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

Science.gov (United States)

Zhang, Zhaoyan

2009-02-01

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

A Rat Excised Larynx Model of Vocal Fold Scar

Science.gov (United States)

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

2009-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1995-09-01

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

FoldEco: A Model for Proteostasis in E. coli

Directory of Open Access Journals (Sweden)

Evan T. Powers

2012-03-01

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

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

Science.gov (United States)

Moisik, Scott R.; Esling, John H.

2014-01-01

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

SDEM modelling of fault-propagation folding

DEFF Research Database (Denmark)

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

2009-01-01

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

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

Science.gov (United States)

Zhang, Wei; Ahmed, Saad; Masters, Sarah; Ounaies, Zoubeida; Frecker, Mary

2017-10-01

The incorporation of smart materials such as electroactive polymers and magnetoactive elastomers in origami structures can result in active folding using external electric and magnetic stimuli, showing promise in many origami-inspired engineering applications. In this study, 3D finite element analysis (FEA) models are developed using COMSOL Multiphysics software for three configurations that incorporate a combination of active and passive material layers, namely: (1) a single-notch unimorph folding configuration actuated using only external electric field, (2) a double-notch unimorph folding configuration actuated using only external electric field, and (3) a bifold configuration which is actuated using multi-field (electric and magnetic) stimuli. The objectives of the study are to verify the effectiveness of the FEA models to simulate folding behavior and to investigate the influence of geometric parameters on folding quality. Equivalent mechanical pressure and surface stress are used as external loads in the FEA to simulate electric and magnetic fields, respectively. Compared quantitatively with experimental data, FEA captured the folding performance of electric actuation well for notched configurations and magnetic actuation for a bifold structure, but underestimated electric actuation for the bifold structure. By investigating the impact of geometric parameters and locations to place smart materials, FEA can be used in design, avoiding trial-and-error iterations of experiments.

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

Science.gov (United States)

Zhang, Zhaoyan

2014-01-01

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

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

Science.gov (United States)

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

2017-09-01

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

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

DEFF Research Database (Denmark)

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

2016-01-01

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

Separable potential approach in the folding model. Pt. 2

International Nuclear Information System (INIS)

Lee, C.L.; Robson, D.

1982-01-01

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

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

DEFF Research Database (Denmark)

Granados, Alba; Brunskog, Jonas

2017-01-01

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

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

Science.gov (United States)

Granados, Alba; Brunskog, Jonas

2017-06-01

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

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

Indian Academy of Sciences (India)

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

NoFold: RNA structure clustering without folding or alignment.

Science.gov (United States)

Middleton, Sarah A; Kim, Junhyong

2014-11-01

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

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

Science.gov (United States)

Glyakina, Anna V; Pereyaslavets, Leonid B; Galzitskaya, Oxana V

2013-09-01

Despite the large number of publications on three-helix protein folding, there is no study devoted to the influence of handedness on the rate of three-helix protein folding. From the experimental studies, we make a conclusion that the left-handed three-helix proteins fold faster than the right-handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three-helix proteins (four right-handed and four left-handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary-structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left-handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right-handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three-helix proteins (238 right- and 94 left-handed). From our analysis, we found that the left-handed three-helix proteins have some less-dense packing that should result in faster folding for some proteins as compared to the case of right-handed proteins. Copyright © 2013 Wiley Periodicals, Inc.

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

International Nuclear Information System (INIS)

Ueta, Keiichi

2011-01-01

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

The Complexity of Folding Self-Folding Origami

Science.gov (United States)

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

2017-10-01

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

Approximate self-similarity in models of geological folding

NARCIS (Netherlands)

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

2000-01-01

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

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

Directory of Open Access Journals (Sweden)

Fabrizio Marinelli

2009-08-01

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

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

Science.gov (United States)

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

2017-04-01

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

Image Analysis for Nail-fold Capillaroscopy

OpenAIRE

Vucic, Vladimir

2015-01-01

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

The Complexity of Folding Self-Folding Origami

Directory of Open Access Journals (Sweden)

Menachem Stern

2017-12-01

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

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

International Nuclear Information System (INIS)

Randrup, J.

1975-09-01

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

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

Science.gov (United States)

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

2018-06-01

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

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

International Nuclear Information System (INIS)

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

1988-02-01

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

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

Directory of Open Access Journals (Sweden)

M. Mihalikova

2012-09-01

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

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

Science.gov (United States)

Krane, Michael; Walters, Gage; McPhail, Michael

2017-11-01

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

Bioinformatics analysis identify novel OB fold protein coding genes in C. elegans.

Directory of Open Access Journals (Sweden)

Daryanaz Dargahi

Full Text Available BACKGROUND: The C. elegans genome has been extensively annotated by the WormBase consortium that uses state of the art bioinformatics pipelines, functional genomics and manual curation approaches. As a result, the identification of novel genes in silico in this model organism is becoming more challenging requiring new approaches. The Oligonucleotide-oligosaccharide binding (OB fold is a highly divergent protein family, in which protein sequences, in spite of having the same fold, share very little sequence identity (5-25%. Therefore, evidence from sequence-based annotation may not be sufficient to identify all the members of this family. In C. elegans, the number of OB-fold proteins reported is remarkably low (n=46 compared to other evolutionary-related eukaryotes, such as yeast S. cerevisiae (n=344 or fruit fly D. melanogaster (n=84. Gene loss during evolution or differences in the level of annotation for this protein family, may explain these discrepancies. METHODOLOGY/PRINCIPAL FINDINGS: This study examines the possibility that novel OB-fold coding genes exist in the worm. We developed a bioinformatics approach that uses the most sensitive sequence-sequence, sequence-profile and profile-profile similarity search methods followed by 3D-structure prediction as a filtering step to eliminate false positive candidate sequences. We have predicted 18 coding genes containing the OB-fold that have remarkably partially been characterized in C. elegans. CONCLUSIONS/SIGNIFICANCE: This study raises the possibility that the annotation of highly divergent protein fold families can be improved in C. elegans. Similar strategies could be implemented for large scale analysis by the WormBase consortium when novel versions of the genome sequence of C. elegans, or other evolutionary related species are being released. This approach is of general interest to the scientific community since it can be used to annotate any genome.

Vocal fold immobility: a longitudinal analysis of etiology over 20 years.

Science.gov (United States)

Rosenthal, Laura H Swibel; Benninger, Michael S; Deeb, Robert H

2007-10-01

To determine the current etiology of vocal fold immobility, identify changing trends over the last 20 years, and compare results to historical reports. The present study is a retrospective analysis of all patients seen within a tertiary care institution between 1996 and 2005 with vocal fold immobility. The results were combined with a previous study of patients within the same institution from 1985 through 1995. Results were compared to the literature. The medical records of all patients assigned a primary or additional diagnostic code for vocal cord paralysis were obtained from the electronic database. Eight hundred twenty-seven patients were available for analysis (435 from the most recent cohort), which is substantially larger than any reported series to date. Vocal fold immobility was most commonly associated with a surgical procedure (37%). Nonthyroid surgeries (66%), such as anterior cervical approaches to the spine and carotid endarterectomies, have surpassed thyroid surgery (33%) as the most common iatrogenic causes. These data represent a change from historical figures in which extralaryngeal malignancies were considered the major cause of unilateral immobility. Thyroidectomy continues to cause the majority (80%) of iatrogenic bilateral vocal fold immobility and 30% of all bilateral immobility. This 20-year longitudinal assessment revealed that the etiology of unilateral vocal fold immobility has changed such that there has been a shift from extralaryngeal malignancies to nonthyroid surgical procedures as the major cause. Thyroid surgery remains the most common cause of bilateral vocal fold immobility.

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

Science.gov (United States)

Peraza Hernandez, Edwin Alexander

model for the structural mechanics of origami continuum bodies with smooth folds is presented. Such a model entails the integration of the presented kinematic model and existing plate theories in order to obtain a structural representation for folds having non-zero thickness and comprised of arbitrary materials. The model is validated against finite element analysis. The last contribution addresses the design and analysis of active material-based self-folding structures that morph via simultaneous folding towards a given three-dimensional goal shape starting from a planar configuration. Implementation examples including shape memory alloy (SMA)-based self-folding structures are provided.

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

Science.gov (United States)

Gray, S. L.

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

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

Science.gov (United States)

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

2009-03-04

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

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

Science.gov (United States)

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

2015-01-01

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

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

Science.gov (United States)

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

2016-11-01

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

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

Science.gov (United States)

Diaz, N; Tischer, I

2016-05-13

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

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

DEFF Research Database (Denmark)

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

2008-01-01

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

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

Science.gov (United States)

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

2016-04-01

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

Analysis of the free-energy surface of proteins from reversible folding simulations.

Directory of Open Access Journals (Sweden)

Lucy R Allen

2009-07-01

Full Text Available Computer generated trajectories can, in principle, reveal the folding pathways of a protein at atomic resolution and possibly suggest general and simple rules for predicting the folded structure of a given sequence. While such reversible folding trajectories can only be determined ab initio using all-atom transferable force-fields for a few small proteins, they can be determined for a large number of proteins using coarse-grained and structure-based force-fields, in which a known folded structure is by construction the absolute energy and free-energy minimum. Here we use a model of the fast folding helical lambda-repressor protein to generate trajectories in which native and non-native states are in equilibrium and transitions are accurately sampled. Yet, representation of the free-energy surface, which underlies the thermodynamic and dynamic properties of the protein model, from such a trajectory remains a challenge. Projections over one or a small number of arbitrarily chosen progress variables often hide the most important features of such surfaces. The results unequivocally show that an unprojected representation of the free-energy surface provides important and unbiased information and allows a simple and meaningful description of many-dimensional, heterogeneous trajectories, providing new insight into the possible mechanisms of fast-folding proteins.

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

Directory of Open Access Journals (Sweden)

Ziv-Ukelson Michal

2009-03-01

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

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

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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).

[Clinical analysis of vocal fold firbrous mass].

Science.gov (United States)

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

2018-03-01

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

Mechanical Modeling and Computer Simulation of Protein Folding

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

2018-04-01

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

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

Science.gov (United States)

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

2016-04-01

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

Probabilistic analysis for identifying the driving force of protein folding

Science.gov (United States)

Tokunaga, Yoshihiko; Yamamori, Yu; Matubayasi, Nobuyuki

2018-03-01

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

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

Science.gov (United States)

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

2017-11-01

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

Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

Science.gov (United States)

Suzuki, Ryo; Katsuno, Tatsuya; Kishimoto, Yo; Nakamura, Ryosuke; Mizuta, Masanobu; Suehiro, Atsushi; Yamashita, Masaru; Nakamura, Tatsuo; Tateya, Ichiro; Omori, Koichi

2018-04-01

The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Animal experiments with controls. Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. NA. Laryngoscope, 128:E150-E156, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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

Science.gov (United States)

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

2014-09-01

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

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

Science.gov (United States)

Gradmann, Sofie; Beaumont, Christopher; Albertz, Markus

2009-04-01

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

Monitoring treatment of vocal fold paralysis by biomechanical analysis of voice

OpenAIRE

Gómez Vilda, Pedro; Martínez de Arellano, Ana; Nieto Lluis, Victor; Rodellar Biarge, M. Victoria; Álvarez Marquina, Agustin; Mazaira Fernández, Luis Miguel

2013-01-01

A case study of vocal fold paralysis treatment is described with the help of the voice quality analysis application BioMet®Phon. The case corresponds to a description of a 40 - year old female patient who was diagnosed of vocal fold paralysis following a cardio - pulmonar intervention which required intubation for 8 days and posterior tracheotomy for 15 days. The patient presented breathy and asthenic phon ation, and dysphagia. Six main examinations were conducted during a full year period th...

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

Science.gov (United States)

Saidi, Hiba; Erath, Byron D.

2015-11-01

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

Folded Sheet Versus Transparent Sheet Models for Human Symmetry Judgments

Directory of Open Access Journals (Sweden)

Jacques Ninio

2011-07-01

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

Radiation Fibrosis of the Vocal Fold: From Man to Mouse

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

Marcelino, Anna Marie C; Gierasch, Lila M

2008-05-01

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

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

Science.gov (United States)

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

2011-07-01

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

High-speed image analysis reveals chaotic vibratory behaviors of pathological vocal folds

Energy Technology Data Exchange (ETDEWEB)

Zhang Yu, E-mail: yuzhang@xmu.edu.c [Key Laboratory of Underwater Acoustic Communication and Marine Information Technology of the Ministry of Education, Xiamen University, Xiamen Fujian 361005 (China); Shao Jun [Shanghai EENT Hospital of Fudan University, Shanghai (China); Krausert, Christopher R. [Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375 (United States); Zhang Sai [Key Laboratory of Underwater Acoustic Communication and Marine Information Technology of the Ministry of Education, Xiamen University, Xiamen Fujian 361005 (China); Jiang, Jack J. [Shanghai EENT Hospital of Fudan University, Shanghai (China); Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-7375 (United States)

2011-01-15

Research highlights: Low-dimensional human glottal area data. Evidence of chaos in human laryngeal activity from high-speed digital imaging. Traditional perturbation analysis should be cautiously applied to aperiodic high speed image signals. Nonlinear dynamic analysis may be helpful for understanding disordered behaviors in pathological laryngeal systems. - Abstract: Laryngeal pathology is usually associated with irregular dynamics of laryngeal activity. High-speed imaging facilitates direct observation and measurement of vocal fold vibrations. However, chaotic dynamic characteristics of aperiodic high-speed image data have not yet been investigated in previous studies. In this paper, we will apply nonlinear dynamic analysis and traditional perturbation methods to quantify high-speed image data from normal subjects and patients with various laryngeal pathologies including vocal fold nodules, polyps, bleeding, and polypoid degeneration. The results reveal the low-dimensional dynamic characteristics of human glottal area data. In comparison to periodic glottal area series from a normal subject, aperiodic glottal area series from pathological subjects show complex reconstructed phase space, fractal dimension, and positive Lyapunov exponents. The estimated positive Lyapunov exponents provide the direct evidence of chaos in pathological human vocal folds from high-speed digital imaging. Furthermore, significant differences between the normal and pathological groups are investigated for nonlinear dynamic and perturbation analyses. Jitter in the pathological group is significantly higher than in the normal group, but shimmer does not show such a difference. This finding suggests that the traditional perturbation analysis should be cautiously applied to high speed image signals. However, the correlation dimension and the maximal Lyapunov exponent reveal a statistically significant difference between normal and pathological groups. Nonlinear dynamic analysis is capable of

High-speed image analysis reveals chaotic vibratory behaviors of pathological vocal folds

International Nuclear Information System (INIS)

Zhang Yu; Shao Jun; Krausert, Christopher R.; Zhang Sai; Jiang, Jack J.

2011-01-01

Research highlights: → Low-dimensional human glottal area data. → Evidence of chaos in human laryngeal activity from high-speed digital imaging. → Traditional perturbation analysis should be cautiously applied to aperiodic high speed image signals. → Nonlinear dynamic analysis may be helpful for understanding disordered behaviors in pathological laryngeal systems. - Abstract: Laryngeal pathology is usually associated with irregular dynamics of laryngeal activity. High-speed imaging facilitates direct observation and measurement of vocal fold vibrations. However, chaotic dynamic characteristics of aperiodic high-speed image data have not yet been investigated in previous studies. In this paper, we will apply nonlinear dynamic analysis and traditional perturbation methods to quantify high-speed image data from normal subjects and patients with various laryngeal pathologies including vocal fold nodules, polyps, bleeding, and polypoid degeneration. The results reveal the low-dimensional dynamic characteristics of human glottal area data. In comparison to periodic glottal area series from a normal subject, aperiodic glottal area series from pathological subjects show complex reconstructed phase space, fractal dimension, and positive Lyapunov exponents. The estimated positive Lyapunov exponents provide the direct evidence of chaos in pathological human vocal folds from high-speed digital imaging. Furthermore, significant differences between the normal and pathological groups are investigated for nonlinear dynamic and perturbation analyses. Jitter in the pathological group is significantly higher than in the normal group, but shimmer does not show such a difference. This finding suggests that the traditional perturbation analysis should be cautiously applied to high speed image signals. However, the correlation dimension and the maximal Lyapunov exponent reveal a statistically significant difference between normal and pathological groups. Nonlinear dynamic

Phi-value analysis of apo-azurin folding: comparison between experiment and theory.

Science.gov (United States)

Zong, Chenghang; Wilson, Corey J; Shen, Tongye; Wolynes, Peter G; Wittung-Stafshede, Pernilla

2006-05-23

Pseudomonas aeruginosa azurin is a 128-residue beta-sandwich metalloprotein; in vitro kinetic experiments have shown that it folds in a two-state reaction. Here, we used a variational free energy functional to calculate the characteristics of the transition state ensemble (TSE) for folding of the apo-form of P. aeruginosa azurin and investigate how it responds to thermal and mutational changes. The variational method directly yields predicted chevron plots for wild-type and mutant apo-forms of azurin. In parallel, we performed in vitro kinetic-folding experiments on the same set of azurin variants using chemical perturbation. Like the wild-type protein, all apo-variants fold in apparent two-state reactions both in calculations and in stopped-flow mixing experiments. Comparisons of phi (phi) values determined from the experimental and theoretical chevron parameters reveal an excellent agreement for most positions, indicating a polarized, highly structured TSE for folding of P. aeruginosa apo-azurin. We also demonstrate that careful analysis of side-chain interactions is necessary for appropriate theoretical description of core mutants.

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

Science.gov (United States)

Mies, J.W.

1993-01-01

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

Fast identification of folded human protein domains expressed in E. coli suitable for structural analysis

Directory of Open Access Journals (Sweden)

Schlegel Brigitte

2004-03-01

Full Text Available Abstract Background High-throughput protein structure analysis of individual protein domains requires analysis of large numbers of expression clones to identify suitable constructs for structure determination. For this purpose, methods need to be implemented for fast and reliable screening of the expressed proteins as early as possible in the overall process from cloning to structure determination. Results 88 different E. coli expression constructs for 17 human protein domains were analysed using high-throughput cloning, purification and folding analysis to obtain candidates suitable for structural analysis. After 96 deep-well microplate expression and automated protein purification, protein domains were directly analysed using 1D 1H-NMR spectroscopy. In addition, analytical hydrophobic interaction chromatography (HIC was used to detect natively folded protein. With these two analytical methods, six constructs (representing two domains were quickly identified as being well folded and suitable for structural analysis. Conclusion The described approach facilitates high-throughput structural analysis. Clones expressing natively folded proteins suitable for NMR structure determination were quickly identified upon small scale expression screening using 1D 1H-NMR and/or analytical HIC. This procedure is especially effective as a fast and inexpensive screen for the 'low hanging fruits' in structural genomics.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-06-15

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

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

International Nuclear Information System (INIS)

Erath, Byron D.; Plesniak, Michael W.

2012-01-01

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

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

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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.

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

Science.gov (United States)

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

2017-02-01

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

Origami-Inspired Folding of Thick, Rigid Panels

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

2014-01-01

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

Fold and Fit: Space Conserving Shape Editing

KAUST Repository

Ibrahim, Mohamed

2017-09-01

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

The nature of folded states of globular proteins.

Science.gov (United States)

Honeycutt, J D; Thirumalai, D

1992-06-01

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

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

Science.gov (United States)

Maghrabi, Ali H A; McGuffin, Liam J

2017-07-03

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

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

International Nuclear Information System (INIS)

Guo, Wei; Zhou, Jinxiong; Li, Meie

2013-01-01

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

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

Science.gov (United States)

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

2017-01-01

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

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

Science.gov (United States)

Bergasa-Caceres, Fernando; Rabitz, Herschel A.

2013-06-01

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

Measurement of flow separation in a human vocal folds model

Czech Academy of Sciences Publication Activity Database

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

2011-01-01

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

Conserved nucleation sites reinforce the significance of Phi value analysis in protein-folding studies.

Science.gov (United States)

Gianni, Stefano; Jemth, Per

2014-07-01

The only experimental strategy to address the structure of folding transition states, the so-called Φ value analysis, relies on the synergy between site directed mutagenesis and the measurement of reaction kinetics. Despite its importance, the Φ value analysis has been often criticized and its power to pinpoint structural information has been questioned. In this hypothesis, we demonstrate that comparing the Φ values between proteins not only allows highlighting the robustness of folding pathways but also provides per se a strong validation of the method. © 2014 International Union of Biochemistry and Molecular Biology.

Self-organized critical model for protein folding

Science.gov (United States)

Moret, M. A.

2011-09-01

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

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

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

2005-01-01

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

Modeling Vocal Fold Intravascular Flow using Synthetic Replicas

Science.gov (United States)

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

2017-11-01

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

Quantification of Porcine Vocal Fold Geometry.

Science.gov (United States)

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

2016-07-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

Pappu, Rohit V.; Nussinov, Ruth

2009-03-01

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

How Many Protein Sequences Fold to a Given Structure? A Coevolutionary Analysis.

Science.gov (United States)

Tian, Pengfei; Best, Robert B

2017-10-17

Quantifying the relationship between protein sequence and structure is key to understanding the protein universe. A fundamental measure of this relationship is the total number of amino acid sequences that can fold to a target protein structure, known as the "sequence capacity," which has been suggested as a proxy for how designable a given protein fold is. Although sequence capacity has been extensively studied using lattice models and theory, numerical estimates for real protein structures are currently lacking. In this work, we have quantitatively estimated the sequence capacity of 10 proteins with a variety of different structures using a statistical model based on residue-residue co-evolution to capture the variation of sequences from the same protein family. Remarkably, we find that even for the smallest protein folds, such as the WW domain, the number of foldable sequences is extremely large, exceeding the Avogadro constant. In agreement with earlier theoretical work, the calculated sequence capacity is positively correlated with the size of the protein, or better, the density of contacts. This allows the absolute sequence capacity of a given protein to be approximately predicted from its structure. On the other hand, the relative sequence capacity, i.e., normalized by the total number of possible sequences, is an extremely tiny number and is strongly anti-correlated with the protein length. Thus, although there may be more foldable sequences for larger proteins, it will be much harder to find them. Lastly, we have correlated the evolutionary age of proteins in the CATH database with their sequence capacity as predicted by our model. The results suggest a trade-off between the opposing requirements of high designability and the likelihood of a novel fold emerging by chance. Published by Elsevier Inc.

Evaluation of single and multi-threshold entropy-based algorithms for folded substrate analysis

Directory of Open Access Journals (Sweden)

Magdolna Apro

2011-10-01

Full Text Available This paper presents a detailed evaluation of two variants of Maximum Entropy image segmentation algorithm(single and multi-thresholding with respect to their performance on segmenting test images showing folded substrates.The segmentation quality was determined by evaluating values of four different measures: misclassificationerror, modified Hausdorff distance, relative foreground area error and positive-negative false detection ratio. Newnormalization methods were proposed in order to combine all parameters into a unique algorithm evaluation rating.The segmentation algorithms were tested on images obtained by three different digitalisation methods coveringfour different surface textures. In addition, the methods were also tested on three images presenting a perfect fold.The obtained results showed that Multi-Maximum Entropy algorithm is better suited for the analysis of imagesshowing folded substrates.

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

Science.gov (United States)

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

2010-12-01

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

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

International Nuclear Information System (INIS)

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

1987-01-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

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

2014-05-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

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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.

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

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Sean P. Ferris

2014-03-01

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

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

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Saha, Mitul; Morais, Marc C

2012-12-15

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

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

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Yongping Yue

2016-01-01

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

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

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

2018-04-27

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

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

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Benesh, Nathan Philip

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

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

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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…

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

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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…

Developing guinea pig brain as a model for cortical folding.

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Hatakeyama, Jun; Sato, Haruka; Shimamura, Kenji

2017-05-01

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

Theoretical study of the folded waveguide

International Nuclear Information System (INIS)

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

1988-01-01

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

Analysis of local concentration in stomach fold pattern by using abdominal X-ray CT image

International Nuclear Information System (INIS)

Watanabe, Shigeto; Hasegawa, Jun-ichi; Mekada, Yoshito; Mori, Kensaku; Nawano, Shigeru

2004-01-01

The paper presents a method for analysis of stomach folds pattern in abdominal X-ray CT images. Many stomach cancers have local concentration of folds at cancer lesions. Therefore, in stomach diagnosis, it is very important to evaluate quantitatively such fold concentration. In this paper, a method for calculation of concentration index for line figure on a curved surface is proposed first. Then, using this method a processing procedure for detection of stomach cancer from an abdominal X-ray CT image is developed. In the experiment using practical X-ray CT images, it is shown that by the proposed procedure, higher values of concentration index are obtained at cancer area. (author)

Design and numerical analysis of an SMA mesh-based self-folding sheet

International Nuclear Information System (INIS)

Peraza-Hernandez, Edwin A; Hartl, Darren J; Malak Jr, Richard J

2013-01-01

Origami engineering, which is the practice of creating useful three-dimensional structures through folding and fold-like operations applied to initially two-dimensional entities, has the potential to impact several areas of design and manufacturing. In some instances, however, it may be impractical to apply external manipulations to produce the desired folds (e.g., as in remote applications such as space systems). In such cases, self-folding capabilities are valuable. A self-folding material or material system is one that can perform folding operations without manipulations from external forces. This work considers a concept for a self-folding material system. The system extends the ‘programmable matter’ concept and consists of an active, self-morphing sheet composed of two meshes of thermally actuated shape memory alloy (SMA) wire separated by a compliant passive layer. The geometric and power input parameters of the self-folding sheet are optimized to achieve the tightest local fold possible subject to stress and temperature constraints. The sheet folding performance considering folds at different angles relative to the orientation of the wire mesh is also analyzed. The optimization results show that a relatively low elastomer thickness is preferable to generate the tightest fold possible. The results also show that the self-folding sheet does not require large power inputs to achieve an optimal folding performance. It was shown that the self-folding sheet is capable of creating similar quality folds at different orientations. (paper)

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

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

2003-04-01

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

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

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

2010-05-01

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

Systematic analysis of short internal indels and their impact on protein folding

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Guo Jun-tao

2010-08-01

Full Text Available Abstract Background Protein sequence insertions/deletions (indels can be introduced during evolution or through alternative splicing (AS. Alternative splicing is an important biological phenomenon and is considered as the major means of expanding structural and functional diversity in eukaryotes. Knowledge of the structural changes due to indels is critical to our understanding of the evolution of protein structure and function. In addition, it can help us probe the evolution of alternative splicing and the diversity of functional isoforms. However, little is known about the effects of indels, in particular the ones involving core secondary structures, on the folding of protein structures. The long term goal of our study is to accurately predict the protein AS isoform structures. As a first step towards this goal, we performed a systematic analysis on the structural changes caused by short internal indels through mining highly homologous proteins in Protein Data Bank (PDB. Results We compiled a non-redundant dataset of short internal indels (2-40 amino acids from highly homologous protein pairs and analyzed the sequence and structural features of the indels. We found that about one third of indel residues are in disordered state and majority of the residues are exposed to solvent, suggesting that these indels are generally located on the surface of proteins. Though naturally occurring indels are fewer than engineered ones in the dataset, there are no statistically significant differences in terms of amino acid frequencies and secondary structure types between the "Natural" indels and "All" indels in the dataset. Structural comparisons show that all the protein pairs with short internal indels in the dataset preserve the structural folds and about 85% of protein pairs have global RMSDs (root mean square deviations of 2Å or less, suggesting that protein structures tend to be conserved and can tolerate short insertions and deletions. A few pairs

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

International Nuclear Information System (INIS)

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

1992-01-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

Analysis of laryngoscopic features in patients with unilateral vocal fold paresis.

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Woo, Peak; Parasher, Arjun K; Isseroff, Tova; Richards, Amanda; Sivak, Mark

2016-08-01

The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. More than 27 clinical parameters have been cited that may signify paresis. We hypothesize that some features are more significant than others. Prospective case series. Two laryngologists rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyography. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A Fisher exact test was completed for each measure. A kappa coefficient was calculated for effectiveness in predicting the laterality of paresis. Left-sided vocal fold paresis (n = 13) was significantly associated with ipsilateral axis deviation, thinner vocal fold, bowing, reduced movement, reduced kinesis, and phase lag (P vocal fold paresis (n = 6) was significantly associated with ipsilateral shorter vocal fold, axis deviation, reduced movement, and reduced kinesis (P vocal fold, vocal fold bowing, reduced movement, reduced kinesis, and phase lag were more likely to be associated with vocal fold paresis. 4 Laryngoscope, 126:1831-1836, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

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

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

1999-09-01

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

Adaptive Origami for Efficiently Folded Structures

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2016-02-01

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

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

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

2017-11-01

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

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

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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.

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

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Yung-An Tsou

2016-01-01

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

Frustration in Condensed Matter and Protein Folding

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

2014-03-01

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

Going beyond clustering in MD trajectory analysis: an application to villin headpiece folding.

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Aruna Rajan

2010-04-01

Full Text Available Recent advances in computing technology have enabled microsecond long all-atom molecular dynamics (MD simulations of biological systems. Methods that can distill the salient features of such large trajectories are now urgently needed. Conventional clustering methods used to analyze MD trajectories suffer from various setbacks, namely (i they are not data driven, (ii they are unstable to noise and changes in cut-off parameters such as cluster radius and cluster number, and (iii they do not reduce the dimensionality of the trajectories, and hence are unsuitable for finding collective coordinates. We advocate the application of principal component analysis (PCA and a non-metric multidimensional scaling (nMDS method to reduce MD trajectories and overcome the drawbacks of clustering. To illustrate the superiority of nMDS over other methods in reducing data and reproducing salient features, we analyze three complete villin headpiece folding trajectories. Our analysis suggests that the folding process of the villin headpiece is structurally heterogeneous.

Approaching climate-adaptive facades with foldings

DEFF Research Database (Denmark)

Sack-Nielsen, Torsten

2014-01-01

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

Solvent Effects on Protein Folding/Unfolding

Science.gov (United States)

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

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

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

Science.gov (United States)

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

2010-05-01

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

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

Directory of Open Access Journals (Sweden)

Shmygelska Alena

2007-09-01

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

Spherical images and inextensible curved folding

Science.gov (United States)

Seffen, Keith A.

2018-02-01

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

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

Science.gov (United States)

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

2012-01-01

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

Fold distributions at clover, crystal and segment levels for segmented clover detectors

International Nuclear Information System (INIS)

Kshetri, R; Bhattacharya, P

2014-01-01

Fold distributions at clover, crystal and segment levels have been extracted for an array of segmented clover detectors for various gamma energies. A simple analysis of the results based on a model independant approach has been presented. For the first time, the clover fold distribution of an array and associated array addback factor have been extracted. We have calculated the percentages of the number of crystals and segments that fire for a full energy peak event

A partially folded intermediate species of the β-sheet protein apo-pseudoazurin ism trapped during proline-limited folding

NARCIS (Netherlands)

Reader, J.S.; van Nuland, N.A.J.; Thompson, G.S.; Ferguson, S.J.; Dobson, C.M.; Radford, S.E.

2001-01-01

The folding of apo-pseudoazurin, a 123-residue, predominantly -sheet protein with a complex Greek key topology, has been investigated using several biophysical techniques. Kinetic analysis of refolding using farand near-ultraviolet circular dichroism (UV CD) shows that the protein folds slowly to

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-08-01

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

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

Science.gov (United States)

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

2014-11-01

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

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

Science.gov (United States)

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

2017-12-01

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

Combinatorial pattern discovery approach for the folding trajectory analysis of a beta-hairpin.

Directory of Open Access Journals (Sweden)

Laxmi Parida

2005-06-01

Full Text Available The study of protein folding mechanisms continues to be one of the most challenging problems in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape versus various reaction coordinates, such as the fraction of native contacts, the radius of gyration, RMSD from the native structure, and so on. In this paper, we present a combinatorial pattern discovery approach toward understanding the global state changes during the folding process. This is a first step toward an unsupervised (and perhaps eventually automated approach toward identification of global states. The approach is based on computing biclusters (or patterned clusters-each cluster is a combination of various reaction coordinates, and its signature pattern facilitates the computation of the Z-score for the cluster. For this discovery process, we present an algorithm of time complexity c in RO((N + nm log n, where N is the size of the output patterns and (n x m is the size of the input with n time frames and m reaction coordinates. To date, this is the best time complexity for this problem. We next apply this to a beta-hairpin folding trajectory and demonstrate that this approach extracts crucial information about protein folding intermediate states and mechanism. We make three observations about the approach: (1 The method recovers states previously obtained by visually analyzing free energy surfaces. (2 It also succeeds in extracting meaningful patterns and structures that had been overlooked in previous works, which provides a better understanding of the folding mechanism of the beta-hairpin. These new patterns also interconnect various states in existing free energy surfaces versus different reaction coordinates. (3 The approach does not require calculating the free energy values, yet it offers an analysis comparable to, and sometimes better than, the methods that use free energy landscapes, thus validating the

Combinatorial Pattern Discovery Approach for the Folding Trajectory Analysis of a beta-Hairpin.

Directory of Open Access Journals (Sweden)

2005-06-01

Full Text Available The study of protein folding mechanisms continues to be one of the most challenging problems in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape versus various reaction coordinates, such as the fraction of native contacts, the radius of gyration, RMSD from the native structure, and so on. In this paper, we present a combinatorial pattern discovery approach toward understanding the global state changes during the folding process. This is a first step toward an unsupervised (and perhaps eventually automated approach toward identification of global states. The approach is based on computing biclusters (or patterned clusters-each cluster is a combination of various reaction coordinates, and its signature pattern facilitates the computation of the Z-score for the cluster. For this discovery process, we present an algorithm of time complexity cinRO((N + nm log n, where N is the size of the output patterns and (n x m is the size of the input with n time frames and m reaction coordinates. To date, this is the best time complexity for this problem. We next apply this to a beta-hairpin folding trajectory and demonstrate that this approach extracts crucial information about protein folding intermediate states and mechanism. We make three observations about the approach: (1 The method recovers states previously obtained by visually analyzing free energy surfaces. (2 It also succeeds in extracting meaningful patterns and structures that had been overlooked in previous works, which provides a better understanding of the folding mechanism of the beta-hairpin. These new patterns also interconnect various states in existing free energy surfaces versus different reaction coordinates. (3 The approach does not require calculating the free energy values, yet it offers an analysis comparable to, and sometimes better than, the methods that use free energy landscapes, thus validating the

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

Science.gov (United States)

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

2018-03-01

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

Classification of protein fold classes by knot theory and prediction of folds by neural networks: A combined theoretical and experimental approach

DEFF Research Database (Denmark)

Ramnarayan, K.; Bohr, Henrik; Jalkanen, Karl J.

2008-01-01

We present different means of classifying protein structure. One is made rigorous by mathematical knot invariants that coincide reasonably well with ordinary graphical fold classification and another classification is by packing analysis. Furthermore when constructing our mathematical fold...... classifications, we utilize standard neural network methods for predicting protein fold classes from amino acid sequences. We also make an analysis of the redundancy of the structural classifications in relation to function and ligand binding. Finally we advocate the use of combining the measurement of the VA...

Do mesoscale faults in a young fold belt indicate regional or local stress?

Science.gov (United States)

Kokado, Akihiro; Yamaji, Atsushi; Sato, Katsushi

2017-04-01

The result of paleostress analyses of mesoscale faults is usually thought of as evidence of a regional stress. On the other hand, the recent advancement of the trishear modeling has enabled us to predict the deformation field around fault-propagation folds without the difficulty of assuming paleo mechanical properties of rocks and sediments. We combined the analysis of observed mesoscale faults and the trishear modeling to understand the significance of regional and local stresses for the formation of mesoscale faults. To this end, we conducted the 2D trishear inverse modeling with a curved thrust fault to predict the subsurface structure and strain field of an anticline, which has a more or less horizontal axis and shows a map-scale plane strain perpendicular to the axis, in the active fold belt of Niigata region, central Japan. The anticline is thought to have been formed by fault-propagation folding under WNW-ESE regional compression. Based on the attitudes of strata and the positions of key tephra beds in Lower Pleistocene soft sediments cropping out at the surface, we obtained (1) a fault-propagation fold with the fault tip at a depth of ca. 4 km as the optimal subsurface structure, and (2) the temporal variation of deformation field during the folding. We assumed that mesoscale faults were activated along the direction of maximum shear strain on the faults to test whether the fault-slip data collected at the surface were consistent with the deformation in some stage(s) of folding. The Wallace-Bott hypothesis was used to estimate the consistence of faults with the regional stress. As a result, the folding and the regional stress explained 27 and 33 of 45 observed faults, respectively, with the 11 faults being consistent with the both. Both the folding and regional one were inconsistent with the remaining 17 faults, which could be explained by transfer faulting and/or the gravitational spreading of the growing anticline. The lesson we learnt from this work was

Thermal analysis for folded solar array of spacecraft in orbit

International Nuclear Information System (INIS)

Yang, W.H.; Cheng, H.E.; Cai, A.

2004-01-01

The combined radiation-conduction heat transfer in folded solar array was considered as a three-dimensional anisotropic conduction without inner heat source. The three-dimensional equivalent conductivity in cell plate were obtained. The especially discrete equation coefficients of the nodes on the surfaces of adjacent cell plates were deduced by utilizing the simplified radiation network among the two adjacent cell plate surfaces and the deep cold space. All the thermal influence factors on the temperature response of the folded solar array were considered carefully. SIP method was used to solve the discrete equation. By comparing the calculation results under three cases, the temperature response and the maximum average difference of the folded solar array was obtained during the period of throw-radome of the launch vehicle and spread of the folded solar array. The obtained result is a valuable reference for the selection of the launch time of the spacecraft

Flips for 3-folds and 4-folds

CERN Document Server

Corti, Alessio

2007-01-01

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

Bifurcation of self-folded polygonal bilayers

Science.gov (United States)

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

2017-09-01

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

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

International Nuclear Information System (INIS)

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

2005-01-01

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

On the use of the observation-wise k-fold operation in PCA cross-validation

NARCIS (Netherlands)

Saccenti, E.; Camacho, J.

2015-01-01

Cross-validation (CV) is a common approach for determining the optimal number of components in a principal component analysis model. To guarantee the independence between model testing and calibration, the observationwise k-fold operation is commonly implemented in each cross-validation step. This

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

Science.gov (United States)

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

2018-03-23

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

A nomenclature paradigm for benign midmembranous vocal fold lesions.

Science.gov (United States)

Rosen, Clark A; Gartner-Schmidt, Jackie; Hathaway, Bridget; Simpson, C Blake; Postma, Gregory N; Courey, Mark; Sataloff, Robert T

2012-06-01

There is a significant lack of uniform agreement regarding nomenclature for benign vocal fold lesions (BVFLs). This confusion results in difficulty for clinicians communicating with their patients and with each other. In addition, BVFL research and comparison of treatment methods are hampered by the lack of a detailed and uniform BVFL nomenclature. Clinical consensus conferences were held to develop an initial BVFL nomenclature paradigm. Perceptual video analysis was performed to validate the stroboscopy component of the paradigm. The culmination of the consensus conferences and the video-perceptual analysis was used to evaluate the BVFL nomenclature paradigm using a retrospective review of patients with BVFL. An initial BVFL nomenclature paradigm was proposed utilizing detailed definitions relating to vocal fold lesion morphology, stroboscopy, response to voice therapy and intraoperative findings. Video-perceptual analysis of stroboscopy demonstrated that the proposed binary stroboscopy system used in the BVFL nomenclature paradigm was valid and widely applicable. Retrospective review of 45 patients with BVFL followed to the conclusion of treatment demonstrated that slight modifications of the initial BVFL nomenclature paradigm were required. With the modified BVFL nomenclature paradigm, 96% of the patients fit into the predicted pattern and definitions of the BVFL nomenclature system. This study has validated a multidimensional BVFL nomenclature paradigm. This vocal fold nomenclature paradigm includes nine distinct vocal fold lesions: vocal fold nodules, vocal fold polyp, pseudocyst, vocal fold cyst (subepithelial or ligament), nonspecific vocal fold lesion, vocal fold fibrous mass (subepithelial or ligament), and reactive lesion. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Geometric U-folds in four dimensions

Science.gov (United States)

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

2018-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

The crystal structure of phenolic acid decarboxylase from B. pumilus strain UI-670 has been determined and refined at 1.69 Å resolution. The enzyme is a dimer, with each subunit adopting a β-barrel structure belonging to the lipocalin fold. 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

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

Science.gov (United States)

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

2017-02-01

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

Melody discrimination and protein fold classification

Directory of Open Access Journals (Sweden)

Robert P. Bywater

2016-10-01

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

Folded Plate Structures as Building Envelopes

DEFF Research Database (Denmark)

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

2012-01-01

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

A comparison of RNA folding measures

Directory of Open Access Journals (Sweden)

Gardner Paul P

2005-10-01

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

The review on tessellation origami inspired folded structure

Science.gov (United States)

Chu, Chai Chen; Keong, Choong Kok

2017-10-01

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

BiP clustering facilitates protein folding in the endoplasmic reticulum.

Directory of Open Access Journals (Sweden)

Marc Griesemer

2014-07-01

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

Fractal Folding and Medium Viscoelasticity Contribute Jointly to Chromosome Dynamics

Science.gov (United States)

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

2018-02-01

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

Vocal Fold Vibratory Changes Following Surgical Intervention.

Science.gov (United States)

Chen, Wenli; Woo, Peak; Murry, Thomas

2016-03-01

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

Folding Membrane Proteins by Deep Transfer Learning

KAUST Repository

Wang, Sheng

2017-08-29

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

Web-based computational chemistry education with CHARMMing II: Coarse-grained protein folding.

Directory of Open Access Journals (Sweden)

Frank C Pickard

2014-07-01

Full Text Available A lesson utilizing a coarse-grained (CG Gō-like model has been implemented into the CHARMM INterface and Graphics (CHARMMing web portal (www.charmming.org to the Chemistry at HARvard Macromolecular Mechanics (CHARMM molecular simulation package. While widely used to model various biophysical processes, such as protein folding and aggregation, CG models can also serve as an educational tool because they can provide qualitative descriptions of complex biophysical phenomena for a relatively cheap computational cost. As a proof of concept, this lesson demonstrates the construction of a CG model of a small globular protein, its simulation via Langevin dynamics, and the analysis of the resulting data. This lesson makes connections between modern molecular simulation techniques and topics commonly presented in an advanced undergraduate lecture on physical chemistry. It culminates in a straightforward analysis of a short dynamics trajectory of a small fast folding globular protein; we briefly describe the thermodynamic properties that can be calculated from this analysis. The assumptions inherent in the model and the data analysis are laid out in a clear, concise manner, and the techniques used are consistent with those employed by specialists in the field of CG modeling. One of the major tasks in building the Gō-like model is determining the relative strength of the nonbonded interactions between coarse-grained sites. New functionality has been added to CHARMMing to facilitate this process. The implementation of these features into CHARMMing helps automate many of the tedious aspects of constructing a CG Gō model. The CG model builder and its accompanying lesson should be a valuable tool to chemistry students, teachers, and modelers in the field.

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

Science.gov (United States)

Mazuz, Keren

2013-06-01

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

CASP10-BCL::Fold efficiently samples topologies of large proteins.

Science.gov (United States)

Heinze, Sten; Putnam, Daniel K; Fischer, Axel W; Kohlmann, Tim; Weiner, Brian E; Meiler, Jens

2015-03-01

During CASP10 in summer 2012, we tested BCL::Fold for prediction of free modeling (FM) and template-based modeling (TBM) targets. BCL::Fold assembles the tertiary structure of a protein from predicted secondary structure elements (SSEs) omitting more flexible loop regions early on. This approach enables the sampling of conformational space for larger proteins with more complex topologies. In preparation of CASP11, we analyzed the quality of CASP10 models throughout the prediction pipeline to understand BCL::Fold's ability to sample the native topology, identify native-like models by scoring and/or clustering approaches, and our ability to add loop regions and side chains to initial SSE-only models. The standout observation is that BCL::Fold sampled topologies with a GDT_TS score > 33% for 12 of 18 and with a topology score > 0.8 for 11 of 18 test cases de novo. Despite the sampling success of BCL::Fold, significant challenges still exist in clustering and loop generation stages of the pipeline. The clustering approach employed for model selection often failed to identify the most native-like assembly of SSEs for further refinement and submission. It was also observed that for some β-strand proteins model refinement failed as β-strands were not properly aligned to form hydrogen bonds removing otherwise accurate models from the pool. Further, BCL::Fold samples frequently non-natural topologies that require loop regions to pass through the center of the protein. © 2015 Wiley Periodicals, Inc.

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

Science.gov (United States)

Samlan, Robin A.; Story, Brad H.

2011-01-01

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

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

Science.gov (United States)

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.

The four-fold way

International Nuclear Information System (INIS)

Terazawa, H.

1986-01-01

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

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

Science.gov (United States)

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

2017-04-04

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

Vocal fold paresis - a debilitating and underdiagnosed condition.

Science.gov (United States)

Harris, G; O'Meara, C; Pemberton, C; Rough, J; Darveniza, P; Tisch, S; Cole, I

2017-07-01

To review the clinical signs of vocal fold paresis on laryngeal videostroboscopy, to quantify its impact on patients' quality of life and to confirm the benefit of laryngeal electromyography in its diagnosis. Twenty-nine vocal fold paresis patients were referred for laryngeal electromyography. Voice Handicap Index 10 results were compared to 43 patients diagnosed with vocal fold paralysis. Laryngeal videostroboscopy analysis was conducted to determine side of paresis. Blinded laryngeal electromyography confirmed vocal fold paresis in 92.6 per cent of cases, with vocal fold lag being the most common diagnostic sign. The laryngology team accurately predicted side of paresis in 76 per cent of cases. Total Voice Handicap Index 10 responses were not significantly different between vocal fold paralysis and vocal fold paresis groups (26.08 ± 0.21 and 22.93 ± 0.17, respectively). Vocal fold paresis has a significant impact on quality of life. This study shows that laryngeal electromyography is an important diagnostic tool. Patients with persisting dysphonia and apparently normal vocal fold movement, who fail to respond to appropriate speech therapy, should be investigated for a diagnosis of vocal fold paresis.

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

Science.gov (United States)

Salvini, Francesco; Storti, Fabrizio

2001-01-01

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

TurboFold: Iterative probabilistic estimation of secondary structures for multiple RNA sequences

Directory of Open Access Journals (Sweden)

Sharma Gaurav

2011-04-01

significance threshold are shown to be more accurate for TurboFold than for alternative methods that estimate base pairing probabilities. TurboFold-MEA, which uses base pairing probabilities from TurboFold in a maximum expected accuracy algorithm for secondary structure prediction, has accuracy comparable to the best performing secondary structure prediction methods. The computational and memory requirements for TurboFold are modest and, in terms of sequence length and number of sequences, scale much more favorably than joint alignment and folding algorithms. Conclusions TurboFold is an iterative probabilistic method for predicting secondary structures for multiple RNA sequences that efficiently and accurately combines the information from the comparative analysis between sequences with the thermodynamic folding model. Unlike most other multi-sequence structure prediction methods, TurboFold does not enforce strict commonality of structures and is therefore useful for predicting structures for homologous sequences that have diverged significantly. TurboFold can be downloaded as part of the RNAstructure package at http://rna.urmc.rochester.edu.

Covering folded shapes

Directory of Open Access Journals (Sweden)

Oswin Aichholzer

2014-05-01

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

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

Directory of Open Access Journals (Sweden)

Jörg C Schlatterer

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

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

Directory of Open Access Journals (Sweden)

Konstantin B Zeldovich

2007-07-01

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

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

NARCIS (Netherlands)

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

2003-01-01

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

Wrinkles, folds, and plasticity in granular rafts

Science.gov (United States)

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

2017-09-01

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

Iterative Controller Tuning for Process with Fold Bifurcations

DEFF Research Database (Denmark)

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

2007-01-01

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

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

OpenAIRE

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

2013-01-01

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

Muscular anatomy of the human ventricular folds.

Science.gov (United States)

Moon, Jerald; Alipour, Fariborz

2013-09-01

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

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

Science.gov (United States)

Sun, Shuai; Hou, Guiting; Zheng, Chunfang

2017-11-01

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

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

Science.gov (United States)

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

2016-09-01

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

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

Science.gov (United States)

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

2015-04-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Sparse RNA folding revisited: space-efficient minimum free energy structure prediction.

Science.gov (United States)

Will, Sebastian; Jabbari, Hosna

2016-01-01

RNA secondary structure prediction by energy minimization is the central computational tool for the analysis of structural non-coding RNAs and their interactions. Sparsification has been successfully applied to improve the time efficiency of various structure prediction algorithms while guaranteeing the same result; however, for many such folding problems, space efficiency is of even greater concern, particularly for long RNA sequences. So far, space-efficient sparsified RNA folding with fold reconstruction was solved only for simple base-pair-based pseudo-energy models. Here, we revisit the problem of space-efficient free energy minimization. Whereas the space-efficient minimization of the free energy has been sketched before, the reconstruction of the optimum structure has not even been discussed. We show that this reconstruction is not possible in trivial extension of the method for simple energy models. Then, we present the time- and space-efficient sparsified free energy minimization algorithm SparseMFEFold that guarantees MFE structure prediction. In particular, this novel algorithm provides efficient fold reconstruction based on dynamically garbage-collected trace arrows. The complexity of our algorithm depends on two parameters, the number of candidates Z and the number of trace arrows T; both are bounded by [Formula: see text], but are typically much smaller. The time complexity of RNA folding is reduced from [Formula: see text] to [Formula: see text]; the space complexity, from [Formula: see text] to [Formula: see text]. Our empirical results show more than 80 % space savings over RNAfold [Vienna RNA package] on the long RNAs from the RNA STRAND database (≥2500 bases). The presented technique is intentionally generalizable to complex prediction algorithms; due to their high space demands, algorithms like pseudoknot prediction and RNA-RNA-interaction prediction are expected to profit even stronger than "standard" MFE folding. SparseMFEFold is free

Thermodynamics of protein folding: a random matrix formulation.

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Shukla, Pragya

2010-10-20

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

A comparison of RNA folding measures

DEFF Research Database (Denmark)

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

2005-01-01

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

Miniaturization of Multiple-Layer Folded Patch Antennas

DEFF Research Database (Denmark)

Zhang, Jiaying; Breinbjerg, Olav

2009-01-01

A new folded patch antenna with multiple layers was developed in this paper, by folding the patch in a proper way, and a highly miniaturized antenna can be realized. The multiple layer patch with 4-layer and 6-layer are designed and evaluated at 2.4 GHz, 915 MHz, and 415 MHz respectively. Then a 4...... layer patch is fabricated and measured to validate the design method. The theoretical analysis, design and simulations, fabrications, as well as the measurements are presented in this paper. All the results show that the folded patch antenna is a good candidate in making a highly miniaturized compact...

Physics of protein folding

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

2004-04-01

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

Quantification of Drive-Response Relationships Between Residues During Protein Folding.

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Qi, Yifei; Im, Wonpil

2013-08-13

Mutual correlation and cooperativity are commonly used to describe residue-residue interactions in protein folding/function. However, these metrics do not provide any information on the causality relationships between residues. Such drive-response relationships are poorly studied in protein folding/function and difficult to measure experimentally due to technical limitations. In this study, using the information theory transfer entropy (TE) that provides a direct measurement of causality between two times series, we have quantified the drive-response relationships between residues in the folding/unfolding processes of four small proteins generated by molecular dynamics simulations. Instead of using a time-averaged single TE value, the time-dependent TE is measured with the Q-scores based on residue-residue contacts and with the statistical significance analysis along the folding/unfolding processes. The TE analysis is able to identify the driving and responding residues that are different from the highly correlated residues revealed by the mutual information analysis. In general, the driving residues have more regular secondary structures, are more buried, and show greater effects on the protein stability as well as folding and unfolding rates. In addition, the dominant driving and responding residues from the TE analysis on the whole trajectory agree with those on a single folding event, demonstrating that the drive-response relationships are preserved in the non-equilibrium process. Our study provides detailed insights into the protein folding process and has potential applications in protein engineering and interpretation of time-dependent residue-based experimental observables for protein function.

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

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Kapoor, Abhijeet; Travesset, Alex

2014-03-01

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

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

International Nuclear Information System (INIS)

Xie, Wei; Zeng, Pan; Lei, Liping

2015-01-01

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

Nonsurgical Treatment for Vocal Fold Leukoplakia: An Analysis of 178 Cases

Directory of Open Access Journals (Sweden)

Min Chen

2017-01-01

Full Text Available Objective. To assess the effectiveness and identify vocal fold leukoplakia types appropriate for nonsurgical treatment. Methods. The vocal fold leukoplakia in 178 patients was divided by gross appearance into three subtypes: flat and smooth, elevated and smooth, and rough. All patients received nonsurgical treatment including smoking and drinking cessation, voice rest, omeprazole, and Chinese medication therapy. The clinical response of three subtypes was assessed after a 6-month follow-up. Results. Vocal fold leukoplakia subtypes included flat and smooth (n=66; 37.1%, elevated and smooth (n=103; 57.9%, and rough (n=9; 5.0%. The rate of complete response was 80.3%, 66.0%, and 0.0% for the 3 lesion types, respectively (rough versus flat and smooth, P<0.001; rough versus elevated and smooth, P<0.001, Fisher’s exact test. The incidence of carcinoma in rough leukoplakia was significantly higher than that in smooth leukoplakia (44.4% versus 2.4%, P=0.002, Fisher’s exact test. Clinical type was the only significant factor for clinical response of nonsurgical treatment (P=0.005, ordinal logistic regression. Conclusions. The effectiveness of nonsurgical treatment for smooth vocal fold leukoplakia is better in comparison to rough vocal fold leukoplakia. Smooth leukoplakia could be managed with nonsurgical treatment; more aggressive treatments should be considered for rough leukoplakia.

Factors that affect coseismic folds in an overburden layer

Science.gov (United States)

Zeng, Shaogang; Cai, Yongen

2018-03-01

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

Vocal Fold Paralysis

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

The role of the mesenchyme in cranial neural fold elevation

International Nuclear Information System (INIS)

Morris-Wiman, J.A.

1988-01-01

It has been previously postulated that the expansion of an hyaluronate-rich extracellular matrix in the fold mesenchyme is responsible for neural fold elevation. In this study we provide evidence that such expansions may play an important role in cranial neural fold elevation by pushing the folds towards the dorsal midline to assist in their elevation. For mesenchymal expansion to result in fold elevation, hyaluronate (HA) and mesenchymal cells must be non-randomly distributed within the mesenchyme. Patterns of mesenchymal cell distribution and cell proliferation were analyzed using the computer-assisted method of smoothed spatial averaging. The distribution of Alcian blue-stained and 3 H-glucosamine-labelled HA was also analyzed during cranial neural fold elevation using established image processing techniques. Analysis of the distribution of 3 H-thymidine-labelled mesenchymal cells indicated that differential mitotic activity was not responsible for decreased mesenchymal cell density. Likewise, analysis of distribution patterns of 3 H-glucosamine-labelled HA indicated that decreased HA concentration was not produced by regional differences in HA synthesis. These results suggest that decreases in mesenchymal cell density and HA concentration that occur during neural fold elevation are produced by mesenchymal expansion

MARATHON DESPITE UNILATERAL VOCAL FOLD PARALYSIS

Directory of Open Access Journals (Sweden)

Matthias Echternach

2008-06-01

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

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

International Nuclear Information System (INIS)

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

1991-01-01

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

Ligand-promoted protein folding by biased kinetic partitioning.

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

2017-04-01

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

Impact of hydrodynamic interactions on protein folding rates depends on temperature

Science.gov (United States)

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

2018-03-01

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

Competition between folding and glycosylation in the endoplasmic reticulum

DEFF Research Database (Denmark)

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

1996-01-01

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

Two states or not two states: Single-molecule folding studies of protein L

Science.gov (United States)

Aviram, Haim Yuval; Pirchi, Menahem; Barak, Yoav; Riven, Inbal; Haran, Gilad

2018-03-01

Experimental tools of increasing sophistication have been employed in recent years to study protein folding and misfolding. Folding is considered a complex process, and one way to address it is by studying small proteins, which seemingly possess a simple energy landscape with essentially only two stable states, either folded or unfolded. The B1-IgG binding domain of protein L (PL) is considered a model two-state folder, based on measurements using a wide range of experimental techniques. We applied single-molecule fluorescence resonance energy transfer (FRET) spectroscopy in conjunction with a hidden Markov model analysis to fully characterize the energy landscape of PL and to extract the kinetic properties of individual molecules of the protein. Surprisingly, our studies revealed the existence of a third state, hidden under the two-state behavior of PL due to its small population, ˜7%. We propose that this minority intermediate involves partial unfolding of the two C-terminal β strands of PL. Our work demonstrates that single-molecule FRET spectroscopy can be a powerful tool for a comprehensive description of the folding dynamics of proteins, capable of detecting and characterizing relatively rare metastable states that are difficult to observe in ensemble studies.

Stretched versus compressed exponential kinetics in α-helix folding

International Nuclear Information System (INIS)

Hamm, Peter; Helbing, Jan; Bredenbeck, Jens

2006-01-01

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

Intermediates and the folding of proteins L and G

Energy Technology Data Exchange (ETDEWEB)

Brown, Scott; Head-Gordon, Teresa

2003-07-01

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

Vocal fold contact patterns based on normal modes of vibration.

Science.gov (United States)

Smith, Simeon L; Titze, Ingo R

2018-05-17

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

Unraveling metamaterial properties in zigzag-base folded sheets.

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Eidini, Maryam; Paulino, Glaucio H

2015-09-01

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

New variants of known folds: do they bring new biology?

International Nuclear Information System (INIS)

Koonin, Eugene V.

2010-01-01

New distinct versions of known protein folds provide a powerful means of protein-function prediction that complements sequence and genomic context analysis. New distinct versions of known protein folds provide a powerful means of protein-function prediction that complements sequence and genomic context analysis. These structures do not supplant direct biochemical experiments, but are indispensable for the complete characterization of proteins

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

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Maity, Hiranmay; Reddy, Govardhan

2018-04-01

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

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

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

2017-05-10

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

Coarsely resolved topography along protein folding pathways

Science.gov (United States)

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

2000-03-01

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

Specific features of vocal fold paralysis in functional computed tomography

International Nuclear Information System (INIS)

Laskowska, K.; Mackiewicz-Nartowicz, H.; Serafin, Z.; Nawrocka, E.

2008-01-01

Vocal fold paralysis is usually recognized in laryngological examination, and detailed vocal fold function may be established based on laryngovideostroboscopy. Additional imaging should exclude any morphological causes of the paresis, which should be treated pharmacologically or surgically. The aim of this paper was to analyze the computed tomography (CT) images of the larynx in patients with unilateral vocal fold paralysis. CT examinations of the larynx were performed in 10 patients with clinically defined unilateral vocal fold paralysis. The examinations consisted of unenhanced acquisition and enhanced 3-phased acquisition: during free breathing, Valsalva maneuver, and phonation. The analysis included the following morphologic features of the paresis.the deepened epiglottic vallecula, the deepened piriform recess, the thickened and medially positioned aryepiglottic fold, the widened laryngeal pouch, the anteriorly positioned arytenoid cartilage, the thickened vocal fold, and the filled infraglottic space in frontal CT reconstruction. CT images were compared to laryngovideostroboscopy. The most common symptoms of vocal cord paralysis in CT were the deepened epiglottic vallecula and piriform recess, the widened laryngeal pouch with the filled infraglottic space, and the thickened aryepiglottic fold. Regarding the efficiency of the paralysis determination, the three functional techniques of CT larynx imaging used did not differ significantly, and laryngovideostroboscopy demonstrated its advantage over CT. CT of the larynx is a supplementary examination in the diagnosis of vocal fold paralysis, which may enable topographic analysis of the fold dysfunction. The knowledge of morphological CT features of the paralysis may help to prevent false-positive diagnosis of laryngeal cancer. (author)

Morphotectonic aspects of active folding in Zagros Mountains (Fin, SE of Iran)

Science.gov (United States)

Roustaei, M.; Abbasi, M.

2008-05-01

Active deformation in Iran, structural province of Zagros is a result of the convergence between the Arabian & Eurasian plates. The Zagros Mountains in southern Iran are one of the seismically active region & is introduced as fold-thrust belt trending NW-SE within the Arabian plate. Fin lies in Hormozgan province; the south of Iran. The vastness is surrounded by central Iran in the north, High Zagros in the North West and west, Folded Zagros in the east, Makran in the south east and Persian Gulf in the south. The study area is determined by complex structures, alternation of folding, salt diapers and faulting. The surface geology mainly comprises Neogene; Marls, Conglomerate, Sandstones (Mishan, Aghajari, Bakhtiyari formations), old fans and alluvium as syncline that Shur River cuts its north limb and passes from the middle of core .The older formations( Ghachsaran, Rzak and Guri member) folded into prominent anticlines. The fold axes mostly follow the parallel trends .Folds trending are NW-SE (Tashkend anticline), NE-SW (Khur anticline), E-W (Guniz & Handun anticline) and the trend of axes Baz fold in the main part is E-W. Hormoz salt also outcrops in the cores of many whaleback anticlines. Thus, anticlines may be cored with evaporates, even though no salt is currently exposed at the surface. Reason of selecting this area as an example referred to active seismcity. Release of energy is gradually in every events, this seismic character cusses that there was not earthquake with high magnitude in the area but it can not be a role. Answer to the question concerning relationship between folding of the crust layer and faulting at depth is more difficult. There is 2 terms to describe this relationship; "detachment folds" and" forced folds". In this paper, we try to analysis of different satellite imagery; Aster, spot and digital elevation model with high resolution (10 m) in order to detect geomorphic indicators which can help us to find a relationship between faulting

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

Science.gov (United States)

Hoque, Shahedul; Ito, Hiroyuki; Nishi, Ryuji

2018-04-01

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

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

Science.gov (United States)

Barone, Fabrizio; Giordano, Gerardo

2018-02-01

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

Double folded Yukawa interaction potential between two heavy ions

International Nuclear Information System (INIS)

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

1980-02-01

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

Kinetics and Thermodynamics of Membrane Protein Folding

Directory of Open Access Journals (Sweden)

Ernesto A. Roman

2014-03-01

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

In vivo measurement of vocal fold surface resistance.

Science.gov (United States)

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

2017-10-01

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

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

Science.gov (United States)

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

2016-03-01

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

Quantitative electromyographic characteristics of idiopathic unilateral vocal fold paralysis.

Science.gov (United States)

Chang, Wei-Han; Fang, Tuan-Jen; Li, Hsueh-Yu; Jaw, Fu-Shan; Wong, Alice M K; Pei, Yu-Cheng

2016-11-01

Unilateral vocal fold paralysis with no preceding causes is diagnosed as idiopathic unilateral vocal fold paralysis. However, comprehensive guidelines for evaluating the defining characteristics of idiopathic unilateral vocal fold paralysis are still lacking. In the present study, we hypothesized that idiopathic unilateral vocal fold paralysis may have different clinical and neurologic characteristics from unilateral vocal fold paralysis caused by surgical trauma. Retrospective, case series study. Patients with unilateral vocal fold paralysis were evaluated using quantitative laryngeal electromyography, videolaryngostroboscopy, voice acoustic analysis, the Voice Outcome Survey, and the Short Form-36 Health Survey quality-of-life questionnaire. Patients with idiopathic and iatrogenic vocal fold paralysis were compared. A total of 124 patients were recruited. Of those, 17 with no definite identified causes after evaluation and follow-up were assigned to the idiopathic group. The remaining 107 patients with surgery-induced vocal fold paralysis were assigned to the iatrogenic group. Patients in the idiopathic group had higher recruitment of the thyroarytenoid-lateral cricoarytenoid muscle complex and better quality of life compared with the iatrogenic group. Idiopathic unilateral vocal fold paralysis has a distinct clinical presentation, with relatively minor denervation changes in the involved laryngeal muscles, and less impact on quality of life compared with iatrogenic vocal fold paralysis. 4. Laryngoscope, 126:E362-E368, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Partial wave analysis for folded differential cross sections

Science.gov (United States)

Machacek, J. R.; McEachran, R. P.

2018-03-01

The value of modified effective range theory (MERT) and the connection between differential cross sections and phase shifts in low-energy electron scattering has long been recognized. Recent experimental techniques involving magnetically confined beams have introduced the concept of folded differential cross sections (FDCS) where the forward (θ ≤ π/2) and backward scattered (θ ≥ π/2) projectiles are unresolved, that is the value measured at the angle θ is the sum of the signal for particles scattered into the angles θ and π - θ. We have developed an alternative approach to MERT in order to analyse low-energy folded differential cross sections for positrons and electrons. This results in a simplified expression for the FDCS when it is expressed in terms of partial waves and thereby enables one to extract the first few phase shifts from a fit to an experimental FDCS at low energies. Thus, this method predicts forward and backward angle scattering (0 to π) using only experimental FDCS data and can be used to determine the total elastic cross section solely from experimental results at low-energy, which are limited in angular range.

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

Directory of Open Access Journals (Sweden)

Angelou Valerie

2016-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

Ruh, Jonas B.; Gerya, Taras

2015-04-01

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

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

Science.gov (United States)

Hindle, David; Kley, Jonas

2016-04-01

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

Vocal Fold Immobility due to Birth Trauma: A Systematic Review and Pooled Analysis.

Science.gov (United States)

Jabbour, Jad; North, Lauren M; Bougie, David; Robey, Thomas

2017-12-01

Objectives To describe the present understanding of birth trauma-related vocal fold immobility and quantitatively compare it with idiopathic congenital vocal fold immobility to explore whether it is a discrete entity. Data Sources PubMed, Ovid, and Cochrane databases. Review Methods English-language, observational, or experimental studies involving infants with idiopathic congenital or birth trauma-related vocal fold immobility were included. Data from these studies were pooled with our institution's vocal fold immobility database, with the resultant idiopathic congenital and birth trauma cohorts compared regarding patterns and outcomes of immobility. Results The search returned 288 articles, with 24 meeting inclusion criteria. Of studies reviewing all-cause immobility, 8 of 9 (88.9%) identified birth trauma as an etiology, although birth trauma definitions and proposed mechanisms of immobility varied. The study subjects, combined with our institution's database, yielded 188 idiopathic congenital and 113 birth trauma cases. Compared with idiopathic congenital cases, birth trauma cases had a higher proportion of unilateral immobility (72 of 113 [63.7%] vs 52 of 188 [27.7%], P vocal fold immobility warrant further investigation, these findings suggest that it is distinct from idiopathic congenital vocal fold immobility, with a unique presentation and potentially more favorable outcomes. This can inform counseling and management for infants with otherwise unexplained immobility but known birth trauma.

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

DEFF Research Database (Denmark)

Jin, Emma Yu; Nebel, M. E.

2016-01-01

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

Evolution of a protein folding nucleus.

Science.gov (United States)

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

2016-07-01

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

Vascular lesions of the vocal fold.

Science.gov (United States)

Gökcan, Kürşat Mustafa; Dursun, Gürsel

2009-04-01

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

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

Science.gov (United States)

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

2017-04-01

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

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

Science.gov (United States)

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

2018-03-27

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

Comparing the Folding and Misfolding Energy Landscapes of Phosphoglycerate Kinase

OpenAIRE

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

2012-01-01

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

A folding algorithm for extended RNA secondary structures.

Science.gov (United States)

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

2011-07-01

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

Status report on the folded tandem ion accelerator at BARC

Indian Academy of Sciences (India)

Folded tandem ion accelerator; charged particle beams; voltage stability; Rutherford backscattering; ion optics; beam lines. Abstract. The folded tandem ion accelerator (FOTIA) facility set up at BARC has become operational. At present, it is used for elemental analysis studies using the Rutherford backscattering technique.

A Method for Extracting the Free Energy Surface and Conformational Dynamics of Fast-Folding Proteins from Single Molecule Photon Trajectories

Science.gov (United States)

2015-01-01

Single molecule fluorescence spectroscopy holds the promise of providing direct measurements of protein folding free energy landscapes and conformational motions. However, fulfilling this promise has been prevented by technical limitations, most notably, the difficulty in analyzing the small packets of photons per millisecond that are typically recorded from individual biomolecules. Such limitation impairs the ability to accurately determine conformational distributions and resolve sub-millisecond processes. Here we develop an analytical procedure for extracting the conformational distribution and dynamics of fast-folding proteins directly from time-stamped photon arrival trajectories produced by single molecule FRET experiments. Our procedure combines the maximum likelihood analysis originally developed by Gopich and Szabo with a statistical mechanical model that describes protein folding as diffusion on a one-dimensional free energy surface. Using stochastic kinetic simulations, we thoroughly tested the performance of the method in identifying diverse fast-folding scenarios, ranging from two-state to one-state downhill folding, as a function of relevant experimental variables such as photon count rate, amount of input data, and background noise. The tests demonstrate that the analysis can accurately retrieve the original one-dimensional free energy surface and microsecond folding dynamics in spite of the sub-megahertz photon count rates and significant background noise levels of current single molecule fluorescence experiments. Therefore, our approach provides a powerful tool for the quantitative analysis of single molecule FRET experiments of fast protein folding that is also potentially extensible to the analysis of any other biomolecular process governed by sub-millisecond conformational dynamics. PMID:25988351

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

Science.gov (United States)

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

2013-03-01

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

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

Science.gov (United States)

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

2017-12-01

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

Oral and vocal fold diadochokinesis in dysphonic women.

Science.gov (United States)

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

2011-01-01

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

New Analysis and Theory of Deployable Folded Structures, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — A recently developed mathematical folding theory has great value for deployable space structures and in situ manufacture of large beams, panels and cylinders. The...

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

Science.gov (United States)

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

2011-10-01

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

RNA folding kinetics using Monte Carlo and Gillespie algorithms.

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Clote, Peter; Bayegan, Amir H

2018-04-01

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

Transferable coarse-grained potential for de novo protein folding and design.

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Ivan Coluzza

Full Text Available Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here we provide evidence of how a novel parametrization of the Caterpillar model may be used for both quantitative protein design and folding. With computer simulations it is shown that, for a large set of real protein structures, the model produces designed sequences with similar physical properties to the corresponding natural occurring sequences. The designed sequences require further experimental testing. For an independent set of proteins, previously used as benchmark, the correct folded structure of both the designed and the natural sequences is also demonstrated. The equilibrium folding properties are characterized by free energy calculations. The resulting free energy profiles not only are consistent among natural and designed proteins, but also show a remarkable precision when the folded structures are compared to the experimentally determined ones. Ultimately, the updated Caterpillar model is unique in the combination of its fundamental three features: its simplicity, its ability to produce natural foldable designed sequences, and its structure prediction precision. It is also remarkable that low frustration sequences can be obtained with such a simple and universal design procedure, and that the folding of natural proteins shows funnelled free energy landscapes without the need of any potentials based on the native structure.

Double folding model including the Pauli exclusion principle

International Nuclear Information System (INIS)

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

2002-01-01

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

How do horizontal, frictional discontinuities affect reverse fault-propagation folding?

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Bonanno, Emanuele; Bonini, Lorenzo; Basili, Roberto; Toscani, Giovanni; Seno, Silvio

2017-09-01

The development of new reverse faults and related folds is strongly controlled by the mechanical characteristics of the host rocks. In this study we analyze the impact of a specific kind of anisotropy, i.e. thin mechanical and frictional discontinuities, in affecting the development of reverse faults and of the associated folds using physical scaled models. We perform analog modeling introducing one or two initially horizontal, thin discontinuities above an initially blind fault dipping at 30° in one case, and 45° in another, and then compare the results with those obtained from a fully isotropic model. The experimental results show that the occurrence of thin discontinuities affects both the development and the propagation of new faults and the shape of the associated folds. New faults 1) accelerate or decelerate their propagation depending on the location of the tips with respect to the discontinuities, 2) cross the discontinuities at a characteristic angle (∼90°), and 3) produce folds with different shapes, resulting not only from the dip of the new faults but also from their non-linear propagation history. Our results may have direct impact on future kinematic models, especially those aimed to reconstruct the tectonic history of faults that developed in layered rocks or in regions affected by pre-existing faults.

Single-molecule folding mechanism of an EF-hand neuronal calcium sensor

DEFF Research Database (Denmark)

Heiðarsson, Pétur Orri; Otazo, Mariela R.; Bellucci, Luca

2013-01-01

EF-hand calcium sensors respond structurally to changes in intracellular Ca2+ concentration, triggering diverse cellular responses and resulting in broad interactomes. Despite impressive advances in decoding their structure-function relationships, the folding mechanism of neuronal calcium sensors...... of the N domain, showing striking interdomain dependence. Molecular dynamics results reveal the atomistic details of the unfolding process and rationalize the different domain stabilities during mechanical unfolding. Through constant-force experiments and hidden Markov model analysis, the free energy...

Inverse folding of RNA pseudoknot structures

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Li Linda YM

2010-06-01

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

Folding two dimensional crystals by swift heavy ion irradiation

International Nuclear Information System (INIS)

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

2014-01-01

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

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

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

2016-11-01

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

Radiology findings in adult patients with vocal fold paralysis

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Robinson, S. [Helsinki Medical Imaging Centre, University of Helsinki, Haartmaninkatu, Helsinki (Finland)]. E-mail: s.robinson@dzu.at; Pitkaeranta, A. [Department of Otorhinolaryngology, Haartmaninkatu, Helsinki (Finland)

2006-10-15

Aim: To compile imaging findings in patients with vocal fold paralysis. Materials and methods: A retrospective analysis of the medical charts of 100 consecutive patients, admitted to our department with vocal fold paralysis was undertaken. After laryngoscopy, patients were referred for radiological work-up depending on their clinical history and clinical findings. Ultrasound of the neck and/or contrast-enhanced spiral computed tomography (CT) of the neck and mediastinum was performed, extending to include the whole chest if necessary. In one patient, CT of the brain and in two patients, magnetic resonance angiography was undertaken. Analysis of the clinical and radiological data was performed to assess the most frequent causes for vocal fold paralysis. Results: In 66% of patients, the paralysis was related to previous surgery. Thirty-four percent of cases were labelled idiopathic after clinical examination. After imaging and follow-up, only 8% remained unexplained. Nine patients suffered from neoplasms, four from vascular disease, and 12 from infections. One patient developed encephalomyelitis disseminata on follow-up. Conclusion: Thorough radiological work-up helps to reduce the amount of idiopathic cases of vocal fold paralysis and guides appropriate therapy.

Radiology findings in adult patients with vocal fold paralysis

International Nuclear Information System (INIS)

Robinson, S.; Pitkaeranta, A.

2006-01-01

Aim: To compile imaging findings in patients with vocal fold paralysis. Materials and methods: A retrospective analysis of the medical charts of 100 consecutive patients, admitted to our department with vocal fold paralysis was undertaken. After laryngoscopy, patients were referred for radiological work-up depending on their clinical history and clinical findings. Ultrasound of the neck and/or contrast-enhanced spiral computed tomography (CT) of the neck and mediastinum was performed, extending to include the whole chest if necessary. In one patient, CT of the brain and in two patients, magnetic resonance angiography was undertaken. Analysis of the clinical and radiological data was performed to assess the most frequent causes for vocal fold paralysis. Results: In 66% of patients, the paralysis was related to previous surgery. Thirty-four percent of cases were labelled idiopathic after clinical examination. After imaging and follow-up, only 8% remained unexplained. Nine patients suffered from neoplasms, four from vascular disease, and 12 from infections. One patient developed encephalomyelitis disseminata on follow-up. Conclusion: Thorough radiological work-up helps to reduce the amount of idiopathic cases of vocal fold paralysis and guides appropriate therapy

Protein Folding Free Energy Landscape along the Committor - the Optimal Folding Coordinate.

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Krivov, Sergei V

2018-06-06

Recent advances in simulation and experiment have led to dramatic increases in the quantity and complexity of produced data, which makes the development of automated analysis tools very important. A powerful approach to analyze dynamics contained in such data sets is to describe/approximate it by diffusion on a free energy landscape - free energy as a function of reaction coordinates (RC). For the description to be quantitatively accurate, RCs should be chosen in an optimal way. Recent theoretical results show that such an optimal RC exists; however, determining it for practical systems is a very difficult unsolved problem. Here we describe a solution to this problem. We describe an adaptive nonparametric approach to accurately determine the optimal RC (the committor) for an equilibrium trajectory of a realistic system. In contrast to alternative approaches, which require a functional form with many parameters to approximate an RC and thus extensive expertise with the system, the suggested approach is nonparametric and can approximate any RC with high accuracy without system specific information. To avoid overfitting for a realistically sampled system, the approach performs RC optimization in an adaptive manner by focusing optimization on less optimized spatiotemporal regions of the RC. The power of the approach is illustrated on a long equilibrium atomistic folding simulation of HP35 protein. We have determined the optimal folding RC - the committor, which was confirmed by passing a stringent committor validation test. It allowed us to determine a first quantitatively accurate protein folding free energy landscape. We have confirmed the recent theoretical results that diffusion on such a free energy profile can be used to compute exactly the equilibrium flux, the mean first passage times, and the mean transition path times between any two points on the profile. We have shown that the mean squared displacement along the optimal RC grows linear with time as for

Current Understanding and Future Directions for Vocal Fold Mechanobiology

Science.gov (United States)

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

2013-01-01

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

Finite element modeling of the vocal folds with deformable interface tracking

DEFF Research Database (Denmark)

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

2014-01-01

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

Sulfated glycosaminoglycans in human vocal fold lamina propria

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Sung Woo Park

Full Text Available Abstract Introduction: The distribution, concentration and function of glycosaminoglycans in the various vocal fold tissues are still unclear. Objective: To evaluate the distribution and concentration of sulfated glycosaminoglycans in different layers of the human vocal fold according to gender and age. Methods: We used 11 vocal folds obtained from cadavers (7 men and 4 women with no laryngeal lesion, less than 12 h after death, and aged between 35 and 98 years. The folds underwent glycosaminoglycans extraction from the cover and ligament, and post-electrophoresis analysis. Data were compared according to the layer, age and gender. Results: The concentration of dermatan sulfate was significantly higher in all layers. No differences were observed in the total concentrations of glycosaminoglycans in layers studied according to gender. It is significantly lower in the cover of individuals aged below 60 years. Conclusion: Dermatan sulfate, chondroitin sulfate, and heparan sulfate were observed in the human vocal folds cover and ligament of both genders, with the concentration of dermatan sulfate being significantly higher in all layers. Glycosaminoglycans concentration on the cover is significantly lower in individuals below 60 years compared with elderly.

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

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Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

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

Science.gov (United States)

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

2016-03-01

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

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

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Michael Döllinger

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

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

Science.gov (United States)

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

2017-01-01

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

Morphometric Study of Vocal Folds in Indian Cadavers

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Rawal J.D.

2015-06-01

Full Text Available Introduction: -The larynx is an air passage and a sphincteric device used in respiration and phonation. The larynx, from inside outwards has a framework of mucosa surrounded by fibro-elastic membrane which in turn is surrounded by cartilages and then a layer of muscles. Vocal folds are intrinsic ligament of larynx covered by mucosal folds. Larynx generates sound through rhythmic opening and closing of the vocal folds. The perceived pitch of human voice mainly depends upon fundamental frequency of sound generated by larynx. Aim: - The aim of present study is to measure various dimensions of vocal folds in Indian cadavers. Material & Methods: - 50 larynx were obtained from embalmed cadavers, of which 10 larynx were of females. Vocal cords were dissected from the larynx and morphometric analysis was done. Results and Conclusions: - The average total length of the vocal folds was found to be 16.11 mm. ± 2.62 mm. in male and 14.10 mm. ± 1.54 mm. in female cadavers. The average width of the vocal folds was found to be 4.38 mm. ± 0.74 mm. in male and 3.60 mm. ± 0.64 mm. in female cadavers. The average total length of the membranous part of the vocal folds was found to be 11.90 mm. ± 1.86 mm. in male and 10.45 mm. ± 1.81 mm. in female cadavers. The average ratio of the length of the membranous and the cartilaginous parts of the vocal folds was calculated to be 3.10 ± 0.96in male and 2.85 ± 0.73in female cadavers.

The method of rapid design of the folding bridge based on floating supports

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Jan Marszałek

2016-09-01

Full Text Available The article includes a methodology for the rapid design of the folding bridge based on floating supports. This methodology includes an analysis of the possibilities of using blocks from the park pontoon PP-64 as a support for the floating folding DMS-65 bridge, built as a tem-porary crossing for civilian application. The analysis was carried out for the bridge loaded with a moving vehicle. The results of this analysis have been developed in the form of nomograms that enable rapid development of crossings in different structural systems.[b]Keywords[/b]: civil engineering, folding bridges, floating supports

Estimating Rheological Parameters of Anhydrite from Folded Evaporite sequences: Implications for Internal Dynamics of Salt Structure

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Adamuszek, Marta; Dabrowski, Marcin; Schmalholz, Stefan M.; Urai, Janos L.; Raith, Alexander

2015-04-01

parallel shortening. Mechanical model have been developed to rigorously correlate rheological properties of rock to the fold shape. A quantitative fold shape analysis combined with the folding theory allows deciphering the rock rheology. In this study, we analyse anhydrite layers embedded in the rock salt from the Upper Permian Zechstein salt formation from Dutch offshore. The anhydrite layers are common intercalation in the sequence. Their thickness varies between few millimetres up to hundred meters. The layers are strongly deformed often forming fold structures, which can be observed on a wide range of scales: in core samples, mine galleries, and also in the seismic sections. For our analysis, we select single layer fold trains. Quantitative fold shape analysis is carried out using Fold Geometry Toolbox [3], which allows deciphering the viscosity ratio between anhydrite and salt. The results indicate that anhydrite layer is ca. 10 to 30 times more viscous than the embedding salt. Further, we use the estimated rheological parameters of anhydrite in the numerical analysis of the internal salt dynamics. We solve an incompressible Stokes equation in the presence of the gravity using the finite element method solver MILAMIN [4]. We show that the presence of denser and more viscous anhydrite layers in the tectonically stable regime is insignificant for the internal stability of the salt structures. [1] Chemia, Z., Koyi, H., Schmeling, H. 2008. Numerical modelling of rise and fall of a dense layer in salt diapirs. Geophysical Journal International, 172: 798-816. [2] Muller, W.H., Briegel, U. 1978. The rheological behaviour of polycrystalline Anhydrite. Eclogae Geol. Helv, 71(2): 397-407 [3] Adamuszek M., Schmid D.W., Dabrowski M. 2011. Fold geometry toolbox - Automated determination of fold shape, shortening, and material properties, Journal of Structural Geology, 33: 1406-1416. [4] Dabrowski, M., Krotkiewski, M., and Schmid, D. W. 2008. MILAMIN: MATLAB-based finite element

Thermostability in endoglucanases is fold-specific

Science.gov (United States)

2011-01-01

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

Thermostability in endoglucanases is fold-specific

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Wolt Jeffrey D

2011-02-01

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

Folding pathways explored with artificial potential functions

International Nuclear Information System (INIS)

Ulutaş, B; Bozma, I; Haliloglu, T

2009-01-01

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

Structure of the thioredoxin-fold domain of human phosducin-like protein 2

International Nuclear Information System (INIS)

Lou, Xiaochu; Bao, Rui; Zhou, Cong-Zhao; Chen, Yuxing

2009-01-01

The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Human phosducin-like protein 2 (hPDCL2) has been identified as belonging to subgroup II of the phosducin (Pdc) family. The members of this family share an N-terminal helix domain and a C-terminal thioredoxin-fold (Trx-fold) domain. The X-ray crystal structure of the Trx-fold domain of hPDCL2 was solved at 2.70 Å resolution and resembled the Trx-fold domain of rat phosducin. Comparative structural analysis revealed the structural basis of their putative functional divergence

Using enzyme folding to explore the mechanism of therapeutic touch: a feasibility study.

Science.gov (United States)

Strickland, Mallory L; Boylan, Helen M

2010-07-01

The goal of this research is to design a novel model using protein folding to study Therapeutic Touch, a noncontact form of energy manipulation healing. Presented is a feasibility study suggesting that the denaturation path of ribonuclease A may be a useful model to study the energy exchange underlying therapeutic touch. The folding of ribonuclease A serves as a controlled energy-requiring system in which energy manipulation can be measured by the degree of folding achieved. A kinetic assay and fluorescence spectroscopy are used to assess the enzyme-folding state. The data suggest that the kinetic assay is a useful means of assessing the degree of refolding, and specifically, the enzyme function. However, fluorescence spectroscopy was not shown to be an effective measurement of enzyme structure for the purposes of this work. More research is needed to assess the underlying mechanism of therapeutic touch to complement the existing studies. An enzyme-folding model may provide a useful means of studying the energy exchange in therapeutic touch.

Folding two dimensional crystals by swift heavy ion irradiation

Energy Technology Data Exchange (ETDEWEB)

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

2014-12-01

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

Computational simulations of vocal fold vibration: Bernoulli versus Navier-Stokes.

Science.gov (United States)

Decker, Gifford Z; Thomson, Scott L

2007-05-01

The use of the mechanical energy (ME) equation for fluid flow, an extension of the Bernoulli equation, to predict the aerodynamic loading on a two-dimensional finite element vocal fold model is examined. Three steady, one-dimensional ME flow models, incorporating different methods of flow separation point prediction, were compared. For two models, determination of the flow separation point was based on fixed ratios of the glottal area at separation to the minimum glottal area; for the third model, the separation point determination was based on fluid mechanics boundary layer theory. Results of flow rate, separation point, and intraglottal pressure distribution were compared with those of an unsteady, two-dimensional, finite element Navier-Stokes model. Cases were considered with a rigid glottal profile as well as with a vibrating vocal fold. For small glottal widths, the three ME flow models yielded good predictions of flow rate and intraglottal pressure distribution, but poor predictions of separation location. For larger orifice widths, the ME models were poor predictors of flow rate and intraglottal pressure, but they satisfactorily predicted separation location. For the vibrating vocal fold case, all models resulted in similar predictions of mean intraglottal pressure, maximum orifice area, and vibration frequency, but vastly different predictions of separation location and maximum flow rate.

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

OpenAIRE

Yin, Jun; Zhang, Zhaoyan

2013-01-01

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

Adjustable thermal resistor by reversibly folding a graphene sheet.

Science.gov (United States)

Song, Qichen; An, Meng; Chen, Xiandong; Peng, Zhan; Zang, Jianfeng; Yang, Nuo

2016-08-11

Phononic (thermal) devices such as thermal diodes, thermal transistors, thermal logic gates, and thermal memories have been studied intensively. However, tunable thermal resistors have not been demonstrated yet. Here, we propose an instantaneously adjustable thermal resistor based on folded graphene. Through theoretical analysis and molecular dynamics simulations, we study the phonon-folding scattering effect and the dependence of thermal resistivity on the length between two folds and the overall length. Furthermore, we discuss the possibility of realizing instantaneously adjustable thermal resistors in experiment. Our studies bring new insights into designing thermal resistors and understanding the thermal modulation of 2D materials by adjusting basic structure parameters.

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

Science.gov (United States)

Arviv, Oshrit; Levy, Yaakov

2012-12-01

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

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

Science.gov (United States)

Cao, Yalong

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

Double-folding model including the Pauli exclusion principle

International Nuclear Information System (INIS)

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

2002-01-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Science.gov (United States)

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

2017-01-01

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.

There and back again: Two views on the protein folding puzzle.

Science.gov (United States)

Finkelstein, Alexei V; Badretdin, Azat J; Galzitskaya, Oxana V; Ivankov, Dmitry N; Bogatyreva, Natalya S; Garbuzynskiy, Sergiy O

2017-07-01

The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured folding times of single-domain globular proteins range from microseconds to hours: the difference (10-11 orders of magnitude) is the same as that between the life span of a mosquito and the age of the universe. This review describes physical theories of rates of overcoming the free-energy barrier separating the natively folded (N) and unfolded (U) states of protein chains in both directions: "U-to-N" and "N-to-U". In the theory of protein folding rates a special role is played by the point of thermodynamic (and kinetic) equilibrium between the native and unfolded state of the chain; here, the theory obtains the simplest form. Paradoxically, a theoretical estimate of the folding time is easier to get from consideration of protein unfolding (the "N-to-U" transition) rather than folding, because it is easier to outline a good unfolding pathway of any structure than a good folding pathway that leads to the stable fold, which is yet unknown to the folding protein chain. And since the rates of direct and reverse reactions are equal at the equilibrium point (as follows from the physical "detailed balance" principle), the estimated folding time can be derived from the estimated unfolding time. Theoretical analysis of the "N-to-U" transition outlines the range of protein folding rates in a good agreement with experiment. Theoretical analysis of folding (the "U-to-N" transition), performed at the level of formation and assembly of protein secondary structures, outlines the upper limit of protein folding times (i.e., of the time of search for the most stable fold). Both theories come to essentially the same results; this is not a surprise, because they describe overcoming one and the same free-energy barrier, although the way to the top of this barrier from the side of the unfolded state is very different from the way from the

A multi-directional rapidly exploring random graph (mRRG) for protein folding

KAUST Repository

Nath, Shuvra Kanti; Thomas, Shawna; Ekenna, Chinwe; Amato, Nancy M.

2012-01-01

Modeling large-scale protein motions, such as those involved in folding and binding interactions, is crucial to better understanding not only how proteins move and interact with other molecules but also how proteins misfold, thus causing many devastating diseases. Robotic motion planning algorithms, such as Rapidly Exploring Random Trees (RRTs), have been successful in simulating protein folding pathways. Here, we propose a new multi-directional Rapidly Exploring Random Graph (mRRG) specifically tailored for proteins. Unlike traditional RRGs which only expand a parent conformation in a single direction, our strategy expands the parent conformation in multiple directions to generate new samples. Resulting samples are connected to the parent conformation and its nearest neighbors. By leveraging multiple directions, mRRG can model the protein motion landscape with reduced computational time compared to several other robotics-based methods for small to moderate-sized proteins. Our results on several proteins agree with experimental hydrogen out-exchange, pulse-labeling, and F-value analysis. We also show that mRRG covers the conformation space better as compared to the other computation methods. Copyright © 2012 ACM.

Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue.

Science.gov (United States)

Garcia, Jordan A; Benboujja, Fouzi; Beaudette, Kathy; Rogers, Derek; Maurer, Rie; Boudoux, Caroline; Hartnick, Christopher J

2016-11-01

Vocal fold scarring, a condition defined by increased collagen content, is challenging to treat without a method of noninvasively assessing vocal fold structure in vivo. The goal of this study was to observe the effects of vocal fold collagen content on optical coherence tomography imaging to develop a quantifiable marker of disease. Excised specimen study. Massachusetts Eye and Ear Infirmary. Porcine vocal folds were injected with collagenase to remove collagen from the lamina propria. Optical coherence tomography imaging was performed preinjection and at 0, 45, 90, and 180 minutes postinjection. Mean pixel intensity (or image brightness) was extracted from images of collagenase- and control-treated hemilarynges. Texture analysis of the lamina propria at each injection site was performed to extract image contrast. Two-factor repeated measure analysis of variance and t tests were used to determine statistical significance. Picrosirius red staining was performed to confirm collagenase activity. Mean pixel intensity was higher at injection sites of collagenase-treated vocal folds than control vocal folds (P Fold change in image contrast was significantly increased in collagenase-treated vocal folds than control vocal folds (P = .002). Picrosirius red staining in control specimens revealed collagen fibrils most prominent in the subepithelium and above the thyroarytenoid muscle. Specimens treated with collagenase exhibited a loss of these structures. Collagen removal from vocal fold tissue increases image brightness of underlying structures. This inverse relationship may be useful in treating vocal fold scarring in patients. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Conformational dynamics of a protein in the folded and the unfolded state

Energy Technology Data Exchange (ETDEWEB)

Fitter, Joerg

2003-08-01

In a quasielastic neutron scattering experiment, the picosecond dynamics of {alpha}-amylase was investigated for the folded and the unfolded state of the protein. In order to ensure a reasonable interpretation of the internal protein dynamics, the protein was measured in D{sub 2}O-buffer solution. The much higher structural flexibility of the pH induced unfolded state as compared to the native folded state was quantified using a simple analytical model, describing a local diffusion inside a sphere. In terms of this model the conformational volume, which is explored mainly by confined protein side-chain movements, is parameterized by the radius of a sphere (folded state, r=1.2 A; unfolded state, 1.8 A). Differences in conformational dynamics between the folded and the unfolded state of a protein are of fundamental interest in the field of protein science, because they are assumed to play an important role for the thermodynamics of folding/unfolding transition and for protein stability.

The Ability of Human Nasal Inferior Turbinate-Derived Mesenchymal Stem Cells to Repair Vocal Fold Injuries.

Science.gov (United States)

Kim, Choung-Soo; Choi, Hyunsu; Park, Ki Cheol; Kim, Sung Won; Sun, Dong-Il

2018-03-01

Objective This study investigated the ability of implanted human nasal inferior turbinate-derived mesenchymal stem cells (hTMSCs) to repair injured vocal folds. To this end, we used quantitative real-time polymerase chain reaction (PCR) to analyze the early phase of wound healing and histopathological analysis to explore the late phase of wound healing in xenograft animal models. Study Design Prospective animal study. Setting Research laboratory. Subjects and Methods The right-side lamina propria of the vocal fold was injured in 20 rabbits and 30 rats. Next, hTMSCs were implanted into half of the injured vocal folds (hTMSC groups). As a control, phosphate-buffered saline (PBS) was injected into the other half of the injured vocal folds (PBS groups). Rat vocal folds were harvested for polymerase chain reaction (PCR) at 1 week after injury. Rabbit vocal folds were evaluated endoscopically and the larynges harvested for histological and immunohistochemical examination at 2 and 8 weeks after injury. Results In the hTMSC group, PCR showed that hyaluronan synthase ( HAS) 1, HAS 2, and transforming growth factor ( TGF)-β1 were significantly upregulated compared with the PBS group. Procollagen type III ( COL III) messenger RNA expression was significantly upregulated in the PBS group compared with the normal group. Histological analyses showed that hTMSC administration afforded more favorable collagen and hyaluronic acid deposition than was evident in the controls. Implanted hTMSCs were observed in injured vocal folds 2 weeks after implantation. Conclusions Our results show that hTMSCs implantation into injured vocal folds facilitated vocal fold regeneration, with presenting antifibrotic effects.

Effects of gravity in folding

Science.gov (United States)

Minkel, Donald Howe

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

Radiometric Dating of Folds: A new approach to determine the timing of deformation at shallow-crustal conditions, with examples from the Mexican Fold-Thrust Belt

Science.gov (United States)

Fitz Diaz, E.; van der Pluijm, B. A.

2012-12-01

We are developing a robust method to obtain absolute ages of folds that were formed at shallow crustal conditions. The method takes advantage of illite neocrystallization in folded, clay-bearing layers and the ability to obtain accurate retention and total gas ages from small size fractions using encapsulated Ar analysis, analogous to prior work on fault gouge dating. We illustrate our approach in folded Cretaceous shale-bentonitic layers that are interbedded with carbonates of the Zimapán and the Tampico-Misantla cretaceous basins in central-eastern Mexico. Basinal carbonates were buried by syntectonic turbidites and inverted during the formation of the Mexican Fold-Thrust in the Late Cretaceous. Results were obtained from four chevron folds that are representative of different stages of deformation, burial/temperature conditions and location within this thin-skinned orogenic wedge: two from the Zimapán Basin (Folds 1 and 2) in the west and two from the Tampico-Misantla Basin (Folds 3 and 4) in the east. Mineralogic compositions and variations in illite-polytypes, crystallite-size (CS) and Ar/Ar ages were obtained from size fractions in limbs and hinges of folded layers. Ar retention ages produce a folding age of ~81 Ma for Fold 1 and ~69 Ma for Fold 2, which are fully consistent with stratigraphic limits from syn-orogenic turbidities and observed overprinting events in the Mexican Fold-Thrust Belt. The total gas age of Fold 3, on the easternmost margin of the Tampico-Misantla Basin is similar to that of Fold 2, indicating that the second event is regional in scale. In addition to presenting a new, reliable method to constrain the timing of local deformation, we interpret folding and associated clay neo-mineralization in terms of the regional burial history, and localization and propagation of deformation within a heterogeneous orogenic wedge involving progressive deformation of two basins separated by a platform block.

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

Science.gov (United States)

Hadwin, Paul J; Peterson, Sean D

2017-04-01

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

Fatigue in engineering structures. A three fold analysis approach

International Nuclear Information System (INIS)

Malik, Afzaal M.; Qureshi, Ejaz M.; Dar, Naeem Ullah; Khan, Iqbal

2007-01-01

The integrity in most of the engineering structures in influenced by the presence of cracks or crack like defects. These structures fail, even catastrophically if a crack greater than a critically safe size exist. Although most of the optimal designed structures are initially free from critical cracks, sub-critical cracks can lead to failures under cyclic loadings, called fatigue crack growth. It is nearly impractical to prevent sub-critical crack growth in engineering structures particularly in crack sensitive structures like most of the structures in nuclear, aerospace and aeronautical domains. However, it is essential to predict the fatigue crack growth for these structures to preclude the in service failures causing loss of assets. The present research presents an automatic procedure for the prediction of fatigue crack growth in three dimensional engineering structures and the key data for the fracture mechanics based design: the stress intensity factors. Three fold analysis procedures are adopted to investigate the effects of repetitive (cyclic) loadings on the fatigue life of different geometries of aluminum alloy 2219-O. A general purpose Finite Element (FE) Code ANSYS-8.0 is used to predict/estimate the fatigue life of the geometries. Computer codes utilizing the Green's Function are developed to calculate the stress intensity factors. Another code based on superposition technique presented by Shivakumara and Foreman is developed to calculate the fatigue crack growth rate, fatigue life (No. of loading cycles are developed to validate the results and finally full scale laboratory tests are conducted for the comparison of the results. The results showing a close co-relation between the different techniques employed gives the promising feature of the analysis approach for the future work. (author)

Analysis of residuals from enzyme kinetic and protein folding experiments in the presence of correlated experimental noise.

Science.gov (United States)

Kuzmic, Petr; Lorenz, Thorsten; Reinstein, Jochen

2009-12-01

Experimental data from continuous enzyme assays or protein folding experiments often contain hundreds, or even thousands, of densely spaced data points. When the sampling interval is extremely short, the experimental data points might not be statistically independent. The resulting neighborhood correlation invalidates important theoretical assumptions of nonlinear regression analysis. As a consequence, certain goodness-of-fit criteria, such as the runs-of-signs test and the autocorrelation function, might indicate a systematic lack of fit even if the experiment does agree very well with the underlying theoretical model. A solution to this problem is to analyze only a subset of the residuals of fit, such that any excessive neighborhood correlation is eliminated. Substrate kinetics of the HIV protease and the unfolding kinetics of UMP/CMP kinase, a globular protein from Dictyostelium discoideum, serve as two illustrative examples. A suitable data-reduction algorithm has been incorporated into software DYNAFIT [P. Kuzmic, Anal. Biochem. 237 (1996) 260-273], freely available to all academic researchers from http://www.biokin.com.

Air pulse deformation measurement: a preliminary method for noninvasive vocal fold pliability analysis.

Science.gov (United States)

Larsson, Hans; Lindestad, P Å; Hertegård, S

2011-01-01

A new method, air pulse pliability measurement, is presented, with which the pliability and elasticity of the vocal folds was measured in vitro and in vivo using air pulses. The size of the mucosal movements induced by air pulse stimulation was measured with a laser-based technique. The air pulses fed via a 2-mm tubing, introduced through the working channel of a flexible endoscope. Both in vitro and in vivo tests were performed. Nine normal, vocally healthy subjects were examined by air pulse stimulations of the vocal folds, of the skin (cheek and dorsum of the hand) and of the inside of the lips. The in vitro tests showed a coefficient of variation of 5% within a range of 1-5 mm from the probe to the surface. The elasticity data showed no differences between vocal folds, lips or cheek. The hand data showed a significantly higher stiffness as compared to the other 3 measuring points (p measuring points, but in ideal conditions on skin it was 9%. The results show that the technique allows automatic, quantitative, noninvasive vocal fold pliability measurements on awake subjects. Copyright © 2010 S. Karger AG, Basel.

Oral and vocal fold diadochokinesis in dysphonic women

Directory of Open Access Journals (Sweden)

Talita Louzada

2011-12-01

Full Text Available The evaluation of oral and vocal fold diadochokinesis (DDK in individuals with voice disorders may contribute to the understanding of factors that affect the balanced vocal production. Scientific studies that make use of this assessment tool support the knowledge advance of this area, reflecting the development of more appropriate therapeutic planning. Objective: To compare the results of oral and vocal fold DDK in dysphonic women and in women without vocal disorders. Material and methods: For this study, 28 voice recordings of women from 19 to 54 years old, diagnosed with dysphonia and submitted to a voice assessment from speech pathologist and otorhinolaryngologist, were used. The control group included 30 nondysphonic women evaluated in prior research from normal adults. The analysis parameters like number and duration of emissions, as well as the regularity of the repetition of syllables "pa", "ta", "ka" and the vowels "a" and "i," were provided by the Advanced Motor Speech Profile program (MSP Model-5141, version-2.5.2 (KayPentax. The DDK sequence "pataka" was analyzed quantitatively through the Sound Forge 7.0 program, as well as manually with the audio-visual help of sound waves. Average values of oral and vocal fold DDK dysphonic and nondysphonic women were compared using the "t Student" test and were considered significant when p<0.05. Results: The findings showed no significant differences between populations; however, the coefficient of variation of period (CvP and jitter of period (JittP average of the "ka," "a" and "i" emissions, respectively, were higher in dysphonic women (CvP=10.42%, 12.79%, 12.05%; JittP=2.05%, 6.05%, 3.63% compared to the control group (CvP=8.86%; 10.95%, 11.20%; JittP=1.82%, 2.98%, 3.15%. Conclusion: Although the results do not indicate any difficulties in oral and laryngeal motor control in the dysphonic group, the largest instability in vocal fold DDK in the experimental group should be considered, and

Measurement of stress in vocal folds during phonation using spatiotemporal synchronization

Energy Technology Data Exchange (ETDEWEB)

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

2007-02-19

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

Measurement of stress in vocal folds during phonation using spatiotemporal synchronization

International Nuclear Information System (INIS)

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

2007-01-01

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

Detachments in Shale: Controlling Characteristics on Fold-Thrust Belt Style

Science.gov (United States)

Hansberry, Rowan; King, Ros; Collins, Alan; Morley, Chris

2013-04-01

Fold-thrust belts occur across multiple tectonic settings where thin-skinned deformation is accommodated by one or more detachment zones, both basal and within the fold-thrust belt. These fold-thrust belts exhibit considerable variation in structural style and vergence depending on the characteristics (e.g. strength, thickness, and lithology) and number of detachment zones. Shale as a detachment lithology is intrinsically weaker than more competent silts and sands; however, it can be further weakened by high pore pressures, reducing resistance to sliding and; high temperatures, altering the rheology of the detachment. Despite the implications for petroleum exploration and natural hazard assessment the precise nature by which detachments in shale control and are involved in deformation in fold-thrust belts is poorly understood. Present-day active basal detachment zones are usually located in inaccessible submarine regions. Therefore, this project employs field observations and sample analysis of ancient, exhumed analogues to document the nature of shale detachments (e.g. thickness, lithology, dip and dip direction, deformational temperature and thrust propagation rates) at field sites in Thailand, Norway and New Zealand. X-ray diffraction analysis of illite crystallinity and oxygen stable isotopes analysis are used as a proxy for deformational temperature whilst electron-backscatter diffraction analysis is used to constrain microstructural deformational patterns. K-Ar dating of synkinematic clay fault gouges is being applied to date the final stages of activity on individual faults with a view to constraining thrust activation sequences. It is not possible to directly measure palaeo-data for some key detachment parameters, such as pore pressure and coefficients of friction. However, the use of critical taper wedge theory has been used to successfully infer internal and basal coefficients of friction and depth-normalized pore pressure within a wedge and at its base

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1997-05-27

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

Using Trial Vocal Fold Injection to Select Vocal Fold Scar Patients Who May Benefit From More Durable Augmentation.

Science.gov (United States)

Carroll, Thomas L; Dezube, Aaron; Bauman, Laura A; Mallur, Pavan S

2018-02-01

Clinical indications for vocal fold injection augmentation (VFI) are expanding. Prior studies demonstrate the benefit of trial VFI for select causes of glottic insufficiency. No studies have examined trial VFI for glottic insufficiency resulting from true vocal fold (TVF) scar. Retrospective chart review of patients who underwent trial VFI for a dominant pathology of TVF scar causing dysphonia. Patients who subsequently underwent durable augmentation were identified. The primary study outcome was the difference in Voice Handicap Index-10 (VHI-10) score from pretrial VFI to post-durable augmentation. Twenty-eight patients underwent trial VFI for TVF scar, 22 of whom reported a positive response. Fifteen of 22 subjects who underwent durable augmentation had viable data for analysis. Mean VHI-10 improved from 26.9 to 18.6 ( P 5). A trial VFI is a potentially useful, low-risk procedure that appears to help the patient and clinician identify when global augmentation might improve the voice when vocal fold scar is present. Patients who reported successful trial VFI often demonstrated significant improvement in their VHI-10 after subsequent durable augmentation.

Vocal Fold Vibration Following Surgical Intervention in Three Vocal Pathologies: A Preliminary Study.

Science.gov (United States)

Chen, Wenli; Woo, Peak; Murry, Thomas

2017-09-01

High-speed videoendoscopy captures the cycle-to-cycle vibratory motion of each individual vocal fold in normal and severely disordered phonation. Therefore, it provides a direct method to examine the specific vibratory changes following vocal fold surgery. The purpose of this study was to examine the vocal fold vibratory pattern changes in the surgically treated pathologic vocal fold and the contralateral vocal fold in three vocal pathologies: vocal polyp (n = 3), paresis or paralysis (n = 3), and scar (n = 3). Digital kymography was used to extract high-speed kymographic vocal fold images at the mid-membranous region of the vocal fold. Spectral analysis was subsequently applied to the digital kymography to quantify the cycle-to-cycle movements of each vocal fold, expressed as a spectrum. Surgical modification resulted in significantly improved spectral power of the treated pathologic vocal fold. Furthermore, the contralateral vocal fold also presented with improved spectral power irrespective of vocal pathology. In comparison with normal vocal fold spectrum, postsurgical vocal fold vibrations continued to demonstrate decreased vibratory amplitude in both vocal folds. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Relationship Between Laryngeal Electromyography and Video Laryngostroboscopy in Vocal Fold Paralysis.

Science.gov (United States)

Maamary, Joel A; Cole, Ian; Darveniza, Paul; Pemberton, Cecilia; Brake, Helen Mary; Tisch, Stephen

2017-09-01

The objective of this study was to better define the relationship of laryngeal electromyography and video laryngostroboscopy in the diagnosis of vocal fold paralysis. Retrospective diagnostic cohort study with cross-sectional data analysis METHODS: Data were obtained from 57 patients with unilateral vocal fold paralysis who attended a large tertiary voice referral center. Electromyographic findings were classified according to recurrent laryngeal nerve, superior laryngeal nerve, and high vagal/combined lesions. Video laryngostroboscopy recordings were classified according to the position of the immobile fold into median, paramedian, lateral, and a foreshortened/hooded vocal fold. The position of the paralyzed vocal fold was then analyzed according to the lesion as determined by electromyography. The recurrent laryngeal nerve was affected in the majority of cases with left-sided lesions more common than right. Vocal fold position differed between recurrent laryngeal and combined vagal lesions. Recurrent laryngeal nerve lesions were more commonly associated with a laterally displaced immobile fold. No fold position was suggestive of a combined vagal lesion. The inter-rater reliability for determining fold position was high. Laryngeal electromyography is useful in diagnosing neuromuscular dysfunction of the larynx and best practice recommends its continued implementation along with laryngostroboscopy. While recurrent laryngeal nerve lesions are more likely to present with a lateral vocal fold, this does not occur in all cases. Such findings indicate that further unknown mechanisms contribute to fold position in unilateral paralysis. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site

Directory of Open Access Journals (Sweden)

Misquitta Stephanie A

2004-02-01

Full Text Available Abstract Background Glutaminyl cyclase (QC forms the pyroglutamyl residue at the amino terminus of numerous secretory peptides and proteins. We previously proposed the mammalian QC has some features in common with zinc aminopeptidases. We now have generated a structural model for human QC based on the aminopeptidase fold (pdb code 1AMP and mutated the apparent active site residues to assess their role in QC catalysis. Results The structural model proposed here for human QC, deposited in the protein databank as 1MOI, is supported by a variety of fold prediction programs, by the circular dichroism spectrum, and by the presence of the disulfide. Mutagenesis of the six active site residues present in both 1AMP and QC reveal essential roles for the two histidines (140 and 330, QC numbering and the two glutamates (201 and 202, while the two aspartates (159 and 248 appear to play no catalytic role. ICP-MS analysis shows less than stoichiometric zinc (0.3:1 in the purified enzyme. Conclusions We conclude that human pituitary glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site residues. In contrast to the aminopeptidase, however, QC does not appear to require zinc for enzymatic activity.

Nonlinear vs. linear biasing in Trp-cage folding simulations

Energy Technology Data Exchange (ETDEWEB)

Spiwok, Vojtěch, E-mail: spiwokv@vscht.cz; Oborský, Pavel; Králová, Blanka [Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6 166 28 (Czech Republic); Pazúriková, Jana [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Křenek, Aleš [Institute of Computer Science, Masaryk University, Botanická 554/68a, 602 00 Brno (Czech Republic); Center CERIT-SC, Masaryk Univerzity, Šumavská 416/15, 602 00 Brno (Czech Republic)

2015-03-21

Biased simulations have great potential for the study of slow processes, including protein folding. Atomic motions in molecules are nonlinear, which suggests that simulations with enhanced sampling of collective motions traced by nonlinear dimensionality reduction methods may perform better than linear ones. In this study, we compare an unbiased folding simulation of the Trp-cage miniprotein with metadynamics simulations using both linear (principle component analysis) and nonlinear (Isomap) low dimensional embeddings as collective variables. Folding of the mini-protein was successfully simulated in 200 ns simulation with linear biasing and non-linear motion biasing. The folded state was correctly predicted as the free energy minimum in both simulations. We found that the advantage of linear motion biasing is that it can sample a larger conformational space, whereas the advantage of nonlinear motion biasing lies in slightly better resolution of the resulting free energy surface. In terms of sampling efficiency, both methods are comparable.

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

Science.gov (United States)

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

2012-09-01

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

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

Science.gov (United States)

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

2017-10-01

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

Periodic folding of viscous sheets

Science.gov (United States)

Ribe, Neil M.

2003-09-01

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

Protein fold recognition using geometric kernel data fusion.

Science.gov (United States)

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

2014-07-01

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

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

Science.gov (United States)

Yin, Jun; Zhang, Zhaoyan

2013-01-01

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

Birefringence Optical Feedback with a Folded Cavity in HeNe Laser

International Nuclear Information System (INIS)

Wu Yun; Tan Yi-Dong

2013-01-01

The birefringence optical feedback with a folded cavity in HeNe laser is investigated. A theory model based on the equivalent cavity of the Fabry—Perot interferometer is presented. The phase difference between the two intensities in birefringence feedback is twice the retardation of the wave plate. The phase difference is invariable when the length of the feedback cavity changes. With the adoption of a cube corner prism (CCP) to form a folded cavity, the fringe frequency is doubled, and the resolution of the displacement sensor based on birefringence optical feedback with a folded cavity is improved. A resistance chain of 5-fold subdivision and 4-fold logic subdivision is used as further subdivision. The resolution of λ/80 is obtained eventually; for 632.8 nm HeNe laser it is 7.91 nm. The displacement sensor based on birefringence optical feedback with a folded cavity is simple and of high resolution, large measurement range, low cost, and is of great application potential in industry

Rate constant and reaction coordinate of Trp-cage folding in explicit water

NARCIS (Netherlands)

Juraszek, J.; Bolhuis, P.G.

2008-01-01

We report rate constant calculations and a reaction coordinate analysis of the rate-limiting folding and unfolding process of the Trp-cage mini-protein in explicit solvent using transition interface sampling. Previous transition path sampling simulations revealed that in this (un)folding process the

Vfold: a web server for RNA structure and folding thermodynamics prediction.

Science.gov (United States)

Xu, Xiaojun; Zhao, Peinan; Chen, Shi-Jie

2014-01-01

The ever increasing discovery of non-coding RNAs leads to unprecedented demand for the accurate modeling of RNA folding, including the predictions of two-dimensional (base pair) and three-dimensional all-atom structures and folding stabilities. Accurate modeling of RNA structure and stability has far-reaching impact on our understanding of RNA functions in human health and our ability to design RNA-based therapeutic strategies. The Vfold server offers a web interface to predict (a) RNA two-dimensional structure from the nucleotide sequence, (b) three-dimensional structure from the two-dimensional structure and the sequence, and (c) folding thermodynamics (heat capacity melting curve) from the sequence. To predict the two-dimensional structure (base pairs), the server generates an ensemble of structures, including loop structures with the different intra-loop mismatches, and evaluates the free energies using the experimental parameters for the base stacks and the loop entropy parameters given by a coarse-grained RNA folding model (the Vfold model) for the loops. To predict the three-dimensional structure, the server assembles the motif scaffolds using structure templates extracted from the known PDB structures and refines the structure using all-atom energy minimization. The Vfold-based web server provides a user friendly tool for the prediction of RNA structure and stability. The web server and the source codes are freely accessible for public use at "http://rna.physics.missouri.edu".

Vocal fold motion outcome based on excellent prognosis with laryngeal electromyography.

Science.gov (United States)

Smith, Libby J; Rosen, Clark A; Munin, Michael C

2016-10-01

As laryngeal electromyography (LEMG) becomes more refined, accurate predictions of vocal fold motion recovery are possible. Focus has been on outcomes for patients with poor prognosis for vocal fold motion recovery. Limited information is available regarding the expected rate of purposeful vocal fold motion recovery when there is good to normal motor recruitment, no signs of denervation, and no signs of synkinetic activity with LEMG, termed excellent prognosis. The objective of this study is to determine the rate of vocal fold motion recovery with excellent prognosis findings on LEMG after acute recurrent laryngeal nerve injury. Retrospective review. Patients undergoing a standardized LEMG protocol, consisting of qualitative (evaluation of motor recruitment, motor unit configuration, detection of fibrillations, presence of synkinesis) and quantitative (turns analysis) measurements were evaluated for purposeful vocal-fold motion recovery, calculated after at least 6 months since onset of injury. Twenty-three patients who underwent LEMG for acute vocal fold paralysis met the inclusion criteria of excellent prognosis. Eighteen patients (78.3%) recovered vocal fold motion, as determined by flexible laryngoscopy. Nearly 80% of patients determined to have excellent prognosis for vocal fold motion recovery experienced return of vocal fold motion. This information will help clinicians not only counsel their patients on expectations but will also help guide treatment. 4. Laryngoscope, 126:2310-2314, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments

DEFF Research Database (Denmark)

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

2008-01-01

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

Asymmetric hindwing foldings in rove beetles.

Science.gov (United States)

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

2014-11-18

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

Solitons and protein folding: An In Silico experiment

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-28

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

Solitons and protein folding: An In Silico experiment

International Nuclear Information System (INIS)

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

2015-01-01

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

Deformation and kinematics of the central Kirthar Fold Belt, Pakistan

Science.gov (United States)

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

2017-04-01

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

Tissue Engineering-based Therapeutic Strategies for Vocal Fold Repair and Regeneration

Science.gov (United States)

Li, Linqing; Stiadle, Jeanna M.; Lau, Hang K.; Zerdoum, Aidan B.; Jia, Xinqiao; L.Thibeault, Susan; Kiick, Kristi L.

2016-01-01

Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice. PMID:27619243

Interrater Reliability in Analysis of Laryngoscopic Features for Unilateral Vocal Fold Paresis.

Science.gov (United States)

Isseroff, Tova F; Parasher, Arjun K; Richards, Amanda; Sivak, Mark; Woo, Peak

2016-11-01

The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. In particular, laryngoscopy examination may result in significant disagreement in diagnosis among providers. We hypothesize that systematically evaluating for a standard set of clinical parameters will increase the diagnostic concordance among providers. Prospective case series conducted at a Tertiary referral Laryngology office. Two laryngologists (rater 1) and two trainees (rater 2) rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyogram. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A kappa coefficient was calculated for agreement in laryngoscopy findings and effectiveness in predicting the laterality of paresis. A substantial agreement (kappa coefficient > 0.61) existed between the raters for vocal fold length, vocal fold thickness, bowing, and reduction in movement. A moderate agreement (kappa coefficient > 0.41) existed between raters for piriform opening and reduced kinesis. The senior author was accurately able to diagnose the side of paresis in 89.5% of cases for a kappa coefficient of 0.78, whereas the trainees correctly predicted the side of paresis in 63.1% for a kappa coefficient of 0.35. The raters agreed on the diagnosis in 73.7% of cases for a kappa coefficient of 0.50. Using a standard set of laryngoscopy findings may improve the provider's ability to identify the laterality of vocal fold paresis and increase interrater reliability compared with other series. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Recurrence of vocal fold leukoplakia after carbon dioxide laser therapy.

Science.gov (United States)

Chen, Min; Chen, Jian; Cheng, Lei; Wu, Haitao

2017-09-01

This work aims to analyze the recurrence of vocal fold leukoplakia after carbon dioxide (CO 2 ) laser resection. In this retrospective study, all patients undergoing CO 2 laser resection of vocal fold leukoplakia were followed up for at least 2 years. Recurrence was diagnosed as any presence of leukoplakia in the vocal cord subsequent to previous successful complete resection. A total of 326 patients with complete resection of vocal fold leukoplakia and follow-up subsequent surveillance laryngoscopy were studied. The recurrence rate, the recurrence time, and risk factors were evaluated. Of these, 52 (16.0%) patients experienced recurrence with a mean follow-up time of 50.5 ± 15.4 months. The mean time to recurrence was 16.2 ± 14.1 months. Univariate analysis showed that the size of lesion (P vocal fold leukoplakia, long-term follow-up is required after CO 2 laser resection. In conclusion, the size of lesion combined with the pathological grade are important risk factors that predict vocal fold leukoplakia recurrence.

Possible association between Helicobacter pylori infection and vocal fold leukoplakia.

Science.gov (United States)

Chen, Min; Chen, Jian; Yang, Yue; Cheng, Lei; Wu, Hai-Tao

2018-03-06

Several studies have indicated the larynx as possible Helicobacter pylori (H. pylori) reservoirs. This study explored the association between H. pylori and vocal fold leukoplakia. The case-control study involved 51 patients with vocal fold leukoplakia and 35 control patients with vocal polyps. Helicobacter pylori was detected in tissues by the rapid urease test, nested polymerase chain reaction (PCR), and single-step PCR. The H. pylori-specific immunoglobulin antibodies were detected in plasma by enzyme-linked immunosorbent assay (ELISA). Helicobacter pylori-positive rate of vocal fold leukoplakia and vocal polyps was 23.5% versus 11.4% (P = .157), 37.2% versus 14.3% (P = .020), 27.5% versus 8.6% (P = .031), and 70.6% versus 68.6% (P = .841) detected by rapid urease test, nested PCR, single-step PCR, and ELISA, respectively. Regression analysis indicated that H. pylori infection (P = .044) was the independent risk factor for vocal fold leukoplakia. Helicobacter pylori infection exists in the larynx and may be associated with vocal fold leukoplakia. © 2018 Wiley Periodicals, Inc.

A Summary of Information on the Behavior of the Yakima Fold Belt as a Structural Entity -- Topical Report

Energy Technology Data Exchange (ETDEWEB)

Last, George V.; 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 (PSHA) of the Hanford Site. The purpose of this report is to summarize available data and analyses relevant to the Yakima Fold Belt (YFB) that may bear on the question of whether or not the YFB behaves as a single seismotectonic province in which activity along one fold structure is representative of behavior along all other fold structures. This topic has met with a fairly high level of contention in the expert community and has the potential to result in significant impacts on an evaluation of seismic hazard at the Hanford Site. This report defines the relevant 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, it suggests some possible approaches for reducing uncertainties regarding this issue.

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-07-07

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

Crystallization and preliminary X-ray analysis of tubulin-folding cofactor A from Arabidopsis thaliana

International Nuclear Information System (INIS)

Lu, Lu; Nan, Jie; Mi, Wei; Wei, Chun-Hong; Li, Lan-Fen; Li, Yi

2010-01-01

Tubulin-folding cofactor A from A. thaliana has been crystallized and preliminarily analyzed using X-ray diffraction. Tubulin-folding cofactor A (TFC A) is a molecular post-chaperonin that is involved in the β-tubulin-folding pathway. It has been identified in many organisms including yeasts, humans and plants. In this work, Arabidopsis thaliana TFC A was expressed in Escherichia coli and purified to homogeneity. After thrombin cleavage, a well diffracting crystal was obtained by the sitting-drop vapour-diffusion method at 289 K. The crystal diffracted to 1.6 Å resolution using synchrotron radiation and belonged to space group I4 1 , with unit-cell parameters a = 55.0, b = 55.0, c = 67.4 Å

Folding in and out: passive morphing in flapping wings.

Science.gov (United States)

Stowers, Amanda K; Lentink, David

2015-03-25

We present a new mechanism for passive wing morphing of flapping wings inspired by bat and bird wing morphology. The mechanism consists of an unactuated hand wing connected to the arm wing with a wrist joint. Flapping motion generates centrifugal accelerations in the hand wing, forcing it to unfold passively. Using a robotic model in hover, we made kinematic measurements of unfolding kinematics as functions of the non-dimensional wingspan fold ratio (2-2.5) and flapping frequency (5-17 Hz) using stereo high-speed cameras. We find that the wings unfold passively within one to two flaps and remain unfolded with only small amplitude oscillations. To better understand the passive dynamics, we constructed a computer model of the unfolding process based on rigid body dynamics, contact models, and aerodynamic correlations. This model predicts the measured passive unfolding within about one flap and shows that unfolding is driven by centrifugal acceleration induced by flapping. The simulations also predict that relative unfolding time only weakly depends on flapping frequency and can be reduced to less than half a wingbeat by increasing flapping amplitude. Subsequent dimensional analysis shows that the time required to unfold passively is of the same order of magnitude as the flapping period. This suggests that centrifugal acceleration can drive passive unfolding within approximately one wingbeat in small and large wings. Finally, we show experimentally that passive unfolding wings can withstand impact with a branch, by first folding and then unfolding passively. This mechanism enables flapping robots to squeeze through clutter without sophisticated control. Passive unfolding also provides a new avenue in morphing wing design that makes future flapping morphing wings possibly more energy efficient and light-weight. Simultaneously these results point to possible inertia driven, and therefore metabolically efficient, control strategies in bats and birds to morph or recover

A folded plate clamped along one side only

Science.gov (United States)

Nazarov, Serguei A.; Slutskij, Andrey S.

2017-12-01

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

Modeling and Analysis of Wrinkled Membranes: An Overview

Science.gov (United States)

Yang, B.; Ding, H.; Lou, M.; Fang, H.; Broduer, Steve (Technical Monitor)

2001-01-01

Thin-film membranes are basic elements of a variety of space inflatable/deployable structures. Wrinkling degrades the performance and reliability of these membrane structures, and hence has been a topic of continued interest. Wrinkling analysis of membranes for general geometry and arbitrary boundary conditions is quite challenging. The objective of this presentation is two-fold. Firstly, the existing models of wrinkled membranes and related numerical solution methods are reviewed. The important issues to be discussed are the capability of a membrane model to characterize taut, wrinkled and slack states of membranes in a consistent and physically reasonable manner; the ability of a wrinkling analysis method to predict the formation and growth of wrinkled regions, and to determine out-of-plane deformation and wrinkled waves; the convergence of a numerical solution method for wrinkling analysis; and the compatibility of a wrinkling analysis with general-purpose finite element codes. According to this review, several opening issues in modeling and analysis of wrinkled membranes that are to be addressed in future research are summarized, The second objective of this presentation is to discuss a newly developed membrane model of two viable parameters (2-VP model) and associated parametric finite element method (PFEM) for wrinkling analysis are introduced. The innovations and advantages of the proposed membrane model and PFEM-based wrinkling analysis are: (1) Via a unified stress-strain relation; the 2-VP model treat the taut, wrinkled, and slack states of membranes consistently; (2) The PFEM-based wrinkling analysis has guaranteed convergence; (3) The 2-VP model along with PFEM is capable of predicting membrane out-of-plane deformations; and (4) The PFEM can be integrated into any existing finite element code. Preliminary numerical examples are also included in this presentation to demonstrate the 2-VP model and PFEM-based wrinkling analysis approach.

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

Science.gov (United States)

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

2009-11-01

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

Cation-induced folding of alginate-bearing bilayer gels: an unusual example of spontaneous folding along the long axis.

Science.gov (United States)

Athas, Jasmin C; Nguyen, Catherine P; Kummar, Shailaa; Raghavan, Srinivasa R

2018-04-04

The spontaneous folding of flat gel films into tubes is an interesting example of self-assembly. Typically, a rectangular film folds along its short axis when forming a tube; folding along the long axis has been seen only in rare instances when the film is constrained. Here, we report a case where the same free-swelling gel film folds along either its long or short axis depending on the concentration of a solute. Our gels are sandwiches (bilayers) of two layers: a passive layer of cross-linked N,N'-dimethylyacrylamide (DMAA) and an active layer of cross-linked DMAA that also contains chains of the biopolymer alginate. Multivalent cations like Ca2+ and Cu2+ induce these bilayer gels to fold into tubes. The folding occurs instantly when a flat film of the gel is introduced into a solution of these cations. The likely cause for folding is that the active layer stiffens and shrinks (because the alginate chains in it get cross-linked by the cations) whereas the passive layer is unaffected. The resulting mismatch in swelling degree between the two layers creates internal stresses that drive folding. Cations that are incapable of cross-linking alginate, such as Na+ and Mg2+, do not induce gel folding. Moreover, the striking aspect is the direction of folding. When the Ca2+ concentration is high (100 mM or higher), the gels fold along their long axis, whereas when the Ca2+ concentration is low (40 to 80 mM), the gels fold along their short axis. We hypothesize that the folding axis is dictated by the inhomogeneous nature of alginate-cation cross-linking, i.e., that the edges get cross-linked before the faces of the gel. At high Ca2+ concentration, the stiffer edges constrain the folding; in turn, the gel folds such that the longer edges are deformed less, which explains the folding along the long axis. At low Ca2+ concentration, the edges and the faces of the gel are more similar in their degree of cross-linking; therefore, the gel folds along its short axis. An analogy

The method of rapid design of the folding bridge based on floating supports

OpenAIRE

Jan Marszałek; Mieczysław Piechota

2016-01-01

The article includes a methodology for the rapid design of the folding bridge based on floating supports. This methodology includes an analysis of the possibilities of using blocks from the park pontoon PP-64 as a support for the floating folding DMS-65 bridge, built as a tem-porary crossing for civilian application. The analysis was carried out for the bridge loaded with a moving vehicle. The results of this analysis have been developed in the form of nomograms that enable rapid development ...

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-02-15

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

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

Directory of Open Access Journals (Sweden)

Asdrúbal Bernal

2018-03-01

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

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Yunqiang Bian

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

Araguaia fold belt, new geochronological data

International Nuclear Information System (INIS)

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

1990-01-01

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

Three-Fold Symmetry Restrictions on Two-Dimensional Micropolar Materials

DEFF Research Database (Denmark)

Warren, W. E.; Byskov, Esben

that three-fold symmetry requires both the stress and couple stress tensors to be isotropic in the plane. We obtain the constitutive relations for an equilateral triangle structure and for the hexagonal or honeycomb structure, both of which exhibit three-fold symmetry in the plane. These results are compared......Analysis of the mechanical properties of engineering materials with micro-structure generally requires modification of the concept of a simple material. One approach is the theory of micropolar materials which introduces an independent rotation of a material element and the resulting stress...

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

Directory of Open Access Journals (Sweden)

Fábio L. Custódio

2004-01-01

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

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

Science.gov (United States)

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

2017-06-01

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

Recovery of Vocal Fold Epithelium after Acute Phonotrauma.

Science.gov (United States)

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

2017-01-01

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

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

Science.gov (United States)

Bergasa-Caceres, Fernando; Rabitz, Herschel A.

2014-01-01

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

Phase transition in polypeptides: a step towards the understanding of protein folding

DEFF Research Database (Denmark)

Yakubovich, Alexander V.; Solov'yov, Ilia; Solov'yov, Andrey V.

2006-01-01

We present a formalism which turns out to be very successful in the description of the polypeptide folding. We consider this process as a first-order phase transition and develop a theory which is free of model parameters and is based solely on fundamental physical principles. It describes...... essential thermodynamical properties of the system such as heat capacity, the phase transition temperature and others from the analysis of the polypeptide potential energy surface calculated within ab initio density functional theory and parameterized by two dihedral angles. This problem is viewed...

3D Visualization of Sheath Folds in Roman Marble from Ephesus, Turkey

Science.gov (United States)

Wex, Sebastian; Passchier, Cornelis W.; de Kemp, Eric A.; Ilhan, Sinan

2013-04-01

Excavation of a palatial 2nd century AD house (Terrace House Two) in the ancient city of Ephesus, Turkey in the 1970s produced 10.313 pieces of colored, folded marble which belonged to 54 marble plates of 1.6 cm thickness that originally covered the walls of the banquet hall of the house. The marble plates were completely reassembled and restored by a team of workers over the last 6 years. The plates were recognized as having been sawn from two separate large blocks of "Cipollino verde", a green mylonitized marble from Karystos on the Island of Euboea, Greece. After restoration, it became clear that all slabs had been placed on the wall in approximately the sequence in which they had been cut off by a Roman stone saw. As a result, the marble plates give a full 3D insight in the folded internal structure of 1m3 block of mylonite. The restoration of the slabs was recognized as a first, unique opportunity for detailed reconstruction of the 3D geometry of m-scale folds in mylonitized marble. Photographs were taken of each slab and used to reconstruct their exact arrangement within the originally quarried blocks. Outlines of layers were digitized and a full 3D reconstruction of the internal structure of the block was created using ArcMap and GOCAD. Fold structures in the block include curtain folds and multilayered sheath folds. Several different layers showing these structures were digitized on the photographs of the slab surfaces and virtually mounted back together within the model of the marble block. Due to the serial sectioning into slabs, with cm-scale spacing, the visualization of the 3D geometry of sheath folds was accomplished with a resolution better than 4 cm. Final assembled 3D images reveal how sheath folds emerge from continuous layers and show their overall consistency as well as a constant hinge line orientation of the fold structures. Observations suggest that a single deformation phase was responsible for the evolution of "Cipollino verde" structures

ETIOLOGICAL FACTORS FOR VOCAL FOLD POLYP FORMATION

Directory of Open Access Journals (Sweden)

DAŠA GLUVAJIĆ

2016-05-01

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

On the formation of fold-type oscillation marks in the continuous casting of steel.

Science.gov (United States)

Vynnycky, M; Saleem, S; Devine, K M; Florio, B J; Mitchell, S L; O'Brien, S B G

2017-06-01

Asymptotic methods are employed to revisit an earlier model for oscillation-mark formation in the continuous casting of steel. A systematic non-dimensionalization of the governing equations, which was not carried out previously, leads to a model with 12 dimensionless parameters. Analysis is provided in the same parameter regime as for the earlier model, and surprisingly simple analytical solutions are found for the oscillation-mark profiles; these are found to agree reasonably well with the numerical solution in the earlier model and very well with fold-type oscillation marks that have been obtained in more recent experimental work. The benefits of this approach, when compared with time-consuming numerical simulations, are discussed in the context of auxiliary models for macrosegregation and thermomechanical stresses and strains.

Dynamics in thin folded polymer films

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Croll, Andrew; Rozairo, Damith

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

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

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

2007-05-22

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

Graph-representation of oxidative folding pathways

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Kaján László

2005-01-01

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

Epithelial Folding Driven by Apical or Basal-Lateral Modulation: Geometric Features, Mechanical Inference, and Boundary Effects.

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Wen, Fu-Lai; Wang, Yu-Chiun; Shibata, Tatsuo

2017-06-20

During embryonic development, epithelial sheets fold into complex structures required for tissue and organ functions. Although substantial efforts have been devoted to identifying molecular mechanisms underlying epithelial folding, far less is understood about how forces deform individual cells to sculpt the overall sheet morphology. Here we describe a simple and general theoretical model for the autonomous folding of monolayered epithelial sheets. We show that active modulation of intracellular mechanics along the basal-lateral as well as the apical surfaces is capable of inducing fold formation in the absence of buckling instability. Apical modulation sculpts epithelia into shallow and V-shaped folds, whereas basal-lateral modulation generates deep and U-shaped folds. These characteristic tissue shapes remain unchanged when subject to mechanical perturbations from the surroundings, illustrating that the autonomous folding is robust against environmental variabilities. At the cellular scale, how cells change shape depends on their initial aspect ratios and the modulation mechanisms. Such cell deformation characteristics are verified via experimental measurements for a canonical folding process driven by apical modulation, indicating that our theory could be used to infer the underlying folding mechanisms based on experimental data. The mechanical principles revealed in our model could potentially guide future studies on epithelial folding in diverse systems. Copyright © 2017. Published by Elsevier Inc.

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

International Nuclear Information System (INIS)

Masago, Akira; Suzuki, Naoshi

2001-01-01

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

Understanding ensemble protein folding at atomic detail

International Nuclear Information System (INIS)

Wallin, Stefan; Shakhnovich, Eugene I

2008-01-01

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

Vocal fold injection medialization laryngoplasty.

Science.gov (United States)

Modi, Vikash K

2012-01-01

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

Quantitative Study of Vibrational Symmetry of Injured Vocal Folds via Digital Kymography in Excised Canine Larynges

Science.gov (United States)

Krausert, Christopher R.; Ying, Di; Zhang, Yu; Jiang, Jack J.

2011-01-01

Purpose: Digital kymography and vocal fold curve fitting are blended with detailed symmetry analysis of kymograms to provide a comprehensive characterization of the vibratory properties of injured vocal folds. Method: Vocal fold vibration of 12 excised canine larynges was recorded under uninjured, unilaterally injured, and bilaterally injured…

Association between Laryngeal Pepsin Levels and the Presence of Vocal Fold Polyps.

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Wang, Lu; Tan, Jia-Jie; Wu, Ting; Zhang, Rui; Wu, Jia-Nuan; Zeng, Fang-Fang; Liu, You-Li; Han, Xiao-Yan; Li, Yan-Fei; Li, Xiang-Ping

2017-01-01

Objective To determine whether pepsin, the main component of refluxed gastric contents, is significantly associated with vocal fold polyps and to evaluate the diagnostic value of pepsin in vocal fold polyps' tissues. Study Design Cross-sectional study. Setting Nanfang Hospital of Southern Medical University. Subjects and Methods The study included 32 patients with vocal fold polyps and 16 healthy controls between 2011 and 2012. Reflux symptom index and reflux finding score assessments, 24-hour combined multichannel intraluminal impedance and pH monitoring, and biopsy of the vocal fold polyp tissues or posterior laryngeal mucosa (healthy controls) for immunohistochemical pepsin staining were performed. Results The expression of pepsin was significantly higher in patients with vocal fold polyps than in controls (28/32, 75% vs 5/16, 31.25%; P vocal fold polyps formation. In addition, pepsin immunohistochemical analysis of polyp biopsy samples appears to be a more sensitive and effective test for diagnosing laryngopharyngeal reflux than the reflux symptom index, the reflux finding score, and 24-hour pH monitoring in a clinical setting.

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

Science.gov (United States)

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

2013-07-01

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

Repairing the vibratory vocal fold.

Science.gov (United States)

Long, Jennifer L

2018-01-01

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

Synchrotron radiation circular dichroism spectroscopy study of recombinant T β4 folding

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Huang, Yung-Chin; Chu, Hsueh-Liang; Chen, Peng-Jen; Chang, Chia-Ching

Thymosin beta 4 (T β4) is a 43-amino acid small peptide, has been demonstrated that it can promote cardiac repair, wound repair, tissue protection, and involve in the proliferation of blood cell precursor stem cells of bone marrow. Moreover, T β4 has been identified as a multifunction intrinsically disordered protein, which is lacking the stable tertiary structure. Owing to the small size and disordered character, the T β4 protein degrades rapidly and the storage condition is critical. Therefore, it is not easy to reveal its folding mechanism of native T β4. However, recombinant T β4 protein (rT β4), which fused with a 5-kDa peptide in its amino-terminal, is stable and possesses identical function of T β4. Therefore, rT β4 can be used to study its folding mechanism. By using over-critical folding process, stable folding intermediates of rT β4 can be obtained. Structure analysis of folding intermediates by synchrotron radiation circular dichroism (SRCD) and fluorescence spectroscopies indicate that rT β4 is a random coli major protein and its hydrophobic region becomes compact gradually. Moreover, the rT β4 folding is a two state transition. Thermal denaturation analysis indicates that rT β4 lacks stable tertiary structure. These results indicated that rT β4, similar to T β4, is an intrinsically disordered protein. Research is supported by MOST, Taiwan. MOST 103-2112-M-009-011-MY3. Corresponding author: Chia-Ching Chang; ccchang01@faculty.nctu.edu.tw.

High-speed Imaging of Vocal Fold Vibration Onset Delay: Normal Versus Abnormal.

Science.gov (United States)

Woo, Peak

2017-05-01

Vocal fold vibration onset delay (VFVOD) is heard frequently in spasmodic dysphonia and in muscle tension dysphonia. VFVOD changes due to other vocal pathologies have not been investigated. VFVOD during sustained vowel production was estimated with high-speed video in 10 normal and 40 pathologic subjects (scars, vocal fold paralysis, vocal fold nodules, and polyps). Analysis of high-speed video was done using digital kymography. VFVOD can be divided into two portions. Pre-phonation delay (PPD) is the duration when the vocal folds are nearly approximated to the time of first observed oscillation. Steady state delay (SSD) is the time when vocal folds are observed to come into oscillation until steady state of oscillation is observed. Normal subjects have almost zero PPD with vocal fold oscillation observed before full vocal fold adduction. Pathologic cases showed prolonged PPD because of (1) false cord adduction, (2) prolonged true vocal fold adduction, and (3) delay to onset of vocal fold vibration. Normal subjects have SSD of three to five cycles before steady state. Pathologic states result in increased SSD. Causes for increased SSD include (1) slow ramping up to steady state, (2) partial vibration of vocal folds, and (3) diplophonia with alternating beats before achieving steady state. There are significant differences between normal and pathology groups in both PPD and SSD. VFVOD is elevated in pathologic states. This can be due to increase in PPD or SSD. VFVOD is an under-recognized phenomenon that may contribute to complaints of vocal fatigue and dysphonia. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Kinetic partitioning mechanism of HDV ribozyme folding

Energy Technology Data Exchange (ETDEWEB)

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

2014-01-14

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

S-folds and 4d N=3 superconformal field theories

Energy Technology Data Exchange (ETDEWEB)

Aharony, Ofer [Department of Particle Physics and Astrophysics,Weizmann Institute of Science, Rehovot 7610001 (Israel); Tachikawa, Yuji [Department of Physics, Faculty of Science,University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kavli Institute for the Physics and Mathematics of the Universe,University of Tokyo, Kashiwa, Chiba 277-8583 (Japan)

2016-06-08

S-folds are generalizations of orientifolds in type IIB string theory, such that the geometric identifications are accompanied by non-trivial S-duality transformations. They were recently used by García-Etxebarria and Regalado to provide the first construction of four dimensional N=3 superconformal theories. In this note, we classify the different variants of these N=3-preserving S-folds, distinguished by an analog of discrete torsion, using both a direct analysis of the different torsion classes and the compactification of the S-folds to three dimensional M-theory backgrounds. Upon adding D3-branes, these variants lead to different classes of N=3 superconformal field theories. We also analyze the holographic duals of these theories, and in particular clarify the role of discrete gauge and global symmetries in holography.

Detection of micro calcifications in breast specimen by 4-fold DIMA direct magnification radiography compared to 1.5-fold conventional magnification radiography

International Nuclear Information System (INIS)

Grunert, J.H.; Borchert, B.; Farber, A.; Gmelin, E.

1999-01-01

Aims of the study: The purpose of this study was to investigate the efficacy of 4-fold magnification breast specimen radiography (direct magnification, DIMA) compared to conventional 1.5-fold magnification radiography in evaluating the presence of absence of carcinoma at the surgical margins by detection of microcalcification. Results: In 50 specimen 2821 (1305 within 3 mm distance to the margins) microcalcifications were detected with the DIMA mammography technique compared to 1608 (446) microcalcifications with the conventional technique. This increased detection rate by DIMA-magnetification radiography was accompanied by a decreased specificity in comparison to the conventional magnification radiography (33,3% DIMA versus 83,3% conventional) regarding the evaluation of presence or absence of carcinoma at the surgical margins. Differentiating the microcalcifications into calcifications belonging to the suspicious cluster and those that are located outside the cluster led to an increase in specificity (83,3% DIMA versus 100% conventional). Conclusions: The efficacy of breast specimens radiography in evaluating the presence or absence of carcinoma at the surgical margins by detection of microcalcification is not improved by 4-fold magnification radiography (direct magnification, DIMA) compared to conventional 1.5-fold magnification radiography due to an increase in false-positive results. Analysis of the attachement of the microcalcifications to the cluster can improve the specificity. (orig.) [de

Four residues of propeptide are essential for precursor folding of nattokinase.

Science.gov (United States)

Jia, Yan; Cao, Xinhua; Deng, Yu; Bao, Wei; Tang, Changyan; Ding, Hanjing; Zheng, Zhongliang; Zou, Guolin

2014-11-01

Subtilisin propeptide functions as an intramolecular chaperone that guides precursor folding. Nattokinase, a member of subtilisin family, is synthesized as a precursor consisting of a signal peptide, a propeptide, and a subtilisin domain, and the mechanism of its folding remains to be understood. In this study, the essential residues of nattokinase propeptide which contribute to precursor folding were determined. Deletion analysis showed that the conserved regions in propeptide were important for precursor folding. Single-site and multi-site mutagenesis studies confirmed the role of Tyr10, Gly13, Gly34, and Gly35. During stage (i) and (ii) of precursor folding, Tyr10 and Gly13 would form the part of interface with subtilisin domain. While Gly34 and Gly35 connected with an α-helix that would stabilize the structure of propeptide. The quadruple Ala mutation, Y10A/G13A/G34A/G35A, resulted in a loss of the chaperone function for the propeptide. This work showed the essential residues of propeptide for precursor folding via secondary structure and kinetic parameter analyses. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Seismic attribute analysis and its application to mapping folds and fractures

Science.gov (United States)

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.

Self-folding origami at any energy scale

Science.gov (United States)

Pinson, Matthew B.; Stern, Menachem; Carruthers Ferrero, Alexandra; Witten, Thomas A.; Chen, Elizabeth; Murugan, Arvind

2017-05-01

Programmable stiff sheets with a single low-energy folding motion have been sought in fields ranging from the ancient art of origami to modern meta-materials research. Despite such attention, only two extreme classes of crease patterns are usually studied; special Miura-Ori-based zero-energy patterns, in which crease folding requires no sheet bending, and random patterns with high-energy folding, in which the sheet bends as much as creases fold. We present a physical approach that allows systematic exploration of the entire space of crease patterns as a function of the folding energy. Consequently, we uncover statistical results in origami, finding the entropy of crease patterns of given folding energy. Notably, we identify three classes of Mountain-Valley choices that have widely varying `typical' folding energies. Our work opens up a wealth of experimentally relevant self-folding origami designs not reliant on Miura-Ori, the Kawasaki condition or any special symmetry in space.

Anatomy and Histology of an Epicanthal Fold.

Science.gov (United States)

Park, Jae Woo; Hwang, Kun

2016-06-01

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

Clinical Significance of Contralateral Reactive Lesion in Vocal Fold Polyp and Cyst.

Science.gov (United States)

Cho, Jung-Hae; Choi, Yong-Sug; Joo, Young-Hoon; Park, Young-Hak; Sun, Dong-Il

2018-01-01

We investigated the clinical significance of contralateral reactive lesions in patients undergoing laryngeal microsurgery for benign vocal fold lesions such as vocal polyps and cysts. This was a retrospective, single institution cohort study. Patient medical records were reviewed for demographic characteristics; acoustic, aerodynamic, and perceptual analyses; and Voice Handicap Index score before and after laryngeal microsurgery. Definitive diagnoses were made via intraoperative microlaryngoscopic evaluations. Clinical parameters were assessed to identify risk factors for contralateral reactive lesions. We evaluated surgical outcome using voice analysis. We enrolled 268 patients (109 men and 159 women) with benign vocal fold lesions. A total of 195 (72.8%) had a contralateral reactive vocal fold lesion. A multivariable analysis revealed that being a never smoker and having a hoarseness duration ≥6 months, vocal polyps, and small primary lesions were independent risk factors for contralateral reactive lesions (P vocal fold lesions are frequently detected in patients with vocal polyp and cyst. The reactive lesions had an adverse effect on voice quality. Simultaneous excision of primary and contralateral reactive lesions may be an alternative treatment for better voice outcome. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2011-01-01

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

Self-folding mechanics of graphene tearing and peeling from a substrate

Science.gov (United States)

He, Ze-Zhou; Zhu, Yin-Bo; Wu, Heng-An

2018-06-01

Understanding the underlying mechanism in the tearing and peeling processes of graphene is crucial for the further hierarchical design of origami-like folding and kirigami-like cutting of graphene. However, the complex effects among bending moduli, adhesion, interlayer interaction, and local crystal structure during origami-like folding and kirigami-like cutting remain unclear, resulting in challenges to the practical applications of existing theoretical and experimental findings as well as to potential manipulations of graphene in metamaterials and nanodevices. Toward this end, classical molecular dynamics (MD) simulations are performed with synergetic theoretical analysis to explore the tearing and peeling of self-folded graphene from a substrate driven by external force and by thermal activation. It is found that the elastic energy localized at the small folding ridge plays a significant role in the crack trajectory. Due to the extremely small bending modulus of monolayer graphene, its taper angle when pulled by an external force follows a scaling law distinct from that in case of bilayer graphene. With the increase in the initial width of the folding ridge, the self-folded graphene, motivated by thermal fluctuations, can be self-assembled by spontaneous self-tearing and peeling from a substrate. Simultaneously, the scaling law between the taper angle and adhesive energy is independent of the motivations for thermal activation-induced self-assembly and external force tearing, providing effective insights into the underlying physics for graphene-based origami-like folding and kirigami-like cutting.

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

Science.gov (United States)

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

2018-01-01

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

Folding of non-Euclidean curved shells

Science.gov (United States)

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

2015-03-01

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

Improving Protein Fold Recognition by Deep Learning Networks

Science.gov (United States)

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

2015-12-01

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

Improving Protein Fold Recognition by Deep Learning Networks.

Science.gov (United States)

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

2015-12-04

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

Synovial folds in equine articular process joints

DEFF Research Database (Denmark)

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

2013-01-01

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

Large-scale chromosome folding versus genomic DNA sequences: A discrete double Fourier transform technique.

Science.gov (United States)

Chechetkin, V R; Lobzin, V V

2017-08-07

Using state-of-the-art techniques combining imaging methods and high-throughput genomic mapping tools leaded to the significant progress in detailing chromosome architecture of various organisms. However, a gap still remains between the rapidly growing structural data on the chromosome folding and the large-scale genome organization. Could a part of information on the chromosome folding be obtained directly from underlying genomic DNA sequences abundantly stored in the databanks? To answer this question, we developed an original discrete double Fourier transform (DDFT). DDFT serves for the detection of large-scale genome regularities associated with domains/units at the different levels of hierarchical chromosome folding. The method is versatile and can be applied to both genomic DNA sequences and corresponding physico-chemical parameters such as base-pairing free energy. The latter characteristic is closely related to the replication and transcription and can also be used for the assessment of temperature or supercoiling effects on the chromosome folding. We tested the method on the genome of E. coli K-12 and found good correspondence with the annotated domains/units established experimentally. As a brief illustration of further abilities of DDFT, the study of large-scale genome organization for bacteriophage PHIX174 and bacterium Caulobacter crescentus was also added. The combined experimental, modeling, and bioinformatic DDFT analysis should yield more complete knowledge on the chromosome architecture and genome organization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biosimulation of inflammation and healing in surgically injured vocal folds.

Science.gov (United States)

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

2010-06-01

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

Analysis of elastic scattering cross-section for 18O + 206Pb in the CRC formalism and dependence on the choice of double folding potential

International Nuclear Information System (INIS)

Sonika; Roy, B.J.; Parmar, A.; Jha, V.; Pal, U.K.; Pandit, S.K.; Parkar, V.V.; Ramachandran, K.; Mahata, K.; Pal, A.; Santra, S.; Mohanty, A.K.; Sinha, T.; Parihari, A.

2014-01-01

Measurement and detailed analysis of elastic scattering and inelastic excitations in 206 Pb( 18 O, 18 O) have been reported here. First, the elastic scattering cross-section was calculated with a bare double folded real potential. The DF potential consists of folding of a harmonic oscillator density distribution to simulate 18 O with the sum of two Fermi density distributions for the proton and neutron in 206 Pb with correct normalizations. Our measured higher energy data for the same system was first analyzed with this DF potential

A digitally assisted, signal folding neural recording amplifier.

Science.gov (United States)

Chen, Yi; Basu, Arindam; Liu, Lei; Zou, Xiaodan; Rajkumar, Ramamoorthy; Dawe, Gavin Stewart; Je, Minkyu

2014-08-01

A novel signal folding and reconstruction scheme for neural recording applications that exploits the 1/f(n) characteristics of neural signals is described in this paper. The amplified output is 'folded' into a predefined range of voltages by using comparison and reset circuits along with the core amplifier. After this output signal is digitized and transmitted, a reconstruction algorithm can be applied in the digital domain to recover the amplified signal from the folded waveform. This scheme enables the use of an analog-to-digital convertor with less number of bits for the same effective dynamic range. It also reduces the transmission data rate of the recording chip. Both of these features allow power and area savings at the system level. Other advantages of the proposed topology are increased reliability due to the removal of pseudo-resistors, lower harmonic distortion and low-voltage operation. An analysis of the reconstruction error introduced by this scheme is presented along with a behavioral model to provide a quick estimate of the post reconstruction dynamic range. Measurement results from two different core amplifier designs in 65 nm and 180 nm CMOS processes are presented to prove the generality of the proposed scheme in the neural recording applications. Operating from a 1 V power supply, the amplifier in 180 nm CMOS has a gain of 54.2 dB, bandwidth of 5.7 kHz, input referred noise of 3.8 μVrms and power dissipation of 2.52 μW leading to a NEF of 3.1 in spike band. It exhibits a dynamic range of 66 dB and maximum SNDR of 43 dB in LFP band. It also reduces system level power (by reducing the number of bits in the ADC by 2) as well as data rate to 80% of a conventional design. In vivo measurements validate the ability of this amplifier to simultaneously record spike and LFP signals.

Peptide folding in the presence of interacting protein crowders

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-07

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

Dynamics of Folds in the Plane

Science.gov (United States)

Krylov, Nikolai A.; Rogers, Edwin L.

2011-01-01

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

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

Czech Academy of Sciences Publication Activity Database

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

2016-01-01

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

Teaching computers to fold proteins

DEFF Research Database (Denmark)

Winther, Ole; Krogh, Anders Stærmose

2004-01-01

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

Discriminating trpzip2 and trpzip4 peptides’ folding landscape using the two-dimensional infrared spectroscopy: A simulation study

International Nuclear Information System (INIS)

Wu, Tianmin; Zhang, Ruiting; Li, Huanhuan; Zhuang, Wei; Yang, Lijiang

2014-01-01

We analyzed, based on the theoretical spectroscopic modeling, how the differences in the folding landscapes of two β-hairpin peptides trpzip2 and trpzip4 are reflected in their thermal unfolding infrared measurements. The isotope-edited equilibrium FTIR and two dimensional infrared spectra of the two peptides were calculated, using the nonlinear exciton propagation method, at a series of temperatures. The spectra calculations were based on the configuration distributions generated using the GB OBC implicit solvent MD simulation and the integrated tempering sampling technique. Conformational analysis revealed the different local thermal stabilities for these two peptides, which suggested the different folding landscapes. Our study further suggested that the ellipticities of the isotope peaks in the coherent IR signals are more sensitive to these local stability differences compared with other spectral features such as the peak intensities. Our technique can thus be combined with the relevant experimental measurements to achieve a better understanding of the peptide folding behaviors

Vocal fold hemorrhage: factors predicting recurrence.

Science.gov (United States)

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

2014-01-01

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

Guiding the folding pathway of DNA origami.

Science.gov (United States)

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

2015-09-03

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

A dominant TRPV4 variant underlies osteochondrodysplasia in Scottish fold cats.

Science.gov (United States)

Gandolfi, B; Alamri, S; Darby, W G; Adhikari, B; Lattimer, J C; Malik, R; Wade, C M; Lyons, L A; Cheng, J; Bateman, J F; McIntyre, P; Lamandé, S R; Haase, B

2016-08-01

Scottish fold cats, named for their unique ear shape, have a dominantly inherited osteochondrodysplasia involving malformation in the distal forelimbs, distal hindlimbs and tail, and progressive joint destruction. This study aimed to identify the gene and the underlying variant responsible for the osteochondrodysplasia. DNA samples from 44 Scottish fold and 54 control cats were genotyped using a feline DNA array and a case-control genome-wide association analysis conducted. The gene encoding a calcium permeable ion channel, transient receptor potential cation channel, subfamily V, member 4 (TRPV4) was identified as a candidate within the associated region and sequenced. Stably transfected HEK293 cells were used to compare wild-type and mutant TRPV4 expression, cell surface localisation and responses to activation with a synthetic agonist GSK1016709A, hypo-osmolarity, and protease-activated receptor 2 stimulation. The dominantly inherited folded ear and osteochondrodysplasia in Scottish fold cats is associated with a p.V342F substitution (c.1024G>T) in TRPV4. The change was not found in 648 unaffected cats. Functional analysis in HEK293 cells showed V342F mutant TRPV4 was poorly expressed at the cell surface compared to wild-type TRPV4 and as a consequence the maximum response to a synthetic agonist was reduced. Mutant TRPV4 channels had a higher basal activity and an increased response to hypotonic conditions. Access to a naturally-occurring TRPV4 mutation in the Scottish fold cat will allow further functional studies to identify how and why the mutations affect cartilage and bone development. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Periodic and stochastic thermal modulation of protein folding kinetics.

Science.gov (United States)

Platkov, Max; Gruebele, Martin

2014-07-21

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

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

International Nuclear Information System (INIS)

Luk'yanov, K.V.

2008-01-01

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

Self-folding graphene-polymer bilayers

Energy Technology Data Exchange (ETDEWEB)

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

2015-05-18

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

TMFoldWeb: a web server for predicting transmembrane protein fold class.

Science.gov (United States)

Kozma, Dániel; Tusnády, Gábor E

2015-09-17

Here we present TMFoldWeb, the web server implementation of TMFoldRec, a transmembrane protein fold recognition algorithm. TMFoldRec uses statistical potentials and utilizes topology filtering and a gapless threading algorithm. It ranks template structures and selects the most likely candidates and estimates the reliability of the obtained lowest energy model. The statistical potential was developed in a maximum likelihood framework on a representative set of the PDBTM database. According to the benchmark test the performance of TMFoldRec is about 77 % in correctly predicting fold class for a given transmembrane protein sequence. An intuitive web interface has been developed for the recently published TMFoldRec algorithm. The query sequence goes through a pipeline of topology prediction and a systematic sequence to structure alignment (threading). Resulting templates are ordered by energy and reliability values and are colored according to their significance level. Besides the graphical interface, a programmatic access is available as well, via a direct interface for developers or for submitting genome-wide data sets. The TMFoldWeb web server is unique and currently the only web server that is able to predict the fold class of transmembrane proteins while assigning reliability scores for the prediction. This method is prepared for genome-wide analysis with its easy-to-use interface, informative result page and programmatic access. Considering the info-communication evolution in the last few years, the developed web server, as well as the molecule viewer, is responsive and fully compatible with the prevalent tablets and mobile devices.

High spatial resolution mapping of folds and fractures using Unmanned Aerial Vehicle (UAV) photogrammetry

Science.gov (United States)

Cruden, A. R.; Vollgger, S.

2016-12-01

The emerging capability of UAV photogrammetry combines a simple and cost-effective method to acquire digital aerial images with advanced computer vision algorithms that compute spatial datasets from a sequence of overlapping digital photographs from various viewpoints. Depending on flight altitude and camera setup, sub-centimeter spatial resolution orthophotographs and textured dense point clouds can be achieved. Orientation data can be collected for detailed structural analysis by digitally mapping such high-resolution spatial datasets in a fraction of time and with higher fidelity compared to traditional mapping techniques. Here we describe a photogrammetric workflow applied to a structural study of folds and fractures within alternating layers of sandstone and mudstone at a coastal outcrop in SE Australia. We surveyed this location using a downward looking digital camera mounted on commercially available multi-rotor UAV that autonomously followed waypoints at a set altitude and speed to ensure sufficient image overlap, minimum motion blur and an appropriate resolution. The use of surveyed ground control points allowed us to produce a geo-referenced 3D point cloud and an orthophotograph from hundreds of digital images at a spatial resolution automatically extracted from these high-resolution datasets using open-source software. This resulted in an extensive and statistically relevant orientation dataset that was used to 1) interpret the progressive development of folds and faults in the region, and 2) to generate a 3D structural model that underlines the complex internal structure of the outcrop and quantifies spatial variations in fold geometries. Overall, our work highlights how UAV photogrammetry can contribute to new insights in structural analysis.

How old is your fold?

NARCIS (Netherlands)

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

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

Some physical approaches to protein folding

Science.gov (United States)

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

1993-02-01

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

Transpressional folding and associated cross-fold jointing controlling the geometry of post-orogenic vein-type W-Sn mineralization: examples from Minas da Panasqueira, Portugal

Science.gov (United States)

Jacques, Dominique; Vieira, Romeu; Muchez, Philippe; Sintubin, Manuel

2018-02-01

The world-class W-Sn Panasqueira deposit consists of an extensive, subhorizontal vein swarm, peripheral to a late-orogenic greisen cupola. The vein swarm consists of hundreds of co-planar quartz veins that are overlapping and connected laterally over large distances. Various segmentation structures, a local zigzag geometry, and the occurrence of straight propagation paths indicate that they exploited a regional joint system. A detailed orientation analysis of the systematic joints reveals a geometrical relationship with the subvertical F2 fold generation, reflecting late-Variscan transpression. The joints are consistently orthogonal to the steeply plunging S0-S2 intersection lineation, both on the regional and the outcrop scale, and are thus defined as cross-fold or ac-joints. The joint system developed during the waning stages of the Variscan orogeny, when already uplifted to an upper-crustal level. Veining reactivated these cross-fold joints under the conditions of hydraulic overpressures and low differential stress. The consistent subperpendicular orientation of the veins relative to the non-cylindrical F2 hinge lines, also when having an inclined attitude, demonstrates that veining did not occur during far-field horizontal compression. Vein orientation is determined by local stress states variable on a meter-scale but with the minimum principal stress consistently subparallel to fold hinge lines. The conspicuous subhorizontal attitude of the Panasqueira vein swarm is thus dictated by the geometry of late-orogenic folds, which developed synchronous with oroclinal buckling of the Ibero-Armorican arc.

Prediction of the optimal set of contacts to fold the smallest knotted protein

International Nuclear Information System (INIS)

Dabrowski-Tumanski, P; Jarmolinska, A I; Sulkowska, J I

2015-01-01

Knotted protein chains represent a new motif in protein folds. They have been linked to various diseases, and recent extensive analysis of the Protein Data Bank shows that they constitute 1.5% of all deposited protein structures. Despite thorough theoretical and experimental investigations, the role of knots in proteins still remains elusive. Nonetheless, it is believed that knots play an important role in mechanical and thermal stability of proteins. Here, we perform a comprehensive analysis of native, shadow-specific and non-native interactions which describe free energy landscape of the smallest knotted protein (PDB id 2efv). We show that the addition of shadow-specific contacts in the loop region greatly enhances folding kinetics, while the addition of shadow-specific contacts along the C-terminal region (H3 or H4) results in a new folding route with slower kinetics. By means of direct coupling analysis (DCA) we predict non-native contacts which also can accelerate kinetics. Next, we show that the length of the C-terminal knot tail is responsible for the shape of the free energy barrier, while the influence of the elongation of the N-terminus is not significant. Finally, we develop a concept of a minimal contact map sufficient for 2efv protein to fold and analyze properties of this protein using this map. (paper)

Prediction of the optimal set of contacts to fold the smallest knotted protein

Science.gov (United States)

Dabrowski-Tumanski, P.; Jarmolinska, A. I.; Sulkowska, J. I.

2015-09-01

Knotted protein chains represent a new motif in protein folds. They have been linked to various diseases, and recent extensive analysis of the Protein Data Bank shows that they constitute 1.5% of all deposited protein structures. Despite thorough theoretical and experimental investigations, the role of knots in proteins still remains elusive. Nonetheless, it is believed that knots play an important role in mechanical and thermal stability of proteins. Here, we perform a comprehensive analysis of native, shadow-specific and non-native interactions which describe free energy landscape of the smallest knotted protein (PDB id 2efv). We show that the addition of shadow-specific contacts in the loop region greatly enhances folding kinetics, while the addition of shadow-specific contacts along the C-terminal region (H3 or H4) results in a new folding route with slower kinetics. By means of direct coupling analysis (DCA) we predict non-native contacts which also can accelerate kinetics. Next, we show that the length of the C-terminal knot tail is responsible for the shape of the free energy barrier, while the influence of the elongation of the N-terminus is not significant. Finally, we develop a concept of a minimal contact map sufficient for 2efv protein to fold and analyze properties of this protein using this map.

Exact folded-band chaotic oscillator.

Science.gov (United States)

Corron, Ned J; Blakely, Jonathan N

2012-06-01

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

Folding and insertion thermodynamics of the transmembrane WALP peptide

International Nuclear Information System (INIS)

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

2015-01-01

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

Folding and insertion thermodynamics of the transmembrane WALP peptide

Energy Technology Data Exchange (ETDEWEB)

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

2015-12-28

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

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

Science.gov (United States)

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.

Effects of knot type in the folding of topologically complex lattice proteins

Science.gov (United States)

Soler, Miguel A.; Nunes, Ana; Faísca, Patrícia F. N.

2014-07-01

The folding properties of a protein whose native structure contains a 52 knot are investigated by means of extensive Monte Carlo simulations of a simple lattice model and compared with those of a 31 knot. A 52 knot embedded in the native structure enhances the kinetic stability of the carrier lattice protein in a way that is clearly more pronounced than in the case of the 31 knot. However, this happens at the expense of a severe loss in folding efficiency, an observation that is consistent with the relative abundance of 31 and 52 knots in the Protein Data Bank. The folding mechanism of the 52 knot shares with that of the 31 knot the occurrence of a threading movement of the chain terminus that lays closer to the knotted core. However, co-concomitant knotting and folding in the 52 knot occurs with negligible probability, in sharp contrast to what is observed for the 31 knot. The study of several single point mutations highlights the importance in the folding of knotted proteins of the so-called structural mutations (i.e., energetic perturbations of native interactions between residues that are critical for knotting but not for folding). On the other hand, the present study predicts that mutations that perturb the folding transition state may significantly enhance the kinetic stability of knotted proteins provided they involve residues located within the knotted core.

Multiple routes and milestones in the folding of HIV-1 protease monomer.

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Massimiliano Bonomi

Full Text Available Proteins fold on a time scale incompatible with a mechanism of random search in conformational space thus indicating that somehow they are guided to the native state through a funneled energetic landscape. At the same time the heterogeneous kinetics suggests the existence of several different folding routes. Here we propose a scenario for the folding mechanism of the monomer of HIV-1 protease in which multiple pathways and milestone events coexist. A variety of computational approaches supports this picture. These include very long all-atom molecular dynamics simulations in explicit solvent, an analysis of the network of clusters found in multiple high-temperature unfolding simulations and a complete characterization of free-energy surfaces carried out using a structure-based potential at atomistic resolution and a combination of metadynamics and parallel tempering. Our results confirm that the monomer in solution is stable toward unfolding and show that at least two unfolding pathways exist. In our scenario, the formation of a hydrophobic core is a milestone in the folding process which must occur along all the routes that lead this protein towards its native state. Furthermore, the ensemble of folding pathways proposed here substantiates a rational drug design strategy based on inhibiting the folding of HIV-1 protease.

Spike-adding in parabolic bursters: The role of folded-saddle canards

Science.gov (United States)

Desroches, Mathieu; Krupa, Martin; Rodrigues, Serafim

2016-09-01

The present work develops a new approach to studying parabolic bursting, and also proposes a novel four-dimensional canonical and polynomial-based parabolic burster. In addition to this new polynomial system, we also consider the conductance-based model of the Aplysia R15 neuron known as the Plant model, and a reduction of this prototypical biophysical parabolic burster to three variables, including one phase variable, namely the Baer-Rinzel-Carillo (BRC) phase model. Revisiting these models from the perspective of slow-fast dynamics reveals that the number of spikes per burst may vary upon parameter changes, however the spike-adding process occurs in an explosive fashion that involves special solutions called canards. This spike-adding canard explosion phenomenon is analysed by using tools from geometric singular perturbation theory in tandem with numerical bifurcation techniques. We find that the bifurcation structure persists across all considered systems, that is, spikes within the burst are incremented via the crossing of an excitability threshold given by a particular type of canard orbit, namely the true canard of a folded-saddle singularity. However there can be a difference in the spike-adding transitions in parameter space from one case to another, according to whether the process is continuous or discontinuous, which depends upon the geometry of the folded-saddle canard. Using these findings, we construct a new polynomial approximation of the Plant model, which retains all the key elements for parabolic bursting, including the spike-adding transitions mediated by folded-saddle canards. Finally, we briefly investigate the presence of spike-adding via canards in planar phase models of parabolic bursting, namely the theta model by Ermentrout and Kopell.

Autologous orbicularis muscle for filling facial folds-an experimental and clinical study.

Science.gov (United States)

Schellini, Silvana Artioli; Hirai, Flavio Eduardo; Hoyama, Erika; Mattos, Maila Karina; Chaves, Fernando Rodrigo; Pellizon, Claudia Helena; Padovani, Carlos Roberto

2009-01-01

To present a technique for filling facial folds by using autologous orbicularis oculi muscle, based on an experimental model. two studies are presented: (1) an experimental study using 15 albino guinea-pigs from which a strip of the sural triceps muscle was removed and implanted in the subcutaneous tissue of the dorsal area. The animals were sacrificed 7, 30 and 60 days after the implantation, and the material was histologically evaluated. And (2) an interventional prospective clinical trial carried out on 20 patients referred to blepharoplasty surgery. They received autologous preseptal orbicularis muscle for filling facial folds. The results where evaluated by patients satisfaction and clinical exam. the sural tricep muscle, when implanted in the subcutaneous tissue, resulted in fibrosis. The patients whom received autologous orbicularis muscle implanted for filling facial folds showed that the procedure can be successfully carried out. autologous preseptal orbicularis muscle is a good material for filling facial folds. Cicatricial tissue will be formed on its implantation site, filling the tissue gap that forms the folds on the skin.

Development of a device for real-time light-guided vocal fold injection: A preliminary report.

Science.gov (United States)

Cha, Wonjae; Ro, Jung Hoon; Wang, Soo-Geun; Jang, Jeon Yeob; Cho, Jae Keun; Kim, Geun-Hyo; Lee, Yeon Woo

2016-04-01

Vocal fold injection is a minimally invasive technique for various vocal fold pathologies. The shortcomings of the cricothyroid (CT) membrane approach are mainly related to invisibility of the injection needle. If localization of the needle tip can be improved during vocal fold injection with the CT approach, the current problems of the technique can be overcome. We have conceptualized real-time light-guided vocal fold injection that enables simultaneous injection under precise localization. In this study, we developed a device for real-time light-guided vocal fold injection and applied it in excised canine larynx. Animal model. A single optic fiber was inserted in an unmodified 25-gauge needle. A designated connector for the device was attached to the needle, the optic fiber, and the syringe. A laser diode module was used as the light source. An ex vivo canine larynx model was used to validate the device. The location of the needle tip was accurately indicated, and the depth from the mucosa could be estimated according to the brightness and size of the red light. The needle was inserted and could be localized in the canine vocal fold by the light of the device. Precise injection at the intended location was easily performed with no manipulation of the device or the needle. Real-time light-guided vocal fold injection might be a feasible and promising technique for treatment of vocal fold pathology. It is expected that this technique can improve the precision of vocal fold injection and expand its indication in laryngology. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Vocal fold paralysis secondary to phonotrauma.

Science.gov (United States)

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

2014-01-01

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

Can Natural Proteins Designed with ‘Inverted’ Peptide Sequences Adopt Native-Like Protein Folds?

Science.gov (United States)

Sridhar, Settu; Guruprasad, Kunchur

2014-01-01

We have carried out a systematic computational analysis on a representative dataset of proteins of known three-dimensional structure, in order to evaluate whether it would possible to ‘swap’ certain short peptide sequences in naturally occurring proteins with their corresponding ‘inverted’ peptides and generate ‘artificial’ proteins that are predicted to retain native-like protein fold. The analysis of 3,967 representative proteins from the Protein Data Bank revealed 102,677 unique identical inverted peptide sequence pairs that vary in sequence length between 5–12 and 18 amino acid residues. Our analysis illustrates with examples that such ‘artificial’ proteins may be generated by identifying peptides with ‘similar structural environment’ and by using comparative protein modeling and validation studies. Our analysis suggests that natural proteins may be tolerant to accommodating such peptides. PMID:25210740

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

NARCIS (Netherlands)

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

2011-01-01

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