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

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Yongping Yue

2016-01-01

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

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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.
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...
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 ...
WW domain folding complexity revealed by infrared spectroscopy.

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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.
BiP clustering facilitates protein folding in the endoplasmic reticulum.

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Marc Griesemer

2014-07-01

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

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Jesus, Catarina S H; Cruz, Pedro F; Arnaut, Luis G; Brito, Rui M M; Serpa, Carlos

2018-04-12

discrete side chain interactions, a salt bridge, and in particular a single cation-π interaction in the folding dynamics of a naturally occurring α-helix peptide is uniquely revealed by these data.
The structure of KPN03535 (gi|152972051), a novel putative lipoprotein from Klebsiella pneumoniae, reveals an OB-fold

International Nuclear Information System (INIS)

Das, Debanu; Kozbial, Piotr; Han, Gye Won; Carlton, Dennis; Jaroszewski, Lukasz; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Bakolitsa, Constantina; Chen, Connie; Chiu, Hsiu-Ju; Chiu, Michelle; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Elsliger, Marc-André; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grzechnik, Anna; Grant, Joanna C.; Jin, Kevin K.; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Krishna, S. Sri; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Miller, Mitchell D.; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2009-01-01

KPN03535 is a protein unique to K. pneumoniae. The crystal structure reveals that KPN03535 represents a novel variant of the OB-fold and is likely to be a DNA-binding lipoprotein. KPN03535 (gi|152972051) is a putative lipoprotein of unknown function that is secreted by Klebsiella pneumoniae MGH 78578. The crystal structure reveals that despite a lack of any detectable sequence similarity to known structures, it is a novel variant of the OB-fold and structurally similar to the bacterial Cpx-pathway protein NlpE, single-stranded DNA-binding (SSB) proteins and toxins. K. pneumoniae MGH 78578 forms part of the normal human skin, mouth and gut flora and is an opportunistic pathogen that is linked to about 8% of all hospital-acquired infections in the USA. This structure provides the foundation for further investigations into this divergent member of the OB-fold family
The Complexity of Folding Self-Folding Origami

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

2017-10-01

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

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

2015-01-01

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

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Menachem Stern

2017-12-01

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

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Fazelinia, Hossein; Xu, Ming; Cheng, Hong; Roder, Heinrich

2014-01-15

Many proteins undergo a sharp decrease in chain dimensions during early stages of folding, prior to the rate-limiting step in folding. However, it remains unclear whether compact states are the result of specific folding events or a general hydrophobic collapse of the poly peptide chain driven by the change in solvent conditions. To address this fundamental question, we extended the temporal resolution of NMR-detected H/D exchange labeling experiments into the microsecond regime by adopting a microfluidics approach. By observing the competition between H/D exchange and folding as a function of labeling pH, coupled with direct measurement of exchange rates in the unfolded state, we were able to monitor hydrogen-bond formation for over 50 individual backbone NH groups within the initial 140 microseconds of folding of horse cytochrome c. Clusters of solvent-shielded amide protons were observed in two α-helical segments in the C-terminal half of the protein, while the N-terminal helix remained largely unstructured, suggesting that proximity in the primary structure is a major factor in promoting helix formation and association at early stages of folding, while the entropically more costly long-range contacts between the N- and C-terminal helices are established only during later stages. Our findings clearly indicate that the initial chain condensation in cytochrome c is driven by specific interactions among a subset of α-helical segments rather than a general hydrophobic collapse.
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.
Improving protein fold recognition by extracting fold-specific features from predicted residue-residue contacts.

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

2017-12-01

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

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

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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.
Crystal structure of CobK reveals strand-swapping between Rossmann-fold domains and molecular basis of the reduced precorrin product trap.

Science.gov (United States)

Gu, Shuang; Sushko, Oleksandr; Deery, Evelyne; Warren, Martin J; Pickersgill, Richard W

2015-11-30

CobK catalyzes the essential reduction of the precorrin ring in the cobalamin biosynthetic pathway. The crystal structure of CobK reveals that the enzyme, despite not having the signature sequence, comprises two Rossmann fold domains which bind coenzyme and substrate respectively. The two parallel β-sheets have swapped their last β-strands giving a novel sheet topology which is an interesting variation on the Rossmann-fold. The trapped ternary complex with coenzyme and product reveals five conserved basic residues that bind the carboxylates of the tetrapyrrole tightly anchoring the product. A loop, disordered in both the apoenzyme and holoenzyme structures, closes around the product further tightening binding. The structure is consistent with a mechanism involving protonation of C18 and pro-R hydride transfer from NADPH to C19 of precorrin-6A and reveals the interactions responsible for the specificity of CobK. The almost complete burial of the reduced precorrin product suggests a remarkable form of metabolite channeling where the next enzyme in the biosynthetic pathway triggers product release.

Synthetic oligorotaxanes exert high forces when folding under mechanical load

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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.
Vocal fold paralysis secondary to phonotrauma.

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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.
Autonomously folding protein fragments reveal differences in the energy landscapes of homologous RNases H.

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Laura E Rosen

Full Text Available An important approach to understanding how a protein sequence encodes its energy landscape is to compare proteins with different sequences that fold to the same general native structure. In this work, we compare E. coli and T. thermophilus homologs of the protein RNase H. Using protein fragments, we create equilibrium mimics of two different potential partially-folded intermediates (I(core and I(core+1 hypothesized to be present on the energy landscapes of these two proteins. We observe that both T. thermophilus RNase H (ttRNH fragments are folded and have distinct stabilities, indicating that both regions are capable of autonomous folding and that both intermediates are present as local minima on the ttRNH energy landscape. In contrast, the two E. coli RNase H (ecRNH fragments have very similar stabilities, suggesting that the presence of additional residues in the I(core+1 fragment does not affect the folding or structure as compared to I(core. NMR experiments provide additional evidence that only the I(core intermediate is populated by ecRNH. This is one of the biggest differences that has been observed between the energy landscapes of these two proteins. Additionally, we used a FRET experiment in the background of full-length ttRNH to specifically monitor the formation of the I(core+1 intermediate. We determine that the ttRNH I(core+1 intermediate is likely the intermediate populated prior to the rate-limiting barrier to global folding, in contrast to E. coli RNase H for which I(core is the folding intermediate. This result provides new insight into the nature of the rate-limiting barrier for the folding of RNase H.
Structured pathway across the transition state for peptide folding revealed by molecular dynamics simulations.

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Lipi Thukral

2011-09-01

Full Text Available Small globular proteins and peptides commonly exhibit two-state folding kinetics in which the rate limiting step of folding is the surmounting of a single free energy barrier at the transition state (TS separating the folded and the unfolded states. An intriguing question is whether the polypeptide chain reaches, and leaves, the TS by completely random fluctuations, or whether there is a directed, stepwise process. Here, the folding TS of a 15-residue β-hairpin peptide, Peptide 1, is characterized using independent 2.5 μs-long unbiased atomistic molecular dynamics (MD simulations (a total of 15 μs. The trajectories were started from fully unfolded structures. Multiple (spontaneous folding events to the NMR-derived conformation are observed, allowing both structural and dynamical characterization of the folding TS. A common loop-like topology is observed in all the TS structures with native end-to-end and turn contacts, while the central segments of the strands are not in contact. Non-native sidechain contacts are present in the TS between the only tryptophan (W11 and the turn region (P7-G9. Prior to the TS the turn is found to be already locked by the W11 sidechain, while the ends are apart. Once the ends have also come into contact, the TS is reached. Finally, along the reactive folding paths the cooperative loss of the W11 non-native contacts and the formation of the central inter-strand native contacts lead to the peptide rapidly proceeding from the TS to the native state. The present results indicate a directed stepwise process to folding the peptide.
Adipose-derived mesenchymal stromal cells prevented rat vocal fold scarring.

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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.
Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.

Science.gov (United States)

Sun, Jian; Zhang, Qing; Schlick, Tamar

2005-06-07

Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.
Spherical images and inextensible curved folding

Science.gov (United States)

Seffen, Keith A.

2018-02-01

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

Science.gov (United States)

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

2017-06-01

In this paper, we describe a method for primary culture of a well differentiated electrically tight rabbit vocal fold epithelial cell multilayer and the measurement of transepithelial electrical resistance (TEER) for the evaluation of epithelial barrier function in vitro. Rabbit larynges were harvested and enzymatically treated to isolate vocal fold epithelial cells and to establish primary culture. Vocal fold epithelial cells were co-cultured with mitomycin C-treated feeder cells on collagen-coated plates. After 10-14 days in primary culture, cells were passaged and cultured until they achieved 70-90% confluence on collagen-coated plates. Epithelial cells were then passaged onto collagen-coated cell culture inserts using 4.5cm 2 membrane filters (1.0μm pore size) with 10% fetal bovine serum or 30μg/mL bovine pituitary extract to investigate the effects of growth-promoting additives on TEER. Additional experiments were performed to investigate optimal seeding density (1.1, 2.2, 4.4, or 8.9×10 5 cells/cm 2 ), the effect of co-culture with feeder cells, and the effect of passage number on epithelial barrier function. Characterization of in vitro cultures was performed using hematoxylin and eosin staining and immunostaining for vocal fold epithelial cell markers and tight junctions. Results revealed higher TEER in cells supplemented with fetal bovine serum compared to bovine pituitary extract. TEER was highest in cells passaged at a seeding density of 2.2×10 4 cells/cm 2 , and TEER was higher in cells at passage two than passage three. Ultrastructural experiments revealed a well-differentiated epithelial cell multilayer, expressing the epithelial cell markers CK13, CK14 and the tight junction proteins occludin and ZO-1. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Crystal Structure of Homo Sapiens PTD012 Reveals a Zinc-Containing Hydrolase Fold

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Manjasetty,B.; Bussow, K.; Fieber-ErdMan, M.; Roske, Y.; Gobam, J.; Scheich, C.; Gotz, F.; Niesen, F.; Heinemann, U.

2006-01-01

The human protein PTD012 is the longer product of an alternatively spliced gene and was described to be localized in the nucleus. The X-ray structure analysis at 1.7 Angstroms resolution of PTD012 through SAD phasing reveals a monomeric protein and a novel fold. The shorter splice form was also studied and appears to be unfolded and non-functional. The structure of PTD012 displays an {alpha}{beta}{beta}{alpha} four-layer topology. A metal ion residing between the central {beta}-sheets is partially coordinated by three histidine residues. X-ray absorption near-edge structure (XANES) analysis identifies the PTD012-bound ion as Zn{sup 2+}. Tetrahedral coordination of the ion is completed by the carboxylate oxygen atom of an acetate molecule taken up from the crystallization buffer. The binding of Zn{sup 2+} to PTD012 is reminiscent of zinc-containing enzymes such as carboxypeptidase, carbonic anhydrase, and {beta}-lactamase. Biochemical assays failed to demonstrate any of these enzyme activities in PTD012. However, PTD012 exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.
[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.
Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

Science.gov (United States)

Chang, Joseph; Yung, Katherine C

2014-11-01

This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.
Nonsurgical Treatment for Vocal Fold Leukoplakia: An Analysis of 178 Cases

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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.
Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury.

Science.gov (United States)

Li, Kang; Gesang, Luobu; Dan, Zeng; Gusang, Lamu; Dawa, Ciren; Nie, Yuqiang

2015-01-01

High-altitude polycythemia (HAPC) inducing gastric mucosal lesion (GML) is still out of control and molecular mechanisms remain widely unknown. To address the issues, endoscopy and histopathological analyses were performed. Meanwhile, microarray-based transcriptome profiling was conducted in the gastric mucosa from 3 pairs of healthy subjects and HAPC-induced GML patients. HAPC caused morphological changes and pathological damages of the gastric mucosa of GML patients. A total of 10304 differentially expressed genes (DEGs) were identified, including 4941 up-regulated and 5363 down-regulated DEGs in gastric mucosa of GML patients compared with healthy controls (fold change ≥2, Ppolycythemia while polycythemia raises the risk of GML. Therefore, the present findings reveal that HAPC-induced GML inspires the protection responses by up-regulating APOA4 and APOC3, and down-regulating GIF. These results may offer the basic information for the treatment of HAPC-induced gastric lesion in the future.
Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue.

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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.
Preparation and Characterisation of Crosslinked Natural Rubber (SMR CV 60 and Epoxidised Natural Rubber (ENR-50 Blends

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M. SASITARAN

2018-04-01

Full Text Available In this sudy, the influenceof di(tert-butylperoxyisopropylbenzene (DTBPIB on the properties of natural rubber (NR blend with epoxidized natural rubber (ENR was determined. Fourier transform infrared spectroscopy with attenuated total refletance analysis and gel content confired crosslinking occurred in the rubber blends in the presence of peroxide DTBPIB percentage. Studies including tensile properties, dynamic mechanical properties, thermogravimetric analysis (TGA and water absorptivity showed the changes in properties of the crosslinked NR/ENR blends. Tensile properties analysis disclosed the improvements in the modulus at 300% elongation and tensile stength with increasing NR ratios. Dynamic mechanical analysis revealed the blends to be incompatible and immiscible, with ENR showing a more viscous behaviour compared to the polymer blends. Thermal properties improved by blending NR with ENR as the onset temperature of NR/ENR: 50/50 was higher than pure NR by approximately 10oC and ENR by approximately 2oC. Water absorptivity experiment revealed a two-fold reduction in the presence of crosslinking for all blend ratios.
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....
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
Acute exposure to vibration is an apoptosis-inducing stimulus in the vocal fold epithelium.

Science.gov (United States)

Novaleski, Carolyn K; Kimball, Emily E; Mizuta, Masanobu; Rousseau, Bernard

2016-10-01

Clinical voice disorders pose significant communication-related challenges to patients. The purpose of this study was to quantify the rate of apoptosis and tumor necrosis factor-alpha (TNF-α) signaling in vocal fold epithelial cells in response to increasing time-doses and cycle-doses of vibration. 20 New Zealand white breeder rabbits were randomized to three groups of time-doses of vibration exposure (30, 60, 120min) or a control group (120min of vocal fold adduction and abduction). Estimated cycle-doses of vocal fold vibration were extrapolated based on mean fundamental frequency. Laryngeal tissue specimens were evaluated for apoptosis and gene transcript and protein levels of TNF-α. Results revealed that terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was significantly higher after 120min of vibration compared to the control. Transmission electron microscopy (TEM) revealed no significant effect of time-dose on the mean area of epithelial cell nuclei. Extrapolated cycle-doses of vibration exposure were closely related to experimental time-dose conditions, although no significant correlations were observed with TUNEL staining or mean area of epithelial cell nuclei. TUNEL staining was positively correlated with TNF-α protein expression. Our findings suggest that apoptosis can be induced in the vocal fold epithelium after 120min of modal intensity phonation. In contrast, shorter durations of vibration exposure do not result in apoptosis signaling. However, morphological features of apoptosis are not observed using TEM. Future studies are necessary to examine the contribution of abnormal apoptosis to vocal fold diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.
"Times Higher Education" 100 under 50 Ranking: Old Wine in a New Bottle?

Science.gov (United States)

Soh, Kaycheng

2013-01-01

"Times Higher Education" 100 under 50 ranking is a new twist to the university ranking. It focuses on universities that have a history of 50 years or less with the purpose of offsetting the advantage of prestige of the older ones. This article re-analysed the data publicly available and looked into relevant conceptual and statistical issues. The…
Functional results after external vocal fold medialization thyroplasty with the titanium vocal fold medialization implant.

Science.gov (United States)

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

2003-04-01

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

Structures of the first representatives of Pfam family PF06938 (DUF1285) reveal a new fold with repeated structural motifs and possible involvement in signal transduction

International Nuclear Information System (INIS)

Han, Gye Won; Bakolitsa, Constantina; Miller, Mitchell D.; Kumar, Abhinav; Carlton, Dennis; Najmanovich, Rafael J.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Ernst, Dustin; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Jaroszewski, Lukasz; Jin, Kevin K.; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The crystal structures of SPO0140 and Sbal-2486 revealed a two-domain structure that adopts a novel fold. Analysis of the interdomain cleft suggests a nucleotide-based ligand with a genome context indicating signaling as a possible role for this family. The crystal structures of SPO0140 and Sbal-2486 were determined using the semiautomated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). The structures revealed a conserved core with domain duplication and a superficial similarity of the C-terminal domain to pleckstrin homology-like folds. The conservation of the domain interface indicates a potential binding site that is likely to involve a nucleotide-based ligand, with genome-context and gene-fusion analyses additionally supporting a role for this family in signal transduction, possibly during oxidative stress
Ultra-high-resolution C-arm flat-detector CT angiography evaluation reveals 3-fold higher association rate for sporadic intracranial cavernous malformations and developmental venous anomalies: a retrospective study in consecutive 58 patients with 60 cavernous malformations

Energy Technology Data Exchange (ETDEWEB)

Kocak, Burak [Aksaray State Hospital, Department of Radiology, Aksaray (Turkey); Kizilkilic, Osman; Kocer, Naci; Islak, Civan [Istanbul University, Department of Radiology, Cerrahpasa Medical Faculty, Istanbul (Turkey); Oz, Buge; Bakkaloglu, Dogu Vuralli [Istanbul University, Department of Pathology, Cerrahpasa Medical Faculty, Istanbul (Turkey); Isler, Cihan [Istanbul University, Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul (Turkey)

2017-06-15

The imaging and surgical literature has confusing association rates for the association between sporadic intracranial cavernous malformations (CMs) and developmental venous anomalies (DVAs). In this study, our purpose was to determine the association rate using ultra-high-resolution C-arm flat-detector CT angiography (FDCTA) and compare it with literature. Fifty-eight patients with 60 sporadic intracranial CMs that underwent an FDCTA study were included in our retrospective study. Re-evaluation of radiological data was performed based on the criteria defined by authors. Isotropic volumetric reconstructions with ultra-high resolution (voxel size of 102 μm{sup 3} for initial; 67 μm{sup 3} and 32 μm{sup 3} for further evaluation) were used for assessment. Sixteen patients underwent surgery for excision of their CMs. Fifty-one of all patients (87.9 %) were associated with a DVA. Undefined local venous structures (UD-LVSs) were observed in the remaining 7 patients (12.1 %). The strength of interobserver agreement was excellent [kappa(k) coefficient = 0.923]. Ultra-high-resolution FDCTA evaluation of CMs and DVAs reveals 3-fold higher association rate compared to the literature. FDCTA for patients with sporadic CMs could help identify the associated DVAs that remained undetected or unclear with other imaging modalities, which can be useful in decision-making processes, planning surgery, and during operation. (orig.)
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)
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.
50-Fold EQE Improvement up to 6.27% of Solution-Processed All-Inorganic Perovskite CsPbBr3 QLEDs via Surface Ligand Density Control.

Science.gov (United States)

Li, Jianhai; Xu, Leimeng; Wang, Tao; Song, Jizhong; Chen, Jiawei; Xue, Jie; Dong, Yuhui; Cai, Bo; Shan, Qingsong; Han, Boning; Zeng, Haibo

2017-02-01

Solution-processed CsPbBr 3 quantum-dot light-emitting diodes with a 50-fold external quantum efficiency improvement (up to 6.27%) are achieved through balancing surface passivation and carrier injection via ligand density control (treating with hexane/ethyl acetate mixed solvent), which induces the coexistence of high levels of ink stability, photoluminescence quantum yields, thin-film uniformity, and carrier-injection efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Kinetics and Thermodynamics of Membrane Protein Folding

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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.
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.
Trp-cage: Folding free energy landscape in explicit water

Science.gov (United States)

Zhou, Ruhong

2003-11-01

Trp-cage is a 20-residue miniprotein, which is believed to be the fastest folder known so far. In this study, the folding free energy landscape of Trp-cage has been explored in explicit solvent by using an OPLSAA force field with periodic boundary condition. A highly parallel replica exchange molecular dynamics method is used for the conformation space sampling, with the help of a recently developed efficient molecular dynamics algorithm P3ME/RESPA (particle-particle particle-mesh Ewald/reference system propagator algorithm). A two-step folding mechanism is proposed that involves an intermediate state where two correctly formed partial hydrophobic cores are separated by an essential salt-bridge between residues Asp-9 and Arg-16 near the center of the peptide. This metastable intermediate state provides an explanation for the superfast folding process. The free energy landscape is found to be rugged at low temperatures, and then becomes smooth and funnel-like above 340 K. The lowest free energy structure at 300 K is only 1.50 Å C-RMSD (C-rms deviation) from the NMR structures. The simulated nuclear Overhauser effect pair distances are in excellent agreement with the raw NMR data. The temperature dependence of the Trp-cage population, however, is found to be significantly different from experiment, with a much higher melting transition temperature above 400 K (experimental 315 K), indicating that the current force fields, parameterized at room temperature, need to be improved to correctly predict the temperature dependence.
Cation-induced folding of alginate-bearing bilayer gels: an unusual example of spontaneous folding along the long axis.

Science.gov (United States)

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

2018-04-04

The spontaneous folding of flat gel films into tubes is an interesting example of self-assembly. Typically, a rectangular film folds along its short axis when forming a tube; folding along the long axis has been seen only in rare instances when the film is constrained. Here, we report a case where the same free-swelling gel film folds along either its long or short axis depending on the concentration of a solute. Our gels are sandwiches (bilayers) of two layers: a passive layer of cross-linked N,N'-dimethylyacrylamide (DMAA) and an active layer of cross-linked DMAA that also contains chains of the biopolymer alginate. Multivalent cations like Ca2+ and Cu2+ induce these bilayer gels to fold into tubes. The folding occurs instantly when a flat film of the gel is introduced into a solution of these cations. The likely cause for folding is that the active layer stiffens and shrinks (because the alginate chains in it get cross-linked by the cations) whereas the passive layer is unaffected. The resulting mismatch in swelling degree between the two layers creates internal stresses that drive folding. Cations that are incapable of cross-linking alginate, such as Na+ and Mg2+, do not induce gel folding. Moreover, the striking aspect is the direction of folding. When the Ca2+ concentration is high (100 mM or higher), the gels fold along their long axis, whereas when the Ca2+ concentration is low (40 to 80 mM), the gels fold along their short axis. We hypothesize that the folding axis is dictated by the inhomogeneous nature of alginate-cation cross-linking, i.e., that the edges get cross-linked before the faces of the gel. At high Ca2+ concentration, the stiffer edges constrain the folding; in turn, the gel folds such that the longer edges are deformed less, which explains the folding along the long axis. At low Ca2+ concentration, the edges and the faces of the gel are more similar in their degree of cross-linking; therefore, the gel folds along its short axis. An analogy
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.
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.
Flips for 3-folds and 4-folds

CERN Document Server

Corti, Alessio

2007-01-01

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

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

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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.
Heterochiral Knottin Protein: Folding and Solution Structure.

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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.
The structure of the TFIIH p34 subunit reveals a von Willebrand factor A like fold.

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Dominik R Schmitt

Full Text Available RNA polymerase II dependent transcription and nucleotide excision repair are mediated by a multifaceted interplay of subunits within the general transcription factor II H (TFIIH. A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these vital cellular processes. The importance of this complex becomes further evident in the context of severe diseases like xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy, that arise from single point mutations in TFIIH subunits. Here we describe the structure of the p34 subunit of the TFIIH complex from the eukaryotic thermophilic fungus Chaetomium thermophilum. The structure revealed that p34 contains a von Willebrand Factor A (vWA like domain, a fold which is generally known to be involved in protein-protein interactions. Within TFIIH p34 strongly interacts with p44, a positive regulator of the helicase XPD. Putative protein-protein interfaces are analyzed and possible binding sites for the p34-p44 interaction suggested.
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

Working in Separate Silos? What Citation Patterns Reveal about Higher Education Research Internationally

Science.gov (United States)

Tight, Malcolm

2014-01-01

Higher education research is a growing, inter-disciplinary and increasingly international field of study. This article examines the citation patterns of articles published in six leading higher education journals--three published in the United States and three published elsewhere in the world--for what they reveal about the development of this…
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.
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.
Rate constant and reaction coordinate of Trp-cage folding in explicit water

NARCIS (Netherlands)

Juraszek, J.; Bolhuis, P.G.

2008-01-01

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

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Rawal J.D.

2015-06-01

Full Text Available Introduction: -The larynx is an air passage and a sphincteric device used in respiration and phonation. The larynx, from inside outwards has a framework of mucosa surrounded by fibro-elastic membrane which in turn is surrounded by cartilages and then a layer of muscles. Vocal folds are intrinsic ligament of larynx covered by mucosal folds. Larynx generates sound through rhythmic opening and closing of the vocal folds. The perceived pitch of human voice mainly depends upon fundamental frequency of sound generated by larynx. Aim: - The aim of present study is to measure various dimensions of vocal folds in Indian cadavers. Material & Methods: - 50 larynx were obtained from embalmed cadavers, of which 10 larynx were of females. Vocal cords were dissected from the larynx and morphometric analysis was done. Results and Conclusions: - The average total length of the vocal folds was found to be 16.11 mm. ± 2.62 mm. in male and 14.10 mm. ± 1.54 mm. in female cadavers. The average width of the vocal folds was found to be 4.38 mm. ± 0.74 mm. in male and 3.60 mm. ± 0.64 mm. in female cadavers. The average total length of the membranous part of the vocal folds was found to be 11.90 mm. ± 1.86 mm. in male and 10.45 mm. ± 1.81 mm. in female cadavers. The average ratio of the length of the membranous and the cartilaginous parts of the vocal folds was calculated to be 3.10 ± 0.96in male and 2.85 ± 0.73in female cadavers.
High-Pressure NMR and SAXS Reveals How Capping Modulates Folding Cooperativity of the pp32 Leucine-rich Repeat Protein.

Science.gov (United States)

Zhang, Yi; Berghaus, Melanie; Klein, Sean; Jenkins, Kelly; Zhang, Siwen; McCallum, Scott A; Morgan, Joel E; Winter, Roland; Barrick, Doug; Royer, Catherine A

2018-04-27

Many repeat proteins contain capping motifs, which serve to shield the hydrophobic core from solvent and maintain structural integrity. While the role of capping motifs in enhancing the stability and structural integrity of repeat proteins is well documented, their contribution to folding cooperativity is not. Here we examined the role of capping motifs in defining the folding cooperativity of the leucine-rich repeat protein, pp32, by monitoring the pressure- and urea-induced unfolding of an N-terminal capping motif (N-cap) deletion mutant, pp32-∆N-cap, and a C-terminal capping motif destabilization mutant pp32-Y131F/D146L, using residue-specific NMR and small-angle X-ray scattering. Destabilization of the C-terminal capping motif resulted in higher cooperativity for the unfolding transition compared to wild-type pp32, as these mutations render the stability of the C-terminus similar to that of the rest of the protein. In contrast, deletion of the N-cap led to strong deviation from two-state unfolding. In both urea- and pressure-induced unfolding, residues in repeats 1-3 of pp32-ΔN-cap lost their native structure first, while the C-terminal half was more stable. The residue-specific free energy changes in all regions of pp32-ΔN-cap were larger in urea compared to high pressure, indicating a less cooperative destabilization by pressure. Moreover, in contrast to complete structural disruption of pp32-ΔN-cap at high urea concentration, its pressure unfolded state remained compact. The contrasting effects of the capping motifs on folding cooperativity arise from the differential local stabilities of pp32, whereas the contrasting effects of pressure and urea on the pp32-ΔN-cap variant arise from their distinct mechanisms of action. Copyright © 2018 Elsevier Ltd. All rights reserved.
Covering folded shapes

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Oswin Aichholzer

2014-05-01

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

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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.
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.
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.
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
Biophysical Studies on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions.

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Katia M S Cabral

Full Text Available BEX3 (Brain Expressed X-linked protein 3 is a member of a mammal-specific placental protein family. Several studies have found the BEX proteins to be associated with neurodegeneration, the cell cycle and cancer. BEX3 has been predicted to be intrinsically disordered and also to represent an intracellular hub for cell signaling. The pro-apoptotic activity of BEX3 in association with a number of additional proteins has been widely supported; however, to the best of our knowledge, very limited data are available on the conformation of any of the members of the BEX family. In this study, we structurally characterized BEX3 using biophysical experimental data. Small angle X-ray scattering and atomic force microscopy revealed that BEX3 forms a specific higher-order oligomer that is consistent with a globular molecule. Solution nuclear magnetic resonance, partial proteinase K digestion, circular dichroism spectroscopy, and fluorescence techniques that were performed on the recombinant protein indicated that the structure of BEX3 is composed of approximately 31% α-helix and 20% β-strand, contains partially folded regions near the N- and C-termini, and a core which is proteolysis-resistant around residues 55-120. The self-oligomerization of BEX3 has been previously reported in cell culture and is consistent with our in vitro data.
Biophysical Studies on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions.

Science.gov (United States)

Cabral, Katia M S; Raymundo, Diana P; Silva, Viviane S; Sampaio, Laura A G; Johanson, Laizes; Hill, Luis Fernando; Almeida, Fabio C L; Cordeiro, Yraima; Almeida, Marcius S

2015-01-01

BEX3 (Brain Expressed X-linked protein 3) is a member of a mammal-specific placental protein family. Several studies have found the BEX proteins to be associated with neurodegeneration, the cell cycle and cancer. BEX3 has been predicted to be intrinsically disordered and also to represent an intracellular hub for cell signaling. The pro-apoptotic activity of BEX3 in association with a number of additional proteins has been widely supported; however, to the best of our knowledge, very limited data are available on the conformation of any of the members of the BEX family. In this study, we structurally characterized BEX3 using biophysical experimental data. Small angle X-ray scattering and atomic force microscopy revealed that BEX3 forms a specific higher-order oligomer that is consistent with a globular molecule. Solution nuclear magnetic resonance, partial proteinase K digestion, circular dichroism spectroscopy, and fluorescence techniques that were performed on the recombinant protein indicated that the structure of BEX3 is composed of approximately 31% α-helix and 20% β-strand, contains partially folded regions near the N- and C-termini, and a core which is proteolysis-resistant around residues 55-120. The self-oligomerization of BEX3 has been previously reported in cell culture and is consistent with our in vitro data.
The structure of a conserved Piezo channel domain reveals a novel beta sandwich fold

Science.gov (United States)

Kamajaya, Aron; Kaiser, Jens; Lee, Jonas; Reid, Michelle; Rees, Douglas C.

2014-01-01

Summary Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a novel beta sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in Dehydrated Hereditary Stomatocytosis (DHS) patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. PMID:25242456
Structure of a Reptilian Adenovirus Reveals a Phage Tailspike Fold Stabilizing a Vertebrate Virus Capsid.

Science.gov (United States)

Menéndez-Conejero, Rosa; Nguyen, Thanh H; Singh, Abhimanyu K; Condezo, Gabriela N; Marschang, Rachel E; van Raaij, Mark J; San Martín, Carmen

2017-10-03

Although non-human adenoviruses (AdVs) might offer solutions to problems posed by human AdVs as therapeutic vectors, little is known about their basic biology. In particular, there are no structural studies on the complete virion of any AdV with a non-mammalian host. We combine mass spectrometry, cryo-electron microscopy, and protein crystallography to characterize the composition and structure of a snake AdV (SnAdV-1, Atadenovirus genus). SnAdV-1 particles contain the genus-specific proteins LH3, p32k, and LH2, a previously unrecognized structural component. Remarkably, the cementing protein LH3 has a trimeric β helix fold typical of bacteriophage host attachment proteins. The organization of minor coat proteins differs from that in human AdVs, correlating with higher thermostability in SnAdV-1. These findings add a new piece to the intriguing puzzle of virus evolution, hint at the use of cell entry pathways different from those in human AdVs, and will help development of new, thermostable SnAdV-1-based vectors. Copyright © 2017 Elsevier Ltd. All rights reserved.
Recurrence of vocal fold leukoplakia after carbon dioxide laser therapy.

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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.
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
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.
Accurate Stabilities of Laccase Mutants Predicted with a Modified FoldX Protocol

DEFF Research Database (Denmark)

Christensen, Niels Johan; Kepp, Kasper Planeta

2012-01-01

) with up to 11 simultaneously mutated sites with good correlation against experimental stability trends. Molecular dynamics simulations of the two laccases show that FoldX is very structure-sensitive, since all mutants and the wild-type must share structural configuration to avoid artifacts of local...... sampling. However, using the average of 50 MD snapshots of the equilibrated trajectories restores correlation (r ~0.7-0.9, r2 ~0.49-0.81) and provides a root-mean-square accuracy of ~1.2 kcal/mol for ∆∆G or 3.5 ○C for T50, suggesting that the time-average of the crystal structure is recovered. MD......-averaged input also reduces the spread in ∆∆G, suggesting that local FoldX sampling overestimates free energy changes because of neglected protein relaxation. FoldX can be viewed as a simple “linear interaction energy” method using sampling of wild-type and mutant and a parameterized relative free energy...
Vocal fold submucosal infusion technique in phonomicrosurgery.

Science.gov (United States)

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

1996-05-01

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

Vocal Fold Paralysis

Science.gov (United States)

... here Home » Health Info » Voice, Speech, and Language Vocal Fold Paralysis On this page: What is vocal fold ... Where can I get additional information? What is vocal fold paralysis? Structures involved in speech and voice production ...
Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation

International Nuclear Information System (INIS)

Miller, Mitchell D.; Aravind, L.; Bakolitsa, Constantina; Rife, Christopher L.; Carlton, Dennis; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The crystal structure of the first representative of DUF364 family reveals a combination of enolase N-terminal-like and C-terminal Rossmann-like folds. Analysis of the interdomain cleft combined with sequence and genome context conservation among homologs, suggests a unique catalytic site likely involved in the synthesis of a flavin or pterin derivative. The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation
Fabrication of ten-fold photonic quasicrystalline structures

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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.
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.
Effects of Vocal Fold Nodules on Glottal Cycle Measurements Derived from High-Speed Videoendoscopy in Children

Science.gov (United States)

2016-01-01

The goal of this study is to quantify the effects of vocal fold nodules on vibratory motion in children using high-speed videoendoscopy. Differences in vibratory motion were evaluated in 20 children with vocal fold nodules (5–11 years) and 20 age and gender matched typically developing children (5–11 years) during sustained phonation at typical pitch and loudness. Normalized kinematic features of vocal fold displacements from the mid-membranous vocal fold point were extracted from the steady-state high-speed video. A total of 12 kinematic features representing spatial and temporal characteristics of vibratory motion were calculated. Average values and standard deviations (cycle-to-cycle variability) of the following kinematic features were computed: normalized peak displacement, normalized average opening velocity, normalized average closing velocity, normalized peak closing velocity, speed quotient, and open quotient. Group differences between children with and without vocal fold nodules were statistically investigated. While a moderate effect size was observed for the spatial feature of speed quotient, and the temporal feature of normalized average closing velocity in children with nodules compared to vocally normal children, none of the features were statistically significant between the groups after Bonferroni correction. The kinematic analysis of the mid-membranous vocal fold displacement revealed that children with nodules primarily differ from typically developing children in closing phase kinematics of the glottal cycle, whereas the opening phase kinematics are similar. Higher speed quotients and similar opening phase velocities suggest greater relative forces are acting on vocal fold in the closing phase. These findings suggest that future large-scale studies should focus on spatial and temporal features related to the closing phase of the glottal cycle for differentiating the kinematics of children with and without vocal fold nodules. PMID:27124157
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.
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.
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.
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
Acute Contained Ruptured Aortic Aneurysm Presenting as Left Vocal Fold Immobility

OpenAIRE

Gnagi, Sharon H.; Howard, Brittany E.; Hoxworth, Joseph M.; Lott, David G.

2015-01-01

Objective. To recognize intrathoracic abnormalities, including expansion or rupture of aortic aneurysms, as a source of acute onset vocal fold immobility. Methods. A case report and review of the literature. Results. An 85-year-old female with prior history of an aortic aneurysm presented to a tertiary care facility with sudden onset hoarseness. On laryngoscopy, the left vocal fold was immobile in the paramedian position. A CT scan obtained that day revealed a new, large hematoma surrounding ...
The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.

Science.gov (United States)

Kamajaya, Aron; Kaiser, Jens T; Lee, Jonas; Reid, Michelle; Rees, Douglas C

2014-10-07

Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. Copyright © 2014 Elsevier Ltd. All rights reserved.
ETIOLOGICAL FACTORS FOR VOCAL FOLD POLYP FORMATION

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

DEFF Research Database (Denmark)

Granados, Alba; Brunskog, Jonas

2017-01-01

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

Science.gov (United States)

Granados, Alba; Brunskog, Jonas

2017-06-01

High-speed movies of the vocal fold vibration are valuable data to reveal vocal fold features for voice pathology diagnosis. This work presents a suitable Bayesian model and a purely theoretical discussion for further development of a framework for continuum biomechanical features estimation. A linear and Gaussian nonstationary state-space model is proposed and thoroughly discussed. The evolution model is based on a self-sustained three-dimensional finite element model of the vocal folds, and the observation model involves a dense optical flow algorithm. The results show that the method is able to capture different deformation patterns between the computed optical flow and the finite element deformation, controlled by the choice of the model tissue parameters.
Origin of 6-fold coordinated aluminum at (010-type pyrophyllite edges

Directory of Open Access Journals (Sweden)

M. Okumura

2017-05-01

Full Text Available To better understand the aqueous chemical reactivity of clay mineral edges we explored the relationships between hydration and the structure of (010-type edges of pyrophyllite. In particular, we used density functional theory and the quantum theory of atoms in molecules to evaluate the stability of 6-fold coordinated hydrated aluminum at the edge in terms of the electron density distribution. Geometrical optimization revealed an intra-edge hydrogen bond network between aluminol hydroxyls and water ligands completing the aluminum coordination shell. From the electron density isosurfaces one water ligand is not covalently bonded to aluminum. Bader charge analysis revealed that OH2 ligands have small negative charge. In addition, it is also found that the charge of the 6-fold coordinated aluminum is larger than one of the 5-fold aluminum. From these results, the charging of the OH2 ligands is interpreted as charge transfer originated from the formation of the hydrogen bond network and not from Al-OH2 interaction per se. This suggests that the weakly bound water ligand in question, and more generally 6-fold hydrated edge Al coordination, is stabilized primarily by the hydrogen bond network which in turn leads to weak ionic attraction to the aluminum center itself. The finding highlights the importance of cooperative effects between solvent structure and the coordination of metal cations exposed at clay mineral edges.
Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

International Nuclear Information System (INIS)

Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K.; McMullan, Daniel; Krishna, S. Sri; Miller, Mitchell D.; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; Morse, Andrew T.; Murphy, Kevin D.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Trout, Christina V.; Bedem, Henry van den; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

Structures of the first representatives of PF06684 (DUF1185) reveal a Bacillus chorismate mutase-like fold with a potential role in amino-acid synthesis. The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis
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
Investigation of hindwing folding in ladybird beetles by artificial elytron transplantation and microcomputed tomography.

Science.gov (United States)

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.
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.
Sex Hormone Receptor Expression in the Human Vocal Fold Subunits.

Science.gov (United States)

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

2017-07-01

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

Timing of isoclinal folds in multiply deformed high metamorphic grade region using FIA succession

Science.gov (United States)

Cao, Hui; Cai, Zhihui

2013-04-01

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. The asymmetries of the overprinting foliations preserved as inclusion trails that define the FIAs can be used to investigate whether an enigmatic isoclinal fold is an antiform or synform. This approach also reveals when the fold first formed during the tectonic history of the region. Isoclinally folded rocks in the Arkansas River region of 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 came recognition that large scale regional folds can form early during this process and be preserved throughout orogenesis. This extensive history is lost within the matrix because of reactivational shear on the compositional layering. 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. That is, although it was demonstrated that the largest scale regional folds commonly form early in the total history, other folds can form and be preserved from subsequent destruction in the strain shadows of plutons or through the partitioning of deformation due to heterogeneities at depth.
Energetics, kinetics, and pathway of SNARE folding and assembly revealed by optical tweezers.

Science.gov (United States)

Zhang, Yongli

2017-07-01

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion. A long-standing hypothesis suggests that SNAREs act like a zipper to draw the two membranes into proximity and thereby force them to fuse. However, a quantitative test of this SNARE zippering hypothesis was hindered by difficulties to determine the energetics and kinetics of SNARE assembly and to identify the relevant folding intermediates. Here, we first review different approaches that have been applied to study SNARE assembly and then focus on high-resolution optical tweezers. We summarize the folding energies, kinetics, and pathways of both wild-type and mutant SNARE complexes derived from this new approach. These results show that synaptic SNAREs assemble in four distinct stages with different functions: slow N-terminal domain association initiates SNARE assembly; a middle domain suspends and controls SNARE assembly; and rapid sequential zippering of the C-terminal domain and the linker domain directly drive membrane fusion. In addition, the kinetics and pathway of the stagewise assembly are shared by other SNARE complexes. These measurements prove the SNARE zippering hypothesis and suggest new mechanisms for SNARE assembly regulated by other proteins. © 2017 The Protein Society.
Biological Properties and Characterization of ASL50 Protein from Aged Allium sativum Bulbs.

Science.gov (United States)

Kumar, Suresh; Jitendra, Kumar; Singh, Kusum; Kapoor, Vaishali; Sinha, Mou; Xess, Immaculata; Das, Satya N; Sharma, Sujata; Singh, Tej P; Dey, Sharmistha

2015-08-01

Allium sativum is well known for its medicinal properties. The A. sativum lectin 50 (ASL50, 50 kDa) was isolated from aged A. sativum bulbs and purified by gel filtration chromatography on Sephacryl S-200 column. Agar well diffusion assay were used to evaluate the antimicrobial activity of ASL50 against Candida species and bacteria then minimal inhibitory concentration (MIC) was determined. The lipid A binding to ASL50 was determined by surface plasmon resonance (SPR) technology with varying concentrations. Electron microscopic studies were done to see the mode of action of ASL50 on microbes. It exerted antimicrobial activity against clinical Candida isolates with a MIC of 10-40 μg/ml and clinical Pseudomonas aeruginosa isolates with a MIC of 10-80 μg/ml. The electron microscopic study illustrates that it disrupts the cell membrane of the bacteria and cell wall of fungi. It exhibited antiproliferative activity on oral carcinoma KB cells with an IC50 of 36 μg/ml after treatment for 48 h and induces the apoptosis of cancer cells by inducing 2.5-fold higher caspase enzyme activity than untreated cells. However, it has no cytotoxic effects towards HEK 293 cells as well as human erythrocytes even at higher concentration of ASL50. Biological properties of ASL50 may have its therapeutic significance in aiding infection and cancer treatments.
Fracture zones constrained by neutral surfaces in a fault-related fold: Insights from the Kelasu tectonic zone, Kuqa Depression

Science.gov (United States)

Sun, Shuai; Hou, Guiting; Zheng, Chunfang

2017-11-01

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

CERN Multimedia

2003-01-01

"Researchers based at Lawrence Berkeley National Laboratory and the University of California at Berkeley have used a scanning tunneling microscope (STM) to reveal eight-fold patterns of quasiparticle interference in the high-temperature superconductor Bi-2212 (bismuth strontium calcium copper oxide)" (2 pages).
A Dual-Channel Acquisition Method Based on Extended Replica Folding Algorithm for Long Pseudo-Noise Code in Inter-Satellite Links.

Science.gov (United States)

Zhao, Hongbo; Chen, Yuying; Feng, Wenquan; Zhuang, Chen

2018-05-25

Inter-satellite links are an important component of the new generation of satellite navigation systems, characterized by low signal-to-noise ratio (SNR), complex electromagnetic interference and the short time slot of each satellite, which brings difficulties to the acquisition stage. The inter-satellite link in both Global Positioning System (GPS) and BeiDou Navigation Satellite System (BDS) adopt the long code spread spectrum system. However, long code acquisition is a difficult and time-consuming task due to the long code period. Traditional folding methods such as extended replica folding acquisition search technique (XFAST) and direct average are largely restricted because of code Doppler and additional SNR loss caused by replica folding. The dual folding method (DF-XFAST) and dual-channel method have been proposed to achieve long code acquisition in low SNR and high dynamic situations, respectively, but the former is easily affected by code Doppler and the latter is not fast enough. Considering the environment of inter-satellite links and the problems of existing algorithms, this paper proposes a new long code acquisition algorithm named dual-channel acquisition method based on the extended replica folding algorithm (DC-XFAST). This method employs dual channels for verification. Each channel contains an incoming signal block. Local code samples are folded and zero-padded to the length of the incoming signal block. After a circular FFT operation, the correlation results contain two peaks of the same magnitude and specified relative position. The detection process is eased through finding the two largest values. The verification takes all the full and partial peaks into account. Numerical results reveal that the DC-XFAST method can improve acquisition performance while acquisition speed is guaranteed. The method has a significantly higher acquisition probability than folding methods XFAST and DF-XFAST. Moreover, with the advantage of higher detection
A Dual-Channel Acquisition Method Based on Extended Replica Folding Algorithm for Long Pseudo-Noise Code in Inter-Satellite Links

Directory of Open Access Journals (Sweden)

Hongbo Zhao

2018-05-01

Full Text Available Inter-satellite links are an important component of the new generation of satellite navigation systems, characterized by low signal-to-noise ratio (SNR, complex electromagnetic interference and the short time slot of each satellite, which brings difficulties to the acquisition stage. The inter-satellite link in both Global Positioning System (GPS and BeiDou Navigation Satellite System (BDS adopt the long code spread spectrum system. However, long code acquisition is a difficult and time-consuming task due to the long code period. Traditional folding methods such as extended replica folding acquisition search technique (XFAST and direct average are largely restricted because of code Doppler and additional SNR loss caused by replica folding. The dual folding method (DF-XFAST and dual-channel method have been proposed to achieve long code acquisition in low SNR and high dynamic situations, respectively, but the former is easily affected by code Doppler and the latter is not fast enough. Considering the environment of inter-satellite links and the problems of existing algorithms, this paper proposes a new long code acquisition algorithm named dual-channel acquisition method based on the extended replica folding algorithm (DC-XFAST. This method employs dual channels for verification. Each channel contains an incoming signal block. Local code samples are folded and zero-padded to the length of the incoming signal block. After a circular FFT operation, the correlation results contain two peaks of the same magnitude and specified relative position. The detection process is eased through finding the two largest values. The verification takes all the full and partial peaks into account. Numerical results reveal that the DC-XFAST method can improve acquisition performance while acquisition speed is guaranteed. The method has a significantly higher acquisition probability than folding methods XFAST and DF-XFAST. Moreover, with the advantage of higher
The efficacy of a novel collagen-gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar.

Science.gov (United States)

Hiwatashi, Nao; Hirano, Shigeru; Mizuta, Masanobu; Kobayashi, Toshiki; Kawai, Yoshitaka; Kanemaru, Shin-Ichi; Nakamura, Tatsuo; Ito, Juichi; Kawai, Katsuya; Suzuki, Shigehiko

2017-05-01

Vocal fold scar remains a therapeutic challenge. Basic fibroblast growth factor (bFGF) was reported to have regenerative effects for vocal fold scar, although it has the disadvantage of rapid absorption in vivo. A collagen-gelatin sponge (CGS) can compensate for the disadvantage by providing a sustained release system. The current study evaluated the efficacy of CGS combined with bFGF on vocal fold scar, using rat fibroblasts for an in vitro model and a canine in vivo model. We prepared fibroblasts from scarred vocal folds (sVFs) in rats and showed that bFGF accelerated cell proliferation and suppressed expression levels of cleaved caspase 3 and α-smooth muscle actin. Has 1, Has 3, Fgf2, Hgf and Vegfa mRNA levels were significantly upregulated, while Col1a1 and Col3a1 were dose-dependently downregulated, with a maximum effect at 100 ng/ml bFGF. In an in vivo assay, 6 weeks after lamina propria stripping, beagles were divided into three groups: CGS alone (CGS group); CGS with bFGF (7 µg/cm 2 ; CGS + bFGF group); or a sham-treated group. Vibratory examination revealed that the glottal gap was significantly reduced in the bFGF group and the two implanted groups, whereas the CGS + bFGF group showed higher mucosal wave amplitude. Histological examination revealed significantly restored hyaluronic acid and elastin redistribution in the CGS + bFGF group and reductions in dense collagen deposition. These results provide evidence that CGS and bFGF combination therapy may have therapeutic potential and could be a promising tool for treating vocal fold scar. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
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
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.
Atomistic structural ensemble refinement reveals non-native structure stabilizes a sub-millisecond folding intermediate of CheY

International Nuclear Information System (INIS)

Shi, Jade; Schwantes, Christian; Bilsel, Osman

2017-01-01

The dynamics of globular proteins can be described in terms of transitions between a folded native state and less-populated intermediates, or excited states, which can play critical roles in both protein folding and function. Excited states are by definition transient species, and therefore are difficult to characterize using current experimental techniques. We report an atomistic model of the excited state ensemble of a stabilized mutant of an extensively studied flavodoxin fold protein CheY. We employed a hybrid simulation and experimental approach in which an aggregate 42 milliseconds of all-atom molecular dynamics were used as an informative prior for the structure of the excited state ensemble. The resulting prior was then refined against small-angle X-ray scattering (SAXS) data employing an established method (EROS). The most striking feature of the resulting excited state ensemble was an unstructured N-terminus stabilized by non-native contacts in a conformation that is topologically simpler than the native state. We then predict incisive single molecule FRET experiments, using these results, as a means of model validation. Our study demonstrates the paradigm of uniting simulation and experiment in a statistical model to study the structure of protein excited states and rationally design validating experiments.
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.
Effects of gravity in folding

Science.gov (United States)

Minkel, Donald Howe

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

Science.gov (United States)

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

2016-11-01

The aim of this study was to illustrate the risk of vocal fold atrophy in patients who receive serial subepithelial steroid injections for vocal fold scar. This study is a retrospective case report of two patients who underwent a series of weekly subepithelial infusions of 10 mg/mL dexamethasone for benign vocal fold lesion. Shortly after the procedures, both patients developed a weak and breathy voice. The first patient was a 53-year-old man with radiation-induced vocal fold stiffness. Six injections were performed unilaterally, and 1 week later, he developed unilateral vocal fold atrophy with new glottal insufficiency. The second patient was a 67-year-old woman with severe vocal fold inflammation related to laryngitis and calcinosis, Raynaud's phenomenon, esophagean dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. Five injections were performed bilaterally, and 1 week later, she developed bilateral vocal fold atrophy with a large midline glottal gap during phonation. In both cases, the steroid-induced vocal atrophy resolved spontaneously after 4 months. Serial subepithelial steroid infusions of the vocal folds, although safe in the majority of patients, carry the risk of causing temporary vocal fold atrophy when given at short intervals. Copyright Â© 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
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
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.
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
NoFold: RNA structure clustering without folding or alignment.

Science.gov (United States)

Middleton, Sarah A; Kim, Junhyong

2014-11-01

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

Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in eukaryotes, bacteria, viruses and plasmids

Directory of Open Access Journals (Sweden)

Ogata Hiroyuki

2011-09-01

Full Text Available Abstract Background The Mre11/Rad50 complex and the homologous SbcD/SbcC complex in bacteria play crucial roles in the metabolism of DNA double-strand breaks, including DNA repair, genome replication, homologous recombination and non-homologous end-joining in cellular life forms and viruses. Here we investigated the amino acid sequence of the Mimivirus R555 gene product, originally annotated as a Rad50 homolog, and later shown to have close homologs in marine microbial metagenomes. Results Our bioinformatics analysis revealed that R555 protein sequence is constituted from the fusion of an N-terminal Mre11-like domain with a C-terminal Rad50-like domain. A systematic database search revealed twelve additional cases of Mre11/Rad50 (or SbcD/SbcC fusions in a wide variety of unrelated organisms including unicellular and multicellular eukaryotes, the megaplasmid of a bacterium associated to deep-sea hydrothermal vents (Deferribacter desulfuricans and the plasmid of Clostridium kluyveri. We also showed that R555 homologs are abundant in the metagenomes from different aquatic environments and that they most likely belong to aquatic viruses. The observed phyletic distribution of these fusion proteins suggests their recurrent creation and lateral gene transfers across organisms. Conclusions The existence of the fused version of protein sequences is consistent with known functional interactions between Mre11 and Rad50, and the gene fusion probably enhanced the opportunity for lateral transfer. The abundance of the Mre11/Rad50 fusion genes in viral metagenomes and their sporadic phyletic distribution in cellular organisms suggest that viruses, plasmids and transposons played a crucial role in the formation of the fusion proteins and their propagation into cellular genomes.
Glycoprotein folding and quality-control mechanisms in protein-folding diseases

Directory of Open Access Journals (Sweden)

Sean P. Ferris

2014-03-01

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

Science.gov (United States)

Karzbrun, Eyal; Kshirsagar, Aditya; Cohen, Sidney R.; Hanna, Jacob H.; Reiner, Orly

2018-05-01

Human brain wrinkling has been implicated in neurodevelopmental disorders and yet its origins remain unknown. Polymer gel models suggest that wrinkling emerges spontaneously due to compression forces arising during differential swelling, but these ideas have not been tested in a living system. Here, we report the appearance of surface wrinkles during the in vitro development and self-organization of human brain organoids in a microfabricated compartment that supports in situ imaging over a timescale of weeks. We observe the emergence of convolutions at a critical cell density and maximal nuclear strain, which are indicative of a mechanical instability. We identify two opposing forces contributing to differential growth: cytoskeletal contraction at the organoid core and cell-cycle-dependent nuclear expansion at the organoid perimeter. The wrinkling wavelength exhibits linear scaling with tissue thickness, consistent with balanced bending and stretching energies. Lissencephalic (smooth brain) organoids display reduced convolutions, modified scaling and a reduced elastic modulus. Although the mechanism here does not include the neuronal migration seen in vivo, it models the physics of the folding brain remarkably well. Our on-chip approach offers a means for studying the emergent properties of organoid development, with implications for the embryonic human brain.
Vocal fold immobility from a primary minor salivary gland small-cell carcinoma: case report.

Science.gov (United States)

Witt, Robert L; Wilson, Patrick A

2009-02-01

Small-cell carcinoma of a minor salivary gland is a rare and to the best of our knowledge previously unreported cause of vocal fold immobility. We describe the case of a 68-year-old woman who presented with hoarseness, dysphagia, and weight loss. Examination revealed left vocal fold immobility. She had no other obvious abnormality of the upper airway, neck, or skin. Computed tomography and magnetic resonance imaging demonstrated a 4-cm submucosal oropharyngeal mass with extension to the parapharyngeal space and involvement of the carotid sheath and the foramen ovale at the skull base; imaging also revealed cervical adenopathy. Fine-needle aspiration biopsy identified the mass as a small-cell carcinoma, a finding that was confirmed by immunohistochemistry. Extensive tumor invasion and multiple comorbidities precluded an aggressive management strategy, and the patient was treated palliatively. She died of her disease shortly after her diagnosis. Vocal fold immobility of unknown etiology mandates imaging from the skull base to the upper mediastinum.
It is worth 10 million working hours a year to have your toilet paper folded?

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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?
Interstitial fluid contains higher in vitro IGF bioactivity than serum

DEFF Research Database (Denmark)

Espelund, Ulrick; Søndergaard, Klaus; Bjerring, Peter

2012-01-01

MEASURE: Serum and SBF concentrations of bioactive IGF (determined in vitro by specific IGF-I receptor (IGF-IR) phosphorylation assay), immunoreactive IGF and IGF binding protein (IGFBP) levels, Western ligand blotting (WLB) of IGFBPs and IGFBP-3 Western immunoblotting (WiB). RESULTS: The ability of SBF...... to phosphorylate the IGF-IR in vitro was 41±27% higher than that of serum (P=0.007 by repeated measures ANOVA). By contrast, immunoreactive IGF and IGFBP-concentrations were approximately 50% lower in SBF than in serum (all P≤0.002). A marked difference in the composition of IGFBPs between serum and SBF...... was observed, including 3-fold elevated amounts of IGFBP-3 fragments in SBF (Pvitro IGF bioactivity was higher in SBF than in serum. This may...
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.
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.
Analysis of the free-energy surface of proteins from reversible folding simulations.

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

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

2017-01-01

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

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

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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.
Human Brain Organoids on a Chip Reveal the Physics of Folding.

Science.gov (United States)

Karzbrun, Eyal; Kshirsagar, Aditya; Cohen, Sidney R; Hanna, Jacob H; Reiner, Orly

2018-05-01

Human brain wrinkling has been implicated in neurodevelopmental disorders and yet its origins remain unknown. Polymer gel models suggest that wrinkling emerges spontaneously due to compression forces arising during differential swelling, but these ideas have not been tested in a living system. Here, we report the appearance of surface wrinkles during the in vitro development and self-organization of human brain organoids in a micro-fabricated compartment that supports in situ imaging over a timescale of weeks. We observe the emergence of convolutions at a critical cell density and maximal nuclear strain, which are indicative of a mechanical instability. We identify two opposing forces contributing to differential growth: cytoskeletal contraction at the organoid core and cell-cycle-dependent nuclear expansion at the organoid perimeter. The wrinkling wavelength exhibits linear scaling with tissue thickness, consistent with balanced bending and stretching energies. Lissencephalic (smooth brain) organoids display reduced convolutions, modified scaling and a reduced elastic modulus. Although the mechanism here does not include the neuronal migration seen in in vivo , it models the physics of the folding brain remarkably well. Our on-chip approach offers a means for studying the emergent properties of organoid development, with implications for the embryonic human brain.
Functional and Histological Evaluation following Canine Vocal Fold Reconstruction Using Composite Thyroid Ala Perichondrium Flaps.

Science.gov (United States)

Hoffman, Matthew R; Glab, Rachel; Gunderson, McLean; Maytag, Allison L; Yang, David T; Jiang, Jack J; Dailey, Seth H

2015-07-01

We evaluated the effects of vocal fold reconstruction using a composite thyroid ala perichondrium flap (CTAP) after unilateral vocal fold stripping in beagles. We hypothesized that CTAP would improve glottic closure, decrease phonation threshold pressure, and decrease perturbation. In addition, vocal folds with CTAP would exhibit neovascularization and fat with increased von Willebrand factor (vWF) and smooth muscle actin (SMA), reflecting neoangiogenesis and flap viability. Randomized controlled trial using beagles. University laboratory. Ten beagles underwent unilateral vocal fold stripping. Dogs in the scar-only group (n = 5) were sacrificed at 1 month. Dogs in the CTAP group (n = 5) underwent ipsilateral reconstruction with CTAP at 1 month and were sacrificed at 2 months. Excised larynx experiments evaluated vocal fold vibration using aerodynamic, acoustic, and mucosal wave measurements. Qualitative evaluation of vocal fold morphology and quantitative analysis of elastin, collagen, glycosaminoglycans, vWF, SMA, and hyaluronic acid were performed. Phonation threshold pressure (P = .005), percent jitter (P = .010), percent shimmer (P = .007), and open quotient (P = .007) were lower in the CTAP group. Neovascularization (P = .0079) and fat (P = .1667) occurred more with CTAP, although the difference in fat was not significant. von Willebrand factor was higher with CTAP vs contralateral normal fold (P = .110), although not statistically significant. Smooth muscle actin was higher with CTAP vs contralateral normal fold (P = .038) and scarred vocal folds (P = .022). Composite thyroid ala perichondrium flap restored glottic closure and vibratory periodicity following vocal fold scarring. Additional investigation on biologic response is warranted. Composite thyroid ala perichondrium flap offers an autologous, vascularized implant that can improve both vocal fold structure and function. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.
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...
Electroglottographic parameterization of the effects of gender, vowel and phonatory registers on vocal fold vibratory patterns: an Indian perspective.

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Paul, Nilanjan; Kumar, Suman; Chatterjee, Indranil; Mukherjee, Biswarup

2011-01-01

In-depth study on laryngeal biomechanics and vocal fold vibratory patterns reveal that a single vibratory cycle can be divided into two major phases, the closed and open phase, which is subdivided into opening and closing phases. Studies reveal that the relative time course of abduction and adduction, which in turn is dependent on the relative relaxing and tensing of the vocal fold cover and body, to be the determining factor in production of a particular vocal register like the modal (or chest), falsetto, glottal fry registers. Studies further point out Electroglottography to be particularly suitable for the study of vocal vibratory patterns during register changes. However, to date, there has been limited study on quantitative parameterization of EGG wave form in vocal fry register. Moreover, contradictory findings abound in literature regarding effects of gender and vowel types on vocal vibratory patterns, especially during phonation at different registers. The present study endeavors to find out the effects of vowel and gender differences on the vocal fold vibratory patterns in different registers and how these would be reflected in standard EGG parameters of Contact Quotient (CQ) and Contact Index (CI), taking into consideration the Indian sociolinguistic context. Electroglottographic recordings of 10 young adults (5 males and 5 females) were taken while the subjects phonated the three vowels /a/,/i/,/u/ each in two vocal registers, modal and vocal fry. Obtained raw EGG were further normalized using the Derived EGG algorithm and theCQ and CI values were derived. Obtained data were subject to statistical analysis using the 3-way ANOVA with gender, vowel and vocal register as the three variables. Post-hoc Dunnett C multiple comparison analysis were also performed. Results reveal that CQ values are significantly higher in vocal fry than modal phonation for both males and females, indicating a relatively hyperconstricted vocal system during vocal fry. The males
Vocal fold immobility: a longitudinal analysis of etiology over 20 years.

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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.

Comparison between body mass index, triceps skin fold thickness and mid-arm muscle circumference in Saudi adolescents

International Nuclear Information System (INIS)

Abdalkhail, B.; Shawky, S.

2002-01-01

Adolescence is an important period in an individual's life. Overweight and obesity are fraught with several health problems even late in life. The objective of this study was estimate the overweight, obesity, body fat and muscle content of Saudi adolescents as compared to a recognized reference population. Data were collected from a sample of Saudi adolescents in Jeddah from 42 boys' and 42 girls' school during the month of April 2000. Data collection was done by personal interviews to collect sociodemograhic factors and by direct measurement of weight, height, triceps skin fold thickness (TSF) and mid-arm circumference (MAC). The 50th, 85th and 95th percentiles(P50, P85 and P95) for body mass index (BMI) and triceps skin fold thickness (TSF) were taken, then the 50th, 90th, and 95th percentiles (P50, P90 and P95) for the mid-arm muscle circumference (MAMC) were calculated. These measurements were compared with corresponding values of the National Health and Nutrition Examination Survey I (NHANES I). The P85 and P95 for the BMI and TSF were higher for Saudi adolescents than the NHANES I and the difference was wider for P95. Conversely, there was a lower MAMC at P90 and P95thane the NHANES I reference population curves. The lower MAMC curves were less marked in girls than in boys. On the other hand Saudi boys and girls showed on average similar body mass index indicated by MBI at P50, which was misleading, since those adolescents showing similar body mass index had more fatness than of average reference population indicated by TSF and P50, and less muscularity on average than reference population indicated MAMC at P-50. Overweight and obesity with increased body fat content and decreased body muscle content appear to be widespread among Saudi adolescents even among those adolescents showing average body index. Public health interventions are required to improve quality of food, encourage physical, activity and exercise, as well as correct the perception of
Glass ionomer application for vocal fold augmentation: Histopathological analysis on rabbit vocal fold.

Science.gov (United States)

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

2016-04-01

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

Science.gov (United States)

Pappu, Rohit V.; Nussinov, Ruth

2009-03-01

In appropriate physiological milieux proteins spontaneously fold into their functional three-dimensional structures. The amino acid sequences of functional proteins contain all the information necessary to specify the folds. This remarkable observation has spawned research aimed at answering two major questions. (1) Of all the conceivable structures that a protein can adopt, why is the ensemble of native-like structures the most favorable? (2) What are the paths by which proteins manage to robustly and reproducibly fold into their native structures? Anfinsen's thermodynamic hypothesis has guided the pursuit of answers to the first question whereas Levinthal's paradox has influenced the development of models for protein folding dynamics. Decades of work have led to significant advances in the folding problem. Mean-field models have been developed to capture our current, coarse grain understanding of the driving forces for protein folding. These models are being used to predict three-dimensional protein structures from sequence and stability profiles as a function of thermodynamic and chemical perturbations. Impressive strides have also been made in the field of protein design, also known as the inverse folding problem, thereby testing our understanding of the determinants of the fold specificities of different sequences. Early work on protein folding pathways focused on the specific sequence of events that could lead to a simplification of the search process. However, unifying principles proved to be elusive. Proteins that show reversible two-state folding-unfolding transitions turned out to be a gift of natural selection. Focusing on these simple systems helped researchers to uncover general principles regarding the origins of cooperativity in protein folding thermodynamics and kinetics. On the theoretical front, concepts borrowed from polymer physics and the physics of spin glasses led to the development of a framework based on energy landscape theories. These
DNA Binding and Phosphorylation Regulate the Core Structure of the NF-κB p50 Transcription Factor.

Science.gov (United States)

Vonderach, Matthias; Byrne, Dominic P; Barran, Perdita E; Eyers, Patrick A; Eyers, Claire E

2018-06-05

The NF-κB transcription factors are known to be extensively phosphorylated, with dynamic site-specific modification regulating their ability to dimerize and interact with DNA. p50, the proteolytic product of p105 (NF-κB1), forms homodimers that bind DNA but lack intrinsic transactivation function, functioning as repressors of transcription from κB promoters. Here, we examine the roles of specific phosphorylation events catalysed by either protein kinase A (PKA c ) or Chk1, in regulating the functions of p50 homodimers. LC-MS/MS analysis of proteolysed p50 following in vitro phosphorylation allows us to define Ser328 and Ser337 as PKA c - and Chk1-mediated modifications, and pinpoint an additional four Chk1 phosphosites: Ser65, Thr152, Ser242 and Ser248. Native mass spectrometry (MS) reveals Chk1- and PKA c -regulated disruption of p50 homodimer formation through Ser337. Additionally, we characterise the Chk1-mediated phosphosite, Ser242, as a regulator of DNA binding, with a S242D p50 phosphomimetic exhibiting a > 10-fold reduction in DNA binding affinity. Conformational dynamics of phosphomimetic p50 variants, including S242D, are further explored using ion-mobility MS (IM-MS). Finally, comparative theoretical modelling with experimentally observed p50 conformers, in the absence and presence of DNA, reveals that the p50 homodimer undergoes conformational contraction during electrospray ionisation that is stabilised by complex formation with κB DNA. Graphical Abstract ᅟ.
Symptomatic unilateral vocal fold paralysis following cardiothoracic surgery.

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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.
Tracking Glideosome-associated protein 50 reveals the development and organization of the inner membrane complex of Plasmodium falciparum.

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Yeoman, Jeffrey A; Hanssen, Eric; Maier, Alexander G; Klonis, Nectarios; Maco, Bohumil; Baum, Jake; Turnbull, Lynne; Whitchurch, Cynthia B; Dixon, Matthew W A; Tilley, Leann

2011-04-01

The most deadly of the human malaria parasites, Plasmodium falciparum, has different stages specialized for invasion of hepatocytes, erythrocytes, and the mosquito gut wall. In each case, host cell invasion is powered by an actin-myosin motor complex that is linked to an inner membrane complex (IMC) via a membrane anchor called the glideosome-associated protein 50 (PfGAP50). We generated P. falciparum transfectants expressing green fluorescent protein (GFP) chimeras of PfGAP50 (PfGAP50-GFP). Using immunoprecipitation and fluorescence photobleaching, we show that C-terminally tagged PfGAP50-GFP can form a complex with endogenous copies of the linker protein PfGAP45 and the myosin A tail domain-interacting protein (MTIP). Full-length PfGAP50-GFP is located in the endoplasmic reticulum in early-stage parasites and then redistributes to apical caps during the formation of daughter merozoites. In the final stage of schizogony, the PfGAP50-GFP profile extends further around the merozoite surface. Three-dimensional (3D) structured illumination microscopy reveals the early-stage IMC as a doubly punctured flat ellipsoid that separates to form claw-shaped apposed structures. A GFP fusion of PfGAP50 lacking the C-terminal membrane anchor is misdirected to the parasitophorous vacuole. Replacement of the acid phosphatase homology domain of PfGAP50 with GFP appears to allow correct trafficking of the chimera but confers a growth disadvantage.
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.
Paleomagnetic and structural evidence for oblique slip in a fault-related fold, Grayback monocline, Colorado

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

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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
Evaluation of Dying Vocal Fold Epithelial Cells by Ultrastructural Features and TUNEL Method

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Novaleski, Carolyn K.; Mizuta, Masanobu; Rousseau, Bernard

2016-01-01

Cell death is a regulated mechanism of eliminating cells to maintain tissue homeostasis. This study described two methodological procedures for evaluating cell death in the epithelium of immobilized, approximated, and vibrated vocal folds from 12 New Zealand white breeder rabbits. The gold standard technique of transmission electron microscopy evaluated high-quality ultrastructural criteria of cell death and a common immunohistochemical marker, terminal deoxynucleotidyl transferase dUTP nick end labeling method, to confirm cell death signaling. Results revealed that ultrastructural characteristics of apoptotic cell death, specifically condensed chromatin and apoptotic bodies, were observed after vocal fold vibration and approximation. Although episodes of necrotic cell death were rare, few enlarged cell nuclei were present after vibration and approximation. The vocal fold expresses an immunohistochemical marker for apoptosis along the apical surface of the epithelium. This study provides a solid foundation for future investigations regarding the role of cell death in vocal fold health and disease. PMID:27537846
The structure of SSO2064, the first representative of Pfam family PF01796, reveals a novel two-domain zinc-ribbon OB-fold architecture with a potential acyl-CoA-binding role

International Nuclear Information System (INIS)

Krishna, S. Sri; Aravind, L.; Bakolitsa, Constantina; Caruthers, Jonathan; Carlton, Dennis; Miller, Mitchell D.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The crystal structure of SSO2064, the first structural representative of Pfam family PF01796 (DUF35), reveals a two-domain architecture comprising an N-terminal zinc-ribbon domain and a C-terminal OB-fold domain. Analysis of the domain architecture, operon organization and bacterial orthologs combined with the structural features of SSO2064 suggests a role involving acyl-CoA binding for this family of proteins. SSO2064 is the first structural representative of PF01796 (DUF35), a large prokaryotic family with a wide phylogenetic distribution. The structure reveals a novel two-domain architecture comprising an N-terminal, rubredoxin-like, zinc ribbon and a C-terminal, oligonucleotide/oligosaccharide-binding (OB) fold domain. Additional N-terminal helical segments may be involved in protein–protein interactions. Domain architectures, genomic context analysis and functional evidence from certain bacterial representatives of this family suggest that these proteins form a novel fatty-acid-binding component that is involved in the biosynthesis of lipids and polyketide antibiotics and that they possibly function as acyl-CoA-binding proteins. This structure has led to a re-evaluation of the DUF35 family, which has now been split into two entries in the latest Pfam release (v.24.0)
Vocal Fold Hyperplastic Lesions: an Evaluation of Surgical Outcome with Videolaryngostroboscopy

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Melek Kezban Gürbüz

2013-06-01

Full Text Available Background: Vocal fold hyperplastic lesions are premalignant lesions that can be treated effectively by removal of the lesions surgically. Aims: The aim of this study was to discuss the success of surgery in patients with vocal fold hyperplastic lesions in terms of preserving vibratory function by comparing the preoperative and postoperative videolaryngostroboscopy findings. Study Design: The medical charts and videolaryngostroboscopic recordings of patients diagnosed with hyperplastic lesions on the vocal folds were reviewed retrospectively. Methods: Twenty seven patients with unilateral lesions who underwent type1 subepithelial cordectomy were enrolled in the study. The videolaryngostroboscopic recordings were evaluated by three raters who were not the operating surgeon and who were blinded to the histology of patients. To evaluate the videolaryngostroboscopic findings, a form, which is a modification of criteria described by Hirano and Bless, was used. Preoperative and 6th month postoperative videolaryngostroboscopic recordings were compared with each other and with recordings of the control group, which included 50 healthy volunteers. Results: All videolaryngostroboscopic findings, except false cord vibration, were significantly improved after surgery. Conclusion: The principle of vocal fold surgery in patients with benign lesions is to preserve the vibratory tissue. This principle also applies to patients with hyperplastic lesions that are premalignant. The hydrodissection technique may be beneficial for this purpose.
Six-state, three-level, six-fold ferromagnetic wire system

International Nuclear Information System (INIS)

Blachowicz, T.; Ehrmann, A.

2013-01-01

Six stable states at remanence were identified in iron wire samples of 6-fold spatial symmetry using micromagnetic simulations and the finite element method. Onion and domain-wall magnetic states were tailored by sample shape and guided by an applied magnetic field with a fixed in-plane direction. Different directions of externally applied magnetic fields revealed a tendency for stability or nonstability of the considered states. -- Highlights: ► In a ferromagnetic wire sample six stable states at remanence were discovered. ► Presented wires provide new effects not met in classical thin-layered solutions. ► The mechanism of working results from competing demagnetizing and exchange fields. ► For different physical conditions onion and domain-wall states were observed. ► Wire samples of 6-fold symmetry can lead to many-level information storage devices
Six-state, three-level, six-fold ferromagnetic wire system

Energy Technology Data Exchange (ETDEWEB)

Blachowicz, T., E-mail: tomasz.blachowicz@polsl.pl [Institute of Physics, Silesian University of Technology, 44-100 Gliwice (Poland); Ehrmann, A. [Faculty of Textile and Clothing Technology, Niederrhein University of Applied Sciences, 41065 Mönchengladbach (Germany)

2013-04-15

Six stable states at remanence were identified in iron wire samples of 6-fold spatial symmetry using micromagnetic simulations and the finite element method. Onion and domain-wall magnetic states were tailored by sample shape and guided by an applied magnetic field with a fixed in-plane direction. Different directions of externally applied magnetic fields revealed a tendency for stability or nonstability of the considered states. -- Highlights: ► In a ferromagnetic wire sample six stable states at remanence were discovered. ► Presented wires provide new effects not met in classical thin-layered solutions. ► The mechanism of working results from competing demagnetizing and exchange fields. ► For different physical conditions onion and domain-wall states were observed. ► Wire samples of 6-fold symmetry can lead to many-level information storage devices.
Epithelial Folding Driven by Apical or Basal-Lateral Modulation: Geometric Features, Mechanical Inference, and Boundary Effects.

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

2017-06-20

During embryonic development, epithelial sheets fold into complex structures required for tissue and organ functions. Although substantial efforts have been devoted to identifying molecular mechanisms underlying epithelial folding, far less is understood about how forces deform individual cells to sculpt the overall sheet morphology. Here we describe a simple and general theoretical model for the autonomous folding of monolayered epithelial sheets. We show that active modulation of intracellular mechanics along the basal-lateral as well as the apical surfaces is capable of inducing fold formation in the absence of buckling instability. Apical modulation sculpts epithelia into shallow and V-shaped folds, whereas basal-lateral modulation generates deep and U-shaped folds. These characteristic tissue shapes remain unchanged when subject to mechanical perturbations from the surroundings, illustrating that the autonomous folding is robust against environmental variabilities. At the cellular scale, how cells change shape depends on their initial aspect ratios and the modulation mechanisms. Such cell deformation characteristics are verified via experimental measurements for a canonical folding process driven by apical modulation, indicating that our theory could be used to infer the underlying folding mechanisms based on experimental data. The mechanical principles revealed in our model could potentially guide future studies on epithelial folding in diverse systems. Copyright © 2017. Published by Elsevier Inc.
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
Splenectomy Causes 10-Fold Increased Risk of Portal Venous System Thrombosis in Liver Cirrhosis Patients.

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Qi, Xingshun; Han, Guohong; Ye, Chun; Zhang, Yongguo; Dai, Junna; Peng, Ying; Deng, Han; Li, Jing; Hou, Feifei; Ning, Zheng; Zhao, Jiancheng; Zhang, Xintong; Wang, Ran; Guo, Xiaozhong

2016-07-19

BACKGROUND Portal venous system thrombosis (PVST) is a life-threatening complication of liver cirrhosis. We conducted a retrospective study to comprehensively analyze the prevalence and risk factors of PVST in liver cirrhosis. MATERIAL AND METHODS All cirrhotic patients without malignancy admitted between June 2012 and December 2013 were eligible if they underwent contrast-enhanced CT or MRI scans. Independent predictors of PVST in liver cirrhosis were calculated in multivariate analyses. Subgroup analyses were performed according to the severity of PVST (any PVST, main portal vein [MPV] thrombosis >50%, and clinically significant PVST) and splenectomy. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS Overall, 113 cirrhotic patients were enrolled. The prevalence of PVST was 16.8% (19/113). Splenectomy (any PVST: OR=11.494, 95%CI=2.152-61.395; MPV thrombosis >50%: OR=29.987, 95%CI=3.247-276.949; clinically significant PVST: OR=40.415, 95%CI=3.895-419.295) and higher hemoglobin (any PVST: OR=0.974, 95%CI=0.953-0.996; MPV thrombosis >50%: OR=0.936, 95%CI=0.895-0.980; clinically significant PVST: OR=0.935, 95%CI=0.891-0.982) were the independent predictors of PVST. The prevalence of PVST was 13.3% (14/105) after excluding splenectomy. Higher hemoglobin was the only independent predictor of MPV thrombosis >50% (OR=0.952, 95%CI=0.909-0.997). No independent predictors of any PVST or clinically significant PVST were identified in multivariate analyses. Additionally, PVST patients who underwent splenectomy had a significantly higher proportion of clinically significant PVST but lower MELD score than those who did not undergo splenectomy. In all analyses, the in-hospital mortality was not significantly different between cirrhotic patient with and without PVST. CONCLUSIONS Splenectomy may increase by at least 10-fold the risk of PVST in liver cirrhosis independent of severity of liver dysfunction.
pH-jump induced α-helix folding of poly-L-glutamic acid

International Nuclear Information System (INIS)

Donten, Mateusz L.; Hamm, Peter

2013-01-01

Highlights: ► pH-jump as truly biomimetic tool to initiate non-equilibrium dynamics of biomolecules. ► Design criteria to widen the applicability of pH-jumps are developed. ► Folding of poly-L-Glu in dependence of starting pH, pH jump size and helix length. ► Length dependence provides strong evidence for a nucleation–propagation scenario. - Abstract: pH jumps are a truly biomimetic technique to initiate non-equilibrium dynamics of biomolecules. In this work, the pH jump induced α-helix folding of poly-L-glutamic acid is investigated upon proton release from o-nitrobenzaldehyde. The aim of this work is twofold: On the one hand, design criteria of pH jump experiments are discussed, on the other hand, the folding mechanism of poly-L-glutamic acid is clarified by probing the IR response of the amide I band. Its folding kinetics is studied in dependence of the starting pD, the size of the pD jump and the length of the helix. While no dependence on the first two parameters could be detected, the folding time varies from 0.6 μs to 1.8 μs for helix lengths of 20 residue to 440 residue, respectively. It converges to a long-length limit at about 50 residue, a result which is attributed to a nucleation–propagation mechanism
Structural, micro-structural and kinematic analyses of channel flow in the Karmostaj salt diapir in the Zagros foreland folded belt, Fars province, Iran

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Sarkarinejad, Khalil; Sarshar, Maryam Asadi; Adineh, Sadegh

2018-02-01

One of the main characteristic of the Zagros foreland fold-and-thrust belt and the Zagros foreland folded belt are wide distributions of surface extrusion from the Hormuz salt diapirs. This study examines the structure and kinematic of channel flow in the Karmostaj salt diapir in the southwestern part of the Zagros foreland folded belt. This diapir has reached the surface as a result of the channel flow mechanism and has extruded in the southern limb of the Kuh-Gach anticline which is an asymmetric décollement fold with convergence to the south. Structural and microstructural studies and quantitative finite strain (Rs) and kinematic vorticity number (Wk) analyses were carried out within this salt diapir and its namakier. This was in order to investigate the structural evolution in the salt diapiric system, the characteristics and mechanism of the salt flow and the distribution of flow regimes within the salt diapir and interaction of regional tectonics and salt diaprism. The extruded salt has developed a flow foliation sub-parallel to the remnant bedding recorded by different colors, a variety of internal folds including symmetrical and asymmetrical folds and interference fold patterns, shear zones, and boudins. These structures were used to analyze mechanisms and history of diapiric flow and extrusion. The microstructures, reveal various deformation mechanisms in various parts of salt diapir. The measurements of finite strain show that Rs values in the margin of salt diapir are higher than within its namakier which is consistent with the results of structural studies. Mean kinematic vorticity number (Wm) measured in steady state deformation of diapir and namakier is Wm = 0.45-0.48 ± 0.13. The estimated mean finite deformation (Wm) values indicate that 67.8% pure shear and 32.2% simple shear deformation were involved; the implications of which are discussed. The vorticity of flow indicates that in the early stage of growth, Poiseuille flow was the dominate
Nail-fold excision for the treatment of ingrown toenail in children.

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Haricharan, Ramanath N; Masquijo, Javier; Bettolli, Marcos

2013-02-01

To evaluate the effectiveness of the nail-fold excision procedure in children. Prospectively collected data on patients less than 18 years of age who underwent a nail-fold excision for symptomatic ingrown toenail were analyzed. Patients were seen in 2 centers and data collected included demographics, site of ingrown toenail, complications (including recurrence), patient satisfaction, and duration of follow-up. Overall, 67 procedures were performed on 50 patients between June 2009 and July 2011 at the 2 institutions. The mean age was 14 years (range, 9-18 years) and 30 were male patients. No recurrences were seen after a follow-up for a median of 14 months (range 6-28 months). Patients were very satisfied with the cosmetic outcomes. Six minor complications occurred, including 3 patients with bleeding requiring dressing change, 2 with excessive granulation tissue, and 1 with nail growth abnormality. The nail-fold excision technique is highly effective in the pediatric population, with no recurrence, excellent cosmesis, and very high patient satisfaction. Copyright © 2013 Mosby, Inc. All rights reserved.

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

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Saidi, Hiba; Erath, Byron D.

2015-11-01

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

International Nuclear Information System (INIS)

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

2010-01-01

The crystal structure of phenolic acid decarboxylase from B. pumilus strain UI-670 has been determined and refined at 1.69 Å resolution. The enzyme is a dimer, with each subunit adopting a β-barrel structure belonging to the lipocalin fold. The decarboxylation of phenolic acids, including ferulic and p-coumaric acids, to their corresponding vinyl derivatives is of importance in the flavouring and polymer industries. Here, the crystal structure of phenolic acid decarboxylase (PAD) from Bacillus pumilus strain UI-670 is reported. The enzyme is a 161-residue polypeptide that forms dimers both in the crystal and in solution. The structure of PAD as determined by X-ray crystallography revealed a β-barrel structure and two α-helices, with a cleft formed at one edge of the barrel. The PAD structure resembles those of the lipocalin-fold proteins, which often bind hydrophobic ligands. Superposition of structurally related proteins bound to their cognate ligands shows that they and PAD bind their ligands in a conserved location within the β-barrel. Analysis of the residue-conservation pattern for PAD-related sequences mapped onto the PAD structure reveals that the conservation mainly includes residues found within the hydrophobic core of the protein, defining a common lipocalin-like fold for this enzyme family. A narrow cleft containing several conserved amino acids was observed as a structural feature and a potential ligand-binding site
Characteristics of phonation onset in a two-layer vocal fold model.

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

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

2018-01-01

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

Directory of Open Access Journals (Sweden)

Michael Döllinger

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

Science.gov (United States)

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

2017-01-01

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

Science.gov (United States)

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

2007-05-22

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

Directory of Open Access Journals (Sweden)

Kaján László

2005-01-01

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

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Szabo, Quentin; Jost, Daniel; Chang, Jia-Ming; Cattoni, Diego I.; Papadopoulos, Giorgio L.; Bonev, Boyan; Sexton, Tom; Gurgo, Julian; Jacquier, Caroline; Nollmann, Marcelo; Bantignies, Frédéric; Cavalli, Giacomo

2018-01-01

Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains defined by combinations of specific chromatin marks. However, whether TADs are true physical units in each cell nucleus or whether they reflect statistical frequencies of measured interactions within cell populations is unclear. Using a combination of Hi-C, three-dimensional (3D) fluorescent in situ hybridization, super-resolution microscopy, and polymer modeling, we provide an integrative view of chromatin folding in Drosophila. We observed that repressed TADs form a succession of discrete nanocompartments, interspersed by less condensed active regions. Single-cell analysis revealed a consistent TAD-based physical compartmentalization of the chromatin fiber, with some degree of heterogeneity in intra-TAD conformations and in cis and trans inter-TAD contact events. These results indicate that TADs are fundamental 3D genome units that engage in dynamic higher-order inter-TAD connections. This domain-based architecture is likely to play a major role in regulatory transactions during DNA-dependent processes. PMID:29503869
Understanding ensemble protein folding at atomic detail

International Nuclear Information System (INIS)

Wallin, Stefan; Shakhnovich, Eugene I

2008-01-01

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

Science.gov (United States)

Modi, Vikash K

2012-01-01

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

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Garg, Dushyant K; Tomar, Rachana; Dhoke, Reema R; Srivastava, Ankit; Kundu, Bishwajit

2015-05-01

Here, we report the folding and assembly of a Pyrococcus furiosus-derived protein, L-asparaginase (PfA). PfA functions as a homodimer, with each monomer made of distinct N- and C-terminal domains. The purified individual domains as well as single Trp mutant of each domain were subjected to chemical denaturation/renaturation and probed by combination of spectroscopic, chromatographic, quenching and scattering techniques. We found that the N-domain acts like a folding scaffold and assists the folding of remaining polypeptide. The domains displayed sequential folding with the N-domain having higher thermodynamic stability. We report that the extreme thermal stability of PfA is due to the presence of high intersubunit associative forces supported by extensive H-bonding and ionic interactions network. Our results proved that folding cooperativity in a thermophilic, multisubunit protein is dictated by concomitant folding and association of constituent domains directly into a native quaternary structure. This report gives an account of the factors responsible for folding and stability of a therapeutically and industrially important protein.
Bilateral vocal fold paralysis and dysphagia secondary to diffuse idiopathic skeletal hyperostosis.

Science.gov (United States)

Allensworth, Jordan J; O'Dell, Karla D; Schindler, Joshua S

2017-01-01

Diffuse idiopathic skeletal hyperostosis (DISH) is an idiopathic spinal disease common in the elderly and characterized by flowing ossification and osteophyte formation along the spinal column. Cervical hyperostosis is capable of producing dysphagia, stridor, and airway obstruction; however, there are no extant reports of true paralysis of bilateral vocal folds in patients fulfilling the criteria for DISH. We report a case of a 61-year-old man presenting with dysphagia and dyspnea. Flexible laryngoscopy revealed bilateral true vocal fold paralysis. Cervical radiograph showed flowing ossification of the anterior longitudinal ligament with preservation of intervertebral disc height. Tracheotomy and cervical osteophytectomy were performed, after which the patient showed improved swallowing and speaking ability and was decannulated without complication. In the case presented, cervical osteophytectomy dramatically reversed bilateral vocal fold paralysis and dysphagia secondary to hyperostosis, thus negating the need for prolonged tracheostomy and feeding tube dependence. © 2016 Wiley Periodicals, Inc. Head Neck 39: E1-E3, 2017. © 2016 Wiley Periodicals, Inc.
Synchrotron radiation circular dichroism spectroscopy study of recombinant T β4 folding

Science.gov (United States)

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

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

Science.gov (United States)

Dominguez, Laura M; Tibbetts, Kathleen M; Simpson, C Blake

2017-02-01

To establish the rate of inflammatory reaction to hyaluronic acid (HA) in vocal fold injection augmentation, determine the most common presenting signs and symptoms, and propose an etiology. Retrospective chart review. Patients injected with HA over a 5-year period were reviewed to identify those who had a postoperative inflammatory reaction. Medical records were reviewed for patient demographic information, subjective complaints, Voice Handicap Index-10 (VHI-10) scores, medical intervention, and resolution time. Videolaryngostroboscopy examinations were also evaluated. A total of 186 patients (245 vocal folds) were injected with HA over a 5-year period, with a postoperative inflammatory reaction rate of 3.8%. The most common complaints in these patients were odynophagia, dysphonia, and dyspnea with vocal fold erythema, edema, and loss of pliability on videolaryngostroboscopy. All patients were treated with corticosteroids. Return of vocal fold vibration ranged from 3 weeks to 26 months, with VHI-10 scores normalizing in 50% of patients. This reaction may be a form of hypersensitivity related to small amounts of protein linked to HA. Alternatively, extravascular compression from the HA could lead to venous congestion of the vocal fold. The possibility of equipment contamination is also being investigated. Further studies are needed to determine the etiology and best treatment. 4 Laryngoscope, 2016 127:445-449, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.
Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.

Science.gov (United States)

Su, Tsung-Wei; Yang, Chao-Yu; Kao, Wen-Pin; Kuo, Bai-Jiun; Lin, Shan-Meng; Lin, Jung-Yaw; Lo, Yu-Chih; Lin, Su-Chang

2017-03-07

Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly. Copyright © 2017 Elsevier Ltd. All rights reserved.
A comparison of RNA folding measures

Directory of Open Access Journals (Sweden)

Gardner Paul P

2005-10-01

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

Science.gov (United States)

Eagen, Kyle P

2018-06-01

Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops. Compartmentation was not dependent on CTCF or cohesin. Hi-C contact maps represent the superimposition of CTCF/cohesin-dependent and -independent folding states. Copyright © 2018 Elsevier Ltd. All rights reserved.
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.

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

Science.gov (United States)

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

2017-04-01

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

Energy Technology Data Exchange (ETDEWEB)

McGrath, S.P., E-mail: steve.mcgrath@bbsrc.ac.u [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Mico, C.; Zhao, F.J.; Stroud, J.L. [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Zhang, H.; Fozard, S. [Division of Environmental Science, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

2010-10-15

Four plant species (oilseed rape, Brassica napus L.; red clover, Trifolium pratense L.; ryegrass, Lolium perenne L.; and tomato, Lycopersicon esculentum L.) were tested on ten soils varying widely in soil properties to assess molybdenum (Mo) toxicity. A larger range (66-fold-609-fold) of added Mo concentrations resulting in 50% inhibition of yield (ED{sub 50}) was found among soils than among plant species (2-fold-38-fold), which illustrated that the soils differed widely in the expression of Mo toxicity. Toxicity thresholds based on soil solution Mo narrowed the variation among soils compared to thresholds based on added Mo concentrations. We conclude that plant bioavailability of Mo in soil depends on Mo solubility, but this alone did not decrease the variability in observed toxicity enough to be used in risk assessment and that other soil properties influencing Mo toxicity to plants need to be considered. - Mo toxicity thresholds varied widely in different soils and therefore soil properties need to be taken into account in order to assess the risk of Mo exposure.
Structural and magnetic properties of Mn{sub 50}Fe{sub 50−x}Sn{sub x} (x=10, 15 and 20) alloys

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Tanmoy [LCMP, S.N. Bose National Centre for Basic Sciences, Kolkata 700106 (India); Agarwal, Sandeep [Haldia Institute of Technology, Haldia 721657 (India); Mukhopadhyay, P.K., E-mail: pkm@bose.res.in [LCMP, S.N. Bose National Centre for Basic Sciences, Kolkata 700106 (India)

2016-11-15

In this work we report measurements and comparisons of the structural, magnetic and transport properties of a series of Mn{sub 50}Fe{sub 50−x}Sn{sub x} alloys (x=10, 15 and 20). We found that while the lower Sn composition sample stabilized in β-Mn-type crystallographic phase, the higher Sn composition alloys contained both β-Mn-type as well as Mn{sub 3}Sn-type hexagonal DO{sub 19} phases. Through d.c. and a.c. magnetic property measurements we have established the existence of a ferromagnetic transition near room temperature followed by a spin reorientation at lower temperature in the Mn{sub 3}Sn-type crystallographic phase of the alloys. Our resistivity study also revealed an interesting behavior with negative temperature coefficient (TCR) in these alloys. - Highlights: • Mn{sub 50}Fe{sub 50-x}Sn{sub x} alloys were studied over a limited concentration range. • Lower Sn alloys behaved similar to ß-Mn alloys both structurally and magnetically. • Higher Sn alloys showed magnetic transitions similar to Mn{sub 3}Sn and Fe{sub 3}Sn. • Resistivity showed bad metallic behavior with negetive temperature coefficient.
Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

Science.gov (United States)

Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

2016-04-05

Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.
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.
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

Science.gov (United States)

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

2017-05-01

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

Science.gov (United States)

Park, Jae Woo; Hwang, Kun

2016-06-01

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

Science.gov (United States)

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

2014-05-01

We present a study that encompasses several software tools (iGIS©, ArcGIS©, Autocad©, etc.) and data (geological mapping, high resolution digital topographic data, high resolution aerial photographs, etc.) to create a detailed 3D geometric model of an active fault propagation growth fold. This 3D model clearly shows structural features of the analysed fold, as well as growth relationships and sedimentary patterns. The results obtained permit us to discuss the kinematics and structural evolution of the fold and the fault in time and space. The study fault propagation fold is the Crevillente syncline. This fold represents the northern limit of the Bajo Segura Basin, an intermontane basin in the Eastern Betic Cordillera (SE Spain) developed from upper Miocene on. 3D features of the Crevillente syncline, including growth pattern, indicate that limb rotation and, consequently, fault activity was higher during Messinian than during Tortonian; consequently, fault activity was also higher. From Pliocene on our data point that limb rotation and fault activity steadies or probably decreases. This in time evolution of the Crevillente syncline is not the same all along the structure; actually the 3D geometric model indicates that observed lateral heterogeneity is related to along strike variation of fault displacement.
The 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.
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.
A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 Å resolution

Science.gov (United States)

Zhang, Xing; Guo, Huatao; Jin, Lei; Czornyj, Elizabeth; Hodes, Asher; Hui, Wong H; Nieh, Angela W; Miller, Jeff F; Zhou, Z Hong

2013-01-01

Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like (‘Johnson’) for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering. DOI: http://dx.doi.org/10.7554/eLife.01299.001 PMID:24347545
Folding of non-Euclidean curved shells

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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.
The effect of vocal fold augmentation on cough symptoms in the presence of glottic insufficiency.

Science.gov (United States)

Litts, Juliana K; Fink, Daniel S; Clary, Matthew S

2017-10-08

To determine the effect of injection augmentation of the vocal folds on chronic cough symptoms in patients with glottic insufficiency. Medical records from 146 consecutive patients who underwent vocal fold injection augmentation by a fellowship-trained laryngologist between 2013 and 2015 were reviewed. Twenty-three patients (12 male) met inclusion criteria of a vocal fold augmentation injection, cough symptoms lasting more than 8 weeks, and glottic insufficiency as determined by shortened closed phase on stroboscopy. Exclusion criteria included lack of cough complaints, diagnosis of vocal fold immobility, previous history of vocal fold augmentation, and incomplete data sets. Data collected included age, gender, pre- and 1-month postinjection Cough Severity Index (CSI) scores, location of injection (unilateral or bilateral), and patient statement of percent change in symptoms that was recorded at 1-month postinjection visit. Paired t test indicated a significant decrease in CSI scores from pre- (m = 18.5) to 1-month postinjection (m = 12.1) (P = 0.004). Eighteen patients (78.2%) reported a 50% or greater improvement in cough symptoms at the 1-month postinjection visit. Injection augmentation of the vocal folds in the presence of glottic insufficiency appears to improve cough symptoms, as was reported by CSI in patients who are refractory to other medical and behavioral treatments. 4. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.
Improving Protein Fold Recognition by Deep Learning Networks

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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.
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.
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....
Spin-four N=7 W-Supergravity: S-fold and Double Copy Construction arXiv

CERN Document Server

Ferrara, Sergio

In the present investigation we consider the possibility of having new massive, higher spin W-supergravity theories, which do not exist as four-dimensional perturbative models. These theories are based on a double copy construction of two supersymmetric field theories, where at least one factor is given by a N=3 field theory, which is a non-perturbative S-fold of N=4 super Yang-Mills theory. In this way, we can obtain as S-folds a new N=7 (corresponding to 28 supercharges) W-supergravity and its N=7 W-superstring counterpart, which both do not exist as four-dimensional perturbative models with an (effective) Langrangian description. The resulting field resp. string theory does not contain any massless states, but instead a massive higher spin-four supermultiplet of the N=7 supersymmetry algebra. Furthermore we also construct a four-dimensional heterotic S-fold with N=3 supersymmetry. It again does not exist as perturbative heterotic string model and can be considered as the heterotic counterpart of the N=3 su...
Evaluation of the Grafted Fascia in the Vocal Fold of Dogs: A Histologic Study.

Science.gov (United States)

Carvalho, Eduardo G B; Pauna, Henrique F; Machado, Almiro J; Nicola, Ester M D; Altemani, Albina M A M; Crespo, Agrício N

2017-09-01

There is no consensus on the ideal graft for medialization surgery of the vocal folds in the literature. One of the most favorable proposals is the use of autologous fascia, which seems limited by the lack of information regarding the integration of grafted tissue. Our study aims to evaluate the degree of fully engrafted fascia integration in the vocal fold lamina propria of dogs. Fourteen adult mongrel dogs that underwent intravenous general anesthesia were selected and kept under spontaneous ventilation. A fascia lata fragment of 4 cm 2 was obtained from the right leg of each dog. The dogs underwent laryngoscopy; a 3 mm incision was made in the vocal process, next to the vestibular process, and the fascia was grafted into the right vocal fold. The left vocal fold was used as a control. The animals were divided into two groups: group A, evaluated after 2 months of the procedure, and group B, evaluated after 6 months of the procedure. Histologic analysis was made semiquantitatively regarding the presence of inflammatory reaction, fibrosis, and neovascularization. Our final studied group comprised 12 dogs. Microscopic examination of the larynx revealed the absence of any detectable inflammation in the incision site. The lamina propria of the grafted vocal fold showed identifiable compact, thick, and eosinophilic collagen bands. The surrounding tissue showed thin collagen bands with some organization, similar to the contralateral vocal fold. The grafted fascia integrates into the vocal fold lamina propria and seems not to cause inflammatory reaction response. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Corrosion behavior of amorphous and crystalline Cu50Ti50 and Cu50Zr50 alloys

International Nuclear Information System (INIS)

Naka, M.; Hoshimoto, K.; Masumoto, T.

1978-01-01

Corrosion rates and anodic polarization curves of amorphous and crystalline Cu 50 Ti 50 and Cu 50 Zr 50 alloys have been examined in various acidic, neutral and alkaline solutions. The amorphous alloys are very stable in acidic and alkaline solutions, but unstable in agressive chloride solutions. The corrosion resistance of these amorphous alloys is higher than that of the crystallized alloys. The high corrosion resistance of amorphous alloys is attributable to the high chemical homogeneity of amorphous alloys without localized crystalline defects such as precipitates, segregates, grain boundaries, etc. Metalloid elements play an important role in the corrosion behavior of amorphous alloys; the addition of phosphorus to amorphous Cu-Ti alloy greatly increases the corrosion resistance, even in 1N HCl. (Auth.)
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...
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
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.
Patterns of Participation and Motivation in Folding@home: The Contribution of Hardware Enthusiasts and Overclockers

Directory of Open Access Journals (Sweden)

Vickie Curtis

2018-04-01

Full Text Available Folding@home is a distributed computing project in which participants run protein folding simulations on their computers. Participants complete work units and are awarded points for their contribution. An investigation into motivations to participate and patterns of participation revealed the significant contribution of a sub-community composed of individuals who custom-build computers to maximise their processing power. These individuals, known as “overclockers” or “hardware enthusiasts,” use distributed computing projects such as Folding@home to benchmark their modified computers and to compete with one another to see who can process the greatest number of project work units. Many are initially drawn to the project to learn about computer hardware from other overclockers and to compete for points. However, once they learn more about the scientific outputs of Folding@home, some participants become more motivated by the desire to contribute to scientific research. Overclockers form numerous online communities where members collaborate and help each other maximise their computing output. They invest heavily in their computers and process the majority of Folding@home’s simulations, thus providing an invaluable (and free resource.
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 \
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
Vocal Fold Immobility due to Birth Trauma: A Systematic Review and Pooled Analysis.

Science.gov (United States)

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

2017-12-01

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

International Nuclear Information System (INIS)

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

2004-01-01

The paper presents a method for analysis of stomach folds pattern in abdominal X-ray CT images. Many stomach cancers have local concentration of folds at cancer lesions. Therefore, in stomach diagnosis, it is very important to evaluate quantitatively such fold concentration. In this paper, a method for calculation of concentration index for line figure on a curved surface is proposed first. Then, using this method a processing procedure for detection of stomach cancer from an abdominal X-ray CT image is developed. In the experiment using practical X-ray CT images, it is shown that by the proposed procedure, higher values of concentration index are obtained at cancer area. (author)
Comparison of passively transferred antibodies in bighorn and domestic lambs reveals one factor in differential susceptibility of these species to Mannheimia haemolytica-induced pneumonia.

Science.gov (United States)

Herndon, Caroline N; Shanthalingam, Sudarvili; Knowles, Donald P; Call, Douglas R; Srikumaran, Subramaniam

2011-07-01

Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries (domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) against M. haemolytica provides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed against M. haemolytica in the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens of M. haemolytica and approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia.
Structural proteomics of minimal organisms: conservation ofprotein fold usage and evolutionary implications

Energy Technology Data Exchange (ETDEWEB)

Chandonia, John-Marc; Kim, Sung-Hou

2006-03-15

Background: Determining the complete repertoire of proteinstructures for all soluble, globular proteins in a single organism hasbeen one of the major goals of several structural genomics projects inrecent years. Results: We report that this goal has nearly been reachedfor several "minimal organisms"--parasites or symbionts with reducedgenomes--for which over 95 percent of the soluble, globular proteins maynow be assigned folds, overall 3-D backbone structures. We analyze thestructures of these proteins as they relate to cellular functions, andcompare conservation off old usage between functional categories. We alsocompare patterns in the conservation off olds among minimal organisms andthose observed between minimal organisms and other bacteria. Conclusion:We find that proteins performing essential cellular functions closelyrelated to transcription and translation exhibit a higher degree ofconservation in fold usage than proteins in other functional categories.Folds related to transcription and translation functional categories werealso over represented in minimal organisms compared to otherbacteria.
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
Higher Capacity, Improved Conductive Matrix VB2/Air Batteries (Postprint)

Science.gov (United States)

2016-02-18

gravimetric capacity five-fold higher than the 2 e− oxidation of the widely used zinc alkaline anode. One challenge to the implementation of VB2/air...VB2 has an intrinsic gravimetric capacity five fold higher than the 2 e− oxidation of the widely used zinc alkaline anode. One challenge to the...to ameliorate this effect through advanced anode configurations with an improved conductive matrix. Materials and Methods Anodes were prepared using
Developing guinea pig brain as a model for cortical folding.

Science.gov (United States)

Hatakeyama, Jun; Sato, Haruka; Shimamura, Kenji

2017-05-01

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

Science.gov (United States)

Nakapelyukh, Mykhaylo; Bubniak, Ihor; Bubniak, Andriy; Jonckheere, Raymond; Ratschbacher, Lothar

2018-01-01

The Carpathians are part of the Alpine-Carpathian-Dinaridic orogen surrounding the Pannonian basin. Their Ukrainian part constitutes an ancient subduction-accretion complex that evolved into a foreland fold-thrust belt with a shortening history that was perpendicular to the orogenic strike. Herein, we constrain the evolution of the Ukrainian part of the Carpathian fold-thrust belt by apatite fission-track dating of sedimentary and volcanic samples and cross-section balancing and restoration. The apatite fission-track ages are uniform in the inner―southwestern part of the fold-thrust belt, implying post-shortening erosion since 12-10 Ma. The ages in the leading and trailing edges record provenance, i.e., sources in the Trans-European suture zone and the Inner Carpathians, respectively, and show that these parts of the fold-thrust were not heated to more than 100 °C. Syn-orogenic strata show sediment recycling: in the interior of the fold-thrust belt―the most thickened and most deeply eroded nappes―the apatite ages were reset, eroded, and redeposited in the syn-orogenic strata closer to the fore- and hinterland; the lag times are only a few million years. Two balanced cross sections, one constructed for this study and based on field and subsurface data, reveal an architecture characterized by nappe stacks separated by high-displacement thrusts; they record 340-390 km shortening. A kinematic forward model highlights the fold-thrust belt evolution from the pre-contractional configuration over the intermediate geometries during folding and thrusting and the post-shortening, erosional-unloading configuration at 12-10 Ma to the present-day geometry. Average shortening rates between 32-20 Ma and 20-12 Ma amounted to 13 and 21 km/Ma, respectively, implying a two-phased deformation of the Ukrainian fold-thrust belt.
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.
Evaluation of 18F-fluorodeoxyglucose accumulation in the larynx of unilateral vocal fold paralysis cases

International Nuclear Information System (INIS)

Nimura, Yoshitsugu; Hayashi, Ibuki; Higashikawa, Masahiko; Okamura, Terue; Nakai, Ken; Ichihara, Kengo

2011-01-01

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is employed to decide the treatment strategy for malignant tumors clinically. Meanwhile, glucose metabolism is enhanced in the exercise of muscles. Because vocal folds always conduct glucose metabolism by phonation and swallowing, physiological accumulation of FDG may be found in the normal larynx. In this study we examined FDG accumulation in the larynx of patients with unilateral vocal fold paralysis established by endoscope. FDG-PET/CT was taken one hour after the FDG administration (early image) and again two hours later (delayed image). All patients had no chance to utter after the FDG administration. In 25 of the 28 patients with unilateral vocal fold paralysis, standardized uptake value (SUV) max was higher, by visual inspection, in the normal side of the larynx than in the paralyzed side. None of the 3 patients in whom no accumulation was seen on the non-paralyzed side had malignant disease. In both images, SUV max of the normal side was significantly higher than paralyzed side (p<0.01). In the delayed images, accumulation of FDG was significantly higher than that in the early images (p<0.01). We believe that strong FDG accumulation in the normal side of the larynx of patients with unilateral vocal fold paralysis may owe to high glucose metabolism of the vocal muscles from muscle hyperkinesis. We conclude that unilateral accumulation in the larynx suggests not only cancer of that same side of the larynx but also paralysis of the other side. (author)
Augmentation surgery on the cartilaginous portion of the vocal fold in a patient with cricoarytenoid joint ankylosis.

Science.gov (United States)

Fukahori, Mioko; Chitose, Shun-Ichi; Sato, Kiminori; Kamimura, Hiroyuki; Sato, Kiminobu; On, Ririko; Umeno, Hirohito

2018-01-04

Surgical management of cricoarytenoid joint (CAJ) ankylosis is challenging and has the risk of worsening voice quality. In the present case, augmentation surgery was performed on the cartilaginous portion of the vocal fold in a patient with CAJ ankylosis. A 24-year-old man sustained blunt trauma to the anterior neck three years prior to developing severe breathiness. Posterior glottal insufficiency resulting from lateral fixation of the right vocal fold was observed during phonation under laryngoscopy. In addition, electromyography and CT scan revealed severe ankylosis of the right CAJ. Type I thyroplasty performed on the right vocal fold did not improve postoperative vocal function. Therefore, augmentation surgery on the cartilaginous portion of the right vocal fold was performed via endolaryngeal microsurgery under general anesthesia with jet ventilation. A piece of temporalis fascia was autotransplanted into the submucosal space created at the posterior cartilaginous portion of the right vocal fold. This resulted in the narrowing of the posterior glottal gap during phonation, leading to improvement in hoarseness. Microsurgical management with autologous fascia augmentation of the cartilaginous portion of the vocal fold can be effective in patients with lateral vocal fold fixation due to CAJ ankylosis. Copyright © 2017 Elsevier B.V. All rights reserved.
Vocal fold paresis - a debilitating and underdiagnosed condition.

Science.gov (United States)

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

2017-07-01

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

Science.gov (United States)

Lignell, Martin; Becker, Hans-Christian

2010-01-01

Abstract We have studied the association of a helix-loop-helix peptide scaffold carrying a benzenesulfonamide ligand to carbonic anhydrase using steady-state and time-resolved fluorescence spectroscopy. The helix-loop-helix peptide, developed for biosensing applications, is labeled with the fluorescent probe dansyl, which serves as a polarity-sensitive reporter of the binding event. Using maximum entropy analysis of the fluorescence lifetime of dansyl at 1:1 stoichiometry reveals three characteristic fluorescence lifetime groups, interpreted as differently interacting peptide/protein structures. We characterize these peptide/protein complexes as mostly bound but unfolded, bound and partly folded, and strongly bound and folded. Furthermore, analysis of the fluorescence anisotropy decay resulted in three different dansyl rotational correlation times, namely 0.18, 1.2, and 23 ns. Using the amplitudes of these times, we can correlate the lifetime groups with the corresponding fluorescence anisotropy component. The 23-ns rotational correlation time, which appears with the same amplitude as a 17-ns fluorescence lifetime, shows that the dansyl fluorophore follows the rotational diffusion of carbonic anhydrase when it is a part of the folded peptide/protein complex. A partly folded and partly hydrated interfacial structure is manifested in an 8-ns dansyl fluorescence lifetime and a 1.2-ns rotational correlation time. This structure, we believe, is similar to a molten-globule-like interfacial structure, which allows segmental movement and has a higher degree of solvent exposure of dansyl. Indirect excitation of dansyl on the helix-loop-helix peptide through Förster energy transfer from one or several tryptophans in the carbonic anhydrase shows that the helix-loop-helix scaffold binds to a tryptophan-rich domain of the carbonic anhydrase. We conclude that binding of the peptide to carbonic anhydrase involves a transition from a disordered to an ordered structure of the
Higher-order structure of Saccharomyces cerevisiae chromatin

International Nuclear Information System (INIS)

Lowary, P.T.; Widom, J.

1989-01-01

We have developed a method for partially purifying chromatin from Saccharomyces cerevisiae (baker's yeast) to a level suitable for studies of its higher-order folding. This has required the use of yeast strains that are free of the ubiquitous yeast killer virus. Results from dynamic light scattering, electron microscopy, and x-ray diffraction show that the yeast chromatin undergoes a cation-dependent folding into 30-nm filaments that resemble those characteristic of higher-cell chromatin; moreover, the packing of nucleosomes within the yeast 30-nm filaments is similar to that of higher cells. These results imply that yeast has a protein or protein domain that serves the role of the histone H 1 found in higher cells; physical and genetic studies of the yeast activity could help elucidate the structure and function of H 1. Images of the yeast 30-nm filaments can be used to test crossed-linker models for 30-nm filament structure
Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation

DEFF Research Database (Denmark)

Garcia-Pino, Abel; Christensen-Dalsgaard, Mikkel; Wyns, Lode

2008-01-01

Prokaryotic toxin-antitoxin modules are involved in major physiological events set in motion under stress conditions. The toxin Doc (death on curing) from the phd/doc module on phage P1 hosts the C-terminal domain of its antitoxin partner Phd (prevents host death) through fold complementation....... This Phd domain is intrinsically disordered in solution and folds into an alpha-helix upon binding to Doc. The details of the interactions reveal the molecular basis for the inhibitory action of the antitoxin. The complex resembles the Fic (filamentation induced by cAMP) proteins and suggests a possible......-antitoxin locus for its action in vivo....
Comparison of Passively Transferred Antibodies in Bighorn and Domestic Lambs Reveals One Factor in Differential Susceptibility of These Species to Mannheimia haemolytica-Induced Pneumonia ▿

Science.gov (United States)

Herndon, Caroline N.; Shanthalingam, Sudarvili; Knowles, Donald P.; Call, Douglas R.; Srikumaran, Subramaniam

2011-01-01

Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries (domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) against M. haemolytica provides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed against M. haemolytica in the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens of M. haemolytica and approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia. PMID:21613459
Two states or not two states: Single-molecule folding studies of protein L

Science.gov (United States)

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

2018-03-01

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

Directory of Open Access Journals (Sweden)

Fujiwara Kazuo

2012-08-01

Full Text Available Abstract Background A large number of studies have been carried out to obtain amino acid propensities for α-helices and β-sheets. The obtained propensities for α-helices are consistent with each other, and the pair-wise correlation coefficient is frequently high. On the other hand, the β-sheet propensities obtained by several studies differed significantly, indicating that the context significantly affects β-sheet propensity. Results We calculated amino acid propensities for α-helices and β-sheets for 39 and 24 protein folds, respectively, and addressed whether they correlate with the fold. The propensities were also calculated for exposed and buried sites, respectively. Results showed that α-helix propensities do not differ significantly by fold, but β-sheet propensities are diverse and depend on the fold. The propensities calculated for exposed sites and buried sites are similar for α-helix, but such is not the case for the β-sheet propensities. We also found some fold dependence on amino acid frequency in β-strands. Folds with a high Ser, Thr and Asn content at exposed sites in β-strands tend to have a low Leu, Ile, Glu, Lys and Arg content (correlation coefficient = −0.90 and to have flat β-sheets. At buried sites in β-strands, the content of Tyr, Trp, Gln and Ser correlates negatively with the content of Val, Ile and Leu (correlation coefficient = −0.93. "All-β" proteins tend to have a higher content of Tyr, Trp, Gln and Ser, whereas "α/β" proteins tend to have a higher content of Val, Ile and Leu. Conclusions The α-helix propensities are similar for all folds and for exposed and buried residues. However, β-sheet propensities calculated for exposed residues differ from those for buried residues, indicating that the exposed-residue fraction is one of the major factors governing amino acid composition in β-strands. Furthermore, the correlations we detected suggest that amino acid composition is related to folding
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.
Improving medical diagnosis reliability using Boosted C5.0 decision tree empowered by Particle Swarm Optimization.

Science.gov (United States)

Pashaei, Elnaz; Ozen, Mustafa; Aydin, Nizamettin

2015-08-01

Improving accuracy of supervised classification algorithms in biomedical applications is one of active area of research. In this study, we improve the performance of Particle Swarm Optimization (PSO) combined with C4.5 decision tree (PSO+C4.5) classifier by applying Boosted C5.0 decision tree as the fitness function. To evaluate the effectiveness of our proposed method, it is implemented on 1 microarray dataset and 5 different medical data sets obtained from UCI machine learning databases. Moreover, the results of PSO + Boosted C5.0 implementation are compared to eight well-known benchmark classification methods (PSO+C4.5, support vector machine under the kernel of Radial Basis Function, Classification And Regression Tree (CART), C4.5 decision tree, C5.0 decision tree, Boosted C5.0 decision tree, Naive Bayes and Weighted K-Nearest neighbor). Repeated five-fold cross-validation method was used to justify the performance of classifiers. Experimental results show that our proposed method not only improve the performance of PSO+C4.5 but also obtains higher classification accuracy compared to the other classification methods.
Adenovirus fibre shaft sequences fold into the native triple beta-spiral fold when N-terminally fused to the bacteriophage T4 fibritin foldon trimerisation motif.

Science.gov (United States)

Papanikolopoulou, Katerina; Teixeira, Susana; Belrhali, Hassan; Forsyth, V Trevor; Mitraki, Anna; van Raaij, Mark J

2004-09-03

Adenovirus fibres are trimeric proteins that consist of a globular C-terminal domain, a central fibrous shaft and an N-terminal part that attaches to the viral capsid. In the presence of the globular C-terminal domain, which is necessary for correct trimerisation, the shaft segment adopts a triple beta-spiral conformation. We have replaced the head of the fibre by the trimerisation domain of the bacteriophage T4 fibritin, the foldon. Two different fusion constructs were made and crystallised, one with an eight amino acid residue linker and one with a linker of only two residues. X-ray crystallographic studies of both fusion proteins shows that residues 319-391 of the adenovirus type 2 fibre shaft fold into a triple beta-spiral fold indistinguishable from the native structure, although this is now resolved at a higher resolution of 1.9 A. The foldon residues 458-483 also adopt their natural structure. The intervening linkers are not well ordered in the crystal structures. This work shows that the shaft sequences retain their capacity to fold into their native beta-spiral fibrous fold when fused to a foreign C-terminal trimerisation motif. It provides a structural basis to artificially trimerise longer adenovirus shaft segments and segments from other trimeric beta-structured fibre proteins. Such artificial fibrous constructs, amenable to crystallisation and solution studies, can offer tractable model systems for the study of beta-fibrous structure. They can also prove useful for gene therapy and fibre engineering applications.
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.
Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

Science.gov (United States)

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

2018-04-01

The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Animal experiments with controls. Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. NA. Laryngoscope, 128:E150-E156, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.
Characterization of fold defects in AZ91D and AE42 magnesium alloy permanent mold castings

International Nuclear Information System (INIS)

Bichler, L.; Ravindran, C.

2010-01-01

Casting premium-quality magnesium alloy components for aerospace and automotive applications poses unique challenges. Magnesium alloys are known to freeze rapidly prior to filling a casting cavity, resulting in misruns and cold shuts. In addition, melt oxidation, solute segregation and turbulent metal flow during casting contribute to the formation of fold defects. In this research, formation of fold defects in AZ91D and AE42 magnesium alloys cast via the permanent mold casting process was investigated. Computer simulations of the casting process predicted the development of a turbulent metal flow in a critical casting region with abrupt geometrical transitions. SEM and light optical microscopy examinations revealed the presence of folds in this region for both alloys. However, each alloy exhibited a unique mechanism responsible for fold formation. In the AZ91D alloy, melt oxidation and velocity gradients in the critical casting region prevented fusion of merging metal front streams. In the AE42 alloy, limited solubility of rare-earth intermetallic compounds in the α-Mg phase resulted in segregation of Al 2 RE particles at the leading edge of a metal front and created microstructural inhomogeneity across the fold.
Acute contained ruptured aortic aneurysm presenting as left vocal fold immobility.

Science.gov (United States)

Gnagi, Sharon H; Howard, Brittany E; Hoxworth, Joseph M; Lott, David G

2015-01-01

Objective. To recognize intrathoracic abnormalities, including expansion or rupture of aortic aneurysms, as a source of acute onset vocal fold immobility. Methods. A case report and review of the literature. Results. An 85-year-old female with prior history of an aortic aneurysm presented to a tertiary care facility with sudden onset hoarseness. On laryngoscopy, the left vocal fold was immobile in the paramedian position. A CT scan obtained that day revealed a new, large hematoma surrounding the upper descending aortic stent graft consistent with an acute contained ruptured aortic aneurysm. She was referred to the emergency department for evaluation and treatment by vascular surgery. She was counseled regarding surgical options and ultimately decided not to pursue further treatment. Her vocal fold immobility was subsequently treated via office-based injection medialization two weeks after presentation and again 5 months after the initial injection which dramatically improved her voice. Follow-up CT scan at 8 months demonstrated a reduction of the hematoma. The left vocal cord remains immobile to date. Conclusion. Ortner's syndrome, or cardiovocal syndrome, is hoarseness secondary to left recurrent laryngeal nerve palsy caused by cardiovascular pathology. It is a rare condition and, while typically presenting gradually, may also present with acute symptomatology.

Acute Contained Ruptured Aortic Aneurysm Presenting as Left Vocal Fold Immobility

Directory of Open Access Journals (Sweden)

Sharon H. Gnagi

2015-01-01

Full Text Available Objective. To recognize intrathoracic abnormalities, including expansion or rupture of aortic aneurysms, as a source of acute onset vocal fold immobility. Methods. A case report and review of the literature. Results. An 85-year-old female with prior history of an aortic aneurysm presented to a tertiary care facility with sudden onset hoarseness. On laryngoscopy, the left vocal fold was immobile in the paramedian position. A CT scan obtained that day revealed a new, large hematoma surrounding the upper descending aortic stent graft consistent with an acute contained ruptured aortic aneurysm. She was referred to the emergency department for evaluation and treatment by vascular surgery. She was counseled regarding surgical options and ultimately decided not to pursue further treatment. Her vocal fold immobility was subsequently treated via office-based injection medialization two weeks after presentation and again 5 months after the initial injection which dramatically improved her voice. Follow-up CT scan at 8 months demonstrated a reduction of the hematoma. The left vocal cord remains immobile to date. Conclusion. Ortner’s syndrome, or cardiovocal syndrome, is hoarseness secondary to left recurrent laryngeal nerve palsy caused by cardiovascular pathology. It is a rare condition and, while typically presenting gradually, may also present with acute symptomatology.
Single-molecule folding mechanism of an EF-hand neuronal calcium sensor

DEFF Research Database (Denmark)

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

2013-01-01

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

Science.gov (United States)

Park, Sangtak; Khater, Mahmoud; Effa, David; Abdel-Rahman, Eihab; Yavuz, Mustafa

2017-08-01

This paper presents a new detection method of cyclic-fold bifurcations in electrostatic MEMS transducers based on a variant of the harmonic detection of resonance method. The electrostatic transducer is driven by an unbiased harmonic signal at half its natural frequency, ω a = 1/2 ω o . The response of the transducer consists of static displacement and a series of harmonics at 2 ω a , 4 ω a , and so on. Its motion-induced current is shifted by the excitation frequency, ω a , to appear at 3 ω a , 5 ω a , and higher odd harmonics, providing higher sensitivity to the measurement of harmonic motions. With this method, we successfully detected the variation in the location of the cyclic-fold bifurcation of an encapsulated electrostatic MEMS transducer. We also detected a regime of tapping mode motions subsequent to the bifurcation.
Detection of cyclic-fold bifurcation in electrostatic MEMS transducers by motion-induced current

International Nuclear Information System (INIS)

Park, Sangtak; Abdel-Rahman, Eihab; Khater, Mahmoud; Effa, David; Yavuz, Mustafa

2017-01-01

This paper presents a new detection method of cyclic-fold bifurcations in electrostatic MEMS transducers based on a variant of the harmonic detection of resonance method. The electrostatic transducer is driven by an unbiased harmonic signal at half its natural frequency, ω a = 1/2 ω o . The response of the transducer consists of static displacement and a series of harmonics at 2 ω a , 4 ω a , and so on. Its motion-induced current is shifted by the excitation frequency, ω a , to appear at 3 ω a , 5 ω a , and higher odd harmonics, providing higher sensitivity to the measurement of harmonic motions. With this method, we successfully detected the variation in the location of the cyclic-fold bifurcation of an encapsulated electrostatic MEMS transducer. We also detected a regime of tapping mode motions subsequent to the bifurcation. (paper)
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
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.
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.
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.
Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures

International Nuclear Information System (INIS)

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

2015-01-01

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

Science.gov (United States)

Smith, Marshall E; Roy, Nelson; Stoddard, Kelly

2008-09-01

To assess the outcomes of management of unilateral vocal fold paralysis by ansa-RLN reinnervation in a series of patients ages 12-21. Clinical outcomes study. Six consecutive adolescents and young adults (ages 12-21 years) seeking treatment for unilateral vocal fold paralysis and glottal incompetence underwent ansa-RLN neurorraphy. Pre- and post-operative voice recordings acquired at least 1 year following surgery were submitted to acoustic and perceptual analysis. Patient-based measures were also taken. Mean perceptual visual analogue scale rating of dysphonia severity (0mm=profoundly abnormal voice, 100mm=completely normal voice) improved from 50mm pre-operatively to 82mm post-operatively. Mean maximum phonation time improved from 6.5s to 13.2s. Pitch and dynamic range were also observed to improve. Global self-ratings of voice function (0-100%) increased from 31.2% to 81.6% of normal. Ansa-RLN reinnervation is an effective treatment option for adolescents and young adults with unilateral vocal fold paralysis. The procedure has the potential to improve vocal function substantially, especially in those with isolated paralysis of the recurrent laryngeal nerve. The procedure alleviates the disadvantages associated with other surgical options for this age group.
A dominant TRPV4 variant underlies osteochondrodysplasia in Scottish fold cats.

Science.gov (United States)

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

2016-08-01

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

Science.gov (United States)

Wu, Johnny C; Gardner, David P; Ozer, Stuart; Gutell, Robin R; Ren, Pengyu

2009-08-28

The accurate prediction of the secondary and tertiary structure of an RNA with different folding algorithms is dependent on several factors, including the energy functions. However, an RNA higher-order structure cannot be predicted accurately from its sequence based on a limited set of energy parameters. The inter- and intramolecular forces between this RNA and other small molecules and macromolecules, in addition to other factors in the cell such as pH, ionic strength, and temperature, influence the complex dynamics associated with transition of a single stranded RNA to its secondary and tertiary structure. Since all of the factors that affect the formation of an RNAs 3D structure cannot be determined experimentally, statistically derived potential energy has been used in the prediction of protein structure. In the current work, we evaluate the statistical free energy of various secondary structure motifs, including base-pair stacks, hairpin loops, and internal loops, using their statistical frequency obtained from the comparative analysis of more than 50,000 RNA sequences stored in the RNA Comparative Analysis Database (rCAD) at the Comparative RNA Web (CRW) Site. Statistical energy was computed from the structural statistics for several datasets. While the statistical energy for a base-pair stack correlates with experimentally derived free energy values, suggesting a Boltzmann-like distribution, variation is observed between different molecules and their location on the phylogenetic tree of life. Our statistical energy values calculated for several structural elements were utilized in the Mfold RNA-folding algorithm. The combined statistical energy values for base-pair stacks, hairpins and internal loop flanks result in a significant improvement in the accuracy of secondary structure prediction; the hairpin flanks contribute the most.
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.
Air pulse deformation measurement: a preliminary method for noninvasive vocal fold pliability analysis.

Science.gov (United States)

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

2011-01-01

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

Science.gov (United States)

Tabaee, Abtin; Murry, Thomas; Zschommler, Anne; Desloge, Rosemary B

2005-04-01

The objective was to examine the incidence and pathophysiology of aspiration in patients with unilateral vocal fold immobility presenting with dysphagia. Retrospective review of flexible endoscopic evaluation of swallowing with sensory testing (FEESST) data and medical records in two tertiary medical care centers. The data for all patients with unilateral vocal fold immobility who underwent FEESST between 2000 and 2003 were reviewed. Eighty-one patients (45 male and 36 female patients) were included in the study. The mean age was 59 years. The most common causes or origins were iatrogenic (42%), malignancy (23%), and neurological (18%). The immobility was left-sided in 59% of patients. A majority of the patients exhibited laryngeal edema/erythema (90%), difficulty with secretions (60%), and decreased laryngopharyngeal sensation (83%). The laryngeal adductor reflex was absent in 34% of the patients. An aspiration rate of 35% was detected with thin liquids. Trials of purees revealed a 76% rate of pooling, 44% rate of spillage, 32% rate of penetration, 18% rate of aspiration, and 24% rate of regurgitation. Rates of penetration and aspiration with purees were significantly higher in patients who had decreased laryngopharyngeal sensation, absent pharyngeal squeeze, and absent laryngeal adductor reflex. Dysphagia in patients with unilateral vocal fold immobility is demonstrated during FEESST by pooling, spillage, penetration, and aspiration. The pathophysiology of dysphagia is multifactorial with decreased sensation and limitation of airway protective mechanisms both acting as contributing factors.
Oral and vocal fold diadochokinesis in dysphonic women

Directory of Open Access Journals (Sweden)

Talita Louzada

2011-12-01

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

Energy Technology Data Exchange (ETDEWEB)

Lu, Jun; Wu, Ruiying; Adkins, Joshua N.; Joachimiak, Andrzej; Glover, Mark

2014-09-16

In the F-family of conjugative plasmids, TraJ is an essential transcriptional activator of the tra operon that encodes most of the proteins required for conjugation. Here we report for the first time the X-ray crystal structures of the TraJ N-terminal regions from the prototypic F plasmid (TraJF11-130) and from the Salmonella virulence plasmid pSLT (TraJpSLT 1-128). Both proteins form similar homodimeric Per-ARNT-Sim (PAS) fold structures. Mutational analysis reveals that the observed dimeric interface is critical for TraJF transcriptional activation, indicating that dimerization of TraJ is required for its in vivo function. An artificial ligand (oxidized dithiothreitol) occupies a cavity in the TraJF dimer interface, while a smaller cavity in corresponding region of the TraJpSLT structure lacks a ligand. Gas chromatography/mass spectrometry-electron ionization analysis of dithiothreitol-free TraJF suggests indole may be the natural TraJ ligand; however, disruption of the indole biosynthetic pathway does not affect TraJF function. Heterologous PAS domains from pSLT and R100 TraJ can functionally replace the TraJF PAS domain, suggesting that TraJ allelic specificity is mediated by the region C-terminal to the PAS domain.
Influence of yarn folding on UV protection properties of hemp knitted fabrics

Directory of Open Access Journals (Sweden)

Kocić Ana A.

2016-01-01

fabrics construction and physical properties were also determined. Bearing in mind that plain knitted fabrics are particularly susceptible to relaxation, they were subjected to relaxation and shrinkage by wetting process, and testing procedure was repeated on the water-treated samples. The results obtained indicated that the folding operation influences UV protection properties of knitted fabrics through an influence on a loop configuration, i.e. the fabric openness. Relaxation and shrinkage of the knitted fabrics due to wet relaxation caused the reduction of macro-porosity increasing the UPF of the knitted fabrics. Although the knitted fabric produced from single hemp yarn was characterized by higher UPF, the UVR transmittance of the folded hemp yarn knitted fabric after wet relaxation placed it in the “excellent UV protection category” (according to European Standard EN 13758-2. This fact together with the better thermal comfort manifested itself in higher air permeability, confirmed the potential of folding operation in terms of UV protection properties of textile materials.
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.

50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

Science.gov (United States)

Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

2016-02-01

The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated
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...
Melody discrimination and protein fold classification

Directory of Open Access Journals (Sweden)

Robert P. Bywater

2016-10-01

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

DEFF Research Database (Denmark)

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

2012-01-01

This paper treats applications of cross-laminated timber (CLT) in structural systems for folded façade solutions. Previous work on CLT-based systems for folded roofs has shown a widening range of structural possibilities to develop timber-based shells. Geometric and material properties play...... CLT-based systems, which are studied and analysed by using a combination of digital tools for structural and environmental design and analysis. The results show gainful, rational properties of folded systems and beneficial effects from an integration of architectural and environmental performance...... criteria in the design of CLT-based façades....
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).
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.
Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

Science.gov (United States)

Ren, Weitong; Ji, Dongqing; Xu, Xiulian

2018-01-01

The HIV-1 nucleocapsid 7 (NCp7) plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3) recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.
Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

Directory of Open Access Journals (Sweden)

Weitong Ren

Full Text Available The HIV-1 nucleocapsid 7 (NCp7 plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3 recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.
Orogen-transverse tectonic window in the Eastern Himalayan fold belt: A superposed buckling model

Science.gov (United States)

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

2014-09-01

The Eastern Lesser Himalayan fold-thrust belt is punctuated by a row of orogen-transverse domal tectonic windows. To evaluate their origin, a variety of thrust-stack models have been proposed, assuming that the crustal shortening occurred dominantly by brittle deformations. However, the Rangit Window (RW) in the Darjeeling-Sikkim Himalaya (DSH) shows unequivocal structural imprints of ductile deformations of multiple episodes. Based on new structural maps, coupled with outcrop-scale field observations, we recognize at least four major episodes of folding in the litho-tectonic units of DSH. The last episode has produced regionally orogen-transverse upright folds (F4), the interference of which with the third-generation (F3) orogen-parallel folds has shaped the large-scale structural patterns in DSH. We propose a new genetic model for the RW, invoking the mechanics of superposed buckling in the mechanically stratified litho-tectonic systems. We substantiate this superposed buckling model with results obtained from analogue experiments. The model explains contrasting F3-F4 interferences in the Lesser Himalayan Sequence (LHS). The lower-order (terrain-scale) folds have undergone superposed buckling in Mode 1, producing large-scale domes and basins, whereas the RW occurs as a relatively higher-order dome nested in the first-order Tista Dome. The Gondwana and the Proterozoic rocks within the RW underwent superposed buckling in Modes 3 and 4, leading to Type 2 fold interferences, as evident from their structural patterns.
Sequencing of 50 human exomes reveals adaptation to high altitude

DEFF Research Database (Denmark)

Yi, Xin; Liang, Yu; Huerta-Sanchez, Emilia

2010-01-01

Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which repres...... in genetic adaptation to high altitude.......Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which...... represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency...
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.
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.
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
Effect of Vocal Fold Medialization on Dysphagia in Patients with Unilateral Vocal Fold Immobility.

Science.gov (United States)

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

2016-09-01

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

Science.gov (United States)

Baron, Eli M; Soliman, Ahmed M S; Gaughan, John P; Simpson, Lisa; Young, William F

2003-11-01

The charts of 100 patients who underwent anterior cervical diskectomy with fusion performed at our institution between January 1996 and February 1999 were reviewed. The incidences of hoarseness, dysphagia, and unilateral true vocal fold motion impairment were calculated. Univariate logistic regression was used to estimate the relationship of several patient and technical factors to the rates of occurrence of hoarseness and dysphagia. Patient age was found to be a significant predictor of postoperative dysphagia (p dysphagia, hoarseness, and unilateral true vocal fold motion impairment in the literature were calculated as 12.3%, 4.9%, and 1.4%, respectively. We conclude that dysphagia, hoarseness, and unilateral vocal fold motion impairment continue to remain significant complications of anterior cervical diskectomy with fusion. Older patients may be at higher risk for dysphagia.

Human telomere sequence DNA in water-free and high-viscosity solvents: G-quadruplex folding governed by Kramers rate theory.

Science.gov (United States)

Lannan, Ford M; Mamajanov, Irena; Hud, Nicholas V

2012-09-19

Structures formed by human telomere sequence (HTS) DNA are of interest due to the implication of telomeres in the aging process and cancer. We present studies of HTS DNA folding in an anhydrous, high viscosity deep eutectic solvent (DES) comprised of choline choride and urea. In this solvent, the HTS DNA forms a G-quadruplex with the parallel-stranded ("propeller") fold, consistent with observations that reduced water activity favors the parallel fold, whereas alternative folds are favored at high water activity. Surprisingly, adoption of the parallel structure by HTS DNA in the DES, after thermal denaturation and quick cooling to room temperature, requires several months, as opposed to less than 2 min in an aqueous solution. This extended folding time in the DES is, in part, due to HTS DNA becoming kinetically trapped in a folded state that is apparently not accessed in lower viscosity solvents. A comparison of times required for the G-quadruplex to convert from its aqueous-preferred folded state to its parallel fold also reveals a dependence on solvent viscosity that is consistent with Kramers rate theory, which predicts that diffusion-controlled transitions will slow proportionally with solvent friction. These results provide an enhanced view of a G-quadruplex folding funnel and highlight the necessity to consider solvent viscosity in studies of G-quadruplex formation in vitro and in vivo. Additionally, the solvents and analyses presented here should prove valuable for understanding the folding of many other nucleic acids and potentially have applications in DNA-based nanotechnology where time-dependent structures are desired.
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...
Accurately controlled sequential self-folding structures by polystyrene film

Science.gov (United States)

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

2017-08-01

Four-dimensional (4D) printing overcomes the traditional fabrication limitations by designing heterogeneous materials to enable the printed structures evolve over time (the fourth dimension) under external stimuli. Here, we present a simple 4D printing of self-folding structures that can be sequentially and accurately folded. When heated above their glass transition temperature pre-strained polystyrene films shrink along the XY plane. In our process silver ink traces printed on the film are used to provide heat stimuli by conducting current to trigger the self-folding behavior. The parameters affecting the folding process are studied and discussed. Sequential folding and accurately controlled folding angles are achieved by using printed ink traces and angle lock design. Theoretical analyses are done to guide the design of the folding processes. Programmable structures such as a lock and a three-dimensional antenna are achieved to test the feasibility and potential applications of this method. These self-folding structures change their shapes after fabrication under controlled stimuli (electric current) and have potential applications in the fields of electronics, consumer devices, and robotics. Our design and fabrication method provides an easy way by using silver ink printed on polystyrene films to 4D print self-folding structures for electrically induced sequential folding with angular control.
Protein folding optimization based on 3D off-lattice model via an improved artificial bee colony algorithm.

Science.gov (United States)

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

2015-10-01

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

Science.gov (United States)

D'Alatri, Lucia; Petrelli, Livia; Calò, Lea; Picciotti, Pasqualina Maria; Marchese, Maria Raffaella; Bussu, Francesco

2015-05-01

To evaluate the presence of symptoms of inattention and hyperactivity/impulsivity in a population of school age children affected by vocal fold nodules. Parents and teachers of 18 children with vocal fold nodules (10 males, eight females; aged between 6 and 12 years) and 20 matched controls without dysphonia and/or vocal fold diseases (11 males, nine females; aged between 6 and 12 years) completed Attention-Deficit/Hyperactivity Disorder (ADHD) rating scale for parents (SDAG [Scala per i Disturbi di Attenzione/Iperattività per Genitori]) and teachers (SDAI [Scala per i Disturbi di Attenzione/Iperattività per Insegnanti) rating scales containing in two subscales items that specifically evaluate the symptoms of ADHD according to the DSM-IV. All children were subjected to videolaryngoscopy. The group with vocal fold nodules scored significantly higher than the controls; the difference between the two groups was statistically significant for both the subscales of both questionnaires (SDAG and SDAI) (P ADHD was formulated. ADHD is a possible risk factor for the development of vocal fold nodules in childhood. SDAG and SDAI rating scales may supplement the diagnostic assessment of children with vocal fold nodules. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Unraveling metamaterial properties in zigzag-base folded sheets.

Science.gov (United States)

Eidini, Maryam; Paulino, Glaucio H

2015-09-01

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

Science.gov (United States)

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

2016-11-01

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

Science.gov (United States)

Maity, Hiranmay; Reddy, Govardhan

2018-04-01

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

Directory of Open Access Journals (Sweden)

P A Chizhov

2005-01-01

Full Text Available Radiologically revealed spine osteoporosis in male with hypertension and coronary heart disease Objective. To study prevalence and intensity of spine osteoporosis (OP in men suffering from hypertension (H and coronary heart disease (CHD. Material and methods. 101 men with H and CHD aged 50 to 78 years (mean age 60,6±0,85 years and 37 men of control group without cardiovascular diseases aged 50-66 years (mean age 58,6±0,74 years were examined. Clinical examination, radiological, radiomorphometric spine examination and echocardioscopy were performed. Results. OP was revealed in 34,65% of main group pts what is 3,2 times more frequent than in control group (10,8%, p<0,05. OP intensity in men with H and CHD was significantly higher than in healthy people. Vfertebral fractures were revealed in 12,87+3,3% of main group pts and only in 2,7±2,7% in control group (p<0,05. OP development dependence from cardiac history duration and cardiac pathology severity was demonstrated. Conclusion. The results of the study show significantly higher prevalence of spine OP among men suffering from H and CHD. Long history and severity of cardiovascular pathology clinical signs promote OP frequency and severity increase.
N-Terminal Domains in Two-Domain Proteins Are Biased to Be Shorter and Predicted to Fold Faster Than Their C-Terminal Counterparts

Directory of Open Access Journals (Sweden)

Etai Jacob

2013-04-01

Full Text Available Computational analysis of proteomes in all kingdoms of life reveals a strong tendency for N-terminal domains in two-domain proteins to have shorter sequences than their neighboring C-terminal domains. Given that folding rates are affected by chain length, we asked whether the tendency for N-terminal domains to be shorter than their neighboring C-terminal domains reflects selection for faster-folding N-terminal domains. Calculations of absolute contact order, another predictor of folding rate, provide additional evidence that N-terminal domains tend to fold faster than their neighboring C-terminal domains. A possible explanation for this bias, which is more pronounced in prokaryotes than in eukaryotes, is that faster folding of N-terminal domains reduces the risk for protein aggregation during folding by preventing formation of nonnative interdomain interactions. This explanation is supported by our finding that two-domain proteins with a shorter N-terminal domain are much more abundant than those with a shorter C-terminal domain.
Aboriginal mitogenomes reveal 50,000 years of regionalism in Australia.

Science.gov (United States)

Tobler, Ray; Rohrlach, Adam; Soubrier, Julien; Bover, Pere; Llamas, Bastien; Tuke, Jonathan; Bean, Nigel; Abdullah-Highfold, Ali; Agius, Shane; O'Donoghue, Amy; O'Loughlin, Isabel; Sutton, Peter; Zilio, Fran; Walshe, Keryn; Williams, Alan N; Turney, Chris S M; Williams, Matthew; Richards, Stephen M; Mitchell, Robert J; Kowal, Emma; Stephen, John R; Williams, Lesley; Haak, Wolfgang; Cooper, Alan

2017-04-13

Aboriginal Australians represent one of the longest continuous cultural complexes known. Archaeological evidence indicates that Australia and New Guinea were initially settled approximately 50 thousand years ago (ka); however, little is known about the processes underlying the enormous linguistic and phenotypic diversity within Australia. Here we report 111 mitochondrial genomes (mitogenomes) from historical Aboriginal Australian hair samples, whose origins enable us to reconstruct Australian phylogeographic history before European settlement. Marked geographic patterns and deep splits across the major mitochondrial haplogroups imply that the settlement of Australia comprised a single, rapid migration along the east and west coasts that reached southern Australia by 49-45 ka. After continent-wide colonization, strong regional patterns developed and these have survived despite substantial climatic and cultural change during the late Pleistocene and Holocene epochs. Remarkably, we find evidence for the continuous presence of populations in discrete geographic areas dating back to around 50 ka, in agreement with the notable Aboriginal Australian cultural attachment to their country.
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
Effect of reinforcement element folds on stresses in NPP containment shell in the zone of technological tunnels

International Nuclear Information System (INIS)

Ul'yanov, A.N.; Medvedev, V.N.; Kiselev, A.S.

1993-01-01

Basing on the results of experimental and calculational studies of stressed state in the zone of a technological tunnel with one-side thicker part the approximated problem solution taking into account the effect of reinforcement element folds on opening zone stressed state is obtained. The great effect of reinforcement ropes on shell stressed state in the zone of technological tunnels, which causes the necessity of its accounting during this zone design, is revealed. Special attention shoul be paid to the sections, where the stretching stresses arising as a result of bundle bending are not compensated (sections of bundle fold origin from normal trajectory)
Quality of the voice after injection of hyaluronic acid into the vocal fold.

Science.gov (United States)

Szkiełkowska, Agata; Miaśkiewicz, Beata; Remacle, Marc; Krasnodębska, Paulina; Skarżyński, Henryk

2013-04-17

Voice disorders resulting from glottic insufficiency are a significant clinical problem in everyday phoniatric practice. One method of treatment is injection laryngoplasty. Our study aimed to assess the voice quality of patients treated with hyaluronic acid injection into the vocal fold. We studied 25 patients suffering from dysphonia, conducting laryngological and phoniatric examination, including videostroboscopy and acoustic voice analysis, before the operation and 1, 3, and 6 months later. In all cases there was complete or almost complete glottic closure after the operation. One month after the procedure, videostroboscopic examination revealed reappearance of vocal fold vibration in 8 cases; after 3 months this had risen to 15 cases. Perceptual voice quality (as assessed by the GRBAS scale) in patients with glottic insufficiency was improved. The most significant improvement was obtained 1 month after surgery (p=0.0002), and within the next months further statistically significant improvements (p=0.000002) were noted. Multidimensional voice analysis showed statistically significant and rapid improvement in frequency parameters, especially vFo. Other parameters were also improved 3 and 6 months after surgery. Injection of hyaluronic acid into the vocal fold improves phonatory functions of the larynx and the quality of voice in patients with glottic insufficiency. It may be a safe and conservative method for treatment of voice disorders. Hyaluronic acid injection to the vocal fold is an easy, effective, and fast method for restoration of good voice quality.
A Portrait of Ribosomal DNA Contacts with Hi-C Reveals 5S and 45S rDNA Anchoring Points in the Folded Human Genome.

Science.gov (United States)

Yu, Shoukai; Lemos, Bernardo

2016-12-31

Ribosomal RNAs (rRNAs) account for >60% of all RNAs in eukaryotic cells and are encoded in the ribosomal DNA (rDNA) arrays. The rRNAs are produced from two sets of loci: the 5S rDNA array resides exclusively on human chromosome 1, whereas the 45S rDNA array resides on the short arm of five human acrocentric chromosomes. The 45S rDNA gives origin to the nucleolus, the nuclear organelle that is the site of ribosome biogenesis. Intriguingly, 5S and 45S rDNA arrays exhibit correlated copy number variation in lymphoblastoid cells (LCLs). Here we examined the genomic architecture and repeat content of the 5S and 45S rDNA arrays in multiple human genome assemblies (including PacBio MHAP assembly) and ascertained contacts between the rDNA arrays and the rest of the genome using Hi-C datasets from two human cell lines (erythroleukemia K562 and lymphoblastoid cells). Our analyses revealed that 5S and 45S arrays each have thousands of contacts in the folded genome, with rDNA-associated regions and genes dispersed across all chromosomes. The rDNA contact map displayed conserved and disparate features between two cell lines, and pointed to specific chromosomes, genomic regions, and genes with evidence of spatial proximity to the rDNA arrays; the data also showed a lack of direct physical interaction between the 5S and 45S rDNA arrays. Finally, the analysis identified an intriguing organization in the 5S array with Alu and 5S elements adjacent to one another and organized in opposite orientation along the array. Portraits of genome folding centered on the ribosomal DNA array could help understand the emergence of concerted variation, the control of 5S and 45S expression, as well as provide insights into an organelle that contributes to the spatial localization of human chromosomes during interphase. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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
Predicted singers' vocal fold lengths and voice classification-a study of x-ray morphological measures.

Science.gov (United States)

Roers, Friederike; Mürbe, Dirk; Sundberg, Johan

2009-07-01

Students admitted to the solo singing education at the University of Music Dresden, Germany have been submitted to a detailed physical examination of a variety of factors with relevance to voice function since 1959. In the years 1959-1991, this scheme of examinations included X-ray profiles of the singers' vocal tracts. This material of 132 X-rays of voice professionals was used to investigate different laryngeal morphological measures and their relation to vocal fold length. Further, the study aimed to investigate if there are consistent anatomical differences between singers of different voice classifications. The study design used was a retrospective analysis. Vocal fold length could be measured in 29 of these singer subjects directly. These data showed a strong correlation with the anterior-posterior diameter of the subglottis and the trachea as well as with the distance from the anterior contour of the thyroid cartilage to the anterior contour of the spine. These relations were used in an attempt to predict the 132 singers' vocal fold lengths. The results revealed a clear covariation between predicted vocal fold length and voice classification. Anterior-posterior subglottic-tracheal diameter yielded mean vocal fold lengths of 14.9, 16.0, 16.6, 18.4, 19.5, and 20.9mm for sopranos, mezzo-sopranos, altos, tenors, baritones, and basses, respectively. The data support the assumption that there are consistent anatomical laryngeal differences between singers of different voice classifications, which are of relevance to pitch range and timbre of the voice.
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.

Adaptive local learning in sampling based motion planning for protein folding.

Science.gov (United States)

Ekenna, Chinwe; Thomas, Shawna; Amato, Nancy M

2016-08-01

Simulating protein folding motions is an important problem in computational biology. Motion planning algorithms, such as Probabilistic Roadmap Methods, have been successful in modeling the folding landscape. Probabilistic Roadmap Methods and variants contain several phases (i.e., sampling, connection, and path extraction). Most of the time is spent in the connection phase and selecting which variant to employ is a difficult task. Global machine learning has been applied to the connection phase but is inefficient in situations with varying topology, such as those typical of folding landscapes. We develop a local learning algorithm that exploits the past performance of methods within the neighborhood of the current connection attempts as a basis for learning. It is sensitive not only to different types of landscapes but also to differing regions in the landscape itself, removing the need to explicitly partition the landscape. We perform experiments on 23 proteins of varying secondary structure makeup with 52-114 residues. We compare the success rate when using our methods and other methods. We demonstrate a clear need for learning (i.e., only learning methods were able to validate against all available experimental data) and show that local learning is superior to global learning producing, in many cases, significantly higher quality results than the other methods. We present an algorithm that uses local learning to select appropriate connection methods in the context of roadmap construction for protein folding. Our method removes the burden of deciding which method to use, leverages the strengths of the individual input methods, and it is extendable to include other future connection methods.
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.
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)

Science.gov (United States)

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
Vaginal fold prolapse during the last third of pregnancy, followed by normal parturition, in a bitch.

Science.gov (United States)

Gouletsou, Pagona G; Galatos, Apostolos D; Apostolidis, Kosmas; Sideri, Aikaterini I

2009-06-01

This article describes a 1.5-year-old female, Greek Hound dog, weighing 16 kg, presented with a type III vaginal prolapse which occurred during the last third of pregnancy. Trans-abdominal ultrasonography revealed four live foetuses in the uterine horns. The animal was hospitalized and 4 days later gave birth without any interference. Three days later, resection of the prolapsed tissue was performed and the bitch recovered completely. Recurrence of a type I vaginal prolapse was observed 4 months later, during subsequent oestrus. This case is unusual because, although vaginal fold prolapse is mainly seen during proestrus/oestrus or during parturition, it was first noticed 47 days after mating and 13 days before parturition. Furthermore, even though the prolapse of vaginal fold was of type III and of considerable size, parturition proceeded normally. Finally, even though resection of the prolapsed tissue was performed 3 days after parturition, recurrence of vaginal fold oedema (type I) was observed in the subsequent oestrus.
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
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.
Fibroid explants reveal a higher sensitivity against MDM2-inhibitor nutlin-3 than matching myometrium

Directory of Open Access Journals (Sweden)

Markowski Dominique N

2012-01-01

Full Text Available Abstract Background Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets. Methods We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14Arf and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's t test. Results An in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14Arf in the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of BAX as well as of p21, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers BAX and p21. Because as a rule fibroids express much higher levels of p14Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium. Conclusions The results show that uterine fibroids represent a cell
Journal of Earth System Science | Indian Academy of Sciences

Indian Academy of Sciences (India)

The varying flattening is also revealed by the geometry of folds. The apparent buckle shortening of folds which ranges between 49 and 67 per cent with a majority of the folds having shortening values between 50% and 55% (exclusive of layer parallel strain) and inverse thickness method strain up to 50%. Besides flattening ...
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.
First passage analysis of the folding of a β-sheet miniprotein: is it more realistic than the standard equilibrium approach?

Science.gov (United States)

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

2014-04-24

Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are significantly different from those for equilibrium folding. Because the folding of a protein in a living system generally corresponds to the former (i.e., the folded protein is stable and unfolding is a rare event), the difference is of interest. In contrast to equilibrium folding, the Ch-curl conformations become very rare because they contain unfavorable parallel β-strand arrangements, which are difficult to form dynamically due to the distant N- and C-terminal strands. At the same time, the formation of helical conformations becomes much easier (particularly in the early stage of folding) due to short-range contacts. The hydrodynamic descriptions of the folding reaction have also revealed that while the equilibrium flow field presented a collection of local vortices with closed "streamlines", the first-passage folding is characterized by a pronounced overall flow from the unfolded states to the native state. The flows through the locally stable structures Cs-or and Ns-or, which are conformationally close to the native state, are negligible due to detailed balance established between these structures and the native state. Although there are significant differences in the general picture of the folding process from the equilibrium and first-passage folding simulations, some aspects of the two are in agreement. The rate of transitions between the clusters of characteristic protein conformations in both cases decreases approximately exponentially with the distance between the clusters in the hydrogen bond distance space of collective variables, and the folding time distribution in the first-passage segments of the equilibrium trajectory is in good agreement with that for the first-passage folding simulations.
First Passage Analysis of the Folding of a β-Sheet Miniprotein: Is it More Realistic Than the Standard Equilibrium Approach?

Science.gov (United States)

2015-01-01

Simulations of first-passage folding of the antiparallel β-sheet miniprotein beta3s, which has been intensively studied under equilibrium conditions by A. Caflisch and co-workers, show that the kinetics and dynamics are significantly different from those for equilibrium folding. Because the folding of a protein in a living system generally corresponds to the former (i.e., the folded protein is stable and unfolding is a rare event), the difference is of interest. In contrast to equilibrium folding, the Ch-curl conformations become very rare because they contain unfavorable parallel β-strand arrangements, which are difficult to form dynamically due to the distant N- and C-terminal strands. At the same time, the formation of helical conformations becomes much easier (particularly in the early stage of folding) due to short-range contacts. The hydrodynamic descriptions of the folding reaction have also revealed that while the equilibrium flow field presented a collection of local vortices with closed ”streamlines”, the first-passage folding is characterized by a pronounced overall flow from the unfolded states to the native state. The flows through the locally stable structures Cs-or and Ns-or, which are conformationally close to the native state, are negligible due to detailed balance established between these structures and the native state. Although there are significant differences in the general picture of the folding process from the equilibrium and first-passage folding simulations, some aspects of the two are in agreement. The rate of transitions between the clusters of characteristic protein conformations in both cases decreases approximately exponentially with the distance between the clusters in the hydrogen bond distance space of collective variables, and the folding time distribution in the first-passage segments of the equilibrium trajectory is in good agreement with that for the first-passage folding simulations. PMID:24669953
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.
Protein folding: Defining a standard set of experimental conditions and a preliminary kinetic data set of two-state proteins

DEFF Research Database (Denmark)

Maxwell, Karen L.; Wildes, D.; Zarrine-Afsar, A.

2005-01-01

Recent years have seen the publication of both empirical and theoretical relationships predicting the rates with which proteins fold. Our ability to test and refine these relationships has been limited, however, by a variety of difficulties associated with the comparison of folding and unfolding ...... efforts is to set uniform standards for the experimental community and to initiate an accumulating, self-consistent data set that will aid ongoing efforts to understand the folding process....... constructs. The lack of a single approach to data analysis and error estimation, or even of a common set of units and reporting standards, further hinders comparative studies of folding. In an effort to overcome these problems, we define here a consensus set of experimental conditions (25°C at pH 7.0, 50 m...... rates, thermodynamics, and structure across diverse sets of proteins. These difficulties include the wide, potentially confounding range of experimental conditions and methods employed to date and the difficulty of obtaining correct and complete sequence and structural details for the characterized...
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…
Vocal fold self-disruption after phonotrauma on a lead actor: a case presentation.

Science.gov (United States)

Behlau, Mara; Oliveira, Gisele; Pontes, Paulo

2009-11-01

It is well known that phonotraumatic events may produce laryngeal inflammation, vocal fold hemorrhage and different types of mass lesions. This study describes a vocal fold self-disruption that occurred on stage to a lead actor in the role of Richard III. The study design is as case presentation. A 43-year-old actor presented with a sudden voice loss that first occurred on stage after a series of presentations. He also had a cold-like condition that had not been treated. His past medical history included an average of ten cigarettes per day for ten years and a 10-year history of gastritis and stomach ulcer. Perceptual, acoustic, and laryngeal analyses were performed following pharmacological and voice therapy. Perceptual and acoustic analyses showed mild deviations whereas laryngeal visual examination revealed a complete right vocal fold detachment from the anterior commissure to the vocal process, with generalized hyperemia. A mild diffuse Reinke's edema was observed on the left vocal fold. Mild discomfort was present only during the first day of the acute period. Modified vocal rest was recommended and a series of vocal exercises were administered. The patient performed again 4 days later, after following a series of behavioral modification techniques that included casting guidelines during the subsequent 15 days. Healing was exceptional and his voice returned to normal. This unique case with an exceptional recovery emphasizes the etiological aspects of scar formation after phonotrauma. Positive contributing factors may include a good vocal technique and adequate training as well as the protective upregulated genes present in Reinke's edema.
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...
THE INFLUENCE OF FOLD AND FRACTURE DEVELOPMENT ON RESERVOIR BEHAVIOR OF THE LISBURNE GROUP OF NORTHERN ALASKA

Energy Technology Data Exchange (ETDEWEB)

Wesley K. Wallace; Catherine L. Hanks; Michael T. Whalen; Jerry Jensen; Paul K. Atkinson; Joseph S. Brinton

2000-05-01

The Lisburne Group is a major carbonate reservoir unit in northern Alaska. The Lisburne is detachment folded where it is exposed throughout the northeastern Brooks Range, but is relatively undeformed in areas of current production in the subsurface of the North Slope. The objectives of this study are to develop a better understanding of four major aspects of the Lisburne: (1) The geometry and kinematics of detachment folds and their truncation by thrust faults. (2) The influence of folding and lithostratigraphy on fracture patterns. (3) Lithostratigraphy and its influence on folding, faulting, fracturing, and reservoir characteristics. (4) The influence of lithostratigraphy and deformation on fluid flow. The results of field work during the summer of 1999 offer some preliminary insights: The Lisburne Limestone displays a range of symmetrical detachment fold geometries throughout the northeastern Brooks Range. The variation in fold geometry suggests a generalized progression in fold geometry with increasing shortening: Straight-limbed, narrow-crested folds at low shortening, box folds at intermediate shortening, and folds with a large height-to-width ratio and thickened hinges at high shortening. This sequence is interpreted to represent a progressive change in the dominant shortening mechanism from flexural-slip at low shortening to bulk strain at higher shortening. Structural variations in bed thickness occur throughout this progression. Parasitic folding accommodates structural thickening at low shortening and is gradually succeeded by penetrative strain as shortening increases. The amount of structural thickening at low to intermediate shortening may be inversely related to the local amount of structural thickening of the Kayak Shale, the incompetent unit that underlies the Lisburne. The Lisburne Limestone displays a different structural style in the south, across the boundary between the northeastern Brooks Range and the main axis of the Brooks Range fold
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.
Parasupersymmetry and N-fold supersymmetry in quantum many-body systems. I: General formalism and second order

International Nuclear Information System (INIS)

Tanaka, Toshiaki

2007-01-01

We propose an elegant formulation of parafermionic algebra and parasupersymmetry of arbitrary order in quantum many-body systems without recourse to any specific matrix representation of parafermionic operators and any kind of deformed algebra. Within our formulation, we show generically that every parasupersymmetric quantum system of order p consists of N-fold supersymmetric pairs with N≤p and thus has weak quasi-solvability and isospectral property. We also propose a new type of non-linear supersymmetries, called quasi-parasupersymmetry, which is less restrictive than parasupersymmetry and is different from N-fold supersymmetry even in one-body systems though the conserved charges are represented by higher-order linear differential operators. To illustrate how our formulation works, we construct second-order parafermionic algebra and three simple examples of parasupersymmetric quantum systems of order 2, one is essentially equivalent to the one-body Rubakov-Spiridonov type and the others are two-body systems in which two supersymmetries are folded. In particular, we show that the first model admits a generalized 2-fold superalgebra
On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.

Science.gov (United States)

Wu, Chun; Shea, Joan-Emma

2010-11-18

FSD-1, a designed small ultrafast folder with a ββα fold, has been actively studied in the last few years as a model system for studying protein folding mechanisms and for testing of the accuracy of computational models. The suitability of this protein to describe the folding of naturally occurring α/β proteins has recently been challenged based on the observation that the melting transition is very broad, with ill-resolved baselines. Using molecular dynamics simulations with the AMBER protein force field (ff96) coupled with the implicit solvent model (IGB = 5), we shed new light into the nature of this transition and resolve the experimental controversies. We show that the melting transition corresponds to the melting of the protein as a whole, and not solely to the helix-coil transition. The breadth of the folding transition arises from the spread in the melting temperatures (from ∼325 K to ∼302 K) of the individual transitions: formation of the hydrophobic core, β-hairpin and tertiary fold, with the helix formed earlier. Our simulations initiated from an extended chain accurately predict the native structure, provide a reasonable estimate of the transition barrier height, and explicitly demonstrate the existence of multiple pathways and multiple transition states for folding. Our exhaustive sampling enables us to assess the quality of the Amber ff96/igb5 combination and reveals that while this force field can predict the correct native fold, it nonetheless overstabilizes the α-helix portion of the protein (Tm = ∼387K) as well as the denatured structures.
Folding kinetics of WW domains with the united residue force field for bridging microscopic motions and experimental measurements.

Science.gov (United States)

Zhou, Rui; Maisuradze, Gia G; Suñol, David; Todorovski, Toni; Macias, Maria J; Xiao, Yi; Scheraga, Harold A; Czaplewski, Cezary; Liwo, Adam

2014-12-23

To demonstrate the utility of the coarse-grained united-residue (UNRES) force field to compare experimental and computed kinetic data for folding proteins, we have performed long-time millisecond-timescale canonical Langevin molecular dynamics simulations of the triple β-strand from the Formin binding protein 28 WW domain and six nonnatural variants, using UNRES. The results have been compared with available experimental data in both a qualitative and a quantitative manner. Complexities of the folding pathways, which cannot be determined experimentally, were revealed. The folding mechanisms obtained from the simulated folding kinetics are in agreement with experimental results, with a few discrepancies for which we have accounted. The origins of single- and double-exponential kinetics and their correlations with two- and three-state folding scenarios are shown to be related to the relative barrier heights between the various states. The rate constants obtained from time profiles of the fractions of the native, intermediate, and unfolded structures, and the kinetic equations fitted to them, correlate with the experimental values; however, they are about three orders of magnitude larger than the experimental ones for most of the systems. These differences are in agreement with the timescale extension derived by scaling down the friction of water and averaging out the fast degrees of freedom when passing from all-atom to a coarse-grained representation. Our results indicate that the UNRES force field can provide accurate predictions of folding kinetics of these WW domains, often used as models for the study of the mechanisms of proein folding.
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
Development of isothermal-isobaric replica-permutation method for molecular dynamics and Monte Carlo simulations and its application to reveal temperature and pressure dependence of folded, misfolded, and unfolded states of chignolin

Science.gov (United States)

Yamauchi, Masataka; Okumura, Hisashi

2017-11-01

We developed a two-dimensional replica-permutation molecular dynamics method in the isothermal-isobaric ensemble. The replica-permutation method is a better alternative to the replica-exchange method. It was originally developed in the canonical ensemble. This method employs the Suwa-Todo algorithm, instead of the Metropolis algorithm, to perform permutations of temperatures and pressures among more than two replicas so that the rejection ratio can be minimized. We showed that the isothermal-isobaric replica-permutation method performs better sampling efficiency than the isothermal-isobaric replica-exchange method and infinite swapping method. We applied this method to a β-hairpin mini protein, chignolin. In this simulation, we observed not only the folded state but also the misfolded state. We calculated the temperature and pressure dependence of the fractions on the folded, misfolded, and unfolded states. Differences in partial molar enthalpy, internal energy, entropy, partial molar volume, and heat capacity were also determined and agreed well with experimental data. We observed a new phenomenon that misfolded chignolin becomes more stable under high-pressure conditions. We also revealed this mechanism of the stability as follows: TYR2 and TRP9 side chains cover the hydrogen bonds that form a β-hairpin structure. The hydrogen bonds are protected from the water molecules that approach the protein as the pressure increases.
Dependence between LD50 for Rodents and LC50 for Adult Fish and Fish Embryos.

Science.gov (United States)

Zolotarev, K V; Belyaeva, N F; Mikhailov, A N; Mikhailova, M V

2017-02-01

We revealed empirical dependences between common logarithm of a ratio of rat oral LD 50 to LC a 50 for adult fish and lgP for 50 different chemicals; and common logarithm of a ratio of the oral LD 50 in rodents to LC e 50 for fish embryos and lgP for 30 different chemicals. The dependences were obtained by constructing a trend line between experimental points and calculation of Pearson's R correlation coefficient as a measure of regression significance. These dependences can show the influence of substance lipophilicity on its toxicity for aquatic organisms comparing to mammals.

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.
Earthworm Lumbricus rubellus MT-2: Metal Binding and Protein Folding of a True Cadmium-MT

Directory of Open Access Journals (Sweden)

Gregory R. Kowald

2016-01-01

Full Text Available Earthworms express, as most animals, metallothioneins (MTs—small, cysteine-rich proteins that bind d10 metal ions (Zn(II, Cd(II, or Cu(I in clusters. Three MT homologues are known for Lumbricus rubellus, the common red earthworm, one of which, wMT-2, is strongly induced by exposure of worms to cadmium. This study concerns composition, metal binding affinity and metal-dependent protein folding of wMT-2 expressed recombinantly and purified in the presence of Cd(II and Zn(II. Crucially, whilst a single Cd7wMT-2 species was isolated from wMT-2-expressing E. coli cultures supplemented with Cd(II, expressions in the presence of Zn(II yielded mixtures. The average affinities of wMT-2 determined for either Cd(II or Zn(II are both within normal ranges for MTs; hence, differential behaviour cannot be explained on the basis of overall affinity. Therefore, the protein folding properties of Cd- and Zn-wMT-2 were compared by 1H NMR spectroscopy. This comparison revealed that the protein fold is better defined in the presence of cadmium than in the presence of zinc. These differences in folding and dynamics may be at the root of the differential behaviour of the cadmium- and zinc-bound protein in vitro, and may ultimately also help in distinguishing zinc and cadmium in the earthworm in vivo.
Biochemical and Genetic Evidence that Enterococcus faecium L50 Produces Enterocins L50A and L50B, the sec-Dependent Enterocin P, and a Novel Bacteriocin Secreted without an N-Terminal Extension Termed Enterocin Q

Science.gov (United States)

Cintas, Luis M.; Casaus, Pilar; Herranz, Carmen; Håvarstein, Leiv Sigve; Holo, Helge; Hernández, Pablo E.; Nes, Ingolf F.

2000-01-01

Enterococcus faecium L50 grown at 16 to 32°C produces enterocin L50 (EntL50), consisting of EntL50A and EntL50B, two unmodified non-pediocin-like peptides synthesized without an N-terminal leader sequence or signal peptide. However, the bacteriocin activity found in the cell-free culture supernatants following growth at higher temperatures (37 to 47°C) is not due to EntL50. A purification procedure including cation-exchange, hydrophobic interaction, and reverse-phase liquid chromatography has shown that the antimicrobial activity is due to two different bacteriocins. Amino acid sequences obtained by Edman degradation and DNA sequencing analyses revealed that one is identical to the sec-dependent pediocin-like enterocin P produced by E. faecium P13 (L. M. Cintas, P. Casaus, L. S. Håvarstein, P. E. Hernández, and I. F. Nes, Appl. Environ. Microbiol. 63:4321–4330, 1997) and the other is a novel unmodified non-pediocin-like bacteriocin termed enterocin Q (EntQ), with a molecular mass of 3,980. DNA sequencing analysis of a 963-bp region of E. faecium L50 containing the enterocin P structural gene (entP) and the putative immunity protein gene (entiP) reveals a genetic organization identical to that previously found in E. faecium P13. DNA sequencing analysis of a 1,448-bp region identified two consecutive but diverging open reading frames (ORFs) of which one, termed entQ, encodes a 34-amino-acid protein whose deduced amino acid sequence was identical to that obtained for EntQ by amino acid sequencing, showing that EntQ, similarly to EntL50A and EntL50B, is synthesized without an N-terminal leader sequence or signal peptide. The second ORF, termed orf2, was located immediately upstream of and in opposite orientation to entQ and encodes a putative immunity protein composed of 221 amino acids. Bacteriocin production by E. faecium L50 showed that EntP and EntQ are produced in the temperature range from 16 to 47°C and maximally detected at 47 and 37 to 47�
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
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
Absorption and folding of melittin onto lipid bilayer membranes via unbiased atomic detail microsecond molecular dynamics simulation.

Science.gov (United States)

Chen, Charles H; Wiedman, Gregory; Khan, Ayesha; Ulmschneider, Martin B

2014-09-01

Unbiased molecular simulation is a powerful tool to study the atomic details driving functional structural changes or folding pathways of highly fluid systems, which present great challenges experimentally. Here we apply unbiased long-timescale molecular dynamics simulation to study the ab initio folding and partitioning of melittin, a template amphiphilic membrane active peptide. The simulations reveal that the peptide binds strongly to the lipid bilayer in an unstructured configuration. Interfacial folding results in a localized bilayer deformation. Akin to purely hydrophobic transmembrane segments the surface bound native helical conformer is highly resistant against thermal denaturation. Circular dichroism spectroscopy experiments confirm the strong binding and thermostability of the peptide. The study highlights the utility of molecular dynamics simulations for studying transient mechanisms in fluid lipid bilayer systems. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014. Published by Elsevier B.V.
Tank 50H Tetraphenylborate Destruction Results

International Nuclear Information System (INIS)

Peters, T.B.

2003-01-01

We conducted several scoping tests with both Tank 50H surrogate materials (KTPB and phenol) as well as with actual Tank 50H solids. These tests examined whether we could destroy the tetraphenylborate in the surrogates or actual Tank 50H material either by use of Fenton's Reagent or by hydrolysis (in Tank 50H conditions at a maximum temperature of 50 degrees C) under a range of conditions. The results of these tests showed that destruction of the solids occurred only under a minority of conditions. (1)Using Fenton's Reagent and KTPB as the Tank 50H surrogate, no reaction occurred at pH ranges greater than 9. (2)Using Fenton's Reagent and phenol as the Tank 50H surrogate, no reaction occurred at a pH of 14. (3)Using Fenton's Reagent and actual Tank 50H slurry, a reaction occurred at a pH of 9.5 in the presence of ECC additives. (4)Using Fenton's Reagent and actual Tank 50H slurry, after a thirty three day period, all attempts at hydrolysis (at pH 14) were too slow to be viable. This happened even in the case of higher temperature (50 degrees C) and added (100 ppm) copper. Tank 50H is scheduled to return to HLW Tank Farm service with capabilities of transferring and receiving salt supernate solutions to and from the Tank Farms and staging feed for the Saltstone Facility. Before returning Tank 50H to Tank Farm service as a non-organic tank, less than 5 kg of TPB must remain in Tank 50H. Recently, camera inspections in Tank 50H revealed two large mounds of solid material, one in the vicinity of the B5 Riser Transfer Pump and the other on the opposite side of the tank. Personnel sampled and analyzed this material to determine its composition. The sample analysis indicated presence of a significant quantity of organics in the solid material. This quantity of organic material exceeds the 5 kg limit for declaring only trace amounts of organic material remain in Tank 50H. Additionally, these large volumes of solids, calculated as approximately 61K gallons, present other
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
Vesicle Encapsulation Studies Reveal that Single Molecule Ribozyme Heterogeneities Are Intrinsic

Science.gov (United States)

Okumus, Burak; Wilson, Timothy J.; Lilley, David M. J.; Ha, Taekjip

2004-01-01

Single-molecule measurements have revealed that what were assumed to be identical molecules can differ significantly in their static and dynamic properties. One of the most striking examples is the hairpin ribozyme, which was shown to exhibit two to three orders of magnitude variation in folding kinetics between molecules. Although averaged behavior of single molecules matched the bulk solution data, it was not possible to exclude rigorously the possibility that the variations around the mean values arose from different ways of interacting with the surface environment. To test this, we minimized the molecules' interaction with the surface by encapsulating DNA or RNA molecules inside 100- to 200-nm diameter unilamellar vesicles, following the procedures described by Haran and coworkers. Vesicles were immobilized on a supported lipid bilayer via biotin-streptavidin linkages. We observed no direct binding of DNA or RNA on the supported bilayer even at concentrations exceeding 100 nM, indicating that these molecules do not bind stably on the membrane. Since the vesicle diameter is smaller than the resolution of optical microscopy, the lateral mobility of the molecules is severely constrained, allowing long observation periods. We used fluorescence correlation spectroscopy, nuclease digestion, and external buffer exchange to show that the molecules were indeed encapsulated within the vesicles. When contained within vesicles, the natural form of the hairpin ribozyme exhibited 50-fold variation in both folding and unfolding rates in 0.5 mM Mg2+, which is identical to what was observed from the molecules tethered directly on the surface. This strongly indicates that the observed heterogeneity in dynamic properties does not arise as an artifact of surface attachment, but is intrinsic to the nature of the molecules. PMID:15454471
Psychosocial risks evaluation factors: study with higher education teachers

Directory of Open Access Journals (Sweden)

Sara Lopes Borges

2018-02-01

Method: The study consisted of the administration of two instruments, one for the characterization of the sample and the other for assessing psychosocial risk factors — the Copenhagen Psychosocial Questionnaire — consisting of 76 items (5-point Likert scale, distributed in five dimensions, which measure indicators of exposure to psychosocial risks and their effects. Results: The study included 59 teachers, mostly men (50.8%, aged between 41 - 50 years (45.8%, with master's degree (59%, assistant professors (47.5%; with a stable employment relationship (68%, years of service between 14-17 years (18.7% and teaching between 11 - 17 hours a week (64.4%. The analysis of the various subscales revealed a psychosocial risk, showing that teachers are in a situation of vulnerability. There were significant differences between the risks experienced in public higher education and those experienced in private higher education. Gender, age, academic background, and professional category influenced the type of psychosocial risk. Conclusions: The study confirms the importance of the evaluation of psychosocial risk factors in the exercise of the teaching profession in higher education. It is recognized that it is necessary to assess and manage psychosocial risks in order to promote healthy working conditions, ensure respect and fair treatment, and encourage the promotion of work / family life balance, in order to minimize psychosocial risks and situations of vulnerability in higher education teachers.
Various design approaches to achieve electric field-driven segmented folding actuation of electroactive polymer (EAP) sheets

Science.gov (United States)

Ahmed, Saad; Hong, Jonathan; Zhang, Wei; Kopatz, Jessica; Ounaies, Zoubeida; Frecker, Mary

2018-03-01

Electroactive polymer (EAPs) based technologies have shown promise in areas such as artificial muscles, aerospace, medical and soft robotics. In this work, we demonstrate ways to harness on-demand segmented folding actuation from pure bending of relaxor-ferroelectric P(VDF-TrFE-CTFE) based films, using various design approaches, such as `stiffener' and `notch' based approaches. The in-plane actuation of the P(VDF-TrFE-CTFE) is converted into bending actuation using unimorph configurations, where one passive substrate layer is attached to the active polymer. First, we experimentally show that placement of thin metal strips as stiffener in between active EAPs and passive substrates leads to segmented actuation as opposed to pure bending actuation; stiffeners made of different materials, such as nickel, copper and aluminum, are studied which reveals that a higher Young's modulus favors more pronounced segmented actuation. Second, notched samples are prepared by mounting passive substrate patches of various materials on top of the passive layers of the unimorph EAP actuators. Effect of notch materials, size of the notches and position of the notches on the folding actuation are studied. The motion of the human finger inspires a finger-like biomimetic actuator, which is realized by assigning multiple notches on the structure; finite element analysis (FEA) is also performed using COMSOL Multiphysics software for the notched finger actuator. Finally, a versatile soft-gripper is developed using the notched approach to demonstrate the capability of a properly designed EAP actuator to hold objects of various sizes and shapes.
Quantitative measurement of vocal fold vibration in male radio performers and healthy controls using high-speed videoendoscopy.

Directory of Open Access Journals (Sweden)

Samantha Warhurst

Full Text Available Acoustic and perceptual studies show a number of differences between the voices of radio performers and controls. Despite this, the vocal fold kinematics underlying these differences are largely unknown. Using high-speed videoendoscopy, this study sought to determine whether the vocal vibration features of radio performers differed from those of non-performing controls.Using high-speed videoendoscopy, recordings of a mid-phonatory/i/ in 16 male radio performers (aged 25-52 years and 16 age-matched controls (aged 25-52 years were collected. Videos were extracted and analysed semi-automatically using High-Speed Video Program, obtaining measures of fundamental frequency (f0, open quotient and speed quotient. Post-hoc analyses of sound pressure level (SPL were also performed (n = 19. Pearson's correlations were calculated between SPL and both speed and open quotients.Male radio performers had a significantly higher speed quotient than their matched controls (t = 3.308, p = 0.005. No significant differences were found for f0 or open quotient. No significant correlation was found between either open or speed quotient with SPL.A higher speed quotient in male radio performers suggests that their vocal fold vibration was characterised by a higher ratio of glottal opening to closing times than controls. This result may explain findings of better voice quality, higher equivalent sound level and greater spectral tilt seen in previous research. Open quotient was not significantly different between groups, indicating that the durations of complete vocal fold closure were not different between the radio performers and controls. Further validation of these results is required to determine the aetiology of the higher speed quotient result and its implications for voice training and clinical management in performers.
Acinetobacter baumannii FolD ligand complexes --potent inhibitors of folate metabolism and a re-evaluation of the structure of LY374571.

Science.gov (United States)

Eadsforth, Thomas C; Maluf, Fernando V; Hunter, William N

2012-12-01

The bifunctional N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclohydrolase (DHCH or FolD), which is widely distributed in prokaryotes and eukaryotes, is involved in the biosynthesis of folate cofactors that are essential for growth and cellular development. The enzyme activities represent a potential antimicrobial drug target. We have characterized the kinetic properties of FolD from the Gram-negative pathogen Acinetobacter baumanni and determined high-resolution crystal structures of complexes with a cofactor and two potent inhibitors. The data reveal new details with respect to the molecular basis of catalysis and potent inhibition. A unexpected finding was that our crystallographic data revealed a different structure for LY374571 (an inhibitor studied as an antifolate) than that previously published. The implications of this observation are discussed. © 2012 The Authors Journal compilation © 2012 FEBS.
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 ...
Folding and unfolding pathway of chaperonin GroEL monomer and elucidation of thermodynamic parameters.

Science.gov (United States)

Puri, Sarita; Chaudhuri, Tapan K

2017-03-01

The conformation and thermodynamic stability of monomeric GroEL were studied by CD and fluorescence spectroscopy. GroEL denaturation with urea and dilution in buffer leads to formation of a folded GroEL monomer. The monomeric nature of this protein was verified by size-exclusion chromatography and native PAGE. It has a well-defined secondary and tertiary structure, folding activity (prevention of aggregation) for substrate protein and is resistant to proteolysis. Being a properly folded and reversibly refoldable, monomeric GroEL is amenable for the study of thermodynamic stability by unfolding transition methods. We present the equilibrium unfolding of monomeric GroEL as studied by urea and heat mediated unfolding processes. The urea mediated unfolding shows two transitions and a single transition in the heat mediated unfolding process. In the case of thermal unfolding, some residual structure unfolds at a higher temperature (70-75°C). The process of folding/unfolding is reversible in both cases. Analysis of folding/unfolding data provides a measure of ΔG NU H 2 O , T m , ΔH van and ΔS van of monomeric GroEL. The thermodynamic stability parameter ΔG NU H 2 O is similar with both CD and intrinsic fluorescence i.e. 7.10±1.0kcal/mol. The calculated T m , ΔH van and ΔS van from the thermal unfolding transition is 46±0.5°C, 43.3±0.1kcal/mol and 143.9±0.1cal/mol/k respectively. Copyright © 2016 Elsevier B.V. All rights reserved.
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...
Studies of protein structure in solution and protein folding using synchrotron small-angle x-ray scattering

Energy Technology Data Exchange (ETDEWEB)

Chen, Lingling [Stanford Univ., CA (United States)

1996-04-01

Synchrotron small angle x-ray scattering (SAXS) has been applied to the structural study of several biological systems, including the nitrogenase complex, the heat shock cognate protein (hsc70), and lysozyme folding. The structural information revealed from the SAXS experiments is complementary to information obtained by other physical and biochemical methods, and adds to our knowledge and understanding of these systems.

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)
[Concordance between self-reported weight and height for nutritional assessment in adults aged between 25 and 50 years without higher education].

Science.gov (United States)

Matínez-Torres, Javier; Lee Osorno, Belinda Inés; Mendoza, Leylis; Mariotta, Sharom; López Epiayu, Yandra; Martínez, Yelitza; Jiménez, Nelly

2014-11-01

Overweight and obesity are metabolic disorders that have become a public health problem due to the current high prevalence; therefore, it is important to create simple monitoring systems to assess their trends. To determine the correlation between weight, height and body mass index reported by patients and the values measured directly in adults between 25 and 50 years old without higher education. A cross-sectional descriptive study was conducted with participation of 207 adults between 25 and 50 years old. Each participant was asked weight and height; and body mass index was calculated with these data. Moreover, a qualified person determined the real value of these variables. The coefficient of intra-class correlation between self-reported and measurements was obtained. The body mass index measured for men was 25.8±3.7 kg/m2 and for women 26.0±4.1 kg/m2. Intraclass correlation coefficients were for weight 0.962 (IC95%: 0.950-0.971), height 0.909 (IC95%: 0.882-0.930), and body mass index 0.929 (IC95% 0.907-0.945); the real prevalence of people with a body mass index greater than 25 kg/m2 was 52.1%, whereas the value obtained by self-reported data was 44%. Self-reported weight and height data are useful for obesity assessment in adults aged between 25 and 50 years without higher education at the population level. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Carbon dioxide therapy and hyaluronic acid for cosmetic correction of the nasolabial folds.

Science.gov (United States)

Nisi, Giuseppe; Cuomo, Roberto; Brandi, Cesare; Grimaldi, Luca; Sisti, Andrea; D'Aniello, Carlo

2016-06-01

The main application of hyaluronic acid filling, in esthetic medicine, is the augmentation of soft tissues. The carbon dioxide therapy, instead, improves quality and elasticity of the dermis and increases the oxygen release to the tissue through an enhancing of the Bohr's effect. The aim of the study was to compare the efficacy, tolerability, and effect duration of hyaluronic acid fillers and the use of carbon dioxide therapy plus hyaluronic acid in the cosmetic correction of nasolabial folds. Forty healthy female patients received a blinded and randomized treatment on nasolabial folds (hyaluronic acid in group A and hyaluronic acid plus subcutaneous injections of carbon dioxide in group B) for cosmetic correction of the nasolabial folds. The results were evaluated by two blinded plastic surgeons after the implant (1 week, 4 and 6 months) using a 1-5 graduated scale (GAIS), and at the same time, each patient was asked to express her opinion about the cosmetic result. Any long-term adverse reaction was reported. The blinded evaluation at 4 and 6 months from the implant shows in all patients a maintenance of a good cosmetic result higher for the side treated with carbon dioxide therapy plus hyaluronic acid. At the control visit, 6 months after the treatment, the patients treated with hyaluronic acid plus carbon dioxide therapy maintain a satisfactory esthetic result while the nasolabial fold treated only with hyaluronic acid shows, in almost all patients, a come back to pretreatment appearance. © 2016 Wiley Periodicals, Inc.
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.
On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.

Directory of Open Access Journals (Sweden)

Chun Wu

Full Text Available FSD-1, a designed small ultrafast folder with a ββα fold, has been actively studied in the last few years as a model system for studying protein folding mechanisms and for testing of the accuracy of computational models. The suitability of this protein to describe the folding of naturally occurring α/β proteins has recently been challenged based on the observation that the melting transition is very broad, with ill-resolved baselines. Using molecular dynamics simulations with the AMBER protein force field (ff96 coupled with the implicit solvent model (IGB = 5, we shed new light into the nature of this transition and resolve the experimental controversies. We show that the melting transition corresponds to the melting of the protein as a whole, and not solely to the helix-coil transition. The breadth of the folding transition arises from the spread in the melting temperatures (from ∼325 K to ∼302 K of the individual transitions: formation of the hydrophobic core, β-hairpin and tertiary fold, with the helix formed earlier. Our simulations initiated from an extended chain accurately predict the native structure, provide a reasonable estimate of the transition barrier height, and explicitly demonstrate the existence of multiple pathways and multiple transition states for folding. Our exhaustive sampling enables us to assess the quality of the Amber ff96/igb5 combination and reveals that while this force field can predict the correct native fold, it nonetheless overstabilizes the α-helix portion of the protein (Tm = ∼387K as well as the denatured structures.
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.
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%.
Structure of a 13-fold superhelix (almost determined from first principles

Directory of Open Access Journals (Sweden)

Guillaume A. Schoch

2015-03-01

Full Text Available Nuclear hormone receptors are cytoplasm-based transcription factors that bind a ligand, translate to the nucleus and initiate gene transcription in complex with a co-activator such as TIF2 (transcriptional intermediary factor 2. For structural studies the co-activator is usually mimicked by a peptide of circa 13 residues, which for the largest part forms an α-helix when bound to the receptor. The aim was to co-crystallize the glucocorticoid receptor in complex with a ligand and the TIF2 co-activator peptide. The 1.82 Å resolution diffraction data obtained from the crystal could not be phased by molecular replacement using the known receptor structures. HPLC analysis of the crystals revealed the absence of the receptor and indicated that only the co-activator peptide was present. The self-rotation function displayed 13-fold rotational symmetry, which initiated an exhaustive but unsuccessful molecular-replacement approach using motifs of 13-fold symmetry such as α- and β-barrels in various geometries. The structure was ultimately determined by using a single α-helix and the software ARCIMBOLDO, which assembles fragments placed by PHASER before using them as seeds for density modification model building in SHELXE. Systematic variation of the helix length revealed upper and lower size limits for successful structure determination. A beautiful but unanticipated structure was obtained that forms superhelices with left-handed twist throughout the crystal, stabilized by ligand interactions. Together with the increasing diversity of structural elements in the Protein Data Bank the results from TIF2 confirm the potential of fragment-based molecular replacement to significantly accelerate the phasing step for native diffraction data at around 2 Å resolution.
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.
Human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site

Directory of Open Access Journals (Sweden)

Misquitta Stephanie A

2004-02-01

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

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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.
F-Type Lectins: A Highly Diversified Family of Fucose-Binding Proteins with a Unique Sequence Motif and Structural Fold, Involved in Self/Non-Self-Recognition

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Gerardo R. Vasta

2017-11-01

Full Text Available The F-type lectin (FTL family is one of the most recent to be identified and structurally characterized. Members of the FTL family are characterized by a fucose recognition domain [F-type lectin domain (FTLD] that displays a novel jellyroll fold (“F-type” fold and unique carbohydrate- and calcium-binding sequence motifs. This novel lectin family comprises widely distributed proteins exhibiting single, double, or greater multiples of the FTLD, either tandemly arrayed or combined with other structurally and functionally distinct domains, yielding lectin subunits of pleiotropic properties even within a single species. Furthermore, the extraordinary variability of FTL sequences (isoforms that are expressed in a single individual has revealed genetic mechanisms of diversification in ligand recognition that are unique to FTLs. Functions of FTLs in self/non-self-recognition include innate immunity, fertilization, microbial adhesion, and pathogenesis, among others. In addition, although the F-type fold is distinctive for FTLs, a structure-based search revealed apparently unrelated proteins with minor sequence similarity to FTLs that displayed the FTLD fold. In general, the phylogenetic analysis of FTLD sequences from viruses to mammals reveals clades that are consistent with the currently accepted taxonomy of extant species. However, the surprisingly discontinuous distribution of FTLDs within each taxonomic category suggests not only an extensive structural/functional diversification of the FTLs along evolutionary lineages but also that this intriguing lectin family has been subject to frequent gene duplication, secondary loss, lateral transfer, and functional co-option.

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.

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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.
Modeling Vocal Fold Intravascular Flow using Synthetic Replicas

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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.
Quantitative Study for the Surface Dehydration of Vocal Folds Based on High-Speed Imaging.

Science.gov (United States)

Li, Lin; Zhang, Yu; Maytag, Allison L; Jiang, Jack J

2015-07-01

From the perspective of the glottal area and mucosal wave, quantitatively estimate the differences of vocal fold on laryngeal activity during phonation at three different dehydration levels. Controlled three sets of tests. A dehydration experiment for 10 excised canine larynges was conducted at 16 cm H2O. According to the dehydration cycle time (H), dehydration levels were divided into three degrees (0% H, 50% H, 75% H). The glottal area and mucosal wave under three dehydration levels were extracted from high-speed images and digital videokymography (DKG) image sequences. Direct and non-direct amplitude components were derived from glottal areas. The amplitude and frequency of mucosal wave were calculated from DKG image sequences. These parameters in condition of three dehydration levels were compared for statistical analysis. The results showed a significant difference in direct (P = 0.001; P = 0.005) and non-direct (P = 0.005; P = 0.016) components of glottal areas between every two different dehydration levels. Considering the right-upper, right-lower, left-upper, and left-lower of vocal fold, the amplitudes of mucosal waves consistently decreased with increasing of dehydration levels. But, there was no significant difference in frequency. Surface dehydration could give rise to complex variation of vocal fold on tissues and vibratory mechanism, which should need analyzing from multiple perspectives. The results suggested that the combination of glottal area and mucosal wave could be better to research the change of vocal fold at different dehydrations. It would become a better crucial research tool for the clinical treatment of dehydration-induced laryngeal pathologies. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
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).
Structure and activity of the Pseudomonas aeruginosa hotdog-fold thioesterases PA5202 and PA2801.

Science.gov (United States)

Gonzalez, Claudio F; Tchigvintsev, Anatoli; Brown, Greg; Flick, Robert; Evdokimova, Elena; Xu, Xiaohui; Osipiuk, Jerzy; Cuff, Marianne E; Lynch, Susan; Joachimiak, Andrzej; Savchenko, Alexei; Yakunin, Alexander F

2012-06-15

The hotdog fold is one of the basic protein folds widely present in bacteria, archaea and eukaryotes. Many of these proteins exhibit thioesterase activity against fatty acyl-CoAs and play important roles in lipid metabolism, cellular signalling and degradation of xenobiotics. The genome of the opportunistic pathogen Pseudomonas aeruginosa contains over 20 genes encoding predicted hotdog-fold proteins, none of which have been experimentally characterized. We have found that two P. aeruginosa hotdog proteins display high thioesterase activity against 3-hydroxy-3-methylglutaryl-CoA and glutaryl-CoA (PA5202), and octanoyl-CoA (PA2801). Crystal structures of these proteins were solved (at 1.70 and 1.75 Å for PA5202 and PA2801 respectively) and revealed a hotdog fold with a potential catalytic carboxylate residue located on the long α-helix (Asp(57) in PA5202 and Glu(35) in PA2801). Alanine residue replacement mutagenesis of PA5202 identified four residues (Asn(42), Arg(43), Asp(57) and Thr(76)) that are critical for its activity and are located in the active site. A P. aeruginosa PA5202 deletion strain showed an increased secretion of the antimicrobial pigment pyocyanine and an increased expression of genes involved in pyocyanin biosynthesis, suggesting a functional link between PA5202 activity and pyocyanin production. Thus the P. aeruginosa hotdog thioesterases PA5202 and PA2801 have similar structures, but exhibit different substrate preferences and functions.
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...
Discriminating trpzip2 and trpzip4 peptides’ folding landscape using the two-dimensional infrared spectroscopy: A simulation study

International Nuclear Information System (INIS)

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

2014-01-01

We analyzed, based on the theoretical spectroscopic modeling, how the differences in the folding landscapes of two β-hairpin peptides trpzip2 and trpzip4 are reflected in their thermal unfolding infrared measurements. The isotope-edited equilibrium FTIR and two dimensional infrared spectra of the two peptides were calculated, using the nonlinear exciton propagation method, at a series of temperatures. The spectra calculations were based on the configuration distributions generated using the GB OBC implicit solvent MD simulation and the integrated tempering sampling technique. Conformational analysis revealed the different local thermal stabilities for these two peptides, which suggested the different folding landscapes. Our study further suggested that the ellipticities of the isotope peaks in the coherent IR signals are more sensitive to these local stability differences compared with other spectral features such as the peak intensities. Our technique can thus be combined with the relevant experimental measurements to achieve a better understanding of the peptide folding behaviors
Biophysical characterisation of calumenin as a charged F508del-CFTR folding modulator.

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Rashmi Tripathi

Full Text Available The cystic fibrosis transmembrane regulator (CFTR is a cyclic-AMP dependent chloride channel expressed at the apical surface of epithelial cells lining various organs such as the respiratory tract. Defective processing and functioning of this protein caused by mutations in the CFTR gene results in loss of ionic balance, defective mucus clearance, increased proliferation of biofilms and inflammation of human airways observed in cystic fibrosis (CF patients. The process by which CFTR folds and matures under the influence of various chaperones in the secretory pathway remains incompletely understood. Recently, calumenin, a secretory protein, belonging to the CREC family of low affinity calcium binding proteins has been identified as a putative CFTR chaperone whose biophysical properties and functions remain uncharacterized. We compared hydropathy, instability, charge, unfoldability, disorder and aggregation propensity of calumenin and other CREC family members with CFTR associated chaperones and calcium binding proteins, wild-type and mutant CFTR proteins and intrinsically disordered proteins (IDPs. We observed that calumenin, along with other CREC proteins, was significantly more charged and less folded compared to CFTR associated chaperones. Moreover like IDPs, calumenin and other CREC proteins were found to be less hydrophobic and aggregation prone. Phylogenetic analysis revealed a close link between calumenin and other CREC proteins indicating how evolution might have shaped their similar biophysical properties. Experimentally, calumenin was observed to significantly reduce F508del-CFTR aggregation in a manner similar to AavLEA1, a well-characterized IDP. Fluorescence microscopy based imaging analysis also revealed altered trafficking of calumenin in bronchial cells expressing F508del-CFTR, indicating its direct role in the pathophysiology of CF. In conclusion, calumenin is characterized as a charged protein exhibiting close similarity with
α-cluster states in {sup 46,54}Cr from double-folding potentials

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Mohr, Peter [Diakonie-Klinikum, Schwaebisch Hall (Germany); Institute for Nuclear Research (Atomki), Debrecen (Hungary)

2017-10-15

α-cluster states in {sup 46}Cr and {sup 54}Cr are investigated in the double-folding model. This study complements a recent similar work by Souza and Miyake, Eur. Phys. J. A 53, 146 (2017), which was based on a specially shaped potential. Excitation energies, reduced widths, intercluster separations, and intra-band transition strengths are calculated and compared to experimental values for the ground state bands in {sup 46}Cr and {sup 54}Cr. The α-cluster potential is also applied to elastic scattering at low and intermediate energies. Here, as a byproduct, a larger radial extent of the neutron density in {sup 50}Ti is found. (orig.)
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)
Protein solubility and folding enhancement by interaction with RNA.

Directory of Open Access Journals (Sweden)

Seong Il Choi

Full Text Available While basic mechanisms of several major molecular chaperones are well understood, this machinery has been known to be involved in folding of only limited number of proteins inside the cells. Here, we report a chaperone type of protein folding facilitated by interaction with RNA. When an RNA-binding module is placed at the N-terminus of aggregation-prone target proteins, this module, upon binding with RNA, further promotes the solubility of passenger proteins, potentially leading to enhancement of proper protein folding. Studies on in vitro refolding in the presence of RNA, coexpression of RNA molecules in vivo and the mutants with impaired RNA binding ability suggests that RNA can exert chaperoning effect on their bound proteins. The results suggest that RNA binding could affect the overall kinetic network of protein folding pathway in favor of productive folding over off-pathway aggregation. In addition, the RNA binding-mediated solubility enhancement is extremely robust for increasing soluble yield of passenger proteins and could be usefully implemented for high-throughput protein expression for functional and structural genomic research initiatives. The RNA-mediated chaperone type presented here would give new insights into de novo folding in vivo.
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
Spike-adding in parabolic bursters: The role of folded-saddle canards

Science.gov (United States)

Desroches, Mathieu; Krupa, Martin; Rodrigues, Serafim

2016-09-01

The present work develops a new approach to studying parabolic bursting, and also proposes a novel four-dimensional canonical and polynomial-based parabolic burster. In addition to this new polynomial system, we also consider the conductance-based model of the Aplysia R15 neuron known as the Plant model, and a reduction of this prototypical biophysical parabolic burster to three variables, including one phase variable, namely the Baer-Rinzel-Carillo (BRC) phase model. Revisiting these models from the perspective of slow-fast dynamics reveals that the number of spikes per burst may vary upon parameter changes, however the spike-adding process occurs in an explosive fashion that involves special solutions called canards. This spike-adding canard explosion phenomenon is analysed by using tools from geometric singular perturbation theory in tandem with numerical bifurcation techniques. We find that the bifurcation structure persists across all considered systems, that is, spikes within the burst are incremented via the crossing of an excitability threshold given by a particular type of canard orbit, namely the true canard of a folded-saddle singularity. However there can be a difference in the spike-adding transitions in parameter space from one case to another, according to whether the process is continuous or discontinuous, which depends upon the geometry of the folded-saddle canard. Using these findings, we construct a new polynomial approximation of the Plant model, which retains all the key elements for parabolic bursting, including the spike-adding transitions mediated by folded-saddle canards. Finally, we briefly investigate the presence of spike-adding via canards in planar phase models of parabolic bursting, namely the theta model by Ermentrout and Kopell.

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.
Unilateral Vocal Fold Paralysis and Risk of Pneumonia: A Nationwide Population-Based Cohort Study.

Science.gov (United States)

Tsai, Ming-Shao; Yang, Yao-Hsu; Liu, Chia-Yen; Lin, Meng-Hung; Chang, Geng-He; Tsai, Yao-Te; Li, Hsueh-Yu; Tsai, Ying-Huang; Hsu, Cheng-Ming

2018-05-01

Objective To investigate pneumonia risk among patients with unilateral vocal fold paralysis (UVFP). Study Design Retrospective population-based cohort study. Setting This study used data from the National Health Insurance Research Database of Taiwan, a nationwide population-based database. Subjects and Methods A total of 419 patients newly diagnosed with UVFP between January 1, 1997, and December 31, 2013, were identified from the Longitudinal Health Insurance Database 2000, a nationally representative database of 1 million randomly selected patients. Moreover, 1676 patients without UVFP were matched to patients with UVFP at a 1:4 ratio based on age, sex, socioeconomic status, urbanization level, and site-specific cancers. Patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of pneumonia. Results The cumulative incidence of pneumonia was significantly higher for patients with UVFP than those without UFVP ( P < .001). The adjusted Cox proportional hazard model showed that UVFP was significantly associated with a higher incidence of pneumonia (hazard ratio, 1.97; 95% CI, 1.35-2.86; P < .001). Subgroup analyses demonstrated that UVFP was an independent risk factor of pneumonia for 4 subgroups: young (18-50 years), older (≥51 years), male, and cancer. Conclusion This is the first nationwide population-based cohort study to investigate the association between UVFP and pneumonia. The findings indicate that UVFP is an independent risk factor of pneumonia. Given the study results, physicians should be aware of the potential for pneumonia occurrence following UVFP.
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

Science.gov (United States)

Moret, M. A.

2011-09-01

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

Science.gov (United States)

Yu, Qin; Hu, Liyan; Yao, Qing; Zhu, Yongqun; Dong, Na; Wang, Da-Cheng; Shao, Feng

2013-06-01

Rab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.
Improved antimicrobial activities of synthetic-hybrid bacteriocins designed from enterocin E50-52 and pediocin PA-1.

Science.gov (United States)

Tiwari, Santosh Kumar; Sutyak Noll, Katia; Cavera, Veronica L; Chikindas, Michael L

2015-03-01

Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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
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.
Mapping of near surface fold structures with GPR and ERT near Steinbrunn (Northern Burgenland, Austria)

Science.gov (United States)

Kreutzer, Ingrid; Chwatal, Werner; Häusler, Hermann; Scheibz, Jürgen; Steirer, Fritz

2014-05-01

In the transition zone between the southern Vienna Basin and the Eisenstadt basin, close to Wr. Neustadt, spectacular fold structures are exposed in the former sand pit of Steinbrunn. The succession of Upper Pannonian age consists of decimetre to meter thick sandy, silty and clayey beds, which are overlain by sandstone beds (Grundtner et al., 2009). The anticline and syncline structures were interpreted as of gravitational origin by Exner et al. (2009), and reinterpreted as of tectonic origin by Häusler (2012a). In order to gain a more detailed insight to the three dimensional distribution and orientation of the folds high resolution geophysics such as electrical resistivity tomography (ERT), ground penetrating radar (GPR) and electromagnetics (EM) were applied to map the surroundings of the sandpit. The ERT- and EM-profiles show that the uppermost layer is more clayey northwest and sandier southeast of the sandpit. This is important for the GPR because clay attenuates the radar signals and therefore no clear layering of the subsurface could be mapped in these areas. In order to directly compare ERT and GPR results with the lithology of the fold structures observed in the sandpit, a reference profile on top of the 140 m long wall of the sandpit was performed. Both methods clearly reveal fold structures paralleling the folded Pannonian strata of the outcrop. While the GPR data displays boundaries and their geometry in the succession, the resistivities in the ERT portrays a more smoothened image of the observed fold structure. In almost all GPR profiles wavelike structures are visible with axes in northern direction and dome-shaped structures with axes in eastern direction, deepening towards the west. In conclusion this pattern is comparable to sections of rounded buckle folds. Although there are clayey areas wave-like and dome-like reflections can be followed in the GPR profiles over a distance of several hundred meters. This is confirmed by the ERT profiles
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

Satellite telemetry reveals higher fishing mortality rates than previously estimated, suggesting overfishing of an apex marine predator.

Science.gov (United States)

Byrne, Michael E; Cortés, Enric; Vaudo, Jeremy J; Harvey, Guy C McN; Sampson, Mark; Wetherbee, Bradley M; Shivji, Mahmood

2017-08-16

Overfishing is a primary cause of population declines for many shark species of conservation concern. However, means of obtaining information on fishery interactions and mortality, necessary for the development of successful conservation strategies, are often fisheries-dependent and of questionable quality for many species of commercially exploited pelagic sharks. We used satellite telemetry as a fisheries-independent tool to document fisheries interactions, and quantify fishing mortality of the highly migratory shortfin mako shark ( Isurus oxyrinchus ) in the western North Atlantic Ocean. Forty satellite-tagged shortfin mako sharks tracked over 3 years entered the Exclusive Economic Zones of 19 countries and were harvested in fisheries of five countries, with 30% of tagged sharks harvested. Our tagging-derived estimates of instantaneous fishing mortality rates ( F = 0.19-0.56) were 10-fold higher than previous estimates from fisheries-dependent data (approx. 0.015-0.024), suggesting data used in stock assessments may considerably underestimate fishing mortality. Additionally, our estimates of F were greater than those associated with maximum sustainable yield, suggesting a state of overfishing. This information has direct application to evaluations of stock status and for effective management of populations, and thus satellite tagging studies have potential to provide more accurate estimates of fishing mortality and survival than traditional fisheries-dependent methodology. © 2017 The Author(s).
Deciphering hierarchical features in the energy landscape of adenylate kinase folding/unfolding

Science.gov (United States)

Taylor, J. Nicholas; Pirchi, Menahem; Haran, Gilad; Komatsuzaki, Tamiki

2018-03-01

Hierarchical features of the energy landscape of the folding/unfolding behavior of adenylate kinase, including its dependence on denaturant concentration, are elucidated in terms of single-molecule fluorescence resonance energy transfer (smFRET) measurements in which the proteins are encapsulated in a lipid vesicle. The core in constructing the energy landscape from single-molecule time-series across different denaturant concentrations is the application of rate-distortion theory (RDT), which naturally considers the effects of measurement noise and sampling error, in combination with change-point detection and the quantification of the FRET efficiency-dependent photobleaching behavior. Energy landscapes are constructed as a function of observation time scale, revealing multiple partially folded conformations at small time scales that are situated in a superbasin. As the time scale increases, these denatured states merge into a single basin, demonstrating the coarse-graining of the energy landscape as observation time increases. Because the photobleaching time scale is dependent on the conformational state of the protein, possible nonequilibrium features are discussed, and a statistical test for violation of the detailed balance condition is developed based on the state sequences arising from the RDT framework.
High porewater exchange in a mangrove-dominated estuary revealed from short-lived radium isotopes

Science.gov (United States)

Sadat-Noori, Mahmood; Santos, Isaac R.; Tait, Douglas R.; Reading, Michael J.; Sanders, Christian J.

2017-10-01

We hypothesise that mangroves play an important role in groundwater exchange processes in sub-tropical and tropical estuarine waters. To investigate this, multiple high resolution time series measurements of radium across a tidal estuary (Coffs Creek, NSW, Australia) were performed as well as a spatial survey in both bottom and surface layers. Results from the spatial survey revealed increasing radium concentrations in parts of the estuary surrounded by mangroves. The average radium concentration in estuary areas lined with mangroves was 2.5 times higher than the average concentration at the mouth of the estuary and 6.5-fold higher than upstream freshwater areas. Additionally, the area enriched in radium coincided with low dissolved oxygen concentrations, implying that porewater exchange may drive anoxia. A radium mass balance model based on 223Ra and 224Ra isotopes at different sections of the estuary confirmed higher porewater exchange rates from areas fringed with mangrove vegetation. Estimated porewater exchange rates were 27.8 ± 5.3 and 13.6 ± 2.1 cm d-1 (0.8 ± 0.1 and 0.4 ± 0.1 m3 s-1) based on 223Ra and 224Ra isotopes, respectively. The average saline porewater exchange was ∼ 10-fold larger than the upstream surface freshwater inputs to the estuary. We suggest that mangrove environments within subtropical estuaries are hotspots for porewater exchange due to the complex belowground structure of crab burrows and the effect of tidal pumping. Because porewater exchange releases carbon and nitrogen from coastal sediments, development and modification of mangrove areas in subtropical estuaries have a significant effect on coastal biogeochemical cycles.
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
Acromegaly Presenting With Bilateral Vocal Fold Immobility: Case Report and Review of the Literature.

Science.gov (United States)

Cooper, Timothy; Dziegielewski, Peter T; Singh, Praby; Seemann, Robert

2016-11-01

To present a case of bilateral vocal fold immobility (BVCI) in a patient with acromegaly and review the current literature describing this presentation. Case report and literature review. Academic tertiary care center. English language literature search of online journal databases. A 56-year-old man presented with 3 months of progressive stridor and shortness of breath. Transnasal flexible endoscopy revealed BVCI. A tracheostomy was performed to secure his airway. Further history was suggestive of acromegaly and imaging demonstrated a pituitary macroadenoma. The diagnosis of acromegaly was made. The patient was treated with octreotide followed by an endoscopic trans sphenoidal resection of the pituitary adenoma. Sixteen months after his initial presentation, a right laser arytenoidectomy was performed and the patient was subsequently decannulated. In the literature to date, 11 cases of BVCI in acromegaly have been reported. These patients often present with stridor and require a tracheostomy. With treatment of their acromegaly, these patients may regain vocal fold mobility and may be decannulated. Acromegaly with BVCI is a rare presentation. Acute management of the airway of patients with acromegaly presenting with BVCI typically requires a tracheostomy. A period of 15 months should be allowed for restoration of vocal fold mobility before airway opening procedures are considered. Copyright Â© 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex

DEFF Research Database (Denmark)

Lou, Chenguang; Christensen, Niels Johan; Martos Maldonado, Manuel Cristo

2017-01-01

by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne-azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex......, small-angle X-ray scattering (SAXS), and molecular modeling. Stabilizing cooperativity was observed between the trimeric peptide and the oligonucleotide triplex domains, and the overall molecular size (ca. 12nm) in solution was revealed to be independent of concentration. The topological folding...
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.
Longitudinal development of cortical thickness, folding, and fiber density networks in the first 2 years of life.

Science.gov (United States)

Nie, Jingxin; Li, Gang; Wang, Li; Shi, Feng; Lin, Weili; Gilmore, John H; Shen, Dinggang

2014-08-01

Quantitatively characterizing the development of cortical anatomical networks during the early stage of life plays an important role in revealing the relationship between cortical structural connection and high-level functional development. The development of correlation networks of cortical-thickness, cortical folding, and fiber-density is systematically analyzed in this article to study the relationship between different anatomical properties during the first 2 years of life. Specifically, longitudinal MR images of 73 healthy subjects from birth to 2 year old are used. For each subject at each time point, its measures of cortical thickness, cortical folding, and fiber density are projected to its cortical surface that has been partitioned into 78 cortical regions. Then, the correlation matrices for cortical thickness, cortical folding, and fiber density at each time point can be constructed, respectively, by computing the inter-regional Pearson correlation coefficient (of any pair of ROIs) across all 73 subjects. Finally, the presence/absence pattern (i.e., binary pattern) of the connection network is constructed from each inter-regional correlation matrix, and its statistical and anatomical properties are adopted to analyze the longitudinal development of anatomical networks. The results show that the development of anatomical network could be characterized differently by using different anatomical properties (i.e., using cortical thickness, cortical folding, or fiber density). Copyright © 2013 Wiley Periodicals, Inc.
Longitudinal Development of Cortical Thickness, Folding, and Fiber Density Networks in the First 2 Years of Life

OpenAIRE

Nie, Jingxin; Li, Gang; Wang, Li; Shi, Feng; Lin, Weili; Gilmore, John H.; Shen, Dinggang

2013-01-01

Quantitatively characterizing the development of cortical anatomical networks during the early stage of life plays an important role in revealing the relationship between cortical structural connection and high-level functional development. The development of correlation networks of cortical-thickness, cortical folding, and fiber-density is systematically analyzed in this article to study the relationship between different anatomical properties during the first 2 years of life. Specifically, ...
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.
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.
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.
Multidimensional effects of voice therapy in patients affected by unilateral vocal fold paralysis due to cancer.

Science.gov (United States)

Barcelos, Camila Barbosa; Silveira, Paula Angélica Lorenzon; Guedes, Renata Lígia Vieira; Gonçalves, Aline Nogueira; Slobodticov, Luciana Dall'Agnol Siqueira; Angelis, Elisabete Carrara-de

2017-08-24

Patients with unilateral vocal fold paralysis may demonstrate different degrees of voice perturbation depending on the position of the paralyzed vocal fold. Understanding the effectiveness of voice therapy in this population may be an important coefficient to define the therapeutic approach. To evaluate the voice therapy effectiveness in the short, medium and long-term in patients with unilateral vocal fold paralysis and determine the risk factors for voice rehabilitation failure. Prospective study with 61 patients affected by unilateral vocal fold paralysis enrolled. Each subject had voice therapy with an experienced speech pathologist twice a week. A multidimensional assessment protocol was used pre-treatment and in three different times after voice treatment initiation: short-term (1-3 months), medium-term (4-6 months) and long-term (12 months); it included videoendoscopy, maximum phonation time, GRBASI scale, acoustic voice analysis and the portuguese version of the voice handicap index. Multiple comparisons for GRBASI scale and VHI revealed statistically significant differences, except between medium and long term (pvocal improvement over time with stabilization results after 6 months (medium term). From the 28 patients with permanent unilateral vocal fold paralysis, 18 (69.2%) reached complete glottal closure following vocal therapy (p=0.001). The logistic regression method indicated that the Jitter entered the final model as a risk factor for partial improvement. For every unit of increased jitter, there was an increase of 0.1% (1.001) of the chance for partial improvement, which means an increase on no full improvement chance during rehabilitation. Vocal rehabilitation improves perceptual and acoustic voice parameters and voice handicap index, besides favor glottal closure in patients with unilateral vocal fold paralysis. The results were also permanent during the period of 1 year. The Jitter value, when elevated, is a risk factor for the voice therapy
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
The murderer is the bed: an unusual case of death by traumatic asphyxia in a hotel folding bunk bed.

Science.gov (United States)

Domènech, Mercè Subirana; Alcázar, Helena Martínez; Pallarès, Antoni Aguilar; Vicente, Ignasi Galtés; García, Josep Castellà; Gutiérrez, Claudina Vidal; Muñiz, Jordi Medallo

2012-07-10

This paper presents the first referenced case on a death by traumatic asphyxia in a folding bunk bed. A middle-aged man was found dead in a hotel room trapped into a lower folding bunk bed where he had been sleeping after a party. The autopsy showed signs of asphyxia and excluded signs of struggle and sexual intercourse. Toxicological analyses revealed alcohol intoxication. A differential diagnosis of the manner of death including a technical study of the bed which contributed to understand the circumstances of death was made. The medico-legal investigation of the case strongly supported the hypothesis of an accidental death by traumatic asphyxia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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...
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)
Towards the theoretical bases of the folding of the 100-A nucleosome filament

International Nuclear Information System (INIS)

Chela Flores, J.

1994-01-01

We attempt to model DNA packaging at the various stages of ever increasing DNA folding from the 100-A nucleosome filament to various further stages leading up to the metaphase chromosome. We have assumed that a phase transition has induced chromatin into a condensed mode. The mean-field model allows the simultaneous discussion of chromatin with packaging ration η and DNA replication at various stages of folding. We derive a formula correlating (during the S phase of the cell cycle) the DNA polymerase velocity r f (measured in nucleotides per minute) in a relation of inverse proportionality with the degree of DNA packaging: r f = λη -1/2 , where the dimensional constant λ has been determined. This model suggests that in the heterochromatic regions of chromatin there is reduced activity of DNA polymerases. We discuss the possible relevance of our model to late replicating telomeres in yeast and several higher eukaryotes. (author). 28 refs, 3 tabs
Utility of Eating Assessment Tool-10 in Predicting Aspiration in Patients with Unilateral Vocal Fold Paralysis.

Science.gov (United States)

Zuniga, Steven A; Ebersole, Barbara; Jamal, Nausheen

2018-03-01

Objective Examine the incidence of penetration/aspiration in patients with unilateral vocal fold immobility and investigate the relationship with self-reported perception of dysphagia. Study Design Case series with chart review. Setting Academic cancer center. Subjects and Methods Adult patients with unilateral vocal fold immobility diagnosed between 2014 and 2016 were reviewed. Patients were stratified into an aspiration group and a nonaspiration group using objective findings on flexible endoscopic evaluation of swallowing, as scored using Rosenbek's Penetration Aspiration Scale. Objective findings were compared to patient perception of dysphagia. Bivariate linear correlation analysis was performed to evaluate correlation between Eating Assessment Tool-10 scores and presence of aspiration. Tests of diagnostic accuracy were calculated to investigate the predictive value of Eating Assessment Tool-10 scores >9 on aspiration risk. Results Of the 35 patients with new-onset unilateral vocal fold immobility were evaluated, 25.7% (9/35) demonstrated tracheal aspiration. Mean ± SD Eating Assessment Tool-10 scores were 19.2 ± 13.7 for aspirators and 7.0 ± 7.8 for nonaspirators ( P = .016). A statistically significant correlation was demonstrated between increasing Eating Assessment Tool-10 scores and Penetration Aspiration Scale scores ( r = 0.511, P = .002). Diagnostic accuracy analysis for aspiration risk in patients with an Eating Assessment Tool-10 score >9 revealed a sensitivity of 77.8% and a specificity of 73.1%. Conclusion Patient perception of swallowing difficulty may have utility in predicting aspiration risk. An EAT-10 of >9 in patients with unilateral vocal fold immobility may portend up to a 5 times greater risk of aspiration. Routine swallow testing to assess for penetration/aspiration may be indicated in patients with unilateral vocal fold immobility.
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.
Changes in Peak Airflow Measurement During Maximal Cough After Vocal Fold Augmentation in Patients With Glottic Insufficiency.

Science.gov (United States)

Dion, Gregory R; Achlatis, Efstratios; Teng, Stephanie; Fang, Yixin; Persky, Michael; Branski, Ryan C; Amin, Milan R

2017-11-01

median improvement was 50 L/min (95% CI, 10-75 L/min; P = .01). Immediate peak airflow measurements during cough collected within 30 minutes of augmentation varied when compared with measurements collected at follow-up (103-380 vs 160-390 L/min). Peak airflow during maximal cough may improve with vocal fold augmentation. Additional assessment and measurements are needed to further delineate which patients will benefit most regarding their cough from vocal fold augmentation.
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.
Global analysis of threat status reveals higher extinction risk in tropical than in temperate bird sister species

Directory of Open Access Journals (Sweden)

Reif Jiří

2016-06-01

Full Text Available Given increasing pressures upon biodiversity, identification of species’ traits related to elevated extinction risk is useful for more efficient allocation of limited resources for nature conservation. Despite its need, such a global analysis was lacking in the case of birds. Therefore, we performed this exercise for avian sister species using information about their global extinction risk from IUCN Red List. We focused on 113 pairs of sister species, each containing a threatened and an unthreatened species to factor out the effects of common evolutionary history on the revealed relationship. We collected data on five traits with expected relationships to species’ extinction risk based on previous studies performed at regional or national levels: breeding habitat (recognizing forest, grassland, wetland and oceanic species, latitudinal range position (temperate and tropics species, migration strategy (migratory and resident species, diet (carnivorous, insectivorous, herbivorous and omnivorous species and body mass. We related the extinction risk using IUCN threat level categories to species’ traits using generalised linear mixed effects models expecting lower risk for forest, temperate, omnivorous and smaller-bodied species. Our expectation was confirmed only in the case of latitudinal range position, as we revealed higher threat level for tropical than for temperate species. This relationship was robust to different methods of threat level expression and cannot be explained by a simple association of high bird species richness with the tropical zone. Instead, it seems that tropical species are more threatened because of their intrinsic characteristics such as slow life histories, adaptations to stable environments and small geographic ranges. These characteristics are obviously disadvantageous in conditions of current human-induced environmental perturbations. Moreover, given the absence of habitat effects, our study indicates that such
Effects of Metal Ions, Temperature, and a Denaturant on the Oxidative Folding Pathways of Bovine α-Lactalbumin

Directory of Open Access Journals (Sweden)

Reina Shinozaki

2017-09-01

Full Text Available Bovine α-lactalbumin (αLA has four disulfide (SS bonds in the native form (N. On the oxidative folding pathways of this protein, two specific SS folding intermediates, i.e., (61–77, 73–91 and des[6–120], which have two and three native SS bonds, respectively, accumulate predominantly in the presence of Ca2+. In this study, we reinvestigated the pathways using a water-soluble cyclic selenoxide reagent, trans-3,4-dihydroxyselenolane oxide (DHSox, as a strong and quantitative oxidant to oxidize the fully reduced form (R. In the presence of ethylenediaminetetraacetic acid (EDTA (under a metal-free condition, SS formation randomly proceeded, and N did not regenerate. On the other hand, two specific SS intermediates transiently generated in the presence of Ca2+. These intermediates could be assigned to (61–77, 73–91 and des[6–120] having two common SS bonds, i.e., Cys61-Cys77 and Cys73-Cys91, near the calcium binding pocket of the β-sheet domain. Much faster folding to N was observed in the presence of Mn2+, whereas Na+, K+, Mg2+, and Zn2+ did not affect the pathways. The two key intermediates were susceptible to temperature and a denaturant. The oxidative folding pathways revealed were significantly different from those of hen egg white lysozyme, which has the same SS-bonding pattern as αLA, suggesting that the folding pathways of SS-containing proteins can alter depending on the amino acid sequence and other factors, even when the SS-bond topologies are similar to each other.
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.
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/.
Fluorescent in situ folding control for rapid optimization of cell-free membrane protein synthesis.

Directory of Open Access Journals (Sweden)

Annika Müller-Lucks

Full Text Available Cell-free synthesis is an open and powerful tool for high-yield protein production in small reaction volumes predestined for high-throughput structural and functional analysis. Membrane proteins require addition of detergents for solubilization, liposomes, or nanodiscs. Hence, the number of parameters to be tested is significantly higher than with soluble proteins. Optimization is commonly done with respect to protein yield, yet without knowledge of the protein folding status. This approach contains a large inherent risk of ending up with non-functional protein. We show that fluorophore formation in C-terminal fusions with green fluorescent protein (GFP indicates the folding state of a membrane protein in situ, i.e. within the cell-free reaction mixture, as confirmed by circular dichroism (CD, proteoliposome reconstitution and functional assays. Quantification of protein yield and in-gel fluorescence intensity imply suitability of the method for membrane proteins of bacterial, protozoan, plant, and mammalian origin, representing vacuolar and plasma membrane localization, as well as intra- and extracellular positioning of the C-terminus. We conclude that GFP-fusions provide an extension to cell-free protein synthesis systems eliminating the need for experimental folding control and, thus, enabling rapid optimization towards membrane protein quality.
Office-Based Autologous Fat Injection Laryngoplasty for Glottic Insufficiency in Patients Under 50 Years Old.

Science.gov (United States)

Hu, Hao-Chun; Hung, Yi-Ting; Lin, Shu-Yi; Tung, Tao-Hsin; Chang, Shyue-Yih

2018-04-17

We sought to determine the outcomes of office-based autologous fat injection laryngoplasty in the treatment of patients under 50 years old with glottic insufficiency but without neurological problems or acquired organic lesions in the vocal fold. We conducted a retrospective chart review of consecutive patients under 50 years of age who underwent office-based autologous fat injection laryngoplasty for glottic insufficiency. None of the patients presented neurological problems or acquired organic lesions in the vocal fold. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were evaluated before and after treatment. The 23 patients (7 men and 16 women) in this study presented significant improvements in phonatory function in terms of maximum phonation time, jitter, grade, asthenia, and Voice Handicap Index-10 (VHI-10) values at 3 months. Significant improvements in terms of jitter, noise-to-harmonic ratio, grade, roughness, breathiness, asthenia, and the VHI-10 values were also observed at 6 months. Glottic insufficiency in younger patients without neurological problems or acquired organic lesions in the vocal fold can be treated effectively using office-based autologous fat injection laryngoplasty. Significant improvements in phonatory function were observed even 6 months after surgery. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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...
Glutathione maintenance mitigates age-related susceptibility to redox cycling agents

Directory of Open Access Journals (Sweden)

Nicholas O. Thomas

2016-12-01

Full Text Available Isolated hepatocytes from young (4–6 mo and old (24–26 mo F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for young: 405 μM; LC50 for old: 275 μM. Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(PH: quinone oxido-reductase 1 (NQO1 protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3, but glutathione peroxidase 4 (GPX4 declined by 70% (p=0.0043; N=3. These results indicate toxicity may stem from vulnerability to lipid peroxidation instead of inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold higher, and GSH declined by a 3-fold greater margin in old versus young rat cells given 300 µM menadione (p2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated GSH-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds.
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)
Context-dependent protein folding of a virulence peptide in the bacterial and host environments: structure of an SycH–YopH chaperone–effector complex

International Nuclear Information System (INIS)

Vujanac, Milos; Stebbins, C. Erec

2013-01-01

The structure of a SycH–YopH chaperone–effector complex from Yersinia reveals the bacterial state of a protein that adopts different folds in the host and pathogen environments. Yersinia pestis injects numerous bacterial proteins into host cells through an organic nanomachine called the type 3 secretion system. One such substrate is the tyrosine phosphatase YopH, which requires an interaction with a cognate chaperone in order to be effectively injected. Here, the first crystal structure of a SycH–YopH complex is reported, determined to 1.9 Å resolution. The structure reveals the presence of (i) a nonglobular polypeptide in YopH, (ii) a so-called β-motif in YopH and (iii) a conserved hydrophobic patch in SycH that recognizes the β-motif. Biochemical studies establish that the β-motif is critical to the stability of this complex. Finally, since previous work has shown that the N-terminal portion of YopH adopts a globular fold that is functional in the host cell, aspects of how this polypeptide adopts radically different folds in the host and in the bacterial environments are analysed
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.
Rapid fold and structure determination of the archaeal translation elongation factor 1{beta} from Methanobacterium thermoautotrophicum

Energy Technology Data Exchange (ETDEWEB)

Kozlov, Guennadi [McGill University, Department of Biochemistry (Canada); Ekiel, Irena [National Research Council of Canada, Biomolecular NMR Group, Sector of Pharmaceutical Biotechnology, Biotechnology Research Institute (Canada); Beglova, Natalia [McGill University, Department of Biochemistry (Canada); Yee, Adelinda; Dharamsi, Akil; Engel, Asaph [University of Toronto, Department of Medical Biophysics (Canada); Siddiqui, Nadeem; Nong, Andrew; Gehring, Kalle [McGill University, Department of Biochemistry (Canada)

2000-07-15

The tertiary fold of the elongation factor, aEF-1{beta}, from Methanobacterium thermoautotrophicum was determined in a high-throughput fashion using a minimal set of NMR experiments. NMR secondary structure prediction, deuterium exchange experiments and the analysis of chemical shift perturbations were combined to identify the protein fold as an alpha-beta sandwich typical of many RNA binding proteins including EF-G. Following resolution of the tertiary fold, a high resolution structure of aEF-1{beta} was determined using heteronuclear and homonuclear NMR experiments and a semi-automated NOESY assignment strategy. Analysis of the aEF-1{beta} structure revealed close similarity to its human analogue, eEF-1{beta}. In agreement with studies on EF-Ts and human EF-1{beta}, a functional mechanism for nucleotide exchange is proposed wherein Phe46 on an exposed loop acts as a lever to eject GDP from the associated elongation factor G-protein, aEF-1{alpha}. aEF-1{beta} was also found to bind calcium in the groove between helix {alpha}2 and strand {beta}4. This novel feature was not observed previously and may serve a structural function related to protein stability or may play a functional role in archaeal protein translation.
Rapid fold and structure determination of the archaeal translation elongation factor 1β from Methanobacterium thermoautotrophicum

International Nuclear Information System (INIS)

Kozlov, Guennadi; Ekiel, Irena; Beglova, Natalia; Yee, Adelinda; Dharamsi, Akil; Engel, Asaph; Siddiqui, Nadeem; Nong, Andrew; Gehring, Kalle

2000-01-01

The tertiary fold of the elongation factor, aEF-1β, from Methanobacterium thermoautotrophicum was determined in a high-throughput fashion using a minimal set of NMR experiments. NMR secondary structure prediction, deuterium exchange experiments and the analysis of chemical shift perturbations were combined to identify the protein fold as an alpha-beta sandwich typical of many RNA binding proteins including EF-G. Following resolution of the tertiary fold, a high resolution structure of aEF-1β was determined using heteronuclear and homonuclear NMR experiments and a semi-automated NOESY assignment strategy. Analysis of the aEF-1β structure revealed close similarity to its human analogue, eEF-1β. In agreement with studies on EF-Ts and human EF-1β, a functional mechanism for nucleotide exchange is proposed wherein Phe46 on an exposed loop acts as a lever to eject GDP from the associated elongation factor G-protein, aEF-1α. aEF-1β was also found to bind calcium in the groove between helix α2 and strand β4. This novel feature was not observed previously and may serve a structural function related to protein stability or may play a functional role in archaeal protein translation
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...
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
How Robust Is the Mechanism of Folding-Upon-Binding for an Intrinsically Disordered Protein?

Science.gov (United States)

Bonetti, Daniela; Troilo, Francesca; Brunori, Maurizio; Longhi, Sonia; Gianni, Stefano

2018-04-24

The mechanism of interaction of an intrinsically disordered protein (IDP) with its physiological partner is characterized by a disorder-to-order transition in which a recognition and a binding step take place. Even if the mechanism is quite complex, IDPs tend to bind their partner in a cooperative manner such that it is generally possible to detect experimentally only the disordered unbound state and the structured complex. The interaction between the disordered C-terminal domain of the measles virus nucleoprotein (N TAIL ) and the X domain (XD) of the viral phosphoprotein allows us to detect and quantify the two distinct steps of the overall reaction. Here, we analyze the robustness of the folding of N TAIL upon binding to XD by measuring the effect on both the folding and binding steps of N TAIL when the structure of XD is modified. Because it has been shown that wild-type XD is structurally heterogeneous, populating an on-pathway intermediate under native conditions, we investigated the binding to 11 different site-directed variants of N TAIL of one particular variant of XD (I504A XD) that populates only the native state. Data reveal that the recognition and the folding steps are both affected by the structure of XD, indicating a highly malleable pathway. The experimental results are briefly discussed in the light of previous experiments on other IDPs. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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...
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.
Medialization thyroplasty in glottis insufficiency due to unilateral vocal fold paralysis and after laser cordectomies - preliminary report.

Science.gov (United States)

Rzepakowska, Anna; Osuch-Wójcikiewicz, Ewa; Sielska-Badurek, Ewelina; Niemczyk, Kazimierz

2017-02-28

Medialization thyroplasty (type I) is surgical procedure performed on the thyroid cartilage. The major indication for this surgery is significant glottis insufficiency due to unilateral vocal fold paresis. However the proce¬dure is also performed after vocal fold resections during cordectomy. The evaluation of voice results in patients after medialisation throplasty. In Otolaryngology Department of Medical University of Warsaw there were performed so far 8 thyroplasty procedures under local anaesthesia with implantation of medical silicon protesis. 6 patients had unilat¬eral vocal fold paresis and the rest two underwent in the past laser cordectomy due to T1a vocal carcinoma. There were no complications during and post the surgery. The follow up examination in 1st , 3rd, 6th i 12th months postoperatively revealed for all patients significant improvement of glottal closure in laryngeal videostrobos¬copy. The voice quality improved both in perceptual evaluation (GRBAS scale) and acoustic analysis (F0, jitter, shim¬mer, NHR) in both patients groups. However the rate of improvement was much more significant in group with uni¬lateral vocal fold paresis. In all patients the maximum phonation time (MPT) increased. The self-evaluation of voice quality with Voice Handicap Index questionnaire confirmed also individual improvement. The speech rehabilitations is not successful in each patient with glottis insufficiency. The medialisation thyroplasty remains the standard procedure for permanent improvement of voice quality in those cases.
Can you see what you feel? Color and folding properties affect visual-tactile material discrimination of fabrics.

Science.gov (United States)

Xiao, Bei; Bi, Wenyan; Jia, Xiaodan; Wei, Hanhan; Adelson, Edward H

2016-01-01

Humans can often estimate tactile properties of objects from vision alone. For example, during online shopping, we can often infer material properties of clothing from images and judge how the material would feel against our skin. What visual information is important for tactile perception? Previous studies in material perception have focused on measuring surface appearance, such as gloss and roughness, and using verbal reports of material attributes and categories. However, in real life, predicting tactile properties of an object might not require accurate verbal descriptions of its surface attributes or categories. In this paper, we use tactile perception as ground truth to measure visual material perception. Using fabrics as our stimuli, we measure how observers match what they see (photographs of fabric samples) with what they feel (physical fabric samples). The data shows that color has a significant main effect in that removing color significantly reduces accuracy, especially when the images contain 3-D folds. We also find that images of draped fabrics, which revealed 3-D shape information, achieved better matching accuracy than images with flattened fabrics. The data shows a strong interaction between color and folding conditions on matching accuracy, suggesting that, in 3-D folding conditions, the visual system takes advantage of chromatic gradients to infer tactile properties but not in flattened conditions. Together, using a visual-tactile matching task, we show that humans use folding and color information in matching the visual and tactile properties of fabrics.
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...
INFLUENCES OF 50HZ ELECTRIC FIELDS ON GROWTH AND MULTIPLICATION OF SOME MICROORGANISMS

Directory of Open Access Journals (Sweden)

VOINA A.

2016-07-01

Full Text Available By dielectric spectroscopy and specific microbiological techniques have been studied the development (cell multiplication of Saccharomyces cerevisiae and Aspergillus niger growing and multiplication - both on culture media with sucrose and on those with starch. The experimental results have been revealed that the biochemical processes of the studied biomasses have significant changes in certain frequencies in the range 1 - 160Hz, characteristic of the different species/metabolized carbon source, respectively species/ metabolized carbon source/ development phase. It has also been found that in the case of Saccharomyces cerevisiae, the electric field of 50 Hz up to 20V/cm reduces the length of the LAG time and increases the growth rate of intensive increasing phase. Cultures of Aspergillus niger on culture medium with sucrose are stimulated (increasing the spores production by approx. 50% and reducing the maturity time of 50Hz signals up to 15V/cm. Electric fields higher than 30 V/cm in all media and investigated cultures carry on to the growth reduction / multiplication - up to a complete inhibition of growth at approx. 50V/cm
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)

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...
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...
Cell surface area and membrane folding in glioblastoma cell lines differing in PTEN and p53 status.

Directory of Open Access Journals (Sweden)

Simon Memmel

Full Text Available Glioblastoma multiforme (GBM is characterized by rapid growth, invasion and resistance to chemo-/radiotherapy. The complex cell surface morphology with abundant membrane folds, microvilli, filopodia and other membrane extensions is believed to contribute to the highly invasive behavior and therapy resistance of GBM cells. The present study addresses the mechanisms leading to the excessive cell membrane area in five GBM lines differing in mutational status for PTEN and p53. In addition to scanning electron microscopy (SEM, the membrane area and folding were quantified by dielectric measurements of membrane capacitance using the single-cell electrorotation (ROT technique. The osmotic stability and volume regulation of GBM cells were analyzed by video microscopy. The expression of PTEN, p53, mTOR and several other marker proteins involved in cell growth and membrane synthesis were examined by Western blotting. The combined SEM, ROT and osmotic data provided independent lines of evidence for a large variability in membrane area and folding among tested GBM lines. Thus, DK-MG cells (wild type p53 and wild type PTEN exhibited the lowest degree of membrane folding, probed by the area-specific capacitance C m = 1.9 µF/cm(2. In contrast, cell lines carrying mutations in both p53 and PTEN (U373-MG and SNB19 showed the highest C m values of 3.7-4.0 µF/cm(2, which corroborate well with their heavily villated cell surface revealed by SEM. Since PTEN and p53 are well-known inhibitors of mTOR, the increased membrane area/folding in mutant GBM lines may be related to the enhanced protein and lipid synthesis due to a deregulation of the mTOR-dependent downstream signaling pathway. Given that membrane folds and extensions are implicated in tumor cell motility and metastasis, the dielectric approach presented here provides a rapid and simple tool for screening the biophysical cell properties in studies on targeting chemo- or radiotherapeutically the
Magnetocrystalline two-fold symmetry in CaFe2O4 single crystal

International Nuclear Information System (INIS)

Gandhi, Ashish Chhaganlal; Das, Rajasree; Chou, Fang-Cheng; Lin, Jauyn Grace

2017-01-01

Understanding of magnetocrystalline anisotropy in CaFe 2 O 4 is a matter of importance for its future applications. A high quality single crystal CaFe 2 O 4 sample is studied by using synchrotron x-ray diffraction, a magnetometer and the electron spin resonance (ESR) technique. A broad feature of the susceptibility curve around room temperature is observed, indicating the development of 1D spin interactions above the on-set of antiferromagnetic transition. The angular dependency of ESR reveals an in-plane two-fold symmetry, suggesting a strong correlation between the room temperature spin structure and magnetocrystalline anisotropy. This finding opens an opportunity for the device utilizing the anisotropy field of CaFe 2 O 4 . (paper)
Magnetocrystalline two-fold symmetry in CaFe2O4 single crystal

Science.gov (United States)

Chhaganlal Gandhi, Ashish; Das, Rajasree; Chou, Fang-Cheng; Lin, Jauyn Grace

2017-05-01

Understanding of magnetocrystalline anisotropy in CaFe2O4 is a matter of importance for its future applications. A high quality single crystal CaFe2O4 sample is studied by using synchrotron x-ray diffraction, a magnetometer and the electron spin resonance (ESR) technique. A broad feature of the susceptibility curve around room temperature is observed, indicating the development of 1D spin interactions above the on-set of antiferromagnetic transition. The angular dependency of ESR reveals an in-plane two-fold symmetry, suggesting a strong correlation between the room temperature spin structure and magnetocrystalline anisotropy. This finding opens an opportunity for the device utilizing the anisotropy field of CaFe2O4.
Folding Membrane Proteins by Deep Transfer Learning

KAUST Repository

Wang, Sheng

2017-08-29

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

Science.gov (United States)

Brunner, Elke; Friedrich, Gerhard; Kiesler, Karl; Chibidziura-Priesching, Jutta; Gugatschka, Markus

2011-01-01

Dysphonia is considered a major symptom of unilateral vocal fold paralysis (UVFP). Besides this, many patients complain of further symptoms such as dysphagia and dyspnea, which might not be expected to such an extent. The aim of this survey was to elucidate these symptoms in a cohort of patients with UVFP. Sixty-three patients (22 men, 41 women) suffering from UVFP were interviewed. Therefore we developed a questionnaire dealing with each of the three symptom categories: voice production, swallowing and breathing. All of the surveyed patients reported voice impairment, almost 60% complained of swallowing problems after the onset of paralysis. Seventy-five percent reported a subjectively impaired breathing sensation, not just phonatory dyspnea but during everyday physical activity as well. Our study revealed a certain discrepancy between objectively assessed laryngoscopic findings and subjective symptoms. A majority of patients suffered from an impairment in each of the three laryngeal functions (dysphonia, dysphagia and dyspnea). The latter two differ from the classic approach to this condition but must be considered as well in clinical diagnostics and therapy. Copyright © 2010 S. Karger AG, Basel.
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.
The 27 February 1997 Sibi double-earthquake (Mw 6.9, 6.7) in the Sulaiman range of Pakistan - implications for the tectonics of fold-and-thrust belts and for earthquake triggering mechanisms

Science.gov (United States)

Nissen, E.; Craig, T. J.; McMullan, K.; Parsons, B. E.; Rickerby, A.; Wright, T. J.

2011-12-01

The Sulaiman mountains form an arcuate fold-and-thrust belt which accommodates oblique shortening between the Indian and Eurasian plates in western Pakistan. Despite being an important component of the India-Eurasia collision zone, little is known about the active tectonics of the range. The Mw ~7 Sibi earthquake of 27 February 1997 was the largest event to strike the Sulaiman mountains in the past eighty years, and provides an excellent opportunity to investigate the regional style of deformation. A pair of radar interferograms constructed from descending-track ERS-2 data reveals two distinct areas containing coseismic surface displacements, spaced ~50 km apart. We model these displacements to yield source parameters for the two sub-events. The larger (Mw 6.9) north-western sub-event occurred on a buried, S-dipping reverse fault, with slip confined to depths of between ~10 km and ~20 km. The elongate pattern of surface deformation lies oblique to the trend of local surface anticlines, suggesting that the fault responsible for this sub-event is disconnected from surface folding, possibly by a weak decollement. The smaller (Mw 6.7) south-eastern sub-event also involved reverse slip on a buried, S-dipping fault, but slip here reached shallower depths of ~4 km. Here, coseismic uplift is concentrated along a prominent surface anticline, which we interpret as a fault-propagation fold whose growth is driven by slip on the underlying thrust. These results suggest that (1) detachment folding and forced folding both contribute towards shortening of the Sulaiman mountains, (2) the range contains active S-dipping reverse faults despite the overall southwards propagation of thrusting, and (3) earthquakes can be generated within the thick sedimentary cover and are not restricted to the underlying basement. Finally, we merge the spatial information provided by InSAR with temporal constraints from seismic body-waveform modelling to investigate possible mechanisms for the
The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

Science.gov (United States)

Ju, Xiang-Chun; Hou, Qiong-Qiong; Sheng, Ai-Li; Wu, Kong-Yan; Zhou, Yang; Jin, Ying; Wen, Tieqiao; Yang, Zhengang; Wang, Xiaoqun; Luo, Zhen-Ge

2016-01-01

Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding. DOI: http://dx.doi.org/10.7554/eLife.18197.001 PMID:27504805
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.
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.

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