Streptococcus pneumonia YlxR at 1.35 A shows a putative new fold.

Science.gov (United States)

Osipiuk, J; Górnicki, P; Maj, L; Dementieva, I; Laskowski, R; Joachimiak, A

2001-11-01

The structure of the YlxR protein of unknown function from Streptococcus pneumonia was determined to 1.35 A. YlxR is expressed from the nusA/infB operon in bacteria and belongs to a small protein family (COG2740) that shares a conserved sequence motif GRGA(Y/W). The family shows no significant amino-acid sequence similarity with other proteins. Three-wavelength diffraction MAD data were collected to 1.7 A from orthorhombic crystals using synchrotron radiation and the structure was determined using a semi-automated approach. The YlxR structure resembles a two-layer alpha/beta sandwich with the overall shape of a cylinder and shows no structural homology to proteins of known structure. Structural analysis revealed that the YlxR structure represents a new protein fold that belongs to the alpha-beta plait superfamily. The distribution of the electrostatic surface potential shows a large positively charged patch on one side of the protein, a feature often found in nucleic acid-binding proteins. Three sulfate ions bind to this positively charged surface. Analysis of potential binding sites uncovered several substantial clefts, with the largest spanning 3/4 of the protein. A similar distribution of binding sites and a large sharply bent cleft are observed in RNA-binding proteins that are unrelated in sequence and structure. It is proposed that YlxR is an RNA-binding protein.

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.

AMT1;1 transgenic rice plants with enhanced NH4(+) permeability show superior growth and higher yield under optimal and suboptimal NH4(+) conditions.

Science.gov (United States)

Ranathunge, Kosala; El-Kereamy, Ashraf; Gidda, Satinder; Bi, Yong-Mei; Rothstein, Steven J

2014-03-01

The major source of nitrogen for rice (Oryza sativa L.) is ammonium (NH4(+)). The NH4(+) uptake of roots is mainly governed by membrane transporters, with OsAMT1;1 being a prominent member of the OsAMT1 gene family that is known to be involved in NH4(+) transport in rice plants. However, little is known about its involvement in NH4(+) uptake in rice roots and subsequent effects on NH4(+) assimilation. This study shows that OsAMT1;1 is a constitutively expressed, nitrogen-responsive gene, and its protein product is localized in the plasma membrane. Its expression level is under the control of circadian rhythm. Transgenic rice lines (L-2 and L-3) overexpressing the OsAMT1;1 gene had the same root structure as the wild type (WT). However, they had 2-fold greater NH4(+) permeability than the WT, whereas OsAMT1;1 gene expression was 20-fold higher than in the WT. Analogous to the expression, transgenic lines had a higher NH4(+) content in the shoots and roots than the WT. Direct NH4(+) fluxes in the xylem showed that the transgenic lines had significantly greater uptake rates than the WT. Higher NH4(+) contents also promoted higher expression levels of genes in the nitrogen assimilation pathway, resulting in greater nitrogen assimilates, chlorophyll, starch, sugars, and grain yield in transgenic lines than in the WT under suboptimal and optimal nitrogen conditions. OsAMT1;1 also enhanced overall plant growth, especially under suboptimal NH4(+) levels. These results suggest that OsAMT1;1 has the potential for improving nitrogen use efficiency, plant growth, and grain yield under both suboptimal and optimal nitrogen fertilizer conditions.

AMT1;1 transgenic rice plants with enhanced NH4 + permeability show superior growth and higher yield under optimal and suboptimal NH4 + conditions

Science.gov (United States)

Rothstein, Steven J.

2014-01-01

The major source of nitrogen for rice (Oryza sativa L.) is ammonium (NH4 +). The NH4 + uptake of roots is mainly governed by membrane transporters, with OsAMT1;1 being a prominent member of the OsAMT1 gene family that is known to be involved in NH4 + transport in rice plants. However, little is known about its involvement in NH4 + uptake in rice roots and subsequent effects on NH4 + assimilation. This study shows that OsAMT1;1 is a constitutively expressed, nitrogen-responsive gene, and its protein product is localized in the plasma membrane. Its expression level is under the control of circadian rhythm. Transgenic rice lines (L-2 and L-3) overexpressing the OsAMT1;1 gene had the same root structure as the wild type (WT). However, they had 2-fold greater NH4 + permeability than the WT, whereas OsAMT1;1 gene expression was 20-fold higher than in the WT. Analogous to the expression, transgenic lines had a higher NH4 + content in the shoots and roots than the WT. Direct NH4 + fluxes in the xylem showed that the transgenic lines had significantly greater uptake rates than the WT. Higher NH4 + contents also promoted higher expression levels of genes in the nitrogen assimilation pathway, resulting in greater nitrogen assimilates, chlorophyll, starch, sugars, and grain yield in transgenic lines than in the WT under suboptimal and optimal nitrogen conditions. OsAMT1;1 also enhanced overall plant growth, especially under suboptimal NH4 + levels. These results suggest that OsAMT1;1 has the potential for improving nitrogen use efficiency, plant growth, and grain yield under both suboptimal and optimal nitrogen fertilizer conditions. PMID:24420570

Elastic scattering of 16O+16O at energies E/A between 5 and 8 MeV

International Nuclear Information System (INIS)

Nicoli, M. P.; Haas, F.; Freeman, R. M.; Aissaoui, N.; Beck, C.; Elanique, A.; Nouicer, R.; Morsad, A.; Szilner, S.; Basrak, Z.

1999-01-01

The elastic scattering of 16 O+ 16 O has been measured at nine energies between E lab =75 and 124 MeV. The data cover up to 100 degree sign in the c.m. and can be described in terms of phenomenological and folding model potentials which reproduce the main features observed. In agreement with studies at higher energies in this and similar systems, refractive effects are present in the angular distributions at all energies. In particular, the passage of Airy minima through 90 degree sign at E c.m. =40, 47.5, and 62 MeV explains the deep minima observed in the excitation function. The real part of the optical potential is found to vary very little with energy over the studied interval, but the imaginary part shows a rapid change in its shape at incident energy about 90 MeV. Nonetheless, the energy dependence of the volume integral of the real and imaginary parts is in agreement with dispersion relation predictions. (c) 1999 The American Physical Society

16 CFR Figure 5 to Part 1512 - Typical Handbrake Actuator Showing Grip Dimension

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Typical Handbrake Actuator Showing Grip Dimension 5 Figure 5 to Part 1512 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS... Actuator Showing Grip Dimension EC03OC91.072 ...

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

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.

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.

Folding of non-Euclidean curved shells

Science.gov (United States)

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

2015-03-01

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

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.

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

Science.gov (United States)

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

2018-01-01

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

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.

Dioscorea alata tuber proteome analysis shows over thirty dioscorin isoforms and novel tuber proteins.

Science.gov (United States)

Sharma, Shruti; Gupta, Ravi; Deswal, Renu

2017-05-01

In Dioscorea, dioscorin (31 kDa) is the major storage protein constituting 85% of the total tuber proteins. An integrated proteomic and biochemical approach was used to understand the physiological role of dioscorin in the two contrasting growth stages (germinating and mature tuber). HPLC analysis showed 3 fold reduction in mannitol and 12.88 and 1.24 fold increase in sucrose and maltose in the germinating tuber. A 1.8 and 3 fold increase in sucrose phosphate synthase and mannitol dehydrogenase activity respectively was observed in the germinating tuber while a 2 fold higher invertase probably lowers the sucrose accumulation in the mature tuber. SDS-PAGE and 2-D maps of the mature and germinating tubers confirmed depletion (more than 50%) of dioscorin on germination. Dioscorin was purified using ion exchange and gel filtration chromatography with 43.32 fold purification and 38.16 yield. Out of a trail of 35 spots at 31 kDa only 12 spots (identified as dioscorin isoforms) were present in the 2D gel of the purified fraction. To search for other tuber proteins besides dioscorin, the unbound fractions of DEAE column were analysed by 2DGE. DREB 1A, caffeic acid 3-O-methyltransferase and Rab-1 small GTP binding protein were identified perhaps for the first time in the Dioscorea proteome. The interactome analysis revealed these to be involved in oxidative stress, carotenoid synthesis and vesicular transport. This is perhaps the first attempt to identify tuber proteome (although limited) and to understand the physiological significance of these proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Improving Protein Fold Recognition by Deep Learning Networks

Science.gov (United States)

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

2015-12-01

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

Improving Protein Fold Recognition by Deep Learning Networks.

Science.gov (United States)

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

2015-12-04

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

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.

E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

International Nuclear Information System (INIS)

Chopjitt, Peechanika; Pientong, Chamsai; Sunthamala, Nuchsupha; Kongyingyoes, Bunkerd; Haonon, Ornuma; Boonmars, Thidarut; Kikawa, Satomi; Nakahara, Tomomi; Kiyono, Tohru; Ekalaksananan, Tipaya

2016-01-01

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.

E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

Energy Technology Data Exchange (ETDEWEB)

Chopjitt, Peechanika; Pientong, Chamsai; Sunthamala, Nuchsupha [Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); HPV & EBV and Carcinogenesis Research Group, Khon Kaen University (Thailand); Kongyingyoes, Bunkerd [Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); Haonon, Ornuma; Boonmars, Thidarut [Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); Kikawa, Satomi; Nakahara, Tomomi [Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 (Japan); Kiyono, Tohru, E-mail: tkiyono@ncc.go.jp [Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 (Japan); Ekalaksananan, Tipaya, E-mail: tipeka@kku.ac.th [Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002 (Thailand); HPV & EBV and Carcinogenesis Research Group, Khon Kaen University (Thailand)

2016-09-09

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.

Sulfated glycosaminoglycans in human vocal fold lamina propria

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Sung Woo Park

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

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

Science.gov (United States)

Arviv, Oshrit; Levy, Yaakov

2012-12-01

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

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

Asymmetric hindwing foldings in rove beetles.

Science.gov (United States)

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

2014-11-18

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

Vocal fold paralysis secondary to phonotrauma.

Science.gov (United States)

Klein, Travis A L; Gaziano, Joy E; Ridley, Marion B

2014-01-01

A unique case of acute onset vocal fold paralysis secondary to phonotrauma is presented. The cause was forceful vocalization by a drill instructor on a firearm range. Imaging studies revealed extensive intralaryngeal and retropharyngeal hemorrhage. Laryngoscopy showed a complete left vocal fold paralysis. Relative voice rest was recommended, and the patient regained normal vocal fold mobility and function after approximately 12 weeks. Copyright © 2014 The Voice Foundation. All rights reserved.

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)

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.

Association between free testosterone levels and anal human papillomavirus types 16/18 infections in a cohort of men who have sex with men.

Directory of Open Access Journals (Sweden)

Hilary K Hsu

Full Text Available Human papillomavirus (HPV types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs. Overall, IAC rates are highest among men who have sex with men (MSM, especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting. While there are direct and indirect physiological effects of testosterone in males, its role in anal HPV16/18 infections in men is unknown.Free testosterone (FT was measured in serum from 340 Multicenter AIDS Cohort Study (MACS participants who were tested for anal HPV16/18-DNA approximately 36 months later. The effect of log10-transformed current FT level on anal HPV16/18 prevalence was modeled using Poisson regression with robust error variance. Multivariate models controlled for other HPV types, cumulative years of exogenous testosterone use, race, age, lifetime number of receptive anal intercourse partnerships, body mass index, tobacco smoking, HIV-infection and CD4+ T-cell counts among HIV-infected, and blood draw timing.Participants were, on average, 60 (+5.4 years of age, White (86%, and HIV-uninfected (56%; Twenty-four percent tested positive for anal HPV16 and/or 18-DNA (HPV16 prevalence=17.1%, HPV18=9.1%. In adjusted analysis, each half-log10 increase of FT was associated with a 1.9-fold (95% Confidence Interval: 1.11, 3.24 higher HPV16/18 prevalence. Additionally, other Group 1 high-risk HPVs were associated with a 1.56-fold (1.03, 2.37 higher HPV16/18 prevalence. Traditional risk factors for HPV16/18 infection (age, tobacco smoking; lifetime number of sexual partners, including the number of receptive anal intercourse partnerships within 24 months preceding HPV testing were poorly correlated with one another and not statistically significantly associated with higher prevalence of HPV16/18 infection in unadjusted and adjusted analyses.Higher free testosterone was associated with increased HPV16/18 prevalence measured approximately three years

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...

Divorcing folding from function: how acylation affects the membrane-perturbing properties of an antimicrobial peptide

DEFF Research Database (Denmark)

Vad, Brian Stougaard; Thomsen, Line Aagot Hede; Bertelsen, Kresten

2010-01-01

Many small cationic peptides, which are unstructured in aqueous solution, have antimicrobial properties. These properties are assumed to be linked to their ability to permeabilize bacterial membranes, accompanied by the transition to an alpha-helical folding state. Here we show that there is no d......Many small cationic peptides, which are unstructured in aqueous solution, have antimicrobial properties. These properties are assumed to be linked to their ability to permeabilize bacterial membranes, accompanied by the transition to an alpha-helical folding state. Here we show...... that there is no direct link between folding of the antimicrobial peptide Novicidin (Nc) and its membrane permeabilization. N-terminal acylation with C8-C16 alkyl chains and the inclusion of anionic lipids both increase Nc's ability to form alpha-helical structure in the presence of vesicles. Nevertheless, both acylation......, this cannot rationalize our results since permeabilization and antimicrobial activities are observed well below concentrations where aggregation occurs. This suggests that significant induction of alpha-helical structure is not a prerequisite for membrane perturbation in this class of antimicrobial peptides...

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

Science.gov (United States)

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

2015-01-01

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

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.

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

Science.gov (United States)

Zhang, Zhaoyan

2009-02-01

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

Financial Health of the Higher Education Sector: 2015-16 Financial Results. Data Analysis. March 2017/02

Science.gov (United States)

Higher Education Funding Council for England, 2016

2016-01-01

This report provides an overview of the financial health of the Higher Education Funding Council for England (HEFCE) funded higher education sector in England. The analysis covers the financial results for 2015-16. This does not include further education or sixth-form colleges, or alternative providers of higher education.

The next 16 higher spin currents and three-point functions in the large N = 4 holography

Energy Technology Data Exchange (ETDEWEB)

Ahn, Changhyun; Kim, Dong-gyu; Kim, Man Hea [Kyungpook National University, Department of Physics, Taegu (Korea, Republic of)

2017-08-15

By using the known operator product expansions (OPEs) between the lowest 16 higher spin currents of spins (1, (3)/(2), (3)/(2), (3)/(2), (3)/(2), 2,2,2,2,2,2, (5)/(2), (5)/(2), (5)/(2), (5)/(2), 3) in an extension of the large N = 4 linear superconformal algebra, one determines the OPEs between the lowest 16 higher spin currents in an extension of the large N = 4 nonlinear superconformal algebra for generic N and k. The Wolf space coset contains the group G = SU(N + 2) and the affine Kac-Moody spin 1 current has the level k. The next 16 higher spin currents of spins (2, (5)/(2), (5)/(2), (5)/(2), (5)/(2), 3,3,3,3,3,3, (7)/(2), (7)/(2), (7)/(2), (7)/(2), 4) arise in the above OPEs. The most general lowest higher spin 2 current in this multiplet can be determined in terms of affine Kac-Moody spin (1)/(2), 1 currents. By careful analysis of the zero mode (higher spin) eigenvalue equations, the three-point functions of bosonic higher spin 2, 3, 4 currents with two scalars are obtained for finite N and k. Furthermore, we also analyze the three-point functions of bosonic higher spin 2, 3, 4 currents in the extension of the large N = 4 linear superconformal algebra. It turns out that the three-point functions of higher spin 2, 3 currents in the two cases are equal to each other at finite N and k. Under the large (N, k) 't Hooft limit, the two descriptions for the three-point functions of higher spin 4 current coincide with each other. The higher spin extension of SO(4) Knizhnik Bershadsky algebra is described. (orig.)

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

Morphometric Study of Vocal Folds in Indian Cadavers

Directory of Open Access Journals (Sweden)

Rawal J.D.

2015-06-01

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

BiP clustering facilitates protein folding in the endoplasmic reticulum.

Directory of Open Access Journals (Sweden)

Marc Griesemer

2014-07-01

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

Gas exchange at whole plant level shows that a less conservative water use is linked to a higher performance in three ecologically distinct pine species

Science.gov (United States)

Salazar-Tortosa, D.; Castro, J.; Rubio de Casas, R.; Viñegla, B.; Sánchez-Cañete, E. P.; Villar-Salvador, P.

2018-04-01

Increasing temperatures and decreasing precipitation in large areas of the planet as a consequence of global warming will affect plant growth and survival. However, the impact of climatic conditions will differ across species depending on their stomatal response to increasing aridity, as this will ultimately affect the balance between carbon assimilation and water loss. In this study, we monitored gas exchange, growth and survival in saplings of three widely distributed European pine species (Pinus halepensis, P. nigra and P. sylvestris) with contrasting distribution and ecological requirements in order to ascertain the relationship between stomatal control and plant performance. The experiment was conducted in a common garden environment resembling rainfall and temperature conditions that two of the three species are expected to encounter in the near future. In addition, gas exchange was monitored both at the leaf and at the whole-plant level using a transient-state closed chamber, which allowed us to model the response of the whole plant to increased air evaporative demand (AED). P. sylvestris was the species with lowest survival and performance. By contrast, P. halepensis showed no mortality, much higher growth (two orders of magnitude), carbon assimilation (ca. 14 fold higher) and stomatal conductance and water transpiration (ca. 4 fold higher) than the other two species. As a consequence, P. halepensis exhibited higher values of water-use efficiency than the rest of the species even at the highest values of AED. Overall, the results strongly support that the weaker stomatal control of P. halepensis, which is linked to lower stem water potential, enabled this species to maximize carbon uptake under drought stress and ultimately outperform the more water conservative P. nigra and P. sylvestris. These results suggest that under a hotter drought scenario P. nigra and P. sylvestris would very likely suffer increased mortality, whereas P. halepensis could maintain

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 \

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.

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

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.

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...

Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Nav1.6 sodium channels

International Nuclear Information System (INIS)

Tan Jianguo; Soderlund, David M.

2010-01-01

We expressed rat Na v 1.6 sodium channels in combination with the rat β 1 and β 2 auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a type I structure, produced transient modification evident in the induction of rapidly decaying sodium tail currents, weak resting modification (5.7% modification at 100 μM), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a type II structure, produced sodium tail currents that were ∼ 9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 μM), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 μM), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration-effect data showed that repetitive depolarization increased the potency of tefluthrin ∼ 15-fold and that tefluthrin was ∼ 10-fold more potent than deltamethrin as a use-dependent modifier of Na v 1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na v 1.2 sodium channel coexpressed with the rat β 1 and β 2 subunits in oocytes showed that the Na v 1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na v 1.2 isoform. These results implicate sodium channels containing the Na v 1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.

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.

Production of xylanases and cellulases by aspergillus fumigatus ms16 using crude lignocellulosic substrates

International Nuclear Information System (INIS)

Naseeb, S.; Sohai, M.; Ahmad, A.; Khan, S.A.

2015-01-01

Xylanolytic and cellulolytic potential of a soil isolate, Aspergillus fumigatus (MS16) was studied by growing it on a variety of lignocellulosics, purified cellulose and xylan supplemented media. It was noted that carboxymethyl cellulose, salicin and xylan induce the -glucosidase and xylanase, respectively production of endoglucanase. The study revealed that Aspergillus fumigatus (MS16) co-secretes xylanase and cellulase in the presence of xylan; the ratio of the two enzymes was influenced by the initial pH of the medium. The maximum titers of xylanase and cellulase were noted at initial pH of 5.0. Relatively higher titers of both the enzymes were obtained when the fungus was cultivated at 35 degree C. Whereas, cellulase production was not detected when the fungus was cultivated at 40 degree C. The volumetric productivity (Qp) of xylanase was much higher than cellulases. The organism produced 2-3 folds higher titers of xylanase when grown on lignocellulosic materials in submerged cultivation than under solid-state cultivation, suggesting a different pattern of enzyme production in presence and in absence of free water. The partial characterization of enzymes showed that xylanase from this organism has -glucosidase. The higher melting temperature than endoglucanase and optimum temperature for activity was higher for xylanases than cellulases, whereas the optimum pH differed slightly i.e. in the range of 4.0-5.0. Enzyme preparation from this organism was loaded on some crude substrates and it showed that the enzyme preparation can be used to hydrolyze a variety of vegetable and agricultural waste materials. (author)

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.

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

Science.gov (United States)

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

High-resolution structure of a retroviral protease folded as a monomer

International Nuclear Information System (INIS)

Gilski, Miroslaw; Kazmierczyk, Maciej; Krzywda, Szymon; Zábranská, Helena; Cooper, Seth; Popović, Zoran; Khatib, Firas; DiMaio, Frank; Thompson, James; Baker, David; Pichová, Iva; Jaskolski, Mariusz

2011-01-01

The crystal structure of Mason–Pfizer monkey virus protease folded as a monomer has been solved by molecular replacement using a model generated by players of the online game Foldit. The structure shows at high resolution the details of a retroviral protease folded as a monomer which can guide rational design of protease dimerization inhibitors as retroviral drugs. Mason–Pfizer monkey virus (M-PMV), a D-type retrovirus assembling in the cytoplasm, causes simian acquired immunodeficiency syndrome (SAIDS) in rhesus monkeys. Its pepsin-like aspartic protease (retropepsin) is an integral part of the expressed retroviral polyproteins. As in all retroviral life cycles, release and dimerization of the protease (PR) is strictly required for polyprotein processing and virion maturation. Biophysical and NMR studies have indicated that in the absence of substrates or inhibitors M-PMV PR should fold into a stable monomer, but the crystal structure of this protein could not be solved by molecular replacement despite countless attempts. Ultimately, a solution was obtained in mr-rosetta using a model constructed by players of the online protein-folding game Foldit. The structure indeed shows a monomeric protein, with the N- and C-termini completely disordered. On the other hand, the flap loop, which normally gates access to the active site of homodimeric retropepsins, is clearly traceable in the electron density. The flap has an unusual curled shape and a different orientation from both the open and closed states known from dimeric retropepsins. The overall fold of the protein follows the retropepsin canon, but the C α deviations are large and the active-site ‘DTG’ loop (here NTG) deviates up to 2.7 Å from the standard conformation. This structure of a monomeric retropepsin determined at high resolution (1.6 Å) provides important extra information for the design of dimerization inhibitors that might be developed as drugs for the treatment of retroviral infections

Covering folded shapes

Directory of Open Access Journals (Sweden)

Oswin Aichholzer

2014-05-01

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

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....

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

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.

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

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

Directory of Open Access Journals (Sweden)

Yongping Yue

2016-01-01

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

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

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.

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.

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.

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 ...

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 ...

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.

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

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.

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.

Multicore and GPU algorithms for Nussinov RNA folding

Science.gov (United States)

2014-01-01

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

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

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...

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

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...

Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: preparation and evaluation of a key series of vinblastine analogues

Science.gov (United States)

Tam, Annie; Gotoh, Hiroaki; Robertson, William M.; Boger, Dale L.

2010-01-01

The examination of the catharanthine C16 substituent effects on the Fe(III)-promoted biomimetic coupling reaction with vindoline is detailed, confirming the importance of the presence of a C16 electron-withdrawing substituent, and establishing an unanticipated unique role (>10-fold) that the C16 methyl ester plays in the expression of the natural product properties. Thus, replacement of the vinblastine C16′ methyl ester with an ethyl ester (10-fold), a cyano group (100-fold), an aldehyde (100-fold), a hydroxymethyl group (1000-fold), or a primary carboxamide (>1000-fold) led to surprisingly large reductions in cytotoxic activity. PMID:20932748

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.

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

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.

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...

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.

Proving the correctness of unfold/fold program transformations using bisimulation

DEFF Research Database (Denmark)

Hamilton, Geoff W.; Jones, Neil

2011-01-01

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

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.

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

OpenAIRE

Yin, Jun; Zhang, Zhaoyan

2013-01-01

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

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

Enthalpy-Driven RNA Folding: Single-Molecule Thermodynamics of Tetraloop–Receptor Tertiary Interaction†

Science.gov (United States)

Fiore, Julie L.; Kraemer, Benedikt; Koberling, Felix; Edmann, Rainer; Nesbitt, David J.

2010-01-01

RNA folding thermodynamics are crucial for structure prediction, which requires characterization of both enthalpic and entropic contributions of tertiary motifs to conformational stability. We explore the temperature dependence of RNA folding due to the ubiquitous GAAA tetraloop–receptor docking interaction, exploiting immobilized and freely diffusing single-molecule fluorescence resonance energy transfer (smFRET) methods. The equilibrium constant for intramolecular docking is obtained as a function of temperature (T = 21–47 °C), from which a van’t Hoff analysis yields the enthalpy (ΔH°) and entropy (ΔS°) of docking. Tetraloop–receptor docking is significantly exothermic and entropically unfavorable in 1 mM MgCl2 and 100 mM NaCl, with excellent agreement between immobilized (ΔH° = −17.4 ± 1.6 kcal/mol, and ΔS° = −56.2 ± 5.4 cal mol−1 K−1) and freely diffusing (ΔH° = −17.2 ± 1.6 kcal/mol, and ΔS° = −55.9 ± 5.2 cal mol−1 K−1) species. Kinetic heterogeneity in the tetraloop–receptor construct is unaffected over the temperature range investigated, indicating a large energy barrier for interconversion between the actively docking and nondocking subpopulations. Formation of the tetraloop–receptor interaction can account for ~60% of the ΔH° and ΔS° of P4–P6 domain folding in the Tetrahymena ribozyme, suggesting that it may act as a thermodynamic clamp for the domain. Comparison of the isolated tetraloop–receptor and other tertiary folding thermodynamics supports a theme that enthalpy- versus entropy-driven folding is determined by the number of hydrogen bonding and base stacking interactions. PMID:19186984

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)

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.

Fish kidney cells show higher tolerance to hyperosmolality than amphibian

Directory of Open Access Journals (Sweden)

Lang Gui

2018-05-01

Full Text Available In contrast to fish, amphibians inhabit both aquatic and terrestrial environments. To better understand osmoregulation in fish and amphibian, we have investigated the morphological changes in kidney cells to osmotic stress. To address this, kidney cell line isolated from the freshwater grass carp (CIK and Chinese giant salamander (GSK were challenged to different mediums with distinct osmotic pressures (100, 300 and 700 mOsm. Morphological alterations of the fish and amphibian cells were compared by optical and electron microscopy. Following hyposmotic treatment (100 mOsm, both CIK and GSK cells became unhealthy and show condensed chromatin, swollen mitochondria and cytoplasmic vacuole. Meanwhile, after hyperosmotic treatment (700 mOsm, shrunken CIK cells with multipolar shape, pale or lightly stained cytoplasm, condensed chromatin, vacuoles and swollen mitochondria were detected. GSK cells were seriously damaged and most were completely lysed. The results suggest that fish kidney cells show a higher degree of tolerance to hyperosmoticity by comparing to amphibians and provide novel insights on the osmoregulatory capacity and adaptability of kidney cells between the two animal groups.

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.

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.

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

Transcervical fat injection laryngoplasty for unilateral vocal fold paralysis: an easy way to do the job.

Science.gov (United States)

Elbadan, Hisham E M; Hussein, Wael K A; Elmaghraby, Riham M

2017-12-01

Unilateral vocal fold paralysis resulting in glottic incompetence can cause impairment of laryngeal functions, including airway protection and phonation. The objective of this study is to present an easy new technique for harvesting and injection of abdominal fat into the vocal fold for patients with unilateral vocal fold paralysis. This is a retrospective study of patients carried out on 16 patients suffering from unilateral vocal fold paralysis resulting from different etiologies. All patients were subjected to the protocol of voice assessment pre- and postoperatively. All patients were subjected to fat injection of the paralyzed vocal fold. There was a statistically significant difference between the pre- and postoperative grade of voice parameters. Vocal fold injection using fat medializes a paralyzed vocal fold by increasing vocal fold volume. Fat injections are safe and easily mastered; and in the absence of the standard settings for fat harvesting and injection, it could be performed with minimal equipment that are readily available in any operating room.

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.

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...

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.

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.

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

A Universal Crease Pattern for Folding Orthogonal Shapes

Science.gov (United States)

2009-09-29

Demaine∗† Martin L. Demaine∗ Aviv Ovadya∗ Abstract We present a universal crease pattern—known in geometry as the tetrakis tiling and in origami as box...13. SUPPLEMENTARY NOTES 14. ABSTRACT We present a universal crease pattern?known in geometry as the tetrakis tiling and in origami as box pleating... origami . Computational Geometry : The- ory and Applications, 16(1):3–21, 2000. [DO07] Erik D. Demaine and Joseph O’Rourke. Geometric Folding Al- gorithms

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.

Modulating Phonation Through Alteration of Vocal Fold Medial Surface Contour

Science.gov (United States)

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

2012-01-01

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

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

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

Science.gov (United States)

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

2010-05-01

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

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

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

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

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

2016-11-01

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

NoFold: RNA structure clustering without folding or alignment.

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Middleton, Sarah A; Kim, Junhyong

2014-11-01

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

Financial Health of the Higher Education Sector: 2015-16 to 2018-19 Forecasts. Data Analysis. November 2016/34

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Higher Education Funding Council for England, 2016

2016-01-01

This report provides an overview of the forecast financial health of the HEFCE-funded higher education (HE) sector in England. The analysis covers the financial forecasts for the period 2015-16 to 2018-19, based on information submitted by higher education institutions (HEIs) to HEFCE in July 2016. Financial Reporting Standard (FRS) 102 is the new…

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.

FoldEco: A Model for Proteostasis in E. coli

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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.

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

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Sean P. Ferris

2014-03-01

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

Evolution of a protein folding nucleus.

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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.

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

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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.

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

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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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Amniotic Fluid Cells Show Higher Pluripotency-Related Gene Expression Than Allantoic Fluid Cells.

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Kehl, Debora; Generali, Melanie; Görtz, Sabrina; Geering, Diego; Slamecka, Jaroslav; Hoerstrup, Simon P; Bleul, Ulrich; Weber, Benedikt

2017-10-01

Amniotic fluid represents an abundant source of multipotent stem cells, referred as broadly multipotent given their differentiation potential and expression of pluripotency-related genes. However, the origin of this broadly multipotent cellular fraction is not fully understood. Several sources have been proposed so far, including embryonic and extraembryonic tissues. In this regard, the ovine developmental model uniquely allows for direct comparison of fetal fluid-derived cells from two separate fetal fluid cavities, the allantois and the amnion, over the entire duration of gestation. As allantoic fluid mainly collects fetal urine, cells originating from the efferent urinary tract can directly be compared with cells deriving from the extraembryonic amniotic tissues and the fetus. This study shows isolation of cells from the amniotic [ovine amniotic fluid cells (oAFCs)] and allantoic fluid [ovine allantoic fluid cells (oALCs)] in a strictly paired fashion with oAFCs and oALCs derived from the same fetus. Both cell types showed cellular phenotypes comparable to standard mesenchymal stem cells (MSCs), with trilineage differentiation potential, and expression of common ovine MSC markers. However, the expression of MSC markers per single cell was higher in oAFCs as measured by flow cytometry. oAFCs exhibited higher proliferative capacities and showed significantly higher expression of pluripotency-related genes OCT4, STAT3, NANOG, and REX1 by quantitative real-time polymerase chain reaction compared with paired oALCs. No significant decrease of pluripotency-related gene expression was noted over gestation, implying that cells with high differentiation potential may be isolated at the end of pregnancy. In conclusion, this study suggests that cells with highest stem cell characteristics may originate from the fetus itself or the amniotic fetal adnexa rather than from the efferent urinary tract or the allantoic fetal adnexa.

Inverse folding of RNA pseudoknot structures

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Li Linda YM

2010-06-01

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

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

A herbicide-resistant ACCase 1781 Setaria mutant shows higher fitness than wild type.

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Wang, T; Picard, J C; Tian, X; Darmency, H

2010-10-01

It is often alleged that mutations conferring herbicide resistance have a negative impact on plant fitness. A mutant ACCase1781 allele endowing resistance to the sethoxydim herbicide was introgressed from a resistant green foxtail (Setaria viridis (L.) Beauv) population into foxtail millet (S. italica (L.) Beauv.). (1) Better and earlier growth of resistant plants was observed in a greenhouse cabinet. (2) Resistant plants of the advanced BC7 backcross generation showed more vigorous juvenile growth in the field, earlier flowering, more tillers and higher numbers of grains than susceptible plants did, especially when both genotypes were grown in mixture, but their seeds were lighter than susceptible seeds. (3) Field populations originating from segregating hybrids had the expected allele frequencies under normal growth conditions, but showed a genotype shift toward an excess of homozygous resistant plants within 3 years in stressful conditions. Lower seed size, lower germination rate and perhaps unexplored differences in seed longevity and predation could explain how the resistant plants have the same field fitness over the whole life cycle as the susceptible ones although they produce more seeds. More rapid growth kinetics probably accounted for higher fitness of the resistant plants in adverse conditions. The likelihood of a linkage with a beneficial gene is discussed versus the hypothesis of a pleiotropic effect of the ACCase resistance allele. It is suggested that autogamous species like Setaria could not develop a resistant population without the help of a linkage with a gene producing a higher fitness.

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 .

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.

Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A).

Science.gov (United States)

Truong, Eric C; Phuan, Puay W; Reggi, Amanda L; Ferrera, Loretta; Galietta, Luis J V; Levy, Sarah E; Moises, Alannah C; Cil, Onur; Diez-Cecilia, Elena; Lee, Sujin; Verkman, Alan S; Anderson, Marc O

2017-06-08

Transmembrane protein 16A (TMEM16A), also called anoctamin 1 (ANO1), is a calcium-activated chloride channel expressed widely mammalian cells, including epithelia, vascular smooth muscle tissue, electrically excitable cells, and some tumors. TMEM16A inhibitors have been proposed for treatment of disorders of epithelial fluid and mucus secretion, hypertension, asthma, and possibly cancer. Herein we report, by screening, the discovery of 2-acylaminocycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as inhibitors of TMEM16A and analysis of 48 synthesized analogs (10ab-10bw) of the original AACT compound (10aa). Structure-activity studies indicated the importance of benzene substituted as 2- or 4-methyl, or 4-fluoro, and defined the significance of thiophene substituents and size of the cycloalkylthiophene core. The most potent compound (10bm), which contains an unusual bromodifluoroacetamide at the thiophene 2-position, had IC 50 of ∼30 nM, ∼3.6-fold more potent than the most potent previously reported TMEM16A inhibitor 4 (Ani9), and >10-fold improved metabolic stability. Direct and reversible inhibition of TMEM16A by 10bm was demonstrated by patch-clamp analysis. AACTs may be useful as pharmacological tools to study TMEM16A function and as potential drug development candidates.

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

Science.gov (United States)

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

2008-01-01

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

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...

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.

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

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Hong Seok Kim, MD, PhD

2013-05-01

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

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

Science.gov (United States)

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

2014-11-01

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

Mutation in cyclophilin B that causes hyperelastosis cutis in American Quarter Horse does not affect peptidylprolyl cis-trans isomerase activity but shows altered cyclophilin B-protein interactions and affects collagen folding.

Science.gov (United States)

Ishikawa, Yoshihiro; Vranka, Janice A; Boudko, Sergei P; Pokidysheva, Elena; Mizuno, Kazunori; Zientek, Keith; Keene, Douglas R; Rashmir-Raven, Ann M; Nagata, Kazuhiro; Winand, Nena J; Bächinger, Hans Peter

2012-06-22

The rate-limiting step of folding of the collagen triple helix is catalyzed by cyclophilin B (CypB). The G6R mutation in cyclophilin B found in the American Quarter Horse leads to autosomal recessive hyperelastosis cutis, also known as hereditary equine regional dermal asthenia. The mutant protein shows small structural changes in the region of the mutation at the side opposite the catalytic domain of CypB. The peptidylprolyl cis-trans isomerase activity of the mutant CypB is normal when analyzed in vitro. However, the biosynthesis of type I collagen in affected horse fibroblasts shows a delay in folding and secretion and a decrease in hydroxylysine and glucosyl-galactosyl hydroxylysine. This leads to changes in the structure of collagen fibrils in tendon, similar to those observed in P3H1 null mice. In contrast to cyclophilin B null mice, where little 3-hydroxylation was found in type I collagen, 3-hydroxylation of type I collagen in affected horses is normal. The mutation disrupts the interaction of cyclophilin B with the P-domain of calreticulin, with lysyl hydroxylase 1, and probably other proteins, such as the formation of the P3H1·CypB·cartilage-associated protein complex, resulting in less effective catalysis of the rate-limiting step in collagen folding in the rough endoplasmic reticulum.

Mutation in Cyclophilin B That Causes Hyperelastosis Cutis in American Quarter Horse Does Not Affect Peptidylprolyl cis-trans Isomerase Activity but Shows Altered Cyclophilin B-Protein Interactions and Affects Collagen Folding*

Science.gov (United States)

Ishikawa, Yoshihiro; Vranka, Janice A.; Boudko, Sergei P.; Pokidysheva, Elena; Mizuno, Kazunori; Zientek, Keith; Keene, Douglas R.; Rashmir-Raven, Ann M.; Nagata, Kazuhiro; Winand, Nena J.; Bächinger, Hans Peter

2012-01-01

The rate-limiting step of folding of the collagen triple helix is catalyzed by cyclophilin B (CypB). The G6R mutation in cyclophilin B found in the American Quarter Horse leads to autosomal recessive hyperelastosis cutis, also known as hereditary equine regional dermal asthenia. The mutant protein shows small structural changes in the region of the mutation at the side opposite the catalytic domain of CypB. The peptidylprolyl cis-trans isomerase activity of the mutant CypB is normal when analyzed in vitro. However, the biosynthesis of type I collagen in affected horse fibroblasts shows a delay in folding and secretion and a decrease in hydroxylysine and glucosyl-galactosyl hydroxylysine. This leads to changes in the structure of collagen fibrils in tendon, similar to those observed in P3H1 null mice. In contrast to cyclophilin B null mice, where little 3-hydroxylation was found in type I collagen, 3-hydroxylation of type I collagen in affected horses is normal. The mutation disrupts the interaction of cyclophilin B with the P-domain of calreticulin, with lysyl hydroxylase 1, and probably other proteins, such as the formation of the P3H1·CypB·cartilage-associated protein complex, resulting in less effective catalysis of the rate-limiting step in collagen folding in the rough endoplasmic reticulum. PMID:22556420

Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

Science.gov (United States)

Wang, Ching-Ying; Huang, Shun-Chueh; Lai, Zhen-Rung; Ho, Yu-Ling; Jou, Yu-Jen; Kung, Szu-Hao; Zhang, Yongjun; Chang, Yuan-Shiun; Lin, Cheng-Wen

2013-01-01

Enterovirus 71 (EV71) and coxsackievirus A16 (CoxA16) are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012) cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS) extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 μg/mL) and CoxA16 (IC50 = 81.41 μg/mL). Ethyl acetate (EA) fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 μg/mL against EV71 and 9.08 μg/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 μM) and CoxA16 (IC50 = 5.24 μM). Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection. PMID:24078828

Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

Directory of Open Access Journals (Sweden)

Ching-Ying Wang

2013-01-01

Full Text Available Enterovirus 71 (EV71 and coxsackievirus A16 (CoxA16 are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012 cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 μg/mL and CoxA16 (IC50 = 81.41 μg/mL. Ethyl acetate (EA fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 μg/mL against EV71 and 9.08 μg/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 μM and CoxA16 (IC50 = 5.24 μM. Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection.

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.

Periodic folding of viscous sheets

Science.gov (United States)

Ribe, Neil M.

2003-09-01

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

HIV positivity but not HPV/p16 status is associated with higher recurrence rate in anal cancer.

Science.gov (United States)

Meyer, Joshua E; Panico, Vinicius J A; Marconato, Heloisa M F; Sherr, David L; Christos, Paul; Pirog, Edyta C

2013-12-01

Human papillomavirus (HPV) is a pathogenic factor of squamous cell carcinoma in various mucosal locations, including anal carcinoma (ACA). It is also known that patients positive for HIV are at high risk of ACA. The goal of this study was to examine clinical outcome in ACA in relation to HPV/p16 positivity, histologic tumor differentiation, and HIV status. Patients with oropharyngeal cancers that are positive for HPV and show overexpression of p16 as well as having non-keratinizing/basaloid histology have been reported to have better outcomes following chemoradiation (CRT). However, such relationships in ACA remain unknown. Forty-two patients with SCC of the anus treated with CRT between 1997 and 2009 were identified. The tumors were subclassified as either non-keratinizing (including basaloid) or keratinizing categories. HPV testing was performed using SPF10-PCR, and all cases were immunostained for p16. There were 23 men and 19 women; 43% of men and 11% of women were HIV-positive (p = 0.04). Fifty-five percent of patients had local disease (stages I and II) and 41% were stages III and IV, with 4% stage unknown. All tumors were positive for high-oncogenic risk HPVs, and all were positive with p16 immunostain. Sixty-four percent of tumors were non-keratinizing/basaloid and 36 % were keratinizing. The keratinizing tumors were more common in HIV-positive patients (67%), whereas non-keratinizing/basaloid tumors were more common in HIV-negative patients (77%) (p = 0.008). Thirty-one percent of patients had recurrence of disease, including 50% HIV-positive patients and 23% HIV-negative patients (p = 0.09). There was no difference in the recurrence rate between non-keratinizing and keratinizing tumor subtypes (p = 0.80). The 24-month recurrence-free survival for the cohort was 66% (95% CI = 46%, 81%), with HIV-positive patients having worse recurrence-free survival compared to HIV-negative patients (HR = 2.85, 95% CI = 0.95, 8.53; p = 0

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

Science.gov (United States)

Benesh, Nathan Philip

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

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

Science.gov (United States)

Peraza Hernandez, Edwin Alexander

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

Percutaneous injection laryngoplasty in the management of acute vocal fold paralysis.

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Damrose, Edward J

2010-08-01

To evaluate the clinical outcome of patients with acute vocal fold paralysis treated with bovine collagen via percutaneous injection laryngoplasty under simple topical anesthesia. Retrospective case series. The charts of 38 consecutive patients with acute unilateral vocal fold paralysis who underwent percutaneous injection laryngoplasty under simple topical anesthesia were reviewed. Symptoms and laryngeal function were assessed pre- and postinjection using the Glottal Function Index (GFI), GRBAS Dysphonia Scale, Functional Outcome Swallowing Scale (FOSS), and maximum phonation time (MPT). Mean GFI, GRBAS, FOSS, and MPT improved from 13.71 to 7.68, 7.24 to 3.95, 3.70 to 2.20, and 12.87 to 16.45, respectively (P dysphagia and aspiration, injection was successful in restoring oral alimentation in only three patients, with the four failures occurring in patients with multiple cranial neuropathies. Percutaneous injection laryngoplasty is a viable option for immediate rehabilitation of acute vocal fold paralysis, and can be performed in the inpatient setting. With dysphagia and aspiration secondary to multiple cranial nerve palsies, medialization of the paralyzed cord alone may be insufficient to restore safe oral alimentation.

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.

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.

Detecting Laryngopharyngeal Reflux by Immunohistochemistry of Pepsin in the Biopsies of Vocal Fold Leukoplakia.

Science.gov (United States)

Gong, Xia; Wang, Xiao-Yun; Yang, Li; Sun, Ming-Jun; Du, Jun; Zhang, Wei

2018-05-01

Laryngopharyngeal reflux (LPR) may contribute to the development of laryngeal diseases including vocal fold leukoplakia. Clinical methods of determining LPR are limited. Pepsin, as an exogenous protein, is considered as a biomarker of LPR. The aim of the current study was, therefore, to detect pepsin by immunohistochemistry in the biopsies from patients with vocal fold leukoplakia, and by which, to determine the potential association of LPR and vocal leukoplakia. A total of 26 biopsies from patients with vocal fold leukoplakia were examined in comparison with 20 vocal fold biopsies from control subjects. We found that 2 out of 26 patients (7.7%) were strongly positive, 4 of the 26 (15.4%) patients were positive, 11 of the 26 (42.3%) patients were weakly positive, and 9 of the 26 (34.6%) were negative staining for pepsin. In contrast, only 4 of the 20 (20.0%) control subjects were weakly positive and the rest (16; 80.0%) were negative staining for pepsin. There was significant difference between the two groups in terms of positivity of pepsin staining (χ 2  = 24.181, P vocal fold leukoplakia. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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.

A comparative method for finding and folding RNA secondary structures within protein-coding regions

DEFF Research Database (Denmark)

Pedersen, Jakob Skou; Meyer, Irmtraud Margret; Forsberg, Roald

2004-01-01

that RNA-DECODER's parameters can be automatically trained to successfully fold known secondary structures within the HCV genome. We scan the genomes of HCV and polio virus for conserved secondary-structure elements, and analyze performance as a function of available evolutionary information. On known...... secondary structures, RNA-DECODER shows a sensitivity similar to the programs MFOLD, PFOLD and RNAALIFOLD. When scanning the entire genomes of HCV and polio virus for structure elements, RNA-DECODER's results indicate a markedly higher specificity than MFOLD, PFOLD and RNAALIFOLD....

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

Science.gov (United States)

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

2016-11-01

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

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

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Ivan Coluzza

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

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

Cognitive profile and disorders affecting higher brain functions in paediatric patients with neurofibromatosis type 1.

Science.gov (United States)

Vaucheret Paz, E; López Ballent, A; Puga, C; García Basalo, M J; Baliarda, F; Ekonen, C; Ilari, R; Agosta, G

2017-04-18

Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome often associated with specific cognitive deficits that are rarely monitored during follow-up of these patients. The purpose of our study is two-fold. First, we aimed to describe the cognitive profile of patients with NF1 and detect disorders in higher brain functions associated with the disease. Second, we identified the reasons for consultation associated with school performance in these patients. We conducted a descriptive cross-sectional study of 24 paediatric patients (ages 5 to 16) with NF1 who underwent neuropsychological assessment. The most frequent reasons for consultation were attention deficits (58.33%), learning disorders (25%), poor motor coordination (25%), and language impairment (0.8%). Although 96% of the patients displayed impairments in at least one of the assessed areas, only 83.34% of the parents had reported such impairments. Attention-deficit/hyperactivity disorder was present in 58.33% of the patients, whereas 33.33% had nonverbal learning disabilities, 20.83% had expressive language disorder, 8.33% had borderline intellectual functioning, 4.16% had mental retardation, and only 4.16% showed no cognitive impairment. Higher brain functions are frequently impaired in paediatric patients with NF1. Although many parents report such disorders, they can go undetected in some cases. Neuropsychological assessment is recommended for all paediatric patients with NF1 to detect cognitive impairment and provide early, effective rehabilitation treatment. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

STRONG ORACLE OPTIMALITY OF FOLDED CONCAVE PENALIZED ESTIMATION.

Science.gov (United States)

Fan, Jianqing; Xue, Lingzhou; Zou, Hui

2014-06-01

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

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

. Shortening is in the order of 21-24% for the frontal structures. The deformation above the weak Eocene Ghazij shales is partly decoupled from the layers underneath, especially where the Ghazij shales are thick. Thus, not all structures visible at surface level in the Kirthar Fold Belt are also present in the deeper section, and vice versa (disharmonic folding). The structural architecture in the frontal central Kirthar Fold Belt shows only convergent structures nearly parallel to the regional plate motion vector of the Indian plate and thus represents an example of extreme strain partitioning.

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.

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)

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.

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.

Fluorescent in situ folding control for rapid optimization of cell-free membrane protein synthesis.

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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.

Stretched versus compressed exponential kinetics in α-helix folding

International Nuclear Information System (INIS)

Hamm, Peter; Helbing, Jan; Bredenbeck, Jens

2006-01-01

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

Structure of the human histone chaperone FACT Spt16 N-terminal domain

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Marcianò, G.; Huang, D. T., E-mail: d.huang@beatson.gla.ac.uk [Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, Scotland (United Kingdom)

2016-01-22

The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.

Structure of the human histone chaperone FACT Spt16 N-terminal domain

International Nuclear Information System (INIS)

Marcianò, G.; Huang, D. T.

2016-01-01

The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding

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

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

2007-05-22

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

Quantification of Porcine Vocal Fold Geometry.

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

2016-07-01

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

Graph-representation of oxidative folding pathways

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Kaján László

2005-01-01

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

Laryngeal electromyography-guided hyaluronic acid vocal fold injection for unilateral vocal fold paralysis: a prospective long-term follow-up outcome report.

Science.gov (United States)

Wang, Chen-Chi; Chang, Ming-Hong; Jiang, Rong-San; Lai, Hsiu-Chin; De Virgilio, Armando; Wang, Ching-Ping; Wu, Shang-Heng; Liu, Shi-An; Liang, Kai-Li

2015-03-01

Unilateral vocal fold paralysis (UVFP) is a common voice disorder that may cause glottal closure insufficiency with hoarseness of voice. Laryngeal electromyography (LEMG)-guided hyaluronic acid vocal fold (VF) injection has been proposed as a treatment option to improve glottal closure with a satisfactory short-term effect. To our knowledge, this study reports the first long-term follow-up result of this treatment modality. To present the long-term treatment results of LEMG-guided hyaluronic acid VF injection for UVFP. Prospective study of the treatment results of 74 patients who received LEMG-guided hyaluronic acid VF injection for UVFP at a tertiary referral medical center from March 2010 to February 2013. In the office-based procedure, 1.0 mL of hyaluronic acid was injected via a 26-gauge monopolar injectable needle electrode into paralyzed thyroarytenoid muscles by LEMG guidance. Various glottal closure evaluations such as normalized glottal gap area, maximal phonation time, phonation quotient, mean airflow rate, perceptual GRBAS (grade, roughness, breathiness, asthenia, strain) scale, and Voice Handicap Index were compared before and after injection using the nonparametric Wilcoxon signed rank test within 1 month, at 6 months, and at the last follow-up examination. Sixty patients had been followed up for at least 6 months. Forty-four patients received only 1 injection, and 16 patients received repeated injections (2 injections for 13 patients and 3 for 3 patients). All the glottal closure parameters improved significantly (P injection and 16 (22%) who received repeated injections did not require another treatment after long-term follow-up. Laryngeal electromyography-guided hyaluronic acid VF injection is an option for treating UVFP with satisfactory results.

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.

Science.gov (United States)

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.

Voz e posição de prega vocal em homens com paralisia unilateral de prega vocal Voice and vocal fold position in men with unilateral vocal fold paralysis

Directory of Open Access Journals (Sweden)

Karine Schwarz

2011-12-01

Full Text Available O posicionamento da prega vocal paralisada e o grau de disfonia são fatores importantes para decidir as opções de tratamento na paralisia de prega vocal unilateral (PPVU. OBJETIVO: Verificar as características perceptivo-auditivas da voz e a posição da prega vocal paralisada, em homens, com PPVU. MATERIAIS E MÉTODOS: Estudo retrospectivo, coorte histórica, com corte transversal, com dados de 24 homens com PPVU, com média de 60,7 anos, submetidos à avaliação vocal perceptivo-auditiva da voz, por três juízas fonoaudiólogas e perceptivo-visual das imagens laríngeas, com a classificação da posição da prega vocal paralisada, por três juízes otorrinolaringologistas. RESULTADOS: A prega vocal paralisada em posição paramediana ocorreu em 45,83% dos casos; a intermediária, em 25%; a lateral, em 20,83%, e a mediana, em 4,16%; a disfonia resultante da PPVU foi caracterizada pela rouquidão, aspereza e tensão, de grau moderado; soprosidade (maior frequência do grau grave; astenia e instabilidade (maior frequência do grau leve; a posição da prega vocal paralisada influenciou significativamente o grau geral de desvio vocal. CONCLUSÃO: O grau geral de disfonia está relacionado com a posição da prega vocal paralisada; a disfonia é caracterizada pela presença de rouquidão, soprosidade, aspereza e tensão de grau moderado a grave.The paralyzed vocal fold positioning and the degree of dysphonia are important inputs when one is deciding upon treatment options for unilateral vocal fold paralysis (UVFP. OBJECTIVE: To check voice characteristics and paralyzed vocal fold position in men with UVFP. MATERIALS AND METHODS: This is a retrospective historical cross-sectional cohort study, with data from 24 men with UVFP with mean age of 60.7 years, submitted to voice assessment by three speech therapists and three ENT physicians used laryngeal images to classify the position of the paralyzed vocal fold. RESULTS: The paralyzed vocal fold

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

Science.gov (United States)

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

2013-07-01

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

Repairing the vibratory vocal fold.

Science.gov (United States)

Long, Jennifer L

2018-01-01

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

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

Science.gov (United States)

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

2014-11-07

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

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.

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.

Large-scale recumbent isoclinal folds in the footwall of the West Cycladic Detachment System (Greece)

Science.gov (United States)

Rice, A. Hugh N.; Grasemann, Bernhard

2017-04-01

The Pindos Zone in the Cyclades underwent Eocene high-pressure metamorphism and syn-orogenic exhumation, overprinted by Miocene low-angled extension. Although this represents a combination of likely high-strain-events, structural evidence of large-scale folding is rare. Here potential examples of such folding on Kea and Kythnos, in the Western Cyclades, are evaluated. These islands lie within the Cycladic Blueschist Nappe (lower nappe) of the Pindos Zone and in the footwall of the top-to-SSW West Cycladic Detachment System (WCDS). On Kea, no lithostratigraphy can be established in the 450 m thick greenschist facies mixed sedimentary-volcanoclastic-marble mylonite/phyllonite succession. On the east side of the island, lensoid marble layers frequently bifurcate, which might be reflecting early, sheared-out isoclinal folding, although no evidence of folded compositional layering has been found in potential fold-hinge zones and the bifurcation points are not arranged in a way suggestive of a fold axes parallel to the NNE-SSW oriented stretching lineation. However, at two localities, medium-scale recumbent isoclinal folding has been mapped, with NNE-SSW fold-axes exposed for up to 250 m and amplitudes of up to 170 m. On Kythnos, stretching lineations in greenschist facies rocks show a rotation from ENE-WSW in the north to NNE-SSW in the south, taken to represent a reorientation of the Eocene exhumation strain during block rotation coincident with top-to-SSW movement of the WCDS. The distribution of the three marble units that crop out in central/southern Kythnos suggest large-scale, likely isoclinal folding occurred. (1) Petroussa Lithodeme - a blue-grey calcite (BGC) marble with quartz-calcite-white-mica (QCWM) schists, forming a continuous outcrop around the island, thinning from >16m in the SE to <8m thick mylonites in the SW, overlain by grey sericite-albite-graphite-schists (Flabouria Lithodeme); (2) Rizou Lithodeme - massive grey to BGC marble, with abundant

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.

Self-folding origami at any energy scale

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

2017-05-01

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

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.

Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.

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Abdelhamid, Rehab F; Obara, Yuji; Kohzuma, Takamitsu

2008-01-01

Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.

Fold maps and positive topological quantum field theories

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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.

An evolutionarily conserved glycine-tyrosine motif forms a folding core in outer membrane proteins.

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Marcin Michalik

Full Text Available An intimate interaction between a pair of amino acids, a tyrosine and glycine on neighboring β-strands, has been previously reported to be important for the structural stability of autotransporters. Here, we show that the conservation of this interacting pair extends to nearly all major families of outer membrane β-barrel proteins, which are thought to have originated through duplication events involving an ancestral ββ hairpin. We analyzed the function of this motif using the prototypical outer membrane protein OmpX. Stopped-flow fluorescence shows that two folding processes occur in the millisecond time regime, the rates of which are reduced in the tyrosine mutant. Folding assays further demonstrate a reduction in the yield of folded protein for the mutant compared to the wild-type, as well as a reduction in thermal stability. Taken together, our data support the idea of an evolutionarily conserved 'folding core' that affects the folding, membrane insertion, and thermal stability of outer membrane protein β-barrels.

Vocal Fold Vibratory Changes Following Surgical Intervention.

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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.

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

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Gradmann, Sofie; Beaumont, Christopher; Albertz, Markus

2009-04-01

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

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

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Qi, Yifei; Im, Wonpil

2013-08-13

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

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....

Laryngeal Electromyographic findings in patients with vocal fold motion asymmetry.

Science.gov (United States)

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

2016-08-01

Vocal fold motion asymmetry (VFMA) is often attributed to vocal fold paresis or an anatomical variant. Although laryngeal electromyography (LEMG) may be used to evaluate patients with vocal fold paresis, electrodiagnostic findings in VFMA have not been well defined. Review of a case series Twenty-five symptomatic patients with VFMA were examined by LEMG, and the findings were analyzed. Although all were thought to have unilateral recurrent laryngeal nerve paresis, LEMG showed only nine to have unilateral recurrent nerve paresis. There were nine with both ipsilateral recurrent laryngeal nerve and superior laryngeal nerve paresis, four with bilateral paresis, and three were normal. Reduced total number of units, reduced recruitment, motor units firing fast, and polyphasic units were more common, whereas fibrillation potentials, fasciculation, positive sharp waves, and complex repetitive discharges were uncommon. The LEMG findings are most consistent with old, healed neuropathy. McNemar's test for the acute versus chronic denervation potentials showed significant differences. VFMA has a high incidence of vocal fold paresis that can be better defined by LEMG. The site and side of paresis is often wrong based on laryngoscopy findings alone. The LEMG findings of VFMA appear to be consistent with old, healed neuropathy 4 Laryngoscope, 126:E273-E277, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Interferences of Silica Nanoparticles in Green Fluorescent Protein Folding Processes.

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Klein, Géraldine; Devineau, Stéphanie; Aude, Jean Christophe; Boulard, Yves; Pasquier, Hélène; Labarre, Jean; Pin, Serge; Renault, Jean Philippe

2016-01-12

We investigated the relationship between unfolded proteins, silica nanoparticles and chaperonin to determine whether unfolded proteins could stick to silica surfaces and how this process could impair heat shock protein activity. The HSP60 catalyzed green fluorescent protein (GFP) folding was used as a model system. The adsorption isotherms and adsorption kinetics of denatured GFP were measured, showing that denaturation increases GFP affinity for silica surfaces. This affinity is maintained even if the surfaces are covered by a protein corona and allows silica NPs to interfere directly with GFP folding by trapping it in its unstructured state. We determined also the adsorption isotherms of HSP60 and its chaperonin activity once adsorbed, showing that SiO2 NP can interfere also indirectly with protein folding through chaperonin trapping and inhibition. This inhibition is specifically efficient when NPs are covered first with a layer of unfolded proteins. These results highlight for the first time the antichaperonin activity of silica NPs and ask new questions about the toxicity of such misfolded proteins/nanoparticles assembly toward cells.

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...

Dynamics of Folds in the Plane

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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...

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

Science.gov (United States)

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

2018-03-01

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

Origami-Inspired Folding of Thick, Rigid Panels

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

2014-01-01

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

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

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Woo, Peak

2017-05-01

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

Vocal fold hemorrhage: factors predicting recurrence.

Science.gov (United States)

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

2014-01-01

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

Guiding the folding pathway of DNA origami.

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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.

MicroRNA-200c modulates the expression of MUC4 and MUC16 by directly targeting their coding sequences in human pancreatic cancer.

Directory of Open Access Journals (Sweden)

Prakash Radhakrishnan

Full Text Available Transmembrane mucins, MUC4 and MUC16 are associated with tumor progression and metastatic potential in human pancreatic adenocarcinoma. We discovered that miR-200c interacts with specific sequences within the coding sequence of MUC4 and MUC16 mRNAs, and evaluated the regulatory nature of this association. Pancreatic cancer cell lines S2.028 and T3M-4 transfected with miR-200c showed a 4.18 and 8.50 fold down regulation of MUC4 mRNA, and 4.68 and 4.82 fold down regulation of MUC16 mRNA compared to mock-transfected cells, respectively. A significant reduction of glycoprotein expression was also observed. These results indicate that miR-200c overexpression regulates MUC4 and MUC16 mucins in pancreatic cancer cells by directly targeting the mRNA coding sequence of each, resulting in reduced levels of MUC4 and MUC16 mRNA and protein. These data suggest that, in addition to regulating proteins that modulate EMT, miR-200c influences expression of cell surface mucins in pancreatic cancer.

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)

Synthetic oligorotaxanes exert high forces when folding under mechanical load

Science.gov (United States)

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

2018-01-01

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

Phorbol 12-myristate 13-acetate enhances nm23 gene expression in murine melanocytes but not in syngeneic B16-BL6 melanoma variants.

Science.gov (United States)

Huijzer, J C; McFarland, M; Niles, R M; Meadows, G G

1996-03-01

The nm23 gene has been described as a potential metastasis suppressor gene in certain rodent and human tumors. We previously demonstrated that tyrosine and phenylalanine restriction suppresses metastatic heterogeneity of B16-BL6 murine melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigated nm23 expression in the highly metastatic B16-BL6 (ND) melanoma, its nutritionally derived poorly metastatic (LT) variant, and the syngeneic non-tumorigenic Mel-ab melanocytes. No differences in nm23 expression were observed between ND and LT cells, and nm23 expression varied between different isolates. Previously, we showed that metastatic potential of 1-ND cells decreases and is not altered in 1-LT cells after prolonged in vitro cell passage; however, nm23 expression is equivalently increased by 2-fold. In 2-ND and 2-LT cells, expression of nm23 is not different at higher in vitro cell passage. Expression of nm23 decreased about 2-fold when phorbol 12-myristate 13-acetate (PMA) was removed from Mel-ab cells, which induces these cells to become quiescent. Although membrane-associated protein kinase C (PKC) activity decreased after prolonged PMA treatment in all cells, neither nm23 expression nor proliferation of ND and LT cells was affected by PMA. These data indicate that nm23 expression is related to proliferative activity rather than to the suppression of metastatic potential.

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

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

Science.gov (United States)

Will, Sebastian; Jabbari, Hosna

2016-01-01

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

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

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9-14 years: Results to month 36 from a randomized trial.

Science.gov (United States)

Leung, Ting Fan; Liu, Anthony Pak-Yin; Lim, Fong Seng; Thollot, Franck; Oh, Helen May Lin; Lee, Bee Wah; Rombo, Lars; Tan, Ngiap Chuan; Rouzier, Roman; De Simoni, Stéphanie; Suryakiran, Pemmaraju; Hezareh, Marjan; Thomas, Florence; Folschweiller, Nicolas; Struyf, Frank

2018-01-02

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9-14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4 + T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9-14 years. NCT0146235. Copyright © 2017. Published by Elsevier Ltd.

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)

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

Directory of Open Access Journals (Sweden)

Magdolna Apro

2011-10-01

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

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.

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)

The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals

Science.gov (United States)

Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun

2015-01-01

Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥7/9 and 8.9～228.1) than in the placebo group (≤1/10 and 0.8～1.7, P Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI. PMID:25715318

Broilers fed dietary vitamins harbor higher diversity of cecal bacteria and higher ratio of Clostridium, Faecalibacterium, and Lactobacillus than broilers with no dietary vitamins revealed by 16S rRNA gene clone libraries.

Science.gov (United States)

Luo, Yu-heng; Peng, Huan-wei; Wright, André-Denis G; Bai, Shi-ping; Ding, Xue-mei; Zeng, Qiu-feng; Li, Hua; Zheng, Ping; Su, Zhuo-wei; Cui, Ren-yong; Zhang, Ke-ying

2013-09-01

Research on the interaction between dietary vitamins and intestinal bacteria is poorly understood. To investigate the effect of dietary vitamins on the cecal bacterial communities, 2 bacterial 16S rRNA gene clone libraries were constructed from pooled PCR products obtained from the cecal digesta of 28-d broilers fed diets with vitamins (V) at the NRC level or with no vitamins (NV). The results showed that BW gain and average feed intake of V broilers was significantly higher (P vitamins can increase the ratio of facultative pathogenic bacteria and decrease the diversity of bacteria in the cecum of broilers. Our results provide new leads for further investigations on the interaction between dietary vitamin additives and the gut health of broilers.

The invasive wetland plant Alternanthera philoxeroides shows a higher tolerance to waterlogging than its native Congener Alternanthera sessilis.

Directory of Open Access Journals (Sweden)

Yue Chen

Full Text Available Plant invasion is one of the major threats to natural ecosystems. Phenotypic plasticity is considered to be important for promoting plant invasiveness. High tolerance of stress can also increase survival of invasive plants in adverse habitats. Limited growth and conservation of carbohydrate are considered to increase tolerance of flooding in plants. However, few studies have examined whether invasive species shows a higher phenotypic plasticity in response to waterlogging or a higher tolerance of waterlogging (lower plasticity than native species. We conducted a greenhouse experiment to compare the growth and morphological and physiological responses to waterlogging of the invasive, clonal, wetland species Alternanthera philoxeroides with those of its co-occurring, native, congeneric, clonal species Alternanthera sessilis. Plants of A. philoxeroides and A. sessilis were subjected to three treatments (control, 0 and 60 cm waterlogging. Both A. philoxeroides and A. sessilis survived all treatments. Overall growth was lower in A. philoxeroides than in A. sessilis, but waterlogging negatively affected the growth of A. philoxeroides less strongly than that of A. sessilis. Alternanthera philoxeroides thus showed less sensitivity of growth traits (lower plasticity and higher waterlogging tolerance. Moreover, the photosynthetic capacity of A. philoxeroides was higher than that of A. sessilis during waterlogging. Alternanthera philoxeroides also had higher total non-structural and non-soluble carbohydrate concentrations than A. sessilis at the end of treatments. Our results suggest that higher tolerance to waterlogging and higher photosynthetic capacity may partly explain the invasion success of A. philoxeroides in wetlands.

A new fold-cross metal mesh filter for suppressing side lobe leakage in terahertz region

Science.gov (United States)

Lu, Changgui; Qi, Zhengqing; Guo, Wengao; Cui, Yiping

2018-04-01

In this paper we propose a new type of fold-cross metal mesh band pass filter, which keeps diffraction side lobe far away from the main transmission peak and shows much better side lobe suppression. Both experimental and theoretical studies are made to analyze the mechanism of side lobe. Compared to the traditional cross filter, the fold-cross filter has a much lower side lobe with almost the same central frequency, bandwidth and highest transmission about 98%. Using the photolithography and electroplating techniques, we experimentally extend the distance between the main peak and diffraction side lobe to larger than 1 THz for the fold-cross filter, which is two times larger than the cross filter while maintaining the main peak transmissions of 89% at 1.25 THz for the two structures. This type of single layer substrate-free fold-cross metal structure shows better design flexibility and structure reliability with the introduction of fold arms for metal mesh band pass filters.

CLINICAL ANALYSIS OF SERUM INTERLEUKIN-16 AND VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS DEPENDING ON MORPHOLOGICAL CHARACTERISTICS OF THE TUMORS AND LONG-TERM TREATMENT OUTCOMES IN PATIENTS WITH BONE NEOPLASMS

Directory of Open Access Journals (Sweden)

I. V. Babkina

2016-01-01

Full Text Available Background: The progress in cancer treatment, including bone malignancies, is associated with advances in molecular biology. Based on the results of a  number of studies, treatment of bone sarcomas have been expanded with targeted therapy that uses drugs with targeted actions, including anti-angiogenic and bevacizumab, in particular. It inhibits the binding of a key activator of neoangiogenesis, vascular endothelial growth factor (VEGF, with its receptors type 1 and 2 (Flt-1 and KDR on the surface of endothelial cells, which results in a  decrease in vascularization and in inhibition of tumor growth. Beyond VEGF, other activators of neoangiogenesis have been identified, such as interleukin 16 (IL-16. Aim: To compare baseline serum IL-16 and VEGF in patients with malignant, borderline and benign bone tumors. Materials and methods: Serum IL-16 and VEGF levels was compared in 138 patients with primary bone tumors: benign (n=10; borderline (giant cell bone, n=22; malignant (n=106, aged 14 to 50 years, by immunoenzyme assay (Biosource, USA for IL-16 and R&D, USA for VEGF before any specific treatment. Bone malignancies were identified as osteosarcoma (n=45, among them 35  typical, 6 parosteal, and 4 periosteal, chondrosarcoma (n=24, Ewing sarcoma (n=27, and undifferentiated pleomorphic sarcoma (n=7 and chordoma (n=3. Results: The rate of IL-16 identification in the serum of bone tumors patients was 93%, with no significant differences depending on the histological structure of the tumor. No association between the size of primary tumors and IL-16 serum levels was found. Overall 3 and 5-year survival of patients with malignant bone tumors with IL-16 serum levels>33 pg/mL was significantly lower than in those IL-16 levels of≤33 pg/mL. Overall 5-year survival in osteosarcoma patients with higher IL-16 serum levels 1.6-fold lower, in Ewing sarcoma patients, 1.7-fold lower, and in chondrosarcoma patients, 1.8-fold lower than that the patients with

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

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.

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

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.

The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals.

Science.gov (United States)

Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun

2015-01-01

Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥ 7/9 and 8.9 ～ 228.1) than in the placebo group (≤ 1/10 and 0.8 ～ 1.7, P < 0.05). But no similar NTAb response trends were found in CA16 and 3 types of Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI.

Chemotherapy and Stem Cell Transplantation Increase p16INK4a Expression, a Biomarker of T-cell Aging

Directory of Open Access Journals (Sweden)

William A. Wood

2016-09-01

Full Text Available The expression of markers of cellular senescence increases exponentially in multiple tissues with aging. Age-related physiological changes may contribute to adverse outcomes in cancer survivors. To investigate the impact of high dose chemotherapy and stem cell transplantation on senescence markers in vivo, we collected blood and clinical data from a cohort of 63 patients undergoing hematopoietic cell transplantation. The expression of p16INK4a, a well-established senescence marker, was determined in T-cells before and 6 months after transplant. RNA sequencing was performed on paired samples from 8 patients pre- and post-cancer therapy. In patients undergoing allogeneic transplant, higher pre-transplant p16INK4a expression was associated with a greater number of prior cycles of chemotherapy received (p = 0.003, prior autologous transplantation (p = 0.01 and prior exposure to alkylating agents (p = 0.01. Transplantation was associated with a marked increase in p16INK4a expression 6 months following transplantation. Patients receiving autologous transplant experienced a larger increase in p16INK4a expression (3.1-fold increase, p = 0.002 than allogeneic transplant recipients (1.9-fold increase, p = 0.0004. RNA sequencing of T-cells pre- and post- autologous transplant or cytotoxic chemotherapy demonstrated increased expression of transcripts associated with cellular senescence and physiological aging. Cytotoxic chemotherapy, especially alkylating agents, and stem cell transplantation strongly accelerate expression of a biomarker of molecular aging in T-cells.

Multi-crease Self-folding by Global Heating.

Science.gov (United States)

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

2015-01-01

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

[Clinical analysis of vocal fold firbrous mass].

Science.gov (United States)

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

2018-03-01

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

Utah System of Higher Education 2015-16 Annual Report

Science.gov (United States)

Utah System of Higher Education, 2016

2016-01-01

This annual report describes Utah System of Higher Education's progress in the 2015-2016 academic year in the following areas: (1) Strategic plan; (2) Enrollment and completion; (3) Paying for college; (4) Funding higher education; (5) College preparation; (6) Concurrent enrollment and math; (7) Outreach and access; and (8) Industry and the…

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)

Autologous orbicularis muscle for filling facial folds-an experimental and clinical study.

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Schellini, Silvana Artioli; Hirai, Flavio Eduardo; Hoyama, Erika; Mattos, Maila Karina; Chaves, Fernando Rodrigo; Pellizon, Claudia Helena; Padovani, Carlos Roberto

2009-01-01

To present a technique for filling facial folds by using autologous orbicularis oculi muscle, based on an experimental model. two studies are presented: (1) an experimental study using 15 albino guinea-pigs from which a strip of the sural triceps muscle was removed and implanted in the subcutaneous tissue of the dorsal area. The animals were sacrificed 7, 30 and 60 days after the implantation, and the material was histologically evaluated. And (2) an interventional prospective clinical trial carried out on 20 patients referred to blepharoplasty surgery. They received autologous preseptal orbicularis muscle for filling facial folds. The results where evaluated by patients satisfaction and clinical exam. the sural tricep muscle, when implanted in the subcutaneous tissue, resulted in fibrosis. The patients whom received autologous orbicularis muscle implanted for filling facial folds showed that the procedure can be successfully carried out. autologous preseptal orbicularis muscle is a good material for filling facial folds. Cicatricial tissue will be formed on its implantation site, filling the tissue gap that forms the folds on the skin.

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

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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.

Physics of protein folding

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

2004-04-01

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

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.

Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

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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.

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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.

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.

Evaluation of the Grafted Fascia in the Vocal Fold of Dogs: A Histologic Study.

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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.

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.

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

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Massimiliano Bonomi

Full Text Available Proteins fold on a time scale incompatible with a mechanism of random search in conformational space thus indicating that somehow they are guided to the native state through a funneled energetic landscape. At the same time the heterogeneous kinetics suggests the existence of several different folding routes. Here we propose a scenario for the folding mechanism of the monomer of HIV-1 protease in which multiple pathways and milestone events coexist. A variety of computational approaches supports this picture. These include very long all-atom molecular dynamics simulations in explicit solvent, an analysis of the network of clusters found in multiple high-temperature unfolding simulations and a complete characterization of free-energy surfaces carried out using a structure-based potential at atomistic resolution and a combination of metadynamics and parallel tempering. Our results confirm that the monomer in solution is stable toward unfolding and show that at least two unfolding pathways exist. In our scenario, the formation of a hydrophobic core is a milestone in the folding process which must occur along all the routes that lead this protein towards its native state. Furthermore, the ensemble of folding pathways proposed here substantiates a rational drug design strategy based on inhibiting the folding of HIV-1 protease.

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.

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.

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

An Intramolecular Chaperone Inserted in Bacteriophage P22 Coat Protein Mediates Its Chaperonin-independent Folding*

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Suhanovsky, Margaret M.; Teschke, Carolyn M.

2013-01-01

The bacteriophage P22 coat protein has the common HK97-like fold but with a genetically inserted domain (I-domain). The role of the I-domain, positioned at the outermost surface of the capsid, is unknown. We hypothesize that the I-domain may act as an intramolecular chaperone because the coat protein folds independently, and many folding mutants are localized to the I-domain. The function of the I-domain was investigated by generating the coat protein core without its I-domain and the isolated I-domain. The core coat protein shows a pronounced folding defect. The isolated I-domain folds autonomously and has a high thermodynamic stability and fast folding kinetics in the presence of a peptidyl prolyl isomerase. Thus, the I-domain provides thermodynamic stability to the full-length coat protein so that it can fold reasonably efficiently while still allowing the HK97-like core to retain the flexibility required for conformational switching during procapsid assembly and maturation. PMID:24126914

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.

Glottal aerodynamics in compliant, life-sized vocal fold models

Science.gov (United States)

McPhail, Michael; Dowell, Grant; Krane, Michael

2013-11-01

This talk presents high-speed PIV measurements in compliant, life-sized models of the vocal folds. A clearer understanding of the fluid-structure interaction of voiced speech, how it produces sound, and how it varies with pathology is required to improve clinical diagnosis and treatment of vocal disorders. Physical models of the vocal folds can answer questions regarding the fundamental physics of speech, as well as the ability of clinical measures to detect the presence and extent of disorder. Flow fields were recorded in the supraglottal region of the models to estimate terms in the equations of fluid motion, and their relative importance. Experiments were conducted over a range of driving pressures with flow rates, given by a ball flowmeter, and subglottal pressures, given by a micro-manometer, reported for each case. Imaging of vocal fold motion, vector fields showing glottal jet behavior, and terms estimated by control volume analysis will be presented. The use of these results for a comparison with clinical measures, and for the estimation of aeroacoustic source strengths will be discussed. Acknowledge support from NIH R01 DC005642.

Two-fold Mellin-Barnes transforms of Usyukina-Davydychev functions

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Kniehl, Bernd [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Kondrashuk, Igor [Univ. del Bio Bio, Chillan (Chile). Dept. de Ciencias Basicas; Bielefeld Univ. (Germany). Fakultaet fuer Physik; Notte-Cuello, Eduardo A. [Univ. de La Serena (Chile). Dept. de Matematicas; Parra-Ferrada, Ivan [Univ. del Bio Bio, Chillan (Chile). Facultad de Educacion y Humanidades; Rojas-Medar, Marko [Univ. del Bio Bio, Chillan (Chile). Dept. de Ciencias Basicas

2013-04-15

In our previous paper (Nucl.Phys.B 870 (2013) 243) we showed that multi-fold Mellin-Barnes (MB) transforms of the Usyukina-Davydychev (UD) functions may be reduced to two-fold MB transforms. The MB transforms were written there as polynomials of logarithms of ratios of squares of the external momenta with certain coefficients. We also showed that these coefficients have a combinatoric origin. In this paper we present an explicit formula for these coefficients. The procedure of recovering the coefficients is based on taking the double uni-form limit in certain series of smooth functions of two variables which is constructed according to a pre-determined iterative way. The result is obtained by using basic methods of mathematical analysis. We observe that the finiteness of the limit of this iterative chain of smooth functions should reflect itself in other mathematical constructions, too, since it is not related in any way to the explicit form of the MB transforms.

Two-fold Mellin-Barnes transforms of Usyukina-Davydychev functions

International Nuclear Information System (INIS)

Kniehl, Bernd; Kondrashuk, Igor; Bielefeld Univ.; Notte-Cuello, Eduardo A.; Parra-Ferrada, Ivan; Rojas-Medar, Marko

2013-04-01

In our previous paper (Nucl.Phys.B 870 (2013) 243) we showed that multi-fold Mellin-Barnes (MB) transforms of the Usyukina-Davydychev (UD) functions may be reduced to two-fold MB transforms. The MB transforms were written there as polynomials of logarithms of ratios of squares of the external momenta with certain coefficients. We also showed that these coefficients have a combinatoric origin. In this paper we present an explicit formula for these coefficients. The procedure of recovering the coefficients is based on taking the double uni-form limit in certain series of smooth functions of two variables which is constructed according to a pre-determined iterative way. The result is obtained by using basic methods of mathematical analysis. We observe that the finiteness of the limit of this iterative chain of smooth functions should reflect itself in other mathematical constructions, too, since it is not related in any way to the explicit form of the MB transforms.

Cenozoic structural evolution, thermal history, and erosion of the Ukrainian Carpathians fold-thrust belt

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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.

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

Science.gov (United States)

Atkinson, Holly J; Babbitt, Patricia C

2009-10-01

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

Predicting protein folding pathways at the mesoscopic level based on native interactions between secondary structure elements

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Sze Sing-Hoi

2008-07-01

Full Text Available Abstract Background Since experimental determination of protein folding pathways remains difficult, computational techniques are often used to simulate protein folding. Most current techniques to predict protein folding pathways are computationally intensive and are suitable only for small proteins. Results By assuming that the native structure of a protein is known and representing each intermediate conformation as a collection of fully folded structures in which each of them contains a set of interacting secondary structure elements, we show that it is possible to significantly reduce the conformation space while still being able to predict the most energetically favorable folding pathway of large proteins with hundreds of residues at the mesoscopic level, including the pig muscle phosphoglycerate kinase with 416 residues. The model is detailed enough to distinguish between different folding pathways of structurally very similar proteins, including the streptococcal protein G and the peptostreptococcal protein L. The model is also able to recognize the differences between the folding pathways of protein G and its two structurally similar variants NuG1 and NuG2, which are even harder to distinguish. We show that this strategy can produce accurate predictions on many other proteins with experimentally determined intermediate folding states. Conclusion Our technique is efficient enough to predict folding pathways for both large and small proteins at the mesoscopic level. Such a strategy is often the only feasible choice for large proteins. A software program implementing this strategy (SSFold is available at http://faculty.cs.tamu.edu/shsze/ssfold.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

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

2015-09-01

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

Influence of yarn folding on UV protection properties of hemp knitted fabrics

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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.

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...

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

Melody discrimination and protein fold classification

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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.

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.

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

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Moye Wang

2016-04-01

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

LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor.

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Maikel Jongsma

Full Text Available Lysophosphatidic acid (LPA, a lipid mediator enriched in serum, stimulates cell migration, proliferation and other functions in many cell types. LPA acts on six known G protein-coupled receptors, termed LPA(1-6, showing both overlapping and distinct signaling properties. Here we show that, unexpectedly, LPA and serum almost completely inhibit the transwell migration of B16 melanoma cells, with alkyl-LPA(18:1 being 10-fold more potent than acyl-LPA(18:1. The anti-migratory response to LPA is highly polarized and dependent on protein kinase A (PKA but not Rho kinase activity; it is associated with a rapid increase in intracellular cAMP levels and PIP3 depletion from the plasma membrane. B16 cells express LPA(2, LPA(5 and LPA(6 receptors. We show that LPA-induced chemorepulsion is mediated specifically by the alkyl-LPA-preferring LPA(5 receptor (GPR92, which raises intracellular cAMP via a noncanonical pathway. Our results define LPA(5 as an anti-migratory receptor and they implicate the cAMP-PKA pathway, along with reduced PIP3 signaling, as an effector of chemorepulsion in B16 melanoma cells.

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.

Modulation of the maladaptive stress response to manage diseases of protein folding.

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Daniela Martino Roth

2014-11-01

Full Text Available Diseases of protein folding arise because of the inability of an altered peptide sequence to properly engage protein homeostasis components that direct protein folding and function. To identify global principles of misfolding disease pathology we examined the impact of the local folding environment in alpha-1-antitrypsin deficiency (AATD, Niemann-Pick type C1 disease (NPC1, Alzheimer's disease (AD, and cystic fibrosis (CF. Using distinct models, including patient-derived cell lines and primary epithelium, mouse brain tissue, and Caenorhabditis elegans, we found that chronic expression of misfolded proteins not only triggers the sustained activation of the heat shock response (HSR pathway, but that this sustained activation is maladaptive. In diseased cells, maladaptation alters protein structure-function relationships, impacts protein folding in the cytosol, and further exacerbates the disease state. We show that down-regulation of this maladaptive stress response (MSR, through silencing of HSF1, the master regulator of the HSR, restores cellular protein folding and improves the disease phenotype. We propose that restoration of a more physiological proteostatic environment will strongly impact the management and progression of loss-of-function and gain-of-toxic-function phenotypes common in human disease.

Idiopathic unilateral vocal-fold paralysis in the adult.

Science.gov (United States)

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

2018-02-02

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

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

Science.gov (United States)

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

2015-10-01

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

Medial arytenoidectomy versus transverse cordotomy as a treatment for bilateral vocal fold paralysis.

Science.gov (United States)

Bosley, Brooke; Rosen, Clark A; Simpson, C Blake; McMullin, Brian T; Gartner-Schmidt, Jackie L

2005-12-01

Transverse cordotomy (TC) and medial arytenoidectomy (MA) are procedures performed to enlarge the glottic airway in patients with bilateral vocal fold paralysis (BVFP). Both are less destructive than total arytenoidectomy and have distinct theoretical advantages for voice preservation, but they have never been compared. The records of patients with BVFP treated with TC or MA were reviewed; information regarding the outcome measures of tracheotomy decannulation, dysphagia, Voice Handicap Index score, voice intensity, clinical course, and preoperative and postoperative voice quality was obtained. Seventeen patients were available for evaluation (11 with TC, 6 with MA). All 6 patients with a preoperative tracheotomy were decannulated. Four patients in the MA group and 2 in the TC group had an increase in their postoperative Voice Handicap Index score. Two of the patients in the MA group had a decrease in phonatory sound pressure level of 3 dB, and 1 in the TC group had a decrease of 2 dB sound pressure level. Patient self-report of airway status following TC or MA showed that 62.5% (10 of 16) were significantly better and 25% (4 of 16) were somewhat better. Blinded audio perceptual analysis comparing preoperative and postoperative voice quality showed no difference between the MA and TC groups. A swallowing quality-of-life instrument confirmed a lack of swallowing difficulties postoperatively. Both TC and MA are good treatment options for BVFP, with a low incidence of complications in postoperative voice or of swallowing difficulties and a consistent improvement of laryngeal airway restriction symptoms.

Two-fold Mellin–Barnes transforms of Usyukina–Davydychev functions

Energy Technology Data Exchange (ETDEWEB)

Kniehl, Bernd A., E-mail: kniehl@desy.de [II. Institut für Theoretische Physik, Universität Hamburg, Luruper Chaussee 149, 22761 Hamburg (Germany); Kondrashuk, Igor [Grupo de Matemática Aplicada, Departamento de Ciencias Básicas, Universidad del Bío-Bío, Campus Fernando May, Casilla 447, Chillán (Chile); Fakultät für Physik, Universität Bielefeld, Universitätsstraße 25, 33615 Bielefeld (Germany); Notte-Cuello, Eduardo A. [Departamento de Matemáticas, Facultad de Ciencias, Universidad de La Serena, Av. Cisternas 1200, La Serena (Chile); Parra-Ferrada, Ivan [Carrera de Pedagogia en Matemática, Facultad de Educación y Humanidades, Universidad del Bío-Bío, Campus Castilla, Casilla 447, Chillán (Chile); Rojas-Medar, Marko [Grupo de Matemática Aplicada, Departamento de Ciencias Básicas, Universidad del Bío-Bío, Campus Fernando May, Casilla 447, Chillán (Chile)

2013-11-01

In our previous paper (Allendes et al., 2013 [10]), we showed that multi-fold Mellin–Barnes (MB) transforms of Usyukina–Davydychev (UD) functions may be reduced to two-fold MB transforms. The MB transforms were written there as polynomials of logarithms of ratios of squares of the external momenta with certain coefficients. We also showed that these coefficients have a combinatoric origin. In this paper, we present an explicit formula for these coefficients. The procedure of recovering the coefficients is based on taking the double-uniform limit in certain series of smooth functions of two variables which is constructed according to a pre-determined iterative way. The result is obtained by using basic methods of mathematical analysis. We observe that the finiteness of the limit of this iterative chain of smooth functions should reflect itself in other mathematical constructions, too, since it is not related in any way to the explicit form of the MB transforms. This finite double-uniform limit is represented in terms of a differential operator with respect to an auxiliary parameter which acts on the integrand of a certain two-fold MB integral. To demonstrate that our result is compatible with original representations of UD functions, we reproduce the integrands of these original integral representations by applying this differential operator to the integrand of the simple integral representation of the scalar triangle four-dimensional integral J(1,1,1−ε)

Two-fold Mellin–Barnes transforms of Usyukina–Davydychev functions

International Nuclear Information System (INIS)

Kniehl, Bernd A.; Kondrashuk, Igor; Notte-Cuello, Eduardo A.; Parra-Ferrada, Ivan; Rojas-Medar, Marko

2013-01-01

In our previous paper (Allendes et al., 2013 [10]), we showed that multi-fold Mellin–Barnes (MB) transforms of Usyukina–Davydychev (UD) functions may be reduced to two-fold MB transforms. The MB transforms were written there as polynomials of logarithms of ratios of squares of the external momenta with certain coefficients. We also showed that these coefficients have a combinatoric origin. In this paper, we present an explicit formula for these coefficients. The procedure of recovering the coefficients is based on taking the double-uniform limit in certain series of smooth functions of two variables which is constructed according to a pre-determined iterative way. The result is obtained by using basic methods of mathematical analysis. We observe that the finiteness of the limit of this iterative chain of smooth functions should reflect itself in other mathematical constructions, too, since it is not related in any way to the explicit form of the MB transforms. This finite double-uniform limit is represented in terms of a differential operator with respect to an auxiliary parameter which acts on the integrand of a certain two-fold MB integral. To demonstrate that our result is compatible with original representations of UD functions, we reproduce the integrands of these original integral representations by applying this differential operator to the integrand of the simple integral representation of the scalar triangle four-dimensional integral J(1,1,1−ε)

Characterization in vitro and in vivo of progressively adriamycin-resistant B16-BL6 mouse melanoma cells.

Science.gov (United States)

Ganapathi, R; Grabowski, D; Schmidt, H; Bell, D; Melia, M

1987-07-01

Adriamycin (ADR)-resistant sublines of B16-BL6 mouse melanoma selected by exposure to increasing concentrations of ADR were characterized in vitro for growth properties and in vivo for tumorigenicity and pulmonary metastases. The progressively resistant sublines adapted to grow in the presence of 0.025, 0.05, 0.1, and 0.25 microgram/ml ADR in monolayer culture were found to be 5-, 10-, 20-, and 40-fold ADR-resistant, respectively, compared to the parental sensitive cells, using a soft-agar colony assay and continuous ADR treatment for 7 days. The doubling time in monolayer culture of the parent sensitive and progressively ADR-resistant sublines of B16-BL6 melanoma cells was approximately 16-18 h. Although the colony-forming efficiency in soft agar of parental sensitive cells was only 0.5-4%, the 5-, 10-, 20-, and 40-fold ADR-resistant sublines had colony-forming efficiencies of 15, 20, 30, and 77%, respectively. Tumorigenicity in C57BL/6 mice of progressively ADR-resistant sublines was similar to parental sensitive cells following s.c. and i.p. implantation of 10(5)-10(6) tumor cells. Experimental pulmonary metastases were significantly lower in ADR-resistant sublines with progressive resistance. Additionally, unlike the parental sensitive and 5-fold ADR-resistant B16-BL6 cells, the 10-, 20-, and 40-fold ADR-resistant sublines were spontaneously nonmetastatic. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical detection of P-glycoprotein revealed the presence of a Mr 170,000 plasma membrane glycoprotein in the 40-fold ADR-resistant subline and its counterpart maintained for 1 year in ADR-free medium. Results from this study suggest that progressively ADR-resistant B16-BL6 mouse melanoma cells selected in vitro demonstrate a marked increase in colony formation in soft agar and a decrease in the ability to produce pulmonary metastases, without alterations in tumorigenicity.

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

Science.gov (United States)

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

2017-09-01

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

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.

Intraoperative imaging of pediatric vocal fold lesions using optical coherence tomography

Science.gov (United States)

Benboujja, Fouzi; Garcia, Jordan A.; Beaudette, Kathy; Strupler, Mathias; Hartnick, Christopher J.; Boudoux, Caroline

2016-01-01

Optical coherence tomography (OCT) has been previously identified as a promising tool for exploring laryngeal pathologies in adults. Here, we present an OCT handheld probe dedicated to imaging the unique geometry involved in pediatric laryngoscopy. A vertical cavity surface emitting laser-based wavelength-swept OCT system operating at 60 frames per second was coupled to the probe to acquire three-dimensional (3-D) volumes in vivo. In order to evaluate the performance of the proposed probe and system, we imaged pediatric vocal fold lesions of patients going under direct laryngoscopy. Through this in vivo study, we extracted OCT features characterizing each pediatric vocal fold lesion, which shows a great potential for noninvasive laryngeal lesion discrimination. We believe OCT vocal fold examination in 3-D will result in improved knowledge of the pediatric anatomy and could aid in managing pediatric laryngeal diseases.

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

Science.gov (United States)

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

2018-01-01

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

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

Science.gov (United States)

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

2017-02-01

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

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.

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

2016-09-01

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

Nomenclature proposal to describe vocal fold motion impairment

NARCIS (Netherlands)

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

2016-01-01

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

Nomenclature proposal to describe vocal fold motion impairment

NARCIS (Netherlands)

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

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

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

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

2010-12-01

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

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.

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.

Dysphagia, hoarseness, and unilateral true vocal fold motion impairment following anterior cervical diskectomy and fusion.

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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.

Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

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Chang, Joseph; Yung, Katherine C

2014-11-01

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

Accurately controlled sequential self-folding structures by polystyrene film

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.

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.

Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

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Colombo Elisa A

2012-01-01

Full Text Available Abstract Background Poikiloderma with Neutropenia (PN is a rare autosomal recessive genodermatosis caused by C16orf57 mutations. To date 17 mutations have been identified in 31 PN patients. Results We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel C16orf57 mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain. Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase. According to bioinformatic prediction, all known C16orf57 mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding. Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect. Conclusions In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of C16orf57 gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance. The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the

Folding and activity of hybrid sequence, disulfide-stabilized peptides

Energy Technology Data Exchange (ETDEWEB)

Pease, J.H.B.; Storrs, R.W.; Wemmer, D.E. (Univ. of California, Berkeley (USA))

1990-08-01

Peptides have been synthesized that have hybrid sequences, partially derived from the bee venom peptide apamin and partially from the S peptide of ribonuclease A. The hybrid peptides were demonstrated by NMR spectroscopy to fold, forming the same disulfides and basic three-dimensional structure as native apamin, containing a {beta}-turn and an {alpha}-helix. These hybrids were active in complementing S protein, reactivating nuclease activity. In addition, the hybrid peptide was effective in inducing antibodies that cross-react with the RNase, without conjugation to a carrier protein. The stability of the folded structure of this peptide suggests that it should be possible to elicit antibodies that will react not only with a specific sequence, but also with a specific secondary structure. Hybrid sequence peptides also provide opportunities to study separately nucleation and propagation steps in formation of secondary structure. The authors show that in S peptide the {alpha}-helix does not end abruptly but rather terminates gradually over four or five residues. In general, these hybrid sequence peptides, which fold predictably because of disulfide bond formation, can provide opportunities for examining structure - function relationships for many biologically active sequences.

Folding and activity of hybrid sequence, disulfide-stabilized peptides

International Nuclear Information System (INIS)

Pease, J.H.B.; Storrs, R.W.; Wemmer, D.E.

1990-01-01

Peptides have been synthesized that have hybrid sequences, partially derived from the bee venom peptide apamin and partially from the S peptide of ribonuclease A. The hybrid peptides were demonstrated by NMR spectroscopy to fold, forming the same disulfides and basic three-dimensional structure as native apamin, containing a β-turn and an α-helix. These hybrids were active in complementing S protein, reactivating nuclease activity. In addition, the hybrid peptide was effective in inducing antibodies that cross-react with the RNase, without conjugation to a carrier protein. The stability of the folded structure of this peptide suggests that it should be possible to elicit antibodies that will react not only with a specific sequence, but also with a specific secondary structure. Hybrid sequence peptides also provide opportunities to study separately nucleation and propagation steps in formation of secondary structure. The authors show that in S peptide the α-helix does not end abruptly but rather terminates gradually over four or five residues. In general, these hybrid sequence peptides, which fold predictably because of disulfide bond formation, can provide opportunities for examining structure - function relationships for many biologically active sequences

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

Science.gov (United States)

Zhang, Zhaoyan

2014-01-01

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

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.

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

Simulation of fluorescence resonance energy transfer experiments: effect of the dyes on protein folding

International Nuclear Information System (INIS)

Allen, Lucy R; Paci, Emanuele

2010-01-01

Fluorescence resonance energy transfer is a powerful technique which is often used to probe the properties of proteins and complex macromolecules. The technique relies on relatively large fluorescent dyes which are engineered into the molecule of interest. In the case of small proteins, these dyes may affect the stability of the protein, and modify the folding kinetics and the folding mechanisms which are being probed. Here we use atomistic simulation to investigate the effect that commonly used fluorescent dyes have on the folding of a four-helix bundle protein. We show that, depending on where the dyes are attached, their effect on the kinetic and thermodynamic properties of the protein may be significant. We find that, while the overall folding mechanism is not affected by the dyes, they can destabilize, or even stabilize, intermediate states.

Mitochondrial Myopathy: A Rare Cause of Early-Onset Vocal Fold Atrophy

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Kelly, Elizabeth A.; Bock, Jonathan M.; Peltier, Amanda C.; Oh, Shin J.; Garrett, C. Gaelyn

2014-01-01

Objectives We present the second published case of laryngeal involvement in mitochondrial myopathy. Methods A patient with laryngeal involvement of mitochondrial myopathy is presented, together with a literature review. Results A 41-year-old man presented with progressive breathy dysphonia. His brother had mitochondrial myopathy. Biopsy of the biceps muscle demonstrated cytochrome C oxidase–negative ragged blue fibers confirming mitochondrial myopathy. Videostroboscopy showed marked vocal fold atrophy, but subsequent injection laryngoplasty did not significantly improve the patient’s voice, despite improved postoperative glottic closure. Conclusions Mitochondrial myopathy should be considered in the differential diagnosis of severe early-onset vocal fold atrophy. PMID:23577570

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

Science.gov (United States)

Tan, Melin; Pitman, Michael J

2011-07-01

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

A Rat Excised Larynx Model of Vocal Fold Scar

Science.gov (United States)

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

2009-01-01

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

Method of generating ploynucleotides encoding enhanced folding variants

Energy Technology Data Exchange (ETDEWEB)

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

2017-05-02

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

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

Science.gov (United States)

Salvini, Francesco; Storti, Fabrizio

2001-01-01

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

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

Science.gov (United States)

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

2018-04-27

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

Multiple molecule effects on the cooperativity of protein folding transitions in simulations

Science.gov (United States)

Lewis, Jacob I.; Moss, Devin J.; Knotts, Thomas A.

2012-06-01

Though molecular simulation of proteins has made notable contributions to the study of protein folding and kinetics, disagreement between simulation and experiment still exists. One of the criticisms levied against simulation is its failure to reproduce cooperative protein folding transitions. This weakness has been attributed to many factors such as a lack of polarizability and adequate capturing of solvent effects. This work, however, investigates how increasing the number of proteins simulated simultaneously can affect the cooperativity of folding transitions — a topic that has received little attention previously. Two proteins are studied in this work: phage T4 lysozyme (Protein Data Bank (PDB) ID: 7LZM) and phage 434 repressor (PDB ID: 1R69). The results show that increasing the number of proteins molecules simulated simultaneously leads to an increase in the macroscopic cooperativity for transitions that are inherently cooperative on the molecular level but has little effect on the cooperativity of other transitions. Taken as a whole, the results identify one area of consideration to improving simulations of protein folding.

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

Science.gov (United States)

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

2003-01-01

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

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.

South African Journal of Higher Education - Vol 16, No 1 (2002)

African Journals Online (AJOL)

Guest Editorial: Globalisation and higher education restructuring in South Africa: ... South African legislation on limiting private and foreign higher education: ... Globalising and internationalising the higher education sector: challenges and ...

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

Heterotic model building: 16 special manifolds

International Nuclear Information System (INIS)

He, Yang-Hui; Lee, Seung-Joo; Lukas, Andre; Sun, Chuang

2014-01-01

We study heterotic model building on 16 specific Calabi-Yau manifolds constructed as hypersurfaces in toric four-folds. These 16 manifolds are the only ones among the more than half a billion manifolds in the Kreuzer-Skarke list with a non-trivial first fundamental group. We classify the line bundle models on these manifolds, both for SU(5) and SO(10) GUTs, which lead to consistent supersymmetric string vacua and have three chiral families. A total of about 29000 models is found, most of them corresponding to SO(10) GUTs. These models constitute a starting point for detailed heterotic model building on Calabi-Yau manifolds in the Kreuzer-Skarke list. The data for these models can be downloaded http://www-thphys.physics.ox.ac.uk/projects/CalabiYau/toricdata/index.html.

Treament Response in the neck: p16+ versus p16- oropharyngeal cancer

International Nuclear Information System (INIS)

Mak, Daisy; Hicks, Rodney J.; Rischin, Danny; Solomon, Ben; Peters, Lester; Corry, June; Bressel, Mathias; Young, Richard J.

2013-01-01

To compare nodal response rates following chemoradiotherapy in patients with p16+ and p16− oropharyngeal squamous cell carcinoma (OPSCC). Patients with node-positive OPSCC treated at Peter MacCallum Cancer Centre on the published phase I–III tirapazamine trials were identified. All patients had conventional assessment (clinical examination (CA), CT and/or MRI) and positron emission tomography (PET) at both baseline and 2–4 months post-treatment. There were 30 p16+ and 18 p16− patients, the former group having significantly higher stage nodal disease (P=0.016). The mean overall reduction in nodal size at post-treatment assessment was similar in p16+ and p16− patients (78% vs. 75%), and no statistically significant difference in nodal complete response (CR) rates was detected by either CA (50% vs. 39%, P=0.35) or PET/PET-CT (93% vs. 83%, P=0.19). PET was significantly more accurate in determining the true nodal CR rate in both groups, with a negative predictive value of 96%. Nodal response rates following chemoradiotherapy appear to be similar in p16+ and p16− patients when assessed by either CA or PET/PET-CT. However, higher nodal CR was seen in PET/PET-CT compared with CA in both groups. Metabolic imaging is more accurate than CA in assessing nodal response post-treatment.

Kinetics and Thermodynamics of Membrane Protein Folding

Directory of Open Access Journals (Sweden)

Ernesto A. Roman

2014-03-01

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

Prediction of folding preference of 10 kDa silk-like proteins using a Lego approach and ab initio calculations.

Science.gov (United States)

Pohl, Gábor; Beke, Tamás; Borbély, János; Perczel, András

2006-11-15

Because of their great flexibility and strength resistance, both spider silks and silkworm silks are of increasing scientific and commercial interest. Despite numerous spectroscopic and theoretical studies, several structural properties at the atomic level have yet to be identified. The present theoretical investigation focuses on these issues by studying three silk-like model peptides: (AG)(64), [(AG)(4)EG](16), and [(AG)(4)PEG](16), using a Lego-type approach to construct these polypeptides. On the basis of these examples it is shown that thermoneutral isodesmic reactions and ab initio calculations provide a capable method to investigate structural properties of repetitive polypeptides. The most probable overall fold schema of these molecules with respect to the type of embedded hairpin structures were determined at the ab initio level of theory (RHF/6-311++G(d,p)//RHF/3-21G). Further on, analysis is carried out on the possible hairpin and turn regions and on their effect on the global fold. In the case of the (AG)(64) model peptide, the optimal beta-sheet/turn ratio was also determined, which provided good support for experimental observations. In addition, lateral shearing of a hairpin "folding unit" was investigated at the quantum chemical level to explain the mechanical properties of spider silk. The unique mechanical characteristics of silk bio-compounds are now investigated at the atomic level.

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.

Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens

Energy Technology Data Exchange (ETDEWEB)

Montani, Claudia [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Steimberg, Nathalie; Boniotti, Jennifer [Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia (Italy); Biasiotto, Giorgio; Zanella, Isabella [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Diafera, Giuseppe [Integrated Systems Engineering (ISE), Milan (Italy); Biunno, Ida [IRGB-CNR, Milan (Italy); IRCCS-Multimedica, Milan (Italy); Caimi, Luigi [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Mazzoleni, Giovanna [Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia (Italy); Di Lorenzo, Diego, E-mail: diego.dilorenzo@yahoo.it [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy)

2014-11-01

Cell differentiation and response to hormonal signals were studied in a 3D environment on an in-house generated mouse fibroblast cell line expressing a reporter gene under the control of estrogen responsive sequences (EREs). 3D cell culture conditions were obtained in a Rotary Cell Culture System; (RCCS™), a microgravity based bioreactor that promotes the aggregation of cells into multicellular spheroids (MCS). In this bioreactor the cells maintained a better differentiated phenotype and more closely resembled in vivo tissue. The RCCS™ cultured fibroblasts showed higher expression of genes regulating cell assembly, differentiation and hormonal functions. Microarray analysis showed that genes related to cell cycle, proliferation, cytoskeleton, migration, adhesion and motility were all down-regulated in 3D as compared to 2D conditions, as well as oncogene expression and inflammatory cytokines. Controlled remodeling of ECM, which is an essential aspect of cell organization, homeostasis and tissue was affected by the culture method as assessed by immunolocalization of β-tubulin. Markers of cell organization, homeostasis and tissue repair, metalloproteinase 2 (MMP2) and its physiological inhibitor (TIMP4) changed expression in association with the relative formation of cell aggregates. The fibroblasts cultured in the RCCS™ maintain a better responsiveness to estrogens, measured as expression of ERα and regulation of an ERE-dependent reporter and of the endogenous target genes CBP, Rarb, MMP1 and Dbp. Our data highlight the interest of this 3D culture model for its potential application in the field of cell response to hormonal signals and the pharmaco-toxicological analyses of chemicals and natural molecules endowed of estrogenic potential. - Highlights: • We here characterized the first cell line derived from an estrogen reporter mouse. • In the RCCS cells express an immortalized behavior but not a transformed phenotype. • The RCCS provides a system for

Microemulsion-based synergistic dual-drug codelivery system for enhanced apoptosis of tumor cells.

Science.gov (United States)

Qu, Ding; Ma, Yihua; Sun, Wenjie; Chen, Yan; Zhou, Jing; Liu, Congyan; Huang, Mengmeng

2015-01-01

A microemulsion-based synergistic dual-drug codelivery system was developed for enhanced cell apoptosis by transporting coix seed oil and etoposide into A549 (human lung carcinoma) cells simultaneously. Results obtained by dynamic light scattering showed that an etoposide (VP16)-loaded coix seed oil microemulsion (EC-ME) delivery system had a small size around 35 nm, a narrow polydispersity index, and a slightly negative surface charge. The encapsulating efficiency and total drug loading rate were 97.01% and 45.48%, respectively, by high-performance liquid chromatography. The release profiles at various pH values showed an obvious pH-responsive difference, with the accumulated amount of VP16 released at pH 4.5 (and pH 5.5) being 2.7-fold higher relative to that at pH 7.4. Morphologic alteration (particle swelling) associated with a mildly acidic pH environment was found on transmission electron microscopy. In the cell study, the EC-ME system showed a significantly greater antiproliferative effect toward A549 cells in comparison with free VP16 and the mixture of VP16 and coix seed oil. The half-maximal inhibitory concentration of the EC-ME system was 3.9-fold and 10.4-fold lower relative to that of free VP16 and a mixture of VP16 and coix seed oil, respectively. Moreover, fluorescein isothiocyanate and VP16 (the green fluorescent probe and entrapped drug, respectively) were efficiently internalized into the cells by means of coix seed oil microemulsion through intuitive observation and quantitative measurement. Importantly, an EC-ME system containing 20 μg/mL of VP16 showed a 3.3-fold and 3.5-fold improvement in induction of cell apoptosis compared with the VP-16-loaded microemulsion and free VP16, respectively. The EC-ME combination strategy holds promise as an efficient drug delivery system for induction of apoptosis and treatment of lung cancer.

Nail fold Capillaroscopic Findings in Iranian Patients with Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Alireza Rajaei

2016-10-01

Full Text Available Background: Systemic Lupus Erythematosus is a progressive autoimmune disease with a wide range of morphological and functional changes in microscopic examination of small blood vessels. Identification of vascular diseases at early stage, plays an essential role in the prevention of its’ vascular complications. Nailfold capillaroscopy (NFC is a non-invasive, easy, painless, and accurate method for evaluation of microcirculation and could be used for this purpose. The vast majority of studies on capillaroscopy in lupus patients have shown that changes are not specified to lupus –unlike Systemic Sclerosis- and are more likely to overlap with other diseases. Therefore, it was decided to check capillaroscopic changes and evaluate morphological changes and capillary structure in terms of quality and quantity in lupus patients.Materials and Methods: Nail fold capillaroscopic findings of 114 patients aged 19-75 years old were reviewed in this study. The results were categorized as: a normal, b non-specific morphological abnormalities, and c Scleroderma-like pattern.  Results were analyzed qualitatively and quantitatively using SPSS 21 software. "Chi square" test was used to analyze the relationships between variables (P<0.05 was considered significant.Results: Our results show that Lupus –independent of any other microvascular risk factor can significantly affect the morphology and structure of blood circulation and these changes are shown with detail by nail fold capillaroscopy.Conclusion: Most of the findings are in line with similar studies performed by other investigators in this field. However, no specific pattern was recognized and microbleeding was higher in our patients with scleroderma-like pattern of involvement.

Studies on the synthesis and anti-radiation effect of 16-β-epiestriol

International Nuclear Information System (INIS)

Tong Zengshou; Zheng Sixin; Wang Peiren; Li Lu; Huang Mingxin

1990-01-01

The synthesis and radioprotective effect of 16 - β - epiestriol(2) are reported. The key intermediate, 16-ketoestradiol(7) was prepared by the reaction of 16α, 17α-epoxide estradiol diacetate(4) and methanolic potassium hydroxide. Epiestriol(2) was obtained by reduction of compound(7). Pharmacological study showed that the radioprotective effect of epiestriol at 9.0 Gy was higher than that of estriol(1) with 0.1 mg per mouse injected peritoneally 24 hr before irradiation, the survival rate with epiestriol was 85% higher than the control group, while estriol only elevated it by 50% under the same conditions. The slope of the survival-radiation dose curve with epiestriol was less steep than that with estriol. The structure-activity relationship and radioprotective effect of epiestriol and estriol suggest that the 16β-effect of steric factors on the receptor is one of the main effects. The 16β-hydroxyestriol appears to have the optimal radioprotective potency, in comparison with the 16β-hydroxyestriol

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

Quantification of change in vocal fold tissue stiffness relative to depth of artificial damage.

Science.gov (United States)

Rohlfs, Anna-Katharina; Schmolke, Sebastian; Clauditz, Till; Hess, Markus; Müller, Frank; Püschel, Klaus; Roemer, Frank W; Schumacher, Udo; Goodyer, Eric

2017-10-01

To quantify changes in the biomechanical properties of human excised vocal folds with defined artificial damage. The linear skin rheometer (LSR) was used to obtain a series of rheological measurements of shear modulus from the surface of 30 human cadaver vocal folds. The tissue samples were initially measured in a native condition and then following varying intensities of thermal damage. Histological examination of each vocal fold was used to determine the depth of artificial alteration. The measured changes in stiffness were correlated with the depth of cell damage. For vocal folds in a pre-damage state the shear modulus values ranged from 537 Pa to 1,651 Pa (female) and from 583 Pa to 1,193 Pa (male). With increasing depth of damage from the intermediate layer of the lamina propria (LP), tissue stiffness increased consistently (compared with native values) following application of thermal damage to the vocal folds. The measurement showed an increase of tissue stiffness when the depth of tissue damage was extending from the intermediate LP layer downwards. Changes in the elastic characteristics of human vocal fold tissue following damage at defined depths were demonstrated in an in vitro experiment. In future, reproducible in vivo measurements of elastic vocal fold tissue alterations may enable phonosurgeons to infer the extent of subepithelial damage from changes in surface elasticity.

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.

The N=16 subshell closure; La fermeture de sous-couche N=16

Energy Technology Data Exchange (ETDEWEB)

Obertelli, A

2005-09-01

The sequence of magic numbers for stable nuclei is now well understood. However the magnitude of shell gap may evolve from stability to drip line. Several observables show that N = 16 neutron-rich isotones present a higher stability compared to their neighbors on the N-Z chart. The spectroscopy of the levels of Ne{sup 27}, involving sd and fp shells, has allowed us to study the evolution of the nuclear shells responsible for the structure changes in N 16 isotones. In this framework we have studied the neutron transfer reaction Ne{sup 26}(d,p)Ne{sup 27} by inverted kinematics at 9,7 MeV/u. A cryogenic D{sub 2} target (17 mg.cm{sup -2}) has been used. The use of the magnetic spectrometer Vamos and that of the Exogam photon detector in coincidence operating mode has allowed us to achieve the spectroscopy of Ne{sup 27}. The results show a reduction in the gap between sd and fp shells for N = 17 isotones as we go from stability toward the neutron drip line. We have also performed a theoretical study in mean-field theory and beyond it through configuration mixing so that we can see the evolution of the isospin of the N = 16 subshell's closure. We have used a HFB (Hartree-Fock-Bogoliubov) with the finite range D1S effective interaction. (A.C.)

Swallowing dysfunction in patients with unilateral vocal fold paralysis: aetiology and outcomes.

Science.gov (United States)

Ollivere, B; Duce, K; Rowlands, G; Harrison, P; O'Reilly, B J

2006-01-01

Although unilateral vocal fold palsy (UVFP) is a common problem, data relating to swallowing dysfunction are sparse. We reviewed the clinical findings (method of presentation, underlying diagnosis and position of the vocal folds) of 30 patients and conducted a follow-up telephone survey. Outcome measures used were direct visualization of fold function, position and compensation. In addition, standardized speech and language assessments for swallowing dysfunction and dysphonia were noted and compared to presentation. Our study indicates that 56 per cent of patients with UVFP have associated dysphagia. Outcome with speech therapy is significant, with 73 per cent showing improvement. These data indicate a significant link between UVFP and swallowing dysfunction. There is a marked therapeutic benefit from voice therapy. Further work is required to evaluate the long-term outcomes and establish the mechanism of swallowing dysfunction in these patients.

Comparing apples and oranges: fold-change detection of multiple simultaneous inputs.

Directory of Open Access Journals (Sweden)

Yuval Hart

Full Text Available Sensory systems often detect multiple types of inputs. For example, a receptor in a cell-signaling system often binds multiple kinds of ligands, and sensory neurons can respond to different types of stimuli. How do sensory systems compare these different kinds of signals? Here, we consider this question in a class of sensory systems - including bacterial chemotaxis- which have a property known as fold-change detection: their output dynamics, including amplitude and response time, depends only on the relative changes in signal, rather than absolute changes, over a range of several decades of signal. We analyze how fold-change detection systems respond to multiple signals, using mathematical models. Suppose that a step of fold F1 is made in input 1, together with a step of F2 in input 2. What total response does the system provide? We show that when both input signals impact the same receptor with equal number of binding sites, the integrated response is multiplicative: the response dynamics depend only on the product of the two fold changes, F1F2. When the inputs bind the same receptor with different number of sites n1 and n2, the dynamics depend on a product of power laws, [Formula: see text]. Thus, two input signals which vary over time in an inverse way can lead to no response. When the two inputs affect two different receptors, other types of integration may be found and generally the system is not constrained to respond according to the product of the fold-change of each signal. These predictions can be readily tested experimentally, by providing cells with two simultaneously varying input signals. The present study suggests how cells can compare apples and oranges, namely by comparing each to its own background level, and then multiplying these two fold-changes.

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

Single-molecule studies of the Im7 folding landscape.

Science.gov (United States)

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

2010-04-23

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

Folds and Etudes

Science.gov (United States)

Bean, Robert

2007-01-01

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

Pathophysiology of the nodular and micronodular small bowel fold

International Nuclear Information System (INIS)

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

1987-01-01

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

A bidirectional shape memory alloy folding actuator

International Nuclear Information System (INIS)

Paik, Jamie K; Wood, Robert J

2012-01-01

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

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

Computed tomography of the small bowel in adult celiac disease: the jejunoileal fold pattern reversal

International Nuclear Information System (INIS)

Tomei, E.; Di Giovambattista, F.; Greco, M.; Marini, M.; Messineo, D.; Passariello, R.; Picarelli, A.

2000-01-01

The aim of this retrospective study was to establish whether the distinctive intestinal fold pattern of celiac disease (CD), known by barium studies as jejunoileal fold pattern reversal (JFPR) may be recognized at CT. The number of intestinal folds per 2.5 cm, seen at CT, were counted in the jejunum and in the ileum of 22 adult patients with CD and compared with the folds of 30 consecutive subjects in whom an intestinal disease had been excluded. The results were submitted to statistical analysis by Student's t-test. In the control group the number of folds per 2.5 cm were 4.88 (SD ± 0.78) in the jejunum and 2.84 (± 0.62) in the ileum; in the CD group the number of folds were 2.42 (± 1.61) in the jejunum and 5.11 (± 1.24) in the ileum. There was a statistically significant difference in the number of jejunal and ileal folds between the CD patients and the control group (in both cases p < 0.001). The JFPR was seen in 15 patients with CD (68.2 %) but in none of the controls. Our study shows that JFPR is not a normal finding and can be demonstrated by CT in the majority of patients with CD. (orig.)

Computed tomography of the small bowel in adult celiac disease: the jejunoileal fold pattern reversal

Energy Technology Data Exchange (ETDEWEB)

Tomei, E.; Di Giovambattista, F.; Greco, M. [Department of Clinical Sciences, University of Rome (Italy); Marini, M.; Messineo, D.; Passariello, R.; Picarelli, A. [Department of Radiology II, University of Rome (Italy)

2000-01-01

The aim of this retrospective study was to establish whether the distinctive intestinal fold pattern of celiac disease (CD), known by barium studies as jejunoileal fold pattern reversal (JFPR) may be recognized at CT. The number of intestinal folds per 2.5 cm, seen at CT, were counted in the jejunum and in the ileum of 22 adult patients with CD and compared with the folds of 30 consecutive subjects in whom an intestinal disease had been excluded. The results were submitted to statistical analysis by Student's t-test. In the control group the number of folds per 2.5 cm were 4.88 (SD {+-} 0.78) in the jejunum and 2.84 ({+-} 0.62) in the ileum; in the CD group the number of folds were 2.42 ({+-} 1.61) in the jejunum and 5.11 ({+-} 1.24) in the ileum. There was a statistically significant difference in the number of jejunal and ileal folds between the CD patients and the control group (in both cases p < 0.001). The JFPR was seen in 15 patients with CD (68.2 %) but in none of the controls. Our study shows that JFPR is not a normal finding and can be demonstrated by CT in the majority of patients with CD. (orig.)

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

Science.gov (United States)

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

2017-10-01

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

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.

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

Science.gov (United States)

Saidi, Hiba; Erath, Byron D.

2015-11-01

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

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

Energetic frustrations in protein folding at residue resolution: a homologous simulation study of Im9 proteins.

Directory of Open Access Journals (Sweden)

Yunxiang Sun

Full Text Available Energetic frustration is becoming an important topic for understanding the mechanisms of protein folding, which is a long-standing big biological problem usually investigated by the free energy landscape theory. Despite the significant advances in probing the effects of folding frustrations on the overall features of protein folding pathways and folding intermediates, detailed characterizations of folding frustrations at an atomic or residue level are still lacking. In addition, how and to what extent folding frustrations interact with protein topology in determining folding mechanisms remains unclear. In this paper, we tried to understand energetic frustrations in the context of protein topology structures or native-contact networks by comparing the energetic frustrations of five homologous Im9 alpha-helix proteins that share very similar topology structures but have a single hydrophilic-to-hydrophobic mutual mutation. The folding simulations were performed using a coarse-grained Gō-like model, while non-native hydrophobic interactions were introduced as energetic frustrations using a Lennard-Jones potential function. Energetic frustrations were then examined at residue level based on φ-value analyses of the transition state ensemble structures and mapped back to native-contact networks. Our calculations show that energetic frustrations have highly heterogeneous influences on the folding of the four helices of the examined structures depending on the local environment of the frustration centers. Also, the closer the introduced frustration is to the center of the native-contact network, the larger the changes in the protein folding. Our findings add a new dimension to the understanding of protein folding the topology determination in that energetic frustrations works closely with native-contact networks to affect the protein folding.

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...

Inpatient injection laryngoplasty for vocal fold immobility: When is it really necessary?

Science.gov (United States)

Zuniga, Steven; Ebersole, Barbara; Jamal, Nausheen

To compare pulmonary and swallow outcomes of injection laryngoplasty when performed in the acute versus subacute setting in head & neck and thoracic cancer patients presenting with new onset unilateral vocal fold immobility. Case series with chart review at an academic cancer center over a 2year period. Based on swallow evaluation, patients diagnosed with vocal fold immobility were grouped into an unsafe swallow group, injected as inpatients, and a safe swallow group, for whom injection laryngoplasty was delayed to the outpatient setting or not performed. Rates of pneumonia, diet recommendations, and swallow outcomes were compared between groups. 24 patients with new-onset vocal fold immobility were evaluated. 7 underwent injection in the inpatient setting, 12 in the outpatient setting, and 5 did not undergo injection. There was no perceived difference in speech and swallow outcomes between the inpatient and outpatient injection groups. Injection laryngoplasty shows promise as an effective intervention for reducing aspiration risk and improving diet normalcy in patients with dysphagia as a result of unilateral vocal fold immobility. In patients determined to have a safe swallow, delay of injection laryngoplasty is not detrimental to swallow outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Folded fabric tunes rock deformation and failure mode in the upper crust.

Science.gov (United States)

Agliardi, F; Dobbs, M R; Zanchetta, S; Vinciguerra, S

2017-11-10

The micro-mechanisms of brittle failure affect the bulk mechanical behaviour and permeability of crustal rocks. In low-porosity crystalline rocks, these mechanisms are related to mineralogy and fabric anisotropy, while confining pressure, temperature and strain rates regulate the transition from brittle to ductile behaviour. However, the effects of folded anisotropic fabrics, widespread in orogenic settings, on the mechanical behaviour of crustal rocks are largely unknown. Here we explore the deformation and failure behaviour of a representative folded gneiss, by combining the results of triaxial deformation experiments carried out while monitoring microseismicity with microstructural and damage proxies analyses. We show that folded crystalline rocks in upper crustal conditions exhibit dramatic strength heterogeneity and contrasting failure modes at identical confining pressure and room temperature, depending on the geometrical relationships between stress and two different anisotropies associated to the folded rock fabric. These anisotropies modulate the competition among quartz- and mica-dominated microscopic damage processes, resulting in transitional brittle to semi-brittle modes under P and T much lower than expected. This has significant implications on scales relevant to seismicity, energy resources, engineering applications and geohazards.

Endoscopic Anatomy of the Tensor Fold and Anterior Attic.

Science.gov (United States)

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

2018-02-01

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

A nomenclature paradigm for benign midmembranous vocal fold lesions.

Science.gov (United States)

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

2012-06-01

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

Benign Lesions of The Vocal Fold

Directory of Open Access Journals (Sweden)

Ozgur Surmelioglu

2013-02-01

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

Wrinkles and Folds of Activated Graphene Nanosheets as Fast and Efficient Adsorptive Sites for Hydrophobic Organic Contaminants.

Science.gov (United States)

Wang, Jun; Chen, Baoliang; Xing, Baoshan

2016-04-05

To create more wrinkles and folds as available adsorption sites, graphene nanosheets (GNS) were thermally treated with KOH for morphological alteration. The surface structures and properties of the activated graphene nanosheets (AGN) were characterized by BET-N2, SEM, TEM, Raman, XRD, XPS, and FTIR. After KOH etching, the highly crystal structure was altered, self-aggregation of graphene layers were evidently relieved, and more single to few layer graphene nanosheets were created with wrinkles and folds. Also both specific surface area and micropore volume of AGN increased relative to GNS. The adsorption of AGN toward p-nitrotoluene, naphthalene and phenanthrene were greatly enhanced in comparison with GNS, and gradually promoted with increasing degree of KOH etching. Adsorption rate of organic contaminants on AGN was very fast and efficient, whereas small molecules showed higher adsorption rates due to the more porous surface of graphene. In addition to π-π interaction, the high affinities of p-nitrotoluene to AGN are suggested from strong electron charge transfer interactions between nitro groups on p-nitrotoluene and defect sites of AGN. A positively linear correlation between organic molecule uptake and the micropore volume of AGN indicated that pore-filling mechanism may play an important role in adsorption. Morphological wrinkles and folds of graphene nanosheets can be regulated to enhance the adsorption capability and kinetics for efficient pollutant removal and to selectively preconcentrate adsorbates with different sizes for detection.

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.

AMP-forming acetyl-CoA synthetases in Archaea show unexpected diversity in substrate utilization

Science.gov (United States)

Ingram-Smith, Cheryl; Smith, Kerry S.

2007-01-01

Adenosine monophosphate (AMP)-forming acetyl-CoA synthetase (ACS; acetate:CoA ligase (AMP-forming), EC 6.2.1.1) is a key enzyme for conversion of acetate to acetyl-CoA, an essential intermediate at the junction of anabolic and catabolic pathways. Phylogenetic analysis of putative short and medium chain acyl-CoA synthetase sequences indicates that the ACSs form a distinct clade from other acyl-CoA synthetases. Within this clade, the archaeal ACSs are not monophyletic and fall into three groups composed of both bacterial and archaeal sequences. Kinetic analysis of two archaeal enzymes, an ACS from Methanothermobacter thermautotrophicus (designated as MT-ACS1) and an ACS from Archaeoglobus fulgidus (designated as AF-ACS2), revealed that these enzymes have very different properties. MT-ACS1 has nearly 11-fold higher affinity and 14-fold higher catalytic efficiency with acetate than with propionate, a property shared by most ACSs. However, AF-ACS2 has only 2.3-fold higher affinity and catalytic efficiency with acetate than with propionate. This enzyme has an affinity for propionate that is almost identical to that of MT-ACS1 for acetate and nearly tenfold higher than the affinity of MT-ACS1 for propionate. Furthermore, MT-ACS1 is limited to acetate and propionate as acyl substrates, whereas AF-ACS2 can also utilize longer straight and branched chain acyl substrates. Phylogenetic analysis, sequence alignment and structural modeling suggest a molecular basis for the altered substrate preference and expanded substrate range of AF-ACS2 versus MT-ACS1. PMID:17350930

AMP-forming acetyl-CoA synthetases in Archaea show unexpected diversity in substrate utilization

Directory of Open Access Journals (Sweden)

Cheryl Ingram-Smith

2006-01-01

Full Text Available Adenosine monophosphate (AMP-forming acetyl-CoA synthetase (ACS; acetate:CoA ligase (AMP-forming, EC 6.2.1.1 is a key enzyme for conversion of acetate to acetyl-CoA, an essential intermediate at the junction of anabolic and catabolic pathways. Phylogenetic analysis of putative short and medium chain acyl-CoA synthetase sequences indicates that the ACSs form a distinct clade from other acyl-CoA synthetases. Within this clade, the archaeal ACSs are not monophyletic and fall into three groups composed of both bacterial and archaeal sequences. Kinetic analysis of two archaeal enzymes, an ACS from Methanothermobacter thermautotrophicus (designated as MT-ACS1 and an ACS from Archaeoglobus fulgidus (designated as AF-ACS2, revealed that these enzymes have very different properties. MT-ACS1 has nearly 11-fold higher affinity and 14-fold higher catalytic efficiency with acetate than with propionate, a property shared by most ACSs. However, AF-ACS2 has only 2.3-fold higher affinity and catalytic efficiency with acetate than with propionate. This enzyme has an affinity for propionate that is almost identical to that of MT-ACS1 for acetate and nearly tenfold higher than the affinity of MT-ACS1 for propionate. Furthermore, MT-ACS1 is limited to acetate and propionate as acyl substrates, whereas AF-ACS2 can also utilize longer straight and branched chain acyl substrates. Phylogenetic analysis, sequence alignment and structural modeling suggest a molecular basis for the altered substrate preference and expanded substrate range of AF-ACS2 versus MT-ACS1.

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

Science.gov (United States)

Luo, Haoxiang; Chang, Siyuan; Chen, Ye; Rousseau, Bernard; PhonoSim Team

2017-11-01

Vocal fold vibration during speech production involves a three-dimensional unsteady glottal jet flow and three-dimensional nonlinear tissue mechanics. A full 3D fluid-structure interaction (FSI) model is computationally expensive even though it provides most accurate information about the system. On the other hand, an efficient reduced-order FSI model is useful for fast simulation and analysis of the vocal fold dynamics, which can be applied in procedures such as optimization and parameter estimation. In this work, we study performance of a reduced-order model as compared with the corresponding full 3D model in terms of its accuracy in predicting the vibration frequency and deformation mode. In the reduced-order model, we use a 1D flow model coupled with a 3D tissue model that is the same as in the full 3D model. Two different hyperelastic tissue behaviors are assumed. In addition, the vocal fold thickness and subglottal pressure are varied for systematic comparison. The result shows that the reduced-order model provides consistent predictions as the full 3D model across different tissue material assumptions and subglottal pressures. However, the vocal fold thickness has most effect on the model accuracy, especially when the vocal fold is thin.

Destiny of autologous bone marrow-derived stromal cells implanted in the vocal fold.

Science.gov (United States)

Kanemaru, Shin-ichi; Nakamura, Tatsuo; Yamashita, Masaru; Magrufov, Akhmar; Kita, Tomoko; Tamaki, Hisanobu; Tamura, Yoshihiro; Iguchi, Fuku-ichiro; Kim, Tae Soo; Kishimoto, Masanao; Omori, Koichi; Ito, Juichi

2005-12-01

The aim of this study was to investigate the destiny of implanted autologous bone marrow-derived stromal cells (BSCs) containing mesenchymal stem cells. We previously reported the successful regeneration of an injured vocal fold through implantation of BSCs in a canine model. However, the fate of the implanted BSCs was not examined. In this study, implanted BSCs were traced in order to determine the type of tissues resulting at the injected site of the vocal fold. After harvest of bone marrow from the femurs of green fluorescent transgenic mice, adherent cells were cultured and selectively amplified. By means of a fluorescence-activated cell sorter, it was confirmed that some cells were strongly positive for mesenchymal stem cell markers, including CD29, CD44, CD49e, and Sca-1. These cells were then injected into the injured vocal fold of a nude rat. Immunohistologic examination of the resected vocal folds was performed 8 weeks after treatment. The implanted cells were alive in the host tissues and showed positive expression for keratin and desmin, markers for epithelial tissue and muscle, respectively. The implanted BSCs differentiated into more than one tissue type in vivo. Cell-based tissue engineering using BSCs may improve the quality of the healing process in vocal fold injuries.

Abaxial growth and steric constraints guide leaf folding and shape in Acer pseudoplatanus.

Science.gov (United States)

Couturier, Etienne; Brunel, Nicole; Douady, Stéphane; Nakayama, Naomi

2012-08-01

How leaf shape is regulated is a long-standing question in botany. For diverse groups of dicotyledon species, lamina folding along the veins and geometry of the space available for the primordia can explain the palmate leaf morphology. Dubbed the kirigami theory, this hypothesis of fold-dependent leaf shape regulation has remained largely theoretical. Using Acer pseudoplatanus, we investigated the mechanisms behind the two key processes of kirigami leaf development. Cytological examination and quantitative analyses were used to examine the course of the vein-dependent lamina folding. Surgical ablation and tissue culturing were employed to test the effects of physical constraints on primordia growth. The final morphology of leaves growing without steric constraints were predicted mathematically. The cytological examination showed that the lamina's abaxial side along the veins grows substantially more than the adaxial side. The abaxial hypergrowth along the veins and the lamina extension correlated with the lamina folding. When a primordium was released from the physical constraints imposed by the other primordia, it rapidly grew into the newly available space, while maintaining the curvature inward. The morphology of such a leaf was predicted to lack symmetry in the lobe shapes. The enhanced growth on the abaxial side of the lamina along the veins is likely to drive lamina folding. The surgical ablation provided clear support for the space-filling nature of leaf growth; thus, steric constraints play a role in determination of the shapes of folded leaves and probably also of the final leaf morphology.

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

Cache and energy efficient algorithms for Nussinov's RNA Folding.

Science.gov (United States)

Zhao, Chunchun; Sahni, Sartaj

2017-12-06

An RNA folding/RNA secondary structure prediction algorithm determines the non-nested/pseudoknot-free structure by maximizing the number of complementary base pairs and minimizing the energy. Several implementations of Nussinov's classical RNA folding algorithm have been proposed. Our focus is to obtain run time and energy efficiency by reducing the number of cache misses. Three cache-efficient algorithms, ByRow, ByRowSegment and ByBox, for Nussinov's RNA folding are developed. Using a simple LRU cache model, we show that the Classical algorithm of Nussinov has the highest number of cache misses followed by the algorithms Transpose (Li et al.), ByRow, ByRowSegment, and ByBox (in this order). Extensive experiments conducted on four computational platforms-Xeon E5, AMD Athlon 64 X2, Intel I7 and PowerPC A2-using two programming languages-C and Java-show that our cache efficient algorithms are also efficient in terms of run time and energy. Our benchmarking shows that, depending on the computational platform and programming language, either ByRow or ByBox give best run time and energy performance. The C version of these algorithms reduce run time by as much as 97.2% and energy consumption by as much as 88.8% relative to Classical and by as much as 56.3% and 57.8% relative to Transpose. The Java versions reduce run time by as much as 98.3% relative to Classical and by as much as 75.2% relative to Transpose. Transpose achieves run time and energy efficiency at the expense of memory as it takes twice the memory required by Classical. The memory required by ByRow, ByRowSegment, and ByBox is the same as that of Classical. As a result, using the same amount of memory, the algorithms proposed by us can solve problems up to 40% larger than those solvable by Transpose.

Systematic review and meta-analysis shows a specific micronutrient profile in people with Down Syndrome: Lower blood calcium, selenium and zinc, higher red blood cell copper and zinc, and higher salivary calcium and sodium.

Directory of Open Access Journals (Sweden)

Amene Saghazadeh

Full Text Available Different metabolic profiles as well as comorbidities are common in people with Down Syndrome (DS. Therefore it is relevant to know whether micronutrient levels in people with DS are also different. This systematic review was designed to review the literature on micronutrient levels in people with DS compared to age and sex-matched controls without DS. We identified sixty nine studies from January 1967 to April 2016 through main electronic medical databases PubMed, Scopus, and Web of knowledge. We carried out meta-analysis of the data on four essential trace elements (Cu, Fe, Se, and Zn, six minerals (Ca, Cl, K, Mg, Na, and P, and five vitamins (vitamin A, B9, B12, D, and E. People with DS showed lower blood levels of Ca (standard mean difference (SMD = -0.63; 95% confidence interval (CI: -1.16 to -0.09, Se (SMD = -0.99; 95% CI: -1.55 to -0.43, and Zn (SMD = -1.30; 95% CI: -1.75 to -0.84, while red cell levels of Zn (SMD = 1.88; 95% CI: 0.48 to 3.28 and Cu (SMD = 2.77; 95% CI: 1.96 to 3.57 were higher. They had also higher salivary levels of Ca (SMD = 0.85; 95% CI: 0.38 to 1.33 and Na (SMD = 1.04; 95% CI: 0.39 to 1.69. Our findings that micronutrient levels are different in people with DS raise the question whether these differences are related to the different metabolic profiles, the common comorbidities or merely reflect DS.

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

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

Science.gov (United States)

Krane, Michael; Walters, Gage; McPhail, Michael

2017-11-01

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

Explicit calculation of multi-fold contour integrals of certain ratios of Euler gamma functions. Pt. 1

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, Ivan [Valparaiso Univ. (Chile). Inst. de Fisica y Astronomia; Kniehl, Bernd A. [Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik; Kondrashuk, Igor [Univ. del Bio-Bio, Chillan (Chile). Dept. de Ciencias Basicas; Notte-Cuello, Eduardo A. [La Serena Univ. (Chile). Dept. de Matematicas; Parra-Ferrada, Ivan [Talca Univ. (Chile). Inst. de Matematica y Fisica; Rojas-Medar, Marko A. [Univ. de Tarapaca, Arica (Chile). Inst. de Alta Investigacion

2016-12-15

In this paper we proceed to study properties of Mellin-Barnes (MB) transforms of Usyukina-Davydychev (UD) functions. In our previous papers [Nuclear Physics B 870 (2013) 243], [Nuclear Physics B 876 (2013) 322] we showed that multi-fold Mellin-Barnes (MB) transforms of Usyukina-Davydychev (UD) functions may be reduced to two-fold MB transforms and that the higher-order UD functions were obtained in terms of a differential operator by applying it to a slightly modified first UD function. The result is valid in d=4 dimensions and its analog in d=4-2ε dimensions exits too [Theoretical and Mathematical Physics 177 (2013) 1515]. In [Nuclear Physics B 870 (2013) 243] the chain of recurrent relations for analytically regularized UD functions was obtained implicitly by comparing the left hand side and the right hand side of the diagrammatic relations between the diagrams with different loop orders. In turn, these diagrammatic relations were obtained due to the method of loop reductions for the triangle ladder diagrams proposed in 1983 by Belokurov and Usyukina. Here we reproduce these recurrent relations by calculating explicitly via Barnes lemmas the contour integrals produced by the left hand sides of the diagrammatic relations. In such a way we explicitly calculate a family of multi-fold contour integrals of certain ratios of Euler gamma functions. We make a conjecture that similar results for the contour integrals are valid for a wider family of smooth functions which includes the MB transforms of UD functions.

PyFolding: Open-Source Graphing, Simulation, and Analysis of the Biophysical Properties of Proteins.

Science.gov (United States)

Lowe, Alan R; Perez-Riba, Albert; Itzhaki, Laura S; Main, Ewan R G

2018-02-06

For many years, curve-fitting software has been heavily utilized to fit simple models to various types of biophysical data. Although such software packages are easy to use for simple functions, they are often expensive and present substantial impediments to applying more complex models or for the analysis of large data sets. One field that is reliant on such data analysis is the thermodynamics and kinetics of protein folding. Over the past decade, increasingly sophisticated analytical models have been generated, but without simple tools to enable routine analysis. Consequently, users have needed to generate their own tools or otherwise find willing collaborators. Here we present PyFolding, a free, open-source, and extensible Python framework for graphing, analysis, and simulation of the biophysical properties of proteins. To demonstrate the utility of PyFolding, we have used it to analyze and model experimental protein folding and thermodynamic data. Examples include: 1) multiphase kinetic folding fitted to linked equations, 2) global fitting of multiple data sets, and 3) analysis of repeat protein thermodynamics with Ising model variants. Moreover, we demonstrate how PyFolding is easily extensible to novel functionality beyond applications in protein folding via the addition of new models. Example scripts to perform these and other operations are supplied with the software, and we encourage users to contribute notebooks and models to create a community resource. Finally, we show that PyFolding can be used in conjunction with Jupyter notebooks as an easy way to share methods and analysis for publication and among research teams. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The drug target genes show higher evolutionary conservation than non-target genes.

Science.gov (United States)

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

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.

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.

Mechanics of the scrolling and folding of graphene

Science.gov (United States)

Li, Hao; Li, Ming; Kang, Zhan

2018-06-01

The competition between the out-of-plane rigidity and the van der Waals interaction leads to the scrolled and folded structural configurations of graphene. These configuration changes, as compared with the initially planar geometry, significantly affect the electronic, optical and mechanical properties of graphene, promising exciting applications in graphene-nanoelectronics. We propose a finite-deformation theoretical model, in which no presumed assumptions on the geometries of deformed configurations are required. Both the predicted deformed profiles and the critical conditions show great agreements with molecular dynamics simulations results when compared with existing studies with simple geometrical assumptions. Moreover, MD simulations are performed to explore the morphology transitions between different configurations. It is observed that the folded configuration is energetically favorable for a short graphene sheet, while a long graphene sheet tends to scroll. Of particular interest, we observe the morphology transition from a Fermat scroll to the Archimedean scroll for the bi-scrolled graphene. These findings are useful for understanding the stability of graphene and may provide guidance to the design of programmable graphene-nanoelectronics.

Mechanics of the scrolling and folding of graphene.

Science.gov (United States)

Li, Hao; Li, Ming; Kang, Zhan

2018-06-15

The competition between the out-of-plane rigidity and the van der Waals interaction leads to the scrolled and folded structural configurations of graphene. These configuration changes, as compared with the initially planar geometry, significantly affect the electronic, optical and mechanical properties of graphene, promising exciting applications in graphene-nanoelectronics. We propose a finite-deformation theoretical model, in which no presumed assumptions on the geometries of deformed configurations are required. Both the predicted deformed profiles and the critical conditions show great agreements with molecular dynamics simulations results when compared with existing studies with simple geometrical assumptions. Moreover, MD simulations are performed to explore the morphology transitions between different configurations. It is observed that the folded configuration is energetically favorable for a short graphene sheet, while a long graphene sheet tends to scroll. Of particular interest, we observe the morphology transition from a Fermat scroll to the Archimedean scroll for the bi-scrolled graphene. These findings are useful for understanding the stability of graphene and may provide guidance to the design of programmable graphene-nanoelectronics.

Vocal Fold Collision Modeling

DEFF Research Database (Denmark)

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

2015-01-01

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

The four-fold way

International Nuclear Information System (INIS)

Terazawa, H.

1986-01-01

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

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

OpenAIRE

Riede, Tobias; Titze, Ingo R.

2008-01-01

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

Folding and insertion thermodynamics of the transmembrane WALP peptide

International Nuclear Information System (INIS)

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

2015-01-01

The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA) n (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide’s insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum—in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence

Folding and insertion thermodynamics of the transmembrane WALP peptide

Energy Technology Data Exchange (ETDEWEB)

Bereau, Tristan, E-mail: bereau@mpip-mainz.mpg.de [Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz (Germany); Bennett, W. F. Drew [Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Pfaendtner, Jim [Department of Chemical Engineering, University of Washington, Seattle, Washington 98195 (United States); Deserno, Markus [Department of Physics, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213 (United States); Karttunen, Mikko [Department of Mathematics and Computer Science & Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, MetaForum, 5600 MB Eindhoven (Netherlands)

2015-12-28

The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA){sub n} (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide’s insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum—in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.

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.

Improvement of a Vocal Fold Imaging System

Energy Technology Data Exchange (ETDEWEB)

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

2017-02-01

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

In vitro folding of inclusion body proteins.

Science.gov (United States)

Rudolph, R; Lilie, H

1996-01-01

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

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

Science.gov (United States)

Young, VyVy N; Rosen, Clark A

2011-12-01

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

Self-Folding Textiles through Manipulation of Knit Stitch Architecture

Directory of Open Access Journals (Sweden)

Chelsea E. Knittel

2015-12-01

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

An Investigation of 16 PF on 692 Under-graduate Students in Teach ers College%692名高等师范生毕业前16PF测评报告

Institute of Scientific and Technical Information of China (English)

樊晓光

2002-01-01

Objective:To study the personality trait an d mental health status o f Teachers College undergraduates. Methods: 692 undergradu ates of Teachers Colle ge were assessed on the Cattell's 16 Personality Factors Questionnaire (16PF). R esults: ①The total score on mental health for Teachers College Gradu ates was ab ove the average score of 22.②Female graduates had higher scores on intelligence , persistence, and gregariousness but they also scored higher on acting impetuou sly and timidity.③ Undergraduates from the Arts stream scored higher on high-se nsitivity and high-doubtness, whereas those in the science stream showed higher scores on mood stability and comprehensive mental health. Conclusion: Psychologi cal health education should consider sex differences and personality characteris tics of arts and science students.

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...

Hierarchical Diagnosis of Vocal Fold Disorders

Science.gov (United States)

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

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

Vascular lesions of the vocal fold.

Science.gov (United States)

Gökcan, Kürşat Mustafa; Dursun, Gürsel

2009-04-01

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

The effect of surface electrical stimulation on vocal fold position.

Science.gov (United States)

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

2008-01-01

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

Experimental investigation of protein folding and misfolding.

Science.gov (United States)

Dobson, Christopher M

2004-09-01

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

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

Science.gov (United States)

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

2011-12-01

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

A case of successfully cured carcinoma of the true vocal folds in the larynx

International Nuclear Information System (INIS)

Shivarov, G.; Tomov, D.

2017-01-01

Objective and subject of the study: Laryngeal carcinoma is a socially significant malignancy in our country as well. Between 1981 and 2010, standardized morbidity (global standard) of 100,000 in Bulgaria increased in men from 6.4 to 9.1, and in women - from 0.3 to 0.7. Recently, a number of reports were published, showing that timely individualized treatment leads to definitive curing of patients with this disease. Methods used: A 37 years old man was hospitalized with a complaint of dysphonia persisting despite conservative treatment for two months. Results: Objectively thickened vocal folds were observed. In this case, the left one was uneven, bruised and with unrestricted mobility. The histological examination of the biopsy material shows moderately differentiated spinocellular carcinoma in the left and squamous papilloma T1 No Mx - in the right fold. A planned hemylarringectomy was performed. Intraoperatively, a susceptible stretch in the right vocal fold was detected, proved in two weeks to be squamous cell carcinoma. A lower tracheotomy was performed, followed by telangatherapy alone. The four-year follow-up indicates a favorable course of the disease and a lack of relapse. Conclusion: The combination of surgical intervention with telegamma therapy in cases of isolated carcinoma of the true vocal folds in the larynx can be applied to strictly selected patients in order to achieve optimal therapeutic outcomes. [bg

Force generation by titin folding.

Science.gov (United States)

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

2017-07-01

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

Multicolor photoluminescence in ITQ-16 zeolite film

KAUST Repository

Chen, Yanli

2016-09-07

Exploring the native defects of zeolites is highly important for understanding the properties of zeolites, such as catalysis and optics. Here, ITQ-16 films were prepared via the secondary growth method in the presence of Ge atoms. Various intrinsic defects of ITQ-16 films were fully studied through photoluminescence and FTIR characterizations. It was found that both the as-synthesized and calcined ITQ-16 films displayed multicolor photoluminescence including ultraviolet, blue, green and red emissions by exciting upon appropriate wavelengths. The results indicate that Si―OH and non-bridging oxygen hole centers(NBOHCs) are responsible for the origin of green and red emissions at 540―800 nm, while according to a variety of emission bands of calcined ITQ-16 film, blue emission bands at around 446 and 462 nm are attributed to peroxy free radicals(≡SiO2), ultraviolet emissions ranging from 250 nm to 450 nm are suggested originating from a singlet-to-triplet transition of two-fold-coordinated Si and Ge, respectively. © 2016, Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH.

Structure of a Trypanosoma brucei α/β-hydrolase fold protein with unknown function

International Nuclear Information System (INIS)

Merritt, Ethan A.; Holmes, Margaret; Buckner, Frederick S.; Van Voorhis, Wesley C.; Quartly, Erin; Phizicky, Eric M.; Lauricella, Angela; Luft, Joseph; DeTitta, George; Neely, Helen; Zucker, Frank; Hol, Wim G. J.

2008-01-01

T. brucei gene Tb10.6k15.0140 codes for an α/β-hydrolase fold protein of unknown function. The 2.2 Å crystal structure shows that members of this sequence family retain a conserved Ser residue at the expected site of a catalytic nucleophile, but that trypanosomatid sequences lack structural homologs for the other expected residues of the catalytic triad. The structure of a structural genomics target protein, Tbru020260AAA from Trypanosoma brucei, has been determined to a resolution of 2.2 Å using multiple-wavelength anomalous diffraction at the Se K edge. This protein belongs to Pfam sequence family PF08538 and is only distantly related to previously studied members of the α/β-hydrolase fold family. Structural superposition onto representative α/β-hydrolase fold proteins of known function indicates that a possible catalytic nucleophile, Ser116 in the T. brucei protein, lies at the expected location. However, the present structure and by extension the other trypanosomatid members of this sequence family have neither sequence nor structural similarity at the location of other active-site residues typical for proteins with this fold. Together with the presence of an additional domain between strands β6 and β7 that is conserved in trypanosomatid genomes, this suggests that the function of these homologs has diverged from other members of the fold family

A novel trivalent HPV 16/18/58 vaccine with anti-HPV 16 and 18 neutralizing antibody responses comparable to those induced by the Gardasil quadrivalent vaccine in rhesus macaque model

Directory of Open Access Journals (Sweden)

Fei Yin

2017-06-01

Full Text Available Persistent infection with human papillomavirus (HPV is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV produced in Escherichia coli (E.coli, with Gardasil quadrivalent vaccine (4vHPV, Merck & Co. as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively, and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA and Enzyme-Linked Immunosorbent Assay (ELISA. Strong immune responses against HPV 16/18/58 were successfully elicited, and dosage-dependence was observed, with likely occurrence of immune interference between different L1-VLP antigens. HPV 16/18 specific neutralizing antibody (nAb and total immunoglobulin G (IgG antibody responses in rhesus macaques receiving 3vHPV at the three dosages tested were generally non-inferior to those observed in rhesus macaques receiving 4vHPV throughout the study period. Particularly, HPV 18 nAb titers induced by the mid-dosage formulation that contained the same amounts of HPV 16/18 L1-VLPs as Gardasil 4vHPV were between 7.3 to 12.7-fold higher compared to the positive control arm from weeks 24–64. The durability of antibody responses specific to HPV 16/18 elicited by 3vHPV vaccines was also shown to be non-inferior to that associated with Gardasil 4vHPV. Keywords: Human papillomavirus, HPV 16/18/58, GMTs, Trivalent, Immunogenicity

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

Science.gov (United States)

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

2017-11-01

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

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).

Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells.

Science.gov (United States)

Slovak, M L; Hoeltge, G A; Ganapathi, R

1986-08-01

B16-BL6 murine melanoma cells were selected for cytogenetic evaluation during the stepwise development of increasing resistance in vitro to the antitumor antibiotic, doxorubicin (DOX). Karyotypic studies demonstrated extensive heteroploidy with both numerical and structural abnormalities which were not present in the parental DOX-sensitive B16-BL6 cells. Trypsin-Giemsa banding revealed the presence of several marker chromosomes containing abnormally banding regions (ABRs) in the 44-fold B16-BL6 DOX-resistant subline. These ABRs appeared to be more homogeneously staining at the higher DOX concentrations. Length measurements (ABR index) in seven banded metaphases indicated a direct correlation with increasing DOX concentration. When the DOX-resistant cells were grown in drug-free medium for 1 yr, the drug-resistant phenotype gradually declined in parallel with the level of resistance and the ABR index. DOX-induced cytogenetic damage examined by sister chromatid exchange methodology in parental B16-BL6 cells indicated a linear sister chromatid exchange:DOX dose-response relationship. However, after continuous treatment of parental B16-BL6 cells with DOX (0.01 microgram/ml) for 30 days, sister chromatid exchange scores were found to return to base-line values. The B16-BL6 resistant cells demonstrated a cross-resistant phenotype with N-trifluoroacetyladriamycin-14-valerate, actinomycin D, and the Vinca alkaloids but not with 1-beta-D-arabinofuranosylcytosine. The results suggest that ABR-containing chromosomes in DOX-resistant sublines may represent cytogenetic alterations of specific amplified genes involved in the expression of DOX resistance. Further studies are required to identify and define the possible gene products and to correlate their relationship to the cytotoxic action of doxorubicin.

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...

Streptococcus pneumonia YlxR at 1.35 Å shows a putative new fold

OpenAIRE

Osipiuk, Jerzy; Górnicki, Piotr; Maj, Luke; Dementieva, Irina; Laskowski, Roman; Joachimiak, Andrzej

2001-01-01

The structure of the YlxR protein of unknown function from Streptococcus pneumonia was determined to 1.35 Å. YlxR is expressed from the nusA/infB operon in bacteria and belongs to a small protein family (COG2740) that shares a conserved sequence motif GRGA(Y/W). The family shows no significant amino-acid sequence similarity with other proteins. Three-wavelength diffraction MAD data were collected to 1.7 Å from orthorhombic crystals using synchrotron radiation and the structure was determined ...

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

Form Exploration of Folded Plate Timber Structures based on Performance Criteria

DEFF Research Database (Denmark)

Falk, Andreas; Buelow, Peter Von

2011-01-01

This paper presents an explorative study on applications of cross-laminated timber (CLT) elements in shell structures. Previous studies of plate tensegrity, folded plate roofs interacting with stabilising steel-based systems and studies inspired by origami show a widening range of possibilities...... to develop timber-based shells. Steadily rising interest in rationality during pre-fabrication, transport and on-site construction in contemporary industrialised production increases the competitiveness of CLT-based elements and systems and the architectural applications are getting more common and more...... experimental. Folded plate structures which are the focus of this paper present several issues of structural importance – potential mechanisms, subdivision of surfaces etc. – and the hereby presented study aims at exploring developed typologies, using computer tools for developed optimisation procedures...

Oxygen vacancy defects in Ta{sub 2}O{sub 5} showing long-range atomic re-arrangements

Energy Technology Data Exchange (ETDEWEB)

Guo, Yuzheng; Robertson, John [Engineering Department, Cambridge University, Cambridge CB2 1PZ (United Kingdom)

2014-03-17

The structure, formation energy, and energy levels of the various oxygen vacancies in Ta{sub 2}O{sub 5} have been calculated using the λ phase model. The intra-layer vacancies give rise to unusual, long-range bonding rearrangements, which are different for each defect charge state. The 2-fold coordinated intra-layer vacancy is the lowest cost vacancy and forms a deep level 1.5 eV below the conduction band edge. The 3-fold intra-layer vacancy and the 2-fold inter-layer vacancy are higher cost defects, and form shallower levels. The unusual bonding rearrangements lead to low oxygen migration barriers, which are useful for resistive random access memory applications.

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.

Molecular and biochemical characterizations of three fructose-1,6-bisphosphate aldolases from Clonorchis sinensis.

Science.gov (United States)

Li, Shan; Bian, Meng; Wang, Xiaoyun; Chen, Xueqing; Xie, Zhizhi; Sun, Hengchang; Jia, Feifei; Liang, Pei; Zhou, Chenhui; He, Lei; Mao, Qiang; Huang, Bo; Liang, Chi; Wu, Zhongdao; Li, Xuerong; Xu, Jin; Huang, Yan; Yu, Xinbing

2014-01-01

Fructose-1,6-bisphosphate aldolase (FbA) is a ubiquitous enzyme in glycolysis. In the present study, we screened out three distinct genes encoding FbA isozymes (CsFbAs, CsFbA-1/2/3) from Clonorchis sinensis (C. sinensis) and characterized their sequences and structures profiles as well as biochemical properties. The amino acid sequences of CsFbAs shared homology with those of Class I FbAs from other species. The putative quaternary structures revealed that CsFbA-2 and CsFbA-3 were tetramers, while CsFbA-1 was dimer. Recombinant CsFbA-2 and CsFbA-3 (rCsFbA-2/3) were confirmed to be Class I FbAs for their stable enzymatic activities in the presence of EDTA or metal ions. However, recombinant CsFbA-1 (rCsFbA-1) did not show the catalytic activity, which might be due to the inappropriate fold and interaction between its subunits. Both rCsFbA-2 and rCsFbA-3 showed similar enzymatic properties such as optimal temperatures and broad pH ranges that similar to human FbA isozymes. They showed relatively higher affinities for fructose-1,6-bisphosphate (FBP) than fructose-1-phosphate (F-1-P). Their kcat ratios of FBP to F-1-P were in accordance with those of human FbA-A or C. In addition, CsFbAs were differentially transcribed in the developmental stages of C. sinensis, suggesting their essential roles throughout the life stages. Extensive distribution of CsFbAs in adult worms indicated that ubiquitous activities of CsFbAs took place in these organs. Collectively, these results suggested that long-term parasitic environment might adapt these isozymes similar to host FbAs for metabolic requirement. Our study will provide new insight into CsFbAs in the glycometabolism of C. sinensis and relationship between the host and the parasite. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Different secondary structure elements as scaffolds for protein folding transition states of two homologous four-helix bundles.

Science.gov (United States)

Teilum, Kaare; Thormann, Thorsten; Caterer, Nigel R; Poulsen, Heidi I; Jensen, Peter H; Knudsen, Jens; Kragelund, Birthe B; Poulsen, Flemming M

2005-04-01

Comparison of the folding processes for homologue proteins can provide valuable information about details in the interactions leading to the formation of the folding transition state. Here the folding kinetics of 18 variants of yACBP and 3 variants of bACBP have been studied by Phi-value analysis. In combination with Phi-values from previous work, detailed insight into the transition states for folding of both yACBP and bACBP has been obtained. Of the 16 sequence positions that have been studied in both yACBP and bACBP, 5 (V12, I/L27, Y73, V77, and L80) have high Phi-values and appear to be important for the transition state formation in both homologues. Y31, A34, and A69 have high Phi-values only in yACBP, while F5, A9, and I74 have high Phi-values only in bACBP. Thus, additional interactions between helices A2 and A4 appear to be important for the transition state of yACBP, whereas additional interactions between helices A1 and A4 appear to be important for the transition state of bACBP. To examine whether these differences could be assigned to different packing of the residues in the native state, a solution structure of yACBP was determined by NMR. Small changes in the packing of the hydrophobic side-chains, which strengthen the interactions between helices A2 and A4, are observed in yACBP relative to bACBP. It is suggested that different structure elements serve as scaffolds for the folding of the 2 ACBP homologues. (c) 2005 Wiley-Liss, Inc.

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

Science.gov (United States)

Cao, Yalong

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

Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding.

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Sandikci, Arzu; Gloge, Felix; Martinez, Michael; Mayer, Matthias P; Wade, Rebecca; Bukau, Bernd; Kramer, Günter

2013-07-01

Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates with ribosomes through a charged loop that is crucial for nascent-chain processing and cell viability. MAP competes with peptide deformylase (PDF), the first enzyme to act on nascent chains, for binding sites at the ribosomal tunnel exit. PDF has extremely fast association and dissociation kinetics, which allows it to frequently sample ribosomes and ensure the processing of nascent chains after their emergence. Premature recruitment of the chaperone trigger factor, or polypeptide folding, negatively affect processing efficiency. Thus, the fast ribosome association kinetics of PDF and MAP are crucial for the temporal separation of nascent-chain processing from later maturation events, including chaperone recruitment and folding.

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.