A four-way junction accelerates hairpin ribozyme folding via a discrete intermediate

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Tan, Elliot; Wilson, Timothy J.; Nahas, Michelle K.; Clegg, Robert M.; Lilley, David M. J.; Ha, Taekjip

2003-01-01

The natural form of the hairpin ribozyme comprises two major structural elements: a four-way RNA junction and two internal loops carried by adjacent arms of the junction. The ribozyme folds into its active conformation by an intimate association between the loops, and the efficiency of this process is greatly enhanced by the presence of the junction. We have used single-molecule spectroscopy to show that the natural form fluctuates among three distinct states: the folded state and two additional, rapidly interconverting states (proximal and distal) that are inherited from the junction. The proximal state juxtaposes the two loop elements, thereby increasing the probability of their interaction and thus accelerating folding by nearly three orders of magnitude and allowing the ribozyme to fold rapidly in physiological conditions. Therefore, the hairpin ribozyme exploits the dynamics of the junction to facilitate the formation of the active site from its other elements. Dynamic interplay between structural elements, as we demonstrate for the hairpin ribozyme, may be a general theme for other functional RNA molecules. PMID:12883002

Folding machineries displayed on a cation-exchanger for the concerted refolding of cysteine- or proline-rich proteins

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Lee Dae-Hee

2009-03-01

Full Text Available Abstract Background Escherichia coli has been most widely used for the production of valuable recombinant proteins. However, over-production of heterologous proteins in E. coli frequently leads to their misfolding and aggregation yielding inclusion bodies. Previous attempts to refold the inclusion bodies into bioactive forms usually result in poor recovery and account for the major cost in industrial production of desired proteins from recombinant E. coli. Here, we describe the successful use of the immobilized folding machineries for in vitro refolding with the examples of high yield refolding of a ribonuclease A (RNase A and cyclohexanone monooxygenase (CHMO. Results We have generated refolding-facilitating media immobilized with three folding machineries, mini-chaperone (a monomeric apical domain consisting of residues 191–345 of GroEL and two foldases (DsbA and human peptidyl-prolyl cis-trans isomerase by mimicking oxidative refolding chromatography. For efficient and simple purification and immobilization simultaneously, folding machineries were fused with the positively-charged consecutive 10-arginine tag at their C-terminal. The immobilized folding machineries were fully functional when assayed in a batch mode. When the refolding-facilitating matrices were applied to the refolding of denatured and reduced RNase A and CHMO, both of which contain many cysteine and proline residues, RNase A and CHMO were recovered in 73% and 53% yield of soluble protein with full enzyme activity, respectively. Conclusion The refolding-facilitating media presented here could be a cost-efficient platform and should be applicable to refold a wide range of E. coli inclusion bodies in high yield with biological function.

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 ...

Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides

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Safavi-Hemami, Helena; Li, Qing; Jackson, Ronneshia L.

2016-01-01

Formation of correct disulfide bonds in the endoplasmic reticulum is a crucial step for folding proteins destined for secretion. Protein disulfide isomerases (PDIs) play a central role in this process. We report a previously unidentified, hypervariable family of PDIs that represents the most...... diverse gene family of oxidoreductases described in a single genus to date. These enzymes are highly expressed specifically in the venom glands of predatory cone snails, animals that synthesize a remarkably diverse set of cysteine-rich peptide toxins (conotoxins). Enzymes in this PDI family, termed...

Designing cooperatively folded abiotic uni- and multimolecular helix bundles

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de, Soumen; Chi, Bo; Granier, Thierry; Qi, Ting; Maurizot, Victor; Huc, Ivan

2018-01-01

Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

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

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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.

Investigation of hindwing folding in ladybird beetles by artificial elytron transplantation and microcomputed tomography.

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Saito, Kazuya; Nomura, Shuhei; Yamamoto, Shuhei; Niiyama, Ryuma; Okabe, Yoji

2017-05-30

Ladybird beetles are high-mobility insects and explore broad areas by switching between walking and flying. Their excellent wing transformation systems enabling this lifestyle are expected to provide large potential for engineering applications. However, the mechanism behind the folding of their hindwings remains unclear. The reason is that ladybird beetles close the elytra ahead of wing folding, preventing the observation of detailed processes occurring under the elytra. In the present study, artificial transparent elytra were transplanted on living ladybird beetles, thereby enabling us to observe the detailed wing-folding processes. The result revealed that in addition to the abdominal movements mentioned in previous studies, the edge and ventral surface of the elytra, as well as characteristic shaped veins, play important roles in wing folding. The structures of the wing frames enabling this folding process and detailed 3D shape of the hindwing were investigated using microcomputed tomography. The results showed that the tape spring-like elastic frame plays an important role in the wing transformation mechanism. Compared with other beetles, hindwings in ladybird beetles are characterized by two seemingly incompatible properties: ( i ) the wing rigidity with relatively thick veins and ( ii ) the compactness in stored shapes with complex crease patterns. The detailed wing-folding process revealed in this study is expected to facilitate understanding of the naturally optimized system in this excellent deployable structure.

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

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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 Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma.

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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.

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.

NoFold: RNA structure clustering without folding or alignment.

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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.

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.

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

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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

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

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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.

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

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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.

Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment

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BARTLETT, R.S.; GUILLE, J.T.; CHEN, X.; CHRISTENSEN, M.B.; WANG, S.F.; THIBEAULT, S.L.

2016-01-01

Background Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. Methods Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. Results and discussion Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]β1, alpha smooth muscle actin, interleukin-1β, interleukin-17β and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC–treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair. PMID:27637759

Exploring the Evolutionary Accident Hypothesis: Are Extant Protein Folds the Fittest or the Luckiest?

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Shannon, G.; Wei, C.; Pohorille, A.

2017-01-01

Considering the range of functions proteins perform, it is surprising they fold into a relatively small set of structures or "folds" that facilitate such function. One explanation is that only a minority were fit enough to emerge from Darwinian selection during the early evolution of life. Alternatively, perhaps only a fraction of all possible folds were trialed. Understanding proto-catalyst selection will aid understanding of the origins and early evolution of life. To investigate which explanation is correct, we study a protein evolved in vitro to bind ATP by Jack Szostak (Fig. 1). This protein adopts a fold which is absent from nature. We are testing whether this fold would have possessed the capability to evolve that would have been essential to survive natural selection on early Earth. Folds that couldn't improve their fitness and evolve to perform new functions would have been replaced by rivals that could. To determine whether the fold is evolvable, we are attempting to change the function of the protein by rationally redesigning to bind GTP. Two design strategies in the region of the nucleobase have been implemented to provide hydrogen bonding partners for the ligand i) an insertion ii) a MET to ASN mutation. Redesigns are being studied computationally at Ames Research Center including free energy of binding calculations. Binding affinities of promising redesigns are to be validated by experimental collaborators at ForteBio using Super Streptavidin Biosensors. If the fold is found to be non-evolvable, this may suggest that many structures were trialed, but the majority were pruned on the basis of their evolvability. Alternatively, if the fold is demonstrated to be evolvable, it would be difficult to explain its absence from nature without considering the possibility that the fold simply wasn't sampled on early Earth. This would not only further our understanding of the origins of life on Earth but also suggest a common phe-nomenon of proto

The paradox of vertical σ2 in foreland fold and thrust belts

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Tavani, Stefano

2014-05-01

Occurrence of aesthetically appealing thrust systems and associated large scale anticlines, in both active and fossil foreland fold and thrust belts, is commonly interpreted as an evidence for Andersonian compressional framework. Indeed, these structures would testify for a roughly vertical σ3. Such a correlation between thrusts occurrence and stress field orientation, however, frequently fails to explain denser observations at a smaller scale. The syn-orogenic deformation meso-structures hosted in exposed km-scale thrust-related folds, in fact, frequently and paradoxically witness for a syn-thrusting strike-slip stress configuration, with a near-vertical σ2 and a sub-horizontal σ3. This apparent widespread inconsistency between syn-orogenic meso-structures and stress field orientation is here named "the σ2 paradox". A possible explanation for such a paradox is provided by inherited extensional deformation structures commonly developed prior to thrusting, in the flexural foreland basins located ahead of fold and thrust belts. Thrust nucleation and propagation is facilitated and driven by the positive inversion of the extensional inheritances, and their subsequent linkage. This process eventually leads to the development of large reverse fault zones and can occur both in compressive and strike-slip stress configurations.

Classification of nasolabial folds in Asians and the corresponding surgical approaches: By Shanghai 9th People's Hospital.

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Zhang, Lu; Tang, Meng-Yao; Jin, Rong; Zhang, Ying; Shi, Yao-Ming; Sun, Bao-Shan; Zhang, Yu-Guang

2015-07-01

One of the earliest signs of aging appears in the nasolabial fold, which is a special anatomical region that requires many factors for comprehensive assessment. Hence, it is inadequate to rely on a single index to facilitate the classification of nasolabial folds. Through clinical observation, we have observed that traditional filling treatments provide little improvement for some patients, which prompted us to seek a more specific and scientific classification standard and assessment system. A total of 900 patients who sought facial rejuvenation treatment in Shanghai 9th People's Hospital were invited in this study. We observed the different nasolabial fold traits for different age groups and in different states, and the results were compared with the Wrinkle Severity Rating Scale (WSRS). We summarized the data, presented a classification scheme, and proposed a selection of treatment options. Consideration of the anatomical and histological features of nasolabial folds allowed us to divide nasolabial folds into five types, namely the skin type, fat pad type, muscular type, bone retrusion type, and hybrid type. Because different types of nasolabial folds require different treatments, it is crucial to accurately assess and correctly classify the conditions. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

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

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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.

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

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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

Periodic folding of viscous sheets

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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.

Asymmetric hindwing foldings in rove beetles.

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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.

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

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

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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

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

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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

Spherical images and inextensible curved folding

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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.

Bi-stable vocal fold adduction: a mechanism of modal-falsetto register shifts and mixed registration.

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Titze, Ingo R

2014-04-01

The origin of vocal registers has generally been attributed to differential activation of cricothyroid and thyroarytenoid muscles in the larynx. Register shifts, however, have also been shown to be affected by glottal pressures exerted on vocal fold surfaces, which can change with loudness, pitch, and vowel. Here it is shown computationally and with empirical data that intraglottal pressures can change abruptly when glottal adductory geometry is changed relatively smoothly from convergent to divergent. An intermediate shape between large convergence and large divergence, namely, a nearly rectangular glottal shape with almost parallel vocal fold surfaces, is associated with mixed registration. It can be less stable than either of the highly angular shapes unless transglottal pressure is reduced and upper stiffness of vocal fold tissues is balanced with lower stiffness. This intermediate state of adduction is desirable because it leads to a low phonation threshold pressure with moderate vocal fold collision. Achieving mixed registration consistently across wide ranges of F0, lung pressure, and vocal tract shapes appears to be a balancing act of coordinating laryngeal muscle activation with vocal tract pressures. Surprisingly, a large transglottal pressure is not facilitative in this process, exacerbating the bi-stable condition and the associated register contrast.

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

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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.

Simple Evaluation of Load-Carrying Capacity of Multi-Span Folding Bridges based on Floating Supports

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Jan Marszałek

2014-12-01

Full Text Available [b]Abstract[/b]. The papers covers simple evaluation of load-carrying capacity of multi-span folding bridges based on floating supports. Combined bridges built in this approach, could be used as a temporary crossing. The methodology of this evaluation is shown graphically on the basis of designed nomograms for two existing bridge structures i.e. MS-54 and DMS-65, mounted on rigid and floating supports. These nomograms facilitate the simple and fast determination of the impact of changing fixed support into floating support with different bridge length spans on the carrying capacity of the bridge. The paper also presents the influence of long-term use (enlarging the mounting backlash in the joints of these structures on the carrying capacity of the bridge.[b]Keywords[/b]: building, folding bridges, nomograms, assembly clearances

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

Quantification of Porcine Vocal Fold Geometry.

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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.

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.

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.

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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.

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

Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.

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Dowdall, Jayme R; Sadow, Peter M; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C; Franco, Ramon A; Rajagopal, Jayaraj

2015-09-01

A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Qualitative study with adult human larynges. Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

A comparison of RNA folding measures

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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.

Dynamics of major histocompatibility complex class I association with the human peptide-loading complex.

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Panter, Michaela S; Jain, Ankur; Leonhardt, Ralf M; Ha, Taekjip; Cresswell, Peter

2012-09-07

Although the human peptide-loading complex (PLC) is required for optimal major histocompatibility complex class I (MHC I) antigen presentation, its composition is still incompletely understood. The ratio of the transporter associated with antigen processing (TAP) and MHC I to tapasin, which is responsible for MHC I recruitment and peptide binding optimization, is particularly critical for modeling of the PLC. Here, we characterized the stoichiometry of the human PLC using both biophysical and biochemical approaches. By means of single-molecule pulldown (SiMPull), we determined a TAP/tapasin ratio of 1:2, consistent with previous studies of insect-cell microsomes, rat-human chimeric cells, and HeLa cells expressing truncated TAP subunits. We also report that the tapasin/MHC I ratio varies, with the PLC population comprising both 2:1 and 2:2 complexes, based on mutational and co-precipitation studies. The MHC I-saturated PLC may be particularly prevalent among peptide-selective alleles, such as HLA-C4. Additionally, MHC I association with the PLC increases when its peptide supply is reduced by inhibiting the proteasome or by blocking TAP-mediated peptide transport using viral inhibitors. Taken together, our results indicate that the composition of the human PLC varies under normal conditions and dynamically adapts to alterations in peptide supply that may arise during viral infection. These findings improve our understanding of the quality control of MHC I peptide loading and may aid the structural and functional modeling of the human PLC.

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.

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

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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

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.

Self-folding origami at any energy scale

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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.

Amino acid alphabet reduction preserves fold information contained in contact interactions in proteins.

Science.gov (United States)

Solis, Armando D

2015-12-01

To reduce complexity, understand generalized rules of protein folding, and facilitate de novo protein design, the 20-letter amino acid alphabet is commonly reduced to a smaller alphabet by clustering amino acids based on some measure of similarity. In this work, we seek the optimal alphabet that preserves as much of the structural information found in long-range (contact) interactions among amino acids in natively-folded proteins. We employ the Information Maximization Device, based on information theory, to partition the amino acids into well-defined clusters. Numbering from 2 to 19 groups, these optimal clusters of amino acids, while generated automatically, embody well-known properties of amino acids such as hydrophobicity/polarity, charge, size, and aromaticity, and are demonstrated to maintain the discriminative power of long-range interactions with minimal loss of mutual information. Our measurements suggest that reduced alphabets (of less than 10) are able to capture virtually all of the information residing in native contacts and may be sufficient for fold recognition, as demonstrated by extensive threading tests. In an expansive survey of the literature, we observe that alphabets derived from various approaches-including those derived from physicochemical intuition, local structure considerations, and sequence alignments of remote homologs-fare consistently well in preserving contact interaction information, highlighting a convergence in the various factors thought to be relevant to the folding code. Moreover, we find that alphabets commonly used in experimental protein design are nearly optimal and are largely coherent with observations that have arisen in this work. © 2015 Wiley Periodicals, Inc.

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.

Bilateral axillary skin fold flaps used for dorsal thoracic skin wound closure in a dog : clinical communication

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B. G. Nevill

2010-05-01

Full Text Available A 10-year-old greyhound-cross dog was presented with a large, chronic skin wound extending over the interscapular region. The substantial skin defect was closed by making use of bilateral axillary skin fold flaps. It was possible to elevate the 2 skin flaps sufficiently to allow them to meet at the dorsal midline and thus facilitate complete closure of a large and awkwardly positioned wound. Small dorsal areas of the skin flaps underwent necrosis, but the resulting defects were closed without difficulty in a subsequent procedure. To the author's knowledge, this is the 1st clinical report of the use of bilateral axillary skin fold flaps in this fashion and describes an additional use of a versatile skin flap procedure.

The effect of vocal fold vertical stiffness gradient on sound production

Science.gov (United States)

Geng, Biao; Xue, Qian; Zheng, Xudong

2015-11-01

It is observed in some experimental studies on canine vocal folds (VFs) that the inferior aspect of the vocal fold (VF) is much stiffer than the superior aspect under relatively large strain. Such vertical difference is supposed to promote the convergent-divergent shape during VF vibration and consequently facilitate the production of sound. In this study, we investigate the effect of vertical variation of VF stiffness on sound production using a numerical model. The vertical variation of stiffness is produced by linearly increasing the Young's modulus and shear modulus from the superior to inferior aspects in the cover layer, and its effect on phonation is examined in terms of aerodynamic and acoustic quantities such as flow rate, open quotient, skewness of flow wave form, sound intensity and vocal efficiency. The flow-induced vibration of the VF is solved with a finite element solver coupled with 1D Bernoulli equation, which is further coupled with a digital waveguide model. This study is designed to find out whether it's beneficial to artificially induce the vertical stiffness gradient by certain implanting material in VF restoring surgery, and if it is beneficial, what gradient is the most favorable.

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 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....

Steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins.

Science.gov (United States)

Huang, Wenxi; Liu, Wanting; Jin, Jingjie; Xiao, Qilan; Lu, Ruibin; Chen, Wei; Xiong, Sheng; Zhang, Gong

2018-03-25

Translational pausing coordinates protein synthesis and co-translational folding. It is a common factor that facilitates the correct folding of large, multi-domain proteins. For small proteins, pausing sites rarely occurs in the gene body, and the 3'-end pausing sites are only essential for the folding of a fraction of proteins. The determinant of the necessity of the pausings remains obscure. In this study, we demonstrated that the steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins. Validated by experiments with 5 model proteins, we found that the rigid protein structures do not, while the flexible structures do need 3'-end pausings to fold correctly. Therefore, rational optimization of translational pausing can improve soluble expression of small proteins with flexible structures, but not the rigid ones. The rigidity of the structure can be quantitatively estimated in silico using molecular dynamic simulation. Nevertheless, we also found that the translational pausing optimization increases the fitness of the expression host, and thus benefits the recombinant protein production, independent from the soluble expression. These results shed light on the structural basis of the translational pausing and provided a practical tool for industrial protein fermentation. Copyright © 2017. Published by Elsevier Inc.

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…

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...

Origami-Inspired Folding of Thick, Rigid Panels

Science.gov (United States)

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

2014-01-01

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

Difficulty Systematized Evaluation of Vocal Folds Exposure in Microsurgery of the Larynx

Directory of Open Access Journals (Sweden)

Ballin, Annelyse Cristine

2010-09-01

Full Text Available Introduction: Several studies addressing preoperative factors that predict difficulty of endotracheal intubation graduated by anesthesiologists, for the scale of the Cormack-Lehane. These parameters were evaluated for the difficulty of location of the laryngoscope in microsurgery of the larynx. There is not a standard scale of difficulty targeted to surgeons of the larynx. Objective: Create a standard scale of difficulty leasing the laryngoscope during microsurgery of the larynx, with a focus on exposure of the vocal folds (vocal cords to evaluate which clinical parameters predict difficulty of exposure of their vocal folds and verify the improvement of laryngeal exposure with the hanger of the laryngoscope. Method: A prospective randomized study, 57 patients undergoing laryngeal microsurgery. The preoperative parameters were evaluated: three epidemiological data, two of history and 13 physical examination. Intraoperatively: the anesthesiologist evaluated the Cormack-Lehane score and the surgeon evaluated according to the proposed scale, before and after placement of the hanger. Results and Conclusion: Several parameters showed sensitivity, specificity, positive predictive value for high inadequate exposure of the larynx. But only distance hiomentual <6.05 cm (p = 0.003 and 2 classes of Cormack-Lehane (p = 0.04 with statistical significance and high sensitivity of 100% and 81% respectively. The use of the hanger of laryngoscope laryngeal exposure improved significantly (p = 0.04. The proposed scale standardizes the visualization and grades the difficulty of exposure of their vocal folds, facilitating comparisons between studies and communication between otolaryngologists.

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.

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 \

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

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

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.

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

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.

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.

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.

Adaptive Origami for Efficiently Folded Structures

Science.gov (United States)

2016-02-01

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

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.

Barriers and facilitators to exchanging health information: a systematic review.

Science.gov (United States)

Eden, Karen B; Totten, Annette M; Kassakian, Steven Z; Gorman, Paul N; McDonagh, Marian S; Devine, Beth; Pappas, Miranda; Daeges, Monica; Woods, Susan; Hersh, William R

2016-04-01

We conducted a systematic review of studies assessing facilitators and barriers to use of health information exchange (HIE). We searched MEDLINE, PsycINFO, CINAHL, and the Cochrane Library databases between January 1990 and February 2015 using terms related to HIE. English-language studies that identified barriers and facilitators of actual HIE were included. Data on study design, risk of bias, setting, geographic location, characteristics of the HIE, perceived barriers and facilitators to use were extracted and confirmed. Ten cross-sectional, seven multiple-site case studies, and two before-after studies that included data from several sources (surveys, interviews, focus groups, and observations of users) evaluated perceived barriers and facilitators to HIE use. The most commonly cited barriers to HIE use were incomplete information, inefficient workflow, and reports that the exchanged information that did not meet the needs of users. The review identified several facilitators to use. Incomplete patient information was consistently mentioned in the studies conducted in the US but not mentioned in the few studies conducted outside of the US that take a collective approach toward healthcare. Individual patients and practices in the US may exercise the right to participate (or not) in HIE which effects the completeness of patient information available to be exchanged. Workflow structure and user roles are key but understudied. We identified several facilitators in the studies that showed promise in promoting electronic health data exchange: obtaining more complete patient information; thoughtful workflow that folds in HIE; and inclusion of users early in implementation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Yongping Yue

2016-01-01

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

Multi-scaled explorations of binding-induced folding of intrinsically disordered protein inhibitor IA3 to its target enzyme.

Directory of Open Access Journals (Sweden)

Jin Wang

2011-04-01

Full Text Available Biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. We explored a biomolecular recognition process that involves a major conformational change - protein folding. In particular, we explore the binding-induced folding of IA3, an intrinsically disordered protein that blocks the active site cleft of the yeast aspartic proteinase saccharopepsin (YPrA by folding its own N-terminal residues into an amphipathic alpha helix. We developed a multi-scaled approach that explores the underlying mechanism by combining structure-based molecular dynamics simulations at the residue level with a stochastic path method at the atomic level. Both the free energy profile and the associated kinetic paths reveal a common scheme whereby IA3 binds to its target enzyme prior to folding itself into a helix. This theoretical result is consistent with recent time-resolved experiments. Furthermore, exploration of the detailed trajectories reveals the important roles of non-native interactions in the initial binding that occurs prior to IA3 folding. In contrast to the common view that non-native interactions contribute only to the roughness of landscapes and impede binding, the non-native interactions here facilitate binding by reducing significantly the entropic search space in the landscape. The information gained from multi-scaled simulations of the folding of this intrinsically disordered protein in the presence of its binding target may prove useful in the design of novel inhibitors of aspartic proteinases.

Chloroplast-Derived Vaccine Antigens and Biopharmaceuticals: Expression, Folding, Assembly and Functionality

Science.gov (United States)

Chebolu, S.; Daniell, H.

2009-01-01

Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance, and multi-gene expression in a single transformation event. Oral delivery is facilitated by hyperexpression of vaccine antigens against cholera, tetanus, anthrax, plague, or canine parvovirus (4%–31% of total soluble protein, TSP) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato) as well as the availability of antibiotic free selectable markers or the ability to excise selectable marker genes. Hyperexpression of several therapeutic proteins, including human serum albumin (11.1% TSP), somatotropin (7% TSP), interferon-alpha (19% TSP), interferon-gamma (6% TSP), and antimicrobial peptide (21.5% TSP), facilitates efficient and economic purification. Also, the presence of chaperones and enzymes in chloroplasts facilitates assembly of complex multisubunit proteins and correct folding of human blood proteins with proper disulfide bonds. Functionality of chloroplast-derived vaccine antigens and therapeutic proteins has been demonstrated by several assays, including the macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLA cells or human lung carcinoma cells against encephalomyocarditis virus, systemic immune response, protection against pathogen challenge, and growth or inhibition of cell cultures. Purification of human proinsulin has been achieved using novel purification strategies (inverse temperature transition property) that do not require expensive column chromatography techniques. Thus, transgenic chloroplasts are ideal bioreactors for production of functional human and animal therapeutic proteins in an environmentally friendly manner. PMID:19401820

Sarcoidosis Presenting as Bilateral Vocal Fold Immobility.

Science.gov (United States)

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

2018-05-01

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

Extreme Mechanics: Self-Folding Origami

Science.gov (United States)

Santangelo, Christian D.

2017-03-01

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

Multi-crease Self-folding by Global Heating.

Science.gov (United States)

Miyashita, Shuhei; Onal, Cagdas D; Rus, Daniela

2015-01-01

This study demonstrates a new approach to autonomous folding for the body of a 3D robot from a 2D sheet, using heat. We approach this challenge by folding a 0.27-mm sheetlike material into a structure. We utilize the thermal deformation of a contractive sheet sandwiched by rigid structural layers. During this baking process, the heat applied on the entire sheet induces contraction of the contracting layer and thus forms an instructed bend in the sheet. To attain the targeted folding angles, the V-fold spans method is used. The targeted angle θout can be kinematically encoded into crease geometry. The realization of this angle in the folded structure can be approximately controlled by a contraction angle θin. The process is non-reversible, is reliable, and is relatively fast. Our method can be applied simultaneously to all the folds in multi-crease origami structures. We demonstrate the use of this method to create a lightweight mobile robot.

[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.

Cooperative role of calnexin and TigA in Aspergillus oryzae glycoprotein folding.

Science.gov (United States)

Wang, Ning; Seko, Akira; Takeda, Yoichi; Kikuma, Takashi; Ito, Yukishige

2015-10-01

Calnexin (CNX), known as a lectin chaperone located in the endoplasmic reticulum (ER), specifically recognizes G1M9GN2-proteins and facilitates their proper folding with the assistance of ERp57 in mammalian cells. However, it has been left unidentified how CNX works in Aspergillus oryzae, which is a filamentous fungus widely exploited in biotechnology. In this study, we found that a protein disulfide isomerase homolog TigA can bind with A. oryzae CNX (AoCNX), which was revealed to specifically recognize monoglucosylated glycans, similarly to CNX derived from other species, and accelerate the folding of G1M9GN2-ribonuclease (RNase) in vitro. For refolding experiments, a homogeneous monoglucosylated high-mannose-type glycoprotein G1M9GN2-RNase was chemoenzymatically synthesized from G1M9GN-oxazoline and GN-RNase. Denatured G1M9GN2-RNase was refolded with highest efficiency in the presence of both soluble form of AoCNX and TigA. TigA contains two thioredoxin domains with CGHC motif, mutation analysis of which revealed that the one in N-terminal regions is involved in binding to AoCNX, while the other in catalyzing protein refolding. The results suggested that in glycoprotein folding process of A. oryzae, TigA plays a similar role as ERp57 in mammalian cells, as a partner protein of AoCNX. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

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.

Physics of protein folding

Science.gov (United States)

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

2004-04-01

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

Facilitation as a teaching strategy : experiences of facilitators

Directory of Open Access Journals (Sweden)

E Lekalakala-Mokgele

2006-09-01

Full Text Available Changes in nursing education involve the move from traditional teaching approaches that are teacher-centred to facilitation, a student centred approach. The studentcentred approach is based on a philosophy of teaching and learning that puts the learner on centre-stage. The aim of this study was to identify the challenges of facilitators of learning using facilitation as a teaching method and recommend strategies for their (facilitators development and support. A qualitative, explorative and contextual design was used. Four (4 universities in South Africa which utilize facilitation as a teaching/ learning process were identified and the facilitators were selected to be the sample of the study. The main question posed during in-depth group interviews was: How do you experience facilitation as a teaching/learning method?. Facilitators indicated different experiences and emotions when they first had to facilitate learning. All of them indicated that it was difficult to facilitate at the beginning as they were trained to lecture and that no format for facilitation was available. They experienced frustrations and anxieties as a result. The lack of knowledge of facilitation instilled fear in them. However they indicated that facilitation had many benefits for them and for the students. Amongst the ones mentioned were personal and professional growth. Challenges mentioned were the fear that they waste time and that they do not cover the content. It is therefore important that facilitation be included in the training of nurse educators.

Natural triple beta-stranded fibrous folds.

Science.gov (United States)

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

2006-01-01

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

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.

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

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.

Self-folding miniature elastic electric devices

International Nuclear Information System (INIS)

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

2014-01-01

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

Microvascular lesions of the true vocal fold.

Science.gov (United States)

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

1998-06-01

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

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...

Design and simulation of origami structures with smooth folds.

Science.gov (United States)

Peraza Hernandez, E A; Hartl, D J; Lagoudas, D C

2017-04-01

Origami has enabled new approaches to the fabrication and functionality of multiple structures. Current methods for origami design are restricted to the idealization of folds as creases of zeroth-order geometric continuity. Such an idealization is not proper for origami structures of non-negligible fold thickness or maximum curvature at the folds restricted by material limitations. For such structures, folds are not properly represented as creases but rather as bent regions of higher-order geometric continuity. Such fold regions of arbitrary order of continuity are termed as smooth folds . This paper presents a method for solving the following origami design problem: given a goal shape represented as a polygonal mesh (termed as the goal mesh ), find the geometry of a single planar sheet, its pattern of smooth folds, and the history of folding motion allowing the sheet to approximate the goal mesh. The parametrization of the planar sheet and the constraints that allow for a valid pattern of smooth folds are presented. The method is tested against various goal meshes having diverse geometries. The results show that every determined sheet approximates its corresponding goal mesh in a known folded configuration having fold angles obtained from the geometry of the goal mesh.

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....

Mechanical Models of Fault-Related Folding

Energy Technology Data Exchange (ETDEWEB)

Johnson, A. M.

2003-01-09

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

Instrumentalization of origami in construction of folded plate structures - design, research and education

Directory of Open Access Journals (Sweden)

Nestorović Miodrag

2016-01-01

Full Text Available The paper deals with the origami used as an abstract tool to describe and represent the form and the structure of physical objects. In that respect, the potentials of this interdisciplinary technique as a medium of exploration of structural forms was introduced in the semester project done within the course Structural Systems at the Belgrade University, Faculty of Architecture. The technique was used as an interface to gain cognitive experience on spatial transformation and computational design. Throughout the intensive project period divided into three successive stages, the objective was to test method which enabled students to analyze geometrical principles of folding in order to apply these principles in the development of new designs. The generative algorithm inspired by the technique of paper folding assisted form-finding. Resulting shapes were verified by a production of small scale prototype models. The applied method, as a guiding design principle, facilitated formal exploration and augmentation of the design process. At the end of the course, students got cognitive experience on structural forms, while this simple technique delivered richness in terms of design solutions. [Projekat Ministarstva nauke Republike Srbije, br. TR36008

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.

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.

Idiopathic unilateral vocal-fold paralysis in the adult.

Science.gov (United States)

Rubin, F; Villeneuve, A; Alciato, L; Slaïm, L; Bonfils, P; Laccourreye, O

2018-02-02

To analyze the characteristics of adult idiopathic unilateral vocal-fold paralysis. Retrospective study of diagnostic problems, clinical data and recovery in an inception cohort of 100 adult patients with idiopathic unilateral vocal-fold paralysis (Group A) and comparison with a cohort of 211 patients with isolated non-idiopathic non-traumatic unilateral vocal-fold paralysis (Group B). Diagnostic problems were noted in 24% of cases in Group A: eight patients with concomitant common upper aerodigestive tract infection, five patients with a concomitant condition liable to induce immunodepression and 11 patients in whom a malignant tumor occurred along the path of the ipsilateral vagus and inferior laryngeal nerves or in the ipsilateral paralyzed larynx. There was no recovery of vocal-fold motion beyond 51 months after onset of paralysis. The 5-year actuarial estimate for recovery differed significantly (Pvocal-fold paralysis. In non-traumatic vocal-fold paralysis in adult patients, without recovery of vocal-fold motion, a minimum three years' regular follow-up is recommended. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Single injection of basic fibroblast growth factor to treat severe vocal fold lesions and vocal fold paralysis.

Science.gov (United States)

Kanazawa, Takeharu; Komazawa, Daigo; Indo, Kanako; Akagi, Yusuke; Lee, Yogaku; Nakamura, Kazuhiro; Matsushima, Koji; Kunieda, Chikako; Misawa, Kiyoshi; Nishino, Hiroshi; Watanabe, Yusuke

2015-10-01

Severe vocal fold lesions such as vocal fold sulcus, scars, and atrophy induce a communication disorder due to severe hoarseness, but a treatment has not been established. Basic fibroblast growth factor (bFGF) therapies by either four-time repeated local injections or regenerative surgery for vocal fold scar and sulcus have previously been reported, and favorable outcomes have been observed. In this study, we modified bFGF therapy using a single of bFGF injection, which may potentially be used in office procedures. Retrospective chart review. Five cases of vocal fold sulcus, six cases of scars, seven cases of paralysis, and 17 cases of atrophy were treated by a local injection of bFGF. The injection regimen involved injecting 50 µg of bFGF dissolved in 0.5 mL saline only once into the superficial lamina propria using a 23-gauge injection needle. Two months to 3 months after the injection, phonological outcomes were evaluated. The maximum phonation time (MPT), mean airflow rate, pitch range, speech fundamental frequency, jitter, and voice handicap index improved significantly after the bFGF injection. Furthermore, improvement in the MPT was significantly greater in patients with (in increasing order) vocal fold atrophy, scar, and paralysis. The improvement in the MPT among all patients was significantly correlated with age; the MPT improved more greatly in younger patients. Regenerative treatments by bFGF injection—even a single injection—effectively improve vocal function in vocal fold lesions. 4 © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

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...

The Ventricular-Fold Dynamics in Human Phonation

OpenAIRE

Bailly , Lucie; Henrich Bernardoni , Nathalie; Müller , Frank; Rohlfs , Anna-Katharina; Hess , Markus

2014-01-01

International audience; Purpose: In this study, the authors aimed (a) to provide a classification of the ventricular-fold dynamics during voicing, (b) to study the aerodynamic impact of these motions on vocal-fold vibrations, and (c) to assess whether ventricularfold oscillations could be sustained by aerodynamic coupling with the vocal folds. Method: A 72-sample database of vocal gestures accompanying different acoustical events comprised highspeed cinematographic, audio, and electroglottogr...

Single-Chain Folding of Synthetic Polymers: A Critical Update.

Science.gov (United States)

Altintas, Ozcan; Barner-Kowollik, Christopher

2015-11-23

The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anterior petroclinoid fold fenestration: an adjunct to clipping of postero-laterally projecting posterior communicating aneurysms.

Science.gov (United States)

Nossek, Erez; Setton, Avi; Dehdashti, Amir R; Chalif, David J

2014-10-01

Proximally located posterior communicating artery (PCoA) aneurysms, projecting postero-laterally in proximity to the tentorium, may pose a technical challenge for microsurgical clipping due to obscuration of the proximal aneurysmal neck by the anterior petroclinoid fold. We describe an efficacious technique utilizing fenestration of the anterior petroclinoid fold to facilitate visualization and clipping of PCoA aneurysms abutting this aspect of the tentorium. Of 86 cases of PCoA aneurysms treated between 2003 and 2013, the technique was used in nine (10.5 %) patients to allow for adequate clipping. A 3 mm fenestration in the anterior petroclinoid ligament is created adjacent and lateral to the anterior clinoid process. This fenestration is then widened into a small wedge corridor by bipolar coagulation. In all cases, the proximal aneurysm neck was visualized after the wedge fenestration. Additionally, an adequate corridor for placement of the proximal clip blade was uniformly established. All cases were adequately clipped, with complete occlusion of the aneurysm neck and fundus with preservation of the PCoA. There were two intraoperative ruptures not related to creation of the wedge fenestration. One patient experienced post-operative partial third nerve palsy, which resolved during follow-up. We describe a technique of fenestration of the anterior petroclinoid fold to establish a critical and safe corridor for both visualization and clipping of PCoA aneurysms.

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

CATHEDRAL: a fast and effective algorithm to predict folds and domain boundaries from multidomain protein structures.

Directory of Open Access Journals (Sweden)

Oliver C Redfern

2007-11-01

Full Text Available We present CATHEDRAL, an iterative protocol for determining the location of previously observed protein folds in novel multidomain protein structures. CATHEDRAL builds on the features of a fast secondary-structure-based method (using graph theory to locate known folds within a multidomain context and a residue-based, double-dynamic programming algorithm, which is used to align members of the target fold groups against the query protein structure to identify the closest relative and assign domain boundaries. To increase the fidelity of the assignments, a support vector machine is used to provide an optimal scoring scheme. Once a domain is verified, it is excised, and the search protocol is repeated in an iterative fashion until all recognisable domains have been identified. We have performed an initial benchmark of CATHEDRAL against other publicly available structure comparison methods using a consensus dataset of domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows superior performance in fold recognition and alignment accuracy when compared with many equivalent methods. If a novel multidomain structure contains a known fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For nearly 80% of assigned domains in a manually validated test set, the boundaries were correctly delineated within a tolerance of ten residues. For the remaining cases, previously classified domains were very remotely related to the query chain so that embellishments to the core of the fold caused significant differences in domain sizes and manual refinement of the boundaries was necessary. To put this performance in context, a well-established sequence method based on hidden Markov models was only able to detect 65% of domains, with 33% of the subsequent boundaries assigned within ten residues. Since, on average, 50% of newly determined protein structures contain more than one domain unit, and typically 90% or more of these

Effect of Vocal Fold Medialization on Dysphagia in Patients with Unilateral Vocal Fold Immobility.

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Cates, Daniel J; Venkatesan, Naren N; Strong, Brandon; Kuhn, Maggie A; Belafsky, Peter C

2016-09-01

The effect of vocal fold medialization (VFM) on vocal improvement in persons with unilateral vocal fold immobility (UVFI) is well established. The effect of VFM on the symptom of dysphagia is uncertain. The purpose of this study is to evaluate dysphagia symptoms in patients with UVFI pre- and post-VFM. Case series with chart review. Academic tertiary care medical center. The charts of 44 persons with UVFI who underwent VFM between June 1, 2013, and December 31, 2014, were abstracted from a prospectively maintained database at the University of California, Davis, Voice and Swallowing Center. Patient demographics, indications, and type of surgical procedure were recorded. Self-reported swallowing impairment was assessed with the validated 10-item Eating Assessment Tool (EAT-10) before and after surgery. A paired samples t test was used to compare pre- and postmedialization EAT-10 scores. Forty-four patients met criteria and underwent either vocal fold injection (73%) or thyroplasty (27%). Etiologies of vocal fold paralysis were iatrogenic (55%), idiopathic (29%), benign or malignant neoplastic (9%), traumatic (5%), or related to the late effects of radiation (2%). EAT-10 (mean ± SD) scores improved from 12.2 ± 11.1 to 7.7 ± 7.2 after medialization (P dysphagia and report significant improvement in swallowing symptoms following VFM. The symptomatic improvement appears to be durable over time. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Nomenclature proposal to describe vocal fold motion impairment

NARCIS (Netherlands)

Rosen, Clark A.; Mau, Ted; Remacle, Marc; Hess, Markus; Eckel, Hans E.; Young, VyVy N.; Hantzakos, Anastasios; Yung, Katherine C.; Dikkers, Frederik G.

2016-01-01

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold

Nomenclature proposal to describe vocal fold motion impairment

NARCIS (Netherlands)

Rosen, Clark A.; Mau, Ted; Remacle, Marc; Hess, Markus; Eckel, Hans E.; Young, VyVy N.; Hantzakos, Anastasios; Yung, Katherine C.; Dikkers, Frederik G.

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold

Curved Folded Plate Timber Structures

OpenAIRE

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

2011-01-01

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

"Facilitated" amino acid transport is upregulated in brain tumors.

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Miyagawa, T; Oku, T; Uehara, H; Desai, R; Beattie, B; Tjuvajev, J; Blasberg, R

1998-05-01

The goal of this study was to determine the magnitude of "facilitated" amino acid transport across tumor and brain capillaries and to evaluate whether amino acid transporter expression is "upregulated" in tumor vessels compared to capillaries in contralateral brain tissue. Aminocyclopentane carboxylic acid (ACPC), a non-metabolized [14C]-labeled amino acid, and a reference molecule for passive vascular permeability, [67Ga]-gallium-diethylenetriaminepentaacetic acid (Ga-DTPA), were used in these studies. Two experimental rat gliomas were studied (C6 and RG2). Brain tissue was rapidly processed for double label quantitative autoradiography 10 minutes after intravenous injection of ACPC and Ga-DTPA. Parametric images of blood-to-brain transport (K1ACPC and K1Ga-DTPA, microL/min/g) produced from the autoradiograms and the histology were obtained from the same tissue section. These three images were registered in an image array processor; regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images to obtain mean values. The facilitated component of ACPC transport (deltaK1ACPC) was calculated from the K1ACPC and K1Ga-DTPA data, and paired comparisons between tumor and contralateral brain were performed. ACPC flux, K1ACPC, across normal brain capillaries (22.6 +/- 8.1 microL/g/min) was >200-fold greater than that of Ga-DTPA (0.09 +/- 0.04 microL/g/min), and this difference was largely (approximately 90%) due to facilitated ACPC transport. Substantially higher K1ACPC values compared to corresponding K1DTPA values were also measured in C6 and RG2 gliomas. The deltaK1ACPC values for C6 glioma were more than twice that of contralateral brain cortex. K1ACPC and deltaK1ACPC values for RG2 gliomas was not significantly higher than that of contralateral cortex, although a approximately 2-fold difference in facilitated transport is obtained after normalization for differences in capillary

Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

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Chang, Joseph; Yung, Katherine C

2014-11-01

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

Accurately controlled sequential self-folding structures by polystyrene film

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Deng, Dongping; Yang, Yang; Chen, Yong; Lan, Xing; Tice, Jesse

2017-08-01

Four-dimensional (4D) printing overcomes the traditional fabrication limitations by designing heterogeneous materials to enable the printed structures evolve over time (the fourth dimension) under external stimuli. Here, we present a simple 4D printing of self-folding structures that can be sequentially and accurately folded. When heated above their glass transition temperature pre-strained polystyrene films shrink along the XY plane. In our process silver ink traces printed on the film are used to provide heat stimuli by conducting current to trigger the self-folding behavior. The parameters affecting the folding process are studied and discussed. Sequential folding and accurately controlled folding angles are achieved by using printed ink traces and angle lock design. Theoretical analyses are done to guide the design of the folding processes. Programmable structures such as a lock and a three-dimensional antenna are achieved to test the feasibility and potential applications of this method. These self-folding structures change their shapes after fabrication under controlled stimuli (electric current) and have potential applications in the fields of electronics, consumer devices, and robotics. Our design and fabrication method provides an easy way by using silver ink printed on polystyrene films to 4D print self-folding structures for electrically induced sequential folding with angular control.

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.

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.

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.

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

Science.gov (United States)

Krivov, Sergei V

2018-06-06

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

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.

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.

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

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 case of bilateral vocal fold mucosal bridges, bilateral trans-vocal fold type III sulci vocales, and an intracordal polyp.

Science.gov (United States)

Tan, Melin; Pitman, Michael J

2011-07-01

We present a patient with a novel finding of bilateral mucosal bridges, bilateral type III trans-vocal fold sulci vocales, and a vocal fold polyp. Although sulci and mucosal bridges occur in the vocal folds, it is rare to find multiples of these lesions in a single patient, and it is even more uncommon when they occur in conjunction with a vocal fold polyp. To our knowledge, this is the first description of a vocal fold polyp in combination with multiple vocal fold bridges and multiple type III sulci vocales in a single patient. To describe and visually present the diagnosis and treatment of a patient with an intracordal polyp, bilateral mucosal bridges, as well as bilateral type III trans-vocal fold sulci vocales. Presentation of a set of high definition intraoperative photos displaying the extent of the vocal fold lesions and the resection of the intracordal polyp. This patient presented with only 6 months of significant dysphonia. It was felt that the recent change in voice was because of the polyp and not the bridges or sulci vocales. Considering the patient's presentation and the possible morbidity of resection of mucosal bridges and sulci, only the polyp was excised. Postoperatively, the patient's voice returned to his acceptable mild baseline dysphonia, and the benefit has persisted 6 months postoperatively. The combination of bilateral mucosal bridges, bilateral type III sulcus vocalis, and an intracordal polyp in one patient is rare if not novel. Treatment of the polyp alone returned the patient's voice to his lifelong baseline of mild dysphonia. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

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…

Method of generating ploynucleotides encoding enhanced folding variants

Energy Technology Data Exchange (ETDEWEB)

Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

2017-05-02

The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

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.

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

Science.gov (United States)

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

2018-04-27

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

Incidence of vocal fold immobility in patients with dysphagia.

Science.gov (United States)

Leder, Steven B; Ross, Douglas A

2005-01-01

This study prospectively investigated the incidence of vocal fold immobility, unilateral and bilateral, and its influence on aspiration status in a referred population of 1452 patients for a dysphagia evaluation from a large, urban, tertiary-care, teaching hospital. Main outcome measures included overall incidence of vocal fold immobility and aspiration status, with specific emphasis on age, etiology, and side of vocal fold immobility, i.e., right, left, or bilateral. Overall incidence of vocal fold immobility was 5.6% (81 of 1452 patients), including 47 males (mean age 55.7 yr) and 34 females (mean age 59.7 yr). In the subgroup of patients with vocal fold immobility, 31% (25 of 81) exhibited unilateral right, 60% (49 of 81) unilateral left, and 9% (7 of 81) bilateral impairment. Overall incidence of aspiration was found to be 29% (426 of 1452) of all patients referred for a swallow evaluation. Aspiration was observed in 44% (36 of 81) of patients presenting with vocal fold immobility, i.e., 44% (11 of 25) unilateral right, 43% (21 of 49) unilateral left, and 57% (4 of 7) bilateral vocal fold immobility. Left vocal fold immobility occurred most frequently due to surgical trauma. A liquid bolus was aspirated more often than a puree bolus. Side of vocal fold immobility and age were not factors that increased incidence of aspiration. In conclusion, vocal fold immobility, with an incidence of 5.6%, is not an uncommon finding in patients referred for a dysphagia evaluation in the acute-care setting, and vocal fold immobility, when present, was associated with a 15% increased incidence of aspiration when compared with a population already being evaluated for dysphagia.

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

Stratigraphy and Folding in the Cenozoic Cover of a Fold-Thrust Belt in the Nallıhan Region (Ankara, Central Turkey)

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Karaaǧaç, Serdal; Koral, Hayrettin

2017-04-01

This study investigates stratigraphy and structural features in the Cenozoic sedimentary sequence of the fold-thrust belt of the Nallıhan-Ankara region, located to the north of the İzmir-Ankara-Erzincan Suture Zone. Permian-Triassic age marble intercalated with schist-phyllites, the upper Jurassic-lower Cretaceous age limestone and the upper Cretaceous age sandstone-shale alternation compose the basement in the study area. These rocks are unconformably overlain by the Cenozoic age terrestrial sedimentary and volcanic units. The Cenozoic stratigraphy begins with the Paleocene-Eocene age coal-bearing, at times, volcanic intercalated conglomerate-sandstone-mudstone alternation of alluvial-fluvial origins (Aksaklar Formation) and the tuff intercalated with lacustrine limestone, bituminous limestone (Kabalar Formation). These units are conformably overlain by the Eocene age basalt-andesite and pyroclastic rocks (Meyildere volcanics). The Paleocene-Eocene aged units are unconformably overlain by the conglomerate-sandstone-mudstone-marl of a lower-middle Miocene lacustrine environment (Hançili Formation). The terrestrial conglomerate-sandstone alternation (Örencik Formation) is the youngest unit in the Cenozoic stratigraphy, and is assumed to be of Pliocene age based its stratigraphic position on older units. Field study shows existence of both folds and faults in the sedimentary cover. Stereographic projections of bedding measured in the field shows N25W/45NW and N60W/4SE-oriented fold axes in the Paleocene-Eocene age units. There are also N76W/12SE and N88E/8NE-oriented folds. The difference in fold-axis orientations suggests that some folds may have been rotated in blocks bound by faults during the post-Paleocene/Eocene period. Whereas, the lower-middle Miocene units manifest N88W/13SE-oriented fold axes. It is thus proposed that the observed difference in the azimuth of fold axes represent two different folding phases, one with NE-SW and the other with N

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.

Thermodynamics of protein folding: a random matrix formulation.

Science.gov (United States)

Shukla, Pragya

2010-10-20

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

Reinke Edema: Watch For Vocal Fold Cysts.

Science.gov (United States)

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

2015-06-01

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

Transiently disordered tails accelerate folding of globular proteins.

Science.gov (United States)

Mallik, Saurav; Ray, Tanaya; Kundu, Sudip

2017-07-01

Numerous biological proteins exhibit intrinsic disorder at their termini, which are associated with multifarious functional roles. Here, we show the surprising result that an increased percentage of terminal short transiently disordered regions with enhanced flexibility (TstDREF) is associated with accelerated folding rates of globular proteins. Evolutionary conservation of predicted disorder at TstDREFs and drastic alteration of folding rates upon point-mutations suggest critical regulatory role(s) of TstDREFs in shaping the folding kinetics. TstDREFs are associated with long-range intramolecular interactions and the percentage of native secondary structural elements physically contacted by TstDREFs exhibit another surprising positive correlation with folding kinetics. These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing. © 2017 Federation of European Biochemical Societies.

Fluorescence of Alexa fluor dye tracks protein folding.

Directory of Open Access Journals (Sweden)

Simon Lindhoud

Full Text Available Fluorescence spectroscopy is an important tool for the characterization of protein folding. Often, a protein is labeled with appropriate fluorescent donor and acceptor probes and folding-induced changes in Förster Resonance Energy Transfer (FRET are monitored. However, conformational changes of the protein potentially affect fluorescence properties of both probes, thereby profoundly complicating interpretation of FRET data. In this study, we assess the effects protein folding has on fluorescence properties of Alexa Fluor 488 (A488, which is commonly used as FRET donor. Here, A488 is covalently attached to Cys69 of apoflavodoxin from Azotobacter vinelandii. Although coupling of A488 slightly destabilizes apoflavodoxin, the three-state folding of this protein, which involves a molten globule intermediate, is unaffected. Upon folding of apoflavodoxin, fluorescence emission intensity of A488 changes significantly. To illuminate the molecular sources of this alteration, we applied steady state and time-resolved fluorescence techniques. The results obtained show that tryptophans cause folding-induced changes in quenching of Alexa dye. Compared to unfolded protein, static quenching of A488 is increased in the molten globule. Upon populating the native state both static and dynamic quenching of A488 decrease considerably. We show that fluorescence quenching of Alexa Fluor dyes is a sensitive reporter of conformational changes during protein folding.

Fold and Fit: Space Conserving Shape Editing

KAUST Repository

Ibrahim, Mohamed; Yan, Dong-Ming

2017-01-01

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

Inverse folding of RNA pseudoknot structures

Directory of Open Access Journals (Sweden)

Li Linda YM

2010-06-01

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

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.

Morphometric Study of Vocal Folds in Indian Cadavers

Directory of Open Access Journals (Sweden)

Rawal J.D.

2015-06-01

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

Merging monads and folds for functional programming

NARCIS (Netherlands)

Meijer, E.; Jeuring, J.T.

1995-01-01

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

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.

Frustration in Condensed Matter and Protein Folding

Science.gov (United States)

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

2014-03-01

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

The impact of intraglottal vortices on vocal fold dynamics

Science.gov (United States)

Erath, Byron; Pirnia, Alireza; Peterson, Sean

2016-11-01

During voiced speech a critical pressure is produced in the lungs that separates the vocal folds and creates a passage (the glottis) for airflow. As air passes through the vocal folds the resulting aerodynamic loading, coupled with the tissue properties of the vocal folds, produces self-sustained oscillations. Throughout each cycle a complex flow field develops, characterized by a plethora of viscous flow phenomena. Air passing through the glottis creates a jet, with periodically-shed vortices developing due to flow separation and the Kelvin-Helmholtz instability in the shear layer. These vortices have been hypothesized to be a crucial mechanism for producing vocal fold vibrations. In this study the effect of vortices on the vocal fold dynamics is investigated experimentally by passing a vortex ring over a flexible beam with the same non-dimensional mechanical properties as the vocal folds. Synchronized particle image velocimetry data are acquired in tandem with the beam dynamics. The resulting impact of the vortex ring loading on vocal fold dynamics is discussed in detail. This work was supported by the National Science Foundation Grant CBET #1511761.

Folding models for elastic and inelastic scattering

International Nuclear Information System (INIS)

Satchler, G.R.

1982-01-01

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

Folds and Etudes

Science.gov (United States)

Bean, Robert

2007-01-01

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

Pathophysiology of the nodular and micronodular small bowel fold

International Nuclear Information System (INIS)

Olmstead, W.W.; Ros, P.R.; Moser, R.P.; Shekitka, K.M.; Lichtenstein, J.E.; Buck, J.L.

1987-01-01

The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is just at the resolution of current roentgenographic technique. When the villi are enlarged, they can be seen radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor, inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold

A bidirectional shape memory alloy folding actuator

International Nuclear Information System (INIS)

Paik, Jamie K; Wood, Robert J

2012-01-01

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

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...

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

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.

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....

Vocal Fold Injection: Review of Indications, Techniques, and Materials for Augmentation

OpenAIRE

Mallur, Pavan S.; Rosen, Clark A.

2010-01-01

Vocal fold injection is a procedure that has over a 100 year history but was rarely done as short as 20 years ago. A renaissance has occurred with respect to vocal fold injection due to new technologies (visualization and materials) and new injection approaches. Awake, un-sedated vocal fold injection offers many distinct advantages for the treatment of glottal insufficiency (vocal fold paralysis, vocal fold paresis, vocal fold atrophy and vocal fold scar). A review of materials available and ...

Experimental investigation into the mechanism of folding

NARCIS (Netherlands)

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

1938-01-01

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

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...

Endoscopic Anatomy of the Tensor Fold and Anterior Attic.

Science.gov (United States)

Li, Bin; Doan, Phi; Gruhl, Robert R; Rubini, Alessia; Marchioni, Daniele; Fina, Manuela

2018-02-01

Objectives The objectives of the study were to (1) study the anatomical variations of the tensor fold and its anatomic relation with transverse crest, supratubal recess, and anterior epitympanic space and (2) explore the most appropriate endoscopic surgical approach to each type of the tensor fold variants. Study Design Cadaver dissection study. Setting Temporal bone dissection laboratory. Subjects and Methods Twenty-eight human temporal bones (26 preserved and 2 fresh) were dissected through an endoscopic transcanal approach between September 2016 and June 2017. The anatomical variations of the tensor fold, transverse crest, supratubal recess, and anterior epitympanic space were studied before and after removing ossicles. Results Three different tensor fold orientations were observed: vertical (type A, 11/28, 39.3%) with attachment to the transverse crest, oblique (type B, 13/28, 46.4%) with attachment to the anterior tegmen tympani, and horizontal (type C, 4/28, 14.3%) with attachment to the tensor tympani canal. The tensor fold was a complete membrane in 20 of 28 (71.4%) specimens, preventing direct ventilation between the supratubal recess and anterior epitympanic space. We identified 3 surgical endoscopic approaches, which allowed visualization of the tensor fold without removing the ossicles. Conclusions The orientation of the tensor fold is the determining structure that dictates the conformation and limits of the epitympanic space. We propose a classification of the tensor fold based on 3 anatomical variants. We also describe 3 different minimally invasive endoscopic approaches to identify the orientation of the tensor fold while maintaining ossicular chain continuity.

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.

Benign Lesions of The Vocal Fold

Directory of Open Access Journals (Sweden)

Ozgur Surmelioglu

2013-02-01

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

Laryngeal ultrasound and pediatric vocal fold nodules.

Science.gov (United States)

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

2017-03-01

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

Diagnostic and therapeutic pitfalls in benign vocal fold diseases

Science.gov (United States)

Bohlender, Jörg

2013-01-01

More than half of patients presenting with hoarseness show benign vocal fold changes. The clinician should be familiar with the anatomy, physiology and functional aspects of voice disorders and also the modern diagnostic and therapeutic possibilities in order to ensure an optimal and patient specific management. This review article focuses on the diagnostic and therapeutic limitations and difficulties of treatment of benign vocal fold tumors, the management and prevention of scarred vocal folds and the issue of unilateral vocal fold paresis. PMID:24403969

Monadic Maps and Folds for Arbitrary Datatypes

NARCIS (Netherlands)

Fokkinga, M.M.

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

Failure of the inflatable penile prosthesis due to abnormal folding of a low-profile reservoir – A selected case from an overall series and systematic review

Directory of Open Access Journals (Sweden)

Roberto Alejandro Navarrete

2017-09-01

Full Text Available We present a case from a running series of inflatable penile prosthesis failure due to improper folding of the Conceal™ reservoir. The Conceal™ Low-Profile reservoir gained popularity due to claims of improved cosmesis and ease of implantation. As the number of patients receiving this and other low-profile reservoirs increases, it is imperative to review and document any novel complications. While the Conceal™ reservoir may be preferred in ectopic placement, it may be more prone to fluid lockout facilitated by conformational change. Our review did not identify prior reports of improper folding, which we believe is unique to these low-profile reservoirs.

Analysis of high-fold gamma data

International Nuclear Information System (INIS)

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

1999-01-01

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

Folds in multilayered rocks of Proterozoic age, Rajasthan, India

Indian Academy of Sciences (India)

R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

Johnson and Johnson 2002 etc) shows that the fold shape modification may be brought about by buckling and flattening operating simultaneously throughout the development of fold. In the present paper a series of F1 folds devel- oped in slates with interlayered alternations with quartzite of Proterozoic age and unaffected ...

Self-folding polymeric containers for encapsulation and delivery of drugs.

Science.gov (United States)

Fernandes, Rohan; Gracias, David H

2012-11-01

Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2nm and fold polyhedra as small as 100nm, with a surface patterning resolution of 15nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges. Copyright © 2012 Elsevier B.V. All rights reserved.

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...

Vocal Fold Collision Modeling

DEFF Research Database (Denmark)

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

2015-01-01

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

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)

Vocal fold elasticity of the Rocky Mountain elk (Cervus elaphus nelsoni) – producing high fundamental frequency vocalization with a very long vocal fold

OpenAIRE

Riede, Tobias; Titze, Ingo R.

2008-01-01

The vocal folds of male Rocky Mountain elk (Cervus elaphus nelsoni) are about 3 cm long. If fundamental frequency were to be predicted by a simple vibrating string formula, as is often done for the human larynx, such long vocal folds would bear enormous stress to produce the species-specific mating call with an average fundamental frequency of 1 kHz. Predictions would be closer to 50 Hz. Vocal fold histology revealed the presence of a large vocal ligament between the vocal fold epithelium and...

Ligand-promoted protein folding by biased kinetic partitioning.

Science.gov (United States)

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

2017-04-01

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

Vocal fold composition and early glottic carcinoma infiltration

Directory of Open Access Journals (Sweden)

Fang Qin

2012-08-01

Full Text Available Abstract Background Current imaging techniques provide only limited information pertaining to the extent of infiltration of laryngeal carcinomas into vocal fold tissue layers. Therefore, it is needed to seek the contribute to the body of knowledge surrounding examination and characterization in laryngeal carcinoma infiltration. Methods Excised larynges were collected from 30 male laryngectomy patients with an average age of 43.5 years (ranging 36 to 55 years and history of smoking (≥10 years exhibiting T1, T2, or subglottal (normal vocal fold carcinomas. Vocal folds were preserved via freezing or immersion in paraffin. The depth of the mucosa, submucosa, and muscular layers in both normal vocal folds and tumor tissues of afflicted vocal folds was measured. Results The average depths of the mucosa, submucosa, and muscular layers in normal vocal folds were 0.15 ± 0.06 mm, 2.30 ± 0.59 mm, and 2.87 ± 0.88 mm, respectively. Infiltration measurements of T1 tumors showed a depth of 1.62 ± 0.51 mm and 1.32 ± 0.49 mm in frozen sections and paraffin-embedded samples, respectively. Similarly, T2 tumors showed a depth of 2.87 ± 0.68 mm and 2.58 ± 0.67 mm in frozen sections and paraffin-embedded samples, respectively. T1 and T2 tumors occupied 24.8 ± 10 and 48.5 ± 15 percent of the normal vocal fold depth, respectively. Conclusion This data provides a baseline for estimating infiltration of laryngeal carcinomas in vocal fold tissue layers, of particular interest to surgeons. This information may be used to assess typical depths of infiltration, thus allowing for more appropriate selection of surgical procedures based on individual patient assessment.

Improvement of a Vocal Fold Imaging System

Energy Technology Data Exchange (ETDEWEB)

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

2017-02-01

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

In vitro folding of inclusion body proteins.

Science.gov (United States)

Rudolph, R; Lilie, H

1996-01-01

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

Arytenoid and posterior vocal fold surgery for bilateral vocal fold immobility.

Science.gov (United States)

Young, VyVy N; Rosen, Clark A

2011-12-01

Many procedures exist to address the airway restriction often seen with bilateral vocal fold immobility. We review the most recent studies involving arytenoid and/or posterior vocal fold surgery to provide an update on the issues related to these procedures. Specific focus is placed on selection of the surgical approach and operative side, use of adjunctive therapies, and outcome measures including decannulation rate, revision and complication rate, and postoperative results. Ten studies were identified between 2004 and 2011. Modifications to the orginal transverse cordotomy and medial arytenoidectomy techniques continue to be investigated to seek improvement in dyspnea symptoms with minimal decline in voice and/or swallowing function. Decannulation rates for these approaches are high. Postoperative dysphagia appears to be less commonly observed but requires continued study. The use of mitomycin-C in these procedures has been poorly studied to date. Both transverse cordotomy and medial arytenoidectomy procedures result in high success rates. However, many questions related to these procedures remain unanswered, particularly with respect to preoperative and postoperative evaluations of voice quality, swallowing function, and pulmonary status. There is need for rigorous prospective clinical studies to address these many issues further.

Self-Folding Textiles through Manipulation of Knit Stitch Architecture

Directory of Open Access Journals (Sweden)

Chelsea E. Knittel

2015-12-01

Full Text Available This research presents a preliminary study on finding predictable methods of controlling the self-folding behaviors of weft knit textiles for use in the development of smart textiles and garment devices, such as those with shape memory, auxetic behavior or transformation abilities. In this work, Shima Seiki SDS-One Apex computer-aided knitting technology, Shima Seiki industrial knitting machines, and the study of paper origami tessellation patterns were used as tools to understand and predict the self-folding abilities of weft knit textiles. A wide range of self-folding weft knit structures was produced, and relationships between the angles and ratios of the knit and purl stitch types were determined. Mechanical testing was used as a means to characterize differences produced by stitch patterns, and to further understand the relationships between angles and folding abilities. By defining a formulaic method for predicting the nature of the folds that occur due to stitch architecture patterns, we can better design self-folding fabrics for smart textile applications.

Design and use of a folded four-ring double-tuned birdcage coil for rat brain sodium imaging at 9.4 T

Science.gov (United States)

Ha, YongHyun; Choi, Chang-Hoon; Worthoff, Wieland A.; Shymanskaya, Aliaksandra; Schöneck, Michael; Willuweit, Antje; Felder, Jörg; Shah, N. Jon

2018-01-01

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1H (400 MHz) and inner low-pass coil for 23Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1H and -27 dB for 23Na. Signal-to-noise ratios (SNRs) were calculated and 23Na flip angle maps were acquired. 23Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo1H and 23Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR.

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.

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.

Hierarchical Diagnosis of Vocal Fold Disorders

Science.gov (United States)

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

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

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.

The effect of surface electrical stimulation on vocal fold position.

Science.gov (United States)

Humbert, Ianessa A; Poletto, Christopher J; Saxon, Keith G; Kearney, Pamela R; Ludlow, Christy L

2008-01-01

Closure of the true and false vocal folds is a normal part of airway protection during swallowing. Individuals with reduced or delayed true vocal fold closure can be at risk for aspiration and may benefit from intervention to ameliorate the problem. Surface electrical stimulation is currently used during therapy for dysphagia, despite limited knowledge of its physiological effects. Prospective single effects study. The immediate physiological effect of surface stimulation on true vocal fold angle was examined at rest in 27 healthy adults using 10 different electrode placements on the submental and neck regions. Fiberoptic nasolaryngoscopic recordings during passive inspiration were used to measure change in true vocal fold angle with stimulation. Vocal fold angles changed only to a small extent during two electrode placements (P vocal fold abduction was 2.4 degrees; while horizontal placements of electrodes in the submental region produced a mean adduction of 2.8 degrees (P = .03). Surface electrical stimulation to the submental and neck regions does not produce immediate true vocal fold adduction adequate for airway protection during swallowing, and one position may produce a slight increase in true vocal fold opening.

Experimental investigation of protein folding and misfolding.

Science.gov (United States)

Dobson, Christopher M

2004-09-01

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

Histopathologic study of human vocal fold mucosa unphonated over a decade.

Science.gov (United States)

Sato, Kiminori; Umeno, Hirohito; Ono, Takeharu; Nakashima, Tadashi

2011-12-01

Mechanotransduction caused by vocal fold vibration could possibly be an important factor in the maintenance of extracellular matrices and layered structure of the human adult vocal fold mucosa as a vibrating tissue after the layered structure has been completed. Vocal fold stellate cells (VFSCs) in the human maculae flavae of the vocal fold mucosa are inferred to be involved in the metabolism of extracellular matrices of the vocal fold mucosa. Maculae flavae are also considered to be an important structure in the growth and development of the human vocal fold mucosa. Tension caused by phonation (vocal fold vibration) is hypothesized to stimulate the VFSCs to accelerate production of extracellular matrices. A human adult vocal fold mucosa unphonated over a decade was investigated histopathologically. Vocal fold mucosa unphonated for 11 years and 2 months of a 64-year-old male with cerebral hemorrhage was investigated by light and electron microscopy. The vocal fold mucosae (including maculae flavae) were atrophic. The vocal fold mucosa did not have a vocal ligament, Reinke's space or a layered structure. The lamina propria appeared as a uniform structure. Morphologically, the VFSCs synthesized fewer extracellular matrices, such as fibrous protein and glycosaminoglycan. Consequently, VFSCs appeared to decrease their level of activity.

Kinetic Dissection of the Pre-existing Conformational Equilibrium in the Trypsin Fold*

Science.gov (United States)

Vogt, Austin D.; Chakraborty, Pradipta; Di Cera, Enrico

2015-01-01

Structural biology has recently documented the conformational plasticity of the trypsin fold for both the protease and zymogen in terms of a pre-existing equilibrium between closed (E*) and open (E) forms of the active site region. How such plasticity is manifested in solution and affects ligand recognition by the protease and zymogen is poorly understood in quantitative terms. Here we dissect the E*-E equilibrium with stopped-flow kinetics in the presence of excess ligand or macromolecule. Using the clotting protease thrombin and its zymogen precursor prethrombin-2 as relevant models we resolve the relative distribution of the E* and E forms and the underlying kinetic rates for their interconversion. In the case of thrombin, the E* and E forms are distributed in a 1:4 ratio and interconvert on a time scale of 45 ms. In the case of prethrombin-2, the equilibrium is shifted strongly (10:1 ratio) in favor of the closed E* form and unfolds over a faster time scale of 4.5 ms. The distribution of E* and E forms observed for thrombin and prethrombin-2 indicates that zymogen activation is linked to a significant shift in the pre-existing equilibrium between closed and open conformations that facilitates ligand binding to the active site. These findings broaden our mechanistic understanding of how conformational transitions control ligand recognition by thrombin and its zymogen precursor prethrombin-2 and have direct relevance to other members of the trypsin fold. PMID:26216877

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.

Force generation by titin folding.

Science.gov (United States)

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

2017-07-01

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

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

Visualization of protein folding funnels in lattice models.

Directory of Open Access Journals (Sweden)

Antonio B Oliveira

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

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.

Sulfated glycosaminoglycans in human vocal fold lamina propria

Directory of Open Access Journals (Sweden)

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.

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.

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)

When fast is better: protein folding fundamentals and mechanisms from ultrafast approaches.

Science.gov (United States)

Muñoz, Victor; Cerminara, Michele

2016-09-01

Protein folding research stalled for decades because conventional experiments indicated that proteins fold slowly and in single strokes, whereas theory predicted a complex interplay between dynamics and energetics resulting in myriad microscopic pathways. Ultrafast kinetic methods turned the field upside down by providing the means to probe fundamental aspects of folding, test theoretical predictions and benchmark simulations. Accordingly, experimentalists could measure the timescales for all relevant folding motions, determine the folding speed limit and confirm that folding barriers are entropic bottlenecks. Moreover, a catalogue of proteins that fold extremely fast (microseconds) could be identified. Such fast-folding proteins cross shallow free energy barriers or fold downhill, and thus unfold with minimal co-operativity (gradually). A new generation of thermodynamic methods has exploited this property to map folding landscapes, interaction networks and mechanisms at nearly atomic resolution. In parallel, modern molecular dynamics simulations have finally reached the timescales required to watch fast-folding proteins fold and unfold in silico All of these findings have buttressed the fundamentals of protein folding predicted by theory, and are now offering the first glimpses at the underlying mechanisms. Fast folding appears to also have functional implications as recent results connect downhill folding with intrinsically disordered proteins, their complex binding modes and ability to moonlight. These connections suggest that the coupling between downhill (un)folding and binding enables such protein domains to operate analogically as conformational rheostats. © 2016 The Author(s).

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...

Microwave-enhanced folding and denaturation of globular proteins

DEFF Research Database (Denmark)

Bohr, Henrik; Bohr, Jakob

2000-01-01

It is shown that microwave irradiation can affect the kinetics of the folding process of some globular proteins, especially beta-lactoglobulin. At low temperature the folding from the cold denatured phase of the protein is enhanced, while at a higher temperature the denaturation of the protein from...... its folded state is enhanced. In the latter case, a negative temperature gradient is needed for the denaturation process, suggesting that the effects of the microwaves are nonthermal. This supports the notion that coherent topological excitations can exist in proteins. The application of microwaves...

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

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.…

Folding worlds between pages

CERN Multimedia

Meier, Matthias

2010-01-01

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

The pathophysiology of the nodular and micronodular small bowel fold

International Nuclear Information System (INIS)

Olmsted, W.W.; Ros, P.R.; Moser, R.P.; Shekita, K.M.; Lichtenstein, J.E.

1986-01-01

The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is at the limit of resolution of current roentgenographic technique. When the villi are enlarged, they appear radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor,inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold

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

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

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.

Technique to achieve the symmetry of the new inframammary fold

Science.gov (United States)

Pozzi, Marcello; Zoccali, Giovanni; Buccheri, Ernesto Maria; de Vita, Roy

2014-01-01

Summary The literature outlines several surgical techniques to restore inframmammary fold definition, but symmetry of the fold is often left to irreproducible procedures. We report our personal technique to restore the symmetry of the inframmammary fold during multistep breast reconstruction. PMID:25078934

Self-organized critical model for protein folding

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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.

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

Science.gov (United States)

Saha, Mitul; Morais, Marc C

2012-12-15

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

Design and use of a folded four-ring double-tuned birdcage coil for rat brain sodium imaging at 9.4 T.

Science.gov (United States)

Ha, YongHyun; Choi, Chang-Hoon; Worthoff, Wieland A; Shymanskaya, Aliaksandra; Schöneck, Michael; Willuweit, Antje; Felder, Jörg; Shah, N Jon

2018-01-01

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1 H (400 MHz) and inner low-pass coil for 23 Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1 H and -27 dB for 23 Na. Signal-to-noise ratios (SNRs) were calculated and 23 Na flip angle maps were acquired. 23 Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo 1 H and 23 Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23 Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR. Copyright © 2017 Elsevier Inc. All rights reserved.

Folding propensity of intrinsically disordered proteins by osmotic stress

International Nuclear Information System (INIS)

Mansouri, Amanda L.; Grese, Laura N.; Rowe, Erica L.

2016-01-01

Proteins imparted with intrinsic disorder conduct a range of essential cellular functions. To better understand the folding and hydration properties of intrinsically disordered proteins (IDPs), we used osmotic stress to induce conformational changes in nuclear co-activator binding domain (NCBD) and activator for thyroid hormone and retinoid receptor (ACTR). Osmotic stress was applied by the addition of small and polymeric osmolytes, where we discovered that water contributions to NCBD folding always exceeded those for ACTR. Both NCBD and ACTR were found to gain a-helical structure with increasing osmotic stress, consistent with their folding upon NCBD/ACTR complex formation. Using small-angle neutron scattering (SANS), we further characterized NCBD structural changes with the osmolyte ethylene glycol. Here a large reduction in overall size initially occurred before substantial secondary structural change. In conclusion, by focusing on folding propensity, and linked hydration changes, we uncover new insights that may be important for how IDP folding contributes to binding.

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

Directory of Open Access Journals (Sweden)

Wolt Jeffrey D

2011-02-01

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

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

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)

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

Science.gov (United States)

Peraza Hernandez, Edwin Alexander

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

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

RNA inverse folding using Monte Carlo tree search.

Science.gov (United States)

Yang, Xiufeng; Yoshizoe, Kazuki; Taneda, Akito; Tsuda, Koji

2017-11-06

Artificially synthesized RNA molecules provide important ways for creating a variety of novel functional molecules. State-of-the-art RNA inverse folding algorithms can design simple and short RNA sequences of specific GC content, that fold into the target RNA structure. However, their performance is not satisfactory in complicated cases. We present a new inverse folding algorithm called MCTS-RNA, which uses Monte Carlo tree search (MCTS), a technique that has shown exceptional performance in Computer Go recently, to represent and discover the essential part of the sequence space. To obtain high accuracy, initial sequences generated by MCTS are further improved by a series of local updates. Our algorithm has an ability to control the GC content precisely and can deal with pseudoknot structures. Using common benchmark datasets for evaluation, MCTS-RNA showed a lot of promise as a standard method of RNA inverse folding. MCTS-RNA is available at https://github.com/tsudalab/MCTS-RNA .

Trends in Utilization of Vocal Fold Injection Procedures.

Science.gov (United States)

Rosow, David E

2015-11-01

Office-based vocal fold injections have become increasingly popular over the past 15 years. Examination of trends in procedure coding for vocal fold injections in the United States from 2000 to 2012 was undertaken to see if they reflect this shift. The US Part B Medicare claims database was queried from 2000 through 2012 for multiple Current Procedural Terminology codes. Over the period studied, the number of nonoperative laryngoscopic injections (31513, 31570) and operative medialization laryngoplasties (31588) remained constant. Operative vocal fold injection (31571) demonstrated marked linear growth over the 12-year study period, from 744 procedures in 2000 to 4788 in 2012-an increase >640%. The dramatic increased incidence in the use of code 31571 reflects an increasing share of vocal fold injections being performed in the operating room and not in an office setting, running counter to the prevailing trend toward awake, office-based injection procedures. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

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

Science.gov (United States)

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.

Surfing the free energy landscape of flavodoxin folding

NARCIS (Netherlands)

Bollen, Y.J.M.

2004-01-01

The research described in this thesis has been carried out to obtain a better understanding of the fundamental rules describing protein folding. Protein folding is the process in which a linear chain of amino acids contracts to a compact state in which it is active. Flavodoxin from Azotobacter

Heterochiral Knottin Protein: Folding and Solution Structure.

Science.gov (United States)

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

2017-10-31

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

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

Practice Facilitators' and Leaders' Perspectives on a Facilitated Quality Improvement Program.

Science.gov (United States)

McHugh, Megan; Brown, Tiffany; Liss, David T; Walunas, Theresa L; Persell, Stephen D

2018-04-01

Practice facilitation is a promising approach to helping practices implement quality improvements. Our purpose was to describe practice facilitators' and practice leaders' perspectives on implementation of a practice facilitator-supported quality improvement program and describe where their perspectives aligned and diverged. We conducted interviews with practice leaders and practice facilitators who participated in a program that included 35 improvement strategies aimed at the ABCS of heart health (aspirin use in high-risk individuals, blood pressure control, cholesterol management, and smoking cessation). Rapid qualitative analysis was used to collect, organize, and analyze the data. We interviewed 17 of the 33 eligible practice leaders, and the 10 practice facilitators assigned to those practices. Practice leaders and practice facilitators both reported value in the program's ability to bring needed, high-quality resources to practices. Practice leaders appreciated being able to set the schedule for facilitation and select among the 35 interventions. According to practice facilitators, however, relying on practice leaders to set the pace of the intervention resulted in a lower level of program intensity than intended. Practice leaders preferred targeted assistance, particularly electronic health record documentation guidance and linkages to state smoking cessation programs. Practice facilitators reported that the easiest interventions were those that did not alter care practices. The dual perspectives of practice leaders and practice facilitators provide a more holistic picture of enablers and barriers to program implementation. There may be greater opportunities to assist small practices through simple, targeted practice facilitator-supported efforts rather than larger, comprehensive quality improvement projects. © 2018 Annals of Family Medicine, Inc.

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.

Reversible Dual-Image-Based Hiding Scheme Using Block Folding Technique

Directory of Open Access Journals (Sweden)

Tzu-Chuen Lu

2017-10-01

Full Text Available The concept of a dual-image based scheme in information sharing consists of concealing secret messages in two cover images; only someone who has both stego-images can extract the secret messages. In 2015, Lu et al. proposed a center-folding strategy where each secret symbol is folded into the reduced digit to reduce the distortion of the stego-image. Then, in 2016, Lu et al. used a frequency-based encoding strategy to reduce the distortion of the frequency of occurrence of the maximum absolute value. Because the folding strategy can obviously reduce the value, the proposed scheme includes the folding operation twice to further decrease the reduced digit. We use a frequency-based encoding strategy to encode a secret message and then use the block folding technique by performing the center-folding operation twice to embed secret messages. An indicator is needed to identify the sequence number of the folding operation. The proposed scheme collects several indicators to produce a combined code and hides the code in a pixel to reduce the size of the indicators. The experimental results show that the proposed method can achieve higher image quality under the same embedding rate or higher payload, which is better than other methods.

RNA folding kinetics using Monte Carlo and Gillespie algorithms.

Science.gov (United States)

Clote, Peter; Bayegan, Amir H

2018-04-01

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

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.

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.

Self-folding micropatterned polymeric containers.

Science.gov (United States)

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

2011-02-01

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

Theory and simulation of explicit solvent effects on protein folding in vitro and in vivo

Science.gov (United States)

England, Jeremy L.

-Ginzburg-type model for solvent free energy and lays out a theoretical argument for a mechanism by which chaperonins may promote the folding of their substrates through a local enhancement of the hydrophobic effect. With this argument in hand, we show results in Chapter 6 from molecular dynamics simulations we performed of different mutants of the bacterial chaperonin GroEL, which demonstrate that the hydrophilicity of the chaperonin cavity correlates with the experimentally measured ability of the cavity to facilitate folding.

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.

Stretching and folding mechanism in foams

International Nuclear Information System (INIS)

Tufaile, Alberto; Pedrosa Biscaia Tufaile, Adriana

2008-01-01

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

Stretching and folding mechanism in foams

Energy Technology Data Exchange (ETDEWEB)

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

2008-10-13

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

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

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.

The use of folding structures in fusion reactors

International Nuclear Information System (INIS)

Haines, T.

1992-01-01

Folding structures can be used with advantage in fusion machines. They have been used in Space for decades to extend antennas, sensors and solar panels; terrestrial versions have been used as retractable antennas and antennas masts. They have also been used in the Joint European Torus (JET) and other nuclear applications. In this paper, three types are described, together with concepts for use in fusion machines. The Storable Tubular Extendible Member (STEM) was conceived by the National Research Council of Canada and developed by Spar Aerospace Limited. The Astromast is a folding truss developed by Astro Aerospace Corporation, a US subsidiary of Spar. The X-Beam is an ultra-stiff folding truss

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

Folding System for the Clothes by a Robot and Tools

OpenAIRE

大澤, 文明; 関, 啓明; 神谷, 好承

2004-01-01

The works of a home robot has the laundering. The purpose of this study is to find a means of folding of the clothes and store the clothes in a drawer by a home robot. Because the shape of cloth tends to change in various ways depending on the situation, it is difficult for robot hands to fold the clothes. In this paper, we propose a realistic folding system for the clothes by a robot and tools. The function of a tool is folding the clothes in half by inserting the clothes using two plates. T...

Targeted transtracheal stimulation for vocal fold closure.

Science.gov (United States)

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

2014-06-01

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

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.

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)

Cotranslational protein folding reveals the selective use of ...

Indian Academy of Sciences (India)

to fold properly by decelerating the translation rate at these sites. Thus the cotranslational protein folding is believed to be true for many proteins and is an important selection factor for the selective codon usage to optimize proper gene expres- sion and function (Komar 2009). A web server CS and S has been created by ...

A pedagogical framework for facilitating parents' learning in nurse-parent partnership.

Science.gov (United States)

Hopwood, Nick; Clerke, Teena; Nguyen, Anne

2018-04-01

Nursing work increasingly demands forms of expertise that complement specialist knowledge. In child and family nursing, this need arises when nurses work in partnership with parents of young children at risk. Partnership means working with parents in respectful, negotiated and empowering ways. Existing partnership literature emphasises communicative and relational skills, but this paper focuses on nurses' capacities to facilitate parents' learning. Referring to data from home visiting, day-stay and specialist toddler clinic services in Sydney, a pedagogical framework is presented. Analysis shows how nurses notice aspects of children, parents and parent-child interactions as a catalyst for building on parents' strengths, enhancing guided chance or challenging unhelpful constructs. Prior research shows the latter can be a sticking point in partnership, but this paper reveals diverse ways in which challenges are folded into learning process that position parents as agents of positive change. Noticing is dependent on embodied and communicative expertise, conceptualised in terms of sensory and reported channels. The framework offers a new view of partnership as mind-expanding for the parent and specifies the nurse's role in facilitating this process. © 2017 John Wiley & Sons Ltd.

WW domain folding complexity revealed by infrared spectroscopy.

Science.gov (United States)

Davis, Caitlin M; Dyer, R Brian

2014-09-02

Although the intrinsic tryptophan fluorescence of proteins offers a convenient probe of protein folding, interpretation of the fluorescence spectrum is often difficult because it is sensitive to both global and local changes. Infrared (IR) spectroscopy offers a complementary measure of structural changes involved in protein folding, because it probes changes in the secondary structure of the protein backbone. Here we demonstrate the advantages of using multiple probes, infrared and fluorescence spectroscopy, to study the folding of the FBP28 WW domain. Laser-induced temperature jumps coupled with fluorescence or infrared spectroscopy have been used to probe changes in the peptide backbone on the submillisecond time scale. The relaxation dynamics of the β-sheets and β-turn were measured independently by probing the corresponding IR bands assigned in the amide I region. Using these wavelength-dependent measurements, we observe three kinetics phases, with the fastest process corresponding to the relaxation kinetics of the turns. In contrast, fluorescence measurements of the wild-type WW domain and tryptophan mutants exhibit single-exponential kinetics with a lifetime that corresponds to the slowest phase observed by infrared spectroscopy. Mutant sequences provide evidence of an intermediate dry molten globule state. The slowest step in the folding of this WW domain is the tight packing of the side chains in the transition from the dry molten globule intermediate to the native structure. This study demonstrates that using multiple complementary probes enhances the interpretation of protein folding dynamics.

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.

Adapted to roar: functional morphology of tiger and lion vocal folds.

Directory of Open Access Journals (Sweden)

Sarah A Klemuk

Full Text Available Vocal production requires active control of the respiratory system, larynx and vocal tract. Vocal sounds in mammals are produced by flow-induced vocal fold oscillation, which requires vocal fold tissue that can sustain the mechanical stress during phonation. Our understanding of the relationship between morphology and vocal function of vocal folds is very limited. Here we tested the hypothesis that vocal fold morphology and viscoelastic properties allow a prediction of fundamental frequency range of sounds that can be produced, and minimal lung pressure necessary to initiate phonation. We tested the hypothesis in lions and tigers who are well-known for producing low frequency and very loud roaring sounds that expose vocal folds to large stresses. In histological sections, we found that the Panthera vocal fold lamina propria consists of a lateral region with adipocytes embedded in a network of collagen and elastin fibers and hyaluronan. There is also a medial region that contains only fibrous proteins and hyaluronan but no fat cells. Young's moduli range between 10 and 2000 kPa for strains up to 60%. Shear moduli ranged between 0.1 and 2 kPa and differed between layers. Biomechanical and morphological data were used to make predictions of fundamental frequency and subglottal pressure ranges. Such predictions agreed well with measurements from natural phonation and phonation of excised larynges, respectively. We assume that fat shapes Panthera vocal folds into an advantageous geometry for phonation and it protects vocal folds. Its primary function is probably not to increase vocal fold mass as suggested previously. The large square-shaped Panthera vocal fold eases phonation onset and thereby extends the dynamic range of the voice.

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.

Protein Folding: Search for Basic Physical Models

Directory of Open Access Journals (Sweden)

Ivan Y. Torshin

2003-01-01

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

Water dynamics clue to key residues in protein folding

International Nuclear Information System (INIS)

Gao, Meng; Zhu, Huaiqiu; Yao, Xin-Qiu; She, Zhen-Su

2010-01-01

A computational method independent of experimental protein structure information is proposed to recognize key residues in protein folding, from the study of hydration water dynamics. Based on all-atom molecular dynamics simulation, two key residues are recognized with distinct water dynamical behavior in a folding process of the Trp-cage protein. The identified key residues are shown to play an essential role in both 3D structure and hydrophobic-induced collapse. With observations on hydration water dynamics around key residues, a dynamical pathway of folding can be interpreted.

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.

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 ion transport and mucin expression following acrolein exposure.

Science.gov (United States)

Levendoski, Elizabeth Erickson; Sivasankar, M Preeti

2014-05-01

The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin (MUC) synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N = 85) were excised and exposed to an acrolein or sham challenge. A 60-min acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent, increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in MUC gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health.

Complete fold annotation of the human proteome using a novel structural feature space.

Science.gov (United States)

Middleton, Sarah A; Illuminati, Joseph; Kim, Junhyong

2017-04-13

Recognition of protein structural fold is the starting point for many structure prediction tools and protein function inference. Fold prediction is computationally demanding and recognizing novel folds is difficult such that the majority of proteins have not been annotated for fold classification. Here we describe a new machine learning approach using a novel feature space that can be used for accurate recognition of all 1,221 currently known folds and inference of unknown novel folds. We show that our method achieves better than 94% accuracy even when many folds have only one training example. We demonstrate the utility of this method by predicting the folds of 34,330 human protein domains and showing that these predictions can yield useful insights into potential biological function, such as prediction of RNA-binding ability. Our method can be applied to de novo fold prediction of entire proteomes and identify candidate novel fold families.

Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2.

Science.gov (United States)

Rosser, Meredith F N; Grove, Diane E; Chen, Liling; Cyr, Douglas M

2008-11-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic membrane protein that functions as a Cl(-) channel and consists of two membrane spanning domains (MSDs), two cytosolic nucleotide binding domains (NBDs), and a cytosolic regulatory domain. Cytosolic 70-kDa heat shock protein (Hsp70), and endoplasmic reticulum-localized calnexin are chaperones that facilitate CFTR biogenesis. Hsp70 functions in both the cotranslational folding and posttranslational degradation of CFTR. Yet, the mechanism for calnexin action in folding and quality control of CFTR is not clear. Investigation of this question revealed that calnexin is not essential for CFTR or CFTRDeltaF508 degradation. We identified a dependence on calnexin for proper assembly of CFTR's membrane spanning domains. Interestingly, efficient folding of NBD2 was also found to be dependent upon calnexin binding to CFTR. Furthermore, we identified folding defects caused by deletion of F508 that occurred before and after the calnexin-dependent association of MSD1 and MSD2. Early folding defects are evident upon translation of the NBD1 and R-domain and are sensed by the RMA-1 ubiquitin ligase complex.

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/.

An update of the DEF database of protein fold class predictions

DEFF Research Database (Denmark)

Reczko, Martin; Karras, Dimitris; Bohr, Henrik

1997-01-01

An update is given on the Database of Expected Fold classes (DEF) that contains a collection of fold-class predictions made from protein sequences and a mail server that provides new predictions for new sequences. To any given sequence one of 49 fold-classes is chosen to classify the structure re...... related to the sequence with high accuracy. The updated predictions system is developed using data from the new version of the 3D-ALI database of aligned protein structures and thus is giving more reliable and more detailed predictions than the previous DEF system.......An update is given on the Database of Expected Fold classes (DEF) that contains a collection of fold-class predictions made from protein sequences and a mail server that provides new predictions for new sequences. To any given sequence one of 49 fold-classes is chosen to classify the structure...

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)

Examining a Thermodynamic Order Parameter of Protein Folding.

Science.gov (United States)

Chong, Song-Ho; Ham, Sihyun

2018-05-08

Dimensionality reduction with a suitable choice of order parameters or reaction coordinates is commonly used for analyzing high-dimensional time-series data generated by atomistic biomolecular simulations. So far, geometric order parameters, such as the root mean square deviation, fraction of native amino acid contacts, and collective coordinates that best characterize rare or large conformational transitions, have been prevailing in protein folding studies. Here, we show that the solvent-averaged effective energy, which is a thermodynamic quantity but unambiguously defined for individual protein conformations, serves as a good order parameter of protein folding. This is illustrated through the application to the folding-unfolding simulation trajectory of villin headpiece subdomain. We rationalize the suitability of the effective energy as an order parameter by the funneledness of the underlying protein free energy landscape. We also demonstrate that an improved conformational space discretization is achieved by incorporating the effective energy. The most distinctive feature of this thermodynamic order parameter is that it works in pointing to near-native folded structures even when the knowledge of the native structure is lacking, and the use of the effective energy will also find applications in combination with methods of protein structure prediction.

Botulinum toxin in the treatment of vocal fold nodules.

Science.gov (United States)

Allen, Jacqui E; Belafsky, Peter C

2009-12-01

Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

Traumatic chorioretinal folds treated with intra-vitreal triamcinolone injection

Directory of Open Access Journals (Sweden)

Kook Young Kim

2013-01-01

Full Text Available A 34-year-old male visited the hospital due to decreased visual acuity in the left eye following an injury from a car accident. In the left eye, best-corrected visual acuity (BCVA was hand motion and intraocular pressure (IOP was 8 mmHg. Choroidal vasodilation and chorioretinal folds were observed by spectral domain-optical coherence tomography (SD-OCT. Topical and systemic steroid treatments did not improve the chorioretinal folds. Twelve months after the injury, intra-vitreal triamcinolone (4 mg/0.1 ml was injected. Six months after intra-vitreal triamcinolone injection, BCVA in the left eye had improved to 20/100. Fundus examination showed improvement in retinal vascular tortuosity and SD-OCT revealed improvements in choroidal vasodilation and chorioretinal folds. Intra-vitreal triamcinolone injection (IVTI was effective against traumatic chorioretinal folds with no recurrence based on objective observation by fundus photography and SD-OCT.

An expanded view of the protein folding landscape of PDZ domains

DEFF Research Database (Denmark)

Hultqvist, Greta; Pedersen, Søren W; Chi, Celestine N.

2012-01-01

state. In light of these results, we have re-analyzed previous folding data on PDZ domains and present a unified folding mechanism with three distinct transition states separated by two high-energy intermediates. Our data show that sequence composition tunes the relative stabilities of folding...

Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

Science.gov (United States)

Liu, Xinxin; Zheng, Wei; Sivasankar, M Preeti

2016-01-01

Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (pacrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (pacrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

SAXS study of transient pre-melting in chain-folded alkanes

International Nuclear Information System (INIS)

Ungar, G.; Wills, H.H.

1990-01-01

A pronounced pre-melting effect is observed in chain-folded crystals of pure monodisperse n-alkane C 246 H 494 . The effect is reversible on a short time scale, but at longer times the once-folded chain crystals are irreversibly lost as slow chain extension proceeds by solid diffusion well below the melting point. The melting process is thus monitored by rapid time-resolved small-angle X-ray (SAXS) measurements, using synchrotron radiation. The results show that the observed pronounced broadening of the DSC melting endotherm for chain-folded crystals is entirely due to genuine pre-melting of lamellar surfaces. Although a significant portion of material is already molten below the final melting point of chain-folded crystals T F , no recrystallization in the chain-extended form can occur until the cores of the crystalline lamellae melt at T F . Pre-melting of extended chain crystals is significantly less pronounced than that of folded chain crystals

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...

Multi-objective room acoustic optimization of timber folded plate structure

DEFF Research Database (Denmark)

Skov, Rasmus; Parigi, Dario; Damkilde, Lars

2017-01-01

This paper investigates the application of multi-objective optimization in the design of timber folded plate structures in the scope of the architectural design process. Considering contrasting objectives of structural displacement, early decay time (EDT), clarity (C50) and sound strength (G......), the methodology applied in two benchmarks tests, encompasses both structural and acoustic performance when determining folding characteristics and directionality of surfaces in a timber folded plate structure....

The Arterial Folding Point During Flexion of the Hip Joint

International Nuclear Information System (INIS)

Park, Sung Il; Won, Je Hwan; Kim, Byung Moon; Kim, Jae Keun; Lee, Do Yun

2005-01-01

Purpose: Endovascular stents placed in periarticular vessels may be at a greater risk of neointimal hyperplasia and eventual occlusion than those placed in non-periarticular vessels. The purpose of this study was to investigate the location of maximal conformational change along the iliac and femoral artery, the folding point, during flexion of the hip joint and its location relative to the hip joint and the inguinal ligament. Methods: Seventy patients undergoing femoral artery catheterization were evaluated. The patients were 47 men and 23 women and ranged in age from 26 to 75 years (mean 54 years). The arteries (right:left = 34:36) were measured using a marked catheter for sizing vessels. Fluoroscopic images were obtained in anteroposterior and lateral projections in neutral position, and in the lateral projection in flexed position of the hip joint. The folding point was determined by comparing the lateral projection images in the neutral and flexed positions. The distance from the acetabular roof to the folding point and the distance from the inguinal ligament to the folding point was evaluated. Results: : The folding point was located 42.8 ± 28.6 mm cranial to the acetabular roof and 35.1 ± 30.1 mm cranial to the inguinal ligament. As the patient’s age increased, the folding point was located more cranially (p < 0.001). Conclusions: The folding point during flexion of the hip joint was located 42.8 ± 28.6 mm cranial to the acetabular roof and 35.1 ± 30.1 mm cranial to the inguinal ligament. As the patient's age increased, the folding point was located more cranially. When a stent is inserted over this region, more attention may be needed during follow-up to monitor possible occlusion and stent failure.

Fold maps and positive topological quantum field theories

Energy Technology Data Exchange (ETDEWEB)

Wrazidlo, Dominik Johannes

2017-04-12

The notion of positive TFT as coined by Banagl is specified by an axiomatic system based on Atiyah's original axioms for TFTs. By virtue of a general framework that is based on the concept of Eilenberg completeness of semirings from computer science, a positive TFT can be produced rigorously via quantization of systems of fields and action functionals - a process inspired by Feynman's path integral from classical quantum field theory. The purpose of the present dissertation thesis is to investigate a new differential topological invariant for smooth manifolds that arises as the state sum of the fold map TFT, which has been constructed by Banagl as a example of a positive TFT. By eliminating an internal technical assumption on the fields of the fold map TFT, we are able to express the informational content of the state sum in terms of an extension problem for fold maps from cobordisms into the plane. Next, we use the general theory of generic smooth maps into the plane to improve known results about the structure of the state sum in arbitrary dimensions, and to determine it completely in dimension two. The aggregate invariant of a homotopy sphere, which is derived from the state sum, naturally leads us to define a filtration of the group of homotopy spheres in order to understand the role of indefinite fold lines beyond a theorem of Saeki. As an application, we show how Kervaire spheres can be characterized by indefinite fold lines in certain dimensions.

Assessment of thyroplasty for vocal fold paralysis

DEFF Research Database (Denmark)

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

2009-01-01

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

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

Origami: Paper Folding--The Algorithmic Way.

Science.gov (United States)

Heukerott, Pamela Beth

1988-01-01

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

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

Folding and Fracturing of Rocks: the background

Science.gov (United States)

Ramsay, John G.

2017-04-01

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

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring

DEFF Research Database (Denmark)

Wingstrand, Vibe Lindeblad; Larsen, Christian Grønhøj; Jensen, David H

2016-01-01

OBJECTIVES: Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance...... the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring. DATA SOURCES: PubMed, Embase, the Cochrane Library and Google Scholar were searched. METHODS: Controlled studies that assessed...... the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude. RESULTS: Seven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic...

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.

Endo-extralaryngeal Laterofixation of the Vocal Folds in Patients with Bilateral Vocal Fold Immobility.

Science.gov (United States)

Wiegand, Susanne; Teymoortash, Afshin; Hanschmann, Holger

2017-01-01

Bilateral vocal fold paralysis can result in shortness of breath and severe dyspnea which can be life-threatening. Thirty-five patients with bilateral vocal fold paralysis who underwent endo-extralaryngeal laterofixation according to Lichtenberger were retrospectively analyzed regarding etiology, symptoms, treatment and complications. In 27 patients, laterofixation of the vocal cord alone was performed. Eight patients underwent laterofixation and additional posterior chordectomy of the opposite vocal cord according to Dennis and Kashima. The time of intervention ranged from 1 day to 38 years after the onset of bilateral vocal cord immobility. The intraoperative course was uneventful in all patients. None of the patients had postoperative aspiration. Postoperative voice function was acceptable in all patients. Complications of suture laterofixation were laryngeal edema, formation of fibrin, and malposition of the suture. Laterofixation of the vocal cords according to Lichtenberger is a safe and easy method that can be used as a first-stage treatment of vocal cord paralysis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.

Five-fold local symmetry in metallic liquids and glasses

International Nuclear Information System (INIS)

Li M Z; Li F X; Zhang H P; Peng H L; Hu Y C; Wang W H

2017-01-01

The structure of metallic glasses has been a long-standing mystery. Owing to the disordered nature of atomic structures in metallic glasses, it is a great challenge to find a simple structural description, such as periodicity for crystals, for establishing the structure–property relationship in amorphous materials. In this paper, we briefly review the recent developments of the five-fold local symmetry in metallic liquids and glasses and the understanding of the structure–property relationship based on this parameter. Experimental evidence demonstrates that five-fold local symmetry is found to be general in metallic liquids and glasses. Comprehensive molecular dynamics simulations show that the temperature evolution of five-fold local symmetry reflects the structural evolution in glass transition in cooling process, and the structure–property relationship such as relaxation dynamics, dynamic crossover phenomena, glass transition, and mechanical deformation in metallic liquids and glasses can be well understood base on the simple and general structure parameter of five-fold local symmetry. (paper)

A history of folding in mathematics mathematizing the margins

CERN Document Server

Friedman, Michael

2018-01-01

While it is well known that the Delian problems are impossible to solve with a straightedge and compass – for example, it is impossible to construct a segment whose length is ∛2 with these instruments – the Italian mathematician Margherita Beloch Piazzolla's discovery in 1934 that one can in fact construct a segment of length ∛2 with a single paper fold was completely ignored (till the end of the 1980s). This comes as no surprise, since with few exceptions paper folding was seldom considered as a mathematical practice, let alone as a mathematical procedure of inference or proof that could prompt novel mathematical discoveries. A few question immediately arise: Why did paper folding become a non-instrument? What caused the marginalisation of this technique? And how was the mathematical knowledge, which was nevertheless transmitted and prompted by paper folding, later treated and conceptualised? Aiming to answer these questions, this volume provides, for the first time, an extensive historical study...

Protein folding and misfolding shining light by infrared spectroscopy

CERN Document Server

Fabian, Heinz

2012-01-01

Infrared spectroscopy is a new and innovative technology to study protein folding/misfolding events in the broad arsenal of techniques conventionally used in this field. The progress in understanding protein folding and misfolding is primarily due to the development of biophysical methods which permit to probe conformational changes with high kinetic and structural resolution. The most commonly used approaches rely on rapid mixing methods to initiate the folding event via a sudden change in solvent conditions. Traditionally, techniques such as fluorescence, circular dichroism or visible absorption are applied to probe the process. In contrast to these techniques, infrared spectroscopy came into play only very recently, and the progress made in this field up to date which now permits to probe folding events over the time scale from picoseconds to minutes has not yet been discussed in a book. The aim of this book is to provide an overview of the developments as seen by some of the main contributors to the field...

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

Science.gov (United States)

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.

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

WW Domain Folding Complexity Revealed by Infrared Spectroscopy

OpenAIRE

Davis, Caitlin M.; Dyer, R. Brian

2014-01-01

Although the intrinsic tryptophan fluorescence of proteins offers a convenient probe of protein folding, interpretation of the fluorescence spectrum is often difficult because it is sensitive to both global and local changes. Infrared (IR) spectroscopy offers a complementary measure of structural changes involved in protein folding, because it probes changes in the secondary structure of the protein backbone. Here we demonstrate the advantages of using multiple probes, infrared and fluorescen...

Vocal fold hemorrhage associated with coumadin therapy in an opera singer.

Science.gov (United States)

Neely, J L; Rosen, C

2000-06-01

Vocal fold hemorrhage can represent a disastrous and potentially career ending injury to a singer or professional voice user. The risk factors of vocal fold hemorrhage, including laryngeal trauma, phonotrauma, aspirin and nonsteroidal antiinflammatories, and hormonal imbalances are well known. We present a case of an opera singer who developed recurrent vocal fold hemorrhage associated with coumadin anticoagulation therapy. This case highlights the importance of the risk of vocal fold hemorrhage to professional singers and professional voice users and offers an alternative to long-term coumadin therapy in this select population.

Interaction of the Zagros Fold-Thrust Belt and the Arabian-type, deep-seated folds in the Abadan Plain and the Dezful Embayment, SW Iran

Energy Technology Data Exchange (ETDEWEB)

Fard, Iraj Abdollahie [National Iranian Oil Co., Exploration Directorate, Tehran (Iran); Braathen, Alvar [Bergen Univ., Centre for Integrated Petroleum Research, Bergen (Norway); Mokhtari, Mohamad [International Institute of Earthquake Engineering and Seismology, Tehran (Iran); Alavi, Seyed Ahmad [Shahid Beheshti Univ., Earth Sciences Faculty, Tehran (Iran)

2006-07-01

The Dezful Embayment and Abadan Plain (SW Iran) contain major parts of the remaining Iranian oil reserves. These oil provinces are characterized by two types of structural closure: very gentle N-S- to NE-SW-trending basement-cored anticlines (Arabian-type highs) in the SE; and open to tight, NW-SE-trending thrust-related folds in the NE (Zagros Fold-Thrust Belt; ZFTB). Most deep-seated anticlines are upright and symmetrical in Cretaceous and older units. In some cases they reveal steep faults in their core which, in the light of regional observations, suggest that the basement is involved in the faulting. Untested plays around these anticlines include reefal build-ups, debris flows, truncated sedimentary sections and onlapping clastic units. The ZFTB shows a classic structural style, with overall shortening reflected in thrust displacement declining from the Dezful Embayment towards the frontal zone in the Abadan Plain. The Early Cambrian Hormuz Salt represents the fundamental sole for the fold-thrust belt and locates major fault-propagation folds in the southwestern Dezful Embayment. These folds represent the main petroleum target of the area. Another important unit is the Mid-Miocene Gachsaran Formation. This detachment reveals both in-sequence and out-of-sequence thrusting. Interaction of deep-seated anticlines and fold-thrust structures results in thrust imbrications and formation of duplexes within the Gachsaran Formation when thrusts abut deep-seated anticlines. Above the crest of the anticlines, thrusts are forced up-section into syn-tectonic deposits, whereas the forelimb reveals out-of-the-syncline thrusts. Several petroleum plays are identified in such zones of structural interaction, including anticlines above buttress-related duplexes, out-of-sequence imbricate thrust fans with associated folds above major anticlines, truncation of footwall layers below potentially sealing thrusts, and sub-thrust anticlines. (Author)

Laryngeal Electromyography for Prognosis of Vocal Fold Paralysis.

Science.gov (United States)

Pardo-Maza, Adriana; García-Lopez, Isabel; Santiago-Pérez, Susana; Gavilán, Javier

2017-01-01

This study aimed to determine the value of laryngeal electromyography in the prognosis of vocal fold paralysis. This is a retrospective descriptive study. This study included 80 patients diagnosed with unilateral or bilateral vocal fold paralysis on flexible laryngoscopy between 2002 and 2014 in a tertiary medical center. Laryngeal electromyography using a standardized protocol was performed; the outcome measures were classified and analyzed into two groups according to the degree of injury. Group 1 included patients with mild to moderate injury, and group 2 included patients with severe to complete injury. Prognosis was correlated with vocal fold motion recovery status with a minimum of 6 months of follow-up since the symptoms onset using positive and negative predictive values. Sixty patients showed acute or chronic recurrent laryngeal neuropathy in laryngeal electromyography. Twelve of 41 patients included in group 1 recovered motion, and 30 of 35 patients included in group 2 did not recover, resulting in 88.2% of positive predictive value and 35.7% of negative predictive value. Our data confirm that laryngeal electromyography is a useful clinical tool in predicting poor recovery in patients with vocal fold paralysis. It allows identification of candidates for early intervention. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Modeling and imaging of the vocal fold vibration for voice health

DEFF Research Database (Denmark)

Granados, Alba

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

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.

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.

IMPAIRED MOBILITY OF VOCAL FOLDS - etiology and symptoms

Directory of Open Access Journals (Sweden)

Karlo Pintarić

2015-06-01

Full Text Available Paresis or paralysis of one or both vocal cords affects some significant aspects of a human life: breathing, swallowing and speech. The major causes for reduced mobility or even immobility are innervation damage, less often fixation of vocal cord or impaired mobility of crycoarytenoid joint. An injury of the superior or/and inferior laryngeal nerve can be a consequence of different medical procedures, tumor growth, trauma, infection, neurological disorders, radiation exposure, toxic damage, impaired circulation of the area or it is idiopathic. The symptoms are different in the case of unilateral and bilateral paresis of the vocal folds. They also depend on the cause for the impaired mobility. In the patients with unilateral vocal fold paresis, hoarseness and aspiration during swallowing are the leading symptoms. In the bilateral vocal fold paralysis, dyspnea prevails. 

Phonosurgery of vocal fold polyps, cysts and nodules is beneficial

DEFF Research Database (Denmark)

Jensen, Jane Bjerg; Rasmussen, Niels

2013-01-01

This study reports our experience with microscopic phonosurgery (PS) of benign lesions of the vocal folds.......This study reports our experience with microscopic phonosurgery (PS) of benign lesions of the vocal folds....

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.

Fabrication of ten-fold photonic quasicrystalline structures

Directory of Open Access Journals (Sweden)

XiaoHong Sun

2015-05-01

Full Text Available Compared to periodic crystals, quasicrystals have higher point group symmetry and are more favorable in achieving complete band-gaps. In this report, a top-cut prism interferometer is designed to fabricate ten-fold photonic quasicrystalline structures. By optimizing the exposing conditions and material characteristics, appropriate quasicrystals have been obtained in the SU8 photoresist films. Atomic Force Microscopy and laser diffraction are used to characterize the fabricated structures. The measurement results show the consistence between the theoretical design and experiments. This will provide guidance for the large-area and fast production of ten-fold quasicrystalline structures with high quality.

A New Surgical Approach for the Treatment of Conjunctivochalasis: Reduction of the Conjunctival Fold with Bipolar Electrocautery Forceps

Science.gov (United States)

Arenas, Eduardo; Muñoz, Diana

2016-01-01

Aim. To report a new surgical technique for the treatment of conjunctivochalasis. Methods. A new surgical technique in which specially designed bipolar electrocautery forceps facilitate the complete reduction of the conjunctival folds without creating lesions near the corneoscleral limbus was designed. A retrospective revision of the medical records of patients treated with this technique between the years 2011 and 2013 was made, and eighteen eyes of sixteen patients with conjunctivochalasis treated with this new technique were included. Results. All the eyes treated showed a significant improvement with no evidence of scar lesions after a mean follow-up time of 10 months. Conclusions. The surgical technique presented here could be a good alternative for the management of conjunctivochalasis. PMID:27200408

Oral and vocal fold diadochokinesis in dysphonic women

OpenAIRE

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

2011-01-01

The evaluation of oral and vocal fold diadochokinesis (DDK) in individuals with voice disorders may contribute to the understanding of factors that affect the balanced vocal production. Scientific studies that make use of this assessment tool support the knowledge advance of this area, reflecting the development of more appropriate therapeutic planning. Objective: To compare the results of oral and vocal fold DDK in dysphonic women and in women without vocal disorders. Material and methods: F...

Examination of vocal fold movement by ultra-short pulse X radiography

International Nuclear Information System (INIS)

Noscoe, N.J.; Berry, R.J.; Brown, N.J.

1983-01-01

Antero-posterior radiographs of the larynx lack spatial and temporal resolution, due to the movement of the vocal folds during phonation. By utilising the electrolaryngograph to monitor vocal fold movement, single X-ray pulses of 30 nanoseconds duration have been triggered at pre-determined points during the cycle of vocal fold movement to visualise these in normal phonation. (author)

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.

Vocal Fold Mucus Aggregation in Persons with Voice Disorders

Science.gov (United States)

Bonilha, Heather Shaw; White, Lisa; Kuckhahn, Kelsey; Gerlach, Terri Treman; Deliyski, Dimitar D.

2012-01-01

Mucus aggregation on the vocal folds is a common finding from laryngeal endoscopy. Patients with voice disorders report the presence of mucus aggregation. Patients also report that mucus aggregation causes them to clear their throat, a behavior believed to be harmful to vocal fold mucosa. Even though clinicians and patients report and discuss…

Construction of a llama bacterial artificial chromosome library with approximately 9-fold genome equivalent coverage.

Science.gov (United States)

Airmet, K W; Hinckley, J D; Tree, L T; Moss, M; Blumell, S; Ulicny, K; Gustafson, A K; Weed, M; Theodosis, R; Lehnardt, M; Genho, J; Stevens, M R; Kooyman, D L

2012-01-01

The Ilama is an important agricultural livestock in much of South America. The llama is increasing in popularity in the United States as a companion animal. Little work has been done to improve llama production using modern technology. A paucity of information is available regarding the llama genome. We report the construction of a llama bacterial artificial chromosome (BAC) library of about 196,224 clones in the vector pECBAC1. Using flow cytometry and bovine, human, mouse, and chicken as controls, we determined the llama genome size to be 2.4 × 10⁹ bp. The average insert size of the library is 137.8 kb corresponding to approximately 9-fold genome coverage. Further studies are needed to further characterize the library and llama genome. We anticipate that this new library will help facilitate future genomic studies in the llama.

A STUDY OF INTERMEDIATES INVOLVED IN THE FOLDING PATHWAY FOR RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR (M-CSF) - EVIDENCE FOR 2 DISTINCT FOLDING PATHWAYS

NARCIS (Netherlands)

WILKINS, JA; CONE, J; RANDHAWA, ZI; WOOD, D; WARREN, MK; WITKOWSKA, HE

The folding pathway for a 150-amino acid recombinant form of the dimeric cytokine human macrophage colony-stimulating factor (M-CSF) has been studied. All 14 cysteine residues in the biologically active homodimer are involved in disulfide linkages. The structural characteristics of folding

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.

Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation

Directory of Open Access Journals (Sweden)

Joanne Ee Mei Teoh

2018-03-01

Full Text Available In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young’s modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall

Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation.

Science.gov (United States)

Teoh, Joanne Ee Mei; An, Jia; Feng, Xiaofan; Zhao, Yue; Chua, Chee Kai; Liu, Yong

2018-03-03

In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young's modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be

Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation

Science.gov (United States)

Teoh, Joanne Ee Mei; Feng, Xiaofan; Zhao, Yue; Liu, Yong

2018-01-01

In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young’s modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be

Learning facilitating leadership

DEFF Research Database (Denmark)

Rasmussen, Lauge Baungaard; Hansen, Mette Sanne

2016-01-01

This paper explains how engineering students at a Danish university acquired the necessary skills to become emergent facilitators of organisational development. The implications of this approach are discussed and related to relevant viewpoints and findings in the literature. The methodology deplo....... By connecting the literature, the authors’ and engineering students’ reflections on facilitator skills, this paper adds value to existing academic and practical discussions on learning facilitating leadership....

Thermodynamic properties of an extremely rapid protein folding reaction.

Science.gov (United States)

Schindler, T; Schmid, F X

1996-12-24

The cold-shock protein CspB from Bacillus subtilis is a very small beta-barrel protein, which folds with a time constant of 1 ms (at 25 degrees C) in a U reversible N two-state reaction. To elucidate the energetics of this extremely fast reaction we investigated the folding kinetics of CspB as a function of both temperature and denaturant concentration between 2 and 45 degrees C and between 1 and 8 M urea. Under all these conditions unfolding and refolding were reversible monoexponential reactions. By using transition state theory, data from 327 kinetic curves were jointly analyzed to determine the thermodynamic activation parameters delta H H2O++, delta S H2O++, delta G H2O++, and delta C p H2O++ for unfolding and refolding and their dependences on the urea concentration. 90% of the total change in heat capacity and 96% of the change in the m value (m = d delta G/d[urea]) occur between the unfolded state and the activated state. This suggests that for CspB the activated state of folding is unusually well structured and almost equivalent to the native protein in its interactions with the solvent. As a consequence of this native-like activated state a strong temperature-dependent enthalpy/entropy compensation is observed for the refolding kinetics, and the barrier to refolding shifts from being largely enthalpic at low temperature to largely entropic at high temperature. This shift originates not from the changes in the folding protein chains itself, but from the changes in the protein-solvent interactions. We speculate that the absence of intermediates and the native-like activated state in the folding of CspB are correlated with the small size and the structural type of this protein. The stabilization of a small beta-sheet as in CspB requires extensive non-local interactions, and therefore incomplete sheets are unstable. As a consequence, the critical activated state is reached only very late in folding. The instability of partially folded structure is a means to

Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function.

Directory of Open Access Journals (Sweden)

Xinxin Liu

Full Text Available Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3 expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001. Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (p<0.05 and a reduction in transepithelial electrical resistance (TEER by 180.0% (p<0.001. While the expression of tight junctional protein did not change in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05. Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium.

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.

Synthetic oligorotaxanes exert high forces when folding under mechanical load

Science.gov (United States)

Sluysmans, Damien; Hubert, Sandrine; Bruns, Carson J.; Zhu, Zhixue; Stoddart, J. Fraser; Duwez, Anne-Sophie

2018-01-01

Folding is a ubiquitous process that nature uses to control the conformations of its molecular machines, allowing them to perform chemical and mechanical tasks. Over the years, chemists have synthesized foldamers that adopt well-defined and stable folded architectures, mimicking the control expressed by natural systems1,2. Mechanically interlocked molecules, such as rotaxanes and catenanes, are prototypical molecular machines that enable the controlled movement and positioning of their component parts3-5. Recently, combining the exquisite complexity of these two classes of molecules, donor-acceptor oligorotaxane foldamers have been synthesized, in which interactions between the mechanically interlocked component parts dictate the single-molecule assembly into a folded secondary structure6-8. Here we report on the mechanochemical properties of these molecules. We use atomic force microscopy-based single-molecule force spectroscopy to mechanically unfold oligorotaxanes, made of oligomeric dumbbells incorporating 1,5-dioxynaphthalene units encircled by cyclobis(paraquat-p-phenylene) rings. Real-time capture of fluctuations between unfolded and folded states reveals that the molecules exert forces of up to 50 pN against a mechanical load of up to 150 pN, and displays transition times of less than 10 μs. While the folding is at least as fast as that observed in proteins, it is remarkably more robust, thanks to the mechanically interlocked structure. Our results show that synthetic oligorotaxanes have the potential to exceed the performance of natural folding proteins.

Facilitated ion transport in all-solid-state flexible supercapacitors.

Science.gov (United States)

Choi, Bong Gill; Hong, Jinkee; Hong, Won Hi; Hammond, Paula T; Park, HoSeok

2011-09-27

The realization of highly flexible and all-solid-state energy-storage devices strongly depends on both the electrical properties and mechanical integrity of the constitutive materials and the controlled assembly of electrode and solid electrolyte. Herein we report the preparation of all-solid-state flexible supercapacitors (SCs) through the easy assembly of functionalized reduced graphene oxide (f-RGO) thin films (as electrode) and solvent-cast Nafion electrolyte membranes (as electrolyte and separator). In particular, the f-RGO-based SCs (f-RGO-SCs) showed a 2-fold higher specific capacitance (118.5 F/g at 1 A/g) and rate capability (90% retention at 30 A/g) compared to those of all-solid-state graphene SCs (62.3 F/g at 1A/g and 48% retention at 30 A/g). As proven by the 4-fold faster relaxation of the f-RGO-SCs than that of the RGO-SCs and more capacitive behavior of the former at the low-frequency region, these results were attributed to the facilitated ionic transport at the electrical double layer by means of the interfacial engineering of RGO by Nafion. Moreover, the superiority of all-solid-state flexible f-RGO-SCs was demonstrated by the good performance durability under the 1000 cycles of charging and discharging due to the mechanical integrity as a consequence of the interconnected networking structures. Therefore, this research provides new insight into the rational design and fabrication of all-solid-state flexible energy-storage devices as well as the fundamental understanding of ion and charge transport at the interface. © 2011 American Chemical Society

Side chain and backbone contributions of Phe508 to CFTR folding

Energy Technology Data Exchange (ETDEWEB)

Thibodeau, Patrick H.; Brautigam, Chad A.; Machius, Mischa; Thomas, Philip J. (U. of Texas-SMED)

2010-12-07

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an integral membrane protein, cause cystic fibrosis (CF). The most common CF-causing mutant, deletion of Phe508, fails to properly fold. To elucidate the role Phe508 plays in the folding of CFTR, missense mutations at this position were generated. Only one missense mutation had a pronounced effect on the stability and folding of the isolated domain in vitro. In contrast, many substitutions, including those of charged and bulky residues, disrupted folding of full-length CFTR in cells. Structures of two mutant nucleotide-binding domains (NBDs) reveal only local alterations of the surface near position 508. These results suggest that the peptide backbone plays a role in the proper folding of the domain, whereas the side chain plays a role in defining a surface of NBD1 that potentially interacts with other domains during the maturation of intact CFTR.

Proving the correctness of unfold/fold program transformations using bisimulation

DEFF Research Database (Denmark)

Hamilton, Geoff W.; Jones, Neil

2011-01-01

by a labelled transition system whose bisimilarity relation is a congruence that coincides with contextual equivalence. Labelled transition systems are well-suited to represent global program behaviour. On the other hand, unfold/fold program transformations use generalization and folding, and neither is easy......This paper shows that a bisimulation approach can be used to prove the correctness of unfold/fold program transformation algorithms. As an illustration, we show how our approach can be use to prove the correctness of positive supercompilation (due to Sørensen et al). Traditional program equivalence...... to describe contextually, due to use of non-local information. We show that weak bisimulation on labelled transition systems gives an elegant framework to prove contextual equivalence of original and transformed programs. One reason is that folds can be seen in the context of corresponding unfolds....

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

Recoverable and Programmable Collapse from Folding Pressurized Origami Cellular Solids.

Science.gov (United States)

Li, S; Fang, H; Wang, K W

2016-09-09

We report a unique collapse mechanism by exploiting the negative stiffness observed in the folding of an origami solid, which consists of pressurized cells made by stacking origami sheets. Such a collapse mechanism is recoverable, since it only involves rigid folding of the origami sheets and it is programmable by pressure control and the custom design of the crease pattern. The collapse mechanism features many attractive characteristics for applications such as energy absorption. The reported results also suggest a new branch of origami study focused on its nonlinear mechanics associated with folding.

Endoscopic vocal fold injection using a 25-gauge butterfly needle.

Science.gov (United States)

Buchanan, M A; Riffat, F; Palme, C E

2016-04-01

To describe a useful technique for infiltrating a bulking agent using a butterfly needle, as part of a transoral endoscopic vocal fold medialisation procedure. This paper describes the procedure of grasping the needle with phonosurgery forceps and administering the injectate to the vocal fold through careful application of the syringe plunger via a length of rubber tubing from outside the mouth. This procedure is performed routinely in our institution without complication. The advantages of this technique are discussed. This is a safe and easy method of injecting into a vocal fold.

DC-Analyzer-facilitated combinatorial strategy for rapid directed evolution of functional enzymes with multiple mutagenesis sites.

Science.gov (United States)

Wang, Xiong; Zheng, Kai; Zheng, Huayu; Nie, Hongli; Yang, Zujun; Tang, Lixia

2014-12-20

Iterative saturation mutagenesis (ISM) has been shown to be a powerful method for directed evolution. In this study, the approach was modified (termed M-ISM) by combining the single-site saturation mutagenesis method with a DC-Analyzer-facilitated combinatorial strategy, aiming to evolve novel biocatalysts efficiently in the case where multiple sites are targeted simultaneously. Initially, all target sites were explored individually by constructing single-site saturation mutagenesis libraries. Next, the top two to four variants in each library were selected and combined using the DC-Analyzer-facilitated combinatorial strategy. In addition to site-saturation mutagenesis, iterative saturation mutagenesis also needed to be performed. The advantages of M-ISM over ISM were that the screening effort is greatly reduced, and the entire M-ISM procedure was less time-consuming. The M-ISM strategy was successfully applied to the randomization of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) when five interesting sites were targeted simultaneously. After screening 900 clones in total, six positive mutants were obtained. These mutants exhibited 4.0- to 9.3-fold higher k(cat) values than did the wild-type HheC toward 1,3-dichloro-2-propanol. However, with the ISM strategy, the best hit showed a 5.9-fold higher k(cat) value toward 1,3-DCP than the wild-type HheC, which was obtained after screening 4000 clones from four rounds of mutagenesis. Therefore, M-ISM could serve as a simple and efficient version of ISM for the randomization of target genes with multiple positions of interest.

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...

Interpreting whether isoclinal folds are antiforms or synforms using FIA succession

Science.gov (United States)

Cao, H.

2012-12-01

Using the asymmetries of the overprinting foliations preserved as inclusion trails that define the FIAs to investigate whether an enigmatic isoclinal fold in the region is an antiform or synform. This approach also reveals when the fold first formed during the tectonic history of the region. Multiply deformed and isoclinally folded interlayered high metamorphic grade gneisses and schists can be very difficult rocks for resolving early formed stratigraphic and structural relationships. When such rocks contain porphyroblasts a new approach is possible because of the way in which porphyroblast growth is affected by crenulation versus reactivation of compositional layering (Bell et al., 2003). Isoclinally folded rocks in the Arkansas River region of South Central Colorado contain relics of fold hinges that have been very difficult to ascertain whether they are antiforms or synforms because of younger refolding effects and the locally truncated nature of coarse compositional layering. With the realization that rocks with a schistosity parallel to bedding (S0 parallel S1) have undergone lengthy histories of deformation that predate the obvious first deformation (e.g. Bell et al., 2003; Sayab, 2006; Yeh, 2007) came recognition that large scale regional folds can form early during this process and be preserved throughout orogenesis (e.g., Ham and Bell, 2004; Bell and Newman, 2006. This extensive history is lost within the matrix because of reactivational shear on the compositional layering (Bell et al., 1998, 2003, 2004, 2005; Ham and Bell, 2004). However, it can be extracted by measuring FIAs. Recent work using this approach has revealed that the trends of axial planes of all map scale folds, when plotted on a rose diagram, strikingly reflect the FIA trends (e.g., Sanislav, 2009; Shah, 2009). That is, although it was demonstrated by Bell et al. (2003) that the largest scale regional folds commonly form early in the total history, other folds can form and be preserved from

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

Science.gov (United States)

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

2009-06-01

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

Transcutaneous ultrasound for evaluation of vocal fold movement in patients with thyroid disease

International Nuclear Information System (INIS)

Wang, Cheng-Ping; Chen, Tseng-Cheng; Yang, Tsung-Lin; Chen, Chun-Nan; Lin, Chin-Fon; Lou, Pei-Jen; Hu, Ya-Ling; Shieh, Ming-Jium; Hsieh, Fon-Jou

2012-01-01

Background: Preoperative evaluation of recurrent laryngeal nerve function is important in the context of thyroid surgery. Transcutaneous ultrasound may be useful to visualize vocal fold movement when evaluating thyroid disease. Methods: A 7–18 MHz linear array transducer was placed transversely on the midline of the thyroid cartilage at the anterior neck of patients with thyroid disease. The gray-scale technique was used, with the scan setting for the thyroid gland. Results: Between August 2008 and March 2010, 705 patients, including 672 patients with normal vocal fold movement and 33 patients with vocal fold paralysis were enrolled. They included 159 male and 546 female patients. Their ages ranged from 10 to 88 years. Vocal fold movement could be seen by ultrasound in 614 (87%) patients, including 589 (88%) patients with normal vocal fold movement and 25 (76%) patients with vocal fold paralysis (p = 0.06). The mean age of patients with visible and invisible vocal fold movement was 46.6 and 57.9 years old, respectively (p = 0.001). Ultrasound was able to see vocal fold movement in 533 (98%) female patients but only in 81 (51%) male patients (p = 0.001). Among the patients with vocal fold paralysis, ultrasound revealed palsied vocal folds in 17 of 18 (94%) female patients but in only 8 of 15 (53%) male patients (p = 0.01). Conclusion: Transcutaneous ultrasound represents an alternative tool to evaluate vocal fold movement for more than 85% of patients with thyroid disease, including more than 90% of female patients and about half of male patients.

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.

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.

The optimization of peptide cargo bound to MHC class I molecules by the peptide-loading complex.

Science.gov (United States)

Elliott, Tim; Williams, Anthony

2005-10-01

Major histocompatibility complex (MHC) class I complexes present peptides from both self and foreign intracellular proteins on the surface of most nucleated cells. The assembled heterotrimeric complexes consist of a polymorphic glycosylated heavy chain, non-polymorphic beta(2) microglobulin, and a peptide of typically nine amino acids in length. Assembly of the class I complexes occurs in the endoplasmic reticulum and is assisted by a number of chaperone molecules. A multimolecular unit termed the peptide-loading complex (PLC) is integral to this process. The PLC contains a peptide transporter (transporter associated with antigen processing), a thiooxido-reductase (ERp57), a glycoprotein chaperone (calreticulin), and tapasin, a class I-specific chaperone. We suggest that class I assembly involves a process of optimization where the peptide cargo of the complex is edited by the PLC. Furthermore, this selective peptide loading is biased toward peptides that have a longer off-rate from the assembled complex. We suggest that tapasin is the key chaperone that directs this action of the PLC with secondary contributions from calreticulin and possibly ERp57. We provide a framework model for how this may operate at the molecular level and draw parallels with the proposed mechanism of action of human leukocyte antigen-DM for MHC class II complex optimization.

Unilateral Vocal Fold Paralysis in Parkinson Disease: Case Report and Review of the Literature.

Science.gov (United States)

Hamdan, Abdul-Latif; Khalifee, Elie; Tabet, Georges

2017-10-24

The objective of this study was to report the first case of unilateral vocal fold paralysis in a patient with Parkinson disease (PD) and to review the literature. This is a case report and literature review following PubMed search using the keywords "Parkinson," "vocal fold paralysis," "vocal fold palsy," "vocal fold immobility," "vocal fold adductor palsy," "airway obstruction," and "stridor." A total of 18 subjects diagnosed with PD and vocal fold paralysis were described. In all cases, the vocal fold paralysis was bilateral and the main presenting symptoms were stridor and shortness of breath necessitating intubation and tracheostomy. This article describes the first case of PD presenting with dysphonia secondary to unilateral vocal fold paralysis (left). The management consisted of injection laryngoplasty for medialization of the paralyzed vocal fold. Patients with PD can present with unilateral vocal fold paralysis. Early treatment is advocated in view of the advent of injection laryngoplasty as a safe office procedure. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Acute vocal fold hemorrhage caught on video during office exam.

Science.gov (United States)

Carroll, Thomas L; Smith, Libby J

2009-03-01

This article presents a unique video of a laryngeal exam during which a vocal fold hemorrhage occurs. This patient had likely been suffering from intermittent vocal fold hemorrhages for the last decade due to a persistent vascular lesion and an underlying chronic cough.

Eye and sheath folds in turbidite convolute lamination: Aberystwyth Grits Group, Wales

Science.gov (United States)

McClelland, H. L. O.; Woodcock, N. H.; Gladstone, C.

2011-07-01

Eye and sheath folds are described from the turbidites of the Aberystwyth Group, in the Silurian of west Wales. They have been studied at outcrop and on high resolution optical scans of cut surfaces. The folds are not tectonic in origin. They occur as part of the convolute-laminated interval of each sand-mud turbidite bed. The thickness of this interval is most commonly between 20 and 100 mm. Lamination patterns confirm previous interpretations that convolute lamination nucleated on ripples and grew during continued sedimentation of the bed. The folds amplified vertically and were sheared horizontally by continuing turbidity flow, but only to average values of about γ = 1. The strongly curvilinear fold hinges are due not to high shear strains, but to nucleation on sinuous or linguoid ripples. The Aberystwyth Group structures provide a warning that not all eye folds in sedimentary or metasedimentary rocks should be interpreted as sections through high shear strain sheath folds.

Feasibility of Clinical Endoscopy and Stroboscopy in Children With Bilateral Vocal Fold Lesions.

Science.gov (United States)

Zacharias, Stephanie R C; Brehm, Susan Baker; Weinrich, Barbara; Kelchner, Lisa; Tabangin, Meredith; de Alarcon, Alessandro

2016-11-01

The purpose of this study was to examine the utility of flexible and rigid endoscopy and stroboscopy for the identification of anatomical and physiological features in children with bilateral vocal fold lesions. The secondary purpose was to describe the age distribution of patients who could tolerate use of the different types of endoscopes. This cross-sectional clinic-based study included 38 children (ages 5 to 12 years) diagnosed with bilateral vocal fold lesions via videoendoscopy. Vocal fold vibratory characteristics (e.g., mucosal wave) were rated by 4 clinicians by consensus. Bilateral vocal fold lesions could be well described anatomically after visualization with both flexible and rigid endoscopes and were most commonly described as symmetrical and broad based. However, the clinicians' confidence in the accuracy of stroboscopy for rating vocal fold vibratory characteristics was limited for both flexible and rigid stroboscopes. Videoendoscopy was adequate for viewing and characterizing anatomical structures of bilateral vocal fold lesions in pediatric patients; however, vibratory characteristics were often not fully visualized with videostroboscopy. In view of the importance of visualizing vocal fold vibration in the differential diagnosis and treatment of vocal fold lesions, other imaging modalities, such as high-speed videoendoscopy, may provide more accurate descriptions of vocal fold vibratory characteristics in this population.

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

Modulating Phonation Through Alteration of Vocal Fold Medial Surface Contour

Science.gov (United States)

Mau, Ted; Muhlestein, Joseph; Callahan, Sean; Chan, Roger W.

2012-01-01

Objectives 1. To test whether alteration of the vocal fold medial surface contour can improve phonation. 2. To demonstrate that implant material properties affect vibration even when implant is deep to the vocal fold lamina propria. Study Design Induced phonation of excised human larynges. Methods Thirteen larynges were harvested within 24 hours post-mortem. Phonation threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA). Small-volume injections (median 0.0625 mL) were targeted to the infero-medial aspect of the thyroarytenoid (TA) muscle. Implant locations were assessed histologically. Results The effect of implantation on PTP was material-dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP (Wilcoxon test P = 0.00013 for onset). In contrast, the effect of implantation on PTF was similar, with both materials tending to decrease PTF (P = 0.16 for onset). Histology confirmed implant presence in the inferior half of the vocal fold vertical thickness. Conclusions Taken together, these data suggested the implants may have altered the vocal fold medial surface contour, potentially resulting in a less convergent or more rectangular glottal geometry as a means to improve phonation. An implant with a closer viscoelastic match to vocal fold cover is desirable for this purpose, as material properties can affect vibration even when the implant is not placed within the lamina propria. This result is consistent with theoretical predictions and implies greater need for surgical precision in implant placement and care in material selection. PMID:22865592

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

Directory of Open Access Journals (Sweden)

Sharma Gaurav

2011-04-01

Full Text Available Abstract Background The prediction of secondary structure, i.e. the set of canonical base pairs between nucleotides, is a first step in developing an understanding of the function of an RNA sequence. The most accurate computational methods predict conserved structures for a set of homologous RNA sequences. These methods usually suffer from high computational complexity. In this paper, TurboFold, a novel and efficient method for secondary structure prediction for multiple RNA sequences, is presented. Results TurboFold takes, as input, a set of homologous RNA sequences and outputs estimates of the base pairing probabilities for each sequence. The base pairing probabilities for a sequence are estimated by combining intrinsic information, derived from the sequence itself via the nearest neighbor thermodynamic model, with extrinsic information, derived from the other sequences in the input set. For a given sequence, the extrinsic information is computed by using pairwise-sequence-alignment-based probabilities for co-incidence with each of the other sequences, along with estimated base pairing probabilities, from the previous iteration, for the other sequences. The extrinsic information is introduced as free energy modifications for base pairing in a partition function computation based on the nearest neighbor thermodynamic model. This process yields updated estimates of base pairing probability. The updated base pairing probabilities in turn are used to recompute extrinsic information, resulting in the overall iterative estimation procedure that defines TurboFold. TurboFold is benchmarked on a number of ncRNA datasets and compared against alternative secondary structure prediction methods. The iterative procedure in TurboFold is shown to improve estimates of base pairing probability with each iteration, though only small gains are obtained beyond three iterations. Secondary structures composed of base pairs with estimated probabilities higher than a

Novel insights into E. coli's hexuronate metabolism: KduI facilitates the conversion of galacturonate and glucuronate under osmotic stress conditions.

Directory of Open Access Journals (Sweden)

Monique Rothe

Full Text Available Using a gnotobiotic mouse model, we previously observed the upregulation of 2-deoxy-D-gluconate 3-dehydrogenase (KduD in intestinal E. coli of mice fed a lactose-rich diet and the downregulation of this enzyme and of 5-keto 4-deoxyuronate isomerase (KduI on a casein-rich diet. The present study aimed to define the role of the so far poorly characterized E. coli proteins KduD and KduI in vitro. Galacturonate and glucuronate induced kduD and kduI gene expression 3-fold and 7 to 11-fold, respectively, under aerobic conditions as well as 9 to 20-fold and 19 to 54-fold, respectively, under anaerobic conditions. KduI facilitated the breakdown of these hexuronates. In E. coli, galacturonate and glucuronate are normally degraded by UxaABC and UxuAB. However, osmotic stress represses the expression of the corresponding genes in an OxyR-dependent manner. When grown in the presence of galacturonate or glucuronate, kduID-deficient E. coli had a 30% to 80% lower maximal cell density and 1.5 to 2-fold longer doubling times under osmotic stress conditions than wild type E. coli. Growth on lactose promoted the intracellular formation of hexuronates, which possibly explain the induction of KduD on a lactose-rich diet. These results indicate a novel function of KduI and KduD in E. coli and demonstrate the crucial influence of osmotic stress on the gene expression of hexuronate degrading enzymes.

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

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

Vocal Fold Epithelial Barrier in Health and Injury A Research Review

Science.gov (United States)

Levendoski, Elizabeth Erickson; Leydon, Ciara; Thibeault, Susan L.

2015-01-01

Purpose Vocal fold epithelium is composed of layers of individual epithelial cells joined by junctional complexes constituting a unique interface with the external environment. This barrier provides structural stability to the vocal folds and protects underlying connective tissue from injury while being nearly continuously exposed to potentially hazardous insults including environmental or systemic-based irritants such as pollutants and reflux, surgical procedures, and vibratory trauma. Small disruptions in the epithelial barrier may have a large impact on susceptibility to injury and overall vocal health. The purpose of this article is to provide a broad-based review of our current knowledge of the vocal fold epithelial barrier. Methods A comprehensive review of the literature was conducted. Details of the structure of the vocal fold epithelial barrier are presented and evaluated in the context of function in injury and pathology. The importance of the epithelial-associated vocal fold mucus barrier is also introduced. Results/Conclusions Information presented in this review is valuable for clinicians and researchers as it highlights the importance of this understudied portion of the vocal folds to overall vocal health and disease. Prevention and treatment of injury to the epithelial barrier is a significant area awaiting further investigation. PMID:24686981

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.

Management of vocal fold scar with autologous fat implantation: perceptual results.

Science.gov (United States)

Neuenschwander, M C; Sataloff, R T; Abaza, M M; Hawkshaw, M J; Reiter, D; Spiegel, J R

2001-06-01

Vocal fold scar disrupts the mucosal wave and interferes with glottic closure. Treatment involves a multidisciplinary approach that includes voice therapy, medical management, and sometimes surgery. We reviewed the records of the first eight patients who underwent autologous fat implantation for vocal fold scar. Information on the etiology of scar, physical findings, and prior interventions were collected. Videotapes of videostroboscopic findings and perceptual voice ratings [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS)] were randomized and analyzed independently by four blinded observers. Etiology of scar included mass excision (7), vocal fold stripping (3), congenital sulcus (2), and hemorrhage (1). Prior surgical procedures performed included thyroplasty (1), autologous fat injection (9), excision of scar (2), and lysis of adhesions (2). Strobovideolaryngoscopy: Statistically significant improvement was found in glottic closure, mucosal wave, and stiffness (P = 0.05). Perceptual ratings (GRBAS): Statistically significant improvement was found in all five parameters, including overall Grade, Roughness, Breathiness, Asthenia, and Strain (P = 0.05). Patients appear to have improved vocal fold function and quality of voice after autologous fat implantation in the vocal fold. Autologous fat implantation is an important adjunctive procedure in the management of vocal fold scar, and a useful addition to the armamentarium of the experienced phonomicrosurgeon.

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

Science.gov (United States)

Benesh, Nathan Philip

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

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.

Protein folding and the organization of the protein topology universe

DEFF Research Database (Denmark)

Lindorff-Larsen,, Kresten; Røgen, Peter; Paci, Emanuele

2005-01-01

residues and, in addition, that the topology of the transition state is closer to that of the native state than to that of any other fold in the protein universe. Here, we review the evidence for these conclusions and suggest a molecular mechanism that rationalizes these findings by presenting a view...... of protein folds that is based on the topological features of the polypeptide backbone, rather than the conventional view that depends on the arrangement of different types of secondary-structure elements. By linking the folding process to the organization of the protein structure universe, we propose...

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.

Construction and characterization of a novel vocal fold bioreactor.

Science.gov (United States)

Zerdoum, Aidan B; Tong, Zhixiang; Bachman, Brendan; Jia, Xinqiao

2014-08-01

In vitro engineering of mechanically active tissues requires the presentation of physiologically relevant mechanical conditions to cultured cells. To emulate the dynamic environment of vocal folds, a novel vocal fold bioreactor capable of producing vibratory stimulations at fundamental phonation frequencies is constructed and characterized. The device is composed of a function generator, a power amplifier, a speaker selector and parallel vibration chambers. Individual vibration chambers are created by sandwiching a custom-made silicone membrane between a pair of acrylic blocks. The silicone membrane not only serves as the bottom of the chamber but also provides a mechanism for securing the cell-laden scaffold. Vibration signals, generated by a speaker mounted underneath the bottom acrylic block, are transmitted to the membrane aerodynamically by the oscillating air. Eight identical vibration modules, fixed on two stationary metal bars, are housed in an anti-humidity chamber for long-term operation in a cell culture incubator. The vibration characteristics of the vocal fold bioreactor are analyzed non-destructively using a Laser Doppler Vibrometer (LDV). The utility of the dynamic culture device is demonstrated by culturing cellular constructs in the presence of 200-Hz sinusoidal vibrations with a mid-membrane displacement of 40 µm. Mesenchymal stem cells cultured in the bioreactor respond to the vibratory signals by altering the synthesis and degradation of vocal fold-relevant, extracellular matrix components. The novel bioreactor system presented herein offers an excellent in vitro platform for studying vibration-induced mechanotransduction and for the engineering of functional vocal fold tissues.

Time course of recovery of idiopathic vocal fold paralysis.

Science.gov (United States)

Husain, Solomon; Sadoughi, Babak; Mor, Niv; Levin, Ariana M; Sulica, Lucian

2018-01-01

To clarify the time course of recovery in patients with idiopathic vocal fold paralysis. Retrospective chart review. Medical records for all patients with idiopathic vocal fold paralysis over a 10-year period were reviewed to obtain demographic and clinical information, including onset of disease and recovery of vocal function. Stroboscopic exams of patients who recovered voice were reviewed blindly to assess return of vocal fold motion. Thirty-eight of 55 patients (69%) recovered vocal function. Time course of recovery could be assessed in 34 patients who did not undergo injection augmentation. The mean time to recovery was 152.8 ± 109.3 days (left, 179.8 ± 111.3 days; right, 105.3 ± 93.7 days; P = .088). Two-thirds of patients recovered within 6 months. Probability of recovery declined over time. Five of 22 patients who recovered voice had return of vocal fold motion; 17 did not. The mean time to recovery did not differ between these groups (return of motion, 127.4 ± 132.3 days; no return of motion, 160.1 ± 105.1 days; P = .290). Sixty-nine percent of patients with idiopathic vocal fold paralysis recovered vocal function, two-thirds doing so within 6 months of onset. Age, gender, laterality, use of injection augmentation did not influence recovery rate. Declining probability of recovery over time leads us to consider framework surgery after 6 months in patients with idiopathic paralysis. 4. Laryngoscope, 128:148-152, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Ectasias and varices of the vocal fold: clearing the striking zone.

Science.gov (United States)

Hochman, I; Sataloff, R T; Hillman, R E; Zeitels, S M

1999-01-01

Vascular malformations such as ectasias and varices (Es and Vs) are frequently encountered in patients who present with recurrent vocal fold hemorrhage and/or other traumatic vocal fold lesions. This study examined Es and Vs with regard to their anatomic presentation, phonomicrosurgical management, and treatment outcome. Forty-two patients (39 of them singers) were treated for a total of 87 Es and Vs: 67 of 87 (77%) were on the superior surface of the vocal fold and 20 of 87 (23%) were on the medial surface of the vocal fold. Eighty-three percent were located in the middle musculomembranous region (the striking zone), where the greatest aerodynamically induced shearing stresses occur during phonation. Treatment was performed with carbon dioxide laser cauterization (13 patients), or a new technique utilizing cold instrument excision by means of epithelial cordotomies (23 patients), while a combined approach was employed in 6 patients. Comparisons of preoperative and postoperative stroboscopy revealed improvement or no significant change in all patients in whom the cold instrument technique was used, and increased epithelial stiffness was noted in 4 of 19 patients in whom the carbon dioxide laser was used. Clearing the striking zone appears to have halted further hemorrhages by removing the the fragile Es and Vs from this injury-prone region of the vocal fold. Interpretations of stroboscopic examinations were directed at providing new insights into the biomechanical forces of vocal fold vibration that probably contribute to the genesis of Es and Vs in the vocal folds.

Dynamics in thin folded polymer films

Science.gov (United States)

Croll, Andrew; Rozairo, Damith

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

Ability of mini-implant-facilitated micro-osteoperforations to accelerate tooth movement in rats.

Science.gov (United States)

Cheung, Tracy; Park, Juyoung; Lee, Deborah; Kim, Catherine; Olson, Jeffrey; Javadi, Shadi; Lawson, Gregory; McCabe, James; Moon, Won; Ting, Kang; Hong, Christine

2016-12-01

Although current techniques for accelerated tooth movement often involve invasive surgical procedures, micro-osteoperforations (MOPs) using mini-implants may facilitate orthodontic tooth movement without raising flaps, reduce surgical risks, and increase patient acceptance. In this study, we evaluated the effectiveness of mini-implant-facilitated MOPs in inducing accelerated tooth movement and investigated the potential risks for root resorption. Five MOPs were placed on the left side around the maxillary first molars in 6 rats using an automated mini-implant driver, whereas the right side received no MOPs as the control. Closed-coiled springs were secured from incisors to first molars for orthodontic tooth movement. Tooth movement was measured, and samples underwent radiologic and histologic analyses. The MOP side exhibited a 1.86-fold increase in the rate of tooth movement with decreased bone density and bone volume around the first molars compared with the control side. Hematoxylin and eosin and tartrate-resistant acid phosphatase analyses showed increased numbers of osteoclasts as well as new bone formation. Three-dimensional volumetric analysis of all 5 roots of the maxillary first molars demonstrated no statistically significant difference in root volumes. Mini-implant-facilitated MOPs accelerated tooth movement without increased risk for root resorption and therefore may become a readily available and efficient treatment option to shorten orthodontic treatment time with improved patient acceptance. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Swallowing function in pediatric patients with bilateral vocal fold immobility.

Science.gov (United States)

Hsu, Jeffrey; Tibbetts, Kathleen M; Wu, Derek; Nassar, Michel; Tan, Melin

2017-02-01

Infants with bilateral vocal fold immobility (BVFI) often have poor swallow function in addition to potential airway compromise. While there are several reports on BVFI and its effect on patients' airway status, little is known about long term swallow function. We aim to characterize the swallowing function over time in pediatric patients with bilateral vocal fold immobility. A retrospective review of medical records of infants diagnosed with BVFI at a tertiary care children's hospital between 2005 and 2014 was conducted. Patient demographics, nature and etiology of immobility, laryngoscopy findings, comorbidities, and swallow outcomes at diagnosis and follow-up were recorded. Swallowing outcomes as measured by presence or absence of a gastrostomy tube were compared by etiology, vocal fold status, and normal or developmentally delay using the Fisher's exact test. 110 patients with a diagnosis of vocal fold immobility were identified. Twenty-nine (26%) had BVFI and twenty-three had complete medical records. Etiologies of vocal fold immobility include cardiac related in 13% (3/23), idiopathic in 30% (7/23) prolonged intubation in 26% (6/23) central neurologic in 22% (5/23), trauma in 4% (1/23), and infection in 4% (1/23). Average follow-up time was 44 months (range 5-94 months). Ten patients (56.5%) required a gastrostomy tube at time of diagnosis. Of this cohort who received gastrostomy tubes, three (30%) ultimately transitioned to complete oral feeds. Return of vocal fold mobility did not correlate with swallow function. In those with non-neurologic etiologies, the need for gastrostomy tube at end of follow up was unlikely. There was a statistically significant difference in the percentage of gastrostomy tube-free children at most recent follow up in patients who were normally developed (86%) versus those who were developmentally delayed (33%) (p = 0.02). We characterized the swallowing function of 23 pediatric patients with BVFI. Comorbidities are significant

High Pressure ZZ-Exchange NMR Reveals Key Features of Protein Folding Transition States.

Science.gov (United States)

Zhang, Yi; Kitazawa, Soichiro; Peran, Ivan; Stenzoski, Natalie; McCallum, Scott A; Raleigh, Daniel P; Royer, Catherine A

2016-11-23

Understanding protein folding mechanisms and their sequence dependence requires the determination of residue-specific apparent kinetic rate constants for the folding and unfolding reactions. Conventional two-dimensional NMR, such as HSQC experiments, can provide residue-specific information for proteins. However, folding is generally too fast for such experiments. ZZ-exchange NMR spectroscopy allows determination of folding and unfolding rates on much faster time scales, yet even this regime is not fast enough for many protein folding reactions. The application of high hydrostatic pressure slows folding by orders of magnitude due to positive activation volumes for the folding reaction. We combined high pressure perturbation with ZZ-exchange spectroscopy on two autonomously folding protein domains derived from the ribosomal protein, L9. We obtained residue-specific apparent rates at 2500 bar for the N-terminal domain of L9 (NTL9), and rates at atmospheric pressure for a mutant of the C-terminal domain (CTL9) from pressure dependent ZZ-exchange measurements. Our results revealed that NTL9 folding is almost perfectly two-state, while small deviations from two-state behavior were observed for CTL9. Both domains exhibited large positive activation volumes for folding. The volumetric properties of these domains reveal that their transition states contain most of the internal solvent excluded voids that are found in the hydrophobic cores of the respective native states. These results demonstrate that by coupling it with high pressure, ZZ-exchange can be extended to investigate a large number of protein conformational transitions.

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

Numerical construction of the p(fold) (committor) reaction coordinate for a Markov process.

Science.gov (United States)

Krivov, Sergei V

2011-10-06

To simplify the description of a complex multidimensional dynamical process, one often projects it onto a single reaction coordinate. In protein folding studies, the folding probability p(fold) is an optimal reaction coordinate which preserves many important properties of the dynamics. The construction of the coordinate is difficult. Here, an efficient numerical approach to construct the p(fold) reaction coordinate for a Markov process (satisfying the detailed balance) is described. The coordinate is obtained by optimizing parameters of a chosen functional form to make a generalized cut-based free energy profile the highest. The approach is illustrated by constructing the p(fold) reaction coordinate for the equilibrium folding simulation of FIP35 protein reported by Shaw et al. (Science 2010, 330, 341-346). © 2011 American Chemical Society

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Ivan Coluzza

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

Optimal fold symmetry of LH2 rings on a photosynthetic membrane.

Science.gov (United States)

Cleary, Liam; Chen, Hang; Chuang, Chern; Silbey, Robert J; Cao, Jianshu

2013-05-21

An intriguing observation of photosynthetic light-harvesting systems is the N-fold symmetry of light-harvesting complex 2 (LH2) of purple bacteria. We calculate the optimal rotational configuration of N-fold rings on a hexagonal lattice and establish two related mechanisms for the promotion of maximum excitation energy transfer (EET). (i) For certain fold numbers, there exist optimal basis cells with rotational symmetry, extendable to the entire lattice for the global optimization of the EET network. (ii) The type of basis cell can reduce or remove the frustration of EET rates across the photosynthetic network. We find that the existence of a basis cell and its type are directly related to the number of matching points S between the fold symmetry and the hexagonal lattice. The two complementary mechanisms provide selection criteria for the fold number and identify groups of consecutive numbers. Remarkably, one such group consists of the naturally occurring 8-, 9-, and 10-fold rings. By considering the inter-ring distance and EET rate, we demonstrate that this group can achieve minimal rotational sensitivity in addition to an optimal packing density, achieving robust and efficient EET. This corroborates our findings i and ii and, through their direct relation to S, suggests the design principle of matching the internal symmetry with the lattice order.

Facilitating Group Decision-Making: Facilitator's Subjective Theories on Group Coordination

Directory of Open Access Journals (Sweden)

Michaela Kolbe

2008-10-01

Full Text Available A key feature of group facilitation is motivating and coordinating people to perform their joint work. This paper focuses on group coordination which is a prerequisite to group effectiveness, especially in complex tasks. Decision-making in groups is a complex task that consequently needs to be coordinated by explicit rather than implicit coordination mechanisms. Based on the embedded definition that explicit coordination does not just happen but is purposely executed by individuals, we argue that individual coordination intentions and mechanisms should be taken into account. Thus far, the subjective perspective of coordination has been neglected in coordination theory, which is understandable given the difficulties in defining and measuring subjective aspects of group facilitation. We therefore conducted focused interviews with eight experts who either worked as senior managers or as experienced group facilitators and analysed their approaches to group coordination using methods of content analysis. Results show that these experts possess sophisticated mental representations of their coordination behaviour. These subjective coordination theories can be organised in terms of coordination schemes in which coordination-releasing situations are facilitated by special coordination mechanisms that, in turn, lead to the perception of specific consequences. We discuss the importance of these subjective coordination theories for effectively facilitating group decision-making and minimising process losses. URN: urn:nbn:de:0114-fqs0901287

Sex Hormone Receptor Expression in the Human Vocal Fold Subunits.

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Kirgezen, Tolga; Sunter, Ahmet Volkan; Yigit, Ozgur; Huq, Gulben Erdem

2017-07-01

The study aimed to evaluate the existence of sex hormone receptors in the subunits of vocal fold. This is a cadaver study. The androgen, estrogen, and progesterone receptors were examined in the epithelium (EP), superficial layer of the lamina propria (SLP), vocal ligament (VL), and macula flava (MF) of the vocal folds from 42 human cadavers (21 male, 21 female) by immunohistochemical methods. Their staining ratios were scored and statistically compared. The androgen receptor score was significantly higher for the MF than for the EP and SLP (P vocal fold, mostly in the MF and VLs. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Effects of gravity in folding

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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

Lie algebra lattices and strings on T-folds

Energy Technology Data Exchange (ETDEWEB)

Satoh, Yuji [Institute of Physics, University of Tsukuba,Ibaraki 305-8571 (Japan); Sugawara, Yuji [Department of Physical Sciences, College of Science and Engineering, Ritsumeikan University,Shiga 525-8577 (Japan)

2017-02-06

We study the world-sheet conformal field theories for T-folds systematically based on the Lie algebra lattices representing the momenta of strings. The fixed point condition required for the T-duality twist restricts the possible Lie algebras. When the T-duality acts as a simple chiral reflection, one is left with the four cases, A{sub 1},D{sub 2r},E{sub 7},E{sub 8}, among the simple simply-laced algebras. From the corresponding Englert-Neveu lattices, we construct the modular invariant partition functions for the T-fold CFTs in bosonic string theory. Similar construction is possible also by using Euclidean even self-dual lattices. We then apply our formulation to the T-folds in the E{sub 8}×E{sub 8} heterotic string theory. Incorporating non-trivial phases for the T-duality twist, we obtain, as simple examples, a class of modular invariant partition functions parametrized by three integers. Our construction includes the cases which are not reduced to the free fermion construction.

Multicore and GPU algorithms for Nussinov RNA folding

Science.gov (United States)

2014-01-01

Background One segment of a RNA sequence might be paired with another segment of the same RNA sequence due to the force of hydrogen bonds. This two-dimensional structure is called the RNA sequence's secondary structure. Several algorithms have been proposed to predict an RNA sequence's secondary structure. These algorithms are referred to as RNA folding algorithms. Results We develop cache efficient, multicore, and GPU algorithms for RNA folding using Nussinov's algorithm. Conclusions Our cache efficient algorithm provides a speedup between 1.6 and 3.0 relative to a naive straightforward single core code. The multicore version of the cache efficient single core algorithm provides a speedup, relative to the naive single core algorithm, between 7.5 and 14.0 on a 6 core hyperthreaded CPU. Our GPU algorithm for the NVIDIA C2050 is up to 1582 times as fast as the naive single core algorithm and between 5.1 and 11.2 times as fast as the fastest previously known GPU algorithm for Nussinov RNA folding. PMID:25082539

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.

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

Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells

Science.gov (United States)

Fukahori, Mioko; Chitose, Shun-ichi; Sato, Kiminori; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito; Monden, Yu; Yamakawa, Ryoji

2016-01-01

Objectives Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells. Study Design Animal experiment using eight beagles (including three controls). Methods A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed. Results A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site. Conclusion The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds. PMID:26730600

Evaluation of Vocal Fold Motion Abnormalities: Are We All Seeing the Same Thing?

Science.gov (United States)

Madden, Lyndsay L; Rosen, Clark A

2017-01-01

Flexible laryngoscopy is the principle tool for the evaluation of vocal fold motion. As of yet, no consistent, unified outcome metric has been developed for vocal fold paralysis/immobility research. The goal of this study was to evaluate vocal fold motion assessment (inter- and intra-rater reliability) among general otolaryngologists and fellowship-trained laryngologists. Prospective video perceptual analysis study. Flexible laryngoscopic examinations, with sound, of 15 unique patient cases (20 seconds each) were sent to 10 general otolaryngologists and 10 fellowship-trained laryngologists blinded to clinical history. Reviewers were given written definitions of vocal fold mobility and immobility and two video examples. The cases included bilateral vocal fold mobility (six), unilateral vocal fold immobility (five), and unilateral vocal fold hypomobility (four). Five examinations were repeated to determine intra-rater reliability. Participants were asked to judge if there was or there was no purposeful motion, as described by written definitions, for each vocal fold (800 tokens in total). Twenty reviewers (100%) replied. Both general otolaryngologists and fellowship-trained laryngologists had an overall inter-rater reliability of 95%. Difference in inter-rater reliability between the two groups of raters was negligible: 95% for general otolaryngologists and 97.5% for fellowship-trained laryngologists. There was no variability in intra-rater reliability within either rater group (99%). Intra- and inter-rater agreement in determining whether the patient had purposeful vocal fold motion on flexible laryngoscopic examination was excellent in both groups. This study demonstrates that otolaryngologists can consistently and accurately judge the presence and the absence of vocal fold motion. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. 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.

HEMATOMA OF THE PROXIMAL NAIL FOLD. REPORT OF 41 CASES

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Chang Patricia

2011-04-01

Full Text Available Background: The proximal fold is an important part of the nail apparatus it contributes to the formation of the nail plate and through the cuticle acts as an impermeable barrier protecting it from any cause.Objective: To know the proximal nail fold hematoma caused by the use of pulse oximeter.Material and Methods: A descriptive study was conducted in 41 patients with proximal nail hematoma secondary to the use of oximetry in patients hospitalized in the Intermediate and Intensive Care Unit at the Hospital General de Enfermedades from December 1, 2007 to December 31, 2010.Results: We studied 41 patients with proximal nail fold hematoma secondary to the use of oximeter, 30 (73.1% were males and 11 (26.8% females. The numbers of fingers affected by pulse oximeter were in one digit. 30 (73.1% cases, in two digits 6 (14.6%, in three digits 3 (7.3%, in 4 digits 1 (2.4% and in 5 digits 1 (2.4% case. The most affected proximal nail fold was right index: 24 (58.5%, right middle 11 (26.8%, right ring 6 (14.6%, left index 12 (29.2%, and left middle 6 (14.6% cases.Conclusions: Hematomas of the proximal nail fold may be caused by different traumatisms. The use of pulse oximeter is one of them.

Ca-Dependent Folding of Human Calumenin

Science.gov (United States)

Mazzorana, Marco; Hussain, Rohanah; Sorensen, Thomas

2016-01-01

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

Folding model analysis of alpha radioactivity

International Nuclear Information System (INIS)

Basu, D N

2003-01-01

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

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.

Containers, facilitators, innovators?

DEFF Research Database (Denmark)

Makkonen, Teemu; Merisalo, Maria; Inkinen, Tommi

2018-01-01

: are they containers, facilitators or innovators? This is investigated here through empirical material derived from 27 interviews with top departmental management in three Finnish cities (Helsinki, Espoo and Vantaa). The results show that local city governments (LCGs) consider cities as facilitators of innovation...

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)

Protein folding: Over half a century lasting quest. Comment on "There and back again: Two views on the protein folding puzzle" by Alexei V. Finkelstein et al.

Science.gov (United States)

Krokhotin, Andrey; Dokholyan, Nikolay V.

2017-07-01

Most proteins fold into unique three-dimensional (3D) structures that determine their biological functions, such as catalytic activity or macromolecular binding. Misfolded proteins can pose a threat through aberrant interactions with other proteins leading to a number of diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis [1,2]. What does determine 3D structure of proteins? The first clue to this question came more than fifty years ago when Anfinsen demonstrated that unfolded proteins can spontaneously fold to their native 3D structures [3,4]. Anfinsen's experiments lead to the conclusion that proteins fold to unique native structure corresponding to the stable and kinetically accessible free energy minimum, and protein native structure is solely determined by its amino acid sequence. The question of how exactly proteins find their free energy minimum proved to be a difficult problem. One of the puzzles, initially pointed out by Levinthal, was an inconsistency between observed protein folding times and theoretical estimates. A self-avoiding polymer model of a globular protein of 100-residues length on a cubic lattice can sample at least 1047 states. Based on the assumption that conformational sampling occurs at the highest vibrational mode of proteins (∼picoseconds), predicted folding time by searching among all the possible conformations leads to ∼1027 years (much larger than the age of the universe) [5]. In contrast, observed protein folding time range from microseconds to minutes. Due to tremendous theoretical progress in protein folding field that has been achieved in past decades, the source of this inconsistency is currently understood that is thoroughly described in the review by Finkelstein et al. [6].

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/.

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...

NR4A1 is an endogenous inhibitor of vocal fold fibrosis.

Science.gov (United States)

Hiwatashi, Nao; Bing, Renjie; Kraja, Iv; Branski, Ryan C

2017-09-01

NR4A1 was recently identified as an endogenous inhibitor of transforming growth factor (TGF)-β-induced fibrosis, and the role of this nuclear receptor has not been elucidated in tissue health or the response to injury in the vocal folds. Given the clinical implications of vocal fold fibrosis, we investigated NR4A1 expression during vocal fold wound healing in vivo and the regulatory roles of NR4A1 on vocal fold fibroblasts (VFFs) in vitro with the ultimate goal of developing targeted therapies for this challenging patient population. In vivo and in vitro. In vivo, the temporal pattern of NR4A1 mRNA expression was quantified following rat vocal fold injury. In vitro, the role of NR4A1 on TGF-β1-mediated transcription of genes underlying fibrosis as well as myofibroblast differentiation and collagen gel contraction was quantified in our human VFF line. Small interfering RNA was employed to alter NR4A1 expression to further elucidate this complex system. Nr4a1 mRNA increased 1 day after injury and peaked at 7 days. Knockdown of NR4A1 resulted in upregulation of COL1A1 and TGF-β1, with TGF-β1 stimulation (both P vocal fold health or disease. Upregulation of TGF-β following vocal fold injury was concurrent with increased NR4A1 expression. These data provide a foundation for the development of therapeutic strategies given persistent TGF-β signaling in vocal fold fibrosis. N/A Laryngoscope, 127:E317-E323, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

IMPAIRED MOBILITY OF VOCAL FOLDS – DIAGNOSTIC PROCEDURES AND TREATMENT, part 2

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Karlo Pintarić

2015-09-01

Full Text Available Paresis or paralysis of one or both vocal cords affects phonation, swallowing and breathing. The major cause for reduced mobility or even immobility is innervation damage, less often mechanical disorder.The main procedures in the diagnostics of disordered vocal fold mobility are indirect laryngoscopy and videoendostroboscopy. Different imaging techniques (especially computerized tomography are of great value in searching for a cause of the impaired mobility.In unilateral vocal fold immobility, the treatment is focused on the improvement of voice quality and the prevention of aspiration during swallowing. In bilateral paralysis, it is crucial to find a balance between effective breathing and sufficient voice quality. The treatment of unilateral paralysis is started with voice therapy and swallowing rehabilitation. If these procedures are not enough surgical treatment for the medialization of the paralyzed vocal fold is applied. In the case of breathing difficulties in bilateral vocal fold immobility there is a possibility of surgical lateralization of one or both folds or a surgical excision of a part or the entire vocal fold. Surgical reinnervation, functional electrostimulation of certain laryngeal muscles and gene therapy are developing treatment modalities.

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.

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.

Double-Eyelid Surgery Using Septoaponeurosis Junctional Thickening Results in Dynamic Fold in Asians

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Hong Seok Kim, MD, PhD

2013-05-01

Conclusions: The authors introduce a double-eyelid surgery technique using the SAJT. This SAJT fixation technique creates a dynamic double-eyelid fold. Our study showed a high patient satisfaction rate and that the resulting fold mimics the movement of the congenital supratarsal fold in Asians.

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

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David S. Kliger

2009-04-01

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

Functional assessment of the ex vivo vocal folds through biomechanical testing: A review

Science.gov (United States)

Dion, Gregory R.; Jeswani, Seema; Roof, Scott; Fritz, Mark; Coelho, Paulo; Sobieraj, Michael; Amin, Milan R.; Branski, Ryan C.

2016-01-01

The human vocal folds are complex structures made up of distinct layers that vary in cellular and extracellular composition. The mechanical properties of vocal fold tissue are fundamental to the study of both the acoustics and biomechanics of voice production. To date, quantitative methods have been applied to characterize the vocal fold tissue in both normal and pathologic conditions. This review describes, summarizes, and discusses the most commonly employed methods for vocal fold biomechanical testing. Force-elongation, torsional parallel plate rheometry, simple-shear parallel plate rheometry, linear skin rheometry, and indentation are the most frequently employed biomechanical tests for vocal fold tissues and each provide material properties data that can be used to compare native tissue verses diseased for treated tissue. Force-elongation testing is clinically useful, as it allows for functional unit testing, while rheometry provides physiologically relevant shear data, and nanoindentation permits micrometer scale testing across different areas of the vocal fold as well as whole organ testing. Thoughtful selection of the testing technique during experimental design to evaluate a hypothesis is important to optimizing biomechanical testing of vocal fold tissues. PMID:27127075

Reliable protein folding on non-funneled energy landscapes: the free energy reaction path

OpenAIRE

Lois, Gregg; Blawzdziewicz, Jerzy; O'Hern, Corey S.

2008-01-01

A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical denaturant or pH, are adjusted to induce folding. A theory based on this insight predicts that (1) proteins with non-funneled energy landscapes can fold reliably to their native state, (2) reliable folding can occur as an equilibrium or out-of-equilibrium pro...

Folded Sheet Versus Transparent Sheet Models for Human Symmetry Judgments

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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.

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

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.

Bilateral Vocal Fold Medialization: A Treatment for Abductor Spasmodic Dysphonia.

Science.gov (United States)

Dewan, Karuna; Berke, Gerald S

2017-11-10

Abductor spasmodic dysphonia, a difficult-to-treat laryngologic condition, is characterized by spasms causing the vocal folds to remain abducted despite efforts to adduct them during phonation. Traditional treatment for abductor spasmodic dysphonia-botulinum toxin injection into the posterior cricoarytenoid muscle-can be both technically challenging and uncomfortable. Due to the difficulty of needle placement, it is often unsuccessful. The purpose of this investigation is to present a previously undescribed treatment for abductor spasmodic dysphonia-bilateral vocal fold medialization. A retrospective case review of all cases of abductor spasmodic dysphonia treated in a tertiary care laryngology practice with bilateral vocal fold medialization over a 10-year period was performed. The Voice Handicap Index and the Voice-Related Quality of Life surveys were utilized to assess patient satisfaction with voice outcome. Six patients with abductor spasmodic dysphonia treated with bilateral vocal fold medialization were identified. Disease severity ranged from mild to severe. All six patients reported statistically significant improvement in nearly all Voice Handicap Index and Voice-Related Quality of Life parameters. They reported fewer voice breaks and greater ease of communication. Results were noted immediately and symptoms continue to be well controlled for many years following medialization. Bilateral vocal fold medialization is a safe and effective treatment for abductor spasmodic dysphonia. It is performed under local anesthesia and provides phonation improvement in the short and long term. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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.

An atlas of the thioredoxin fold class reveals the complexity of function-enabling adaptations.

Science.gov (United States)

Atkinson, Holly J; Babbitt, Patricia C

2009-10-01

The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features-including variations on a dithiol CxxC active site motif-that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif-only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins.

Folding of the natural hammerhead ribozyme is enhanced by interaction of auxiliary elements

Science.gov (United States)

PENEDO, J. CARLOS; WILSON, TIMOTHY J.; JAYASENA, SUMEDHA D.; KHVOROVA, ANASTASIA; LILLEY, DAVID M.J.

2004-01-01

It has been shown that the activity of the hammerhead ribozyme at μM magnesium ion concentrations is markedly increased by the inclusion of loops in helices I and II. We have studied the effect of such loops on the magnesium ion-induced folding of the ribozyme, using fluorescence resonance energy transfer. We find that with the loops in place, folding into the active conformation occurs in a single step, in the μM range of magnesium ion concentration. Disruption of the loop–loop interaction leads to a reversion to two-step folding, with the second stage requiring mM concentrations of magnesium ion. Sodium ions also promote the folding of the natural form of the ribozyme at high concentrations, but the folding occurs as a two-stage process. The loops clearly act as important auxiliary elements in the function of the ribozyme, permitting folding to occur efficiently under physiological conditions. PMID:15100442

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.

Improvement of high-fold gamma-ray data processing: the spherical gate method

CERN Document Server

Theisen, C; Stezowski, O; Vivien, J P

1999-01-01

A new method for optimizing the processing of events from a highly efficient large array gamma-ray detector is described in this article. The spherical gates technique, developed to project high-fold events, consists of optimizing n-dimensional gate shape as a function of peak width and shape of each detector. Formulas in closed form are proposed for determining the projected statistics from coincidence fold and peak shape and for estimating the increased quality of projected spectra. This procedure has been tested on high-fold, high statistics data sets including superdeformed cascades. Compared to the classical 'square-gate' technique, better peak-to-background ratios as well as a reduction in fluctuations are observed. A quality parameter is defined to characterize the optimal parameter set. This method leads roughly to a gain in spectral quality equivalent of one fold. It is also shown that the efficiency of the method increases with coincidence fold. This should be particularly suited for future higher-f...

Symptomatic unilateral vocal fold paralysis following cardiothoracic surgery.

Science.gov (United States)

Puccinelli, Cassandra; Modzeski, Mara C; Orbelo, Diana; Ekbom, Dale C

Unilateral vocal fold paralysis (UVFP) is a complication associated with cardiothoracic procedures that presents clinically as dysphonia and/or dysphagia with or without aspiration. The literature lacks both data on recovery of mobility and consensus on best management. Herein, our goals are to 1) Identify cardiothoracic procedures associated with symptomatic UVFP at our institution; 2) Review timing and nature of laryngology diagnosis and management; 3) Report spontaneous recovery rate of vocal fold mobility. Retrospective case series at single tertiary referral center between 2002 and 2015. 141 patients were included who underwent laryngology interventions (micronized acellular dermis injection laryngoplasty and/or type 1 thyroplasty) to treat symptomatic UVFP diagnosed subsequent to cardiothoracic surgery. Pulmonary procedures were most often associated with UVFP (n=50/141; 35.5%). 87.2% had left-sided paralysis (n=123/141). Median time to diagnosis was 42days (x¯=114±348). Over time, UVFP was diagnosed progressively earlier after cardiothoracic surgery. 63.4% of patients (n=95/141) underwent injection laryngoplasty as their initial intervention with median time from diagnosis to injection of 11days (x¯=29.6±54). 41.1% (n=58/141) ultimately underwent type 1 thyroplasty at a median of 232.5days (x¯=367±510.2) after cardiothoracic surgery. 10.2% (n=9/88) of those with adequate follow-up recovered full vocal fold mobility. Many cardiothoracic procedures are associated with symptomatic UVFP, predominantly left-sided. Our data showed poor recovery of vocal fold mobility relative to other studies. Early diagnosis and potential surgical medialization is important in the care of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Aggregation of natively folded proteins: a theoretical approach

International Nuclear Information System (INIS)

Trovato, Antonio; Maritan, Amos; Seno, Flavio

2007-01-01

The reliable identification of β-aggregating stretches in protein sequences is essential for the development of therapeutic agents for Alzheimer's and Parkinson's diseases, as well as other pathological conditions associated with protein deposition. While the list of aggregation related diseases is growing, it has also been shown that many proteins that are normally well behaved can be induced to aggregate in vitro. This fact suggests the existence of a unified framework that could explain both folding and aggregation. By assuming this universal behaviour, we have recently introduced an algorithm (PASTA: prediction of amyloid structure aggregation), which is based on a sequence-specific energy function derived from the propensity of two residue types to be found paired in neighbouring strands within β-sheets in globular proteins. The algorithm is able to predict the most aggregation-prone portions of several proteins initially unfolded, in excellent agreement with experimental results. Here, we apply the method to a set of proteins which are known to aggregate, but which are natively folded. The quality of the prediction is again very high, corroborating the hypothesis that the amyloid structure is stabilized by the same physico-chemical determinants as those operating in folded proteins

STRONG ORACLE OPTIMALITY OF FOLDED CONCAVE PENALIZED ESTIMATION.

Science.gov (United States)

Fan, Jianqing; Xue, Lingzhou; Zou, Hui

2014-06-01

Folded concave penalization methods have been shown to enjoy the strong oracle property for high-dimensional sparse estimation. However, a folded concave penalization problem usually has multiple local solutions and the oracle property is established only for one of the unknown local solutions. A challenging fundamental issue still remains that it is not clear whether the local optimum computed by a given optimization algorithm possesses those nice theoretical properties. To close this important theoretical gap in over a decade, we provide a unified theory to show explicitly how to obtain the oracle solution via the local linear approximation algorithm. For a folded concave penalized estimation problem, we show that as long as the problem is localizable and the oracle estimator is well behaved, we can obtain the oracle estimator by using the one-step local linear approximation. In addition, once the oracle estimator is obtained, the local linear approximation algorithm converges, namely it produces the same estimator in the next iteration. The general theory is demonstrated by using four classical sparse estimation problems, i.e., sparse linear regression, sparse logistic regression, sparse precision matrix estimation and sparse quantile regression.

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

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)

Multiple routes and milestones in the folding of HIV-1 protease monomer.

Directory of Open Access Journals (Sweden)

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.

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.

The Folding of de Novo Designed Protein DS119 via Molecular Dynamics Simulations

Directory of Open Access Journals (Sweden)

Moye Wang

2016-04-01

Full Text Available As they are not subjected to natural selection process, de novo designed proteins usually fold in a manner different from natural proteins. Recently, a de novo designed mini-protein DS119, with a βαβ motif and 36 amino acids, has folded unusually slowly in experiments, and transient dimers have been detected in the folding process. Here, by means of all-atom replica exchange molecular dynamics (REMD simulations, several comparably stable intermediate states were observed on the folding free-energy landscape of DS119. Conventional molecular dynamics (CMD simulations showed that when two unfolded DS119 proteins bound together, most binding sites of dimeric aggregates were located at the N-terminal segment, especially residues 5–10, which were supposed to form β-sheet with its own C-terminal segment. Furthermore, a large percentage of individual proteins in the dimeric aggregates adopted conformations similar to those in the intermediate states observed in REMD simulations. These results indicate that, during the folding process, DS119 can easily become trapped in intermediate states. Then, with diffusion, a transient dimer would be formed and stabilized with the binding interface located at N-terminals. This means that it could not quickly fold to the native structure. The complicated folding manner of DS119 implies the important influence of natural selection on protein-folding kinetics, and more improvement should be achieved in rational protein design.

Paleomagnetic and structural evidence for oblique slip in a fault-related fold, Grayback monocline, Colorado

Science.gov (United States)

Tetreault, J.; Jones, C.H.; Erslev, E.; Larson, S.; Hudson, M.; Holdaway, S.

2008-01-01

Significant fold-axis-parallel slip is accommodated in the folded strata of the Grayback monocline, northeastern Front Range, Colorado, without visible large strike-slip displacement on the fold surface. In many cases, oblique-slip deformation is partitioned; fold-axis-normal slip is accommodated within folds, and fold-axis-parallel slip is resolved onto adjacent strike-slip faults. Unlike partitioning strike-parallel slip onto adjacent strike-slip faults, fold-axis-parallel slip has deformed the forelimb of the Grayback monocline. Mean compressive paleostress orientations in the forelimb are deflected 15??-37?? clockwise from the regional paleostress orientation of the northeastern Front Range. Paleomagnetic directions from the Permian Ingleside Formation in the forelimb are rotated 16??-42?? clockwise about a bedding-normal axis relative to the North American Permian reference direction. The paleostress and paleomagnetic rotations increase with the bedding dip angle and decrease along strike toward the fold tip. These measurements allow for 50-120 m of fold-axis-parallel slip within the forelimb, depending on the kinematics of strike-slip shear. This resolved horizontal slip is nearly equal in magnitude to the ???180 m vertical throw across the fold. For 200 m of oblique-slip displacement (120 m of strike slip and 180 m of reverse slip), the true shortening direction across the fold is N90??E, indistinguishable from the regionally inferred direction of N90??E and quite different from the S53??E fold-normal direction. Recognition of this deformational style means that significant amounts of strike slip can be accommodated within folds without axis-parallel surficial faulting. ?? 2008 Geological Society of America.

Rigid Origami via Optical Programming and Deferred Self-Folding of a Two-Stage Photopolymer.

Science.gov (United States)

Glugla, David J; Alim, Marvin D; Byars, Keaton D; Nair, Devatha P; Bowman, Christopher N; Maute, Kurt K; McLeod, Robert R

2016-11-02

We demonstrate the formation of shape-programmed, glassy origami structures using a single-layer photopolymer with two mechanically distinct phases. The latent origami pattern consisting of rigid, high cross-link density panels and flexible, low cross-link density creases is fabricated using a series of photomask exposures. Strong optical absorption of the polymer formulation creates depth-wise gradients in the cross-link density of the creases, enforcing directed folding which enables programming of both mountain and valley folds within the same sheet. These multiple photomask patterns can be sequentially applied because the sheet remains flat until immersed into a photopolymerizable monomer solution that differentially swells the polymer to fold and form the origami structure. After folding, a uniform photoexposure polymerizes the absorbed solution, permanently fixing the shape of the folded structure while simultaneously increasing the modulus of the folds. This approach creates sharp folds by mimicking the stiff panels and flexible creases of paper origami while overcoming the traditional trade-off of self-actuated materials that require low modulus for folding and high modulus for mechanical robustness. Using this process, we demonstrate a waterbomb base capable of supporting 1500 times its own weight.

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.

Dermofat graft in deep nasolabial fold and facial rhytidectomy.

Science.gov (United States)

Hwang, Kun; Han, Jin Yi; Kim, Dae Joong

2003-01-01

Fat and dermis or the combined tissues are used commonly in augmentation of the nasolabial fold. Guyuron obtained the dermofat graft from either the suprapubic or the groin region. The thickness of the preauricular skin was measured in seven Korean cadavers, five male and two female. We used the dermofat graft out of the preauricular skin remnant after facial rhytidectomy to augment the deep nasolabial fold in a patient. The average thickness of the epidermis was 56 +/- 12 microm, the dermis was 1820 +/- 265 microm thick, and the subcutaneous tissue was 4783 +/- 137 microm. More dense connective tissues, such as SMAS, are seen in the preauricular skin. The dermofat graft was easily obtained and prepared from the leftover preauricular skin after dissection of the lax skin in face lifting. This technique could be employed effectively and successfully to alleviate a deep nasolabial fold and concomitant facial rhytidectomy in an Asian with a thick preauricular skin.

It is worth 10 million working hours a year to have your toilet paper folded?

Science.gov (United States)

Ljung, Rickard; Ljung, Hedvig; Ljung, Harald

2016-01-01

From our experience the toilet paper is folded in the bathrooms in rooms in branded hotels. We aimed to study the total time yearly spent in the world on folding hotel toilet paper. Three investigators clocked 60 folding toilet paper events and calculated the mean time. The mean folding time was 5.73 s (interquartile range 4.50-6.56). Using the calculated extra time it takes to fold the toilet paper and the number of hotel nights spent we estimated the total time spent in the world each year to fold the toilet paper. For sensitivity analyses we used different assumptions on number of hotel beds, occupancy rate and folding time. Assuming an extra 10 s spent on folding toilet paper, approximately 10 million hours are globally spent on folding toilet paper every year. This corresponds to more than 5000 man-years of work. In a hotel with yearly full coverage of 200 beds skipping folding the toilet paper corresponds to around 200 h of time that could be spent elsewhere. To take away unnecessary duties from hotel room cleaners would increase their health and well-being and save time that could be better spent. Is it really defendable and appropriate that someone else has spent time on folding the toilet paper you are just about to use?

Novice facilitators and the use of scripts for managing facilitated modelling workshops

DEFF Research Database (Denmark)

Tavella, Elena; Papadopoulos, Thanos

2015-01-01

There is limited research on the use of scripts by novice facilitators (novices) in Facilitated Modelling (FM) workshops. To address this gap, this paper illustrates how novices—supported by scripts—switch between and combine facilitation skills and competencies to successfully manage FM workshops...... and achieve outcomes. This illustration is based on a micro-level analysis of a transcript from a Viable System Model workshop held in a food cooperative in Copenhagen, Denmark. Through our findings we identify two distinct script-supported FM behaviours and related script-supported facilitation practices...... that enable novices to (a) acquire skills and competencies; and (b) switch between and combine skills and competencies to successfully manage workshops and achieve outcomes. Our study links micro-level considerations to a meta-level framework that relates the script-supported FM behaviours and practices...

Fold in Origami and Unfold Math

Science.gov (United States)

Georgeson, Joseph

2011-01-01

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

An atlas of the thioredoxin fold class reveals the complexity of function-enabling adaptations.

Directory of Open Access Journals (Sweden)

Holly J Atkinson

2009-10-01

Full Text Available The group of proteins that contain a thioredoxin (Trx fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features-including variations on a dithiol CxxC active site motif-that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif-only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins.

Circuit topology of self-interacting chains: implications for folding and unfolding dynamics.

Science.gov (United States)

Mugler, Andrew; Tans, Sander J; Mashaghi, Alireza

2014-11-07

Understanding the relationship between molecular structure and folding is a central problem in disciplines ranging from biology to polymer physics and DNA origami. Topology can be a powerful tool to address this question. For a folded linear chain, the arrangement of intra-chain contacts is a topological property because rearranging the contacts requires discontinuous deformations. Conversely, the topology is preserved when continuously stretching the chain while maintaining the contact arrangement. Here we investigate how the folding and unfolding of linear chains with binary contacts is guided by the topology of contact arrangements. We formalize the topology by describing the relations between any two contacts in the structure, which for a linear chain can either be in parallel, in series, or crossing each other. We show that even when other determinants of folding rate such as contact order and size are kept constant, this 'circuit' topology determines folding kinetics. In particular, we find that the folding rate increases with the fractions of parallel and crossed relations. Moreover, we show how circuit topology constrains the conformational phase space explored during folding and unfolding: the number of forbidden unfolding transitions is found to increase with the fraction of parallel relations and to decrease with the fraction of series relations. Finally, we find that circuit topology influences whether distinct intermediate states are present, with crossed contacts being the key factor. The approach presented here can be more generally applied to questions on molecular dynamics, evolutionary biology, molecular engineering, and single-molecule biophysics.

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.

ORIGAMI: DELINEATING HALOS USING PHASE-SPACE FOLDS

Energy Technology Data Exchange (ETDEWEB)

Falck, Bridget L.; Neyrinck, Mark C.; Szalay, Alexander S. [Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States)

2012-08-01

We present the ORIGAMI method of identifying structures, particularly halos, in cosmological N-body simulations. Structure formation can be thought of as the folding of an initially flat three-dimensional manifold in six-dimensional phase space. ORIGAMI finds the outer folds that delineate these structures. Halo particles are identified as those that have undergone shell-crossing along three orthogonal axes, providing a dynamical definition of halo regions that is independent of density. ORIGAMI also identifies other morphological structures: particles that have undergone shell-crossing along 2, 1, or 0 orthogonal axes correspond to filaments, walls, and voids, respectively. We compare this method to a standard friends-of-friends halo-finding algorithm and find that ORIGAMI halos are somewhat larger, more diffuse, and less spherical, though the global properties of ORIGAMI halos are in good agreement with other modern halo-finding algorithms.

ORIGAMI: DELINEATING HALOS USING PHASE-SPACE FOLDS

International Nuclear Information System (INIS)

Falck, Bridget L.; Neyrinck, Mark C.; Szalay, Alexander S.

2012-01-01

We present the ORIGAMI method of identifying structures, particularly halos, in cosmological N-body simulations. Structure formation can be thought of as the folding of an initially flat three-dimensional manifold in six-dimensional phase space. ORIGAMI finds the outer folds that delineate these structures. Halo particles are identified as those that have undergone shell-crossing along three orthogonal axes, providing a dynamical definition of halo regions that is independent of density. ORIGAMI also identifies other morphological structures: particles that have undergone shell-crossing along 2, 1, or 0 orthogonal axes correspond to filaments, walls, and voids, respectively. We compare this method to a standard friends-of-friends halo-finding algorithm and find that ORIGAMI halos are somewhat larger, more diffuse, and less spherical, though the global properties of ORIGAMI halos are in good agreement with other modern halo-finding algorithms.

Vocal Fold Epithelial Barrier in Health and Injury: A Research Review

Science.gov (United States)

Levendoski, Elizabeth Erickson; Leydon, Ciara; Thibeault, Susan L.

2014-01-01

Purpose: Vocal fold epithelium is composed of layers of individual epithelial cells joined by junctional complexes constituting a unique interface with the external environment. This barrier provides structural stability to the vocal folds and protects underlying connective tissue from injury while being nearly continuously exposed to potentially…

Temporalis Fascia Transplantation for Sulcus Vocalis and Vocal Fold Scar: Long-Term Outcomes.

Science.gov (United States)

Karle, William E; Helman, Samuel N; Cooper, Amy; Zhang, Yuan; Pitman, Michael J

2018-04-01

Sulcus vocalis and vocal fold scar involve derangement of the superficial lamina propria of the vocal fold, which results in significant dysphonia. Many options exist for treatment, most of which have unsatisfactory and unpredictable outcomes. Autologous transplantation of temporalis fascia into the vocal fold (ATFV) has the potential to be a better treatment option, but long-term outcomes have not been well studied. Retrospective chart review and patient survey. Twenty-one patients diagnosed with vocal fold scar or sulcus vocalis and treated with ATFV with at least 1-year follow-up were included. Voice Handicap Index 10 (VHI-10) questionnaires were collected preoperatively and 6 months postoperatively. Patients were reached at the time of the study to complete another VHI-10 and a Likert scale survey. The mean decrease in VHI-10 scores between preoperation and 6 months postoperation was 8.35 ( P vocal fold for the treatment of vocal fold scar and sulcus vocalis is a safe surgery with good long-term outcomes and high patient satisfaction.

Topology Explains Why Automobile Sunshades Fold Oddly

Science.gov (United States)

Feist, Curtis; Naimi, Ramin

2009-01-01

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

Visual explorer facilitator's guide

CERN Document Server

Palus, Charles J

2010-01-01

Grounded in research and practice, the Visual Explorer™ Facilitator's Guide provides a method for supporting collaborative, creative conversations about complex issues through the power of images. The guide is available as a component in the Visual Explorer Facilitator's Letter-sized Set, Visual Explorer Facilitator's Post card-sized Set, Visual Explorer Playing Card-sized Set, and is also available as a stand-alone title for purchase to assist multiple tool users in an organization.

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

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.

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.

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.

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.

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.

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.

Anatomical study of minor alterations in neonate vocal folds.

Science.gov (United States)

Silva, Adriano Rezende; Machado, Almiro José; Crespo, Agrício Nubiato

2014-01-01

Minor structural alterations of the vocal fold cover are frequent causes of voice abnormalities. They may be difficult to diagnose, and are expressed in different manners. Cases of intracordal cysts, sulcus vocalis, mucosal bridge, and laryngeal micro-diaphragm form the group of minor structural alterations of the vocal fold cover investigated in the present study. The etiopathogenesis and epidemiology of these alterations are poorly known. To evaluate the existence and anatomical characterization of minor structural alterations in the vocal folds of newborns. 56 larynxes excised from neonates of both genders were studied. They were examined fresh, or defrosted after conservation via freezing, under a microscope at magnifications of 25× and 40×. The vocal folds were inspected and palpated by two examiners, with the aim of finding minor structural alterations similar to those described classically, and other undetermined minor structural alterations. Larynges presenting abnormalities were submitted to histological examination. Six cases of abnormalities were found in different larynges: one (1.79%) compatible with a sulcus vocalis and five (8.93%) compatible with a laryngeal micro-diaphragm. No cases of cysts or mucosal bridges were found. The observed abnormalities had characteristics similar to those described in other age groups. Abnormalities similar to sulcus vocalis or micro-diaphragm may be present at birth. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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...

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

Science.gov (United States)

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

2017-02-01

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

Equilibrium amide hydrogen exchange and protein folding kinetics

International Nuclear Information System (INIS)

Bai Yawen

1999-01-01

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

Incremental fold tests of remagnetized carbonate rocks

Science.gov (United States)

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

2017-12-01

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

Single-molecule studies of the Im7 folding landscape.

Science.gov (United States)

Pugh, Sara D; Gell, Christopher; Smith, D Alastair; Radford, Sheena E; Brockwell, David J

2010-04-23

Under appropriate conditions, the four-helical Im7 (immunity protein 7) folds from an ensemble of unfolded conformers to a highly compact native state via an on-pathway intermediate. Here, we investigate the unfolded, intermediate, and native states populated during folding using diffusion single-pair fluorescence resonance energy transfer by measuring the efficiency of energy transfer (or proximity or P ratio) between pairs of fluorophores introduced into the side chains of cysteine residues placed in the center of helices 1 and 4, 1 and 3, or 2 and 4. We show that while the native states of each variant give rise to a single narrow distribution with high P values, the distributions of the intermediates trapped at equilibrium (denoted I(eqm)) are fitted by two Gaussian distributions. Modulation of the folding conditions from those that stabilize the intermediate to those that destabilize the intermediate enabled the distribution of lower P value to be assigned to the population of the unfolded ensemble in equilibrium with the intermediate state. The reduced stability of the I(eqm) variants allowed analysis of the effect of denaturant concentration on the compaction and breadth of the unfolded state ensemble to be quantified from 0 to 6 M urea. Significant compaction is observed as the concentration of urea is decreased in both the presence and absence of sodium sulfate, as previously reported for a variety of proteins. In the presence of Na(2)SO(4) in 0 M urea, the P value of the unfolded state ensemble approaches that of the native state. Concurrent with compaction, the ensemble displays increased peak width of P values, possibly reflecting a reduction in the rate of conformational exchange among iso-energetic unfolded, but compact conformations. The results provide new insights into the initial stages of folding of Im7 and suggest that the unfolded state is highly conformationally constrained at the outset of folding. (c) 2010 Elsevier Ltd. All rights reserved.

Mapping the universe of RNA tetraloop folds

DEFF Research Database (Denmark)

Bottaro, Sandro; Lindorff-Larsen, Kresten

2017-01-01

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

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

Science.gov (United States)

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

2012-11-01

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

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.

Folded membrane dialyzer with mechanically sealed edges

Energy Technology Data Exchange (ETDEWEB)

Markley, F.W.

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

Vocal-fold vibration of patients with Reinke's edema observed using high-speed digital imaging.

Science.gov (United States)

Watanabe, Takeshi; Kaneko, Kenichi; Sakaguchi, Koichi; Takahashi, Haruo

2016-12-01

We aimed to assess the vocal-fold vibration of patients with moderate-to-severe Reinke's edema using high-speed digital imaging (HSDI) and videostroboscopy and to confirm HSDI usefulness in examining the vocal folds with Reinke's edema. We examined the vocal folds of seven patients (six severe and one moderate; six females and one male; aged 55-74 years; mean 64.7 years) with Reinke's edema using HSDI and videostroboscopy. The following characteristics were analyzed: glottic closure, mucosal-wave propagation, left-right asymmetry, phase shift, frequency difference, periodicity, and contact of the true vocal fold with the false vocal fold. HSDI revealed complete glottic closure, anterior-posterior phase shift, and obvious contact of at least one side of the edematous true vocal fold with the ipsilateral false vocal fold in all patients. Mucosal-wave propagation increased in six patients and decreased in one. Left-right asymmetry was observed in six patients. Left-right phase shifts and left-right frequency differences were observed in four and two patients, respectively. The vibration was periodic in four patients, quasi-periodic in three, and aperiodic in none. Anterior-posterior frequency differences were not observed for any patient. The vocal-fold vibration always synchronized with strobolights in two patients, while the vibration occasionally and never synchronized in two and three patients, respectively. In one patient whose vibration occasionally synchronized, videostroboscopy could not reveal the slight left-right frequency difference of the vibration. It was often difficult to observe vocal-fold vibration correctly in patients with severe Reinke's edema using videostroboscopy. However, HSDI was useful for examining these patients. Our results suggest that HSDI can be very useful for examining the vocal folds of patients with severe Reinke's edema. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Adipose-derived mesenchymal stromal cells prevented rat vocal fold scarring.

Science.gov (United States)

Morisaki, Tsuyoshi; Kishimoto, Yo; Tateya, Ichiro; Kawai, Yoshitaka; Suzuki, Ryo; Tsuji, Takuya; Hiwatashi, Nao; Nakamura, Tatsuo; Omori, Koichi; Kitano, Hiroya; Takeuchi, Hiromi; Hirano, Shigeru

2018-01-01

This study aimed to reveal the effects of adipose-derived mesenchymal stromal cells (ASCs) on prevention of vocal fold scarring by investigating how the immediate ASCs transplantation into the injured rat vocal fold affect the levels of gene transcription and translation. Prospective animal experiments with controls. ASCs harvested from green fluorescent protein transgenic rat (ASCs group) or saline (sham group) were injected into the thyroarytenoid muscle of Sprague-Dawley rats immediately after stripping the vocal fold. For histological examinations, larynges were extirpated at 3, 14, and 56 days after the injection. Quantitative real-time polymerase chain reaction (PCR) analyses were performed at 3 and 14 days after the injection. Transplanted ASCs were detected only in larynges at day 3. At days 14 and 56, histological examination showed significantly higher amounts of hyaluronic acid and lower deposition of collagen in the ASCs group compared to the sham group. Real-time PCR revealed that the ASCs group showed low expression of procollagen (Col)1a1, Col1a3, matrix metalloproteinase (Mmp)1 and Mmp8 in each time points. The ASCs group showed high expression of fibroblast growth factor (Fgf)2 and Hepatocyte growth factor (Hgf) compared to the sham group at day 14. ASCs increased expressions of Fgf2 and Hgf, and suppressed excessive collagen deposition during vocal fold wound healing. Given the fact that ASCs survived no more than 14 days, ASCs were thought to induce upregulations of growth factors' genes in surrounding cells. These results suggested that ASCs have potential to prevent vocal fold scarring. NA. Laryngoscope, 128:E33-E40, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

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

Science.gov (United States)

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

2017-09-01

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

Strange temperature dependence of the folding rate of a 16-residue β-hairpin

International Nuclear Information System (INIS)

Xu Yao; Wang Ting; Gai Feng

2006-01-01

The folding/unfolding kinetics of a 16-residue β-hairpin that undergoes cold denaturation at ambient temperatures were investigated by time-resolved infrared spectroscopy coupled with the laser-induced temperature jump (T-jump) initiation method. We found that the relaxation kinetics of this β-hairpin following a T-jump, obtained by probing the amide I' band of the peptide backbone, show strange temperature dependence. At temperatures below approximately 35 deg. C where this β-hairpin mainly exhibits cold denaturation, the T-jump induced relaxation rate is ∼5 μs -1 , whereas at temperatures where heat denaturation takes place, the relaxation rate increases to ∼1 μs -1 . These results cannot be readily explained by a two-state folding model that has been used to describe the folding thermodynamics of this β-hairpin. In addition, these results suggest that the folding free energy barrier separating the cold-denatured state from the folded state is different from that separating the heat-denatured state from the folded state, coinciding with the idea that the mechanism leading to cold denaturation is different from that leading to heat denaturation

A Review of Hyaluronic Acid and Hyaluronic Acid-based Hydrogels for Vocal Fold Tissue Engineering.

Science.gov (United States)

Walimbe, Tanaya; Panitch, Alyssa; Sivasankar, Preeti M

2017-07-01

Vocal fold scarring is a common cause of dysphonia. Current treatments involving vocal fold augmentation do not yield satisfactory outcomes in the long term. Tissue engineering and regenerative medicine offer an attractive treatment option for vocal fold scarring, with the aim to restore the native extracellular matrix microenvironment and biomechanical properties of the vocal folds by inhibiting progression of scarring and thus leading to restoration of normal vocal function. Hyaluronic acid is a bioactive glycosaminoglycan responsible for maintaining optimum viscoelastic properties of the vocal folds and hence is widely targeted in tissue engineering applications. This review covers advances in hyaluronic acid-based vocal fold tissue engineering and regeneration strategies. Copyright © 2017. Published by Elsevier Inc.