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Sample records for folding model analysis

  1. Kinetic Analysis of Protein Folding Lattice Models

    NASA Astrophysics Data System (ADS)

    Chen, Hu; Zhou, Xin; Liaw, Chih Young; Koh, Chan Ghee

    Based on two-dimensional square lattice models of proteins, the relation between folding time and temperature is studied by Monte Carlo simulation. The results can be represented by a kinetic model with three states — random coil, molten globule, and native state. The folding process is composed of nonspecific collapse and final searching for the native state. At high temperature, it is easy to escape from local traps in the folding process. With decreasing temperature, because of the trapping in local traps, the final searching speed decreases. Then the folding shows chevron rollover. Through the analysis of the fitted parameters of the kinetic model, it is found that the main difference between the energy landscapes of the HP model and the Go model is that the number of local minima of the Go model is less than that of the HP model.

  2. 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.

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

    PubMed

    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

  4. 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

  5. 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

  6. Using Strahler's analysis to reduce up to 200-fold the run time of realistic neuron models

    NASA Astrophysics Data System (ADS)

    Marasco, Addolorata; Limongiello, Alessandro; Migliore, Michele

    2013-10-01

    The cellular mechanisms underlying higher brain functions/dysfunctions are extremely difficult to investigate experimentally, and detailed neuron models have proven to be a very useful tool to help these kind of investigations. However, realistic neuronal networks of sizes appropriate to study brain functions present the major problem of requiring a prohibitively high computational resources. Here, building on our previous work, we present a general reduction method based on Strahler's analysis of neuron morphologies. We show that, without any fitting or tuning procedures, it is possible to map any morphologically and biophysically accurate neuron model into an equivalent reduced version. Using this method for Purkinje cells, we demonstrate how run times can be reduced up to 200-fold, while accurately taking into account the effects of arbitrarily located and activated synaptic inputs.

  7. 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

    2015-01-01

    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

  8. 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

  9. 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.

  10. ANALYSIS OF FLOW-STRUCTURE COUPLING IN A MECHANICAL MODEL OF THE VOCAL FOLDS AND THE SUBGLOTTAL SYSTEM

    PubMed Central

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

    2009-01-01

    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. PMID:20161450

  11. Elastic models of vocal fold tissues.

    PubMed

    Alipour-Haghighi, F; Titze, I R

    1991-09-01

    Elastic properties of canine vocal fold tissue (muscle and mucosa) were obtained through a series of experiments conducted in vitro and were modeled mathematically. The elastic properties play a significant role in quantitative analysis of vocal fold vibrations and theory of pitch control. Samples of vocalis muscle and mucosa were dissected and prepared from dog larynges a few minutes premortem and kept in a Krebs solution at a temperature of 37 +/- 1 degrees C and a pH of 7.4 +/- 0.05. Samples of muscle tissue and mucosa were stretched and released in a slow, sinusoidal fashion. Force and displacement of the samples were measured with a dual-servo system (ergometer). After digitization, stress-strain data for samples of muscle tissue and cover tissue were averaged. The stress-strain data were then fitted numerically by polynomial and exponential models. PMID:1939897

  12. A parametric vocal fold model based on magnetic resonance imaging.

    PubMed

    Wu, Liang; Zhang, Zhaoyan

    2016-08-01

    This paper introduces a parametric three-dimensional body-cover vocal fold model based on magnetic resonance imaging (MRI) of the human larynx. Major geometric features that are observed in the MRI images but missing in current vocal fold models are discussed, and their influence on vocal fold vibration is evaluated using eigenmode analysis. Proper boundary conditions for the model are also discussed. Based on control parameters corresponding to anatomic landmarks that can be easily measured, this model can be adapted toward a subject-specific vocal fold model for voice production research and clinical applications. PMID:27586774

  13. 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).

  14. 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.

  15. Analysis of High-Fold Gamma Data

    SciTech Connect

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

    1998-08-10

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

  16. 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.

  17. 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.

  18. Stratified analysis of lectin-like chaperones in the folding disease-related metabolic syndrome rat model.

    PubMed

    Hirano, Makoto; Imagawa, Ayami; Totani, Kiichiro

    2016-09-01

    The metabolic syndrome including obesity and diabetes mellitus is known to be a major health problem worldwide. A recent study reported that obesity causes endoplasmic reticulum (ER) stress and subsequently leads to insulin resistance and type 2 diabetes. However, little is known about the alterations in the components of the calnexin/calreticulin (CNX/CRT) cycle, which promote glycoprotein folding in obese and diabetic conditions. To understand the operating status of the lectin-like chaperones related to the CNX/CRT cycle in the metabolic syndrome, we analyzed the chaperones for the activity, protein expression, and mRNA expression levels using Zucker fatty (ZF) and Zucker diabetic fatty (ZDF) rat models for obesity and diabetes, respectively. We demonstrated that misfolded proteins were gradually increased with progression of the syndrome, obesity to diabetes. The individual chaperone activities of CNX and CRT were both decreased in the ZF rat ER and, in contrast, were increased in the ZDF rat ER. The protein quantities and mRNA expressions of CNX and CRT were decreased in the ZF rats, but increased in the ZDF rats compared with those of the healthy model. Therefore, these results indicate that obesity down-regulates CNX and CRT expressions and their activities and diabetes up-regulates the expressions and activities of CNX and CRT. Our findings clearly suggest that metabolic syndrome affects the lectin-like chaperones in the CNX/CRT cycle at both the activity and expression levels. PMID:27425249

  19. Protein folding at atomic resolution: analysis of autonomously folding supersecondary structure motifs by nuclear magnetic resonance.

    PubMed

    Sborgi, Lorenzo; Verma, Abhinav; Sadqi, Mourad; de Alba, Eva; Muñoz, Victor

    2013-01-01

    The study of protein folding has been conventionally hampered by the assumption that all single-domain proteins fold by an all-or-none process (two-state folding) that makes it impossible to resolve folding mechanisms experimentally. Here we describe an experimental method for the thermodynamic analysis of protein folding at atomic resolution using nuclear magnetic resonance (NMR). The method is specifically developed for the study of small proteins that fold autonomously into basic supersecondary structure motifs, and that do so in the sub-millisecond timescale (folding archetypes). From the NMR experiments we obtain hundreds of atomic unfolding curves that are subsequently analyzed leading to the determination of the characteristic network of folding interactions. The application of this approach to a comprehensive catalog of elementary folding archetypes holds the promise of becoming the first experimental approach capable of unraveling the basic rules connecting protein structure and folding mechanism. PMID:22987355

  20. 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

  1. 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.

  2. Hinge-migrated fold-scarp model based on an analysis of bed geometry: A study from the Mingyaole anticline, southern foreland of Chinese Tian Shan

    NASA Astrophysics Data System (ADS)

    Li, Tao; Chen, Jie; Thompson, Jessica A.; Burbank, Douglas W.; Yang, Huili

    2015-09-01

    Fold scarps, a type of geomorphic scarp formed by folding mechanisms of hinge migration or limb rotation, serve to delineate both fault-bend characteristics and folding histories, which can, in turn, illuminate tectonic processes and seismic hazards associated with thrust systems. Because the subsurface geometry of folds is commonly difficult to determine, existing fold-scarp models, which rely on both the fold type and its causative fault geometries, remain uncertain with respect to the kinematic evolution of a given fold. In this paper, we develop a model to illustrate that, irrespective of specific fold type and subsurface geometries, fold-scarp growth in the mechanism of hinge migration can be successfully reconstructed based on analyses of bed geometry. This model reveals that the underlying bed dips and the ratio of hinge migration distance/hinge width control the fold-scarp shape and slope. During initial growth (ratio < 1), the scarp slope increases gradually with migration of the hinge. When the hinge totally exits from its original position (ratio > 1), the slope reaches a maximum, which solely depends on underlying bed dips. The scarp height, however, is independent of the hinge width and can be used to quantify folding magnitude. Application of our model to fold scarps in the Mingyaole anticline in the southern foreland of Chinese Tian Shan indicates that the modeled fold-scarp geometry can roughly match with field observations. The Mingyaole shortening rate is estimated to be ≥5.0 mm/a since ~15 ka, such that this single fold has accommodated about half of the regional convergence during the Holocene.

  3. Predicting RNA folding thermodynamics with a reduced chain representation model.

    PubMed

    Cao, Song; Chen, Shi-Jie

    2005-12-01

    Based on the virtual bond representation for the nucleotide backbone, we develop a reduced conformational model for RNA. We use the experimentally measured atomic coordinates to model the helices and use the self-avoiding walks in a diamond lattice to model the loop conformations. The atomic coordinates of the helices and the lattice representation for the loops are matched at the loop-helix junction, where steric viability is accounted for. Unlike the previous simplified lattice-based models, the present virtual bond model can account for the atomic details of realistic three-dimensional RNA structures. Based on the model, we develop a statistical mechanical theory for RNA folding energy landscapes and folding thermodynamics. Tests against experiments show that the theory can give much more improved predictions for the native structures, the thermal denaturation curves, and the equilibrium folding/unfolding pathways than the previous models. The application of the model to the P5abc region of Tetrahymena group I ribozyme reveals the misfolded intermediates as well as the native-like intermediates in the equilibrium folding process. Moreover, based on the free energy landscape analysis for each and every loop mutation, the model predicts five lethal mutations that can completely alter the free energy landscape and the folding stability of the molecule. PMID:16251382

  4. Robustness of downhill folding: guidelines for the analysis of equilibrium folding experiments on small proteins.

    PubMed

    Naganathan, Athi N; Perez-Jimenez, Raúl; Sanchez-Ruiz, Jose M; Muñoz, Victor

    2005-05-24

    Previously, we identified the protein BBL as a downhill folder. This conclusion was based on the statistical mechanical analysis of equilibrium experiments performed in two variants of BBL, one with a fluorescent label at the N-terminus, and another one labeled at both ends. A recent report has claimed that our results are an artifact of label-induced aggregation and that BBL with no fluorescent labels and a longer N-terminal tail folds in a two-state fashion. Here, we show that singly and doubly labeled BBL do not aggregate, unfold reversibly, and have the same thermodynamic properties when studied under appropriate experimental conditions (e.g., our original conditions (1)). With an elementary analysis of the available data on the nonlabeled BBL (2), we also show that this slightly more stable BBL variant is not a two-state folder. We discuss the problems that led to its previous misclassification and how they can be avoided. Finally, we investigate the equilibrium unfolding of the singly labeled BBL with both ends protected by acetylation and amidation. This variant has the same thermodynamic stability of the nonlabeled BBL and displays all the equilibrium signatures of downhill folding. From all these observations, we conclude that fluorescent labels do not perturb the thermodynamic properties of BBL, which consistently folds downhill regardless of its stability and specific protein tails. The work on BBL illustrates the shortcomings of applying conventional procedures intended to distinguish between two-state and three-state folding models to small fast-folding proteins. PMID:15895987

  5. 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

  6. Fold interaction and wavelength selection in 3D models of multilayer detachment folding

    NASA Astrophysics Data System (ADS)

    Fernandez, Naiara; Kaus, Boris J. P.

    2014-09-01

    Many fold-and-thrust belts are dominated by folding and exhibit a fairly regular fold-spacing. Yet, in map-view, the aspect ratio of doubly-plunging anticlines varies considerably from very elongated, and sometimes slightly curved, cylindrical folds to nearly circular, dome-like structures. In addition, the fold spacing often varies significantly around an average value. So far, it remains unclear whether these features are consistent with a folding instability. Therefore, we here study the dynamics of multilayer detachment folding, process by which shortening can be accommodated in thin-skinned fold-and-thrust belts. We start by analysing the physics of this process by using both a semi-analytical thick plate theory and numerical simulations. Results show that several different folding modes occur, about half of which are affected by gravity and have a wavelength that depends on the background deformation rate. Non-dimensional expressions are derived that predict the dominant wavelength and growth rate of each of these folding modes and mechanical phase diagrams are presented that illustrate the applicability of each of the modes. Next, we perform 3D simulations and compare the results with those of 2D models and analytical theory. Both 2D and 3D numerical simulations have wavelengths that are in good agreement with the analytical predictions. In the high-resolution 3D simulations the lateral growth of folds is studied, in particular with respect to fold segment interactions and evolution of fold width-length aspect ratio. The numerical simulations show a number of similarities with the Fars region of the Zagros fold-and-thrust belt including a large range of fold aspect ratio and a normally distributed fold wavelength around a dominant one.

  7. 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

  8. 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. PMID:17905832

  9. 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…

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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. PMID:21117769

  15. 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

  16. 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.

  17. Conjugate-shear folding: A model for the relationships between foliations, folds and shear zones

    NASA Astrophysics Data System (ADS)

    Aerden, Domingo G. A. M.; Sayab, Mohammad; Bouybaouene, Mohamed L.

    2010-08-01

    Microstructural mapping of whole thin sections cut from two samples of micaschist containing cm-scale folds plus garnet porphyroblasts has provided new insight in the relationships between folding, shearing and foliation development. The garnets exhibit coherent inclusion-trail patterns that place important constraints on the kinematic development of both samples, which are shown to be representative of coaxial versus non-coaxial deformation in rocks containing a pre-existing schistosity. A comparison of crenulations-cleavages geometries in both samples and a review of the geometry of natural and experimental multilayer folds leads to the conclusion that folding involves conjugate shearing at different scales. At microscopic scales, crenulation cleavages nucleate as conjugate-kink or shear instabilities and develop further as a function of the macroscopic partitioning of deformation. In fold-hinge domains, bulk-coaxial deformation results in equal development of conjugate crenulations that progressively coalescence into symmetrical crenulation patterns so that, macroscopically, parallelism is achieved between foliation, fold-axial planes and long axes of strain ellipses. Fold-limb domains represent a system of conjugate-shear zones where single sets of crenulation instabilities with synthetic shearing component preferentially develop producing oblique relationships between the aforementioned elements. Cleavage fanning is inferred as a direct consequence of this conjugate-shear origin of folds. The model implies that crenulation cleavages and S-C fabrics in shear zones form by analogous processes, in both cases involving a component of shearing along foliation planes. The development of conjugate sets of foliation planes surrounding porphyroblasts during early, relatively coaxial stages of deformation explains continued "gyrostatic" behaviour during more advanced non-coaxial stages, as indicated by consistently oriented inclusion trails in the studied samples.

  18. 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.

  19. Fault-related fold styles and progressions in fold-thrust belts: Insights from sandbox modeling

    NASA Astrophysics Data System (ADS)

    Yan, Dan-Ping; Xu, Yan-Bo; Dong, Zhou-Bin; Qiu, Liang; Zhang, Sen; Wells, Michael

    2016-03-01

    Fault-related folds of variable structural styles and assemblages commonly coexist in orogenic belts with competent-incompetent interlayered sequences. Despite their commonality, the kinematic evolution of these structural styles and assemblages are often loosely constrained because multiple solutions exist in their structural progression during tectonic restoration. We use a sandbox modeling instrument with a particle image velocimetry monitor to test four designed sandbox models with multilayer competent-incompetent materials. Test results reveal that decollement folds initiate along selected incompetent layers with decreasing velocity difference and constant vorticity difference between the hanging wall and footwall of the initial fault tips. The decollement folds are progressively converted to fault-propagation folds and fault-bend folds through development of fault ramps breaking across competent layers and are followed by propagation into fault flats within an upper incompetent layer. Thick-skinned thrust is produced by initiating a decollement fault within the metamorphic basement. Progressive thrusting and uplifting of the thick-skinned thrust trigger initiation of the uppermost incompetent decollement with formation of a decollement fold and subsequent converting to fault-propagation and fault-bend folds, which combine together to form imbricate thrust. Breakouts at the base of the early formed fault ramps along the lowest incompetent layers, which may correspond to basement-cover contacts, domes the upmost decollement and imbricate thrusts to form passive roof duplexes and constitute the thin-skinned thrust belt. Structural styles and assemblages in each of tectonic stages are similar to that in the representative orogenic belts in the South China, Southern Appalachians, and Alpine orogenic belts.

  20. Item Analysis of the Paper Folding Test (Wks. 622). Technical Report No. 1988-6.

    ERIC Educational Resources Information Center

    Wothke, Werner; Zimowski, Michele F.

    Large-sample item response data for the 10-item Paper Folding worksample 622 (N=2,749) and for five new experimental paper folding items (N=2,514) are analyzed with the logistic item response model and with full-information item factor analysis. The main results of the unidimensional analysis are that: (1) item discrimination is heterogeneous, so…

  1. The folding transition state theory in simple model systems

    NASA Astrophysics Data System (ADS)

    Niewieczerzał, Szymon; Cieplak, Marek

    2008-06-01

    We present the results of an exact analysis of several model free energy landscapes of a protein to clarify the notion of the transition state and the physical meaning of the phi values determined in protein engineering experiments. We argue that a proper search strategy for the transition state in more realistic models should involve identification of a common part of various methods. Two of the models considered involve explicit conformations instead of just points on the free energy axis. These models are minimalistic as they are endowed only with five or 36 states to enumerate folding paths and to identify the transition state easily. Even though they display much of the two-state behavior, the phi values are found not to correspond to the conformation of the transition state.

  2. 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

  3. 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

  4. Material parameter computation for multi-layered vocal fold models

    PubMed Central

    Schmidt, Bastian; Stingl, Michael; Leugering, Günter; Berry, David A.; Döllinger, Michael

    2011-01-01

    Today, the prevention and treatment of voice disorders is an ever-increasing health concern. Since many occupations rely on verbal communication, vocal health is necessary just to maintain one’s livelihood. Commonly applied models to study vocal fold vibrations and air flow distributions are self sustained physical models of the larynx composed of artificial silicone vocal folds. Choosing appropriate mechanical parameters for these vocal fold models while considering simplifications due to manufacturing restrictions is difficult but crucial for achieving realistic behavior. In the present work, a combination of experimental and numerical approaches to compute material parameters for synthetic vocal fold models is presented. The material parameters are derived from deformation behaviors of excised human larynges. The resulting deformations are used as reference displacements for a tracking functional to be optimized. Material optimization was applied to three-dimensional vocal fold models based on isotropic and transverse-isotropic material laws, considering both a layered model with homogeneous material properties on each layer and an inhomogeneous model. The best results exhibited a transversal-isotropic inhomogeneous (i.e., not producible) model. For the homogeneous model (three layers), the transversal-isotropic material parameters were also computed for each layer yielding deformations similar to the measured human vocal fold deformations. PMID:21476672

  5. Simulating the folding of HP-sequences with a minimalist model in an inhomogeneous medium.

    PubMed

    Alas, S J; González-Pérez, P P

    2016-01-01

    The phenomenon of protein folding is a fundamental issue in the field of the computational molecular biology. The protein folding inside the cells is performed in a highly inhomogeneous, tortuous, and correlated environment. Therefore, it is important to include in the theoretical studies the medium where the protein folding is developed. In this work we present the combination of three models to mimic the protein folding inside of an inhomogeneous medium. The models used here are Hydrophobic-Polar (HP) in 2D square arrangement, Evolutionary Algorithms (EA), and the Dual Site Bond Model (DSBM). The DSBM model is used to simulate the environment where the HP beads are folded; in this case the medium is correlated and is fractal-like. The analysis of five benchmark HP sequences shows that the inhomogeneous space provided with a given correlation length and fractal dimension plays an important role for correct folding of these sequences, which does not occur in a homogeneous space. PMID:27020756

  6. Criteria for folding in structure-based models of proteins

    NASA Astrophysics Data System (ADS)

    Wołek, Karol; Cieplak, Marek

    2016-05-01

    In structure-based models of proteins, one often assumes that folding is accomplished when all contacts are established. This assumption may frequently lead to a conceptual problem that folding takes place in a temperature region of very low thermodynamic stability, especially when the contact map used is too sparse. We consider six different structure-based models and show that allowing for a small, but model-dependent, percentage of the native contacts not being established boosts the folding temperature substantially while affecting the time scales of folding only in a minor way. We also compare other properties of the six models. We show that the choice of the description of the backbone stiffness has a substantial effect on the values of characteristic temperatures that relate both to equilibrium and kinetic properties. Models without any backbone stiffness (like the self-organized polymer) are found to perform similar to those with the stiffness, including in the studies of stretching.

  7. Criteria for folding in structure-based models of proteins.

    PubMed

    Wołek, Karol; Cieplak, Marek

    2016-05-14

    In structure-based models of proteins, one often assumes that folding is accomplished when all contacts are established. This assumption may frequently lead to a conceptual problem that folding takes place in a temperature region of very low thermodynamic stability, especially when the contact map used is too sparse. We consider six different structure-based models and show that allowing for a small, but model-dependent, percentage of the native contacts not being established boosts the folding temperature substantially while affecting the time scales of folding only in a minor way. We also compare other properties of the six models. We show that the choice of the description of the backbone stiffness has a substantial effect on the values of characteristic temperatures that relate both to equilibrium and kinetic properties. Models without any backbone stiffness (like the self-organized polymer) are found to perform similar to those with the stiffness, including in the studies of stretching. PMID:27179507

  8. 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

  9. 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.

  10. 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. PMID:18832007

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

    PubMed

    Murray, Preston R; Thomson, Scott L

    2012-11-01

    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

  12. The role of finite displacements in vocal fold modeling.

    PubMed

    Chang, Siyuan; Tian, Fang-Bao; Luo, Haoxiang; Doyle, James F; Rousseau, Bernard

    2013-11-01

    Human vocal folds experience flow-induced vibrations during phonation. In previous computational models, the vocal fold dynamics has been treated with linear elasticity theory in which both the strain and the displacement of the tissue are assumed to be infinitesimal (referred to as model I). The effect of the nonlinear strain, or geometric nonlinearity, caused by finite displacements is yet not clear. In this work, a two-dimensional model is used to study the effect of geometric nonlinearity (referred to as model II) on the vocal fold and the airflow. The result shows that even though the deformation is under 1 mm, i.e., less than 10% of the size of the vocal fold, the geometric nonlinear effect is still significant. Specifically, model I underpredicts the gap width, the flow rate, and the impact stress on the medial surfaces as compared to model II. The study further shows that the differences are caused by the contact mechanics and, more importantly, the fluid-structure interaction that magnifies the error from the small-displacement assumption. The results suggest that using the large-displacement formulation in a computational model would be more appropriate for accurate simulations of the vocal fold dynamics. PMID:24008392

  13. 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.

  14. 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.

  15. 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

  16. Assessment of optimized Markov models in protein fold classification.

    PubMed

    Lampros, Christos; Simos, Thomas; Exarchos, Themis P; Exarchos, Konstantinos P; Papaloukas, Costas; Fotiadis, Dimitrios I

    2014-08-01

    Protein fold classification is a challenging task strongly associated with the determination of proteins' structure. In this work, we tested an optimization strategy on a Markov chain and a recently introduced Hidden Markov Model (HMM) with reduced state-space topology. The proteins with unknown structure were scored against both these models. Then the derived scores were optimized following a local optimization method. The Protein Data Bank (PDB) and the annotation of the Structural Classification of Proteins (SCOP) database were used for the evaluation of the proposed methodology. The results demonstrated that the fold classification accuracy of the optimized HMM was substantially higher compared to that of the Markov chain or the reduced state-space HMM approaches. The proposed methodology achieved an accuracy of 41.4% on fold classification, while Sequence Alignment and Modeling (SAM), which was used for comparison, reached an accuracy of 38%. PMID:25152041

  17. 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

  18. 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.

  19. 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

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

    NASA Astrophysics Data System (ADS)

    Šidlof, Petr; Doaré, Olivier; Cadot, Olivier; Chaigne, Antoine

    2011-07-01

    The paper provides experimental data on flow separation from a model of the human vocal folds. Data were measured on a four times scaled physical model, where one vocal fold was fixed and the other oscillated due to fluid-structure interaction. The vocal folds were fabricated from silicone rubber and placed on elastic support in the wall of a transparent wind tunnel. A PIV system was used to visualize the flow fields immediately downstream of the glottis and to measure the velocity fields. From the visualizations, the position of the flow separation point was evaluated using a semiautomatic procedure and plotted for different airflow velocities. The separation point position was quantified relative to the orifice width separately for the left and right vocal folds to account for flow asymmetry. The results indicate that the flow separation point remains close to the narrowest cross-section during most of the vocal fold vibration cycle, but moves significantly further downstream shortly prior to and after glottal closure.

  1. A Rat Excised Larynx Model of Vocal Fold Scar

    PubMed Central

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

    2008-01-01

    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 one of four experimental groups: Chronic vocal fold scar, chronic vocal fold scar treated with 100 ng basic fibroblast growth factor (bFGF), chronic vocal fold scar treated with saline (sham treatment), and unscarred untreated control. Following tissue harvest, histological and immunohistochemical data were collected to confirm extracellular matrix alteration in the chronic scar group, and acoustic, aerodynamic and high speed digital imaging data were collected using an excised larynx setup in all groups. Phonation threshold pressure (Pth), glottal resistance (Rg), glottal efficiency (Eg), vibratory amplitude and vibratory area were employed as dependent variables. Results Chronically scarred vocal folds were characterized by elevated collagen I and III and reduced hyaluronic acid abundance. Phonation was achieved and data were collected from all control and bFGF treated larynges, however phonation was not achieved with 3 of 6 chronically scarred and 1 of 6 saline treated larynges. Compared to control, the chronic scar group was characterized by elevated Pth, reduced Eg, and intra-larynx vibratory amplitude and area asymmetry. The bFGF group was characterized by Pth below control group levels, Eg comparable to control, and vocal fold vibratory amplitude and area symmetry comparable to control. The sham group was characterized by Pth comparable to control, Eg superior to control, and vocal fold vibratory amplitude and area symmetry comparable to control. Conclusions The excised larynx model reported here demonstrated robust deterioration across phonatory indices under the scar condition and sensitivity to treatment induced change under the bFGF condition. The improvement observed under the sham condition may reflect

  2. 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

  3. 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…

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

    PubMed

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

    2016-07-01

    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 with 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 with 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

  5. Modal response of a computational vocal fold model with a substrate layer of adipose tissue.

    PubMed

    Jones, Cameron L; Achuthan, Ajit; Erath, Byron D

    2015-02-01

    This study demonstrates the effect of a substrate layer of adipose tissue on the modal response of the vocal folds, and hence, on the mechanics of voice production. Modal analysis is performed on the vocal fold structure with a lateral layer of adipose tissue. A finite element model is employed, and the first six mode shapes and modal frequencies are studied. The results show significant changes in modal frequencies and substantial variation in mode shapes depending on the strain rate of the adipose tissue. These findings highlight the importance of considering adipose tissue in computational vocal fold modeling. PMID:25698044

  6. Local analysis near a folded saddle-node singularity

    NASA Astrophysics Data System (ADS)

    Krupa, Martin; Wechselberger, Martin

    Folded saddle-nodes occur generically in one parameter families of singularly perturbed systems with two slow variables. We show that these folded singularities are the organizing centers for two main delay phenomena in singular perturbation problems: canards and delayed Hopf bifurcations. We combine techniques from geometric singular perturbation theory—the blow-up technique—and from delayed Hopf bifurcation theory—complex time path analysis—to analyze the flow near such folded saddle-nodes. In particular, we show the existence of canards as intersections of stable and unstable slow manifolds. To derive these canard results, we extend the singularly perturbed vector field into the complex domain and study it along elliptic paths. This enables us to extend the invariant slow manifolds beyond points where normal hyperbolicity is lost. Furthermore, we define a way-in/way-out function describing the maximal delay expected for generic solutions passing through a folded saddle-node singularity. Branch points associated with the change from a complex to a real eigenvalue structure in the variational equation along the critical (slow) manifold make our analysis significantly different from the classical delayed Hopf bifurcation analysis where these eigenvalues are complex only.

  7. 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

  8. Count ratio model reveals bias affecting NGS fold changes.

    PubMed

    Erhard, Florian; Zimmer, Ralf

    2015-11-16

    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

  9. Kinematic modeling of folding above listric propagating thrusts

    NASA Astrophysics Data System (ADS)

    Cardozo, Nestor; Brandenburg, J. P.

    2014-03-01

    We describe a kinematic approach to simulate folds above listric propagating thrusts. The model is based on a pre-defined circular thrust geometry with a maximum central angle beyond which the thrust is planar, inclined shear above the circular thrust, and trishear in front of the thrust. Provided the trajectory of thrust propagation is established, the model can be run forward and backwards. We use this last feature to implement a global simulated annealing, inverse modeling strategy. This inverse modeling strategy is applied to synthetic folds as well as two real examples in offshore Venezuela and the Niger Delta toe-thrust system. These three examples illustrate the benefits of the algorithm, particularly in predicting the possible range of models that can fit the structures. Thrust geometry, depth to detachment level, and backlimb geometry have high impact in model parameters such as backlimb shear angle and fault slip; while forelimb geometry is critical to constrain parameters such as fault propagation to fault slip ratio and trishear angle. Steep to overturned beds in forelimb areas are often not imaged by seismic, so in the absence of additional well data, considering all possible thrust-fold geometries is critical for the modeling and whatever prediction (e.g. hydrocarbon trap integrity) is made from it.

  10. The geometry and topology of natural sheath folds: a new tool for structural analysis

    NASA Astrophysics Data System (ADS)

    Alsop, G. I.; Holdsworth, R. E.

    2004-09-01

    Curvilinear sheath folds are classically depicted as displaying symmetrical geometries about two orthogonal mirror planes centred along the (X-Y) axial surface and the (X-Z) medial (culmination/depression) surface which bisects the fold nose. However, 10,000 geometric analyses of minor folds and fabrics formed during ductile thrusting in the Caledonides of northern Scotland reveals that major dome and basin sheath folds can display distinct and predictable asymmetries across both axial and medial surfaces. The strain is typically heterogeneous so that structural fabrics and younging evidence are preserved within sheath folds at varying stages of development. This allows an analysis of the evolution of such structures from 'tongue' folds to more extreme 'tubular' forms. Geometric relationships between measured orientations of fold hinges, axial planes, extension lineations and foliations are compared on fabric topology plots (FTPs), which provide an effective tool for monitoring planar and linear fabric rotations with increasing progressive non-coaxial deformation. They consistently display systematic variation from regions of lower to higher strain on passing from upper to lower fold limbs across major axial surfaces, and on crossing medial surfaces from short to long hinge-line segments. Axial and medial surfaces effectively therefore divide major sheath folds into quadrants with different amounts, senses and combinations of planar and linear fabric rotation within each domain. Such heterogeneous deformation implies that models of intense non-coaxial deformation uniformly affecting pre-existing folds may overestimate bulk displacement and shear strain. Variable fold hinge-line rotation about medial surfaces also provides an effective mechanism for the closure of major sheaths, which may otherwise project for unfeasible distances in the X direction. Bedding/cleavage intersections are developed at greater angles to the transport direction than fold hinges which they

  11. 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.

  12. 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.

  13. 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.

  14. Geometric models of folding at Loch Monar, Scotland, using computer simulation

    NASA Astrophysics Data System (ADS)

    Watkinson, A. J.; Thiessen, R. L.

    1988-06-01

    Small-scale hand specimens were collected at Loch Monar, Scotland, one of the classic areas of fold interference patterns. From the analysis of these, the geometries of the F 1 and F 2 folds were derived. By computer simulation, the complex three-dimensional form of the fold interference shapes can then be reproduced very closely. F 2 fold shapes and motion directions derived from the small-scale structures, along with those derived from field observations of F 1 lineations deformed about F 2 folds, were then applied to an extrapolated pre-F 2 shape of the Loch Monar synform. This generated a map pattern strikingly similar to that mapped by Ramsay (1958). The geometric models provide useful information for mechanical hypotheses of the folding observed at Loch Monar. The simulation reveals an interesting problem that whereas many small-scale interference patterns reflect the map pattern of the major structure, there are exposures of interference patterns that do not. These are dome and basin (type 1) patterns found in an area where a major F 2 fold hinge crosses an F 1 fold hinge zone. By examining the deformed L 1 lineation patterns found in this area, along with the computed D 2 strain orientations and the field observations of F 2 fold geometries, we suggest that those patterns formed due to local variations in the displacement directions during the F 2 folding, perhaps due to the mechanical influence of relatively competent pegmatite veins on the small-scale F 2 folds. The very high D 2 strain has then amplified the dome and basin elements to very elongate cone and cylinder forms. This creates local type 1 patterns within a regional type 2 interference pattern structure.

  15. Modelling of shape memory polymer sheets that self-fold in response to localized heating.

    PubMed

    Mailen, Russell W; Liu, Ying; Dickey, Michael D; Zikry, Mohammed; Genzer, Jan

    2015-10-21

    We report a nonlinear finite element analysis (FEA) of the thermo-mechanical shrinking and self-folding behavior of pre-strained polystyrene polymer sheets. Self-folding is useful for actuation, packaging, and remote deployment of flat surfaces that convert to 3D objects in response to a stimulus such as heat. The proposed FEA model accounts for the viscoelastic recovery of pre-strained polystyrene sheets in response to localized heating on the surface of the polymer. Herein, the heat results from the localized absorption of light by ink patterned on the surface of the sheet. This localized delivery of heat results in a temperature gradient through the thickness of the sheet, and thus a gradient of strain recovery, or shrinkage, develops causing the polymer sheet to fold. This process transforms a 2D pattern into a 3D shape through an origami-like behavior. The FEA predictions indicate that shrinking and folding are sensitive to the thermo-mechanical history of the polymer during pre-straining. The model also shows that shrinkage does not vary linearly through the thickness of the polymer during folding due to the accumulation of mass in the hinged region. Counterintuitively, the maximum shrinkage does not occur at the patterned surface. Rather, it occurs considerably below the top surface of the polymer. This investigation provides a fundamental understanding of shrinking, self-folding dynamics, and bending angles, and provides design guidelines for origami shapes and structures. PMID:26324954

  16. 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.

  17. 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.

  18. 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.

  19. Simple off-lattice model to study the folding and aggregation of peptides

    NASA Astrophysics Data System (ADS)

    Combe, Nicolas; Frenkel, Daan

    We present a numerical study of a new protein model. This off-lattice model takes into account both the hydrogen bonds and the amino-acid interactions. It reproduces the folding of a small protein (peptide): morphological analysis of the conformations at low temperature shows two well-known substructures α-helix and β-sheet depending on the chosen sequence. The folding pathway in the scope of this model is studied through a free-energy analysis. We then study the aggregation of proteins. Proteins in the aggregate are mainly bound via hydrogen bonds. Performing a free-energy analysis we show that the addition of a peptide to such an aggregate is not favourable. We qualitatively reproduce the abnormal aggregation of proteins in prion diseases.

  20. 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.

  1. Generic Coarse-Grained Model for Protein Folding and Aggregation

    NASA Astrophysics Data System (ADS)

    Bereau, Tristan; Deserno, Markus

    2009-03-01

    The complexity involved in protein structure is not only due to the rich variety of amino acids, but also the inherent weak interactions, comparable to thermal energy, and important cooperative phenomena. This presents a challenge in atomistic simulations, as it is associated with high-dimensionality and ruggedness of the energy landscape as well as long equilibration times. We have recently developed a coarse-grained (CG) implicit solvent peptide model which has been designed to reproduce key consequences of the abovementioned weak interactions. Its intermediate level of resolution, four beads per amino acid, allows for accurate sampling of local conformations by designing a force field that relies on simple interactions. A realistic ratio of α-helix to β-sheet content is achieved by mimicking a nearest-neighbor dipole interaction. We tune the model in order to fold helical proteins while systematically comparing the structure with NMR data. Very good agreement is achieved for proteins that have simple tertiary structures. We further probe the effects of cooperativity between amino acids by looking at peptide aggregation, where hydrophobic peptide fragments cooperatively form large-scale β-sheet structures. The model is able to reproduce features from atomistic simulations on a qualitative basis.

  2. The Zagros folded belt (Fars, Iran): constraints from topography and critical wedge modelling

    NASA Astrophysics Data System (ADS)

    Mouthereau, F.; Lacombe, O.; Meyer, B.

    2006-04-01

    The Late Miocene tectonics of the Zagros folded belt (Fars province) has for long been related solely to folding of the cover controlled by a ductile décollement between basement and the sedimentary cover. However, geological constraints, topography analysis and seismotectonic studies reveal that basement thrusting may produce locally significant deformation in the cover. To determine how the deep-seated deformation in the basement may contribute to the overall topography we first examine the filtered large and short wavelengths of the topography. We find that the short-wavelength component of the topography (20-25 km), including the Zagros folds, is superimposed on the differential uplift at the regional scale. In other words, the regional base level of folded marker horizons remains parallel to the regional topography of interest. Modelling reveals that the salt-based wedge model, alone, is not able to reproduce the large-wavelength component of the topography of the Zagros Folded Belt. This reveals that when a thick (relatively to its overburden) layer of salt forms the basal décollement it is generally too weak and cannot support the growth of significant topography. We then test an alternative thick-skinned crustal wedge model involving the crust of the Arabian margin, which is decoupled above a viscous lower crust. This model satisfactorily reproduces the observed topography and is consistent with present-day basement thrusting, topography analyses and geological constraints. We conclude that basement-involved thickening and shortening is mechanically required to produce the shape of the Zagros Folded Belt since at least 10 Ma. Finally, the involvement of the basement provides mechanical and kinematic constraints that should be accounted for cross-sections balancing and further assessing the evolution of Zagros at crustal or lithospheric scales.

  3. Flow separation in a computational oscillating vocal fold model

    NASA Astrophysics Data System (ADS)

    Alipour, Fariborz; Scherer, Ronald C.

    2004-09-01

    A finite-volume computational model that solves the time-dependent glottal airflow within a forced-oscillation model of the glottis was employed to study glottal flow separation. Tracheal input velocity was independently controlled with a sinusoidally varying parabolic velocity profile. Control parameters included flow rate (Reynolds number), oscillation frequency and amplitude of the vocal folds, and the phase difference between the superior and inferior glottal margins. Results for static divergent glottal shapes suggest that velocity increase caused glottal separation to move downstream, but reduction in velocity increase and velocity decrease moved the separation upstream. At the fixed frequency, an increase of amplitude of the glottal walls moved the separation further downstream during glottal closing. Increase of Reynolds number caused the flow separation to move upstream in the glottis. The flow separation cross-sectional ratio ranged from approximately 1.1 to 1.9 (average of 1.47) for the divergent shapes. Results suggest that there may be a strong interaction of rate of change of airflow, inertia, and wall movement. Flow separation appeared to be ``delayed'' during the vibratory cycle, leading to movement of the separation point upstream of the glottal end only after a significant divergent angle was reached, and to persist upstream into the convergent phase of the cycle.

  4. Analysis of 140 gigahertz folded frame travelling wave tube

    SciTech Connect

    Guo, Guo; Wei, Yanyu; Zhang, Minghao; Yue, Lingna; Xu, Jin; Yin, Hairong; Huang, Minzhi; Gong, Yubin; Wang, Wenxiang; Travish, Gil

    2013-10-15

    A study on the low voltage, high efficiency and wide bandwidth travelling wave tube by using a novel folded frame slow-wave structure is carried out in this paper. The radio frequency characteristics of the folded frame structure, including dispersion property, interaction impedances, and reflection property are investigated and compared to the similar symmetric double V-shape meander-line structure. Then, the beam-wave interaction process of the folded frame travelling wave tube (TWT) with rectangular sheet electron beam is simulated by 3-D particle-in-cell algorithms. The results show that the output power and electron efficiency can reach 259 W and 13.5% at the center frequency of 140 GHz, respectively. Simultaneously, the instantaneous 3-dB bandwidth is 24 GHz. Compared to the symmetric double V-shaped TWT, the output power and electron efficiency of the folded frame TWT are increased.

  5. Analysis of 140 gigahertz folded frame travelling wave tube

    NASA Astrophysics Data System (ADS)

    Guo, Guo; Wei, Yanyu; Zhang, Minghao; Travish, Gil; Yue, Lingna; Xu, Jin; Yin, Hairong; Huang, Minzhi; Gong, Yubin; Wang, Wenxiang

    2013-10-01

    A study on the low voltage, high efficiency and wide bandwidth travelling wave tube by using a novel folded frame slow-wave structure is carried out in this paper. The radio frequency characteristics of the folded frame structure, including dispersion property, interaction impedances, and reflection property are investigated and compared to the similar symmetric double V-shape meander-line structure. Then, the beam-wave interaction process of the folded frame travelling wave tube (TWT) with rectangular sheet electron beam is simulated by 3-D particle-in-cell algorithms. The results show that the output power and electron efficiency can reach 259 W and 13.5% at the center frequency of 140 GHz, respectively. Simultaneously, the instantaneous 3-dB bandwidth is 24 GHz. Compared to the symmetric double V-shaped TWT, the output power and electron efficiency of the folded frame TWT are increased.

  6. Folding analysis of the most complex Stevedore's protein knot.

    PubMed

    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

  7. Wavelength selection and evolution in high-resolution 3D numerical models of multilayer detachment folding

    NASA Astrophysics Data System (ADS)

    Fernandez, N.; Kaus, B. J. P.

    2012-04-01

    Many fold-and-thrust belts are dominated by crustal scale folding that exhibits fairly regular fold spacing. For example, the Fars region in the Zagros Mountains shows a fold spacing with a normal distribution around a dominant wavelength of 14 Km ± 3 Km, yet having a wide variability of aspect ratios (length to wavelength ratios; Yamato et al., 2011). To which extend this is consistent with a crustal-scale folding instability or how the regional spacing of folding can be used to constrain regional rheological parameters are not fully resolved questions. To get insights into these problems we have investigated the dominant wavelength selection and evolution in a true multilayer system (Schmid and Podlachikov, 2006) with three different viscosities: lower salt layer (ηs), and overlying weak layers (ηw) and competent layers (ηc). This has been done by means of two tools: a semi-analytical solution and numerical models. The 2D semi-analytical approach was applied to derive mechanical phase diagrams that can be used to distinguish different folding modes using two viscosity ratios (R1= ηc/ ηs and R2= ηc/ ηw). To test the validity of the phase diagrams beyond the initial stages of folding for which the analytical approach is valid, we performed several 3D high-resolution forward numerical runs using a finite element code (LaMEM). Additionally, irregular bottom topography was implemented in the numerical runs in order to account for variable salt thickness distribution and consequently study its effect on the wavelength selection. A straight but gradual salt thickness variation, sudden thickness variations due to a basement step or an arc shaped salt basin among other cases could be investigated. It was observed that the bottom topography exerts an impact on the velocity field of the different folding modes and as a result, its influence can be observed on the resulting topography. However, not all the folding modes exhibit an initial wavelength that is dependent

  8. 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.

  9. 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.…

  10. 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.

  11. A framework for describing topological frustration in models of protein folding.

    PubMed

    Norcross, Todd S; Yeates, Todd O

    2006-09-22

    In a natively folded protein of moderate or larger size, the protein backbone may weave through itself in complex ways, raising questions about what sequence of events might have to occur in order for the protein to reach its native configuration from the unfolded state. A mathematical framework is presented here for describing the notion of a topological folding barrier, which occurs when a protein chain must pass through a hole or opening, formed by other regions of the protein structure. Different folding pathways encounter different numbers of such barriers and therefore different degrees of frustration. A dynamic programming algorithm finds the optimal theoretical folding path and minimal degree of frustration for a protein based on its natively folded configuration. Calculations over a database of protein structures provide insights into questions such as whether the path of minimal frustration might tend to favor folding from one or from many sites of folding nucleation, or whether proteins favor folding around the N terminus, thereby providing support for the hypothesis that proteins fold co-translationally. The computational methods are applied to a multi-disulfide bonded protein, with computational findings that are consistent with the experimentally observed folding pathway. Attention is drawn to certain complex protein folds for which the computational method suggests there may be a preferred site of nucleation or where folding is likely to proceed through a relatively well-defined pathway or intermediate. The computational analyses lead to testable models for protein folding. PMID:16930616

  12. 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

  13. Modeling folding related multi-scale deformation of sedimentary rock using ALSM and fracture characterization at Raplee Ridge, UT

    NASA Astrophysics Data System (ADS)

    Mynatt, I.; Hilley, G. E.; Pollard, D. D.

    2006-12-01

    Understanding and predicting the characteristics of folding induced fracturing is an important and intriguing structural problem. Folded sequences of sedimentary rock at depth are common traps for hydrocarbons and water and fractures can strongly effect (both positively and negatively) this trapping capability. For these reasons fold-fracture relationships are well studied, but due to the complex interactions between the remote tectonic stress, rheologic properties, underlying fault geometry and slip, and pre-existing fractures, fracture characteristics can vary greatly from fold to fold. Additionally, examination of the relationships between fundamental characteristics such as fold geometry and fracture density are difficult even in thoroughly studied producing fields as measurements of fold shape are hampered by the low resolution of seismic surveying and measurements of fractures are limited to sparse well-bore locations. Due to the complexity of the system, the limitations of available data and small number of detailed case studies, prediction of fracture characteristics, e.g. the distribution of fracture density, are often difficult to make for a particular fold. We suggest a combination of mechanical and numerical modeling and analysis combined with detailed field mapping can lead to important insights into fold-fracture relationships. We develop methods to quantify both fold geometry and fracture characteristics, and summarize their relationships for an exhumed analogue reservoir case study. The field area is Raplee Monocline, a Laramide aged, N-S oriented, ~14-km long fold exposed in the Monument Upwarp of south-eastern Utah and part of the larger Colorado Plateau geologic province. The investigation involves three distinct parts: 1) Field based characterization and mapping of the fractures on and near the fold; 2) Development of accurate models of the fold geometry using high resolution data including ~3.5x107 x, y, z topographic points collected using

  14. 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

  15. INVITED PAPER: On the single-mass model of the vocal folds

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  16. 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

  17. 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.

  18. Histomorphometric analysis of collagen and elastic fibres in the cranial and caudal fold of the porcine glottis.

    PubMed

    Lang, A; Koch, R; Rohn, K; Gasse, H

    2015-06-01

    The porcine glottis differs from the human glottis in its cranial and caudal vocal folds (CraF, CauF). The fibre apparatus of these folds was studied histomorphometrically in adult minipigs. For object definition and quantification, the colour-selection tools of the Adobe-Photoshop program were used. Another key feature was the subdivision of the cross-sections of the folds into proportional subunits. This allowed a statistical analysis irrespective of differences in thickness of the folds. Both folds had a distinct, dense subepithelial layer equivalent to the basement membrane zone in humans. The subsequent, loose layer was interpreted - in principle - as being equivalent to Reinke's space of the human vocal fold. The next two layers were not clearly separated. Due to this, the concept of a true vocal ligament did not appear applicable to neither CauF nor CraF. Instead, the body-cover model was emphasized by our findings. The missing vocalis muscle in the CraF is substituted by large collagen fibre bundles in a proportional depth corresponding to the position of the muscle of the CauF. The distribution of elastic fibres made the CraF rather than the CauF more similar to the human vocal fold. We suggest that these data are useful for those wishing to use the porcine glottis as a model for studying oscillatory properties during phonation. PMID:24995486

  19. 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.

  20. 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.

  1. Contact prediction in protein modeling: Scoring, folding and refinement of coarse-grained models

    PubMed Central

    Latek, Dorota; Kolinski, Andrzej

    2008-01-01

    Background Several different methods for contact prediction succeeded within the Sixth Critical Assessment of Techniques for Protein Structure Prediction (CASP6). The most relevant were non-local contact predictions for targets from the most difficult categories: fold recognition-analogy and new fold. Such contacts could provide valuable structural information in case a template structure cannot be found in the PDB. Results We described comprehensive tests of the effectiveness of contact data in various aspects of de novo modeling with CABS, an algorithm which was used successfully in CASP6 by the Kolinski-Bujnicki group. We used the predicted contacts in a simple scoring function for the post-simulation ranking of protein models and as a soft bias in the folding simulations and in the fold-refinement procedure. The latter approach turned out to be the most successful. The CABS force field used in the Replica Exchange Monte Carlo simulations cooperated with the true contacts and discriminated the false ones, which resulted in an improvement of the majority of Kolinski-Bujnicki's protein models. In the modeling we tested different sets of predicted contact data submitted to the CASP6 server. According to our results, the best performing were the contacts with the accuracy balanced with the coverage, obtained either from the best two predictors only or by a consensus from as many predictors as possible. Conclusion Our tests have shown that theoretically predicted contacts can be very beneficial for protein structure prediction. Depending on the protein modeling method, a contact data set applied should be prepared with differently balanced coverage and accuracy of predicted contacts. Namely, high coverage of contact data is important for the model ranking and high accuracy for the folding simulations. PMID:18694501

  2. 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.

  3. 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

  4. Theoretical Modeling and Experimental High-Speed Imaging of Elongated Vocal Folds

    PubMed Central

    Zhang, Yu; Regner, Michael F.; Jiang, Jack J.

    2014-01-01

    In this paper, the role of vocal fold elongation in governing glottal movement dynamics was theoretically and experimentally investigated. A theoretical model was first proposed to incorporate vocal fold elongation into the two-mass model. This model predicted the direct and nondirect components of the glottal time series as a function of vocal fold elongation. Furthermore, high-speed digital imaging was applied in excised larynx experiments to visualize vocal fold vibrations with variable vocal fold elongation from –10% to 50% and subglottal pressures of 18- and 24-cm H2O. Comparison between theoretical model simulations and experimental observations showed good agreement. A relative maximum was seen in the nondirect component of glottal area, suggesting that an optimal elongation could maximize the vocal fold vibratory power. However, sufficiently large vocal fold elongations caused the nondirect component to approach zero and the direct component to approach a constant. These results showed that vocal fold elongation plays an important role in governing the dynamics of glottal area movement and validated the applicability of the proposed theoretical model and high-speed imaging to investigate laryngeal activity. PMID:21118763

  5. Theoretical modeling and experimental high-speed imaging of elongated vocal folds.

    PubMed

    Zhang, Yu; Regner, Michael F; Jiang, Jack J

    2011-10-01

    In this paper, the role of vocal fold elongation in governing glottal movement dynamics was theoretically and experimentally investigated. A theoretical model was first proposed to incorporate vocal fold elongation into the two-mass model. This model predicted the direct and nondirect components of the glottal time series as a function of vocal fold elongation. Furthermore, high-speed digital imaging was applied in excised larynx experiments to visualize vocal fold vibrations with variable vocal fold elongation from -10% to 50% and subglottal pressures of 18- and 24-cm H(2)O. Comparison between theoretical model simulations and experimental observations showed good agreement. A relative maximum was seen in the nondirect component of glottal area, suggesting that an optimal elongation could maximize the vocal fold vibratory power. However, sufficiently large vocal fold elongations caused the nondirect component to approach zero and the direct component to approach a constant. These results showed that vocal fold elongation plays an important role in governing the dynamics of glottal area movement and validated the applicability of the proposed theoretical model and high-speed imaging to investigate laryngeal activity. PMID:21118763

  6. LAF: Theoretical Model of Large Amplitude Folding of a Single Viscous Layer

    NASA Astrophysics Data System (ADS)

    Adamuszek, M.; Schmid, D. W.; Dabrowski, M.

    2012-04-01

    We present a theoretical model for Large Amplitude Folding (LAF) during buckling of a single, viscous layer. The model accurately predicts the evolution of geometrical fold parameters (amplitude, wavelength, and thickness) and is not restricted to any viscosity ratio or type of perturbation. The model employs two corrections to the formula of the initial growth rate of folds that is calculated using the thick-plate solution of Fletcher (Tectonophysics, 1977). The growth rate is modified by incorporating 1) the evolution of wavelength to thickness ratio, after Fletcher (American Journal of Science, 1974) and 2) the reduction of the growth rate, originally introduced by Schmalholz and Podladchikov (EPSL, 2000). The former correction is a consequence of the layer shortening and thickening. The latter modification is the result of using an effective rate of layer shortening as the driving force for fold growth, rather than the applied background shortening rate. The effective rate of the layer shortening is approximated by the rate of fold arclength shortening. In the model, we use an analytical expression derived based on the evolution of sinusoidal waveforms. These two modifications to the growth rate were already separately employed in previous studies. Through comparison with numerical models, we show that the simultaneous application of both corrections in LAF provides a better prediction of the evolution of the fold geometry parameters up to large amplitudes, compared to the models with only one correction. Our studies of the fold evolution from initial single and multiple (random noise, step and bell-shape function) waveforms show a remarkable fit between LAF and the numerical results. In the multiple waveform models, we predict a coupling between the components. In LAF, folds developed from initial random perturbations exhibit irregular but periodic shapes, characteristic for folds observed in nature. We also show that the evolution of folds from localized

  7. 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

  8. Model for coupled insertion and folding of membrane-spanning proteins

    NASA Astrophysics Data System (ADS)

    Hausrath, Andrew C.

    2014-08-01

    Current understanding of the forces directing the folding of integral membrane proteins is very limited compared to the detailed picture available for water-soluble proteins. While mechanistic studies of the folding process in vitro have been conducted for only a small number of membrane proteins, the available evidence indicates that their folding process is thermodynamically driven like that of soluble proteins. In vivo, however, the majority of integral membrane proteins are installed in membranes by dedicated machinery, suggesting that the cellular systems may act to facilitate and regulate the spontaneous physical process of folding. Both the in vitro folding process and the in vivo pathway must navigate an energy landscape dominated by the energetically favorable burial of hydrophobic segments in the membrane interior and the opposition to folding due to the need for passage of polar segments across the membrane. This manuscript describes a simple, exactly solvable model which incorporates these essential features of membrane protein folding. The model is used to compare the folding time under conditions which depict both the in vitro and in vivo pathways. It is proposed that the cellular complexes responsible for insertion of membrane proteins act by lowering the energy barrier for passage of polar regions through the membrane, thereby allowing the chain to more rapidly achieve the folded state.

  9. Recovery of Vibratory Function After Vocal Fold Microflap in a Rabbit Model

    PubMed Central

    Kojima, Tsuyoshi; Mitchell, Joshua R.; Garrett, C. Gaelyn; Rousseau, Bernard

    2015-01-01

    Objectives/Hypothesis The purpose of this study was to evaluate the return of vibratory function and restoration of vibration amplitude and symmetry after vocal fold microflap surgery. Study Design Prospective in vivo animal model. Methods Microflap surgery was performed on 30 New Zealand white breeder rabbits. The left vocal fold received a 3-mm epithelial incision and mucosal elevation, while the contralateral vocal fold was left intact to serve as an internal control. Quantitative analysis of amplitude ratio and lateral phase difference were measured using high-speed laryngeal imaging at a frame rate of 10,000 frames per second from animals undergoing evoked phonation on postoperative days 0, 1, 3, 5, and 7. Results Quantitative measures revealed a significantly reduced amplitude ratio and lateral phase difference on day 0 after microflap. These impairments of vibratory function on day 0 were associated with separation of the vocal fold’s bodycover layer. Amplitude ratio increased significantly by day 3 after microflap, with further increases in vibration amplitude on days 5 and 7. While the amplitude ratio improved significantly on day 3, lateral phase difference decreased significantly on day 3, and returned to normal on days 5 and 7. Conclusions High-speed laryngeal imaging was used to investigate the natural time course of postmicroflap recovery of vibratory function. Results revealed the restoration of vibration amplitude and lateral phase difference by days 3 to 7 after microflap. The time period of improved vibratory function observed in this study coincides with the end of the well-documented inflammatory phase of vocal fold wound repair. PMID:23901003

  10. Simple geometric model to describe self-folding of polymer sheets.

    PubMed

    Liu, Ying; Mailen, Russell; Zhu, Yong; Dickey, Michael D; Genzer, Jan

    2014-04-01

    Self-folding is the autonomous folding of two-dimensional shapes into three-dimensional forms in response to an external stimulus. This paper focuses on light-induced self-folding of prestrained polymer sheets patterned with black ink. The ink absorbs the light and the resulting heat induces the polymer beneath the ink to relax faster than the rest of the sheet. A simple geometric model captures both the folding angle and folding kinetics associated with this localized shrinkage. The model assumes that (1) the polymer in contact with the ink shrinks at a rate determined by the temporal temperature profile of the hinge surface; (2) the bottom of the sheet, which is cooler, does not shrink considerably; and (3) a linear gradient of strain relaxation exists across the film between these two extremes. Although there are more complex approaches for modeling folding, the appeal of this model is its simplicity and ease of use. Measurements of the macroscopic, thermally driven shrinkage behavior of the sheets help predict the kinetics of folding by determining how fast the top of the hinge shrinks as a function of temperature and time. These measurements also provide information about the temperature required to induce folding and offer indirect measurement of the glass transition temperature of the polymer that comprises the sheet. PMID:24827268

  11. Simple geometric model to describe self-folding of polymer sheets

    NASA Astrophysics Data System (ADS)

    Liu, Ying; Mailen, Russell; Zhu, Yong; Dickey, Michael D.; Genzer, Jan

    2014-04-01

    Self-folding is the autonomous folding of two-dimensional shapes into three-dimensional forms in response to an external stimulus. This paper focuses on light-induced self-folding of prestrained polymer sheets patterned with black ink. The ink absorbs the light and the resulting heat induces the polymer beneath the ink to relax faster than the rest of the sheet. A simple geometric model captures both the folding angle and folding kinetics associated with this localized shrinkage. The model assumes that (1) the polymer in contact with the ink shrinks at a rate determined by the temporal temperature profile of the hinge surface; (2) the bottom of the sheet, which is cooler, does not shrink considerably; and (3) a linear gradient of strain relaxation exists across the film between these two extremes. Although there are more complex approaches for modeling folding, the appeal of this model is its simplicity and ease of use. Measurements of the macroscopic, thermally driven shrinkage behavior of the sheets help predict the kinetics of folding by determining how fast the top of the hinge shrinks as a function of temperature and time. These measurements also provide information about the temperature required to induce folding and offer indirect measurement of the glass transition temperature of the polymer that comprises the sheet.

  12. Simulating replica exchange simulations of protein folding with a kinetic network model

    PubMed Central

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

    2007-01-01

    Replica exchange (RE) is a generalized ensemble simulation method for accelerating the exploration of free-energy landscapes, which define many challenging problems in computational biophysics, including protein folding and binding. Although temperature RE (T-RE) is a parallel simulation technique whose implementation is relatively straightforward, kinetics and the approach to equilibrium in the T-RE ensemble are very complicated; there is much to learn about how to best employ T-RE to protein folding and binding problems. We have constructed a kinetic network model for RE studies of protein folding and used this reduced model to carry out “simulations of simulations” to analyze how the underlying temperature dependence of the conformational kinetics and the basic parameters of RE (e.g., the number of replicas, the RE rate, and the temperature spacing) all interact to affect the number of folding transitions observed. When protein folding follows anti-Arrhenius kinetics, we observe a speed limit for the number of folding transitions observed at the low temperature of interest, which depends on the maximum of the harmonic mean of the folding and unfolding transition rates at high temperature. The results shown here for the network RE model suggest ways to improve atomic-level RE simulations such as the use of “training” simulations to explore some aspects of the temperature dependence for folding of the atomic-level models before performing RE studies. PMID:17878309

  13. 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…

  14. A New Heuristic Algorithm for Protein Folding in the HP Model.

    PubMed

    Traykov, Metodi; Angelov, Slav; Yanev, Nicola

    2016-08-01

    This article presents an efficient heuristic for protein folding. The protein folding problem is to predict the compact three-dimensional structure of a protein based on its amino acid sequence. The focus is on an original integer programming model derived from a platform used for Contact Map Overlap problem. PMID:27153764

  15. Analysis of Carbon Nanotubes and Graphene Nanoribbons with Folded Racket Shapes

    NASA Astrophysics Data System (ADS)

    Borum, Andy; Plaut, Raymond; Dillard, David

    2011-10-01

    When carbon nanotubes and graphene nanoribbons become long, they may self-fold and form tennis racket-like shapes. This phenomenon is analyzed in two ways by treating a nanotube or nanoribbon as an elastica. First, an approach from adhesion science is used, in which the two sides of the racket handle are assumed to be straight and bonded together with constant or no separation. New analytical results are obtained involving the shape, bending energy, and adhesion energy of the self-folded structures. These relations show that the dimensions of the racket loop are proportional to the square root of the flexural rigidity. The second analysis uses the Lennard-Jones potential to model the van der Waals forces between the two sides of the racket. A nanoribbon is considered, and the interatomic forces are integrated along the length and across the width of the nanoribbon. The resulting integro-differential equations are solved using the finite difference method. The racket handle is found to be in compression and the separation between the two sides of the racket handle decreases in the direction of the racket loop. The results for the Lennard-Jones model approximately satisfy the relationship between the dimensions and the flexural rigidity found using the adhesion model.

  16. 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

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

    PubMed

    Shurtz, Timothy E; Thomson, Scott L

    2013-06-01

    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

  18. 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.

  19. 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

  20. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy.

    PubMed

    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

  1. 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.

  2. 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. PMID:21074529

  3. 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

  4. 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. PMID:23585700

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

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

    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.

  6. 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. PMID:20161071

  7. Non-stationary Bayesian estimation of parameters from a body cover model of the vocal folds.

    PubMed

    Hadwin, Paul J; Galindo, Gabriel E; Daun, Kyle J; Zañartu, Matías; Erath, Byron D; Cataldo, Edson; Peterson, Sean D

    2016-05-01

    The evolution of reduced-order vocal fold models into clinically useful tools for subject-specific diagnosis and treatment hinges upon successfully and accurately representing an individual patient in the modeling framework. This, in turn, requires inference of model parameters from clinical measurements in order to tune a model to the given individual. Bayesian analysis is a powerful tool for estimating model parameter probabilities based upon a set of observed data. In this work, a Bayesian particle filter sampling technique capable of estimating time-varying model parameters, as occur in complex vocal gestures, is introduced. The technique is compared with time-invariant Bayesian estimation and least squares methods for determining both stationary and non-stationary parameters. The current technique accurately estimates the time-varying unknown model parameter and maintains tight credibility bounds. The credibility bounds are particularly relevant from a clinical perspective, as they provide insight into the confidence a clinician should have in the model predictions. PMID:27250162

  8. Large-scale Folding: Implications For Effective Lithospheric Rheology And Thin Sheet Models.

    NASA Astrophysics Data System (ADS)

    Schmalholz, S. M.; Podladchikov, Yu. Yu.; Burg, J.-P.

    We show that folding of a non-Newtonian layer resting on a homogeneous Newto- nian matrix with finite thickness under influence of gravity can occur by three modes: (i) matrix-controlled folding, dependent on the effective viscosity contrast between layer and matrix, (ii) gravity-controlled folding, dependent on the Argand number (the ratio of the stress caused by gravity to the stress caused by shortening) and (iii) detachment folding, dependent on the ratio of matrix thickness to layer thickness. We construct a phase diagram that defines the transitions between each of the three fold- ing modes. Our priority is transparency of the analytical derivations (e.g. thin-plate versus thick-plate approximations), which permits complete classification of the fold- ing modes involving a minimum number of dimensionless parameters. Accuracy and sensitivity of the analytical results to model assumptions are investigated. In particu- lar, depth-dependence of matrix rheology is only important for folding over a narrow range of material parameters. In contrast, strong depth-dependence of the folding layer viscosity limits applicability of ductile rheology and leads to a viscoelastic transition for layers on the crustal and lithospheric scales. This transition allows estimating the critical elastic thickness of the oceanic lithosphere, which determines if the oceanic lithosphere deforms effectively ductile or elastic. Considering applicability conditions of thin viscous sheet models for large-scale lithospheric deformation, derived in terms of the Argand number, our results show that the uplift rates caused by folding (which are neglected by the thin sheet models) are of the same order than the uplift rates caused by layer thickening. This result further indicates that large-scale folding and not crustal thickening was the dominant deformation mode during the evolution of the Himalayan syntaxes. Our theory is applied to estimate the effective thickness of the folded Central Asian

  9. 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

  10. 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

  11. 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

  12. Analysis of curved folds and fault/fold terminations in the southern Upper Magdalena Valley of Colombia

    NASA Astrophysics Data System (ADS)

    Jiménez, Giovanny; Rico, John; Bayona, German; Montes, Camilo; Rosero, Alexis; Sierra, Daniel

    2012-11-01

    We use surface and subsurface fold and fault geometries to document curved geometry of folds, along-strike termination of faults/folds and the change of dip of regional faults in four structural areas in the southern part of the Upper Magdalena Valley Basin. In La Cañada area, strike-slip deformation is dominant and cuts former compressional structures; faults and folds of this area end northward abruptly near Rio Paez. To the north of Paez River is the La Hocha area that includes the Tesalia Syncline and La Hocha Anticline, two curved folds that plunge at the same latitude. The southern domain of La Hocha Anticline is asymmetric and bounded by faults in both flanks, whereas the symmetry of the northern domain is related to subsurface fault bending. Paleomagnetic components uncovered in Jurassic rocks suggest a clockwise rotation of 15.2 ± 11.4 in the southern domain, and 31.7 ± 14.4 in the northern domain. The Iquira Area, North of La Hocha, the internal structure is controlled by east-verging faults that end abruptly to the north of this area. The northernmost area is the Upar area that includes fault systems with opposite vergence; west-verging faults at the east of this area decapitate east-verging faults and folds. Paleomagnetic data, geologic mapping and regional structural cross-sections suggest that: (1) pre-existing basement structure controls the curved geometry of La Hocha Anticline; (2) along-strike changes in structural style between adjacent areas and along-strike termination of faults and folds are related to the location of northwest-striking transverse structures in the subsurface; and (3) at least two deformation phases are documented: an Eocene-Oligocene phase associated with the growth of folds along detachment levels within Mesozoic rocks; and a late Miocene phase associated with transpressive faulting along the Chusma and San Jacinto faults. The latter event drove clockwise rotation of the La Hocha Anticline.

  13. Examination of Flow in a Scaled-Up Vocal Fold Model for Diseased Conditions

    NASA Astrophysics Data System (ADS)

    Sherman, Erica; Zhang, Lucy; Xinshi, Wang; Timothy, Wei; Krane, Michael

    2010-11-01

    An experiment to provide DPIV measurements in a scaled up dynamic human vocal fold model is presented. The 10x scale vocal fold model is a new design that incorporates both the rocking as well as the oscillatory open/close motions characteristic of vocal fold motions. The experiment is run in a free-stream water tunnel where the oscillation frequencies and flow speeds are dynamically matched to physiologic conditions for both male and female phonation. The effects associated with vocal fold paralysis will be discussed. Flow measurements showing fluid kinematics including jet velocity and orientation, and vortex shedding as a function of time through an oscillation cycle will be presented. In addition, key data relevant to phonation, such as volumetric flow rate and glottal behavior will be presented.

  14. Investigating the three-dimensional flow separation induced by a model vocal fold polyp.

    PubMed

    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

  15. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    PubMed

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

    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. PMID:26723626

  18. 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

  19. 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.

  20. 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.

  1. Feasibility and acute healing of vocal fold microflap incisions in a rabbit model

    PubMed Central

    Suehiro, Atsushi; Bock, Jonathan M.; Hall, Joseph E.; Garrett, C. Gaelyn; Rousseau, Bernard

    2012-01-01

    Objectives The purpose of this study was to: 1) investigate the feasibility of performing mucosal elevation of a vocal fold microflap in a rabbit model, and 2) measure the acute healing of rabbit microflap incisions compared to control vocal folds. Study Design Prospective animal study Methods Ten New Zealand white rabbits were used in this study. All rabbits received a 3mm incision through the epithelium of one vocal fold using a sickle knife and mucosal elevation through this incision using a microlaryngeal fine angled spatula. The contralateral vocal fold was left intact to serve as an internal control. Student t tests were used to investigate differences in epithelial thickness, immunohistochemical staining of CD 45, and inflammatory and pro-fibrotic gene expression between vocal folds undergoing microflap and control. Results Exposure of the rabbit larynx was achieved, allowing for the identification of a surgical plane and the creation of a microflap and elevation of the vocal fold mucosa. Hematoxylin-eosin staining revealed no significant differences in epithelial thickness, immunohistochemistry for CD 45 showed no significant differences in CD 45 positive cells, and quantitative PCR revealed no significant differences in IL-1β, TGFβ-1, or COX-2 gene expression between vocal folds undergoing microflap and control. Conclusions We demonstrate the feasibility of vocal fold microflap surgery in a rabbit model. With the advantage of greater access to primers and antibodies for molecular biological studies, the application of the microflap technique in a small animal model such as rabbit has broad implications for future experimental investigations in laryngology. Level of Evidence Animal Research. PMID:22253007

  2. Potential application of FoldX force field based protein modeling in zinc finger nucleases design.

    PubMed

    He, ZuYong; Mei, Gui; Zhao, ChunPeng; Chen, YaoSheng

    2011-05-01

    Engineered sequence-specific zinc finger nucleases (ZFNs) make the highly efficient modification of eukaryotic genomes possible. However, most current strategies for developing zinc finger nucleases with customized sequence specificities require the construction of numerous tandem arrays of zinc finger proteins (ZFPs), and subsequent largescale in vitro validation of their DNA binding affinities and specificities via bacterial selection. The labor and expertise required in this complex process limits the broad adoption of ZFN technology. An effective computational assisted design strategy will lower the complexity of the production of a pair of functional ZFNs. Here we used the FoldX force field to build 3D models of 420 ZFP-DNA complexes based on zinc finger arrays developed by the Zinc Finger Consortium using OPEN (oligomerized pool engineering). Using nonlinear and linear regression analysis, we found that the calculated protein-DNA binding energy in a modeled ZFP-DNA complex strongly correlates to the failure rate of the zinc finger array to show significant ZFN activity in human cells. In our models, less than 5% of the three-finger arrays with calculated protein-DNA binding energies lower than -13.132 kcal mol(-1) fail to form active ZFNs in human cells. By contrast, for arrays with calculated protein-DNA binding energies higher than -5 kcal mol(-1), as many as 40% lacked ZFN activity in human cells. Therefore, we suggest that the FoldX force field can be useful in reducing the failure rate and increasing efficiency in the design of ZFNs. PMID:21455692

  3. 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.

  4. Experimental study of the aeroacoustic-aeroelastic behavior of model vocal folds

    NASA Astrophysics Data System (ADS)

    Campo, Elizabeth; Camarena, Ernesto; Krane, Michael

    2010-11-01

    The effect of vocal fold body stiffness and bilateral asymmetry was studied using a life-size physical model of the human airway using interchangeable silicone rubber models of the human vocal folds. The two layer vocal fold models are comprised of an inner body layer and an outside cover layer. The following measures were used to assess the effect of body stiffness and asymmetry: radiated sound power, phonation threshold pressure and aeroacoustic source strengths. Results obtained from the human airway model compared favorably with behavior observed in human subjects. Furthermore, the results reveal that the asymmetric cases required a higher subglottal pressure to initiate phonation and radiated less intense sound, in comparison to the symmetrical configuration.

  5. Structure-approximating inverse protein folding problem in the 2D HP model.

    PubMed

    Gupta, Arvind; Manuch, Ján; Stacho, Ladislav

    2005-12-01

    The inverse protein folding problem is that of designing an amino acid sequence which has a particular native protein fold. This problem arises in drug design where a particular structure is necessary to ensure proper protein-protein interactions. In this paper, we show that in the 2D HP model of Dill it is possible to solve this problem for a broad class of structures. These structures can be used to closely approximate any given structure. One of the most important properties of a good protein (in drug design) is its stability--the aptitude not to fold simultaneously into other structures. We show that for a number of basic structures, our sequences have a unique fold. PMID:16379538

  6. Strobokymographic and videostroboscopic analysis of vocal fold motion in unilateral superior laryngeal nerve paralysis.

    PubMed

    Mendelsohn, Abie H; Sung, Myung-Whun; Berke, Gerald S; Chhetri, Dinesh K

    2007-02-01

    The clinical diagnosis of superior laryngeal nerve paralysis (SLNp) is infrequently made, because of the heterogeneity of clinical presentations and laryngoscopic findings. Laryngeal electromyography (LEMG) can provide the definitive diagnosis of this abnormality. With increasing use of LEMG in clinical practice, this condition is now more frequently appreciated by otolaryngologists. A characteristic, but infrequently reported, videostroboscopic vocal fold motion termed Gegenschlagen ("dashing-against-each-other") has previously been described to occur in unilateral SLNp. We encountered such motion in a clinical case, which we subsequently verified as unilateral SLNp by means of LEMG. This characteristic glottic motion was then verified in an in vivo canine model of phonation after unilateral SLNp. Videostrobokymography was performed to generate kymograms that illustrated this vocal fold motion clearly. Kymograms of both human and canine subjects with SLNp demonstrated an undulating motion of the horizontally shifting glottic space as the medial edges of the vocal folds chased each other 90 degrees out of phase. As one vocal fold mucosal edge was opening, the other was closing, and this repeated motion appeared as vocal folds chasing or dashing against each other. Although not uniformly seen in all cases, this vocal fold motion appears to be unique to SLNp. PMID:17388230

  7. 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.

  8. Insights into the damage zones in fault-bend folds from geomechanical models and field data

    NASA Astrophysics Data System (ADS)

    Ju, Wei; Hou, Guiting; Zhang, Bo

    2014-01-01

    Understanding the rock mass deformation and stress states, the fracture development and distribution are critical to a range of endeavors including oil and gas exploration and development, and geothermal reservoir characterization and management. Geomechanical modeling can be used to simulate the forming processes of faults and folds, and predict the onset of failure and the type and abundance of deformation features along with the orientations and magnitudes of stresses. This approach enables the development of forward models that incorporate realistic mechanical stratigraphy (e.g., the bed thickness, bedding planes and competence contrasts), include faults and bedding-slip surfaces as frictional sliding interfaces, reproduce the geometry of the fold structures, and allow tracking strain and stress through the whole deformation process. In this present study, we combine field observations and finite element models to calibrate the development and distribution of fractures in the fault-bend folds, and discuss the mechanical controls (e.g., the slip displacement, ramp cutoff angle, frictional coefficient of interlayers and faults) that are able to influence the development and distribution of fractures during fault-bend folding. A linear relationship between the slip displacement and the fracture damage zone, the ramp cutoff angle and the fracture damage zone, and the frictional coefficient of interlayers and faults and the fracture damage zone was established respectively based on the geomechanical modeling results. These mechanical controls mentioned above altogether contribute to influence and control the development and distribution of fractures in the fault-bend folds.

  9. 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…

  10. 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.

  11. 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

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

    PubMed

    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. 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

  13. 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

  14. Analog Models of Crustal-Scale Folding with Special Reference to the Archean

    NASA Astrophysics Data System (ADS)

    Peschler, A. P.; Benn, K.; Roest, W. R.

    2004-05-01

    We use analog experiments to investigate folding of continental crust subjected to different geothermal gradients and displacement rates. The experiments are designed with an eye to crustal-scale folding of Archean greenstone belts, however, the results may also be pertinent for crustal folding of younger terranes. Localized thermal anomalies are used to investigate effects of major additions of heat to the crust, such as might occur above a plume or in response to magmatic underplating. The scaled models are composed of five layers. The model upper crust is composed of silica sand overlying a thin base of silicone gum. Two paraffin waxes of different densities and with different melting temperatures are used for the middle and lower crust. The viscosities of paraffin waxes are modified by addition of heat from a source below the models, which leads to lower viscosities and eventually to melting. The upper mantle is modeled by a thick layer of the same silicone gum used for the lowermost upper crust. In our experiments, folding is the main response to shortening of the analog crust. The middle and lower crust analogs behave essentially as one ductile layer and respond to the shortening by buckling. Folding is accompanied by thickening of the paraffin wax layers in the intrados of folds and thinning in the extrados. In the upper crust analog, the first-order folding imposed by the middle and lower crustal layers is accompanied, in some experiments, by higher-order folding, by the formation of grabens above anticlines, and by reverse shear zones located near inflection lines on limbs of synclines. For the coolest thermal gradients, one anticline-syncline pair is formed. For warmer gradients, multiple folds develop that have shorter wavelengths and smaller amplitudes. Based on our models, we interpret that the increase of crustal temperatures may result in a decrease in wavelength and a decrease of the amplitude of the crustal folds. Changing the displacement rates

  15. 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.

  16. A Simple Lattice Model That Captures Protein Folding, Aggregation and Amyloid Formation

    PubMed Central

    Abeln, Sanne; Vendruscolo, Michele; Dobson, Christopher M.; Frenkel, Daan

    2014-01-01

    The ability of many proteins to convert from their functional soluble state to amyloid fibrils can be attributed to inter-molecular beta strand formation. Such amyloid formation is associated with neurodegenerative disorders like Alzheimer's and Parkinson's. Molecular modelling can play a key role in providing insight into the factors that make proteins prone to fibril formation. However, fully atomistic models are computationally too expensive to capture the length and time scales associated with fibril formation. As the ability to form fibrils is the rule rather than the exception, much insight can be gained from the study of coarse-grained models that capture the key generic features associated with amyloid formation. Here we present a simple lattice model that can capture both protein folding and beta strand formation. Unlike standard lattice models, this model explicitly incorporates the formation of hydrogen bonds and the directionality of side chains. The simplicity of our model makes it computationally feasible to investigate the interplay between folding, amorphous aggregation and fibril formation, and maintains the capability of classic lattice models to simulate protein folding with high specificity. In our model, the folded proteins contain structures that resemble naturally occurring beta-sheets, with alternating polar and hydrophobic amino acids. Moreover, fibrils with intermolecular cross-beta strand conformations can be formed spontaneously out of multiple short hydrophobic peptide sequences. Both the formation of hydrogen bonds in folded structures and in fibrils is strongly dependent on the amino acid sequence, indicating that hydrogen-bonding interactions alone are not strong enough to initiate the formation of beta sheets. This result agrees with experimental observations that beta sheet and amyloid formation is strongly sequence dependent, with hydrophobic sequences being more prone to form such structures. Our model should open the way to a

  17. 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. PMID:20810950

  18. 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

  19. 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.

  20. A simple model for calculating the kinetics of protein folding from three-dimensional structures.

    PubMed

    Muñoz, V; Eaton, W A

    1999-09-28

    An elementary statistical mechanical model was used to calculate the folding rates for 22 proteins from their known three-dimensional structures. In this model, residues come into contact only after all of the intervening chain is in the native conformation. An additional simplifying assumption is that native structure grows from localized regions that then fuse to form the complete native molecule. The free energy function for this model contains just two contributions-conformational entropy of the backbone and the energy of the inter-residue contacts. The matrix of inter-residue interactions is obtained from the atomic coordinates of the three-dimensional structure. For the 18 proteins that exhibit two-state equilibrium and kinetic behavior, profiles of the free energy versus the number of native peptide bonds show two deep minima, corresponding to the native and denatured states. For four proteins known to exhibit intermediates in folding, the free energy profiles show additional deep minima. The calculated rates of folding the two-state proteins, obtained by solving a diffusion equation for motion on the free energy profiles, reproduce the experimentally determined values surprisingly well. The success of these calculations suggests that folding speed is largely determined by the distribution and strength of contacts in the native structure. We also calculated the effect of mutations on the folding kinetics of chymotrypsin inhibitor 2, the most intensively studied two-state protein, with some success. PMID:10500173

  1. Fold-preserving electronic cleansing using a reconstruction model integrating material fractions and structural responses.

    PubMed

    Lee, Hyunna; Kim, Bohyoung; Lee, Jeongjin; Kim, Se Hyung; Shin, Yeong-Gil; Kim, Tae-Gong

    2013-06-01

    In this paper, we propose an electronic cleansing method using a novel reconstruction model for removing tagged materials (TMs) in computed tomography (CT) images. To address the partial volume (PV) and pseudoenhancement (PEH) effects concurrently, material fractions and structural responses are integrated into a single reconstruction model. In our approach, colonic components including air, TM, an interface layer between air and TM, and an interface layer between soft-tissue (ST) and TM (IL ST/TM ) are first segmented. For each voxel in IL ST/TM, the material fractions of ST and TM are derived using a two-material transition model, and the structural response to identify the folds submerged in the TM is calculated by the rut-enhancement function based on the eigenvalue signatures of the Hessian matrix. Then, the CT density value of each voxel in IL ST/TM is reconstructed based on both the material fractions and structural responses. The material fractions remove the aliasing artifacts caused by a PV effect in IL ST/TM effectively while the structural responses avoid the erroneous cleansing of the submerged folds caused by the PEH effect. Experimental results using ten clinical datasets demonstrated that the proposed method showed higher cleansing quality and better preservation of submerged folds than the previous method, which was validated by the higher mean density values and fold preservation rates for manually segmented fold regions. PMID:23335656

  2. 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.

  3. Statistical mechanics of a correlated energy landscape model for protein folding funnels

    NASA Astrophysics Data System (ADS)

    Plotkin, Steven S.; Wang, Jin; Wolynes, Peter G.

    1997-02-01

    In heteropolymers, energetic correlations exist due to polymeric constraints and the locality of interactions. Pair correlations in conjunction with the a priori specification of the existence of a particularly low energy state provide a method of introducing the aspect of minimal frustration to the energy landscapes of random heteropolymers. The resulting funneled landscape exhibits both a phase transition from a molten globule to a folded state, and the heteropolymeric glass transition in the globular state. We model the folding transition in the self-averaging regime, which together with a simple theory of collapse allows us to depict folding as a double-well free energy surface in terms of suitable reaction coordinates. Observed trends in barrier positions and heights with protein sequence length and thermodynamic conditions are discussed within the context of the model. We also discuss the new physics which arises from the introduction of explicitly cooperative many-body interactions, as might arise from sidechain packing and nonadditive hydrophobic forces.

  4. 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

  5. Simplified protein models can rival all atom simulations in predicting folding pathways and structure

    PubMed Central

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

    2014-01-01

    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 native-like 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 native-like propensities in the unfolded state do not necessarily determine the order of structure formation, a departure from a major conclusion of the MD 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. PMID:23889448

  6. 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).

  7. 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.

  8. 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. PMID:23503699

  9. 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

  10. Accurate Estimation of Protein Folding and Unfolding Times: Beyond Markov State Models.

    PubMed

    Suárez, Ernesto; Adelman, Joshua L; Zuckerman, Daniel M

    2016-08-01

    Because standard molecular dynamics (MD) simulations are unable to access time scales of interest in complex biomolecular systems, it is common to "stitch together" information from multiple shorter trajectories using approximate Markov state model (MSM) analysis. However, MSMs may require significant tuning and can yield biased results. Here, by analyzing some of the longest protein MD data sets available (>100 μs per protein), we show that estimators constructed based on exact non-Markovian (NM) principles can yield significantly improved mean first-passage times (MFPTs) for protein folding and unfolding. In some cases, MSM bias of more than an order of magnitude can be corrected when identical trajectory data are reanalyzed by non-Markovian approaches. The NM analysis includes "history" information, higher order time correlations compared to MSMs, that is available in every MD trajectory. The NM strategy is insensitive to fine details of the states used and works well when a fine time-discretization (i.e., small "lag time") is used. PMID:27340835

  11. Elastic instabilities in a layered cerebral cortex: A revised axonal tension model for cortex folding

    NASA Astrophysics Data System (ADS)

    Schwarz, J. M.

    Despite decades of research, there is still no consensus regarding the mechanism(s) driving cerebral cortex folding. Two different mechanisms--axonal tension based on efficient wiring of the neurons and differential growth-induced buckling--are the prevailing hypotheses, though quantitative comparison with data raises issues with both of them. I will present a model for the elasticity of the cerebral cortex as a layered material with bending energy along the layers and elastic energy between them. The cortex is also subjected to axons pulling from the underlying white matter. Above a critical threshold force, a 'flat' cortex configuration becomes unstable and periodic undulations emerge, i.e. a buckling instability occurs, to presumably initiate folds in the cortex. This model builds on the original axonal tension model for cortex folding based on the efficient wiring of neurons but with no buckling mechanism and allows one to understand why small mice brains exhibit no folds, while larger human brains do. Finally, an estimate of the bending rigidity constant for the cortex can be made based on the critical wavelength to quantitatively test this revised axonal tensional model. This work was done in collaboration with Oksana Manyuhina and David Mayett.

  12. Protein folding in hydrophobic-polar lattice model: a flexible ant-colony optimization approach.

    PubMed

    Hu, Xiao-Min; Zhang, Jun; Xiao, Jing; Li, Yun

    2008-01-01

    This paper proposes a flexible ant colony (FAC) algorithm for solving protein folding problems based on the hydrophobic-polar square lattice model. Collaborations of novel pheromone and heuristic strategies in the proposed algorithm make it more effective in predicting structures of proteins compared with other state-of-the-art algorithms. PMID:18537736

  13. A max-margin model for efficient simultaneous alignment and folding of RNA sequences

    PubMed Central

    Do, Chuong B.; Foo, Chuan-Sheng; Batzoglou, Serafim

    2008-01-01

    Motivation: The need for accurate and efficient tools for computational RNA structure analysis has become increasingly apparent over the last several years: RNA folding algorithms underlie numerous applications in bioinformatics, ranging from microarray probe selection to de novo non-coding RNA gene prediction. In this work, we present RAF (RNA Alignment and Folding), an efficient algorithm for simultaneous alignment and consensus folding of unaligned RNA sequences. Algorithmically, RAF exploits sparsity in the set of likely pairing and alignment candidates for each nucleotide (as identified by the CONTRAfold or CONTRAlign programs) to achieve an effectively quadratic running time for simultaneous pairwise alignment and folding. RAF's fast sparse dynamic programming, in turn, serves as the inference engine within a discriminative machine learning algorithm for parameter estimation. Results: In cross-validated benchmark tests, RAF achieves accuracies equaling or surpassing the current best approaches for RNA multiple sequence secondary structure prediction. However, RAF requires nearly an order of magnitude less time than other simultaneous folding and alignment methods, thus making it especially appropriate for high-throughput studies. Availability: Source code for RAF is available at:http://contra.stanford.edu/contrafold/ Contact: chuongdo@cs.stanford.edu PMID:18586747

  14. Validation of theoretical models of phonation threshold pressure with data from a vocal fold mechanical replica.

    PubMed

    Lucero, Jorge C; Van Hirtum, Annemie; Ruty, Nicolas; Cisonni, Julien; Pelorson, Xavier

    2009-02-01

    This paper analyzes the capability of a mucosal wave model of the vocal fold to predict values of phonation threshold lung pressure. Equations derived from the model are fitted to pressure data collected from a mechanical replica of the vocal folds. The results show that a recent extension of the model to include an arbitrary delay of the mucosal wave in its travel along the glottal channel provides a better approximation to the data than the original version of the model, which assumed a small delay. They also show that modeling the vocal tract as a simple inertive load, as has been proposed in recent analytical studies of phonation, fails to capture the effect of the vocal tract on the phonation threshold pressure with reasonable accuracy. PMID:19206840

  15. Three-dimensional flow patterns in a scaled, physical vocal fold model with a unilateral polyp

    NASA Astrophysics Data System (ADS)

    Seawright, Angela; Erath, Byron; Plesniak, Michael

    2009-11-01

    Trauma to the vocal folds often causes the formation of polyps; affecting the efficiency of speech and making voice rough and breathy. The change in flow characteristics due to a unilateral polyp positioned on the medial surface of a 7.5 times life-size physical vocal fold model was investigated. Previously reported phase-averaged intraglottal particle image velocimetry (PIV) investigations in a coronal plane indicated significant variations in the flow behavior on different anterior offset planes relative to the polyp. Flow three-dimensionality was investigated by resolving the temporal evolution of the flow with laser Doppler velocimetry (LDV). Data were acquired superior to the glottal exit. Physiological values of Reynolds, Strouhal, and Euler numbers were matched. Results were compared to velocity fields generated by healthy vocal fold motion. The glottal jet trajectory, flow separation points, and the velocity distribution along the vocal fold walls were influenced. Thus, a polyp significantly disturbs and modifies the airflow through the vocal folds, which has implications on both the fluid-structure energy exchange and the sound production.

  16. 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.

  17. Geomechanical modeling of stress and strain evolution during contractional fault-related folding

    NASA Astrophysics Data System (ADS)

    Smart, Kevin J.; Ferrill, David A.; Morris, Alan P.; McGinnis, Ronald N.

    2012-11-01

    Understanding stress states and rock mass deformation deep underground is critical to a range of endeavors including oil and gas exploration and production, geothermal reservoir characterization and management, and subsurface disposal of CO2. Geomechanical modeling can predict the onset of failure and the type and abundance of deformation features along with the orientations and magnitudes of stresses. This approach enables development of forward models that incorporate realistic mechanical stratigraphy (e.g., including competence contrasts, bed thicknesses, and bedding planes), include faults and bedding-slip surfaces as frictional sliding interfaces, reproduce the overall geometry of the fold structures of interest, and allow tracking of stress and strain through the deformation history. Use of inelastic constitutive relationships (e.g., elastic-plastic behavior) allows permanent strains to develop in response to the applied loads. This ability to capture permanent deformation is superior to linear elastic models, which are often used for numerical convenience, but are incapable of modeling permanent deformation or predicting permanent deformation processes such as faulting, fracturing, and pore collapse. Finite element modeling results compared with field examples of a natural contractional fault-related fold show that well-designed geomechanical modeling can match overall fold geometries and be applied to stress, fracture, and subseismic fault prediction in geologic structures. Geomechanical modeling of this type allows stress and strain histories to be obtained throughout the model domain.

  18. Overturned folds in ice sheets: Insights from a kinematic model of traveling sticky patches and comparisons with observations

    NASA Astrophysics Data System (ADS)

    Wolovick, Michael J.; Creyts, Timothy T.

    2016-05-01

    Overturned folds are observed in regions of the Greenland ice sheet where driving stress is highly variable. Three mechanisms have been proposed to explain these folds: freezing subglacial water, traveling basal slippery patches, and englacial rheological contrasts. Here we explore how traveling basal sticky patches can produce overturned folds. Transitions from low to high stress cause a tradeoff in ice flow between basal slip and internal deformation that deflects ice stratigraphy vertically. If these transitions move, the slip-deformation tradeoff can produce large folds. Those folds record the integrated effects of time-varying basal slip. To understand how dynamic changes in basal slip influence ice sheet stratigraphy, we develop a kinematic model of ice flow in a moving reference frame that follows a single traveling sticky patch. The ice flow field forms a vortex when viewed in the moving reference frame, and this vortex traps ice above the traveling patch and produces overturned folds. Sticky patches that travel downstream faster produce larger overturned folds. We use the model as an interpretive tool to infer properties of basal slip from three example folds. Our model suggests that the sticky patches underneath these folds propagated downstream at rates between one half and the full ice velocity. The regional flow regime for the smaller two folds requires substantial internal deformation whereas the regime for the largest fold requires substantially more basal slip. The distribution and character of stratigraphic folds reflect the evolution and propagation of individual sticky patches and their effects on ice sheet flow.

  19. 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…

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

    PubMed

    Diaz, N; Tischer, I

    2016-01-01

    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. PMID:27323045

  1. 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

    2012-10-01

    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. PMID:22988072

  2. Protein family and fold occurrence in genomes: power-law behaviour and evolutionary model.

    PubMed

    Qian, J; Luscombe, N M; Gerstein, M

    2001-11-01

    Global surveys of genomes measure the usage of essential molecular parts, defined here as protein families, superfamilies or folds, in different organisms. Based on surveys of the first 20 completely sequenced genomes, we observe that the occurrence of these parts follows a power-law distribution. That is, the number of distinct parts (F) with a given genomic occurrence (V) decays as F=aV(-b), with a few parts occurring many times and most occurring infrequently. For a given organism, the distributions of families, superfamilies and folds are nearly identical, and this is reflected in the size of the decay exponent b. Moreover, the exponent varies between different organisms, with those of smaller genomes displaying a steeper decay (i.e. larger b). Clearly, the power law indicates a preference to duplicate genes that encode for molecular parts which are already common. Here, we present a minimal, but biologically meaningful model that accurately describes the observed power law. Although the model performs equally well for all three protein classes, we focus on the occurrence of folds in preference to families and superfamilies. This is because folds are comparatively insensitive to the effects of point mutations that can cause a family member to diverge beyond detectable similarity. In the model, genomes evolve through two basic operations: (i) duplication of existing genes; (ii) net flow of new genes. The flow term is closely related to the exponent b and can accommodate considerable gene loss; however, we demonstrate that the observed data is reproduced best with a net inflow, i.e. with more gene gain than loss. Moreover, we show that prokaryotes have much higher rates of gene acquisition than eukaryotes, probably reflecting lateral transfer. A further natural outcome from our model is an estimation of the fold composition of the initial genome, which potentially relates to the common ancestor for modern organisms. Supplementary material pertaining to this work

  3. Influence of acoustic loading on an effective single mass model of the vocal folds.

    PubMed

    Zañartu, Matías; Mongeau, Luc; Wodicka, George R

    2007-02-01

    Three-way interactions between sound waves in the subglottal and supraglottal tracts, the vibrations of the vocal folds, and laryngeal flow were investigated. Sound wave propagation was modeled using a wave reflection analog method. An effective single-degree-of-freedom model was designed to model vocal-fold vibrations. The effects of orifice geometry changes on the flow were considered by enforcing a time-varying discharge coefficient within a Bernoulli flow model. The resulting single-degree-of-freedom model allowed for energy transfer from flow to structural vibrations, an essential feature usually incorporated through the use of higher order models. The relative importance of acoustic loading and the time-varying flow resistance for fluid-structure energy transfer was established for various configurations. The results showed that acoustic loading contributed more significantly to the net energy transfer than the time-varying flow resistance, especially for less inertive supraglottal loads. The contribution of supraglottal loading was found to be more significant than that of subglottal loading. Subglottal loading was found to reduce the net energy transfer to the vocal-fold oscillation during phonation, balancing the effects of the supraglottal load. PMID:17348533

  4. Viroporins, Examples of the Two-Stage Membrane Protein Folding Model.

    PubMed

    Martinez-Gil, Luis; Mingarro, Ismael

    2015-07-01

    Viroporins are small, α-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way to bury their hydrophobic regions into the lipid bilayer. Once within the membrane, the hydrophobic helices of viroporins interact with each other to form higher ordered structures required to correctly perform their porating activities. This two-step process resembles the two-stage model proposed for membrane protein folding by Engelman and Poppot. In this review we use the membrane protein folding model as a leading thread to analyze the mechanism and forces behind the membrane insertion and folding of viroporins. We start by describing the transmembrane segment architecture of viroporins, including the number and sequence characteristics of their membrane-spanning domains. Next, we connect the differences found among viroporin families to their viral genome organization, and finalize focusing on the pathways used by viroporins in their way to the membrane and on the transmembrane helix-helix interactions required to achieve proper folding and assembly. PMID:26131957

  5. Viroporins, Examples of the Two-Stage Membrane Protein Folding Model

    PubMed Central

    Martinez-Gil, Luis; Mingarro, Ismael

    2015-01-01

    Viroporins are small, α-helical, hydrophobic virus encoded proteins, engineered to form homo-oligomeric hydrophilic pores in the host membrane. Viroporins participate in multiple steps of the viral life cycle, from entry to budding. As any other membrane protein, viroporins have to find the way to bury their hydrophobic regions into the lipid bilayer. Once within the membrane, the hydrophobic helices of viroporins interact with each other to form higher ordered structures required to correctly perform their porating activities. This two-step process resembles the two-stage model proposed for membrane protein folding by Engelman and Poppot. In this review we use the membrane protein folding model as a leading thread to analyze the mechanism and forces behind the membrane insertion and folding of viroporins. We start by describing the transmembrane segment architecture of viroporins, including the number and sequence characteristics of their membrane-spanning domains. Next, we connect the differences found among viroporin families to their viral genome organization, and finalize focusing on the pathways used by viroporins in their way to the membrane and on the transmembrane helix-helix interactions required to achieve proper folding and assembly. PMID:26131957

  6. TOPICAL REVIEW: Simple models of protein folding and of non-conventional drug design

    NASA Astrophysics Data System (ADS)

    Broglia, R. A.; Tiana, G.; Provasi, D.

    2004-02-01

    While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information in order to predict the three-dimensional, biologically active, native conformation of a protein whose sequence is known. Using insights obtained from simple model simulations of the folding of proteins, in particular the fact that this phenomenon is essentially controlled by conserved (native) contacts among (few) strongly interacting ('hot'), as a rule hydrophobic, amino acids, which also stabilize local elementary structures (LES, hidden, incipient secondary structures such as agr-helices and bgr-sheets) formed early in the folding process and leading to the postcritical folding nucleus (i.e. the minimum set of native contacts which brings the system beyond the highest free-energy barrier found in the whole folding process) it is possible to work out a successful strategy for reading the native structure of designed proteins from a knowledge of only their amino acid sequence and of the contact energies among the amino acids. Because LES have undergone millions of years of evolution to selectively dock to their complementary structures, small peptides made out of the same amino acids as the LES are expected to selectively attach to the newly expressed (unfolded) protein and inhibit its folding, or to the native (fluctuating) native conformation and denature it. These peptides, or their mimetic molecules, can thus be used as effective non-conventional drugs to those already existing (and directed at neutralizing the active site of enzymes), displaying the advantage of not suffering from the increase in resistance.

  7. The earliest events in protein folding: Helix dynamics in proteins and model peptides

    SciTech Connect

    Dyer, R.B.; Williams, S.; Woodruff, W.H.

    1996-12-31

    The earliest events in protein folding are critically important in determining the folding pathway, but have proved difficult to study by conventional approaches. We have developed new rapid initiation methods and structure-specific probes to interrogate the earliest events of protein folding. Our focus is the pathways. Folding or unfolding reactions are initiated on a fast timescale (10 ns) using a laser induced temperature jump (15 C) and probed with time-resolved infrared spectroscopy. We obtained the kinetics of the helix-coil transition for a model 21-residue peptide. The observed rate constant k{sub obs} = k{sub f} + k{sub u} for reversible kinetics; from the observed rate (6 x 10{sup 6} s{sup -1}) and the equilibrium constant favoring folding of 7.5 at 27 C, we calculate a folding lifetime of 180 ns and an unfolding lifetime of 1.4 {mu}s. The {open_quotes}molten globule{close_quotes} form of apomyoglobin (horse, pH*3, 0.15M NaCl) shows similar kinetics for helix that is unconstrained by tertiary structure (helix with an unusually low Amide I frequency, near 1633 cm{sup -1}). In {open_quotes}native{close_quotes} apomyoglobin (horse, pH*5.3, 10 mM NaCl) two very different rates (45 ns and 70 {mu}s) are observed and we infer that a third occurs on a timescales inaccessible to our experiment (> 1 ms). We suggest that the slower processes are due to helix formation that is rate-limited by the formation of tertiary structure.

  8. 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.

  9. 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.

  10. Superimposed folding and thrusting by two phases of mutually orthogonal or oblique shortening in analogue models

    NASA Astrophysics Data System (ADS)

    Deng, Hongling; Koyi, Hemin A.; Nilfouroushan, Faramarz

    2016-02-01

    Orogens may suffer more than one phase shortening resulting in superposition of structures of different generations. Superimposition of orthogonal or oblique shortening is studied using sandbox and centrifuge modelling. Results of sand models show that in orthogonal superimposition, the two resulting structural trends are approximately orthogonal to each other. In oblique superimposition, structures trend obliquely to each other in the relatively thin areas of the model (foreland), and mutually orthogonal in areas where the model is thickened during the first phase of shortening (i.e. the hinterland). Thrusts formed during the first shortening phase may be reactivated during the later shortening phase. Spacing of the later phase structures is not as wide as expected, considering they across the pre-existing thickened wedge. Superposition of structures results in formation of type 1 fold interference pattern. Bedding is curved outwards both in the dome and basin structures. Folded layers are dipping and plunging outwards in a dome, while they are dipping and plunging inwards in a basin. In the areas between two adjacent domes or basins (i.e. where an anticline is superimposed by a syncline or a syncline is superimposed by an anticline), bedding is curved inwards, and the anticlines plunge inwards and the synclines outwards. The latter feature could be helpful to determine the age relationship for type 2 fold interference pattern. In tectonic regions where multiple phases of shortening have occurred, the orogenic-scale dome-and-basin and arrowhead-shaped interference patterns are commonly formed, as in the models. However, in some areas, the fold interference pattern might be modified by a later phase of thrusting. Similar to models results, superimposition of two and/or even more deformation phases may not be recorded by structures all over the tectonic area.

  11. Quantifying spatiotemporal properties of vocal fold dynamics based on a multiscale analysis of phonovibrograms.

    PubMed

    Unger, Jakob; Hecker, Dietmar J; Kunduk, Melda; Schuster, Maria; Schick, Bernhard; Lohscheller, Joerg

    2014-09-01

    In order to objectively assess the laryngeal vibratory behavior, endoscopic high-speed cameras capture several thousand frames per second of the vocal folds during phonation. However, judging all inherent clinically relevant features is a challenging task and requires well-founded expert knowledge. In this study, an automated wavelet-based analysis of laryngeal high-speed videos based on phonovibrograms is presented. The phonovibrogram is an image representation of the spatiotemporal pattern of vocal fold vibration and constitutes the basis for a computer-based analysis of laryngeal dynamics. The features extracted from the wavelet transform are shown to be closely related to a basic set of video-based measurements categorized by the European Laryngological Society for a subjective assessment of pathologic voices. The wavelet-based analysis further offers information about irregularity and lateral asymmetry and asynchrony. It is demonstrated in healthy and pathologic subjects as well as for a surgical group that was examined before and after the removal of a vocal fold polyp. The features were found to not only classify glottal closure characteristics but also quantify the impact of pathologies on the vibratory behavior. The interpretability and the discriminative power of the proposed feature set show promising relevance for a computer-assisted diagnosis and classification of voice disorders. PMID:24771562

  12. 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.

  13. 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

  14. Study of extracellular matrix in vocal fold biomechanics using a two-phase model

    PubMed Central

    Li, Nicole Y. K.; Avazmohammadi, Reza; Thibeault, Susan L.; Mongrain, Rosaire; Mongeau, Luc

    2014-01-01

    The extracellular matrix (ECM) of the vocal fold tissue consists primarily of fibrous and interstitial proteins. The purpose of this study was to investigate the effects of selective enzymatic digestion of two ECM proteins, namely elastin and versican, on the elasticity of rabbit vocal fold tissue. Quasi-static, sinusoidal, uniaxial tensile tests were performed. The data were analyzed within the framework of a model of the ECM as a two-phase composite material consisting of collagen fibrils as the reinforcing fibers and noncollagenous ECM proteins as the matrix. To validate the two-phase model, the regression parameters for the fibers’ volume fraction and shear modulus in a different animal model were compared with corresponding published data. The proposed model was then used to analyze rabbit vocal fold tissues. The mean value and the standard deviation of the fiber volume fraction were found to be 8.49 ±3.75% for the control samples (n =4), 0.59 ±1.13 % after elastin removal (n =4), and 8.22 ±1.06% after versican removal (n =4). The results suggest that elastin removal may lead to a reduction in tissue stiffness, through counteracting the reinforcement of collagen fibrils. PMID:24792897

  15. Study of extracellular matrix in vocal fold biomechanics using a two-phase model.

    PubMed

    Miri, Amir K; Li, Nicole Y K; Avazmohammadi, Reza; Thibeault, Susan L; Mongrain, Rosaire; Mongeau, Luc

    2015-01-01

    The extracellular matrix (ECM) of the vocal fold tissue consists primarily of fibrous and interstitial proteins. The purpose of this study was to investigate the effects of selective enzymatic digestion of two ECM proteins, namely elastin and versican, on the elasticity of rabbit vocal fold tissue. Quasi-static, sinusoidal, uniaxial tensile tests were performed. The data were analyzed within the framework of a model of the ECM as a two-phase composite material consisting of collagen fibrils as the reinforcing fibers and noncollagenous ECM proteins as the matrix. To validate the two-phase model, the regression parameters for the fibers' volume fraction and shear modulus in a different animal model were compared with corresponding published data. The proposed model was then used to analyze rabbit vocal fold tissues. The mean value and the standard deviation of the fiber volume fraction were found to be 8.49 ± 3.75 % for the control samples (n = 4), 0.59 ± 1.13 % after elastin removal (n = 4), and 8.22 ± 1.06 % after versican removal (n = 4). The results suggest that elastin removal may lead to a reduction in tissue stiffness, through counteracting the reinforcement of collagen fibrils. PMID:24792897

  16. Prediction of RNA Pseudoknots Using Heuristic Modeling with Mapping and Sequential Folding

    PubMed Central

    Dawson, Wayne K.; Fujiwara, Kazuya; Kawai, Gota

    2007-01-01

    Predicting RNA secondary structure is often the first step to determining the structure of RNA. Prediction approaches have historically avoided searching for pseudoknots because of the extreme combinatorial and time complexity of the problem. Yet neglecting pseudoknots limits the utility of such approaches. Here, an algorithm utilizing structure mapping and thermodynamics is introduced for RNA pseudoknot prediction that finds the minimum free energy and identifies information about the flexibility of the RNA. The heuristic approach takes advantage of the 5′ to 3′ folding direction of many biological RNA molecules and is consistent with the hierarchical folding hypothesis and the contact order model. Mapping methods are used to build and analyze the folded structure for pseudoknots and to add important 3D structural considerations. The program can predict some well known pseudoknot structures correctly. The results of this study suggest that many functional RNA sequences are optimized for proper folding. They also suggest directions we can proceed in the future to achieve even better results. PMID:17878940

  17. Characterizing liquid redistribution in a biphasic vibrating vocal fold using finite element analysis

    PubMed Central

    Kvit, Anton A.; Devine, Erin E.; Vamos, Andrew C.; Tao, Chao; Jiang, Jack J.

    2015-01-01

    OBJECTIVE Vocal fold tissue is biphasic and consists of a solid extracellular matric skeleton swelled with interstitial fluid. Interactions between the liquid and solid impact the material properties and stress response of the tissue. The objective of this study was to model the movement of liquid during vocal fold vibration and estimate the volume of liquid accumulation and stress experienced by the tissue near the anterior-posterior midline, where benign lesions are observed to form. METHODS A three-dimensional biphasic finite element model of a single vocal fold was built to solve for the liquid velocity, pore pressure, and von Mises stress during and just after vibration using the commercial finite element software COMSOL Multiphysics (Version 4.3a, 2013, Structural Mechanics and Subsurface Flow Modules). Vibration was induced by applying direct-load pressures to the subglottal and intraglottal surfaces. Pressure ranges, frequency and material parameters were chosen based on those reported in the literature. Post-processing included liquid velocity, pore pressure and von Mises stress calculations, as well as the frequency-stress and amplitude-stress relationships. RESULTS Resulting time-averaged velocity vectors during vibration indicated liquid movement towards the midline of the fold, as upwards movement in the inferior-superior direction. Pore pressure and von Misses stresses were higher in this region just following vibration. A linear relationship was found between the amplitude and pore pressure, while a nonlinear relationship was found between the frequency and pore pressure. CONCLUSIONS While this study had certain computational simplifications, it is the first biphasic finite element model to employ a realistic geometry and demonstrated the ability to characterize liquid movement due to vibration. Results indicate that there is a significant amount of liquid that accumulates at the midline, however the role of this accumulation still requires

  18. Protein folding simulations of the hydrophobic-hydrophilic model by combining tabu search with genetic algorithms

    NASA Astrophysics Data System (ADS)

    Jiang, Tianzi; Cui, Qinghua; Shi, Guihua; Ma, Songde

    2003-08-01

    In this paper, a novel hybrid algorithm combining genetic algorithms and tabu search is presented. In the proposed hybrid algorithm, the idea of tabu search is applied to the crossover operator. We demonstrate that the hybrid algorithm can be applied successfully to the protein folding problem based on a hydrophobic-hydrophilic lattice model. The results show that in all cases the hybrid algorithm works better than a genetic algorithm alone. A comparison with other methods is also made.

  19. 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.

  20. 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. PMID:26831041

  1. 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

  2. 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

  3. 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. PMID:15134461

  4. Towards 4D modeling of transpressional fold-and-thrust belts

    NASA Astrophysics Data System (ADS)

    Ruh, J. B.; Gerya, T.; Burg, J.

    2012-12-01

    Latest developments in computer power and computational solutions open new ways to envision complex natural systems. Advances in high-resolution 3D geodynamic modeling, in particular, allow investigating complex tectonic processes like the evolution of non-cylindrical fold-and-thrust belts. We demonstrate that implementing the 4 dimensions (space and time) provides and constrains new answers to long lasting discussions. Numerically simulating fold-and-thrust belts needs accurate treatment of brittle/plastic rheology with high resolution to produce spontaneously localizing narrow high strain rate shear bands. Thrusts and flats occur where stresses overcome the material yield stress. Therefore, a numerical approach must allow very high strain rates within the décollement and the "thrusts" while respecting the rigidity of the modelled wedge sediments. Effective viscosity variations across narrow shear bands often range six orders of magnitude. This poses a strong challenge for numerically solving the Stokes and continuity equations. For this purpose, we developed a three-dimensional, high-resolution, fully staggered grid, finite difference, marker in cell model with a visco-brittle/plastic rheology and an efficient OpenMP-parallelized multigrid solver. As a case study, we chose the Zagros Simply Folded Belt in Iran. There, the recent shortening direction is oblique to the Main Zagros Thrust, which represents the suture between the Arabian and Central Iranian continental plates. This obliquity impels lateral backstop variations that can only be introduced in a three dimensional setup. Furthermore, along-strike structural variations are observed between the the Fars domain, in the SE, towards the Izeh domain, in the NW. Results shows how a low-viscosity décollement becoming frictional towards the Dezful embayment influences the exposed fold patterns (Figure 1). They also emphasize the importance of an oblique backstop geometry to produce en-échelon arranged folds

  5. 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

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

    PubMed

    Pickup, Brian A; Thomson, Scott L

    2010-09-01

    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

  7. 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.

  8. A three-dimensional model of vocal fold abductionÕadduction

    PubMed Central

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

    2006-01-01

    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. PMID:15101653

  9. 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

  10. Thermodynamic linkage analysis of pH-induced folding and unfolding transitions of i-motifs.

    PubMed

    Kim, Byul G; Chalikian, Tigran V

    2016-09-01

    We describe the pH-induced folding/unfolding transitions of i-motifs by a linkage thermodynamics-based formalism in terms of three pKa's of cytosines, namely, an apparent pKa in the unfolded conformation, pKau, and two apparent pKa's in the folded state, pKaf1 and pKaf2. For the 5'-TTACCCACCCTACCCACCCTCA-3' sequence from the human c-MYC oncogene promoter region, the values of pKau, pKaf1, and pKaf2 are 4.8, 6.0, and 3.6, respectively. With these pKa's, we calculate the differential number of protons bound to the folded and unfolded states as a function of pH. Analysis along these lines offers an alternative interpretation to the experimentally observed shift in the pH-induced unfolded-to-i-motif transitions to neutral pH in the presence of cosolvents and crowders. PMID:27322499

  11. 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.

  12. 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.

  13. 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.

  14. Brane brick models, toric Calabi-Yau 4-folds and 2d (0,2) quivers

    NASA Astrophysics Data System (ADS)

    Franco, Sebastián; Lee, Sangmin; Seong, Rak-Kyeong

    2016-02-01

    We introduce brane brick models, a novel type of Type IIA brane configurations consisting of D4-branes ending on an NS5-brane. Brane brick models are T-dual to D1-branes over singular toric Calabi-Yau 4-folds. They fully encode the infinite class of 2 d (generically) {N}=(0,2) gauge theories on the worldvolume of the D1-branes and streamline their connection to the probed geometries. For this purpose, we also introduce new combinatorial procedures for deriving the Calabi-Yau associated to a given gauge theory and vice versa.

  15. Slow histidine H/D exchange protocol for thermodynamic analysis of protein folding and stability using mass spectrometry.

    PubMed

    Tran, Duc T; Banerjee, Sambuddha; Alayash, Abdu I; Crumbliss, Alvin L; Fitzgerald, Michael C

    2012-02-01

    Described here is a mass spectrometry-based protocol to study the thermodynamic stability of proteins and protein-ligand complexes using the chemical denaturant dependence of the slow H/D exchange reaction of the imidazole C(2) proton in histidine side chains. The protocol is developed using several model protein systems including: ribonuclease (Rnase) A, myoglobin, bovine carbonic anhydrase (BCA) II, hemoglobin (Hb), and the hemoglobin-haptoglobin (Hb-Hp) protein complex. Folding free energies consistent with those previously determined by other more conventional techniques were obtained for the two-state folding proteins, Rnase A and myoglobin. The protocol successfully detected a previously observed partially unfolded intermediate stabilized in the BCA II folding/unfolding reaction, and it could be used to generate a K(d) value of 0.24 nM for the Hb-Hp complex. The compatibility of the protocol with conventional mass spectrometry-based proteomic sample preparation and analysis methods was also demonstrated in an experiment in which the protocol was used to detect the binding of zinc to superoxide dismutase in the yeast cell lysate sample. The yeast cell sample analyses also helped define the scope of the technique, which requires the presence of globally protected histidine residues in a protein's three-dimensional structure for successful application. PMID:22185579

  16. 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.

  17. Fold and fabric relationships in temporally and spatially evolving slump systems: A multi-cell flow model

    NASA Astrophysics Data System (ADS)

    Alsop, G. Ian; Marco, Shmuel

    2014-06-01

    Folds generated in ductile metamorphic terranes and within unlithified sediments affected by slumping are geometrically identical to one another, and distinguishing the origin of such folds in ancient lithified rocks is therefore challenging. Foliation is observed to lie broadly parallel to the axial planes of tectonic folds, whilst it is frequently regarded as absent in slump folds. The presence of foliation is therefore often considered as a reliable criterion for distinguishing tectonic folds from those created during slumping. To test this assertion, we have examined a series of well exposed slump folds within the late Pleistocene Lisan Formation of the Dead Sea Basin. These slumps contain a number of different foliation types, including an axial-planar grain-shape fabric and a crenulation cleavage formed via microfolding of bedding laminae. Folds also contain a spaced disjunctive foliation characterised by extensional displacements across shear fractures. This spaced foliation fans around recumbent fold hinges, with kinematics reversing across the axial plane indicating a flexural shear fold mechanism. Overall, the spaced foliation is penecontemporaneous with each individual slump where it occurs, although in detail it is pre, syn or post the local folds. The identification of foliations within undoubted slump folds indicates that the presence or absence of foliation is not in itself a robust criterion to distinguish tectonic from soft-sediment folds. Extensional shear fractures displaying a range of temporal relationships with slump folds suggests that traditional single-cell flow models, where extension is focussed at the head and contraction in the lower toe of the slump, are a gross simplification. We therefore propose a new multi-cell flow model involving coeval second-order flow cells that interact with neighbouring cells during translation of the slump.

  18. High fold computer disk storage DATABASE for fast extended analysis of γ-rays events

    NASA Astrophysics Data System (ADS)

    Stézowski, O.; Finck, Ch.; Prévost, D.

    1999-03-01

    Recently spectacular technical developments have been achieved to increase the resolving power of large γ-ray spectrometers. With these new eyes, physicists are able to study the intricate nature of atomic nuclei. Concurrently more and more complex multidimensional analyses are needed to investigate very weak phenomena. In this article, we first present a software (DATABASE) allowing high fold coincidences γ-rays events to be stored on hard disk. Then, a non-conventional method of analysis, anti-gating procedure, is described. Two physical examples are given to explain how it can be used and Monte Carlo simulations have been performed to test the validity of this method.

  19. Protein Folding Simulation of Mutant Go Models of the Wild-Type Trp-cage Protein

    NASA Astrophysics Data System (ADS)

    Linhananta, Apichart; Liu, Junmin

    2008-03-01

    For the past three decades, Go models of protein folding have played important roles in the understanding of how proteins fold from random conformations to their unique native structures. Unfortunately Go models reliance on known NMR or x-ray structures to construct Go interaction potentials severely limit their predictive powers. In this work, we introduce a novel method for constructing Go interaction potentials of mutant proteins based on Go interaction potentials of wild type proteins. As a template we employ the all-atom Go model of the 20-residue Trp-cage protein (A. Linhananta, J. Boer and I. MacKay, J. Chem. Phys., 2005, 122, 114901) as the wild type Go model. Trp-cage mutants are constructed by replacing a Trp-cage residue with a different residue. In particular the Pro-12 residue of the Trp-cage is substituted by Trp-12 to produce the Trp2-cage mutant, whose native structure is not yet known. Monte Carlo simulations, using CHARMM force fields, are performed to determine the ground-state structure mutant. The resulting mutant structures are used to construct the Go interaction potential of the Trp2-cage mutant Go model.

  20. 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. PMID:12784210

  1. 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

  2. Simulation based estimation of dynamic mechanical properties for viscoelastic materials used for vocal fold models

    NASA Astrophysics Data System (ADS)

    Rupitsch, Stefan J.; Ilg, Jürgen; Sutor, Alexander; Lerch, Reinhard; Döllinger, Michael

    2011-08-01

    In order to obtain a deeper understanding of the human phonation process and the mechanisms generating sound, realistic setups are built up containing artificial vocal folds. Usually, these vocal folds consist of viscoelastic materials (e.g., polyurethane mixtures). Reliable simulation based studies on the setups require the mechanical properties of the utilized viscoelastic materials. The aim of this work is the identification of mechanical material parameters (Young's modulus, Poisson's ratio, and loss factor) for those materials. Therefore, we suggest a low-cost measurement setup, the so-called vibration transmission analyzer (VTA) enabling to analyze the transfer behavior of viscoelastic materials for propagating mechanical waves. With the aid of a mathematical Inverse Method, the material parameters are adjusted in a convenient way so that the simulation results coincide with the measurement results for the transfer behavior. Contrary to other works, we determine frequency dependent functions for the mechanical properties characterizing the viscoelastic material in the frequency range of human speech (100-250 Hz). The results for three different materials clearly show that the Poisson's ratio is close to 0.5 and that the Young's modulus increases with higher frequencies. For a frequency of 400 Hz, the Young's modulus of the investigated viscoelastic materials is approximately 80% higher than for the static case (0 Hz). We verify the identified mechanical properties with experiments on fabricated vocal fold models. Thereby, only small deviations between measurements and simulations occur.

  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. Biochemical Basis of Vocal Fold Mobilization After Microflap Surgery in a Rabbit Model

    PubMed Central

    Mitchell, Joshua R.; Kojima, Tsuyoshi; Wu, Hongmei; Garrett, C. Gaelyn; Rousseau, Bernard

    2015-01-01

    Objectives/Hypothesis To investigate phonation-related extracellular matrix (ECM) changes in the vocal fold lamina propria after microflap surgery using an in vivo rabbit phonation model. Study Design Prospective animal study. Methods Twenty-four New Zealand White rabbits were used in this study. Quantitative polymerase chain reaction and immunohistochemistry were used to investigate alterations in vocal fold ECM proinflammatory and profibrotic gene, and protein expression from a control group of animals receiving a microflap without phonation and a separate group of animals receiving experimentally induced phonation on postmicroflap days 0, 3, and 7. Results IHC demonstrated the highest concentration of CD45 in vocal folds on postoperative day 0. Staining for CD45 was absent by postoperative day 7, with no differences in CD45 staining between groups. Fibronectin gene expression increased significantly on postoperative day 3 in the control and experimentally induced phonation groups, with maximal staining of fibronectin around the microflap incision on postoperative day 7. No alterations in cyclooxygenase-2, interleukin-1β, and transforming growth factor-β1 gene expression were observed between groups. Conclusions Results of the present study revealed an acute inflammatory response in the vocal fold at the time of microflap (day 0) and up to 3 days post-microflap. By post-operative day 3, staining of CD45 positive cells decreased, with essentially no evidence of inflammation by post-operative day 7. With the end of the acute inflammatory response occurring around day 3, these data may provide support for mobilizing tissue after inflammation has subsided and the process of active tissue remodeling has ensued (days 3–7). PMID:23775575

  5. Thermodynamic analysis of protein folding and stability using a tryptophan modification protocol.

    PubMed

    Xu, Yingrong; Strickland, Erin C; Fitzgerald, Michael C

    2014-07-15

    Described here is the development of a mass spectrometry-based covalent labeling protocol that utilizes the reaction of dimethyl(2-hydroxy-5-nitrobenzyl)sulfonium bromide (HNSB) with tryptophan (Trp) residues to measure protein folding free energies (ΔG(f) values). In the protocol, the chemical denaturant dependence of the rate at which globally protected Trp residues in a protein react with HNSB is evaluated using either a matrix assisted laser desorption ionization time-of-flight analysis of the intact protein or a quantitative, bottom-up proteomics analysis using isobaric mass tags. In the proof-of-principle studies performed here, the protocol yielded accurate ΔG(f) values for the two-state folding proteins, lysozyme and cytochrome c. The protocol also yielded an accurate measure of the dissociation constant (K(d) value) for the binding of N,N',N″-triacetylchitotriose to lysozyme, and it successfully detected the binding of brinzolamide to BCA II, a non-two-state folding protein. The HNSB protocol can be used in combination with SPROX (stability of proteins from rates of oxidation), a previously reported technique that exploits the hydrogen peroxide oxidation of methionine (Met) residues in proteins to make ΔG(f) value measurements. Incorporating the HNSB protocol into SPROX increased the peptide and protein coverage in proteome-wide SPROX experiments by 50% and 25%, respectively. As part of this work, the precision of proteome-wide ΔG(f) value measurements using the combined HNSB and SPROX protocol is also evaluated. PMID:24896224

  6. A cortical folding model incorporating stress-dependent growth explains gyral wavelengths and stress patterns in the developing brain

    PubMed Central

    Bayly, PV; Okamoto, RJ; Xu, G.; Shi, Y; Taber, LA

    2013-01-01

    In humans and many other mammals, the cortex (the outer layer of the brain) folds during development. The mechanics of folding are not well understood; leading explanations are either incomplete or at odds with physical measurements. We propose a mathematical model in which (i) folding is driven by tangential expansion of the cortex and (ii) deeper layers grow in response to the resulting stress. In this model the wavelength of cortical folds depends predictably on the rate of cortical growth relative to the rate of stress-induced growth. We show analytically and in simulations that faster cortical expansion leads to shorter gyral wavelengths; slower cortical expansion leads to long wavelengths or even smooth (lissencephalic) surfaces. No inner or outer (skull) constraint is needed to produce folding, but initial shape and mechanical heterogeneity influence the final shape. The proposed model predicts patterns of stress in the tissue that are consistent with experimental observations. PMID:23357794

  7. Quantifying the similarities within fold space.

    PubMed

    Harrison, Andrew; Pearl, Frances; Mott, Richard; Thornton, Janet; Orengo, Christine

    2002-11-01

    We have used GRATH, a graph-based structure comparison algorithm, to map the similarities between the different folds observed in the CATH domain structure database. Statistical analysis of the distributions of the fold similarities has allowed us to assess the significance for any similarity. Therefore we have examined whether it is best to represent folds as discrete entities or whether, in fact, a more accurate model would be a continuum wherein folds overlap via common motifs. To do this we have introduced a new statistical measure of fold similarity, termed gregariousness. For a particular fold, gregariousness measures how many other folds have a significant structural overlap with that fold, typically comprising 40% or more of the larger structure. Gregarious folds often contain commonly occurring super-secondary structural motifs, such as beta-meanders, greek keys, alpha-beta plait motifs or alpha-hairpins, which are matching similar motifs in other folds. Apart from one example, all the most gregarious folds matching 20% or more of the other folds in the database, are alpha-beta proteins. They also occur in highly populated architectural regions of fold space, adopting sandwich-like arrangements containing two or more layers of alpha-helices and beta-strands.Domains that exhibit a low gregariousness, are those that have very distinctive folds, with few common motifs or motifs that are packed in unusual arrangements. Most of the superhelices exhibit low gregariousness despite containing some commonly occurring super-secondary structural motifs. In these folds, these common motifs are combined in an unusual way and represent a small proportion of the fold (<10%). Our results suggest that fold space may be considered as continuous for some architectural arrangements (e.g. alpha-beta sandwiches), in that super-secondary motifs can be used to link neighbouring fold groups. However, in other regions of fold space much more discrete topologies are observed with

  8. Nanopore analysis of the effect of metal ions on the folding of peptides and proteins.

    PubMed

    Lee, Jeremy S

    2014-03-01

    In this minireview, the nanopore analysis of peptides and proteins in the presence of divalent metal ions will be surveyed. In all cases the binding of the metal ions causes the peptide or protein to adopt a more compact conformation which can no longer enter the α-hemolysin pore. In the absence of Zn(II) the 30-amino acid Zn-finger peptide can readily translocate the pore; but upon addition of Zn(II) the peptide folds and only bumping events are observed. Similarly, the octapeptide repeat from the N-terminus of the prion protein binds Cu(II), which prevents it from translocating. The full-length prion protein also undergoes conformational changes upon binding Cu(II), which results in an increase in the proportion of bumping events. Myelin basic protein of 170 residues is intrinsically disordered and, perhaps surprisingly, for a basic protein of this size, can translocate against the electric field based on the observation that the event time increases with increasing voltage. It, too, folds into a more compact conformation upon binding Cu(II) and Zn(II), which prevents translocation. Finally even proteins such as maltose binding protein which does not contain a formal binding site for metal ions undergoes conformational changes in the presence of the metal chelator, EDTA. Thus, contamination of proteins with trace metal ions should be considered when studying proteins and peptides by nanopore analysis. PMID:24370255

  9. 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. PMID:17902863

  10. Simple Continuous and Discrete Models for Simulating Replica Exchange Simulations of Protein Folding

    PubMed Central

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

    2010-01-01

    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 timescale of conformational rearrangements within free energy basins. PMID:18251533

  11. Cluster folding model for /sup 12/C(/sup 6/Li,/sup 6/Li) scattering at 156 Mev

    SciTech Connect

    Majka, Z.; Gils, H.J.; Rebel, H.

    1982-06-01

    A double-folding cluster model generated from d-..cap alpha.. and ..cap alpha..-..cap alpha.. interactions and internal cluster wave functions of the projectile and the target nuclei is proposed to describe the differential cross sections for /sup 6/Li elastic scattering from /sup 12/C at 156 MeV. Results of these calculations are compared with standard double-folding models and the phenomenological optical model predictions.

  12. 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.

  13. 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

  14. Core-Shell Model of Folding-Unfolding Transitions (UFT) in Proteins

    NASA Astrophysics Data System (ADS)

    Aroutiounian, Svetlana

    2008-03-01

    There are ˜10^N conformations for a protein of length N to sort out randomly in search of lowest free energy state. Can protein folding be simple and fast? Core-shell model introduces principles, proposes mechanisms and scores residues of fast, reversible UFT in protein. According to it, during UFT the realm of intra-residual interactions leads the residue motion. The scaffold of hydrophilic residues forms external shell of unstructured, tube-like protein in unfolded state, just as the hydrophobic residues form internal scaffold -- core, of the protein in folded state. As UFT proceeds, residue slides into lowest-score position permitted by its structure. Model accounts for experimentally observed features of UFT. It is based on three principles: 1) During UFT protein is virtual - its features or structure are inferred only statistically and with limited precision; 2) Mechanism of UFT memory is not longitudinal, but transverse; 3) Native design overrides specific features of residues - the alphabet of amino acids assumes an intrinsic score-function. Per-residue mechanism of UFT is proposed and score-function is described. Difference graphs of transitional score-function and average genome-wide abundance index show that our score-function is the order parameter of UFT in protein and by virtue of being it, reveals transitional key residues. It echoes the multiple-tier and funnel concepts of FEL perspective. Monte Carlo simulations of UFT in myoglobin illustrate the idea.

  15. 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.

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

    PubMed

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

    2010-11-01

    The decarboxylation of phenolic acids, including ferulic and p-coumaric acids, to their corresponding vinyl derivatives is of importance in the flavouring 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 β-barrel structure and two α-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 β-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. PMID:21045284

  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. 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.

  19. 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. PMID:26526675

  20. 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. PMID:23304406

  1. Cooperativity, Local-Nonlocal Coupling, and Nonnative Interactions: Principles of Protein Folding from Coarse-Grained Models

    NASA Astrophysics Data System (ADS)

    Chan, Hue Sun; Zhang, Zhuqing; Wallin, Stefan; Liu, Zhirong

    2011-05-01

    Coarse-grained, self-contained polymer models are powerful tools in the study of protein folding. They are also essential to assess predictions from less rigorous theoretical approaches that lack an explicit-chain representation. Here we review advances in coarse-grained modeling of cooperative protein folding, noting in particular that the Levinthal paradox was raised in response to the experimental discovery of two-state-like folding in the late 1960s, rather than to the problem of conformational search per se. Comparisons between theory and experiment indicate a prominent role of desolvation barriers in cooperative folding, which likely emerges generally from a coupling between local conformational preferences and nonlocal packing interactions. Many of these principles have been elucidated by native-centric models, wherein nonnative interactions may be treated perturbatively. We discuss these developments as well as recent applications of coarse-grained chain modeling to knotted proteins and to intrinsically disordered proteins.

  2. Cooperativity, local-nonlocal coupling, and nonnative interactions: principles of protein folding from coarse-grained models.

    PubMed

    Chan, Hue Sun; Zhang, Zhuqing; Wallin, Stefan; Liu, Zhirong

    2011-01-01

    Coarse-grained, self-contained polymer models are powerful tools in the study of protein folding. They are also essential to assess predictions from less rigorous theoretical approaches that lack an explicit-chain representation. Here we review advances in coarse-grained modeling of cooperative protein folding, noting in particular that the Levinthal paradox was raised in response to the experimental discovery of two-state-like folding in the late 1960s, rather than to the problem of conformational search per se. Comparisons between theory and experiment indicate a prominent role of desolvation barriers in cooperative folding, which likely emerges generally from a coupling between local conformational preferences and nonlocal packing interactions. Many of these principles have been elucidated by native-centric models, wherein nonnative interactions may be treated perturbatively. We discuss these developments as well as recent applications of coarse-grained chain modeling to knotted proteins and to intrinsically disordered proteins. PMID:21453060

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

    NASA Astrophysics Data System (ADS)

    Osipov, V. Al.

    2016-05-01

    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.

  4. 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.

  5. Protein folds and protein folding

    PubMed Central

    Schaeffer, R. Dustin; Daggett, Valerie

    2011-01-01

    The classification of protein folds is necessarily based on the structural elements that distinguish domains. Classification of protein domains consists of two problems: the partition of structures into domains and the classification of domains into sets of similar structures (or folds). Although similar topologies may arise by convergent evolution, the similarity of their respective folding pathways is unknown. The discovery and the characterization of the majority of protein folds will be followed by a similar enumeration of available protein folding pathways. Consequently, understanding the intricacies of structural domains is necessary to understanding their collective folding pathways. We review the current state of the art in the field of protein domain classification and discuss methods for the systematic and comprehensive study of protein folding across protein fold space via atomistic molecular dynamics simulation. Finally, we discuss our large-scale Dynameomics project, which includes simulations of representatives of all autonomous protein folds. PMID:21051320

  6. Nonlinear vocal fold dynamics resulting from asymmetric fluid loading on a two-mass model of speech

    NASA Astrophysics Data System (ADS)

    Erath, Byron D.; Zañartu, Matías; Peterson, Sean D.; Plesniak, Michael W.

    2011-09-01

    Nonlinear vocal fold dynamics arising from asymmetric flow formations within the glottis are investigated using a two-mass model of speech with asymmetric vocal fold tensioning, representative of unilateral vocal fold paralysis. A refined theoretical boundary-layer flow solver is implemented to compute the intraglottal pressures, providing a more realistic description of the flow than the standard one-dimensional, inviscid Bernoulli flow solution. Vocal fold dynamics are investigated for subglottal pressures of 0.6 < ps < 1.5 kPa and tension asymmetries of 0.5 < Q < 0.8. As tension asymmetries become pronounced the asymmetric flow incites nonlinear behavior in the vocal fold dynamics at subglottal pressures that are associated with normal speech, behavior that is not captured with standard Bernoulli flow solvers. Regions of bifurcation, coexistence of solutions, and chaos are identified.

  7. Two-dimensional model of vocal fold vibration for sound synthesis of voice and soprano singing.

    PubMed

    Adachi, Seiji; Yu, Jason

    2005-05-01

    Voiced sounds were simulated with a computer model of the vocal fold composed of a single mass vibrating both parallel and perpendicular to the airflow. Similarities with the two-mass model are found in the amplitudes of the glottal area and the glottal volume flow velocity, the variation in the volume flow waveform with the vocal tract shape, and the dependence of the oscillation amplitude upon the average opening area of the glottis, among other similar features. A few dissimilarities are also found in the more symmetric glottal and volume flow waveforms in the rising and falling phases. The major improvement of the present model over the two-mass model is that it yields a smooth transition between oscillations with an inductive load and a capacitive load of the vocal tract with no sudden jumps in the vibration frequency. Self-excitation is possible both below and above the first formant frequency of the vocal tract. By taking advantage of the wider continuous frequency range, the two-dimensional model can successfully be applied to the sound synthesis of a high-pitched soprano singing, where the fundamental frequency sometimes exceeds the first formant frequency. PMID:15957788

  8. Two-dimensional model of vocal fold vibration for sound synthesis of voice and soprano singing

    NASA Astrophysics Data System (ADS)

    Adachi, Seiji; Yu, Jason

    2005-05-01

    Voiced sounds were simulated with a computer model of the vocal fold composed of a single mass vibrating both parallel and perpendicular to the airflow. Similarities with the two-mass model are found in the amplitudes of the glottal area and the glottal volume flow velocity, the variation in the volume flow waveform with the vocal tract shape, and the dependence of the oscillation amplitude upon the average opening area of the glottis, among other similar features. A few dissimilarities are also found in the more symmetric glottal and volume flow waveforms in the rising and falling phases. The major improvement of the present model over the two-mass model is that it yields a smooth transition between oscillations with an inductive load and a capacitive load of the vocal tract with no sudden jumps in the vibration frequency. Self-excitation is possible both below and above the first formant frequency of the vocal tract. By taking advantage of the wider continuous frequency range, the two-dimensional model can successfully be applied to the sound synthesis of a high-pitched soprano singing, where the fundamental frequency sometimes exceeds the first formant frequency. .

  9. Modulating DNA configuration by interfacial traction: an elastic rod model to characterize DNA folding and unfolding.

    PubMed

    Huang, Zaixing

    2011-01-01

    As a continuum model of DNA, a thin elastic rod subjected to interfacial interactions is used to investigate the equilibrium configuration of DNA in intracellular solution. The interfacial traction between the rod and the solution environment is derived in detail. Kirchhoff's theory of elastic rods is used to analyze the equilibrium configuration of a DNA segment under the action of the interfacial traction. The influences of the interfacial energy factor and bending stiffness on the toroidal spool formation of the DNA segment are discussed. The results show that the equilibrium configuration of DNA is mainly determined by competition between the interfacial energy and elastic strain energy of the DNA itself, and the interfacial traction is one of the forces that drives DNA folding and unfolding. PMID:22210963

  10. Global relativistic folding optical potential and the relativistic Green's function model

    NASA Astrophysics Data System (ADS)

    Ivanov, M. V.; Vignote, J. R.; Álvarez-Rodríguez, R.; Meucci, A.; Giusti, C.; Udías, J. M.

    2016-07-01

    Optical potentials provide critical input for calculations on a wide variety of nuclear reactions, in particular, for neutrino-nucleus reactions, which are of great interest in the light of the new neutrino oscillation experiments. We present the global relativistic folding optical potential (GRFOP) fits to elastic proton scattering data from 12C nucleus at energies between 20 and 1040 MeV. We estimate observables, such as the differential cross section, the analyzing power, and the spin rotation parameter, in elastic proton scattering within the relativistic impulse approximation. The new GRFOP potential is employed within the relativistic Green's function model for inclusive quasielastic electron scattering and for (anti)neutrino-nucleus scattering at MiniBooNE kinematics.

  11. 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.

  12. 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.

  13. Transient dynamic phenotypes as criteria for model discrimination: fold-change detection in Rhodobacter sphaeroides chemotaxis.

    PubMed

    Hamadeh, Abdullah; Ingalls, Brian; Sontag, Eduardo

    2013-03-01

    The chemotaxis pathway of the bacterium Rhodobacter sphaeroides shares many similarities with that of Escherichia coli. It exhibits robust adaptation and has several homologues of the latter's chemotaxis proteins. Recent theoretical results have correctly predicted that the E. coli output behaviour is unchanged under scaling of its ligand input signal; this property is known as fold-change detection (FCD). In the light of recent experimental results suggesting that R. sphaeroides may also show FCD, we present theoretical assumptions on the R. sphaeroides chemosensory dynamics that can be shown to yield FCD behaviour. Furthermore, it is shown that these assumptions make FCD a property of this system that is robust to structural and parametric variations in the chemotaxis pathway, in agreement with experimental results. We construct and examine models of the full chemotaxis pathway that satisfy these assumptions and reproduce experimental time-series data from earlier studies. We then propose experiments in which models satisfying our theoretical assumptions predict robust FCD behaviour where earlier models do not. In this way, we illustrate how transient dynamic phenotypes such as FCD can be used for the purposes of discriminating between models that reproduce the same experimental time-series data. PMID:23293140

  14. Using massively parallel simulation and Markovian models to study protein folding: examining the dynamics of the villin headpiece.

    PubMed

    Jayachandran, Guha; Vishal, V; Pande, Vijay S

    2006-04-28

    We report on the use of large-scale distributed computing simulation and novel analysis techniques for examining the dynamics of a small protein. Matters addressed include folding rate, very long time scale kinetics, ensemble properties, and interaction with water. The target system for the study, the villin headpiece, has been of great interest to experimentalists and theorists both. Sampling totaled nearly 500 mus-the most extensive published to date for a system of villin's size in explicit solvent with all atom detail-and was in the form of tens of thousands of independent molecular dynamics trajectories, each several tens of nanoseconds in length. We report on kinetics sensitivity analyses that, using a set of short simulations, probed the role of water in villin's folding and sensitivity to the simulation's electrostatics treatment. By constructing Markovian state models (MSMs) from the collected data, we were able to propagate dynamics to times far beyond those directly simulated and to rapidly compute mean first passage times, long time kinetics (tens of microseconds), and evolution of ensemble property distributions over long times, otherwise currently impossible. We also tested our MSM by using it to predict the structure of villin de novo. PMID:16674165

  15. Modularity of Protein Folds as a Tool for Template-Free Modeling of Structures

    PubMed Central

    Vallat, Brinda; Madrid-Aliste, Carlos; Fiser, Andras

    2015-01-01

    Predicting the three-dimensional structure of proteins from their amino acid sequences remains a challenging problem in molecular biology. While the current structural coverage of proteins is almost exclusively provided by template-based techniques, the modeling of the rest of the protein sequences increasingly require template-free methods. However, template-free modeling methods are much less reliable and are usually applicable for smaller proteins, leaving much space for improvement. We present here a novel computational method that uses a library of supersecondary structure fragments, known as Smotifs, to model protein structures. The library of Smotifs has saturated over time, providing a theoretical foundation for efficient modeling. The method relies on weak sequence signals from remotely related protein structures to create a library of Smotif fragments specific to the target protein sequence. This Smotif library is exploited in a fragment assembly protocol to sample decoys, which are assessed by a composite scoring function. Since the Smotif fragments are larger in size compared to the ones used in other fragment-based methods, the proposed modeling algorithm, SmotifTF, can employ an exhaustive sampling during decoy assembly. SmotifTF successfully predicts the overall fold of the target proteins in about 50% of the test cases and performs competitively when compared to other state of the art prediction methods, especially when sequence signal to remote homologs is diminishing. Smotif-based modeling is complementary to current prediction methods and provides a promising direction in addressing the structure prediction problem, especially when targeting larger proteins for modeling. PMID:26252221

  16. 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

  17. 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

  18. Direct-numerical simulation of the glottal jet and vocal-fold dynamics in a three-dimensional laryngeal model.

    PubMed

    Zheng, X; Mittal, R; Xue, Q; Bielamowicz, S

    2011-07-01

    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

  19. Can Local Probes Go Global? A Joint Experiment-Simulation Analysis of λ6-85 Folding.

    PubMed

    Sukenik, Shahar; Pogorelov, Taras V; Gruebele, Martin

    2016-06-01

    The process of protein folding is known to involve global motions in a cooperative affair; the structure of most of the protein sequences is gained or lost over a narrow range of temperature, denaturant, or pressure perturbations. At the same time, recent simulations and experiments reveal a complex structural landscape with a rich set of local motions and conformational changes. We couple experimental kinetic and thermodynamic measurements with specifically tailored analysis of simulation data to isolate local versus global folding probes. We find that local probes exhibit lower melting temperatures, smaller surface area changes, and faster kinetics compared to global ones. We also see that certain local probes of folding match the global behavior more closely than others. Our work highlights the importance of using multiple probes to fully characterize protein folding dynamics by theory and experiment. PMID:27101436

  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. PMID:23643604

  1. 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

  2. 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).

  3. Enhancement of a Spring-mass System Model for Numerical Simulations of Centrifugal Deployment Dynamics of Folded Square Membranes

    NASA Astrophysics Data System (ADS)

    Okuizumi, Nobukatsu; Muta, Azusa; Matunaga, Saburo

    In this paper, the spring-mass system model developed for simple numerical simulations of thin membranes is enhanced by taking into account the properties of buckling and creases. The model is applied to the numerical simulations of centrifugal deployments of folded square membranes that are small-scale models for solar sail spacecraft “IKAROS”. First the folding and deployment methods are reviewed. Then the formulation of the enhanced spring-mass system model is explained. Numerical simulations of the centrifugal deployments of two kinds of folded square membranes with different crease intervals are performed and the numerical results are compared with the corresponding experimental results. The deployment behaviors are discussed and the validity of the spring-mass system model is examined.

  4. 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.

  5. Residue-specific analysis of frustration in the folding landscape of repeat beta/alpha protein apoflavodoxin.

    PubMed

    Stagg, Loren; Samiotakis, Antonios; Homouz, Dirar; Cheung, Margaret S; Wittung-Stafshede, Pernilla

    2010-02-12

    Flavodoxin adopts the common repeat beta/alpha topology and folds in a complex kinetic reaction with intermediates. To better understand this reaction, we analyzed a set of Desulfovibrio desulfuricans apoflavodoxin variants with point mutations in most secondary structure elements by in vitro and in silico methods. By equilibrium unfolding experiments, we first revealed how different secondary structure elements contribute to overall protein resistance to heat and urea. Next, using stopped-flow mixing coupled with far-UV circular dichroism, we probed how individual residues affect the amount of structure formed in the experimentally detected burst-phase intermediate. Together with in silico folding route analysis of the same point-mutated variants and computation of growth in nucleation size during early folding, computer simulations suggested the presence of two competing folding nuclei at opposite sides of the central beta-strand 3 (i.e., at beta-strands 1 and 4), which cause early topological frustration (i.e., misfolding) in the folding landscape. Particularly, the extent of heterogeneity in folding nuclei growth correlates with the in vitro burst-phase circular dichroism amplitude. In addition, phi-value analysis (in vitro and in silico) of the overall folding barrier to apoflavodoxin's native state revealed that native-like interactions in most of the beta-strands must form in transition state. Our study reveals that an imbalanced competition between the two sides of apoflavodoxin's central beta-sheet directs initial misfolding, while proper alignment on both sides of beta-strand 3 is necessary for productive folding. PMID:19913555

  6. 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).

  7. 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

  8. Strains and folds within thrust sheets: An analysis of the Heilam sheet, northwest Scotland

    NASA Astrophysics Data System (ADS)

    Fischer, M. W.; Coward, M. P.

    1982-10-01

    The changes of shape and orientation of fossil worm burrows have been used to carry out a detailed strain analysis of the Heilam thrust sheet in the Moine Thrust zone, northwest Scotland. The strains have been factorised into components of layer parallel shear ( γ1), layer normal shear ( γ2) and layer parallel shortening or elongation (√ λ). Variations in the γ1 shear are largely lithologically controlled. Some strain is due to flexural processes as the thrusts and overlying beds change dip over thrust ramps, or are tightened by later deformation, while there may also be a component of drag which increases towards the overlying thrust, this predating the shear due to flexure. A contoured map of the √ λ' values suggests that major folds within the thrust sheet developed as a result of stick or drag on the floor thrust prior to ramp climb. This led to differential movement in the transport direction causing layer parallel shortening accompanied, or followed by, buckling of the layers. A map showing layer normal shear strains, γ2, suggests that the Heilam sheet forms a major surge zone, the central part having moved further WNW than the northern and southern parts. This has led to components of lateral shear along parts of the sheet, especially in the north, producing curvature of the imbricate faults.

  9. Teaching polymers to fold

    SciTech Connect

    Judson, R.S. )

    1992-12-10

    A new method is presented for predicting folding pathways of polymers. The folding pathway is described as a generic program or sequence of logical steps of such a form that a computer can carry them out to produce a folded structure. A genetic (GA) is used to learn specific sequences or folding pathways that carry a denatured conformation into a target final conformation. The method is demonstrated on a model 2-dimensional polymer for which the global energy minimum is known. The GA learns a program that will fold a denatured polymer into its global energy minimum conformation. 27 refs., 4 figs.

  10. 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.

  11. 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. PMID:26381910

  12. Wavelet analysis of hemispheroid flow separation toward understanding human vocal fold pathologies

    NASA Astrophysics Data System (ADS)

    Plesniak, Daniel H.; Carr, Ian A.; Bulusu, Kartik V.; Plesniak, Michael W.

    2014-11-01

    Physiological flows observed in human vocal fold pathologies, such as polyps and nodules, can be modeled by flow over a wall-mounted protuberance. The experimental investigation of flow separation over a surface-mounted hemispheroid was performed using particle image velocimetry (PIV) and measurements of surface pressure in a low-speed wind tunnel. This study builds on the hypothesis that the signatures of vortical structures associated with flow separation are imprinted on the surface pressure distributions. Wavelet decomposition methods in one- and two-dimensions were utilized to elucidate the flow behavior. First, a complex Gaussian wavelet was used for the reconstruction of surface pressure time series from static pressure measurements acquired from ports upstream, downstream, and on the surface of the hemispheroid. This was followed by the application of a novel continuous wavelet transform algorithm (PIVlet 1.2) using a 2D-Ricker wavelet for coherent structure detection on instantaneous PIV-data. The goal of this study is to correlate phase shifts in surface pressure with Strouhal numbers associated with the vortex shedding. Ultimately, the wavelet-based analytical framework will be aimed at addressing pulsatile flows. This material is based in part upon work supported by the National Science Foundation under Grant Number CBET-1236351, and GW Center for Biomimetics and Bioinspired Engineering (COBRE).

  13. 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. PMID:25779043

  14. 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

  15. Anisotropic diffusion of tensor fields for fold shape analysis on surfaces.

    PubMed

    Boucher, Maxime; Evans, Alan; Siddiqi, Kaleem

    2011-01-01

    The folding pattern of the human cortical surface is organized in a coherent set of troughs and ridges, which mark important anatomical demarcations that are similar across subjects. Cortical surface shape is often analyzed in the literature using isotropic diffusion, a strategy that is questionable because many anatomical regions are known to follow the direction of folds. This paper introduces anisotropic diffusion kernels to follow neighboring fold directions on surfaces, extending recent literature on enhancing curve-like patterns in images. A second contribution is to map deformations that affect sulcal length, i.e., are parallel to neighboring folds, with other deformations that affect sulcal length, within the diffusion process. Using the proposed method, we demonstrate anisotropic shape differences of the cortical surface associated with aging in a database of 95 healthy subjects, such as a contraction of the cingulate sulcus, shorter gyri in the temporal lobe and a contraction in the frontal lobe. PMID:21761663

  16. Liquid accumulation in vibrating vocal fold tissue: A simplified model based on a fluid-saturated porous solid theory

    PubMed Central

    Tao, Chao; Jiang, Jack J.; Czerwonka, Lukasz

    2011-01-01

    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). PMID:19660905

  17. 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.

  18. 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.

  19. Finite-difference, time-domain analysis of a folded acoustic transmission line.

    PubMed

    Jackson, Charles M

    2005-03-01

    Recently designed, modern versions of renais sance woodwind instruments such as the recorder and serpent use square cross sections and a folded acoustic transmission line. Conventional microwave techniques would expect that this bend would cause unwanted reflections and impedance discontinuities. This paper analyses the folded acoustic transmission line using finite-difference, time-domain techniques and shows that the discontinuity can be compensated with by the use of a manufacturable method. PMID:15857045

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Halo structure of 11Li in proton scattering: A folding model description with isospin, density and momentum dependent effective interaction

    NASA Astrophysics Data System (ADS)

    Kanungo, Rituparna; Samanta, C.

    1997-02-01

    Recent 11Li+p elastic scattering data at 62, 68.4, and 75 MeV and inelastic scattering data at 68.4 MeV, taken at RIKEN, are analysed with an isospin, density and momentum dependent finite range effective interaction (SBM) and M3Y interaction in a single folding model. The M3Y folded 11Li+p potentials are found to be almost similar to the folded 9Li+p potentials. But the SBM folded 11Li+p potentials are distinctly different, causing small but significant change in the angular distribution. Folded potentials need appreciable reduction factors indicating possible effects of strong breakup channel coupling. No significant change in results is found if 9Li core + Gaussian two-neutron halo density is used instead of the COSM density of 11Li although the radial extent of the latter is much larger. The angular distribution of the recently discovered excited state at 1.3 MeV, well reproduced by the SBM folded potential, is found to be predominantly dipole in nature.

  5. 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

  6. 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. PMID:25173237

  7. 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

  8. 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.

  9. 3D FEM modeling of fold nappe formation in the Western Swiss Alps

    NASA Astrophysics Data System (ADS)

    von Tscharner, M.; Schmalholz, S.

    2012-04-01

    Fold nappes are recumbent folds with amplitudes exceeding 10 km and have been presumably formed by heterogeneous simple shear. They often exhibit a constant sense of shearing and a non-linear increase of shear strain towards their overturned limb. The fold axes of the Morcles fold nappe in western Switzerland plunges to the ENE whereas the fold axes in the more eastern Doldenhorn nappe plunges to the WSW. These opposite plunge directions characterize the Wildstrubel depression (Rawil depression, Ramsay, 1981). The Morcles nappe is mainly the result of layer contraction and shearing (Ramsay, 1981). During the compression the massive limestones were more competent than the surrounding marls and shales, which led to the buckling characteristics of the Morcles nappe, especially in the north-dipping normal limb. There are still no 3D numerical studies which investigate the fundamental dynamics of the formation of the large-scale 3D structure including the Morcles and Doldenhorn fold nappes and the related Wildstrubel depression. Such studies require a numerical algorithm that can accurately track material interfaces for large differences in material properties (e.g. between limestone and shale) and for large deformations. We present a numerical algorithm based on the finite element method (FEM) which can simulate 3D fluid flow for a power-law viscous rheology. Our FEM code combines a numerical marker technique and a deformable Lagrangian mesh with re-meshing (Poliakov and Podladchikov, 1992) and is used to study the formation of 3D fold nappes similar to the ones in the Western Swiss Alps. The numerical method requires the interpolation of material properties to the integration points because the layer interface can lie within a finite element. To guarantee accuracy the number of integration points in the finite elements is increased considerably. The interpolation is only performed during several re-meshing steps when the deformed Lagrangian mesh is too distorted

  10. 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

  11. Reconstructing folding energy landscapes from splitting probability analysis of single-molecule trajectories

    PubMed Central

    Manuel, Ajay P.; Lambert, John; Woodside, Michael T.

    2015-01-01

    Structural self-assembly in biopolymers, such as proteins and nucleic acids, involves a diffusive search for the minimum-energy state in a conformational free-energy landscape. The likelihood of folding proceeding to completion, as a function of the reaction coordinate used to monitor the transition, can be described by the splitting probability, pfold(x). Pfold encodes information about the underlying energy landscape, and it is often used to judge the quality of the reaction coordinate. Here, we show how pfold can be used to reconstruct energy landscapes from single-molecule folding trajectories, using force spectroscopy measurements of single DNA hairpins. Calculating pfold(x) directly from trajectories of the molecular extension measured for hairpins fluctuating in equilibrium between folded and unfolded states, we inverted the result expected from diffusion over a 1D energy landscape to obtain the implied landscape profile. The results agreed well with the landscapes reconstructed by established methods, but, remarkably, without the need to deconvolve instrumental effects on the landscape, such as tether compliance. The same approach was also applied to hairpins with multistate folding pathways. The relative insensitivity of the method to the instrumental compliance was confirmed by simulations of folding measured with different tether stiffnesses. This work confirms that the molecular extension is a good reaction coordinate for these measurements, and validates a powerful yet simple method for reconstructing landscapes from single-molecule trajectories. PMID:26039984

  12. 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. PMID:17437718

  13. 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

  14. 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.

  15. 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…

  16. Energy and Mass Dependences of the Parameters of the Semimicroscopic Folding Model for Alpha Particles at Low and Intermediate Energies

    SciTech Connect

    Kuterbekov, K.A.; Zholdybayev, T.K.; Kukhtina, I.N.; Penionzhkevich, Yu.E.

    2005-06-01

    The energy and mass dependences of the parameters of the semimicroscopic alpha-particle potential are investigated for the first time in the region of low and intermediate energies. Within the semimicroscopic folding model, both elastic and inelastic differential and total cross sections for reactions on various nuclei are well described by using global parameters obtained in this study.

  17. 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.

  18. 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. PMID:27106298

  19. 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.

  20. The initial step of DNA hairpin folding: a kinetic analysis using fluorescence correlation spectroscopy

    PubMed Central

    Kim, Jiho; Doose, Sören; Neuweiler, Hannes; Sauer, Markus

    2006-01-01

    Conformational fluctuations of single-stranded DNA (ssDNA) oligonucleotides were studied in aqueous solution by monitoring contact-induced fluorescence quenching of the oxazine fluorophore MR121 by intrinsic guanosine residues (dG). We applied fluorescence correlation spectroscopy as well as steady-state and time-resolved fluorescence spectroscopy to analyze kinetics of DNA hairpin folding. We first characterized the reporter system by investigating bimolecular quenching interactions between MR121 and guanosine monophosphate in aqueous solution estimating rate constants, efficiency and stability for formation of quenched complexes. We then studied the kinetics of complex formation between MR121 and dG residues site-specifically incorporated in DNA hairpins. To uncover the initial steps of DNA hairpin folding we investigated complex formation in ssDNA carrying one or two complementary base pairs (dC–dG pairs) that could hybridize to form a short stem. Our data show that incorporation of a single dC–dG pair leads to non-exponential decays for opening and closing kinetics and reduces rate constants by one to two orders of magnitude. We found positive activation enthalpies independent of the number of dC–dG pairs. These results imply that the rate limiting step of DNA hairpin folding is not determined by loop dynamics, or by mismatches in the stem, but rather by interactions between stem and loop nucleotides. PMID:16687657

  1. 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. PMID:16938987

  2. Linking aptamer-ligand binding and expression platform folding in riboswitches: prospects for mechanistic modeling and design.

    PubMed

    Aboul-ela, Fareed; Huang, Wei; Abd Elrahman, Maaly; Boyapati, Vamsi; Li, Pan

    2015-01-01

    The power of riboswitches in regulation of bacterial metabolism derives from coupling of two characteristics: recognition and folding. Riboswitches contain aptamers, which function as biosensors. Upon detection of the signaling molecule, the riboswitch transduces the signal into a genetic decision. The genetic decision is coupled to refolding of the expression platform, which is distinct from, although overlapping with, the aptamer. Early biophysical studies of riboswitches focused on recognition of the ligand by the aptamer-an important consideration for drug design. A mechanistic understanding of ligand-induced riboswitch RNA folding can further enhance riboswitch ligand design, and inform efforts to tune and engineer riboswitches with novel properties. X-ray structures of aptamer/ligand complexes point to mechanisms through which the ligand brings together distal strand segments to form a P1 helix. Transcriptional riboswitches must detect the ligand and form this P1 helix within the timescale of transcription. Depending on the cell's metabolic state and cellular environmental conditions, the folding and genetic outcome may therefore be affected by kinetics of ligand binding, RNA folding, and transcriptional pausing, among other factors. Although some studies of isolated riboswitch aptamers found homogeneous, prefolded conformations, experimental, and theoretical studies point to functional and structural heterogeneity for nascent transcripts. Recently it has been shown that some riboswitch segments, containing the aptamer and partial expression platforms, can form binding-competent conformers that incorporate an incomplete aptamer secondary structure. Consideration of the free energy landscape for riboswitch RNA folding suggests models for how these conformers may act as transition states-facilitating rapid, ligand-mediated aptamer folding. PMID:26361734

  3. 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.

  4. Dependence of Internal Friction on Folding Mechanism

    PubMed Central

    2016-01-01

    An outstanding challenge in protein folding is understanding the origin of “internal friction” in folding dynamics, experimentally identified from the dependence of folding rates on solvent viscosity. A possible origin suggested by simulation is the crossing of local torsion barriers. However, it was unclear why internal friction varied from protein to protein or for different folding barriers of the same protein. Using all-atom simulations with variable solvent viscosity, in conjunction with transition-path sampling to obtain reaction rates and analysis via Markov state models, we are able to determine the internal friction in the folding of several peptides and miniproteins. In agreement with experiment, we find that the folding events with greatest internal friction are those that mainly involve helix formation, while hairpin formation exhibits little or no evidence of friction. Via a careful analysis of folding transition paths, we show that internal friction arises when torsion angle changes are an important part of the folding mechanism near the folding free energy barrier. These results suggest an explanation for the variation of internal friction effects from protein to protein and across the energy landscape of the same protein. PMID:25721133

  5. 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.

  6. Kinematics of constant arc length folding for different fold shapes

    NASA Astrophysics Data System (ADS)

    Ghassemi, Mohammad R.; Schmalholz, Stefan M.; Ghassemi, Ali R.

    2010-06-01

    Basic mathematical functions are applied for the two-dimensional geometrical and kinematical analysis of different fold shapes. Relationships between different fold parameters are established and related to the bulk shortening taking place during folding under upper crustal conditions. The bulk shortening taking place during constant arc length folding is mathematically related to the bulk shortening during homogenous pure shear using a particular aspect ratio, which is for folding the ratio of amplitude to half wavelength and for pure shear the ratio of vertical to horizontal length of the deformed, initially square body. The evolution of the fold aspect ratio with bulk shortening is similar for a wide range of fold shapes and indicates that the fold aspect ratio allows a good estimate of the bulk shortening. The change of the geometry of individual layers across a multilayer sequence in disharmonic folding indicates a specific kinematics of multilayer folding, referred to here as "wrap folding", which does not require significant flexural slip nor flexural flow. The kinematic analysis indicates that there is a critical value for constant arc length folding between shortening values of 30-40% (depending on the fold geometry). For shortening values smaller than the critical value limb rotation and fold amplitude growth are dominating. For shortening larger than this value, faulting, boudinage and foliation development are likely the dominating deformation process during continued shortening. The kinematical analysis of constant arc length folding can be used for estimating the bulk shortening taking place during multilayer folding which is an important component of the deformation of crustal rocks during the early history of shortening. The bulk shortening is estimated for a natural, multilayer detachment fold and the shortening estimates based on the kinematic analysis are compared and supported by numerical finite element simulations of multilayer detachment

  7. 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.

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

    PubMed

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

    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. PMID:25240340

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  10. 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

  11. 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. PMID:17630830

  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. 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

  14. Modeling the effects of a posterior glottal opening on vocal fold dynamics with implications for vocal hyperfunction.

    PubMed

    Zañartu, Matías; Galindo, Gabriel E; Erath, Byron D; Peterson, Sean D; Wodicka, George R; Hillman, Robert E

    2014-12-01

    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 cm(2) 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

  15. 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

  16. Accurate cortical tissue classification on MRI by modeling cortical folding patterns.

    PubMed

    Kim, Hosung; Caldairou, Benoit; Hwang, Ji-Wook; Mansi, Tommaso; Hong, Seok-Jun; Bernasconi, Neda; Bernasconi, Andrea

    2015-09-01

    Accurate tissue classification is a crucial prerequisite to MRI morphometry. Automated methods based on intensity histograms constructed from the entire volume are challenged by regional intensity variations due to local radiofrequency artifacts as well as disparities in tissue composition, laminar architecture and folding patterns. Current work proposes a novel anatomy-driven method in which parcels conforming cortical folding were regionally extracted from the brain. Each parcel is subsequently classified using nonparametric mean shift clustering. Evaluation was carried out on manually labeled images from two datasets acquired at 3.0 Tesla (n = 15) and 1.5 Tesla (n = 20). In both datasets, we observed high tissue classification accuracy of the proposed method (Dice index >97.6% at 3.0 Tesla, and >89.2% at 1.5 Tesla). Moreover, our method consistently outperformed state-of-the-art classification routines available in SPM8 and FSL-FAST, as well as a recently proposed local classifier that partitions the brain into cubes. Contour-based analyses localized more accurate white matter-gray matter (GM) interface classification of the proposed framework compared to the other algorithms, particularly in central and occipital cortices that generally display bright GM due to their highly degree of myelination. Excellent accuracy was maintained, even in the absence of correction for intensity inhomogeneity. The presented anatomy-driven local classification algorithm may significantly improve cortical boundary definition, with possible benefits for morphometric inference and biomarker discovery. PMID:26037453

  17. Computational modeling of protein folding assistance by the eukaryotic chaperonin CCT

    NASA Astrophysics Data System (ADS)

    Jayasinghe, Manori; Stan, George

    2009-03-01

    Chaperonins are biological nanomachines that promote protein folding using energy derived from ATP hydrolysis. Structurally, chaperonins are large oligomeric complexes that form double-ring construct, enclosing a central cavity that serves as folding chamber. Our focus is on the substrate binding mechanisms of the Eukaryotic chaperonin CCT and Archaeal chaperonin Thermosome. We contrast our results with the annealing action of the bacterial chaperonin GroEL of E. coli., currently the best studied for chaperonin machinery. CCT was suggested to be more selective towards the substrate recognition where as GroEL is more promiscuous due to the hydrophobic interactions. We study the interaction of CCT with Tubulin, one of its stringent substrates. Using molecular docking and molecular dynamics simulations, we probe binding of a βtubulin peptide (205-274) to the CCTγ apical domain. We identify a versatile binding mechanism, involving mostly hydrophobic interactions with the helical region and electrostatic interactions with the helical protrusion region. This specific substrate-protein recognition mechanism is likely to be optimized for specific substrate protein-CCT subunit pairs.

  18. Thermodynamic features characterizing good and bad folding sequences obtained using a simplified off-lattice protein model

    NASA Astrophysics Data System (ADS)

    Amatori, A.; Ferkinghoff-Borg, J.; Tiana, G.; Broglia, R. A.

    2006-06-01

    The thermodynamics of the small SH3 protein domain is studied by means of a simplified model where each beadlike amino acid interacts with the others through a contact potential controlled by a 20×20 random matrix. Good folding sequences, characterized by a low native energy, display three main thermodynamical ensembles, namely, a coil-like ensemble, an unfolded globule, and a folded ensemble (plus two other states, frozen and random coils, populated only at extreme temperatures). Interestingly, the unfolded globule has some regions already structured. Poorly designed sequences, on the other hand, display a wide transition from the random coil to a frozen state. The comparison with the analytic theory of heteropolymers is discussed.

  19. Role of the Closing Base Pair for d(GCA) Hairpin Stability: Free Energy Analysis and Folding Simulations

    SciTech Connect

    Kannan, Srinivasaraghavan; Zacharias, Martin W.

    2011-06-30

    Hairpin loops belong to the most important structural motifs in folded nucleic acids. The d(GNA) sequence in DNA can form very stable trinucleotide hairpin loops depending, however, strongly on the closing base pair. Replica-exchange molecular dynamics (REMD) were employed to study hairpin folding of two DNA sequences, d(gcGCAgc) and d(cgGCAcg), with the same central loop motif but different closing base pairs starting from singlestranded structures. In both cases, conformations of the most populated conformational cluster at the lowest temperature showed close agreement with available experimental structures. For the loop sequence with the less stable G:C closing base pair, an alternative loop topology accumulated as second most populated conformational state indicating a possible loop structural heterogeneity. Comparative-free energy simulations on induced loop unfolding indicated higher stability of the loop with a C:G closing base pair by 3 kcal mol1 (compared to a G:C closing base pair) in very good agreement with experiment. The comparative energetic analysis of sampled unfolded, intermediate and folded conformational states identified electrostatic and packing interactions as the main contributions to the closing base pair dependence of the d(GCA) loop stability.

  20. Analysis of the pH-dependent thermodynamic stability, local motions, and microsecond folding kinetics of carbonmonoxycytochrome c.

    PubMed

    Kumar, Rajesh

    2016-09-15

    This paper analyzes the effect of pH on thermodynamic stability, low-frequency local motions and microsecond folding kinetics of carbonmonoxycytochrome c (Cyt-CO) all across the alkaline pH-unfolding transition of protein. Thermodynamic analysis of urea-induced unfolding transitions of Cyt-CO measured between pH 6 and pH 11.9 reveals that Cyt-CO is maximally stable at pH∼9.5. Dilution of unfolded Cyt-CO into refolding medium forms a native-like compact state (NCO-state), where Fe(2+)-CO interaction persists. Kinetic and thermodynamic parameters measured for slow thermally-driven CO dissociation (NCO→N+CO) and association (N+CO→NCO) reactions between pH 6.5 and pH 13 reveal that the thermal-motions of M80-containing Ω-loop are decreased in subdenaturing limit of alkaline pH. Laser photolysis of Fe(2+)-CO bond in NCO-state triggers the microsecond folding (NCO→N). The microsecond kinetics measured all across the alkaline pH-unfolding transition of Cyt-CO produce rate rollover in the refolding limb of chevron plot, which suggests a glass transition of NCO en route to N. Between pH 7 and pH 11.9, the natural logarithm of the microsecond folding rate varies by < 1.5 units while the natural logarithm of apparent equilibrium constant varies by 11.8 units. This finding indicates that the pH-dependent ionic-interactions greatly affect the global stability of protein but have very small effect on folding kinetics. PMID:27424489

  1. High precision analysis of an embryonic extensional fault-related fold using 3D orthorectified virtual outcrops: The viewpoint importance in structural geology

    NASA Astrophysics Data System (ADS)

    Tavani, Stefano; Corradetti, Amerigo; Billi, Andrea

    2016-05-01

    Image-based 3D modeling has recently opened the way to the use of virtual outcrop models in geology. An intriguing application of this method involves the production of orthorectified images of outcrops using almost any user-defined point of view, so that photorealistic cross-sections suitable for numerous geological purposes and measurements can be easily generated. These purposes include the accurate quantitative analysis of fault-fold relationships starting from imperfectly oriented and partly inaccessible real outcrops. We applied the method of image-based 3D modeling and orthorectification to a case study from the northern Apennines, Italy, where an incipient extensional fault affecting well-layered limestones is exposed on a 10-m-high barely accessible cliff. Through a few simple steps, we constructed a high-quality image-based 3D model of the outcrop. In the model, we made a series of measurements including fault and bedding attitudes, which allowed us to derive the bedding-fault intersection direction. We then used this direction as viewpoint to obtain a distortion-free photorealistic cross-section, on which we measured bed dips and thicknesses as well as fault stratigraphic separations. These measurements allowed us to identify a slight difference (i.e. only 0.5°) between the hangingwall and footwall cutoff angles. We show that the hangingwall strain required to compensate the upward-decreasing displacement of the fault was accommodated by this 0.5° rotation (i.e. folding) and coeval 0.8% thickening of strata in the hangingwall relatively to footwall strata. This evidence is consistent with trishear fault-propagation folding. Our results emphasize the viewpoint importance in structural geology and therefore the potential of using orthorectified virtual outcrops.

  2. Identification of folding intermediates of streblin, the most stable serine protease: biophysical analysis.

    PubMed

    Kumar, Reetesh; Tripathi, Pinki; de Moraes, Fabio Rogerio; Caruso, Icaro P; Jagannadham, Medicherla V

    2014-01-01

    Streblin, a serine proteinase from plant Streblus asper, has been used to investigate the conformational changes induced by pH, temperature, and chaotropes. The near/far UV circular dichroism activities under fluorescence emission spectroscopy and 8-aniline-1-naphthalene sulfonate (ANS) binding have been carried out to understand the unfolding of the protein in the presence of denaturants. Spectroscopic studies reveal that streblin belongs to the α+β class of proteins and exhibits stability towards chemical denaturants, guanidine hydrochloride (GuHCl). The pH-induced transition of this protein is noncooperative for transition phases between pH 0.5 and 2.5 (midpoint, 1.5) and pH 2.5 and 10.0 (midpoint, 6.5). At pH 1.0 or lower, the protein unfolds to form acid-unfolded state, and for pH 7.5 and above, protein turns into an alkaline denatured state characterized by the absence of ANS binding. At pH 2.0 (1 M GuHCl), streblin exists in a partially unfolded state with characteristics of a molten globule state. The protein is found to exhibit strong and predominant ANS binding. In total, six different intermediate states has been identified to show protein folding pathways. PMID:24108566

  3. Analysis of the Human Kinome Using Methods Including Fold Recognition Reveals Two Novel Kinases

    PubMed Central

    Bourne, Philip E.

    2008-01-01

    Background Protein sequence similarity is a commonly used criterion for inferring the unknown function of a protein from a protein of known function. However, proteins can diverge significantly over time such that sequence similarity is difficult, if not impossible, to find. In some cases, a structural similarity remains over long evolutionary time scales and once detected can be used to predict function. Methodology/Principal Findings Here we employed a high-throughput approach to assign structural and functional annotation to the human proteome, focusing on the collection of human protein kinases, the human kinome. We compared human protein sequences to a library of domains from known structures using WU-BLAST, PSI-BLAST, and 123D. This approach utilized both sequence comparison and fold recognition methods. The resulting set of potential protein kinases was cross-checked against previously identified human protein kinases, and analyzed for conserved kinase motifs. Conclusions/Significance We demonstrate that our structure-based method can be used to identify both typical and atypical human protein kinases. We also identify two potentially novel kinases that contain an interesting combination of kinase and acyl-CoA dehydrogenase domains. PMID:18270584

  4. Structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion

    PubMed Central

    O’Brien, Darragh P.; Hernandez, Belen; Durand, Dominique; Hourdel, Véronique; Sotomayor-Pérez, Ana-Cristina; Vachette, Patrice; Ghomi, Mahmoud; Chamot-Rooke, Julia; Ladant, Daniel; Brier, Sébastien; Chenal, Alexandre

    2015-01-01

    Many Gram-negative bacteria use Type I secretion systems, T1SS, to secrete virulence factors that contain calcium-binding Repeat-in-ToXin (RTX) motifs. Here, we present structural models of an RTX protein, RD, in both its intrinsically disordered calcium-free Apo-state and its folded calcium-bound Holo-state. Apo-RD behaves as a disordered polymer chain comprising several statistical elements that exhibit local rigidity with residual secondary structure. Holo-RD is a folded multi-domain protein with an anisometric shape. RTX motifs thus appear remarkably adapted to the structural and mechanistic constraints of the secretion process. In the low calcium environment of the bacterial cytosol, Apo-RD is an elongated disordered coil appropriately sized for transport through the narrow secretion machinery. The progressive folding of Holo-RD in the extracellular calcium-rich environment as it emerges form the T1SS may then favor its unidirectional export through the secretory channel. This process is relevant for hundreds of bacterial species producing virulent RTX proteins. PMID:26374675

  5. Folding patterns and shape optimization using SMA-based self-folding laminates

    NASA Astrophysics Data System (ADS)

    Peraza-Hernandez, Edwin A.; Frei, Katherine R.; Hartl, Darren J.; Lagoudas, Dimitris C.

    2014-03-01

    Origami engineering, a discipline encompassing the creation of practical three-dimensional structures from two- dimensional entities via folding operations, has the potential to impact multiple fields of manufacturing and design. In some circumstances, it may be practical to have self-folding capabilities instead of creating folds by external manipulations (as in morphing structures in outer space or on the ocean floor). This paper considers the use of a self-folding laminate composite consisting of two outer layers of thermally actuated shape memory alloy (SMA) wire meshes separated by an inner compliant insulating layer. Methods for designing folding patterns and determining temperature fields to obtain desired shapes and behaviors are proposed. Sheets composed of the self-folding laminate are modeled via finite element analysis (FEA) and the proposed methods are implemented to test their capabilities. One method uses a previously developed and freely available software called Freeform Origami for folding pattern design. The second method entails the use of optimization to determine the localized activation temperatures required to obtain desired shapes or to perform specific functions. The proposed methods are demonstrated to be applicable for the design of folding patterns and determination of activation temperatures for the self-folding laminate by showing successful examples of their implementation. This exploratory study provides new tools that can be integrated into the design framework of self-folding origami structures.

  6. Evolution of a fold-thrust belt deforming a unit with pre-existing linear asperities: Insights from analog models

    NASA Astrophysics Data System (ADS)

    Burberry, Caroline M.; Swiatlowski, Jerlyn L.

    2016-06-01

    Heterogeneity, whether geometric or rheologic, in crustal material undergoing compression affects the geometry of the structures produced. This study documents the thrust fault geometries produced when discrete linear asperities are introduced into an analog model, scaled to represent bulk upper crustal properties, and compressed. Varying obliquities of the asperities are used, relative to the imposed compression, and the resultant development of thrust fault traces and branch lines in map view is tracked. Once the model runs are completed, cross-sections are created and analyzed. The models show that asperities confined to the base layer promote the clustering of branch lines in the surface thrusts. Strong clustering in branch lines is also noted where several asperities are in close proximity or cross. Slight reverse-sense reactivation of asperities cut through the sedimentary sequence is noted in cross-section, where the asperity and the subsequent thrust belt interact. The model results are comparable to the situation in the Dinaric Alps, where pre-existing faults to the SW of the NE Adriatic Fault Zone contribute to the clustering of branch lines developed in the surface fold-thrust belt. These results can therefore be used to evaluate the evolution of other basement-involved fold-thrust belts worldwide.

  7. Network measures for protein folding state discrimination

    PubMed Central

    Menichetti, Giulia; Fariselli, Piero; Remondini, Daniel

    2016-01-01

    Proteins fold using a two-state or multi-state kinetic mechanisms, but up to now there is not a first-principle model to explain this different behavior. We exploit the network properties of protein structures by introducing novel observables to address the problem of classifying the different types of folding kinetics. These observables display a plain physical meaning, in terms of vibrational modes, possible configurations compatible with the native protein structure, and folding cooperativity. The relevance of these observables is supported by a classification performance up to 90%, even with simple classifiers such as discriminant analysis. PMID:27464796

  8. A critical assessment of the topomer search model of protein folding using a continuum explicit-chain model with extensive conformational sampling

    PubMed Central

    Wallin, Stefan; Chan, Hue Sun

    2005-01-01

    Recently, a series of closely related theoretical constructs termed the “topomer search model” (TSM) has been proposed for the folding mechanism of small, single-domain proteins. A basic assumption of the proposed scenarios is that the rate-limiting step in folding is an essentially unbiased, diffusive search for a conformational state called the native topomer defined by an overall native-like topological pattern. Successes in correlating TSM-predicted folding rates with that of real proteins have been interpreted as experimental support for the model. To better delineate the physics entailed, key TSM concepts are examined here using extensive Langevin dynamics simulations of continuum Cα chain models. The theoretical native topomers of four experimentally well-studied two-state proteins are characterized. Consistent with the TSM perspective, we found that the sizes of the native topomers increase with experimental folding rate. However, a careful determination of the corresponding probabilities that the native topomers are populated during a random search fails to reproduce the previously predicted folding rates. Instead, our results indicate that an unbiased TSM search for the native topomer amounts to a Levinthal-like process that would take an impossibly long average time to complete. Furthermore, intraprotein contacts in all four native topomers considered exhibit no apparent correlation with the experimental φ-values determined from the folding kinetics of these proteins. Thus, the present findings suggest that certain basic, generic yet essential energetic features in protein folding are not accounted for by TSM scenarios to date. PMID:15930009

  9. Analysis of inter-residue contacts reveals folding stabilizers in P-loops of potassium, sodium, and TRPV channels.

    PubMed

    Korkosh, V S; Zhorov, B S; Tikhonov, D B

    2016-05-01

    The family of P-loop channels includes potassium, sodium, calcium, cyclic nucleotide-gated and TRPV channels, as well as ionotropic glutamate receptors. Despite vastly different physiological and pharmacological properties, the channels have structurally conserved folding of the pore domain. Furthermore, crystallographic data demonstrate surprisingly similar mutual disposition of transmembrane and membrane-diving helices. To understand determinants of this conservation, here we have compared available high-resolution structures of sodium, potassium, and TRPV1 channels. We found that some residues, which are in matching positions of the sequence alignment, occur in different positions in the 3D alignment. Surprisingly, we found 3D mismatches in well-packed P-helices. Analysis of energetics of individual residues in Monte Carlo minimized structures revealed cyclic patterns of energetically favorable inter- and intra-subunit contacts of P-helices with S6 helices. The inter-subunit contacts are rather conserved in all the channels, whereas the intra-subunit contacts are specific for particular types of the channels. Our results suggest that these residue-residue contacts contribute to the folding stabilization. Analysis of such contacts is important for structural and phylogenetic studies of homologous proteins. PMID:26646260

  10. New insights into the folding of a β-sheet miniprotein in a reduced space of collective hydrogen bond variables: application to a hydrodynamic analysis of the folding flow.

    PubMed

    Kalgin, Igor V; Caflisch, Amedeo; Chekmarev, Sergei F; Karplus, Martin

    2013-05-23

    A new analysis of the 20 μs equilibrium folding/unfolding molecular dynamics simulations of the three-stranded antiparallel β-sheet miniprotein (beta3s) in implicit solvent is presented. The conformation space is reduced in dimensionality by introduction of linear combinations of hydrogen bond distances as the collective variables making use of a specially adapted principal component analysis (PCA); i.e., to make structured conformations more pronounced, only the formed bonds are included in determining the principal components. It is shown that a three-dimensional (3D) subspace gives a meaningful representation of the folding behavior. The first component, to which eight native hydrogen bonds make the major contribution (four in each beta hairpin), is found to play the role of the reaction coordinate for the overall folding process, while the second and third components distinguish the structured conformations. The representative points of the trajectory in the 3D space are grouped into conformational clusters that correspond to locally stable conformations of beta3s identified in earlier work. A simplified kinetic network based on the three components is constructed, and it is complemented by a hydrodynamic analysis. The latter, making use of "passive tracers" in 3D space, indicates that the folding flow is much more complex than suggested by the kinetic network. A 2D representation of streamlines shows there are vortices which correspond to repeated local rearrangement, not only around minima of the free energy surface but also in flat regions between minima. The vortices revealed by the hydrodynamic analysis are apparently not evident in folding pathways generated by transition-path sampling. Making use of the fact that the values of the collective hydrogen bond variables are linearly related to the Cartesian coordinate space, the RMSD between clusters is determined. Interestingly, the transition rates show an approximate exponential correlation with distance

  11. A new computational model for protein folding based on atomic solvation.

    PubMed Central

    Wang, Y.; Zhang, H.; Scott, R. A.

    1995-01-01

    A new model for calculating the solvation energy of proteins is developed and tested for its ability to identify the native conformation as the global energy minimum among a group of thousands of computationally generated compact non-native conformations for a series of globular proteins. In the model (called the WZS model), solvation preferences for a set of 17 chemically derived molecular fragments of the 20 amino acids are learned by a training algorithm based on maximizing the solvation energy difference between native and non-native conformations for a training set of proteins. The performance of the WZS model confirms the success of this learning approach; the WZS model misrecognizes (as more stable than native) only 7 of 8,200 non-native structures. Possible applications of this model to the prediction of protein structure from sequence are discussed. PMID:7670381

  12. COS NUV MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2010-09-01

    The performance of the 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 MAMA Fold Analysis {11891} during Cycle 17.

  13. COS NUV MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2012-10-01

    The performance of the 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 MAMA Fold Analysis {12723} during Cycle 19.

  14. Nuclear mass formula with a finite-range droplet model and a folded-Yukawa single-particle potential

    SciTech Connect

    Moeller, P.; Myers, W.D.; Swiatecki, W.J.; Treiner, J.

    1988-07-01

    We calculate ground-state masses for 4678 nuclei ranging from /sup 16/O to /sup 318/122 by use of a macroscopic-microscopic model, which incorporates several new features. For the macroscopic model we use the finite-range droplet model which we introduced in 1984. The microscopic contribution is taken from a calculation based on a folded-Yukawa single-particle potential. Some new features now incorporated are a new model for the average pairing strength and the solution of the microscopic pairing equations by use of the Lipkin-Nogami method with approximate particle number conservation. To estimate the parameters of the macroscopic model we use an approach that starts by defining the error of a mass formula in a rigorous way, which leads naturally to the use of experimental uncertainties and of the maximum-likelihood method to derive a set of equations for estimating the parameters and error of the theoretical model. By considering 1593 experimental masses from /sup 16/O to /sup 263/106 we estimate the error of the theoretical model to be 0.769 MeV. The model retains its accuracy far from stability and the values of the model parameters are very insensitive to details of the adjustment procedure. copyright 1988 Academic Press, Inc.

  15. An investigation of asymmetric flow features in a scaled-up driven model of the human vocal folds

    NASA Astrophysics Data System (ADS)

    Erath, Byron D.; Plesniak, Michael W.

    2010-07-01

    Flow through a driven, 7.5 times life-size vocal fold model was investigated at corresponding life-size flow rates of Q mean = 89.1 ml/s, 159.4 ml/s, and 253.0 ml/s. The flow was scaled to match physiological values for Reynolds, Strouhal, and Euler numbers. The models were driven at a life-size frequency of 94 Hz. Particle image velocimetry (PIV) data were acquired in the anterior-posterior midplane of the glottis, and the unsteady transglottal pressure drop across the vocal folds was simultaneously measured. Flow and pressure data were obtained at four discrete instances during the closing phases of the phonatory cycle for which t/T open = 0.60, 0.70, 0.80, and 0.90. The glottal jet trajectory exhibited a bimodal distribution of flow attachment between the two medial surfaces of the glottis. Vortex shedding at the trailing edge separation point generated instabilities in the shear layer, which caused large oscillations in the glottal jet orientation downstream of the glottal exit. The development of the Coanda effect during the glottal cycle was found to have minimal impact on the transglottal pressure drop, suggesting that flow orientation does not directly influence the dipole sound source. The change in transglottal pressure drop as a result of jet trajectory was less than 2% for all three investigated flow rates.

  16. Techniques for the Analysis of Cysteine Sulfhydryls and Oxidative Protein Folding

    PubMed Central

    Sherma, Nisha D.

    2014-01-01

    Abstract Significance: Modification of cysteine thiols dramatically affects protein function and stability. Hence, the abilities to quantify specific protein sulfhydryl groups within complex biological samples and map disulfide bond structures are crucial to gaining greater insights into how proteins operate in human health and disease. Recent Advances: Many different molecular probes are now commercially available to label and track cysteine residues at great sensitivity. Coupled with mass spectrometry, stable isotope-labeled sulfhydryl-specific reagents can provide previously unprecedented molecular insights into the dynamics of cysteine modification. Likewise, the combined application of modern mass spectrometers with improved sample preparation techniques and novel data mining algorithms is beginning to routinize the analysis of complex protein disulfide structures. Critical Issues: Proper application of these modern tools and techniques, however, still requires fundamental understanding of sulfhydryl chemistry as well as the assumptions that accompany sample preparation and underlie effective data interpretation. Future Directions: The continued development of tools, technical approaches, and corresponding data processing algorithms will, undoubtedly, facilitate site-specific protein sulfhydryl quantification and disulfide structure analysis from within complex biological mixtures with ever-improving accuracy and sensitivity. Fully routinizing disulfide structure analysis will require an equal but balanced focus on sample preparation and corresponding mass spectral dataset reproducibility. Antioxid. Redox Signal. 21, 511–531. PMID:24383618

  17. Testing thick-skinned vs thin-skinned faulting in the Yakima fold and thrust belt, Washington: kinematic modeling based on new geologic mapping

    NASA Astrophysics Data System (ADS)

    Miller, B. A.; Crider, J. G.

    2012-12-01

    /magnetostratigraphic laboratory analyses. This mapping and analysis informs the kinematic models, also presented. On the basis of work to date, we hypothesize that faults rooted deep beneath the CRBG adequately explain deformation apparent in both the surficial and existing borehole data from the area. Thin-skinned models may be sufficient to produce the observed surface deformation; however, existing borehole log data indicate that pre-Miocene sedimentary units are significantly folded at depth, suggesting that the faults responsible root well beneath the CRBG. Additional subsurface data are required to further constrain the deep structure of the faults beneath Umtanum Ridge.

  18. Models of single-molecule experiments with periodic perturbations reveal hidden dynamics in RNA folding.

    PubMed

    Li, Ying; Qu, Xiaohui; Ma, Ao; Smith, Glenna J; Scherer, Norbert F; Dinner, Aaron R

    2009-05-28

    Traditionally, microscopic fluctuations of molecules have been probed by measuring responses of an ensemble to perturbations. Now, single-molecule experiments are capable of following fluctuations without introducing perturbations. However, dynamics not readily sampled at equilibrium should be accessible to nonequilibrium single-molecule measurements. In a recent study [Qu, X. et al. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 6602-6607], the efficiency of fluorescence resonance energy transfer (FRET) between probes on the L18 loop and 3' terminus of the 260 nucleotide RNase P RNA from Bacillus stearothermophilus was found to exhibit complex kinetics that depended on the (periodically alternating) concentration of magnesium ions ([Mg2+]) in solution. Specifically, this time series was found to exhibit a quasi-periodic response to a square-wave pattern of [Mg2+] changes. Because these experiments directly probe only one of the many degrees of freedom in the macromolecule, models are needed to interpret these data. We find that Hidden Markov Models are inadequate for describing the nonequilibrium dynamics, but they serve as starting points for the construction of models in which a discrete observable degree of freedom is coupled to a continuously evolving (hidden) variable. Consideration of several models of this general form indicates that the quasi-periodic response in the nonequilibrium experiments results from the switching (back and forth) in positions of the minima of the effective potential for the hidden variable. This switching drives oscillation of that variable and synchronizes the population to the changing [Mg2+]. We set the models in the context of earlier theoretical and experimental studies and conclude that single-molecule experiments with periodic peturbations can indeed yield qualitatively new information beyond that obtained at equilibrium. PMID:19415919

  19. Using COMSOL Multiphysics Software to Model Anisotropic Dielectric and Metamaterial Effects in Folded-Waveguide Traveling-Wave Tube Slow-Wave Circuits

    NASA Technical Reports Server (NTRS)

    Starinshak, David P.; Smith, Nathan D.; Wilson, Jeffrey D.

    2008-01-01

    The electromagnetic effects of conventional dielectrics, anisotropic dielectrics, and metamaterials were modeled in a terahertz-frequency folded-waveguide slow-wave circuit. Results of attempts to utilize these materials to increase efficiency are presented.

  20. An effective evolutionary algorithm for protein folding on 3D FCC HP model by lattice rotation and generalized move sets

    PubMed Central

    2013-01-01

    Background Proteins are essential biological molecules which play vital roles in nearly all biological processes. It is the tertiary structure of a protein that determines its functions. Therefore the prediction of a protein's tertiary structure based on its primary amino acid sequence has long been the most important and challenging subject in biochemistry, molecular biology and biophysics. In the past, the HP lattice model was one of the ab initio methods that many researchers used to forecast the protein structure. Although these kinds of simplified methods could not achieve high resolution, they provided a macrocosm-optimized protein structure. The model has been employed to investigate general principles of protein folding, and plays an important role in the prediction of protein structures. Methods In this paper, we present an improved evolutionary algorithm for the protein folding problem. We study the problem on the 3D FCC lattice HP model which has been widely used in previous research. Our focus is to develop evolutionary algorithms (EA) which are robust, easy to implement and can handle various energy functions. We propose to combine three different local search methods, including lattice rotation for crossover, K-site move for mutation, and generalized pull move; these form our key components to improve previous EA-based approaches. Results We have carried out experiments over several data sets which were used in previous research. The results of the experiments show that our approach is able to find optimal conformations which were not found by previous EA-based approaches. Conclusions We have investigated the geometric properties of the 3D FCC lattice and developed several local search techniques to improve traditional EA-based approaches to the protein folding problem. It is known that EA-based approaches are robust and can handle arbitrary energy functions. Our results further show that by extensive development of local searches, EA can also be very

  1. Single-Molecule Analysis of Cytochrome c Folding by Monitoring the Lifetime of an Attached Fluorescent Probe

    PubMed Central

    Stern, Harry A.; Bren, Kara L.; Krauss, Todd D.

    2013-01-01

    Conformational dynamics of proteins are important for function. However, obtaining information about specific conformations is difficult for samples displaying heterogeneity. Here, time-resolved fluorescence resonance energy transfer is used to characterize the folding of single cytochrome c molecules. In particular, measurements of the fluorescence lifetimes of individual cytochrome c molecules labeled with a single dye that is quenched by energy transfer to the heme were used to monitor conformational transitions of the protein under partially denaturing conditions. These studies indicate significantly more conformational heterogeneity than has been described previously. Importantly, the use of a purified singly-labeled sample made a direct comparison to ensemble data possible. The distribution of lifetimes of single-proteins was compared to the distribution of lifetimes determined from analysis of ensemble lifetime fluorescence data. The results show broad agreement between single-molecule and ensemble data, with a similar range of lifetimes. However, the single-molecule data reveal greater conformational heterogeneity. PMID:24116268

  2. Computational study of false vocal folds effects on unsteady airflows through static models of the human larynx

    PubMed Central

    de Luzan, Charles Farbos; Chen, Jie; Mihaescu, Mihai; Khosla, Sid M.; Gutmark, Ephraim

    2016-01-01

    Compressible large eddy simulation is employed to numerically investigate the laryngeal flow. Symmetric static models of the human larynx with a divergent glottis are considered, with the presence of false vocal folds (FVFs). The compressible study agrees well with that of the incompressible study. Due to the high enough Reynolds number, the flow is unsteady and develops asymmetric states downstream of the glottis. The glottal jet curvature decreases with the presence of FVFs or the ventricular folds. The gap between the FVFs stretches the flow structure and reduces the jet curvature. The presence of FVFs has a significant effect on the laryngeal flow resistance. The intra-glottal vortex structures are formed on the divergent wall of the glottis, immediately downstream of the separation point. The vortices are then convected downstream and characterized by a significant negative static pressure. The FVFs are a main factor in the generation of stronger vortices, and thus on the closure of the TVFs. The direct link between the FVFs geometry and the motion of the TVFs, and by extension to the voice production, is of interest for medical applications as well as future research works. The presence of the FVFs also changes the dominant frequencies in the velocity and pressure spectra. PMID:25835787

  3. Single-Molecule Protein Folding: A Study of the Surface-Mediated Conformational Dynamics of a Model Amphipathic Peptide

    NASA Astrophysics Data System (ADS)

    Cunningham, Joy; English, Douglas

    2004-03-01

    Most surface-active polypeptides, composed of 10-50 amino acids, are devoid of well-defined tertiary structure. The conformation of these proteins is greatly dependent upon their environment and may assume totally different characteristics in an aqueous environment, in a detergent micelle, or in an organic solvent. Most antimicrobial peptides are helix-forming and are activated upon interaction with a membrane-mimicking environment. We are seeking to physically characterize the mechanism of membrane-peptide interaction through studying a simple model peptide, MT-1. MT-1 was designed as a nonhomologous analogue of melittin, the principle component in bee venom. We are using single molecule spectroscopy to examine the induction of secondary structure upon interaction of MT-1 with various membrane-mimicking interfaces. Specifically, we monitor coil-to-helix transition through single molecule fluorescence resonance energy transfer (sm-FRET) to determine conformational distributions of folded and unfolded peptides at an interface. Studies with MT-1 will focus upon the biologically relevant issues of orientation, aggregation, and folding at surfaces using both ensemble and single molecule experiments.

  4. Computational study of false vocal folds effects on unsteady airflows through static models of the human larynx.

    PubMed

    Farbos de Luzan, Charles; Chen, Jie; Mihaescu, Mihai; Khosla, Sid M; Gutmark, Ephraim

    2015-05-01

    Compressible large eddy simulation is employed to numerically investigate the laryngeal flow. Symmetric static models of the human larynx with a divergent glottis are considered, with the presence of false vocal folds (FVFs). The compressible study agrees well with that of the incompressible study. Due to the high enough Reynolds number, the flow is unsteady and develops asymmetric states downstream of the glottis. The glottal jet curvature decreases with the presence of FVFs or the ventricular folds. The gap between the FVFs stretches the flow structure and reduces the jet curvature. The presence of FVFs has a significant effect on the laryngeal flow resistance. The intra-glottal vortex structures are formed on the divergent wall of the glottis, immediately downstream of the separation point. The vortices are then convected downstream and characterized by a significant negative static pressure. The FVFs are a main factor in the generation of stronger vortices, and thus on the closure of the TVFs. The direct link between the FVFs geometry and the motion of the TVFs, and by extension to the voice production, is of interest for medical applications as well as future research works. The presence of the FVFs also changes the dominant frequencies in the velocity and pressure spectra. PMID:25835787

  5. Summation of time-dependent folded diagrams for effective interactions with a non-degenerate model space

    NASA Astrophysics Data System (ADS)

    Kuo, T. T. S.; Krmpotić, F.; Suzuki, K.; Okamoto, R.

    1995-02-01

    We analyze the diagrammatic structure of the effective interaction for the case of a non-degenerate model space. A time-dependent folded-diagram formulation is used. It is found that the valence-linked time-ordered diagrams contained in such effective interactions can also be expressed in terms of the multi-energy Q¯-boxes of the form overlineQn(ɛ 1ɛ 2…ɛ n+1), which were introduced by Suzuki et al. for a time-independent description of the effective interaction. A partial-fraction method for the evaluation of the multi-energy Q¯-box, in terms of valence-linked diagrams, is discussed. A generalized Krenciglowa-Kuo iteration method for summing up the folded-diagram series is also designed. A schematic mosel is solved to compare the non-degenerate theory with the usual degenerate theory. It is shown that the present approach makes a distinct improvement in the calculation of effective interactions.

  6. Chemical and Structural Analysis of an Antibody Folding Intermediate Trapped during Glycan Biosynthesis

    PubMed Central

    2012-01-01

    Human IgG Fc glycosylation modulates immunological effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. Engineering of Fc glycans therefore enables fine-tuning of the therapeutic properties of monoclonal antibodies. The N-linked glycans of Fc are typically complex-type, forming a network of noncovalent interactions along the protein surface of the Cγ2 domain. Here, we manipulate the mammalian glycan-processing pathway to trap IgG1 Fc at sequential stages of maturation, from oligomannose- to hybrid- to complex-type glycans, and show that the Fc is structurally stabilized following the transition of glycans from their hybrid- to complex-type state. X-ray crystallographic analysis of this hybrid-type intermediate reveals that N-linked glycans undergo conformational changes upon maturation, including a flip within the trimannosyl core. Our crystal structure of this intermediate reveals a molecular basis for antibody biogenesis and provides a template for the structure-guided engineering of the protein–glycan interface of therapeutic antibodies. PMID:23025485

  7. Protein folding of the H0P model: A parallel Wang-Landau study

    SciTech Connect

    Shi, Guangjie; Wuest, Thomas; Li, Ying Wai; Landau, David P

    2015-01-01

    We propose a simple modication to the hydrophobic-polar (HP) protein model, by introducing a new type of monomer, "0", with intermediate hydrophobicity of some amino acids between H and P. With the replica-exchange Wang-Landau sampling method, we investigate some widely studied HP sequences as well as their H0P counterparts and observe that the H0P sequences exhibit dramatically reduced ground state degeneracy and more signicant transition signals at low temperature for some thermodynamic properties, such as the specific heat.

  8. Protein folding of the HOP model: A parallel Wang—Landau study

    NASA Astrophysics Data System (ADS)

    Shi, G.; Wüst, T.; Li, Y. W.; Landau, D. P.

    2015-09-01

    We propose a simple modification to the hydrophobic-polar (HP) protein model, by introducing a new type of monomer, “0”, with intermediate hydrophobicity of some amino acids between H and P. With the replica-exchange Wang-Landau sampling method, we investigate some widely studied HP sequences as well as their H0P counterparts and observe that the H0P sequences exhibit dramatically reduced ground state degeneracy and more significant transition signals at low temperature for some thermodynamic properties, such as the specific heat.

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

    NASA Astrophysics Data System (ADS)

    Olson, Wilma

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

  10. Evolution of the Chos Malal and Agrio fold and thrust belts, Andes of Neuquén: Insights from structural analysis and apatite fission track dating

    NASA Astrophysics Data System (ADS)

    Rojas Vera, E. A.; Mescua, J.; Folguera, A.; Becker, T. P.; Sagripanti, L.; Fennell, L.; Orts, D.; Ramos, V. A.

    2015-12-01

    The Chos Malal and Agrio fold and thrust belts are located in the western part of the Neuquén basin, an Andean retroarc basin of central-western Argentina. Both belts show evidence of tectonic inversion at the western part during Late Cretaceous times. The eastern part is dominated by late Miocene deformation which also partially reactivated the western structures. This work focuses on the study of the regional structure and the deformational event that shaped the relief of this part of the Andes. Based on new field work and structural data and previously published works a detailed map of the central part of the Neuquén basin is presented. Three regional structural cross sections were surveyed and balanced using the 2d Move™ software. In order to define a more accurate uplift history, new apatite fission track analyses were carried on selected structures. These data was used for new thermal history modeling of the inner part of the Agrio and Chos Malal fold and thrust belts. The results of the fission track analyses improve the knowledge of how these fold and thrust belts have grown trough time. Two main deformational events are defined in Late Cretaceous to Paleocene and Late Miocene times. Based on this regional structural analysis and the fission track data the precise location of the orogenic front for the Late Cretaceous-Paleocene times is reconstructed and it is proposed a structural evolution of this segment of the Andes. This new exhumation data show how the Late Cretaceous to Paleocene event was a continuous and uninterrupted deformational event.

  11. COS NUV MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2013-10-01

    The performance of the 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 Cycle 20 proposal 13128.

  12. Folding of a miniprotein with mixed fold.

    PubMed

    Mohanty, Sandipan; Hansmann, U H E

    2007-07-21

    Using the 28 residue betabetaalpha protein FSD-EY as a target system, we examine correction terms for the ECEPP/3 force field. We find an increased probability of formation of the native state at low temperatures resulting from a reduced propensity to form alpha helices and increased formation of beta sheets. Our analysis of the observed folding events suggests that the C-terminal helix of FSD-EY is much more stable than the N-terminal beta hairpin and forms first. The hydrophobic groups of the helix provide a template which promotes the formation of the beta hairpin that is never observed to form without the helix. PMID:17655464

  13. Protein Folding and Structure Prediction from the Ground Up: The Atomistic Associative Memory, Water Mediated, Structure and Energy Model

    PubMed Central

    Chen, Mingchen; Lin, Xingcheng; Zheng, Weihua; Onuchic, José N.; Wolynes, Peter G.

    2016-01-01

    The associative memory, water mediated, structure and energy model (AWSEM) is a coarse-grained force field with transferable tertiary interactions that incorporates local in sequence energetic biases using bioinformatically derived structural information about peptide fragments with locally similar sequence that we call memories. The memory information from the protein data bank (PDB) database guides proper protein folding. The structural information about available sequences in the database varies in quality and can sometimes lead to frustrated free energy landscapes locally. One way out of this difficulty is to construct the input fragment memory information from all-atom simulations of portions of the complete polypeptide chain. In this paper, we investigate this approach first put forward by Kwac and Wolynes in a more complete way by studying the structure prediction capabilities of this approach for six alpha-helical proteins. This scheme which we call the atomistic associative memory, water mediated, structure and energy model (AAWSEM) amounts to an ab initio protein structure prediction method that starts from the ground-up without using bioinformatic input. The free energy profiles from AAWSEM show that atomistic fragment memories are sufficient to guide the correct folding when tertiary forces are included. AAWSEM combines the efficiency of coarse-grained simulations on the full protein level with the local structural accuracy achievable from all-atom simulations of only parts of a large protein. The results suggest that a hybrid use of atomistic fragment memory and database memory in structural predictions may well be optimal for many practical applications. PMID:27148634

  14. Protein Folding and Structure Prediction from the Ground Up: The Atomistic Associative Memory, Water Mediated, Structure and Energy Model.

    PubMed

    Chen, Mingchen; Lin, Xingcheng; Zheng, Weihua; Onuchic, José N; Wolynes, Peter G

    2016-08-25

    The associative memory, water mediated, structure and energy model (AWSEM) is a coarse-grained force field with transferable tertiary interactions that incorporates local in sequence energetic biases using bioinformatically derived structural information about peptide fragments with locally similar sequences that we call memories. The memory information from the protein data bank (PDB) database guides proper protein folding. The structural information about available sequences in the database varies in quality and can sometimes lead to frustrated free energy landscapes locally. One way out of this difficulty is to construct the input fragment memory information from all-atom simulations of portions of the complete polypeptide chain. In this paper, we investigate this approach first put forward by Kwac and Wolynes in a more complete way by studying the structure prediction capabilities of this approach for six α-helical proteins. This scheme which we call the atomistic associative memory, water mediated, structure and energy model (AAWSEM) amounts to an ab initio protein structure prediction method that starts from the ground up without using bioinformatic input. The free energy profiles from AAWSEM show that atomistic fragment memories are sufficient to guide the correct folding when tertiary forces are included. AAWSEM combines the efficiency of coarse-grained simulations on the full protein level with the local structural accuracy achievable from all-atom simulations of only parts of a large protein. The results suggest that a hybrid use of atomistic fragment memory and database memory in structural predictions may well be optimal for many practical applications. PMID:27148634

  15. Relation of structural and vibratory kinematics of the vocal folds to two acoustic measures of breathy voice based on computational modeling

    PubMed Central

    Samlan, Robin A.; Story, Brad H.

    2011-01-01

    Purpose To relate vocal fold structure and kinematics to two acoustic measures: cepstral peak prominence (CPP) and the amplitude of the first harmonic relative to the second (H1-H2). Method A computational, kinematic model of the medial surfaces of the vocal folds was used to specify features of vocal fold structure and vibration in a manner consistent with breathy voice. Four model parameters were altered: degree of vocal fold adduction, surface bulging, vibratory nodal point, and supraglottal constriction. CPP and H1-H2 were measured from simulated glottal area, glottal flow and acoustic waveforms and related to the underlying vocal fold kinematics. Results CPP decreased with increased separation of the vocal processes, whereas the nodal point location had little effect. H1-H2 increased as a function of separation of the vocal processes in the range of 1–1.5 mm and decreased with separation > 1.5 mm. Conclusions CPP is generally a function of vocal process separation. H1*-H2* will increase or decrease with vocal process separation based on vocal fold shape, pivot point for the rotational mode, and supraglottal vocal tract shape, limiting its utility as an indicator of breathy voice. Future work will relate the perception of breathiness to vocal fold kinematics and acoustic measures. PMID:21498582

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

    NASA Astrophysics Data System (ADS)

    Hindle, David; Kley, Jonas

    2016-04-01

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

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

    PubMed

    Jin, Emma Yu; Nebel, Markus E

    2016-02-01

    Various tools used to predict the secondary structure for a given RNA sequence are based on dynamic programming used to compute a conformation of minimum free energy. For structures without pseudoknots, a worst-case runtime proportional to n3, with n being the length of the sequence, results since a table of dimension n2 has to be filled in while a single entry gives rise to a linear computational effort. However, it was recently observed that reformulating the corresponding dynamic programming recursion together with the bookkeeping of potential folding alternatives (a technique called sparsification) may reduce the runtime to n2 on average, assuming that nucleotides of distance d form a hydrogen bond (i..e., are paired) with probability b/d(c) for some constants b > 0, c > 1. The latter is called the polymer-zeta model and plays a crucial role in speeding up the above mentioned algorithm. In this paper we discuss the application of the polymer-zeta property for the analysis of sparsification, showing that it must be applied conditionally on first and last positions to pair. Afterwards, we will investigate the combinatorics of RNA secondary structures assuming that the corresponding conditional probabilities behave according to a polymer-zeta probability model. We show that even if some of the structural parameters exhibit an almost realistic behavior on average, the expected shape of a folding in that model must be assumed to highly differ from those observed in nature. More precisely, we prove our polymer-zeta model to be appropriate for mRNA molecules but to fail in connection with almost every other family of RNA. Those findings explain the huge speedup of the dynamic programming algorithm observed empirically by Wexler et al. when applying sparsification in connection with mRNA data. PMID:26001743

  18. [THE MODEL OF NUCLEOSOME STRUCTURE BASED ON THE LOCAL ROTATION OF THE NUCLEOHISTONE CHAIN, WHICH INDUCES ITS FOLDING].

    PubMed

    Priyatkina, T N

    2015-01-01

    An alternative model to the "double turn of DNA on the histone core" approach is forwarded based on the biochemical, cytological, and crystallographic data on the structural organization of the chromatin units--nucleosomes. The model assumes that the initial structure is a linear nucleohistone cord with a repeating symmetrical histone sequence. The compact (core) particle (a minimal nucleosome) is forming upon a stepwise rotation of DNA (kinks) at the centre and at two symmetrical sites into each repeating fragment stemming from the electrostatic binding of the lysine ε-NH2-groups with the followed one by one phosphates of the sugar-phosphate chain. As a result, we have a rhomboid structure composed of two counter-symmetrical DNA folds stabilized by histone-histone interactions. Based on disposable data, the histone sequence along nucleosome DNA is deduced. The following characteristics of the sequence are considered: continuity, non-overlapping, versatility, and dyadic symmetry in dispose of two every kind histone molecules and the sequence on the whole. The model is in agreement with a topology of nucleosome DNA, as well as the pattern of DNA-histone and histone-histone interactions in chromatin. PMID:26495705

  19. A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

    PubMed Central

    Li, Nicole Y. K.; Verdolini, Katherine; Clermont, Gilles; Mi, Qi; Rubinstein, Elaine N.; Hebda, Patricia A.; Vodovotz, Yoram

    2008-01-01

    The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains. PMID:18665229

  20. Nonlinear dynamic-based analysis of severe dysphonia in patients with vocal fold scar and sulcus vocalis

    PubMed Central

    Choi, Seong Hee; Zhang, Yu; Jiang, Jack J.; Bless, Diane M.; Welham, Nathan V.

    2011-01-01

    Objective The primary goal of this study was to evaluate a nonlinear dynamic approach to the acoustic analysis of dysphonia associated with vocal fold scar and sulcus vocalis. Study Design Case-control study. Methods Acoustic voice samples from scar/sulcus patients and age/sex-matched controls were analyzed using correlation dimension (D2) and phase plots, time-domain based perturbation indices (jitter, shimmer, signal-to-noise ratio [SNR]), and an auditory-perceptual rating scheme. Signal typing was performed to identify samples with bifurcations and aperiodicity. Results Type 2 and 3 acoustic signals were highly represented in the scar/sulcus patient group. When data were analyzed irrespective of signal type, all perceptual and acoustic indices successfully distinguished scar/sulcus patients from controls. Removal of type 2 and 3 signals eliminated the previously identified differences between experimental groups for all acoustic indices except D2. The strongest perceptual-acoustic correlation in our dataset was observed for SNR; the weakest correlation was observed for D2. Conclusions These findings suggest that D2 is inferior to time-domain based perturbation measures for the analysis of dysphonia associated with scar/sulcus; however, time-domain based algorithms are inherently susceptible to inflation under highly aperiodic (i.e., type 2 and 3) signal conditions. Auditory-perceptual analysis, unhindered by signal aperiodicity, is therefore a robust strategy for distinguishing scar/sulcus patient voices from normal voices. Future acoustic analysis research in this area should consider alternative (e.g., frequency- and quefrency-domain based) measures alongside additional nonlinear approaches. PMID:22516315

  1. Two- and three-dimensional modeling and optimization applied to the design of a fast hydrodynamic focusing microfluidic mixer for protein folding

    NASA Astrophysics Data System (ADS)

    Ivorra, Benjamin; Redondo, Juana L.; Santiago, Juan G.; Ortigosa, Pilar M.; Ramos, Angel M.

    2013-03-01

    We present a design of a microfluidic mixer based on hydrodynamic focusing which is used to initiate the folding process (i.e., changes of the molecular structure) of a protein. The folding process is initiated by diluting (from 90% to 30%) the local denaturant concentration (initially 6 M GdCl solution) in a short time interval we refer to as mixing time. Our objective is to optimize this mixer by choosing suitable shape and flow conditions in order to minimize this mixing time. To this end, we first introduce a numerical model that enables computation of the mixing time of a mixer. This model is based on a finite element method approximation of the incompressible Navier-Stokes equations coupled with the convective diffusion equation. To reduce the computational time, this model is implemented in both full three-dimensional (3D) and simplified two-dimensional (2D) versions; and we analyze the ability of the 2D model to approximate the mixing time predicted by the 3D model. We found that the 2D model approximates the mixing time predicted by the 3D model with a mean error of about 15%, which is considered reasonable. Then, we define a mixer optimization problem considering the 2D model and solve it using a hybrid global optimization algorithm. In particular, we consider geometrical variables and injection velocities as optimization parameters. We achieve a design with a predicted mixing time of 0.10 μs, approximately one order of magnitude faster than previous mixer designs. This improvement can be in part explained by the new mixer geometry including an angle of π/5 radians at the channel intersection and injections velocities of 5.2 m s-1 and 0.038 m s-1 for the side and central inlet channels, respectively. Finally, we verify the robustness of the optimized result by performing a sensitivity analysis of its parameters considering the 3D model. During this study, the optimized mixer was demonstrated to be robust by exhibiting mixing time variations of the same

  2. Direct dating of folding events by 40Ar/39Ar analysis of synkinematic muscovite from flexural-slip planes

    NASA Astrophysics Data System (ADS)

    Wang, Yu; Zwingmann, Horst; Zhou, Liyun; Lo, Ching-hua; Viola, Giulio; Hao, Jinhua

    2016-02-01

    Timing of folding is usually dated indirectly, with limited isotopic dating studies reported in the literature. The present study investigated the timing of intracontinental, multi-stage folding in Upper Proterozoic sandstone, limestone, and marble near Beijing, North China, and adjacent regions. Detailed field investigations with microstructural, backscattered electron (BSE) images and electron microprobe analyses indicate that authigenic muscovite and sericite crystallized parallel to stretching lineations/striations or along thin flexural-slip surfaces, both developed during the complex deformation history of the study area, involving repeated compressional, extensional and strike-slip episodes. Muscovite/sericite separates from interlayer-slip surfaces along the limbs and from dilatant sites in the hinges of folded sandstones yield muscovite 40Ar/39Ar plateau ages of ∼158-159 Ma, whereas those from folded marble and limestone samples yield ages of 156 ± 1 Ma. Muscovite from thin flexural-slip planes on fold limbs and hinges yields ages within analytical error of ∼155-165 Ma. Further muscovite samples collected from extensionally folded limestone and strike-slip drag folds yield younger ages of 128-125 Ma with well-defined plateaus. To assess the potential influence of the detrital mica component of the host rock on the age data, two additional muscovite samples were investigated, one from a folded upper Proterozoic-Cambrian sandstone outside the Western Hills of Beijing and one from a folded sandstone sampled 20 cm from folding-related slip planes. Muscovite separates from these samples yield significantly older ages of 575 ± 2 Ma and 587 ± 2 Ma, suggesting that the timing of folding can be directly determined using the 40Ar/39Ar method. This approach enables the identification and dating of distinct deformation events that occur during multi-stage regional folding. 40Ar/39Ar dating can be used to constrain the timing of muscovite and sericite growth at

  3. Evolution of pore-fluid pressure during folding and basin contraction in overpressured reservoirs assessed by combined fracture analysis and calcite twinning paleopiezometry

    NASA Astrophysics Data System (ADS)

    Beaudoin, Nicolas; Lacombe, Olivier; Bellahsen, Nicolas; Amrouch, Khalid; Daniel, Jean-Marc

    2014-05-01

    enhancement of vertical hydraulic permeability that affect the strata during the curvature-related fracture development. Another result of our approach is the possible estimate of syn-folding exhumation of strata. The inferred exhumation values range from 0,6 km to 1,3 km at Sheep Mountain and from 0,8 km to 2,0 km at Rattlesnake Mountain. These values are consistent with fold growth models predicting exhumation rates ranging from 0.03 to 0.40 mm/yr and with published exhumation rates from fission track studies in other Laramide uplifts. This case study illustrates how the combination of stress inversion of fault-slip and calcite twin data with rock mechanics can be used to discuss which are the natural factors that control the pressure evolution in a carbonate reservoir during its large-scale deformation in an orogenic foreland.

  4. Direct folding simulation of a long helix in explicit water

    NASA Astrophysics Data System (ADS)

    Gao, Ya; Lu, Xiaoliang; Duan, Lili; Zhang, Dawei; Mei, Ye; Zhang, John Z. H.

    2013-05-01

    A recently proposed Polarizable Hydrogen Bond (PHB) method has been employed to simulate the folding of a 53 amino acid helix (PDB ID 2KHK) in explicit water. Under PHB simulation, starting from a fully extended structure, the peptide folds into the native state as confirmed by measured time evolutions of radius of gyration, root mean square deviation (RMSD), and native hydrogen bond. Free energy and cluster analysis show that the folded helix is thermally stable under the PHB model. Comparison of simulation results under, respectively, PHB and standard nonpolarizable force field demonstrates that polarization is critical for stable folding of this long α-helix.

  5. Heuristic-based tabu search algorithm for folding two-dimensional AB off-lattice model proteins.

    PubMed

    Liu, Jingfa; Sun, Yuanyuan; Li, Gang; Song, Beibei; Huang, Weibo

    2013-12-01

    The protein structure prediction problem is a classical NP hard problem in bioinformatics. The lack of an effective global optimization method is the key obstacle in solving this problem. As one of the global optimization algorithms, tabu search (TS) algorithm has been successfully applied in many optimization problems. We define the new neighborhood conformation, tabu object and acceptance criteria of current conformation based on the original TS algorithm and put forward an improved TS algorithm. By integrating the heuristic initialization mechanism, the heuristic conformation updating mechanism, and the gradient method into the improved TS algorithm, a heuristic-based tabu search (HTS) algorithm is presented for predicting the two-dimensional (2D) protein folding structure in AB off-lattice model which consists of hydrophobic (A) and hydrophilic (B) monomers. The tabu search minimization leads to the basins of local minima, near which a local search mechanism is then proposed to further search for lower-energy conformations. To test the performance of the proposed algorithm, experiments are performed on four Fibonacci sequences and two real protein sequences. The experimental results show that the proposed algorithm has found the lowest-energy conformations so far for three shorter Fibonacci sequences and renewed the results for the longest one, as well as two real protein sequences, demonstrating that the HTS algorithm is quite promising in finding the ground states for AB off-lattice model proteins. PMID:24077543

  6. Evolutionary optimization of protein folding.

    PubMed

    Debès, Cédric; Wang, Minglei; Caetano-Anollés, Gustavo; Gräter, Frauke

    2013-01-01

    Nature has shaped the make up of proteins since their appearance, [Formula: see text]3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last [Formula: see text]1.5 billion years that began during the "big bang" of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions. PMID:23341762

  7. Chirality and protein folding

    NASA Astrophysics Data System (ADS)

    Kwiecinska, Joanna I.; Cieplak, Marek

    2005-05-01

    There are several simple criteria of folding to a native state in model proteins. One of them involves crossing of a threshold value of the root mean square deviation distance away from the native state. Another checks whether all native contacts are established, i.e. whether the interacting amino acids come closer than some characteristic distance. We use Go-like models of proteins and show that such simple criteria may prompt one to declare folding even though fragments of the resulting conformations have a wrong sense of chirality. We propose that a better condition of folding should augment the simple criteria with the requirement that most of the local values of the chirality should be nearly native. The kinetic discrepancy between the simple and compound criteria can be substantially reduced in the Go-like models by providing the Hamiltonian with a term which favours native values of the local chirality. We study the effects of this term as a function of its amplitude and compare it to other models such as ones with side groups and ones with angle-dependent potentials.

  8. Structural analysis of hanging wall and footwall blocks within the Río Guanajibo fold-and-thrust belt in Southwest Puerto Rico

    NASA Astrophysics Data System (ADS)

    Laó-Dávila, Daniel A.; Llerandi-Román, Pablo A.

    2015-12-01

    The Río Guanajibo fold-and-thrust belt (RGFT), composed of Cretaceous serpentinite and volcano-sedimentary rocks, represents the deformation front of a contractional event in SW Puerto Rico during the Paleogene. Previous studies inferred structural and stratigraphic relationships from poorly exposed outcrops. New road cuts exposed the Yauco (YF) and El Rayo Formations (ERF) providing insights on the deformation of the hanging wall and footwall. We described the nature and orientation of faults and folds and analyzed the kinematic indicators to characterize the deformation. The YF occurs in the hanging wall and shows a sequence of folded, medium-bedded mudstone and thinly bedded shale and sandstone. Major folds strike NW-SE and are gentle with steeply inclined axial planes and sub-horizontal fold axes. Minor folds are open with moderately inclined axial planes and gently to moderately inclined SE-plunging fold axes. NW-SE striking reverse and thrust faults cut layers and show movement to the SW. Steep left-lateral faults strike NW-SE and NE-SW, and smaller right-lateral strike-slip faults strike NNE-SSW. At the footwall, the ERF consists of bioclastic limestone and polymictic orthoconglomerates and paraconglomerates. Reverse and strike-slip faults cut along lithological contacts. Results suggest that the hanging wall and footwall accommodated strain along preexisting weaknesses, which are dependent on lithology and sedimentary structures. The kinematic analysis suggests that shortening in the NE-SW direction was partitioned between folding and interlayer shortening, accommodated by flexural slip, and reverse and left-lateral faults that resulted from contraction. The RGFT represents the Paleogene back arc deformation of a bivergent thrust system.

  9. Modeling the effect of codon translation rates on co-translational protein folding mechanisms of arbitrary complexity

    NASA Astrophysics Data System (ADS)

    Caniparoli, Luca; O'Brien, Edward P.

    2015-04-01

    In a cell, the folding of a protein molecule into tertiary structure can begin while it is synthesized by the ribosome. The rate at which individual amino acids are incorporated into the elongating nascent chain has been shown to affect the likelihood that proteins will populate their folded state, indicating that co-translational protein folding is a far from equilibrium process. Developing a theoretical framework to accurately describe this process is, therefore, crucial for advancing our understanding of how proteins acquire their functional conformation in living cells. Current state-of-the-art computational approaches, such as molecular dynamics simulations, are very demanding in terms of the required computer resources, making the simulation of co-translational protein folding difficult. Here, we overcome this limitation by introducing an efficient approach that predicts the effects that variable codon translation rates have on co-translational folding pathways. Our approach is based on Markov chains. By using as an input a relatively small number of molecular dynamics simulations, it allows for the computation of the probability that a nascent protein is in any state as a function of the translation rate of individual codons along a mRNA's open reading frame. Due to its computational efficiency and favorable scalability with the complexity of the folding mechanism, this approach could enable proteome-wide computational studies of the influence of translation dynamics on co-translational folding.

  10. Modeling the effect of codon translation rates on co-translational protein folding mechanisms of arbitrary complexity.

    PubMed

    Caniparoli, Luca; O'Brien, Edward P

    2015-04-14

    In a cell, the folding of a protein molecule into tertiary structure can begin while it is synthesized by the ribosome. The rate at which individual amino acids are incorporated into the elongating nascent chain has been shown to affect the likelihood that proteins will populate their folded state, indicating that co-translational protein folding is a far from equilibrium process. Developing a theoretical framework to accurately describe this process is, therefore, crucial for advancing our understanding of how proteins acquire their functional conformation in living cells. Current state-of-the-art computational approaches, such as molecular dynamics simulations, are very demanding in terms of the required computer resources, making the simulation of co-translational protein folding difficult. Here, we overcome this limitation by introducing an efficient approach that predicts the effects that variable codon translation rates have on co-translational folding pathways. Our approach is based on Markov chains. By using as an input a relatively small number of molecular dynamics simulations, it allows for the computation of the probability that a nascent protein is in any state as a function of the translation rate of individual codons along a mRNA's open reading frame. Due to its computational efficiency and favorable scalability with the complexity of the folding mechanism, this approach could enable proteome-wide computational studies of the influence of translation dynamics on co-translational folding. PMID:25877595

  11. Graphene folding on flat substrates

    SciTech Connect

    Chen, Xiaoming; Zhao, Yadong; Ke, Changhong; Zhang, Liuyang; Wang, Xianqiao

    2014-10-28

    We present a combined experimental-theoretical study of graphene folding on flat substrates. The structure and deformation of the folded graphene sheet are experimentally characterized by atomic force microscopy. The local graphene folding behaviors are interpreted based on nonlinear continuum mechanics modeling and molecular dynamics simulations. Our study on self-folding of a trilayer graphene sheet reports a bending stiffness of about 6.57 eV, which is about four times the reported values for monolayer graphene. Our results reveal that an intriguing free sliding phenomenon occurs at the interlayer van der Waals interfaces during the graphene folding process. This work demonstrates that it is a plausible venue to quantify the bending stiffness of graphene based on its self-folding conformation on flat substrates. The findings reported in this work are useful to a better understanding of the mechanical properties of graphene and in the pursuit of its applications.

  12. Folding of proteins with diverse folds.

    PubMed

    Mohanty, Sandipan; Hansmann, Ulrich H E

    2006-11-15

    Using parallel tempering simulations with high statistics, we investigate the folding and thermodynamic properties of three small proteins with distinct native folds: the all-helical 1RIJ, the all-sheet beta3s, and BBA5, which has a mixed helix-sheet fold. In all three cases, simulations with our energy function find the native structures as global minima in free energy at experimentally relevant temperatures. However, the folding process strongly differs for the three molecules, indicating that the folding mechanism is correlated with the form of the native structure. PMID:16950845

  13. Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori

    NASA Astrophysics Data System (ADS)

    Wang, Liang-Wei; Liu, Yu-Nan; Lyu, Ping-Chiang; Jackson, Sophie E.; Hsu, Shang-Te Danny

    2015-09-01

    Understanding the mechanism by which a polypeptide chain thread itself spontaneously to attain a knotted conformation has been a major challenge in the field of protein folding. HP0242 is a homodimeric protein from Helicobacter pylori with intertwined helices to form a unique pseudo-knotted folding topology. A tandem HP0242 repeat has been constructed to become the first engineered trefoil-knotted protein. Its small size renders it a model system for computational analyses to examine its folding and knotting pathways. Here we report a multi-parametric study on the folding stability and kinetics of a library of HP0242 variants, including the trefoil-knotted tandem HP0242 repeat, using far-UV circular dichroism and fluorescence spectroscopy. Equilibrium chemical denaturation of HP0242 variants shows the presence of highly populated dimeric and structurally heterogeneous folding intermediates. Such equilibrium folding intermediates retain significant amount of helical structures except those at the N- and C-terminal regions in the native structure. Stopped-flow fluorescence measurements of HP0242 variants show that spontaneous refolding into knotted structures can be achieved within seconds, which is several orders of magnitude faster than previously observed for other knotted proteins. Nevertheless, the complex chevron plots indicate that HP0242 variants are prone to misfold into kinetic traps, leading to severely rolled-over refolding arms. The experimental observations are in general agreement with the previously reported molecular dynamics simulations. Based on our results, kinetic folding pathways are proposed to qualitatively describe the complex folding processes of HP0242 variants.

  14. Protein folding in a force clamp

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Szymczak, P.

    2006-05-01

    Kinetics of folding of a protein held in a force clamp are compared to an unconstrained folding. The comparison is made within a simple topology-based dynamical model of ubiquitin. We demonstrate that the experimentally observed variations in the end-to-end distance reflect microscopic events during folding. However, the folding scenarios in and out of the force clamp are distinct.

  15. Single molecule fluorescence experiments determine protein folding transition path times

    PubMed Central

    Chung, Hoi Sung; McHale, Kevin; Louis, John M.; Eaton, William A.

    2013-01-01

    The transition path is the tiny fraction of an equilibrium molecular trajectory when a transition occurs by crossing the free-energy barrier between two states. It is a single-molecule property that contains all the mechanistic information on how a process occurs. As a step toward observing transition paths in protein folding we determined the average transition-path time for a fast- and a slow-folding protein from a photon-by-photon analysis of fluorescence trajectories in single-molecule Förster-resonance-energy-transfer experiments. While the folding rate coefficients differ by a factor of 10,000, the transition-path times differ by less than a factor of 5, showing that a fast-and a slow-folding protein take almost the same time to fold when folding actually happens. A very simple model based on energy landscape theory can explain this result. PMID:22363011

  16. Unusual folding propensity of an unsubstituted β,γ-hybrid model peptide: importance of the C-H⋅⋅⋅O intramolecular hydrogen bond.

    PubMed

    Venugopalan, Paloth; Kishore, Raghuvansh

    2013-07-22

    The single-crystal X-ray diffraction analysis of a β,γ-hybrid model peptide Boc-β-Ala-γ-Abu-NH2 revealed the existence of four crystallographically independent molecules (A, B, C and D conformers) in the asymmetric unit. The analysis revealed that unusual β-turn-like folded structures predominate, wherein the conformational space of non-proteinogenic β-Ala and γ-Abu residues are restricted to gauche-gauche-skew and skew-gauche-trans-skew orientations, respectively. Interestingly, the U-shaped conformers are seemingly stabilised by an effective unconventional C-H⋅⋅⋅O intramolecular hydrogen bond, encompassing a non-covalent 14-membered ring-motif. Taking into account the signs of torsion angles, these conformers could be grouped into two distinct categories, A/B and C/D, establishing the incidence of non-superimposable stereogeometrical features across a non-chiral one-component peptide model system, that is, "mirror-image-like" relationships. The natural occurrence of β-Ala and γ-Abu entities in various pharmacologically important molecules, coupled with their biocompatibilities, highlight how the non-functionalised β,γ-hybrid segment may offer unique advantages for introducing and/or manipulating a wide spectrum of biologically relevant hydrogen bonded secondary structural mimics in short synthetic peptides. PMID:23775881

  17. Timing analysis by model checking

    NASA Technical Reports Server (NTRS)

    Naydich, Dimitri; Guaspari, David

    2000-01-01

    The safety of modern avionics relies on high integrity software that can be verified to meet hard real-time requirements. The limits of verification technology therefore determine acceptable engineering practice. To simplify verification problems, safety-critical systems are commonly implemented under the severe constraints of a cyclic executive, which make design an expensive trial-and-error process highly intolerant of change. Important advances in analysis techniques, such as rate monotonic analysis (RMA), have provided a theoretical and practical basis for easing these onerous restrictions. But RMA and its kindred have two limitations: they apply only to verifying the requirement of schedulability (that tasks meet their deadlines) and they cannot be applied to many common programming paradigms. We address both these limitations by applying model checking, a technique with successful industrial applications in hardware design. Model checking algorithms analyze finite state machines, either by explicit state enumeration or by symbolic manipulation. Since quantitative timing properties involve a potentially unbounded state variable (a clock), our first problem is to construct a finite approximation that is conservative for the properties being analyzed-if the approximation satisfies the properties of interest, so does the infinite model. To reduce the potential for state space explosion we must further optimize this finite model. Experiments with some simple optimizations have yielded a hundred-fold efficiency improvement over published techniques.

  18. Limited cooperativity in protein folding.

    PubMed

    Muñoz, Victor; Campos, Luis A; Sadqi, Mourad

    2016-02-01

    Theory and simulations predict that the structural concert of protein folding reactions is relatively low. Experimentally, folding cooperativity has been difficult to study, but in recent years we have witnessed major advances. New analytical procedures in terms of conformational ensembles rather than discrete states, experimental techniques with improved time, structural, or single-molecule resolution, and combined thermodynamic and kinetic analysis of fast folding have contributed to demonstrate a general scenario of limited cooperativity in folding. Gradual structural disorder is already apparent on the unfolded and native states of slow, two-state folding proteins, and it greatly increases in magnitude for fast folding domains. These results demonstrate a direct link between how fast a single-domain protein folds and unfolds, and how cooperative (or structurally diverse) is its equilibrium unfolding process. Reducing cooperativity also destabilizes the native structure because it affects unfolding more than folding. We can thus define a continuous cooperativity scale that goes from the 'pliable' two-state character of slow folders to the gradual unfolding of one-state downhill, and eventually to intrinsically disordered proteins. The connection between gradual unfolding and intrinsic disorder is appealing because it suggests a conformational rheostat mechanism to explain the allosteric effects of folding coupled to binding. PMID:26845039

  19. Origin and evolution of protein fold designs inferred from phylogenomic analysis of CATH domain structures in proteomes.

    PubMed

    Bukhari, Syed Abbas; Caetano-Anollés, Gustavo

    2013-01-01

    The spatial arrangements of secondary structures in proteins, irrespective of their connectivity, depict the overall shape and organization of protein domains. These features have been used in the CATH and SCOP classifications to hierarchically partition fold space and define the architectural make up of proteins. Here we use phylogenomic methods and a census of CATH structures in hundreds of genomes to study the origin and diversification of protein architectures (A) and their associated topologies (T) and superfamilies (H). Phylogenies that describe the evolution of domain structures and proteomes were reconstructed from the structural census and used to generate timelines of domain discovery. Phylogenies of CATH domains at T and H levels of structural abstraction and associated chronologies revealed patterns of reductive evolution, the early rise of Archaea, three epochs in the evolution of the protein world, and patterns of structural sharing between superkingdoms. Phylogenies of proteomes confirmed the early appearance of Archaea. While these findings are in agreement with previous phylogenomic studies based on the SCOP classification, phylogenies unveiled sharing patterns between Archaea and Eukarya that are recent and can explain the canonical bacterial rooting typically recovered from sequence analysis. Phylogenies of CATH domains at A level uncovered general patterns of architectural origin and diversification. The tree of A structures showed that ancient structural designs such as the 3-layer (αβα) sandwich (3.40) or the orthogonal bundle (1.10) are comparatively simpler in their makeup and are involved in basic cellular functions. In contrast, modern structural designs such as prisms, propellers, 2-solenoid, super-roll, clam, trefoil and box are not widely distributed and were probably adopted to perform specialized functions. Our timelines therefore uncover a universal tendency towards protein structural complexity that is remarkable. PMID:23555236

  20. Ab initio RNA folding

    NASA Astrophysics Data System (ADS)

    Cragnolini, Tristan; Derreumaux, Philippe; Pasquali, Samuela

    2015-06-01

    RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, the experimental determination of RNA structures through x-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, the need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties, when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.

  1. Ab initio RNA folding.

    PubMed

    Cragnolini, Tristan; Derreumaux, Philippe; Pasquali, Samuela

    2015-06-17

    RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, the experimental determination of RNA structures through x-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, the need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties, when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding. PMID:25993396

  2. Integrated Molecular Analysis Indicates Undetectable Change in DNA Damage in Mice after Continuous Irradiation at ~ 400-fold Natural Background Radiation

    PubMed Central

    Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C

    2012-01-01

    Background: In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. Objectives: DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. Methods: We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. Results: We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break–induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. Conclusions: These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation. PMID:22538203

  3. Deformation of Fold-and-Thrust Belts above a Viscous Detachment: New Insights from Analogue Modelling Experiments

    NASA Astrophysics Data System (ADS)

    Nogueira, Carlos R.; Marques, Fernando O.

    2015-04-01

    Theoretical and experimental studies on fold-and-thrusts belts (FTB) have shown that, under Coulomb conditions, deformation of brittle thrust wedges above a dry frictional basal contact is characterized by dominant frontward vergent thrusts (forethrusts) with thrust spacing and taper angle being directly influenced by the basal strength (increase in basal strength leading to narrower thrust spacing and higher taper angles); whereas thrust wedges deformed above a weak viscous detachment, such as salt, show a more symmetric thrust style (no prevailing vergence of thrusting) with wider thrust spacing and shallower wedges. However, different deformation patterns can be found on this last group of thrust wedges both in nature and experimentally. Therefore we focused on the strength (friction) of the wedge basal contact, the basal detachment. We used a parallelepiped box with four fixed walls and one mobile that worked as a vertical piston drove by a computer controlled stepping motor. Fine dry sand was used as the analogue of brittle rocks and silicone putty (PDMS) with Newtonian behaviour as analogue of the weak viscous detachment. To investigate the strength of basal contact on thrust wedge deformation, two configurations were used: 1) a horizontal sand pack with a dry frictional basal contact; and 2) a horizontal sand pack above a horizontal PDMS layer, acting as a basal weak viscous contact. Results of the experiments show that: the model with a dry frictional basal detachment support the predictions for the Coulomb wedges, showing a narrow wedge with dominant frontward vergence of thrusting, close spacing between FTs and high taper angle. The model with a weak viscous frictional basal detachment show that: 1) forethrusts (FT) are dominant showing clearly an imbricate asymmetric geometry, with wider spaced thrusts than the dry frictional basal model; 2) after FT initiation, the movement on the thrust can last up to 15% model shortening, leading to great amount of

  4. Kinematic 3-D Retro-Modeling of an Orogenic Bend in the South Limón Fold-and-Thrust Belt, Eastern Costa Rica: Prediction of the Incremental Internal Strain Distribution

    NASA Astrophysics Data System (ADS)

    Brandes, Christian; Tanner, David C.; Winsemann, Jutta

    2016-03-01

    The South Limón fold-and-thrust belt, in the back-arc area of southern Costa Rica, is characterized by a 90° curvature of the strike of the thrust planes and is therefore a natural laboratory for the analysis of curved orogens. The analysis of curved fold-and-thrust belts is a challenge because of the varying structural orientations within the belt. Based on seismic reflection lines, we created a 3-D subsurface model containing three major thrust faults and three stratigraphic horizons. 3-D kinematic retro-deformation modeling was carried out to analyze the spatial evolution of the fold-and-thrust belt. The maximum amount of displacement on each of the faults is (from hinterland to foreland); thrust 1: 800 m; thrust 2: 600 m; thrust 3: 250 m. The model was restored sequentially to its pre-deformational state. The strain history of the stratigraphic horizons in the model was calculated at every step. This shows that the internal strain pattern has an abrupt change at the orogenic bend. Contractional strain occurs in the forelimbs of the hanging-wall anticlines, while a zone of dilative strain spreads from the anticline crests to the backlimbs. The modeling shows that a NNE-directed transport direction best explains the structural evolution of the bend. This would require a left-lateral strike-slip zone in the North to compensate for the movement and thereby decoupling the South Limón fold-and-thrust belt from northern Costa Rica. Therefore, our modeling supports the presence of the Trans-Isthmic fault system, at least during the Plio-Pleistocene.

  5. Protein Aggregation/Folding: The Role of Deterministic Singularities of Sequence Hydrophobicity as Determined by Nonlinear Signal Analysis of Acylphosphatase and Aβ(1–40)

    PubMed Central

    Zbilut, Joseph P.; Colosimo, Alfredo; Conti, Filippo; Colafranceschi, Mauro; Manetti, Cesare; Valerio, MariaCristina; Webber, Charles L.; Giuliani, Alessandro

    2003-01-01

    The problem of protein folding vs. aggregation was investigated in acylphosphatase and the amyloid protein Aβ(1–40) by means of nonlinear signal analysis of their chain hydrophobicity. Numerical descriptors of recurrence patterns provided the basis for statistical evaluation of folding/aggregation distinctive features. Static and dynamic approaches were used to elucidate conditions coincident with folding vs. aggregation using comparisons with known protein secondary structure classifications, site-directed mutagenesis studies of acylphosphatase, and molecular dynamics simulations of amyloid protein, Aβ(1–40). The results suggest that a feature derived from principal component space characterized by the smoothness of singular, deterministic hydrophobicity patches plays a significant role in the conditions governing protein aggregation. PMID:14645049

  6. The protein folding network

    NASA Astrophysics Data System (ADS)

    Rao, Francesco; Caflisch, Amedeo

    2004-03-01

    Networks are everywhere. The conformation space of a 20-residue antiparallel beta-sheet peptide [1], sampled by molecular dynamics simulations, is mapped to a network. Conformations are nodes of the network, and the transitions between them are links. As previously found for the World-Wide Web as well as for social and biological networks , the conformation space contains highly connected hubs like the native state which is the most populated free energy basin. Furthermore, the network shows a hierarchical modularity [2] which is consistent with the funnel mechanism of folding [3] and is not observed for a random heteropolymer lacking a native state. Here we show that the conformation space network describes the free energy landscape without requiring projections into arbitrarily chosen reaction coordinates. The network analysis provides a basis for understanding the heterogeneity of the folding transition state and the existence of multiple pathways. [1] P. Ferrara and A. Caflisch, Folding simulations of a three-stranded antiparallel beta-sheet peptide, PNAS 97, 10780-10785 (2000). [2] Ravasz, E. and Barabási, A. L. Hierarchical organization in complex networks. Phys. Rev. E 67, 026112 (2003). [3] Dill, K. and Chan, H From Levinthal to pathways to funnels. Nature Struct. Biol. 4, 10-19 (1997)

  7. Folding superfunnel to describe cooperative folding of interacting proteins.

    PubMed

    Smeller, László

    2016-07-01

    This paper proposes a generalization of the well-known folding funnel concept of proteins. In the funnel model the polypeptide chain is treated as an individual object not interacting with other proteins. Since biological systems are considerably crowded, protein-protein interaction is a fundamental feature during the life cycle of proteins. The folding superfunnel proposed here describes the folding process of interacting proteins in various situations. The first example discussed is the folding of the freshly synthesized protein with the aid of chaperones. Another important aspect of protein-protein interactions is the folding of the recently characterized intrinsically disordered proteins, where binding to target proteins plays a crucial role in the completion of the folding process. The third scenario where the folding superfunnel is used is the formation of aggregates from destabilized proteins, which is an important factor in case of several conformational diseases. The folding superfunnel constructed here with the minimal assumption about the interaction potential explains all three cases mentioned above. Proteins 2016; 84:1009-1016. © 2016 Wiley Periodicals, Inc. PMID:27090200

  8. From static to dynamic: The need for structural ensembles and a predictive model of RNA folding and function

    PubMed Central

    Herschlag, Daniel; Allred, Benjamin E.; Gowrishankar, Seshadri

    2015-01-01

    To understand RNA, it is necessary to move beyond a descriptive categorization towards quantitative predictions of its molecular conformations and functional behavior. An incisive approach to understanding the function and folding of biological RNA systems involves characterizing small, simple components that are largely responsible for the behavior of complex systems including helix-junction-helix elements and tertiary motifs. State-of-the-art methods have permitted unprecedented insight into the conformational ensembles of these elements revealing, for example, that conformations of helix-junction-helix elements are confined to a small region of the ensemble, that this region is highly dependent on the junction’s topology, and that the correct alignment of tertiary motifs may be a rare conformation on the overall folding landscape. Further characterization of RNA components and continued development of experimental and computational methods with the goal of quantitatively predicting RNA folding and functional behavior will be critical to understanding biological RNA systems. PMID:25744941

  9. Active folding and thrusting in North Africa: A framework for a seismotectonic model of the Atlas Mountains

    NASA Astrophysics Data System (ADS)

    Meghraoui, Mustapha; Maouche, Said; Timoulali, Youssef; Bouhadad, Youcef; Bouaziz, Samir

    2013-04-01

    Large earthquakes in the Atlas Mountains of North Africa are often generated on thrust or reverse faults. For inland faults, surface ruptures and long-term active tectonics appear as a thrust escarpment and fold-related faulting visible in the field and using remote sensing images, or measured using space-borne geodesy (GPS or INSAR). For coastal faults, major uplifts of late Quaternary marine terraces and folding with steplike morphology are exposed indicating the incremental development of coastal active deformation. We have investigated the similarities and differences between different active fault-related folding along the Africa - Eurasia convergent plate boundary. These active structures are seismogenic and the striking case studies are the 1960 Agadir (Mw 5.9), the 1954 Orleansville (Mw 6.7), the 1980 El Asnam (Mw 7.3), the 1992 Gafsa (Mw 5.3), the 1999 Ain Temouchent (Mw 6.0), and the 2003 Zemmouri (Mw 6.8) earthquakes. From paleoseismic investigations the El Asnam active fold shows 0.6 to 1.0 mm/yr uplift rate. West of Algiers on the Sahel anticline, the levelling of uplifted successive coastal benches and notches document the incremental folding uplift with ~ 0.84 - 1.2 mm/yr uplift rate in the last 120-140 ka. The relatively fast folding growth during late Pleistocene and Holocene in the Atlas Mountains attests for the significance of earthquake activity and the importance of convergent movements between Africa and Eurasia in the Western Mediterranean. This work is prepared in the framework of the UNESCO (SIDA) - IGCP Project 601 "Seismotectonics and Seismic Hazards in Africa".

  10. Analysis of Longitudinal Phase Differences in Vocal-Fold Vibration Using Synchronous High-Speed Videoendoscopy and Electroglottography

    PubMed Central

    Orlikoff, Robert F.; Golla, Maria E.; Deliyski, Dimitar D.

    2012-01-01

    Objective This investigation used synchronous high-speed videoendoscopy (HSV) and electroglottography (EGG) to systematically study contact and separation behavior along the length of the vocal folds. Design Repeated measures. Methods Facilitated by EGG and digital kymograms derived at 20%, 35%, 50%, 65%, and 80% of the posteroanterior length of the vocal folds, the pattern of vocal-fold contact and separation was determined for 7 female and 7 male vocally healthy subjects while producing “breathy,” “comfortable,” and “pressed” phonations. Results The female subjects consistently used an anterior-to-posterior contact pattern and posterior-to-anterior separation pattern when producing a breathy or comfortable voice, with several employing a simultaneous pattern of contact and/or separation for pressed phonation. The male subjects showed more variable “zipperlike” separation patterns, but consistently used a simultaneous contact pattern for pressed voice that was also commonly used when producing comfortable phonation. Conclusions Findings indicate longitudinal phase differences in vocal-fold vibration are both common and expected in vocally healthy speakers. The implications for vocal assessment, as well as for the use and interpretation of the EGG signal, are discussed. PMID:23059188

  11. Pseudoknots in RNA folding landscapes

    PubMed Central

    Kucharík, Marcel; Hofacker, Ivo L.; Stadler, Peter F.; Qin, Jing

    2016-01-01

    Motivation: The function of an RNA molecule is not only linked to its native structure, which is usually taken to be the ground state of its folding landscape, but also in many cases crucially depends on the details of the folding pathways such as stable folding intermediates or the timing of the folding process itself. To model and understand these processes, it is necessary to go beyond ground state structures. The study of rugged RNA folding landscapes holds the key to answer these questions. Efficient coarse-graining methods are required to reduce the intractably vast energy landscapes into condensed representations such as barrier trees or basin hopping graphs (BHG) that convey an approximate but comprehensive picture of the folding kinetics. So far, exact and heuristic coarse-graining methods have been mostly restricted to the pseudoknot-free secondary structures. Pseudoknots, which are common motifs and have been repeatedly hypothesized to play an important role in guiding folding trajectories, were usually excluded. Results: We generalize the BHG framework to include pseudoknotted RNA structures and systematically study the differences in predicted folding behavior depending on whether pseudoknotted structures are allowed to occur as folding intermediates or not. We observe that RNAs with pseudoknotted ground state structures tend to have more pseudoknotted folding intermediates than RNAs with pseudoknot-free ground state structures. The occurrence and influence of pseudoknotted intermediates on the folding pathway, however, appear to depend very strongly on the individual RNAs so that no general rule can be inferred. Availability and implementation: The algorithms described here are implemented in C++ as standalone programs. Its source code and Supplemental material can be freely downloaded from http://www.tbi.univie.ac.at/bhg.html. Contact: qin@bioinf.uni-leipzig.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID

  12. How do chaperonins fold protein?

    PubMed Central

    Motojima, Fumihiro

    2015-01-01

    Protein folding is a biological process that is essential for the proper functioning of proteins in all living organisms. In cells, many proteins require the assistance of molecular chaperones for their folding. Chaperonins belong to a class of molecular chaperones that have been extensively studied. However, the mechanism by which a chaperonin mediates the folding of proteins is still controversial. Denatured proteins are folded in the closed chaperonin cage, leading to the assumption that denatured proteins are completely encapsulated inside the chaperonin cage. In contrast to the assumption, we recently found that denatured protein interacts with hydrophobic residues at the subunit interfaces of the chaperonin, and partially protrude out of the cage. In this review, we will explain our recent results and introduce our model for the mechanism by which chaperonins accelerate protein folding, in view of recent findings.

  13. Identification of geometric parameters influencing the flow-induced vibration of a two-layer self-oscillating computational vocal fold model.

    PubMed

    Pickup, Brian A; Thomson, Scott L

    2011-04-01

    Simplified models have been used to simulate and study the flow-induced vibrations of the human vocal folds. While it is clear that the models' responses are sensitive to geometry, it is not clear how and to what extent specific geometric features influence model motion. In this study geometric features that played significant roles in governing the motion of a two-layer (body-cover), two-dimensional, finite element vocal fold model were identified. The model was defined using a flow solver based on the viscous, unsteady, Navier-Stokes equations and a solid solver that allowed for large strain and deformation. A screening-type design-of-experiments approach was used to identify the relative importance of 13 geometric parameters. Five output measures were analyzed to assess the magnitude of each geometric parameter's effect on the model's motion. The measures related to frequency, glottal width, flow rate, intraglottal angle, and intraglottal phase delay. The most significant geometric parameters were those associated with the cover--primarily the pre-phonatory intraglottal angle--as well as the body inferior angle. Some models exhibited evidence of improved model motion, including mucosal wave-like motion and alternating convergent-divergent glottal profiles, although further improvements are still needed to more closely mimic human vocal fold motion. PMID:21476668

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

    NASA Astrophysics Data System (ADS)

    Ruh, Jonas B.; Gerya, Taras

    2015-04-01

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

  15. Peptide folding simulations.

    PubMed

    Gnanakaran, S; Nymeyer, Hugh; Portman, John; Sanbonmatsu, Kevin Y; García, Angel E

    2003-04-01

    Developments in the design of small peptides that mimic proteins in complexity, recent advances in nanosecond time-resolved spectroscopy methods to study peptides and the development of modern, highly parallel simulation algorithms have come together to give us a detailed picture of peptide folding dynamics. Two newly implemented simulation techniques, parallel replica dynamics and replica exchange molecular dynamics, can now describe directly from simulations the kinetics and thermodynamics of peptide formation, respectively. Given these developments, the simulation community now has the tools to verify and validate simulation protocols and models (forcefields). PMID:12727509

  16. 3D Reservoir Modeling of Semutang Gas Field: A lonely Gas field in Chittagong-Tripura Fold Belt, with Integrated Well Log, 2D Seismic Reflectivity and Attributes.

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  17. Towards a systematic classification of protein folds

    NASA Astrophysics Data System (ADS)

    Lindgård, Per-Anker; Bohr, Henrik

    1997-10-01

    A lattice model Hamiltonian is suggested for protein structures that can explain the division into structural fold classes during the folding process. Proteins are described by chains of secondary structure elements, with the hinges in between being the important degrees of freedom. The protein structures are given a unique name, which simultaneously represent a linear string of physical coupling constants describing hinge spin interactions. We have defined a metric and a precise distance measure between the fold classes. An automated procedure is constructed in which any protein structure in the usual protein data base coordinate format can be transformed into the proposed chain representation. Taking into account hydrophobic forces we have found a mechanism for the formation of domains with a unique fold containing predicted magic numbers \\{4,6,9,12,16,18,...\\} of secondary structures and multiples of these domains. It is shown that the same magic numbers are robust and occur as well for packing on other nonclosed packed lattices. We have performed a statistical analysis of available protein structures and found agreement with the predicted preferred abundances of proteins with a predicted magic number of secondary structures. Thermodynamic arguments for the increased abundance and a phase diagram for the folding scenario are given. This includes an intermediate high symmetry phase, the parent structures, between the molten globule and the native states. We have made an exhaustive enumeration of dense lattice animals on a cubic lattice for acceptance number Z=4 and Z=5 up to 36 vertices.

  18. Understanding complex structures in fold-and-thrust belts. Integration of geometric and growth strata analyses, paleomagnetism, AMS and analogue models in the Western termination of the Southern Pyrenees

    NASA Astrophysics Data System (ADS)

    Pueyo, Emilio L.; Sánchez, Elisa; Oliva-Urcia, Belén; José Ramón, Ma

    2014-05-01

    Classic 2D approaches have helped the understanding of the geometry and kinematics of fold-and-thrust belts belts (FAT belts) but are insufficient to unravel many natural cases. This is because deformation is 3D from the geometric point of view and, thus, cylindrical features may be considered as a simplification. On the other hand, deformation kinematics is usually complex, diachronic and poliphasic in real cases. Therefore, FAT belts have to be always considered in 4D. In this sense, the Southern Pyrenees is a perfect location to study the evolution of FAT belts because of the exceptional outcropping conditions of growth strata, the proven diachronic kinematics and the non-coaxial interference of deformation events. Within the vast catalogue of complex structures that includes superposed folding, conical and plunging folds, oblique thrust ramps, etc here, we have selected the westernmost termination of the South Pyrenean sole thrust to illustrate how the integration of geometric and kinematic analysis can help unraveling complex structures in FAT belts. The San Marzal pericline (4 km2 surface extension) is the lateral termination of the Sto. Domingo deca-kilometric fold. San Marzal looks like a large 70° plunging cylindrical structure. However the large magnitude (≡ 60-70°) of vertical axis rotations accommodated between its flanks cannot be explained without a conical geometry. In this work we will show how the structural analysis performed on this structure has disentangled its complex geometry. This analyses comprises several hundreds of bedding data, joints and veins and more than 150 standard paleomagnetic and AMS sites. Besides, we will show how the kinematic information derived from magnetostratigraphic sections (more than 8 km of sampled profiles) has helped to constraint the folding and rotation ages and velocities. Finally, all these complex geometric and kinematic features have inspired us to build an analogue model where we can explore the 3D

  19. Structural analysis of the Hasan-Robat marbles as traces of folded basement in the Sanandaj-Sirjan Zone, Iran

    NASA Astrophysics Data System (ADS)

    Nadimi, Alireza

    2015-11-01

    Cherty marbles of Hasan-Robat area, northwest of Isfahan, in the Sanandaj-Sirjan Zone of Iran preserves evidences of multiple deformational events. The Sanandaj-Sirjan Zone is the inner crystalline zone of the Zagros Orogen, which has been highly deformed and exhumed during continental collision between the Arabian Plate and Central Iran. The Hasan-Robat area is an example of the exposed Precambrian-Paleozoic basement rocks that stretched along two NW-SE-trending faults and located in the inner part of the HasanRobat positive flower strcuture. The Hasan-Robat marbles record a complex shortening and shearing history. This lead to the development of disharmonic ptygmatic folds with vertical to sub-vertical axes and some interference patterns of folding that may have been created from deformations during the Pan-African Orogeny and later phases. Based on this research, tectonic evolution of the Hasan-Robat area is interpreted as the product of three major geotectonic events that have been started after Precambrian to Quaternary: (1) old deformation phases (2) contractional movements and (3) strike-slip movements. Different sets and distributions of joints, faults and folds are confirmed with effect of several deformational stages of the area and formation of the flower structure.

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

    PubMed Central

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

    2014-01-01

    Membrane proteins comprise a significant fraction of the proteomes of sequenced organisms and are the targets of approximately half of marketed drugs. However, in spite of their prevalence and biomedical importance, relatively few experimental structures are available due to technical challenges. Computational simulations can potentially address this deficit by providing structural models of membrane proteins. Solvation within the spatially heterogeneous membrane/solvent environment provides a major component of the energetics driving protein folding and association within the membrane. We have developed an implicit solvation model for membranes that is both computationally efficient and accurate enough to enable molecular mechanics predictions for the folding and association of peptides within the membrane. We derived the new atomic solvation model parameters using an unbiased fitting procedure to experimental data and have applied it to diverse problems in order to test its accuracy and to gain insight into membrane protein folding. First, we predicted the positions and orientations of peptides and complexes within the lipid bilayer and compared the simulation results with solid-state NMR structures. Next, we performed folding simulations for a series of host-guest peptides with varying propensities to form alpha helices in a hydrophobic environment and compared the structures with experimental measurements. We were also able to successfully predict the structures of amphipathic peptides as well as the structures for dimeric complexes of short hexapeptides that have experimentally characterized propensities to form beta sheets within the membrane. Finally, we compared calculated relative transfer energies with data from experiments measuring the effects of mutations on the free energies of translocon-mediated insertion of proteins into lipid bilayers and of combined folding and membrane insertion of a beta barrel protein. PMID:21904908

  1. Deformation history during chain building deduced by outcrop structural analysis: The case of the Sicilian fold-and-thrust belt (Central Mediterranean)

    NASA Astrophysics Data System (ADS)

    Napoli, G.; Nigro, F.; Favara, R.; Renda, P.; Salvaggio, G.

    2015-11-01

    The Sicilian fold-and-thrust belt is located in the central Mediterranean area, and it represents the south-eastern arcuate segment of the Apennine-Maghrebide orogen. The tectonic evolution of the Sicilian belt is documented after outcrop analysis of small-scale structural features carried out throughout the region. Results are consistent with the following four main deformation stages having affected the study area, from the oldest to the youngest: (i) multilayer weakening; (ii) folding-and-thrusting, (iii) extension, and (iv) renewed thrusting. The first deformation stage included three different substages (layer-parallel shortening, bed-parallel simple shear and fold nucleation), the second one by both thrusting and fold amplification and tightening. The third deformation stage involved re-activation of the pre-existing mechanical discontinuities and formation of low-to-high angle normal faults. Out-of-sequence thrusting postdated the aforementioned extensional stage, and formed the latest orogenic deformation stage that affected the Sicilian belt.

  2. Let Them Fold

    ERIC Educational Resources Information Center

    Grant, Nicholas; Tobin, Alexander

    1972-01-01

    Directions are given for seven activities involving the folding of paper strips to illustrate geometric concepts. Properties of pentagons, triangles, hexagons, and Mobius bands resulting from the various foldings are discussed. (DT)

  3. Kinematics and thermodynamics of a folding heteropolymer.

    PubMed Central

    Fukugita, M; Lancaster, D; Mitchard, M G

    1993-01-01

    In order to elucidate the folding dynamics of protein, we have carried out numerical simulations of a heteropolymer model of self-interacting random chains. We find that folding propensity depends strongly on sequence and that both folding and nonfolding sequences exist. Furthermore we show that folding is a two-step process: the transition from coil state to unique folded state takes place through a globule phase. In addition to the continuous coil-globule transition, there exists an abrupt transition that separates the unique folded state from the globule state and ensures the stability of the native state. PMID:8327518

  4. Fast events in protein folding

    SciTech Connect

    Woodruff, W.; Callender, R.; Causgrove, T.; Dyer, R.; Williams, S.

    1996-04-01

    The primary objective of this work was to develop a molecular understanding of how proteins achieve their native three-dimensional (folded) structures. This requires the identification and characterization of intermediates in the protein folding process on all relevant timescales, from picoseconds to seconds. The short timescale events in protein folding have been entirely unknown. Prior to this work, state-of-the-art experimental approaches were limited to milliseconds or longer, when much of the folding process is already over. The gap between theory and experiment is enormous: current theoretical and computational methods cannot realistically model folding processes with lifetimes longer than one nanosecond. This unique approach to employ laser pump-probe techniques that combine novel methods of laser flash photolysis with time-resolved vibrational spectroscopic probes of protein transients. In this scheme, a short (picosecond to nanosecond) laser photolysis pulse was used to produce an instantaneous pH or temperature jump, thereby initiating a protein folding or unfolding reaction. Structure-specific, time-resolved vibrational probes were then used to identify and characterize protein folding intermediates.

  5. An FFT-based method for modeling protein folding and binding under crowding: benchmarking on ellipsoidal and all-atom crowders.

    PubMed

    Qin, Sanbo; Zhou, Huan-Xiang

    2013-10-01

    It is now well recognized that macromolecular crowding can exert significant effects on protein folding and binding stability. In order to calculate such effects in direct simulations of proteins mixed with bystander macromolecules, the latter (referred to as crowders) are usually modeled as spheres and the proteins represented at a coarse-grained level. Our recently developed postprocessing approach allows the proteins to be represented at the all-atom level but, for computational efficiency, has only been implemented for spherical crowders. Modeling crowder molecules in cellular environments and in vitro experiments as spheres may distort their effects on protein stability. Here we present a new method that is capable for treating aspherical crowders. The idea, borrowed from protein-protein docking, is to calculate the excess chemical potential of the proteins in crowded solution by fast Fourier transform (FFT). As the first application, we studied the effects of ellipsoidal crowders on the folding and binding free energies of all-atom proteins, and found, in agreement with previous direct simulations with coarse-grained protein models, that the aspherical crowders exert greater stabilization effects than spherical crowders of the same volume. Moreover, as demonstrated here, the FFT-based method has the important property that its computational cost does not increase strongly even when the level of details in representing the crowders is increased all the way to all-atom, thus significantly accelerating realistic modeling of protein folding and binding in cell-like environments. PMID:24187527

  6. Comparison of alternative representations of hydraulic-conductivity anisotropy in folded fractured-sedimentary rock: Modeling groundwater flow in the Shenandoah Valley (USA)

    USGS Publications Warehouse

    Yager, R.M.; Voss, C.I.; Southworth, S.

    2009-01-01

    A numerical representation that explicitly represents the generalized three-dimensional anisotropy of folded fractured-sedimentary rocks in a groundwater model best reproduces the salient features of the flow system in the Shenandoah Valley, USA. This conclusion results from a comparison of four alternative representations of anisotropy in which the hydraulic-conductivity tensor represents the bedrock structure as (model A) anisotropic with variable strikes and dips, (model B) horizontally anisotropic with a uniform strike, (model C) horizontally anisotropic with variable strikes, and (model D) isotropic. Simulations using the US Geological Survey groundwater flow and transport model SUTRA are based on a representation of hydraulic conductivity that conforms to bedding planes in a three-dimensional structural model of the valley that duplicates the pattern of folded sedimentary rocks. In the most general representation, (model A), the directions of maximum and medium hydraulic conductivity conform to the strike and dip of bedding, respectively, while the minimum hydraulic-conductivity direction is perpendicular to bedding. Model A produced a physically realistic flow system that reflects the underlying bedrock structure, with a flow field that is significantly different from those produced by the other three models. ?? Springer-Verlag 2009.

  7. Improving protein fold recognition by random forest

    PubMed Central

    2014-01-01

    Background Recognizing the correct structural fold among known template protein structures for a target protein (i.e. fold recognition) is essential for template-based protein structure modeling. Since the fold recognition problem can be defined as a binary classification problem of predicting whether or not the unknown fold of a target protein is similar to an already known template protein structure in a library, machine learning methods have been effectively applied to tackle this problem. In our work, we developed RF-Fold that uses random forest - one of the most powerful and scalable machine learning classification methods - to recognize protein folds. Results RF-Fold consists of hundreds of decision trees that can be trained efficiently on very large datasets to make accurate predictions on a highly imbalanced dataset. We evaluated RF-Fold on the standard Lindahl's benchmark dataset comprised of 976 × 975 target-template protein pairs through cross-validation. Compared with 17 different fold recognition methods, the performance of RF-Fold is generally comparable to the best performance in fold recognition of different difficulty ranging from the easiest family level, the medium-hard superfamily level, and to the hardest fold level. Based on the top-one template protein ranked by RF-Fold, the correct recognition rate is 84.5%, 63.4%, and 40.8% at family, superfamily, and fold levels, respectively. Based on the top-five template protein folds ranked by RF-Fold, the correct recognition rate increases to 91.5%, 79.3% and 58.3% at family, superfamily, and fold levels. Conclusions The good performance achieved by the RF-Fold demonstrates the random forest's effectiveness for protein fold recognition. PMID:25350499

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

    NASA Astrophysics Data System (ADS)

    Pappu, Rohit V.; Nussinov, Ruth

    2009-03-01

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

  9. Tectonic models for the Patagonian orogenic curve (southernmost Andes): An appraisal based on analog experiments from the Fuegian thrust-fold belt

    NASA Astrophysics Data System (ADS)

    Torres Carbonell, Pablo J.; Guzmán, Cecilia; Yagupsky, Daniel; Dimieri, Luis V.

    2016-03-01

    Tectonic models for the evolution of the Patagonian orogenic curve were evaluated using analog experiments that considered either a rotational or a non-rotational orogenic backstop, combined with a basement promontory on the foreland cratonic margin. Five different kinematic configurations were used, aiming to evaluate the influence of the Río Chico Arc as a rigid obstacle on the evolution of the Fuegian thrust-fold belt. Rotations, strains and displacement fields obtained from each analog experiment were compared with the structural geology known from the Fuegian thrust-fold belt, in order to appraise the tectonic models that are more consistent with the natural structure. The push of a counterclockwise rotational backstop, combined with the buttressing effect of a foreland promontory, seem of major importance in controlling the final structure and map-view shape of the thrust wedge.

  10. Observation and analysis of in vivo vocal fold tissue instabilities produced by nonlinear source-filter coupling: A case studya

    PubMed Central

    Zañartu, Matías; Mehta, Daryush D.; Ho, Julio C.; Wodicka, George R.; Hillman, Robert E.

    2011-01-01

    Different source-related factors can lead to vocal fold instabilities and bifurcations referred to as voice breaks. Nonlinear coupling in phonation suggests that changes in acoustic loading can also be responsible for this unstable behavior. However, no in vivo visualization of tissue motion during these acoustically induced instabilities has been reported. Simultaneous recordings of laryngeal high-speed videoendoscopy, acoustics, aerodynamics, electroglottography, and neck skin acceleration are obtained from a participant consistently exhibiting voice breaks during pitch glide maneuvers. Results suggest that acoustically induced and source-induced instabilities can be distinguished at the tissue level. Differences in vibratory patterns are described through kymography and phonovibrography; measures of glottal area, open∕speed quotient, and amplitude∕phase asymmetry; and empirical orthogonal function decomposition. Acoustically induced tissue instabilities appear abruptly and exhibit irregular vocal fold motion after the bifurcation point, whereas source-induced ones show a smoother transition. These observations are also reflected in the acoustic and acceleration signals. Added aperiodicity is observed after the acoustically induced break, and harmonic changes appear prior to the bifurcation for the source-induced break. Both types of breaks appear to be subcritical bifurcations due to the presence of hysteresis and amplitude changes after the frequency jumps. These results are consistent with previous studies and the nonlinear source-filter coupling theory. PMID:21303014

  11. Numerical study of human vocal folds vibration using Immersed Finite Element Method

    NASA Astrophysics Data System (ADS)

    Wang, Xingshi; Zhang, Lucy; Krane, Michael

    2011-11-01

    The voice production procedure is a self-oscillating, fluid-structure interaction problem. In this study, the vocal folds vibration during phonation will be simulated by self-oscillated layered-structure vocal folds model, using Immersed Finite Element Method. With the numerical results, we will find out the vocal folds vibration pattern, and also show how the lung pressure, stiffness and geometry of vocal folds will affect the vocal folds vibration. With further analysis, we shall get better understanding of the dynamics of voice production. National Institute on Deafness and Other Communication Disorders.

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

    PubMed

    Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

    2016-07-01

    Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules. PMID:27394096

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

    NASA Astrophysics Data System (ADS)

    Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang

    2016-07-01

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

  14. Petroleum generation and migration in the Mesopotamian Basin and Zagros fold belt of Iraq: Results from a basin-modeling study

    USGS Publications Warehouse

    Pitman, J.K.; Steinshouer, D.; Lewan, M.D.

    2004-01-01

    A regional 3-D total petroleum-system model was developed to evaluate petroleum generation and migration histories in the Mesopotamian Basin and Zagros fold belt in Iraq. The modeling was undertaken in conjunction with Middle East petroleum assessment studies conducted by the USGS. Regional structure maps, isopach and facies maps, and thermal maturity data were used as input to the model. The oil-generation potential of Jurassic source-rocks, the principal known source of the petroleum in Jurassic, Cretaceous, and Tertiary reservoirs in these regions, was modeled using hydrous pyrolysis (Type II-S) kerogen kinetics. Results showed that oil generation in source rocks commenced in the Late Cretaceous in intrashelf basins, peak expulsion took place in the late Miocene and Pliocene when these depocenters had expanded along the Zagros foredeep trend, and generation ended in the Holocene when deposition in the foredeep ceased. The model indicates that, at present, the majority of Jurassic source rocks in Iraq have reached or exceeded peak oil generation and most rocks have completed oil generation and expulsion. Flow-path simulations demonstrate that virtually all oil and gas fields in the Mesopotamian Basin and Zagros fold belt overlie mature Jurassic source rocks (vertical migration dominated) and are situated on, or close to, modeled migration pathways. Fields closest to modeled pathways associated with source rocks in local intrashelf basins were charged earliest from Late Cretaceous through the middle Miocene, and other fields filled later when compression-related traps were being formed. Model results confirm petroleum migration along major, northwest-trending folds and faults, and oil migration loss at the surface.

  15. Protein folding in a force-clamp

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Szymczak, Piotr

    2006-03-01

    Kinetics of folding of a protein held in a force-clamp are compared to an unconstrained folding. The comparison is made within a simple topology-based dynamical model of ubiquitin. We demonstrate that the experimentally observed rapid changes in the end-to-end distance mirror microscopic events during folding. However, the folding scenarios in and out of the force-clamp are distinct.

  16. Chevron folding patterns and heteroclinic orbits

    NASA Astrophysics Data System (ADS)

    Budd, Christopher J.; Chakhchoukh, Amine N.; Dodwell, Timothy J.; Kuske, Rachel

    2016-09-01

    We present a model of multilayer folding in which layers with bending stiffness EI are separated by a very stiff elastic medium of elasticity k2 and subject to a horizontal load P. By using a dynamical system analysis of the resulting fourth order equation, we show that as the end shortening per unit length E is increased, then if k2 is large there is a smooth transition from small amplitude sinusoidal solutions at moderate values of P to larger amplitude chevron folds, with straight limbs separated by regions of high curvature when P is large. The chevron solutions take the form of near heteroclinic connections in the phase-plane. By means of this analysis, values for P and the slope of the limbs are calculated in terms of E and k2.

  17. Native and non-native structure in a protein-folding intermediate: spectroscopic studies of partially reduced IGF-I and an engineered alanine model.

    PubMed

    Hua, Q X; Narhi, L; Jia, W; Arakawa, T; Rosenfeld, R; Hawkins, N; Miller, J A; Weiss, M A

    1996-06-01

    The structure of a metastable folding intermediate of human insulin-like growth factor I (IGF-I) and an engineered model are investigated by circular dichroism and two-dimensional 1H NMR spectroscopy. The intermediate, which contains two of three native disulfide bonds, was trapped by acid quenching and isolated by reverse-phase HPLC. The reduced cysteine residues were mapped to residues 47 and 52 (corresponding to A6-A11 in insulin). In the native state this disulfide bridge anchors an adjoining amphipathic alpha-helix (helix 2; residues 42 to 49) against the hydrophobic core. Comparison of CD and 1H-NMR spectra demonstrates that the acid-quenched intermediate is partially folded and contains elements of native secondary and tertiary structure. Spectra are similar to those of an equilibrium model in which the reduced cysteine residues are replaced by alanine. Complete 1H-NMR sequential assignment of the alanine model has been obtained and demonstrates that removal of the disulfide bond is associated with local unfolding of the adjoining alpha-helix. Native secondary structure (including helices 1 and 3) is otherwise retained and defines a folded subdomain. Long-range nuclear Overhauser effects (NOE) within this subdomain are similar to those of native IGF-I; no non-native NOE is observed. Our results support the hypothesis that folding of the insulin motif is directed by a subset of native structural elements and that these elements form at an early step in the pathway. Formation of helix 2, despite its prominence in the native state, is likely to represent a late step. Hydrophobic collapse of this segment appears to precede helix formation. PMID:8656430

  18. Automatic colonic fold segmentation for computed tomography colonography

    NASA Astrophysics Data System (ADS)

    Zhu, Hongbin; Barish, Matthew; Li, Lihong; Song, Bowen; Harrington, Donald; Pickhardt, Perry; Liang, Zhengrong

    2012-03-01

    Human colon has complex structures mostly because of the haustral folds. Haustral folds are thin flat protrusions on the colon wall, which inherently attached on the colon wall. These structures may complicate the shape analysis for computer-aided detection of colonic polyps (CADpolyp); however, they can serve as solid reference during image interpretation in computed tomographic colonography (CTC). Therefore, in this study, based on a clear model of the haustral fold boundaries, we employ level set method to automatically segment the fold surfaces. We believe the segmented folds have the potential to significantly benefit various post-procedures in CTC, e.g., supine-prone registration, synchronized image interpretation, automatic polyp matching, CADpolyp, teniae coli extraction, etc. For the first time, with assistance from physician experts, we established the ground truth of haustral fold boundaries of 15 real patient data from two medical centers, based on which we evaluated our algorithm. The results demonstrated that about 92.7% of the folds are successfully detected. Furthermore, we explored the segmented area ratio (SAR), i.e., the ratio between the areas of the intersection and the union of the expert-drawn and the automatically-segmented folds, to measure the accuracy of the segmentation algorithm. The averaged result of SAR=86.2% shows a good match between the ground truth and our segmentation results.

  19. Targeting Fold Stiffness to Design Enhanced Origami Structures

    NASA Astrophysics Data System (ADS)

    Buskohl, Philip; Bazzan, Giorgio; Abbott, Andrew; Durstock, Michael; Vaia, Richard

    2014-03-01

    Structures with adaptive geometry are increasingly of interest for actuation, sensing and packaging applications. Origami structures, by definition, can ``shape-shift'' between multiple geometric configurations that are predefined by a pattern of folds. Plastic deformation and local failure at the fold lines transform an originally homogenous material into a grid with locally tailored mechanical properties that bias the response of the overall structure to external loading. Typically, origami structures focus on uniformly stiff fold lines with rigid facets. In this study, we discuss how localized variations in stiffness can influence global properties, including energy budget to transition from flat to folded structure, the preferred path through configuration space, and the final mechanical response of the folded architecture. A simple, bi-stable origami fold pattern is laser machined into polypropylene sheets of different compliance and the critical load of the transition is measured. We model the structure as a truss with bar elongation, folding, and facet bending in order to predict ways to enhance or mitigate the critical load. Targeting local folding properties to modify global performance directly extends to the analysis of more complex architectures.

  20. 3D fold and fault reconstruction with an uncertainty model: An example from an Alpine tunnel case study

    NASA Astrophysics Data System (ADS)

    Bistacchi, Andrea; Massironi, Matteo; Dal Piaz, Giorgio V.; Dal Piaz, Giovanni; Monopoli, Bruno; Schiavo, Alessio; Toffolon, Giovanni

    2008-04-01

    In order to improve the railway connection between Austria and Italy, a base tunnel, extending from Fortezza to Innsbruck (57 km), is under study. The design corridor crosscuts a large and strongly tectonized section of the Eastern Alpine chain, characterized by complex metamorphic and igneous lithology and polyphase structures developed under ductile to brittle deformation conditions. In order to model the sub-surface geology of the area, surface and sub-surface geological data have been integrated in a spatial database. 3D geological models of the Italian part of the corridor have been constructed on the basis of this data using two approaches. The first is a more traditional approach, involving the reconstruction of several parallel and intersecting cross-sections. It has been implemented using ArcGIS ® software with custom-developed scripts that enable one to automatically project structural data, collected at the surface and along boreholes, onto cross-sections. The projection direction can be controlled and is based on structural trends obtained from a detailed statistical analysis of orientation data. Other ArcGIS ® scripts enable linking of the network of crosscutting profiles and help to secure their consistency. The second approach involves the compilation of a true 3D geological model in gOcad ®. As far as time efficiency and visualization are concerned, the second approach is more powerful. The basic structural geology assumptions, however, are similar to those applied in the first approach. In addition to the 3D model, compilation scripts (ArcGIS ® and gOcad ®) have been developed, which allow estimation of the uncertainties in the depth extrapolation of structures observed at the surface or along boreholes. These scripts permit the assignment of each projected structural element (i.e., geological boundaries, faults and shear zones) to a parameter estimating reliability. Basic differences between "data-driven" interpolation and "knowledge

  1. COS Side 2 NUV MAMA Fold Test

    NASA Astrophysics Data System (ADS)

    Bacinski, John

    2013-10-01

    The performance of the 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 MAMA Fold Analysis {13128} during Cycle 20.This proposal is an exact duplication of nominal COS MAMA Fold Analysis {proposal 13128, Cycle 20}. Any changes 13128 or subsequent cycle submissions should be reflected in this proposal and vice versa.

  2. Acoustooptical spectrum analysis modeling

    NASA Astrophysics Data System (ADS)

    Carmody, M. J.

    1981-06-01

    A summary of Bragg deflection theory and various approaches to direct detection acoustooptic spectrum analysis (AOSA) modeling is presented. A suitable model is chosen and extended to include the effects of diffraction efficiency, transducer efficiency, irradiance profiles of incident laser illumination, aperture size of the Bragg cell, and the acoustic attenuation experienced by the acoustic wavetrain generated by the input r-f signal. A FORTRAN program is developed to model the AOSA and predict the output image plane intensity profiles. A second version of the program includes a time variable permitting dynamic simulation of the system response.

  3. Multiscale tectonic analysis of the basement-involved Malargüe fold-and-thrust-belt, Northern Neuquén Basin, (Argentina).

    NASA Astrophysics Data System (ADS)

    Branellec, Matthieu; Callot, Jean-Paul; Nivière, Bertrand; Aubourg, Charles; Ringenbach, Jean-Claude

    2015-04-01

    The Malargüe fold-and-thrust-belt (MFTB), which is located in the northern part of the Neuquén basin (Argentina), is known as a basement-involved orogenic wedge. The results presented here aim to make the link between the macroscopic structure and the strain record at both mesoscopic and microscopic scales (i.e damage). The cross-sections we produced show that basement contraction is strongly controlled by the extensive structural inheritance localizing deep seated thrusts. The second part of this work is dedicated to mesoscopic strain pattern analysis recorded by fracture networks. Throughout the MFTB, we are able to describe the occurrence of four main fractures sets emplaced in several stress regime that are linked (1) to the inheritance and (2) to the well-known compression phases from pre-folding to syn-folding settings. Finally the third part of this work describes the microscopic damage measured by the anisotropy of magnetic susceptibility. We evidence that there is no clear gradient of magnetic fabric intensity from foreland to hinterland, and that deformation is compartmentalized by structural inheritance and particularly by the localization of basement thrusts. This atypical pattern of magnetic fabrics succession reveals that the matrix damage is governed by the same strain distribution as those observed at macroscopic scale, thus providing a supplementary argument to consider the dynamics of the Andean system, at these latitudes, as singularly different from a classical Coulomb wedge propagation.

  4. Folding of Layers of Finite Length

    NASA Astrophysics Data System (ADS)

    Schmid, D. W.; Podladchikov, Yu. Yu.; Marques, F.

    All existing folding theories assume that the layers are infinitely long or, which is mathematically equivalent, that the compression is directly applied to the lateral boundaries. These assumptions are not always justified for natural geological sys- tems. In fact we can observe that on all scales, from veins to sub-ducting slabs, the layers are of finite length and that there are no distinct, rigid walls pushing the lay- ers from the side. Using the method of Muskhelishvili we have derived the complete two-dimensional solution of an elliptic object embedded in a matrix and subject to far field boundary conditions; pure shear, simple shear and arbitrary combinations thereof. The rheology of the matrix is viscous, the layer may behave either elastically or viscous. Using the values from this background state analysis, stress, pressure and strain rate, we performed the classical linear stability analysis to examine the mech- anism of folding in the described setup. The resulting expressions maximum growth rates and dominant wavelengths are applicable to general geological systems; in the limit of an infinite aspect ratio of the layer the classical expressions of Biot are ob- tained for all other cases new expressions result. Our main results are: 1. Folding of finite length layers is controlled by the ratio of aspect ratio to competence contrast. 2. The described setup explains why in nature only folds can be observed with a rela- tively small wavelength to thickness ratio, suggesting small viscosity contrast 3. The problem of the unknown compressive stress value for the elastic layer is solved. 4. For finite length elastic layers the dominant wavelength selection shows a cubic, instead of square, root dependence. 5. A complete table, describing the folding in all the possible limits is presented and the applicability to natural systems discussed. All the presented results were checked numerically and/or with analogue models.

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

    PubMed Central

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

    2013-01-01

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

  6. Analogue modeling of 3-D structural segmentation in fold-and-thrust belts: interactions between frictional and viscous provinces in foreland basins

    NASA Astrophysics Data System (ADS)

    Borderie, Sandra; Graveleau, Fabien; Witt, César; Vendeville, Bruno C.

    2016-04-01

    Accretionary wedges are generally segmented both across and along strike because of diverse factors including tectonic and stratigraphic inheritance. In fold-and-thrust belts, along-strike stratigraphic changes in the foreland sequence are classically observed and cause a curvature of the deformation front. Although the parameters controlling this curvature are well documented, the structural interactions and mutual influences between adjacent provinces are much less analyzed. To investigate this question, we deformed analogue models in a compressional box equipped with digital cameras and a topographic measurement apparatus. Models where shortened above a basal frictional detachment (glass microbeads) and segmentation was tested by having a region in which we added an interbedded viscous level (silicone polymer) within the sedimentary cover (dry sand). By changing the number (2 or 3) and the relative width of the purely frictional and viscous provinces, our goal was to characterize geometrically and kinematically the interactions between the viscous and the purely frictional provinces. We used a commercial geomodeller to generate 3-D geometrical models. The results indicate that regardless of the relative width of the purely frictional vs. viscous provinces, the deformation style in the frictional province is not influenced by the presence of the adjacent viscous province. On the contrary, the structural style and the deformation kinematics in the viscous province is significantly impacted by the presence or absence of an adjacent purely frictional province. At first order, the deformation style in the viscous province depends on its width, and three structural styles can be defined along strike. Far from the frictional area, structures are primarily of salt-massif type, and they do not seem to be influenced by the frictional wedge province. Towards the frictional province, deformation changes gradually to a zone of purely forethrusts (foreland verging), and

  7. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2013-10-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold distribution procedure. The fold distribution provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of change in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Distribution, Proposal 13149, as Cycle 20.

  8. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2012-10-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold distribution procedure. The fold distribution provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of change in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Distribution, Proposal 12778, as Cycle 19.

  9. Computational Modeling and Analysis of Phonation in a Diseased Larynx

    NASA Astrophysics Data System (ADS)

    Xue, Qian; Zheng, Xudong; Mittal, Rajat; Bielamowicz, Steven

    2009-11-01

    The goal of our current research is to study the fundamental biophysics of phonation in healthy and pathological larynges. We have developed a coupled flow-structure interaction solver to help gain insight into the fundamental biophysics underlying unilateral laryngeal paralysis. The solver models the incompressible Navier-Stokes equations for the glottal aerodynamics and employs the classic two-mass model for the vocal folds. The effect of tension imbalance and subglottal pressure on the vocal fold dynamics is investigated. An analysis of the vibration modes as well as the frequency spectra and sound quality has been conducted. Results from these studies will be presented.

  10. A galaxy of folds.

    PubMed

    Alva, Vikram; Remmert, Michael; Biegert, Andreas; Lupas, Andrei N; Söding, Johannes

    2010-01-01

    Many protein classification systems capture homologous relationships by grouping domains into families and superfamilies on the basis of sequence similarity. Superfamilies with similar 3D structures are further grouped into folds. In the absence of discernable sequence similarity, these structural similarities were long thought to have originated independently, by convergent evolution. However, the growth of databases and advances in sequence comparison methods have led to the discovery of many distant evolutionary relationships that transcend the boundaries of superfamilies and folds. To investigate the contributions of convergent versus divergent evolution in the origin of protein folds, we clustered representative domains of known structure by their sequence similarity, treating them as point masses in a virtual 2D space which attract or repel each other depending on their pairwise sequence similarities. As expected, families in the same superfamily form tight clusters. But often, superfamilies of the same fold are linked with each other, suggesting that the entire fold evolved from an ancient prototype. Strikingly, some links connect superfamilies with different folds. They arise from modular peptide fragments of between 20 and 40 residues that co-occur in the connected folds in disparate structural contexts. These may be descendants of an ancestral pool of peptide modules that evolved as cofactors in the RNA world and from which the first folded proteins arose by amplification and recombination. Our galaxy of folds summarizes, in a single image, most known and many yet undescribed homologous relationships between protein superfamilies, providing new insights into the evolution of protein domains. PMID:19937658

  11. Fast protein folding kinetics

    PubMed Central

    Gelman, Hannah; Gruebele, Martin

    2014-01-01

    Fast folding proteins have been a major focus of computational and experimental study because they are accessible to both techniques: they are small and fast enough to be reasonably simulated with current computational power, but have dynamics slow enough to be observed with specially developed experimental techniques. This coupled study of fast folding proteins has provided insight into the mechanisms which allow some proteins to find their native conformation well less than 1 ms and has uncovered examples of theoretically predicted phenomena such as downhill folding. The study of fast folders also informs our understanding of even “slow” folding processes: fast folders are small, relatively simple protein domains and the principles that govern their folding also govern the folding of more complex systems. This review summarizes the major theoretical and experimental techniques used to study fast folding proteins and provides an overview of the major findings of fast folding research. Finally, we examine the themes that have emerged from studying fast folders and briefly summarize their application to protein folding in general as well as some work that is left to do. PMID:24641816

  12. Stem Cell Therapy in Injured Vocal Folds: A Three-Month Xenograft Analysis of Human Embryonic Stem Cells

    PubMed Central

    Svensson, Bengt; Nagubothu, Srinivasa R.; Nord, Christoffer; Cedervall, Jessica; Hultman, Isabell; Ährlund-Richter, Lars; Tolf, Anna; Hertegård, Stellan

    2015-01-01

    We have previously shown that human embryonic stem cell (hESC) therapy to injured rabbit vocal folds (VFs) induces human tissue generation with regained VF vibratory capacity. The aims of this study were to test the sustainability of such effect and to what extent derivatives of the transplanted hESCs are propagated in the VFs. The VFs of 14 New Zealand rabbits were injured by a localized resection. HESCs were transplanted to 22 VFs which were analyzed for persistence of hESCs after six weeks and after three months. At three months, the VFs were also analyzed for viscoelasticity, measured as dynamic viscosity and elastic modulus, for the lamina propria (Lp) thickness and relative content of collagen type I. Three months after hESC cell therapy, the dynamic viscosity and elastic modulus of the hESC treated VFs were similar to normal controls and lower than untreated VFs (p ≤ 0.011). A normalized VF architecture, reduction in collagen type I, and Lp thickness were found compared with untreated VFs (p ≤ 0.031). At three months, no derivatives of hESCs were detected. HESCs transplanted to injured rabbit VFs restored the vibratory characteristics of the VFs, with maintained restored function for three months without remaining hESCs or derivatives. PMID:26557696

  13. Stem Cell Therapy in Injured Vocal Folds: A Three-Month Xenograft Analysis of Human Embryonic Stem Cells.

    PubMed

    Svensson, Bengt; Nagubothu, Srinivasa R; Nord, Christoffer; Cedervall, Jessica; Hultman, Isabell; Ährlund-Richter, Lars; Tolf, Anna; Hertegård, Stellan

    2015-01-01

    We have previously shown that human embryonic stem cell (hESC) therapy to injured rabbit vocal folds (VFs) induces human tissue generation with regained VF vibratory capacity. The aims of this study were to test the sustainability of such effect and to what extent derivatives of the transplanted hESCs are propagated in the VFs. The VFs of 14 New Zealand rabbits were injured by a localized resection. HESCs were transplanted to 22 VFs which were analyzed for persistence of hESCs after six weeks and after three months. At three months, the VFs were also analyzed for viscoelasticity, measured as dynamic viscosity and elastic modulus, for the lamina propria (Lp) thickness and relative content of collagen type I. Three months after hESC cell therapy, the dynamic viscosity and elastic modulus of the hESC treated VFs were similar to normal controls and lower than untreated VFs (p ≤ 0.011). A normalized VF architecture, reduction in collagen type I, and Lp thickness were found compared with untreated VFs (p ≤ 0.031). At three months, no derivatives of hESCs were detected. HESCs transplanted to injured rabbit VFs restored the vibratory characteristics of the VFs, with maintained restored function for three months without remaining hESCs or derivatives. PMID:26557696

  14. AIR Model Preflight Analysis

    NASA Technical Reports Server (NTRS)

    Tai, H.; Wilson, J. W.; Maiden, D. L.

    2003-01-01

    The atmospheric ionizing radiation (AIR) ER-2 preflight analysis, one of the first attempts to obtain a relatively complete measurement set of the high-altitude radiation level environment, is described in this paper. The primary thrust is to characterize the atmospheric radiation and to define dose levels at high-altitude flight. A secondary thrust is to develop and validate dosimetric techniques and monitoring devices for protecting aircrews. With a few chosen routes, we can measure the experimental results and validate the AIR model predictions. Eventually, as more measurements are made, we gain more understanding about the hazardous radiation environment and acquire more confidence in the prediction models.

  15. Structural analysis of some bis-(8-isopropyl-isoquinolinium) derivatives reveals a preferential folded conformation leading to a stereoselective attack by sodium borohydride

    NASA Astrophysics Data System (ADS)

    Dilly, Sébastien; Badarau, Eduard; Dufour, Fabien; Nistor, Iolanda; Hubert, Philippe; Seutin, Vincent; Wouters, Johan; Liégeois, Jean-François

    2014-09-01

    Reduction of symmetrical bis-isoquinolinium derivatives with sodium borohydride generates normally a mixture of three 1,2,3,4-tetrahydroisoquinoline stereoisomers. In a series of 8-isopropyl analogues, chiral resolution failed for the analogues with propyl and m-xylyl linkers since two and one peaks respectively were detected by HPLC. Further analysis by MS and CD of both peaks of the propyl analogue revealed that each peak corresponds to an enantiomer. Conformational analysis and X-ray cristallography showed a folded conformation of the propyl and m-xylyl analogues responsible for the observed stereoselectivity following the reduction step. Additional 1H NMR investigations confirm structural features detected by theoretical analysis.

  16. Mutational analysis of target enzyme recognition of the beta-trefoil fold barley alpha-amylase/subtilisin inhibitor.

    PubMed

    Bønsager, Birgit C; Nielsen, Peter K; Abou Hachem, Maher; Fukuda, Kenji; Praetorius-Ibba, Mette; Svensson, Birte

    2005-04-15

    The barley alpha-amylase/subtilisin inhibitor (BASI) inhibits alpha-amylase 2 (AMY2) with subnanomolar affinity. The contribution of selected side chains of BASI to this high affinity is discerned in this study, and binding to other targets is investigated. Seven BASI residues along the AMY2-BASI interface and four residues in the putative protease-binding loop on the opposite side of the inhibitor were mutated. A total of 15 variants were compared with the wild type by monitoring the alpha-amylase and protease inhibitory activities using Blue Starch and azoalbumin, respectively, and the kinetics of binding to target enzymes by surface plasmon resonance. Generally, the mutations had little effect on k(on), whereas the k(off) values were increased up to 67-fold. The effects on the inhibitory activity, however, were far more pronounced, and the K(i) values of some mutants on the AMY2-binding side increased 2-3 orders of magnitude, whereas mutations on the other side of the inhibitor had virtually no effect. The mutants K140L, D150N, and E168T lost inhibitory activity, revealing the pivotal role of charge interactions for BASI activity on AMY2. A fully hydrated Ca(2+) at the AMY2-BASI interface mediates contacts to the catalytic residues of AMY2. Mutations involving residues contacting the solvent ligands of this Ca(2+) had weaker affinity for AMY2 and reduced sensitivity to the Ca(2+) modulation of the affinity. These results suggest that the Ca(2+) and its solvation sphere are integral components of the AMY2-BASI complex, thus illuminating a novel mode of inhibition and a novel role for calcium in relation to glycoside hydrolases. PMID:15657043

  17. Multiply folded graphene

    NASA Astrophysics Data System (ADS)

    Kim, Kwanpyo; Lee, Zonghoon; Malone, Brad D.; Chan, Kevin T.; Alemán, Benjamín; Regan, William; Gannett, Will; Crommie, M. F.; Cohen, Marvin L.; Zettl, A.

    2011-06-01

    The folding of paper, hide, and woven fabric has been used for millennia to achieve enhanced articulation, curvature, and visual appeal for intrinsically flat, two-dimensional materials. For graphene, an ideal two-dimensional material, folding may transform it to complex shapes with new and distinct properties. Here, we present experimental results that folded structures in graphene, termed grafold, exist, and their formations can be controlled by introducing anisotropic surface curvature during graphene synthesis or transfer processes. Using pseudopotential-density-functional-theory calculations, we also show that double folding modifies the electronic band structure of graphene. Furthermore, we demonstrate the intercalation of C60 into the grafolds. Intercalation or functionalization of the chemically reactive folds further expands grafold's mechanical, chemical, optical, and electronic diversity.

  18. X-ray diffraction analysis of scrapie prion: intermediate and folded structures in a peptide containing two putative alpha-helices.

    PubMed

    Inouye, H; Kirschner, D A

    1997-05-01

    Small proteinaceous infectious particles called prions cause certain neurodegenerative diseases in human and animals. Limited proteolysis of infectious scrapie prions PrP(Sc) yields an N-truncated polypeptide termed PrP 27-30, which encompasses residues 90 to 231 of PrP(Sc) and which assembles into 100 to 200 A wide amyloid rods. It has been hypothesized that the infectious prion is converted from its non-infectious cellular form (PrP(C)) by means of an alpha-helical to beta-sheet conformational change. Secondary structure analysis, computer modeling, and structural biophysics methods support this hypothesis. Residues 90 to 145 of PrP, which contain two putative alpha-helical domains H1 and H2, may be of particular relevance to the disease pathogenesis, as C-terminal truncation at residue 145 was found in a patient with an inherited prion disease. Moreover, our recent X-ray diffraction analysis suggests that the peptide consisting of these residues (designated SHa 90-145) closely models the amyloidogenic beta-sheet core of PrP. In the current study, we have analyzed in detail the X-ray diffraction patterns of SHa 90-145. Two samples were examined: one that was dehydrated under ambient conditions whilst in an external magnetic field (to induce fibril orientation), and another that was sealed after partial drying. The dried, magnetically oriented sample showed a cross-beta diffraction pattern in which the fiber axis (rotation axis) was parallel to the H-bonding direction of the beta-sheets. The major wide-angle peaks indicate the presence of approximately 40 A wide beta-crystallites, which constitute the protofilament. Each crystallite is composed of several orthogonal unit cells, normal to the fiber (a-axis) direction, having lattice constants a = 9.69 A, b = 6.54 A, and c = 18.06 A. Electron density maps were calculated by iterative Fourier synthesis using beta-silk as an initial phase model. The distribution of density indicated that there were two types of beta

  19. Folding of a finite length power law layer

    NASA Astrophysics Data System (ADS)

    Schmid, Daniel W.; Podladchikov, Yuri Y.; Marques, Fernando O.

    2004-03-01

    Folding of an isolated finite length power law layer embedded in a Newtonian viscous matrix is investigated and compared to conventional folding experiments where the layer is of infinite length or in direct contact with lateral boundaries. The approach employed is a combination of the complex potential method for the basic state and the thin plate approximation for the linear stability analysis and is verified by finite element models. The resulting theory reveals that the aspect ratio of a layer has a first-order influence on the development of folds. The aspect ratio competes with the effective viscosity contrast for dominant influence on the folding process. If the aspect ratio is substantially larger than the effective viscosity contrast, the conventional theories are applicable. In other situations, where the aspect ratio is smaller than the effective viscosity contrast, substantial corrections must be taken into account, which lead to a new folding mode that is mainly characterized by decreasing growth rates with increasing effective viscosity contrast (relative to the far-field shortening rate). This new folding mode helps explain the absence of large wavelength to thickness ratio folds in nature, which may be due to the limitations of aspect ratios rather than large effective viscosity contrasts.

  20. Rapid compaction during RNA folding

    NASA Astrophysics Data System (ADS)

    Russell, Rick; Millett, Ian S.; Tate, Mark W.; Kwok, Lisa W.; Nakatani, Bradley; Gruner, Sol M.; Mochrie, Simon G. J.; Pande, Vijay; Doniach, Sebastian; Herschlag, Daniel; Pollack, Lois

    2002-04-01

    We have used small angle x-ray scattering and computer simulations with a coarse-grained model to provide a time-resolved picture of the global folding process of the Tetrahymena group I RNA over a time window of more than five orders of magnitude. A substantial phase of compaction is observed on the low millisecond timescale, and the overall compaction and global shape changes are largely complete within one second, earlier than any known tertiary contacts are formed. This finding indicates that the RNA forms a nonspecifically collapsed intermediate and then searches for its tertiary contacts within a highly restricted subset of conformational space. The collapsed intermediate early in folding of this RNA is grossly akin to molten globule intermediates in protein folding.

  1. Nonlinear dynamic mechanism of vocal tremor from voice analysis and model simulations

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Jiang, Jack J.

    2008-09-01

    Nonlinear dynamic analysis and model simulations are used to study the nonlinear dynamic characteristics of vocal folds with vocal tremor, which can typically be characterized by low-frequency modulation and aperiodicity. Tremor voices from patients with disorders such as paresis, Parkinson's disease, hyperfunction, and adductor spasmodic dysphonia show low-dimensional characteristics, differing from random noise. Correlation dimension analysis statistically distinguishes tremor voices from normal voices. Furthermore, a nonlinear tremor model is proposed to study the vibrations of the vocal folds with vocal tremor. Fractal dimensions and positive Lyapunov exponents demonstrate the evidence of chaos in the tremor model, where amplitude and frequency play important roles in governing vocal fold dynamics. Nonlinear dynamic voice analysis and vocal fold modeling may provide a useful set of tools for understanding the dynamic mechanism of vocal tremor in patients with laryngeal diseases.

  2. Predicting RNA pseudoknot folding thermodynamics.

    PubMed

    Cao, Song; Chen, Shi-Jie

    2006-01-01

    Based on the experimentally determined atomic coordinates for RNA helices and the self-avoiding walks of the P (phosphate) and C4 (carbon) atoms in the diamond lattice for the polynucleotide loop conformations, we derive a set of conformational entropy parameters for RNA pseudoknots. Based on the entropy parameters, we develop a folding thermodynamics model that enables us to compute the sequence-specific RNA pseudoknot folding free energy landscape and thermodynamics. The model is validated through extensive experimental tests both for the native structures and for the folding thermodynamics. The model predicts strong sequence-dependent helix-loop competitions in the pseudoknot stability and the resultant conformational switches between different hairpin and pseudoknot structures. For instance, for the pseudoknot domain of human telomerase RNA, a native-like and a misfolded hairpin intermediates are found to coexist on the (equilibrium) folding pathways, and the interplay between the stabilities of these intermediates causes the conformational switch that may underlie a human telomerase disease. PMID:16709732

  3. Modelling the role of basement block rotation and strike-slip faulting on structural pattern in the cover units of fold-and-thrust belts

    NASA Astrophysics Data System (ADS)

    Koyi, Hemin; Nilfouroushan, Faramarz; Hessami, Khaled

    2015-04-01

    A series of scaled analogue models are run to study the degree of coupling between basement block kinematics and cover deformation. In these models, rigid basal blocks were rotated about vertical axis in a "bookshelf" fashion, which caused strike-slip faulting along the blocks and, to some degrees, in the overlying cover units of loose sand. Three different combinations of cover basement deformations are modeled; cover shortening prior to basement fault movement; basement fault movement prior to shortening of cover units; and simultaneous cover shortening with basement fault movement. Model results show that the effect of basement strike-slip faults depends on the timing of their reactivation during the orogenic process. Pre- and syn-orogen basement strike-slip faults have a significant impact on the structural pattern of the cover units, whereas post-orogenic basement strike-slip faults have less influence on the thickened hinterland of the overlying fold-and-thrust belt. The interaction of basement faulting and cover shortening results in formation of rhomb features. In models with pre- and syn-orogen basement strike-slip faults, rhomb-shaped cover blocks develop as a result of shortening of the overlying cover during basement strike-slip faulting. These rhombic blocks, which have resemblance to flower structures, differ in kinematics, genesis and structural extent. They are bounded by strike-slip faults on two opposite sides and thrusts on the other two sides. In the models, rhomb-shaped cover blocks develop as a result of shortening of the overlying cover during basement strke-slip faulting. Such rhomb features are recognized in the Alborz and Zagros fold-and-thrust belts where cover units are shortened simultaneously with strike-slip faulting in the basement. Model results are also compared with geodetic results obtained from combination of all available GPS velocities in the Zagros and Alborz FTBs. Geodetic results indicate domains of clockwise and

  4. How the genome folds

    NASA Astrophysics Data System (ADS)

    Lieberman Aiden, Erez

    2012-02-01

    I describe Hi-C, a novel technology for probing the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. Working with collaborators at the Broad Institute and UMass Medical School, we used Hi-C to construct spatial proximity maps of the human genome at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

  5. SDI CFD MODELING ANALYSIS

    SciTech Connect

    Lee, S.

    2011-05-05

    The Savannah River Remediation (SRR) Organization requested that Savannah River National Laboratory (SRNL) develop a Computational Fluid Dynamics (CFD) method to mix and blend the miscible contents of the blend tanks to ensure the contents are properly blended before they are transferred from the blend tank; such as, Tank 50H, to the Salt Waste Processing Facility (SWPF) feed tank. The work described here consists of two modeling areas. They are the mixing modeling analysis during miscible liquid blending operation, and the flow pattern analysis during transfer operation of the blended liquid. The transient CFD governing equations consisting of three momentum equations, one mass balance, two turbulence transport equations for kinetic energy and dissipation rate, and one species transport were solved by an iterative technique until the species concentrations of tank fluid were in equilibrium. The steady-state flow solutions for the entire tank fluid were used for flow pattern analysis, for velocity scaling analysis, and the initial conditions for transient blending calculations. A series of the modeling calculations were performed to estimate the blending times for various jet flow conditions, and to investigate the impact of the cooling coils on the blending time of the tank contents. The modeling results were benchmarked against the pilot scale test results. All of the flow and mixing models were performed with the nozzles installed at the mid-elevation, and parallel to the tank wall. From the CFD modeling calculations, the main results are summarized as follows: (1) The benchmark analyses for the CFD flow velocity and blending models demonstrate their consistency with Engineering Development Laboratory (EDL) and literature test results in terms of local velocity measurements and experimental observations. Thus, an application of the established criterion to SRS full scale tank will provide a better, physically-based estimate of the required mixing time, and

  6. Double folding analysis of 3He elastic and inelastic scattering to low lying states on 90Zr, 116Sn and 208Pb at 270 MeV

    NASA Astrophysics Data System (ADS)

    Marwa, N. El-Hammamy

    2015-03-01

    The experimental data on elastic and inelastic scattering of 270 MeV 3He particles to several low lying states in 90Zr, 116Sn and 208Pb are analyzed within the double folding model (DFM). Fermi density distribution (FDD) of target nuclei is used to obtain real potentials with different powers. DF results are introduced into a modified DWUCK4 code to calculate the elastic and inelastic scattering cross sections. Two choices of potentials form factors are used; Woods Saxon (WS) and Woods Saxon Squared (WS2) for real potential, while the imaginary part is taken as phenomenological Woods Saxon (PWS) and phenomenological Woods Saxon Squared (PWS2). This comparison provides information about the similarities and differences of the models used in calculations.

  7. Folding with thermal-mechanical feedback: Discussion

    NASA Astrophysics Data System (ADS)

    Treagus, Susan H.; Hudleston, Peter J.

    2009-07-01

    A recent paper in this Journal by Bruce Hobbs, Klaus Regenauer-Lieb and Alison Ord [Hobbs, B., Regenauer-Lieb, K., Ord, A., 2008. Folding with thermal-mechanical feedback. Journal of Structural Geology 30, 1572-1592] presents an alternative theory to the traditional Biot-Ramberg theory for folding of viscous rocks that involves non-equilibrium thermodynamics and thermal-mechanical feedback. The authors convey a strong message throughout their paper that the folds produced by this theoretical and numerical modelling are geologically realistic and provide a better explanation for many natural folds than the traditional theory. They promise the same approach for boudinage, and present this folding paper as part of a "unified framework for rock deformation processes". Readers of the Journal of Structural Geology might be led to conclude that this paper provides a good alternative model for folding of rocks. Our discussion will disagree, on four counts.

  8. Multiscale modeling of cellular epigenetic states: stochasticity in molecular networks, chromatin folding in cell nuclei, and tissue pattern formation of cells

    PubMed Central

    Liang, Jie; Cao, Youfang; Gürsoy, Gamze; Naveed, Hammad; Terebus, Anna; Zhao, Jieling

    2016-01-01

    Genome sequences provide the overall genetic blueprint of cells, but cells possessing the same genome can exhibit diverse phenotypes. There is a multitude of mechanisms controlling cellular epigenetic states and that dictate the behavior of cells. Among these, networks of interacting molecules, often under stochastic control, depending on the specific wirings of molecular components and the physiological conditions, can have a different landscape of cellular states. In addition, chromosome folding in three-dimensional space provides another important control mechanism for selective activation and repression of gene expression. Fully differentiated cells with different properties grow, divide, and interact through mechanical forces and communicate through signal transduction, resulting in the formation of complex tissue patterns. Developing quantitative models to study these multi-scale phenomena and to identify opportunities for improving human health requires development of theoretical models, algorithms, and computational tools. Here we review recent progress made in these important directions. PMID:27480462

  9. The structural evolution of sheath folds: A case study from Cap de Creus

    NASA Astrophysics Data System (ADS)

    Alsop, G. I.; Carreras, J.

    2007-12-01

    It has long been recognised that within zones of intense non-coaxial deformation, fold hinges may rotate progressively towards the transport direction ultimately resulting in highly curvilinear sheath folds. However, there is a surprising lack of detailed and systematic field analysis of such "evolving" sheath folds. This case study therefore focuses on the sequential development of cm-scale curvilinear folds in the greenschist-facies El Llimac shear zone, Cap de Creus, Spain. This simple shear-dominated dextral shear zone displays superb three dimensional exposures of sheath folds defined by mylonitic quartz bands within phyllonite. Increasing amounts of fold hinge curvature ( δ) are marked by hinge segments rotating into sub-parallelism with the mineral lineation (Lm), whilst the acute angle between the axial-planar hinge girdle and foliation ( ω) also displays a sequential reduction. Although Lm bisects the noses of sheath folds, it is also clearly folded and wrapped-around the sheath hinges. Lm typically preserves a larger angle ( θ) with the fold hinge on the lower limb ( L) compared to the upper ( U) limb ( θL > θU), suggesting that Lm failed to achieve a steady orientation on the lower limb. Adjacent sheath fold hinges forming fold pairs may display the same sense of hinge arcing to define synthetic curvature, or alternatively opposing directions of antithetic curvature. Such patterns reflect original buckle fold geometries coupled with the direction of shearing. The ratio of long/short fold limbs decreases with increasing hinge curvilinearity, indicating sheath folds developed via stretching of the short limb, rather than migrating or rolling hinge models. This study unequivocally demonstrates that both hinges of fold pairs become curvilinear with sheaths closing in the transport direction recording greater hinge-line curvilinearity compared to adjacent return hinges. This may provide a useful guide to bulk shear sense.

  10. A hydrodynamic view of the first-passage folding of Trp-cage miniprotein.

    PubMed

    Andryushchenko, Vladimir A; Chekmarev, Sergei F

    2016-04-01

    We study folding of Trp-cage miniprotein in the conditions when the native state of the protein is stable and unfolding events are improbable, which corresponds to physiological conditions. Using molecular dynamics simulations with an implicit solvent model, an ensemble of folding trajectories from unfolded (practically extended) states of the protein to the native state was generated. To get insight into the folding kinetics, the free energy surface and kinetic network projected on this surface were constructed. This, "conventional" analysis of the folding reaction was followed by a recently proposed hydrodynamic description of protein folding (Chekmarev et al. in Phys Rev Lett 100(1):018107, 2008), in which the process of the first-passage folding is viewed as a stationary flow of a folding "fluid" from the unfolded to native state. This approach is conceptually different from the previously used approaches and thus allows an alternative view of the folding dynamics and kinetics of Trp-cage, the conclusions about which are very diverse. In agreement with most previous studies, we observed two characteristic folding pathways: in one pathway (I), the collapse of the hydrophobic core precedes the formation of the [Formula: see text]-helix, and in the other pathway (II), these events occur in the reverse order. We found that although pathway II is complicated by a repeated partial protein unfolding, it contributes to the total folding flow as little as ≈10%, so that the folding kinetics remain essentially single-exponential. PMID:26559408

  11. Folded supersymmetry with a twist

    NASA Astrophysics Data System (ADS)

    Cohen, Timothy; Craig, Nathaniel; Lou, Hou Keong; Pinner, David

    2016-03-01

    Folded supersymmetry ( f-SUSY) stabilizes the weak scale against radiative corrections from the top sector via scalar partners whose gauge quantum numbers differ from their Standard Model counterparts. This non-trivial pairing of states can be realized in extra-dimensional theories with appropriate supersymmetry-breaking boundary conditions. We present a class of calculable f-SUSY models that are parametrized by a non-trivial twist in 5D boundary conditions and can accommodate the observed Higgs mass and couplings. Although the distinctive phenomenology associated with the novel folded states should provide strong evidence for this mechanism, the most stringent constraints are currently placed by conventional supersymmetry searches. These models remain minimally fine-tuned in light of LHC8 data and provide a range of both standard and exotic signatures accessible at LHC13.

  12. The energy landscape for folding and function

    NASA Astrophysics Data System (ADS)

    Onuchic, Jose

    2006-03-01

    Globally the energy landscape of a folding protein resembles a partially rough funnel. The local roughness of the funnel reflects transient trapping of the protein configurations in local free energy minima. The kinetics of folding is best considered as a progressive organization of an ensemble of partially folded structures through which the protein passes through on its way to the folded structure. The folding mechanisms for several fast-folding proteins can be described using an energy landscape theory to set up the correspondence with simulations of protein minimalist models. Using these simulations together with analytical theory, we can learn about good (minimally frustrated) folding sequences and non-folding (frustrated) sequences. An important idea that emerges from this theory is that subtle features of the protein landscape can profoundly affect the apparent mechanism of folding. Experiments on the dependence of the folding/unfolding times, and the stability of these proteins to denaturant concentration and site-directed mutagenesis, and on the early events of folding allow to infer the global characteristics of the landscape. In addition to need to minimize energetic frustration, the topology of the native fold also plays a major role in the folding mechanism. Some folding motifs are easier to design than others suggesting the possibility that evolution not only selected sequences with sufficiently small energetic frustration but also selected more easily designable native structures. Several proteins (such as CI2 and SH3) have sufficiently reduced energetic frustration) that much of the heterogeneity observed in their transition state ensemble (TSE) is determined by topology. Topological effects go beyond the structure of the TSE. The overall structure of the on-route and off-route (traps) intermediates for the folding of more complex proteins is also influenced by topology. Utilizing this theoretical framework, simulations of minimalist models and

  13. Model Analysis ToolKit

    SciTech Connect

    Harp, Dylan R.

    2015-05-15

    MATK provides basic functionality to facilitate model analysis within the Python computational environment. Model analysis setup within MATK includes: - define parameters - define observations - define model (python function) - define samplesets (sets of parameter combinations) Currently supported functionality includes: - forward model runs - Latin-Hypercube sampling of parameters - multi-dimensional parameter studies - parallel execution of parameter samples - model calibration using internal Levenberg-Marquardt algorithm - model calibration using lmfit package - model calibration using levmar package - Markov Chain Monte Carlo using pymc package MATK facilitates model analysis using: - scipy - calibration (scipy.optimize) - rpy2 - Python interface to R

  14. Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model.

    PubMed

    Krishnan, Rahul; Arora, Rajan P; Alexander, Michael; White, Sean M; Lamb, Morgan W; Foster, Clarence E; Choi, Bernard; Lakey, Jonathan R T

    2014-01-01

    Alginate encapsulation reduces the risk of transplant rejection by evading immune-mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature noninvasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses. PMID:24176195

  15. Noninvasive evaluation of the vascular response to transplantation of alginate encapsulated islets using the dorsal skin-fold model

    PubMed Central

    Krishnan, Rahul; Arora, Rajan P.; Alexander, Michael; White, Sean M.; Lamb, Morgan W.; Foster, Clarence E.; Choi, Bernard; Lakey, Jonathan R.T.

    2014-01-01

    Alginate encapsulation reduces the risk of transplant rejection by evading immune-mediated cell injury and rejection; however, poor vascular perfusion results in graft failure. Since existing imaging models are incapable of quantifying the vascular response to biomaterial implants after transplantation, in this study, we demonstrate the use of in vivo laser speckle imaging (LSI) and wide-field functional imaging (WiFI) to monitor the microvascular environment surrounding biomaterial implants. The vascular response to two islet-containing biomaterial encapsulation devices, alginate microcapsules and a high-guluronate alginate sheet, was studied and compared after implantation into the mouse dorsal window chamber (N = 4 per implant group). Images obtained over a 14-day period using LSI and WiFI were analyzed using algorithms to quantify blood flow, hemoglobin oxygen saturation and vascular density. Using our method, we were able to monitor the changes in the peri-implant microvasculature non-invasively without the use of fluorescent dyes. Significant changes in blood flow, hemoglobin oxygen saturation and vascular density were noted as early as the first week post-transplant. The dorsal window chamber model enables comparison of host responses to transplanted biomaterials. Future experiments will study the effect of changes in alginate composition on the vascular and immune responses. PMID:24176195

  16. Programmable matter by folding

    PubMed Central

    Hawkes, E.; An, B.; Benbernou, N. M.; Tanaka, H.; Kim, S.; Demaine, E. D.; Rus, D.; Wood, R. J.

    2010-01-01

    Programmable matter is a material whose properties can be programmed to achieve specific shapes or stiffnesses upon command. This concept requires constituent elements to interact and rearrange intelligently in order to meet the goal. This paper considers achieving programmable sheets that can form themselves in different shapes autonomously by folding. Past approaches to creating transforming machines have been limited by the small feature sizes, the large number of components, and the associated complexity of communication among the units. We seek to mitigate these difficulties through the unique concept of self-folding origami with universal crease patterns. This approach exploits a single sheet composed of interconnected triangular sections. The sheet is able to fold into a set of predetermined shapes using embedded actuation. To implement this self-folding origami concept, we have developed a scalable end-to-end planning and fabrication process. Given a set of desired objects, the system computes an optimized design for a single sheet and multiple controllers to achieve each of the desired objects. The material, called programmable matter by folding, is an example of a system capable of achieving multiple shapes for multiple functions. PMID:20616049

  17. Folding without charges

    PubMed Central

    Kurnik, Martin; Hedberg, Linda; Danielsson, Jens; Oliveberg, Mikael

    2012-01-01

    Surface charges of proteins have in several cases been found to function as “structural gatekeepers,” which avoid unwanted interactions by negative design, for example, in the control of protein aggregation and binding. The question is then if side-chain charges, due to their desolvation penalties, play a corresponding role in protein folding by avoiding competing, misfolded traps? To find out, we removed all 32 side-chain charges from the 101-residue protein S6 from Thermus thermophilus. The results show that the charge-depleted S6 variant not only retains its native structure and cooperative folding transition, but folds also faster than the wild-type protein. In addition, charge removal unleashes pronounced aggregation on longer timescales. S6 provides thus an example where the bias toward native contacts of a naturally evolved protein sequence is independent of charges, and point at a fundamental difference in the codes for folding and intermolecular interaction: specificity in folding is governed primarily by hydrophobic packing and hydrogen bonding, whereas solubility and binding relies critically on the interplay of side-chain charges. PMID:22454493

  18. Operations and Modeling Analysis

    NASA Technical Reports Server (NTRS)

    Ebeling, Charles

    2005-01-01

    The Reliability and Maintainability Analysis Tool (RMAT) provides NASA the capability to estimate reliability and maintainability (R&M) parameters and operational support requirements for proposed space vehicles based upon relationships established from both aircraft and Shuttle R&M data. RMAT has matured both in its underlying database and in its level of sophistication in extrapolating this historical data to satisfy proposed mission requirements, maintenance concepts and policies, and type of vehicle (i.e. ranging from aircraft like to shuttle like). However, a companion analyses tool, the Logistics Cost Model (LCM) has not reached the same level of maturity as RMAT due, in large part, to nonexistent or outdated cost estimating relationships and underlying cost databases, and it's almost exclusive dependence on Shuttle operations and logistics cost input parameters. As a result, the full capability of the RMAT/LCM suite of analysis tools to take a conceptual vehicle and derive its operations and support requirements along with the resulting operating and support costs has not been realized.

  19. Quantitative Morphology of Epithelial Folds.

    PubMed

    Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož

    2016-01-01

    The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429

  20. Protein Folding and Self-Organized Criticality

    NASA Astrophysics Data System (ADS)

    Bajracharya, Arun; Murray, Joelle

    Proteins are known to fold into tertiary structures that determine their functionality in living organisms. However, the complex dynamics of protein folding and the way they consistently fold into the same structures is not fully understood. Self-organized criticality (SOC) has provided a framework for understanding complex systems in various systems (earthquakes, forest fires, financial markets, and epidemics) through scale invariance and the associated power law behavior. In this research, we use a simple hydrophobic-polar lattice-bound computational model to investigate self-organized criticality as a possible mechanism for generating complexity in protein folding.

  1. Protein Folding in Confined and Crowded Environments

    PubMed Central

    Zhou, Huan-Xiang

    2007-01-01

    Confinement and crowding are two major factors that can potentially impact protein folding in cellular environments. Theories based on considerations of excluded volumes predict disparate effects on protein folding stability for confinement and crowding: confinement can stabilize proteins by over 10kBT but crowding has a very modest effect on stability. On the other hand, confinement and crowding are both predicted to favor conformations of the unfolded state which are compact, and consequently may increase the folding rate. These predictions are largely borne out by experimental studies of protein folding under confined and crowded conditions in the test tube. Protein folding in cellular environments is further complicated by interactions with surrounding surfaces and other factors. Concerted theoretical modeling and test-tube and in vivo experiments promise to elucidate the complexity of protein folding in cellular environments. PMID:17719556

  2. Synthesizing folded band chaos.

    PubMed

    Corron, Ned J; Hayes, Scott T; Pethel, Shawn D; Blakely, Jonathan N

    2007-04-01

    A randomly driven linear filter that synthesizes Lorenz-like, reverse-time chaos is shown also to produce Rössler-like folded band wave forms when driven using a different encoding of the random source. The relationship between the topological entropy of the random source, dissipation in the linear filter, and the positive Lyapunov exponent for the reverse-time wave form is exposed. The two drive encodings are viewed as grammar restrictions on a more general encoding that produces a chaotic superset encompassing both the Lorenz butterfly and Rössler folded band paradigms of nonlinear dynamics. PMID:17500950

  3. Model Analysis ToolKit

    Energy Science and Technology Software Center (ESTSC)

    2015-05-15

    MATK provides basic functionality to facilitate model analysis within the Python computational environment. Model analysis setup within MATK includes: - define parameters - define observations - define model (python function) - define samplesets (sets of parameter combinations) Currently supported functionality includes: - forward model runs - Latin-Hypercube sampling of parameters - multi-dimensional parameter studies - parallel execution of parameter samples - model calibration using internal Levenberg-Marquardt algorithm - model calibration using lmfit package - modelmore » calibration using levmar package - Markov Chain Monte Carlo using pymc package MATK facilitates model analysis using: - scipy - calibration (scipy.optimize) - rpy2 - Python interface to R« less

  4. Solvent–amino acid interaction energies in three-dimensional-lattice Monte Carlo simulations of a model 27-mer protein: Folding thermodynamics and kinetics

    PubMed Central

    Leonhard, Kai; Prausnitz, John M.; Radke, Clayton J.

    2004-01-01

    Amino acid residue–solvent interactions are required for lattice Monte Carlo simulations of model proteins in water. In this study, we propose an interaction-energy scale that is based on the interaction scale by Miyazawa and Jernigan. It permits systematic variation of the amino acid–solvent interactions by introducing a contrast parameter for the hydrophobicity, Cs, and a mean attraction parameter for the amino acids, ω. Changes in the interaction energies strongly affect many protein properties. We present an optimized energy parameter set for best representing realistic behavior typical for many proteins (fast folding and high cooperativity for single chains). Our optimal parameters feature a much weaker hydrophobicity contrast and mean attraction than does the original interaction scale. The proposed interaction scale is designed for calculating the behavior of proteins in bulk and at interfaces as a function of solvent characteristics, as well as protein size and sequence. PMID:14739322

  5. Using Sequential Kinematic and Thermochronometric Modeling to Temporally and Spatially Link Thrust Belt Exhumation with Basin Development in the Bolivian Fold-Thrust-Belt-Foreland Basin System.

    NASA Astrophysics Data System (ADS)

    Rak, A. J.; McQuarrie, N.

    2014-12-01

    Applying isostasy and erosion to sequentially deformed balanced cross sections links the growth of hinterland structures to the developing foreland basins (FB) adjacent to fold-thrust belts (FTB), adding geologic constraints to modeled exhumation pathways. We sequentially deform the Rio Beni cross section in northern Bolivia (McQuarrie et al., 2008) with kinematic modeling software Move. In our model, topography evolves and basins develop for each model step as deformation, erosion, and isostasy are applied; and are a direct function of the geometry and kinematics of the cross section. The model is constrained by the depth of the foreland and hinterland basins, geology present at the surface, the depth and angle of the decollement, and the shape of the modern observed topography. Topography develops as thrusting occurs and loads the crust, producing a flexural wave and creating accommodation space in adjacent basins. Erosion of material above a newly generated topographic profile unloads the section while basin space is filled. Once the model sufficiently duplicates geologic constraints, a 0.5 km X 0.5 km grid of unique points is deformed with the model and used to determine displacement vectors for each 10 km shortening step. These displacement vectors, in conjunction with a prescribed time interval for each step, determine a velocity field that can be used in a modified version of the advection diffusion modeling software Pecube. Cooling ages predicted using this method are based on deformation rates, geometry, topography, and thermal parameters, and offer insight into possible rates of deformation, erosion, and deposition throughout FTB and FB development. Incorporating erosion, deposition, and isostasy in sequentially deformed balanced cross sections highlights the spatiotemporal aspects of sedimentary wedge propagation, identifies necessary external negative buoyancy affects, and provides additional geologic constraints to modeled exhumation pathways.

  6. Structure of the beta 2 homodimer of bacterial luciferase from Vibrio harveyi: X-ray analysis of a kinetic protein folding trap.

    PubMed Central

    Thoden, J. B.; Holden, H. M.; Fisher, A. J.; Sinclair, J. F.; Wesenberg, G.; Baldwin, T. O.; Rayment, I.

    1997-01-01

    Luciferase, as isolated from Vibrio harveyi, is an alpha beta heterodimer. When allowed to fold in the absence of the alpha subunit, either in vitro or in vivo, the beta subunit of enzyme will form a kinetically stable homodimer that does not unfold even after prolonged incubation in 5 M urea at pH 7.0 and 18 degrees C. This form of the beta subunit, arising via kinetic partitioning on the folding pathway, appears to constitute a kinetically trapped alternative to the heterodimeric enzyme (Sinclair JF, Ziegler MM, Baldwin TO. 1994. Kinetic partitioning during protein folding yields multiple native states. Nature Struct Biol 1: 320-326). Here we describe the X-ray crystal structure of the beta 2 homodimer of luciferase from V. harveyi determined and refined at 1.95 A resolution. Crystals employed in the investigational belonged to the orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions of a = 58.8 A, b = 62.0 A, and c = 218.2 A and contained one dimer per asymmetric unit. Like that observed in the functional luciferase alpha beta heterodimer, the major tertiary structural motif of each beta subunit consists of an (alpha/beta)8 barrel (Fisher AJ, Raushel FM, Baldwin TO, Rayment I. 1995. Three-dimensional structure of bacterial luciferase from Vibrio harveyi at 2.4 A resolution. Biochemistry 34: 6581-6586). The root-mean-square deviation of the alpha-carbon coordinates between the beta subunits of the hetero- and homodimers is 0.7 A. This high resolution X-ray analysis demonstrated that "domain" or "loop" swapping has not occurred upon formation of the beta 2 homodimer and thus the stability of the beta 2 species to denaturation cannot be explained in such simple terms. In fact, the subunit:subunit interfaces observed in both the beta 2 homodimer and alpha beta heterodimer are remarkably similar in hydrogen-bonding patterns and buried surface areas. PMID:9007973

  7. Multiple folding pathways of proteins with shallow knots and co-translational folding

    NASA Astrophysics Data System (ADS)

    Chwastyk, Mateusz; Cieplak, Marek

    2015-07-01

    We study the folding process in the shallowly knotted protein MJ0366 within two variants of a structure-based model. We observe that the resulting topological pathways are much richer than identified in previous studies. In addition to the single knot-loop events, we find novel, and dominant, two-loop mechanisms. We demonstrate that folding takes place in a range of temperatures and the conditions of most successful folding are at temperatures which are higher than those required for the fastest folding. We also demonstrate that nascent conditions are more favorable to knotting than off-ribosome folding.

  8. Multiple folding pathways of proteins with shallow knots and co-translational folding.

    PubMed

    Chwastyk, Mateusz; Cieplak, Marek

    2015-07-28

    We study the folding process in the shallowly knotted protein MJ0366 within two variants of a structure-based model. We observe that the resulting topological pathways are much richer than identified in previous studies. In addition to the single knot-loop events, we find novel, and dominant, two-loop mechanisms. We demonstrate that folding takes place in a range of temperatures and the conditions of most successful folding are at temperatures which are higher than those required for the fastest folding. We also demonstrate that nascent conditions are more favorable to knotting than off-ribosome folding. PMID:26233164

  9. Homogeneous Crystal Nucleation: To Fold or Not to Fold?

    NASA Astrophysics Data System (ADS)

    Crist, Buckley

    2007-03-01

    Recent simulations and related theories have addressed interesting aspects of homogeneous nucleation of polymer crystals in very dilute solutions; embryos and very small crystals are composed of folded chains. At the same time there has been renewed activity with experimental studies of homogeneous nucleation in molten polymers, either with dispersed droplets or with microphase-separated block copolymers. Compared to dilute solutions, melts offer enhanced possibilities for nucleation by fringed micelle structures with stems from different chains. Basal or ``end'' surface energy is estimated for unfolded and folded chain nuclei and employed with classical nucleation theory to distinguish between nucleation rates in the two cases. The effect of chain length on the nucleation barrier offers a way to test model predictions.

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  11. Modeling of aerodynamic interaction between vocal folds and vocal tract during production of a vowel-voiceless plosive-vowel sequence.

    PubMed

    Delebecque, Louis; Pelorson, Xavier; Beautemps, Denis

    2016-01-01

    The context of this study is the physical modeling of speech production. The objective is, by using a mechanical replica of the vocal tract, to test quantitatively an aerodynamic model of the interaction between the vocal folds and the vocal tract during the production of a vowel-voiceless plosive-vowel sequence. The first step is to realize acoustic and aerodynamic measurements on a speaker during the production of an /apa/ sequence. The aperture and width of the lips are also derived from a high-speed video recording of the subject's face. Theoretical models to describe the flow through the lips and the effect of an expansion of the supraglottal cavity are proposed and validated by comparison with measurements made using a self-oscillating replica of the phonatory system. Finally, using these models, numerical simulations of an /apa/ sequence are performed using the measured lip parameters as the only time-varying input parameters. The results of these simulations suggest that the realization of an occlusion of the vocal tract produces a passive increase in glottal area associated with a voice offset and that the expansion of the supraglottal cavity is responsible for the extension of the phonation up to 40 ms after closure of the lips. PMID:26827030

  12. Evolutionary Strategies for Protein Folding

    NASA Astrophysics Data System (ADS)

    Murthy Gopal, Srinivasa; Wenzel, Wolfgang

    2006-03-01

    The free energy approach for predicting the protein tertiary structure describes the native state of a protein as the global minimum of an appropriate free-energy forcefield. The low-energy region of the free-energy landscape of a protein is extremely rugged. Efficient optimization methods must therefore speed up the search for the global optimum by avoiding high energy transition states, adapt large scale moves or accept unphysical intermediates. Here we investigate an evolutionary strategies(ES) for optimizing a protein conformation in our all-atom free-energy force field([1],[2]). A set of random conformations is evolved using an ES to get a diverse population containing low energy structure. The ES is shown to balance energy improvement and yet maintain diversity in structures. The ES is implemented as a master-client model for distributed computing. Starting from random structures and by using this optimization technique, we were able to fold a 20 amino-acid helical protein and 16 amino-acid beta hairpin[3]. We compare ES to basin hopping method. [1]T. Herges and W. Wenzel,Biophys.J. 87,3100(2004) [2] A. Verma and W. Wenzel Stabilization and folding of beta-sheet and alpha-helical proteins in an all-atom free energy model(submitted)(2005) [3] S. M. Gopal and W. Wenzel Evolutionary Strategies for Protein Folding (in preparation)

  13. Single-molecule Studies of Riboswitch Folding

    PubMed Central

    Savinov, Andrew; Perez, Christian F.; Block, Steven M.

    2014-01-01

    The folding dynamics of riboswitches are central to their ability to modulate gene expression in response to environmental cues. In most cases, a structural competition between the formation of a ligand-binding aptamer and an expression platform (or some other competing off-state) determines the regulatory outcome. Here, we review single-molecule studies of riboswitch folding and function, predominantly carried out using single-molecule FRET or optical trapping approaches. Recent results have supplied new insights into riboswitch folding energy landscapes, the mechanisms of ligand binding, the roles played by divalent ions, the applicability of hierarchical folding models, and kinetic vs. thermodynamic control schemes. We anticipate that future work, based on improved data sets and potentially combining multiple experimental techniques, will enable the development of more complete models for complex RNA folding processes. PMID:24727093

  14. EXPOSURE ANALYSIS MODELING SYSTEM (EXAMS)

    EPA Science Inventory

    The Exposure Analysis Modeling System (EXAMS), first published in 1982 (EPA-600/3-82-023), provides interactive computer software for formulating aquatic ecosystem models and rapidly evaluating the fate, transport, and exposure concentrations of synthetic organic chemicals--pesti...

  15. Small scale folding observed in the NEEM ice core

    NASA Astrophysics Data System (ADS)

    Jansen, Daniela; Llorens, Maria-Gema; Westhoff, Julien; Steinbach, Florian; Bons, Paul D.; Kipfstuhl, Sepp; Griera, Albert; Weikusat, Ilka

    2015-04-01

    Disturbances on the centimeter scale in the layering of the NEEM ice core (North Greenland) can be mapped by means of visual stratigraphy as long as the ice does have a visual layering, such as, for example, cloudy bands. Different focal depths of the visual stratigraphy method allow, to a certain extent, a three dimensional view of the structures. In this study we present a structural analysis of the visible folds, discuss characteristics and frequency and present examples of typical fold structures. With this study we aim to quantify the potential impact of small scale folding on the integrity of climate proxy data. We also analyze the structures with regard to the stress environment under which they formed. The structures evolve from gentle waves at about 1700 m to overturned z-folds with increasing depth. Occasionally, the folding causes significant thickening of layers. Their shape indicates that they are passive features and are probably not initiated by rheology differences between layers. Layering is heavily disturbed and tracing of single layers is no longer possible below a depth of 2160 m. Lattice orientation distributions for the corresponding core sections were analyzed where available in addition to visual stratigraphy. The data show axial-plane parallel strings of grains with c.axis orientations that deviate from that of the matrix, which has more or less a single-maximum fabric at the depth where the folding occurs. We conclude from these data that folding is a consequence of deformation along localized shear planes and kink bands. The findings are compared with results from other deep ice cores. The observations presented are supplemented by microstructural modeling using a crystal plasticity code that reproduces deformation, applying a Fast Fourier Transform (FFT), coupled with ELLE to include dynamic recrystallization processes. The model results reproduce the development of bands of grains with a tilted orientation relative to the single maximum

  16. The uteroglobin fold.

    PubMed

    Callebaut, I; Poupon, A; Bally, R; Demaret, J P; Housset, D; Delettré, J; Hossenlopp, P; Mornon, J P

    2000-01-01

    Uteroglobin (UTG) forms a fascinating homodimeric structure that binds small- to medium-sized ligands through an internal hydrophobic cavity, located at the interface between the two monomers. Previous studies have shown that UTG fold is not limited to the UTG/CC10 family, whose sequence/structure relationships are highlighted here, but can be extended to the cap domain of Xanthobacter autotrophicus haloalkane dehalogenase. We show here that UTG fold is adopted by several other cap domains within the alpha/beta hydrolase family, making it a well-suited "geode" structure allowing it to sequester various hydrophobic molecules. Additionally, some data about a new crystal form of oxidized rabbit UTG are presented, completing previous structural studies, as well as results from molecular dynamics, suggesting an alternative way for the ligand to reach the internal cavity. PMID:11193783

  17. Folding within seconds

    NASA Astrophysics Data System (ADS)

    Kenkmann, Thomas

    2002-03-01

    Hypervelocity impacts of cosmic projectiles larger than ˜200 m diameter are capable of forming complex craters on Earth. At these craters, shock loading, shock damage, and excavation flow are followed by a gravity-driven collapse of the deep transient cavity. Such impact structures are characterized by a central uplift, a flat crater floor, and a terraced crater rim. Collapse-induced deformation features, like folds and brittle fault zones, have many similarities to tectonic structures. Typical deformation patterns of complex terrestrial impact craters of 5 15 km diameter are compiled and analyzed with respect to their kinematic development. Unlike their tectonic counterparts, deformation structures are always the result of non-plane-strain deformation and are formed in a single event that takes place in seconds to minutes. To understand the high-strain-rate processes, the microstructure of an impact-induced fold of the Crooked Creek impact crater (˜7 km diameter), Missouri, United States, is investigated in detail. A period of 20 30 s at the most is determined for the collapse phase of this crater. The gross plastic deformation behavior of the fold is achieved by localized brittle deformation along millimeter- to centimeter-spaced fault zones, forming a network of veins. Shock damage has fractured ˜40% of grain boundaries. The onset of collapse and associated deformation started in rocks with a reduced cohesion and is friction controlled.

  18. Folded waveguide coupler

    DOEpatents

    Owens, Thomas L.

    1988-03-01

    A resonant cavity waveguide coupler for ICRH of a magnetically confined plasma. The coupler consists of a series of inter-leaved metallic vanes disposed withn an enclosure analogous to a very wide, simple rectangular waveguide that has been "folded" several times. At the mouth of the coupler, a polarizing plate is provided which has coupling apertures aligned with selected folds of the waveguide through which rf waves are launched with magnetic fields of the waves aligned in parallel with the magnetic fields confining the plasma being heated to provide coupling to the fast magnetosonic wave within the plasma in the frequency usage of from about 50-200 mHz. A shorting plate terminates the back of the cavity at a distance approximately equal to one-half the guide wavelength from the mouth of the coupler to ensure that the electric field of the waves launched through the polarizing plate apertures are small while the magnetic field is near a maximum. Power is fed into the coupler folded cavity by means of an input coaxial line feed arrangement at a point which provides an impedance match between the cavity and the coaxial input line.

  19. Cotranslational folding of deeply knotted proteins

    NASA Astrophysics Data System (ADS)

    Chwastyk, Mateusz; Cieplak, Marek

    2015-09-01

    Proper folding of deeply knotted proteins has a very low success rate even in structure-based models which favor formation of the native contacts but have no topological bias. By employing a structure-based model, we demonstrate that cotranslational folding on a model ribosome may enhance the odds to form trefoil knots for protein YibK without any need to introduce any non-native contacts. The ribosome is represented by a repulsive wall that keeps elongating the protein. On-ribosome folding proceeds through a a slipknot conformation. We elucidate the mechanics and energetics of its formation. We show that the knotting probability in on-ribosome folding is a function of temperature and that there is an optimal temperature for the process. Our model often leads to the establishment of the native contacts without formation of the knot.

  20. Cotranslational folding of deeply knotted proteins.

    PubMed

    Chwastyk, Mateusz; Cieplak, Marek

    2015-09-01

    Proper folding of deeply knotted proteins has a very low success rate even in structure-based models which favor formation of the native contacts but have no topological bias. By employing a structure-based model, we demonstrate that cotranslational folding on a model ribosome may enhance the odds to form trefoil knots for protein YibK without any need to introduce any non-native contacts. The ribosome is represented by a repulsive wall that keeps elongating the protein. On-ribosome folding proceeds through a a slipknot conformation. We elucidate the mechanics and energetics of its formation. We show that the knotting probability in on-ribosome folding is a function of temperature and that there is an optimal temperature for the process. Our model often leads to the establishment of the native contacts without formation of the knot. PMID:26292194

  1. Strain analysis in the Sanandaj-Sirjan HP-LT Metamorphic Belt, SW Iran: Insights from small-scale faults and associated drag folds

    NASA Astrophysics Data System (ADS)

    Sarkarinejad, Khalil; Keshavarz, Saeede; Faghih, Ali

    2015-05-01

    This study is aimed at quantifying the kinematics of deformation using a population of drag fold structures associated with small-scale faults in deformed quartzites from Seh-Ghalatoun area within the HP-LT Sanandaj-Sirjan Metamorphic Belt, SW Iran. A total 30 small-scale faults in the quartzite layers were examined to determine the deformation characteristics. Obtained data revealed α0 (initial fault angle) and ω (angle between flow apophyses) are equal to 83° and 32°, respectively. These data yield mean kinematic vorticity number (Wm) equal to 0.79 and mean finite strain (Rs) of 2.32. These results confirm the relative contribution of ∼43% pure shear and ∼57% simple shear components, respectively. The strain partitioning inferred from this quantitative analysis is consistent with a sub-simple or general shear deformation pattern associated with a transpressional flow regime in the study area as a part of the Zagros Orogen. This type of deformation resulted from oblique convergence between the Afro-Arabian and Central-Iranian plates.

  2. Stochastic Resonance in Protein Folding Dynamics.

    PubMed

    Davtyan, Aram; Platkov, Max; Gruebele, Martin; Papoian, Garegin A

    2016-05-01

    Although protein folding reactions are usually studied under static external conditions, it is likely that proteins fold in a locally fluctuating cellular environment in vivo. To mimic such behavior in in vitro experiments, the local temperature of the solvent can be modulated either harmonically or using correlated noise. In this study, coarse-grained molecular simulations are used to investigate these possibilities, and it is found that both periodic and correlated random fluctuations of the environment can indeed accelerate folding kinetics if the characteristic frequencies of the applied fluctuations are commensurate with the internal timescale of the folding reaction; this is consistent with the phenomenon of stochastic resonance observed in many other condensed-matter processes. To test this theoretical prediction, the folding dynamics of phosphoglycerate kinase under harmonic temperature fluctuations are experimentally probed using Förster resonance energy transfer fluorescence measurements. To analyze these experiments, a combination of theoretical approaches is developed, including stochastic simulations of folding kinetics and an analytical mean-field kinetic theory. The experimental observations are consistent with the theoretical predictions of stochastic resonance in phosphoglycerate kinase folding. When combined with an alternative experiment on the protein VlsE using a power spectrum analysis, elaborated in Dave et al., ChemPhysChem 2016, 10.1002/cphc.201501041, the overall data overwhelmingly point to the experimental confirmation of stochastic resonance in protein folding dynamics. PMID:26992148

  3. The nature of protein folding pathways.

    PubMed

    Englander, S Walter; Mayne, Leland

    2014-11-11

    How do proteins fold, and why do they fold in that way? This Perspective integrates earlier and more recent advances over the 50-y history of the protein folding problem, emphasizing unambiguously clear structural information. Experimental results show that, contrary to prior belief, proteins are multistate rather than two-state objects. They are composed of separately cooperative foldon building blocks that can be seen to repeatedly unfold and refold as units even under native conditions. Similarly, foldons are lost as units when proteins are destabilized to produce partially unfolded equilibrium molten globules. In kinetic folding, the inherently cooperative nature of foldons predisposes the thermally driven amino acid-level search to form an initial foldon and subsequent foldons in later assisted searches. T