; Yoshizoe, Kazuki; Taneda, Akito; Tsuda, Koji

    2017-11-06

    Artificially synthesized RNA molecules provide important ways for creating a variety of novel functional molecules. State-of-the-art RNA inverse folding algorithms can design simple and short RNA sequences of specific GC content, that fold into the target RNA structure. However, their performance is not satisfactory in complicated cases. We present a new inverse folding algorithm called MCTS-RNA, which uses Monte Carlo tree search (MCTS), a technique that has shown exceptional performance in Computer Go recently, to represent and discover the essential part of the sequence space. To obtain high accuracy, initial sequences generated by MCTS are further improved by a series of local updates. Our algorithm has an ability to control the GC content precisely and can deal with pseudoknot structures. Using common benchmark datasets for evaluation, MCTS-RNA showed a lot of promise as a standard method of RNA inverse folding. MCTS-RNA is available at https://github.com/tsudalab/MCTS-RNA .

  1. Evidence for multiphase folding of the central Indian Ocean lithosphere

    Digital Repository Service at National Institute of Oceanography (India)

    Krishna, K.S.; Bull, J.M.; Scrutton, R.A.

    Long-wavelength (100-300 km) folding in the central Indian Ocean associated with the diffuse plate boundary separating the Indian, Australian, and Capricorn plates is Earth's most convincing example of organized large-scale lithospheric deformation...

  2. Nonlinear vs. linear biasing in Trp-cage folding simulations

    Energy Technology Data Exchange (ETDEWEB)

    Spiwok, Vojtěch, E-mail: spiwokv@vscht.cz; Oborský, Pavel; Králová, Blanka [Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6 166 28 (Czech Republic); Pazúriková, Jana [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Křenek, Aleš [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Center CERIT-SC, Masaryk Univerzity, Šumavská 416/15, 602 00 Brno (Czech Republic)

    2015-03-21

    Biased simulations have great potential for the study of slow processes, including protein folding. Atomic motions in molecules are nonlinear, which suggests that simulations with enhanced sampling of collective motions traced by nonlinear dimensionality reduction methods may perform better than linear ones. In this study, we compare an unbiased folding simulation of the Trp-cage miniprotein with metadynamics simulations using both linear (principle component analysis) and nonlinear (Isomap) low dimensional embeddings as collective variables. Folding of the mini-protein was successfully simulated in 200 ns simulation with linear biasing and non-linear motion biasing. The folded state was correctly predicted as the free energy minimum in both simulations. We found that the advantage of linear motion biasing is that it can sample a larger conformational space, whereas the advantage of nonlinear motion biasing lies in slightly better resolution of the resulting free energy surface. In terms of sampling efficiency, both methods are comparable.

  3. Trends in Utilization of Vocal Fold Injection Procedures.

    Science.gov (United States)

    Rosow, David E

    2015-11-01

    Office-based vocal fold injections have become increasingly popular over the past 15 years. Examination of trends in procedure coding for vocal fold injections in the United States from 2000 to 2012 was undertaken to see if they reflect this shift. The US Part B Medicare claims database was queried from 2000 through 2012 for multiple Current Procedural Terminology codes. Over the period studied, the number of nonoperative laryngoscopic injections (31513, 31570) and operative medialization laryngoplasties (31588) remained constant. Operative vocal fold injection (31571) demonstrated marked linear growth over the 12-year study period, from 744 procedures in 2000 to 4788 in 2012-an increase >640%. The dramatic increased incidence in the use of code 31571 reflects an increasing share of vocal fold injections being performed in the operating room and not in an office setting, running counter to the prevailing trend toward awake, office-based injection procedures. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  4. Traumatic chorioretinal folds treated with intra-vitreal triamcinolone injection

    Directory of Open Access Journals (Sweden)

    Kook Young Kim

    2013-01-01

    Full Text Available A 34-year-old male visited the hospital due to decreased visual acuity in the left eye following an injury from a car accident. In the left eye, best-corrected visual acuity (BCVA was hand motion and intraocular pressure (IOP was 8 mmHg. Choroidal vasodilation and chorioretinal folds were observed by spectral domain-optical coherence tomography (SD-OCT. Topical and systemic steroid treatments did not improve the chorioretinal folds. Twelve months after the injury, intra-vitreal triamcinolone (4 mg/0.1 ml was injected. Six months after intra-vitreal triamcinolone injection, BCVA in the left eye had improved to 20/100. Fundus examination showed improvement in retinal vascular tortuosity and SD-OCT revealed improvements in choroidal vasodilation and chorioretinal folds. Intra-vitreal triamcinolone injection (IVTI was effective against traumatic chorioretinal folds with no recurrence based on objective observation by fundus photography and SD-OCT.

  5. Phonosurgery of the vocal folds : a classification proposal

    NARCIS (Netherlands)

    Remacle, M; Friedrich, G; Dikkers, FG; de Jong, F

    The Phonosurgery Committee of the European Laryngological Society (ELS) has examined the definition and technical description of phonosurgical procedures. Based on this review, the committee has proposed a working classification. The current presentation is restricted to vocal fold surgery (VFS)

  6. Protein folding and misfolding shining light by infrared spectroscopy

    CERN Document Server

    Fabian, Heinz

    2012-01-01

    Infrared spectroscopy is a new and innovative technology to study protein folding/misfolding events in the broad arsenal of techniques conventionally used in this field. The progress in understanding protein folding and misfolding is primarily due to the development of biophysical methods which permit to probe conformational changes with high kinetic and structural resolution. The most commonly used approaches rely on rapid mixing methods to initiate the folding event via a sudden change in solvent conditions. Traditionally, techniques such as fluorescence, circular dichroism or visible absorption are applied to probe the process. In contrast to these techniques, infrared spectroscopy came into play only very recently, and the progress made in this field up to date which now permits to probe folding events over the time scale from picoseconds to minutes has not yet been discussed in a book. The aim of this book is to provide an overview of the developments as seen by some of the main contributors to the field...

  7. Thermal analysis for folded solar array of spacecraft in orbit

    International Nuclear Information System (INIS)

    Yang, W.H.; Cheng, H.E.; Cai, A.

    2004-01-01

    The combined radiation-conduction heat transfer in folded solar array was considered as a three-dimensional anisotropic conduction without inner heat source. The three-dimensional equivalent conductivity in cell plate were obtained. The especially discrete equation coefficients of the nodes on the surfaces of adjacent cell plates were deduced by utilizing the simplified radiation network among the two adjacent cell plate surfaces and the deep cold space. All the thermal influence factors on the temperature response of the folded solar array were considered carefully. SIP method was used to solve the discrete equation. By comparing the calculation results under three cases, the temperature response and the maximum average difference of the folded solar array was obtained during the period of throw-radome of the launch vehicle and spread of the folded solar array. The obtained result is a valuable reference for the selection of the launch time of the spacecraft

  8. Morphometric Study of Vocal Folds in Indian Cadavers

    Directory of Open Access Journals (Sweden)

    Rawal J.D.

    2015-06-01

    Full Text Available Introduction: -The larynx is an air passage and a sphincteric device used in respiration and phonation. The larynx, from inside outwards has a framework of mucosa surrounded by fibro-elastic membrane which in turn is surrounded by cartilages and then a layer of muscles. Vocal folds are intrinsic ligament of larynx covered by mucosal folds. Larynx generates sound through rhythmic opening and closing of the vocal folds. The perceived pitch of human voice mainly depends upon fundamental frequency of sound generated by larynx. Aim: - The aim of present study is to measure various dimensions of vocal folds in Indian cadavers. Material & Methods: - 50 larynx were obtained from embalmed cadavers, of which 10 larynx were of females. Vocal cords were dissected from the larynx and morphometric analysis was done. Results and Conclusions: - The average total length of the vocal folds was found to be 16.11 mm. ± 2.62 mm. in male and 14.10 mm. ± 1.54 mm. in female cadavers. The average width of the vocal folds was found to be 4.38 mm. ± 0.74 mm. in male and 3.60 mm. ± 0.64 mm. in female cadavers. The average total length of the membranous part of the vocal folds was found to be 11.90 mm. ± 1.86 mm. in male and 10.45 mm. ± 1.81 mm. in female cadavers. The average ratio of the length of the membranous and the cartilaginous parts of the vocal folds was calculated to be 3.10 ± 0.96in male and 2.85 ± 0.73in female cadavers.

  9. WW Domain Folding Complexity Revealed by Infrared Spectroscopy

    OpenAIRE

    Davis, Caitlin M.; Dyer, R. Brian

    2014-01-01

    Although the intrinsic tryptophan fluorescence of proteins offers a convenient probe of protein folding, interpretation of the fluorescence spectrum is often difficult because it is sensitive to both global and local changes. Infrared (IR) spectroscopy offers a complementary measure of structural changes involved in protein folding, because it probes changes in the secondary structure of the protein backbone. Here we demonstrate the advantages of using multiple probes, infrared and fluorescen...

  10. Cervical osteophytes presenting as unilateral vocal fold paralysis and dysphagia.

    Science.gov (United States)

    Yoskovitch, A; Kantor, S

    2001-05-01

    Any process involving either the vagus nerve, its recurrent laryngeal branch or the external branch of the superior laryngeal nerve may cause paralysis of the vocal fold. The most common cause is neoplasm. Clinically, the patients often present with a hoarse, breathy voice as well as symptoms of aspiration. The following represents a unique case of unilateral vocal fold paralysis and dysphagia caused by a degenerative disease of the cervical spine, resluting in extrinsic compression of the recurrent laryngeal nerve.

  11. The Arterial Folding Point During Flexion of the Hip Joint

    International Nuclear Information System (INIS)

    Park, Sung Il; Won, Je Hwan; Kim, Byung Moon; Kim, Jae Keun; Lee, Do Yun

    2005-01-01

    Purpose: Endovascular stents placed in periarticular vessels may be at a greater risk of neointimal hyperplasia and eventual occlusion than those placed in non-periarticular vessels. The purpose of this study was to investigate the location of maximal conformational change along the iliac and femoral artery, the folding point, during flexion of the hip joint and its location relative to the hip joint and the inguinal ligament. Methods: Seventy patients undergoing femoral artery catheterization were evaluated. The patients were 47 men and 23 women and ranged in age from 26 to 75 years (mean 54 years). The arteries (right:left = 34:36) were measured using a marked catheter for sizing vessels. Fluoroscopic images were obtained in anteroposterior and lateral projections in neutral position, and in the lateral projection in flexed position of the hip joint. The folding point was determined by comparing the lateral projection images in the neutral and flexed positions. The distance from the acetabular roof to the folding point and the distance from the inguinal ligament to the folding point was evaluated. Results: : The folding point was located 42.8 ± 28.6 mm cranial to the acetabular roof and 35.1 ± 30.1 mm cranial to the inguinal ligament. As the patient’s age increased, the folding point was located more cranially (p < 0.001). Conclusions: The folding point during flexion of the hip joint was located 42.8 ± 28.6 mm cranial to the acetabular roof and 35.1 ± 30.1 mm cranial to the inguinal ligament. As the patient's age increased, the folding point was located more cranially. When a stent is inserted over this region, more attention may be needed during follow-up to monitor possible occlusion and stent failure.

  12. Oral and vocal fold diadochokinesis in dysphonic women

    OpenAIRE

    Louzada,Talita; Beraldinelle,Roberta; Berretin-Felix,Giédre; Brasolotto,Alcione Ghedini

    2011-01-01

    The evaluation of oral and vocal fold diadochokinesis (DDK) in individuals with voice disorders may contribute to the understanding of factors that affect the balanced vocal production. Scientific studies that make use of this assessment tool support the knowledge advance of this area, reflecting the development of more appropriate therapeutic planning. Objective: To compare the results of oral and vocal fold DDK in dysphonic women and in women without vocal disorders. Material and methods: F...

  13. Towards the theoretical bases of the folding of the 100-A nucleosome filament

    International Nuclear Information System (INIS)

    Chela Flores, J.

    1994-01-01

    We attempt to model DNA packaging at the various stages of ever increasing DNA folding from the 100-A nucleosome filament to various further stages leading up to the metaphase chromosome. We have assumed that a phase transition has induced chromatin into a condensed mode. The mean-field model allows the simultaneous discussion of chromatin with packaging ration η and DNA replication at various stages of folding. We derive a formula correlating (during the S phase of the cell cycle) the DNA polymerase velocity r f (measured in nucleotides per minute) in a relation of inverse proportionality with the degree of DNA packaging: r f = λη -1/2 , where the dimensional constant λ has been determined. This model suggests that in the heterochromatic regions of chromatin there is reduced activity of DNA polymerases. We discuss the possible relevance of our model to late replicating telomeres in yeast and several higher eukaryotes. (author). 28 refs, 3 tabs

  14. Vocal fold ion transport and mucin expression following acrolein exposure.

    Science.gov (United States)

    Levendoski, Elizabeth Erickson; Sivasankar, M Preeti

    2014-05-01

    The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health.

  15. Protein solubility and folding enhancement by interaction with RNA.

    Directory of Open Access Journals (Sweden)

    Seong Il Choi

    Full Text Available While basic mechanisms of several major molecular chaperones are well understood, this machinery has been known to be involved in folding of only limited number of proteins inside the cells. Here, we report a chaperone type of protein folding facilitated by interaction with RNA. When an RNA-binding module is placed at the N-terminus of aggregation-prone target proteins, this module, upon binding with RNA, further promotes the solubility of passenger proteins, potentially leading to enhancement of proper protein folding. Studies on in vitro refolding in the presence of RNA, coexpression of RNA molecules in vivo and the mutants with impaired RNA binding ability suggests that RNA can exert chaperoning effect on their bound proteins. The results suggest that RNA binding could affect the overall kinetic network of protein folding pathway in favor of productive folding over off-pathway aggregation. In addition, the RNA binding-mediated solubility enhancement is extremely robust for increasing soluble yield of passenger proteins and could be usefully implemented for high-throughput protein expression for functional and structural genomic research initiatives. The RNA-mediated chaperone type presented here would give new insights into de novo folding in vivo.

  16. Self-Folding Textiles through Manipulation of Knit Stitch Architecture

    Directory of Open Access Journals (Sweden)

    Chelsea E. Knittel

    2015-12-01

    Full Text Available This research presents a preliminary study on finding predictable methods of controlling the self-folding behaviors of weft knit textiles for use in the development of smart textiles and garment devices, such as those with shape memory, auxetic behavior or transformation abilities. In this work, Shima Seiki SDS-One Apex computer-aided knitting technology, Shima Seiki industrial knitting machines, and the study of paper origami tessellation patterns were used as tools to understand and predict the self-folding abilities of weft knit textiles. A wide range of self-folding weft knit structures was produced, and relationships between the angles and ratios of the knit and purl stitch types were determined. Mechanical testing was used as a means to characterize differences produced by stitch patterns, and to further understand the relationships between angles and folding abilities. By defining a formulaic method for predicting the nature of the folds that occur due to stitch architecture patterns, we can better design self-folding fabrics for smart textile applications.

  17. Multi-crease Self-folding by Global Heating.

    Science.gov (United States)

    Miyashita, Shuhei; Onal, Cagdas D; Rus, Daniela

    2015-01-01

    This study demonstrates a new approach to autonomous folding for the body of a 3D robot from a 2D sheet, using heat. We approach this challenge by folding a 0.27-mm sheetlike material into a structure. We utilize the thermal deformation of a contractive sheet sandwiched by rigid structural layers. During this baking process, the heat applied on the entire sheet induces contraction of the contracting layer and thus forms an instructed bend in the sheet. To attain the targeted folding angles, the V-fold spans method is used. The targeted angle θout can be kinematically encoded into crease geometry. The realization of this angle in the folded structure can be approximately controlled by a contraction angle θin. The process is non-reversible, is reliable, and is relatively fast. Our method can be applied simultaneously to all the folds in multi-crease origami structures. We demonstrate the use of this method to create a lightweight mobile robot.

  18. Synthetic oligorotaxanes exert high forces when folding under mechanical load

    Science.gov (United States)

    Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

    2018-01-01

    Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

  19. CATHEDRAL: a fast and effective algorithm to predict folds and domain boundaries from multidomain protein structures.

    Directory of Open Access Journals (Sweden)

    Oliver C Redfern

    2007-11-01

    Full Text Available We present CATHEDRAL, an iterative protocol for determining the location of previously observed protein folds in novel multidomain protein structures. CATHEDRAL builds on the features of a fast secondary-structure-based method (using graph theory to locate known folds within a multidomain context and a residue-based, double-dynamic programming algorithm, which is used to align members of the target fold groups against the query protein structure to identify the closest relative and assign domain boundaries. To increase the fidelity of the assignments, a support vector machine is used to provide an optimal scoring scheme. Once a domain is verified, it is excised, and the search protocol is repeated in an iterative fashion until all recognisable domains have been identified. We have performed an initial benchmark of CATHEDRAL against other publicly available structure comparison methods using a consensus dataset of domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows superior performance in fold recognition and alignment accuracy when compared with many equivalent methods. If a novel multidomain structure contains a known fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For nearly 80% of assigned domains in a manually validated test set, the boundaries were correctly delineated within a tolerance of ten residues. For the remaining cases, previously classified domains were very remotely related to the query chain so that embellishments to the core of the fold caused significant differences in domain sizes and manual refinement of the boundaries was necessary. To put this performance in context, a well-established sequence method based on hidden Markov models was only able to detect 65% of domains, with 33% of the subsequent boundaries assigned within ten residues. Since, on average, 50% of newly determined protein structures contain more than one domain unit, and typically 90% or more of these

  20. Comparing apples and oranges: fold-change detection of multiple simultaneous inputs.

    Directory of Open Access Journals (Sweden)

    Yuval Hart

    Full Text Available Sensory systems often detect multiple types of inputs. For example, a receptor in a cell-signaling system often binds multiple kinds of ligands, and sensory neurons can respond to different types of stimuli. How do sensory systems compare these different kinds of signals? Here, we consider this question in a class of sensory systems - including bacterial chemotaxis- which have a property known as fold-change detection: their output dynamics, including amplitude and response time, depends only on the relative changes in signal, rather than absolute changes, over a range of several decades of signal. We analyze how fold-change detection systems respond to multiple signals, using mathematical models. Suppose that a step of fold F1 is made in input 1, together with a step of F2 in input 2. What total response does the system provide? We show that when both input signals impact the same receptor with equal number of binding sites, the integrated response is multiplicative: the response dynamics depend only on the product of the two fold changes, F1F2. When the inputs bind the same receptor with different number of sites n1 and n2, the dynamics depend on a product of power laws, [Formula: see text]. Thus, two input signals which vary over time in an inverse way can lead to no response. When the two inputs affect two different receptors, other types of integration may be found and generally the system is not constrained to respond according to the product of the fold-change of each signal. These predictions can be readily tested experimentally, by providing cells with two simultaneously varying input signals. The present study suggests how cells can compare apples and oranges, namely by comparing each to its own background level, and then multiplying these two fold-changes.