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Sample records for folding model analysis

  1. The influence of modeling assumptions on the modal analysis of vocal fold structures

    NASA Astrophysics Data System (ADS)

    Cook, Douglas D.; Mongeau, Luc

    2005-09-01

    Finite-element modal analysis studies of several vocal fold structural models were performed in vacuo under a variety of assumptions. The sensitivity of the vocal folds to changes in geometry and tissue properties was investigated. The Ritz method and the finite-element code ADINA were used to perform linear modal analysis of two-dimensional and three-dimensional models of the human vocal folds. The results allow for comparison and evaluation of various modeling approaches. In particular, the influence of geometrical constraints was shown to introduce errors of varying magnitude depending on the degree of anisotropy of the vocal fold tissue. [Research supported by the National Institute for Deafness and Other Communication Disorders.

  2. Comprehensive, Population-Based Sensitivity Analysis of a Two-Mass Vocal Fold Model

    PubMed Central

    Robertson, Daniel; Zañartu, Matías; Cook, Douglas

    2016-01-01

    Previous vocal fold modeling studies have generally focused on generating detailed data regarding a narrow subset of possible model configurations. These studies can be interpreted to be the investigation of a single subject under one or more vocal conditions. In this study, a broad population-based sensitivity analysis is employed to examine the behavior of a virtual population of subjects and to identify trends between virtual individuals as opposed to investigating a single subject or model instance. Four different sensitivity analysis techniques were used in accomplishing this task. Influential relationships between model input parameters and model outputs were identified, and an exploration of the model’s parameter space was conducted. Results indicate that the behavior of the selected two-mass model is largely dominated by complex interactions, and that few input-output pairs have a consistent effect on the model. Results from the analysis can be used to increase the efficiency of optimization routines of reduced-order models used to investigate voice abnormalities. Results also demonstrate the types of challenges and difficulties to be expected when applying sensitivity analyses to more complex vocal fold models. Such challenges are discussed and recommendations are made for future studies. PMID:26845452

  3. Analysis of repeat-protein folding using nearest-neighbor statistical mechanical models

    PubMed Central

    Aksel, Tural; Barrick, Doug

    2010-01-01

    The linear “Ising” model, which has been around for nearly a century, treats the behavior of linear arrays of repetitive, interacting subunits. Linear “repeat-proteins” have only been described in the last decade or so, and their folding energies have only been characterized very recently. Owing to their repetitive structures, linear repeat-proteins are particularly well suited for analysis by the nearest-neighbor Ising formalism. After briefly describing the historical origins and applications of the Ising model to biopolymers, and introducing repeat protein structure, this chapter will focus on the application of the linear Ising model to repeat proteins. When applied to homopolymers, the model can be represented and applied in a fairly simplified form. When applied to heteropolymers, where differences in energies among individual subunits (i.e. repeats) must be included, some (but not all) of this simplicity is lost. Derivations of the linear Ising model for both homopolymer and heteropolymer repeat-proteins will be presented. With the increased complexity required for analysis of heteropolymeric repeat proteins, the ability to resolve different energy terms from experimental data can be compromised. Thus, a simple matrix approach will be developed to help inform on the degree to which different thermodynamic parameters can be extracted from a particular set of unfolding curves. Finally, we will describe the application of these models to analyze repeat-protein folding equilibria, focusing on simplified repeat proteins based on “consensus” sequence information. PMID:19289204

  4. Protein Folding: Detailed Models

    NASA Astrophysics Data System (ADS)

    Pande, Vijay

    Proteins play a fundamental role in biology. With their ability to perform numerous biological roles, including acting as catalysts, antibodies, and molecular signals, proteins today realize many of the goals that modern nanotechnology aspires to. However, before proteins can carry out these remarkable molecular functions, they must perform another amazing feat — they must assemble themselves. This process of protein self-assembly into a particular shape, or "fold" is called protein folding. Due to the importance of the folded state in the biological activity of proteins, recent interest from misfolding related diseases [1], as well as a fascination of just how this process occurs [2-4], there has been much work performed in order to unravel the mechanism of protein folding [5].

  5. Universality and diversity of the protein folding scenarios: a comprehensive analysis with the aid of a lattice model.

    PubMed

    Mirny, L A; Abkevich, V; Shakhnovich, E I

    1996-01-01

    The role of intermediates in protein folding has been a matter of great controversy. Although it was widely believed that intermediates play a key role in minimizing the search problem associated with the Levinthal paradox, experimental evidence has been accumulating that small proteins fold fast without any detectable intermediates. We study the thermodynamics and kinetics of folding using a simple lattice model. Two folding sequences obtained by the design procedure exhibit different folding scenarios. The first sequence folds fast to the native state and does not exhibit any populated intermediates during folding. In contrast, the second sequence folds much slower, often being trapped in misfolded low-energy conformations. However, a small fraction of folding molecules for the second sequence fold on a fast track avoiding misfolded traps. In equilibrium at the same temperature the second sequence has a highly populated intermediate with structure similar to that of the kinetics intermediate. Our analysis suggests that intermediates may often destabilize native conformations and derail the folding process leading it to traps. Less-optimized sequences fold via parallel pathways involving misfolded intermediates. A better designed sequence is more stable in the native state and folds fast without intermediates in a two-state process.

  6. Statistical analysis of native contact formation in the folding of designed model proteins

    NASA Astrophysics Data System (ADS)

    Tiana, Guido; Broglia, Ricardo A.

    2001-02-01

    The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds emerge: (a) local, fast forming highly stable native bonds built by some of the most strongly interacting amino acids of the protein; (b) nonlocal bonds formed late in the folding process, in coincidence with the folding nucleus, and involving essentially the same strongly interacting amino acids already participating in the fast bonds; (c) the rest of the native bonds whose behavior is subordinated, to a large extent, to that of the strong local and nonlocal native contacts.

  7. Folding of a model three-helix bundle protein: a thermodynamic and kinetic analysis.

    PubMed

    Zhou, Y; Karplus, M

    1999-11-05

    The kinetics and thermodynamics of an off-lattice model for a three-helix bundle protein are investigated as a function of a bias gap parameter that determines the energy difference between native and non-native contacts. A simple dihedral potential is used to introduce the tendency to form right-handed helices. For each value of the bias parameter, 100 trajectories of up to one microsecond are performed. Such statistically valid sampling of the kinetics is made possible by the use of the discrete molecular dynamics method with square-well interactions. This permits much faster simulations for off-lattice models than do continuous potentials. It is found that major folding pathways can be defined, although ensembles with considerable structural variation are involved. The large gap models generally fold faster than those with a smaller gap. For the large gap models, the kinetic intermediates are non-obligatory, while both obligatory and non-obligatory intermediates are present for small gap models. Certain large gap intermediates have a two-helix microdomain with one helix extended outward (as in domain-swapped dimers); the small gap intermediates have more diverse structures. The importance of studying the kinetic, as well as the thermodynamics, of folding for an understanding of the mechanism is discussed and the relation between kinetic and equilibrium intermediates is examined. It is found that the behavior of this model system has aspects that encompass both the "new" view and the "old" view of protein folding.

  8. Cerebral Cortical Folding Analysis with Multivariate Modeling and Testing: Studies on Gender Differences and Neonatal Development

    PubMed Central

    Awate, Suyash P.; Yushkevich, Paul A.; Song, Zhuang; Licht, Daniel J.; Gee, James C.

    2010-01-01

    This paper presents a novel statistical framework for human cortical folding pattern analysis that relies on a rich multivariate descriptor of folding patterns in a region of interest (ROI). The ROI-based approach avoids problems faced by spatial-normalization-based approaches stemming from the deficiency of homologous features between typical human cerebral cortices. Unlike typical ROI-based methods that summarize folding by a single number, the proposed descriptor unifies multiple characteristics of surface geometry in a high-dimensional space (hundreds/thousands of dimensions). In this way, the proposed framework couples the reliability of ROI-based analysis with the richness of the novel cortical folding pattern descriptor. This paper presents new mathematical insights into the relationship of cortical complexity with intra-cranial volume (ICV). It shows that conventional complexity descriptors implicitly handle ICV Differences in Different ways, thereby lending Different meanings to “complexity”. The paper proposes a new application of a non-parametric permutation-based approach for rigorous statistical hypothesis testing with multivariate cortical descriptors. The paper presents two cross-sectional studies applying the proposed framework to study folding Differences between genders and in neonates with complex congenital heart disease. Both studies lead to novel interesting results. PMID:20630489

  9. Moho topography, ranges and folds of Tibet by analysis of global gravity models and GOCE data

    PubMed Central

    Shin, Young Hong; Shum, C.K.; Braitenberg, Carla; Lee, Sang Mook; Na, Sung -Ho; Choi, Kwang Sun; Hsu, Houtse; Park, Young-Sue; Lim, Mutaek

    2015-01-01

    The determination of the crustal structure is essential in geophysics, as it gives insight into the geohistory, tectonic environment, geohazard mitigation, etc. Here we present the latest advance on three-dimensional modeling representing the Tibetan Mohorovičić discontinuity (topography and ranges) and its deformation (fold), revealed by analyzing gravity data from GOCE mission. Our study shows noticeable advances in estimated Tibetan Moho model which is superior to the results using the earlier gravity models prior to GOCE. The higher quality gravity field of GOCE is reflected in the Moho solution: we find that the Moho is deeper than 65 km, which is twice the normal continental crust beneath most of the Qinghai-Tibetan plateau, while the deepest Moho, up to 82 km, is located in western Tibet. The amplitude of the Moho fold is estimated to be ranging from −9 km to 9 km with a standard deviation of ~2 km. The improved GOCE gravity derived Moho signals reveal a clear directionality of the Moho ranges and Moho fold structure, orthogonal to deformation rates observed by GPS. This geophysical feature, clearly more evident than the ones estimated using earlier gravity models, reveals that it is the result of the large compressional tectonic process. PMID:26114224

  10. Moho topography, ranges and folds of Tibet by analysis of global gravity models and GOCE data.

    PubMed

    Shin, Young Hong; Shum, C K; Braitenberg, Carla; Lee, Sang Mook; Na, Sung-Ho; Choi, Kwang Sun; Hsu, Houtse; Park, Young-Sue; Lim, Mutaek

    2015-06-26

    The determination of the crustal structure is essential in geophysics, as it gives insight into the geohistory, tectonic environment, geohazard mitigation, etc. Here we present the latest advance on three-dimensional modeling representing the Tibetan Mohorovičić discontinuity (topography and ranges) and its deformation (fold), revealed by analyzing gravity data from GOCE mission. Our study shows noticeable advances in estimated Tibetan Moho model which is superior to the results using the earlier gravity models prior to GOCE. The higher quality gravity field of GOCE is reflected in the Moho solution: we find that the Moho is deeper than 65 km, which is twice the normal continental crust beneath most of the Qinghai-Tibetan plateau, while the deepest Moho, up to 82 km, is located in western Tibet. The amplitude of the Moho fold is estimated to be ranging from -9 km to 9 km with a standard deviation of ~2 km. The improved GOCE gravity derived Moho signals reveal a clear directionality of the Moho ranges and Moho fold structure, orthogonal to deformation rates observed by GPS. This geophysical feature, clearly more evident than the ones estimated using earlier gravity models, reveals that it is the result of the large compressional tectonic process.

  11. Moho topography, ranges and folds of Tibet by analysis of global gravity models and GOCE data

    NASA Astrophysics Data System (ADS)

    Shin, Young Hong; Shum, C. K.; Braitenberg, Carla; Lee, Sang Mook; Na, Sung-Ho; Choi, Kwang Sun; Hsu, Houtse; Park, Young-Sue; Lim, Mutaek

    2015-06-01

    The determination of the crustal structure is essential in geophysics, as it gives insight into the geohistory, tectonic environment, geohazard mitigation, etc. Here we present the latest advance on three-dimensional modeling representing the Tibetan Mohorovičić discontinuity (topography and ranges) and its deformation (fold), revealed by analyzing gravity data from GOCE mission. Our study shows noticeable advances in estimated Tibetan Moho model which is superior to the results using the earlier gravity models prior to GOCE. The higher quality gravity field of GOCE is reflected in the Moho solution: we find that the Moho is deeper than 65 km, which is twice the normal continental crust beneath most of the Qinghai-Tibetan plateau, while the deepest Moho, up to 82 km, is located in western Tibet. The amplitude of the Moho fold is estimated to be ranging from -9 km to 9 km with a standard deviation of ~2 km. The improved GOCE gravity derived Moho signals reveal a clear directionality of the Moho ranges and Moho fold structure, orthogonal to deformation rates observed by GPS. This geophysical feature, clearly more evident than the ones estimated using earlier gravity models, reveals that it is the result of the large compressional tectonic process.

  12. Mesoscale Modeling of Chromatin Folding

    NASA Astrophysics Data System (ADS)

    Schlick, Tamar

    2009-03-01

    Eukaryotic chromatin is the fundamental protein/nucleic acid unit that stores the genetic material. Understanding how chromatin fibers fold and unfold in physiological conditions is important for interpreting fundamental biological processes like DNA replication and transcription regulation. Using a mesoscopic model of oligonucleosome chains and tailored sampling protocols, we elucidate the energetics of oligonucleosome folding/unfolding and the role of each histone tail, linker histones, and divalent ions in regulating chromatin structure. The resulting compact topologies reconcile features of the zigzag model with straight linker DNAs with the solenoid model with bent linker DNAs for optimal fiber organization and reveal dynamic and energetic aspects involved.

  13. Modelling of lateral fold growth and fold linkage: Applications to fold-and-thrust belt tectonics

    NASA Astrophysics Data System (ADS)

    Grasemann, Bernhard; Schmalholz, Stefan

    2013-04-01

    We use a finite element model to investigate the three-dimensional fold growth and interference of two initially isolated fold segments. The most critical parameter, which controls the fold linkage mode, is the phase difference between the laterally growing fold hinge lines: 1) "Linear-linkage" yields a sub-cylindrical fold with a saddle at the location where the two initial folds linked. 2) "Oblique-linkage" produces a curved fold resembling a Type II refold structure. 3) "Oblique-no-linkage" results in two curved folds with fold axes plunging in opposite directions. 4) "Linear-no-linkage" yields a fold train of two separate sub-cylindrical folds with fold axes plunging in opposite directions. The transition from linkage to no-linkage occurs when the fold separation between the initially isolated folds is slightly larger than one half of the low-amplitude fold wavelength. The model results compare well with previously published plasticine analogue models and can be directly applied to the investigation of fold growth history in fold-and-thust belts. An excellent natural example of lateral fold linkage is described from the Zagros fold-and-thrust belt in the Kurdistan Region of Iraq. The fold growth in this region is not controlled by major thrust faults but the shortening of the Paleozoic to Cenozoic passive margin sediments of the Arabian plate occurred mainly by detachment folding. The sub-cylindrical anticlines with hinge-parallel lengths of more than 50 km have not developed from single sub-cylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification and lateral fold growth. Linkage points are marked by geomorphological saddle points which are structurally the lowermost points of antiforms and points of principal curvatures with opposite sign. Linkage points can significantly influence the migration of mineral-rich fluids and hydrocarbons and are therefore of great economic importance.

  14. Cluster folding model analysis of 3He elastic and inelastic scattering from 12C

    NASA Astrophysics Data System (ADS)

    Khallaf, S. A. E.; Nossair, A. M. A.; Ebrahim, A. A.; Ebraheem, Awad A.

    2003-02-01

    Angular distributions of differential cross sections for the 12C( 3He, 3He) 12C, 12C( 3He, 3He) 12C ∗ reactions at E=72 MeV have been analyzed with a double folding cluster model DFC based on five sets of the effective N-N interaction of Gaussian form with different parameters. The transition to the (2 +; 4.44 MeV) state in 12C is studied and the deformation length δ2 is extracted. It is found that the extracted deformation length is sensitive to the nuclear model used and it is similar to the corresponding value found in the literature.

  15. Folding Model Analysis of Elastic Scattering of 11B from Light, Medium, and Heavy Nuclei

    NASA Astrophysics Data System (ADS)

    Aygun, M.

    2016-11-01

    The elastic scattering angular distributions of 11B projectile on light, medium, and heavy target nuclei including 7Li, 9Be, 12C, 16O, 24,25,26Mg, 27Al, 28Si, 40Ca, 58Ni, 59Co, 60Ni, 197Au, 208Pb, and 209Bi have been analyzed at various incident energies. The theoretical results have been obtained by using two different nuclear potentials within the framework of the optical model (OM). Firstly, the double folding potential for real part and the Wood—Saxon (WS) potential for imaginary part have been applied. Secondly, the calculations with double folding potential for both real and imaginary part have been performed and compared with the experimental data. It has been seen that the results are in very good agreement with the experimental data. Also, the volume integrals and cross-sections for each reaction have been obtained. Finally, a new and simple formula for the imaginary potential depth has been derived to clarify the nuclear interactions of 11B nucleus at low energy reactions.

  16. Establishment and Analysis of False Vocal Folds Hypertrophy Model in Excised Canine Larynges.

    PubMed

    Jiao, Yanchao; Wang, Ruiqing; Zeng, Qingkai; Xu, Xinlin; Zhang, Yu; Leggon, Bobby; Jiang, Jack; Zhuang, Peiyun

    2017-09-18

    This study aimed to investigate the role of false vocal folds (FVFs) medialization in phonation and the acoustic impact of ventricular hypertrophy by establishing an FVF hypertrophy model. A prospective in vitro experiment was carried out. The study was carried out using a pseudolung platform with high-speed camera in a soundproof room. Control, degree I, and degree II FVFs hypertrophy were simulated in 10 excised larynges via fructose injection of 0.1 mL for degree I and 0.25 mL for degree II. Mean flow rate (MFR), fundamental frequencies (F0), formants, and sound pressure level were measured with a subglottal pressure of 1.5 kPa and 2.5 kPa, respectively. When the subglottal pressure was controlled at both at 1.5 kPa and at 2.5 kPa, the degree of FVF hypertrophy significantly influenced the distribution of the formants, F0, and MFR in excised canine larynges. Increasing the degree of hypertrophy was associated with a decrease in F0 and an increase in MFR. In degree II FVF hypertrophy models, the sound pressure level and the first formant were significantly higher (P < 0.05) than in normal models. Hypertrophy of the FVFs has a significant influence on the distribution of sound energy and is associated with changes in sound quality. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  17. Simple Model of Protein Folding Kinetics

    NASA Astrophysics Data System (ADS)

    Zwanzig, Robert

    1995-10-01

    A simple model of the kinetics of protein folding is presented. The reaction coordinate is the "correctness" of a configuration compared with the native state. The model has a gap in the energy spectrum, a large configurational entropy, a free energy barrier between folded and partially folded states, and a good thermodynamic folding transition. Folding kinetics is described by a master equation. The folding time is estimated by means of a local thermodynamic equilibrium assumption and then is calculated both numerically and analytically by solving the master equation. The folding time has a maximum near the folding transition temperature and can have a minimum at a lower temperature.

  18. Component Modal Analysis of a Folding Wing

    NASA Astrophysics Data System (ADS)

    Wang, Ivan

    This thesis explores the aeroelastic stability of a folding wing with an arbitrary number of wing segments. Simplifying assumptions are made such that it is possible to derive the equations of motion analytically. First, a general structural dynamics model based on beam theory is derived from a modal analysis using Lagrange's equations, and is used to predict the natural frequencies of different folding wing configurations. Next, the structural model is extended to an aeroelastic model by incorporating the effects of unsteady aerodynamic forces. The aeroelastic model is used to predict the flutter speed and flutter frequencies of folding wings. Experiments were conducted for three folding wing configurations---a two-segment wing, a three-segment wing, and a four-segment wing---and the outboard fold angle was varied over a wide range for each configuration. Very good agreement in both magnitude and overall trend was obtained between the theoretical and experimental structural natural frequencies, as well as the flutter frequency. For the flutter speed, very good agreement was obtained for the two-segment model, but the agreement worsens as the number of wing segments increases. Possible sources of error and attempts to improve correlation are described. Overall, the aeroelastic model predicts the general trends to good accuracy, offers some additional physical insight, and can be used to efficiently compute flutter boundaries and frequency characteristics for preliminary design or sensitivity studies.

  19. Balanced cross section, kinematic deformation model, and palinspastic facies analysis for the Bogota fold belt, Eastern Cordillera, Colombia

    SciTech Connect

    Villamil, T. ); Restrepo, P. ); Ratliff, R.; Wu, S.; Kligfield, R.; Geiser, P. )

    1993-02-01

    The Bogota fold belt of the Eastern Cordillera, Colombia has long been considered a relatively simple zone of Tertiary-aged folding. To a large degree this picture is due to the presence of a monotonous sequence of turbidites which containes very few distinct formation boundaries useful for delineating the structural geometry. However, new surface mapping together with biostratigraphic and sequence stratigraphic zonation have been used to define a complex thrust system involving southeast vergent imbricate and duplex structures. Biozone and facies boundaries are recognizable throughout the mapped area and provide a high resolution stratigraphic template for structural analysis. The thrustbell architecture is illustrated by a 17 km long balanced cross section which has been constructed using kinematic fault bend and fault propagation fold models. The use of balanced section construction techniques has in turn allowed further refinement of the stratigraphic model and facies analysis in the palinspastic restoration. The cross section constrains an overall breakforward sequence of thrust initiation with a lower detachment in shales at the base of the Cretaceous Caqueza Group. There are a minimum of 16 major ramps through the Cretaceous section and an irregularly developed upper detachment near the top of the Caqueza Group. The deformation has resulted in a minimum of 13 km of horizontal shortening in this portion of the Eastern Cordillera.

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

    NASA Astrophysics Data System (ADS)

    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. How Kinetics within the Unfolded State Affects Protein Folding: an Analysis Based on Markov State Models and an Ultra-Long MD Trajectory

    PubMed Central

    Deng, Nan-jie; Dai, Wei

    2013-01-01

    Understanding how kinetics in the unfolded state affects protein folding is a fundamentally important yet less well-understood issue. Here we employ three different models to analyze the unfolded landscape and folding kinetics of the miniprotein Trp-cage. The first is a 208 μs explicit solvent molecular dynamics (MD) simulation from D. E. Shaw Research containing tens of folding events. The second is a Markov state model (MSM-MD) constructed from the same ultra-long MD simulation; MSM-MD can be used to generate thousands of folding events. The third is a Markov state model built from temperature replica exchange MD simulations in implicit solvent (MSM-REMD). All the models exhibit multiple folding pathways, and there is a good correspondence between the folding pathways from direct MD and those computed from the MSMs. The unfolded populations interconvert rapidly between extended and collapsed conformations on time scales ≤ 40 ns, compared with the folding time of ≈ 5 μs. The folding rates are independent of where the folding is initiated from within the unfolded ensemble. About 90 % of the unfolded states are sampled within the first 40 μs of the ultra-long MD trajectory, which on average explores ~27 % of the unfolded state ensemble between consecutive folding events. We clustered the folding pathways according to structural similarity into “tubes”, and kinetically partitioned the unfolded state into populations that fold along different tubes. From our analysis of the simulations and a simple kinetic model, we find that when the mixing within the unfolded state is comparable to or faster than folding, the folding waiting times for all the folding tubes are similar and the folding kinetics is essentially single exponential despite the presence of heterogeneous folding paths with non-uniform barriers. When the mixing is much slower than folding, different unfolded populations fold independently leading to non-exponential kinetics. A kinetic partition of

  2. Analysis of flow-structure coupling in a mechanical model of the vocal folds and the subglottal system

    NASA Astrophysics Data System (ADS)

    Howe, M. S.; McGowan, R. S.

    2009-11-01

    An analysis is made of the nonlinear interactions between flow in the subglottal vocal tract and glottis, sound waves in the subglottal system and a mechanical model of the vocal folds. The mean flow through the system is produced by a nominally steady contraction of the lungs, and mechanical experiments frequently involve a ‘lung cavity’ coupled to an experimental subglottal tube of arbitrary or ill-defined effective length L, on the basis that the actual value of L has little or no influence on excitation of the vocal folds. A simple, self-exciting single-mass mathematical model of the vocal folds is used to investigate the sound generated within the subglottal domain and the unsteady volume flux from the glottis for experiments where it is required to suppress feedback of sound from the supraglottal vocal tract. In experiments where the assumed absorption of sound within the sponge-like interior of the lungs is small, the influence of changes in L can be very significant: when the subglottal tube behaves as an open-ended resonator (when L is as large as half the acoustic wavelength) there is predicted to be a mild increase in volume flux magnitude and a small change in waveform. However, the strong appearance of second harmonics of the acoustic field is predicted at intermediate lengths, when L is roughly one quarter of the acoustic wavelength. In cases of large lung damping, however, only modest changes in the volume flux are predicted to occur with variations in L.

  3. Strain modelling of extensional fault-propagation folds based on an improved non-linear trishear model: A numerical simulation analysis

    NASA Astrophysics Data System (ADS)

    Zhao, Haonan; Guo, Zhaojie; Yu, Xiangjiang

    2017-02-01

    This paper focuses on the strain modelling of extensional fault-propagation folds to reveal the effects of key factors on the strain accumulation and the relationship between the geometry and strain distribution of fault-related folds. A velocity-geometry-strain method is proposed for the analysis of the total strain and its accumulation process within the trishear zone of an extensional fault-propagation fold. This paper improves the non-linear trishear model proposed by Jin and Groshong (2006). Based on the improved model, the distribution of the strain rate within the trishear zone and the total strain are obtained. The numerical simulations of different parameters performed in this study indicate that the shape factor R, the total apical angle, and the P/S ratio control the final geometry and strain distribution of extensional fault-propagation folds. A small P/S ratio, a small apical angle, and an R value far greater or far smaller than 1 produce an asymmetric, narrow, and strongly deformed trishear zone. The velocity-geometry-strain analysis method is applied to two natural examples from Big Brushy Canyon in Texas and the northwestern Red Sea in Egypt. The strain distribution within the trishear zone is closely related to the geometry of the folds.

  4. Microcanonical versus Canonical Analysis of Protein Folding

    NASA Astrophysics Data System (ADS)

    Hernández-Rojas, J.; Gomez Llorente, J. M.

    2008-06-01

    The microcanonical analysis is shown to be a powerful tool to characterize the protein folding transition and to neatly distinguish between good and bad folders. An off-lattice model with parameter chosen to represent polymers of these two types is used to illustrate this approach. Both canonical and microcanonical ensembles are employed. The required calculations were performed using parallel tempering Monte Carlo simulations. The most revealing features of the folding transition are related to its first-order-like character, namely, the S-bend pattern in the caloric curve, which gives rise to negative microcanonical specific heats, and the bimodality of the energy distribution function at the transition temperatures. Models for a good folder are shown to be quite robust against perturbations in the interaction potential parameters.

  5. Implicit modeling of folds and overprinting deformation

    NASA Astrophysics Data System (ADS)

    Laurent, Gautier; Ailleres, Laurent; Grose, Lachlan; Caumon, Guillaume; Jessell, Mark; Armit, Robin

    2016-12-01

    Three-dimensional structural modeling is gaining importance for a broad range of quantitative geoscientific applications. However, existing approaches are still limited by the type of structural data they are able to use and by their lack of structural meaning. Most techniques heavily rely on spatial data for modeling folded layers, but are unable to completely use cleavage and lineation information for constraining the shape of modeled folds. This lack of structural control is generally compensated by expert knowledge introduced in the form of additional interpretive data such as cross-sections and maps. With this approach, folds are explicitly designed by the user instead of being derived from data. This makes the resulting structures subjective and deterministic. This paper introduces a numerical framework for modeling folds and associated foliations from typical field data. In this framework, a parametric description of fold geometry is incorporated into the interpolation algorithm. This way the folded geometry is implicitly derived from observed data, while being controlled through structural parameters such as fold wavelength, amplitude and tightness. A fold coordinate system is used to support the numerical description of fold geometry and to modify the behavior of classical structural interpolators. This fold frame is constructed from fold-related structural elements such as axial foliations, intersection lineations, and vergence. Poly-deformed terranes are progressively modeled by successively modeling each folding event going backward through time. The proposed framework introduces a new modeling paradigm, which enables the building of three-dimensional geological models of complex poly-deformed terranes. It follows a process based on the structural geologist approach and is able to produce geomodels that honor both structural data and geological knowledge.

  6. Analysis of folded pulse forming line operation.

    PubMed

    Domonkos, M T; Watrous, J; Parker, J V; Cavazos, T; Slenes, K; Heidger, S; Brown, D; Wilson, D

    2014-09-01

    A compact pulse forming line (CPFL) concept based on a folded transmission line and high-breakdown strength dielectric was explored through an effort combining proof-of-principle experiments with electromagnetic modeling. A small-scale folded CPFL was fabricated using surface-mount ceramic multilayer capacitors. The line consisted of 150 capacitors close-packed in parallel and delivered a 300 ns flat-top pulse. The concept was carried to a 10 kV class device using a polymer-ceramic nanocomposite dielectric with a permittivity of 37.6. The line was designed for a 161 ns FWHM length pulse into a matched load. The line delivered a 110 ns FWHM pulse, and the pulse peak amplitude exceeded the matched load ideal. Transient electromagnetic analysis using the particle-in-cell code ICEPIC was conducted to examine the nature of the unexpected pulse shortening and distortion. Two-dimensional analysis failed to capture the anomalous behavior. Three-dimensional analysis replicated the pulse shape and revealed that the bends were largely responsible for the pulse shortening. The bends not only create the expected reflection of the incident TEM wave but also produce a non-zero component of the Poynting vector perpendicular to the propagation direction of the dominant electromagnetic wave, resulting in power flow largely external to the PFL. This analysis explains both the pulse shortening and the amplitude of the pulse.

  7. A Computational Model of Cerebral Cortex Folding

    PubMed Central

    Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Miller, L Stephen; Liu, Tianming

    2010-01-01

    The geometric complexity and variability of the human cerebral cortex has long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3-dimensional geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: 1) Mechanical constraints of the skull regulate the cortical folding process. 2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. 3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. 4) The cortical folding pattern is dependent on the initial geometry of the cortex. PMID:20167224

  8. Mechanical Models of Fault-Related Folding

    SciTech Connect

    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).

  9. Regional structural analysis and velocity model (Vp) of the Chittagong-Myanmar Fold and Thrust Belt, Bangladesh

    NASA Astrophysics Data System (ADS)

    Burgi, P.; Hubbard, J.; Peterson, D. E.; Akhter, S. H.

    2015-12-01

    Bangladesh sits on the seismically active Chittagong-Myanmar Fold and Thrust Belt (CMFB), a partially exposed accretionary prism associated with the India-Eurasia collision. Ground shaking due to local and regional earthquakes presents a potential hazard to Bangladesh, one of the most populated areas in the world. In order to constrain this hazard, we first investigate potential seismic sources (active faults), and second we analyze the material through which seismic energy propagates. To address potential earthquake sources, we focus on the Comilla Anticline, which is the frontal-most exposed structure of the CMFB as well as the most proximal to the capital city of Dhaka. We present several industry-acquired and depth-converted seismic reflection profiles, which exhibit an asymmetric detachment fold rising from a relatively deep décollement (5-6 km). Because there is no strong evidence for an associated emergent thrust, this actively growing fold may have low seismic potential. We place this work into a regional context by integrating previous research of CMFB structures to create a regional structural model, which reveals laterally varying wedge geometry. To address ground shaking, the second component of this work, we assess stacking velocities from our seismic reflection data in conjunction with sonic log velocities from several locations in Bangladesh. These data show varying velocity versus depth trends by region. Following similar, data-rich studies performed in the Los Angeles and adjacent basins, we use data and theory-driven fitting techniques to analyze depth-velocity trends for these different regions, and interpolate to create a laterally varying regional seismic velocity model. Velocities generally slow from east to west, consistent with the younging trend as we move from older, exhumed CMFB formations to recent and undeformed deposits.

  10. The Numba ductile deformation zone (northwest Cameroon): A geometric analysis of folds based on the Fold Profiler method

    NASA Astrophysics Data System (ADS)

    Njanko, T.; Chatué, C. Njiki; Kwékam, M.; Nké, B. E. Bella; Sandjo, A. F. Yakeu; Fozing, E. M.

    2017-03-01

    The Numba ductile deformation zone (NDDZ) is characterised by folds recorded during the three deformation phases that affected the banded amphibole gneiss. Fold-shape analyses using the program Fold Profiler with the aim to show the importance of folding events in the structural analysis of the NDDZ and its contribution to the Pan-African orogeny in central Africa have been made. Classical field method, conic sections method and Ramsay's fold classification method were applied to (i) have the general orientation of folds, (ii) analyze the fold shapes and (iii) classify the geometry of the folded bands. Fold axes in banded amphibole gneiss plunge moderately (<15°) towards the NNE or SSW. The morphology of F1, F2 and F3 folds in the study area clearly points to (i) Z-shape folds with SE vergence and (ii) a dextral sense of shear motion. Conic section method reveals two dominant families: F1 and F3 folds belong to parabolic shape folds, while F2 folds belong to parabolic shape and hyperbolic shape folds. Ramsay's scheme emphasizes class 1C (for F1, F2 and F3 folds) and class 3 (for F2 folds) as main fold classes. The co-existence of the various fold shapes can be explained by (i) the structuration of the banded gneiss, (ii) the folding mechanisms that associate shear with a non-least compressive or flattening component in a ductile shear zone and (iii) the change in rheological properties of the band during the period of fold formation. These data allow us to conclude that the Numba region underwent ductile dextral shear and can be integrated (i) in a correlation model with the Central Cameroon Shear Zone (CCSZ) and associated syn-kinematic intrusions and (ii) into the tectonic model of Pan-African belt of central Africa in Cameroon.

  11. Predictive Computational Modeling of Chromatin Folding

    NASA Astrophysics Data System (ADS)

    di Pierro, Miichele; Zhang, Bin; Wolynes, Peter J.; Onuchic, Jose N.

    In vivo, the human genome folds into well-determined and conserved three-dimensional structures. The mechanism driving the folding process remains unknown. We report a theoretical model (MiChroM) for chromatin derived by using the maximum entropy principle. The proposed model allows Molecular Dynamics simulations of the genome using as input the classification of loci into chromatin types and the presence of binding sites of loop forming protein CTCF. The model was trained to reproduce the Hi-C map of chromosome 10 of human lymphoblastoid cells. With no additional tuning the model was able to predict accurately the Hi-C maps of chromosomes 1-22 for the same cell line. Simulations show unknotted chromosomes, phase separation of chromatin types and a preference of chromatin of type A to sit at the periphery of the chromosomes.

  12. 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

    NASA Astrophysics Data System (ADS)

    Mihalikova, M.; Kirkwood, S.; Arnault, J.; Mikhaylova, D.

    2012-09-01

    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.

  13. A Simple Model for Protein Folding

    NASA Astrophysics Data System (ADS)

    Henry, Eric R.; Eaton, William A.

    We describe a simple Ising-like statistical mechanical model for folding proteins based on the α-carbon contact map of the native structure. In this model residues can adopt two microscopic states corresponding to the native and non-native conformations. In order to exactly enumerate the large number of possible configurations, structure is considered to grow as continuous sequences of native residues, with no more than two sequences in each molecule. Inter-residue contacts can only form within each sequence and between residues of the two native sequences. As structure grows there is a tradeoff between the stabilizing effect of inter-residue contacts and the entropy losses from ordering residues in their native conformation and from forming a disordered loop to connect two continuous sequences. Folding kinetics are calculated from the dynamics on the free energy profile, as in Kramers' reaction rate theory. Although non-native interactions responsible for roughness in the energy landscape are not explicitly considered in the model, they are implicitly included by determining the absolute rates for motion on the free energy profile. With the exception of α-helical proteins, the kinetic progress curves exhibit single exponential time courses, consistent with two state behavior, as observed experimentally. The calculated folding rates are in remarkably good agreement with the measured values for the 25 two-state proteins investigated, with a correlation coefficient of 0.8. With its coarse-grained description of both the energy and entropy, and only three independently adjustable parameters, the model may be regarded as the simplest possible analytical model of protein folding capable of predicting experimental properties of specific proteins.

  14. Abstract folding space analysis based on helices

    PubMed Central

    Huang, Jiabin; Backofen, Rolf; Voß, Björn

    2012-01-01

    RNA has many pivotal functions especially in the regulation of gene expression by ncRNAs. Identification of their structure is an important requirement for understanding their function. Structure prediction alone is often insufficient for this task, due to algorithmic problems, parameter inaccuracies, and biological peculiarities. Among the latter, there are base modifications, cotranscriptional folding leading to folding traps, and conformational switching as in the case of riboswitches. All these require more in-depth analysis of the folding space. The major drawback, which all methods have to cope with, is the exponential growth of the folding space. Therefore, methods are often limited in the sequence length they can analyze, or they make use of heuristics, sampling, or abstraction. Our approach adopts the abstraction strategy and remedies some problems of existing methods. We introduce a position-specific abstraction based on helices that we term helix index shapes, or hishapes for short. Utilizing a dynamic programming framework, we have implemented this abstraction in the program RNAHeliCes. Furthermore, we developed two hishape-based methods, one for energy barrier estimation, called HiPath, and one for abstract structure comparison, termed HiTed. We demonstrate the superior performance of HiPath compared to other existing methods and the competitive accuracy of HiTed. RNAHeliCes, together with HiPath and HiTed, are available for download at http://www.cyanolab.de/software/RNAHeliCes.htm. PMID:23104999

  15. Inframammary Fold Reconstruction: A Biomechanical Analysis

    PubMed Central

    Schell, Julia; Uener, Jens; Prescher, Andreas; Scaal, Martin; Puppe, Julian; Warm, Mathias

    2016-01-01

    Background: Inframammary fold reconstruction has scarcely been evaluated in literature. No biomechanical analyses have been performed comparing different reconstructive methods. This evaluation compares the gold-standard suture reconstruction with an intrarib anchor system (Micro BioComposite SutureTak, Arthrex). Methods: Three analysis groups were compared including 8 Sawbone blocks, 22 embalmed cadaver, and 27 regular cadaver specimens (N = 57). Transient mechanical analysis was performed at 5 N/s using an Instron 5565 test frame. Results: Ultimate load favored the anchor system (compared with the gold-standard suture) by a factor of 9.8 (P < 0.0001) for the regular cadaver group and a factor of 1.7 (P < 0.038) for the embalmed cadaver group. A similar statistically significant benefit was shown for stiffness and load at 2-mm displacement. Conclusions: This analysis showed an anchor system to be the biomechanically superior fixation method in terms of ultimate load, fixation stiffness, and displacement at failure when compared with the gold-standard suture method in inframammary fold reconstruction. Because of superior stability in every aspect, an anchor system may be considered for inframammary fold reconstruction. PMID:27257564

  16. 3D Numerical Modelling and Finite Strain Analysis of the Lateral Transition between Overthrusting and Folding with Application to the Helvetic Nappe system

    NASA Astrophysics Data System (ADS)

    Spitz, Richard; Schmalholz, Stefan; Kaus, Boris

    2017-04-01

    The Helvetic nappe system in Switzerland is generally described as fold and thrust belt. While the overall geology has been studied in detail, the tectonic development and mechanical interconnection between overthrusting and folding is still not fully understood. One important clue comes from the mechanical stratigraphy and the corresponding lateral transition from overthrusting to folding, which is characteristic for the Helvetic nappe system. We employ a three-dimensional numerical model with linear and non-linear viscous rheology to investigate the control of the lateral variation in the thickness of a weak detachment horizon on the transition from folding to overthrusting during bulk shortening. The lateral variation of the thickness of the detachment horizon mimicks the lateral variation of the pre-Alpine half-graben depth. Our model configuration is based on published work based on 2D numerical simulations and consists of a stiff viscous layer, with a pre-existing weak zone, resting within a weaker viscous matrix. The thickness of the stiff layer HL is constant at 1 km, the detachment horizon thickness HD ranges from 0.2 to 1 km. The reference viscosity ratio μL/μM(for the same strain rate) between the layer and matrix is 100 and both of the units employ a power-law stress exponent of n = 3. We consider two different initial geometries. In the first configuration the detachment horizon thickness is increased linearly throughout the model domain. In the second configuration the increase of detachment horizon thickness is restricted to a certain width in the model domain, creating a flat ramp geometry. Additionally to the geometrical analysis we compute the finite strain and finite stress ellipsoids at any point in the model domain. These ellipsoids help to study the transition zone in detail and to monitor any variations in the local tectonic regime e.g. quantifiying strike-slip components.

  17. Modern Analysis of Protein Folding by Differential Scanning Calorimetry.

    PubMed

    Ibarra-Molero, Beatriz; Naganathan, Athi N; Sanchez-Ruiz, Jose M; Muñoz, Victor

    2016-01-01

    Differential scanning calorimetry (DSC) is a very powerful tool for investigating protein folding and stability because its experimental output reflects the energetics of all conformations that become minimally populated during thermal unfolding. Accordingly, analysis of DSC experiments with simple thermodynamic models has been key for developing our understanding of protein stability during the past five decades. The discovery of ultrafast folding proteins, which have naturally broad conformational ensembles and minimally cooperative unfolding, opens the possibility of probing the complete folding free energy landscape, including those conformations at the top of the barrier to folding, via DSC. Exploiting this opportunity requires high-quality experiments and the implementation of novel analytical methods based on statistical mechanics. Here, we cover the recent exciting developments in this front, describing the new analytical procedures in detail as well as providing experimental guidelines for performing such analysis. © 2016 Elsevier Inc. All rights reserved.

  18. Modelling RNA folding under mechanical tension

    PubMed Central

    VIEREGG, JEFFREY R.; TINOCO, IGNACIO

    2006-01-01

    We investigate the thermodynamics and kinetics of RNA unfolding and refolding under mechanical tension. The hierarchical nature of RNA structure and the existence of thermodynamic parameters for base pair formation based on nearest-neighbour interactions allows modelling of sequence-dependent folding dynamics for any secondary structure. We calculate experimental observables such as the transition force for unfolding, the end-to-end distribution function and its variance, as well as kinetic information, for a representative RNA sequence and for a sequence containing two homopolymer segments: A.U and G.C. PMID:16969426

  19. A Canonical Biomechanical Vocal Fold Model

    PubMed Central

    Bhattacharya, Pinaki; Siegmund, Thomas H.

    2012-01-01

    Summary The present article aimed at constructing a canonical geometry of the human vocal fold (VF) from subject-specific image slice data. A computer-aided design approach automated the model construction. A subject-specific geometry available in literature, three abstractions (which successively diminished in geometric detail) derived from it, and a widely used quasi two-dimensional VF model geometry were used to create computational models. The first three natural frequencies of the models were used to characterize their mechanical response. These frequencies were determined for a representative range of tissue biomechanical properties, accounting for underlying VF histology. Compared with the subject-specific geometry model (baseline), a higher degree of abstraction was found to always correspond to a larger deviation in model frequency (up to 50% in the relevant range of tissue biomechanical properties). The model we deemed canonical was optimally abstracted, in that it significantly simplified the VF geometry compared with the baseline geometry but can be recalibrated in a consistent manner to match the baseline response. Models providing only a marginally higher degree of abstraction were found to have significant deviation in predicted frequency response. The quasi two-dimensional model presented an extreme situation: it could not be recalibrated for its frequency response to match the subject-specific model. This deficiency was attributed to complex support conditions at anterior-posterior extremities of the VFs, accentuated by further issues introduced through the tissue biomechanical properties. In creating canonical models by leveraging advances in clinical imaging techniques, the automated design procedure makes VF modeling based on subject-specific geometry more realizable. PMID:22209063

  20. Fold assessment for comparative protein structure modeling.

    PubMed

    Melo, Francisco; Sali, Andrej

    2007-11-01

    Accurate and automated assessment of both geometrical errors and incompleteness of comparative protein structure models is necessary for an adequate use of the models. Here, we describe a composite score for discriminating between models with the correct and incorrect fold. To find an accurate composite score, we designed and applied a genetic algorithm method that searched for a most informative subset of 21 input model features as well as their optimized nonlinear transformation into the composite score. The 21 input features included various statistical potential scores, stereochemistry quality descriptors, sequence alignment scores, geometrical descriptors, and measures of protein packing. The optimized composite score was found to depend on (1) a statistical potential z-score for residue accessibilities and distances, (2) model compactness, and (3) percentage sequence identity of the alignment used to build the model. The accuracy of the composite score was compared with the accuracy of assessment by single and combined features as well as by other commonly used assessment methods. The testing set was representative of models produced by automated comparative modeling on a genomic scale. The composite score performed better than any other tested score in terms of the maximum correct classification rate (i.e., 3.3% false positives and 2.5% false negatives) as well as the sensitivity and specificity across the whole range of thresholds. The composite score was implemented in our program MODELLER-8 and was used to assess models in the MODBASE database that contains comparative models for domains in approximately 1.3 million protein sequences.

  1. Fold assessment for comparative protein structure modeling

    PubMed Central

    Melo, Francisco; Sali, Andrej

    2007-01-01

    Accurate and automated assessment of both geometrical errors and incompleteness of comparative protein structure models is necessary for an adequate use of the models. Here, we describe a composite score for discriminating between models with the correct and incorrect fold. To find an accurate composite score, we designed and applied a genetic algorithm method that searched for a most informative subset of 21 input model features as well as their optimized nonlinear transformation into the composite score. The 21 input features included various statistical potential scores, stereochemistry quality descriptors, sequence alignment scores, geometrical descriptors, and measures of protein packing. The optimized composite score was found to depend on (1) a statistical potential z-score for residue accessibilities and distances, (2) model compactness, and (3) percentage sequence identity of the alignment used to build the model. The accuracy of the composite score was compared with the accuracy of assessment by single and combined features as well as by other commonly used assessment methods. The testing set was representative of models produced by automated comparative modeling on a genomic scale. The composite score performed better than any other tested score in terms of the maximum correct classification rate (i.e., 3.3% false positives and 2.5% false negatives) as well as the sensitivity and specificity across the whole range of thresholds. The composite score was implemented in our program MODELLER-8 and was used to assess models in the MODBASE database that contains comparative models for domains in approximately 1.3 million protein sequences. PMID:17905832

  2. Kinematic Analysis of Fold-Thrust-Belt Using Integrated Analogue Sandbox Modeling and 3D Palinspatic Reconstructions in Babar-Selaru Area, Banda Sea Region, Indonesia

    NASA Astrophysics Data System (ADS)

    Sapiie, Benyamin; Hadiana, Meli; Kurniawan, Ade; Daniel, Dicky; Danio, Harya; Fujimoto, Masamichi; Ohara, Michio; Alam Perdana, Lisnanda; Saputra, Afif

    2016-04-01

    Kinematic analysis of Babar-Selaru fold-thrust-belt is challenging and often difficult particularly in conducting seismic interpretation due to complex structural geometries. Resolving such as issue, in this study we proposed to use integrated seismic interpretation, analogue sandbox modeling and 3D palinspatic reconstructions. This paper is presented results of detail kinematic analysis for understanding tectonic evolution as well as mechanism of fold-thrust-belt in relation to their hydrocarbon prospect. Babar-Selaru Area is located within the collisional boundary between Australian continental margin and Banda Arc region of Indonesia. The area is characterized by complex deformation zone of fold-thrust-belt, involving Mesozoic and Tertiary sedimentary sequences of Australian continental margin. The age of deformation is ranging from 8-5 Ma. Seismic interpretations show two styles of faults developed in the area, which are thrust and normal faults system. The last deformation observed in the Babar Selaru area is controlled by south verging imbricated thin-skinned thrust fault system, with the staircase style of fault detachment. Although, both structural styles occurred in separated locations, they are formed not only in the same time but also related in time and space. Total extension is ranging from 1-3 % where average shortening is in the order of 35-38%. Sandbox modeling is an effective way to study and understand the style, pattern and geometry of the deformed sedimentary sequences in the study area. Based on comparison of five settings experiments (mainly different geological boundary condition) with more than 50 different modeling; deformation is particularly controlled by types and thickness of lithology package and detachment geometry. These two parameters were quite sensitive in generating different deformation style and pattern in Babar-Selaru fold-thrust-belt. Therefore, choosing the right combination of stratigraphy model and material setting are

  3. Dissecting Ubiquitin Folding Using the Self-Organized Polymer Model.

    PubMed

    Reddy, Govardhan; Thirumalai, D

    2015-08-27

    Folding of Ubiquitin (Ub), a functionally important protein found in eukaryotic organisms, is investigated at low and neutral pH at different temperatures using simulations of the coarse-grained self-organized-polymer model with side chains (SOP-SC). The melting temperatures (Tm's), identified with the peaks in the heat capacity curves, decrease as pH decreases, in qualitative agreement with experiments. The calculated radius of gyration, showing dramatic variations with pH, is in excellent agreement with scattering experiments. At Tm, Ub folds in a two-state manner at low and neutral pH. Clustering analysis of the conformations sampled in equilibrium folding trajectories at Tm, with multiple transitions between the folded and unfolded states, shows a network of metastable states connecting the native and unfolded states. At low and neutral pH, Ub folds with high probability through a preferred set of conformations resulting in a pH-dependent dominant folding pathway. Folding kinetics reveal that Ub assembly at low pH occurs by multiple pathways involving a combination of nucleation-collapse and diffusion collision mechanism. The mechanism by which Ub folds is dictated by the stability of the key secondary structural elements responsible for establishing long-range contacts and collapse of Ub. Nucleation collapse mechanism holds if the stability of these elements are marginal, as would be the case at elevated temperatures. If the lifetimes associated with these structured microdomains are on the order of hundreds of microseconds, then Ub folding follows the diffusion-collision mechanism with intermediates, many of which coincide with those found in equilibrium. Folding at neutral pH is a sequential process with a populated intermediate resembling that sampled at equilibrium. The transition state structures, obtained using a Pfold analysis, are homogeneous and globular with most of the secondary and tertiary structures being native-like. Many of our findings for

  4. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    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…

  5. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    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…

  6. Visualization of Protein Folding Funnels in Lattice Models

    PubMed Central

    Oliveira, Antonio B.; Fatore, Francisco M.; Paulovich, Fernando V.; Oliveira, Osvaldo N.; Leite, Vitor B. P.

    2014-01-01

    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. PMID:25010343

  7. Learning generative models for protein fold families.

    PubMed

    Balakrishnan, Sivaraman; Kamisetty, Hetunandan; Carbonell, Jaime G; Lee, Su-In; Langmead, Christopher James

    2011-04-01

    We introduce a new approach to learning statistical models from multiple sequence alignments (MSA) of proteins. Our method, called GREMLIN (Generative REgularized ModeLs of proteINs), learns an undirected probabilistic graphical model of the amino acid composition within the MSA. The resulting model encodes both the position-specific conservation statistics and the correlated mutation statistics between sequential and long-range pairs of residues. Existing techniques for learning graphical models from MSA either make strong, and often inappropriate assumptions about the conditional independencies within the MSA (e.g., Hidden Markov Models), or else use suboptimal algorithms to learn the parameters of the model. In contrast, GREMLIN makes no a priori assumptions about the conditional independencies within the MSA. We formulate and solve a convex optimization problem, thus guaranteeing that we find a globally optimal model at convergence. The resulting model is also generative, allowing for the design of new protein sequences that have the same statistical properties as those in the MSA. We perform a detailed analysis of covariation statistics on the extensively studied WW and PDZ domains and show that our method out-performs an existing algorithm for learning undirected probabilistic graphical models from MSA. We then apply our approach to 71 additional families from the PFAM database and demonstrate that the resulting models significantly out-perform Hidden Markov Models in terms of predictive accuracy.

  8. Tectonic analysis of folds in the Colorado plateau of Arizona

    NASA Technical Reports Server (NTRS)

    Davis, G. H.

    1975-01-01

    Structural mapping and analysis of folds in Phanerozoic rocks in northern Arizona, using LANDSAT-1 imagery, yielded information for a tectonic model useful in identifying regional fracture zones within the Colorado Plateau tectonic province. Since the monoclines within the province developed as a response to differential movements of basement blocks along high-angle faults, the monoclinal fold pattern records the position and trend of many elements of the regional fracture system. The Plateau is divided into a mosaic of complex, polyhedral crustal blocks whose steeply dipping faces correspond to major fracture zones. Zones of convergence and changes in the trend of the monoclinal traces reveal the corners of the blocks. Igneous (and salt) diapirs have been emplaced into many of the designated zones of crustal weakness. As loci of major fracturing, folding, and probably facies changes, the fractures exert control on the entrapment of oil and gas.

  9. Palaeomagnetic analysis of plunging fold structures: Errors and a simple fold test

    NASA Astrophysics Data System (ADS)

    Stewart, Simon A.

    1995-02-01

    The conventional corrections for bedding dip in palaeomagnetic studies involve either untilting about strike or about some inclined axis—the choice is usually governed by the perceived fold hinge orientation. While it has been recognised that untilting bedding about strike can be erroneous if the beds lie within plunging fold structures, there are several types of fold which have plunging hinges, but whose limbs have rotated about horizontal axes. Examples are interference structures and forced folds; restoration about inclined axes may be incorrect in these cases. The angular errors imposed upon palaeomagnetic lineation data via the wrong choice of rotation axis during unfolding are calculated here and presented for lineations in any orientation which could be associated with an upright, symmetrical fold. This extends to palaeomagnetic data previous analyses which were relevant to bedding-parallel lineations. This numerical analysis highlights the influence of various parameters which describe fold geometry and relative lineation orientation upon the angular error imparted to lineation data by the wrong unfolding method. The effect of each parameter is described, and the interaction of the parameters in producing the final error is discussed. Structural and palaeomagnetic data are cited from two field examples of fold structures which illustrate the alternative kinematic histories. Both are from thin-skinned thrust belts, but the data show that one is a true plunging fold, formed by rotation about its inclined hinge, whereas the other is an interference structure produced by rotation of the limbs about non-parallel horizontal axes. Since the angle between the palaeomagnetic lineations and the inclined fold hinge is equal on both limbs in the former type of structure, but varies from limb to limb in the latter, a simple test can be defined which uses palaeomagnetic lineation data to identify rotation axes and hence fold type. This test can use pre- or syn-folding

  10. Analysis of 12C+12C Elastic and Inelastic Scatterings in the Framework of the Cluster Double Folding Model and Coupled-Channels Mechanism

    NASA Astrophysics Data System (ADS)

    Hassanain, M. A.

    2011-08-01

    A double folding cluster (DFC) model is proposed for the analysis of (12) C+(12) C elastic and inelastic scatterings. The DFC procedure is performed using the alpha-clusters structure of (12) C nucleus. Angular distributions of the (12) C+(12) C elastic and inelastic scatterings in the energy range 70.7-126 MeV were analyzed using the derived DFC potentials in the framework of the coupled-channels (CC) mechanism. Successful descriptions of the data are obtained over the full measured angular range without the need to normalize the DFC potentials. Furthermore, the deduced deformation length and the quadrupole deformation parameter are quite consistent with the corresponding electromagnetic measurements.

  11. Folding model analysis of pion elastic and inelastic scattering from {sup 6}Li and {sup 12}C

    SciTech Connect

    Ebrahim, A. A.

    2013-04-15

    {pi}{sup {+-}}-Nucleus scattering cross sections are calculated applying the Watanabe superposition model with a phenomenological Woods-Saxon potential. The phenomenological potential parameters are searched for {pi}{sup {+-}} scattering from {sup 6}Li and {sup 12}C to reproduce not only differential elastic cross sections but also inelastic and total and reaction cross sections at pion kinetic energies from 50 to 672 MeV. The optical potentials of {sup 6}Li and {sup 12}C are calculated in terms of the alpha particle and deuteron optical potentials. Inelastic scattering has been analyzed using the distorted waves from elastic-scattering data. The values of deformation lengths thus obtained compare very well with the ones reported earlier.

  12. Computational analysis of hydrogenated graphyne folding

    NASA Astrophysics Data System (ADS)

    Lenear, Christopher; Becton, Matthew; Wang, Xianqiao

    2016-02-01

    This letter employs molecular mechanics simulations to analyze the geometric changes of foreign-atom-doped graphyne. Simulation results show that higher the density of dopant and the greater area covered by the dopant correlates to a greater folding angle of the graphyne sheet. Compared to graphene, graphyne folding could prove to be more effective for various nanodevices based on its unique band gap, especially when doped, and its tunable interactions with and absorption of foreign molecules. Therefore, our findings may offer unique perspectives into the development of novel graphyne-based nanodevices and stimulate the community's research interest in graphene-related origami.

  13. Folded-path optical analysis gas cell

    DOEpatents

    Carangelo, R.M.; Wright, D.D.

    1995-08-08

    A folded-path gas cell employs an elliptical concave mirror in confronting relationship to two substantially spherical concave mirrors. At least one of the spherical mirrors, and usually both, are formed with an added cylindrical component to increase orthogonal foci coincidence and thereby to increase the radiation energy throughput characteristic of the cell. 10 figs.

  14. Folded-path optical analysis gas cell

    DOEpatents

    Carangelo, Robert M.; Wright, David D.

    1995-01-01

    A folded-path gas cell employs an elliptical concave mirror in confronting relationship to two substantially spherical concave mirrors. At least one of the spherical mirrors, and usually both, are formed with an added cylindrical component to increase orthogonal focii coincidence and thereby to increase the radiation energy throughput characteristic of the cell.

  15. Geometric analysis of superposed folds in the Kimbi area (Cameroon Pan-African fold belt) based on the Fold Profiler method

    NASA Astrophysics Data System (ADS)

    Sylvestre, Ganno; Jean Paul, Nzenti; Boniface, Kankeu; Timoléon, Ngnotue

    2010-08-01

    Fold shape analyses using the program Fold Profiler method are presented for folds with interference in the Kimbi area with the aim of deciphering their geometry. Two types of functions, conic sections and cubic Bézier curves, were fitted to the natural fold profiles to analyse the fold shape. Two dominant families have been distinguished: parabolic folds for F 1 folds and parabolic to elliptical folds for F 2 and F 3 folds. We also use Ramsay's scheme ( t versus α plot) for classifying the geometry of the folded layers. In this classification, F 1 and F 3 folds belong to class 1C and class 3 folds while F 2 are of classes 1B, 1C and 3. Class 1B folds are formed by buckling while class 1C folds are formed by flattening of parallel folds. The variation of fold shape can be explained by the variation in the rheological properties of the folded layers as a result of changes in physical conditions, or by changes in the kinematics of the folding processes. These data, which are the first ever folding results in this region, can be integrated into the tectonic evolution models Northwestern Cameroon's Pan-African fold belt.

  16. Effect of the ventricular folds in a synthetic larynx model.

    PubMed

    Kniesburges, Stefan; Birk, Veronika; Lodermeyer, Alexander; Schützenberger, Anne; Bohr, Christopher; Becker, Stefan

    2017-04-11

    Within the human larynx, the ventricular folds serve primarily as a protecting valve during swallowing. They are located directly above the sound-generating vocal folds. During normal phonation, the ventricular folds are passive structures that are not excited to periodical oscillations. However, the impact of the ventricular folds on the phonation process has not yet been finally clarified. An experimental synthetic human larynx model was used to investigate the effect of the ventricular folds on the phonation process. The model includes self-oscillating vocal fold models and allows the comparison of the pressure distribution at multiple locations in the larynx for configurations with and without ventricular folds. The results indicate that the ventricular folds increase the efficiency of the phonation process by reducing the phonation threshold level of the pressure below the vocal folds. Two effects caused by the ventricular folds could be identified as reasons: (1) a decrease in the mean pressure level in the region between vocal and ventricular folds (ventricles) and (2) an increase in the glottal flow resistance. The reason for the first effect is a reduction of the pressure level in the ventricles due to the jet entrainment and the low static pressure in the glottal jet. The second effect results from an increase in the glottal flow resistance that enhances the aerodynamic energy transfer into the vocal folds. This effect reduces the onset threshold of the pressure difference across the glottis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Vocal fold and ventricular fold vibration in period-doubling phonation: physiological description and aerodynamic modeling.

    PubMed

    Bailly, Lucie; Henrich, Nathalie; Pelorson, Xavier

    2010-05-01

    Occurrences of period-doubling are found in human phonation, in particular for pathological and some singing phonations such as Sardinian A Tenore Bassu vocal performance. The combined vibration of the vocal folds and the ventricular folds has been observed during the production of such low pitch bass-type sound. The present study aims to characterize the physiological correlates of this acoustical production and to provide a better understanding of the physical interaction between ventricular fold vibration and vocal fold self-sustained oscillation. The vibratory properties of the vocal folds and the ventricular folds during phonation produced by a professional singer are analyzed by means of acoustical and electroglottographic signals and by synchronized glottal images obtained by high-speed cinematography. The periodic variation in glottal cycle duration and the effect of ventricular fold closing on glottal closing time are demonstrated. Using the detected glottal and ventricular areas, the aerodynamic behavior of the laryngeal system is simulated using a simplified physical modeling previously validated in vitro using a larynx replica. An estimate of the ventricular aperture extracted from the in vivo data allows a theoretical prediction of the glottal aperture. The in vivo measurements of the glottal aperture are then compared to the simulated estimations.

  18. A dynamic skull model for simulation of cerebral cortex folding.

    PubMed

    Chen, Hanbo; Guo, Lei; Nie, Jingxin; Zhang, Tuo; Hu, Xintao; Liu, Tianming

    2010-01-01

    The mechanisms of human cerebral cortex folding and their interactions during brain development are largely unknown, partly due to the difficulties in biological experiments and data acquisition for the developing fetus brain. Computational modeling and simulation provide a novel approach to the understanding of cortex folding processes in normal or aberrant neurodevelopment. Based on our recently developed computational model of the cerebral cortex folding using neuronal growth model and mechanical skull constraint, this paper presents a computational dynamic model of the brain skull that regulates the cortical folding simulation. Our simulation results show that the dynamic skull model is more biologically realistic and significantly improves our cortical folding simulation results. This work provides further computational support to the hypothesis that skull is an important regulator of cortical folding.

  19. Sampling Kinetic Protein Folding Pathways using All-Atom Models

    NASA Astrophysics Data System (ADS)

    Bolhuis, P. G.

    This chapter summarizes several computational strategies to study the kinetics of two-state protein folding using all atom models. After explaining the background of two state folding using energy landscapes I introduce common protein models and computational tools to study folding thermodynamics and kinetics. Free energy landscapes are able to capture the thermodynamics of two-state protein folding, and several methods for efficient sampling of these landscapes are presented. An accurate estimate of folding kinetics, the main topic of this chapter, is more difficult to achieve. I argue that path sampling methods are well suited to overcome the problems connected to the sampling of folding kinetics. Some of the major issues are illustrated in the case study on the folding of the GB1 hairpin.

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

    NASA Astrophysics Data System (ADS)

    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.

  1. ON THE SINGLE-MASS MODEL OF THE VOCAL FOLDS

    PubMed Central

    Howe, M. S.; McGowan, R. S.

    2010-01-01

    SUMMARY 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. PMID:20419082

  2. Image analysis of vocal fold histology

    NASA Astrophysics Data System (ADS)

    Reinisch, Lou; Garrett, C. Gaelyn

    2001-05-01

    To visualize the concentration gradients of collagen, elastin and ground substance in histologic sections of vocal folds, an image enhancement scheme was devised. Slides stained with Movat's solution were viewed on a light microscope. The image was digitally photographed. Using commercially available software, all pixels within a color range are selected from the mucosa presented on the image. Using the Movat's pentachrome stain, yellow to yellow-brown pixels represented mature collagen, blue to blue-green pixels represented young collagen (collagen that is not fully cross-linked) and black to dark violet pixels represented elastin. From each of the color range selections, a black and white image was created. The pixels not within the color range were black. The selected pixels within the color range were white. The image was averaged and smoothed to produce 256 levels of gray with less spatial resolution. This new grey-scale image showed the concentration gradient. These images were further enhanced with contour lines surrounding equivalent levels of gray. This technique is helpful to compare the micro-anatomy of the vocal folds. For instance, we find large concentration of the collagen deep in the mucosa and adjacent to the vocalis muscle.

  3. Numerical modeling of fold-and-thrust belts: Applications to Kuqa foreland fold belt, China

    NASA Astrophysics Data System (ADS)

    Yin, H.; Morgan, J. K.; Zhang, J.; Wang, Z.

    2009-12-01

    We constructed discrete element models to simulate the evolution of fold-and-thrust belts. The impact of rock competence and decollement strength on the geometric pattern and deformation mechanics of fold-and-thrust belts has been investigated. The models reproduced some characteristic features of fold-and-thrust belts, such as faulted detachment folds, pop-ups, far-traveled thrust sheets, passive-roof duplexes, and back thrusts. In general, deformation propagates farther above a weak decollement than above a strong decollement. Our model results confirm that fold-and-thrust belts with strong frictional decollements develop relatively steep and narrow wedges formed by closely spaced imbricate thrust slices, whereas fold belts with weak decollements form wide low-taper wedges composed of faulted detachment folds, pop-ups, and back thrusts. Far-traveled thrust sheets and passive-roof duplexes are observed in the model with a strong lower decollement and a weak upper detachment. Model results also indicate that the thickness of the weak layer is critical. If it is thick enough, it acts as a ductile layer that is able to flow under differential stress, which helps to partition deformation above and below it. The discrete element modeling results were used to interpret the evolution of Kuqa Cenozoic fold-and-thrust belt along northern Tarim basin, China. Seismic and well data show that the widely distributed Paleogene rock salt has a significant impact on the deformation in this area. Structures beneath salt are closely spaced imbricate thrust and passive-roof duplex systems. Deformation above salt propagates much farther than below the salt. Faults above salt are relatively wide spaced. A huge controversy over the Kuqa fold-and-thrust belt is whether it is thin-skinned or thick-skinned. With the insights from DEM results, we suggest that Kuqa structures are mostly thin-skinned with Paleogene salt as decollement, except for the rear part near the backstop, where the

  4. Modeling Protein Folding and Applying It to a Relevant Activity

    ERIC Educational Resources Information Center

    Nelson, Allan; Goetze, Jim

    2004-01-01

    The different levels of protein structure that can be easily understood by creating a model that simulates protein folding, which can then be evaluated by applying it to a relevant activity, is presented. The materials required and the procedure for constructing a protein folding model are mentioned.

  5. Fold-structure analysis of paleozoic rocks in the Variscan Harz Mountains (Lautenthal, Central Germany) based on laserscanning and 3D modelling

    NASA Astrophysics Data System (ADS)

    Wagner, Bianca; Leiss, Bernd; Stöpler, Ralf; Zahnow, Fabian

    2017-04-01

    Folded paleozoic sedimentary rocks of Upper Devonian to Lower Carboniferous age are very well exposed in the abandoned chert quarry of Lautenthal in the western Harz Mountains. The outcrop represents typical structures of the Rhenohercynian thrust and fold belt of the Variscan orogen and therefore allows quantitative studies for the understanding of e.g. fold mechanisms and the amount of shortening. The sequence is composed of alternating beds of cherts, shales and tuffites, which show varying thicknesses, undulating and thinning out of certain layers. Irregularly occurring lenses of greywackes are interpreted as sedimentary intrusions. The compressive deformation style is expressed by different similar and parallel fold structures at varying scales as well as small-scale reverse faults and triangle structures. An accurate mapping of the outcrop in the classical way is very challenging due to distant and unconnected outcrop parts with differing elevations and orientations. Furthermore, the visibility is limited because of nearby trees, diffuse vegetation cover and no available total view. Therefore, we used a FARO 120 3D laserscanner and Trimble GNSS device to generate a referenced and drawn to scale point cloud of the complete quarry. Based on the point cloud a geometric 3D model of prominent horizons and structural features of various sizes was constructed. Thereafter, we analyzed the structures in matters of orientation and deformation mechanisms. Finally, we applied a retrodeformation algorithm on the model to restore the original sedimentary sequence and to calculate shortening including the amount of pressure solution. Only digital mapping allows such a time-saving, accurate and especially complete 3D survey of this excellent study object. We demonstrated that such 3D-models enable spatial correlations with other complex structures cropping out in the area. Moreover, we confirmed that a structural upscaling to the 100 to 1000 m scale is much easier and much

  6. Lattice model for rapidly folding protein-like heteropolymers.

    PubMed Central

    Shrivastava, I; Vishveshwara, S; Cieplak, M; Maritan, A; Banavar, J R

    1995-01-01

    Protein folding is a relatively fast process considering the astronomical number of conformations in which a protein could find itself. Within the framework of a lattice model, we show that one can design rapidly folding sequences by assigning the strongest attractive couplings to the contacts present in a target native state. Our protein design can be extended to situations with both attractive and repulsive contacts. Frustration is minimized by ensuring that all the native contacts are again strongly attractive. Strikingly, this ensures the inevitability of folding and accelerates the folding process by an order of magnitude. The evolutionary implications of our findings are discussed. PMID:7568102

  7. Atom-by-atom analysis of global downhill protein folding

    NASA Astrophysics Data System (ADS)

    Sadqi, Mourad; Fushman, David; Muñoz, Victor

    2006-07-01

    Protein folding is an inherently complex process involving coordination of the intricate networks of weak interactions that stabilize native three-dimensional structures. In the conventional paradigm, simple protein structures are assumed to fold in an all-or-none process that is inaccessible to experiment. Existing experimental methods therefore probe folding mechanisms indirectly. A widely used approach interprets changes in protein stability and/or folding kinetics, induced by engineered mutations, in terms of the structure of the native protein. In addition to limitations in connecting energetics with structure, mutational methods have significant experimental uncertainties and are unable to map complex networks of interactions. In contrast, analytical theory predicts small barriers to folding and the possibility of downhill folding. These theoretical predictions have been confirmed experimentally in recent years, including the observation of global downhill folding. However, a key remaining question is whether downhill folding can indeed lead to the high-resolution analysis of protein folding processes. Here we show, with the use of nuclear magnetic resonance (NMR), that the downhill protein BBL from Escherichia coli unfolds atom by atom starting from a defined three-dimensional structure. Thermal unfolding data on 158 backbone and side-chain protons out of a total of 204 provide a detailed view of the structural events during folding. This view confirms the statistical nature of folding, and exposes the interplay between hydrogen bonding, hydrophobic forces, backbone conformation and side-chain entropy. From the data we also obtain a map of the interaction network in this protein, which reveals the source of folding cooperativity. Our approach can be extended to other proteins with marginal barriers (less than 3RT), providing a new tool for the study of protein folding.

  8. Ranking vocal fold model parameters by their influence on modal frequencies

    PubMed Central

    Cook, Douglas D.; Nauman, Eric; Mongeau, Luc

    2009-01-01

    The purpose of this study was to identify, using computational models, the vocal fold parameters which are most influential in determining the vibratory characteristics of the vocal folds. The sensitivities of vocal folds modal frequencies to variations model parameters were used to determine the most influential parameters. A detailed finite element model of the human vocal fold was created. The model was defined by eight geometric and six material parameters. The model included transitional boundary regions to idealize the complex physiological structure of real human subjects. Parameters were simultaneously varied over ranges representative of actual human vocal folds. Three separate statistical analysis techniques were used to identify the most and least sensitive model parameters with respect to modal frequency. The results from all three methods consistently suggest that a set of five parameters are most influential in determining the vibratory characteristics of the vocal folds. PMID:19813811

  9. Analysis of complete fold shape based on quadratic Bézier curves

    NASA Astrophysics Data System (ADS)

    Liu, Chun; Zhang, Yikun; Wang, Yuan

    2009-06-01

    Six segments of quadratic Bézier curve are joined together according to some geometrical rules to approximate fold shape. In a classification of folds based on this method, an ideal fold shape is determined by two parameters. The first one, u c, termed the axial lift-up ratio of the central part, generates the folds within a broad spectrum of forms ranging from box folds to chevron folds. The other one, γ, is the interlimb angle. In the quantitative description of complete folds with multiple layers, three new parameters, θ, T and E are used to describe the deflection angle of the axial plane, the thickness increment of hinge zone and the limb elongation, respectively. Based on the modeling method, the program "Bézier Fold Profiler" has been developed, with which most types of folds can be simulated by varying thirteen parameters. Two description methods, complete fold description and individual layer description, can be used for the quantitative analysis of folds. The description methods are carried out by the visual matching of the fold profile displayed on-screen from an imported digital image. The layer curves of the model are displayed on the fold image. This method has the advantage of speed and simplicity.

  10. Thermodynamics of downhill folding: multi-probe analysis of PDD, a protein that folds over a marginal free energy barrier.

    PubMed

    Naganathan, Athi N; Muñoz, Victor

    2014-07-31

    Downhill folding proteins fold in microseconds by crossing a very low or no free energy barrier (<3 RT), and exhibit a complex unfolding behavior in equilibrium. Such unfolding complexity is due to the weak thermodynamic coupling that exists between the various structural segments of these proteins, and it is manifested in unfolding curves that differ depending on the structural probe employed to monitor the process. Probe-dependent unfolding has important practical implications because it permits one to investigate the folding energy landscape in detail using multiprobe thermodynamic experiments. This type of thermodynamic behavior has been investigated in depth on the protein BBL, an example of extreme (one-state) downhill folding in which there is no free energy barrier at any condition, including the denaturation midpoint. However, an open question is, to what extent is such thermodynamic behavior observed on less extreme downhill folders? Here we perform a multiprobe spectroscopic characterization of the microsecond folder PDD, a structural and functional homologue of BBL that folds within the downhill regime, but is not an example of one-state downhill folding; rather at the denaturation midpoint PDD folds by crossing an incipient free energy barrier. Model-free analysis of the unfolding curves from four different spectroscopic probes together with differential scanning calorimetry reveals a dispersion of ∼9 K in the apparent melting temperature and also marked differences in unfolding broadness (from ∼50 to ∼130 kJ mol(-1) when analyzed with a two-state model), confirming that such properties are also observed on less extreme downhill folders. We subsequently perform a global quantitative analysis of the unfolding data of PDD using the same ME statistical mechanical model that was used before for the BBL domain. The analysis shows that this simple model captures all of the features observed on the unfolding of PDD (i.e., the intensity and temperature

  11. Persistent homology analysis of protein structure, flexibility and folding

    PubMed Central

    Xia, Kelin; Wei, Guo-Wei

    2014-01-01

    Proteins are the most important biomolecules for living organisms. The understanding of protein structure, function, dynamics and transport is one of most challenging tasks in biological science. In the present work, persistent homology is, for the first time, introduced for extracting molecular topological fingerprints (MTFs) based on the persistence of molecular topological invariants. MTFs are utilized for protein characterization, identification and classification. The method of slicing is proposed to track the geometric origin of protein topological invariants. Both all-atom and coarse-grained representations of MTFs are constructed. A new cutoff-like filtration is proposed to shed light on the optimal cutoff distance in elastic network models. Based on the correlation between protein compactness, rigidity and connectivity, we propose an accumulated bar length generated from persistent topological invariants for the quantitative modeling of protein flexibility. To this end, a correlation matrix based filtration is developed. This approach gives rise to an accurate prediction of the optimal characteristic distance used in protein B-factor analysis. Finally, MTFs are employed to characterize protein topological evolution during protein folding and quantitatively predict the protein folding stability. An excellent consistence between our persistent homology prediction and molecular dynamics simulation is found. This work reveals the topology-function relationship of proteins. PMID:24902720

  12. Effects of confinement and crowding on folding of model proteins.

    PubMed

    Wojciechowski, M; Cieplak, Marek

    2008-12-01

    We perform molecular dynamics simulations for a simple coarse-grained model of crambin placed inside of a softly repulsive sphere of radius R. The confinement makes folding at the optimal temperature slower and affects the folding scenarios, but both effects are not dramatic. The influence of crowding on folding are studied by placing several identical proteins within the sphere, denaturing them, and then by monitoring refolding. If the interactions between the proteins are dominated by the excluded volume effects, the net folding times are essentially like for a single protein. An introduction of inter-proteinic attractive contacts hinders folding when the strength of the attraction exceeds about a half of the value of the strength of the single protein contacts. The bigger the strength of the attraction, the more likely is the occurrence of aggregation and misfolding.

  13. Analysis and implementation of an improved recycling folded cascode amplifier

    NASA Astrophysics Data System (ADS)

    Yilei, Li; Kefeng, Han; Na, Yan; Xi, Tan; Hao, Min

    2012-02-01

    A generally improved recycling folded cascode (IRFC) is analyzed and implemented. Analysis and comparisons among the IRFC, the original recycling folded cascode (RFC) and the conventional folded cascode (FC) are made, and it is shown that with the flexible structure of IRFC, significant enhancement in transconductance, slew rate and noise can be achieved. Prototype amplifiers were fabricated in 0.13 μm technology. Measurement shows that IRFC has 3× enhancement in gain-bandwidth and slew rate over conventional FC, and the enhancement is 1.5× when compared with the RFC.

  14. Vibratory responses of synthetic, self-oscillating vocal fold models

    PubMed Central

    Murray, Preston R.; Thomson, Scott L.

    2012-01-01

    The flow-induced responses of four self-oscillating synthetic vocal fold models are compared. All models were life-sized and fabricated using flexible silicone compounds with material properties comparable to those of human vocal fold tissue. Three of the models had two layers of different stiffness to represent the body–cover grouping of vocal fold tissue. Two of the two-layer models were based on the “M5” geometry [Scherer et al., J. Acoust. Soc. Am. 109, 1616–1630 (2001)], while the third was based on magnetic resonance imaging data. The fourth model included several layers, including a thin epithelial layer, an exceedingly flexible superficial lamina propria layer, a ligament layer that included an anteriorly–posteriorly oriented fiber to restrict vertical motion, and a body layer. Measurements were performed with these models in full larynx and hemilarynx configurations. Data included onset pressure, vibration frequency, glottal flow rate, maximum glottal width, and medial surface motion, the latter two of which were acquired using high-speed imaging techniques. The fourth, multi-layer model exhibited onset pressure, frequency, and medial surface motion traits that are comparable to published human vocal fold data. Importantly, the model featured an alternating convergent–divergent glottal profile and mucosal wave-like motion, characteristics which are important markers of human vocal fold vibration. PMID:23145623

  15. $\\cN$-FOLD SUPERSYMMETRY IN QUANTUM MECHANICAL MATRIX MODELS

    NASA Astrophysics Data System (ADS)

    Tanaka, Toshiaki

    2012-03-01

    We formulate Ņ-fold supersymmetry in quantum mechanical matrix models. As an example, we construct general two-by-two Hermitian matrix two-fold supersymmetric quantum mechanical systems. We find that there are two inequivalent such systems, both of which are characterized by two arbitrary scalar functions, and one of which does not reduce to the scalar system. The obtained systems are all weakly quasi-solvable.

  16. Microscopic folding model analysis of the radiative (n ,γ ) reactions near the Z =28 shell closure and the weak s process

    NASA Astrophysics Data System (ADS)

    Dutta, Saumi; Gangopadhyay, G.; Bhattacharyya, Abhijit

    2016-11-01

    Radiative thermal neutron capture cross sections over the range of thermal energies from 1 keV to 1 MeV are studied in the statistical Hauser-Feshbach formalism. The optical model potential is constructed by folding the density-dependent M3Y nucleon-nucleon interaction with radial matter densities of target nuclei obtained from relativistic-mean-field (RMF) theory. The standard nuclear reaction code talys1.8 is used for calculation of cross sections. The nuclei studied in the present work reside near the Z =28 proton shell closure and are of astrophysical interest, taking part in p ,s , and r processes of nucleosynthesis. The Maxwellian-averaged cross-section (MACS) values for energies important for astrophysical applications are presented.

  17. Dynamically Scaled Glottal Flow Through Symmetrically Oscillating Vocal Fold Models

    NASA Astrophysics Data System (ADS)

    Halvorson, Lori; Baitinger, Andrew; Sherman, Erica; Krane, Michael; Zhang, Lucy; Wei, Timothy

    2011-11-01

    Experimental results derived from DPIV measurements in a scaled up dynamic human vocal fold model are presented. The 10x scale vocal fold model is a new design that incorporates key features of vocal fold oscillatory motion. This includes coupling of down/upstream rocking as well as the oscillatory open/close motions. 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 will be shown. In this talk, effects associated with paralysis of one vocal fold will be discussed. This talk provides the baseline fluid dynamics for the vocal fold paralysis study presented in Sherman, et al. Supported by the NIH.

  18. Velocity field measurements in oblique static divergent vocal fold models

    NASA Astrophysics Data System (ADS)

    Erath, Byron

    2005-11-01

    During normal phonation, the vocal fold cycle is characterized by the glottal opening transitioning from a convergent to a divergent passage and then closing before the cycle is repeated. Under ordinary phonatory conditions, both vocal folds, which form the glottal passage, move in phase with each other, creating a time-varying symmetric opening. However, abnormal pathological conditions, such as unilateral paralysis, and polyps, can result in geometrical asymmetries between the vocal folds throughout the phonatory cycle. This study investigates pulsatile flow fields through 7.5 times life-size vocal fold models with included divergence angles of 5 to 30 degrees, and obliquities between the vocal folds of up to 15 degrees. Flow conditions were scaled to match physiological parameters. Data were taken at the anterior posterior mid-plane using phase-averaged Particle Image Velocimetry (PIV). Viscous flow phenomena including the Coanda effect, flow separation points, and jet "flapping" were investigated. The results are compared to previously reported work of flow through symmetric divergent vocal fold models.

  19. A theoretical model of sheath fold morphology in simple shear

    NASA Astrophysics Data System (ADS)

    Reber, Jacqueline E.; Dabrowski, Marcin; Galland, Olivier; Schmid, Daniel W.

    2013-04-01

    Sheath folds are highly non-cylindrical structures often associated with shear zones. The geometry of sheath folds, especially cross-sections perpendicular to the stretching direction that display eye-patterns, have been used in the field to deduce kinematic information such as shear sense and bulk strain type. However, how sheath folds form and how they evolve with increasing strain is still a matter of debate. We investigate the formation of sheath folds around a weak inclusion acting as a slip surface in simple shear by means of an analytical model. We systematically vary the slip surface orientation and shape and evaluate the impact on the evolving eye-pattern. In addition we compare our results to existing classifications. Based on field observations it has been suggested that the shear sense of a shear zone can be determined by knowing the position of the center of an eye-pattern and the closing direction of the corresponding sheath fold. In our modeled sheath folds we can observe for a given strain that the center of the eye-structure is subject to change in height with respect to the upper edge of the outermost closed contour for different cross-sections perpendicular to the shear direction. This results in a large variability in layer thickness, questioning the usefulness of sheath folds as shear sense indicators. The location of the center of the eye structure, however, is largely invariant to the initial configurations of the slip surface as well as to strain. It has been suggested that the ratio of the aspect ratio of the innermost and outermost closed contour in eye-patterns could be linked to the bulk strain type based on filed observations. We apply this classification to our modeled sheath folds and we observe that the values of the aspect ratios of the closed contours within the eye-pattern are dependent on the strain and the cross-section location. The ratio (R') of the aspect ratios of the outermost closed contour (Ryz) and the innermost closed

  20. Characterization of protein folding by a Φ-value calculation with a statistical-mechanical model

    PubMed Central

    Wako, Hiroshi; Abe, Haruo

    2016-01-01

    The Φ-value analysis approach provides information about transition-state structures along the folding pathway of a protein by measuring the effects of an amino acid mutation on folding kinetics. Here we compared the theoretically calculated Φ values of 27 proteins with their experimentally observed Φ values; the theoretical values were calculated using a simple statistical-mechanical model of protein folding. The theoretically calculated Φ values reflected the corresponding experimentally observed Φ values with reasonable accuracy for many of the proteins, but not for all. The correlation between the theoretically calculated and experimentally observed Φ values strongly depends on whether the protein-folding mechanism assumed in the model holds true in real proteins. In other words, the correlation coefficient can be expected to illuminate the folding mechanisms of proteins, providing the answer to the question of which model more accurately describes protein folding: the framework model or the nucleation-condensation model. In addition, we tried to characterize protein folding with respect to various properties of each protein apart from the size and fold class, such as the free-energy profile, contact-order profile, and sensitivity to the parameters used in the Φ-value calculation. The results showed that any one of these properties alone was not enough to explain protein folding, although each one played a significant role in it. We have confirmed the importance of characterizing protein folding from various perspectives. Our findings have also highlighted that protein folding is highly variable and unique across different proteins, and this should be considered while pursuing a unified theory of protein folding. PMID:28409079

  1. Protein folding in HP model on hexagonal lattices with diagonals

    PubMed Central

    2014-01-01

    Three dimensional structure prediction of a protein from its amino acid sequence, known as protein folding, is one of the most studied computational problem in bioinformatics and computational biology. Since, this is a hard problem, a number of simplified models have been proposed in literature to capture the essential properties of this problem. In this paper we introduce the hexagonal lattices with diagonals to handle the protein folding problem considering the well researched HP model. We give two approximation algorithms for protein folding on this lattice. Our first algorithm is a 53-approximation algorithm, which is based on the strategy of partitioning the entire protein sequence into two pieces. Our next algorithm is also based on partitioning approaches and improves upon the first algorithm. PMID:24564789

  2. Collective aspects of protein folding illustrated by a toy model

    SciTech Connect

    Stillinger, F.H.; Head-Gordon, T.

    1995-09-01

    A simple toy model for polypeptides serves as a testbed to illuminate some nonlocal, or collective, aspects of protein folding phenomena. The model is two dimensional and has only two amino acids, but involves a continuous range of backbone bend angles. Global potential energy minima and their folding structures have been determined for leading members of two special and contrasting polypeptide sequences, center doped and Fibonacci, named descriptively for their primary structures. The results display the presence of spontaneous symmetry breaking, elastic strain, and substantial conformational variation for specific embedded amino acid strings. We conclude that collective variables generated by the primary amino acid structure may be required for fully effective protein folding predictors, including those based on neural networks.

  3. Detachment folds versus thrust-folds: numerical modelling and applications to the Swiss Jura Mountains and the Canadian Foothills

    NASA Astrophysics Data System (ADS)

    Humair, Florian; Bauville, Arthur; Epard, Jean-Luc; Schmalholz, Stefan

    2016-04-01

    The Jura Mountains and the Foothills of the Canadian Rockies fold-and-thrust belts are classical examples of thin-skinned belts where folds develop over weak detachment horizons. They offer the possibility to observe and measure strain in folds. In these two belts, a large spectrum of fold geometries is expressed, from symmetric box-fold or pop-up structures to asymmetric thrust-related folds. In this study, we focus on the quantification and prediction of the brittle strain distribution in folds as a function of the fold geometry. Fold geometry is considered as a continuum between two end-member structural styles: symmetric detachment folds and asymmetric foreland-vergent thrust-folds. We performed two-dimensional numerical simulations of visco-plastic detachment folding. The models are used (1) to systematically examine the influence of different initial parameters on the resulting geometry and style of folding and (2) to quantify the local strain pattern through time. The different parameters tested are the following: presence and size of initial geometrical perturbation at the detachment-sediment interface, rheology of the detachment (frictional vs. viscous), additional detachment layer within the series and overbunden thickness. Results of single detachment layer models show that the asymmetry of folds is primarily controlled by the height of the initial geometrical perturbation, regardless to the rheology of the detachment (frictional vs. viscous). Additional detachment interlayer within the series decreases the brittle strain within the stiff layers and favours more rounded anticlines geometry. The models were then adapted to the Swiss Jura and the Canadian Foothills settings. Compared to field observations and cross-sections of existing fault-related anticlines, the proposed simulations agree with the first order geometry and the development of associated localized zones of brittle deformation.

  4. Influence of Asymmetric Stiffness on the Structural and Aerodynamic Response of Synthetic Vocal Fold Models

    PubMed Central

    Pickup, B.A.; Thomson, S.L.

    2012-01-01

    The influence of asymmetric vocal fold stiffness on voice production was evaluated using life-sized, self-oscillating vocal fold models with an idealized geometry based on the human vocal folds. The models were fabricated using flexible, materially-linear silicone compounds with Young’s modulus values comparable to that of vocal fold tissue. The models included a two-layer design to simulate the vocal fold layered structure. The respective Young’s moduli of elasticity of the “left” and “right” vocal fold models were varied to create asymmetric conditions. High-speed videokymography was used to measure maximum vocal fold excursion, vibration frequency, and left-right phase shift, all of which were significantly influenced by asymmetry. Onset pressure, a measure of vocal effort, increased with asymmetry. Particle image velocimetry (PIV) analysis showed significantly greater skewing of the glottal jet in the direction of the stiffer vocal fold model. Potential applications to various clinical conditions are mentioned, and suggestions for future related studies are presented. PMID:19664777

  5. Aeroelastic and Flight Dynamics Analysis of Folding Wing Systems

    NASA Astrophysics Data System (ADS)

    Wang, Ivan

    This dissertation explores the aeroelastic stability of a folding wing using both theoretical and experimental methods. The theoretical model is based on the existing clamped-wing aeroelastic model that uses beam theory structural dynamics and strip theory aerodynamics. A higher-fidelity theoretical model was created by adding several improvements to the existing model, namely a structural model that uses ANSYS for individual wing segment modes and an unsteady vortex lattice aerodynamic model. The comparison with the lower-fidelity model shows that the higher-fidelity model typical provides better agreement between theory and experiment, but the predicted system behavior in general does not change, reinforcing the effectiveness of the low-fidelity model for preliminary design of folding wings. The present work also conducted more detailed aeroelastic analyses of three-segment folding wings, and in particular considers the Lockheed-type configurations to understand the existence of sudden changes in predicted aeroelastic behavior with varying fold angle for certain configurations. These phenomena were observed in carefully conducted experiments, and nonlinearities---structural and geometry---were shown to suppress the phenomena. Next, new experimental models with better manufacturing tolerances are designed to be tested in the Duke University Wind Tunnel. The testing focused on various configurations of three-segment folding wings in order to obtain higher quality data. Next, the theoretical model was further improved by adding aircraft longitudinal degrees of freedom such that the aeroelastic model may predict the instabilities for the entire aircraft and not just a clamped wing. The theoretical results show that the flutter instabilities typically occur at a higher air speed due to greater frequency separation between modes for the aircraft system than a clamped wing system, but the divergence instabilities occur at a lower air speed. Lastly, additional

  6. Statistical mechanics of simple models of protein folding and design.

    PubMed Central

    Pande, V S; Grosberg, A Y; Tanaka, T

    1997-01-01

    It is now believed that the primary equilibrium aspects of simple models of protein folding are understood theoretically. However, current theories often resort to rather heavy mathematics to overcome some technical difficulties inherent in the problem or start from a phenomenological model. To this end, we take a new approach in this pedagogical review of the statistical mechanics of protein folding. The benefit of our approach is a drastic mathematical simplification of the theory, without resort to any new approximations or phenomenological prescriptions. Indeed, the results we obtain agree precisely with previous calculations. Because of this simplification, we are able to present here a thorough and self contained treatment of the problem. Topics discussed include the statistical mechanics of the random energy model (REM), tests of the validity of REM as a model for heteropolymer freezing, freezing transition of random sequences, phase diagram of designed ("minimally frustrated") sequences, and the degree to which errors in the interactions employed in simulations of either folding and design can still lead to correct folding behavior. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 6 PMID:9414231

  7. Mechanical Modeling and Computer Simulation of Protein Folding

    ERIC Educational Resources Information Center

    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…

  8. Mechanical Modeling and Computer Simulation of Protein Folding

    ERIC Educational Resources Information Center

    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…

  9. Modeling fibrosis using fibroblasts isolated from scarred rat vocal folds

    PubMed Central

    Kishimoto, Yo; Kishimoto, Ayami Ohno; Ye, Shuyun; Kendziorski, Christina; Welham, Nathan V.

    2016-01-01

    Following injury, pathologically activated vocal fold fibroblasts (VFFs) can engage in disordered extracellular matrix (ECM) remodeling, leading to VF fibrosis and impaired voice function. Given the importance of scar VFFs to phenotypically appropriate in vitro modeling of VF fibrosis, we pursued detailed characterization of scar VFFs obtained from surgically injured rat VF mucosae, compared to those obtained from experimentally naïve, age-matched tissue. Scar VFFs initially exhibited a myofibroblast phenotype characterized by increased proliferation, increased Col1a1 transcription and collagen, type I synthesis, increased Acta2 transcription and α-smooth muscle actin synthesis, and enhanced contractile function. These features were most distinct at passage 1 (P1); we observed a coalescence of the scar and naïve VFF phenotypes at later passages. An empirical Bayes statistical analysis of the P1 cell transcriptome identified 421 genes that were differentially expressed by scar, compared to naïve, VFFs. These genes were primarily associated with the wound response, ECM regulation, and cell proliferation. Follow-up comparison of P1 scar VFFs and their in vivo tissue source showed substantial transcriptomic differences. Finally, P1 scar VFFs responded to treatment with hepatocyte growth factor and transforming growth factor-β3, two biologics with reported therapeutic value. Despite the practical limitations inherent to working with early passage cells, this experimental model is easily implemented in any suitably equipped laboratory and has the potential to improve the applicability of preclinical VF fibrosis research. PMID:27111284

  10. Count ratio model reveals bias affecting NGS fold changes

    PubMed Central

    Erhard, Florian; Zimmer, Ralf

    2015-01-01

    Various biases affect high-throughput sequencing read counts. Contrary to the general assumption, we show that bias does not always cancel out when fold changes are computed and that bias affects more than 20% of genes that are called differentially regulated in RNA-seq experiments with drastic effects on subsequent biological interpretation. Here, we propose a novel approach to estimate fold changes. Our method is based on a probabilistic model that directly incorporates count ratios instead of read counts. It provides a theoretical foundation for pseudo-counts and can be used to estimate fold change credible intervals as well as normalization factors that outperform currently used normalization methods. We show that fold change estimates are significantly improved by our method by comparing RNA-seq derived fold changes to qPCR data from the MAQC/SEQC project as a reference and analyzing random barcoded sequencing data. Our software implementation is freely available from the project website http://www.bio.ifi.lmu.de/software/lfc. PMID:26160885

  11. Curvature of the energy landscape and folding of model proteins.

    PubMed

    Mazzoni, Lorenzo N; Casetti, Lapo

    2006-11-24

    We study the geometric properties of the energy landscape of coarse-grained, off-lattice models of polymers by endowing the configuration space with a suitable metric, depending on the potential energy function, such that the dynamical trajectories are the geodesics of the metric. Using numerical simulations, we show that the fluctuations of the curvature clearly mark the folding transition, and that this quantity allows to distinguish between polymers having a proteinlike behavior (i.e., that fold to a unique configuration) and polymers which undergo a hydrophobic collapse but do not have a folding transition. These geometrical properties are defined by the potential energy without requiring any prior knowledge of the native configuration.

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

    PubMed

    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.

  13. Saddles of the energy landscape and folding of model proteins

    NASA Astrophysics Data System (ADS)

    Angelani, L.; Ruocco, G.

    2009-07-01

    We numerically investigate the Potential Energy Landscape of an off-lattice β-sheet model protein, looking at saddles and minima probed by the system during the folding process. G {\\bar o} - like (with native-state-dependent force field and funnel-like landscape) and non-G {\\bar o} -like models are considered. In the G {\\bar o} -like case, on varying the temperature, we observe: i) a pronounced peak at the collapse/folding temperature T θsimeTf in the energy elevation of visited saddles from underlying minima, ii) a crossover at the same point of the saddle order. Saddles-based quantities seem then to be good candidates as indicators of the funneled shape of the landscape in protein models.

  14. Thermodynamics of folding and association of lattice-model proteins

    NASA Astrophysics Data System (ADS)

    Cellmer, Troy; Bratko, Dusan; Prausnitz, John M.; Blanch, Harvey

    2005-05-01

    Closely related to the "protein folding problem" is the issue of protein misfolding and aggregation. Protein aggregation has been associated with the pathologies of nearly 20 human diseases and presents serious difficulties during the manufacture of pharmaceutical proteins. Computational studies of multiprotein systems have recently emerged as a powerful complement to experimental efforts aimed at understanding the mechanisms of protein aggregation. We describe the thermodynamics of systems containing two lattice-model 64-mers. A parallel tempering algorithm abates problems associated with glassy systems and the weighted histogram analysis method improves statistical quality. The presence of a second chain has a substantial effect on single-chain conformational preferences. The melting temperature is substantially reduced, and the increase in the population of unfolded states is correlated with an increase in interactions between chains. The transition from two native chains to a non-native aggregate is entropically favorable. Non-native aggregates receive ˜25% of their stabilizing energy from intraprotein contacts not found in the lowest-energy structure. Contact maps show that for non-native dimers, nearly 50% of the most probable interprotein contacts involve pairs of residues that form native contacts, suggesting that a domain-swapping mechanism is involved in self-association.

  15. Multiple-probe analysis of folding and unfolding pathways of human serum albumin. Evidence for a framework mechanism of folding.

    PubMed

    Santra, Manas Kumar; Banerjee, Abhijit; Krishnakumar, Shyam Sundar; Rahaman, Obaidur; Panda, Dulal

    2004-05-01

    The changes in the far-UV CD signal, intrinsic tryptophan fluorescence and bilirubin absorbance showed that the guanidine hydrochloride (GdnHCl)-induced unfolding of a multidomain protein, human serum albumin (HSA), followed a two-state process. However, using environment sensitive Nile red fluorescence, the unfolding and folding pathways of HSA were found to follow a three-state process and an intermediate was detected in the range 0.25-1.5 m GdnHCl. The intermediate state displayed 45% higher fluorescence intensity than that of the native state. The increase in the Nile red fluorescence was found to be due to an increase in the quantum yield of the HSA-bound Nile red. Low concentrations of GdnHCl neither altered the binding affinity of Nile red to HSA nor induced the aggregation of HSA. In addition, the secondary structure of HSA was not perturbed during the first unfolding transition (<1.5 m GdnHCl); however, the secondary structure was completely lost during the second transition. The data together showed that the half maximal loss of the tertiary structure occurred at a lower GdnHCl concentration than the loss of the secondary structure. Further kinetic studies of the refolding process of HSA using multiple spectroscopic techniques showed that the folding occurred in two phases, a burst phase followed by a slow phase. An intermediate with native-like secondary structure but only a partial tertiary structure was found to form in the burst phase of refolding. Then, the intermediate slowly folded into the native state. An analysis of the refolding data suggested that the folding of HSA could be best explained by the framework model.

  16. Resolving pressure from DPIV measurements in a dynamically scaled-up vocal fold model

    NASA Astrophysics Data System (ADS)

    Lambert, Lori; Krane, Michael; Sherman, Erica; Wei, Timothy

    2012-11-01

    This presentation highlights application of control volume analysis to DPIV measurements in a dynamically scaled human vocal fold model. For the first time spatially and temporally resolved pressure field information can be extracted from voice experiments. The vocal fold model was built around a computer driven mechanism that replicates both the transverse vibrations as well as the streamwise rocking of human vocal folds. A range of experiments were conducted corresponding to 50 - 200 Hz life frequencies. Volumetric flow rate and maximum velocity measurements will be presented for several control surfaces in the glottal flow. The direction of the glottal jet (coandă) was noted for each instantaneous oscillation cycle. The pressure forces acting in the glottis were calculated using the streamwise and transverse linear momentum equations and control volume analysis. In addition to serving as a baseline study, data from these experiments provide the comparison for follow on studies of diseased and abnormal vocal fold vibrations. Supported by NIH.

  17. α-α folding cluster model for α-radioactivity

    NASA Astrophysics Data System (ADS)

    Soylu, A.; Bayrak, O.

    2015-04-01

    The -decay half-lives are calculated for heavy and superheavy nuclei for and from the ground state to ground state transitions within the framework of the Wentzel-Kramers-Brillouin (WKB) method and the Bohr-Sommerfeld quantization. In the calculations, the - single folding cluster potential obtained with the folded integral of the - potential with the -cluster density distributions is used in order to model the nuclear interaction between the -particle and core nucleus. While the results show very good agreement with the experimental ones in the heavy-nuclei region, especially for even-even nuclei, smaller values than the experimental ones are obtained for superheavy nuclei. As both the density of the core and the interaction term in the folding integral include the -clustering effects and, in this way, all cluster effects are taken into account in the model, the results of calculations are more physical and reasonable than the calculations done in the other models. The present method could be applied to light nuclei with different types of nuclear densities.

  18. Browsing gene banks for Fe2S2 ferredoxins and structural modeling of 88 plant-type sequences: an analysis of fold and function.

    PubMed

    Bertini, Ivano; Luchinat, Claudio; Provenzani, Alessandro; Rosato, Antonio; Vasos, Paul R

    2002-01-01

    One-hundred-and-seventy-nine sequences of Fe2S2 ferredoxins and ferredoxin precursors were identified in and retrieved from currently available protein and cDNA databases. On the basis of their cluster-binding patterns, these sequences were divided into three groups: those containing the CX4CX2CXnC pattern (plant-type ferredoxins), those with the CX5CX2CXnC pattern (adrenodoxins), and those with a different pattern. These three groups contain, respectively, 139, 36, and 4 sequences. After excluding ferredoxin precursors in the first group, two subgroups were identified, again based on their cluster-binding patterns: 88 sequences had the CX4CX2CX29C pattern, and 29 had the CX4CX2CXmC (m not equal 29) pattern. The structures of the 88 ferredoxins with the CX4CX2CX29C pattern were modeled based on the available experimental structures of nine proteins within this same group. The modeling procedure was tested by building structural models for the ferredoxins with known structures. The models resulted, on average, in being within 1 A of the backbone root-mean-square deviation from the corresponding experimental structures. In addition, these structural models were shown to be of high quality by using assessment procedures based on energetic and stereochemical parameters. Thus, these models formed a reliable structural database for this group of ferredoxins, which is meaningful within the framework of current structural genomics efforts. From the analysis of the structural database generated it was observed that the secondary structural elements and the overall three-dimensional structures are maintained throughout the superfamily. In particular, the residues in the hydrophobic core of the protein were found to be either absolutely conserved or conservatively substituted. In addition, certain solvent-accessible charged groups, as well as hydrophobic groups, were found to be conserved to the same degree as the core residues. The patterns of conservation of exposed

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

    NASA Astrophysics Data System (ADS)

    Chang, Siyuan; Luo, Haoxiang; Luo's lab Team

    2016-11-01

    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 is often needed in procedures such as optimization and parameter estimation. In this work, we study the 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. 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. Supported by the NSF.

  20. Dynamic Folding Pathway Models of the Trp-Cage Protein

    PubMed Central

    Kim, Seung-Yeon

    2013-01-01

    Using action-derived molecular dynamics (ADMD), we study the dynamic folding pathway models of the Trp-cage protein by providing its sequential conformational changes from its initial disordered structure to the final native structure at atomic details. We find that the numbers of native contacts and native hydrogen bonds are highly correlated, implying that the native structure of Trp-cage is achieved through the concurrent formations of native contacts and native hydrogen bonds. In early stage, an unfolded state appears with partially formed native contacts (~40%) and native hydrogen bonds (~30%). Afterward, the folding is initiated by the contact of the side chain of Tyr3 with that of Trp6, together with the formation of the N-terminal α-helix. Then, the C-terminal polyproline structure docks onto the Trp6 and Tyr3 rings, resulting in the formations of the hydrophobic core of Trp-cage and its near-native state. Finally, the slow adjustment processes of the near-native states into the native structure are dominant in later stage. The ADMD results are in agreement with those of the experimental folding studies on Trp-cage and consistent with most of other computational studies. PMID:23865078

  1. Simulations of the protein folding process using topology-based models depend on the experimental structure

    NASA Astrophysics Data System (ADS)

    Prieto, Lidia; Rey, Antonio

    2008-09-01

    Topology-based potentials (also known as Gō-type models) have been widely used in the study of the protein folding problem. When a topology-based potential is applied, the structure of the native state of the protein considered has to be known in advance. This fact gives to these models a semiempirical character, and therefore the quality of the simulation results obtained for the folding transition relies, among other factors, on the accuracy of the experimental structural data employed. In this work, we use a topology-based potential to carry out folding simulations of a protein whose structure has been determined both with NMR spectroscopy and x-ray crystallography. This way, we have been able to establish to which extent the differences in the topologies of the two experimental structures, easily ignored in a standard structural analysis for this protein, affect the thermodynamic characteristics of the folding transition defined in the simulations.

  2. Structural evolution of fold-thrust structures in analog models deformed in a large geotechnical centrifuge

    NASA Astrophysics Data System (ADS)

    Noble, Todd E.; Dixon, John M.

    2011-02-01

    We investigate the structural evolution of fault-propagation folds and fold-thrust systems with scaled analog modeling carried out using the 5.5 m radius geotechnical centrifuge at C-CORE, St. John's NL. The experiments presented here are the first of their kind, scaled ten times larger than predecessors and deformed using a custom rig with load monitoring and displacement control. Plane-layered models approximately 1 m long and representing 50 km sections are shortened horizontally under an enhanced gravity field of 160 g. The large model scale allows for a proportionally large number of bedding laminations that act as strain markers. This allows detailed analysis of strain partitioning and interplay, both at the scale of a fold-thrust system and the individual fold-thrust structure. Layer-parallel shortening ("LPS") and rotation of fault-bounded blocks are revealed by mapping contraction fault populations and bedding-contraction fault intersection angles. Low-angle contraction faulting and LPS are found to be dominant at early stages of development and rotation of fault-bounded blocks occurs during progressive folding of the hanging-wall panel during fault-propagation folding. Displacement-distance data obtained from major thrusts in the model show relative stretch values, and consequently fault slip/propagation ratios, that are similar to natural structures.

  3. Coarse-grained models of protein folding: toy models or predictive tools?

    PubMed

    Clementi, Cecilia

    2008-02-01

    Coarse-grained models are emerging as a practical alternative to all-atom simulations for the characterization of protein folding mechanisms over long time scales. While a decade ago minimalist toy models were mainly designed to test general hypotheses on the principles regulating protein folding, the latest coarse-grained models are increasingly realistic and can be used to characterize quantitatively the detailed folding mechanism of specific proteins. The ability of such models to reproduce the essential features of folding dynamics suggests that each single atomic degree of freedom is not by itself particularly relevant to folding and supports a statistical mechanical approach to characterize folding transitions. When combined with more refined models and with experimental studies, the systematic investigation of protein systems and complexes using coarse-grained models can advance our theoretical understanding of the actual organizing principles that emerge from the complex network of interactions among protein atomic constituents.

  4. Inflation model building with an accurate measure of e -folding

    NASA Astrophysics Data System (ADS)

    Chongchitnan, Sirichai

    2016-08-01

    It has become standard practice to take the logarithmic growth of the scale factor as a measure of the amount of inflation, despite the well-known fact that this is only an approximation for the true amount of inflation required to solve the horizon and flatness problems. The aim of this work is to show how this approximation can be completely avoided using an alternative framework for inflation model building. We show that using the inverse Hubble radius, H =a H , as the key dynamical parameter, the correct number of e -folding arises naturally as a measure of inflation. As an application, we present an interesting model in which the entire inflationary dynamics can be solved analytically and exactly, and, in special cases, reduces to the familiar class of power-law models.

  5. Development of Vibrational Culture Model Mimicking Vocal Fold Tissues.

    PubMed

    Kim, Dongjoo; Lim, Jae-Yol; Kwon, Soonjo

    2016-10-01

    The vocal folds (VFs) are connective tissues with complex matrix structures that provide the required mechanical properties for voice generation. VF injury leads to changes in tissue structure and properties, resulting in reduced voice quality. However, injury-induced biochemical changes and repair in scarred VF tissues have not been well characterized to date. To treat scarred VFs, it is essential to understand how physiological characteristics of VFs tissue change in response to external perturbation. In this study, we designed a simple vibrational culture model to mimic vibratory microenvironments observed in vivo. This model consists of a flexible culture plate, three linear actuators, a stereo splitter, and a function generator. Human vocal fold fibroblast (hVFF) monolayers were established on the flexible membrane, to which normal phonatory vibrations were delivered from linear actuators and a function generator. The hVFF monolayers were exposed to the vibrational stresses at a frequency of 205 Hz for 2, 6, and 10 h with maximum displacement of 47.1 μm, followed by a 6 h rest. We then observed the changes in cell morphology, cell viability, and gene expression related to extracellular matrix components. In our dynamic culture device mimicking normal phonatory frequencies, cell proliferation increased and expression of hyaluronic acid synthase 2 was downregulated in response to vibrational stresses. The results presented herein will be useful for evaluating cellular responses following VF injuries in the presence or absence of vibrational stresses.

  6. A rabbit vocal fold laser scarring model for testing lamina propria tissue engineering therapies

    PubMed Central

    Mau, Ted; Du, Mindy; Xu, Chet C.

    2015-01-01

    Objectives/Hypothesis To develop a vocal fold scarring model using an ablative laser in the rabbit as a platform for testing bioengineered therapies for missing or damaged lamina propria. Study Design Prospective controlled animal study. Methods An optimal laser energy level was first determined by assessing the depths of vocal fold injury created by a Holmium:YAG laser at various energy levels on fresh cadaveric rabbit larynges. The selected energy level was then used to create controlled unilateral injuries in vocal folds of New Zealand white rabbits, with the contralateral folds serving as uninjured controls. After 4 weeks, the larynges were harvested and subjected to excised-larynx phonation with high-speed imaging and immunohistochemical staining for collagen types I and III, elastin, and hyaluronic acid (HA) with quantitative histological analysis. Results 1.8 joules produced full-thickness injury of the lamina propria without extensive muscle injury. After 4 weeks, the injured vocal folds vibrated with reduced amplitude (P = 0.036) in excised-larynx phonation compared to normal vocal folds. The injured vocal folds contained a higher relative density of collagen type I (P = 0.004), higher elastin (P = 0.022), and lower HA (P = 0.030) compared to normal controls. Collagen type III was unchanged. Conclusions With its potential for higher precision of injury, this laser vocal fold scarring model may serve as an alternative to scarring produced by cold instruments for studying the effects of vocal fold lamina propria bioengineered therapies. Level of Evidence N/A. PMID:24715695

  7. Folding model calculations for 6He+12C elastic scattering

    NASA Astrophysics Data System (ADS)

    Awad, A. Ibraheem

    2016-03-01

    In the framework of the double folding model, we used the α+2n and di-triton configurations for the nuclear matter density of the 6He nucleus to generate the real part of the optical potential for the system 6He+12C. As an alternative, we also use the high energy approximation to generate the optical potential for the same system. The derived potentials are employed to analyze the elastic scattering differential cross section at energies of 38.3, 41.6 and 82.3 MeV/u. For the imaginary part of the potential we adopt the squared Woods-Saxon form. The obtained results are compared with the corresponding measured data as well as with available results in the literature. The calculated total reaction cross sections are investigated and compared with the optical limit Glauber model description.

  8. A workflow for 3D model building in fold-thrust belts

    NASA Astrophysics Data System (ADS)

    Watkins, Hannah; Bond, Clare; Butler, Rob

    2016-04-01

    3D geological models can be used in fold-thrust belts for many purposes such as analysing geometric variation in folds, kinematic modelling to restore fold surfaces, generating strain distribution maps and predicting fracture network distribution. We present a workflow for 3D model building using outcrop bedding data, geological maps, Digital Terrain Models (DTM's), air photos and field photographs. We discuss the challenges of software limitations for 3D kinematic restoration and forward modelling in fold-thrust belt settings. We then discuss the sensitivity of model building approaches to the application of 3D geological models in fold-thrust belts for further analysis e.g. changes in along strike fold geometry, restoration using kinematic and geomechanical modelling, strain prediction and Discrete Fracture Network (DFN) modelling. To create 3D models geological maps and bedding data are digitised using Move software; digitised maps and data are then draped onto DTM's. A series of closely spaced cross section lines are selected; the orientation of these is calculated by determining the average orientation of bedding dip direction. Fault and horizon line intersections, along with bedding data from within a narrow margin of the section lines are projected onto each cross section. Field photographs and sketches are integrated into the cross sections to determine thrust angles at the surface. Horizon lines are then constructed using bedding data. Displacement profiles for thrusts are plotted to ensure thrust displacements are valid with respect to neighbouring cross section interpretations; any discrepancies are alleviated by making minor adjustments to horizon and thrust lines, while ensuring that resultant cross section geometries still adhere to bedding data and other field observations. Once the cross sections have been finalised, 3D surfaces are created using the horizon and thrust line interpretations on each cross section. The simple curvature of 3D surfaces

  9. Parameter Optimization for the Gaussian Model of Folded Proteins

    NASA Astrophysics Data System (ADS)

    Erman, Burak; Erkip, Albert

    2000-03-01

    Recently, we proposed an analytical model of protein folding (B. Erman, K. A. Dill, J. Chem. Phys, 112, 000, 2000) and showed that this model successfully approximates the known minimum energy configurations of two dimensional HP chains. All attractions (covalent and non-covalent) as well as repulsions were treated as if the monomer units interacted with each other through linear spring forces. Since the governing potential of the linear springs are derived from a Gaussian potential, the model is called the ''Gaussian Model''. The predicted conformations from the model for the hexamer and various 9mer sequences all lie on the square lattice, although the model does not contain information about the lattice structure. Results of predictions for chains with 20 or more monomers also agreed well with corresponding known minimum energy lattice structures. However, these predicted conformations did not lie exactly on the square lattice. In the present work, we treat the specific problem of optimizing the potentials (the strengths of the spring constants) so that the predictions are in better agreement with the known minimum energy structures.

  10. Finite element analysis of electroactive polymer and magnetoactive elastomer based actuation for origami folding

    NASA Astrophysics Data System (ADS)

    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.

  11. Rapid analysis of fold shape using Bézier curves

    NASA Astrophysics Data System (ADS)

    Srivastava, Deepak C.; Lisle, Richard J.

    2004-09-01

    We approximate and classify the forms of profile sections of folded surfaces by comparison with cubic Bézier curves. The method analyses a digital image of the fold profile, by interactive visual comparison, with the curves generated by the Bézier drawing tool available commonly in graphics software products. Simplified equations of cubic Bézier curves form the basis of the classification in terms of two parameters. The first parameter, L, is related to the distribution of curvature on a single limb of a fold between the hinge point and the inflection point. It places the fold within a shape spectrum that ranges from straight-limbed chevron folds ( L=0) in which curvature is concentrated in the hinge region through to rounded folds with a uniform curvature distribution ( L=1). The second parameter, R, is related to the ratio of amplitude to wavelength. A graph of L against R serves to group samples of folds into 'shape groups'. This classification can be used as a tool to assist the determination of relative competence of folded layers and of the folding mechanism. The new method, which has the advantages of speed and simplicity, is applied to examples of natural and experimentally developed folds to demonstrate its versatility for analysing a wide range of fold geometries.

  12. Topology-based modeling of intrinsically disordered proteins: balancing intrinsic folding and intermolecular interactions.

    PubMed

    Ganguly, Debabani; Chen, Jianhan

    2011-04-01

    Coupled binding and folding is frequently involved in specific recognition of so-called intrinsically disordered proteins (IDPs), a newly recognized class of proteins that rely on a lack of stable tertiary fold for function. Here, we exploit topology-based Gō-like modeling as an effective tool for the mechanism of IDP recognition within the theoretical framework of minimally frustrated energy landscape. Importantly, substantial differences exist between IDPs and globular proteins in both amino acid sequence and binding interface characteristics. We demonstrate that established Gō-like models designed for folded proteins tend to over-estimate the level of residual structures in unbound IDPs, whereas under-estimating the strength of intermolecular interactions. Such systematic biases have important consequences in the predicted mechanism of interaction. A strategy is proposed to recalibrate topology-derived models to balance intrinsic folding propensities and intermolecular interactions, based on experimental knowledge of the overall residual structure level and binding affinity. Applied to pKID/KIX, the calibrated Gō-like model predicts a dominant multistep sequential pathway for binding-induced folding of pKID that is initiated by KIX binding via the C-terminus in disordered conformations, followed by binding and folding of the rest of C-terminal helix and finally the N-terminal helix. This novel mechanism is consistent with key observations derived from a recent NMR titration and relaxation dispersion study and provides a molecular-level interpretation of kinetic rates derived from dispersion curve analysis. These case studies provide important insight into the applicability and potential pitfalls of topology-based modeling for studying IDP folding and interaction in general. Copyright © 2011 Wiley-Liss, Inc.

  13. Geomechanical Modeling in Fold-and-Thrust Belts Systems

    NASA Astrophysics Data System (ADS)

    Gao, B.; Flemings, P. B.

    2015-12-01

    We present a large-strain poro-mechanical model to investigate the evolution of stress and strain in fold and thrust belt systems. We impose horizontal shortening in the model and observe that a tapered wedge develops. Inside the accretionary wedge, the horizontal effective stress increases to about 2.3 times the vertical effective stress. The maximum principle stress direction rotates gradually from the initial vertical direction to the horizontal direction as the sediment gets closer to the backstop. We use stress paths to illustrate how the stresses evolve during the thrust loading. We find the sediment stress path starts from uniaxial condition and moves towards critical state condition. We categorize the thrust belt into 3 zones according to their stress conditions from the backstop to the farfield: critical state region, transition region, and uniaxial region. We show that the sediments within the accretionary wedge are at critical state, which indicate they lost their strength to resist deformation. The sediment porosity decreases dramatically within the wedge due to high mean effective and differential stress. We built the model in finite element program Elfen. The sediments are modeled as poro-elastoplastic materials with a critical state soil model. Overall, our results provide insights of stress and porosity evolution in compressional regimes and can assist field stress and pressure predictions.

  14. Modeling chain folding in protein-constrained circular DNA.

    PubMed Central

    Martino, J A; Olson, W K

    1998-01-01

    An efficient method for sampling equilibrium configurations of DNA chains binding one or more DNA-bending proteins is presented. The technique is applied to obtain the tertiary structures of minimal bending energy for a selection of dinucleosomal minichromosomes that differ in degree of protein-DNA interaction, protein spacing along the DNA chain contour, and ring size. The protein-bound portions of the DNA chains are represented by tight, left-handed supercoils of fixed geometry. The protein-free regions are modeled individually as elastic rods. For each random spatial arrangement of the two nucleosomes assumed during a stochastic search for the global minimum, the paths of the flexible connecting DNA segments are determined through a numerical solution of the equations of equilibrium for torsionally relaxed elastic rods. The minimal energy forms reveal how protein binding and spacing and plasmid size differentially affect folding and offer new insights into experimental minichromosome systems. PMID:9591675

  15. Emergent protein folding modeled with evolved neural cellular automata using the 3D HP model.

    PubMed

    Santos, José; Villot, Pablo; Diéguez, Martin

    2014-11-01

    We used cellular automata (CA) for the modeling of the temporal folding of proteins. Unlike the focus of the vast research already done on the direct prediction of the final folded conformations, we will model the temporal and dynamic folding process. To reduce the complexity of the interactions and the nature of the amino acid elements, lattice models like HP were used, a model that categorizes the amino acids regarding their hydrophobicity. Taking into account the restrictions of the lattice model, the CA model defines how the amino acids interact through time to obtain a folded conformation. We extended the classical CA models using artificial neural networks for their implementation (neural CA), and we used evolutionary computing to automatically obtain the models by means of Differential Evolution. As the iterative folding also provides the final folded conformation, we can compare the results with those from direct prediction methods of the final protein conformation. Finally, as the neural CA that provides the iterative folding process can be evolved using several protein sequences and used as operators in the folding of another protein with different length, this represents an advantage over the NP-hard complexity of the original problem of the direct prediction.

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

    PubMed Central

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

    2009-01-01

    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 < N), the consecutive windows folding problem is to compute the minimal 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. 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. PMID:19257906

  17. Thermal stability and folding kinetics analysis of intrinsically disordered protein, securin

    NASA Astrophysics Data System (ADS)

    Chang, Chia-Ching; Chu, Hsueh-Liang; Ho, Li-Ping

    2014-03-01

    Lacking a stable tertiary structure, intrinsically disordered proteins (IDPs) possess particular functions in cell regulation, signaling, and controlling pathways. The study of their unique structure features, thermal stabilities, and folding kinetics is intriguing. In this study, an identified IDP, securin, was used as a model protein. By using a quasi-static five-step (on-path) folding process, the function of securin was restored and analyzed by isothermal titration calorimetry. Fluorescence spectroscopy and particle size analysis indicated that securin possessed a compact hydrophobic core and particle size. The glass transition of securin was characterized using differential scanning microcalorimetry. Furthermore, the folding/unfolding rates (kobs) of securin were undetectable, implying that the folding/unfolding rate is very fast and that the conformation of securin is sensitive to solvent environment change. Therefore, securin may fold properly under specific physiological conditions. In summary, the thermal glass transition behavior and undetectable kobs of folding/unfolding reactions may be two of the indices of IDP. This study was supported in part by grants NSC 97-2112-M-009-009-YM3 and NSC 100-2112-M-009-004-MY3, Taiwan, R.O.C.

  18. Modulation of folding energy landscape by charge-charge interactions: linking experiments with computational modeling.

    PubMed

    Tzul, Franco O; Schweiker, Katrina L; Makhatadze, George I

    2015-01-20

    The kinetics of folding-unfolding of a structurally diverse set of four proteins optimized for thermodynamic stability by rational redesign of surface charge-charge interactions is characterized experimentally. The folding rates are faster for designed variants compared with their wild-type proteins, whereas the unfolding rates are largely unaffected. A simple structure-based computational model, which incorporates the Debye-Hückel formalism for the electrostatics, was used and found to qualitatively recapitulate the experimental results. Analysis of the energy landscapes of the designed versus wild-type proteins indicates the differences in refolding rates may be correlated with the degree of frustration of their respective energy landscapes. Our simulations indicate that naturally occurring wild-type proteins have frustrated folding landscapes due to the surface electrostatics. Optimization of the surface electrostatics seems to remove some of that frustration, leading to enhanced formation of native-like contacts in the transition-state ensembles (TSE) and providing a less frustrated energy landscape between the unfolded and TS ensembles. Macroscopically, this results in faster folding rates. Furthermore, analyses of pairwise distances and radii of gyration suggest that the less frustrated energy landscapes for optimized variants are a result of more compact unfolded and TS ensembles. These findings from our modeling demonstrates that this simple model may be used to: (i) gain a detailed understanding of charge-charge interactions and their effects on modulating the energy landscape of protein folding and (ii) qualitatively predict the kinetic behavior of protein surface electrostatic interactions.

  19. Natural and forced asymmetries in flow through a vocal fold model

    NASA Astrophysics Data System (ADS)

    Drain, Bethany; Lambert, Lori; Krane, Michael; Wei, Timothy

    2012-11-01

    Much of the complexity and richness of voice production stems from asymmetries in flow through the vocal folds. There are naturally occurring asymmetries, such as the Coanda effect (i . e . deviation of the glottal jet from the centerline as air passes through the nominally symmetric vocal folds). There are also asymmetries which arise from disease or dysfunction of the vocal folds. This study uses DPIV measurements in a dynamically scaled-up human vocal fold model to compare the flow characteristics between symmetric versus asymmetric oscillations. For this study, asymmetries were introduced by running one vocal fold out of phase with the other. Three phase lags, 0 18 and 36, were examined over a range of frequencies corresponding to the physiological frequencies of 50-200 Hz. Control volume analysis was applied and time traces of terms from the conservation of linear momentum equation were generated. This allowed analysis of how differences in the glottal jet flow manifest themselves in the fluid pressure field. In addition, further examination of the Coanda effect in the context of fluid pressure will be discussed. Supported by NIH.

  20. Viscous overthrusting versus folding: 2-D quantitative modeling and its application to the Helvetic and Jura fold and thrust belts

    NASA Astrophysics Data System (ADS)

    Jaquet, Y.; Bauville, A.; Schmalholz, S. M.

    2013-12-01

    This paper presents two-dimensional (2-D) numerical simulations of the shortening of a stiff viscous layer with pre-existing weak zones that is embedded in a weaker viscous matrix above a rigid detachment. Four deformation styles are observed that depend on the ratio of the layer and matrix viscosities, μL/μM; the ratio of the distance between the layer and the detachment to the layer thickness, HM/HL; and the power-law stress exponent of the matrix, nM. The results show that (1) pure shear-dominated deformation occurs for μL/μM<~50 and nM=1 (i.e., linear viscous); (2) overthrusting-dominated deformation occurs for nM>1 (i.e., power-law viscous fluid), μL/μM>~50 and HM/HL<~0.5; (3) folding-dominated deformation occurs for nM=1, μL/μM>~50, and HM/HL>~1; and (4) folding and overthrusting occur for nM>1 and ~0.5folding of the thrust plane; this finding was proposed in a profile of the Jura fold and thrust belt. The agreement of the results with first-order observations from the Helvetic fold and thrust belt suggest that ductile deformation dominated this fold and thrust belt. The development of the model geometry with increasing shortening. The layer (black) is linear viscous, whereas the matrix (gray) is power-law viscous (nM=5). a-e) The model has a viscosity ratio (μL/μM) of 200 and a thickness ratio (HM/HL) of 0.25. During shortening, the layer deforms by essentially overthrusting. f

  1. Optimized parameter selection reveals trends in Markov state models for protein folding

    NASA Astrophysics Data System (ADS)

    Husic, Brooke E.; McGibbon, Robert T.; Sultan, Mohammad M.; Pande, Vijay S.

    2016-11-01

    As molecular dynamics simulations access increasingly longer time scales, complementary advances in the analysis of biomolecular time-series data are necessary. Markov state models offer a powerful framework for this analysis by describing a system's states and the transitions between them. A recently established variational theorem for Markov state models now enables modelers to systematically determine the best way to describe a system's dynamics. In the context of the variational theorem, we analyze ultra-long folding simulations for a canonical set of twelve proteins [K. Lindorff-Larsen et al., Science 334, 517 (2011)] by creating and evaluating many types of Markov state models. We present a set of guidelines for constructing Markov state models of protein folding; namely, we recommend the use of cross-validation and a kinetically motivated dimensionality reduction step for improved descriptions of folding dynamics. We also warn that precise kinetics predictions rely on the features chosen to describe the system and pose the description of kinetic uncertainty across ensembles of models as an open issue.

  2. Precursory signatures of protein folding/unfolding: From time series correlation analysis to atomistic mechanisms

    SciTech Connect

    Hsu, P. J.; Lai, S. K.; Cheong, S. A.

    2014-05-28

    Folded conformations of proteins in thermodynamically stable states have long lifetimes. Before it folds into a stable conformation, or after unfolding from a stable conformation, the protein will generally stray from one random conformation to another leading thus to rapid fluctuations. Brief structural changes therefore occur before folding and unfolding events. These short-lived movements are easily overlooked in studies of folding/unfolding for they represent momentary excursions of the protein to explore conformations in the neighborhood of the stable conformation. The present study looks for precursory signatures of protein folding/unfolding within these rapid fluctuations through a combination of three techniques: (1) ultrafast shape recognition, (2) time series segmentation, and (3) time series correlation analysis. The first procedure measures the differences between statistical distance distributions of atoms in different conformations by calculating shape similarity indices from molecular dynamics simulation trajectories. The second procedure is used to discover the times at which the protein makes transitions from one conformation to another. Finally, we employ the third technique to exploit spatial fingerprints of the stable conformations; this procedure is to map out the sequences of changes preceding the actual folding and unfolding events, since strongly correlated atoms in different conformations are different due to bond and steric constraints. The aforementioned high-frequency fluctuations are therefore characterized by distinct correlational and structural changes that are associated with rate-limiting precursors that translate into brief segments. Guided by these technical procedures, we choose a model system, a fragment of the protein transthyretin, for identifying in this system not only the precursory signatures of transitions associated with α helix and β hairpin, but also the important role played by weaker correlations in such protein

  3. Modeling Fold-And Belts Using Numerical Simulations and Physical Experiments: the Aconcagua and Mexican Fold-And Belts

    NASA Astrophysics Data System (ADS)

    Cruz, L.; Hilley, G. E.; Fitz, E.; Hudleston, P. J.; Malinski, J.; Hernandez, M.; Take, A.

    2010-12-01

    In this contribution we first investigate the impact of erosion on the geometry and kinematics of the central Argentine Aconcagua Fold-and-Thrust Belt (AFTB) using an integrated analog (sandbox) and numerical (Gale) modeling approach in which mass removal from the topographic surface is limited by the rate of fluvial bedrock incision. This method unifies principles of frictional failure used in Critical Coulomb Wedge (CCW) theory with a quasi-mechanistic erosion rule, which allows us to explicitly relate temporal changes in erosional efficiency in this fold-and-thrust belt to its kinematics. We show that theoretical predictions of AFTB geometry, as well as the kinematics predicted by both physical and numerical experiments are both internally consistent and correctly predict the interpreted and measured field geometries. Specifically, the geometric evolution of the AFTB requires relatively high erosion efficiency values (K) during the initial stage of deformation, and relatively low K values during the latter stages, which is consistent with the progressive exposure of different rock types during the different stages of deformation. Model results indicate that the activity of the faults in the hinterland is high when erosion is most efficient during the initial stage of deformation; this activity is facilitated by increased out-of-sequence thrusting. In contrast, the models predict that forward-propagating thrusts dominate the latter stages of deformation when erosion is far less efficient. We next explore the role of the initial configuration of materials with differing constitutive properties using the Gale numerical code, and published and new structural data from the well-documented Mexican Fold-and-Thrust Belt (MFTB). This fold-and-thrust belt is located in central Mexico and its kinematics appear to be influenced by spatially varying material properties within the accreted foreland rocks. Preliminary results from the MFTB simulations show that rheological

  4. Aeroelastic-aeroacoustic measurements in a self-oscillating physical model of the human vocal folds

    NASA Astrophysics Data System (ADS)

    Krane, Michael; Cates, Zachary

    2009-11-01

    Measurements are presented characterizing the relationship between the structure of physical models of the human vocal folds and the sound produced by their vibration by airflow from the lungs. The model vocal folds are fabricated by molding two layers of silicone rubber of specified stiffness, approximating the body/cover structure. These are mounted in a model vocal tract, where the prephonatory gap adjusted using micropositioners. Measurements conducted in an anechoic chamber include radiated sound pressure, and high-speed video of the vibrating model vocal folds, using prephonatory separation, body stiffness, and subglottal pressure as input parameters.. Essential behavior of the vocal fold models is presented. Vibration fundamental frequency and radiated sound pressure level outside the model vocal tract as a function of subglottal pressure and prephonatory gap are presented for the cases of two identical vocal folds and one vocal fold with lower stiffness, approximating vocal fold paralysis.

  5. FE Modelling of the Fluid-Structure-Acoustic Interaction for the Vocal Folds Self-Oscillation

    NASA Astrophysics Data System (ADS)

    Švancara, Pavel; Horáček, J.; Hrůza, V.

    The flow induced self-oscillation of the human vocal folds in interaction with acoustic processes in the simplified vocal tract model was explored by three-dimensional (3D) finite element (FE) model. Developed FE model includes vocal folds pretension before phonation, large deformations of the vocal fold tissue, vocal folds contact, fluid-structure interaction, morphing the fluid mesh according the vocal folds motion (Arbitrary Lagrangian-Eulerian approach), unsteady viscous compressible airflow described by the Navier-Stokes equations and airflow separation during the glottis closure. Iterative partitioned approach is used for modelling the fluid-structure interaction. Computed results prove that the developed model can be used for simulation of the vocal folds self-oscillation and resulting acoustic waves. The developed model enables to numerically simulate an influence of some pathological changes in the vocal fold tissue on the voice production.

  6. Self-organized critical model for protein folding

    NASA Astrophysics Data System (ADS)

    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.

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

    ERIC Educational Resources Information Center

    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.…

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

    ERIC Educational Resources Information Center

    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.…

  9. Folding model description of reactions with exotic nuclei

    SciTech Connect

    Ibraheem, Awad A.; Hassanain, M. A.; Mokhtar, S. R.; Zaki, M. A.; Mahmoud, Zakaria M. M.; Farid, M. El-Azab

    2012-08-15

    Microscopic folding calculations based upon the effective M3Y nucleon-nucleon interaction and the nuclearmatter densities of the interacting nuclei have been carried out to explain recently measured experimental data of the {sup 6}He+{sup 120}Sn elastic scattering cross section at four different laboratory energies near the Coulomb barrier. The extracted reaction cross sections are also considered.

  10. The topomer-sampling model of protein folding

    PubMed Central

    Debe, Derek A.; Carlson, Matt J.; Goddard, William A.

    1999-01-01

    Clearly, a protein cannot sample all of its conformations (e.g., ≈3100 ≈ 1048 for a 100 residue protein) on an in vivo folding timescale (<1 s). To investigate how the conformational dynamics of a protein can accommodate subsecond folding time scales, we introduce the concept of the native topomer, which is the set of all structures similar to the native structure (obtainable from the native structure through local backbone coordinate transformations that do not disrupt the covalent bonding of the peptide backbone). We have developed a computational procedure for estimating the number of distinct topomers required to span all conformations (compact and semicompact) for a polypeptide of a given length. For 100 residues, we find ≈3 × 107 distinct topomers. Based on the distance calculated between different topomers, we estimate that a 100-residue polypeptide diffusively samples one topomer every ≈3 ns. Hence, a 100-residue protein can find its native topomer by random sampling in just ≈100 ms. These results suggest that subsecond folding of modest-sized, single-domain proteins can be accomplished by a two-stage process of (i) topomer diffusion: random, diffusive sampling of the 3 × 107 distinct topomers to find the native topomer (≈0.1 s), followed by (ii) intratopomer ordering: nonrandom, local conformational rearrangements within the native topomer to settle into the precise native state. PMID:10077555

  11. Thermodynamic aspects in a simplified model for the folding of two-stranded coiled-coils

    NASA Astrophysics Data System (ADS)

    Prolongo, Silvia G.; Rubio, Ana M.; Rey, Antonio

    2000-12-01

    We have investigated the thermodynamic properties of a simple model representing the thermal folding/unfolding transition of two-stranded coiled-coils. The transition temperature and the energy change for the process are analyzed in terms of the peptide concentration, using the standard properties and calculations involved in experimental work. The integration of the heat capacity curves provides realistic and correct results for the model, as it does the variation of the transition temperature with concentration. On the other hand, the van't Hoff analysis of the equilibrium constant for the unfolding process produces apparently odd results. They can only be rationalized through a careful analysis of the reaction stoichiometry, according to the reference state defined for the very simple model interactions, and the definition of the unfolded state. This point is extensively discussed, for its possible implications in the correct analysis of this and other simulation models.

  12. Design and analysis of a folded Fresnel Zone Plate antenna

    NASA Astrophysics Data System (ADS)

    Ji, Yu; Fujita, Masaharu

    1994-08-01

    Based on the Kirchhoff-Huygens diffraction theory, a simple analytical method of a planar folded Fresnel zone-plate (FZP), that is the case when a planar reflector is placed behind the zone plates, has been developed. According to the numerical calculation results, the design procedure of the FZP antenna has been presented, and its focusing characteristics and gain-optimized conditions have been discussed. The variations of the focal field distribution with the antenna parameters such as zone numbers, focal length and antenna diameter and the radiation power patterns of the FZP have been simulated numerically. To take a good balance of both receiving and transmitting antennas, at 60GHz operating frequency, the focal length should be designed as a half of the antenna diameter and the zone number should be from 10 to 15. The results in this work show that the folded FZP has good focal characteristics and off-axis performance, and its antenna gain can be optimized by the suitable antenna parameter design. The possibility of applying the folded FZP as a low cost and high gain antenna without strict manufacturing requirement for millimeter-wave communications has been shown.

  13. Complex RNA Folding Kinetics Revealed by Single-Molecule FRET and Hidden Markov Models

    PubMed Central

    2014-01-01

    We have developed a hidden Markov model and optimization procedure for photon-based single-molecule FRET data, which takes into account the trace-dependent background intensities. This analysis technique reveals an unprecedented amount of detail in the folding kinetics of the Diels–Alderase ribozyme. We find a multitude of extended (low-FRET) and compact (high-FRET) states. Five states were consistently and independently identified in two FRET constructs and at three Mg2+ concentrations. Structures generally tend to become more compact upon addition of Mg2+. Some compact structures are observed to significantly depend on Mg2+ concentration, suggesting a tertiary fold stabilized by Mg2+ ions. One compact structure was observed to be Mg2+-independent, consistent with stabilization by tertiary Watson–Crick base pairing found in the folded Diels–Alderase structure. A hierarchy of time scales was discovered, including dynamics of 10 ms or faster, likely due to tertiary structure fluctuations, and slow dynamics on the seconds time scale, presumably associated with significant changes in secondary structure. The folding pathways proceed through a series of intermediate secondary structures. There exist both compact pathways and more complex ones, which display tertiary unfolding, then secondary refolding, and, subsequently, again tertiary refolding. PMID:24568646

  14. Predicting the equilibrium protein folding pathway: structure-based analysis of staphylococcal nuclease.

    PubMed

    Hilser, V J; Freire, E

    1997-02-01

    The equilibrium folding pathway of staphylococcal nuclease (SNase) has been approximated using a statistical thermodynamic formalism that utilizes the high-resolution structure of the native state as a template to generate a large ensemble of partially folded states. Close to 400,000 different states ranging from the native to the completely unfolded states were included in the analysis. The probability of each state was estimated using an empirical structural parametrization of the folding energetics. It is shown that this formalism predicts accurately the stability of the protein, the cooperativity of the folding/unfolding transition observed by differential scanning calorimetry (DSC) or urea denaturation and the thermodynamic parameters for unfolding. More importantly, this formalism provides a quantitative account of the experimental hydrogen exchange protection factors measured under native conditions for SNase. These results suggest that the computer-generated distribution of states approximates well the ensemble of conformations existing in solution. Furthermore, this formalism represents the first model capable of quantitatively predicting within a unified framework the probability distribution of states seen under native conditions and its change upon unfolding.

  15. Viscous overthrusting versus folding: 2-D quantitative modeling and its application to the Helvetic and Jura fold and thrust belts

    NASA Astrophysics Data System (ADS)

    Jaquet, Yoann; Bauville, Arthur; Schmalholz, Stefan M.

    2014-05-01

    We apply a viscous model to study the tectonic evolution of the Jura and Helvetic fold-and-thrust belts of the European Alps. We present two-dimensional (2-D) numerical simulations of the shortening of a stiff viscous layer, with a pre-existing weak zone, that is embedded in a weaker viscous matrix. The model bottom remains straight during shortening and represents a detachment surface. Four deformation styles are observed that depend on the ratio of the layer and matrix viscosities, μL/μM; the thickness ratio of the bottom matrix and the overlying stiff layer, HM/HL; and the power-law stress exponent of the matrix, nM. The numerical results are used to quantify the conditions for which each deformation style occurs: (1) pure shear-dominated deformation occurs for μL/μM ~50 and HM/HL ~50, and HM/HL >~1; and (4) folding and overthrusting occur for a power-law viscous matrix and ~0.5< HM/HL

  16. Viscous overthrusting versus folding: 2-D quantitative modeling and its application to the Helvetic and Jura fold and thrust belts

    NASA Astrophysics Data System (ADS)

    Jaquet, Yoann; Bauville, Arthur; Schmalholz, Stefan M.

    2014-05-01

    This paper presents two-dimensional (2-D) numerical simulations of the shortening of a stiff viscous layer, with a pre-existing weak zone, that is embedded in a weaker viscous matrix. The model bottom remains straight during shortening and represents a detachment surface. Four deformation styles are observed that depend on the ratio of the layer and matrix viscosities, μL/μM; the thickness ratio of the bottom matrix and the overlying stiff layer, HM/HL; and the power-law stress exponent of the matrix, nM. The numerical results are used to quantify the conditions for which each deformation style occurs: (1) pure shear-dominated deformation occurs for μL/μM < ˜50 and nM = 1 (i.e., linear viscous); (2) overthrusting-dominated deformation occurs for a power-law viscous matrix (nM = 5), μL/μM > ˜50 and HM/HL < ˜0.5; (3) folding-dominated deformation occurs for nM = 1, μL/μM > ˜50, and HM/HL > ˜1; and (4) folding and overthrusting occur for a power-law viscous matrix and ˜0.5 < HM/HL < ˜2. The power-law stress exponent of the stiff layer has a minor effect on the deformation style. Simulations with layers that contain two weak zones show the formation of a nappe stack. The simulations also show that multi-layers can overthrust like a single layer. The change in deformation style as a function of HM/HL corroborates field observations from the Helvetic nappe system. The agreement of the numerical results with first-order observations from the Helvetic nappe system suggest that ductile deformation dominated this fold and thrust belt. The results further suggest that overthrusting on an effectively viscous weak layer only occurs if the rheology of the weak layer is power-law viscous.

  17. Geometry of the energy landscape and folding transition in a simple model of a protein.

    PubMed

    Mazzoni, Lorenzo N; Casetti, Lapo

    2008-05-01

    A geometric analysis of the global properties of the energy landscape of a minimalistic model of a polypeptide is presented, which is based on the relation between dynamical trajectories and geodesics of a suitable manifold, whose metric is completely determined by the potential energy. We consider different sequences, some with a definite proteinlike behavior, a unique native state and a folding transition, and others undergoing a hydrophobic collapse with no tendency to a unique native state. The global geometry of the energy landscape appears to contain relevant information on the behavior of the various sequences: in particular, the fluctuations of the curvature of the energy landscape, measured by means of numerical simulations, clearly mark the folding transition and allow the proteinlike sequences to be distinguished from the others.

  18. Laryngeal muscular control of vocal fold posturing: Numerical modeling and experimental validation

    PubMed Central

    Yin, Jun; Zhang, Zhaoyan

    2016-01-01

    A three-dimensional continuum model of vocal fold posturing was developed to investigate laryngeal muscular control of vocal fold geometry, stiffness, and tension, which are difficult to measure in live humans or in vivo models. This model was able to qualitatively reproduce in vivo experimental observations of laryngeal control of vocal fold posturing, despite the many simplifications which are necessary due to the lack of accurate data of laryngeal geometry and material properties. The results present a first comprehensive study of the co-variations between glottal width, vocal fold length, stiffness, tension at different conditions of individual, and combined laryngeal muscle activation. PMID:27914396

  19. Web-based toolkits for topology prediction of transmembrane helical proteins, fold recognition, structure and binding scoring, folding-kinetics analysis and comparative analysis of domain combinations.

    PubMed

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

    2005-07-01

    We have developed the following web servers for protein structural modeling and analysis at http://theory.med.buffalo.edu: THUMBUP, UMDHMM(TMHP) and TUPS, predictors of transmembrane helical protein topology based on a mean-burial-propensity scale of amino acid residues (THUMBUP), hidden Markov model (UMDHMM(TMHP)) and their combinations (TUPS); SPARKS 2.0 and SP3, two profile-profile alignment methods, that match input query sequence(s) to structural templates by integrating sequence profile with knowledge-based structural score (SPARKS 2.0) and structure-derived profile (SP3); DFIRE, a knowledge-based potential for scoring free energy of monomers (DMONOMER), loop conformations (DLOOP), mutant stability (DMUTANT) and binding affinity of protein-protein/peptide/DNA complexes (DCOMPLEX & DDNA); TCD, a program for protein-folding rate and transition-state analysis of small globular proteins; and DOGMA, a web-server that allows comparative analysis of domain combinations between plant and other 55 organisms. These servers provide tools for prediction and/or analysis of proteins on the secondary structure, tertiary structure and interaction levels, respectively.

  20. Right- and left-handed three-helix proteins. I. Experimental and simulation analysis of differences in folding and structure.

    PubMed

    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.

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

    PubMed

    Sidlof, Petr; Svec, Jan G; Horácek, Jaromír; Veselý, Jan; Klepácek, Ivo; Havlík, Radan

    2008-01-01

    Current models of the vocal folds derive their shape from approximate information rather than from exactly measured data. The objective of this study was to obtain detailed measurements on the geometry of human vocal folds and the glottal channel in phonatory position. A non-destructive casting methodology was developed to capture the vocal fold shape from excised human larynges on both medial and superior surfaces. Two female larynges, each in two different phonatory configurations corresponding to low and high fundamental frequency of the vocal fold vibrations, were measured. A coordinate measuring machine was used to digitize the casts yielding 3D computer models of the vocal fold shape. The coronal sections were located in the models, extracted and fitted by piecewise-defined cubic functions allowing a mathematical expression of the 2D shape of the glottal channel. Left-right differences between the cross-sectional shapes of the vocal folds were found in both the larynges.

  2. Modulation of folding energy landscape by charge–charge interactions: Linking experiments with computational modeling

    PubMed Central

    Tzul, Franco O.; Schweiker, Katrina L.; Makhatadze, George I.

    2015-01-01

    The kinetics of folding–unfolding of a structurally diverse set of four proteins optimized for thermodynamic stability by rational redesign of surface charge–charge interactions is characterized experimentally. The folding rates are faster for designed variants compared with their wild-type proteins, whereas the unfolding rates are largely unaffected. A simple structure-based computational model, which incorporates the Debye–Hückel formalism for the electrostatics, was used and found to qualitatively recapitulate the experimental results. Analysis of the energy landscapes of the designed versus wild-type proteins indicates the differences in refolding rates may be correlated with the degree of frustration of their respective energy landscapes. Our simulations indicate that naturally occurring wild-type proteins have frustrated folding landscapes due to the surface electrostatics. Optimization of the surface electrostatics seems to remove some of that frustration, leading to enhanced formation of native-like contacts in the transition-state ensembles (TSE) and providing a less frustrated energy landscape between the unfolded and TS ensembles. Macroscopically, this results in faster folding rates. Furthermore, analyses of pairwise distances and radii of gyration suggest that the less frustrated energy landscapes for optimized variants are a result of more compact unfolded and TS ensembles. These findings from our modeling demonstrates that this simple model may be used to: (i) gain a detailed understanding of charge–charge interactions and their effects on modulating the energy landscape of protein folding and (ii) qualitatively predict the kinetic behavior of protein surface electrostatic interactions. PMID:25564663

  3. Spatiotemporal analysis of vocal fold vibrations between children and adults

    PubMed Central

    Döllinger, Michael; Dubrovskiy, Denis; Patel, Rita

    2012-01-01

    Objectives/Hypothesis Aim of the study is to quantify differences in spatiotemporal features of vibratory motion in typically developing pre-pubertal children and adults with use of high speed digital imaging. Study Design Prospective case-control study. Methods Vocal fold oscillations of 31 children and 35 adults were analysed. Endoscopic high-speed imaging was performed during sustained phonation at typical pitch and loudness. Quantitative technique of Phonovibrogram was used to compute spatiotemporal features. Spatial features are represented by opening and closing angles along the anterior and posterior parts of the vocal folds, as well as by left-right symmetry ratio. Temporal features are represented by the cycle-to-cycle variability of the spatial features. Group differences (adult females, adult males, and children) were statistically investigated. Results Statistical differences were more pronounced in the temporal behavior compared to the spatial behavior. Children demonstrated greater cycle-to-cycle variability in oscillations compared to adults. Most differences between children and adults were found for temporal characteristics along the anterior parts during closing phase. The spatiotemporal features differed more between children and males than between children and females. Both adults and children showed equally high left-right symmetry. Conclusions Results suggest a more unstable phonation in children than in adults yielding increased perturbation in periodicity. Children demonstrated longer phase delay in the anterior/posterior and medio-lateral parts during the opening phase compared to adults. The data presented may provide the bases for differentiating normal vibratory characteristics from the disordered in the pediatric population and eventually assist in aiding the clinical utility of high speed imaging. PMID:22965771

  4. Constraints on bed scale fracture chronology with a FEM mechanical model of folding: The case of Split Mountain (Utah, USA)

    NASA Astrophysics Data System (ADS)

    Sassi, W.; Guiton, M. L. E.; Leroy, Y. M.; Daniel, J.-M.; Callot, J.-P.

    2012-11-01

    A technique is presented for improving the structural analysis of natural fractures development in large scale fold structures. A 3D restoration of a fold provides the external displacement loading conditions to solve, by the finite element method, the forward mechanical problem of an idealized rock material with a stress-strain relationship based on the activation of pervasive fracture sets. In this elasto-plasticity constitutive law, any activated fracture set contributes to the total plastic strain by either an opening or a sliding mode of rock failure. Inherited versus syn-folding fracture sets development can be studied using this mechanical model. The workflow of this methodology was applied to the Weber sandstone formation deformed by forced folding at Split Mountain Anticline, Utah for which the different fracture sets were created and developed successively during the Sevier and the syn-folding Laramide orogenic phases. The field observations at the top stratigraphic surface of the Weber sandstone lead to classify the fracture sets into a pre-fold WNW-ESE fracture set, and a NE-SW fracture set post-dating the former. The development and relative chronology of the fracture sets are discussed based on the geomechanical modeling results. Starting with a 3D restoration of the Split Mountain Anticline, three fold-fracture development models were generated, alternately assuming that the WNW-ESE fracture set is either present or absent prior to folding process. Depending on the initial fracture configuration, the calculated fracture patterns are markedly different, showing that assuming a WNW-ESE joint set to predate the fold best correlates with field observations. This study is a first step addressing the complex problem of identification of fold-related fracturing events using an elementary concept of rock mechanics. When tight to complementary field observations, including petrography, diagenesis and burial history, the approach can be used to better

  5. Geometric and kinematic modeling of detachment folds with growth strata based on Bézier curves

    NASA Astrophysics Data System (ADS)

    Liu, Chun; Zhang, Yikun; Shi, Bin

    2009-03-01

    In our geometric modeling, the inner layer of competent rock units in a detachment fold is approximated by several quadratic Bézier curves, which are joined together according to some geometrical rules, whereas the outer layers are calculated from the inner layer by parallel folding mechanism. In this model, an ideal fold is determined by three parameters: w, half of the distance between the locations of the fold's two limbs where their dips are measured, θ1 and θ2, the dip angles of its two limbs. Two more parameters, respectively the axial lift-up ratio ( u) and the limb elongation ( E) may be used to change the ideal fold shape, if necessary. In kinematic modeling, downward deflection in the two synclines flanking an anticline is assumed to maintain constant area during folding. Both mathematical derivation and numerical simulation show that the reduction of the balanced area ( Ar) is directly proportional to the downward deflection angle ( φ), and there is an approximate linear relationship between the detachment depth and the downward deflection angle. Based on this relationship, an iterative method is used to find the approximate value of φ. Furthermore, syn-folding growth strata can be modeled through calculating the velocity field above a detachment fold during folding. The method is applied to three seismic interpretation cross-sections of detachment folds respectively in Tarim Basin (western China), Zagros fold-belt (Iran) and Niger delta (western Africa). Variations of φ with the development of the detachment folds indicate the transfer of rock materials between the synclinal and anticlinal areas of the folds.

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

    PubMed

    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.

  7. Modelling of Folding Patterns in Flat Membranes and Cylinders by Origami

    NASA Astrophysics Data System (ADS)

    Nojima, Taketoshi

    This paper describes folding methods of thin flat sheets as well as cylindrical shells by modelling folding patterns through Japanese traditional Origami technique. New folding patterns have been devised in thin flat squared or circular membrane by modifying so called Miura-Ori in Japan (one node with 4 folding lines). Some folding patterns in cylindrical shells have newly been developed including spiral configurations. Devised foldable cylindrical shells were made by using polymer sheets, and it has been assured that they can be folded quite well. The devised models will make it possible to construct foldable/deployable space structures as well as to manufacture foldable industrial products and living goods, e. g., bottles for soft drinks.

  8. Comments on single-mass models of vocal fold vibration

    PubMed Central

    McGowan, Richard S.; Howe, Michael S.

    2010-01-01

    Proposed mechanisms for single-mass oscillation in the vocal tract are examined critically. There are two areas that distinguish single-mass models: in the sophistication of the air flow modeling near the oscillator and whether or not oscillation depends on acoustic feedback. Two recent models that do not depend on acoustic feedback are examined in detail. One model that depends on changing flow separation points is extended with approximate calculations. PMID:21117717

  9. Irregular vocal fold dynamics incited by asymmetric fluid loading in a model of recurrent laryngeal nerve paralysis

    NASA Astrophysics Data System (ADS)

    Sommer, David; Erath, Byron D.; Zanartu, Matias; Peterson, Sean D.

    2011-11-01

    Voiced speech is produced by dynamic fluid-structure interactions in the larynx. Traditionally, reduced order models of speech have relied upon simplified inviscid flow solvers to prescribe the fluid loadings that drive vocal fold motion, neglecting viscous flow effects that occur naturally in voiced speech. Viscous phenomena, such as skewing of the intraglottal jet, have the most pronounced effect on voiced speech in cases of vocal fold paralysis where one vocal fold loses some, or all, muscular control. The impact of asymmetric intraglottal flow in pathological speech is captured in a reduced order two-mass model of speech by coupling a boundary-layer estimation of the asymmetric pressures with asymmetric tissue parameters that are representative of recurrent laryngeal nerve paralysis. Nonlinear analysis identifies the emergence of irregular and chaotic vocal fold dynamics at values representative of pathological speech conditions.

  10. Modeling the Pathophysiology of Phonotraumatic Vocal Hyperfunction With a Triangular Glottal Model of the Vocal Folds.

    PubMed

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

    2017-09-18

    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. A numerical model with a triangular glottis, posterior glottal opening, and arytenoid posturing is proposed. Normal voice is altered by introducing various prephonatory configurations. Potential compensatory mechanisms (increased subglottal pressure, muscle activation, and supraglottal constriction) are adjusted to restore an acoustic target output through a control loop that mimics a simplified version of auditory feedback. The degree of incomplete glottal closure in both the membranous and posterior portions of the folds consistently leads to a reduction in sound pressure level, fundamental frequency, harmonic richness, and harmonics-to-noise ratio. The compensatory mechanisms lead to significantly increased vocal-fold collision forces, maximum flow-declination rate, and amplitude of unsteady flow, without significantly altering the acoustic output. Modeling provided potentially important insights into the pathophysiology of phonotraumatic vocal hyperfunction by demonstrating that compensatory mechanisms can counteract deterioration in the voice acoustic signal due to incomplete glottal closure, but this also leads to high vocal-fold collision forces (reflected in aerodynamic measures), which significantly increases the risk of developing phonotrauma.

  11. Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model

    SciTech Connect

    Agarwala, R.; Batzoglou, S.; Dancik, V.

    1997-06-01

    We consider the problem of determining the three-dimensional folding of a protein given its one-dimensional amino acid sequence. We use the HP model for protein folding proposed by Dill, which models protein as a chain of amino acid residues that are either hydrophobic or polar, and hydrophobic interactions are the dominant initial driving force for the protein folding. Hart and Istrail gave approximation algorithms for folding proteins on the cubic lattice under HP model. In this paper, we examine the choice of a lattice by considering its algorithmic and geometric implications and argue that triangular lattice is a more reasonable choice. We present a set of folding rules for a triangular lattice and analyze the approximation ratio which they achieve. In addition, we introduce a generalization of the HP model to account for residues having different levels of hydrophobicity. After describing the biological foundation for this generalization, we show that in the new model we are able to achieve similar constant factor approximation guarantees on the triangular lattice as were achieved in the standard HP model. While the structures derived from our folding rules are probably still far from biological reality, we hope that having a set of folding rules with different properties will yield more interesting folds when combined.

  12. A rapid Bézier curve method for shape analysis and point representation of asymmetric folds

    NASA Astrophysics Data System (ADS)

    Srivastava, Deepak C.; Rastogi, Vipul; Ghosh, Rajit

    2010-05-01

    Point representation of fold shapes is useful, in particular, for classification of a large number of folds into different geometric populations. The methods for shape analysis and point representation of asymmetric folds are a few and tedious, although several methods exist for the analysis of the individual fold limbs, or symmetric folds. This article gives a rapid method that uses the Bézier curve tool, available in any common computer graphics software, for the analysis of a complete asymmetric fold and its point representation in the two-dimensional frame. The new method is based on the reduction of variables in the parametric equations of a cubic Bézier curve. It makes the length of one Bézier handle zero, pins the end point of the other Bézier handle at the origin of the X- Y frame and drags its control point along the Y-axis to fit the Bézier curve on the given asymmetric fold. A Cartesian plot between normalised length of the Bézier handle and the lift, i.e., difference between the heights of the two inflection points, gives the unique point that represents the given asymmetric fold shape. We test the validity of the new method on several computer simulated asymmetric folds and demonstrate its usefulness with the help of a natural example.

  13. Folding model analysis of 240 MeV {sup 6}Li elastic scattering on {sup 116}Sn and inelastic scattering to low-lying states of {sup 116}Sn

    SciTech Connect

    Chen, X.; Lui, Y.-W.; Clark, H. L.; Tokimoto, Y.; Youngblood, D. H.

    2007-11-15

    Elastic scattering of 240 MeV {sup 6}Li ions from {sup 116}Sn was measured from 4 deg.{<=}{theta}{sub c.m.}{<=}32 deg. The data were fitted with a Woods-Saxon phenomenological potential and with double folding models using the M3Y NN effective interaction with and without density dependence. DWBA calculations with the fitted parameters were used to calculate cross sections for inelastic scattering to low-lying 2{sup +}and 3{sup -} states. B(E2) and B(E3) values were extracted and compared with electromagnetic values and those obtained from {alpha} inelastic scattering.

  14. Information from folds: A review

    NASA Astrophysics Data System (ADS)

    Hudleston, Peter J.; Treagus, Susan H.

    2010-12-01

    Folds are spectacular geological structures that are seen in layered rock on many different scales. To mark 30 years of the Journal of Structural Geology, we review the information that can be gained from studies of folds in theory, experiment and nature. We first review theoretical considerations and modeling, from classical approaches to current developments. The subject is dominated by single-layer fold theory, with the assumption of perfect layer-parallel shortening, but we also review multilayer fold theory and modeling, and folding of layers that are oblique to principal stresses and strains. This work demonstrates that viscosity ratio, degree of non-linearity of the flow law, anisotropy, and the thickness and spacing distribution of layers of different competence are all important in determining the nature and strength of the folding instability. Theory and modeling provide the basis for obtaining rheological information from natural folds, through analysis of wavelength/thickness ratios of single layer folds, and fold shapes. They also provide a basis for estimating the bulk strain from folded layers. Information about folding mechanisms can be obtained by analysis of cleavage and fabric patterns in folded rocks, and the history of deformation can be revealed by understanding how asymmetry can develop in folds, by how folds develop in shear zones, and how folds develop in more complex three-dimensional deformations.

  15. Local versus global fold switching in protein evolution: insight from a three-letter continuous model

    NASA Astrophysics Data System (ADS)

    Holzgräfe, Christian; Wallin, Stefan

    2015-04-01

    Recent design experiments have demonstrated that some proteins can switch their folds in response to a small number of point mutations either directly, in a single mutational step, or via intermediate bistable sequences, which populate two different folds simultaneously. Here we explore the hypothesis that bistable intermediates are more common in switches between structurally similar folds while direct switches are more common between dissimilar folds. To this end, we use a reduced model with seven atoms per amino acid and three amino acid types as a biophysical basis for protein folding and stability. We compare a set of mutational pathways, selected for optimal stability properties, that lead to switches between β-hairpin and α-helix folds with 16 amino acids and between α +2β and 2α folds with 35 amino acids, respectively. Fold switching in each case is sharp, taking only a few mutations to be completed. While the sharpness of mutationally driven protein fold switching can be traced to a shift in the energy balance of the two native states, conformational entropy contributes to determining the point at which fold switching occurs along a pathway.

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

    PubMed Central

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

    PubMed

    Zhang, Zhaoyan

    2014-03-01

    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.

  18. Insights from Coarse-Grained Gō Models for Protein Folding and Dynamics

    PubMed Central

    Hills, Ronald D.; Brooks, Charles L.

    2009-01-01

    Exploring the landscape of large scale conformational changes such as protein folding at atomistic detail poses a considerable computational challenge. Coarse-grained representations of the peptide chain have therefore been developed and over the last decade have proved extremely valuable. These include topology-based Gō models, which constitute a smooth and funnel-like approximation to the folding landscape. We review the many variations of the Gō model that have been employed to yield insight into folding mechanisms. Their success has been interpreted as a consequence of the dominant role of the native topology in folding. The role of local contact density in determining protein dynamics is also discussed and is used to explain the ability of Gō-like models to capture sequence effects in folding and elucidate conformational transitions. PMID:19399227

  19. Folding and stability of helical bundle proteins from coarse-grained models.

    PubMed

    Kapoor, Abhijeet; Travesset, Alex

    2013-07-01

    We develop a coarse-grained model where solvent is considered implicitly, electrostatics are included as short-range interactions, and side-chains are coarse-grained to a single bead. The model depends on three main parameters: hydrophobic, electrostatic, and side-chain hydrogen bond strength. The parameters are determined by considering three level of approximations and characterizing the folding for three selected proteins (training set). Nine additional proteins (containing up to 126 residues) as well as mutated versions (test set) are folded with the given parameters. In all folding simulations, the initial state is a random coil configuration. Besides the native state, some proteins fold into an additional state differing in the topology (structure of the helical bundle). We discuss the stability of the native states, and compare the dynamics of our model to all atom molecular dynamics simulations as well as some general properties on the interactions governing folding dynamics. Copyright © 2013 Wiley Periodicals, Inc.

  20. Folding in a semi-flexible lattice model for Crambin

    NASA Astrophysics Data System (ADS)

    Shi, Guangjie; Farris, Alfred C. K.; Wüst, Thomas; Landau, David P.

    2016-01-01

    Using the Replica-Exchange Wang-Landau sampling method, we investigated and compared three different coarse-grained lattice protein models for the small, hydrophobic protein Crambin. We show that slight extensions of the HP lattice protein model, including the stiffness of bonds can lead to a significant decrease in ground-state degeneracies (up to 5 orders of magnitudes). Moreover, the ground-state structures begin to bear resemblance to native structures observed in real Crambin.

  1. Mathematics, Thermodynamics, and Modeling to Address Ten Common Misconceptions about Protein Structure, Folding, and Stability

    ERIC Educational Resources Information Center

    Robic, Srebrenka

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative…

  2. Mathematics, Thermodynamics, and Modeling to Address Ten Common Misconceptions about Protein Structure, Folding, and Stability

    ERIC Educational Resources Information Center

    Robic, Srebrenka

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative…

  3. Fuzzy-oil-drop hydrophobic force field--a model to represent late-stage folding (in silico) of lysozyme.

    PubMed

    Brylinski, Michal; Konieczny, Leszek; Roterman, Irena

    2006-04-01

    A model of hydrophobic collapse (in silico), which is generally considered to be the driving force for protein folding, is presented in this work. The model introduces the external field in the form of a fuzzy-oil-drop assumed to represent the environment. The drop is expressed in the form of a three-dimensional Gauss function. The usual probability value is assumed to represent the hydrophobicity distribution in the three-dimensional space of the virtual environment. The differences between this idealized hydrophobicity distribution and the one represented by the folded polypeptide chain is the parameter to be minimized in the structure optimization procedure. The size of fuzzy-oil-drop is critical for the folding process. A strong correlation between protein length and the dimension of the native and early-stage molecular form was found on the basis of single-domain proteins analysis. A previously presented early-stage folding (in silico) model was used to create the starting structure for the procedure of late-stage folding of lysozyme. The results of simulation were found to be promising, although additional improvements for the formation of beta-structure and disulfide bonds as well as the participation of natural ligand in folding process seem to be necessary.

  4. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

    PubMed Central

    Yue, Yongping; Wasala, Nalinda B; Bostick, Brian; Duan, Dongsheng

    2016-01-01

    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. PMID:27419194

  5. Influence of numerical model decisions on the flow-induced vibration of a computational vocal fold model

    PubMed Central

    Shurtz, Timothy E.; Thomson, Scott L.

    2012-01-01

    Computational vocal fold models are often used to study the physics of voice production. In this paper the sensitivity of predicted vocal fold flow-induced vibration and resulting airflow patterns to several modeling selections is explored. The location of contact lines used to prevent mesh collapse and assumptions of symmetry were found to influence airflow patterns. However, these variables had relatively little effect on the vibratory response of the vocal fold model itself. Model motion was very sensitive to Poisson’s ratio. The importance of these parameter sensitivities in the context of vocal fold modeling is discussed. PMID:23794762

  6. Using Kinetic Network Models To Probe Non-Native Salt-Bridge Effects on α-Helix Folding.

    PubMed

    Zhou, Guangfeng; Voelz, Vincent A

    2016-02-11

    Salt-bridge interactions play an important role in stabilizing many protein structures, and have been shown to be designable features for protein design. In this work, we study the effects of non-native salt bridges on the folding of a soluble alanine-based peptide (Fs peptide) using extensive all-atom molecular dynamics simulations performed on the Folding@home distributed computing platform. Using Markov State Models, we show how non-native salt-bridges affect the folding kinetics of Fs peptide by perturbing specific conformational states. Furthermore, we present methods for the automatic detection and analysis of such states. These results provide insight into helix folding mechanisms and useful information to guide simulation-based computational protein design.

  7. Stable structure-approximating inverse protein folding in 2D hydrophobic-polar-cysteine (HPC) model.

    PubMed

    Khodabakhshi, Alireza Hadj; Manuch, Ján; Rafiey, Arash; Gupta, Arvind

    2009-01-01

    The inverse protein folding problem is that of designing an amino acid sequence which folds into a prescribed conformation/structure. This problem arises in drug design where a particular structure is necessary to ensure proper protein-protein interactions. Gupta et al. (2005) introduced a design in the two-dimensional (2D) hydrophobic-polar (HP) model of Dill that can be used to approximate any given (2D) shape. They conjectured that the protein sequences of their design are stable but only proved the stability for an infinite class of very basic structures. We introduce a refinement of the HP model, in which the cysteine and non-cysteine hydrophobic monomers are distinguished and SS-bridges, which two cysteines can form, are taken into account in the energy function. We call this model the HPC model. We consider a subclass of linear structures designed in Gupta et al. (2005) which is rich enough to approximate (although more coarsely) any given structure. We refine these structures for the HPC model by setting approximately a half of H amino acids to cysteine ones and call them snake structures. We first prove that the proteins of the snake structures are stable under the strong HPC model in which we make an additional assumption that non-cysteine amino acids act as cysteine ones, i.e., they can form their own bridges to reduce the energy. Then we consider a subclass of snake structures called wave structures that can still approximate any given shape and prove that their proteins are stable under the proper HPC model. This partially confirms the conjecture stated in Gupta et al. (2005). To prove the above results we developed a computational tool, called 2DHPSolver, which we used to perform large case analysis required for the proofs. We conjecture that the proteins of snake structures are stable under the proper HPC model.

  8. Glottal jet measurements in synthetic, MRI-based human vocal fold models

    NASA Astrophysics Data System (ADS)

    Thomson, Scott; Pickup, Brian; Gollnick, Paul

    2007-11-01

    Human vocal fold vibration generates a time-varying elliptically-shaped glottal jet that produces sound in speech. Improved understanding of glottal jet dynamics can yield insight into voice production mechanisms and improve the diagnosis and treatment of voice disorders. Experiments using recently developed life-sized synthetic models of the vocal folds are presented. The fabrication process of converting MRI images to synthetic models is described. The process allows for varying the Young's modulus of the models, allowing for asymmetric conditions to be created by casting opposing vocal folds using materials of different stiffness. The models are shown to oscillate at frequencies, pressures, and flow rates typical of human speech. Phase-locked particle image velocimetry (PIV) results are presented which characterize the glottal jet, including jet direction, vortical structures, and turbulence levels. Results are shown for symmetric and asymmetric vocal fold models. The degree of material asymmetry required to cause significant asymmetry in the glottal jet is reported.

  9. Acoustically-coupled flow-induced vibration of a computational vocal fold model.

    PubMed

    Daily, David Jesse; Thomson, Scott L

    2013-01-15

    The flow-induced vibration of synthetic vocal fold models has been previously observed to be acoustically-coupled with upstream flow supply tubes. This phenomenon was investigated using a finite element model that included flow-structure-acoustic interactions. The length of the upstream duct was varied to explore the coupling between model vibration and subglottal acoustics. Incompressible and slightly compressible flow models were tested. The slightly compressible model exhibited acoustic coupling between fluid and solid domains in a manner consistent with experimental observations, whereas the incompressible model did not, showing the slightly compressible approach to be suitable for simulating acoustically-coupled vocal fold model flow-induced vibration.

  10. Acoustically-coupled flow-induced vibration of a computational vocal fold model

    PubMed Central

    Daily, David Jesse; Thomson, Scott L.

    2012-01-01

    The flow-induced vibration of synthetic vocal fold models has been previously observed to be acoustically-coupled with upstream flow supply tubes. This phenomenon was investigated using a finite element model that included flow–structure–acoustic interactions. The length of the upstream duct was varied to explore the coupling between model vibration and subglottal acoustics. Incompressible and slightly compressible flow models were tested. The slightly compressible model exhibited acoustic coupling between fluid and solid domains in a manner consistent with experimental observations, whereas the incompressible model did not, showing the slightly compressible approach to be suitable for simulating acoustically-coupled vocal fold model flow-induced vibration. PMID:23585700

  11. Folding style controlled by intermediate decollement thickness change in the Lurestan region (NW of the Zagros fold-and-thrust belt), using analogue models

    NASA Astrophysics Data System (ADS)

    Farzipour Saein, Ali

    2017-07-01

    The basal and intermediate decollements play an important role in structural style of fold-and-thrust belts. The decollement units, or different mechanical stratigraphy within the rock units, are not uniform throughout the ZFTB and show a strong spatial variation. The Lurestan region with varied thickness of the intermediate decollement in its northern and southern parts is one of the most important parts of the Zagros fold-and-thrust belt, regarding its hydrocarbon exploration-extraction projects. Thickness variation of the intermediate decollement in different parts of the Lurestan region allows us to address its role on folding style. Based on scaled analogue modeling, this study outlines the impact of thickness and facies variation of sedimentary rocks in the northern and southern parts of this region on folding style. Two models simulated the mechanical stratigraphy and its consequent different folding styles of the northern and southern parts of the region. In the models, only thickness of the intermediate decollement (thick and thin) for the northern and southern parts of the Lurestan region was varied. Detached minor folds above the intermediate decollement were created in response to the presence of the thicker intermediate decollement, northern part of the study area, which consequently deformed complexly and disharmonically folded, in contrast to polyharmonic folding style in the section, compared to polyharmonic folding style in the southern part, where thin intermediate decollement exists. The model results documented that thickness variation of intermediate decollement levels could explain complex and different folding styles in natural examples which must be taken into account for hydrocarbon exploration throughout these areas.

  12. Folding style controlled by intermediate decollement thickness change in the Lurestan region (NW of the Zagros fold-and-thrust belt), using analogue models

    NASA Astrophysics Data System (ADS)

    Farzipour Saein, Ali

    2016-07-01

    The basal and intermediate decollements play an important role in structural style of fold-and-thrust belts. The decollement units, or different mechanical stratigraphy within the rock units, are not uniform throughout the ZFTB and show a strong spatial variation. The Lurestan region with varied thickness of the intermediate decollement in its northern and southern parts is one of the most important parts of the Zagros fold-and-thrust belt, regarding its hydrocarbon exploration-extraction projects. Thickness variation of the intermediate decollement in different parts of the Lurestan region allows us to address its role on folding style. Based on scaled analogue modeling, this study outlines the impact of thickness and facies variation of sedimentary rocks in the northern and southern parts of this region on folding style. Two models simulated the mechanical stratigraphy and its consequent different folding styles of the northern and southern parts of the region. In the models, only thickness of the intermediate decollement (thick and thin) for the northern and southern parts of the Lurestan region was varied. Detached minor folds above the intermediate decollement were created in response to the presence of the thicker intermediate decollement, northern part of the study area, which consequently deformed complexly and disharmonically folded, in contrast to polyharmonic folding style in the section, compared to polyharmonic folding style in the southern part, where thin intermediate decollement exists. The model results documented that thickness variation of intermediate decollement levels could explain complex and different folding styles in natural examples which must be taken into account for hydrocarbon exploration throughout these areas.

  13. Modelling proteins: conformational sampling and reconstruction of folding kinetics.

    PubMed

    Klenin, Konstantin; Strodel, Birgit; Wales, David J; Wenzel, Wolfgang

    2011-08-01

    In the last decades biomolecular simulation has made tremendous inroads to help elucidate biomolecular processes in-silico. Despite enormous advances in molecular dynamics techniques and the available computational power, many problems involve long time scales and large-scale molecular rearrangements that are still difficult to sample adequately. In this review we therefore summarise recent efforts to fundamentally improve this situation by decoupling the sampling of the energy landscape from the description of the kinetics of the process. Recent years have seen the emergence of many advanced sampling techniques, which permit efficient characterisation of the relevant family of molecular conformations by dispensing with the details of the short-term kinetics of the process. Because these methods generate thermodynamic information at best, they must be complemented by techniques to reconstruct the kinetics of the process using the ensemble of relevant conformations. Here we review recent advances for both types of methods and discuss their perspectives to permit efficient and accurate modelling of large-scale conformational changes in biomolecules. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. 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.

    PubMed

    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/.

  15. Analysis of Rectangular Folded-Waveguide Millimeter-Wave Slow-wave Structures using Conformal Transformations

    NASA Astrophysics Data System (ADS)

    Sumathy, M.; Vinoy, K. J.; Datta, S. K.

    2009-03-01

    An analysis of rectangular folded-waveguide slow-wave structure was developed using conformal mapping technique through Schwarz’s polygon transformation and closed form expressions for the lumped capacitance and inductance per period of the slow-wave structure were derived in terms of the physical dimensions of the structure, incorporating the effects of the beam hole in the lumped parameters. The lumped parameters were subsequently interpreted for obtaining the dispersion and interaction impedance characteristics of the structure. The analysis was benchmarked for two typical millimeter-wave structures, one operating in Ka-band and the other operating in Q-band, against measurement and 3D electromagnetic modeling using MAFIA.

  16. Lattice and off-lattice side chain models of protein folding: linear time structure prediction better than 86% of optimal.

    PubMed

    Hart, W E; Istrail, S

    1997-01-01

    This paper considers the protein energy minimization problem for lattice and off-lattice protein folding models that explicitly represent side chains. Lattice models of proteins have proven useful tools for reasoning about protein folding in unrestricted continuous space through analogy. This paper provides the first illustration of how rigorous algorithmic analyses of lattice models can lead to rigorous algorithmic analyses of off-lattice models. We consider two side chain models: a lattice model that generalizes the HP model (Dill, 1985) to explicitly represent side chains on the cubic lattice and a new off-lattice model, the HP Tangent Spheres Side Chain model (HP-TSSC), that generalizes this model further by representing the backbone and side chains of proteins with tangent spheres. We describe algorithms with mathematically guaranteed error bounds for both of these models. In particular, we describe a linear time performance guaranteed approximation algorithm for the HP side chain model that constructs conformations whose energy is better than 86% of optimal in a face-centered cubic lattice, and we demonstrate how this provides a better than 70% performance guarantee for the HP-TSSC model. Our analysis provides a mathematical methodology for transferring performance guarantees on lattices to off-lattice models. These results partially answer the open question of Ngo et al. (1994) concerning the complexity of protein folding models that include side chains.

  17. Equilibrium folding and stability of myotrophin: a model ankyrin repeat protein.

    PubMed

    Mosavi, Leila K; Williams, Suzanna; Peng Zy, Zheng-yu

    2002-07-05

    Proteins containing stretches of repeating amino acid sequences are prevalent throughout nature, yet little is known about the general folding and assembly mechanisms of these systems. Here we propose myotrophin as a model system to study the folding of ankyrin repeat proteins. Myotrophin is folded over a large pH range and is soluble at high concentrations. Thermal and urea denaturation studies show that the protein displays cooperative two-state folding properties despite its modular nature. Taken together with previous studies on other ankyrin repeat proteins, our data suggest that the two-state folding pathway may be characteristic of ankyrin repeat proteins and other integrated alpha-helical repeat proteins in general.

  18. Influence of vocal fold stiffness and acoustic loading on flow-induced vibration of a single-layer vocal fold model

    PubMed Central

    Zhang, Zhaoyan; Neubauer, Juergen; Berry, David A.

    2009-01-01

    The flow-induced vibrations of a single-layer vocal fold model were investigated as a function of vocal fold stiffness, and subglottal and supraglottal acoustic loading. Previously, it was reported that the single-layer vocal fold model failed to vibrate when short, clinically-relevant tracheal tubes were used. Moreover, it was reported that the model had a propensity to be acoustically driven, and aerodynamically driven vibration was observed only when a vertical restraint was applied superiorly to the vocal folds. However, in this study involving a wider range of source/tract conditions, the previous conclusions were shown to apply only for the special case of a stiff vocal fold model, for which self-oscillation occurred only when the vocal fold vibration synchronized to either a subglottal or supraglottal resonance. For a more general case, when vocal fold stiffness was decreased, the model did exhibit self-oscillation at short tracheal tubes, and no vertical restraint was needed to induce aerodynamically driven phonation. Nevertheless, the vocal fold vibration transitioned from aerodynamically-driven to acoustically-driven vibration when one of the subglottal resonance frequencies approximated one of the natural frequencies of the vocal folds. In this region, strong superior-inferior vibrations were observed, the phonation threshold pressure was significantly reduced, and the phonation onset frequency was heavily influenced by the dominant acoustic resonance. For acoustically-driven phonation, a compliant subglottal system always lowered phonation threshold. However, an inertive vocal tract could either increase or decrease phonation threshold pressure, depending on the phonation frequency. PMID:20161071

  19. Influence of vocal fold stiffness and acoustic loading on flow-induced vibration of a single-layer vocal fold model.

    PubMed

    Zhang, Zhaoyan; Neubauer, Juergen; Berry, David A

    2009-04-24

    The flow-induced vibrations of a single-layer vocal fold model were investigated as a function of vocal fold stiffness, and subglottal and supraglottal acoustic loading. Previously, it was reported that the single-layer vocal fold model failed to vibrate when short, clinically-relevant tracheal tubes were used. Moreover, it was reported that the model had a propensity to be acoustically driven, and aerodynamically driven vibration was observed only when a vertical restraint was applied superiorly to the vocal folds. However, in this study involving a wider range of source/tract conditions, the previous conclusions were shown to apply only for the special case of a stiff vocal fold model, for which self-oscillation occurred only when the vocal fold vibration synchronized to either a subglottal or supraglottal resonance. For a more general case, when vocal fold stiffness was decreased, the model did exhibit self-oscillation at short tracheal tubes, and no vertical restraint was needed to induce aerodynamically driven phonation. Nevertheless, the vocal fold vibration transitioned from aerodynamically-driven to acoustically-driven vibration when one of the subglottal resonance frequencies approximated one of the natural frequencies of the vocal folds. In this region, strong superior-inferior vibrations were observed, the phonation threshold pressure was significantly reduced, and the phonation onset frequency was heavily influenced by the dominant acoustic resonance. For acoustically-driven phonation, a compliant subglottal system always lowered phonation threshold. However, an inertive vocal tract could either increase or decrease phonation threshold pressure, depending on the phonation frequency.

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

    PubMed

    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.

  1. Flow fields and acoustics in a unilateral scarred vocal fold model.

    PubMed

    Murugappan, Shanmugam; Khosla, Sid; Casper, Keith; Oren, Liran; Gutmark, Ephraim

    2009-01-01

    From prior work in an excised canine larynx model, it has been shown that intraglottal vortices form between the vocal folds during the latter part of closing. It has also been shown that the vortices generate a negative pressure between the folds, producing a suction force that causes sudden, rapid closing of the folds. This rapid closing will produce increased loudness and increased higher harmonics. We used a unilateral scarred excised canine larynx model to determine whether the intraglottal vortices and resulting acoustics were changed, compared to those of normal larynges. Acoustic, flow field, and high-speed imaging measurements from 5 normal and 5 unilaterally scarred canine larynges are presented in this report. Scarring was produced by complete resection of the vocal fold mucosa and superficial layer of the lamina propria on the right vocal fold only. Two months later, these dogs were painlessly sacrificed, and testing was done on the excised larynges during phonation. High-speed video imaging was then used to measure vocal fold displacement during different phases. Particle image velocimetry and acoustic measurements were used to describe possible acoustic effects of the vortices. A higher phonation threshold was required to excite the motion of the vocal fold in scarred larynges. As the subglottal pressure increased, the strength of the vortices and the higher harmonics both consistently increased. However, it was seen that increasing the maximum displacement of the scarred fold did not consistently increase the higher harmonics. The improvements that result from increasing subglottal pressure may be due to a combination of increasing the strength of the intraglottal vortices and increasing the maximum displacement of the vocal fold; however, the data in this study suggest that the vortices play a much more important role. The current study indicates that higher subglottal pressures may excite higher harmonics and improve loudness for patients with

  2. Efficient traversal of beta-sheet protein folding pathways using ensemble models.

    PubMed

    Shenker, Solomon; O'Donnell, Charles W; Devadas, Srinivas; Berger, Bonnie; Waldispühl, Jérôme

    2011-11-01

    Molecular dynamics (MD) simulations can now predict ms-timescale folding processes of small proteins; however, this presently requires hundreds of thousands of CPU hours and is primarily applicable to short peptides with few long-range interactions. Larger and slower-folding proteins, such as many with extended β-sheet structure, would require orders of magnitude more time and computing resources. Furthermore, when the objective is to determine only which folding events are necessary and limiting, atomistic detail MD simulations can prove unnecessary. Here, we introduce the program tFolder as an efficient method for modelling the folding process of large β-sheet proteins using sequence data alone. To do so, we extend existing ensemble β-sheet prediction techniques, which permitted only a fixed anti-parallel β-barrel shape, with a method that predicts arbitrary β-strand/β-strand orientations and strand-order permutations. By accounting for all partial and final structural states, we can then model the transition from random coil to native state as a Markov process, using a master equation to simulate population dynamics of folding over time. Thus, all putative folding pathways can be energetically scored, including which transitions present the greatest barriers. Since correct folding pathway prediction is likely determined by the accuracy of contact prediction, we demonstrate the accuracy of tFolder to be comparable with state-of-the-art methods designed specifically for the contact prediction problem alone. We validate our method for dynamics prediction by applying it to the folding pathway of the well-studied Protein G. With relatively very little computation time, tFolder is able to reveal critical features of the folding pathways which were only previously observed through time-consuming MD simulations and experimental studies. Such a result greatly expands the number of proteins whose folding pathways can be studied, while the algorithmic integration of

  3. Protein folding dynamics: the diffusion-collision model and experimental data.

    PubMed Central

    Karplus, M.; Weaver, D. L.

    1994-01-01

    The diffusion-collision model of protein folding is assessed. A description is given of the qualitative aspects and quantitative results of the diffusion-collision model and their relation to available experimental data. We consider alternative mechanisms for folding and point out their relationship to the diffusion-collision model. We show that the diffusion-collision model is supported by a growing body of experimental and theoretical evidence, and we outline future directions for developing the model and its applications. PMID:8003983

  4. Transtensional folding

    NASA Astrophysics Data System (ADS)

    Fossen, Haakon; Teyssier, Christian; Whitney, Donna L.

    2014-05-01

    For now three decades transpression has dominated the concepts that underlie oblique tectonics, but in more recent years transtension has garnered much interest as a simple model that can be applied to shallow and deep crustal tectonics. One fundamental aspect that distinguishes transtension from transpression is that material lines in transtension rotate toward the direction of oblique divergence. Another point that may be less intuitive when thinking of transtension is that while transtensional strain involves shortening in the vertical direction, one of the horizontal axes is also a shortening axis, whatever the angle of divergence. It is the combination of these two shortening axes that leads to constrictional finite strain in transtension. The existence of a horizontal shortening strain axis implies that transtension offers the potential for folds of horizontal layers to form and then rotate toward the direction of oblique divergence. An investigation of transtensional folding using 3D strain modeling reveals that folding is more likely for simple shear dominated transtension (large wrench component). Transtensional folds can only accumulate a fixed amount of horizontal shortening and tightness that are prescribed by the angle of oblique divergence, regardless of finite strain. Transtensional folds are characterized by hinge-parallel stretching that exceeds that expected from pure wrenching. In addition, the magnitude of hinge-parallel stretching always exceeds hinge-perpendicular shortening, causing constrictional fabrics and hinge-parallel boudinage to develop. Because the dominant vertical strain axis is shortening, transtensional fold growth is generally suppressed, but when folds do develop their limbs enter the field of shortening, resulting in possible fold interference patterns akin to cascading folds. Application of these transtensional folding principles to regions of oblique rifting (i.e. Gulf of California) or exhumation of deep crust (i.e. Western

  5. Pipette aspiration applied to the characterization of nonhomogeneous, transversely isotropic materials used for vocal fold modeling

    PubMed Central

    Weiβ, S.; Thomson, S.L.; Lerch, R.; Döllinger, M.; Sutor, A.

    2012-01-01

    The etiology and treatment of voice disorders are still not completely understood. Since the vibratory characteristics of vocal folds are strongly influenced by both anatomy and mechanical material properties, measurement methods to analyze the material behavior of vocal fold tissue are required. Due to the limited life time of real tissue in the laboratory, synthetic models are often used to study vocal fold vibrations. In this paper we focus on two topics related to synthetic and real vocal fold materials. First, because certain tissues within the human vocal folds are transversely isotropic, a fabrication process for introducing this characteristic in commonly-used vocal fold modeling materials is presented. Second, the pipette aspiration technique is applied to the characterization of these materials. By measuring the displacement profiles of stretched specimens that exhibit varying degrees of transverse isotropy, it is shown that local anisotropy can be quantified using a parameter describing the deviation from an axisymmetric profile. The potential for this technique to characterize homogeneous, anisotropic materials, including soft biological tissues such as those found in the human vocal folds, is supplemented by a computational study. PMID:23127628

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

    USGS Publications Warehouse

    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.

  7. Biomechanical modeling of the three-dimensional aspects of human vocal fold dynamics

    PubMed Central

    Yang, Anxiong; Lohscheller, Jörg; Berry, David A.; Becker, Stefan; Eysholdt, Ulrich; Voigt, Daniel; Döllinger, Michael

    2010-01-01

    Human voice originates from the three-dimensional (3D) oscillations of the vocal folds. In previous studies, biomechanical properties of vocal fold tissues have been predicted by optimizing the parameters of simple two-mass-models to fit its dynamics to the high-speed imaging data from the clinic. However, only lateral and longitudinal displacements of the vocal folds were considered. To extend previous studies, a 3D mass-spring, cover-model is developed, which predicts the 3D vibrations of the entire medial surface of the vocal fold. The model consists of five mass planes arranged in vertical direction. Each plane contains five longitudinal, mass-spring, coupled oscillators. Feasibility of the model is assessed using a large body of dynamical data previously obtained from excised human larynx experiments, in vivo canine larynx experiments, physical models, and numerical models. Typical model output was found to be similar to existing findings. The resulting model enables visualization of the 3D dynamics of the human vocal folds during phonation for both symmetric and asymmetric vibrations. PMID:20136223

  8. 2-D modelling of the anticlinal structures and structural development of the eastern fold belt of the Bengal Basin, Bangladesh

    NASA Astrophysics Data System (ADS)

    Sikder, Arif Mohiuddin; Alam, M. Mustafa

    2003-02-01

    Structural architecture of the Bengal Basin has been strongly controlled by the collision pattern of the Indian plate with the Burma and Tibetan plates. The eastern fold belt (EFB) of the basin, comprising a series of north-south-trending curvilinear anticlines and synclines, represents a fold-and-thrust belt that constitutes the westward continuation of Arakan-Chin fold system of the Indo-Burman Ranges. The present study is mainly concerned with the 2-D modelling of the anticlinal structures in order to develop an understanding about the process-response relationships between the structural style and tectonic evolution of the eastern fold belt. The dominant fold-generating mechanism is believed to be the east-west-directed compressional force arising from oblique subduction of the Indian plate beneath the Burma plate that resulted in the growth of fault-propagation folds above a detachment or decollement at depth, giving rise to the Neogene accretionary prism complex development. A prominent feature of the region is the major east-dipping thrusts separating successive accretionary wedges. In seismic sections, evidence for several phases of compressional deformation suggests that multiphase stress conditions were responsible for the structural expression of the fold belt. Deep seismic sections reveal that the base of folding is characterized by a low-interval velocity horizon that represents a detachment separating the upper folded zone from the lower, seismically coherent, nearly unfolded zone. This detachment coincides with the undercompacted pressured shale unit, which is thought to have played an important role in the structural development of the eastern fold belt. Clay mineralogical analysis reveals the presence of a low-density shale horizon within the dense and thick shale sequence that is thought to be an undercompacted pressured shale during the geological past, and was responsible for the initiation of decollement and incipient diapirism involving thin

  9. Information-Theoretic Uncertainty of SCFG-Modeled Folding Space of The Non-coding RNA

    PubMed Central

    Manzourolajdad, Amirhossein; Wang, Yingfeng; Shaw, Timothy I.; Malmberg, Russell L.

    2012-01-01

    RNA secondary structure ensembles define probability distributions for alternative equilibrium secondary structures of an RNA sequence. Shannon’s Entropy is a measure for the amount of diversity present in any ensemble. In this work, Shannon’s entropy of the SCFG ensemble on an RNA sequence is derived and implemented in polynomial time for both structurally ambiguous and unambiguous grammars. Micro RNA sequences generally have low folding entropy, as previously discovered. Surprisingly, signs of significantly high folding entropy were observed in certain ncRNA families. More effective models coupled with targeted randomization tests can lead to a better insight into folding features of these families. PMID:23160142

  10. Estimating the probability for a protein to have a new fold: A statistical computational model

    PubMed Central

    Portugaly, Elon; Linial, Michal

    2000-01-01

    Structural genomics aims to solve a large number of protein structures that represent the protein space. Currently an exhaustive solution for all structures seems prohibitively expensive, so the challenge is to define a relatively small set of proteins with new, currently unknown folds. This paper presents a method that assigns each protein with a probability of having an unsolved fold. The method makes extensive use of protomap, a sequence-based classification, and scop, a structure-based classification. According to protomap, the protein space encodes the relationship among proteins as a graph whose vertices correspond to 13,354 clusters of proteins. A representative fold for a cluster with at least one solved protein is determined after superposition of all scop (release 1.37) folds onto protomap clusters. Distances within the protomap graph are computed from each representative fold to the neighboring folds. The distribution of these distances is used to create a statistical model for distances among those folds that are already known and those that have yet to be discovered. The distribution of distances for solved/unsolved proteins is significantly different. This difference makes it possible to use Bayes' rule to derive a statistical estimate that any protein has a yet undetermined fold. Proteins that score the highest probability to represent a new fold constitute the target list for structural determination. Our predicted probabilities for unsolved proteins correlate very well with the proportion of new folds among recently solved structures (new scop 1.39 records) that are disjoint from our original training set. PMID:10792051

  11. Modeling of wind gap formation and development of sedimentary basins during fold growth: application to the Zagros Fold Belt, Iran.

    NASA Astrophysics Data System (ADS)

    Collignon, Marine; Yamato, Philippe; Castelltort, Sébastien; Kaus, Boris

    2016-04-01

    Mountain building and landscape evolution are controlled by the interactions between river dynamics and tectonic forces. Such interactions have been largely studied but a quantitative evaluation of tectonic/geomorphic feedbacks remains required for understanding sediments routing within orogens and fold-and-thrust belts. Here, we employ numerical simulations to assess the conditions of uplift and river incision necessary to deflect an antecedent drainage network during the growth of one or several folds. We propose that a partitioning of the river network into internal (endorheic) and longitudinal drainage arises as a result of lithological differences within the deforming crustal sedimentary cover. We show with examples from the Zagros Fold Belt (ZFB) that drainage patterns can be linked to the incision ratio R between successive lithological layers, corresponding to the ratio between their relative erodibilities or incision coefficients. Transverse drainage networks develop for uplift rates smaller than 0.8 mm.yr-1 and -10 < R < 10. Intermediate drainage network are obtained for uplift rates up to 2 mm.yr-1 and incision ratios of 20. Parallel drainage networks and formation of sedimentary basins occur for large values of incision ratio (R >20) and uplift rates between 1 and 2 mm.yr-1. These results have implications for predicting the distribution of sediment depocenters in fold-and-thrust belts, which can be of direct economic interest for hydrocarbon exploration.

  12. Mutational analysis of the BPTI folding pathway: I. Effects of aromatic-->leucine substitutions on the distribution of folding intermediates.

    PubMed Central

    Zhang, J. X.; Goldenberg, D. P.

    1997-01-01

    The roles of aromatic residues in determining the folding pathway of bovine pancreatic trypsin inhibitor (BPTI) were analyzed mutationally by examining the distribution of disulfide-bonded intermediates that accumulated during the refolding of protein variants in which tyrosine or phenylalanine residues were individually replaced with leucine. The eight substitutions examined all caused significant changes in the intermediate distribution. In some cases, the major effect was to decrease the accumulation of intermediates containing two of the three disulfides found in the native protein, without affecting the distribution of earlier intermediates. Other substitutions, however, led to much more random distributions of the intermediates containing only one disulfide. These results indicate that the individual residues making up the hydrophobic core of the native protein make clearly distinguishable contributions to conformation and stability early in folding: The early distribution of intermediates does not appear to be determined by a general hydrophobic collapse. The effects of the substitutions were generally consistent with the structures of the major intermediates determined by NMR studies of analogs, confirming that the distribution of disulfide-bonded species is determined by stabilizing interactions within the ordered regions of the intermediates. The plasticity of the BPTI folding pathway implied by these results can be described using conformational funnels to illustrate the degree to which conformational entropy is lost at different stages in the folding of the wild-type and mutant proteins. PMID:9232656

  13. Study of the pure double folding optical model for 100 MeV/u deuteron scattering

    NASA Astrophysics Data System (ADS)

    Howard, Kevin; Patel, Darshana; Garg, Umesh

    2014-09-01

    The centroid energies of the giant monopole resonance (GMR) in nuclei are important because they are directly related to the nuclear incompressibility, an important quantity in the nuclear equation of state. It is necessary to examine the properties of the GMR in nuclei far from stability using advanced experimental techniques. The optical model for deuteron scattering is important from the point of view of performing these studies in inverse kinematics. Most studies on deuteron optical potentials have been done at lower energies and using the phenomenological optical model. However this model has been shown to overestimate the cross-sections for the low-lying discrete state. Recent developments in theory allow for the optical model real and imaginary volume potentials to be calculated using a double folding model with the help of the computer code dfpd5. For the first time these calculations are used to model the elastic and inelastic angular distributions in 28Si, 58Ni, and 116Sn nuclei. The experiment was performed at the Research Center for Nuclear Physics, Osaka University, Japan, using a 100 MeV/u deuteron beam. Results of the analysis will be presented.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

    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. Project supported by the Innovative Research Foundation of China Academy of Engineering Physics (Grant No. 426050502-2).

  15. Using Innovative Acoustic Analysis to Predict the Postoperative Outcomes of Unilateral Vocal Fold Paralysis

    PubMed Central

    Tsou, Yung-An; Chen, Wei-Chen; Ke, Hsiang-Chun; Lin, Wen-Yang; Yang, Hsing-Rong; Shie, Dung-Yun; Tsai, Ming-Hsui

    2016-01-01

    Objective. Autologous fat injection laryngoplasty is ineffective for some patients with iatrogenic vocal fold paralysis, and additional laryngeal framework surgery is often required. An acoustically measurable outcome predictor for lipoinjection laryngoplasty would assist phonosurgeons in formulating treatment strategies. Methods. Seventeen thyroid surgery patients with unilateral vocal fold paralysis participated in this study. All subjects underwent lipoinjection laryngoplasty to treat postsurgery vocal hoarseness. After treatment, patients were assigned to success and failure groups on the basis of voice improvement. Linear prediction analysis was used to construct a new voice quality indicator, the number of irregular peaks (NIrrP). It compared with the measures used in the Multi-Dimensional Voice Program (MDVP), such as jitter (frequency perturbation) and shimmer (perturbation of amplitude). Results. By comparing the [i] vowel produced by patients before the lipoinjection laryngoplasty (AUC = 0.98, 95% CI = 0.78–0.99), NIrrP was shown to be a more accurate predictor of long-term surgical outcomes than jitter (AUC = 0.73, 95% CI = 0.47–0.91) and shimmer (AUC = 0.63, 95% CI = 0.37–0.85), as identified by the receiver operating characteristic curve. Conclusions. NIrrP measured using the LP model could be a more accurate outcome predictor than the parameters used in the MDVP. PMID:27738634

  16. Balancing energy and entropy: a minimalist model for the characterization of protein folding landscapes.

    PubMed

    Das, Payel; Matysiak, Silvina; Clementi, Cecilia

    2005-07-19

    Coarse-grained models have been extremely valuable in promoting our understanding of protein folding. However, the quantitative accuracy of existing simplified models is strongly hindered either from the complete removal of frustration (as in the widely used Gō-like models) or from the compromise with the minimal frustration principle and/or realistic protein geometry (as in the simple on-lattice models). We present a coarse-grained model that "naturally" incorporates sequence details and energetic frustration into an overall minimally frustrated folding landscape. The model is coupled with an optimization procedure to design the parameters of the protein Hamiltonian to fold into a desired native structure. The application to the study of src-Src homology 3 domain shows that this coarse-grained model contains the main physical-chemical ingredients that are responsible for shaping the folding landscape of this protein. The results illustrate the importance of nonnative interactions and energetic heterogeneity for a quantitative characterization of folding mechanisms.

  17. Balancing energy and entropy: A minimalist model for the characterization of protein folding landscapes

    PubMed Central

    Das, Payel; Matysiak, Silvina; Clementi, Cecilia

    2005-01-01

    Coarse-grained models have been extremely valuable in promoting our understanding of protein folding. However, the quantitative accuracy of existing simplified models is strongly hindered either from the complete removal of frustration (as in the widely used Gō-like models) or from the compromise with the minimal frustration principle and/or realistic protein geometry (as in the simple on-lattice models). We present a coarse-grained model that “naturally” incorporates sequence details and energetic frustration into an overall minimally frustrated folding landscape. The model is coupled with an optimization procedure to design the parameters of the protein Hamiltonian to fold into a desired native structure. The application to the study of src-Src homology 3 domain shows that this coarse-grained model contains the main physical-chemical ingredients that are responsible for shaping the folding landscape of this protein. The results illustrate the importance of nonnative interactions and energetic heterogeneity for a quantitative characterization of folding mechanisms. PMID:16006532

  18. Asymptotic distribution of motifs in a stochastic context-free grammar model of RNA folding.

    PubMed

    Poznanović, Svetlana; Heitsch, Christine E

    2014-12-01

    We analyze the distribution of RNA secondary structures given by the Knudsen-Hein stochastic context-free grammar used in the prediction program Pfold. Our main theorem gives relations between the expected number of these motifs--independent of the grammar probabilities. These relations are a consequence of proving that the distribution of base pairs, of helices, and of different types of loops is asymptotically Gaussian in this model of RNA folding. Proof techniques use singularity analysis of probability generating functions. We also demonstrate that these asymptotic results capture well the expected number of RNA base pairs in native ribosomal structures, and certain other aspects of their predicted secondary structures. In particular, we find that the predicted structures largely satisfy the expected relations, although the native structures do not.

  19. De Novo Design of Helical Bundles as Models for Understanding Protein Folding and Function

    PubMed Central

    HILL, R. BLAKE; RALEIGH, DANIEL P.; LOMBARDI, ANGELA; DEGRADO, WILLIAM F.

    2011-01-01

    De novo protein design has proven to be a powerful tool for understanding protein folding, structure, and function. In this Account, we highlight aspects of our research on the design of dimeric, four-helix bundles. Dimeric, four-helix bundles are found throughout nature, and the history of their design in our laboratory illustrates our hierarchic approach to protein design. This approach has been successfully applied to create a completely native-like protein. Structural and mutational analysis allowed us to explore the determinants of native protein structure. These determinants were then applied to the design of a dinuclear metal-binding protein that can now serve as a model for this important class of proteins. PMID:11087311

  20. Capturing the essence of folding and functions of biomolecules using coarse-grained models.

    PubMed

    Hyeon, Changbong; Thirumalai, D

    2011-09-27

    The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example, during chromosome organization. Describing phenomena that cover such diverse length, and also time, scales requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.

  1. Monte Carlo simulations of the HP model (the "Ising model" of protein folding)

    NASA Astrophysics Data System (ADS)

    Li, Ying Wai; Wüst, Thomas; Landau, David P.

    2011-09-01

    Using Wang-Landau sampling with suitable Monte Carlo trial moves (pull moves and bond-rebridging moves combined) we have determined the density of states and thermodynamic properties for a short sequence of the HP protein model. For free chains these proteins are known to first undergo a collapse "transition" to a globule state followed by a second "transition" into a native state. When placed in the proximity of an attractive surface, there is a competition between surface adsorption and folding that leads to an intriguing sequence of "transitions". These transitions depend upon the relative interaction strengths and are largely inaccessible to "standard" Monte Carlo methods.

  2. Monte Carlo simulations of the HP model (the "Ising model" of protein folding).

    PubMed

    Li, Ying Wai; Wüst, Thomas; Landau, David P

    2011-09-01

    Using Wang-Landau sampling with suitable Monte Carlo trial moves (pull moves and bond-rebridging moves combined) we have determined the density of states and thermodynamic properties for a short sequence of the HP protein model. For free chains these proteins are known to first undergo a collapse "transition" to a globule state followed by a second "transition" into a native state. When placed in the proximity of an attractive surface, there is a competition between surface adsorption and folding that leads to an intriguing sequence of "transitions". These transitions depend upon the relative interaction strengths and are largely inaccessible to "standard" Monte Carlo methods.

  3. Investigating the Three-dimensional Flow Separation Induced by a Model Vocal Fold Polyp

    PubMed Central

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

    2014-01-01

    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. Our laboratory has reported particle image velocimetry (PIV) measurements, within an investigation of a model polyp located on the medial surface of an in vitro driven vocal fold model, which show that such a geometric abnormality considerably disrupts the glottal jet behavior. This flow field adjustment is a likely reason for the severe degradation of the vocal quality in patients with polyps. A more complete understanding of the formation and propagation of vortical structures from a geometric protuberance, such as a vocal fold polyp, and the resulting influence on the aerodynamic loadings that drive the vocal fold dynamics, is necessary for 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, using an oil-film visualization technique. Unsteady, three-dimensional flow separation and its impact of the wall pressure loading are examined using skin friction line visualization and wall pressure measurements. PMID:24513707

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

    SciTech Connect

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

    2015-12-28

    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.

  5. Modeling of the transient responses of the vocal fold lamina propria

    PubMed Central

    Zhang, Kai; Siegmund, Thomas; Chan, Roger W.

    2008-01-01

    The human voice is produced by flow-induced self-sustained oscillation of the vocal fold lamina propria. The mechanical properties of vocal fold tissues are important for understanding phonation, including the time-dependent and transient changes in fundamental frequency (F0). Cyclic uniaxial tensile tests were conducted on a group of specimens of the vocal fold lamina propria, including the superficial layer (vocal fold cover) (5 male, 5 female) and the deeper layers (vocal ligament) (6 male, 6 female). Results showed that the vocal fold lamina propria, like many other soft tissues, exhibits both elastic and viscous behavior. Specifically, the transient mechanical responses of cyclic stress relaxation and creep were observed. A three-network constitutive model composed of a hyperelastic equilibrium network in parallel with two viscoplastic time-dependent networks proves effective in characterizing the cyclic stress relaxation and creep behavior. For male vocal folds at a stretch of 1.4, significantly higher peak stress was found in the vocal ligament than in the vocal fold cover. Also, the male vocal ligament was significantly stiffer than the female vocal ligament. Our findings may help explain the mechanisms of some widely observed transient phenomena in F0 regulation during phonation, such as the global declination in F0 during the production of declarative sentences, and local F0 changes such as overshoot and undershoot. PMID:19122858

  6. Modeling coupled aerodynamics and vocal fold dynamics using immersed boundary methods.

    PubMed

    Duncan, Comer; Zhai, Guangnian; Scherer, Ronald

    2006-11-01

    The penalty immersed boundary (PIB) method, originally introduced by Peskin (1972) to model the function of the mammalian heart, is tested as a fluid-structure interaction model of the closely coupled dynamics of the vocal folds and aerodynamics in phonation. Two-dimensional vocal folds are simulated with material properties chosen to result in self-oscillation and volume flows in physiological frequency ranges. Properties of the glottal flow field, including vorticity, are studied in conjunction with the dynamic vocal fold motion. The results of using the PIB method to model self-oscillating vocal folds for the case of 8 cm H20 as the transglottal pressure gradient are described. The volume flow at 8 cm H20, the transglottal pressure, and vortex dynamics associated with the self-oscillating model are shown. Volume flow is also given for 2, 4, and 12 cm H2O, illustrating the robustness of the model to a range of transglottal pressures. The results indicate that the PIB method applied to modeling phonation has good potential for the study of the interdependence of aerodynamics and vocal fold motion.

  7. Comparative analysis of vocal fold vibration using high-speed videoendoscopy and digital kymography.

    PubMed

    Baravieira, Paula Belini; Brasolotto, Alcione Ghedini; Hachiya, Adriana; Takahashi-Ramos, Marystella Tomoe; Tsuji, Domingos Hiroshi; Montagnoli, Arlindo Neto

    2014-09-01

    To compare high-speed videoendoscopy (HSV) and digital kymography (DKG) in the vocal fold vibration analysis of normophonic women with no vocal fold abnormalities. Prospective study comparing quantitative parameters extracted by HSV and DKG. Eighteen normophonic women whose age ranged from 18 to 45 years participated in the study. The procedures comprised HSV and DKG of the medial line of the vocal folds. The parameters evaluated were fundamental frequency (F0), open quotient (OQ), and duration of vibration cycle phases (open phase, closed phase, opening phase, and closing phase). The F0 results of HSV and DKG were similar. However, significant differences were found in both duration of vibration cycle phases and OQ, indicating a longer open phase in the vocal fold vibration when this phase was measured by HSV. The results emphasize the need to set up different normative threshold values for both HSV and DKG. Copyright © 2014 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  8. Critical State Finite Element Models of Contractional Fault-Related Folding: Structural and Mechanical Analyses

    NASA Astrophysics Data System (ADS)

    Albertz, M.; Lingrey, S.; Sanz, P. F.

    2011-12-01

    Geometric/kinematic models of the common fault-related fold types (fault-bend, fault-propagation, detachment folding) typically assume a simplified flexural-slip based bed-parallel simple shear mechanism. The magnitude of local strain is a function of layer dip change irrespective of material properties. Line-lengths parallel to and layer thicknesses orthogonal to the flexural-slip surface remain constant. This study reports on a range of more complicated kinematic and mechanical responses observed in fourteen idealized forward numerical models of contractional fault-related folding. The models test the effects of material properties, initial fault dip, and the presence of weak inter-layer detachment horizons. We employ a Lagrangian finite element method with adaptive remeshing and a constitutive model that is based on critical state mechanics. This approach allows for large, volumetric deformation and realistic evolution of the failure envelope during progressive deformation. We demonstrate that material properties affect the way faults propagate and thus exert a significant control on resultant fold layer geometry. In most cases, these geometries differ from the flexural-slip based kinematic idealizations. For instance, models of uniform sandstone properties exhibit efficient strain localization and clear patterns of fault tip propagation. Uniform shale properties tends to inhibit fault propagation due to distributed plastic deformation. Models with mixed inter-layered sandstone and shale deform in a disharmonic manner, resembling lobate-cuspate arrangements that are common to many outcrop-scale folds. Inter-layer detachments accommodate shortening by bed-parallel slip, resulting in fault-bend fold kinematics, imbrication of sand layers, and a general absence of fault propagation across layers. Constant area based plane strain restoration of the deformed models recovers the first-order contractional deformation (80-90% of true contractional strain). Constant line

  9. Denatured-state energy landscapes of a protein structural database reveal the energetic determinants of a framework model for folding.

    PubMed

    Wang, Suwei; Gu, Jenny; Larson, Scott A; Whitten, Steven T; Hilser, Vincent J

    2008-09-19

    Position-specific denatured-state thermodynamics were determined for a database of human proteins by use of an ensemble-based model of protein structure. The results of modeling denatured protein in this manner reveal important sequence-dependent thermodynamic properties in the denatured ensembles as well as fundamental differences between the denatured and native ensembles in overall thermodynamic character. The generality and robustness of these results were validated by performing fold-recognition experiments, whereby sequences were matched with their respective folds based on amino acid propensities for the different energetic environments in the protein, as determined through cluster analysis. Correlation analysis between structure and energetic information revealed that sequence segments destined for beta-sheet in the final native fold are energetically more predisposed to a broader repertoire of states than are sequence segments destined for alpha-helix. These results suggest that within the subensemble of mostly unstructured states, the energy landscapes are dominated by states in which parts of helices adopt structure, whereas structure formation for sequences destined for beta-strand is far less probable. These results support a framework model of folding, which suggests that, in general, the denatured state has evolutionarily evolved to avoid low-energy conformations in sequences that ultimately adopt beta-strand. Instead, the denatured state evolved so that sequence segments that ultimately adopt alpha-helix and coil will have a high intrinsic structure formation capability, thus serving as potential nucleation sites.

  10. Experimental and Numerical Analysis of Composite Folded Sandwich Core Structures Under Compression

    NASA Astrophysics Data System (ADS)

    Heimbs, S.; Middendorf, P.; Kilchert, S.; Johnson, A. F.; Maier, M.

    2007-11-01

    The characterisation of the mechanical behaviour of folded core structures for advanced sandwich composites under flatwise compression load using a virtual testing approach is presented. In this context dynamic compression test simulations with the explicit solvers PAM-CRASH and LS-DYNA are compared to experimental data of two different folded core structures made of aramid paper and carbon fibre-reinforced plastic (CFRP). The focus of the investigations is the constitutive modelling of the cell wall material, the consideration of imperfections and the representation of cell wall buckling, folding or crushing phenomena. The consistency of the numerical results shows that this can be a promising and efficient approach for the determination of the effective mechanical properties and a cell geometry optimisation of folded core structures.

  11. Imaging and Analysis of Human Vocal Fold Vibration Using Two-Dimensional (2D) Scanning Videokymography.

    PubMed

    Park, Hee-June; Cha, Wonjae; Kim, Geun-Hyo; Jeon, Gye-Rok; Lee, Byung Joo; Shin, Bum-Joo; Choi, Yang-Gyu; Wang, Soo-Geun

    2016-05-01

    Laryngeal videokymography and high-speed digital kymography are the currently available techniques for studying aperiodic vibration of the vocal folds. However, videokymography has a fundamental limitation that only linear portions of the vocal fold mucosa can be visualized, whereas high-speed digital kymography has the disadvantages of lack of immediate feedback during examination and considerable waiting time before kymographic visualization. We developed a new system, two-dimensional (2D) scanning videokymography, that provides a possible alternative for evaluation of the vibratory pattern of the vocal folds. Herein, we report the application of 2D scanning videokymography for visualization of vocal fold vibration in humans and an analysis of its parameters. Two young healthy volunteers (one man and one woman) took part in this study. The vibratory patterns of their vocal folds were evaluated using 2D scanning videokymography and laryngeal stroboscopy. Two-dimensional scanning videokymography provided a high-definition image of the vibratory movements of the vocal folds. In analysis of the images acquired by the device, various parameters including fundamental frequency; ratio of the vibratory phases; phase, amplitude, and glottal area symmetry; and cycle-to-cycle variability were extracted. Our results indicate that 2D scanning videokymography is a useful and promising tool for visualization of the vibratory movement of the vocal folds. This new technique might improve our understanding of the mechanism of vocal fold vibration and contribute to voice research as well as clinical practice. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  12. Lattice and off-lattice side chain models of protein folding: Linear time structure prediction better than 86% of optimal

    SciTech Connect

    Hart, W.E.; Istrail, S.

    1996-08-09

    This paper considers the protein structure prediction problem for lattice and off-lattice protein folding models that explicitly represent side chains. Lattice models of proteins have proven extremely useful tools for reasoning about protein folding in unrestricted continuous space through analogy. This paper provides the first illustration of how rigorous algorithmic analyses of lattice models can lead to rigorous algorithmic analyses of off-lattice models. The authors consider two side chain models: a lattice model that generalizes the HP model (Dill 85) to explicitly represent side chains on the cubic lattice, and a new off-lattice model, the HP Tangent Spheres Side Chain model (HP-TSSC), that generalizes this model further by representing the backbone and side chains of proteins with tangent spheres. They describe algorithms for both of these models with mathematically guaranteed error bounds. In particular, the authors describe a linear time performance guaranteed approximation algorithm for the HP side chain model that constructs conformations whose energy is better than 865 of optimal in a face centered cubic lattice, and they demonstrate how this provides a 70% performance guarantee for the HP-TSSC model. This is the first algorithm in the literature for off-lattice protein structure prediction that has a rigorous performance guarantee. The analysis of the HP-TSSC model builds off of the work of Dancik and Hannenhalli who have developed a 16/30 approximation algorithm for the HP model on the hexagonal close packed lattice. Further, the analysis provides a mathematical methodology for transferring performance guarantees on lattices to off-lattice models. These results partially answer the open question of Karplus et al. concerning the complexity of protein folding models that include side chains.

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

    ERIC Educational Resources Information Center

    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…

  14. A Turing Reaction-Diffusion Model for Human Cortical Folding Patterns and Cortical Pattern Malformations

    NASA Astrophysics Data System (ADS)

    Hurdal, Monica K.; Striegel, Deborah A.

    2011-11-01

    Modeling and understanding cortical folding pattern formation is important for quantifying cortical development. We present a biomathematical model for cortical folding pattern formation in the human brain and apply this model to study diseases involving cortical pattern malformations associated with neural migration disorders. Polymicrogyria is a cortical malformation disease resulting in an excessive number of small gyri. Our mathematical model uses a Turing reaction-diffusion system to model cortical folding. The lateral ventricle (LV) and ventricular zone (VZ) of the brain are critical components in the formation of cortical patterning. In early cortical development the shape of the LV can be modeled with a prolate spheroid and the VZ with a prolate spheroid surface. We use our model to study how global cortex characteristics, such as size and shape of the LV, affect cortical pattern formation. We demonstrate increasing domain scale can increase the number of gyri and sulci formed. Changes in LV shape can account for sulcus directionality. By incorporating LV size and shape, our model is able to elucidate which parameters can lead to excessive cortical folding.

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

    ERIC Educational Resources Information Center

    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…

  16. Synthetic, Multi-Layer, Self-Oscillating Vocal Fold Model Fabrication

    PubMed Central

    Murray, Preston R.; Thomson, Scott L.

    2011-01-01

    Sound for the human voice is produced via flow-induced vocal fold vibration. The vocal folds consist of several layers of tissue, each with differing material properties 1. Normal voice production relies on healthy tissue and vocal folds, and occurs as a result of complex coupling between aerodynamic, structural dynamic, and acoustic physical phenomena. Voice disorders affect up to 7.5 million annually in the United States alone 2 and often result in significant financial, social, and other quality-of-life difficulties. Understanding the physics of voice production has the potential to significantly benefit voice care, including clinical prevention, diagnosis, and treatment of voice disorders. Existing methods for studying voice production include in vivo experimentation using human and animal subjects, in vitro experimentation using excised larynges and synthetic models, and computational modeling. Owing to hazardous and difficult instrument access, in vivo experiments are severely limited in scope. Excised larynx experiments have the benefit of anatomical and some physiological realism, but parametric studies involving geometric and material property variables are limited. Further, they are typically only able to be vibrated for relatively short periods of time (typically on the order of minutes). Overcoming some of the limitations of excised larynx experiments, synthetic vocal fold models are emerging as a complementary tool for studying voice production. Synthetic models can be fabricated with systematic changes to geometry and material properties, allowing for the study of healthy and unhealthy human phonatory aerodynamics, structural dynamics, and acoustics. For example, they have been used to study left-right vocal fold asymmetry 3,4, clinical instrument development 5, laryngeal aerodynamics 6-9, vocal fold contact pressure 10, and subglottal acoustics 11 (a more comprehensive list can be found in Kniesburges et al. 12) Existing synthetic vocal fold models

  17. Synthetic, multi-layer, self-oscillating vocal fold model fabrication.

    PubMed

    Murray, Preston R; Thomson, Scott L

    2011-12-02

    Sound for the human voice is produced via flow-induced vocal fold vibration. The vocal folds consist of several layers of tissue, each with differing material properties. Normal voice production relies on healthy tissue and vocal folds, and occurs as a result of complex coupling between aerodynamic, structural dynamic, and acoustic physical phenomena. Voice disorders affect up to 7.5 million annually in the United States alone and often result in significant financial, social, and other quality-of-life difficulties. Understanding the physics of voice production has the potential to significantly benefit voice care, including clinical prevention, diagnosis, and treatment of voice disorders. Existing methods for studying voice production include in vivo experimentation using human and animal subjects, in vitro experimentation using excised larynges and synthetic models, and computational modeling. Owing to hazardous and difficult instrument access, in vivo experiments are severely limited in scope. Excised larynx experiments have the benefit of anatomical and some physiological realism, but parametric studies involving geometric and material property variables are limited. Further, they are typically only able to be vibrated for relatively short periods of time (typically on the order of minutes). Overcoming some of the limitations of excised larynx experiments, synthetic vocal fold models are emerging as a complementary tool for studying voice production. Synthetic models can be fabricated with systematic changes to geometry and material properties, allowing for the study of healthy and unhealthy human phonatory aerodynamics, structural dynamics, and acoustics. For example, they have been used to study left-right vocal fold asymmetry, clinical instrument development, laryngeal aerodynamics, vocal fold contact pressure, and subglottal acoustics (a more comprehensive list can be found in Kniesburges et al.) Existing synthetic vocal fold models, however, have either

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Designability and cooperative folding in a four-letter hydrophobic-polar model of proteins

    NASA Astrophysics Data System (ADS)

    Liu, Hai-Guang; Tang, Lei-Han

    2006-11-01

    The two-letter hydrophobic-polar (HP) model of Lau and Dill [Macromolecules 22, 3986 (1989)] has been widely used in theoretical studies of protein folding due to its conceptual and computational simplicity. Despite its success in elucidating various aspects of the sequence-structure relationship, thermodynamic behavior of the model is not in agreement with a sharp two-state folding transition of many single-domain proteins. To gain a better understanding of this discrepancy, we consider an extension of the HP model by including an “antiferromagnetic” (AF) interaction in the contact potential that favors amino acid residues with complementary attributes. With an enlarged four-letter alphabet, the density of states on the low energy side can be significantly decreased. Computational studies of the four-letter HP model are performed on 36-mer sequences on a square lattice. It is found that the designability of folded structures in the extended model exhibits strong correlation with that of the two-letter HP model, while the AF interaction alone selects a very different class of structures that resembles the Greek key motif for beta sheets. A procedure is introduced to select sequences which have the largest energy gap to the native state. Based on density of states and specific heat calculations in the full configuration space, we show that the optimized sequence is able to fold nearly as cooperatively as a corresponding Gō model.

  20. Characterization of the vocal fold vertical stiffness in a canine model

    PubMed Central

    Oren, Liran; Dembinski, Doug; Gutmark, Ephraim; Khosla, Sid

    2014-01-01

    Objectives/Hypothesis Characterizing the vertical stiffness gradient that exists between the superior and inferior aspects of the medial surface of the vocal fold. Characterization of this stiffness gradient could elucidate the mechanism behind the divergent glottal shape observed during closing. Study Design Basic science. Methods Indentation testing of the folds was done in a canine model. Stress-strain curves are generated using a customized load-cell and the differential Young's modulus is calculated as a function of strain. Results Results from 11 larynges show that stress increases as a function of strain more rapidly in the inferior aspect of the fold. The calculations for local Young's modulus show that at high strain values a stiffness gradient is formed between the superior and inferior aspects of the fold. Conclusions For small strain values, which are observed at low subglottal pressures, the stiffness of the tissue is similar in both the superior and inferior aspects of the vocal fold. Consequently, the lateral force that is applied by the glottal flow at both aspects results in almost identical displacements, yielding no divergence angle. Conversely, at higher strain values, which are measured in high subglottal pressure, the inferior aspect of the vocal fold is much stiffer than the superior edge; thus any lateral force that is applied at both aspects will result in a much greater displacement of the superior edge, yielding a large divergence angle. The increased stiffness observed at the inferior edge could be due to the proximity of the conus elasticus. PMID:24495431

  1. Mathematics, thermodynamics, and modeling to address ten common misconceptions about protein structure, folding, and stability.

    PubMed

    Robic, Srebrenka

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability.

  2. An investigation of jet trajectory in flow through scaled vocal fold models with asymmetric glottal passages

    NASA Astrophysics Data System (ADS)

    Erath, Byron D.; Plesniak, Michael W.

    2006-11-01

    Pulsatile two-dimensional flow through asymmetric static divergent models of the human vocal folds is investigated. Included glottal divergence angles are varied between 10° and 30°, with asymmetry angles between the vocal fold pairs ranging from 5° to 15°. The model glottal configurations represent asymmetries that arise during a phonatory cycle due to voice disorders. The flow is scaled to physiological values of Reynolds, Strouhal, and Euler numbers. Data are acquired in the anterior posterior mid-plane of the vocal fold models using phase-averaged Particle Image Velocimetry (PIV) acquired at ten discrete locations in a phonatory cycle. Glottal jet stability arising from the vocal fold asymmetries is investigated and compared to previously reported work for symmetric vocal fold passages. Jet stability is enhanced with an increase in the included divergence angle, and the glottal asymmetry. Concurrently, the bi-modal jet trajectory and flow unsteadiness diminishes. Consistent with previous findings, the flow attachment due to the Coanda effect occurs when the acceleration of the forcing function is zero.

  3. Mathematics, Thermodynamics, and Modeling to Address Ten Common Misconceptions about Protein Structure, Folding, and Stability

    PubMed Central

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability. PMID:20810950

  4. Steric confinement and enhanced local flexibility assist knotting in simple models of protein folding.

    PubMed

    Soler, Miguel A; Rey, Antonio; Faísca, Patrícia F N

    2016-09-29

    The chaperonin complex GroEL-GroES is able to accelerate the folding process of knotted proteins considerably. However, the folding mechanism inside the chaperonin cage is elusive. Here we use a combination of lattice and off-lattice Monte Carlo simulations of simple Gō models to study the effect of physical confinement and local flexibility on the folding process of protein model systems embedding a trefoil knot in their native structure. This study predicts that steric confinement plays a specific role in the folding of knotted proteins by increasing the knotting probability for very high degrees of confinement. This effect is observed for protein MJ0366 even above the melting temperature for confinement sizes compatible with the size of the GroEL/GroES chaperonin cage. An enhanced local flexibility produces the same qualitative effects on the folding process. In particular, we observe that knotting probability increases up to 40% in the transition state of protein MJ0366 when flexibility is enhanced. This is underlined by a structural change in the transition state, which becomes devoid of helical content. No relation between the knotting mechanism and flexibility was found in the context of the off-lattice model adopted in this work.

  5. Principles of protein folding--a perspective from simple exact models.

    PubMed Central

    Dill, K. A.; Bromberg, S.; Yue, K.; Fiebig, K. M.; Yee, D. P.; Thomas, P. D.; Chan, H. S.

    1995-01-01

    General principles of protein structure, stability, and folding kinetics have recently been explored in computer simulations of simple exact lattice models. These models represent protein chains at a rudimentary level, but they involve few parameters, approximations, or implicit biases, and they allow complete explorations of conformational and sequence spaces. Such simulations have resulted in testable predictions that are sometimes unanticipated: The folding code is mainly binary and delocalized throughout the amino acid sequence. The secondary and tertiary structures of a protein are specified mainly by the sequence of polar and nonpolar monomers. More specific interactions may refine the structure, rather than dominate the folding code. Simple exact models can account for the properties that characterize protein folding: two-state cooperativity, secondary and tertiary structures, and multistage folding kinetics--fast hydrophobic collapse followed by slower annealing. These studies suggest the possibility of creating "foldable" chain molecules other than proteins. The encoding of a unique compact chain conformation may not require amino acids; it may require only the ability to synthesize specific monomer sequences in which at least one monomer type is solvent-averse. PMID:7613459

  6. Frequency response of synthetic vocal fold models with linear and nonlinear material properties.

    PubMed

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

    2012-10-01

    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 (F0) during anterior-posterior stretching. Three materially linear and 3 materially nonlinear models were created and stretched up to 10 mm in 1-mm increments. Phonation onset pressure (Pon) and F0 at Pon were recorded for each length. Measurements were repeated as the models were relaxed in 1-mm increments back to their resting lengths, and tensile tests were conducted to determine the stress-strain responses of linear versus nonlinear models. Nonlinear models demonstrated a more substantial frequency response than did linear models and a more predictable pattern of F0 increase with respect to increasing length (although range was inconsistent across models). Pon generally increased with increasing vocal fold length for nonlinear models, whereas for linear models, Pon decreased with increasing length. Nonlinear synthetic models appear to more accurately represent the human vocal folds than do linear models, especially with respect to F0 response.

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

    PubMed Central

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

    2014-01-01

    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 during anterior-posterior stretching. Method Three materially linear and three materially nonlinear models were created and stretched up to 10 mm in 1 mm increments. Phonation onset pressure (Pon) and fundamental frequency (F0) at Pon were recorded for each length. Measurements were repeated as the models were relaxed in 1 mm increments back to their resting lengths, and tensile tests were conducted to determine the stress-strain responses of linear versus nonlinear models. Results Nonlinear models demonstrated a more substantial frequency response than did linear models and a more predictable pattern of F0 increase with respect to increasing length (although range was inconsistent across models). Pon generally increased with increasing vocal fold length for nonlinear models, whereas for linear models, Pon decreased with increasing length. Conclusions Nonlinear synthetic models appear to more accurately represent the human vocal folds than linear models, especially with respect to F0 response. PMID:22271874

  8. Computational Modeling of Ductile Folding in Sedimentary Rocks of the Sheep Mountain Anticline, Wyoming

    NASA Astrophysics Data System (ADS)

    Borja, R. I.; Sanz, P. F.; Fiore, P. E.; Pollard, D. D.

    2005-12-01

    Folding of sedimentary rocks occurs at depths in Earth's crust where some layers respond by brittle deformation while others respond by ductile deformation. Folding results from a number of mechanisms including buckling due to lateral tectonic compression and/or slip on thrust faults in the underlying strata. Movements experienced by folded strata are typically very large (tens to hundreds of meters or more) and may include significant rigid body translation and rotation, in addition to the straining of the folded layers. More specific types of straining could include any one or a combination of the following: plate-like bending, in-plane extension, in-plane contraction, and either in-plane or out-of-plane shearing. The stress state resulting from the overburden load, slip on underlying faults, and the associated folding could induce strain localization even as the layer continues to deform plastically. In this paper we present a mathematical model for capturing isothermal ductile folding processes and the accompanying strain localization in sedimentary rocks using nonlinear continuum mechanics and finite element modeling. We use a fully Lagrangian approach along with multiplicative plasticity theory for finite deformations, considering the effects of all three invariants of the stress tensor in the constitutive description. We also simulate the rigid body translation, finite rotation, and subsequent rupturing of preexisting faults using finite deformation kinematics and stick-slip contact mechanics. We apply the technique to simulate the three-dimensional folding of selected Paleozoic and Mesozoic formations located above the Madison limestone in the Sheep Mountain anticline, formed during the Laramide orogeny in the Bighorn Basin, Wyoming. Supported by U.S. Department of Energy, Grant No. DE-FG02-03ER15454, and U.S. National Science Foundation, Grant No. CMG-0417521.

  9. Multidimensional Analysis on the Effect of Vocal Function Exercises on Aged Vocal Fold Atrophy.

    PubMed

    Kaneko, Mami; Hirano, Shigeru; Tateya, Ichiro; Kishimoto, Yo; Hiwatashi, Nao; Fujiu-Kurachi, Masako; Ito, Juichi

    2015-09-01

    Age-related voice change is characterized as weak, harsh, and breathy. These changes are caused by histologic alteration of the lamina propria of the vocal fold mucosa as well as atrophy of the thyroarytenoid muscle. Several therapeutic strategies involving laryngeal framework surgery and injection laryngoplasty have been tried, but effects have been limited. Vocal function exercises (VFE) have been used to treat age-related vocal fold atrophy although the effectiveness has been shown with limited analysis. The present study aims to determine the effectiveness of VFE for the treatment of aged atrophy using multidimensional analysis. This is a retrospective study. Sixteen patients with vocal fold atrophy aged 65-81 years underwent voice therapy using VFE. Six patients with vocal fold atrophy aged 65-85 years were involved as a historical control group. The grade, roughness, breathiness, asthenia, strain (GRBAS) scale, stroboscopic examinations, aerodynamic assessment, acoustic analysis, and Voice Handicap Index-10 (VHI-10) were performed before and after VFE. Normalized mucosal wave amplitude (NMWA), normalized glottal gap (NGG), and bowing index (BI) were measured by image analysis during stroboscopic examinations. After VFE, significant improvements were shown in GRBAS, maximum phonation time, jitter, NMWA, NGG, and VHI-10 although BI has not changed significantly. There were no significant improvements in the historical control. The data suggest that VFE produces significant improvement in subjective, objective, and patient self-evaluation and deserves further attention as a treatment for aged atrophy of the vocal fold. It was also suggested that VFE does not improve the vocal fold bowing but may improve muscular function during voicing. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  10. A Top-Down Approach to Mechanistic Biological Modeling: Application to the Single-Chain Antibody Folding Pathway

    PubMed Central

    Hildebrandt, Scott; Raden, David; Petzold, Linda; Robinson, Anne Skaja; Doyle, Francis J.

    2008-01-01

    A top-down approach to mechanistic modeling of biological systems is presented and exemplified with the development of a hypothesis-driven mathematical model for single-chain antibody fragment (scFv) folding in Saccharomyces cerevisiae by mediators BiP and PDI. In this approach, model development starts with construction of the most basic mathematical model—typically consisting of predetermined or newly-elucidated biological behavior motifs—capable of reproducing desired biological behaviors. From this point, mechanistic detail is added incrementally and systematically, and the effects of each addition are evaluated. This approach follows the typical progression of experimental data availability in that higher-order, lumped measurements are often more prevalent initially than specific, mechanistic ones. It also necessarily provides the modeler with insight into the structural requirements and performance capabilities of the resulting detailed mechanistic model, which facilitates further analysis. The top-down approach to mechanistic modeling identified three such requirements and a branched dependency-degradation competition motif critical for the scFv folding model to reproduce experimentally observed scFv folding dependencies on BiP and PDI and increased production when both species are overexpressed and promoted straightforward prediction of parameter dependencies. It also prescribed modification of the guiding hypothesis to capture BiP and PDI synergy. PMID:18641066

  11. Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains.

    PubMed

    Jost, Daniel; Carrivain, Pascal; Cavalli, Giacomo; Vaillant, Cédric

    2014-09-01

    Genomes of eukaryotes are partitioned into domains of functionally distinct chromatin states. These domains are stably inherited across many cell generations and can be remodeled in response to developmental and external cues, hence contributing to the robustness and plasticity of expression patterns and cell phenotypes. Remarkably, recent studies indicate that these 1D epigenomic domains tend to fold into 3D topologically associated domains forming specialized nuclear chromatin compartments. However, the general mechanisms behind such compartmentalization including the contribution of epigenetic regulation remain unclear. Here, we address the question of the coupling between chromatin folding and epigenome. Using polymer physics, we analyze the properties of a block copolymer model that accounts for local epigenomic information. Considering copolymers build from the epigenomic landscape of Drosophila, we observe a very good agreement with the folding patterns observed in chromosome conformation capture experiments. Moreover, this model provides a physical basis for the existence of multistability in epigenome folding at sub-chromosomal scale. We show how experiments are fully consistent with multistable conformations where topologically associated domains of the same epigenomic state interact dynamically with each other. Our approach provides a general framework to improve our understanding of chromatin folding during cell cycle and differentiation and its relation to epigenetics.

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

    NASA Astrophysics Data System (ADS)

    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. Simplified Protein Models: Predicting Folding Pathways and Structure Using Amino Acid Sequences

    NASA Astrophysics Data System (ADS)

    Adhikari, Aashish N.; Freed, Karl F.; Sosnick, Tobin R.

    2013-07-01

    We demonstrate the ability of simultaneously determining a protein’s folding pathway and structure using a properly formulated model without prior knowledge of the native structure. Our model employs a natural coordinate system for describing proteins and a search strategy inspired by the observation that real proteins fold in a sequential fashion by incrementally stabilizing nativelike substructures or “foldons.” Comparable folding pathways and structures are obtained for the twelve proteins recently studied using atomistic molecular dynamics simulations [K. Lindorff-Larsen, S. Piana, R. O. Dror, D. E. Shaw, Science 334, 517 (2011)], with our calculations running several orders of magnitude faster. We find that nativelike propensities in the unfolded state do not necessarily determine the order of structure formation, a departure from a major conclusion of the molecular dynamics study. Instead, our results support a more expansive view wherein intrinsic local structural propensities may be enhanced or overridden in the folding process by environmental context. The success of our search strategy validates it as an expedient mechanism for folding both in silico and in vivo.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Influence of subglottic stenosis on the flow-induced vibration of a computational vocal fold model.

    PubMed

    Smith, Simeon L; Thomson, Scott L

    2013-04-01

    The effect of subglottic stenosis on vocal fold vibration is investigated. An idealized stenosis is defined, parameterized, and incorporated into a two-dimensional, fully-coupled finite element model of the vocal folds and laryngeal airway. Flow-induced responses of the vocal fold model to varying severities of stenosis are compared. The model vibration was not appreciably affected by stenosis severities of up to 60% occlusion. Model vibration was altered by stenosis severities of 90% or greater, evidenced by decreased superior model displacement, glottal width amplitude, and flow rate amplitude. Predictions of vibration frequency and maximum flow declination rate were also altered by high stenosis severities. The observed changes became more pronounced with increasing stenosis severity and inlet pressure, and the trends correlated well with flow resistance calculations. Flow visualization was used to characterize subglottal flow patterns in the space between the stenosis and the vocal folds. Underlying mechanisms for the observed changes, possible implications for human voice production, and suggestions for future work are discussed.

  17. Influence of subglottic stenosis on the flow-induced vibration of a computational vocal fold model

    NASA Astrophysics Data System (ADS)

    Smith, Simeon L.; Thomson, Scott L.

    2013-04-01

    The effect of subglottic stenosis on vocal fold vibration is investigated. An idealized stenosis is defined, parameterized, and incorporated into a two-dimensional, fully coupled finite element model of the vocal folds and laryngeal airway. Flow-induced responses of the vocal fold model to varying severities of stenosis are compared. The model vibration was not appreciably affected by stenosis severities of up to 60% occlusion. Model vibration was altered by stenosis severities of 90% or greater, evidenced by decreased superior model displacement, glottal width amplitude, and flow rate amplitude. Predictions of vibration frequency and maximum flow declination rate were also altered by high stenosis severities. The observed changes became more pronounced with increasing stenosis severity and inlet pressure, and the trends correlated well with flow resistance calculations. Flow visualization was used to characterize subglottal flow patterns in the space between the stenosis and the vocal folds. Underlying mechanisms for the observed changes, possible implications for human voice production, and suggestions for future work are discussed.

  18. Influence of subglottic stenosis on the flow-induced vibration of a computational vocal fold model

    PubMed Central

    Smith, Simeon L.; Thomson, Scott L.

    2012-01-01

    The effect of subglottic stenosis on vocal fold vibration is investigated. An idealized stenosis is defined, parameterized, and incorporated into a two-dimensional, fully-coupled finite element model of the vocal folds and laryngeal airway. Flow-induced responses of the vocal fold model to varying severities of stenosis are compared. The model vibration was not appreciably affected by stenosis severities of up to 60% occlusion. Model vibration was altered by stenosis severities of 90% or greater, evidenced by decreased superior model displacement, glottal width amplitude, and flow rate amplitude. Predictions of vibration frequency and maximum flow declination rate were also altered by high stenosis severities. The observed changes became more pronounced with increasing stenosis severity and inlet pressure, and the trends correlated well with flow resistance calculations. Flow visualization was used to characterize subglottal flow patterns in the space between the stenosis and the vocal folds. Underlying mechanisms for the observed changes, possible implications for human voice production, and suggestions for future work are discussed. PMID:23503699

  19. The Fold Analysis Challenge: A virtual globe-based educational resource

    NASA Astrophysics Data System (ADS)

    De Paor, Declan G.; Dordevic, Mladen M.; Karabinos, Paul; Tewksbury, Barbara J.; Whitmeyer, Steven J.

    2016-04-01

    We present an undergraduate structural geology laboratory exercise using the Google Earth virtual globe with COLLADA models, optionally including an interactive stereographic projection and JavaScript controls. The learning resource challenges students to identify bedding traces and estimate bedding orientation at several locations on a fold, to fit the fold axis and axial plane to stereographic projection data, and to fit a doubly-plunging fold model to the large-scale structure. The chosen fold is the Sheep Mountain Anticline, a Laramide uplift in the Big Horn Basin of Wyoming. We take an education research-based approach, guiding students through three levels of difficulty. The exercise aims to counter common student misconceptions and stumbling blocks regarding penetrative structures. It can be used in preparation for an in-person field trip, for post-trip reinforcement, or as a virtual field experience in an online-only course. Our KML scripts can be easily transferred to other fold structures around the globe.

  20. Quantitative tests of a reconstitution model for RNA folding thermodynamics and kinetics.

    PubMed

    Bisaria, Namita; Greenfeld, Max; Limouse, Charles; Mabuchi, Hideo; Herschlag, Daniel

    2017-09-12

    Decades of study of the architecture and function of structured RNAs have led to the perspective that RNA tertiary structure is modular, made of locally stable domains that retain their structure across RNAs. We formalize a hypothesis inspired by this modularity-that RNA folding thermodynamics and kinetics can be quantitatively predicted from separable energetic contributions of the individual components of a complex RNA. This reconstitution hypothesis considers RNA tertiary folding in terms of ΔGalign, the probability of aligning tertiary contact partners, and ΔGtert, the favorable energetic contribution from the formation of tertiary contacts in an aligned state. This hypothesis predicts that changes in the alignment of tertiary contacts from different connecting helices and junctions (ΔGHJH) or from changes in the electrostatic environment (ΔG+/-) will not affect the energetic perturbation from a mutation in a tertiary contact (ΔΔGtert). Consistent with these predictions, single-molecule FRET measurements of folding of model RNAs revealed constant ΔΔGtert values for mutations in a tertiary contact embedded in different structural contexts and under different electrostatic conditions. The kinetic effects of these mutations provide further support for modular behavior of RNA elements and suggest that tertiary mutations may be used to identify rate-limiting steps and dissect folding and assembly pathways for complex RNAs. Overall, our model and results are foundational for a predictive understanding of RNA folding that will allow manipulation of RNA folding thermodynamics and kinetics. Conversely, the approaches herein can identify cases where an independent, additive model cannot be applied and so require additional investigation.

  1. Amnion formation in the mouse embryo: the single amniochorionic fold model.

    PubMed

    Pereira, Paulo N G; Dobreva, Mariya P; Graham, Liz; Huylebroeck, Danny; Lawson, Kirstie A; Zwijsen, A N

    2011-08-01

    Despite the detailed knowledge obtained over the last decade on the molecular regulation of gastrulation in amniotes, the process of amnion development has been poorly described and illustrated in mice, and conflicting descriptions exist. Understanding the morphogenesis and development not only of the early mouse embryo, but also of its extraembryonic tissues, is crucial for correctly interpreting fate-mapping data and mouse mutants with gastrulation defects. Moreover, the recent isolation from amnion of cells with stem cell features further argues for a better understanding of the process of amnion formation. Here, we revisit the highly dynamic process of amnion formation in the mouse. Amnion development starts early during gastrulation and is intimately related to the formation of the exocoelom and the expansion of the amniotic fold. The authoritative description involves the fusion of two amniotic folds, a big posterior and a smaller anterior fold. We challenged this 'two amniotic folds' model by performing detailed histomorphological analyses of dissected, staged embryos and 3D reconstructions using historical sections. A posterior fold of extraembryonic ectoderm and associated epiblast is formed early during gastrulation by accumulation of extraembryonic mesoderm posterior to the primitive streak. Previously called the "posterior amniotic fold", we rename it the "amniochorionic fold" (ACF) because it forms both amnion and chorion. Exocoelom formation within the ACF seems not to involve apoptosis within the mesoderm. The ACF and exocoelom expand without disrupting the anterior junction of epiblast, extraembryonic ectoderm and visceral endoderm. No separate anterior fold is formed; its absence was confirmed in 3D reconstructions. Amnion and chorion closure is eccentric, close to the anterior margin of the egg cylinder: we name it the "anterior separation point". Here, we reconcile previous descriptions of amnion formation and provide new nomenclature, as well as

  2. Amnion formation in the mouse embryo: the single amniochorionic fold model

    PubMed Central

    2011-01-01

    Background Despite the detailed knowledge obtained over the last decade on the molecular regulation of gastrulation in amniotes, the process of amnion development has been poorly described and illustrated in mice, and conflicting descriptions exist. Understanding the morphogenesis and development not only of the early mouse embryo, but also of its extraembryonic tissues, is crucial for correctly interpreting fate-mapping data and mouse mutants with gastrulation defects. Moreover, the recent isolation from amnion of cells with stem cell features further argues for a better understanding of the process of amnion formation. Here, we revisit the highly dynamic process of amnion formation in the mouse. Amnion development starts early during gastrulation and is intimately related to the formation of the exocoelom and the expansion of the amniotic fold. The authoritative description involves the fusion of two amniotic folds, a big posterior and a smaller anterior fold. We challenged this 'two amniotic folds' model by performing detailed histomorphological analyses of dissected, staged embryos and 3D reconstructions using historical sections. Results A posterior fold of extraembryonic ectoderm and associated epiblast is formed early during gastrulation by accumulation of extraembryonic mesoderm posterior to the primitive streak. Previously called the "posterior amniotic fold", we rename it the "amniochorionic fold" (ACF) because it forms both amnion and chorion. Exocoelom formation within the ACF seems not to involve apoptosis within the mesoderm. The ACF and exocoelom expand without disrupting the anterior junction of epiblast, extraembryonic ectoderm and visceral endoderm. No separate anterior fold is formed; its absence was confirmed in 3D reconstructions. Amnion and chorion closure is eccentric, close to the anterior margin of the egg cylinder: we name it the "anterior separation point". Conclusions Here, we reconcile previous descriptions of amnion formation and

  3. Will it fold? Structural and statistical analysis of a 10mer of Fdu

    NASA Astrophysics Data System (ADS)

    Melvin, Ryan; Salsbury, Freddie

    2014-03-01

    Small strands of RNA are often drawn as extended structures in both journal articles and textbooks. However, a microsecond all-atom GPU-based simulation of a 10mer therapeutic, Fdu, shows folding into stable hairpin-like structures. After a 300ns equilibration phase, this 10mer has a 90 percent probability of existing in 1 of 5 folded states. A Markov analysis shows that despite the existence of a kinetically trapped state, the dynamics among the folded state converges on the nanosecond scale and is ergodic. Knowledge of these structures and probability of their occurrence will allow for estimates of free energies for binding proteins to potentially improve the delivery and design of this therapeutic.

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

    NASA Astrophysics Data System (ADS)

    Guo, Wei; Li, Meie; Zhou, Jinxiong

    2013-11-01

    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.

  5. Structural model of the eastern Achara-Trialeti fold and thrust belt using seismic reflection profiles

    NASA Astrophysics Data System (ADS)

    Alania, Victor; Chabukiani, Alexander; Enukidze, Onise; Razmadze, Alexander; Sosson, Marc; Tsereteli, Nino; Varazanashvili, Otar

    2017-04-01

    Our study focused on the structural geometry at the eastern Achara-Trialeti fold and thrust belt (ATFTB) located at the retro-wedge of the Lesser Caucasus orogen (Alania et al., 2016a). Our interpretation has integrated seismic reflection profiles, several oil-wells, and the surface geology data to reveal structural characteristics of the eastern ATFTB. Fault-related folding theories were used to seismic interpretation (Shaw et al., 2004). Seismic reflection data reveal the presence of basement structural wedge, south-vergent backthrust, north-vergent forethrust and some structural wedges (or duplex). The rocks are involved in the deformation range from Paleozoic basement rocks to Tertiary strata. Building of thick-skinned structures of eastern Achara-Trialeti was formed by basement wedges propagated from south to north along detachment horizons within the cover generating thin-skinned structures. The kinematic evolution of the south-vergent backthrust zone with respect to the northward propagating structural wedge (or duplexes). The main style of deformation within the backthrust belt is a series of fault-propagation folds. Frontal part of eastern ATFTB are represent by triangle zone (Alania et al., 2016b; Sosson et al., 2016). A detailed study was done for Tbilisi area: seismic refection profiles, serial balanced cross-sections, and earthquakes reveal the presence of an active blind thrust fault beneath Tbilisi. 2 & 3-D structural models show that 2002 Mw 4.5 Tbilisi earthquake related to a north-vergent blind thrust. Empirical relations between blind fault rupture area and magnitude suggest that these fault segments could generate earthquakes of Mw 6.5. The growth fault-propagation fold has been observed near Tbilisi in the frontal part of eastern ATFTB. Seismic reflection profile through Ormoiani syncline shows that south-vergent growth fault-propagation fold related to out-of-the-syncline thrust. The outcrop of fault-propagation fold shown the geometry of the

  6. Quantitative analysis of vocal fold vibration during register change by high-speed digital imaging system

    NASA Astrophysics Data System (ADS)

    Kumada, Masanobu; Kobayashi, Noriko; Hirose, Hajime; Tayama, Niro; Imagawa, Hiroshi; Sakakibara, Ken-Ichi; Nito, Takaharu; Kakurai, Shin'ichi; Kumada, Chieko; Wada, Mamiko; Niimi, Seiji

    2002-05-01

    The physiological study of prosody is indispensable in terms not only of the physiological interest but also of the evaluation and treatment for pathological cases of prosody. In free talk, the changes of vocal fold vibration are found frequently and these phenomena are very important prosodic events. To analyze quantitatively the vocal fold vibration at the register change as the model of prosodic event, our high-speed digital imaging system was used at a rate of 4500 images of 256-256 pixels per second. Four healthy Japanese adults (2 males and 2 females) were served as subjects. Tasks were sustained phonation containing register changes. Two major categories (Category A and B) were found in the ways of changing of vocal fold vibrations at the register change. In Category A, changes were very smooth in terms of the vocal fold vibration. In Category B, changes were not so smooth with some additional events at the register change, such as the anterior-posterior phase difference of the vibration, the abduction of the vocal folds, or the interruption of the phonation. The number of the subtypes for Category B is thought to increase if more subjects with a wider range of variety are analyzed. For the study of prosody, our high-speed digital imaging system is a very powerful tool by which physiological information can be obtained.

  7. Folding of proteins with an all-atom Go-model.

    PubMed

    Wu, L; Zhang, J; Qin, M; Liu, F; Wang, W

    2008-06-21

    The Go-like potential at a residual level has been successfully applied to the folding of proteins in many previous works. However, taking into consideration more detailed structural information in the atomic level, the definition of contacts used in these traditional Go-models may not be suitable for all-atom simulations. Here, in this work, we develop a rational definition of contacts considering the screening effect in the crowded intramolecular environment. In such a scheme, a large amount of screened atom pairs are excluded and the number of contacts is decreased compared to the case of the traditional definition. These contacts defined by such a new definition are compatible with the all-atom representation of protein structures. To verify the rationality of the new definition of contacts, the folding of proteins CI2 and SH3 is simulated by all-atom molecular dynamics simulations. A high folding cooperativity and good correlation of the simulated Phi-values with those obtained experimentally, especially for CI2, are found. This suggests that the all-atom Go-model is improved compared to the traditional Go-model. Based on the comparison of the Phi-values, the roles of side chains in the folding are discussed, and it is concluded that the side-chain structures are more important for local contacts in determining the transition state structures. Moreover, the relations between side chain and backbone orderings are also discussed.

  8. Complexity of chromatin folding is captured by the strings and binders switch model.

    PubMed

    Barbieri, Mariano; Chotalia, Mita; Fraser, James; Lavitas, Liron-Mark; Dostie, Josée; Pombo, Ana; Nicodemi, Mario

    2012-10-02

    Chromatin has a complex spatial organization in the cell nucleus that serves vital functional purposes. A variety of chromatin folding conformations has been detected by single-cell imaging and chromosome conformation capture-based approaches. However, a unified quantitative framework describing spatial chromatin organization is still lacking. Here, we explore the "strings and binders switch" model to explain the origin and variety of chromatin behaviors that coexist and dynamically change within living cells. This simple polymer model recapitulates the scaling properties of chromatin folding reported experimentally in different cellular systems, the fractal state of chromatin, the processes of domain formation, and looping out. Additionally, the strings and binders switch model reproduces the recently proposed "fractal-globule" model, but only as one of many possible transient conformations.

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

    PubMed

    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.

  10. Folding and association of a homotetrameric protein complex in an all-atom Go model.

    PubMed

    Berhanu, W M; Jiang, P; Hansmann, U H E

    2013-01-01

    The 84-residue homotetrameric BBAT1 is one of the smallest stable protein complexes and therefore is a good test system to study the self-assembly of multimeric proteins. We have researched for this protein the interplay between the folding of monomers and their assembly into tetramers. Replica exchange molecular dynamics simulations relying on a Go model are compared with earlier simulations that use the physics-based coarse-grained UNRES model.

  11. Modeling the dynamic folding and surface-activity of a helical peptide adsorbing to a pendant bubble interface.

    PubMed

    Jain, Vikas P; Maldarelli, Charles; Tu, Raymond S

    2009-03-15

    We have designed a peptide with switchable surface activity, where the folded (alpha-helical) form of the peptide is amphiphilic and the unfolded form is not. To understand the factors influencing the dynamics of the switchability, a model is developed for the transport of the surface active form of the peptide from the solution onto air-water interface. As is the case with the low molecular weight head-tail surfactants, the transport involves the bulk diffusion of the folded form to the surface and the kinetic adsorption onto the interface. Unlike the head-tail surfactants, the diffusion can be augmented by the kinetics of the folding of the peptide from the unfolded form. The model is formulated within the context of the transport of the peptide from a uniform bulk solution onto an initially clean air-water interface in a pendant bubble system, where the transport rate can be measured by recording the reduction in surface tension using the shape analysis of the bubble. Experiments are undertaken and compared to the predictions of the model simulations of the tension reduction for a range of values of the kinetic adsorption constant and the folding kinetic constant. The results indicate that the kinetic adsorption rate of the folded peptide onto air-water interface dominates the dynamic process, which contrasts many head-tail surfactants where diffusion typically dominates over kinetics adsorption. Moreover, our 'best-fits' suggest that there is a phase transition at high surface concentrations that slows the long-time adsorption of the peptides to the interface. Finally, the numerical solution is compared with an asymptotic solution, showing agreement with our findings that the fundamental dynamics of the tunable surface-active peptide are indeed controlled by the adsorption step.

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  14. Multiparametric analysis of vocal fold vibrations in healthy and disordered voices in high-speed imaging.

    PubMed

    Inwald, Elisabeth C; Döllinger, Michael; Schuster, Maria; Eysholdt, Ulrich; Bohr, Christopher

    2011-09-01

    The aim of this study was to look for visual subjective and objective parameters of vocal fold dynamics being capable of differentiating healthy from pathologic voices in daily clinical practice applying endoscopic high-speed digital imaging (HSI). Four hundred ninety-six datasets containing 80 healthy and 416 pathologic subjects (232 functional dysphonia (FD), 13 bilateral, and 171 unilateral vocal fold nerve paralysis) were analyzed retrospectively. Videos at 4000Hz (256×256 pixel) were recorded during sustained phonation. Subjective parameters were visually evaluated and complemented by an analysis of objective parameters. Visual subjective parameters were mucosal wave, glottal closure type, glottal closure insufficiency (GI), asymmetries of the vocal folds, and phonovibrogram (PVG) symmetry. After image segmentation, objective parameters were computed: closed quotient, perturbation measures (PMs) of glottal area, and left-right asymmetry values. HSI evaluation enabled to distinguish healthy from pathologic voices. For visual subjective parameters, GI, symmetrical behavior, and PVG symmetry exhibited statistical significant differences. For 95% of the data, objective parameters could be computed. Among objective parameters, closed quotient, jitter, shimmer, harmonic-to-noise ratio, and signal-to-noise ratio for the glottal area function differentiated statistically significant normal from pathologic voices. Applying linear discriminant analysis by combining visual subjective and objective parameters, accurate classifications were made for 63.2% of the female and 87.5% of the male group for the three-class problem (healthy, FD, and unilateral vocal fold nerve paralysis). Actual acoustically applied PMs can be transferred to clinical beneficial HSI analysis. Combining visual subjective and objective basic parameters succeeds in differentiating pathologic from healthy voices. The presented evaluation can easily be included into everyday clinical practice. However

  15. An in vitro setup to test the relevance and the accuracy of low-order vocal folds models.

    PubMed

    Ruty, Nicolas; Pelorson, Xavier; Van Hirtum, Annemie; Lopez-Arteaga, Ines; Hirschberg, Avraham

    2007-01-01

    An experimental setup and human vocal folds replica able to produce self-sustained oscillations are presented. The aim of the setup is to assess the relevance and the accuracy of theoretical vocal folds models. The applied reduced mechanical models are a variation of the classical two-mass model, and a simplification inspired on the delayed mass model for which the coupling between the masses is expressed as a fixed time delay. The airflow is described as a laminar flow with flow separation. The influence of a downstream resonator is taken into account. The oscillation pressure threshold and fundamental frequency are predicted by applying a stability analysis to the mechanical models. The measured frequency response of the mechanical replica together with the initial (rest) area allows us to determine the model parameters (spring stiffness, damping, geometry, masses). Validation of theoretical model predictions to experimental data shows the relevance of low-order models in gaining a qualitative understanding of phonation. However, quantitative discrepancies remain large due to an inaccurate estimation of the model parameters and the crudeness in either flow or mechanical model description. As an illustration it is shown that significant improvements can be made by accounting for viscous flow effects.

  16. Note: Network random walk model of two-state protein folding: Test of the theory

    NASA Astrophysics Data System (ADS)

    Berezhkovskii, Alexander M.; Murphy, Ronan D.; Buchete, Nicolae-Viorel

    2013-01-01

    We study two-state protein folding in the framework of a toy model of protein dynamics. This model has an important advantage: it allows for an analytical solution for the sum of folding and unfolding rate constants [A. M. Berezhkovskii, F. Tofoleanu, and N.-V. Buchete, J. Chem. Theory Comput. 7, 2370 (2011), 10.1021/ct200281d] and hence for the reactive flux at equilibrium. We use the model to test the Kramers-type formula for the reactive flux, which was derived assuming that the protein dynamics is described by a Markov random walk on a network of complex connectivity [A. Berezhkovskii, G. Hummer, and A. Szabo, J. Chem. Phys. 130, 205102 (2009), 10.1063/1.3139063]. It is shown that the Kramers-type formula leads to the same result for the reactive flux as the sum of the rate constants.

  17. Comparing a simple theoretical model for protein folding with all-atom molecular dynamics simulations.

    PubMed

    Henry, Eric R; Best, Robert B; Eaton, William A

    2013-10-29

    Advances in computing have enabled microsecond all-atom molecular dynamics trajectories of protein folding that can be used to compare with and test critical assumptions of theoretical models. We show that recent simulations by the Shaw group (10, 11, 14, 15) are consistent with a key assumption of an Ising-like theoretical model that native structure grows in only a few regions of the amino acid sequence as folding progresses. The distribution of mechanisms predicted by simulating the master equation of this native-centric model for the benchmark villin subdomain, with only two adjustable thermodynamic parameters and one temperature-dependent kinetic parameter, is remarkably similar to the distribution in the molecular dynamics trajectories.

  18. Studying vocal fold vibrations in Parkinson's disease with a nonlinear model

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Jiang, Jack; Rahn, Douglas A.

    2005-09-01

    A nonlinear model is applied to study pathologic vocal vibratory characteristics and voice treatments of Parkinson's disease. We find that a number of pathologic vocal characteristics commonly observed in Parkinson's disease, including reduced vibratory intensity, incomplete vocal closure, increased phonation threshold pressure, glottal tremor, subharmonics, and chaotic vocal fold vibrations, can be studied with this nonlinear model. We also find that two kinds of clinical voice treatments for Parkinson's disease, including respiratory effort treatment and Lee Silverman voice treatment can be studied with this computer model. Results suggest that respiratory effort treatment, in which subglottal pressure is increased, might aid in enhancing vibratory intensity, improving glottal closure, and avoiding vibratory irregularity. However, the Lee Silverman voice treatment, in which both subglottal pressure and vocal fold adduction are increased, might be better than respiratory effort treatment. Increasing vocal fold thickness would be further helpful to improve these pathologic characteristics. The model studies show consistencies with clinical observations. Computer models may be of value in understanding the dynamic mechanism of disordered voices and studying voice treatment effects in Parkinson's disease.

  19. Inverse protein folding in 3D hexagonal prism lattice under HPC model.

    PubMed

    Khodabakhshi, Alireza Hadj; Manuch, Ján; Rafiey, Arash; Gupta, Arvind

    2009-06-01

    The inverse protein folding problem is that of designing an amino acid sequence which has a prescribed native protein fold. This problem arises in drug design where a particular structure is necessary to ensure proper protein-protein interactions. Previously, tubular structures for a three-dimensional (3D) hexagonal prism lattice were introduced and their stability was formally proved for simple instances under the hydrophobic-polar (HP) model of Dill. In this article, we generalize the design of tubular structures to allow for much larger variety of designable structures by allowing branching of tubes. Our generalized design could be used to roughly approximate given 3D shapes in the considered lattice. Although the generalized tubular structures are not stable under the HP model, we can prove that a simple instance of generalized tubular structures is structurally stable (all native folds have the designed shape) under a refined version of the HP model, called the HPC model. We conjecture that there is a way to choose which hydrophobic monomers are cysteines in all generalized tubular structures such that the designed proteins are structurally stable under the HPC model.

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

    NASA Astrophysics Data System (ADS)

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

    PubMed

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

    2013-02-02

    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.

  2. A Synthetic Self-Oscillating Vocal Fold Model Platform for Studying Augmentation Injection

    PubMed Central

    Murray, Preston R.; Thomson, Scott L.; Smith, Marshall E.

    2013-01-01

    Objective Design and evaluate a platform for studying the mechanical effects of augmentation injections using synthetic self-oscillating vocal fold models. Study Design Basic science. Methods Life-sized, synthetic, multi-layer, self-oscillating vocal fold models were created that simulated bowing via volumetric reduction of the body layer relative to that of a normal, unbowed model. Material properties of the layers were unchanged. Models with varying degrees of bowing were created and paired with normal models. Following initial acquisition of data (onset pressure, vibration frequency, flow rate, and high-speed image sequences), bowed models were injected with silicone that had material properties similar to those used in augmentation procedures. Three different silicone injection quantities were tested: sufficient to close the glottal gap, insufficient to close the glottal gap, and excess silicone to create convex bowing of the bowed model. The above-mentioned metrics were again taken and compared. Pre- and post-injection high-speed image sequences were acquired using a hemilarynx setup, from which medial surface dynamics were quantified. Results The models vibrated with mucosal wave-like motion and at onset pressures and frequencies typical of human phonation. The models successfully exhibited various degrees of bowing which were then mitigated by injecting filler material. The models showed general pre- to post-injection decreases in onset pressure, flow rate, and open quotient, and a corresponding increase in vibration frequency. Conclusion The model may be useful in further explorations of the mechanical consequences of augmentation injections. PMID:24476985

  3. Computerized Analysis of Vocal Folds Vibration From Laryngeal Videostroboscopy.

    PubMed

    Gora, Silvia; Yavin, Noy; Elad, David; Wolf, Michael; Primov-Fever, Adi

    2016-07-01

    To develop an objective analysis of laryngeal videostroboscopy (VSS) movies in the space-time domain for quantitative determination of the true vocal folds (TVFs) vibratory pattern to allow for detection of local pathologies at early stages of development. Contours of the TVF and false vocal folds (FVFs) were tracked on each frame of a VSS movie. A registration algorithm was used with respect to the centerline of the FVF to eliminate movements not related to TVF vibration. The registered contours of the TVF were analyzed in time and frequency domains. The TVF vibration demonstrated a sinusoidal pattern with the same fundamental frequency at every section along the folds of healthy subjects, as well as detection of an abnormal area with a different fundamental frequency in TVF with local pathologies. Analysis of the TVF vibration time delay of healthy subject revealed a posterior-to-anterior longitudinal wave that was not detected by visual observation. An objective analysis of laryngeal VSS movies was developed for quantitative determination of the TVF vibration. This analysis was able to detect and quantify TVF characteristics in normal subjects as well as in patients with pathologies beyond the ability of examinee's naked eyes. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  4. Dissecting the stability of a beta-hairpin peptide that folds in water: NMR and molecular dynamics analysis of the beta-turn and beta-strand contributions to folding.

    PubMed

    Griffiths-Jones, S R; Maynard, A J; Searle, M S

    1999-10-08

    NMR studies of the folding and conformational properties of a beta-hairpin peptide, several peptide fragments of the hairpin, and sequence-modified analogues, have enabled the various contributions to beta-hairpin stability in water to be dissected. Temperature and pH-induced unfolding studies indicate that the folding-unfolding equilibrium approximates to a two-state model. The hairpin is highly resistant to denaturation and is still significantly folded in 7 M urea at 298 K. Thermodynamic analysis shows the hairpin to fold in water with a significant change in heat capacity, however, DeltaCp degrees in 7 M urea is reduced. V/Y-->A mutations on one strand of the hairpin reduce folding to <10 %, consistent with a hydrophobic stabilisation model. We show that in a truncated peptide (residues 6-16) lacking the hydrophobic residues on one beta-strand, the type I' Asn-Gly turn in the sequence SINGKK is significantly populated in water in the absence of interstrand hydrophobic contacts. Unrestrained molecular dynamics simulations of unfolding, using an explicit solvation model, show that the conformation of the NG turn persists for longer than the AG analogue, which has a much lower propensity for type I' turn formation from a data base analysis of preferred turns. The origin of the high stability of the Asn-Gly turn is not entirely clear; data base analysis of 66 NG turns, together with molecular dynamics simulations, reveals no participation of the Asn side-chain in turn-stabilising interactions with the peptide backbone. However, hydration analysis of the molecular dynamics simulations reveals a pocket of "high density" water bridging between the Asn side-chain and peptide main-chain that suggests solvent-mediated interactions may play an important role in modulating phi,psi propensities in the NG turn region.

  5. A mechanical model of vocal-fold collision with high spatial and temporal resolution

    NASA Astrophysics Data System (ADS)

    Gunter, Heather E.

    2003-02-01

    The tissue mechanics governing vocal-fold closure and collision during phonation are modeled in order to evaluate the role of elastic forces in glottal closure and in the development of stresses that may be a risk factor for pathology development. The model is a nonlinear dynamic contact problem that incorporates a three-dimensional, linear elastic, finite-element representation of a single vocal fold, a rigid midline surface, and quasistatic air pressure boundary conditions. Qualitative behavior of the model agrees with observations of glottal closure during normal voice production. The predicted relationship between subglottal pressure and peak collision force agrees with published experimental measurements. Accurate predictions of tissue dynamics during collision suggest that elastic forces play an important role during glottal closure and are an important determinant of aerodynamic variables that are associated with voice quality. Model predictions of contact force between the vocal folds are directly proportional to compressive stress (r2=0.79), vertical shear stress (r2=0.69), and Von Mises stress (r2=0.83) in the tissue. These results guide the interpretation of experimental measurements by relating them to a quantity that is important in tissue damage.

  6. Smoothing Protein Energy Landscapes by Integrating Folding Models with Structure Prediction

    PubMed Central

    Pritchard-Bell, Ari; Shell, M. Scott

    2011-01-01

    Decades of work has investigated the energy landscapes of simple protein models, but what do the landscapes of real, large, atomically detailed proteins look like? We explore an approach to this problem that systematically extracts simple funnel models of actual proteins using ensembles of structure predictions and physics-based atomic force fields and sampling. Central to our effort are calculations of a quantity called the relative entropy, which quantifies the extent to which a given set of structure decoys and a putative native structure can be projected onto a theoretical funnel description. We examine 86 structure prediction targets and one coupled folding-binding system, and find that in a majority of cases the relative entropy robustly signals which structures are nearest to native (i.e., which appear to lie closest to a funnel bottom). Importantly, the landscape model improves substantially upon purely energetic measures in scoring decoys. Our results suggest that physics-based models—including both folding theories and all-atom force fields—may be successfully integrated with structure prediction efforts. Conversely, detailed predictions of structures and the relative entropy approach enable one to extract coarse topographic features of protein landscapes that may enhance the development and application of simpler folding models. PMID:22067165

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

    NASA Astrophysics Data System (ADS)

    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. Intermediate decollement activation in response to the basal friction variation and its effect on folding style in the Zagros fold-thrust belt, an analogue modeling approach

    NASA Astrophysics Data System (ADS)

    Farzipour-Saein, Ali; Koyi, Hemin

    2016-09-01

    Although the role of various basal and intermediate decollement levels on structural style is well documented individually in many folded terrains, the interaction between basal and intermediate decollements is poorly constrained. This study uses results of two scaled sand-box models shortened from one end to study the variation in structural development in response to varying basal friction and its consequent interaction with intermediate decollement horizons. Two models with similar incompetent intermediate decollement, but with different basal friction (with and without a thick basal decollement), were prepared analogous for the eastern and the western parts of the Razak basement fault in the Fars Region of the eastern part of the Zagros fold thrust belt (ZFTB). Combined results of scaled models with geological observations are used to argue that the basal decollement friction characteristics govern propagation of deformation front. In addition, model results, analogues to north-south direction, show that deformation complexity and disharmonic folding exist in the section where the intermediate decollement has been activated in response to the shortening without the basal decollement (throughout the western part of the Razak basement fault where less thickness of the Hormuz series as the basal decollement has been documented compared to its eastern part). In other words, the complexity in deformation is less portrayed along sections where basal friction beneath the model decreases (e.g. the eastern part of the Razak basement fault). We argue here that, in addition to other parameters (not presented in this study) interaction of intermediate decollement levels with basal decollement friction characteristics could explain decoupling between structures within the sedimentary column of the Fars Region of the eastern part of the Zagros fold thrust belt.

  9. Polymer models of the hierarchical folding of the Hox-B chromosomal locus

    NASA Astrophysics Data System (ADS)

    Annunziatella, Carlo; Chiariello, Andrea M.; Bianco, Simona; Nicodemi, Mario

    2016-10-01

    As revealed by novel technologies, chromosomes in the nucleus of mammalian cells have a complex spatial organization that serves vital functional purposes. Here we use models from polymer physics to identify the mechanisms that control their three-dimensional spatial organization. In particular, we investigate a model of the Hox-B locus, an important genomic region involved in embryo development, to expose the principles regulating chromatin folding and its complex behaviors in mouse embryonic stem cells. We reconstruct with high accuracy the pairwise contact matrix of the Hox-B locus as derived by Hi-C experiments and investigate its hierarchical folding dynamics. We trace back the observed behaviors to general scaling properties of polymer physics.

  10. A lumped mucosal wave model of the vocal folds revisited: Recent extensions and oscillation hysteresis

    PubMed Central

    Lucero, Jorge C.; Koenig, Laura L.; Lourenço, Kelem G.; Ruty, Nicolas; Pelorson, Xavier

    2011-01-01

    This paper examines an updated version of a lumped mucosal wave model of the vocal fold oscillation during phonation. Threshold values of the subglottal pressure and the mean (DC) glottal airflow for the oscillation onset are determined. Depending on the nonlinear characteristics of the model, an oscillation hysteresis phenomenon may occur, with different values for the oscillation onset and offset threshold. The threshold values depend on the oscillation frequency, but the occurrence of the hysteresis is independent of it. The results are tested against pressure data collected from a mechanical replica of the vocal folds, and oral airflow data collected from speakers producing intervocalic ∕h∕. In the human speech data, observed differences between voice onset and offset may be attributed to variations in voice pitch, with a very small or inexistent hysteresis phenomenon. PMID:21428520

  11. Rapid Sampling of Folding Equilibria of β-Peptides in Methanol Using a Supramolecular Solvent Model.

    PubMed

    Huang, Wei; Riniker, Sereina; van Gunsteren, Wilfred F

    2014-06-10

    Molecular dynamics simulation of biomolecules in solvent using an atomic model for both the biomolecules and the solvent molecules is still computationally rather demanding considering the time scale of the biomolecular motions. The use of a supramolecular coarse-grained (CG) model can speed up the simulation considerably, but it also reduces the accuracy inevitably. Combining an atomic fine-grained (FG) level of modeling for the biomolecules and a supramolecular CG level for the solvent into a hybrid system, the increased computational efficiency may outweigh the loss of accuracy with respect to the biomolecular properties in the hybrid FG/CG simulation. Here, a previously published CG methanol model is reparametrized, and then a 1:1 mixture of FG and CG methanol is used to calibrate the FG-CG interactions using thermodynamic and dielectric screening data for liquid methanol. The FG-CG interaction parameter set is applied in hybrid FG/CG solute/solvent simulations of the folding equilibria of three β-peptides that adopt different folds. The properties of the peptides are compared with those obtained in FG solvent simulations and with experimental NMR data. The comparison shows that the folding equilibria in the pure CG solvent simulations are different from those in the FG solvent simulations because of the lack of hydrogen-bonding partners in the supramolecular CG solvent. Next, we introduced an FG methanol layer around the peptides in CG solvent to recover the hydrogen-bonding pattern of the FG solvent simulations. The result shows that with the FG methanol layer, the folding equilibria of the three β-peptides are very similar to those in the FG solvent simulations, while the computational efficiency is at least 3 times higher and the cutoff radius for nonbonded interactions could be increased from 1.4 to 2.0 nm.

  12. Differences between the deformed-potential and folding-model descriptions of inelastic nuclear scattering

    SciTech Connect

    Hnizdo, V. )

    1994-08-01

    The differences between the deformed-potential and folding-model descriptions of inelastic nuclear scattering, attention to which has been called recently by Beene, Horen, and Satchler [Phys. Rev. C 48, 3128 (1993)], were pointed out already some time ago by contrasting the rules of equal deformation lengths and equal normalized multipole moments for the optical potential and the underlying nucleon distribution of the excited nucleus.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Double Folding Potential of Different Interaction Models for 16O + 12C Elastic Scattering

    NASA Astrophysics Data System (ADS)

    Hamada, Sh.; Bondok, I.; Abdelmoatmed, M.

    2016-12-01

    The elastic scattering angular distributions for 16O + 12C nuclear system have been analyzed using double folding potential of different interaction models: CDM3Y1, CDM3Y6, DDM3Y1 and BDM3Y1. We have extracted the renormalization factor N r for the different concerned interaction models. Potential created by BDM3Y1 model of interaction has the shallowest depth which reflects the necessity to use higher renormalization factor. The experimental angular distributions for 16O + 12C nuclear system in the energy range 115.9-230 MeV exhibited unmistakable refractive features and rainbow phenomenon.

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

    PubMed Central

    Kwag, Hye Rin; Serbo, Janna V.; Korangath, Preethi; Sukumar, Saraswati

    2016-01-01

    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. PMID:26831041

  16. Understanding protein domain-swapping using structure-based models of protein folding.

    PubMed

    Mascarenhas, Nahren Manuel; Gosavi, Shachi

    2017-09-01

    In domain-swapping, two or more identical protein monomers exchange structural elements and fold into dimers or multimers whose units are structurally similar to the original monomer. Domain-swapping is of biotechnological interest because inhibiting domain-swapping can reduce disease-causing fibrillar protein aggregation. To achieve such inhibition, it is important to understand both the energetics that stabilize the domain-swapped structure and the protein dynamics that enable the swapping. Structure-based models (SBMs) encode the folded structure of the protein in their potential energy functions. SBMs have been successfully used to understand diverse aspects of monomer folding. Symmetrized SBMs model interactions between two identical protein chains using only intra-monomer interactions. Molecular dynamics simulations of such symmetrized SBMs have been used to correctly predict the domain-swapped structure and to understand the mechanism of domain-swapping. Here, we review such models and illustrate that monomer topology determines key aspects of domain-swapping. However, in some proteins, specifics of local energetic interactions modulate domain-swapping and these need to be added to the symmetrized SBMs. We then summarize some general principles of the mechanism of domain-swapping that emerge from the symmetrized SBM simulations. Finally, using our own results, we explore how symmetrized SBMs could be used to design domain-swapping in proteins. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  18. Chemically Based Mathematical Model for Development of Cerebral Cortical Folding Patterns

    PubMed Central

    Striegel, Deborah A.; Hurdal, Monica K.

    2009-01-01

    The mechanism for cortical folding pattern formation is not fully understood. Current models represent scenarios that describe pattern formation through local interactions, and one recent model is the intermediate progenitor model. The intermediate progenitor (IP) model describes a local chemically driven scenario, where an increase in intermediate progenitor cells in the subventricular zone correlates to gyral formation. Here we present a mathematical model that uses features of the IP model and further captures global characteristics of cortical pattern formation. A prolate spheroidal surface is used to approximate the ventricular zone. Prolate spheroidal harmonics are applied to a Turing reaction-diffusion system, providing a chemically based framework for cortical folding. Our model reveals a direct correlation between pattern formation and the size and shape of the lateral ventricle. Additionally, placement and directionality of sulci and the relationship between domain scaling and cortical pattern elaboration are explained. The significance of this model is that it elucidates the consistency of cortical patterns among individuals within a species and addresses inter-species variability based on global characteristics and provides a critical piece to the puzzle of cortical pattern formation. PMID:19779554

  19. Perturbations of the denatured state ensemble: modeling their effects on protein stability and folding kinetics.

    PubMed Central

    Wrabl, J. O.; Shortle, D.

    1996-01-01

    By considering the denatured state of a protein as an ensemble of conformations with varying numbers of sequence-specific interactions, the effects on stability, folding kinetics, and aggregation of perturbing these interactions can be predicted from changes in the molecular partition function. From general considerations, the following conclusions are drawn: (1) A perturbation that enhances a native interaction in denatured state conformations always increases the stability of the native state. (2) A perturbation that promotes a non-native interaction in the denatured state always decreases the stability of the native state. (3) A change in the denatured state ensemble can alter the kinetics of aggregation and folding. (4) The loss (or increase) in stability accompanying two mutations, each of which lowers (or raises) the free energy of the denatured state, will be less than the sum of the effects of the single mutations, except in cases where both mutations affect the same set of partially folded conformations. By modeling the denatured state as the ensemble of all non-native conformations of hydrophobic-polar (HP) chains configured on a square lattice, it can be shown that the stabilization obtained from enhancement of native interactions derives in large measure from the avoidance of non-native interactions in the D state. In addition, the kinetic effects of fixing single native contacts in the denatured state or imposing linear gradients in the HH contact probabilities are found, for some sequences, to significantly enhance the efficiency of folding by a simple hydrophobic zippering algorithm. Again, the dominant mechanism appears to be avoidance of non-native interactions. These results suggest stabilization of native interactions and imposition of gradients in the stability of local structure are two plausible mechanisms involving the denatured state that could play a role in the evolution of protein folding and stability. PMID:8931153

  20. β-hairpin-forming peptides; models of early stages of protein folding

    PubMed Central

    Lewandowska, Agnieszka; Ołdziej, Stanisław; Liwo, Adam; Scheraga, Harold A.

    2010-01-01

    Formation of β-hairpins is considered the initial step of folding of many proteins and, consequently, peptides constituting the β-hairpin sequence of proteins (the β-hairpin-forming peptides) are considered as models of early stages of protein folding. In this article, we discuss the results of experimental studies (circular-dichroism, infrared and nuclear magnetic resonance spectroscopy, and differential scanning calorimetry) of the structure of β-hairpin-forming peptides excised from the B1 domain of protein G, which are known to fold on their own. We demonstrate that local interactions at the turn sequence and hydrophobic interactions between nonpolar residues are the dominant structure-determining factors, while there is no convincing evidence that stable backbone hydrogen bonds are formed in these peptides in aqueous solution. Consequently, the most plausible mechanism for folding of the β-hairpin sequence appears to be the broken-zipper mechanism consisting of the following three steps: (i) bending the chain at the turn sequence owing to favorable local interactions, (ii) formation of loose hydrophobic contacts between nonpolar residues, which occur close to the contacts in the native structure of the protein but not exactly in the same position and, finally, (iii) formation of backbone hydrogen bonds and locking the hydrophobic contacts in the native positions as a hydrophobic core develops, sufficient to dehydrate the backbone peptide groups. This mechanism provides sufficient uniqueness (contacts form between residues that become close together because the chain is bent at the turn position) and robustness (contacts need not occur at once in the native positions) for folding a β-hairpin sequence. PMID:20494507

  1. A geometric model of faulted detachment folding with pure shear and its application in the Tarim Basin, NW China

    NASA Astrophysics Data System (ADS)

    Yao, Zewei; He, Guangyu; Zheng, Xiaoli; Dong, Chuanwan; Cao, Zicheng; Yang, Suju; Gu, Yi

    2016-11-01

    We present an improved geometric model of faulted detachment folding with pure shear that is characterized by core thickening and a ramp-discordant backlimb. The model includes a two-stage evolution: 1) detachment folding involving pure shear with fixed hinges, and 2) faulted detachment folding, in which the core of anticline thrusts above a break-through fault in forelimb by limb rotation. The growth strata patterns of the model are also discussed with respect to factors such as limb rotation, tectonic uplift rate, and sedimentation rate. A thrust-related fold, called a TBE thrust fold, in the Tarim Basin in NW China, is analyzed as an example of the theoretical model. The result indicates that the TBE thrust fold has undergone a two-stage evolution with shortening of a few hundred meters. Both the theoretical model and the actual example indicate that the shortening in the detachment folding stage takes up a large proportion of the total shortening. The structural restoration of the TBE thrust fold also provides new evidence that the formation of a series of thin-skinned structures in the SE Tarim Basin initiated in the Late Ordovician. The model may be applicable to lowamplitude faulted detachment folds.

  2. Structure of the adenovirus E4 Orf6 protein predicted by fold recognition and comparative protein modeling.

    PubMed

    Brown, L M; Gonzalez, R A; Novotny, J; Flint, S J

    2001-08-01

    To facilitate investigation of the molecular and biochemical functions of the adenovirus E4 Orf6 protein, we sought to derive three-dimensional structural information using computational methods, particularly threading and comparative protein modeling. The amino acid sequence of the protein was used for secondary structure and hidden Markov model (HMM) analyses, and for fold recognition by the ProCeryon program. Six alternative models were generated from the top-scoring folds identified by threading. These models were examined by 3D-1D analysis and evaluated in the light of available experimental evidence. The final model of the E4 protein derived from these and additional threading calculations was a chimera, with the tertiary structure of its C-terminal 226 residues derived from a TIM barrel template and a mainly alpha-nonbundle topology for its poorly conserved N-terminal 68 residues. To assess the accuracy of this model, additional threading calculations were performed with E4 Orf6 sequences altered as in previous experimental studies. The proposed structural model is consistent with the reported secondary structure of a functionally important C-terminal sequence and can account for the properties of proteins carrying alterations in functionally important sequences or of those that disrupt an unusual zinc-coordination motif.

  3. A three-dimensional statistical mechanical model of folding double-stranded chain molecules

    NASA Astrophysics Data System (ADS)

    Zhang, Wenbing; Chen, Shi-Jie

    2001-05-01

    Based on a graphical representation of intrachain contacts, we have developed a new three-dimensional model for the statistical mechanics of double-stranded chain molecules. The theory has been tested and validated for the cubic lattice chain conformations. The statistical mechanical model can be applied to the equilibrium folding thermodynamics of a large class of chain molecules, including protein β-hairpin conformations and RNA secondary structures. The application of a previously developed two-dimensional model to RNA secondary structure folding thermodynamics generally overestimates the breadth of the melting curves [S-J. Chen and K. A. Dill, Proc. Natl. Acad. Sci. U.S.A. 97, 646 (2000)], suggesting an underestimation for the sharpness of the conformational transitions. In this work, we show that the new three-dimensional model gives much sharper melting curves than the two-dimensional model. We believe that the new three-dimensional model may give much improved predictions for the thermodynamic properties of RNA conformational changes than the previous two-dimensional model.

  4. A three-dimensional model of vocal fold abduction/adduction

    NASA Astrophysics Data System (ADS)

    Hunter, Eric J.; Titze, Ingo R.; Alipour, Fariborz

    2004-04-01

    A three-dimensional biomechanical model of tissue deformation was developed to simulate dynamic vocal fold abduction and adduction. The model was made of 1721 nearly incompressible finite elements. The cricoarytenoid joint was modeled as a rocking-sliding motion, similar to two concentric cylinders. The vocal ligament and the thyroarytenoid muscle's fiber characteristics were implemented as a fiber-gel composite made of an isotropic ground substance imbedded with fibers. These fibers had contractile and/or passive nonlinear stress-strain characteristics. The verification of the model was made by comparing the range and speed of motion to published vocal fold kinematic data. The model simulated abduction to a maximum glottal angle of about 31°. Using the posterior-cricoarytenoid muscle, the model produced an angular abduction speed of 405° per second. The system mechanics seemed to favor abduction over adduction in both peak speed and response time, even when all intrinsic muscle properties were kept identical. The model also verified the notion that the vocalis and muscularis portions of the thyroarytenoid muscle play significantly different roles in posturing, with the muscularis portion having the larger effect on arytenoid movement. Other insights into the mechanisms of abduction/adduction were given.

  5. Spatio-temporal analysis of irregular vocal fold oscillations: Biphonation due to desynchronization of spatial modes

    NASA Astrophysics Data System (ADS)

    Neubauer, Jürgen; Mergell, Patrick; Eysholdt, Ulrich; Herzel, Hanspeter

    2001-12-01

    This report is on direct observation and modal analysis of irregular spatio-temporal vibration patterns of vocal fold pathologies in vivo. The observed oscillation patterns are described quantitatively with multiline kymograms, spectral analysis, and spatio-temporal plots. The complex spatio-temporal vibration patterns are decomposed by empirical orthogonal functions into independent vibratory modes. It is shown quantitatively that biphonation can be induced either by left-right asymmetry or by desynchronized anterior-posterior vibratory modes, and the term ``AP (anterior-posterior) biphonation'' is introduced. The presented phonation examples show that for normal phonation the first two modes sufficiently explain the glottal dynamics. The spatio-temporal oscillation pattern associated with biphonation due to left-right asymmetry can be explained by the first three modes. Higher-order modes are required to describe the pattern for biphonation induced by anterior-posterior vibrations. Spatial irregularity is quantified by an entropy measure, which is significantly higher for irregular phonation than for normal phonation. Two asymmetry measures are introduced: the left-right asymmetry and the anterior-posterior asymmetry, as the ratios of the fundamental frequencies of left and right vocal fold and of anterior-posterior modes, respectively. These quantities clearly differentiate between left-right biphonation and anterior-posterior biphonation. This paper proposes methods to analyze quantitatively irregular vocal fold contour patterns in vivo and complements previous findings of desynchronization of vibration modes in computer modes and in in vitro experiments.

  6. 3D Fault modeling of the active Chittagong-Myanmar fold belt, Bangladesh

    NASA Astrophysics Data System (ADS)

    Peterson, D. E.; Hubbard, J.; Akhter, S. H.; Shamim, N.

    2013-12-01

    The Chittagong-Myanmar fold belt (CMFB), located in eastern Bangladesh, eastern India and western Myanmar, accommodates east-west shortening at the India-Burma plate boundary. Oblique subduction of the Indian Plate beneath the Burma Plate since the Eocene has led to the development of a large accretionary prism complex, creating a series of north-south trending folds. A continuous sediment record from ~55 Ma to the present has been deposited in the Bengal Basin by the Ganges-Brahmaputra-Meghna rivers, providing an opportunity to learn about the history of tectonic deformation and activity in this fold-and-thrust belt. Surface mapping indicates that the fold-and-thrust belt is characterized by extensive N-S-trending anticlines and synclines in a belt ~150-200 km wide. Seismic reflection profiles from the Chittagong and Chittagong Hill Tracts, Bangladesh, indicate that the anticlines mapped at the surface narrow with depth and extend to ~3.0 seconds TWTT (two-way travel time), or ~6.0 km. The folds of Chittagong and Chittagong Hill Tracts are characterized by doubly plunging box-shaped en-echelon anticlines separated by wide synclines. The seismic data suggest that some of these anticlines are cored by thrust fault ramps that extend to a large-scale décollement that dips gently to the east. Other anticlines may be the result of detachment folding from the same décollement. The décollement likely deepens to the east and intersects with the northerly-trending, oblique-slip Kaladan fault. The CMFB region is bounded to the north by the north-dipping Dauki fault and the Shillong Plateau. The tectonic transition from a wide band of E-W shortening in the south to a narrow zone of N-S shortening along the Dauki fault is poorly understood. We integrate surface and subsurface datasets, including topography, geological maps, seismicity, and industry seismic reflection profiles, into a 3D modeling environment and construct initial 3D surfaces of the major faults in this

  7. Computation of physiological human vocal fold parameters by mathematical optimization of a biomechanical model

    PubMed Central

    Yang, Anxiong; Stingl, Michael; Berry, David A.; Lohscheller, Jörg; Voigt, Daniel; Eysholdt, Ulrich; Döllinger, Michael

    2011-01-01

    With the use of an endoscopic, high-speed camera, vocal fold dynamics may be observed clinically during phonation. However, observation and subjective judgment alone may be insufficient for clinical diagnosis and documentation of improved vocal function, especially when the laryngeal disease lacks any clear morphological presentation. In this study, biomechanical parameters of the vocal folds are computed by adjusting the corresponding parameters of a three-dimensional model until the dynamics of both systems are similar. First, a mathematical optimization method is presented. Next, model parameters (such as pressure, tension and masses) are adjusted to reproduce vocal fold dynamics, and the deduced parameters are physiologically interpreted. Various combinations of global and local optimization techniques are attempted. Evaluation of the optimization procedure is performed using 50 synthetically generated data sets. The results show sufficient reliability, including 0.07 normalized error, 96% correlation, and 91% accuracy. The technique is also demonstrated on data from human hemilarynx experiments, in which a low normalized error (0.16) and high correlation (84%) values were achieved. In the future, this technique may be applied to clinical high-speed images, yielding objective measures with which to document improved vocal function of patients with voice disorders. PMID:21877808

  8. Folding of small knotted proteins: Insights from a mean field coarse-grained model

    NASA Astrophysics Data System (ADS)

    Najafi, Saeed; Potestio, Raffaello

    2015-12-01

    A small but relevant number of proteins whose native structure is known features nontrivial topology, i.e., they are knotted. Understanding the process of folding from a swollen unknotted state to the biologically relevant native conformation is, for these proteins, particularly difficult, due to their rate-limiting topological entanglement. To shed some light into this conundrum, we introduced a structure-based coarse-grained model of the protein, where the information about the folded conformation is encoded in bonded angular interactions only, which do not favor the formation of native contacts. A stochastic search scheme in parameter space is employed to identify a set of interactions that maximizes the probability to attain the knotted state. The optimal knotting pathways of the two smallest knotted proteins, obtained through this approach, are consistent with the results derived by means of coarse-grained as well as full atomistic simulations.

  9. Folding of small knotted proteins: Insights from a mean field coarse-grained model

    SciTech Connect

    Najafi, Saeed; Potestio, Raffaello

    2015-12-28

    A small but relevant number of proteins whose native structure is known features nontrivial topology, i.e., they are knotted. Understanding the process of folding from a swollen unknotted state to the biologically relevant native conformation is, for these proteins, particularly difficult, due to their rate-limiting topological entanglement. To shed some light into this conundrum, we introduced a structure-based coarse-grained model of the protein, where the information about the folded conformation is encoded in bonded angular interactions only, which do not favor the formation of native contacts. A stochastic search scheme in parameter space is employed to identify a set of interactions that maximizes the probability to attain the knotted state. The optimal knotting pathways of the two smallest knotted proteins, obtained through this approach, are consistent with the results derived by means of coarse-grained as well as full atomistic simulations.

  10. Derivation of a solubility condition for proteins from an analysis of the competition between folding and aggregation.

    PubMed

    Pechmann, Sebastian; Vendruscolo, Michele

    2010-12-01

    Failure in maintaining protein solubility in vivo impairs protein homeostasis and results in protein misfolding and aggregation, which are often associated with severe neurodegenerative and systemic disorders that include Alzheimer's and Parkinson's diseases and type II diabetes. In this work we formulate a model of the competition between folding and aggregation, and derive a condition on the solubility of proteins in terms of the stability of their folded states, their aggregation propensities and their degradation rates. From our model, the bistability between folding and aggregation emerges as an intrinsic aspect of protein homeostasis. The analysis of the conditions that determine such a bistability provides a rationalization of the recently observed relationship between the cellular abundance and the aggregation propensity of proteins. We then discuss how the solubility condition that we derive can help rationalise the correlation that has been reported between evolutionary rates and expression levels or proteins, as well as in vivo protein solubility and expression level measurements, and recently elucidated trends of proteome evolution.

  11. Flow-induced vibratory response of idealized versus magnetic resonance imaging-based synthetic vocal fold models

    PubMed Central

    Pickup, Brian A.; Thomson, Scott L.

    2010-01-01

    Recent vocal fold vibration studies have used models defined using idealized geometry. Although these models exhibit important similarities with human vocal fold vibration, some aspects of their motion are less than realistic. In this report it is demonstrated that more realistic motion may be obtained when using geometry derived from magnetic resonance imaging (MRI) data. The dynamic response of both idealized and MRI-based synthetic vocal fold models are presented. MRI-based model improvements include evidence of mucosal wave-like motion and less vertical movement. Limitations of the MRI-based model are discussed and suggestions for further synthetic model development are offered. PMID:20815428

  12. Influence of supraglottal structures on the glottal jet exiting a two-layer synthetic, self-oscillating vocal fold model

    PubMed Central

    Drechsel, James S.; Thomson, Scott L.

    2008-01-01

    A synthetic two-layer, self-oscillating, life-size vocal fold model was used to study the influence of the vocal tract and false folds on the glottal jet. The model vibrated at frequencies, pressures, flow rates, and amplitudes consistent with human phonation, although some differences in behavior between the model and the human vocal folds are noted. High-speed images of model motion and flow visualization were acquired. Phase-locked ensemble-averaged glottal jet velocity measurements using particle image velocimetry (PIV) were acquired with and without an idealized vocal tract, with and without false folds. PIV data were obtained with varying degrees of lateral asymmetric model positioning. Glottal jet velocity magnitudes were consistent with those measured using excised larynges. A starting vortex was observed in all test cases. The false folds interfered with the starting vortex, and in some cases vortex shedding from the false folds was observed. In asymmetric cases without false folds, the glottal jet tended to skew toward the nearest wall; with the false folds, the opposite trend was observed. rms velocity calculations showed the jet shear layer and laminar core. The rms velocities were higher in the vocal tract cases compared to the open jet and false fold cases. PMID:18537394

  13. Control of syntectonic erosion and sedimentation on kinematic evolution of a multidecollement fold and thrust zone: Analogue modeling of folding in the southern subandean of Bolivia

    NASA Astrophysics Data System (ADS)

    Darnault, Romain; Callot, Jean-Paul; Ballard, Jean-François; Fraisse, Guillaume; Mengus, Jean-Marie; Ringenbach, Jean-Claude

    2016-08-01

    Several analogue modeling studies have been conducted during the past fifteen years with the aim to discuss the effects of sedimentation and erosion on Foreland Fold and Thrust Belt, among which a few have analyzed these processes at kilometric scale (Malavieille et al., 1993; Nalpas et al., 1999; Barrier et al., 2002; Pichot and Nalpas, 2009). The influence of syn-deformation sedimentation and erosion on the structural evolution of FFTB has been clearly demonstrated. Here, we propose to go further in this approach by the study of a more complex system with a double decollement level. The natural study case is the Bolivian sub-Andean thrust and fold belt, which present all the required criteria, such as the double decollement level. A set of analogue models performed under a CT-scan have been used to test the influence of several parameters on a fold and thrust belt system, among which: (i) the spatial variation of the sediment input, (ii) the spatial variation of the erosion rate, (iii) the relative distribution of sedimentation between foreland and hinterland. These experiments led to the following observations: 1. The upper decollement level acts as a decoupling level in case of increased sedimentation rate: it results in the verticalization of the shallower part (above the upper decollement level), while the deeper parts are not impacted. 2. Similarly, the increase of the erosion rate involves the uplift of the deeper part (below the upper decollement level), whereas the shallower parts are not impacted. 3. A high sedimentation rate in the foreland involves a fault and fold vergence reversal, followed by a back-thrusting of the shallower part. 4. A high sedimentation rate in the hinterland favours thrust development toward the foreland in the shallower parts.

  14. Folding of polyglutamine chains

    NASA Astrophysics Data System (ADS)

    Chopra, Manan; Reddy, Allam S.; Abbott, N. L.; de Pablo, J. J.

    2008-10-01

    Long polyglutamine chains have been associated with a number of neurodegenerative diseases. These include Huntington's disease, where expanded polyglutamine (PolyQ) sequences longer than 36 residues are correlated with the onset of symptoms. In this paper we study the folding pathway of a 54-residue PolyQ chain into a β-helical structure. Transition path sampling Monte Carlo simulations are used to generate unbiased reactive pathways between unfolded configurations and the folded β-helical structure of the polyglutamine chain. The folding process is examined in both explicit water and an implicit solvent. Both models reveal that the formation of a few critical contacts is necessary and sufficient for the molecule to fold. Once the primary contacts are formed, the fate of the protein is sealed and it is largely committed to fold. We find that, consistent with emerging hypotheses about PolyQ aggregation, a stable β-helical structure could serve as the nucleus for subsequent polymerization of amyloid fibrils. Our results indicate that PolyQ sequences shorter than 36 residues cannot form that nucleus, and it is also shown that specific mutations inferred from an analysis of the simulated folding pathway exacerbate its stability.

  15. Equivalent Circuit Analysis of Serpentine Folded-waveguide Slow-wave Structures for Millimeter-wave Traveling-wave Tubes

    NASA Astrophysics Data System (ADS)

    Sumathy, M.; Vinoy, K. J.; Datta, S. K.

    2009-02-01

    A simple equivalent circuit model for the analysis of dispersion and interaction impedance characteristics of serpentine folded-waveguide slow-wave structure was developed by considering the straight and curved portions of structure supporting the dominant TE 10-mode of the rectangular waveguide. Expressions for the lumped capacitance and inductance per period of the slow-wave structure were derived in terms of the physical dimensions of the structure, incorporating the effects of the beam-hole in the lumped parameters. The lumped parameters were subsequently interpreted for obtaining the dispersion and interaction impedance characteristics of the structure. The analysis was simple yet accurate in predicting the dispersion and interaction impedance behaviour at millimeter-wave frequencies. The analysis was benchmarked against measurement as well as with 3D electromagnetic modeling using MAFIA for two typical slow-wave structures (one at the Ka-band and the other at the W-band) and close agreement observed.

  16. Entropy-Driven Folding of an RNA Helical Junction: An Isothermal Titration Calorimetric Analysis of the Hammerhead Ribozyme†

    PubMed Central

    Mikulecky, Peter J.; Takach, Jennifer C.; Feig, Andrew L.

    2008-01-01

    Helical junctions are extremely common motifs in naturally occurring RNAs, but little is known about the thermodynamics that drive their folding. Studies of junction folding face several challenges: non-two-state folding behavior, superposition of secondary and tertiary structural energetics, and drastically opposing enthalpic and entropic contributions to folding. Here we describe a thermodynamic dissection of the folding of the hammerhead ribozyme, a three-way RNA helical junction, by using isothermal titration calorimetry of bimolecular RNA constructs. By using this method, we show that tertiary folding of the hammerhead core occurs with a highly unfavorable enthalpy change, and is therefore entropically driven. Furthermore, the enthalpies and heat capacities of core folding are the same whether supported by monovalent or divalent ions. These properties appear to be general to the core sequence of bimolecular hammerhead constructs. We present a model for the ion-induced folding of the hammerhead core that is similar to those advanced for the folding of much larger RNAs, involving ion-induced collapse to a structured, non-native state accompanied by rearrangement of core residues to produce the native fold. In agreement with previous enzymological and structural studies, our thermodynamic data suggest that the hammerhead structure is stabilized in vitro predominantly by diffusely bound ions. Our approach addresses several significant challenges that accompany the study of junction folding, and should prove useful in defining the thermodynamic determinants of stability in these important RNA motifs. PMID:15134461

  17. Entropy-driven folding of an RNA helical junction: an isothermal titration calorimetric analysis of the hammerhead ribozyme.

    PubMed

    Mikulecky, Peter J; Takach, Jennifer C; Feig, Andrew L

    2004-05-18

    Helical junctions are extremely common motifs in naturally occurring RNAs, but little is known about the thermodynamics that drive their folding. Studies of junction folding face several challenges: non-two-state folding behavior, superposition of secondary and tertiary structural energetics, and drastically opposing enthalpic and entropic contributions to folding. Here we describe a thermodynamic dissection of the folding of the hammerhead ribozyme, a three-way RNA helical junction, by using isothermal titration calorimetry of bimolecular RNA constructs. By using this method, we show that tertiary folding of the hammerhead core occurs with a highly unfavorable enthalpy change, and is therefore entropically driven. Furthermore, the enthalpies and heat capacities of core folding are the same whether supported by monovalent or divalent ions. These properties appear to be general to the core sequence of bimolecular hammerhead constructs. We present a model for the ion-induced folding of the hammerhead core that is similar to those advanced for the folding of much larger RNAs, involving ion-induced collapse to a structured, non-native state accompanied by rearrangement of core residues to produce the native fold. In agreement with previous enzymological and structural studies, our thermodynamic data suggest that the hammerhead structure is stabilized in vitro predominantly by diffusely bound ions. Our approach addresses several significant challenges that accompany the study of junction folding, and should prove useful in defining the thermodynamic determinants of stability in these important RNA motifs.

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

    NASA Astrophysics Data System (ADS)

    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. Generic folding and transition hierarchies for surface adsorption of hydrophobic-polar lattice model proteins.

    PubMed

    Li, Ying Wai; Wüst, Thomas; Landau, David P

    2013-01-01

    The thermodynamic behavior and structural properties of hydrophobic-polar (HP) lattice proteins interacting with attractive surfaces are studied by means of Wang-Landau sampling. Three benchmark HP sequences (48mer, 67mer, and 103mer) are considered with different types of surfaces, each of which attract either all monomers, only hydrophobic (H) monomers, or only polar (P) monomers, respectively. The diversity of folding behavior in dependence of surface strength is discussed. Analyzing the combined patterns of various structural observables, such as, e.g., the derivatives of the numbers of surface contacts, together with the specific heat, we are able to identify generic categories of folding and transition hierarchies. We also infer a connection between these transition categories and the relative surface strengths, i.e., the ratio of the surface attractive strength to the interchain attraction among H monomers. The validity of our proposed classification scheme is reinforced by the analysis of additional benchmark sequences. We thus believe that the folding hierarchies and identification scheme are generic for HP proteins interacting with attractive surfaces, regardless of chain length, sequence, or surface attraction.

  20. Generic folding and transition hierarchies for surface adsorption of hydrophobic-polar lattice model proteins

    NASA Astrophysics Data System (ADS)

    Li, Ying Wai; Wüst, Thomas; Landau, David P.

    2013-01-01

    The thermodynamic behavior and structural properties of hydrophobic-polar (HP) lattice proteins interacting with attractive surfaces are studied by means of Wang-Landau sampling. Three benchmark HP sequences (48mer, 67mer, and 103mer) are considered with different types of surfaces, each of which attract either all monomers, only hydrophobic (H) monomers, or only polar (P) monomers, respectively. The diversity of folding behavior in dependence of surface strength is discussed. Analyzing the combined patterns of various structural observables, such as, e.g., the derivatives of the numbers of surface contacts, together with the specific heat, we are able to identify generic categories of folding and transition hierarchies. We also infer a connection between these transition categories and the relative surface strengths, i.e., the ratio of the surface attractive strength to the interchain attraction among H monomers. The validity of our proposed classification scheme is reinforced by the analysis of additional benchmark sequences. We thus believe that the folding hierarchies and identification scheme are generic for HP proteins interacting with attractive surfaces, regardless of chain length, sequence, or surface attraction.

  1. A discriminative feature selection approach for shape analysis: Application to fetal brain cortical folding.

    PubMed

    Pontabry, J; Rousseau, F; Studholme, C; Koob, M; Dietemann, J-L

    2017-01-01

    The development of post-processing reconstruction techniques has opened new possibilities for the study of in-utero fetal brain MRI data. Recent cortical surface analysis have led to the computation of quantitative maps characterizing brain folding of the developing brain. In this paper, we describe a novel feature selection-based approach that is used to extract the most discriminative and sparse set of features of a given dataset. The proposed method is used to sparsely characterize cortical folding patterns of an in-utero fetal MR dataset, labeled with heterogeneous gestational age ranging from 26 weeks to 34 weeks. The proposed algorithm is validated on a synthetic dataset with both linear and non-linear dynamics, supporting its ability to capture deformation patterns across the dataset within only a few features. Results on the fetal brain dataset show that the temporal process of cortical folding related to brain maturation can be characterized by a very small set of points, located in anatomical regions changing across time. Quantitative measurements of growth against time are extracted from the set selected features to compare multiple brain regions (e.g. lobes and hemispheres) during the considered period of gestation.

  2. Structural Disorder of Folded Proteins: Isotope-Edited 2D IR Spectroscopy and Markov State Modeling

    PubMed Central

    Baiz, Carlos R.; Tokmakoff, Andrei

    2015-01-01

    The conformational heterogeneity of the N-terminal domain of the ribosomal protein L9 (NTL91-39) in its folded state is investigated using isotope-edited two-dimensional infrared spectroscopy. Backbone carbonyls are isotope-labeled (13C=18O) at five selected positions (V3, V9, V9G13, G16, and G24) to provide a set of localized spectroscopic probes of the structure and solvent exposure at these positions. Structural interpretation of the amide I line shapes is enabled by spectral simulations carried out on structures extracted from a recent Markov state model. The V3 label spectrum indicates that the β-sheet contacts between strands I and II are well folded with minimal disorder. The V9 and V9G13 label spectra, which directly probe the hydrogen-bond contacts across the β-turn, show significant disorder, indicating that molecular dynamics simulations tend to overstabilize ideally folded β-turn structures in NTL91-39. In addition, G24-label spectra provide evidence for a partially disordered α-helix backbone that participates in hydrogen bonding with the surrounding water. PMID:25863066

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Medial surface dynamics of the vocal folds in an in vivo canine model

    NASA Astrophysics Data System (ADS)

    Doellinger, Michael; Berke, Gerald S.; Chhetri, Dinesh K.; Berry, David A.

    2004-05-01

    Quantitative measurement of the medial surface dynamics of the vocal folds is important for understanding how sound is generated in the larynx. However, such data are hard to gather because of the inaccessibility of the vocal folds. Recent studies have applied hemi-larynx methodology to excised human larynges, to visualize these dynamics. The present study extends this methodology to obtain similar quantitative measurements using an in vivo canine hemi-larynx setup, with varying levels of stimulation to the recurrent laryngeal nerve. Use of an in vivo model allows us to examine effects of intrinsic muscle contraction on the medial surface of the vocal folds, to provide greater insight into mechanisms of vocal control. Data were collected using digital high-speed imaging with a sampling frequency of up to 4000 Hz, and a spatial resolution of up to 1024×1024 pixels. Three-dimensional motion will be extracted, computed, visualized, and contrasted as a function of the level of stimulation to the recurrent laryngeal nerve. Results will also be compared to patterns of vibration in excised larynges. Finally, commonly applied quantitative analyses will be performed to investigate the underlying modes of vibration. [Work supported by NIH/NIDCD.

  5. Hidden Markov models that use predicted local structure for fold recognition: alphabets of backbone geometry.

    PubMed

    Karchin, Rachel; Cline, Melissa; Mandel-Gutfreund, Yael; Karplus, Kevin

    2003-06-01

    An important problem in computational biology is predicting the structure of the large number of putative proteins discovered by genome sequencing projects. Fold-recognition methods attempt to solve the problem by relating the target proteins to known structures, searching for template proteins homologous to the target. Remote homologs that may have significant structural similarity are often not detectable by sequence similarities alone. To address this, we incorporated predicted local structure, a generalization of secondary structure, into two-track profile hidden Markov models (HMMs). We did not rely on a simple helix-strand-coil definition of secondary structure, but experimented with a variety of local structure descriptions, following a principled protocol to establish which descriptions are most useful for improving fold recognition and alignment quality. On a test set of 1298 nonhomologous proteins, HMMs incorporating a 3-letter STRIDE alphabet improved fold recognition accuracy by 15% over amino-acid-only HMMs and 23% over PSI-BLAST, measured by ROC-65 numbers. We compared two-track HMMs to amino-acid-only HMMs on a difficult alignment test set of 200 protein pairs (structurally similar with 3-24% sequence identity). HMMs with a 6-letter STRIDE secondary track improved alignment quality by 62%, relative to DALI structural alignments, while HMMs with an STR track (an expanded DSSP alphabet that subdivides strands into six states) improved by 40% relative to CE.

  6. Competition between protein folding and aggregation: A three-dimensional lattice-model simulation

    NASA Astrophysics Data System (ADS)

    Bratko, D.; Blanch, H. W.

    2001-01-01

    Aggregation of protein molecules resulting in the loss of biological activity and the formation of insoluble deposits represents a serious problem for the biotechnology and pharmaceutical industries and in medicine. Considerable experimental and theoretical efforts are being made in order to improve our understanding of, and ability to control, the process. In the present work, we describe a Monte Carlo study of a multichain system of coarse-grained model proteins akin to lattice models developed for simulations of protein folding. The model is designed to examine the competition between intramolecular interactions leading to the native protein structure, and intermolecular association, resulting in the formation of aggregates of misfolded chains. Interactions between the segments are described by a variation of the Go potential [N. Go and H. Abe, Biopolymers 20, 1013 (1981)] that extends the recognition between attracting types of segments to pairs on distinct chains. For the particular model we adopt, the global free energy minimum of a pair of protein molecules corresponds to a dimer of native proteins. When three or more molecules interact, clusters of misfolded chains can be more stable than aggregates of native folds. A considerable fraction of native structure, however, is preserved in these cases. Rates of conformational changes rapidly decrease with the size of the protein cluster. Within the timescale accessible to computer simulations, the folding-aggregation balance is strongly affected by kinetic considerations. Both the native form and aggregates can persist in metastable states, even if conditions such as temperature or concentration favor a transition to an alternative form. Refolding yield can be affected by the presence of an additional polymer species mimicking the function of a molecular chaperone.

  7. An ISO-surface folding analysis method applied to premature neonatal brain development

    NASA Astrophysics Data System (ADS)

    Rodriguez-Carranza, Claudia E.; Rousseau, Francois; Iordanova, Bistra; Glenn, Orit; Vigneron, Daniel; Barkovich, James; Studholme, Colin

    2006-03-01

    In this paper we describe the application of folding measures to tracking in vivo cortical brain development in premature neonatal brain anatomy. The outer gray matter and the gray-white matter interface surfaces were extracted from semi-interactively segmented high-resolution T1 MRI data. Nine curvature- and geometric descriptor-based folding measures were applied to six premature infants, aged 28-37 weeks, using a direct voxelwise iso-surface representation. We have shown that using such an approach it is feasible to extract meaningful surfaces of adequate quality from typical clinically acquired neonatal MRI data. We have shown that most of the folding measures, including a new proposed measure, are sensitive to changes in age and therefore applicable in developing a model that tracks development in premature infants. For the first time gyrification measures have been computed on the gray-white matter interface and on cases whose age is representative of a period of intense brain development.

  8. Asymmetric folding pathways and transient misfolding in a coarse-grained model of proteins

    NASA Astrophysics Data System (ADS)

    Wolff, K.; Vendruscolo, M.; Porto, M.

    2011-05-01

    Coarse-grained approaches to study the protein folding process provide the possibility to explore timescales longer than those accessible to all-atom models and thus provide access, albeit in less detail, to larger regions of the conformational space. Here, we investigate the behaviour of a coarse-grained model whose two primary characteristics are a tube-like geometry to describe the self-avoidance effects of the polypeptide chain, and an energy function based on a one-dimensional structural representation that specifies the sequence's connectivity in a given conformation. Such an energy function, rather than favouring the formation of specific native pairwise contacts, promotes the establishment of a specific target connectivity for each amino acid. We illustrate the use of this model by showing that it enables to follow the complete process of folding and to efficiently determine the free energy landscapes of two small α-helical proteins, the villin headpiece domain and the ubiquitin associated domain, providing results that closely resemble those found in extensive molecular dynamics studies. These results support the idea that the use of coarse-grained models that capture the self-avoidance and the connectivity of a polypeptide chain represents a promising approach for obtaining effective descriptions of many aspects of the behaviour of proteins.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Structurally induced errors in paleomagnetic analysis of fold and thrust belts: Types, causes and detection techniques.

    NASA Astrophysics Data System (ADS)

    Pueyo, E. L.

    2008-12-01

    Paleomagnetic vectors are unique kinematics indicators allowing for the real understanding of the lateral transference of deformation processes and they are essential for a real 3D understanding of fold and thrust belts. The association with the bedding surface gives the only 3D reference system able to unambiguously relate the deformed and undeformed stages and their implications are, until now, relatively unexplored in structural geology. However paleomagnetic data are sometimes, misinterpreted or ignored due to the lack of reliability of some databases, where a geometric control of errors seems evident from the structural point of view. An analysis of the implicit assumptions in paleomagnetic studies of fold and thrust belts reveals three possible sources of error with an intrinsic structural (geometric) control: Assumption 1) The laboratory procedures are able to completely isolate of the original paleomagnetic vectors When this fails, the subsequent overlapped paleomagnetic directions (eg. primary record and the recent overprint) will display both declination and inclination errors, that will be controlled by the fold axis orientation, the degree of flank rotation (dip), the primary magnetic polarity as well as the degree of vector overlapping. Assumption 2) The rigid-body behavior during deformation and the absence of rock volume changes. When the rock volume undergoes active internal deformation during folding or shearing, the deformed paleomagnetic vectors will display again declination and inclination errors, but both polarities will behave similarly. In this case the errors will depend on the relation between the primary field orientation and the deformation tensor, which in fact, can be reduced to the orientation and magnitude of the shear in most cases. Assumption 3) The bedding correction is able to restore the bedding-vector couple to the ancient (paleo)geographical reference system. This restoration may fail in complex deformation zones affected by

  12. Asymmetric vibration in a two-layer vocal fold model with left-right stiffness asymmetry: Experiment and simulation

    PubMed Central

    Zhang, Zhaoyan; Hieu Luu, Trung

    2012-01-01

    Vibration characteristics of a self-oscillating two-layer vocal fold model with left-right asymmetry in body-layer stiffness were experimentally and numerically investigated. Two regimes of distinct vibratory pattern were identified as a function of left-right stiffness mismatch. In the first regime with extremely large left-right stiffness mismatch, phonation onset resulted from an eigenmode synchronization process that involved only eigenmodes of the soft fold. Vocal fold vibration in this regime was dominated by a large-amplitude vibration of the soft fold, and phonation frequency was determined by the properties of the soft fold alone. The stiff fold was only enslaved to vibrate at a much reduced amplitude. In the second regime with small left-right stiffness mismatch, eigenmodes of both folds actively participated in the eigenmode synchronization process. The two folds vibrated with comparable amplitude, but the stiff fold consistently led the soft fold in phase for all conditions. A qualitatively good agreement was obtained between experiment and simulation, although the simulations generally underestimated phonation threshold pressure and onset frequency. The clinical implications of the results of this study are also discussed. PMID:22978891

  13. Replica-exchange Wang-Landau simulations of the H0P model of protein folding

    NASA Astrophysics Data System (ADS)

    Shi, Guangjie; Landau, David P.; Wüst, Thomas; Li, Ying Wai Li

    2015-03-01

    The hydrophobic-polar (HP) model has served as a coarse-grained lattice protein folding model attracting scientists from various disciplines. However, simplification into H and P monomers may yield high ground state degeneracies which stands in contrast to the generally unique native states of natural proteins. We propose a simple modification, by introducing a new type of ``neutral'' monomer, 0, i.e. neither hydrophobic nor polar, rendering the model more realistic without increasing the difficulties of sampling significantly. With the newly developed parallel Wang-Landau (replica exchange Wang-Landau) scheme and an innovative method of estimating the ground state degeneracies, we investigated some widely studied HP proteins and their H0P counterparts. Dramatic differences in ground state and thermodynamic properties have been observed, e.g. the estimation of ground state degeneracy for the 46mer is 460,000 for the HP version and only 20 for the H0P mapping. Similarly, the specific heat and structural properties: radius of gyration and etc. show more pronounced signals associated with folding. Supported by NSF.

  14. Viscoelastic shear properties of human vocal fold mucosa: theoretical characterization based on constitutive modeling.

    PubMed

    Chan, R W; Titze, I R

    2000-01-01

    The viscoelastic shear properties of human vocal fold mucosa (cover) were previously measured as a function of frequency [Chan and Titze, J. Acoust. Soc. Am. 106, 2008-2021 (1999)], but data were obtained only in a frequency range of 0.01-15 Hz, an order of magnitude below typical frequencies of vocal fold oscillation (on the order of 100 Hz). This study represents an attempt to extrapolate the data to higher frequencies based on two viscoelastic theories, (1) a quasilinear viscoelastic theory widely used for the constitutive modeling of the viscoelastic properties of biological tissues [Fung, Biomechanics (Springer-Verlag, New York, 1993), pp. 277-292], and (2) a molecular (statistical network) theory commonly used for the rheological modeling of polymeric materials [Zhu et al., J. Biomech. 24, 1007-1018 (1991)]. Analytical expressions of elastic and viscous shear moduli, dynamic viscosity, and damping ratio based on the two theories with specific model parameters were applied to curve-fit the empirical data. Results showed that the theoretical predictions matched the empirical data reasonably well, allowing for parametric descriptions of the data and their extrapolations to frequencies of phonation.

  15. Nuclear mean field and double-folding model of the nucleus-nucleus optical potential

    NASA Astrophysics Data System (ADS)

    Khoa, Dao T.; Phuc, Nguyen Hoang; Loan, Doan Thi; Loc, Bui Minh

    2016-09-01

    Realistic density dependent CDM3Yn versions of the M3Y interaction have been used in an extended Hartree-Fock (HF) calculation of nuclear matter (NM), with the nucleon single-particle potential determined from the total NM energy based on the Hugenholtz-van Hove theorem that gives rise naturally to a rearrangement term (RT). Using the RT of the single-nucleon potential obtained exactly at different NM densities, the density and energy dependence of the CDM3Yn interactions was modified to account properly for both the RT and observed energy dependence of the nucleon optical potential. Based on a local density approximation, the double-folding model of the nucleus-nucleus optical potential has been extended to take into account consistently the rearrangement effect and energy dependence of the nuclear mean-field potential, using the modified CDM3Yn interactions. The extended double-folding model was applied to study the elastic 12C+12C and 16O+12C scattering at the refractive energies, where the Airy structure of the nuclear rainbow has been well established. The RT was found to affect significantly the real nucleus-nucleus optical potential at small internuclear distances, giving a potential strength close to that implied by the realistic optical model description of the Airy oscillation.

  16. Unraveling protein folding mechanism by analyzing the hierarchy of models with increasing level of detail

    NASA Astrophysics Data System (ADS)

    Hayashi, Tomohiko; Yasuda, Satoshi; Škrbić, Tatjana; Giacometti, Achille; Kinoshita, Masahiro

    2017-09-01

    Taking protein G with 56 residues for a case study, we investigate the mechanism of protein folding. In addition to its native structure possessing α-helix and β-sheet contents of 27% and 39%, respectively, we construct a number of misfolded decoys with a wide variety of α-helix and β-sheet contents. We then consider a hierarchy of 8 different models with increasing level of detail in terms of the number of entropic and energetic physical factors incorporated. The polyatomic structure is always taken into account, but the side chains are removed in half of the models. The solvent is formed by either neutral hard spheres or water molecules. Protein intramolecular hydrogen bonds (H-bonds) and protein-solvent H-bonds (the latter is present only in water) are accounted for or not, depending on the model considered. We then apply a physics-based free-energy function (FEF) corresponding to each model and investigate which structures are most stabilized. This special approach taken on a step-by-step basis enables us to clarify the role of each physical factor in contributing to the structural stability and separately elucidate its effect. Depending on the model employed, significantly different structures such as very compact configurations with no secondary structures and configurations of associated α-helices are optimally stabilized. The native structure can be identified as that with lowest FEF only when the most detailed model is employed. This result is significant for at least the two reasons: The most detailed model considered here is able to capture the fundamental aspects of protein folding notwithstanding its simplicity; and it is shown that the native structure is stabilized by a complex interplay of minimal multiple factors that must be all included in the description. In the absence of even a single of these factors, the protein is likely to be driven towards a different, more stable state.

  17. Kinetic modelling indicates that fast-translating codons can coordinate cotranslational protein folding by avoiding misfolded intermediates

    NASA Astrophysics Data System (ADS)

    O'Brien, Edward P.; Vendruscolo, Michele; Dobson, Christopher M.

    2014-01-01

    It has been observed for several proteins that slowing down the rate at which individual codons are translated can increase their probability of cotranslational protein folding, while speeding up codon translation can decrease it. Here we investigate whether or not this inverse relationship between translation speed and the cotranslational folding probability is a general phenomenon or if other scenarios are possible. We first derive chemical kinetic equations that relate individual codon translation rates to the probability that a domain will fold, populate an intermediate or misfold, and examine the cotranslational folding scenarios that are possible within these models. We find that speeding up codon translation through misfolding-prone segments can, in some cases, increase the folding probability of a domain immediately before the nascent protein is released from the ribosome and decrease its chances of misfolding. Thus, for some proteins fast-translating codons could be as important as slow-translating codons in coordinating cotranslational protein folding.

  18. Simple continuous and discrete models for simulating replica exchange simulations of protein folding.

    PubMed

    Zheng, Weihua; Andrec, Michael; Gallicchio, Emilio; Levy, Ronald M

    2008-05-15

    The efficiency of temperature replica exchange (RE) simulations hinge on their ability to enhance conformational sampling at physiological temperatures by taking advantage of more rapid conformational interconversions at higher temperatures. While temperature RE is a parallel simulation technique that is relatively straightforward to implement, kinetics in the RE ensemble is complicated, and there is much to learn about how best to employ RE simulations in computational biophysics. Protein folding rates often slow down above a certain temperature due to entropic bottlenecks. This "anti-Arrhenius" behavior represents a challenge for RE. However, it is far from straightforward to systematically explore the impact of this on RE by brute force molecular simulations, since RE simulations of protein folding are very difficult to converge. To understand some of the basic mechanisms that determine the efficiency of RE, it is useful to study simplified low dimensionality systems that share some of the key characteristics of molecular systems. Results are presented concerning the efficiency of temperature RE on a continuous two-dimensional potential that contains an entropic bottleneck. Optimal efficiency was obtained when the temperatures of the replicas did not exceed the temperature at which the harmonic mean of the folding and unfolding rates is maximized. This confirms a result we previously obtained using a discrete network model of RE. Comparison of the efficiencies obtained using the continuous and discrete models makes it possible to identify non-Markovian effects, which slow down equilibration of the RE ensemble on the more complex continuous potential. In particular, the rate of temperature diffusion and also the efficiency of RE is limited by the time scale of conformational rearrangements within free energy basins.

  19. Asymmetric airflow and vibration induced by the Coanda effect in a symmetric model of the vocal folds.

    PubMed

    Tao, Chao; Zhang, Yu; Hottinger, Daniel G; Jiang, Jack J

    2007-10-01

    A model constructed from Navier-Stokes equations and a two-mass vocal fold description is proposed in this study. The composite model not only has the capability to describe the aerodynamics in a vibratory glottis but also can be used to study the vocal fold vibration under the driving of the complex airflow in the glottis. Numerical simulations show that this model can predict self-oscillations of the coupled glottal aerodynamics and vocal fold system. The Coanda effect could occur in the vibratory glottis even though the vocal folds have left-right symmetric prephonatory shape and tissue properties. The Coanda effect causes the asymmetric flow in the glottis and the difference in the driving force on the left and right vocal folds. The different pressures applied to the left and right vocal folds induce their displacement asymmetry. By using various lung pressures (0.6-2.0 kPa) to drive the composite model, it was found that the asymmetry of the vocal fold displacement is increased from 1.87% to 11.2%. These simulation results provide numerical evidence for the presence of asymmetric flow in the vibratory glottis; moreover, they indicate that glottal aerodynamics is an important factor in inducing the asymmetric vibration of the vocal folds.

  20. Influence of a constriction in the near field of the vocal folds: physical modeling and experimental validation.

    PubMed

    Bailly, Lucie; Pelorson, Xavier; Henrich, Nathalie; Ruty, Nicolas

    2008-11-01

    The involvement of the ventricular folds is often observed in human phonation and, in particular, in pathological and or some throat-singing phonation. This study aims to explore and model the possible aerodynamic interaction between the ventricular and vocal folds using suitable in vitro setups allowing steady and unsteady flow conditions. The two experimental setups consist of a rigid and a self-oscillating vocal-fold replica, coupled to a downstream rigid ventricular-fold replica in both cases. A theoretical flow modeling is proposed to quantify the aerodynamic impact of the ventricular folds on the pressure distribution and thereby on the vocal-fold vibrations. The mechanical behavior of the vocal folds is simulated by a distributed model accounting for this impact. The influence of the ventricular constriction is measured in both flow conditions and compared to the model outcome. This study objectively evaluates the additional pressure drop implied by the presence of a ventricular constriction in the larynx. It is demonstrated that such constriction can either facilitate or impede the glottal vibrations depending on the laryngeal geometrical configuration. The relevance of using static or dynamic vocal-fold replicas is discussed.

  1. Biophysical analysis of the MHR motif in folding and domain swapping of the HIV capsid protein C-terminal domain.

    PubMed

    Bocanegra, Rebeca; Fuertes, Miguel Ángel; Rodríguez-Huete, Alicia; Neira, José Luis; Mateu, Mauricio G

    2015-01-20

    Infection by human immunodeficiency virus (HIV) depends on the function, in virion morphogenesis and other stages of the viral cycle, of a highly conserved structural element, the major homology region (MHR), within the carboxyterminal domain (CTD) of the capsid protein. In a modified CTD dimer, MHR is swapped between monomers. While no evidence for MHR swapping has been provided by structural models of retroviral capsids, it is unknown whether it may occur transiently along the virus assembly pathway. Whatever the case, the MHR-swapped dimer does provide a novel target for the development of anti-HIV drugs based on the concept of trapping a nonnative capsid protein conformation. We have carried out a thermodynamic and kinetic characterization of the domain-swapped CTD dimer in solution. The analysis includes a dissection of the role of conserved MHR residues and other amino acids at the dimerization interface in CTD folding, stability, and dimerization by domain swapping. The results revealed some energetic hotspots at the domain-swapped interface. In addition, many MHR residues that are not in the protein hydrophobic core were nevertheless found to be critical for folding and stability of the CTD monomer, which may dramatically slow down the swapping reaction. Conservation of MHR residues in retroviruses did not correlate with their contribution to domain swapping, but it did correlate with their importance for stable CTD folding. Because folding is required for capsid protein function, this remarkable MHR-mediated conformational stabilization of CTD may help to explain the functional roles of MHR not only during immature capsid assembly but in other processes associated with retrovirus infection. This energetic dissection of the dimerization interface in MHR-swapped CTD may also facilitate the design of anti-HIV compounds that inhibit capsid assembly by conformational trapping of swapped CTD dimers. Copyright © 2015 Biophysical Society. Published by Elsevier

  2. Biophysical Analysis of the MHR Motif in Folding and Domain Swapping of the HIV Capsid Protein C-Terminal Domain

    PubMed Central

    Bocanegra, Rebeca; Fuertes, Miguel Ángel; Rodríguez-Huete, Alicia; Neira, José Luis; Mateu, Mauricio G.

    2015-01-01

    Infection by human immunodeficiency virus (HIV) depends on the function, in virion morphogenesis and other stages of the viral cycle, of a highly conserved structural element, the major homology region (MHR), within the carboxyterminal domain (CTD) of the capsid protein. In a modified CTD dimer, MHR is swapped between monomers. While no evidence for MHR swapping has been provided by structural models of retroviral capsids, it is unknown whether it may occur transiently along the virus assembly pathway. Whatever the case, the MHR-swapped dimer does provide a novel target for the development of anti-HIV drugs based on the concept of trapping a nonnative capsid protein conformation. We have carried out a thermodynamic and kinetic characterization of the domain-swapped CTD dimer in solution. The analysis includes a dissection of the role of conserved MHR residues and other amino acids at the dimerization interface in CTD folding, stability, and dimerization by domain swapping. The results revealed some energetic hotspots at the domain-swapped interface. In addition, many MHR residues that are not in the protein hydrophobic core were nevertheless found to be critical for folding and stability of the CTD monomer, which may dramatically slow down the swapping reaction. Conservation of MHR residues in retroviruses did not correlate with their contribution to domain swapping, but it did correlate with their importance for stable CTD folding. Because folding is required for capsid protein function, this remarkable MHR-mediated conformational stabilization of CTD may help to explain the functional roles of MHR not only during immature capsid assembly but in other processes associated with retrovirus infection. This energetic dissection of the dimerization interface in MHR-swapped CTD may also facilitate the design of anti-HIV compounds that inhibit capsid assembly by conformational trapping of swapped CTD dimers. PMID:25606682

  3. Quasy-3D models of restored folded sedimentary cover of Alpine Greater Caucasus and evidences of isostasy participation in processes of folding formation and of mountain building

    NASA Astrophysics Data System (ADS)

    Yakovlev, Fedor

    2015-04-01

    scale of Earth crust) shows that rocks on level of possible Moho at J1 period (-40 km) now may have position at -100/-110 km for south part of GC [3]. It means that considerable part of crust rocks inevitably got a "mantle" density. Together with above-stated analysis of 1-6 parameters behavior, it means that isostasy take very important participation in processes of folding formation and mountain building. 1. Yakovlev F.L. // Izvestiya, Physics of the Solid Earth. 2009. 45. 11. 1023-1034. 2. Yakovlev F.L. // Comptes Rendus Geoscience. 2012. 344 (3-4). 125-137. 3. Yakovlev F.L. // Bulletin of "KRAESC". Earth Sciences. 2012. 1 (19). 191-214. (in Russian) 4. Yakovlev F.L. // XLVII Moscow Tectonics Conference Proceedings, 2015, in press (in Russian)

  4. Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model

    SciTech Connect

    Agarwala, R.; Batzoglou, S.; Dancik, V.

    1997-12-01

    A long standing problem in molecular biology is to determine the three-dimensional structure of a protein, given its amino acid sequence. A variety of simplifying models have been proposed abstracting only the {open_quotes}essential physical properties{close_quotes} of real proteins. In these models, the three dimensional space is often represented by a lattice. Residues which are adjacent in the primary sequence (i.e. covalently linked) must be placed at adjacent points in the lattice. A conformation of a protein is simply a self-avoiding walk along the lattice. The protein folding problem STRING-FOLD is that of finding a conformation of the protein sequence on the lattice such that the overall energy is minimized, for some reasonable definition of energy. This formulation leaves open the choices of a lattice and an energy function. Once these choices are made, one may then address the algorithmic complexity of optimizing the energy function for the lattice. For a variety of such simple models, this minimization problem is in fact NP-hard. In this paper, we consider the Hydrophobic-Polar (HP) Model introduced by Dill. The HP model abstracts the problem by grouping the 20 amino acids into two classes: hydrophobic (or non-polar) residues and hydrophilic (or polar) residues. For concreteness, we will take our input to be a string from (H,P){sup +}, where P represents polar residues, and H represents hydrophobic residues. Dill et.al. survey the literature analyzing this model. 8 refs., 2 figs., 1 tab.

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

    PubMed Central

    Thachuk, Chris; Shmygelska, Alena; Hoos, Holger H

    2007-01-01

    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 neighbourhood

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

    NASA Astrophysics Data System (ADS)

    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

  7. Mola Topography Supports Drape-Folding Models for Polygonal Terrain of Utopia Planitia, Mars

    NASA Technical Reports Server (NTRS)

    McGill, George E.; Buczkowski, D. L.

    2002-01-01

    One of the most important questions we ask about Mars is whether or not there have ever been large bodies of standing water on the surface. The polygonal terrains of Utopia and Acidalia Planitiae are located in the lowest parts of the northern lowlands, the most logical places for water to pond and sediments to accumulate. Showing that polygonal terrain is sedimentary in origin would represent strong evidence in favor of a northern ocean. A number of hypotheses for the origin of the giant martian polygons have been proposed, from the cooling of lava to frost wedging to the desiccation of wet sediments, but Pechman showed that none of these familiar processes could be scaled up to martian dimensions. Two models for polygon origin attempt to explain the scale of the martian polygons by postulating drape folding of a cover material, either sedimentary or volcanic, over an uneven, buried surface. The drape folding would produce bending stresses in the surface layers that increase the probability of Fracturing over drape anticlines and suppress the probability of fracturing over drape synclines. However, both models require an additional source of extensional strain to produce the total strain needed to produce the observed troughs.

  8. Mola Topography Supports Drape-Folding Models for Polygonal Terrain of Utopia Planitia, Mars

    NASA Technical Reports Server (NTRS)

    McGill, George E.; Buczkowski, D. L.

    2002-01-01

    One of the most important questions we ask about Mars is whether or not there have ever been large bodies of standing water on the surface. The polygonal terrains of Utopia and Acidalia Planitiae are located in the lowest parts of the northern lowlands, the most logical places for water to pond and sediments to accumulate. Showing that polygonal terrain is sedimentary in origin would represent strong evidence in favor of a northern ocean. A number of hypotheses for the origin of the giant martian polygons have been proposed, from the cooling of lava to frost wedging to the desiccation of wet sediments, but Pechman showed that none of these familiar processes could be scaled up to martian dimensions. Two models for polygon origin attempt to explain the scale of the martian polygons by postulating drape folding of a cover material, either sedimentary or volcanic, over an uneven, buried surface. The drape folding would produce bending stresses in the surface layers that increase the probability of Fracturing over drape anticlines and suppress the probability of fracturing over drape synclines. However, both models require an additional source of extensional strain to produce the total strain needed to produce the observed troughs.

  9. Mechanical analysis of fault activation in southern Longmen Shan fold-and- thrust belt

    NASA Astrophysics Data System (ADS)

    Zhang, Zhen; Zhang, Huai; Wang, Liangshu; Shi, Yaolin; Leroy, Yves M.

    2017-04-01

    A mixed fault activation mode with obvious hinterland rupture in the southern Longmen Shan, the eastern margin of Tibetan Plateau, is revealed by recent 2008 Mw7.9 Wenchuan and 2013 Mw6.6 Lushan earthquakes together with GPS measurements. How to systematically understand the coexistence and competition mechanisms of fault activation, especially the principal-subordinate relationship on deformation absorption, in essence, involves mechanical onset analysis of this fold- and-thrust belt. However, due to the two-décollement- level thrust system with active 'flat-ramp- flat' geometry décollement, the predication of fault activation in the LMS has beyond the scope of Critical Coulomb wedge theory, not to mention the synchronous listric-type splay fault rupturing in the Beichuan fault (BCF) and Pengguan fault (PGF). For that purpose, we adopted maximum strength theorem, the kinematic approach of limit analysis, to deal with mechanical analysis of fault activation. Four end-member failure modes, or collapse mechanisms (CMs) in classical limit analysis, are proposed corresponding to the rupture of BCF, PGF, Range Frontal Blind Fault (RFBF) and the rupture of the flat-ramp- flat décollement into Sichuan Basin via RFBF. By selecting the available CMs via finite element limit analysis, the listric geometry of BCF and PGF is demonstrated to the dominant factor in trapping deformation in the hinterland. To activate the high-angle Beichuan splay fault, low cohesion and low friction angle on the BCF are combined effects on the rupturing of BCF. The change in cohesion and friction on BCF eventually forms the transition state between high angle BCF and low-angle PGF. Besides, due to the existence of low frictional upper décollement layer in Sichuan Basin (the Triassic evaporate layer), small amount of deformation is attracted into the Sichuan Basin forming small-scale thrusting folding. Moreover, favorable deformation migration toward Sichuan Basin is jointly influenced by

  10. Prognostic physiology: modeling patient severity in Intensive Care Units using radial domain folding.

    PubMed

    Joshi, Rohit; Szolovits, Peter

    2012-01-01

    Real-time scalable predictive algorithms that can mine big health data as the care is happening can become the new "medical tests" in critical care. This work describes a new unsupervised learning approach, radial domain folding, to scale and summarize the enormous amount of data collected and to visualize the degradations or improvements in multiple organ systems in real time. Our proposed system is based on learning multi-layer lower dimensional abstractions from routinely generated patient data in modern Intensive Care Units (ICUs), and is dramatically different from most of the current work being done in ICU data mining that rely on building supervised predictive models using commonly measured clinical observations. We demonstrate that our system discovers abstract patient states that summarize a patient's physiology. Further, we show that a logistic regression model trained exclusively on our learned layer outperforms a customized SAPS II score on the mortality prediction task.

  11. Prognostic Physiology: Modeling Patient Severity in Intensive Care Units Using Radial Domain Folding

    PubMed Central

    Joshi, Rohit; Szolovits, Peter

    2012-01-01

    Real-time scalable predictive algorithms that can mine big health data as the care is happening can become the new “medical tests” in critical care. This work describes a new unsupervised learning approach, radial domain folding, to scale and summarize the enormous amount of data collected and to visualize the degradations or improvements in multiple organ systems in real time. Our proposed system is based on learning multi-layer lower dimensional abstractions from routinely generated patient data in modern Intensive Care Units (ICUs), and is dramatically different from most of the current work being done in ICU data mining that rely on building supervised predictive models using commonly measured clinical observations. We demonstrate that our system discovers abstract patient states that summarize a patient’s physiology. Further, we show that a logistic regression model trained exclusively on our learned layer outperforms a customized SAPS II score on the mortality prediction task. PMID:23304406

  12. 3-D geomechanical restoration and paleomagnetic analysis of fault-related folds: An example from the Yanjinggou anticline, southern Sichuan Basin

    NASA Astrophysics Data System (ADS)

    Li, Yiquan; Jia, Dong; Plesch, Andreas; Hubbard, Judith; Shaw, John H.; Wang, Maomao

    2013-09-01

    We examine the development of the Yanjinggou anticline, a fault-propagation-fold in the southern Longmen Shan, through an integrated study of structural geometry, strain, and paleomagnetism. The 3-D structural and strain restoration models generated in our analysis reveal that the NE-trending Yanjinggou fold has a curved map trace that is convex to the southeast. The fold has three distinct regions characterized by different strain patterns: contraction in the core of the fold, extension in the outer arc, and a forelimb with distributed shear. To further understand the kinematics of the Yanjinggou anticline, we performed paleomagnetic analysis on 184 oriented samples collected across the structure. Anisotropy of magnetic susceptibility (AMS) measurements and stepwise thermal demagnetization were conducted. A strike test was applied to the high temperature component (HTC) in order to identify rotation around the arc. The result indicates that the Yanjinggou anticline is a progressive arc, with a minor initial curvature and a dominant secondary curvature related to vertical-axis rotation synchronous with thrusting. The primary curvature and initial development of the structure correlates with the growth of the southern Longmen Shan in Late Miocene. The secondary curvature correlates with displacement extending since Late Pleistocene toward the southeast into the central basin along the detachments that underlie the structure. Lateral gradients in displacement along this underlying detachment provide a mechanism for producing the vertical rotation of the anticline. AMS results and historical earthquake analysis imply that the fault-propagation fold, along with other NE trending structures in the southern Sichuan basin, are tectonically active and accommodate east-west crustal shortening in the basin. By integrating 3-D structural and strain restoration modeling with systematic AMS and paleomagnetic methods using statistical analysis, we closely constrain how the

  13. Predictions of fundamental frequency changes during phonation based on a biomechanical model of the vocal fold lamina propria

    PubMed Central

    Zhang, Kai; Siegmund, Thomas; Chan, Roger W.; Fu, Min

    2009-01-01

    This study examines the local and global changes of fundamental frequency (F0) during phonation and proposes a biomechanical model of predictions of F0 contours based on the mechanics of vibration of vocal fold lamina propria. The biomechanical model integrates the constitutive description of the tissue mechanical response with a structural model of beam vibration. The constitutive model accounts for the nonlinear and time dependent response of the vocal fold cover and the vocal ligament. The structural model of the vocal fold lamina propria is based on a composite beam model with axial stress. Results show that local fluctuations such as F0 overshoots and undershoots can be characterized by the biomechanical model and might be related to the processes of stress relaxation of vocal fold tissues during length changes. The global changes of F0 declination in declarative sentence production can also be characterized by the model. Such F0 declination is partially attributed to the peak stress decay associated with stress relaxation of the vocal fold lamina propria and partially to neuromuscular control of the vocal fold length. PMID:18191379

  14. Predictions of fundamental frequency changes during phonation based on a biomechanical model of the vocal fold lamina propria.

    PubMed

    Zhang, Kai; Siegmund, Thomas; Chan, Roger W; Fu, Min

    2009-05-01

    This study examines the local and global changes of fundamental frequency (F(0)) during phonation and proposes a biomechanical model of predictions of F(0) contours based on the mechanics of vibration of vocal fold lamina propria. The biomechanical model integrates the constitutive description of the tissue mechanical response with a structural model of beam vibration. The constitutive model accounts for the nonlinear and time-dependent response of the vocal fold cover and the vocal ligament. The structural model of the vocal fold lamina propria is based on a composite beam model with axial stress. Results show that local fluctuations such as F(0) overshoots and undershoots can be characterized by the biomechanical model and might be related to the processes of stress relaxation of vocal fold tissues during length changes. The global changes of F(0) declination in declarative sentence production can also be characterized by the model. Such F(0) declination is partially attributed to the peak stress decay associated with stress relaxation of the vocal fold lamina propria and partially to neuromuscular control of the vocal fold length.

  15. Folding Beauties

    ERIC Educational Resources Information Center

    Berman, Leah Wrenn

    2006-01-01

    This article has its genesis in an MAA mini-course on origami, where a way to get a parabola by folding paper was presented. This article discusses the methods and mathematics of other curves obtained by paper-folding.

  16. Folding Beauties

    ERIC Educational Resources Information Center

    Berman, Leah Wrenn

    2006-01-01

    This article has its genesis in an MAA mini-course on origami, where a way to get a parabola by folding paper was presented. This article discusses the methods and mathematics of other curves obtained by paper-folding.

  17. Structural analysis of Bacillus pumilus phenolic acid decarboxylase, a lipocalin-fold enzyme

    SciTech Connect

    Matte, Allan; Grosse, Stephan; Bergeron, Hélène; Abokitse, Kofi; Lau, Peter C.K.

    2012-04-30

    The decarboxylation of phenolic acids, including ferulic and p-coumaric acids, to their corresponding vinyl derivatives is of importance in the flavoring and polymer industries. Here, the crystal structure of phenolic acid decarboxylase (PAD) from Bacillus pumilus strain UI-670 is reported. The enzyme is a 161-residue polypeptide that forms dimers both in the crystal and in solution. The structure of PAD as determined by X-ray crystallography revealed a -barrel structure and two -helices, with a cleft formed at one edge of the barrel. The PAD structure resembles those of the lipocalin-fold proteins, which often bind hydrophobic ligands. Superposition of structurally related proteins bound to their cognate ligands shows that they and PAD bind their ligands in a conserved location within the -barrel. Analysis of the residue-conservation pattern for PAD-related sequences mapped onto the PAD structure reveals that the conservation mainly includes residues found within the hydrophobic core of the protein, defining a common lipocalin-like fold for this enzyme family. A narrow cleft containing several conserved amino acids was observed as a structural feature and a potential ligand-binding site.

  18. Structure optimisation by thermal cycling for the hydrophobic-polar lattice model of protein folding

    NASA Astrophysics Data System (ADS)

    Günther, Florian; Möbius, Arnulf; Schreiber, Michael

    2017-03-01

    The function of a protein depends strongly on its spatial structure. Therefore the transition from an unfolded stage to the functional fold is one of the most important problems in computational molecular biology. Since the corresponding free energy landscapes exhibit huge numbers of local minima, the search for the lowest-energy configurations is very demanding. Because of that, efficient heuristic algorithms are of high value. In the present work, we investigate whether and how the thermal cycling (TC) approach can be applied to the hydrophobic-polar (HP) lattice model of protein folding. Evaluating the efficiency of TC for a set of two- and three-dimensional examples, we compare the performance of this strategy with that of multi-start local search (MSLS) procedures and that of simulated annealing (SA). For this aim, we incorporated several simple but rather efficient modifications into the standard procedures: in particular, a strong improvement was achieved by also allowing energy conserving state modifications. Furthermore, the consideration of ensembles instead of single samples was found to greatly improve the efficiency of TC. In the framework of different benchmarks, for all considered HP sequences, we found TC to be far superior to SA, and to be faster than Wang-Landau sampling.

  19. Linking rates of folding in lattice models of proteins with underlying thermodynamic characteristics

    NASA Astrophysics Data System (ADS)

    Klimov, D. K.; Thirumalai, D.

    1998-09-01

    We investigate the sequence-dependent properties of proteins that determine the dual requirements of stability of the native state and its kinetic accessibility using simple cubic lattice models. Three interaction schemes are used to describe the potentials between nearest neighbor nonbonded beads. We show that, under the simulation conditions when the native basin of attraction (NBA) is the most stable, there is an excellent correlation between folding times τF and the dimensionless parameter σT=(Tθ-TF)/Tθ, where Tθ is the collapse temperature and TF is the folding transition temperature. There is also a significant correlation between τF and another dimensionless quantity Z=(EN-Ems)/δ, where EN is the energy of the native state, Ems is the average energy of the ensemble of misfolded structures, and δ is the dispersion in the contact energies. In contrast, there is no significant correlation between τF and the Z-score gap ΔZ=EN-Ems. An approximate relationship between σT and the Z-score is derived, which explains the superior correlation seen between τF and σT. For two state folders τF is linked to the free energy difference (not simply energy gap, however it is defined) between the unfolded states and the NBA.

  20. Activity, stability and folding analysis of the chitinase from Entamoeba histolytica.

    PubMed

    Muñoz, Patricia L A; Minchaca, Alexis Z; Mares, Rosa E; Ramos, Marco A

    2016-02-01

    Human amebiasis, caused by the parasitic protozoan Entamoeba histolytica, remains as a significant public health issue in developing countries. The life cycle of the parasite compromises two main stages, trophozoite and cyst, linked by two major events: encystation and excystation. Interestingly, the cyst stage has a chitin wall that helps the parasite to withstand harsh environmental conditions. Since the amebic chitinase, EhCHT1, has been recognized as a key player in both encystation and excystation, it is plausible to consider that specific inhibition could arrest the life cycle of the parasite and, thus, stop the infection. However, to selectively target EhCHT1 it is important to recognize its unique biochemical features to have the ability to control its cellular function. Hence, to gain further insights into the structure-function relationship, we conducted an experimental approach to examine the effects of pH, temperature, and denaturant concentration on the enzymatic activity and protein stability. Additionally, dependence on in vivo oxidative folding was further studied using a bacterial model. Our results attest the potential of EhCHT1 as a target for the design and development of new or improved anti-amebic therapeutics. Likewise, the potential of the oxidoreductase EhPDI, involved in oxidative folding of amebic proteins, was also confirmed.

  1. Strain and vorticity analysis using small-scale faults and associated drag folds

    NASA Astrophysics Data System (ADS)

    Gomez-Rivas, Enrique; Bons, Paul D.; Griera, Albert; Carreras, Jordi; Druguet, Elena; Evans, Lynn

    2007-12-01

    Small-scale faults with associated drag folds in brittle-ductile rocks can retain detailed information on the kinematics and amount of deformation the host rock experienced. Measured fault orientation ( α), drag angle ( β) and the ratio of the thickness of deflected layers at the fault ( L) and further away ( T) can be compared with α, β and L/ T values that are calculated with a simple analytical model. Using graphs or a numerical best-fit routine, one can then determine the kinematic vorticity number and initial fault orientation that best fits the data. The proposed method was successfully tested on both analogue experiments and numerical simulations with BASIL. Using this method, a kinematic vorticity number of one (dextral simple shear) and a minimum finite strain of 2.5-3.8 was obtained for a population of antithetic faults with associated drag folds in a case study area at Mas Rabassers de Dalt on Cap de Creus in the Variscan of the easternmost Pyrenees, Spain.

  2. A new method for modeling and solving the protein fold recognition problem

    SciTech Connect

    Xu, Ying; Xu, Dong; Uberbacher, E.C.

    1998-12-31

    Computational recognition of native-like folds from a protein fold database is considered to be a promising alternative approach to the ab initio fold prediction. We present a new and effective method for protein fold recognition through optimally aligning (threading) an amino acid sequence and a protein fold (template). A protein fold, in our database, is represented as a series of core secondary structures, and the alignment quality is determined by three factors. They are (1) the fitness between each amino acid and the environment of its assigned (aligned) template position; (2) pairwise interaction preferences between amino acids that are spatially close; and (3) alignment gap penalties. Our threading algorithm constructs an optimum alignment between an amino acid sequence of size n and a protein fold template of size m in 0((m + n{sup 1+0.5C}-M log(n))n{sup C+1}) time and 0(nm + n{sup C+2}) space, where M is the number of core secondary structures in the fold, and C is a (small) nonnegative integer, determined by a mathematical property of the pairwise interactions in the fold. C is less than or equal to 3 for about 90% of the 296 unique folds in our database, when pairwise interactions are restricted to amino acids < 6{angstrom} apart (measured between their beta carbon atoms). An approximation scheme is developed for fold templates with C > 3, when threading requires too much memory and time to be practical on a typical workstation.

  3. Thermodynamic stability of polypeptides folding within modeled ribosomal exit tunnel: a density functional study.

    PubMed

    Xu, Xiaofei; Cao, Dapeng

    2010-07-01

    The mechanism of polypeptide folding, especially for the formation of tertiary structures, within the ribosomal exit tunnel, remains one of the most important unsolved problems in biophysical chemistry and molecular biology. In this work, we use a density functional theory (DFT) to explore the polypeptide folding within a modified nanopore, which mimics the confined environment of ribosomal exit tunnel. Results indicate that too long polypeptides (N>100 cannot fold into a helix state within the nanopore, and the helix polypeptides favor folding into a negative coiled coil rather than a positive one, because the negative coiled coil has a lower grand potential than the positive one, and the polypeptide folding into the negative coiled coil therefore needs less driving force than the positive one. To fold into the positive coiled coil, the helix polypeptides must have a small minor radius or a short chain length, which provides helpful insights into the design of nanodevices for manipulating the positive coiled coil. In the presence of attractive interaction, helices need more driving force to fold into coiled coil. Importantly, we have also proposed a scaling relation to understand the folding behavior. The scaling relation gives a good estimate for the computational results, and provides a reasonable explanation for the folding behavior. In summary, it is expected that the proposed DFT approach and the scaling relation provide alternative means for the investigation of polypeptide folding in confined environment, and these impressive results could give useful insights into nascent polypeptide folding.

  4. Comparing Folding Codes in Simple Heteropolymer Models of Protein Evolutionary Landscape: Robustness of the Superfunnel Paradigm

    PubMed Central

    Wroe, Richard; Bornberg-Bauer, Erich; Chan, Hue Sun

    2005-01-01

    Understanding the evolution of biopolymers is a key element in rationalizing their structures and functions. Simple exact models (SEMs) are well-positioned to address general principles of evolution as they permit the exhaustive enumeration of both sequence and structure (conformational) spaces. The physics-based models of the complete mapping between genotypes and phenotypes afforded by SEMs have proven valuable for gaining insight into how adaptation and selection operate among large collections of sequences and structures. This study compares the properties of evolutionary landscapes of a variety of SEMs to delineate robust predictions and possible model-specific artifacts. Among the models studied, the ruggedness of evolutionary landscape is significantly model-dependent; those derived from more proteinlike models appear to be smoother. We found that a common practice of restricting protein structure space to maximally compact lattice conformations results in (i.e., “designs in”) many encodable (designable) structures that are not otherwise encodable in the corresponding unrestrained structure space. This discrepancy is especially severe for model potentials that seek to mimic the major role of hydrophobic interactions in protein folding. In general, restricting conformations to be maximally compact leads to larger changes in the model genotype-phenotype mapping than a moderate shifting of reference state energy of the model potential function to allow for more specific encoding via the “designing out” effects of repulsive interactions. Despite these variations, the superfunnel paradigm applies to all SEMs we have tested: For a majority of neutral nets across different models, there exists a funnel-like organization of native stabilities for the sequences in a neutral net encoding for the same structure, and the thermodynamically most stable sequence is also the most robust against mutation. PMID:15501948

  5. Extreme Folding

    NASA Astrophysics Data System (ADS)

    Demaine, Erik

    2012-02-01

    Our understanding of the mathematics and algorithms behind paper folding, and geometric folding in general, has increased dramatically over the past several years. These developments have found a surprisingly broad range of applications. In the art of origami, it has helped spur the technical origami revolution. In engineering and science, it has helped solve problems in areas such as manufacturing, robotics, graphics, and protein folding. On the recreational side, it has led to new kinds of folding puzzles and magic. I will give an overview of the mathematics and algorithms of folding, with a focus on new mathematics and sculpture.

  6. The RIP and block-RIP analysis of Nyquist folding receiver for recovering signals

    NASA Astrophysics Data System (ADS)

    Jiang, Kaili; Chen, Sujuan; Tang, Bin

    2016-12-01

    Modern radar and communication systems require the detection and parameter estimation of signal under a broadband radio frequency (RF) environment. The Nyquist folding receiver (NYFR) is an efficient analog-to-information (A2I) architecture. It can use the compressive sensing (CS) techniques to break the limitations of the analog-to-digital converter (ADC). This paper demonstrates the restricted isometry property (RIP) of the NYFR deterministically by applying the Gershgorin circle theory. And, the NYFR suffers a poor RIP for the broadband signal, which will lead the conventional CS algorithms to be invalid. So, we derive the Fourier spectrum of the broadband signal, which covered multiple Nyquist zones and received by the NYFR. Then, the broadband signal can be regarded as the block-sparse signal. And, the block CS algorithms are applied for recovering the signal based on the analysis of the block-RIP. Finally, the simulation experiments demonstrate the validity of the findings.

  7. Wavelet Analysis on Symbolic Sequences and Two-Fold de Bruijn Sequences

    NASA Astrophysics Data System (ADS)

    Osipov, V. Al.

    2016-07-01

    The concept of symbolic sequences play important role in study of complex systems. In the work we are interested in ultrametric structure of the set of cyclic sequences naturally arising in theory of dynamical systems. Aimed at construction of analytic and numerical methods for investigation of clusters we introduce operator language on the space of symbolic sequences and propose an approach based on wavelet analysis for study of the cluster hierarchy. The analytic power of the approach is demonstrated by derivation of a formula for counting of two-fold de Bruijn sequences, the extension of the notion of de Bruijn sequences. Possible advantages of the developed description is also discussed in context of applied problem of construction of efficient DNA sequence assembly algorithms.

  8. Ab Initio structure prediction for Escherichia coli: towards genome-wide protein structure modeling and fold assignment

    PubMed Central

    Xu, Dong; Zhang, Yang

    2013-01-01

    Genome-wide protein structure prediction and structure-based function annotation have been a long-term goal in molecular biology but not yet become possible due to difficulties in modeling distant-homology targets. We developed a hybrid pipeline combining ab initio folding and template-based modeling for genome-wide structure prediction applied to the Escherichia coli genome. The pipeline was tested on 43 known sequences, where QUARK-based ab initio folding simulation generated models with TM-score 17% higher than that by traditional comparative modeling methods. For 495 unknown hard sequences, 72 are predicted to have a correct fold (TM-score > 0.5) and 321 have a substantial portion of structure correctly modeled (TM-score > 0.35). 317 sequences can be reliably assigned to a SCOP fold family based on structural analogy to existing proteins in PDB. The presented results, as a case study of E. coli, represent promising progress towards genome-wide structure modeling and fold family assignment using state-of-the-art ab initio folding algorithms. PMID:23719418

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

    SciTech Connect

    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.

    1993-12-01

    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.

  10. In-medium full-folding optical model for nucleon-nucleus elastic scattering

    SciTech Connect

    Arellano, H.F.; Brieva, F.A.; Love, W.G. |

    1995-07-01

    We develop an approach for incorporating both medium and off-shell effects in the calculation of full-folding nucleon-nucleus optical potentials for elastic scattering. The approach is based on a flexible scheme for calculating the nucleon-nucleon effective interaction in the nuclear medium. Using this scheme, we calculate a fully off-shell, energy-dependent effective force which includes effects arising from Pauli blocking and the nuclear mean field via an interacting nuclear matter model. Calculations of the elastic scattering observables for {ital p}+{sup 40}Ca and for {ital p}+{sup 208}Pb at energies between 30 and 400 MeV are presented and discussed. We also study total cross sections for neutron scattering off {sup 40}Ca, {sup 90}Zr, and {sup 208}Pb in the 5--400 MeV energy range. The theory gives a reasonable overall description of the data in the energy range under study.

  11. Characterization and functional analysis of the nucleotide binding fold in human peroxisomal ATP binding cassette transporters.

    PubMed

    Roerig, P; Mayerhofer, P; Holzinger, A; Gärtner, J

    2001-03-09

    The 70-kDa peroxisomal membrane protein (PMP70) and the adrenoleukodystrophy protein (ALDP) are half ATP binding cassette (ABC) transporters in the peroxisome membrane. Mutations in the ALD gene encoding ALDP result in the X-linked neurodegenerative disorder adrenoleukodystrophy. Plausible models exist to show a role for ATP hydrolysis in peroxisomal ABC transporter functions. Here, we describe the first measurements of the rate of ATP binding and hydrolysis by purified nucleotide binding fold (NBF) fusion proteins of PMP70 and ALDP. Both proteins act as an ATP specific binding subunit releasing ADP after ATP hydrolysis; they did not exhibit GTPase activity. Mutations in conserved residues of the nucleotidases (PMP70: G478R, S572I; ALDP: G512S, S606L) altered ATPase activity. Furthermore, our results indicate that these mutations do not influence homodimerization or heterodimerization of ALDP or PMP70. The study provides evidence that peroxisomal ABC transporters utilize ATP to become a functional transporter.

  12. Finite Element Analysis of Folded Airbag in Frontal Impact of Adapted Vehicles for Disabled Drivers

    NASA Astrophysics Data System (ADS)

    Masiá, J.; Eixerés, B.; Dols, J. F.; Esquerdo, T. V.

    2009-11-01

    The car control adaptations are used in vehicles in order to facilitate the driving to persons with physical handicaps. This does not have to suppose a decrease of the passive safety that is required to the vehicles. In order to analyze this relation there will be characterized the different control adaptations that are in use together with the different devices of passive safety that can be mounted in the vehicles in diverse cases of impact in order to generate models of simulation. The methodology used to generate this simulation consists of the first phase in which there develops the three-dimensional model of the driving place. For it, there has been used a commercial software of three-dimensional design. Once realized this one divides, the model is imported to the finite elements software in which meshing is generated. Finally, dynamic simulation software is used to assign the most important characteristics like material properties, contact interfaces, gas expansion models, airbag fold types, etc.

  13. Central Zagros fold-thrust belt (Iran): New insights from seismic data, field observation, and sandbox modeling

    NASA Astrophysics Data System (ADS)

    Sherkati, S.; Letouzey, J.; Frizon de Lamotte, D.

    2006-08-01

    We present five generalized cross sections across the central Zagros fold-and-thrust belt (Iran). These sections show that the fold geometry varies significantly both horizontally and vertically. The style is closely related to the changes in the mechanical behavior of the lithostratigraphic horizons and, in particular, to the presence of intermediate décollements within the sedimentary pile. Restoration of the sections shows amounts of shortening of the same order from one section to the other. However, it appears to be unequally distributed, suggesting variations in basal décollement shear strength. Analogue modeling has been performed to systematically investigate the effect of an intermediate décollement level at different depths on the style of folding. The models demonstrate that the position of intermediate décollements is an important factor controlling both structural style and fold wavelength. Models with shallow intermediate décollement show regularly and widely spaced anticlines. In these models, the fold wavelength depends directly on the thickness of the dominant competent layer and short-wavelength superficial structures mask broad anticlines at depth. Models with deep intermediate décollement are characterized by the rapid propagation of deformation (with small rate of shortening) along this décollement influencing localization of forthcoming anticlines in the upper levels. Such propagation favors the development of duplexes and multiwavelength folds. On this basis, fold kinematics in central Zagros is discussed using the variation of structural style along different folds as an indicator of the sequence of deformation. Detachment folding is the main folding style at least for the initial stages of deformation and thrust faults developed only at later stages. Some of these faults, branched on décollement levels, express the progression of folding, whereas others are linked to late basement faults cutting through early structures. In general

  14. Analysis of the kinetics of folding of proteins and peptides using circular dichroism

    PubMed Central

    Greenfield, Norma J.

    2009-01-01

    Circular dichroism (CD) is a useful spectroscopic technique for studying the secondary structure, folding and binding properties of proteins. This protocol covers how to use the intrinsic circular dichroic properties of proteins to follow their folding and unfolding as a function of time. Included will be methods of obtaining data and how to analyze the folding and unfolding data to determine the rate constants and the order of the folding/unfolding reactions. The protocol focuses on the use of CD to follow folding when it is relatively slow, on the order of minutes to days. The methods for analyzing the data, however, can also be applied to data collected with a CD machine equipped with stopped-flow accessories in the millisecond to second range and folding analyzed by other spectroscopic methods including changes in absorption or fluorescence spectra as a function of time. PMID:17406548

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

    PubMed Central

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

    2016-01-01

    Objectives 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. Methods 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. Results 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. Conclusion Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring. PMID:26976028

  16. Bioinformatic analysis of fold-type III PLP-dependent enzymes discovers multimeric racemases.

    PubMed

    Knight, Anders M; Nobili, Alberto; van den Bergh, Tom; Genz, Maika; Joosten, Henk-Jan; Albrecht, Dirk; Riedel, Katharina; Pavlidis, Ioannis V; Bornscheuer, Uwe T

    2017-02-01

    Pyridoxal-5'-phosphate (PLP)-dependent enzymes are ubiquitous in nature and catalyze a variety of important metabolic reactions. The fold-type III PLP-dependent enzyme family is primarily comprised of decarboxylases and alanine racemases. In the development of a multiple structural alignment database (3DM) for the enzyme family, a large subset of 5666 uncharacterized proteins with high structural, but low sequence similarity to alanine racemase and decarboxylases was found. Compared to these two classes of enzymes, the protein sequences being the object of this study completely lack the C-terminal domain, which has been reported important for the formation of the dimer interface in other fold-type III enzymes. The 5666 sequences cluster around four protein templates, which also share little sequence identity to each other. In this work, these four template proteins were solubly expressed in Escherichia coli, purified, and their substrate profiles were evaluated by HPLC analysis for racemase activity using a broader range of amino acids. They were found active only against alanine or serine, where they exhibited Michaelis constants within the range of typical bacterial alanine racemases, but with significantly lower turnover numbers. As the already described racemases were proposed to be active and appeared to be monomers as judged from their crystal structures, we also investigated this aspect for the four new enzymes. Here, size exclusion chromatography indicated the presence of oligomeric states of the enzymes and a native-PAGE in-gel assay showed that the racemase activity was present only in an oligomeric state but not as monomer. This suggests the likelihood of a different behavior of these enzymes in solution compared to the one observed in crystalline form.

  17. Microstructural Characterization of Vocal Folds toward a Strain-Energy Model of Collagen Remodeling

    PubMed Central

    Miri, Amir K.; Heris, Hossein K.; Tripathy, Umakanta; Wiseman, Paul W.; Mongeau, Luc

    2013-01-01

    Collagen fibrils are believed to control the immediate deformation of soft tissues under biomechanical load. Most extracellular matrix proteins remain intact during frozen sectioning, which allows them to be scanned using atomic force microscopy (AFM). Collagen fibrils are distinguishable because of their helical shape. In the present study, the shape and organization of collagen fibrils in dissected porcine vocal folds were quantified using nonlinear laser scanning microscopy data at the micrometer scale and AFM data at the nanometer scale. Rope-shape collagen fibrils were observed. Geometric characteristics for the fibrils were fed to a hyperelastic model to predict the biomechanical response of the tissue. The model simulates the micrometer-scale unlocking behavior of collagen bundles when extended from their unloaded configuration. Force spectroscopy using AFM was used to estimate the stiffness of collagen fibrils (1 ± 0.5 MPa). The presence of rope-shape fibrils is postulated to change the slope of the force-deflection response near the onset of nonlinearity. The proposed model could ultimately be used to evaluate changes in elasticity of soft tissues that result from the collagen remodeling. PMID:23643604

  18. q-Space Deep Learning: Twelve-Fold Shorter and Model-Free Diffusion MRI Scans.

    PubMed

    Golkov, Vladimir; Dosovitskiy, Alexey; Sperl, Jonathan I; Menzel, Marion I; Czisch, Michael; Samann, Philipp; Brox, Thomas; Cremers, Daniel

    2016-05-01

    Numerous scientific fields rely on elaborate but partly suboptimal data processing pipelines. An example is diffusion magnetic resonance imaging (diffusion MRI), a non-invasive microstructure assessment method with a prominent application in neuroimaging. Advanced diffusion models providing accurate microstructural characterization so far have required long acquisition times and thus have been inapplicable for children and adults who are uncooperative, uncomfortable, or unwell. We show that the long scan time requirements are mainly due to disadvantages of classical data processing. We demonstrate how deep learning, a group of algorithms based on recent advances in the field of artificial neural networks, can be applied to reduce diffusion MRI data processing to a single optimized step. This modification allows obtaining scalar measures from advanced models at twelve-fold reduced scan time and detecting abnormalities without using diffusion models. We set a new state of the art by estimating diffusion kurtosis measures from only 12 data points and neurite orientation dispersion and density measures from only 8 data points. This allows unprecedentedly fast and robust protocols facilitating clinical routine and demonstrates how classical data processing can be streamlined by means of deep learning.

  19. Self-oscillating Vocal Fold Model Mechanics: Healthy, Diseased, and Aging

    NASA Astrophysics Data System (ADS)

    Hiubler, Elizabeth P.; Pollok, Lucas F. E.; Apostoli, Adam G.; Hancock, Adrienne B.; Plesniak, Michael W.

    2014-11-01

    Voice disorders have been estimated to have a substantial economic impact of 2.5 billion annually. Approximately 30% of people will suffer from a voice disorder at some point in their lives. Life-sized, self-oscillating, synthetic vocal fold (VF) models are fabricated to exhibit material properties representative of human VFs. These models are created both with and without a polyp-like structure, a pathology that has been shown to produce rich viscous flow structures not normally observed for healthy VFs during normal phonation. Pressure measurements are acquired upstream of the VFs and high-speed images are captured at varying flow rates during VF oscillation to facilitate an understanding of the characteristics of healthy and diseased VFs. The images are analyzed using a videokymography line-scan technique. Clinically-relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to human data collected from two groups of males aged 18-30 and 60-80. This study extends the use of synthetic VF models by assessing their ability to replicate behaviors observed in human subject data to advance a means of investigating changes associated with normal, pathological, and the aging voice. Supported by the GWU Institute for Biomedical Engineering (GWIBE) and GWU Center for Biomimetics and Bioinspired Engineering (COBRE).

  20. Microstructural characterization of vocal folds toward a strain-energy model of collagen remodeling.

    PubMed

    Miri, Amir K; Heris, Hossein K; Tripathy, Umakanta; Wiseman, Paul W; Mongeau, Luc

    2013-08-01

    Collagen fibrils are believed to control the immediate deformation of soft tissues under mechanical load. Most extracellular matrix proteins remain intact during frozen sectioning, which allows them to be scanned using atomic force microscopy (AFM). Collagen fibrils are distinguishable because of their periodic roughness wavelength. In the present study, the shape and organization of collagen fibrils in dissected porcine vocal folds were quantified using nonlinear laser scanning microscopy data at the micrometer scale and AFM data at the nanometer scale. Rope-shaped collagen fibrils were observed. The geometric characteristics for the fibrils were fed into a hyperelastic model to predict the biomechanical response of the tissue. The model simulates the micrometer-scale unlocking behavior of collagen bundles when extended from their unloaded configuration. Force spectroscopy using AFM was used to estimate the stiffness of collagen fibrils (1±0.5MPa). The presence of rope-shaped fibrils is postulated to change the slope of the force-deflection response near the onset of nonlinearity. The proposed model could ultimately be used to evaluate changes in elasticity of soft tissues that result from the collagen remodeling.

  1. A polymer model explains the complexity of large-scale chromatin folding.

    PubMed

    Barbieri, Mariano; Fraser, James; Lavitas, Liron-Mark; Chotalia, Mita; Dostie, Josée; Pombo, Ana; Nicodemi, Mario

    2013-01-01

    The underlying global organization of chromatin within the cell nucleus has been the focus of intense recent research. Hi-C methods have allowed for the detection of genome-wide chromatin interactions, revealing a complex large-scale organization where chromosomes tend to partition into megabase-sized "topological domains" of local chromatin interactions and intra-chromosomal contacts extends over much longer scales, in a cell-type and chromosome specific manner. Until recently, the distinct chromatin folding properties observed experimentally have been difficult to explain in a single conceptual framework. We reported that a simple polymer-physics model of chromatin, the strings and binders switch (SBS) model, succeeds in describing the full range of chromatin configurations observed in vivo. The SBS model simulates the interactions between randomly diffusing binding molecules and binding sites on a polymer chain. It explains how polymer architectural patterns can be established, how different stable conformations can be produced and how conformational changes can be reliably regulated by simple strategies, such as protein upregulation or epigenetic modifications, via fundamental thermodynamics mechanisms.

  2. A polymer model explains the complexity of large-scale chromatin folding

    PubMed Central

    Barbieri, Mariano; Fraser, James; Lavitas, Liron-Mark; Chotalia, Mita; Dostie, Josée; Pombo, Ana; Nicodemi, Mario

    2013-01-01

    The underlying global organization of chromatin within the cell nucleus has been the focus of intense recent research. Hi-C methods have allowed for the detection of genome-wide chromatin interactions, revealing a complex large-scale organization where chromosomes tend to partition into megabase-sized “topological domains” of local chromatin interactions and intra-chromosomal contacts extends over much longer scales, in a cell-type and chromosome specific manner. Until recently, the distinct chromatin folding properties observed experimentally have been difficult to explain in a single conceptual framework. We reported that a simple polymer-physics model of chromatin, the strings and binders switch (SBS) model, succeeds in describing the full range of chromatin configurations observed in vivo. The SBS model simulates the interactions between randomly diffusing binding molecules and binding sites on a polymer chain. It explains how polymer architectural patterns can be established, how different stable conformations can be produced and how conformational changes can be reliably regulated by simple strategies, such as protein upregulation or epigenetic modifications, via fundamental thermodynamics mechanisms. PMID:23823730

  3. Spiraling Complexity: A Test of the Snowball Effect in a Computational Model of RNA Folding.

    PubMed

    Kalirad, Ata; Azevedo, Ricardo B R

    2016-12-22

    Genetic incompatibilities can emerge as a by-product of genetic divergence. According to Dobzhansky and Muller, an allele that fixes in one population may be incompatible with an allele at a different locus in another population when the two alleles are brought together in hybrids. Orr showed that the number of Dobzhansky-Muller incompatibilities (DMIs) should accumulate faster than linearly-i.e., snowball-as two lineages diverge. Several studies have attempted to test the snowball effect using data from natural populations. One limitation of these studies is that they have focused on predictions of the Orr model but not on its underlying assumptions. Here we use a computational model of RNA folding to test both predictions and assumptions of the Orr model. Two populations are allowed to evolve in allopatry on a holey fitness landscape. We find that the number of inviable introgressions (an indicator for the number of DMIs) snowballs, but does so more slowly than expected. We show that this pattern is explained, in part, by the fact that DMIs can disappear after they have arisen, contrary to the assumptions of the Orr model. This occurs because DMIs become progressively more complex (i.e., involve alleles at more loci) as a result of later substitutions. We also find that most DMIs involve more than two loci-i.e., they are complex. Reproductive isolation does not snowball because DMIs do not act independently of each other. We conclude that the RNA model supports the central prediction of the Orr model that the number of DMIs snowballs, but challenges other predictions, as well as some of its underlying assumptions.

  4. Relevance of structural segregation and chain compaction for the thermodynamics of folding of a hydrophobic protein model.

    PubMed

    Barbosa, Marco Aurélio A; de Araújo, Antônio F Pereira

    2003-05-01

    The relevance of inside-outside segregation and chain compaction for the thermodynamics of folding of a hydrophobic protein model is probed by complete enumeration of two-dimensional chains of up to 18 monomers in the square lattice. The exact computation of Z scores for uniquely designed sequences confirms that Z tends to decrease linearly with sigma square root of N, as previously suggested by theoretical analysis and Monte Carlo simulations, where sigma, the standard deviation of the number of contacts made by different monomers in the target structure, is a measure of structural segregation and N is the chain length. The probability that the target conformation is indeed the unique global energy minimum of the designed sequence is found to increase dramatically with sigma, approaching unity at maximal segregation. However, due to the huge number of conformations with sub-maximal values of sigma, which correspond to intermediate, only mildly discriminative, values of Z, in addition to significant oscillations of Z around its estimated value, the probability that a correctly designed sequence corresponds to a maximally segregated conformation is small. This behavior of Z also explains the observed relation between sigma and different measures of folding cooperativity of correctly designed sequences.

  5. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2011-10-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Analysis, Proposal 12416, as Cycle 18.

  6. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2009-07-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Analysis {10035} during Cycle 12.

  7. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2010-09-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Analysis {11863} during Cycle 17.

  8. Improvements in Markov State Model Construction Reveal Many Non-Native Interactions in the Folding of NTL9

    PubMed Central

    Schwantes, Christian R.; Pande, Vijay S.

    2013-01-01

    Markov State Models (MSMs) provide an automated framework to investigate the dynamical properties of high-dimensional molecular simulations. These models can provide a human-comprehensible picture of the underlying process, and have been successfully used to study protein folding, protein aggregation, protein ligand binding, and other biophysical systems. The MSM requires the construction of a discrete state-space such that two points are in the same state if they can interconvert rapidly. In the following, we suggest an improved method, which utilizes second order Independent Components Analysis (also known as time-structure based Independent Components Analysis, or tICA), to construct the state-space. We apply this method to simulations of NTL9 (provided by Lindorff-Larsen et al. Science 2011), and show that the MSM is an improvement over previously built models using conventional distance metrics. Additionally, the resulting model provides insight into the role of non-native contacts by revealing many slow timescales associated with compact, non-native states. PMID:23750122

  9. Direct-numerical simulation of the glottal jet and vocal-fold dynamics in a three-dimensional laryngeal model

    PubMed Central

    Zheng, X.; Mittal, R.; Xue, Q.; Bielamowicz, S.

    2011-01-01

    An immersed-boundary method based flow solver coupled with a finite-element solid dynamics solver is employed in order to conduct direct-numerical simulations of phonatory dynamics in a three-dimensional model of the human larynx. The computed features of the glottal flow including mean and peak flow rates, and the open and skewness quotients are found to be within the normal physiological range. The flow-induced vibration pattern shows the classical “convergent-divergent” glottal shape, and the vibration amplitude is also found to be typical for human phonation. The vocal fold motion is analyzed through the method of empirical eigenfunctions and this analysis indicates a 1:1 modal entrainment between the “adduction-abduction” mode and the “mucosal wave” mode. The glottal jet is found to exhibit noticeable cycle-to-cycle asymmetric deflections and the mechanism underlying this phenomenon is examined. PMID:21786908

  10. Correlation of the Vocal Fold Vibratory Pattern to the Post-Operative Surgical Wound in the Porcine Model.

    DTIC Science & Technology

    1992-02-15

    critical depth of vocal fold injury causing significant disruption of the vocal fold vibration. Materials and Methods Twelve adult, male, castrated ...near the apex of the vestibule, were away from the biopsy site. 14 Discussion Miniswine were selected for this study for several reasons. Castrated male...Nerve Stimulation on Phonation: A Glottographic Study Using in vivo Canine Model. J. Acoust. Soc. Am., 83:705-715, 1988. 10. Tanabe, M., Isshiki, N

  11. Statistical analysis of differential gene expression relative to a fold change threshold on NanoString data of mouse odorant receptor genes.

    PubMed

    Vaes, Evelien; Khan, Mona; Mombaerts, Peter

    2014-02-04

    A challenge in gene expression studies is the reliable identification of differentially expressed genes. In many high-throughput studies, genes are accepted as differentially expressed only if they satisfy simultaneously a p value criterion and a fold change criterion. A statistical method, TREAT, has been developed for microarray data to assess formally if fold changes are significantly higher than a predefined threshold. We have recently applied the NanoString digital platform to study expression of mouse odorant receptor genes, which form with 1,200 members the largest gene family in the mouse genome. Our objectives are, on these data, to decrease false discoveries when formally assessing the genes relative to a fold change threshold, and to provide a guided selection in the choice of this threshold. Statistical tests have been developed for microarray data to identify genes that are differentially expressed relative to a fold change threshold. Here we report that another approach, which we refer to as tTREAT, is more appropriate for our NanoString data, where false discoveries lead to costly and time-consuming follow-up experiments. Methods that we refer to as tTREAT2 and the running fold change model improve the performance of the statistical tests by protecting or selecting the fold change threshold more objectively. We show the benefits on simulated and real data. Gene-wise statistical analyses of gene expression data, for which the significance relative to a fold change threshold is important, give reproducible and reliable results on NanoString data of mouse odorant receptor genes. Because it can be difficult to set in advance a fold change threshold that is meaningful for the available data, we developed methods that enable a better choice (thus reducing false discoveries and/or missed genes) or avoid this choice altogether. This set of tools may be useful for the analysis of other types of gene expression data.

  12. Evaluation of Synthetic Self-Oscillating Models of the Vocal Folds

    NASA Astrophysics Data System (ADS)

    Hubler, Elizabeth P.; Weiland, Kelley S.; Hancock, Adrienne B.; Plesniak, Michael W.

    2013-11-01

    Approximately 30% of people will suffer from a voice disorder at some point in their lives. The probability doubles for those who rely heavily on their voice, such as teachers and singers. Synthetic vocal fold (VF) models are fabricated and evaluated experimentally in a vocal tract simulator to replicate physiological conditions. Pressure measurements are acquired along the vocal tract and high-speed images are captured at varying flow rates during VF oscillation to facilitate understanding of the characteristics of healthy and damaged VFs. The images are analyzed using a videokymography line-scan technique that has been used to examine VF motion and mucosal wave dynamics in vivo. Clinically relevant parameters calculated from the volume-velocity output of a circumferentially-vented mask (Rothenberg mask) are compared to patient data. This study integrates speech science with engineering and flow physics to overcome current limitations of synthetic VF models to properly replicate normal phonation in order to advance the understanding of resulting flow features, progression of pathological conditions, and medical techniques. Supported by the GW Institute for Biomedical Engineering (GWIBE) and GW Center for Biomimetics and Bioinspired Engineering (COBRE).

  13. Seismic attribute analysis and its application to mapping folds and fractures

    NASA Astrophysics Data System (ADS)

    Mai, Ha Thanh

    Geometric attributes such as coherence and curvature have been very successful in delineating faults in sedimentary basins. While not a common exploration objective, fractured and faulted basement forms important reservoirs in Venezuela, USA (Southern California), Brazil, Libya, Algeria, Egypt, Russia, and Vietnam (Landes, 1960; Canh, 2008). Because of the absence of stratified, coherent reflectors, illumination of basement faults is more problematic than illumination of faults within the sedimentary column. In order to address these problems, it is important to carefully analyze alternative forms of the 3D seismic data, which in this dissertation will be primarily combinations of one or more seismic attributes, and interpret them within the context of an appropriate structural deformation model. For that purpose, in this research, I concentrate on analyzing structural dip and azimuth, amplitude energy gradients, and a large family of attributes based on curvature to better illuminate fracture 'sweet spots' and estimate their density and orientation. I develop and calibrate these attribute and interpretation workflows through application to a complexly folded and faulted, but otherwise typical, geologic target in the Chicontepec Basin of Mexico. I then apply this calibrated workflow to better characterize faults and build fracture models in the granite basement of the Cuu Long Basin, Vietnam, and the granite and rhyolite-metarhyolite basement of Osage County, Oklahoma, USA. In the Cuu Long granite basement, it forms an important unconventional reservoir. In Osage County, we suspect basement control of overlying fractures in the Mississippian chat deposits.

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

    PubMed

    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.

  15. Application of motion analysis in the study of the effect of botulinum toxin to rat vocal folds

    NASA Astrophysics Data System (ADS)

    Saadah, Abdul K.; Galatsanos, Nikolas P.; Inagi, K.; Bless, D.

    1997-05-01

    In the past we have proposed a system that measures the deformations of the vocal folds from videostroboscopic images of the larynx, in that system: (1) we extract the boundaries of the vocal folds, (2) we register elastically the vocal fold boundaries in successive frames. This yields the displacement vector field (DVF) between adjacent frames, and (3) we fit using a least-squares approach an affine transformation model to succinctly describe the deformations between adjacent frames. In this paper, we present as an example of the capabilities of this system, an initial study of the deformation changes in rat vocal folds pre and post injection with Botulinum toxin. For this application the generated DVF was segmented into right DVF and left DVF and the deformation of each segment is studied separately.

  16. Analysis of the distributed computing approach applied to the folding of a small beta peptide.

    PubMed

    Paci, Emanuele; Cavalli, Andrea; Vendruscolo, Michele; Caflisch, Amedeo

    2003-07-08

    In the recently proposed distributed computing approach to protein folding a very large number of short independent simulations is performed. Using this method, folding events on a time scale orders of magnitude shorter than the experimental one have been reported. However, it has also been observed that the folding process is not an elementary kinetic step and that the presence of initial lag phases can bias short simulations toward atypical pathways. We study here a 20-residue three-stranded antiparallel beta-sheet peptide whose equilibrium properties can be characterized by atomistic molecular dynamics simulations. We found that the folding rate of this peptide is estimated correctly by the distributed computing approach when trajectories > approximately 1/100 of the equilibrium folding time are considered. We also found that the fastest folding events occur through high-energy pathways, which are unlikely under equilibrium conditions. These very fast folding pathways do not relax within the equilibrium denatured state that is stabilized by the transient presence of both native and non-native interactions, and they are characterized by the nearly simultaneous formation of the two beta-hairpins and a very small number of non-native contacts.

  17. A Cervid Vocal Fold Model Suggests Greater Glottal Efficiency in Calling at High Frequencies

    PubMed Central

    Titze, Ingo R.; Riede, Tobias

    2010-01-01

    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. PMID:20808882

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

    PubMed

    Titze, Ingo R; Riede, Tobias

    2010-08-19

    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.

  19. Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum

    PubMed Central

    Legué, Emilie; Riedel, Elyn; Joyner, Alexandra L.

    2015-01-01

    The mammalian cerebellum consists of folds of different sizes and shapes that house distinct neural circuits. A crucial factor underlying foliation is the generation of granule cells (gcs), the most numerous neuron type in the brain. We used clonal analysis to uncover global as well as folium size-specific cellular behaviors that underlie cerebellar morphogenesis. Unlike most neural precursors, gc precursors divide symmetrically, accounting for their massive expansion. We found that oriented cell divisions underlie an overall anteroposteriorly polarized growth of the cerebellum and gc clone geometry. Clone geometry is further refined by mediolateral oriented migration and passive dispersion of differentiating gcs. Most strikingly, the base of each fissure acts as a boundary for gc precursor dispersion, which we propose allows each folium to be regulated as a developmental unit. Indeed, the geometry and size of clones in long and short folia are distinct. Moreover, in engrailed 1/2 mutants with shorter folia, clone cell number and geometry are most similar to clones in short folia of wild-type mice. Thus, the cerebellum has a modular mode of development that allows the plane of cell division and number of divisions to be differentially regulated to ensure that the appropriate number of cells are partitioned into each folium. PMID:25834018

  20. Conformational analysis of HAMLET, the folding variant of human alpha-lactalbumin associated with apoptosis.

    PubMed

    Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro

    2004-05-01

    A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-alpha-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the beta-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the beta-domain of alpha-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed.

  1. Conformational analysis of HAMLET, the folding variant of human α-lactalbumin associated with apoptosis

    PubMed Central

    Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro

    2004-01-01

    A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human α-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-α-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the β-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the β-domain of α-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed. PMID:15075403

  2. Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum.

    PubMed

    Legué, Emilie; Riedel, Elyn; Joyner, Alexandra L

    2015-05-01

    The mammalian cerebellum consists of folds of different sizes and shapes that house distinct neural circuits. A crucial factor underlying foliation is the generation of granule cells (gcs), the most numerous neuron type in the brain. We used clonal analysis to uncover global as well as folium size-specific cellular behaviors that underlie cerebellar morphogenesis. Unlike most neural precursors, gc precursors divide symmetrically, accounting for their massive expansion. We found that oriented cell divisions underlie an overall anteroposteriorly polarized growth of the cerebellum and gc clone geometry. Clone geometry is further refined by mediolateral oriented migration and passive dispersion of differentiating gcs. Most strikingly, the base of each fissure acts as a boundary for gc precursor dispersion, which we propose allows each folium to be regulated as a developmental unit. Indeed, the geometry and size of clones in long and short folia are distinct. Moreover, in engrailed 1/2 mutants with shorter folia, clone cell number and geometry are most similar to clones in short folia of wild-type mice. Thus, the cerebellum has a modular mode of development that allows the plane of cell division and number of divisions to be differentially regulated to ensure that the appropriate number of cells are partitioned into each folium.

  3. Mechanics of Curved Folds

    NASA Astrophysics Data System (ADS)

    Dias, Marcelo A.; Santangelo, Christian D.

    2011-03-01

    Despite an almost two thousand year history, origami, the art of folding paper, remains a challenge both artistically and scientifically. Traditionally, origami is practiced by folding along straight creases. A whole new set of shapes can be explored, however, if, instead of straight creases, one folds along arbitrary curves. We present a mechanical model for curved fold origami in which the energy of a plastically-deformed crease is balanced by the bending energy of developable regions on either side of the crease. Though geometry requires that a sheet buckle when folded along a closed curve, its shape depends on the elasticity of the sheet. NSF DMR-0846582.

  4. RETRACTED: Design and analytical modeling of folded waveguide traveling wave tube

    NASA Astrophysics Data System (ADS)

    Malek, Fareq

    2009-12-01

    This article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the editors and author. The author has used without acknowledgement part of the PhD thesis by Yap Soon Tan, "Modeling of folded waveguide travelling wave", University of Liverpool, 2007, available from the British Library at http://ethos.bl.uk/ ILS catalogue number: 13826409. Shelfmark: DXN108794. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and we apologize to readers of the journal that this was not detected during the submission process. The author deeply regrets this and offers his sincere and unreserved apologies to the readers of the journal, and especially to Dr. Yap S. Tan, author of the above-mentioned thesis.

  5. Constitutive characterization of vocal fold viscoelasticity based on a modified Arruda-Boyce eight-chain model

    NASA Astrophysics Data System (ADS)

    Chan, Roger W.

    2003-10-01

    Previous studies have shown that vocal fold tissues exhibit nonlinear viscoelastic behavior under different loading conditions. Hysteresis and strain rate dependence of stress-strain curves have been observed for vocal fold ligament and muscle tissues when subjected to sinusoidal tensile loading. Nonlinear viscoelastic response and tissue failure have also been described for vocal fold mucosa subjected to constant strain-rate tests under large-strain shear. These findings cannot be adequately described by the traditional constitutive formulations of linear and quasilinear viscoelasticity. This study attempts to characterize some nonlinear behavior of vocal fold tissues under tensile loading based on a modified version of the Arruda-Boyce (Bergström-Boyce) hyperelastic model for polymers, which has been shown to adequately predict the rate-dependent behavior of some elastomers and biological tissues. Results indicated that the model was only capable of describing the relatively linear portion of the nonlinear stress-strain curves of the vocal fold muscle (at strain smaller than 20%), while failing to predict the exponential increase of stress at higher strain. However, the model was capable of predicting the dependence of stress on strain rate reasonably well. This finding was consistent with the model's assumptions on the constitutive behavior of the two constituent polymer networks.

  6. Liquid accumulation in vibrating vocal fold tissue: a simplified model based on a fluid-saturated porous solid theory.

    PubMed

    Tao, Chao; Jiang, Jack J; Czerwonka, Lukasz

    2010-05-01

    The human vocal fold is treated as a continuous, transversally isotropic, porous solid saturated with liquid. A set of mathematical equations, based on the theory of fluid-saturated porous solids, is developed to formulate the vibration of the vocal fold tissue. As the fluid-saturated porous tissue model degenerates to the continuous elastic tissue model when the relative movement of liquid in the porous tissue is ignored, it can be considered a more general description of vocal fold tissue than the continuous, elastic model. Using the fluid-saturated porous tissue model, the vibration of a bunch of one-dimensional fibers in the vocal fold is analytically solved based on the small-amplitude assumption. It is found that the vibration of the tissue will lead to the accumulation of excess liquid in the midmembranous vocal fold. The degree of liquid accumulation is positively proportional to the vibratory amplitude and frequency. The correspondence between the liquid distribution predicted by the porous tissue theory and the location of vocal nodules observed in clinical practice, provides theoretical evidence for the liquid accumulation hypothesis of vocal nodule formation (Jiang, Ph.D., dissertation, 1991, University of Iowa). (c) 2010 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  7. Quantitative analysis of single-molecule force spectroscopy on folded chromatin fibers.

    PubMed

    Meng, He; Andresen, Kurt; van Noort, John

    2015-04-20

    Single-molecule techniques allow for picoNewton manipulation and nanometer accuracy measurements of single chromatin fibers. However, the complexity of the data, the heterogeneity of the composition of individual fibers and the relatively large fluctuations in extension of the fibers complicate a structural interpretation of such force-extension curves. Here we introduce a statistical mechanics model that quantitatively describes the extension of individual fibers in response to force on a per nucleosome basis. Four nucleosome conformations can be distinguished when pulling a chromatin fiber apart. A novel, transient conformation is introduced that coexists with single wrapped nucleosomes between 3 and 7 pN. Comparison of force-extension curves between single nucleosomes and chromatin fibers shows that embedding nucleosomes in a fiber stabilizes the nucleosome by 10 kBT. Chromatin fibers with 20- and 50-bp linker DNA follow a different unfolding pathway. These results have implications for accessibility of DNA in fully folded and partially unwrapped chromatin fibers and are vital for understanding force unfolding experiments on nucleosome arrays. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Quantitative analysis of single-molecule force spectroscopy on folded chromatin fibers

    PubMed Central

    Meng, He; Andresen, Kurt; van Noort, John

    2015-01-01

    Single-molecule techniques allow for picoNewton manipulation and nanometer accuracy measurements of single chromatin fibers. However, the complexity of the data, the heterogeneity of the composition of individual fibers and the relatively large fluctuations in extension of the fibers complicate a structural interpretation of such force-extension curves. Here we introduce a statistical mechanics model that quantitatively describes the extension of individual fibers in response to force on a per nucleosome basis. Four nucleosome conformations can be distinguished when pulling a chromatin fiber apart. A novel, transient conformation is introduced that coexists with single wrapped nucleosomes between 3 and 7 pN. Comparison of force-extension curves between single nucleosomes and chromatin fibers shows that embedding nucleosomes in a fiber stabilizes the nucleosome by 10 kBT. Chromatin fibers with 20- and 50-bp linker DNA follow a different unfolding pathway. These results have implications for accessibility of DNA in fully folded and partially unwrapped chromatin fibers and are vital for understanding force unfolding experiments on nucleosome arrays. PMID:25779043

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

    SciTech Connect

    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.

  10. ReFOLD: a server for the refinement of 3D protein models guided by accurate quality estimates.

    PubMed

    Shuid, Ahmad N; Kempster, Robert; McGuffin, Liam J

    2017-04-10

    ReFOLD is a novel hybrid refinement server with integrated high performance global and local Accuracy Self Estimates (ASEs). The server attempts to identify and to fix likely errors in user supplied 3D models of proteins via successive rounds of refinement. The server is unique in providing output for multiple alternative refined models in a way that allows users to quickly visualize the key residue locations, which are likely to have been improved. This is important, as global refinement of a full chain model may not always be possible, whereas local regions, or individual domains, can often be much improved. Thus, users may easily compare the specific regions of the alternative refined models in which they are most interested e.g. key interaction sites or domains. ReFOLD was used to generate hundreds of alternative refined models for the CASP12 experiment, boosting our group's performance in the main tertiary structure prediction category. Our successful refinement of initial server models combined with our built-in ASEs were instrumental to our second place ranking on Template Based Modeling (TBM) and Free Modeling (FM)/TBM targets. The ReFOLD server is freely available at: http://www.reading.ac.uk/bioinf/ReFOLD/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. 3D numerical modeling of the lateral transition between viscous overthrusting and folding with application to the Helvetic nappe system

    NASA Astrophysics Data System (ADS)

    Spitz, Richard; Schmalholz, Stefan; Kaus, Boris

    2016-04-01

    The Helvetic nappe system of the European Alps is generally described as a complex of fold and thrust belts. While the overall geology of the system has been studied in detail, the understanding of the tectonic development and mechanical interconnection between overthrusting and folding is still incomplete. One clue comes from the mechanical stratigraphy and the corresponding lateral transition from overthrusting to folding, which is characteristic for the Helvetic nappe system. We employ a three-dimensional numerical model with linear and non-linear viscous rheology to investigate the control of the lateral variation in the thickness of a weak detachment horizon on the transition from folding to overthrusting during continental shortening. The model configuration is based on published work based on 2D numerical simulations. The simulations are conducted with the three-dimensional staggered-grid finite difference code LaMEM (Lithosphere and Mantle Evolution Model), which allows for coupled nonlinear thermo-mechanical modeling of lithospheric deformation with visco-elasto-plastic rheology and computation on massive parallel machines. Our model configuration consists of a stiff viscous layer, with a pre-existing weak zone, resting within a weaker viscous matrix. The reference viscosity ratio μL/μM (for the same strain rate) between the layer and matrix ranges from 10 to 200. The simulations were run with several distinct initial geometries by altering the thickness of the detachment horizon below the stiff layer across the configurations. Shortening with a constant bulk rate is induced by the prescription of a horizontal velocity on one side of the model. The first results of our simulations highlight the general importance of the initial geometry on the lateral transition from overthrusting to folding. Additionally, models with a stepwise lateral variation of the detachment horizon indicate a fold development orthogonal to the main compressional axis.

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

    NASA Astrophysics Data System (ADS)

    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

  13. Effect of subglottic stenosis on the flow-induced vibration of a self-oscillating computational vocal fold model

    NASA Astrophysics Data System (ADS)

    Smith, Simeon L.; Thomson, Scott L.

    2010-11-01

    The subglottis plays an important role in voice production; however, in general the role of subglottal geometry in phonation is not well understood. This research focuses on studying how subglottic stenosis, or a narrowing of the airway below the vocal folds, affects the response of a self-oscillating computational vocal fold model. Methods are described for computational model development, including stenotic geometry definition from CT scan images, incorporation of the stenosis into a finite element fluid-structure interaction model, and parametric variation of the degree of stenosis severity. Results are presented for a normal (no stenosis) case and five cases of varying degrees of stenosis severity. Qualitative and quantitative comparisons of vocal fold vibratory motion and of flow behavior for the six cases are made, including characterization of flow patterns in the subglottis, glottal width and flow rate time histories, vibration frequency, and airway resistance.

  14. Life prediction of expulsion bladders through fatigue test and fold strain analysis

    NASA Technical Reports Server (NTRS)

    Chu, H. N.; Unterberg, W.

    1972-01-01

    Cycle life data are presented in terms of true maximum strain for four metals, two plastics, and two elastomers. The Coffin-Manson fatigue theory was applied for metals and plastics, and cut-growth fatigue theory for elastomers. The data are based on measurements made at room and elevated temperatures. It was found that double folds give rise to far severer folding strains than do simple folds. It was also found that, except for the elastomers, all the bladder materials develop surface cracks due to double folds after only one cycle. The findings indicate that metals, which are bets for premeation resistance, are worst for fatigue resistance, and vice versa for elastomers. The intermediate plastics were found to be unsatisfactory for both permeation and fatigue resistance for missions of extended duration.

  15. Direct assay for endo-α-mannosidase substrate preference on correctly folded and misfolded model glycoproteins.

    PubMed

    Dedola, Simone; Izumi, Masayuki; Makimura, Yutaka; Seko, Akira; Kanamori, Akiko; Takeda, Yoichi; Ito, Yukishige; Kajihara, Yasuhiro

    2016-11-03

    We previously reported a unique assay system for UDP-glucose glycoprotein glucosyltransferase (UGGT) toward glycoprotein folding intermediates during the folding process. The assay involved the in vitro folding of both high-mannose type oligosaccharyl crambin, which yielded only the correctly folded glycoprotein form (M9-glycosyl-native-crambin), and its mutant, which yielded misfolded glycoproteins (M9-glycosyl-misfolded-crambin), in the presence of UGGT. The process successfully yielded both mono-glucosylated M9-glycosyl-native-crambin (G1M9-glycosyl-native-crambin) and M9-glycosyl-misfolded-crambin (G1M9-glycosyl-misfolded-crambin). Here, we report the use of our in vitro folding system to evaluate the substrate preference of Golgi endo-α-mannosidase against G1M9-native and -misfolded glycoprotein forms. In our assay Golgi endo-α-mannosidase removed Glc-α-1-3-Man unit from G1M9-native and -misfolded-crambins clearly proving that Golgi endo-α-mannosidase does not have specific preference for correctly folded or misfolded protein structure.

  16. Determination of the elastic properties of rabbit vocal fold tissue using uniaxial tensile testing and a tailored finite element model.

    PubMed

    Latifi, Neda; Miri, Amir K; Mongeau, Luc

    2014-11-01

    The aim of the present study was to quantify the effects of the specimen shape on the accuracy of mechanical properties determined from a shape-specific model generation strategy. Digital images of five rabbit vocal folds (VFs) in their initial undeformed conditions were used to build corresponding specific solid models. The displacement field of the VFs under uniaxial tensile test was then measured over the visible portion of the surface using digital image correlation. A three-dimensional finite element model was built, using ABAQUS, for each solid model, while imposing measured boundary conditions. An inverse-problem method was used, assuming a homogeneous isotropic linear elastic constitutive model. Unknown elastic properties were identified iteratively through an error minimization technique between simulated and measured force-time data. The longitudinal elastic moduli of the five rabbit VFs were calculated and compared to values from a simple analytical method and those obtained by approximating the cross-section as elliptical. The use of shape-specific models significantly reduced the standard deviation of the Young׳s moduli of the tested specimens. However, a non-parametric statistical analysis test, i.e., the Friedman test, yielded no statistically significant differences between the shape-specific method and the elliptic cylindrical finite element model. Considering the required procedures to reconstruct the shape-specific finite element model for each tissue specimen, it might be expedient to use the simpler method when large numbers of tissue specimens are to be compared regarding their Young׳s moduli. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Analysis of proteins with the 'hot dog' fold: Prediction of function and identification of catalytic residues of hypothetical proteins

    PubMed Central

    Pidugu, Lakshmi S; Maity, Koustav; Ramaswamy, Karthikeyan; Surolia, Namita; Suguna, Kaza

    2009-01-01

    Background The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago. The fold appears to have a strong association with fatty acid biosynthesis, its regulation and metabolism, as the proteins with this fold are predominantly coenzyme A-binding enzymes with a variety of substrates located at their active sites. Results We have analyzed the structural features and sequences of proteins having the hot dog fold. This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization. Segments with certain conserved sequence motifs seem to play crucial structural and functional roles in various classes of these proteins. Conclusion The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects. PMID:19473548

  18. Fold-related-fracturing at the Livingstone River anticline (AB; Canada) by coupling field surveying and numerical modelling

    NASA Astrophysics Data System (ADS)

    Humair, Florian; Epard, Jean-Luc; Bauville, Arthur; Jaboyedoff, Michel; Pana, Dinu; Kaus, Boris; Schmalholz, Stefan

    2016-04-01

    The interpretation of fold-related joints and faults is of primary importance in terms of fluids prospection (e.g. water, oil, gas, C02) since anticlines are potential structural trap while fracturing can strongly influence the storage capacity as well as the migration pathways. Located at the front of the Foothills of the Rocky Mountains in Alberta (Canada), the Livingstone Range (LRA) is analogous to hydrocarbon reservoir that occur elsewhere in the Foothills (Cooley et al., 2011). The Livingstone Range fold system is related to the development of the Livingstone thrust that cuts around 1000m up-section from a regional decollement in the Palliser Formation (Devonian) to another in the Fernie Formation (Jurassic). Our study focuses on the detailed structural investigation of the Livingstone River anticline (northern part of the LRA). It aims at characterizing the anticline geometry as well as the fracturing pattern (orientation, mode, infilling, spacing, trace length, density, and cross-cutting relationships) in order to propose a kinematic interpretation of the fold-related fracturing genesis. The study area is investigated at different scales by combining field surveys with remote sensing (HR-Digital Elevation Model, Ground-based LiDAR, Gigapixel photography) and thin-sections analyses. In a second step we performed finite difference 3D numerical simulations in order to compute the evolution of local principal stress orientation during folding. We compared the fracture (or plastic bands) distribution in the field with 1) a dynamic numerical model of detachment folding; and 2) an instantaneous numerical model based on the final fold geometry. Cooley, M.A., Price, R.A., Dixon, J.M., Kyser, T.K. 2011. Along-strike variations and internal details of chevron-style flexural slip thrust-propagation folds within the southern Livingstone Range anticlinorium, a paleo-hydrocarbon reservoir in southern Alberta Foothills, Canada. AAPG bulletin, 95 (11), 1821-1849.

  19. Folding analysis of the most complex Stevedore’s protein knot

    PubMed Central

    Wang, Iren; Chen, Szu-Yu; Hsu, Shang-Te Danny

    2016-01-01

    DehI is a homodimeric haloacid dehalogenase from Pseudomonas putida that contains the most complex 61 Stevedore’s protein knot within its folding topology. To examine how DehI attains such an intricate knotted topology we combined far-UV circular dichroism (CD), intrinsic fluorescence spectroscopy and small angle X-ray scattering (SAXS) to investigate its folding mechanism. Equilibrium unfolding of DehI by chemical denaturation indicated the presence of two highly populated folding intermediates, I and I’. While the two intermediates vary in secondary structure contents and tertiary packing according to CD and intrinsic fluorescence, respectively, their overall dimension and compactness are similar according to SAXS. Three single-tryptophan variants (W34, W53, and W196) were generated to probe non-cooperative unfolding events localized around the three fluorophores. Kinetic fluorescence measurements indicated that the transition from the intermediate I’ to the unfolded state is rate limiting. Our multiparametric folding analyses suggest that DehI unfolds through a linear folding pathway with two distinct folding intermediates by initial hydrophobic collapse followed by nucleation condensation, and that knotting precedes the formation of secondary structures. PMID:27527519

  20. Analysis of MHC class I folding: novel insights into intermediate forms

    PubMed Central

    Simone, Laura C.; Tuli, Amit; Simone, Peter D.; Wang, Xiaojian; Solheim, Joyce C.

    2012-01-01

    Folding around a peptide ligand is integral to the antigen presentation function of major histocompatibility complex (MHC) class I molecules. Several lines of evidence indicate that the broadly cross-reactive 34-1-2 antibody is sensitive to folding of the MHC class I peptide-binding groove. Here, we show that peptide-loading complex proteins associated with the murine MHC class I molecule Kd are found primarily in association with the 34-1-2+ form. This led us to hypothesize that the 34-1-2 antibody may recognize intermediately, as well as fully, folded MHC class I molecules. In order to further characterize the form(s) of MHC class I molecules recognized by 34-1-2, we took advantage of its cross-reactivity with Ld. Recognition of the open and folded forms of Ld by the 64-3-7 and 30-5-7 antibodies, respectively, has been extensively characterized, providing us with parameters against which to compare 34-1-2 reactivity. We found that the 34-1-2+ Ld molecules displayed characteristics indicative of incomplete folding, including increased tapasin association, endoplasmic reticulum retention, and instability at the cell surface. Moreover, we demonstrate that an Ld-specific peptide induced folding of the 34-1-2+ Ld intermediate. Altogether, these results yield novel insights into the nature of MHC class I molecules recognized by the 34-1-2 antibody. PMID:22329842

  1. Fold-Related Fractures and Postfolding Fracturing, Rock Mass Condition Analyses and Geological Modelling in Turtle Mountain (Alberta Canada).

    NASA Astrophysics Data System (ADS)

    Humair, Florian; Epard, Jean-Luc; Jaboyedoff, Michel; Pedrazzini, Andrea; Froese, Corey

    2010-05-01

    Turtle Mountain is located in the Foothills in southwest Alberta and is formed by highly fractured Paleozoic carbonates rocks and Mesozoic clastic rocks. This area is mainly affected by two major geological structures that are the Turtle Mountain anticline and the Turtle Mountain thrust. This site has become famous after a 30 M m3 rock avalanche of massive limestone and dolostone affecting the eastern mountainside of Turtle Mountain on April 1903. This resulted in more than 70 casualties and buried part of the Frank village. A detailed analysis of predisposing factors leading to failure has been performed using a structural and rock mass condition field analysis (geological and geotechnical mapping, rock mass classification, Schmidt hammer). In addition remote sensing analyses have been provided (High Resolution Digital Elevation Model, Coltop 3D software). The local variations of discontinuity sets and rock mass conditions has been estimated in order to separate the study zone into homogenous structural domains and to correlate them with unstable areas (volumes and failure mechanisms). The aim of this study is to build a theoretical model that shows the relationship between the anticline geometry and the fracturating density. It should be able to determine the origin and the chronology of the discontinuity sets in relation to the tectonic phases (mainly the folding one). A 3D geological model based on several geological profiles performed perpendicular to the Turtle Mountain anticline is necessary to make a detailed analysis. The preliminary results indicate the role of discontinuity sets in the failure mechanisms of the mountain. Moreover if some sets only appear in one limb of the anticline, some others are present in both limbs indicating their posteriority compared with the first ones. Furthermore, a relation between the distance to the fold axis and the quality of the rock mass (Geological Strength Index) has been statistically pointed out, illustrating the

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Common Structural Errors in Paleomagnetic Analysis of Fold-And Belts

    NASA Astrophysics Data System (ADS)

    Pueyo, E.

    2013-05-01

    Paleomagnetism is essential to decipher vertical axis rotations (VAR) in orogens, an elusive variable in tectonic studies. While unraveling the significance of VAR in the internal parts of orogenic belts might be made difficult due to the complex superposition of deformation events, it has provided timely insights into the geometry and kinematics of the external parts; the fold-and-thrust belts (FAT belts). Accurate quantification of VAR demands a reliable recording of the Earth's magnetic field. Inclination flattening or non-dipolar geometries of the geomagnetic field are well known to affect the reliability of paleomagnetic directions. Other factors are related to the geometry and mechanisms of deformation and are often overlooked: 1) Overlapping of vectors has to do with the technical limitation to isolating components in the laboratory. Secondary remagnetizations may be a common post tectonic process. The orientation of the overlapped vector will change along the fold geometry. Their restoration will result in different DEC and INC errors depending upon the degree of overlapping, the fold axis orientation (FAO), dip of the beds and the polarity of the components. 2) Many paleomagnetic studies implicitly assume the rigid-body behavior of rock volumes during deformation (absence of internal strain). However, pure shear may appear at the fold hinges and simple shear is frequent at the fold limbs and around fault planes. The bedding correction (BC) will induce DEC and INC errors controlled by the FAO and shear magnitude. 3) Different stages of folding and thrusting may happen in FAT belts and may be responsible for the superposition of non-coaxial axis of deformation. Besides, folds are not always cylindrical. These factors are responsible for the generation of plunging, conical and superposed folds, etc… The BC, instead of the reverse sequential restoration, will produce declination errors that depend upon the non-coaxility angle and the folding and tilting

  4. Quasi-atomic model of bacteriophage t7 procapsid shell: insights into the structure and evolution of a basic fold.

    PubMed

    Agirrezabala, Xabier; Velázquez-Muriel, Javier A; Gómez-Puertas, Paulino; Scheres, Sjors H W; Carazo, José M; Carrascosa, José L

    2007-04-01

    The existence of similar folds among major structural subunits of viral capsids has shown unexpected evolutionary relationships suggesting common origins irrespective of the capsids' host life domain. Tailed bacteriophages are emerging as one such family, and we have studied the possible existence of the HK97-like fold in bacteriophage T7. The procapsid structure at approximately 10 A resolution was used to obtain a quasi-atomic model by fitting a homology model of the T7 capsid protein gp10 that was based on the atomic structure of the HK97 capsid protein. A number of fold similarities, such as the fitting of domains A and P into the L-shaped procapsid subunit, are evident between both viral systems. A different feature is related to the presence of the amino-terminal domain of gp10 found at the inner surface of the capsid that might play an important role in the interaction of capsid and scaffolding proteins.

  5. Phonation thresholds as a function of laryngeal size in a two-mass model of the vocal folds

    NASA Astrophysics Data System (ADS)

    Lucero, Jorge C.; Koenig, Laura L.

    2005-11-01

    This letter analyzes the oscillation onset-offset conditions of the vocal folds as a function of laryngeal size. A version of the two-mass model of the vocal folds is used, coupled to a two-tube approximation of the vocal tract in configuration for the vowel /a/. The standard male configurations of the laryngeal and vocal tract models are used as reference, and their dimensions are scaled using a single factor. Simulations of the vocal fold oscillation and oral output are produced for varying values of the scaling factor. The results show that the oscillation threshold conditions become more restricted for smaller laryngeal sizes, such as those appropriate for females and children.

  6. Multivariate high-dimensional cortical folding analysis, combining complexity and shape, in neonates with congenital heart disease.

    PubMed

    Awate, Suyash P; Yushkevich, Paul; Song, Zhuang; Licht, Daniel; Gee, James C

    2009-01-01

    The paper presents a novel statistical framework for cortical folding pattern analysis that relies on a rich multivariate descriptor of folding patterns in a region of interest (ROI). The ROI-based approach avoids problems faced by spatial-normalization-based approaches stemming from the severe deficiency of homologous features between typical human cerebral cortices. Unlike typical ROI-based methods that summarize folding complexity or shape by a single number, the proposed descriptor unifies complexity and shape of the surface in a high-dimensional space. In this way, the proposed framework couples the reliability of ROI-based analysis with the richness of the novel cortical folding pattern descriptor. Furthermore, the descriptor can easily incorporate additional variables, e.g. cortical thickness. The paper proposes a novel application of a nonparametric permutation-based approach for statistical hypothesis testing for any multivariate high-dimensional descriptor. While the proposed framework has a rigorous theoretical underpinning, it is straightforward to implement. The framework is validated via simulated and clinical data. The paper is the first to quantitatively evaluate cortical folding in neonates with complex congenital heart disease.

  7. Detecting Selection on Protein Stability through Statistical Mechanical Models of Folding and Evolution

    PubMed Central

    Bastolla, Ugo

    2014-01-01

    The properties of biomolecules depend both on physics and on the evolutionary process that formed them. These two points of view produce a powerful synergism. Physics sets the stage and the constraints that molecular evolution has to obey, and evolutionary theory helps in rationalizing the physical properties of biomolecules, including protein folding thermodynamics. To complete the parallelism, protein thermodynamics is founded on the statistical mechanics in the space of protein structures, and molecular evolution can be viewed as statistical mechanics in the space of protein sequences. In this review, we will integrate both points of view, applying them to detecting selection on the stability of the folded state of proteins. We will start discussing positive design, which strengthens the stability of the folded against the unfolded state of proteins. Positive design justifies why statistical potentials for protein folding can be obtained from the frequencies of structural motifs. Stability against unfolding is easier to achieve for longer proteins. On the contrary, negative design, which consists in destabilizing frequently formed misfolded conformations, is more difficult to achieve for longer proteins. The folding rate can be enhanced by strengthening short-range native interactions, but this requirement contrasts with negative design, and evolution has to trade-off between them. Finally, selection can accelerate functional movements by favoring low frequency normal modes of the dynamics of the native state that strongly correlate with the functional conformation change. PMID:24970217

  8. Aerodynamic and acoustic effects of false vocal folds and epiglottis in excised larynx models.

    PubMed

    Alipour, Fariborz; Jaiswal, Sanyukta; Finnegan, Eileen

    2007-02-01

    The purpose of this study was to examine the aerodynamic and acoustic effects of the false vocal folds and the epiglottis on excised larynx phonation. Several canine larynges were prepared and mounted over a tapered tube that supplied pressurized, heated, and humidified air. Glottal adduction was accomplished either by using two-pronged probes to press the arytenoids together or by passing a suture to simulate lateral cricoarytenoid muscle activation. First, the excised larynx with false vocal folds and epiglottis intact was subjected to a series of pressure-flow experiments with longitudinal tension and adduction as major control parameters. Then, the epiglottis and finally the false vocal folds were removed and the experiment was repeated. The subglottal pressure and the electroglottographic, flow rate, audio, and sound pressure signals were recorded during each experiment. Glottal flow resistance was calculated from the pressure and flow signals. The electroglottographic signal was used to extract the fundamental frequency. It was found that the false vocal folds and the epiglottis offer a positive contribution to the glottal resistance and sound intensity of the larynx. Also, vocal fold elongation and glottal medial compression caused an increase in glottal resistance. The pressure-flow relationships were approximately linear regardless of the structure. The addition of the supraglottic laryngeal structures has a significant impact on both aerodynamic and acoustic characteristics of excised larynges.

  9. Comparative analysis of clinical profile: chronic cough vs paradoxical vocal fold motion

    PubMed Central

    Hartley, Naomi A.; Petty, Brian E.; Johnson, Bethany; Thibeault, Susan L.

    2015-01-01

    Background Ongoing contention surrounding typical demographic and clinical attributes of chronic cough (CC) and paradoxical vocal fold motion (PVFM) impedes timely diagnosis and optimum patient care. Designed to reduce preventable patient morbidity through improved recognition and differentiation, the current study aimed to determine representative clinical profiles for CC and PVFM, with identification of distinctive attributes from the general population and risk factors associated with each diagnosis. Methods Self-reported medical questionnaires, demographic and lifestyle attributes of CC and PVFM cases from a disease-specific outcomes database were compared to US population data and published normative values. Univariate comparison and multivariate regression modelling of age, sex, alcohol intake, smoking, Reflux Symptom Index (RSI), Voice Handicap Index (VHI), and Generalized Anxiety Disorder 7-item Scale (GAD-7) determined distinguishing features between the clinical groups, including odds ratios for presenting with CC versus PVFM. Results Clinical profiles developed from 283 (128 CC, 155 PVFM) adults (18–91years) were significantly different from the general population across each demographic, lifestyle and clinical variable (all p<.01), with the exception of obesity. Age (55.39 ± 13.54 vs 45.07 ± 16.51years, p<.01) and mean RSI score (21.5 ±9.02 vs 18.1±9.08, p<.01) most reliably distinguished CC from PVFM, with those aged 60–69 years (OR=9.45) most likely to be diagnosed with CC. Conclusions Standard clinical profiles of CC and PVFM are distinct from the general population, aiding determination of relative probabilities and risk factors in the differential diagnostic process. Variations between CC and PVFM were subtle, reliably distinguished by age and relative severity of laryngopharyngeal reflux symptomatology. PMID:26507903

  10. Single-molecule analysis of Mss116-mediated group II intron folding

    PubMed Central

    Karunatilaka, Krishanthi S.; Solem, Amanda; Pyle, Anna Marie; Rueda, David

    2015-01-01

    DEAD-box helicases are conserved enzymes involved in nearly all aspects of RNA metabolism, but their mechanisms of action remain unclear. Here, we investigated the mechanism of the DEAD-box protein Mss116 on its natural substrate, the group II intron ai5γ. Group II introns are structurally complex catalytic RNAs considered evolutionarily related to the eukaryotic spliceosome, and an interesting paradigm for large RNA folding. We used single-molecule fluorescence to monitor the effect of Mss116 on folding dynamics of a minimal active construct, ai5γ–D135. The data show that Mss116 stimulates dynamic sampling between states along the folding pathway, an effect previously observed only with high Mg2+ concentrations. Furthermore, the data indicate that Mss116 promotes folding through discrete ATP-independent and ATP-dependent steps. We propose that Mss116 stimulates group II intron folding through a multi-step process that involves electrostatic stabilization of early intermediates and ATP hydrolysis during the final stages of native state assembly. PMID:20944626

  11. Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli.

    PubMed

    Kerner, Michael J; Naylor, Dean J; Ishihama, Yasushi; Maier, Tobias; Chang, Hung-Chun; Stines, Anna P; Georgopoulos, Costa; Frishman, Dmitrij; Hayer-Hartl, Manajit; Mann, Matthias; Hartl, F Ulrich

    2005-07-29

    The E. coli chaperonin GroEL and its cofactor GroES promote protein folding by sequestering nonnative polypeptides in a cage-like structure. Here we define the contribution of this system to protein folding across the entire E. coli proteome. Approximately 250 different proteins interact with GroEL, but most of these can utilize either GroEL or the upstream chaperones trigger factor (TF) and DnaK for folding. Obligate GroEL-dependence is limited to only approximately 85 substrates, including 13 essential proteins, and occupying more than 75% of GroEL capacity. These proteins appear to populate kinetically trapped intermediates during folding; they are stabilized by TF/DnaK against aggregation but reach native state only upon transfer to GroEL/GroES. Interestingly, substantially enriched among the GroEL substrates are proteins with (betaalpha)8 TIM-barrel domains. We suggest that the chaperonin system may have facilitated the evolution of this fold into a versatile platform for the implementation of numerous enzymatic functions.

  12. Dissecting electrostatic screening, specific ion binding, and ligand binding in an energetic model for glycine riboswitch folding

    SciTech Connect

    Lipfert, Jan; Sim, Adelene Y.L.; Herschlag, Daniel; Doniach, Sebastian

    2010-09-17

    Riboswitches are gene-regulating RNAs that are usually found in the 5{prime}-untranslated regions of messenger RNA. As the sugar-phosphate backbone of RNA is highly negatively charged, the folding and ligand-binding interactions of riboswitches are strongly dependent on the presence of cations. Using small angle X-ray scattering (SAXS) and hydroxyl radical footprinting, we examined the cation dependence of the different folding stages of the glycine-binding riboswitch from Vibrio cholerae. We found that the partial folding of the tandem aptamer of this riboswitch in the absence of glycine is supported by all tested mono- and divalent ions, suggesting that this transition is mediated by nonspecific electrostatic screening. Poisson-Boltzmann calculations using SAXS-derived low-resolution structural models allowed us to perform an energetic dissection of this process. The results showed that a model with a constant favorable contribution to folding that is opposed by an unfavorable electrostatic term that varies with ion concentration and valency provides a reasonable quantitative description of the observed folding behavior. Glycine binding, on the other hand, requires specific divalent ions binding based on the observation that Mg{sup 2+}, Ca{sup 2+}, and Mn{sup 2+} facilitated glycine binding, whereas other divalent cations did not. The results provide a case study of how ion-dependent electrostatic relaxation, specific ion binding, and ligand binding can be coupled to shape the energetic landscape of a riboswitch and can begin to be quantitatively dissected.

  13. Controls on SEDEX Mineralization in the Aravalli-Delhi Fold Belt: Insights from Integrated 3D Geological and Geophysical Modelling

    NASA Astrophysics Data System (ADS)

    Yadav, Shilpi; Porwal, Alok

    2017-04-01

    3D modelling provides a representation of the uncertainty when sparse or no data are available for a region. 3D geological model can provide important insights on the geometrical behavior of the rock units and also the locations of the crustal scale structures which in turn can provide the 3D (depth) and 4D (time) geodynamic evolution of the region. The Aravalli-Delhi Fold Belt which is located in the state of Rajasthan, India covers the geological history from Archaean to Recent. It underwent two stage tectonic evolution during Proterozoic, which lead to the formation of substantial Sediment-Hosted Lead-Zinc deposits i.e. Rampura-Agucha deposit ( 1800 Ma.), Rajpura-Dariba deposit ( 1800 Ma), Pur-Banera deposit ( 1800 Ma) and Zawar deposit ( 1700 Ma). The Sediment-Hosted Lead-Zinc deposits with easy surface expressions have already been discovered based on the conventional 2D conceptual geological models approach, therefore now it is very important to discover and explore the deep-seated deposits which have no or indirect surface expressions. These deposits are formed due to the mineralization process which run in three dimensional space and time, and hence are the result of the 3D and 4D geodynamic processes operating in the region. The 3D geological modelling of the Aravalli-Delhi Fold Belt and the mineral system of the Sediment-Hosted Lead-Zinc deposit will identify the new controls of mineralization for the Lead-Zinc deposits in the fold belt.. A 3D crustal model for Aravalli-Delhi Fold Belt will be created for an area of about 275×200 square kilometers of Aravalli-Delhi Fold Belt, which will convert into a 3D block of about 275×200×60 cubic kilometers by applying forward gravity modelling technique. The 3D geological model will be based on the detailed geological and structural mapping, and the use of the 2D forward gravity models created for the entire fold belt. Keywords: Aravalli-Delhi Fold Belt; 3D Geological Modelling; 3D and 4D Geological Evolution

  14. Structural modeling of the Zagros fold-and-thrust belt (Iraq) combining field work and remote sensing techniques

    NASA Astrophysics Data System (ADS)

    Reif, D.; Grasemann, B.; Faber, R.; Lockhart, D.

    2009-04-01

    The Zagros fold-and-thrust belt is known for its spectacular fold trains, which have formed in detached Phanerozoic sedimentary cover rocks above a shortened crystalline Precambrian basement. Orogeny evolved through the Late Cretaceous to Miocene collision between the Arabian and Eurasian plate, during which the Neotethys oceanic basin was closed. Still active deformation shortening in the order of 2-2.5 cm/yr is partitioned in S-SW directed folding and thrusting of the Zagros fold-and-thrust belt and NW-SE to N-S trending dextral strike slip faults. The sub-cylindrical doubly-plunging fold trains with wavelengths of 5 - 10 km host more than half of the world's hydrocarbon reserves in mostly anticlinal traps. In this work we investigate the three dimensional structure of the Zagros fold-and-thrust belt in the Kurdistan region of Iraq. The mapped region is situated NE from the city of Erbil and comprises mainly Cretaceous to Cenozoic folded sediments consisting of mainly limestones, dolomites, sandstones, siltstones, claystones and conglomerates. Although the overall security situation in Kurdistan is much better than in the rest of Iraq, structural field mapping was restricted to sections along the main roads perpendicular to the strike of the fold trains, mainly because of the contamination of the area with landmines and unexploded ordnance, a problem that dates back to the end of World War Two. Landmines were also used by the central government in the 1960s and 1970s in order to subdue Kurdish groups. During the 1980-1988 Iran-Iraq War, the north was mined again. In order to extend the structural measurements statistically over the investigated area resulting in a three-dimensional model of the fold trains, we used the Fault Trace module of the WinGeol software (www.terramath.com). This package allows the interactive mapping and visualization of the spatial orientations (i.e. dip and strike) of geological finite planar structures (e.g. faults, lithological

  15. Facies analysis and diagenetic features of the Aptian Dariyan Formation in Zagros Fold-Thrust Belt, SW Iran

    NASA Astrophysics Data System (ADS)

    Haghighi, Arash Shaabanpour; Sahraeyan, Mohammad

    2014-12-01

    The Aptian Dariyan Formation (upper part of the Khami Group), is one of the important reservoir rocks in the Zagros Fold-Thrust Belt. The Zagros Fold-Thrust Belt is located on the boundary between the Arabian and Eurasian lithospheric plates and formed from collision between Eurasia and advancing Arabia during the Cenozoic. In these studied area, the Dariyan Formation with a thickness of 136 meters (Fahliyan section) and 100 meters (Kuh-e-Rahmat section), consists of carbonate rocks. Based on the facies analysis and sedimentological data, 16 microfacies were identified. The microfacies are attributed to five facies belts: tidal flat (lime mudstone, dolomitic mudstone and stromatolitic boundstone), lagoon (bioclastic packstone, orbitolinids bioclastic packstone and orbitolinids peloidal packstone), shoal (orbitolinids grainstone and peloidal grainstone), restricted (peloidal packstone, rudist floatstone/rudstone and orbitolinid wackestone), and open marine (orbitolinid floatstone, dasycladacean algae floatstone, bioclast pelagic foraminiferal wackestone/packstone, pelagic foraminiferal mudstone/wackestone, and calcispere packstone/wackestone). The depositional model relates to the carbonate ramp. The allochems of the Dariyan Formation are dominated by foraminifera, bioclasts and green algae. Peloids, and intraclasts are less abundant in this formation. Due to the great diversity and abundance of the foraminifera, this carbonate ramp is referred to as a "foraminifera-dominated carbonate ramp system". This carbonate system reflects a local regression in the Fahliyan section which can be related to the vertical movement of the Kazeroon Fault. The carbonates of Dariyan Formation have been affected by a variety of diagenetic processes such as compaction, dissolution, cementation, neomorphism, and dolomitization.

  16. A bionic approach to mathematical modeling the fold geometry of deployable reflector antennas on satellites

    NASA Astrophysics Data System (ADS)

    Feng, C. M.; Liu, T. S.

    2014-10-01

    Inspired from biology, this study presents a method for designing the fold geometry of deployable reflectors. Since the space available inside rockets for transporting satellites with reflector antennas is typically cylindrical in shape, and its cross-sectional area is considerably smaller than the reflector antenna after deployment, the cross-sectional area of the folded reflector must be smaller than the available rocket interior space. Membrane reflectors in aerospace are a type of lightweight structure that can be packaged compactly. To design membrane reflectors from the perspective of deployment processes, bionic applications from morphological changes of plants are investigated. Creating biologically inspired reflectors, this paper deals with fold geometry of reflectors, which imitate flower buds. This study uses mathematical formulation to describe geometric profiles of flower buds. Based on the formulation, new designs for deployable membrane reflectors derived from bionics are proposed. Adjusting parameters in the formulation of these designs leads to decreases in reflector area before deployment.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Analysis of RNA Folding and Ribonucleoprotein Assembly by Single-Molecule Fluorescence Spectroscopy

    PubMed Central

    Pljevaljčić, Goran; Robertson-Anderson, Rae; van der Schans, Edwin; Millar, David

    2013-01-01

    Summary To execute their diverse range of biological functions, RNA molecules must fold into specific tertiary structures and/or associate with one or more proteins to form ribonucleoprotein (RNP) complexes. Single-molecule fluorescence spectroscopy is a powerful tool for the study of RNA folding and RNP assembly processes, directly revealing different conformational subpopulations that are hidden in conventional ensemble measurements. Moreover, kinetic processes can be observed without the need to synchronize a population of molecules. In this chapter, we describe the fluorescence spectroscopic methods used for single-molecule measurements of freely diffusing or immobilized RNA molecules or RNA-protein complexes. We also provide practical protocols to prepare the fluorescently labeled RNA and protein molecules required for such studies. Finally, we provide two examples of how these various preparative and spectroscopic methods are employed in the study of RNA folding and RNP assembly processes. PMID:22573447

  19. Metal induced folding: synthesis and conformational analysis of the lanthanide complexes of two 44-membered hydrazone macrocycles.

    PubMed

    Klein, Jörg M; Clegg, Jack K; Saggiomo, Vittorio; Reck, Lisa; Lüning, Ulrich; Sanders, Jeremy K M

    2012-04-07

    Six new lanthanide complexes of two 44-membered macrocycles have been prepared and characterised in solution. An analysis of the conformations of the free macrocycles and their lanthanide complexes both in solution (2D NMR) and in solid state (X-ray crystallography) demonstrate that the complexation induces changes in folding of the macrocycles.

  20. Knotted and topologically complex proteins as models for studying folding and stability

    PubMed Central

    Yeates, Todd O.; Norcross, Todd S.; King, Neil P.

    2008-01-01

    SUMMARY Among proteins of known three dimensional structure, only a few possess complex topological features such as knotted or interlinked (catenated) protein backbones. Such unusual proteins offer potentially unique insights into folding pathways and stabilization mechanisms. They also present special challenges for both theorists and computational scientists interested in understanding and predicting protein folding behavior. Here we review complex topological features in proteins with a focus on recent progress on the identification and characterization of knotted and interlinked protein systems. Also, an approach is described for designing an expanded set of knotted proteins. PMID:17967433

  1. Effects of vocal fold epithelium removal on vibration in an excised human larynx model

    PubMed Central

    Tse, Justin R.; Zhang, Zhaoyan; Long, Jennifer L.

    2015-01-01

    This study investigated the impact of selective epithelial injury on phonation in an excised human larynx apparatus. With intact epithelium, the vocal folds exhibited a symmetrical vibration pattern with complete glottal closure during vibration. The epithelium was then enzymatically removed from one, then both vocal folds, which led to left-right asymmetric vibration and a decreased closed quotient. Although the mechanisms underlying these vibratory changes are unclear, these results demonstrate that some component of an intact surface layer may play an important role in achieving normal symmetric vibration and glottal closure. PMID:26233062

  2. Real-Time Analysis of Folding upon Binding of a Disordered Protein by Using Dissolution DNP NMR Spectroscopy.

    PubMed

    Ragavan, Mukundan; Iconaru, Luigi I; Park, Cheon-Gil; Kriwacki, Richard W; Hilty, Christian

    2017-06-12

    The kinase inhibitory domain of the cell cycle regulatory protein p27(Kip1) (p27) was nuclear spin hyperpolarized using dissolution dynamic nuclear polarization (D-DNP). While intrinsically disordered in isolation, p27 adopts secondary structural motifs, including an α-helical structure, upon binding to cyclin-dependent kinase 2 (Cdk2)/cyclin A. The sensitivity gains obtained with hyperpolarization enable the real-time observation of (13) C NMR signals during p27 folding upon binding to Cdk2/cyclin A on a time scale of several seconds. Time-dependent intensity changes are dependent on the extent of folding and binding, as manifested in differential spin relaxation. The analysis of signal decay rates suggests the existence of a partially folded p27 intermediate during the timescale of the D-DNP NMR experiment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Microscopic Description of the Exotic Nuclei Reactions by Using Folding model Potentials

    SciTech Connect

    Ibraheem, Awad A.; Hassanain, M. A.; Mokhtar, S. R.; El-Azab Farid, M.; Zaki, M. A.; Mahmoud, Zakaria M. M.

    2011-10-27

    A microscopic folding approach based upon the effective M3Y nucleon-nucleon interaction and the nuclear matter densities of the interacting nuclei has been carried out to explain recently measured experimental data of the {sup 6}He+{sup 120}Sn elastic scattering reaction at four different laboratory energies near the Coulomb barrier. The corresponding reaction cross sections are also considered.

  4. Cause-effect relationship between vocal fold physiology and voice production in a three-dimensional phonation model.

    PubMed

    Zhang, Zhaoyan

    2016-04-01

    The goal of this study is to better understand the cause-effect relation between vocal fold physiology and the resulting vibration pattern and voice acoustics. Using a three-dimensional continuum model of phonation, the effects of changes in vocal fold stiffness, medial surface thickness in the vertical direction, resting glottal opening, and subglottal pressure on vocal fold vibration and different acoustic measures are investigated. The results show that the medial surface thickness has dominant effects on the vertical phase difference between the upper and lower margins of the medial surface, closed quotient, H1-H2, and higher-order harmonics excitation. The main effects of vocal fold approximation or decreasing resting glottal opening are to lower the phonation threshold pressure, reduce noise production, and increase the fundamental frequency. Increasing subglottal pressure is primarily responsible for vocal intensity increase but also leads to significant increase in noise production and an increased fundamental frequency. Increasing AP stiffness significantly increases the fundamental frequency and slightly reduces noise production. The interaction among vocal fold thickness, stiffness, approximation, and subglottal pressure in the control of F0, vocal intensity, and voice quality is discussed.

  5. Cause-effect relationship between vocal fold physiology and voice production in a three-dimensional phonation model

    PubMed Central

    Zhang, Zhaoyan

    2016-01-01

    The goal of this study is to better understand the cause-effect relation between vocal fold physiology and the resulting vibration pattern and voice acoustics. Using a three-dimensional continuum model of phonation, the effects of changes in vocal fold stiffness, medial surface thickness in the vertical direction, resting glottal opening, and subglottal pressure on vocal fold vibration and different acoustic measures are investigated. The results show that the medial surface thickness has dominant effects on the vertical phase difference between the upper and lower margins of the medial surface, closed quotient, H1-H2, and higher-order harmonics excitation. The main effects of vocal fold approximation or decreasing resting glottal opening are to lower the phonation threshold pressure, reduce noise production, and increase the fundamental frequency. Increasing subglottal pressure is primarily responsible for vocal intensity increase but also leads to significant increase in noise production and an increased fundamental frequency. Increasing AP stiffness significantly increases the fundamental frequency and slightly reduces noise production. The interaction among vocal fold thickness, stiffness, approximation, and subglottal pressure in the control of F0, vocal intensity, and voice quality is discussed. PMID:27106298

  6. Moving control volume analysis of compressible flow-structure interactions - An application to sustained vocal folds vibration in glottis

    NASA Astrophysics Data System (ADS)

    Zhang, Lucy; Yang, Jubiao; Krane, Michael

    2016-11-01

    The fundamental mechanism of a self-sustained vibration can be analyzed and explained using a moving control volume analysis. In contrast to the conventional "textbook" derivation of control volume analysis, this work shows the derivation of a moving control volume based the "first principles" of physics where the control volume changes its size and location with time. This generalized derivation is demonstrated in a framework for compressible flow-structure interactions where the structure moves and deforms in a compressible fluid medium, e.g. air, within a control volume. The moving control volume analysis helps explain self-sustained vibrations of structures in fluid. An application to the vocal folds vibration in glottis is studied, where the interaction between laryngeal airflow and vocal folds are successfully simulated using the modified Immersed Finite Element Method (mIFEM), a fully coupled approach to simulate fluid-structure interactions. Control volume equations are derived for compressible airflow in a moving control volume in the vicinity of the moving vocal folds. Utilization of mechanical energy is evaluated to understand how vocal folds vibration is self-sustained. We acknowledge the funding support of NIH 2R01DC005642-10A1.

  7. Deciphering the mechanisms of binding induced folding at nearly atomic resolution: The Φ value analysis applied to IDPs

    PubMed Central

    Gianni, Stefano; Dogan, Jakob; Jemth, Per

    2014-01-01

    The Φ value analysis is a method to analyze the structure of metastable states in reaction pathways. Such a methodology is based on the quantitative analysis of the effect of point mutations on the kinetics and thermodynamics of the probed reaction. The Φ value analysis is routinely used in protein folding studies and is potentially an extremely powerful tool to analyze the mechanism of binding induced folding of intrinsically disordered proteins. In this review we recapitulate the key equations and experimental advices to perform the Φ value analysis in the perspective of the possible caveats arising in intrinsically disordered systems. Finally, we briefly discuss some few examples already available in the literature. PMID:28232881

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

    ERIC Educational Resources Information Center

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

    ERIC Educational Resources Information Center

    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…

  10. Mechanics of non-critical fold-thrust belts based on finite element models

    NASA Astrophysics Data System (ADS)

    Simpson, Guy

    2011-03-01

    The mechanics of fold-thrust belts and accretionary wedges is investigated using a two dimensional, plane strain, elastic-plastic (cohesive Mohr-Coulomb) mechanical model solved with the Finite Element Method. Results show that when a layer with an initially non-critical geometry is compressed from the rear, it does not form a wedge that is at failure throughout, as assumed in critical wedge theory. Rather, the wedge consists of narrow plastic shear zones that propagate sequentially outward with time, loading rocks ahead while unloading rocks behind. Not only are stress states within the wedge not everywhere at failure but principal stress orientations vary strongly in time and space, particularly across shear zones, near the basal detachment and in the hanging wall of active structures, where local surface extension may be observed. The reason the investigated wedges are not stressed to compressive failure throughout is related to strength reduction associated with strain localisation that enables material outside shear zones to unload and return to an elastic stress state. This mechanism is intrinsic to elastic-plastic materials and occurs regardless of any material degradation such as loss of cohesion. Even though the stress state of the investigated wedges is generally non-critical, the overall geometry may still be consistent with cohesionless critical wedge theory, since the local surface slope is created when a particular part of the wedge is at a limit state. Prowedge tapers display non self-similar growth through time but eventually evolve to the minimum critical taper. Retrowedges on the other hand, may get caught within this initial transient state and thus may have tapers anywhere between the minimum and maximum critical taper. However, if the basal detachment is such that lateral propagation is not kinematically inhibited, retrowedges are shown to also eventually evolve towards minimum critical tapers, resulting in a symmetrical doubly-vergent orogen

  11. The occurrence of the Coanda effect in pulsatile flow through static models of the human vocal folds.

    PubMed

    Erath, Byron D; Plesniak, Michael W

    2006-08-01

    Pulsatile flow through a one-sided diffuser and static divergent vocal-fold models is investigated to ascertain the relevance of viscous-driven flow asymmetries in the larynx. The models were 7.5 times real size, and the flow was scaled to match Reynolds and Strouhal numbers, as well as the translaryngeal pressure drop. The Reynolds number varied from 0-2000, for flow oscillation frequencies corresponding to 100 and 150 Hz life-size. Of particular interest was the development of glottal flow skewing by attachment to the bounding walls, or Coanda effect, in a pulsatile flow field, and its impact on speech. The vocal folds form a divergent passage during phases of the phonation cycle when viscous effects such as flow separation are important. It was found that for divergence angles of less than 20 degrees, the attachment of the flow to the vocal-fold walls occurred when the acceleration of the forcing function was zero, and the flow had reached maximum velocity. For a divergence angle of 40 degrees, the fully separated central jet never attached to the vocal-fold walls. Inferences are made regarding the impact of the Coanda effect on the sound source contribution in speech.

  12. Chain folding and A:T pairing in human telomeric DNA: a model-building and molecular dynamics study.

    PubMed Central

    Mohanty, D; Bansal, M

    1995-01-01

    The various types of chain folding and possible intraloop as well as interloop base pairing in human telomeric DNA containing d(TTAG3) repeats have been investigated by model-building, molecular mechanics, and molecular dynamics techniques. Model-building and molecular mechanics studies indicate that it is possible to build a variety of energetically favorable folded-back structures with the two TTA loops on same side and the 5' end thymines in the two loops forming TATA tetrads involving a number of different intraloop as well as interloop A:T pairing schemes. In these folded-back structures, although both intraloop and interloop Watson-Crick pairing is feasible, no structure is possible with interloop Hoogsteen pairing. MD studies of representative structures indicate that the guanine-tetraplex stem is very rigid and, while the loop regions are relatively much more flexible, most of the hydrogen bonds remain intact throughout the 350-ps in vacuo simulation. The various possible TTA loop structures, although they are energetically similar, have characteristic inter proton distances, which could give rise to unique cross-peaks in two-dimensional nuclear Overhauser effect spectroscopy (NOESY) experiments. These folded-back structures with A:T pairings in the loop region help in rationalizing the data from chemical probing and other biochemical studies on human telomeric DNA. PMID:8519959

  13. Effect of high-dose vocal fold injection of cidofovir and bevacizumab in a porcine model.

    PubMed

    Ahmed, Mostafa M; Connor, Matthew P; Palazzolo, Mitzi; Thompson, Michelle E; Lospinoso, Josh; O'Connor, Peter; Howard, N Scott; Maturo, Stephen C

    2017-03-01

    Perform a follow-up study to investigate the histologic impact of high-dose intralaryngeal cidofovir injections in porcine vocal cords, either alone or in combination with bevacizumab, and compared to saline controls. This was an in vivo study involving 24 pigs with blinded pathologist review of specimens. Six groups were created, with four subjects in each group. Each subject received 10 or 20 mg of either cidofovir or bevacizumab alone, or in combination, injected into the right vocal cord. The left vocal fold was used as a saline control. Three separate injections were made at 2-week intervals. Larynges were harvested at 8 and 12 weeks, stained with hematoxylin and eosin and trichrome stain, and reviewed for histologic changes by two blinded pathologists. Minimal inflammation, edema, and atypia were noted with all treatments. Increased glandular inflammation was noted with 10 mg bevacizumab (P < 0.05), which decreased when combined with 10 mg cidofovir (P < 0.05). No lamina propria or muscle fibrosis was observed. Drug duration had no statistically significant histologic impact. High-dose cidofovir and bevacizumab do not induce detrimental vocal fold changes. Combination cidofovir and bevacizumab do not cause vocal fold scarring. Further work is needed to assess systemic concentration with this high-dose combination in humans. N/A. Laryngoscope, 127:671-675, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Unprecedented folding in linker based flexible tripodal molecule and their conformational analysis

    NASA Astrophysics Data System (ADS)

    Gaurav, Archana; Kumar, Ranjeet; Gupta, Hariom; Ravikumar, K.; Sridhar, B.; Tewari, Ashish Kumar

    2017-04-01

    Here, we first time report the flexible tripodal molecules, contained propylene as a linker, thiocyanuric acid as central core and, p-nitro phenol 1 and pyridazinone 2 as terminal for conformational studies. The conformational studies of these tripodal molecules have been carried by X-ray crystallography, 2D-NOESY spectra and computational studies. Both the molecules have shown folded conformations in solid and solution state however solid state conformation is not stable in gaseous state.

  15. Structural Analysis of Protein Folding by the Long-Chain Archaeal Chaperone FKBP26

    SciTech Connect

    E Martinez-Hackert; W Hendrickson

    2011-12-31

    In the cell, protein folding is mediated by folding catalysts and chaperones. The two functions are often linked, especially when the catalytic module forms part of a multidomain protein, as in Methanococcus jannaschii peptidyl-prolyl cis/trans isomerase FKBP26. Here, we show that FKBP26 chaperone activity requires both a 50-residue insertion in the catalytic FKBP domain, also called 'Insert-in-Flap' or IF domain, and an 80-residue C-terminal domain. We determined FKBP26 structures from four crystal forms and analyzed chaperone domains in light of their ability to mediate protein-protein interactions. FKBP26 is a crescent-shaped homodimer. We reason that folding proteins are bound inside the large crescent cleft, thus enabling their access to inward-facing peptidyl-prolyl cis/trans isomerase catalytic sites and ipsilateral chaperone domain surfaces. As these chaperone surfaces participate extensively in crystal lattice contacts, we speculate that the observed lattice contacts reflect a proclivity for protein associations and represent substrate interactions by FKBP26 chaperone domains. Finally, we find that FKBP26 is an exceptionally flexible molecule, suggesting a mechanism for nonspecific substrate recognition.

  16. The role of sidechain packing and native contact interactions in folding: Discontinuous molecular dynamics folding simulations of an all-atom Gō model of fragment B of Staphylococcal protein A

    NASA Astrophysics Data System (ADS)

    Linhananta, Apichart; Zhou, Yaoqi

    2002-11-01

    Protein topology, which refers to the arrangement of secondary structures of proteins, has been extensively investigated to examine its role in protein folding. However, recent studies show that topology alone cannot account for the variation of folding behaviors observed in some proteins of the same structural family. In a recent work, we showed that the native structure of the second β hairpin of protein G predicts a folding mechanism that is different from topology-based models. Here, we continue to examine how much one can learn about folding mechanism from native structure. This work focuses on fragment B of Staphylococcal protein A (BpA) - a three-helix (H1, H2, and H3) bundle protein. Using a recently developed all-atom (except nonpolar hydrogen) Gō model interacting with simple discontinuous potentials, the folding of the model BpA was observed in 112 out of 249 trajectories within 50 h of CPU times on a Pentium PC (1 GHz). The model successfully captured several specific properties of BpA that have been observed experimentally. These include the higher stability of H3 compared to H1 and H2, and the higher stability of the H2-H3 microdomain compared to the H1-H2 microdomain. These specific details were not produced by a topology-based square-well model of BpA. Thus, the result further supports the important role of sidechain packing in determining the specific pathway of protein folding. Additional 96 000 short simulations were performed to locate the transition states of the two folding pathways. The limitation of the Gō model and its possible improvement are also discussed.

  17. Quantitative analysis of the ion-dependent folding stability of DNA triplexes.

    PubMed

    Chen, Gengsheng; Chen, Shi-Jie

    2011-12-01

    A DNA triplex is formed through binding of a third strand to the major groove of a duplex. Due to the high charge density of a DNA triplex, metal ions are critical for its stability. We recently developed the tightly bound ion (TBI) model for ion-nucleic acids interactions. The model accounts for the potential correlation and fluctuations of the ion distribution. We now apply the TBI model to analyze the ion dependence of the thermodynamic stability for DNA triplexes. We focus on two experimentally studied systems: a 24-base DNA triplex and a pair of interacting 14-base triplexes. Our theoretical calculations for the number of bound ions indicate that the TBI model provides improved predictions for the number of bound ions than the classical Poisson-Boltzmann (PB) equation. The improvement is more significant for a triplex, which has a higher charge density than a duplex. This is possibly due to the higher ion concentration around the triplex and hence a stronger ion correlation effect for a triplex. In addition, our analysis for the free energy landscape for a pair of 14-mer triplexes immersed in an ionic solution shows that divalent ions could induce an attractive force between the triplexes. Furthermore, we investigate how the protonated cytosines in the triplexes affect the stability of the triplex helices.

  18. Quantitative analysis of the ion-dependent folding stability of DNA triplexes

    NASA Astrophysics Data System (ADS)

    Chen, Gengsheng; Chen, Shi-Jie

    2011-12-01

    A DNA triplex is formed through binding of a third strand to the major groove of a duplex. Due to the high charge density of a DNA triplex, metal ions are critical for its stability. We recently developed the tightly bound ion (TBI) model for ion-nucleic acids interactions. The model accounts for the potential correlation and fluctuations of the ion distribution. We now apply the TBI model to analyze the ion dependence of the thermodynamic stability for DNA triplexes. We focus on two experimentally studied systems: a 24-base DNA triplex and a pair of interacting 14-base triplexes. Our theoretical calculations for the number of bound ions indicate that the TBI model provides improved predictions for the number of bound ions than the classical Poisson-Boltzmann (PB) equation. The improvement is more significant for a triplex, which has a higher charge density than a duplex. This is possibly due to the higher ion concentration around the triplex and hence a stronger ion correlation effect for a triplex. In addition, our analysis for the free energy landscape for a pair of 14-mer triplexes immersed in an ionic solution shows that divalent ions could induce an attractive force between the triplexes. Furthermore, we investigate how the protonated cytosines in the triplexes affect the stability of the triplex helices.

  19. Protein folding pathways and state transitions described by classical equations of motion of an elastic network model.

    PubMed

    Williams, Gareth; Toon, Andrew J

    2010-12-01

    Protein topology defined by the matrix of residue contacts has proved to be a fruitful basis for the study of protein dynamics. The widely implemented coarse-grained elastic network model of backbone fluctuations has been used to describe crystallographic temperature factors, allosteric couplings, and some aspects of the folding pathway. In the present study, we develop a model of protein dynamics based on the classical equations of motion of a damped network model (DNM) that describes the folding path from a completely unfolded state to the native conformation through a single-well potential derived purely from the native conformation. The kinetic energy gained through the collapse of the protein chain is dissipated through a friction term in the equations of motion that models the water bath. This approach is completely general and sufficiently fast that it can be applied to large proteins. Folding pathways for various proteins of different classes are described and shown to correlate with experimental observations and molecular dynamics and Monte Carlo simulations. Allosteric transitions between alternative protein structures are also modeled within the DNM through an asymmetric double-well potential.

  20. Optimized Wang-Landau sampling of lattice polymers: Ground state search and folding thermodynamics of HP model proteins

    NASA Astrophysics Data System (ADS)

    Wüst, Thomas; Landau, David P.

    2012-08-01

    Coarse-grained (lattice-) models have a long tradition in aiding efforts to decipher the physical or biological complexity of proteins. Despite the simplicity of these models, however, numerical simulations are often computationally very demanding and the quest for efficient algorithms is as old as the models themselves. Expanding on our previous work [T. Wüst and D. P. Landau, Phys. Rev. Lett. 102, 178101 (2009)], 10.1103/PhysRevLett.102.178101, we present a complete picture of a Monte Carlo method based on Wang-Landau sampling in combination with efficient trial moves (pull, bond-rebridging, and pivot moves) which is particularly suited to the study of models such as the hydrophobic-polar (HP) lattice model of protein folding. With this generic and fully blind Monte Carlo procedure, all currently known putative ground states for the most difficult benchmark HP sequences could be found. For most sequences we could also determine the entire energy density of states and, together with suitably designed structural observables, explore the thermodynamics and intricate folding behavior in the virtually inaccessible low-temperature regime. We analyze the differences between random and protein-like heteropolymers for sequence lengths up to 500 residues. Our approach is powerful both in terms of robustness and speed, yet flexible and simple enough for the study of many related problems in protein folding.

  1. Optimized Wang-Landau sampling of lattice polymers: ground state search and folding thermodynamics of HP model proteins.

    PubMed

    Wüst, Thomas; Landau, David P

    2012-08-14

    Coarse-grained (lattice-) models have a long tradition in aiding efforts to decipher the physical or biological complexity of proteins. Despite the simplicity of these models, however, numerical simulations are often computationally very demanding and the quest for efficient algorithms is as old as the models themselves. Expanding on our previous work [T. Wüst and D. P. Landau, Phys. Rev. Lett. 102, 178101 (2009)], we present a complete picture of a Monte Carlo method based on Wang-Landau sampling in combination with efficient trial moves (pull, bond-rebridging, and pivot moves) which is particularly suited to the study of models such as the hydrophobic-polar (HP) lattice model of protein folding. With this generic and fully blind Monte Carlo procedure, all currently known putative ground states for the most difficult benchmark HP sequences could be found. For most sequences we could also determine the entire energy density of states and, together with suitably designed structural observables, explore the thermodynamics and intricate folding behavior in the virtually inaccessible low-temperature regime. We analyze the differences between random and protein-like heteropolymers for sequence lengths up to 500 residues. Our approach is powerful both in terms of robustness and speed, yet flexible and simple enough for the study of many related problems in protein folding.

  2. FunFOLD: an improved automated method for the prediction of ligand binding residues using 3D models of proteins

    PubMed Central

    2011-01-01

    Background The accurate prediction of ligand binding residues from amino acid sequences is important for the automated functional annotation of novel proteins. In the previous two CASP experiments, the most successful methods in the function prediction category were those which used structural superpositions of 3D models and related templates with bound ligands in order to identify putative contacting residues. However, whilst most of this prediction process can be automated, visual inspection and manual adjustments of parameters, such as the distance thresholds used for each target, have often been required to prevent over prediction. Here we describe a novel method FunFOLD, which uses an automatic approach for cluster identification and residue selection. The software provided can easily be integrated into existing fold recognition servers, requiring only a 3D model and list of templates as inputs. A simple web interface is also provided allowing access to non-expert users. The method has been benchmarked against the top servers and manual prediction groups tested at both CASP8 and CASP9. Results The FunFOLD method shows a significant improvement over the best available servers and is shown to be competitive with the top manual prediction groups that were tested at CASP8. The FunFOLD method is also competitive with both the top server and manual methods tested at CASP9. When tested using common subsets of targets, the predictions from FunFOLD are shown to achieve a significantly higher mean Matthews Correlation Coefficient (MCC) scores and Binding-site Distance Test (BDT) scores than all server methods that were tested at CASP8. Testing on the CASP9 set showed no statistically significant separation in performance between FunFOLD and the other top server groups tested. Conclusions The FunFOLD software is freely available as both a standalone package and a prediction server, providing competitive ligand binding site residue predictions for expert and non

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

    SciTech Connect

    Nedialkova, Lilia V.; Amat, Miguel A.; Kevrekidis, Ioannis G. E-mail: gerhard.hummer@biophys.mpg.de; Hummer, Gerhard E-mail: gerhard.hummer@biophys.mpg.de

    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.

  4. Observation of a summer tropopause fold by ozonesonde at Changchun, China: Comparison with reanalysis and model simulation

    NASA Astrophysics Data System (ADS)

    Li, Dan; Bian, Jianchun

    2015-10-01

    Tropopause folds are one of the key mechanisms of stratosphere-troposphere exchange (STE) in extratropical regions, transporting ozone-rich stratospheric air into the middle and lower troposphere. Although there have been many studies of tropopause folds that have occurred over Europe and North America, a very limited amount of work has been carried out over northeastern Asia. Ozonesondes produced by the Institute of Atmospheric Physics were launched in Changchun (43.9°N, 125.2°E), Northeast China, in June 2013, and observed an ozone-enriched layer with thickness of 3 km and an ozone peak of 180 ppbv at 6 km in the troposphere. The circulation field from the European Centre for Medium-Range Weather Forecasts Interim Reanalysis (ERA-Interim) dataset shows that this ozone peak was caused by a tropopause fold associated with a jet stream at the eastern flank of the East Asian trough. By analyzing the ozone data from the ozone monitoring instrument and Weather Research and Forecasting model with Chemistry (WRF-Chem) simulations, it was found that a high ozone concentration tongue originating from the lower stratosphere at high latitude (near central Siberia) intruded into the middle troposphere over Changchun between 5 and 8 km on 12 June 2013. The high-resolution WRF-Chem simulation was capable of describing events such as the tropopause fold that occurred on the cyclonic shear side of the jet stream. In addition, the TRAJ3D trajectory model was used to trace the origin of measured secondary ozone peaks in the middle troposphere back, for example, to stratospheric intrusion through the tropopause fold.

  5. The Sensitive Balance Between the Fully Folded and Locally Unfolded Conformations of a Model Peroxiredoxin†

    PubMed Central

    Perkins, Arden; Nelson, Kimberly J.; Williams, Jared R.; Parsonage, Derek; Poole, Leslie B.; Karplus, P. Andrew

    2014-01-01

    To reduce peroxides, peroxiredoxins (Prx) require a key ‘peroxidatic’ cysteine, that in a substrate-ready fully folded (FF) conformation becomes oxidized to sulfenic acid, and then after a local unfolding (LU) of the active site, forms a disulfide bond with a second ‘resolving’ Cys. For Salmonella typhimurium alkyl hydroperoxide reductase C (StAhpC) and some other Prxs, the FF structure is only known for a peroxidatic Cys→Ser variant, which may not accurately represent the wild type enzyme. Here, we obtain the structure of authentic reduced wild type StAhpC by dithiothreitol treatment of disulfide form crystals that fortuitously accommodate both the LU and FF conformations. The unique environment of one molecule in the crystal reveals a thermodynamic linkage between the folding of the active site loop and C-terminal regions, and comparisons with the Ser-variant show structural and mobility differences from which we infer that the Cys→Ser mutation stabilizes the FF active site. A structure for the C165A variant (a resolving Cys to Ala mutant) in the same crystal form reveals that this mutation destabilizes the folding of the C-terminal region. These structures prove that subtle modifications to Prx structures can substantially influence enzymatic properties. We also present a simple thermodynamic framework for understanding the various mixtures of FF and LU conformations seen in these structures. Based on this framework, we rationalize how physiologically-relevant regulatory posttranslational modifications may modulate activity and propose a non-conventional strategy for designing selective Prx inhibitors. PMID:24175952

  6. The novel double-folded structure of d(GCATGCATGC): a possible model for triplet-repeat sequences.

    PubMed

    Thirugnanasambandam, Arunachalam; Karthik, Selvam; Mandal, Pradeep Kumar; Gautham, Namasivayam

    2015-10-01

    The structure of the decadeoxyribonucleotide d(GCATGCATGC) is presented at a resolution of 1.8 Å. The decamer adopts a novel double-folded structure in which the direction of progression of the backbone changes at the two thymine residues. Intra-strand stacking interactions (including an interaction between the endocylic O atom of a ribose moiety and the adjacent purine base), hydrogen bonds and cobalt-ion interactions stabilize the double-folded structure of the single strand. Two such double-folded strands come together in the crystal to form a dimer. Inter-strand Watson-Crick hydrogen bonds form four base pairs. This portion of the decamer structure is similar to that observed in other previously reported oligonucleotide structures and has been dubbed a `bi-loop'. Both the double-folded single-strand structure, as well as the dimeric bi-loop structure, serve as starting points to construct models for triplet-repeat DNA sequences, which have been implicated in many human diseases.

  7. NUV MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2009-07-01

    The performance of MAMA microchannel plate can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the COS SMOV as proposal 13555 {visit 5}.

  8. Topological Constraints: Using RNA Secondary Structure to Model 3D Conformation, Folding Pathways, and Dynamic Adaptation

    PubMed Central

    Bailor, Maximillian; Mustoe, Anthony M.

    2012-01-01

    Summary Accompanying recent advances in determining RNA secondary structure is the growing appreciation for the importance of relatively simple topological constraints, encoded at the secondary structure level, in defining the overall architecture, folding pathways, and dynamic adaptability of RNA. A new view is emerging in which tertiary interactions do not define RNA 3D structure, but rather, help select specific conformers from an already narrow, topologically pre-defined conformational distribution. Studies are providing fundamental insights into the nature of these topological constraints, how they are encoded by the RNA secondary structure, and how they interplay with other interactions, breathing new meaning to RNA secondary structure. New approaches have been developed that take advantage of topological constraints in determining RNA backbone conformation based on secondary structure, and a limited set of other, easily accessible constraints. Topological constraints are also providing a much-needed framework for rationalizing and describing RNA dynamics and structural adaptation. Finally, studies suggest that topological constraints may play important roles steering RNA folding pathways. Here, we review recent advances in our understanding of topological constraints encoded by the RNA secondary structure. PMID:21497083

  9. A First-Principles Model of Early Evolution: Emergence of Gene Families, Species, and Preferred Protein Folds

    PubMed Central

    Zeldovich, Konstantin B; Chen, Peiqiu; Shakhnovich, Boris E; Shakhnovich, Eugene I

    2007-01-01

    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. PMID:17630830

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

    PubMed

    Zeldovich, Konstantin B; Chen, Peiqiu; Shakhnovich, Boris E; Shakhnovich, Eugene I

    2007-07-01

    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.

  11. Investigating acoustic correlates of human vocal fold vibratory phase asymmetry through modeling and laryngeal high-speed videoendoscopya

    PubMed Central

    Mehta, Daryush D.; Zañartu, Matías; Quatieri, Thomas F.; Deliyski, Dimitar D.; Hillman, Robert E.

    2011-01-01

    Vocal fold vibratory asymmetry is often associated with inefficient sound production through its impact on source spectral tilt. This association is investigated in both a computational voice production model and a group of 47 human subjects. The model provides indirect control over the degree of left–right phase asymmetry within a nonlinear source–filter framework, and high-speed videoendoscopy provides in vivo measures of vocal fold vibratory asymmetry. Source spectral tilt measures are estimated from the inverse-filtered spectrum of the simulated and recorded radiated acoustic pressure. As expected, model simulations indicate that increasing left–right phase asymmetry induces steeper spectral tilt. Subject data, however, reveal that none of the vibratory asymmetry measures correlates with spectral tilt measures. Probing further into physiological correlates of spectral tilt that might be affected by asymmetry, the glottal area waveform is parameterized to obtain measures of the open phase (open/plateau quotient) and closing phase (speed/closing quotient). Subjects’ left–right phase asymmetry exhibits low, but statistically significant, correlations with speed quotient (r = 0.45) and closing quotient (r = −0.39). Results call for future studies into the effect of asymmetric vocal fold vibration on glottal airflow and the associated impact on voice source spectral properties and vocal efficiency. PMID:22225054

  12. Modeling the effects of a posterior glottal opening on vocal fold dynamics with implications for vocal hyperfunctiona)

    PubMed Central

    Zañartu, Matías; Galindo, Gabriel E.; Erath, Byron D.; Peterson, Sean D.; Wodicka, George R.; Hillman, Robert E.

    2014-01-01

    Despite the frequent observation of a persistent opening in the posterior cartilaginous glottis in normal and pathological phonation, its influence on the self-sustained oscillations of the vocal folds is not well understood. The effects of a posterior gap on the vocal fold tissue dynamics and resulting acoustics were numerically investigated using a specially designed flow solver and a reduced-order model of human phonation. The inclusion of posterior gap areas of 0.03–0.1 cm2 reduced the energy transfer from the fluid to the vocal folds by more than 42%–80% and the radiated sound pressure level by 6–14 dB, respectively. The model was used to simulate vocal hyperfucntion, i.e., patterns of vocal misuse/abuse associated with many of the most common voice disorders. In this first approximation, vocal hyperfunction was modeled by introducing a compensatory increase in lung air pressure to regain the vocal loudness level that was produced prior to introducing a large glottal gap. This resulted in a significant increase in maximum flow declination rate and amplitude of unsteady flow, thereby mimicking clinical studies. The amplitude of unsteady flow was found to be linearly correlated with collision forces, thus being an indicative measure of vocal hyperfunction. PMID:25480072

  13. Folding of apomyoglobin: Analysis of transient intermediate structure during refolding using quick hydrogen deuterium exchange and NMR

    PubMed Central

    NISHIMURA, Chiaki

    2017-01-01

    The structures of apomyoglobin folding intermediates have been widely analyzed using physical chemistry methods including fluorescence, circular dichroism, small angle X-ray scattering, NMR, mass spectrometry, and rapid mixing. So far, at least two intermediates (on sub-millisecond- and millisecond-scales) have been demonstrated for apomyoglobin folding. The combination of pH-pulse labeling and NMR is a useful tool for analyzing the kinetic intermediates at the atomic level. Its use has revealed that the latter-phase kinetic intermediate of apomyoglobin (6 ms) was composed of helices A, B, G and H, whereas the equilibrium intermediate, called the pH 4 molten-globule intermediate, was composed mainly of helices A, G and H. The improved strategy for the analysis of the kinetic intermediate was developed to include (1) the dimethyl sulfoxide method, (2) data processing with the various labeling times, and (3) a new in-house mixer. Particularly, the rapid mixing revealed that helices A and G were significantly more protected at the earlier stage (400 µs) of the intermediate (former-phase intermediate) than the other helices. Mutation studies, where each hydrophobic residue was replaced with an alanine in helices A, B, E, F, G and H, indicated that both non-native and native-like structures exist in the latter-phase folding intermediate. The N-terminal part of helix B is a weak point in the intermediate, and the docking of helix E residues to the core of the A, B, G and H helices was interrupted by a premature helix B, resulting in the accumulation of the intermediate composed of helices A, B, G and H. The prediction-based protein engineering produced important mutants: Helix F in a P88K/A90L/S92K/A94L mutant folded in the latter-phase intermediate, although helix F in the wild type does not fold even at the native state. Furthermore, in the L11G/W14G/A70L/G73W mutant, helix A did not fold but helix E did, which is similar to what was observed in the kinetic

  14. Folding of apomyoglobin: Analysis of transient intermediate structure during refolding using quick hydrogen deuterium exchange and NMR.

    PubMed

    Nishimura, Chiaki

    2017-01-01

    The structures of apomyoglobin folding intermediates have been widely analyzed using physical chemistry methods including fluorescence, circular dichroism, small angle X-ray scattering, NMR, mass spectrometry, and rapid mixing. So far, at least two intermediates (on sub-millisecond- and millisecond-scales) have been demonstrated for apomyoglobin folding. The combination of pH-pulse labeling and NMR is a useful tool for analyzing the kinetic intermediates at the atomic level. Its use has revealed that the latter-phase kinetic intermediate of apomyoglobin (6 ms) was composed of helices A, B, G and H, whereas the equilibrium intermediate, called the pH 4 molten-globule intermediate, was composed mainly of helices A, G and H. The improved strategy for the analysis of the kinetic intermediate was developed to include (1) the dimethyl sulfoxide method, (2) data processing with the various labeling times, and (3) a new in-house mixer. Particularly, the rapid mixing revealed that helices A and G were significantly more protected at the earlier stage (400 µs) of the intermediate (former-phase intermediate) than the other helices. Mutation studies, where each hydrophobic residue was replaced with an alanine in helices A, B, E, F, G and H, indicated that both non-native and native-like structures exist in the latter-phase folding intermediate. The N-terminal part of helix B is a weak point in the intermediate, and the docking of helix E residues to the core of the A, B, G and H helices was interrupted by a premature helix B, resulting in the accumulation of the intermediate composed of helices A, B, G and H. The prediction-based protein engineering produced important mutants: Helix F in a P88K/A90L/S92K/A94L mutant folded in the latter-phase intermediate, although helix F in the wild type does not fold even at the native state. Furthermore, in the L11G/W14G/A70L/G73W mutant, helix A did not fold but helix E did, which is similar to what was observed in the kinetic

  15. Structural and thermodynamic investigations on the aggregation and folding of acylphosphatase by molecular dynamics simulations and solvation free energy analysis.

    PubMed

    Chong, Song-Ho; Lee, Chewook; Kang, Guipeun; Park, Mirae; Ham, Sihyun

    2011-05-11

    Protein engineering method to study the mutation effects on muscle acylphosphatase (AcP) has been actively applied to describe kinetics and thermodynamics associated with AcP aggregation as well as folding processes. Despite the extensive mutation experiments, the molecular origin and the structural motifs for aggregation and folding kinetics as well as thermodynamics of AcP have not been rationalized at the atomic resolution. To this end, we have investigated the mutation effects on the structures and thermodynamics for the aggregation and folding of AcP by using the combination of fully atomistic, explicit-water molecular dynamics simulations, and three-dimensional reference interaction site model theory. The results indicate that the A30G mutant with the fastest experimental aggregation rate displays considerably decreased α1-helical contents as well as disrupted hydrophobic core compared to the wild-type AcP. Increased solvation free energy as well as hydrophobicity upon A30G mutation is achieved due to the dehydration of hydrophilic side chains in the disrupted α1-helix region of A30G. In contrast, the Y91Q mutant with the slowest aggregation rate shows a non-native H-bonding network spanning the mutation site to hydrophobic core and α1-helix region, which rigidifies the native state protein conformation with the enhanced α1-helicity. Furthermore, Y91Q exhibits decreased solvation free energy and hydrophobicity compared to wild type due to more exposed and solvated hydrophilic side chains in the α1-region. On the other hand, the experimentally observed slower folding rates in both mutants are accompanied by decreased helicity in α2-helix upon mutation. We here provide the atomic-level structures and thermodynamic quantities of AcP mutants and rationalize the structural origin for the changes that occur upon introduction of those mutations along the AcP aggregation and folding processes.

  16. Entropy reduction effect imposed by hydrogen bond formation on protein folding cooperativity: Evidence from a hydrophobic minimalist model

    NASA Astrophysics Data System (ADS)

    Barbosa, Marco Aurélio A.; Garcia, Leandro G.; Pereira de Araújo, Antônio F.

    2005-11-01

    Conformational restrictions imposed by hydrogen bond formation during protein folding are investigated by Monte Carlo simulations of a non-native-centric, two-dimensional, hydrophobic model in which the formation of favorable contacts is coupled to an effective reduction in lattice coordination. This scheme is intended to mimic the requirement that polar backbone groups of real proteins must form hydrogen bonds concomitantly to their burial inside the apolar protein core. In addition to the square lattice, with z=3 conformations per monomer, we use extensions in which diagonal step vectors are allowed, resulting in z=5 and z=7 . Thermodynamics are governed by the hydrophobic energy function, according to which hydrophobic monomers tend to make contacts unspecifically while the reverse is true for hydrophilic monomers, with the additional restriction that only contacts between monomers adopting one of zhfolding transition abruptness and van’t Hoff-to-calorimetric-enthalpy ratio are found to increase dramatically by this simple and physically motivated mechanism. The observed increase in folding cooperativity is correlated to an increase in the convexity of the underlying microcanonical conformational entropy as a function of energy. Preliminary simulations in three dimensions, even though using a smaller relative reduction in lattice effective coordination zh/z=4/5 , display a slight increase in cooperativity for a hydrophobic model of 40 monomers and a more pronounced increase in cooperativity for a native-centric Go-model with the same native conformation, suggesting that this purely entropic effect is not an artifact of dimensionality and is likely to be of fundamental importance in the theoretical understanding of folding cooperativity.

  17. Effect of Cohesion Uncertainty of Granular Materials on the Kinematics of Scaled Models of Fold-and-Thrust Belts

    NASA Astrophysics Data System (ADS)

    Nilfouroushan, F.; Pysklywec, R.; Cruden, S.

    2009-05-01

    Cohesionless or very low cohesion granular materials are widely used in analogue/physical models to simulate brittle rocks in the upper crust. Selection of materials with appropriate cohesion values in such models is important for the simulation of the dynamics of brittle rock deformation in nature. Uncertainties in the magnitude of cohesion (due to measurement errors, extrapolations at low normal stresses, or model setup) in laboratory experiments can possibly result in misinterpretation of the styles and mechanisms of deformation in natural fold-and thrust belts. We ran a series of 2-D numerical models to investigate systematically the effect of cohesion uncertainties on the evolution of models of fold-and-thrust belts. The analyses employ SOPALE, a geodynamic code based on the arbitrary Lagrangian-Eulerian (ALE) finite element method. Similar to analogue models, the material properties of sand and transparent silicone (PDMS) are used to simulate brittle and viscous behaviors of upper crustal rocks. The suite of scaled brittle and brittle-viscous numerical experiments have the same initial geometry but the cohesion value of the brittle layers is increased systematically from 0 to 100 Pa. The stress and strain distribution in different sets of models with different cohesion values are compared and analyzed. The kinematics and geometry of thrust wedges including the location and number of foreland- and hinterland- verging thrust faults, pop-up structures, tapers and topography are also explored and their sensitivity to cohesion value is discussed.

  18. Theoretical analysis, design and development of a 27-MHz folded loop antenna as a potential applicator in hyperthermia treatment.

    PubMed

    Kouloulias, Vassilis; Karanasiou, Irene; Giamalaki, Melina; Matsopoulos, George; Kouvaris, John; Kelekis, Nikolaos; Uzunoglu, Nikolaos

    2015-02-01

    A hyperthermia system using a folded loop antenna applicator at 27 MHz for soft tissue treatment was investigated both theoretically and experimentally to evaluate its clinical value. The electromagnetic analysis of a 27-MHz folded loop antenna for use in human tissue was based on a customised software tool and led to the design and development of the proposed hyperthermia system. The system was experimentally validated using specific absorption rate (SAR) distribution estimations through temperature distribution measurements of a muscle tissue phantom after electromagnetic exposure. Various scenarios for optimal antenna positioning were also performed. Comparison of the theoretical and experimental analysis results shows satisfactory agreement. The SAR level of 50% reaches 8 cm depth in the tissue phantom. Thus, based on the maximum observed SAR values that were of the order of 100 W/kg, the antenna specified is suitable for deep tumour heating. Theoretical and experimental SAR distribution results as derived from this study are in agreement. The proposed folded loop antenna seems appropriate for use in hyperthermia treatment, achieving proper planning and local treatment of deeply seated affected areas and lesions.

  19. Advancing the Accuracy of Protein Fold Recognition by Utilizing Profiles From Hidden Markov Models.

    PubMed

    Lyons, James; Dehzangi, Abdollah; Heffernan, Rhys; Yang, Yuedong; Zhou, Yaoqi; Sharma, Alok; Paliwal, Kuldip

    2015-10-01

    Protein fold recognition is an important step towards solving protein function and tertiary structure prediction problems. Among a wide range of approaches proposed to solve this problem, pattern recognition based techniques have achieved the best results. The most effective pattern recognition-based techniques for solving this problem have been based on extracting evolutionary-based features. Most studies have relied on the Position Specific Scoring Matrix (PSSM) to extract these features. However it is known that profile-profile sequence alignment techniques can identify more remote homologs than sequence-profile approaches like PSIBLAST. In this study we use a profile-profile sequence alignment technique, namely HHblits, to extract HMM profiles. We will show that unlike previous studies, using the HMM profile to extract evolutionary information can significantly enhance the protein fold prediction accuracy. We develop a new pattern recognition based system called HMMFold which extracts HMM based evolutionary information and captures remote homology information better than previous studies. Using HMMFold we achieve up to 93.8% and 86.0% prediction accuracies when the sequential similarity rates are less than 40% and 25%, respectively. These results are up to 10% better than previously reported results for this task. Our results show significant enhancement especially for benchmarks with sequential similarity as low as 25% which highlights the effectiveness of HMMFold to address this problem and its superiority over previously proposed approaches found in the literature. The HMMFold is available online at: http://sparks-lab.org/pmwiki/download/index.php?Download =HMMFold.tar.bz2.

  20. Analysis of RNA folding and ligand binding by conventional and high-throughput calorimetry.

    PubMed

    Sokoloski, Joshua E; Bevilacqua, Philip C

    2012-01-01

    Noncoding RNAs serve myriad functions in the cell, but their biophysical properties are not well understood. Calorimetry offers direct and label-free means for characterizing the ligand-binding and thermostability properties of these RNA. We apply two main types of calorimetry--isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC)--to the characterization of these functional RNA molecules. ITC can describe ligand binding in terms of stoichiometry, affinity, and heat (enthalpy), while DSC can provide RNA stability in terms of heat capacity, melting temperature, and folding enthalpy. Here, we offer detailed experimental protocols for studying such RNA systems with commercially available conventional and high-throughput ITC and DSC instruments.

  1. Folding above faults, Rocky Mountains

    SciTech Connect

    McConnell, D.A. . Dept. of Geology)

    1992-01-01

    Asymmetric folds formed above basement faults can be observed throughout the Rocky Mountains. Several previous interpretations of the folding process made the implicit assumption that one or both fold hinges migrated or rolled'' through the steep forelimb of the fold as the structure evolved (rolling hinge model). Results of mapping in the Bighorn and Seminoe Mountains, WY, and Sangre de Cristo Range, CO, do not support this hypothesis. An alternative interpretation is presented in which fold hinges remained fixed in position during folding (fixed hinge model). Mapped folds share common characteristics: (1) axial traces of the folds intersect faults at or near the basement/cover interface, and diverge from faults upsection; (2) fold hinges are narrow and interlimb angles cluster around 80--100[degree] regardless of fold location; (3) fold shape is typically angular, despite published cross sections that show concentric folds; and, (4) beds within the folds show thickening and/or thinning, most commonly adjacent to fold hinges. The rolling hinge