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Sample records for modulates folding mechanism

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

    Science.gov (United States)

    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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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).

  7. Stretching and folding mechanism in foams

    International Nuclear Information System (INIS)

    Tufaile, Alberto; Pedrosa Biscaia Tufaile, Adriana

    2008-01-01

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

  8. Stretching and folding mechanism in foams

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-10-13

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

  9. 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

  10. Intradomain Confinement of Disulfides in the Folding of Two Consecutive Modules of the LDL Receptor.

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    Juan Martínez-Oliván

    Full Text Available The LDL receptor internalizes circulating LDL and VLDL particles for degradation. Its extracellular binding domain contains ten (seven LA and three EGF cysteine-rich modules, each bearing three disulfide bonds. Despite the enormous number of disulfide combinations possible, LDLR oxidative folding leads to a single native species with 30 unique intradomain disulfides. Previous folding studies of the LDLR have shown that non native disulfides are initially formed that lead to compact species. Accordingly, the folding of the LDLR has been described as a "coordinated nonvectorial" reaction, and it has been proposed that early compaction funnels the reaction toward the native structure. Here we analyze the oxidative folding of LA4 and LA5, the modules critical for ApoE binding, isolated and in the LA45 tandem. Compared to LA5, LA4 folding is slow and inefficient, resembling that of LA5 disease-linked mutants. Without Ca++, it leads to a mixture of many two-disulfide scrambled species and, with Ca++, to the native form plus two three-disulfide intermediates. The folding of the LA45 tandem seems to recapitulate that of the individual repeats. Importantly, although the folding of the LA45 tandem takes place through formation of scrambled isomers, no interdomain disulfides are detected, i.e. the two adjacent modules fold independently without the assistance of interdomain covalent interactions. Reduction of incredibly large disulfide combinatorial spaces, such as that in the LDLR, by intradomain confinement of disulfide bond formation might be also essential for the efficient folding of other homologous disulfide-rich receptors.

  11. 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.

  12. 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.

  13. Periodic and stochastic thermal modulation of protein folding kinetics.

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    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.

  14. Folded membrane dialyzer with mechanically sealed edges

    Energy Technology Data Exchange (ETDEWEB)

    Markley, F.W.

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

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

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    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).

  16. Strain modulations as a mechanism to reduce stress relaxation in laryngeal tissues.

    Science.gov (United States)

    Hunter, Eric J; Siegmund, Thomas; Chan, Roger W

    2014-01-01

    Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so), cyclic and faster posturing often found in speech tasks or vocal embellishment (1-10 Hz), and shear strain associated with vocal fold vibration during phonation (100 Hz and higher). Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxation and recovery. In the current study, a large strain time-dependent constitutive model of human vocal fold tissue is used to investigate effects of phonatory posturing cyclic strain in the range of 1 Hz to 10 Hz. Tissue data for two subjects are considered and used to contrast the potential effects of age. Results suggest that modulation frequency and extent (amplitude), as well as the amount of vocal fold overall strain, all affect the change in stress relaxation with modulation added. Generally, the vocal fold cover reduces the rate of relaxation while the opposite is true for the vocal ligament. Further, higher modulation frequencies appear to reduce the rate of relaxation, primarily affecting the ligament. The potential benefits of cyclic strain, often found in vibrato (around 5 Hz modulation) and intonational inflection, are discussed in terms of vocal effort and vocal pitch maintenance. Additionally, elderly tissue appears to not exhibit these benefits to modulation. The exacerbating effect such modulations may have on certain voice disorders, such as muscle tension dysphonia, are explored.

  17. Strain modulations as a mechanism to reduce stress relaxation in laryngeal tissues.

    Directory of Open Access Journals (Sweden)

    Eric J Hunter

    Full Text Available Vocal fold tissues in animal and human species undergo deformation processes at several types of loading rates: a slow strain involved in vocal fold posturing (on the order of 1 Hz or so, cyclic and faster posturing often found in speech tasks or vocal embellishment (1-10 Hz, and shear strain associated with vocal fold vibration during phonation (100 Hz and higher. Relevant to these deformation patterns are the viscous properties of laryngeal tissues, which exhibit non-linear stress relaxation and recovery. In the current study, a large strain time-dependent constitutive model of human vocal fold tissue is used to investigate effects of phonatory posturing cyclic strain in the range of 1 Hz to 10 Hz. Tissue data for two subjects are considered and used to contrast the potential effects of age. Results suggest that modulation frequency and extent (amplitude, as well as the amount of vocal fold overall strain, all affect the change in stress relaxation with modulation added. Generally, the vocal fold cover reduces the rate of relaxation while the opposite is true for the vocal ligament. Further, higher modulation frequencies appear to reduce the rate of relaxation, primarily affecting the ligament. The potential benefits of cyclic strain, often found in vibrato (around 5 Hz modulation and intonational inflection, are discussed in terms of vocal effort and vocal pitch maintenance. Additionally, elderly tissue appears to not exhibit these benefits to modulation. The exacerbating effect such modulations may have on certain voice disorders, such as muscle tension dysphonia, are explored.

  18. Co-Transcriptional Folding and Regulation Mechanisms of Riboswitches

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    Sha Gong

    2017-07-01

    Full Text Available Riboswitches are genetic control elements within non-coding regions of mRNA. These self-regulatory elements have been found to sense a range of small metabolites, ions, and other physical signals to exert regulatory control of transcription, translation, and splicing. To date, more than a dozen riboswitch classes have been characterized that vary widely in size and secondary structure. Extensive experiments and theoretical studies have made great strides in understanding the general structures, genetic mechanisms, and regulatory activities of individual riboswitches. As the ligand-dependent co-transcriptional folding and unfolding dynamics of riboswitches are the key determinant of gene expression, it is important to investigate the thermodynamics and kinetics of riboswitches both in the presence and absence of metabolites under the transcription. This review will provide a brief summary of the studies about the regulation mechanisms of the pbuE, SMK, yitJ, and metF riboswitches based on the ligand-dependent co-transcriptional folding of the riboswitches.

  19. Protein solubility and folding enhancement by interaction with RNA.

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    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.

  20. From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.

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    Farinha, Carlos M; Canato, Sara

    2017-01-01

    CFTR biogenesis starts with its co-translational insertion into the membrane of endoplasmic reticulum and folding of the cytosolic domains, towards the acquisition of a fully folded compact native structure. Efficiency of this process is assessed by the ER quality control system that allows the exit of folded proteins but targets unfolded/misfolded CFTR to degradation. If allowed to leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi compartments to be delivered to the plasma membrane where it functions as a cAMP- and phosphorylation-regulated chloride/bicarbonate channel. CFTR residence at the membrane is a balance of membrane delivery, endocytosis, and recycling. Several adaptors, motor, and scaffold proteins contribute to the regulation of CFTR stability and are involved in continuously assessing its structure through peripheral quality control systems. Regulation of CFTR biogenesis and traffic (and its dysregulation by mutations, such as the most common F508del) determine its overall activity and thus contribute to the fine modulation of chloride secretion and hydration of epithelial surfaces. This review covers old and recent knowledge on CFTR folding and trafficking from its synthesis to the regulation of its stability at the plasma membrane and highlights how several of these steps can be modulated to promote the rescue of mutant CFTR.

  1. 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.

  2. Neuromuscular compensation mechanisms in vocal fold paralysis and paresis.

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    Dewan, Karuna; Vahabzadeh-Hagh, Andrew; Soofer, Donna; Chhetri, Dinesh K

    2017-07-01

    Vocal fold paresis and paralysis are common conditions. Treatment options include augmentation laryngoplasty and voice therapy. The optimal management for this condition is unclear. The objective of this study was to assess possible neuromuscular compensation mechanisms that could potentially be used in the treatment of vocal fold paresis and paralysis. In vivo canine model. In an in vivo canine model, we examined three conditions: 1) unilateral right recurrent laryngeal nerve (RLN) paresis and paralysis, 2) unilateral superior laryngeal nerve (SLN) paralysis, and 3) unilateral vagal nerve paresis and paralysis. Phonatory acoustics and aerodynamics were measured in each of these conditions. Effective compensation was defined as improved acoustic and aerodynamic profile. The most effective compensation for all conditions was increasing RLN activation and decreasing glottal gap. Increasing RLN activation increased the percentage of possible phonatory conditions that achieved phonation onset. SLN activation generally led to decreased number of total phonation onset conditions within each category. Differential effects of SLN (cricothyroid [CT] muscle) activation were seen. Ipsilateral SLN activation could compensate for RLN paralysis; normal CT compensated well in unilateral SLN paralysis; and in vagal paresis/paralysis, contralateral SLN and RLN displayed antagonistic relationships. Methods to improve glottal closure should be the primary treatment for large glottal gaps. Neuromuscular compensation is possible for paresis. This study provides insights into possible compensatory mechanisms in vocal fold paresis and paralysis. NA Laryngoscope, 127:1633-1638, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Mechanical versus kinematical shortening reconstructions of the Zagros High Folded Zone (Kurdistan region of Iraq)

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    Frehner, Marcel; Reif, Daniel; Grasemann, Bernhard

    2012-06-01

    This paper compares kinematical and mechanical techniques for the palinspastic reconstruction of folded cross sections in collision orogens. The studied area and the reconstructed NE-SW trending, 55.5 km long cross section is located in the High Folded Zone of the Zagros fold-and-thrust belt in the Kurdistan region of Iraq. The present-day geometry of the cross section has been constructed from field as well as remote sensing data. In a first step, the structures and the stratigraphy are simplified and summarized in eight units trying to identify the main geometric and mechanical parameters. In a second step, the shortening is kinematically estimated using the dip domain method to 11%-15%. Then the same cross section is used in a numerical finite element model to perform dynamical unfolding simulations taking various rheological parameters into account. The main factor allowing for an efficient dynamic unfolding is the presence of interfacial slip conditions between the mechanically strong units. Other factors, such as Newtonian versus power law viscous rheology or the presence of a basement, affect the numerical simulations much less strongly. If interfacial slip is accounted for, fold amplitudes are reduced efficiently during the dynamical unfolding simulations, while welded layer interfaces lead to unrealistic shortening estimates. It is suggested that interfacial slip and decoupling of the deformation along detachment horizons is an important mechanical parameter that controlled the folding processes in the Zagros High Folded Zone.

  4. Toward modular biological models: defining analog modules based on referent physiological mechanisms.

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    Petersen, Brenden K; Ropella, Glen E P; Hunt, C Anthony

    2014-08-16

    Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project's requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale. This report demonstrates

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

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    Benesh, Nathan Philip

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

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

    Science.gov (United States)

    Peraza Hernandez, Edwin Alexander

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

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

    Science.gov (United States)

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

    2018-06-01

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

  8. Effects of a mutation on the folding mechanism of a β-hairpin

    NARCIS (Netherlands)

    Juraszek, J.; Bolhuis, P.G.

    2009-01-01

    The folding mechanism of a protein is determined by its primary sequence. Yet, how the mechanism is changed by a mutation is still poorly understood, even for basic secondary structures such as β-hairpins. We perform an extensive simulation study of the effects of mutating the GB1 β-hairpin into

  9. 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.

  10. 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.

  11. 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.

  12. Study of wire electrical discharge machined folded-up corner cube retroreflector with a tunable cantilever beam

    Science.gov (United States)

    Chen, Yu-Fan; Wang, Yen-Hung; Tsai, Jui-che

    2018-03-01

    This work has developed an approach to construct a corner cube retroreflector (CCR). A two-dimensional cutout pattern is first fabricated with wire electrical discharge machining process. It is then folded up into a three-dimensional CCR suspended on a cantilever beam. The folded-up CCR may be driven through external actuators for optical modulation; it can also mechanically respond to perturbation, acceleration, etc., to function as a sensor. Mechanical (static and dynamic modeling) and optical (ray tracing) analyses are also performed.

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

    Science.gov (United States)

    Strickland, Mallory L; Boylan, Helen M

    2010-07-01

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

  14. Construction and characterization of a novel vocal fold bioreactor.

    Science.gov (United States)

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

    2014-08-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  16. 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.

  17. Fracture mechanics in new designed power module under thermo-mechanical loads

    Directory of Open Access Journals (Sweden)

    Durand Camille

    2014-06-01

    Full Text Available Thermo-mechanically induced failure is a major reliability issue in the microelectronic industry. On this account, a new type of Assembly Interconnected Technology used to connect MOSFETs in power modules has been developed. The reliability is increased by using a copper clip soldered on the top side of the chip, avoiding the use of aluminium wire bonds, often responsible for the failure of the device. Thus the new designed MOSFET package does not follow the same failure mechanisms as standard modules. Thermal and power cycling tests were performed on these new packages and resulting failures were analyzed. Thermo-mechanical simulations including cracks in the aluminium metallization and intermetallics (IMC were performed using Finite Element Analysis in order to better understand crack propagation and module behaviour.

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

    Science.gov (United States)

    Gray, S. L.

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

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

    Science.gov (United States)

    Sun, Jian; Zhang, Qing; Schlick, Tamar

    2005-06-07

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

  20. Isolated and modulated effects of topology and material type on the mechanical properties of additively manufactured porous biomaterials.

    Science.gov (United States)

    Hedayati, R; Ahmadi, S M; Lietaert, K; Pouran, B; Li, Y; Weinans, H; Rans, C D; Zadpoor, A A

    2018-03-01

    In this study, we tried to quantify the isolated and modulated effects of topological design and material type on the mechanical properties of AM porous biomaterials. Towards this aim, we assembled a large dataset comprising the mechanical properties of AM porous biomaterials with different topological designs (i.e. different unit cell types and relative densities) and material types. Porous structures were additively manufactured from Co-Cr using a selective laser melting (SLM) machine and tested under quasi-static compression. The normalized mechanical properties obtained from those structures were compared with mechanical properties available from our previous studies for porous structures made from Ti-6Al-4V and pure titanium as well as with analytical solutions. The normalized values of elastic modulus and yield stress were found to be relatively close to each other as well as in agreement with analytical solutions regardless of material type. However, the material type was found to systematically affect the mechanical properties of AM porous biomaterials in general and the post-elastic/post-yield range (plateau stress and energy absorption capacity) in particular. To put this in perspective, topological design could cause up to 10-fold difference in the mechanical properties of AM porous biomaterials while up to 2-fold difference was observed as a consequence of changing the material type. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Interaction of ATP with acid-denatured cytochrome c via coupled folding-binding mechanism

    International Nuclear Information System (INIS)

    Ahluwalia, Unnati; Deep, Shashank

    2012-01-01

    Highlights: ► Interaction between ATP and cyt c takes place via coupled binding–folding mechanism. ► Binding of ATP to cyt c is endothermic. ► GTP and CTP induce similar level of helicity in acid-denatured cyt c as with ATP. ► Compactness induced by ATP is far greater than ADP or AMP. - Abstract: The non-native conformations of the cytochrome c (cyt c) are believed to play key roles in a number of physiological processes. Nucleotides are supposed to act as allosteric effectors in these processes by regulating structural transitions among different conformations of cyt c. To understand the interaction between acid denatured cytochrome c and nucleotides, spectroscopic and calorimetric techniques were utilized to observe the structural features of the induced conformation and the energetics of interaction of acid denatured cyt c with different nucleotides. Structure induction in the acid denatured cyt c was observed on the addition of the ∼1 mM nucleotide tri-phosphates (ATP/GTP/CTP) at 25 °C, however, not in the presence of 1 mM nucleotide mono and diphosphates. ATP-bound cyt c at pH 2.0 is likely to have a conformation that has intact α-helical domain. However, Met80-Fe(III) axial bond is still ruptured. Observed thermodynamics reflect interaction between nucleotide and cyt c via coupled binding–folding mechanism. DSC data suggest the preferential binding of the ATP to the folded conformation with respect to the acid denatured cyt c. ITC data indicate that the exothermic folding of cyt c was accompanied by endothermic binding of ATP to cyt c.

  2. Field failure mechanisms for photovoltaic modules

    Science.gov (United States)

    Dumas, L. N.; Shumka, A.

    1981-01-01

    Beginning in 1976, Department of Energy field centers have installed and monitored a number of field tests and application experiments using current state-of-the-art photovoltaic modules. On-site observations of module physical and electrical degradation, together with in-depth laboratory analysis of failed modules, permits an overall assessment of the nature and causes of early field failures. Data on failure rates are presented, and key failure mechanisms are analyzed with respect to origin, effect, and prospects for correction. It is concluded that all failure modes identified to date are avoidable or controllable through sound design and production practices.

  3. Differential conformational modulations of MreB folding upon interactions with GroEL/ES and TRiC chaperonin components

    Science.gov (United States)

    Moparthi, Satish Babu; Carlsson, Uno; Vincentelli, Renaud; Jonsson, Bengt-Harald; Hammarström, Per; Wenger, Jérôme

    2016-01-01

    Here, we study and compare the mechanisms of action of the GroEL/GroES and the TRiC chaperonin systems on MreB client protein variants extracted from E. coli. MreB is a homologue to actin in prokaryotes. Single-molecule fluorescence correlation spectroscopy (FCS) and time-resolved fluorescence polarization anisotropy report the binding interaction of folding MreB with GroEL, GroES and TRiC. Fluorescence resonance energy transfer (FRET) measurements on MreB variants quantified molecular distance changes occurring during conformational rearrangements within folding MreB bound to chaperonins. We observed that the MreB structure is rearranged by a binding-induced expansion mechanism in TRiC, GroEL and GroES. These results are quantitatively comparable to the structural rearrangements found during the interaction of β-actin with GroEL and TRiC, indicating that the mechanism of chaperonins is conserved during evolution. The chaperonin-bound MreB is also significantly compacted after addition of AMP-PNP for both the GroEL/ES and TRiC systems. Most importantly, our results showed that GroES may act as an unfoldase by inducing a dramatic initial expansion of MreB (even more than for GroEL) implicating a role for MreB folding, allowing us to suggest a delivery mechanism for GroES to GroEL in prokaryotes. PMID:27328749

  4. 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

  5. Fabrication and characterization of self-folding thermoplastic sheets using unbalanced thermal shrinkage.

    Science.gov (United States)

    Danielson, Christian; Mehrnezhad, Ali; YekrangSafakar, Ashkan; Park, Kidong

    2017-06-14

    Self-folding or micro-origami technologies are actively investigated as a novel manufacturing process to fabricate three-dimensional macro/micro-structures. In this paper, we present a simple process to produce a self-folding structure with a biaxially oriented polystyrene sheet (BOPS) or Shrinky Dinks. A BOPS sheet is known to shrink to one-third of its original size in plane, when it is heated above 160 °C. A grid pattern is engraved on one side of the BOPS film with a laser engraver to decrease the thermal shrinkage of the engraved side. The thermal shrinkage of the non-engraved side remains the same and this unbalanced thermal shrinkage causes folding of the structure as the structure shrinks at high temperature. We investigated the self-folding mechanism and characterized how the grid geometry, the grid size, and the power of the laser engraver affect the bending curvature. The developed fabrication process to locally modulate thermomechanical properties of the material by engraving the grid pattern and the demonstrated design methodology to harness the unbalanced thermal shrinkage can be applied to develop complicated self-folding macro/micro structures.

  6. Design of thermoelectric modules for both mechanical reliability and performance using FE simulation

    DEFF Research Database (Denmark)

    Sarhadi, Ali; Bjørk, Rasmus; Pryds, Nini

    for these two objectives. The current study deals with FE simulation of the TE modules to optimize their geometrical dimension in terms of mechanical reliability and performance. First, FE simulation of a TE module consisting of bismuth telluride alloys is carried out and the induced thermal stresses, output......, the geometrical dimensions of the TE elements for both mechanical reliability and performance are optimized to obtain a compromise design. The present work provides a basis for optimizing the TE modules in terms of their life time and performance.......Thermo-mechanical modeling of the TE modules provides an efficient tool for assessing the mechanical strength of the modules against the induced thermal stresses and subsequently optimizing them in terms of the mechanical reliability. However, the design of TE modules in terms of mechanical...

  7. How Robust Is the Mechanism of Folding-Upon-Binding for an Intrinsically Disordered Protein?

    Science.gov (United States)

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

    2018-04-24

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

  8. Electrothermal Frequency Modulated Resonator for Mechanical Memory

    KAUST Repository

    Hafiz, Md Abdullah Al; Kosuru, Lakshmoji; Younis, Mohammad I.

    2016-01-01

    In this paper, we experimentally demonstrate a mechanical memory device based on the nonlinear dynamics of an electrostatically actuated microelectromechanical resonator utilizing an electrothermal frequency modulation scheme. The microstructure

  9. 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.

  10. 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.

  11. Thermo-Mechanical tests for the CLIC two-beam module study

    CERN Document Server

    Xydou, A; Riddone, G; Daskalaki, E

    2014-01-01

    The luminosity goal of CLIC requires micron level precision with respect to the alignment of the components on its two-meter long modules, composing the two main linacs. The power dissipated inside the module components introduces mechanical deformations affecting their alignment and therefore the resulting machine performance. Several two-beam prototype modules must be assembled to extensively measure their thermo-mechanical behavior under different operation modes. In parallel, the real environmental conditions present in the CLIC tunnel should be studied. The air conditioning and ventilation system providing specified air temperature and flow has been installed in the dedicated laboratory. The power dissipation occurring in the modules is being reproduced by the electrical heaters inserted inside the RF structure mock-ups and the quadrupoles. The efficiency of the cooling systems is being verified and the alignment of module components is monitored. The measurement results will be compared to finite elemen...

  12. Modulation of neuronal dynamic range using two different adaptation mechanisms

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-01-01

    Full Text Available The capability of neurons to discriminate between intensity of external stimulus is measured by its dynamic range. A larger dynamic range indicates a greater probability of neuronal survival. In this study, the potential roles of adaptation mechanisms (ion currents in modulating neuronal dynamic range were numerically investigated. Based on the adaptive exponential integrate-and-fire model, which includes two different adaptation mechanisms, i.e. subthreshold and suprathreshold (spike-triggered adaptation, our results reveal that the two adaptation mechanisms exhibit rather different roles in regulating neuronal dynamic range. Specifically, subthreshold adaptation acts as a negative factor that observably decreases the neuronal dynamic range, while suprathreshold adaptation has little influence on the neuronal dynamic range. Moreover, when stochastic noise was introduced into the adaptation mechanisms, the dynamic range was apparently enhanced, regardless of what state the neuron was in, e.g. adaptive or non-adaptive. Our model results suggested that the neuronal dynamic range can be differentially modulated by different adaptation mechanisms. Additionally, noise was a non-ignorable factor, which could effectively modulate the neuronal dynamic range.

  13. 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.

  14. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-02-01

    The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Brakes. Auto Mechanics Curriculum Guide. Module 6. Instructor's Guide.

    Science.gov (United States)

    Allain, Robert

    This module is the sixth of nine modules in the competency-based Missouri Auto Mechanics Curriculum Guide. Eight units cover: introduction to automotive brake systems; disc and drum brake system components and how they operate; properties of brake fluid and procedures for bleeding the brake system; diagnosing and determining needed repairs on…

  17. 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.

  18. Optimization of the Mechanical and Electrical Performance of a Thermoelectric Module

    DEFF Research Database (Denmark)

    Sarhadi, Ali; Bjørk, Rasmus; Pryds, Nini

    2015-01-01

    Finite element (FE) simulation of a thermoelectric (TE) module was conducted to optimize its geometrical dimensions in terms of mechanical reliability and performance. The TE module consisted of bismuth telluride, nand p-type legs. The geometrical dimensions of the module, i.e. leg length and leg...

  19. Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Wenjun, E-mail: wjzheng@buffalo.edu; Glenn, Paul [Department of Physics, University at Buffalo, Buffalo, New York 14260 (United States)

    2015-01-21

    The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

  20. Impaired folding and subunit assembly as disease mechanism

    DEFF Research Database (Denmark)

    Bross, P; Andresen, B S; Gregersen, N

    1998-01-01

    folding is a common effect of missense mutations occurring in genetic diseases, (ii) increasing the level of available chaperones may augment the level of functional mutant protein in vivo, and (iii) one mutation may have multiple effects. The interplay between the chaperones assisting folding......Rapid progress in DNA technology has entailed the possibility of readily detecting mutations in disease genes. In contrast to this, techniques to characterize the effects of mutations are still very time consuming. It has turned out that many of the mutations detected in disease genes are missense...... mutations. Characterization of the effect of these mutations is particularly important in order to establish that they are disease causing and to estimate their severity. We use the experiences with investigation of medium-chain acyl-CoA dehydrogenase deficiency as an example to illustrate that (i) impaired...

  1. Analyses of the mechanisms of amplitude modulation of aero-acoustic wind turbine sound

    DEFF Research Database (Denmark)

    Fischer, Andreas; Aagaard Madsen, Helge; Kragh, Knud Abildgaard

    2014-01-01

    This paper explores the source mechanism which cause amplitude modulation of the emitted sound of a wind turbine at large distances from the turbine, named as other amplitude modulation. Measurements of the fluctuating surface pressure on a 2.3MW wind turbine showed a considerable variation over...... give further evidence that transient stall is a main mechanism to cause other amplitude modulation. Wind shear was identified as a critical condition to cause angle of attack variations. Dierent control strategies to mitigate other amplitude modulation were proposed....

  2. Recoverable and Programmable Collapse from Folding Pressurized Origami Cellular Solids.

    Science.gov (United States)

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

    2016-09-09

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

  3. Adjustable thermal resistor by reversibly folding a graphene sheet.

    Science.gov (United States)

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

    2016-08-11

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

  4. NoFold: RNA structure clustering without folding or alignment.

    Science.gov (United States)

    Middleton, Sarah A; Kim, Junhyong

    2014-11-01

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

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Yunqiang Bian

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

  8. Mechanical Modeling and Computer Simulation of Protein Folding

    Science.gov (United States)

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

    2014-01-01

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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    David S. Kliger

    2009-04-01

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

  11. 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...

  12. Supersymmetric quantum mechanics method for the Fokker-Planck equation with applications to protein folding dynamics

    Science.gov (United States)

    Polotto, Franciele; Drigo Filho, Elso; Chahine, Jorge; Oliveira, Ronaldo Junio de

    2018-03-01

    This work developed analytical methods to explore the kinetics of the time-dependent probability distributions over thermodynamic free energy profiles of protein folding and compared the results with simulation. The Fokker-Planck equation is mapped onto a Schrödinger-type equation due to the well-known solutions of the latter. Through a semi-analytical description, the supersymmetric quantum mechanics formalism is invoked and the time-dependent probability distributions are obtained with numerical calculations by using the variational method. A coarse-grained structure-based model of the two-state protein Tm CSP was simulated at a Cα level of resolution and the thermodynamics and kinetics were fully characterized. Analytical solutions from non-equilibrium conditions were obtained with the simulated double-well free energy potential and kinetic folding times were calculated. It was found that analytical folding time as a function of temperature agrees, quantitatively, with simulations and experiments from the literature of Tm CSP having the well-known 'U' shape of the Chevron Plots. The simple analytical model developed in this study has a potential to be used by theoreticians and experimentalists willing to explore, quantitatively, rates and the kinetic behavior of their system by informing the thermally activated barrier. The theory developed describes a stochastic process and, therefore, can be applied to a variety of biological as well as condensed-phase two-state systems.

  13. 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

  14. Mechanical and Thermal Characterisation of a TT Half-Module Prototype

    CERN Document Server

    Lehner, F; Pangilinan, M; Siegler, M

    2005-01-01

    This note describes the mechanical effects of thermal cycles on a TT half-module, to demonstrate that the detectors can withstand the expected thermal gradients without damage. The stress transferred by the carbon fiber rails and the ceramic to the silicon sensors was investigated, and the deformation that occurred during these tests was measured by strain gauges that were attached to sensors on a test half-module. In addition, heat transfer through the carbon fiber rails was studied. Furthermore, we present a comparison of different materials proposed to build the carbon fiber rails of the modules.

  15. Neuro-cognitive mechanisms underlying the emotional modulation of word reading

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A novel neural model for emotional modulation of word reading is proposed. This model has four principal hypotheses: the dominant activation region hypothesis, the emotional modulation hypothesis, the attentional level hypothesis, and the interaction hypothesis. Four lines of research were reviewed to provide evidence for these hypotheses: (1) neuro-cognitive studies on the mechanisms of word reading (i.e., neural networks for reading); (2) studies on the influence of words' emotional valence on word reading; (3) studies of the effect of attention on word reading; and (4) studies on emotional modulation of word reading under different attentional levels.

  16. 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

  17. 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.

  18. Light-activated control of protein channel assembly mediated by membrane mechanics

    Science.gov (United States)

    Miller, David M.; Findlay, Heather E.; Ces, Oscar; Templer, Richard H.; Booth, Paula J.

    2016-12-01

    Photochemical processes provide versatile triggers of chemical reactions. Here, we use a photoactivated lipid switch to modulate the folding and assembly of a protein channel within a model biological membrane. In contrast to the information rich field of water-soluble protein folding, there is only a limited understanding of the assembly of proteins that are integral to biological membranes. It is however possible to exploit the foreboding hydrophobic lipid environment and control membrane protein folding via lipid bilayer mechanics. Mechanical properties such as lipid chain lateral pressure influence the insertion and folding of proteins in membranes, with different stages of folding having contrasting sensitivities to the bilayer properties. Studies to date have relied on altering bilayer properties through lipid compositional changes made at equilibrium, and thus can only be made before or after folding. We show that light-activation of photoisomerisable di-(5-[[4-(4-butylphenyl)azo]phenoxy]pentyl)phosphate (4-Azo-5P) lipids influences the folding and assembly of the pentameric bacterial mechanosensitive channel MscL. The use of a photochemical reaction enables the bilayer properties to be altered during folding, which is unprecedented. This mechanical manipulation during folding, allows for optimisation of different stages of the component insertion, folding and assembly steps within the same lipid system. The photochemical approach offers the potential to control channel assembly when generating synthetic devices that exploit the mechanosensitive protein as a nanovalve.

  19. Folding to Curved Surfaces: A Generalized Design Method and Mechanics of Origami-based Cylindrical Structures

    Science.gov (United States)

    Wang, Fei; Gong, Haoran; Chen, Xi; Chen, C. Q.

    2016-09-01

    Origami structures enrich the field of mechanical metamaterials with the ability to convert morphologically and systematically between two-dimensional (2D) thin sheets and three-dimensional (3D) spatial structures. In this study, an in-plane design method is proposed to approximate curved surfaces of interest with generalized Miura-ori units. Using this method, two combination types of crease lines are unified in one reprogrammable procedure, generating multiple types of cylindrical structures. Structural completeness conditions of the finite-thickness counterparts to the two types are also proposed. As an example of the design method, the kinematics and elastic properties of an origami-based circular cylindrical shell are analysed. The concept of Poisson’s ratio is extended to the cylindrical structures, demonstrating their auxetic property. An analytical model of rigid plates linked by elastic hinges, consistent with numerical simulations, is employed to describe the mechanical response of the structures. Under particular load patterns, the circular shells display novel mechanical behaviour such as snap-through and limiting folding positions. By analysing the geometry and mechanics of the origami structures, we extend the design space of mechanical metamaterials and provide a basis for their practical applications in science and engineering.

  20. 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.

  1. Automatic Transmissions and Transaxles. Auto Mechanics Curriculum Guide. Module 8. Instructor's Guide.

    Science.gov (United States)

    Hevel, David; Tannehill, Dana, Ed.

    This module is the eighth of nine modules in the competency-based Missouri Auto Mechanics Curriculum Guide. Six units cover: introduction to automatic transmission/transaxle; hydraulic control systems; transmission/transaxle diagnosis; automatic transmission/transaxle maintenance and adjustment; in-vehicle transmission repair; and off-car…

  2. The Complexity of Folding Self-Folding Origami

    Science.gov (United States)

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

    2017-10-01

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

  3. The Complexity of Folding Self-Folding Origami

    Directory of Open Access Journals (Sweden)

    Menachem Stern

    2017-12-01

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

  4. Modelling of the Thermo-Mechanical Behavior of the Two-Beam Module for the Compact Linear Collider

    CERN Document Server

    Raatikainen, Riku; Österberg, K; Lehtovaara, A; Pajunen, S

    2011-01-01

    To fulfil the mechanical requirements set by the luminosity goals of the compact linear collider, the 2-m long two-beam modules, the shortest repetitive elements in the main linear accelerator, have to be controlled at micrometer level. At the same time these modules are exposed to high power dissipation that varies while the accelerator is ramped up to nominal power and when the mode of the accelerator operation is modified. These variations will give rise to inevitable temperature transients driving mechanical distortions in and between different module components. Therefore, the thermo-mechanical behaviour of the module is of a high importance. This thesis describes a finite element method model for the two-beam compact linear collider module. The components are described in detail compared to earlier models, which should result in a realistic description of the module. Due to the complexity of the modules, the modelling is divided into several phases from geometrical simplification and modification to the...

  5. Predicting Folding Sequences Based on the Maximum Rock Strength and Mechanical Equilibrium

    Science.gov (United States)

    Cubas, N.; Souloumiac, P.; Maillot, B.; Leroy, Y. M.

    2007-12-01

    The objective is to propose and validate simple procedures, compared to the finite-element method, to select and optimize the dominant mode of folding in fold-and-thrust belts and accretionary wedges, and to determine its stress distribution. Mechanical equilibrium as well as the constraints due to the limited rock strength of the bulk material and of major discontinuities, such as décollements, are accounted for. The first part of the proposed procedure, which is at the core of the external approach of classical limit analysis, consists in estimating the least upper bound on the tectonic force by minimisation of the internal dissipation and part of the external work. The new twist to the method is that the optimization is also done with respect to the geometry of the evolving fold. If several folding events are possible, the dominant mode is the one leading to the least upper bound. The second part of the procedure is based on the Equilibrium Element Method, which is an application of the internal approach of limit analysis. The optimum stress field, obtained by spatial discretisation of the fold, provides the best lower bound on the tectonic force. The difference between the two bounds defines an error estimate of the exact unknown tectonic force. To show the merits of the proposed procedure, its first part is applied to predict the life span of a thrust within an accretionary prism, from its onset, its development with a relief build up and its arrest because of the onset of a more favorable new thrust (Cubas et al., 2007). This life span is sensitive to the friction angles over the ramp and the décollement. It is shown how the normal sequence of thrusting in a supercritical wedge is ended with the first out-of sequence event. The second part of the procedure provides the stress state over each thrust showing that the active back thrust is a narrow fan which dip is sensitive to the friction angle over the ramp and the amount of relief build up (Souloumiac et

  6. Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5)

    DEFF Research Database (Denmark)

    Karlshøj, Stefanie; Amarandi, Roxana Maria; Larsen, Olav

    2016-01-01

    The small molecule metal ion chelators bipyridine and terpyridine complexed with Zn(2+) (ZnBip and ZnTerp) act as CCR5 agonists and strong positive allosteric modulators of CCL3 binding to CCR5, weak modulators of CCL4 binding, and competitors for CCL5 binding. Here we describe their binding site......Terp binds deeply in the major binding pocket and, in contrast to ZnBip, interacts directly with the Trp-248(VI:13/6.48) microswitch, contributing to its 8-fold higher potency. The impact of Trp-248 was further confirmed by ZnClTerp, a chloro-substituted version of ZnTerp that showed no inherent agonism...

  7. The mechanical environment modulates intracellular calcium oscillation activities of myofibroblasts.

    Directory of Open Access Journals (Sweden)

    Charles Godbout

    Full Text Available Myofibroblast contraction is fundamental in the excessive tissue remodeling that is characteristic of fibrotic tissue contractures. Tissue remodeling during development of fibrosis leads to gradually increasing stiffness of the extracellular matrix. We propose that this increased stiffness positively feeds back on the contractile activities of myofibroblasts. We have previously shown that cycles of contraction directly correlate with periodic intracellular calcium oscillations in cultured myofibroblasts. We analyze cytosolic calcium dynamics using fluorescent calcium indicators to evaluate the possible impact of mechanical stress on myofibroblast contractile activity. To modulate extracellular mechanics, we seeded primary rat subcutaneous myofibroblasts on silicone substrates and into collagen gels of different elastic modulus. We modulated cell stress by cell growth on differently adhesive culture substrates, by restricting cell spreading area on micro-printed adhesive islands, and depolymerizing actin with Cytochalasin D. In general, calcium oscillation frequencies in myofibroblasts increased with increasing mechanical challenge. These results provide new insight on how changing mechanical conditions for myofibroblasts are encoded in calcium oscillations and possibly explain how reparative cells adapt their contractile behavior to the stresses occurring in normal and pathological tissue repair.

  8. Understanding the mechanical properties of DNA origami tiles and controlling the kinetics of their folding and unfolding reconfiguration.

    Science.gov (United States)

    Chen, Haorong; Weng, Te-Wei; Riccitelli, Molly M; Cui, Yi; Irudayaraj, Joseph; Choi, Jong Hyun

    2014-05-14

    DNA origami represents a class of highly programmable macromolecules that can go through conformational changes in response to external signals. Here we show that a two-dimensional origami rectangle can be effectively folded into a short, cylindrical tube by connecting the two opposite edges through the hybridization of linker strands and that this process can be efficiently reversed via toehold-mediated strand displacement. The reconfiguration kinetics was experimentally studied as a function of incubation temperature, initial origami concentration, missing staples, and origami geometry. A kinetic model was developed by introducing the j factor to describe the reaction rates in the cyclization process. We found that the cyclization efficiency (j factor) increases sharply with temperature and depends strongly on the structural flexibility and geometry. A simple mechanical model was used to correlate the observed cyclization efficiency with origami structure details. The mechanical analysis suggests two sources of the energy barrier for DNA origami folding: overcoming global twisting and bending the structure into a circular conformation. It also provides the first semiquantitative estimation of the rigidity of DNA interhelix crossovers, an essential element in structural DNA nanotechnology. This work demonstrates efficient DNA origami reconfiguration, advances our understanding of the dynamics and mechanical properties of self-assembled DNA structures, and should be valuable to the field of DNA nanotechnology.

  9. 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

  10. Cellular Mechanisms Underlying Behavioral State-Dependent Bidirectional Modulation of Motor Cortex Output

    Directory of Open Access Journals (Sweden)

    Julia Schiemann

    2015-05-01

    Full Text Available Neuronal activity in primary motor cortex (M1 correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1 a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons, and (2 a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior.

  11. 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)

  12. 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)

  13. Fluvial-Deltaic Strata as a High-Resolution Recorder of Fold Growth and Fault Slip

    Science.gov (United States)

    Anastasio, D. J.; Kodama, K. P.; Pazzaglia, F. P.

    2008-12-01

    Fluvial-deltaic systems characterize the depositional record of most wedge-top and foreland basins, where the synorogenic stratigraphy responds to interactions between sediment supply driven by tectonic uplift, climate modulated sea level change and erosion rate variability, and fold growth patterns driven by unsteady fault slip. We integrate kinematic models of fault-related folds with growth strata and fluvial terrace records to determine incremental rates of shortening, rock uplift, limb tilting, and fault slip with 104-105 year temporal resolution in the Pyrenees and Apennines. At Pico del Aguila anticline, a transverse dècollement fold along the south Pyrenean mountain front, formation-scale synorogenic deposition and clastic facies patterns in prodeltaic and slope facies reflect tectonic forcing of sediment supply, sea level variability controlling delta front position, and climate modulated changes in terrestrial runoff. Growth geometries record a pinned anticline and migrating syncline hinges during folding above the emerging Guarga thrust sheet. Lithologic and anhysteretic remanent magnetization (ARM) data series from the Eocene Arguis Fm. show cyclicity at Milankovitch frequencies allowing detailed reconstruction of unsteady fold growth. Multiple variations in limb tilting rates from roof ramp and basal dècollement. Along the northern Apennine mountain front, the age and geometry of strath terraces preserved across the Salsomaggiore anticline records the Pleistocene-Recent kinematics of the underlying fault-propagation fold as occurring with a fixed anticline hinge, a rolling syncline hinge, and along-strike variations in uplift and forelimb tilting. The uplifted intersection of terrace deposits documents syncline axial surface migration and underlying fault-tip propagation at a rate of ~1.4 cm/yr since the Middle Pleistocene. Because this record of fault slip coincides with the well-known large amplitude oscillations in global climate that contribute

  14. Intermediates and the folding of proteins L and G

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Scott; Head-Gordon, Teresa

    2003-07-01

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

  15. Thermo-mechanical actuator-based miniature tagging module for localization in capsule endoscopy

    Science.gov (United States)

    Chandrappan, Jayakrishnan; Ruiqi, Lim; Su, Nandar; Yen Yi, Germaine Hoe; Vaidyanathan, Kripesh

    2011-04-01

    Capsule endoscopy is a frontline medical diagnostic tool for the gastro intestinal tract disorders. During diagnosis, efficient localization techniques are essential to specify a pathological area that may require further diagnosis or treatment. This paper presents the development of a miniature tagging module that relies on a novel concept to label the region of interest and has the potential to integrate with a capsule endoscope. The tagging module is a compact thermo-mechanical actuator loaded with a biocompatible micro tag. A low power microheater attached to the module serves as the thermal igniter for the mechanical actuator. At optimum temperature, the actuator releases the micro tag instantly and penetrates the mucosa layer of a GI tract, region of interest. Ex vivo animal trials are conducted to verify the feasibility of the tagging module concept. X-ray imaging is used to detect the location of the micro tag embedded in the GI tract wall. The method is successful, and radiopaque micro tags can provide valuable pre-operative position information on the infected area to facilitate further clinical procedures.

  16. Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  17. 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...

  18. Study of the Thermo-Mechanical Behavior of the CLIC Two-Beam Modules

    CERN Document Server

    Rossi, F; Riddone, G; Österberg, K; Kossyvakis, I; Gudkov, D; Samochkine, A

    2013-01-01

    The final luminosity target of the Compact LInear Collider (CLIC) imposes a micron-level stability requirement on the two-meter repetitive two-beam modules constituting the main linacs. Two-beam prototype modules are being assembled to extensively study their thermo-mechanical behaviour under different operation modes. The power dissipation occurring in the modules will be reproduced and the efficiency of the corresponding cooling systems validated. At the same time, the real environmental conditions present in the CLIC tunnel will be studied. Air conditioning and ventilation systems have been installed in the dedicated laboratory. The air temperature will be changed from 20 to 40°C, while the air flow rate will be varied up to 0.8 m/s. During all experimental tests, the alignment of the RF structures will be monitored to investigate the influence of power dissipation and air temperature on the overall thermo-mechanical behaviour. \

  19. Understanding curcumin-induced modulation of protein aggregation.

    Science.gov (United States)

    Ahmad, Basir; Borana, Mohanish S; Chaudhary, Ankur P

    2017-07-01

    Curcumin, a diarylheptanoid compound, found in spice turmeric is known to alter the aggregation of proteins and reduce the toxicity of the aggregates. This review looks at the molecular basis of modulating protein aggregation and toxicity of the aggregates. Foremost, we identify the interaction of curcumin and its derivatives with proteins/peptides and the effect of their interaction on the conformational stability and unfolding/folding pathway(s). The unfolding/folding processes generate partially folded/unfolded intermediate, which serve as aggregation precursor state. Secondly, we discuss the effect of curcumin binding on the kinetics parameters of the aggregation process, which give information about the mechanism of the aggregation inhibition. We describe, in addition, that curcumin can accelerate/promote fibril formation by binding to oligomeric intermediate(s) accumulated in the aggregation pathway. Finally, we discuss the correlation of curcumin-induced monomeric and/or oligomeric precursor states with aggregate structure and toxicity. On the basis of these discussions, we propose a model describing curcumin-induced inhibition/promotion of formation of amyloid-like fibrils. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Vocal fold ion transport and mucin expression following acrolein exposure.

    Science.gov (United States)

    Levendoski, Elizabeth Erickson; Sivasankar, M Preeti

    2014-05-01

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

  1. 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.

  2. Engine Performance (Section C: Emission Control Systems). Auto Mechanics Curriculum Guide. Module 3. Instructor's Guide.

    Science.gov (United States)

    Rains, Larry

    This engine performance (emission control systems) module is one of a series of competency-based modules in the Missouri Auto Mechanics Curriculum Guide. Topics of this module's five units are: positive crankcase ventilation (PCV) and evaporative emission control systems; exhaust gas recirculation (EGR); air injection and catalytic converters;…

  3. Thermo-mechanical modelling and experimental validation of CLIC prototype module type 0

    CERN Document Server

    Kortelainen, Lauri; Koivurova, Hannu; Riddone, Germana; Österberg, Kenneth

    Micron level stability of the two-meter repetitive modules constituting the two main linacs is one of the most important requirements to achieve the luminosity goal for the Compact Linear Collider. Structural deformations due to thermal loads and related to the RF power dissipated inside the modules affect the alignment of the linacs and therefore the resulting luminosity performance. A CLIC prototype module has been assembled in a dedicated laboratory and a thermal test program has been started in order to study its thermo-mechanical behaviour. This thesis focuses on the finite elements modelling of the first CLIC prototype module 0. The aim of the modelling is to examine the temperature distributions and the resulting deformations of the module in different operating conditions defined in the thermal test program. The theoretical results have been compared to the experimental ones; the comparison shows that the results are in good agreement both for the thermal behaviour of the module and for the resulting ...

  4. 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

    multi-scale dynamical problem when one considers the synergies between protein expression, spontaneous folding, chaperonin-assisted folding, protein targeting, the kinetics of post-translational modifications, protein degradation, and of course the drive to avoid aggregation. Further, there is growing recognition that cells not only tolerate but select for proteins that are intrinsically disordered. These proteins are essential for many crucial activities, and yet their inability to fold in isolation makes them prone to proteolytic processing and aggregation. In the series of papers that make up this special focus on protein folding in physical biology, leading researchers provide insights into diverse cross-sections of problems in protein folding. Barrick provides a concise review of what we have learned from the study of two-state folders and draws attention to how several unanswered questions are being approached using studies on large repeat proteins. Dissecting the contribution of hydration-mediated interactions to driving forces for protein folding and assembly has been extremely challenging. There is renewed interest in using hydrostatic pressure as a tool to access folding intermediates and decipher the role of partially hydrated states in folding, misfolding, and aggregation. Silva and Foguel review many of the nuances that have been uncovered by perturbing hydrostatic pressure as a thermodynamic parameter. As noted above, protein folding in vivo is expected to be considerably more complex than the folding of two-state proteins in dilute solutions. Lucent et al review the state-of-the-art in the development of quantitative theories to explain chaperonin-assisted folding in vivo. Additionally, they highlight unanswered questions pertaining to the processing of unfolded/misfolded proteins by the chaperone machinery. Zhuang et al present results that focus on the effects of surface tethering on transition state ensembles and folding mechanisms of a model two

  5. Standard Test Methods for Determining Mechanical Integrity of Photovoltaic Modules

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2009-01-01

    1.1 These test methods cover procedures for determining the ability of photovoltaic modules to withstand the mechanical loads, stresses and deflections used to simulate, on an accelerated basis, high wind conditions, heavy snow and ice accumulation, and non-planar installation effects. 1.1.1 A static load test to 2400 Pa is used to simulate wind loads on both module surfaces 1.1.2 A static load test to 5400 Pa is used to simulate heavy snow and ice accumulation on the module front surface. 1.1.3 A twist test is used to simulate the non-planar mounting of a photovoltaic module by subjecting it to a twist angle of 1.2°. 1.1.4 A cyclic load test of 10 000 cycles duration and peak loading to 1440 Pa is used to simulate dynamic wind or other flexural loading. Such loading might occur during shipment or after installation at a particular location. 1.2 These test methods define photovoltaic test specimens and mounting methods, and specify parameters that must be recorded and reported. 1.3 Any individual mech...

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

    Science.gov (United States)

    Barone, Fabrizio; Giordano, Gerardo

    2018-02-01

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

  7. 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.

  8. 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...

  9. Estrogen Receptor Folding Modulates cSrc Kinase SH2 Interaction via a Helical Binding Mode.

    Science.gov (United States)

    Nieto, Lidia; Tharun, Inga M; Balk, Mark; Wienk, Hans; Boelens, Rolf; Ottmann, Christian; Milroy, Lech-Gustav; Brunsveld, Luc

    2015-11-20

    The estrogen receptors (ERs) feature, next to their transcriptional role, important nongenomic signaling actions, with emerging clinical relevance. The Src Homology 2 (SH2) domain mediated interaction between cSrc kinase and ER plays a key role in this; however the molecular determinants of this interaction have not been elucidated. Here, we used phosphorylated ER peptide and semisynthetic protein constructs in a combined biochemical and structural study to, for the first time, provide a quantitative and structural characterization of the cSrc SH2-ER interaction. Fluorescence polarization experiments delineated the SH2 binding motif in the ER sequence. Chemical shift perturbation analysis by nuclear magnetic resonance (NMR) together with molecular dynamics (MD) simulations allowed us to put forward a 3D model of the ER-SH2 interaction. The structural basis of this protein-protein interaction has been compared with that of the high affinity SH2 binding sequence GpYEEI. The ER features a different binding mode from that of the "two-pronged plug two-hole socket" model in the so-called specificity determining region. This alternative binding mode is modulated via the folding of ER helix 12, a structural element directly C-terminal of the key phosphorylated tyrosine. The present findings provide novel molecular entries for understanding nongenomic ER signaling and targeting the corresponding disease states.

  10. 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.

  11. 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.

  12. Measuring high-frequency responses of an electro-optic phase modulator based on dispersion induced phase modulation to intensity modulation conversion

    Science.gov (United States)

    Zhang, Shangjian; Wang, Heng; Wang, Yani; Zou, Xinhai; Zhang, Yali; Liu, Shuang; Liu, Yong

    2014-11-01

    We investigate the phase modulation to intensity modulation conversion in dispersive fibers for measuring frequency responses of electro-optic phase modulators, and demonstrate two typical measurements with cascade path and fold-back path. The measured results achieve an uncertainty of less than 2.8% within 20 GHz. Our measurements show stable and repeatable results because the optical carrier and its phase-modulated sidebands are affected by the same fiber impairments. The proposed method requires only dispersive fibers and works without any small-signal assumption, which is applicable for swept frequency measurement at different driving levels and operating wavelengths.

  13. Modulation of cavity-polaritons by surface acoustic waves

    DEFF Research Database (Denmark)

    de Lima, M. M.; Poel, Mike van der; Hey, R.

    2006-01-01

    We modulate cavity-polaritons using surface acoustic waves. The corresponding formation of a mini-Brillouin zone and band folding of the polariton dispersion is demonstrated for the first time. Results are in good agreement with model calculations.......We modulate cavity-polaritons using surface acoustic waves. The corresponding formation of a mini-Brillouin zone and band folding of the polariton dispersion is demonstrated for the first time. Results are in good agreement with model calculations....

  14. Effects of thermo-mechanical behavior and hinge geometry on folding response of shape memory polymer sheets

    Science.gov (United States)

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

    2017-11-01

    Shape memory polymer (SMP) sheets patterned with black ink hinges change shape in response to external stimuli, such as absorbed thermal energy from an infrared (IR) light. The geometry of these hinges, including size, orientation, and location, and the applied thermal loads significantly influence the final folded shape of the sheet, but these variables have not been fully investigated. We perform a systematic study on SMP sheets to fundamentally understand the effects of single and double hinge geometries, hinge orientation and spacing, initial temperature, heat flux intensity, and pattern width on the folding behavior. We have developed thermo-viscoelastic finite element models to characterize and quantify the stresses, strains, and temperatures as they relate to SMP shape changes. Our predictions indicate that hinge orientation can be used to reduce the total bending angle, which is the angle traversed by the folding face of the sheet. Two parallel hinges increase the total bending angle, and heat conduction between the hinges affects the transient folding response. IR intensity and initial temperatures can also influence the transient folding behavior. These results can provide guidelines to optimize the transient folding response and the three-dimensional folded structure obtained from self-folding polymer origami sheets that can be applied for myriad applications.

  15. 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.

  16. Assessment of citalopram and escitalopram on neuroblastoma cell lines: Cell toxicity and gene modulation

    Science.gov (United States)

    Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

    2017-01-01

    Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram. PMID:28467792

  17. Assessment of citalopram and escitalopram on neuroblastoma cell lines. Cell toxicity and gene modulation.

    Science.gov (United States)

    Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

    2017-06-27

    Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram.

  18. Micropatterned Azopolymer Surfaces Modulate Cell Mechanics and Cytoskeleton Structure.

    Science.gov (United States)

    Rianna, Carmela; Ventre, Maurizio; Cavalli, Silvia; Radmacher, Manfred; Netti, Paolo A

    2015-09-30

    Physical and chemical characteristics of materials are important regulators of cell behavior. In particular, cell elasticity is a fundamental parameter that reflects the state of a cell. Surface topography finely modulates cell fate and function via adhesion mediated signaling and cytoskeleton generated forces. However, how topographies alter cell mechanics is still unclear. In this work we have analyzed the mechanical properties of peripheral and nuclear regions of NIH-3T3 cells on azopolymer substrates with different topographic patterns. Micrometer scale patterns in the form of parallel ridges or square lattices of surface elevations were encoded on light responsive azopolymer films by means of contactless optical methods. Cell mechanics was investigated by atomic force microscopy (AFM). Cells and consequently the cell cytoskeleton were oriented along the linear patterns affecting cytoskeletal structures, e.g., formation of actin stress fibers. Our data demonstrate that topographic substrate patterns are recognized by cells and mechanical information is transferred by the cytoskeleton. Furthermore, cytoskeleton generated forces deform the nucleus, changing its morphology that appears to be related to different mechanical properties in the nuclear region.

  19. Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes.

    Science.gov (United States)

    Kazmier, Kelli; Claxton, Derek P; Mchaourab, Hassane S

    2017-08-01

    Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na + -coupled amino acid transporter LeuT and the Na + -coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Modulation of human IAPP fibrillation: cosolutes, crowders and chaperones.

    Science.gov (United States)

    Gao, Mimi; Estel, Kathrin; Seeliger, Janine; Friedrich, Ralf P; Dogan, Susanne; Wanker, Erich E; Winter, Roland; Ebbinghaus, Simon

    2015-04-07

    The cellular environment determines the structure and function of proteins. Marginal changes of the environment can severely affect the energy landscape of protein folding. However, despite the important role of chaperones on protein folding, less is known about chaperonal modulation of protein aggregation and fibrillation considering different classes of chaperones. We find that the pharmacological chaperone O4, the chemical chaperone proline as well as the protein chaperone serum amyloid P component (SAP) are inhibitors of the type 2 diabetes mellitus-related aggregation process of islet amyloid polypeptide (IAPP). By applying biophysical methods such as thioflavin T fluorescence spectroscopy, fluorescence anisotropy, total reflection Fourier-transform infrared spectroscopy, circular dichroism spectroscopy and atomic force microscopy we analyse and compare their inhibition mechanism. We demonstrate that the fibrillation reaction of human IAPP is strongly inhibited by formation of globular, amorphous assemblies by both, the pharmacological and the protein chaperones. We studied the inhibition mechanism under cell-like conditions by using the artificial crowding agents Ficoll 70 and sucrose. Under such conditions the suppressive effect of proline was decreased, whereas the pharmacological chaperone remains active.

  1. 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

  2. FoldEco: A Model for Proteostasis in E. coli

    Directory of Open Access Journals (Sweden)

    Evan T. Powers

    2012-03-01

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

  3. Investigation of the impact of mechanical stress on the properties of silicon sensor modules for the ATLAS Phase II upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Stegler, Martin; Polay, Luise; Spehrlich, Dennis; Bloch, Ingo [DESY, Zeuthen (Germany)

    2016-07-01

    The new ATLAS tracker for phase II will be composed of silicon pixel and strip sensor modules. Such a module consists of silicon sensors, boards and readout chips. In a currently ongoing study new adhesives to connect the modular components thermally and mechanically are examined. It was shown that the silicon sensor is exposed to mechanical stress when part of a module. Mechanical stress can cause damage to a sensor and can change the tensors of electrical properties. The study of the effects of mechanical stress on characteristics of the silicon sensor modules are the focus in this presentation. The thermal induced tensile stress near to the surface of a silicon sensor build in a module was simulated. A four point bending setup was used to measure the maximum tensile stress of silicon and to verify the piezoresistive effect on ATLAS07 sensors. The results of the electrical measurements and simulations of stressed silicon sensor modules are shown in the presentation.

  4. 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.

  5. Analysis of the status and problems of mechanical module manufacturing schedule of nuclear power plant

    International Nuclear Information System (INIS)

    Zhao Shuyu; Lu Qinwu; Li Yi

    2014-01-01

    An important feature of the 3rd generation nuclear power projects of AP1000 is the scale application of the modular design and construction technology. The world's first AP1000 project has been started in 2008 in our country, some problems existing in project construction process, such as the mechanical module manufacturing progress can't well meet the needs of the practical engineering. In this article, through investigating and analyzing the main cause of affecting plant mechanical module manufacturing progress, according to our country's actual situation in design, procurement and construction, explore the measures to improve module building progress in the process of AP1000 modular construction project at this stage, provide suggestions for project smooth implementation. (authors)

  6. Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5).

    Science.gov (United States)

    Karlshøj, Stefanie; Amarandi, Roxana Maria; Larsen, Olav; Daugvilaite, Viktorija; Steen, Anne; Brvar, Matjaž; Pui, Aurel; Frimurer, Thomas Michael; Ulven, Trond; Rosenkilde, Mette Marie

    2016-12-23

    The small molecule metal ion chelators bipyridine and terpyridine complexed with Zn 2+ (ZnBip and ZnTerp) act as CCR5 agonists and strong positive allosteric modulators of CCL3 binding to CCR5, weak modulators of CCL4 binding, and competitors for CCL5 binding. Here we describe their binding site using computational modeling, binding, and functional studies on WT and mutated CCR5. The metal ion Zn 2+ is anchored to the chemokine receptor-conserved Glu-283 VII:06/7.39 Both chelators interact with aromatic residues in the transmembrane receptor domain. The additional pyridine ring of ZnTerp binds deeply in the major binding pocket and, in contrast to ZnBip, interacts directly with the Trp-248 VI:13/6.48 microswitch, contributing to its 8-fold higher potency. The impact of Trp-248 was further confirmed by ZnClTerp, a chloro-substituted version of ZnTerp that showed no inherent agonism but maintained positive allosteric modulation of CCL3 binding. Despite a similar overall binding mode of all three metal ion chelator complexes, the pyridine ring of ZnClTerp blocks the conformational switch of Trp-248 required for receptor activation, thereby explaining its lack of activity. Importantly, ZnClTerp becomes agonist to the same extent as ZnTerp upon Ala mutation of Ile-116 III:16/3.40 , a residue that constrains the Trp-248 microswitch in its inactive conformation. Binding studies with 125 I-CCL3 revealed an allosteric interface between the chemokine and the small molecule binding site, including residues Tyr-37 I:07/1.39 , Trp-86 II:20/2.60 , and Phe-109 III:09/3.33 The small molecules and CCL3 approach this interface from opposite directions, with some residues being mutually exploited. This study provides new insight into the molecular mechanism of CCR5 activation and paves the way for future allosteric drugs for chemokine receptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

    Zhang, Yu; Jiang, Jack J.

    2008-09-01

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

  8. 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.

  9. Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

    Directory of Open Access Journals (Sweden)

    Yanxiong Gan

    2015-11-01

    Full Text Available Curcumin, the medically active component from Curcuma longa (Turmeric, is widely used to treat inflammatory diseases. Protein interaction network (PIN analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein–protein interactions (PPIs were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO enrichment analysis based on molecular complex detection (MCODE. A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation.

  10. 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.

  11. 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.

  12. Vascular remodeling: A redox-modulated mechanism of vessel caliber regulation.

    Science.gov (United States)

    Tanaka, Leonardo Y; Laurindo, Francisco R M

    2017-08-01

    Vascular remodeling, i.e. whole-vessel structural reshaping, determines lumen caliber in (patho)physiology. Here we review mechanisms underlying vessel remodeling, with emphasis in redox regulation. First, we discuss confusing terminology and focus on strictu sensu remodeling. Second, we propose a mechanobiological remodeling paradigm based on the concept of tensional homeostasis as a setpoint regulator. We first focus on shear-mediated models as prototypes of remodeling closely dominated by highly redox-sensitive endothelial function. More detailed discussions focus on mechanosensors, integrins, extracellular matrix, cytoskeleton and inflammatory pathways as potential of mechanisms potentially coupling tensional homeostasis to redox regulation. Further discussion of remodeling associated with atherosclerosis and injury repair highlights important aspects of redox vascular responses. While neointima formation has not shown consistent responsiveness to antioxidants, vessel remodeling has been more clearly responsive, indicating that despite the multilevel redox signaling pathways, there is a coordinated response of the whole vessel. Among mechanisms that may orchestrate redox pathways, we discuss roles of superoxide dismutase activity and extracellular protein disulfide isomerase. We then discuss redox modulation of aneurysms, a special case of expansive remodeling. We propose that the redox modulation of vascular remodeling may reflect (1) remodeling pathophysiology is dominated by a particularly redox-sensitive cell type, e.g., endothelial cells (2) redox pathways are temporospatially coordinated at an organ level across distinct cellular and acellular structures or (3) the tensional homeostasis setpoint is closely connected to redox signaling. The mechanobiological/redox model discussed here can be a basis for improved understanding of remodeling and helps clarifying mechanisms underlying prevalent hard-to-treat diseases. Copyright © 2017 Elsevier Inc. All

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

    Science.gov (United States)

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

    2011-10-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  15. Optimal fold symmetry of LH2 rings on a photosynthetic membrane.

    Science.gov (United States)

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

    2013-05-21

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

  16. Mechanical design of a PERMCAT reactor module

    Energy Technology Data Exchange (ETDEWEB)

    Tosti, S. [Associazione ENEA Euratom sulla Fusione, C.R. ENEA Frascati, Via E. Fermi 45, Frascati, Roma I-00044 (Italy)], E-mail: tosti@frascati.enea.it; Bettinali, L. [Associazione ENEA Euratom sulla Fusione, C.R. ENEA Frascati, Via E. Fermi 45, Frascati, Roma I-00044 (Italy); Borgognoni, F. [Tesi Sas, Via Bolzano 28, Rome (Italy); Murdoch, D.K. [EFDA CSU, Boltzmannstr. 2, D-85748 Garching bei Munchen (Germany)

    2007-02-15

    The PERMCAT is a membrane reactor proposed for processing fusion reactor plasma exhaust gas: tritium removal is obtained by isotopic swamping operating in counter-current mode. In this work, a membrane reactor using a permeator tube of length about 500 mm produced via diffusion welding of Pd-Ag thin foils is described. An appropriate mechanical design of the membrane module has been developed in order to avoid any significant compressive and bending stresses on the very long and thin wall permeator tube: two expanded bellows have been applied to the Pd-Ag tube, so that it has been pre-tensioned before operating. The elongation of the metal permeator under hydrogenation has been theoretically estimated and experimentally verified for properly designing the membrane reactor.

  17. Effect of stiffness modulation on mechanical stability of stretchable a-IGZO TFTs

    Science.gov (United States)

    Park, Hyungjin; Cho, Kyoungah; Oh, Hyungon; Kim, Sangsig

    2018-05-01

    In this study, we fabricate the amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) on a stretchable substrate with a buffer stage and investigate the mechanical stability and electrical characteristics when the length of the substrate is stretched by 1.7 times. The buffer stage is responsible for the stiffness modulation of the stretchable substrate. The mobility, the threshold voltage and the on/off ratio of the stretchable a-IGZO TFT are measured to be 18.1 cm2/V·s, 1 V, and 3 × 107, respectively. Our simulation conducted by a three dimensional finite elements method reveals that the stiffness modulation reduces the stress experienced by the substrate in the stretched state by about one-tenth. In addition, the mechanical stability and electrical characteristics of the a-IGZO TFT are maintained even when the substrate is stretched by 1.7 times.

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

    Science.gov (United States)

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

    2016-11-02

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

  19. [Intestinal microbiota and cardiometabolic risk: mechanisms and diet modulation].

    Science.gov (United States)

    Moraes, Ana Carolina Franco de; Silva, Isis Tande da; Almeida-Pititto, Bianca de; Ferreira, Sandra Roberta G

    2014-06-01

    The gut microbiota obtained after birth is composed of a large range of bacteria that play different roles in the human host, such as nutrient uptake, protection against pathogens and immune modulation. The intestinal bacterial content is not completely known, but it is influenced by internal, and mainly by external factors, which modulate its composition and function. Studies indicate that the gut microbiota differs in lean and obese individuals, and in individuals with different food habits. There is evidence that the relationship between diet, inflammation, insulin resistance, and cardiometabolic risk are, in part, mediated by the composition of intestinal bacteria. Knowledge about the gut microbiota may result in different strategies to manipulate bacterial populations and promote health. This review discusses the relevance of understanding the role of dietary factors or patterns in the composition of the microbiota, as well as pathophysiological mechanisms of chronic metabolic diseases, and the potential of prebiotics and probiotics on the cardiometabolic risk profile.

  20. 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.

  1. 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 ...

  2. Feedback of mechanical effectiveness induces adaptations in motor modules during cycling

    Science.gov (United States)

    De Marchis, Cristiano; Schmid, Maurizio; Bibbo, Daniele; Castronovo, Anna Margherita; D'Alessio, Tommaso; Conforto, Silvia

    2013-01-01

    Recent studies have reported evidence that the motor system may rely on a modular organization, even if this behavior has yet to be confirmed during motor adaptation. The aim of the present study is to investigate the modular motor control mechanisms underlying the execution of pedaling by untrained subjects in different biomechanical conditions. We use the muscle synergies framework to characterize the muscle coordination of 11 subjects pedaling under two different conditions. The first one consists of a pedaling exercise with a strategy freely chosen by the subjects (Preferred Pedaling Technique, PPT), while the second condition constrains the gesture by means of a real time visual feedback of mechanical effectiveness (Effective Pedaling Technique, EPT). Pedal forces, recorded using a pair of instrumented pedals, were used to calculate the Index of Effectiveness (IE). EMG signals were recorded from eight muscles of the dominant leg and Non-negative Matrix Factorization (NMF) was applied for the extraction of muscle synergies. All the synergy vectors, extracted cycle by cycle for each subject, were pooled across subjects and conditions and underwent a 2-dimensional Sammon's non-linear mapping. Seven representative clusters were identified on the Sammon's projection, and the corresponding eight-dimensional synergy vectors were used to reconstruct the repertoire of muscle activation for all subjects and all pedaling conditions (VAF > 0.8 for each individual muscle pattern). Only 5 out of the 7 identified modules were used by the subjects during the PPT pedaling condition, while 2 additional modules were found specific for the pedaling condition EPT. The temporal recruitment of three identified modules was highly correlated with IE. The structure of the identified modules was found similar to that extracted in other studies of human walking, partly confirming the existence of shared and task specific muscle synergies, and providing further evidence on the modularity

  3. High-Pressure NMR and SAXS Reveals How Capping Modulates Folding Cooperativity of the pp32 Leucine-rich Repeat Protein.

    Science.gov (United States)

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

    2018-04-27

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

  4. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

    Directory of Open Access Journals (Sweden)

    Wei-Ming Xu

    2018-01-01

    Full Text Available Background: Ischemic heart disease (IHD has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated.Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures.Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules. These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620 and Renin-angiotensin system (hsa04614, with the molecular functions of angiotensin maturation (GO:0002003 and response to bacterium (GO:0009617, which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO and published biomedical literatures.Conclusion: A network medicine

  5. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

    Science.gov (United States)

    Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

    2018-01-01

    Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

  6. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

    Science.gov (United States)

    Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

    2018-01-01

    Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

  7. Folding and Fracturing of Rocks: the background

    Science.gov (United States)

    Ramsay, John G.

    2017-04-01

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

  8. Mitogen-activated protein kinase phosphatase-1 modulates regional effects of injurious mechanical ventilation in rodent lungs.

    Science.gov (United States)

    Park, Moo Suk; He, Qianbin; Edwards, Michael G; Sergew, Amen; Riches, David W H; Albert, Richard K; Douglas, Ivor S

    2012-07-01

    Mechanical ventilation induces heterogeneous lung injury by mitogen-activated protein kinase (MAPK) and nuclear factor-κB. Mechanisms regulating regional injury and protective effects of prone positioning are unclear. To determine the key regulators of the lung regional protective effects of prone positioning in rodent lungs exposed to injurious ventilation. Adult rats were ventilated with high (18 ml/kg, positive end-expiratory pressure [PEEP] 0) or low Vt (6 ml/kg; PEEP 3 cm H(2)O; 3 h) in supine or prone position. Dorsal-caudal lung mRNA was analyzed by microarray and MAPK phosphatases (MKP)-1 quantitative polymerase chain reaction. MKP-1(-/-) or wild-type mice were ventilated with very high (24 ml/kg; PEEP 0) or low Vt (6-7 ml/kg; PEEP 3 cm H(2)O). The MKP-1 regulator PG490-88 (MRx-108; 0.75 mg/kg) or phosphate-buffered saline was administered preventilation. Injury was assessed by lung mechanics, bronchioalveolar lavage cell counts, protein content, and lung injury scoring. Immunoblotting for MKP-1, and IκBα and cytokine ELISAs were performed on lung lysates. Prone positioning was protective against injurious ventilation in rats. Expression profiling demonstrated MKP-1 20-fold higher in rats ventilated prone rather than supine and regional reduction in p38 and c-jun N-terminal kinase activation. MKP-1(-/-) mice experienced amplified injury. PG490-88 improved static lung compliance and injury scores, reduced bronchioalveolar lavage cell counts and cytokine levels, and induced MKP-1 and IκBα. Injurious ventilation induces MAPK in an MKP-1-dependent fashion. Prone positioning is protective and induces MKP-1. PG490-88 induced MKP-1 and was protective against high Vt in a nuclear factor-κB-dependent manner. MKP-1 is a potential target for modulating regional effects of injurious ventilation.

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

    Science.gov (United States)

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

    2017-04-01

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

  10. Protein folding and the organization of the protein topology universe

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Massimiliano Bonomi

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

  12. Role of the N-terminus for the stability of an amyloid-β fibril with three-fold symmetry.

    Directory of Open Access Journals (Sweden)

    Christian A Söldner

    Full Text Available A key player in Alzheimer's disease is the peptide amyloid-beta (Aβ, whose aggregation into small soluble oligomers, protofilaments, and fibrils finally leads to plaque deposits in human brains. The aggregation behavior of Aβ is strongly modulated by the nature and composition of the peptide's environment and by its primary sequence properties. The N-terminal residues of Aβ play an important role, because they are known to change the peptide's aggregation propensity. Since these residues are for the first time completely resolved at the molecular level in a three-fold symmetric fibril structure derived from a patient, we chose that system as template for a systematic investigation of the influence of the N-terminus upon structural stability. Using atomistic molecular dynamics simulations, we examined several fibrillar systems comprising three, six, twelve and an infinite number of layers, both with and without the first eight residues. First, we found that three layers are not sufficient to stabilize the respective Aβ topology. Second, we observed a clear stabilizing effect of the N-terminal residues upon the overall fibril fold: truncated Aβ systems were less stable than their full-length counterparts. The N-terminal residues Arg5, Asp7, and Ser8 were found to form important interfilament contacts stabilizing the overall fibril structure of three-fold symmetry. Finally, similar structural rearrangements of the truncated Aβ species in different simulations prompted us to suggest a potential mechanism involved in the formation of amyloid fibrils with three-fold symmetry.

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

    Science.gov (United States)

    Hindle, David; Kley, Jonas

    2016-04-01

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

  14. 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.

  15. Modeling and imaging of the vocal fold vibration for voice health

    DEFF Research Database (Denmark)

    Granados, Alba

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

  16. Nuclear Technology. Course 30: Mechanical Inspection. Module 30-6, Protective Coating Inspection.

    Science.gov (United States)

    Espy, John

    This sixth in a series of eight modules for a course titled Mechanical Inspection describes the duties of the nuclear quality assurance/quality control technician that are associated with protective coatings, and the national standards that govern the selection, application, and inspection of protective coatings for the reactor containment…

  17. Polymorphism and Module-Reuse Mechanisms for Algebraic Petri Nets in CoopnTools

    OpenAIRE

    Buffo, Mathieu; Buchs, Didier; Donatelli, S.; Kleijn, J.

    1999-01-01

    This paper introduces CoopnTools, a tool set allowing the support of object-oriented specifications written by means of the language CO-OPN/2, based on synchronised algebraic Petri nets. In particular, this paper shows how concrete mechanisms dealing with polymorphism and module-reuse are implemented in CoopnTools.

  18. 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.

  19. 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.

  20. Influence of Flavonoids on Mechanism of Modulation of Insulin Secretion.

    Science.gov (United States)

    Soares, Juliana Mikaelly Dias; Pereira Leal, Ana Ediléia Barbosa; Silva, Juliane Cabral; Almeida, Jackson R G S; de Oliveira, Helinando Pequeno

    2017-01-01

    The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells. Twelve articles were included and represent the basis of discussion on mechanisms of insulin secretion of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44, PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases. According to the literature, the majority of flavonoid subclasses can modulate insulin secretion through several pathways, in an indication that corresponding molecule is a potential candidate for active materials to be applied in the treatment of diabetes. The action of natural products on insulin secretion represents an important investigation topic due to their importance in the diabetes controlIn addition to their typical antioxidant properties, flavonoids contribute to the insulin secretionThe modulation of insulin secretion is induced by flavonoids according to different mechanisms. Abbreviations used: K ATP channels: ATP-sensitive K + channels, GLUT4: Glucose transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L-VDCCs: L-type voltage-dependent Ca +2 channels, GLUT1: Glucose transporter 1, AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II: Ca 2+ /calmodulin

  1. 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.

  2. 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.

  3. 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)

  4. Rubber and gel origami: visco- and poro-elastic behavior of folded structures

    Science.gov (United States)

    Evans, Arthur; Bende, Nakul; Na, Junhee; Hayward, Ryan; Santangelo, Christian

    2014-11-01

    The Japanese art of origami is rapidly becoming a platform for material design, as researchers develop systematic methods to exploit the purely geometric rules that allow paper to folded without stretching. Since any thin sheet couples mechanics strongly to geometry, origami provides a natural template for generating length-scale independent structures from a variety of different materials. In this talk I discuss some of the implications of using polymeric sheets and shells over many length scales to create folded materials with tunable shapes and properties. These implications include visco-elastic snap-through transitions and poro-elastically driven micro origami. In each case, mechanical response, dynamics, and reversible folding is tuned through a combination of geometry and constitutive properties, demonstrating the efficacy of using origami principles for designing functional materials.

  5. 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.

  6. Modulation of the Extent of Cooperative Structural Change During Protein Folding by Chemical Denaturant.

    Science.gov (United States)

    Jethva, Prashant N; Udgaonkar, Jayant B

    2017-09-07

    Protein folding and unfolding reactions invariably appear to be highly cooperative reactions, but the structural and sequence determinants of cooperativity are poorly understood. Importantly, it is not known whether cooperative structural change occurs throughout the protein, or whether some parts change cooperatively and other parts change noncooperatively. In the current study, hydrogen exchange mass spectrometry has been used to show that the mechanism of unfolding of the PI3K SH3 domain is similar in the absence and presence of 5 M urea. The data are well described by a four state N ↔ I N ↔ I 2 ↔ U model, in which structural changes occur noncooperatively during the N ↔ I N and I N ↔ I 2 transitions, and occur cooperatively during the I 2 ↔ U transition. The nSrc-loop and RT-loop, as well as β strands 4 and 5 undergo noncooperative unfolding, while β strands 1, 2, and 3 unfold cooperatively in the absence of urea. However, in the presence of 5 M urea, the unfolding of β strand 4 switches to become cooperative, leading to an increase in the extent of cooperative structural change. The current study highlights the relationship between protein stability and cooperativity, by showing how the extent of cooperativity can be varied, using chemical denaturant to alter protein stability.

  7. Mechanical modulation method for ultrasensitive phase measurements in photonics biosensing.

    Science.gov (United States)

    Patskovsky, S; Maisonneuve, M; Meunier, M; Kabashin, A V

    2008-12-22

    A novel polarimetry methodology for phase-sensitive measurements in single reflection geometry is proposed for applications in optical transduction-based biological sensing. The methodology uses altering step-like chopper-based mechanical phase modulation for orthogonal s- and p- polarizations of light reflected from the sensing interface and the extraction of phase information at different harmonics of the modulation. We show that even under a relatively simple experimental arrangement, the methodology provides the resolution of phase measurements as low as 0.007 deg. We also examine the proposed approach using Total Internal Reflection (TIR) and Surface Plasmon Resonance (SPR) geometries. For TIR geometry, the response appears to be strongly dependent on the prism material with the best values for high refractive index Si. The detection limit for Si-based TIR is estimated as 10(-5) in terms Refractive Index Units (RIU) change. SPR geometry offers much stronger phase response due to a much sharper phase characteristics. With the detection limit of 3.2*10(-7) RIU, the proposed methodology provides one of best sensitivities for phase-sensitive SPR devices. Advantages of the proposed method include high sensitivity, simplicity of experimental setup and noise immunity as a result of a high stability modulation.

  8. Biophysical characterisation of calumenin as a charged F508del-CFTR folding modulator.

    Directory of Open Access Journals (Sweden)

    Rashmi Tripathi

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

  9. Mechanism for iron control of the Vibrio fischeri luminescence system: involvement of cyclic AMP and cyclic AMP receptor protein and modulation of DNA level.

    Science.gov (United States)

    Dunlap, P V

    1992-07-01

    Iron controls luminescence in Vibrio fischeri by an indirect but undefined mechanism. To gain insight into that mechanism, the involvement of cyclic AMP (cAMP) and cAMP receptor protein (CRP) and of modulation of DNA levels in iron control of luminescence were examined in V. fischeri and in Escherichia coli containing the cloned V. fischeri lux genes on plasmids. For V. fischeri and E. coli adenylate cyclase (cya) and CRP (crp) mutants containing intact lux genes (luxR luxICDABEG), presence of the iron chelator ethylenediamine-di(o-hydroxyphenyl acetic acid) (EDDHA) increased expression of the luminescence system like in the parent strains only in the cya mutants in the presence of added cAMP. In the E. coli strains containing a plasmid with a Mu dl(lacZ) fusion in luxR, levels of beta-galactosidase activity (expression from the luxR promoter) and luciferase activity (expression from the lux operon promoter) were both 2-3-fold higher in the presence of EDDHA in the parent strain, and for the mutants this response to EDDHA was observed only in the cya mutant in the presence of added cAMP. Therefore, cAMP and CRP are required for the iron restriction effect on luminescence, and their involvement in iron control apparently is distinct from the known differential control of transcription from the luxR and luxICDABEG promoters by cAMP-CRP. Furthermore, plasmid and chromosomal DNA levels were higher in E. coli and V. fischeri in the presence of EDDHA. The higher DNA levels correlated with an increase in expression of chromosomally encoded beta-galactosidase in E. coli and with a higher level of autoinducer in cultures of V. fischeri. These results implicate cAMP-CRP and modulation of DNA levels in the mechanism of iron control of the V. fischeri luminescence system.

  10. 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.

  11. Three-Fold Symmetry Restrictions on Two-Dimensional Micropolar Materials

    DEFF Research Database (Denmark)

    Warren, W. E.; Byskov, Esben

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

  12. Mechanical loading prevents the stimulating effect of IL-1{beta} on osteocyte-modulated osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kulkarni, Rishikesh N.; Bakker, Astrid D.; Everts, Vincent [Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Amsterdam (Netherlands); Klein-Nulend, Jenneke, E-mail: j.kleinnulend@acta.nl [Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Amsterdam (Netherlands)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Osteocyte incubation with IL-1{beta} stimulated osteocyte-modulated osteoclastogenesis. Black-Right-Pointing-Pointer Conditioned medium from IL-1{beta}-treated osteocytes increased osteoclastogenesis. Black-Right-Pointing-Pointer IL-1{beta} upregulated RANKL and downregulated OPG gene expression by osteocytes. Black-Right-Pointing-Pointer CYR61 is upregulated in mechanically stimulated osteocytes. Black-Right-Pointing-Pointer Mechanical loading of osteocytes may abolish IL-1{beta}-induced osteoclastogenesis. -- Abstract: Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1{beta} (IL-1{beta}), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1{beta} affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes. MLO-Y4 osteocytes were pre-incubated with IL-1{beta} (0.1-1 ng/ml) for 24 h. Cells were either or not subjected to mechanical loading by 1 h pulsating fluid flow (PFF; 0.7 {+-} 0.3 Pa, 5 Hz) in the presence of IL-1{beta} (0.1-1 ng/ml). Conditioned medium was collected after 1 h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1{beta}-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1{beta}-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF. Incubation of osteocytes with IL-1{beta}, as well as conditioned medium from static IL-1{beta}-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL

  13. Mechanical loading prevents the stimulating effect of IL-1β on osteocyte-modulated osteoclastogenesis

    International Nuclear Information System (INIS)

    Kulkarni, Rishikesh N.; Bakker, Astrid D.; Everts, Vincent; Klein-Nulend, Jenneke

    2012-01-01

    Highlights: ► Osteocyte incubation with IL-1β stimulated osteocyte-modulated osteoclastogenesis. ► Conditioned medium from IL-1β-treated osteocytes increased osteoclastogenesis. ► IL-1β upregulated RANKL and downregulated OPG gene expression by osteocytes. ► CYR61 is upregulated in mechanically stimulated osteocytes. ► Mechanical loading of osteocytes may abolish IL-1β-induced osteoclastogenesis. -- Abstract: Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1β (IL-1β), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1β affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes. MLO-Y4 osteocytes were pre-incubated with IL-1β (0.1–1 ng/ml) for 24 h. Cells were either or not subjected to mechanical loading by 1 h pulsating fluid flow (PFF; 0.7 ± 0.3 Pa, 5 Hz) in the presence of IL-1β (0.1–1 ng/ml). Conditioned medium was collected after 1 h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1β-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1β-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF. Incubation of osteocytes with IL-1β, as well as conditioned medium from static IL-1β-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL-1β-treated osteocytes prevented osteoclast formation. Incubation with IL-1β upregulated RANKL and downregulated OPG gene expression by static osteocytes. PFF upregulated

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

    Science.gov (United States)

    Titze, Ingo R

    2014-04-01

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

  15. Correlation of magnetic and mechanical properties of hydrogenated, compositionally modulated, amorphous Fe80Zr20 films (abstract)

    International Nuclear Information System (INIS)

    Rengarajan, S.; Yun, E.J.; Lee, B.H.; Cho, B.I.; Walser, R.M.

    1996-01-01

    Recent research has demonstrated that large amounts of hydrogen can be electrolytically incorporated in amorphous, compositionally modulated (CM) FeZr films. The first irreversible changes in the magnetic state of an electrolytically hydrogenated iron-rich amorphous alloy were observed. The hydrogen-induced changes in the magnetization were interpreted in terms of specific structural rearrangements. In this work, simultaneous measurements of the variations in the magnetization and mechanical properties of these films were measured as a function of hydrogen charging to further clarify the hydrogen-induced structure changes. The Young close-quote s moduli E and internal friction d of as-deposited, and as-hydrogenated CM Fe 80 Zr 20 thin films were calculated from the displacements of a vibrating composite cantilever, measured using a laser heterodyne interferometer (LHI) having a displacement sensitivity of ∼0.01 A. E and d were measured using the resonant frequency method. CM films with thickness 1390 A and modulation wavelength ∼10 A were deposited on glass cantilevers (5 mm long, 2 mm wide, and 150 μm thick) by sequentially sputtering (rf diode) elemental Fe and Zr targets. The samples were electrolytically hydrogenated for various times in 2 N phosphoric acid with a current density of 26.3 mA/cm 2 . The maximum change in magnetization of the film (from 71.5 to 551 emu/cm 3 ) was observed after 5 min. During this time, E increased 18-fold from 535 GPa to 9.63 TPa. The unusually high Young close-quote s modulus of the as-deposited CM film is comparable to those previously observed in other CM films. The change is three times larger than the change in the E of carbon steel at the martensitic transformation, and nine times larger than the hydrogen induced increase in E of pure single crystals of iron. (Abstract Truncated)

  16. A repeated-measures analysis of the effects of soft tissues on wrist range of motion in the extant phylogenetic bracket of dinosaurs: Implications for the functional origins of an automatic wrist folding mechanism in Crocodilia.

    Science.gov (United States)

    Hutson, Joel David; Hutson, Kelda Nadine

    2014-07-01

    A recent study hypothesized that avian-like wrist folding in quadrupedal dinosaurs could have aided their distinctive style of locomotion with semi-pronated and therefore medially facing palms. However, soft tissues that automatically guide avian wrist folding rarely fossilize, and automatic wrist folding of unknown function in extant crocodilians has not been used to test this hypothesis. Therefore, an investigation of the relative contributions of soft tissues to wrist range of motion (ROM) in the extant phylogenetic bracket of dinosaurs, and the quadrupedal function of crocodilian wrist folding, could inform these questions. Here, we repeatedly measured wrist ROM in degrees through fully fleshed, skinned, minus muscles/tendons, minus ligaments, and skeletonized stages in the American alligator Alligator mississippiensis and the ostrich Struthio camelus. The effects of dissection treatment and observer were statistically significant for alligator wrist folding and ostrich wrist flexion, but not ostrich wrist folding. Final skeletonized wrist folding ROM was higher than (ostrich) or equivalent to (alligator) initial fully fleshed ROM, while final ROM was lower than initial ROM for ostrich wrist flexion. These findings suggest that, unlike the hinge/ball and socket-type elbow and shoulder joints in these archosaurs, ROM within gliding/planar diarthrotic joints is more restricted to the extent of articular surfaces. The alligator data indicate that the crocodilian wrist mechanism functions to automatically lock their semi-pronated palms into a rigid column, which supports the hypothesis that this palmar orientation necessitated soft tissue stiffening mechanisms in certain dinosaurs, although ROM-restricted articulations argue against the presence of an extensive automatic mechanism. Anat Rec, 297:1228-1249, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  17. In-Situ Measurement of Power Loss for Crystalline Silicon Modules Undergoing Thermal Cycling and Mechanical Loading Stress Testing

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso

    We analyze the degradation of multi-crystalline silicon photovoltaic modules undergoing simultaneous thermal, mechanical, and humidity-freeze stress testing to develop a dark environmental chamber in-situ measurement procedure for determining module power loss. We analyze dark I-V curves measured...

  18. 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.

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Laxmi Parida

    2005-06-01

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

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

    Directory of Open Access Journals (Sweden)

    2005-06-01

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

  3. 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

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

    Science.gov (United States)

    Marcelino, Anna Marie C; Gierasch, Lila M

    2008-05-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

  6. Mechanical study of the Chartreuse Fold-and-Thrust Belt: relationships between fluids overpressure and decollement within the Toarcian source-rock

    Science.gov (United States)

    Berthelon, Josselin; Sassi, William; Burov, Evgueni

    2016-04-01

    Many source-rocks are shale and constitute potential detachment levels in Fold-and-Thrust Belts (FTB): the toarcian Schistes-Cartons in the French Chartreuse FTB for example. Their mechanical properties can change during their burial and thermal maturation, as for example when large amount of hydrocarbon fluids are generated. A structural reconstruction of the Chartreuse FTB geo-history places the Toarcian Formation as the major decollement horizon. In this work, a mechanical analysis integrating the fluids overpressuring development is proposed to discuss on the validity of the structural interpretation. At first, an analogue of the Chartreuse Toarcian Fm, the albanian Posidonia Schist, is documented as it can provide insights on its initial properties and composition of its kerogen content. Laboratory characterisation documents the vertical evolution of the mineralogical, geochemical and mechanical parameters of this potential decollement layer. These physical parameters (i.e. Total Organic Carbon (TOC), porosity/permeability relationship, friction coefficient) are used to address overpressure buildup in the frontal part of the Chartreuse FTB with TEMISFlow Arctem Basin modelling approach (Faille et al, 2014) and the structural emplacement of the Chartreuse thrust units using the FLAMAR thermo-mechanical model (Burov et al, 2014). The hydro-mechanical modeling results highlight the calendar, distribution and magnitude of the overpressure that developed within the source-rock in the footwall of a simple fault-bend fold structure localized in the frontal part of the Chartreuse FTB. Several key geological conditions are required to create an overpressure able to fracture the shale-rocks and induce a significant change in the rheological behaviour: high TOC, low permeability, favourable structural evolution. These models highlight the importance of modeling the impact of a diffuse natural hydraulic fracturing to explain fluids propagation toward the foreland within

  7. pH-jump induced α-helix folding of poly-L-glutamic acid

    International Nuclear Information System (INIS)

    Donten, Mateusz L.; Hamm, Peter

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Pharmacological chaperoning: a primer on mechanism and pharmacology.

    Science.gov (United States)

    Leidenheimer, Nancy J; Ryder, Katelyn G

    2014-05-01

    Approximately forty percent of diseases are attributable to protein misfolding, including those for which genetic mutation produces misfolding mutants. Intriguingly, many of these mutants are not terminally misfolded since native-like folding, and subsequent trafficking to functional locations, can be induced by target-specific, small molecules variably termed pharmacological chaperones, pharmacoperones, or pharmacochaperones (PCs). PC targets include enzymes, receptors, transporters, and ion channels, revealing the breadth of proteins that can be engaged by ligand-assisted folding. The purpose of this review is to provide an integrated primer of the diverse mechanisms and pharmacology of PCs. In this regard, we examine the structural mechanisms that underlie PC rescue of misfolding mutants, including the ability of PCs to act as surrogates for defective intramolecular interactions and, at the intermolecular level, overcome oligomerization deficiencies and dominant negative effects, as well as influence the subunit stoichiometry of heteropentameric receptors. Not surprisingly, PC-mediated structural correction of misfolding mutants normalizes interactions with molecular chaperones that participate in protein quality control and forward-trafficking. A variety of small molecules have proven to be efficacious PCs and the advantages and disadvantages of employing orthostatic antagonists, active-site inhibitors, orthostatic agonists, and allosteric modulator PCs are considered. Also examined is the possibility that several therapeutic agents may have unrecognized activity as PCs, and this chaperoning activity may mediate/contribute to therapeutic action and/or account for adverse effects. Lastly, we explore evidence that pharmacological chaperoning exploits intrinsic ligand-assisted folding mechanisms. Given the widespread applicability of PC rescue of mutants associated with protein folding disorders, both in vitro and in vivo, the therapeutic potential of PCs is vast

  10. Electrothermal Frequency Modulated Resonator for Mechanical Memory

    KAUST Repository

    Hafiz, Md Abdullah Al

    2016-08-18

    In this paper, we experimentally demonstrate a mechanical memory device based on the nonlinear dynamics of an electrostatically actuated microelectromechanical resonator utilizing an electrothermal frequency modulation scheme. The microstructure is deliberately fabricated as an in-plane shallow arch to achieve geometric quadratic nonlinearity. We exploit this inherent nonlinearity of the arch and drive it at resonance with minimal actuation voltage into the nonlinear regime, thereby creating softening behavior, hysteresis, and coexistence of states. The hysteretic frequency band is controlled by the electrothermal actuation voltage. Binary values are assigned to the two allowed dynamical states on the hysteretic response curve of the arch resonator with respect to the electrothermal actuation voltage. Set-and-reset operations of the memory states are performed by applying controlled dc pulses provided through the electrothermal actuation scheme, while the read-out operation is performed simultaneously by measuring the motional current through a capacitive detection technique. This novel memory device has the advantages of operating at low voltages and under room temperature. [2016-0043

  11. Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

    Science.gov (United States)

    Wei, Min; Li, Song; Le, Weidong

    2017-10-25

    Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

  12. Synchrotron radiation circular dichroism spectroscopy study of recombinant T β4 folding

    Science.gov (United States)

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

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

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

    Science.gov (United States)

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

    2016-11-01

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

  14. Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients

    Directory of Open Access Journals (Sweden)

    Ákos Tényi

    2018-02-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD patients often show skeletal muscle dysfunction that has a prominent negative impact on prognosis. The study aims to further explore underlying mechanisms of skeletal muscle dysfunction as a characteristic systemic effect of COPD, potentially modifiable with preventive interventions (i.e. muscle training. The research analyzes network module associated pathways and evaluates the findings using independent measurements. Methods We characterized the transcriptionally active network modules of interacting proteins in the vastus lateralis of COPD patients (n = 15, FEV1 46 ± 12% pred, age 68 ± 7 years and healthy sedentary controls (n = 12, age 65 ± 9  years, at rest and after an 8-week endurance training program. Network modules were functionally evaluated using experimental data derived from the same study groups. Results At baseline, we identified four COPD specific network modules indicating abnormalities in creatinine metabolism, calcium homeostasis, oxidative stress and inflammatory responses, showing statistically significant associations with exercise capacity (VO2 peak, Watts peak, BODE index and blood lactate levels (P < 0.05 each, but not with lung function (FEV1. Training-induced network modules displayed marked differences between COPD and controls. Healthy subjects specific training adaptations were significantly associated with cell bioenergetics (P < 0.05 which, in turn, showed strong relationships with training-induced plasma metabolomic changes; whereas, effects of training in COPD were constrained to muscle remodeling. Conclusion In summary, altered muscle bioenergetics appears as the most striking finding, potentially driving other abnormal skeletal muscle responses. Trial registration The study was based on a retrospectively registered trial (May 2017, ClinicalTrials.gov identifier: NCT03169270

  15. Unstart Coupling Mechanism Analysis of Multiple-Modules Hypersonic Inlet

    Directory of Open Access Journals (Sweden)

    Jichao Hu

    2013-01-01

    Full Text Available The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

  16. Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.

    Science.gov (United States)

    Hu, Jichao; Chang, Juntao; Wang, Lei; Cao, Shibin; Bao, Wen

    2013-01-01

    The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

  17. Nonstationary behavior in a delayed feedback traveling wave tube folded waveguide oscillator

    International Nuclear Information System (INIS)

    Ryskin, N.M.; Titov, V.N.; Han, S.T.; So, J.K.; Jang, K.H.; Kang, Y.B.; Park, G.S.

    2004-01-01

    Folded waveguide traveling-wave tubes (FW TWT) are among the most promising candidates for powerful compact amplifiers and oscillators in millimeter and submillimeter wave bands. In this paper, the nonstationary behavior of a FW TWT oscillator with delayed feedback is investigated. Starting conditions of the oscillations are derived analytically. Results of numerical simulation of single-frequency, self-modulation (multifrequency) and chaotic generation regimes are presented. Mode competition phenomena, multistability and hysteresis are discussed

  18. 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.

  19. Folding and Function of Proteorhodopsins in Photoenergy Transducing Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Spudich, John L. [University of Texas Medical School, Houston, TX (United States). Health Science Center, Dept. of Biochemistry and Molecular Biology

    2012-08-10

    The overall research objectives are to develop proteorhodopsin (PR) proteins as a model system for α-helical membrane protein insertion and folding, and to advance understanding of the diversity and mechanisms of PRs, a large family of photoenergy transducers (~4000 identified) abundant in the world’s oceans. Specific aims are: (1) To develop a high-efficiency genetic selection procedure for light-driven proton-pumping in E. coli cells. Such a procedure would provide a positive selection method for proper folding and function of PRs in the E. coli membrane. (2) Characterize flash-induced absorption changes and photocurrents in PR variants in organisms from various environments, and their expression level and function when expressed in E. coli. Subaims are to: (a) elucidate the relationship of the transport mechanism to mechanisms of other microbial rhodopsins, some of which like PRs function as ion transporters and some of which use light energy to activate signaling pathways (sensory rhodopsins); and (b) identify important residues and chemical events in light-driven proton transport by PRs. In addition to their importance to the energy of the biosphere PRs have attracted interest for their potential for use in making photoenergy-transducing membranes for bioengineering applications.

  20. [Mechanisms of retroviral immunosuppressive domain-induced immune modulation].

    Science.gov (United States)

    Blinov, V M; Krasnov, G S; Shargunov, A V; Shurdov, M A; Zverev, V V

    2013-01-01

    Immunosuppressive domains (ISD) of viral envelope glycoproteins provide highly pathogenic phenotypes of various retroviruses. ISD interaction with immune cells leads to an inhibition of a response. In the 1980s it was shown that the fragment of ISD comprising of 17 amino acids (named CKS-17) is carrying out such immune modulation. However the underlying mechanisms were not known. The years of thorough research allowed to identify the regulation of Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR cellular pathways as a result of ISD interaction with immune cells. By the way, this leads to decrease of secretion of stimulatory cytokines (e.g., IL-12) and increase of inhibitory, anti-inflammatory ones (e.g., IL-10). One of the receptor tyrosine kinases inducing signal in these pathways acts as the primary target of ISD while other key regulators--cAMP and diacylglycerol (DAG), act as secondary messengers of signal transduction. Immunosuppressive-like domains can be found not only in retroviruses; the presence of ISD within Ebola viral envelope glycoproteins caused extremely hard clinical course of virus-induced hemorrhagic fever. A number of retroviral-origin fragments encoding ISD can be found in the human genome. These regions are expressed in the placenta within genes of syncytins providing a tolerance of mother's immune system to an embryo. The present review is devoted to molecular aspects of retroviral ISD-induced modulation of host immune system.

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

    Directory of Open Access Journals (Sweden)

    Sarah A Klemuk

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

  2. 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.

  3. 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.

  4. Mechanical Design of the Radio-Isotope Source Driver Module for an Initial Prototype of Medium Dose Rate Brachytherapy

    International Nuclear Information System (INIS)

    Ari Satmoko; Tri Harjanto; Hendra Prasetia

    2012-01-01

    High dose rate brachytherapy equipment for therapy against cervical cancer is developed by empowering local products. An Iridium-192 with 5 Curies of energy is used. The source is wrapped in a capsule and combined with a wire diameter of 1 mm and length 1800 mm. The therapy is carried out by inserting the radiation source into the patient's body through an applicator. The system for loading-unloading the isotope source is divided into three modules: the source driver module, the source container modules, and channel distributor module. In this paper, the discussion is focused on engineering activities of the first module that serves to drive forward and backward position of the Iridium-192 isotope sources. The activity begins with the development of preliminary design sketches that produces drawings of mechanical components required. Furthermore, the calculations are carried out in order to establish the main component specifications. From this stage, a stepper motor type M66-A50K-G10 as a mechanical driver is chosen. The next stage is developing the detailed design and producing detailed drawings for all components. The fabrication of each component refers to the detailed design drawings. All components are assembled completely into the source driver module. Test also shows that the module works manually well. By rotating the manual handle in both directions, the tip of the wire moves alternately in forward and backward directions. (author)

  5. Interleukin 1β induces rapid phosphorylation and redistribution of talin: A possible mechanism for modulation of fibroblast focal adhesion

    International Nuclear Information System (INIS)

    Qwarnstroem, E.E.; MacFarlane, S.A.; Page, R.C.; Dower, S.K.

    1991-01-01

    The majority of interleukin 1 (IL-1) receptors in human fibroblasts has been shown to be localized at focal adhesions. This study describes rapid alterations caused by IL-1β/IL-1-receptor interaction at these sites. Fibroblast monolayers, incubated with IL-1β and prepared for electron microscopy, showed successive loss of cell-substratum contact and fewer and less-pronounced processes. Immunocytochemistry revealed loss and redistribution of the talin staining initially observed after 5-15 min of IL-1β incubation. Similarly, the cytoskeleton showed a decrease in staining and a disorganization starting from 15 to 30 min after IL-1 addition, whereas extracellular fibronectin appeared largely unaffected. Prelabeling with [ 32 P]phosphate showed a 2- to 3-fold increase in the level of talin phosphorylation, peaking at 15 min. Phospho amino acid analyses revealed a higher level of serine and threonine phosphorylation. The data suggest that the action of IL-1β on fibroblasts may be partially mediated by direct phosphorylation of talin via activation of a protein serine/threonine kinase, leading to changes in transmembrane linkage proteins and the cytoskeleton. Such alterations at focal adhesions may provide a mechanism by which IL-1 can rapidly modulate cell-matrix interactions during inflammation and wound healing

  6. Network analysis of S. aureus response to ramoplanin reveals modules for virulence factors and resistance mechanisms and characteristic novel genes.

    Science.gov (United States)

    Subramanian, Devika; Natarajan, Jeyakumar

    2015-12-10

    Staphylococcus aureus is a major human pathogen and ramoplanin is an antimicrobial attributed for effective treatment. The goal of this study was to examine the transcriptomic profiles of ramoplanin sensitive and resistant S. aureus to identify putative modules responsible for virulence and resistance-mechanisms and its characteristic novel genes. The dysregulated genes were used to reconstruct protein functional association networks for virulence-factors and resistance-mechanisms individually. Strong link between metabolic-pathways and development of virulence/resistance is suggested. We identified 15 putative modules of virulence factors. Six hypothetical genes were annotated with novel virulence activity among which SACOL0281 was discovered to be an essential virulence factor EsaD. The roles of MazEF toxin-antitoxin system, SACOL0202/SACOL0201 two-component system and that of amino-sugar and nucleotide-sugar metabolism in virulence are also suggested. In addition, 14 putative modules of resistance mechanisms including modules of ribosomal protein-coding genes and metabolic pathways such as biotin-synthesis, TCA-cycle, riboflavin-biosynthesis, peptidoglycan-biosynthesis etc. are also indicated. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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.

  8. Development of a device for real-time light-guided vocal fold injection: A preliminary report.

    Science.gov (United States)

    Cha, Wonjae; Ro, Jung Hoon; Wang, Soo-Geun; Jang, Jeon Yeob; Cho, Jae Keun; Kim, Geun-Hyo; Lee, Yeon Woo

    2016-04-01

    Vocal fold injection is a minimally invasive technique for various vocal fold pathologies. The shortcomings of the cricothyroid (CT) membrane approach are mainly related to invisibility of the injection needle. If localization of the needle tip can be improved during vocal fold injection with the CT approach, the current problems of the technique can be overcome. We have conceptualized real-time light-guided vocal fold injection that enables simultaneous injection under precise localization. In this study, we developed a device for real-time light-guided vocal fold injection and applied it in excised canine larynx. Animal model. A single optic fiber was inserted in an unmodified 25-gauge needle. A designated connector for the device was attached to the needle, the optic fiber, and the syringe. A laser diode module was used as the light source. An ex vivo canine larynx model was used to validate the device. The location of the needle tip was accurately indicated, and the depth from the mucosa could be estimated according to the brightness and size of the red light. The needle was inserted and could be localized in the canine vocal fold by the light of the device. Precise injection at the intended location was easily performed with no manipulation of the device or the needle. Real-time light-guided vocal fold injection might be a feasible and promising technique for treatment of vocal fold pathology. It is expected that this technique can improve the precision of vocal fold injection and expand its indication in laryngology. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  9. NMR structure of the first Ig module of mouse FGFR1

    DEFF Research Database (Denmark)

    Kiselyov, V.V.; Bock, Elisabeth Marianne; Berezin, V.

    2006-01-01

    of this module. We describe here the NMR structure of the Ig1 module of mouse FGFR1. The three-dimensional fold of the module belongs to the intermediate Ig subgroup and can be described as a beta-barrel consisting of two beta-sheets. One sheet is formed by A', G, F, C, and C', and the other by A, B, B', E...

  10. Structural and functional studies of the modulator NS9283 reveal agonist-like mechanism of action at α4β2 nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Olsen, Jeppe A; Ahring, Philip K; Kastrup, Jette Sandholm Jensen

    2014-01-01

    Modulation of Cys loop receptor ion channels is a proven drug discovery strategy, but many underlying mechanisms of the mode of action are poorly understood. We report the x-ray structure of the acetylcholine-binding protein from Lymnaea stagnalis with NS9283, a stoichiometry selective positive...... on efficacy. The shared modulatory profile along with a binding site located in an extracellular subunit interface suggest that modulation via an agonist-like mechanism may be a common mechanism of action that potentially could apply to Cys loop receptors beyond the α4β2 nAChRs....... modulator that targets the α4-α4 interface of α4β2 nicotinic acetylcholine receptors (nAChRs). Together with homology modeling, mutational data, quantum mechanical calculations, and pharmacological studies on α4β2 nAChRs, the structure reveals a modulator binding mode that overlaps the α4-α4 interface...

  11. Development of Component Mechanisms and Novel Actuation for Origami Inspired Designs

    Science.gov (United States)

    2016-11-17

    distribution unlimited. All structural components of the robot were fabricated with a 3D printer . The communication module, cooling fan, and battery for...wire actuator. The module has bi- stability so that it can maintain its shape without actuator force. Morphing Voxel Sheet Modular morphing...is the complexity of geometrical relationships between folding units requires complex pattern generation and folding sequence to build diverse 3D

  12. 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.

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

    Science.gov (United States)

    Decker, Gifford Z; Thomson, Scott L

    2007-05-01

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

  14. A new mechanism of ionizing radiation detection for positron emission tomography: modulation of optical properties

    Science.gov (United States)

    Tao, Li; Daghighian, Henry M.; Levin, Craig S.

    2016-10-01

    Using conventional scintillation detection, the fundamental limit in positron emission tomography (PET) annihilation photon pair coincidence time resolution is strongly dependent on the inherent temporal variances generated during the scintillation process, yielding an intrinsic physical limit of around 100 ps. On the other hand, modulation mechanisms of a material's optical properties as exploited in the optical telecommunications industry can be orders of magnitude faster. In this paper we borrow from the concept of optics pump-probe measurement to study whether ionizing radiation can also produce fast modulations of optical properties, which can be utilized as a novel method for radiation detection. We show that a refractive index modulation of approximately 5x10-6 is induced by interactions in a cadmium telluride (CdTe) crystal from a 511 keV photon source. Furthermore, using additional radionuclide sources, we show that the amplitude of the optical modulation signal varies linearly with both the radiation source flux rate and average photon energy.

  15. Positive therapy of andrographolide in vocal fold leukoplakia.

    Science.gov (United States)

    Xu, Jue; Xue, Tao; Bao, Ying; Wang, Dong-Hai; Ma, Bing-Liang; Yin, Chen-Yi; Yang, Guang-Hui; Ren, Gang; Lan, Long-Jiang; Wang, Jian-Qiu; Zhang, Xiao-Lan; Zhao, Yu-Qin

    2014-01-01

    Vocal fold leukoplakia is a premalignant precursor of squamous cell carcinoma. Although many efforts have been contributed to therapy of this disease, none exhibits a satisfactory result. The aims of this study were to investigate the effectiveness and feasibility of andrographolide therapy in vocal fold leukoplakia and to explore the preliminary mechanism underlying. Forty-one eligible patients were enrolled in the study. The patients were treated for 10-minute exposures of 5 ml (25mg/ml) andrographolide injection aerosols twice a day, and 2 weeks was considered as one treatment course. Electronic laryngoscope was used to observe the condition of vocal fold leukoplakia during the treatment. Every patient received one or two treatment courses, and the follow-up was carried out for 12 months. Toxic reactions of treatments were evaluated on the basis of the standards of the United States MD Anderson Cancer Center. Moreover, laryngeal carcinoma cell line Hep2 was applied to explore the mechanism of effect of andrographolide. Anti-proliferative effect on Hep2, cell nuclear morphology, express of mitogen-activated protein kinases (MAPK) and pro-apoptotic protein were detected after andrographolide treatment. We found that andrographolide exhibited significant curative effects on treatments, which were accompanied by thinning of the lesion of leukoplakia, reduction in the whitish surface area, and return of pink or red epithelium. A complete response up to 85% was observed, and no toxic side effect events occurred during the study. No patient with a complete response had a recurrence in the follow-up. Moreover, cellular experiments in Hep2 indicated that andrographolide activated MAPK pathway and caspase cascade, and finally induced apoptosis in laryngeal carcinoma cell. The advantages of andrographolide are connected with minimally invasive and localized character of the treatment and no damage of collagenous tissue structures, which are more convenient and less painful

  16. CONCEPTION OF BI-FOLD AUTHENTICATED AGENT – MONITORED TRANSACTION ARCHITECTURE

    Directory of Open Access Journals (Sweden)

    Srivatsan Sridharan

    2014-06-01

    Full Text Available The aim of this paper is to provide an introduction towards the architectural design of a bi-fold authenticated agent-monitored transaction model. The focus is primarily on implementation in ATM systems which provide the following facilities of withdrawing currency at any remote terminal, verification of the end users identity using Personal Identification Number and an authentic One-Time-Session-Dependent Key generation and validation through the mobile. This system requires building up of an third party agent which would establish a secure session to the bank application with the terminal only after a series of authentication mechanism without compromising the privacy of any individual. The customers, without any insider privileges, can withdraw currency without being detected by any mechanisms of theft of card and eaves dropping of the Password from the card holders within the terminal software are also a major threat yet to be addressed. A basic solution is the terminals having bi-fold authentication mechanisms where mobile dependent one time session dependent key is being generated with authenticity being ensured and the confidentiality being maintained. In such a system, the correctness burden on the terminal’s code is significantly less as the customers have been given the chance to authorize themselves from their hand-held devices and are allowed to withdraw currency in terminal only after their identity is proved by a series of authentication procedures. In this paper along with the bi-fold authentication implementation, architectural design of the agent which is being introduced is also briefed.

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

    Directory of Open Access Journals (Sweden)

    Jörg C Schlatterer

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

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

    Directory of Open Access Journals (Sweden)

    Karlo Pintarić

    2015-09-01

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

  19. Folding and self-assembly of polypeptides: Dynamics and thermodynamics from molecular simulation

    Science.gov (United States)

    Fluitt, Aaron Michael

    Empowered by their exquisite three-dimensional structures, or "folds," proteins carry out biological tasks with high specificity, efficiency, and fidelity. The fold that optimizes biological function represents a stable configuration of the constituent polypeptide molecule(s) under physiological conditions. Proteins and polypeptides are not static, however: battered by thermal motion, they explore a distribution of folds that is determined by the sequence of amino acids, the presence and identity of other molecules, and the thermodynamic conditions. In this dissertation, we apply molecular simulation techniques to the study of two polypeptides that have unusually diffuse distributions of folds under physiological conditions: polyglutamine (polyQ) and islet amyloid polypeptide (IAPP). Neither polyQ nor IAPP adopts a predominant fold in dilute aqueous solution, but at sufficient concentrations, both are prone to self-assemble into stable, periodic, and highly regular aggregate structures known as amyloid. The appearance of amyloid deposits of polyQ in the brain, and of IAPP in the pancreas, are associated with Huntington's disease and type 2 diabetes, respectively. A molecular view of the mechanism(s) by which polyQ and IAPP fold and self-assemble will enhance our understanding of disease pathogenesis, and it has the potential to accelerate the development of therapeutics that target early-stage aggregates. Using molecular simulations with spatial and temporal resolution on the atomic scale, we present analyses of the structural distributions of polyQ and IAPP under various conditions, both in and out of equilibrium. In particular, we examine amyloid fibers of polyQ, the IAPP dimer in solution, and single IAPP fragments at a lipid bilayer. We also benchmark the molecular models, or "force fields," available for such studies, and we introduce a novel simulation algorithm.

  20. 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.

  1. Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences.

    Science.gov (United States)

    Donzis, Elissa J; Tronson, Natalie C

    2014-11-01

    This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. A hydrogel actuator with flexible folding deformation and shape programming via using sodium carboxymethyl cellulose and acrylic acid.

    Science.gov (United States)

    Wu, Shuiping; Yu, Feng; Dong, Hua; Cao, Xiaodong

    2017-10-01

    Hydrogel actuator is an intelligent material, which can work as artificial muscle. However, most present hydrogel actuators, due to the inferior mechanical property and uncontrolled folding property, have always resulted in slipping off or the failure of grasping an object with specific shape and required weight. In order to solve this problem, here a tough hydrogel actuator with programmable folding deformation has been prepared by combining the "selective implanting method" and "ionic coordination". The shape and folding angle (from 0 to 180 o ) of hydrogel actuator can be precisely controlled by altering the location and size of the implanting parts that seems like the joints of finger. The ionic coordination is not only the force to trigger the folding of hydrogel, but also utilized to reinforce the mechanical property. We believed the superior mechanical and shape-programmable property can endow the hydrogel actuator with great application prospect in soft machine. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Module theory endomorphism rings and direct sum decompositions in some classes of modules

    CERN Document Server

    Facchini, Alberto

    1998-01-01

    The purpose of this expository monograph is three-fold. First, the solution of a problem posed by Wolfgang Krull in 1932 is presented. He asked whether what is now called the "Krull-Schmidt Theorem" holds for artinian modules. A negative answer was published only in 1995 by Facchini, Herbera, Levy and Vámos. Second, the answer to a question posed by Warfield in 1975, namely, whether the Krull-Schmidt-Theorem holds for serial modules, is described. Facchini published a negative answer in 1996. The solution to the Warfield problem shows an interesting behavior; in fact, it is a phenomena so rare in the history of Krull-Schmidt type theorems that its presentation to a wider mathematical audience provides the third incentive for this monograph. Briefly, the Krull-Schmidt-Theorem holds for some, not all, classes of modules. When it does hold, any two indecomposable decompositions are uniquely determined up to one permutation. For serial modules the theorem does not hold, but any two indecomposable decompositions ...

  5. 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.

  6. The ribosome uses two active mechanisms to unwind messenger RNA during translation.

    Science.gov (United States)

    Qu, Xiaohui; Wen, Jin-Der; Lancaster, Laura; Noller, Harry F; Bustamante, Carlos; Tinoco, Ignacio

    2011-07-06

    The ribosome translates the genetic information encoded in messenger RNA into protein. Folded structures in the coding region of an mRNA represent a kinetic barrier that lowers the peptide elongation rate, as the ribosome must disrupt structures it encounters in the mRNA at its entry site to allow translocation to the next codon. Such structures are exploited by the cell to create diverse strategies for translation regulation, such as programmed frameshifting, the modulation of protein expression levels, ribosome localization and co-translational protein folding. Although strand separation activity is inherent to the ribosome, requiring no exogenous helicases, its mechanism is still unknown. Here, using a single-molecule optical tweezers assay on mRNA hairpins, we find that the translation rate of identical codons at the decoding centre is greatly influenced by the GC content of folded structures at the mRNA entry site. Furthermore, force applied to the ends of the hairpin to favour its unfolding significantly speeds translation. Quantitative analysis of the force dependence of its helicase activity reveals that the ribosome, unlike previously studied helicases, uses two distinct active mechanisms to unwind mRNA structure: it destabilizes the helical junction at the mRNA entry site by biasing its thermal fluctuations towards the open state, increasing the probability of the ribosome translocating unhindered; and it mechanically pulls apart the mRNA single strands of the closed junction during the conformational changes that accompany ribosome translocation. The second of these mechanisms ensures a minimal basal rate of translation in the cell; specialized, mechanically stable structures are required to stall the ribosome temporarily. Our results establish a quantitative mechanical basis for understanding the mechanism of regulation of the elongation rate of translation by structured mRNAs. ©2011 Macmillan Publishers Limited. All rights reserved

  7. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

    Science.gov (United States)

    Brattsand, R; Linden, M

    1996-01-01

    Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in

  8. The microstructure and mechanical properties of multilayer diamond-like carbon films with different modulation ratios

    International Nuclear Information System (INIS)

    Xu Zhaoying; Zheng, Y.J.; Jiang, F.; Leng, Y.X.; Sun Hong; Huang Nan

    2013-01-01

    Highlights: ► The multilayer DLC films with different modulation ratios have been fabricated by FCVA. ► The multilayer DLC films can effectively decrease the residual stress of the DLC films. ► The multilayer DLC film with modulation ratio of 1:1 shows the best wear resistance. - Abstract: The multilayer DLC films consisting of sp 2 -rich DLC layers (soft DLC) and sp 3 -rich DLC layers (hard DLC) with different modulation ratios (thickness ratio of the hard DLC to soft DLC) ranging from 2:1, 1:1 to 1:2 had been deposited on Si (1 0 0) wafer and Ti–6Al–4V alloy substrates by filtered cathodic vacuum arc (FCVA) deposition. The effect of modulation ratio on the microstructure and properties of the multilayer DLC films including sp 3 content, residual stress, mechanical properties, adhesion strength and wear resistance were studied by Raman spectroscopy, profilometry technique, nanoindenter, Vickers indentation test, scanning electron microscopy (SEM) and ball-on-disc reciprocating friction test. The results showed that the sp 3 content and the hardness of the multilayer DLC films decreased with modulation ratios decreasing. The stress of the multilayer DLC films could be effectively reduced and the stress decreased with the modulation ratio decreasing. The multilayer DLC film with modulation ratio of 1:1 had the best wear resistance due to a balance between hardness and residual stress.

  9. Simulated potential for enhanced performance of mechanically stacked hybrid III-V/Si tandem photovoltaic modules using DC-DC converters

    Science.gov (United States)

    MacAlpine, Sara; Bobela, David C.; Kurtz, Sarah; Lumb, Matthew P.; Schmieder, Kenneth J.; Moore, James E.; Walters, Robert J.; Alberi, Kirstin

    2017-10-01

    This work examines a tandem module design with GaInP2 mechanically stacked on top of crystalline Si, using a detailed photovoltaic (PV) system model to simulate four-terminal (4T) unconstrained and two-terminal voltage-matched (2T VM) parallel architectures. Module-level power electronics is proposed for the 2T VM module design to enhance its performance over the breadth of temperatures experienced by a typical PV installation. Annual, hourly simulations of various scenarios indicate that this design can reduce annual energy losses to ˜0.5% relative to the 4T module configuration. Consideration is given to both performance and practical design for building or ground mount installations, emphasizing compatibility with existing standard Si modules.

  10. Developing guinea pig brain as a model for cortical folding.

    Science.gov (United States)

    Hatakeyama, Jun; Sato, Haruka; Shimamura, Kenji

    2017-05-01

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

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

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

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

  12. Notch-dependent epithelial fold determines boundary formation between developmental fields in the Drosophila antenna.

    Science.gov (United States)

    Ku, Hui-Yu; Sun, Y Henry

    2017-07-01

    Compartment boundary formation plays an important role in development by separating adjacent developmental fields. Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation. We studied the boundary separating the proximal A1 segment and the distal segments, defined respectively by Lim1 and Dll expression in the eye-antenna disc. Sharp segregation of the Lim1 and Dll expression domains precedes activation of Notch at the Dll/Lim1 interface. By repressing bantam miRNA and elevating the actin regulator Enable, Notch signaling then induces actomyosin-dependent apical constriction and epithelial fold. Disruption of Notch signaling or the actomyosin network reduces apical constriction and epithelial fold, so that Dll and Lim1 cells become intermingled. Our results demonstrate a new mechanism of boundary formation by actomyosin-dependent tissue folding, which provides a physical barrier to prevent mixing of cells from adjacent developmental fields.

  13. C-Si solar cell modules

    International Nuclear Information System (INIS)

    Tomita, Takashi

    2005-01-01

    In order to meet the rapidly growing demand for solar power photovoltaic systems which is based on public consciousness of global environmental issues, SHARP has increased the production of solar cells and modules over 10-fold in the last 5 years. Silicon-based technologies are expected to be dominant in the coming decade. In the course of an increase of the annual production scale to 1000 MW, the efficiency of modules will be improved and the thickness of wafers will be decreased and all this will lead to a drastic price reduction of PV systems. (Author)

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

    Directory of Open Access Journals (Sweden)

    Xinxin Liu

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

  15. Effects of knot type in the folding of topologically complex lattice proteins

    Science.gov (United States)

    Soler, Miguel A.; Nunes, Ana; Faísca, Patrícia F. N.

    2014-07-01

    The folding properties of a protein whose native structure contains a 52 knot are investigated by means of extensive Monte Carlo simulations of a simple lattice model and compared with those of a 31 knot. A 52 knot embedded in the native structure enhances the kinetic stability of the carrier lattice protein in a way that is clearly more pronounced than in the case of the 31 knot. However, this happens at the expense of a severe loss in folding efficiency, an observation that is consistent with the relative abundance of 31 and 52 knots in the Protein Data Bank. The folding mechanism of the 52 knot shares with that of the 31 knot the occurrence of a threading movement of the chain terminus that lays closer to the knotted core. However, co-concomitant knotting and folding in the 52 knot occurs with negligible probability, in sharp contrast to what is observed for the 31 knot. The study of several single point mutations highlights the importance in the folding of knotted proteins of the so-called structural mutations (i.e., energetic perturbations of native interactions between residues that are critical for knotting but not for folding). On the other hand, the present study predicts that mutations that perturb the folding transition state may significantly enhance the kinetic stability of knotted proteins provided they involve residues located within the knotted core.

  16. Universal deformation pathways and flexural hardening of nanoscale 2D-material standing folds

    Science.gov (United States)

    Chacham, Helio; Barboza, Ana Paula M.; de Oliveira, Alan B.; de Oliveira, Camilla K.; Batista, Ronaldo J. C.; Neves, Bernardo R. A.

    2018-03-01

    In the present work, we use atomic force microscopy nanomanipulation of 2D-material standing folds to investigate their mechanical deformation. Using graphene, h-BN and talc nanoscale wrinkles as testbeds, universal force-strain pathways are clearly uncovered and well-accounted for by an analytical model. Such universality further enables the investigation of each fold bending stiffness κ as a function of its characteristic height h 0. We observe a more than tenfold increase of κ as h 0 increases in the 10-100 nm range, with power-law behaviors of κ versus h 0 with exponents larger than unity for the three materials. This implies anomalous scaling of the mechanical responses of nano-objects made from these materials.

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

    Directory of Open Access Journals (Sweden)

    Lucy R Allen

    2009-07-01

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

  18. Identifying links between origami and compliant mechanisms

    Directory of Open Access Journals (Sweden)

    H. C. Greenberg

    2011-12-01

    Full Text Available Origami is the art of folding paper. In the context of engineering, orimimetics is the application of folding to solve problems. Kinetic origami behavior can be modeled with the pseudo-rigid-body model since the origami are compliant mechanisms. These compliant mechanisms, when having a flat initial state and motion emerging out of the fabrication plane, are classified as lamina emergent mechanisms (LEMs. To demonstrate the feasibility of identifying links between origami and compliant mechanism analysis and design methods, four flat folding paper mechanisms are presented with their corresponding kinematic and graph models. Principles from graph theory are used to abstract the mechanisms to show them as coupled, or inter-connected, mechanisms. It is anticipated that this work lays a foundation for exploring methods for LEM synthesis based on the analogy between flat-folding origami models and linkage assembly.

  19. 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

  20. Therapeutic potential of gel-based injectables for vocal fold regeneration

    Science.gov (United States)

    Bartlett, Rebecca S.; Thibeault, Susan L.; Prestwich, Glenn D.

    2012-01-01

    Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. PMID:22456756

  1. Therapeutic potential of gel-based injectables for vocal fold regeneration

    International Nuclear Information System (INIS)

    Bartlett, Rebecca S; Thibeault, Susan L; Prestwich, Glenn D

    2012-01-01

    Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. (paper)

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

    Science.gov (United States)

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

    2016-11-23

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

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

    International Nuclear Information System (INIS)

    Xu Yao; Wang Ting; Gai Feng

    2006-01-01

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

  4. 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

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

    Science.gov (United States)

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

    2014-11-01

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

  6. ATLAS Liquid Argon Calorimeter Module Zero

    CERN Multimedia

    1993-01-01

    This module was built and tested with beam to validate the ATLAS electromagnetic calorimeter design. One original design feature is the folding. 10 000 lead plates and electrodes are folded into an accordion shape and immersed in liquid argon. As they cross the folds, particles are slowed down by the lead. As they collide with the lead atoms, electrons and photons are ejected. There is a knock-on effect and as they continue on into the argon, a whole shower is produced. The electrodes collect up all the electrons and this signal gives a measurement of the energy of the initial particle. The M0 was fabricated by French institutes (LAL, LAPP, Saclay, Jussieu) in the years 1993-1994. It was tested in the H6/H8 beam lines in 1994, leading to the Technical Design Report in 1996.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  8. 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.

  9. Analysis of the thermo-mechanical behaviour of the DEMO Water-Cooled Lithium Lead breeding blanket module under normal operation steady state conditions

    Energy Technology Data Exchange (ETDEWEB)

    Di Maio, P.A.; Arena, P. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Aubert, J. [CEA Saclay, DEN/DANS/DM2S/SEMT, 91191 Gif sur Yvette Cedex (France); Bongiovì, G. [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Chiovaro, P., E-mail: pierluigi.chiovaro@unipa.it [Dipartimento di Energia, Ingegneria dell’Informazione e Modelli Matematici, Università di Palermo, Viale delle Scienze, 90128 Palermo (Italy); Giammusso, R. [ENEA – C.R. Brasimone, 40032 Camugnano (Italy); Li Puma, A. [CEA Saclay, DEN/DANS/DM2S/SEMT, 91191 Gif sur Yvette Cedex (France); Tincani, A. [ENEA – C.R. Brasimone, 40032 Camugnano (Italy)

    2015-10-15

    Highlights: • A DEMO WCLL blanket module thermo-mechanical behaviour has been investigated. • Two models of the WCLL blanket module have been set-up adopting a code based on FEM. • The water flow domain in the module has been considered. • A set of uncoupled steady state thermo-mechanical analyses has been carried out. • Critical temperature is not overcome. Safety verifications are generally satisfied. - Abstract: Within the framework of DEMO R&D activities, a research cooperation has been launched between ENEA, the University of Palermo and CEA to investigate the thermo-mechanical behaviour of the outboard equatorial module of the DEMO1 Water-Cooled Lithium Lead (WCLL) blanket under normal operation steady state scenario. The research campaign has been carried out following a theoretical–computational approach based on the Finite Element Method (FEM) and adopting a qualified commercial FEM code. In particular, two different 3D FEM models (Model 1 and Model 2), reproducing respectively the central and the lateral poloidal–radial slices of the WCLL blanket module, have been set up. A particular attention has been paid to the modelling of water flow domain, within both the segment box channels and the breeder zone tubes, to simulate realistically the coolant-box thermal coupling. Results obtained are herewith reported and critically discussed.

  10. First modules of ATLAS's great accordion

    CERN Multimedia

    2001-01-01

    The first CERN-built module of the barrel section of ATLAS's electromagnetic calorimeter has just been completed. This is the second in a series of 32 modules that will make up the final detector. These accordion-shaped structures will give precise measurements of the energy of particles produced in the LHC. The first CERN-built module of the barrel section of ATLAS's electromagnetic calorimeter nearing completion. Behind the module, from left to right: Ralf Huber, Andreas Bies and Jorgen Beck Hansen. In front of the module, from left to right: Philippe Lançon and Edward Wood. The builders of the ATLAS electromagnetic calorimeter are masters in the art of folding! To find out why, just take a look inside Hall 184, where the first CERN-built module of ATLAS's electromagnetic calorimeter has just been completed. It is the second in a long series, the first having been completed at the Saclay Laboratory of France's Commissariat à l'Energie Atomique just a few weeks ago. Thirty more remain...

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

    Science.gov (United States)

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

    2009-06-01

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

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

    Science.gov (United States)

    Gradmann, Sofie; Beaumont, Christopher; Albertz, Markus

    2009-04-01

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

  13. Folding and membrane insertion of the pore-forming peptide gramicidin occur as a concerted process.

    Science.gov (United States)

    Hicks, Matthew R; Damianoglou, Angeliki; Rodger, Alison; Dafforn, Timothy R

    2008-11-07

    Many antibiotic peptides function by binding and inserting into membranes. Understanding this process provides an insight into the fundamentals of both membrane protein folding and antibiotic peptide function. For the first time, in this work, flow-aligned linear dichroism (LD) is used to study the folding of the antibiotic peptide gramicidin. LD provides insight into the combined processes of peptide folding and insertion and has the advantage over other similar techniques of being insensitive to off-membrane aggregation events. By combining LD data with conventional measurements of protein fluorescence and circular dichroism, the mechanism of gramicidin insertion is elucidated. The mechanism consists of five separately assignable steps that include formation of a water-insoluble gramicidin aggregate, dissociation from the aggregate, partitioning of peptide to the membrane surface, oligomerisation on the surface and concerted insertion and folding of the peptide to the double-helical form of gramicidin. Measurement of the rates of each step shows that although changes in the fluorescence signal cease 10 s after the initiation of the process, the insertion of the peptide into the membrane is actually not complete for a further 60 min. This last membrane insertion phase is only apparent by measurement of LD and circular dichroism signal changes. In summary, this study demonstrates the importance of multi-technique approaches, including LD, in studies of membrane protein folding.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  15. Transcranial alternating current stimulation: A review of the underlying mechanisms and modulation of cognitive processes

    Directory of Open Access Journals (Sweden)

    Christoph S Herrmann

    2013-06-01

    Full Text Available Brain oscillations of different frequencies have been associated with a variety of cognitive functions. Convincing evidence supporting those associations has been provided by studies using intracranial stimulation, pharmacological interventions and lesion studies. The emergence of novel non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS and transcranial alternating current stimulation (tACS now allows to modulate brain oscillations directly. Particularly, tACS offers the unique opportunity to causally link brain oscillations of a specific frequency range to cognitive processes, because it uses sinusoidal currents that are bound to one frequency only. Using tACS allows to modulate brain oscillations and in turn to influence cognitive processes, thereby demonstrating the causal link between the two. Here, we review findings about the physiological mechanism of tACS and studies that have used tACS to modulate basic motor and sensory processes as well as higher cognitive processes like memory, ambiguous perception, and decision making.

  16. Protein folding simulations by generalized-ensemble algorithms.

    Science.gov (United States)

    Yoda, Takao; Sugita, Yuji; Okamoto, Yuko

    2014-01-01

    In the protein folding problem, conventional simulations in physical statistical mechanical ensembles, such as the canonical ensemble with fixed temperature, face a great difficulty. This is because there exist a huge number of local-minimum-energy states in the system and the conventional simulations tend to get trapped in these states, giving wrong results. Generalized-ensemble algorithms are based on artificial unphysical ensembles and overcome the above difficulty by performing random walks in potential energy, volume, and other physical quantities or their corresponding conjugate parameters such as temperature, pressure, etc. The advantage of generalized-ensemble simulations lies in the fact that they not only avoid getting trapped in states of energy local minima but also allows the calculations of physical quantities as functions of temperature or other parameters from a single simulation run. In this article we review the generalized-ensemble algorithms. Four examples, multicanonical algorithm, replica-exchange method, replica-exchange multicanonical algorithm, and multicanonical replica-exchange method, are described in detail. Examples of their applications to the protein folding problem are presented.

  17. On the single-mass model of the vocal folds

    International Nuclear Information System (INIS)

    Howe, M S; McGowan, R S

    2010-01-01

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

  18. Folding and unfolding of large-size shell construction for application in Earth orbit

    Science.gov (United States)

    Kondyurin, Alexey; Pestrenina, Irena; Pestrenin, Valery; Rusakov, Sergey

    2016-07-01

    A future exploration of space requires a technology of large module for biological, technological, logistic and other applications in Earth orbits [1-3]. This report describes the possibility of using large-sized shell structures deployable in space. Structure is delivered to the orbit in the spaceship container. The shell is folded for the transportation. The shell material is either rigid plastic or multilayer prepreg comprising rigid reinforcements (such as reinforcing fibers). The unfolding process (bringing a construction to the unfolded state by loading the internal pressure) needs be considered at the presence of both stretching and bending deformations. An analysis of the deployment conditions (the minimum internal pressure bringing a construction from the folded state to the unfolded state) of large laminated CFRP shell structures is formulated in this report. Solution of this mechanics of deformable solids (MDS) problem of the shell structure is based on the following assumptions: the shell is made of components whose median surface has a reamer; in the separate structural element relaxed state (not stressed and not deformed) its median surface coincides with its reamer (this assumption allows choose the relaxed state of the structure correctly); structural elements are joined (sewn together) by a seam that does not resist rotation around the tangent to the seam line. The ways of large shell structures folding, whose median surface has a reamer, are suggested. Unfolding of cylindrical, conical (full and truncated cones), and large-size composite shells (cylinder-cones, cones-cones) is considered. These results show that the unfolding pressure of such large-size structures (0.01-0.2 atm.) is comparable to the deploying pressure of pneumatic parts (0.001-0.1 atm.) [3]. It would be possible to extend this approach to investigate the unfolding process of large-sized shells with ruled median surface or for non-developable surfaces. This research was

  19. Altering protein surface charge with chemical modification modulates protein–gold nanoparticle aggregation

    International Nuclear Information System (INIS)

    Jamison, Jennifer A.; Bryant, Erika L.; Kadali, Shyam B.; Wong, Michael S.; Colvin, Vicki L.; Matthews, Kathleen S.; Calabretta, Michelle K.

    2011-01-01

    Gold nanoparticles (AuNP) can interact with a wide range of molecules including proteins. Whereas significant attention has focused on modifying the nanoparticle surface to regulate protein–AuNP assembly or influence the formation of the protein “corona,” modification of the protein surface as a mechanism to modulate protein–AuNP interaction has been less explored. Here, we examine this possibility utilizing three small globular proteins—lysozyme with high isoelectric point (pI) and established interactions with AuNP; α-lactalbumin with similar tertiary fold to lysozyme but low pI; and myoglobin with a different globular fold and an intermediate pI. We first chemically modified these proteins to alter their charged surface functionalities, and thereby shift protein pI, and then applied multiple methods to assess protein–AuNP assembly. At pH values lower than the anticipated pI of the modified protein, AuNP exposure elicits changes in the optical absorbance of the protein–NP solutions and other properties due to aggregate formation. Above the expected pI, however, protein–AuNP interaction is minimal, and both components remain isolated, presumably because both species are negatively charged. These data demonstrate that protein modification provides a powerful tool for modulating whether nanoparticle–protein interactions result in material aggregation. The results also underscore that naturally occurring protein modifications found in vivo may be critical in defining nanoparticle–protein corona compositions.

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

    Science.gov (United States)

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

    2007-05-22

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

  1. Quantification of Porcine Vocal Fold Geometry.

    Science.gov (United States)

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

    2016-07-01

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

  2. Graph-representation of oxidative folding pathways

    Directory of Open Access Journals (Sweden)

    Kaján László

    2005-01-01

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

  3. A promising new mechanism of ionizing radiation detection for positron emission tomography: modulation of optical properties

    Science.gov (United States)

    Tao, Li; Daghighian, Henry M.; Levin, Craig S.

    2016-11-01

    Using conventional scintillation detection, the fundamental limit in positron emission tomography (PET) time resolution is strongly dependent on the inherent temporal variances generated during the scintillation process, yielding an intrinsic physical limit for the coincidence time resolution of around 100 ps. On the other hand, modulation mechanisms of the optical properties of a material exploited in the optical telecommunications industry can be orders of magnitude faster. In this paper we borrow from the concept of optics pump-probe measurement to for the first time study whether ionizing radiation can produce modulations of optical properties, which can be utilized as a novel method for radiation detection. We show that a refractive index modulation of approximately 5× {{10}-6} is induced by interactions in a cadmium telluride (CdTe) crystal from a 511 keV photon source. Furthermore, using additional radionuclide sources, we show that the amplitude of the optical modulation signal varies linearly with both the detected event rate and average photon energy of the radiation source.

  4. 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)

  5. 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.

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

    Science.gov (United States)

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

    2003-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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

  9. Signal modulation as a mechanism for handicap disposal

    Science.gov (United States)

    Gavassa, Sat; Silva, Ana C.; Gonzalez, Emmanuel; Stoddard, Philip K.

    2012-01-01

    Signal honesty may be compromised when heightened competition provides incentive for signal exaggeration. Some degree of honesty might be maintained by intrinsic handicap costs on signalling or through imposition of extrinsic costs, such as social punishment of low quality cheaters. Thus, theory predicts a delicate balance between signal enhancement and signal reliability that varies with degree of social competition, handicap cost, and social cost. We investigated whether male sexual signals of the electric fish Brachyhypopomus gauderio would become less reliable predictors of body length when competition provides incentives for males to boost electric signal amplitude. As expected, social competition under natural field conditions and in controlled lab experiments drove males to enhance their signals. However, signal enhancement improved the reliability of the information conveyed by the signal, as revealed in the tightening of the relationship between signal amplitude and body length. Signal augmentation in male B. gauderio was independent of body length, and thus appeared not to be curtailed through punishment of low quality (small) individuals. Rather, all individuals boosted their signals under high competition, but those whose signals were farthest from the predicted value under low competition boosted signal amplitude the most. By elimination, intrinsic handicap cost of signal production, rather than extrinsic social cost, appears to be the basis for the unexpected reinforcement of electric signal honesty under social competition. Signal modulation may provide its greatest advantage to the signaller as a mechanism for handicap disposal under low competition rather than as a mechanism for exaggeration of quality under high competition. PMID:22665940

  10. 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.

  11. Six-state, three-level, six-fold ferromagnetic wire system

    International Nuclear Information System (INIS)

    Blachowicz, T.; Ehrmann, A.

    2013-01-01

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

  12. Six-state, three-level, six-fold ferromagnetic wire system

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-15

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

  13. 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.

  14. The Mechanism Research of Qishen Yiqi Formula by Module-Network Analysis

    Directory of Open Access Journals (Sweden)

    Shichao Zheng

    2015-01-01

    Full Text Available Qishen Yiqi formula (QSYQ has the effect of tonifying Qi and promoting blood circulation, which is widely used to treat the cardiovascular diseases with Qi deficiency and blood stasis syndrome. However, the mechanism of QSYQ to tonify Qi and promote blood circulation is rarely reported at molecular or systems level. This study aimed to elucidate the mechanism of QSYQ based on the protein interaction network (PIN analysis. The targets’ information of the active components was obtained from ChEMBL and STITCH databases and was further used to search against protein-protein interactions by String database. Next, the PINs of QSYQ were constructed by Cytoscape and were analyzed by gene ontology enrichment analysis based on Markov Cluster algorithm. Finally, based on the topological parameters, the properties of scale-free, small world, and modularity of the QSYQ’s PINs were analyzed. And based on function modules, the mechanism of QSYQ was elucidated. The results indicated that Qi-tonifying efficacy of QSYQ may be partly attributed to the regulation of amino acid metabolism, carbohydrate metabolism, lipid metabolism, and cAMP metabolism, while QSYQ improves the blood stasis through the regulation of blood coagulation and cardiac muscle contraction. Meanwhile, the “synergy” of formula compatibility was also illuminated.

  15. 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.

  16. How Does Mg2+ Modulate the RNA Folding Mechanism: A Case Study of the G:C W:W Trans Basepair.

    Science.gov (United States)

    Halder, Antarip; Roy, Rohit; Bhattacharyya, Dhananjay; Mitra, Abhijit

    2017-07-25

    Reverse Watson-Crick G:C basepairs (G:C W:W Trans) occur frequently in different functional RNAs. This is one of the few basepairs whose gas-phase-optimized isolated geometry is inconsistent with the corresponding experimental geometry. Several earlier studies indicate that through post-transcriptional modification, direct protonation, or coordination with Mg 2+ , accumulation of positive charge near N7 of guanine can stabilize the experimental geometry. Interestingly, recent studies reveal significant variation in the position of putatively bound Mg 2+ . This, in conjunction with recently raised doubts regarding some of the Mg 2+ assignments near the imino nitrogen of guanine, is suggestive of the existence of multiple Mg 2+ binding modes for this basepair. Our detailed investigation of Mg 2+ -bound G:C W:W Trans pairs occurring in high-resolution RNA crystal structures shows that they are found in 14 different contexts, eight of which display Mg 2+ binding at the Hoogsteen edge of guanine. Further examination of occurrences in these eight contexts led to the characterization of three different Mg 2+ binding modes: 1) direct binding via N7 coordination, 2) direct binding via O6 coordination, and 3) binding via hydrogen-bonding interaction with the first-shell water molecules. In the crystal structures, the latter two modes are associated with a buckled and propeller-twisted geometry of the basepair. Interestingly, respective optimized geometries of these different Mg 2+ binding modes (optimized using six different DFT functionals) are consistent with their corresponding experimental geometries. Subsequent interaction energy calculations at the MP2 level, and decomposition of its components, suggest that for G:C W:W Trans , Mg 2+ binding can fine tune the basepair geometries without compromising with their stability. Our results, therefore, underline the importance of the mode of binding of Mg 2+ ions in shaping RNA structure, folding and function. Copyright

  17. 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.

  18. Longitudinal On-Column Thermal Modulation for Comprehensive Two-Dimensional Liquid Chromatography.

    Science.gov (United States)

    Creese, Mari E; Creese, Mathew J; Foley, Joe P; Cortes, Hernan J; Hilder, Emily F; Shellie, Robert A; Breadmore, Michael C

    2017-01-17

    Longitudinal on-column thermal modulation for comprehensive two-dimensional liquid chromatography is introduced. Modulation optimization involved a systematic investigation of heat transfer, analyte retention, and migration velocity at a range of temperatures. Longitudinal on-column thermal modulation was realized using a set of alkylphenones and compared to a conventional valve-modulator employing sample loops. The thermal modulator showed a reduced modulation-induced pressure impact than valve modulation, resulting in reduced baseline perturbation by a factor of 6; yielding a 6-14-fold improvement in signal-to-noise. A red wine sample was analyzed to demonstrate the potential of the longitudinal on-column thermal modulator for separation of a complex sample. Discrete peaks in the second dimension using the thermal modulator were 30-55% narrower than with the valve modulator. The results shown herein demonstrate the benefits of an active focusing modulator, such as reduced detection limits and increased total peak capacity.

  19. Current Treatment Options for Bilateral Vocal Fold Paralysis: A State-of-the-Art Review

    Science.gov (United States)

    Li, Yike; Garrett, Gaelyn; Zealear, David

    2017-01-01

    Vocal fold paralysis (VFP) refers to neurological causes of reduced or absent movement of one or both vocal folds. Bilateral VFP (BVFP) is characterized by inspiratory dyspnea due to narrowing of the airway at the glottic level with both vocal folds assuming a paramedian position. The primary objective of intervention for BVFP is to relieve patients’ dyspnea. Common clinical options for management include tracheostomy, arytenoidectomy and cordotomy. Other options that have been used with varying success include reinnervation techniques and botulinum toxin (Botox) injections into the vocal fold adductors. More recently, research has focused on neuromodulation, laryngeal pacing, gene therapy, and stem cell therapy. These newer approaches have the potential advantage of avoiding damage to the voicing mechanism of the larynx with an added goal of restoring some physiologic movement of the affected vocal folds. However, clinical data are scarce for these new treatment options (i.e., reinnervation and pacing), so more investigative work is needed. These areas of research are expected to provide dramatic improvements in the treatment of BVFP. PMID:28669149

  20. 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.

  1. Self-folding origami at any energy scale

    Science.gov (United States)

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

    2017-05-01

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

  2. 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.

  3. Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

    Science.gov (United States)

    Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

    2015-12-15

    Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Photodynamic therapy induces antifibrotic alterations in primary human vocal fold fibroblasts.

    Science.gov (United States)

    Zhang, Chi; Wang, Jiajia; Chou, Adriana; Gong, Ting; Devine, Erin E; Jiang, Jack J

    2018-04-18

    Photodynamic therapy (PDT) is a promising treatment modality for laryngeal dysplasia, early-stage carcinoma, and papilloma, and was reported to have the ability to preserve laryngeal function and voice quality without clinical fibrotic response. We aimed to investigate the mechanism behind the antifibrotic effects of PDT on primary human vocal fold fibroblasts (VFFs) in vitro. In vitro analysis from one human donor. Cell viability of VFFs in response to varying doses of PDT was investigated by the Cell Counting Kit-8 method. Sublethal-dose PDT (SL-PDT) was used for the following experiments. Expression of genes related to vocal fold extracellular matrix formation was analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. Effects of PDT on cell migration, collagen contraction, and transforming growth factor β-1 (TGF-β1)-induced myofibroblast differentiation were also analyzed. PDT affects the viability of VFFs in a dose-dependent manner. SL-PDT significantly changed the expression profile of VFFs with antifibrotic effects. It also inhibited cell migration, reduced collagen contraction, and reversed the fibroblast-myofibroblast differentiation induced by TGF-β1. SL-PDT induces antifibrotic alterations in VFFs. This could explain the low incidence of vocal fold scar associated with PDT. Moreover, PDT may be useful in treating existing vocal fold scars. Further studies should focus on the in vivo effect of PDT on vocal fold wound healing and scar remodeling. NA Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Vocal Fold Vibratory Changes Following Surgical Intervention.

    Science.gov (United States)

    Chen, Wenli; Woo, Peak; Murry, Thomas

    2016-03-01

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

  6. 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.

  7. 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.

  8. 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.

  9. Mechanical and structural modules in a nuclear power plant advantages of the innovative approach

    International Nuclear Information System (INIS)

    Orlandi, S.; De Angelis, F.; Marconi, M.

    2010-01-01

    The modular layout design of a Nuclear Power Plant like the Westinghouse AP600/AP1000 has been developed basically to gain advantages in erection time schedule as well as in minimizing commissioning and start up test to be performed in the field. It is the first time for a Nuclear Power Plant to have a layout configuration fully designed as structured integrated mechanical Modules; this approach has been studied and implemented also to consider already in design phase decommissioning requirements which are mandatory to be able to perform dismantling at the end of the Plant Operation Life. Nevertheless it is the first time the possibility has been investigated to erect the civil structures as structural prefabricated modules: it means to have developed special composite structures which cannot be considered traditional reinforced concrete structures as well as structural beams frames. An approach like the above promotes impressive advantages in terms of extensive prefabrication in the workshops both for mechanical and structural modules, arranging in the workshops also factory acceptance tests as well as specific pre-acceptance commissioning activities. It means also that specific requirements have to be implemented in order to promote the implementation of this technology. Construction and adjustments flexibility in the field during NPP erection is heavily decreased due to modular prefabricated assemblies as well as it is mandatory to complete all the lay out plant design before entering the prefabrication phase in the workshops. Also structural design codes have to be qualified or properly readjusted to manage structural problems in composite structural frames which are innovative for organization, structural behaviour and which have different working ways starting from prefabrication, transportation, lifting up to the installation in the field and concrete pouring. (authors)

  10. 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....

  11. 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.

  12. Dynamics of Folds in the Plane

    Science.gov (United States)

    Krylov, Nikolai A.; Rogers, Edwin L.

    2011-01-01

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

  13. The optical-mechanical design of DMD modulation imaging device

    Science.gov (United States)

    Li, Tianting; Xu, Xiping; Qiao, Yang; Li, Lei; Pan, Yue

    2014-09-01

    In order to avoid the phenomenon of some image information were lost, which is due to the jamming signals, such as incident laser, make the pixels dot on CCD saturated. In this article a device of optical-mechanical structure was designed, which utilized the DMD (Digital Micro mirror Device) to modulate the image. The DMD reflection imaging optical system adopts the telecentric light path. However, because the design is not only required to guarantee a 66° angle between the optical axis of the relay optics and the DMD, but also to ensure that the optical axis of the projection system keeps parallel with the perpendicular bisector of the micro-mirror which is in the "flat" state, so the TIR prism is introduced,and making the relay optics and the DMD satisfy the optical institution's requirements. In this paper, a mechanical structure of the imaging optical system was designed and at the meanwhile the lens assembly has been well connected and fixed and fine-tuned by detailed structural design, which included the tilt decentered lens, wedge flanges, prisms. By optimizing the design, the issues of mutual restraint between the inverting optical system and the projecting system were well resolved, and prevented the blocking of the two systems. In addition, the structure size of the whole DMD reflection imaging optical system was minimized; it reduced the energy loss and ensured the image quality.

  14. 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...

  15. Origami-Inspired Folding of Thick, Rigid Panels

    Science.gov (United States)

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

    2014-01-01

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

  16. Modulational effects in accelerators

    International Nuclear Information System (INIS)

    Satogata, T.

    1997-01-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed

  17. 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.

  18. 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.

  19. 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 \

  20. A3 Adenosine Receptor Allosteric Modulator Induces an Anti-Inflammatory Effect: In Vivo Studies and Molecular Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Shira Cohen

    2014-01-01

    Full Text Available The A3 adenosine receptor (A3AR is overexpressed in inflammatory cells and in the peripheral blood mononuclear cells of individuals with inflammatory conditions. Agonists to the A3AR are known to induce specific anti-inflammatory effects upon chronic treatment. LUF6000 is an allosteric compound known to modulate the A3AR and render the endogenous ligand adenosine to bind to the receptor with higher affinity. The advantage of allosteric modulators is their capability to target specifically areas where adenosine levels are increased such as inflammatory and tumor sites, whereas normal body cells and tissues are refractory to the allosteric modulators due to low adenosine levels. LUF6000 administration induced anti-inflammatory effect in 3 experimental animal models of rat adjuvant induced arthritis, monoiodoacetate induced osteoarthritis, and concanavalin A induced liver inflammation in mice. The molecular mechanism of action points to deregulation of signaling proteins including PI3K, IKK, IκB, Jak-2, and STAT-1, resulting in decreased levels of NF-κB, known to mediate inflammatory effects. Moreover, LUF6000 induced a slight stimulatory effect on the number of normal white blood cells and neutrophils. The anti-inflammatory effect of LUF6000, mechanism of action, and the differential effects on inflammatory and normal cells position this allosteric modulator as an attractive and unique drug candidate.

  1. Guiding the folding pathway of DNA origami.

    Science.gov (United States)

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

    2015-09-03

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  3. Microarray and pathway analysis reveal distinct mechanisms underlying cannabinoid-mediated modulation of LPS-induced activation of BV-2 microglial cells.

    Directory of Open Access Journals (Sweden)

    Ana Juknat

    Full Text Available Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS to activate BV-2 microglial cells, we examined how Δ(9-tetrahydrocannabinol (THC, the major psychoactive component of marijuana, and cannabidiol (CBD the non-psychoactive component, modulate the inflammatory response. Microarray analysis of genome-wide mRNA levels was performed using Illumina platform and the resulting expression patterns analyzed using the Ingenuity Pathway Analysis to identify functional subsets of genes, and the Ingenuity System Database to denote the gene networks regulated by CBD and THC. From the 5338 transcripts that were differentially expressed across treatments, 400 transcripts were found to be upregulated by LPS, 502 by CBD+LPS and 424 by THC+LPS, while 145 were downregulated by LPS, 297 by CBD+LPS and 149 by THC+LPS, by 2-fold or more (p≤0.005. Results clearly link the effects of CBD and THC to inflammatory signaling pathways and identify new cannabinoid targets in the MAPK pathway (Dusp1, Dusp8, Dusp2, cell cycle related (Cdkn2b, Gadd45a as well as JAK/STAT regulatory molecules (Socs3, Cish, Stat1. The impact of CBD on LPS-stimulated gene expression was greater than that of THC. We attribute this difference to the fact that CBD highly upregulated several genes encoding negative regulators of both NFκB and AP-1 transcriptional activities, such as Trib3 and Dusp1 known to be modulated through Nrf2 activation. The CBD-specific expression profile reflected changes associated with oxidative stress and glutathione depletion via Trib3 and expression of ATF4 target genes. Furthermore, the CBD affected genes were shown to be controlled by nuclear factors usually involved in regulation of stress response and inflammation, mainly via Nrf2/Hmox1 axis and the Nrf2/ATF4-Trib3 pathway. These observations indicate that CBD, and less so THC, induce a cellular stress

  4. Folding kinetics of WW domains with the united residue force field for bridging microscopic motions and experimental measurements.

    Science.gov (United States)

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

    2014-12-23

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

  5. 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...

  6. 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

  7. Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.

    Science.gov (United States)

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

    2017-03-07

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

  8. 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.

  9. Structural basis of the 9-fold symmetry of centrioles.

    Science.gov (United States)

    Kitagawa, Daiju; Vakonakis, Ioannis; Olieric, Natacha; Hilbert, Manuel; Keller, Debora; Olieric, Vincent; Bortfeld, Miriam; Erat, Michèle C; Flückiger, Isabelle; Gönczy, Pierre; Steinmetz, Michel O

    2011-02-04

    The centriole, and the related basal body, is an ancient organelle characterized by a universal 9-fold radial symmetry and is critical for generating cilia, flagella, and centrosomes. The mechanisms directing centriole formation are incompletely understood and represent a fundamental open question in biology. Here, we demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization is essential for centriole formation in C. elegans and human cells. We further generate a structural model of the related protein Bld12p from C. reinhardtii, in which nine homodimers assemble into a ring from which nine coiled-coil rods radiate outward. Moreover, we demonstrate that recombinant Bld12p self-assembles into structures akin to the central hub of the cartwheel, which serves as a scaffold for centriole formation. Overall, our findings establish a structural basis for the universal 9-fold symmetry of centrioles. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Modulating conscious movement intention by noninvasive brain stimulation and the underlying neural mechanisms.

    Science.gov (United States)

    Douglas, Zachary H; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M; He, Biyu J

    2015-05-06

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60-70 ms earlier. Slow brain waves recorded ∼2-3 s before movement onset, as well as hundreds of milliseconds after movement onset, independently correlated with the modulation of conscious intention by brain stimulation. These brain activities together accounted for 81% of interindividual variability in the modulation of movement intention by brain stimulation. A computational model using coupled leaky integrator units with biophysically plausible assumptions about the effect of tDCS captured the effects of stimulation on both neural activity and behavior. These results reveal a temporally extended brain process underlying conscious movement intention that spans seconds around movement commencement. Copyright © 2015 Douglas et al.

  11. 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.

  12. 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.

  13. A mechanism for frequency modulation in songbirds shared with humans.

    Science.gov (United States)

    Amador, Ana; Margoliash, Daniel

    2013-07-03

    In most animals that vocalize, control of fundamental frequency is a key element for effective communication. In humans, subglottal pressure controls vocal intensity but also influences fundamental frequency during phonation. Given the underlying similarities in the biomechanical mechanisms of vocalization in humans and songbirds, songbirds offer an attractive opportunity to study frequency modulation by pressure. Here, we present a novel technique for dynamic control of subsyringeal pressure in zebra finches. By regulating the opening of a custom-built fast valve connected to the air sac system, we achieved partial or total silencing of specific syllables, and could modify syllabic acoustics through more complex manipulations of air sac pressure. We also observed that more nuanced pressure variations over a limited interval during production of a syllable concomitantly affected the frequency of that syllable segment. These results can be explained in terms of a mathematical model for phonation that incorporates a nonlinear description for the vocal source capable of generating the observed frequency modulations induced by pressure variations. We conclude that the observed interaction between pressure and frequency was a feature of the source, not a result of feedback control. Our results indicate that, beyond regulating phonation or its absence, regulation of pressure is important for control of fundamental frequencies of vocalizations. Thus, although there are separate brainstem pathways for syringeal and respiratory control of song production, both can affect airflow and frequency. We hypothesize that the control of pressure and frequency is combined holistically at higher levels of the vocalization pathways.

  14. Kinetics, Ca2+ dependence, and biophysical properties of integrin-mediated mechanical modulation of transmitter release from frog motor nerve terminals

    Science.gov (United States)

    Chen, B. M.; Grinnell, A. D.

    1997-01-01

    Neurotransmitter release from frog motor nerve terminals is strongly modulated by change in muscle length. Over the physiological range, there is an approximately 10% increase in spontaneous and evoked release per 1% muscle stretch. Because many muscle fibers do not receive suprathreshold synaptic inputs at rest length, this stretch-induced enhancement of release constitutes a strong peripheral amplifier of the spinal stretch reflex. The stretch modulation of release is inhibited by peptides that block integrin binding of natural ligands. The modulation varies linearly with length, with a delay of no more than approximately 1-2 msec and is maintained constant at the new length. Moreover, the stretch modulation persists in a zero Ca2+ Ringer and, hence, is not dependent on Ca2+ influx through stretch activated channels. Eliminating transmembrane Ca2+ gradients and buffering intraterminal Ca2+ to approximately normal resting levels does not eliminate the modulation, suggesting that it is not the result of release of Ca2+ from internal stores. Finally, changes in temperature have no detectable effect on the kinetics of stretch-induced changes in endplate potential (EPP) amplitude or miniature EPP (mEPP) frequency. We conclude, therefore, that stretch does not act via second messenger pathways or a chemical modification of molecules involved in the release pathway. Instead, there is direct mechanical modulation of release. We postulate that tension on integrins in the presynaptic membrane is transduced mechanically into changes in the position or conformation of one or more molecules involved in neurotransmitter release, altering sensitivity to Ca2+ or the equilibrium for a critical reaction leading to vesicle fusion.

  15. 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.

  16. Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

    Science.gov (United States)

    Song, Min Jae; Dean, David; Knothe Tate, Melissa L

    2013-07-01

    Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Insights into the role of elastin in vocal fold health and disease

    Science.gov (United States)

    Moore, Jaime

    2011-01-01

    Elastic fibers are large, complex and surprisingly poorly understood extracellular matrix (ECM) macromolecules. The elastin fiber, generated from a single human gene - elastin (ELN), is a self assembling integral protein that endows critical mechanic proprieties to elastic tissues and organs such as the skin, lungs, and arteries. The biology of elastic fibers is complex because they have multiple components, a tightly regulated developmental deposition, a multi-step hierarchical assembly and unique biomechanical functions. Elastin is present in vocal folds, where it plays a pivotal role in the quality of phonation. This review article provides an overview of the genesis of elastin and its wide- ranging structure and function. Specific distribution within the vocal fold lamina propria across the lifespan in normal and pathological states and its contribution to vocal fold biomechanics will be examined. Elastin and elastin-derived molecules are increasingly investigated for their application in tissue engineering. The properties of various elastin– based materials will be discussed and their current and future applications evaluated. A new level of understanding of the biomechanical properties of vocal fold elastin composites and their molecular basis should lead to new strategies for elastic fiber repair and regeneration in aging and disease. PMID:21708449

  2. Response to a temperature modulation as a signature of chemical mechanisms.

    Science.gov (United States)

    Berthoumieux, H; Jullien, L; Lemarchand, A

    2007-11-01

    We consider n reactive species involved in unimolecular reactions and submitted to a temperature modulation of small amplitude. We determine the conditions on the rate constants for which the deviations from the equilibrium concentrations of each species can be optimized and find the analytical expression of the frequency associated with an extremum of concentration shift in the case n=3. We prove that the frequency dependence of the displacement of equilibrium gives access to the number n of species involved in the mechanism. We apply the results to the case of the transformation of a reactant into a product through a possible reactive intermediate and find the order relation obeyed by the activation energies of the different barriers. The results typically apply to enzymatic catalysis with kinetics of Michaelis-Menten type.

  3. 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.

  4. Differential saturation study of radial and angular modulation mechanisms of electron spin--lattice relaxation for trapped hydrogen atoms in sulfuric acid glasses. [X radiation

    Energy Technology Data Exchange (ETDEWEB)

    Plonka, A; Kevan, L

    1976-11-01

    A differential ESR saturation study of allowed transitions and forbidden proton spin-flip satellite transitions for trapped hydrogen atoms in sulfuric acid glasses indicates that angular modulation dominates the spin-lattice relaxation mechanisms and suggests that the modulation arises from motion of the H atom.

  5. Electromagneto-mechanical coupling analysis of a test module in J-TEXT Tokamak during plasma disruption

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Haijie; Yuan, Zhensheng; Yuan, Hongwei; Pei, Cuixiang [State Key Laboratory for Strength and Vibration of Mechanical Structures, Shanxi Engineering Research Center for NDT and Structural Integrity Evaluation Xi’an Jiaotong University, Xi’an 710049 (China); Chen, Zhenmao, E-mail: chenzm@mail.xjtu.edu.cn [State Key Laboratory for Strength and Vibration of Mechanical Structures, Shanxi Engineering Research Center for NDT and Structural Integrity Evaluation Xi’an Jiaotong University, Xi’an 710049 (China); Yang, Jinhong; Wang, Weihua [Institute of Applied Physics of AOA, Hefei 230031 (China)

    2016-11-01

    In this paper, the dynamic response during plasma disruption of a test blanket module in vacuum vessel (VV) of the Joint TEXT (J-TEXT), which is an experimental Tokamak device with iron core, was simulated by applying a program developed by authors on the ANSYS platform using its parametric design language (APDL). The moving coordinate method as well as the load transfer and sequential coupling strategy were adopted to cope with the electromagneto-mechanical coupling effect. To establish the numerical model, the influence of the iron core on the eddy current and electromagnetic (EM) force during disruption was numerically investigated at first and the influence was found not significant. Together with the geometrical features of the J-TEXT Tokamak structure, 180° sector models without magnetic core were finally established for the EM field and the structural response simulations. To obtain the source plasma current, the plasma current evolution during disruption was simulated by using the Tokamak Simulation Code (TSC). With the numerical models and the source plasma current, the dynamic response of both the VV structure and the test module were calculated. The numerical results show that the maximum stress of the test module is in safe range, and the magnetic damping effect can weaken vibration of the test module. In addition, simulation without considering the coupling effect was carried out, which shows that the influence of coupling effect is not significant for the peak stress of the J-TEXT disruption problem.

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

    Science.gov (United States)

    Sun, Shuai; Hou, Guiting; Zheng, Chunfang

    2017-11-01

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

  7. Excavation of attractor modules for nasopharyngeal carcinoma via integrating systemic module inference with attract method.

    Science.gov (United States)

    Jiang, T; Jiang, C-Y; Shu, J-H; Xu, Y-J

    2017-07-10

    The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

  8. A Bystander Mechanism Explains the Specific Phenotype of a Broadly Expressed Misfolded Protein.

    Directory of Open Access Journals (Sweden)

    Lauren Klabonski

    2016-12-01

    Full Text Available Misfolded proteins in transgenic models of conformational diseases interfere with proteostasis machinery and compromise the function of many structurally and functionally unrelated metastable proteins. This collateral damage to cellular proteins has been termed 'bystander' mechanism. How a single misfolded protein overwhelms the proteostasis, and how broadly-expressed mutant proteins cause cell type-selective phenotypes in disease are open questions. We tested the gain-of-function mechanism of a R37C folding mutation in an endogenous IGF-like C.elegans protein DAF-28. DAF-28(R37C is broadly expressed, but only causes dysfunction in one specific neuron, ASI, leading to a distinct developmental phenotype. We find that this phenotype is caused by selective disruption of normal biogenesis of an unrelated endogenous protein, DAF-7/TGF-β. The combined deficiency of DAF-28 and DAF-7 biogenesis, but not of DAF-28 alone, explains the gain-of-function phenotype-deficient pro-growth signaling by the ASI neuron. Using functional, fluorescently-tagged protein, we find that, in animals with mutant DAF-28/IGF, the wild-type DAF-7/TGF-β is mislocalized to and accumulates in the proximal axon of the ASI neuron. Activation of two different branches of the unfolded protein response can modulate both the developmental phenotype and DAF-7 mislocalization in DAF-28(R37C animals, but appear to act through divergent mechanisms. Our finding that bystander targeting of TGF-β explains the phenotype caused by a folding mutation in an IGF-like protein suggests that, in conformational diseases, bystander misfolding may specify the distinct phenotypes caused by different folding mutations.

  9. [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.

  10. Effects of Jae-Seng Acupuncture Treatment on the Improvement of Nasolabial Folds and Eye Wrinkles

    Directory of Open Access Journals (Sweden)

    Jin Hyong Cho

    2015-01-01

    Full Text Available The microneedle therapy system (MTS, a mechanical method involving making minute multiple holes in the skin, reportedly improves skin condition, such as by reducing flushing and melanin. A newly attempted bloodletting therapy, Jae-Seng Acupuncture, has several advantages over traditional mechanical punching methods because it allows the practitioner to regulate the depth and direction of needle stimulations and to choose whether to stimulate the muscle layers. This study was conducted to determine the efficacy of Jae-Seng Acupuncture in the treatment of nasolabial folds and eye wrinkles. The nasolabial folds and eye wrinkles of 107 patients ranging in age from their 20s to their 70s were subjected to DermaVision, a digital skin image analyzer, before the treatment and one to six months after treatment. Additionally, stimulation of the meridians, such as Taeyang, Tongjaryo, Chongmyong, Sungup, Sabaek, Yonghyang, Chichang, Taeyong, was performed to improve the function of the stomach, large intestine. Analyses of the images indicate that Jae-Seng Acupuncture improved nasolabial folds and eye wrinkles, suggesting that this technique is a safe and effective method for the improvement of facial skin conditions.

  11. Exploiting the gain-modulation mechanism in parieto-motor neurons: application to visuomotor transformations and embodied simulation.

    Science.gov (United States)

    Mahé, Sylvain; Braud, Raphaël; Gaussier, Philippe; Quoy, Mathias; Pitti, Alexandre

    2015-02-01

    The so-called self-other correspondence problem in imitation demands to find the transformation that maps the motor dynamics of one partner to our own. This requires a general purpose sensorimotor mechanism that transforms an external fixation-point (partner's shoulder) reference frame to one's own body-centered reference frame. We propose that the mechanism of gain-modulation observed in parietal neurons may generally serve these types of transformations by binding the sensory signals across the modalities with radial basis functions (tensor products) on the one hand and by permitting the learning of contextual reference frames on the other hand. In a shoulder-elbow robotic experiment, gain-field neurons (GF) intertwine the visuo-motor variables so that their amplitude depends on them all. In situations of modification of the body-centered reference frame, the error detected in the visuo-motor mapping can serve then to learn the transformation between the robot's current sensorimotor space and the new one. These situations occur for instance when we turn the head on its axis (visual transformation), when we use a tool (body modification), or when we interact with a partner (embodied simulation). Our results defend the idea that the biologically-inspired mechanism of gain modulation found in parietal neurons can serve as a basic structure for achieving nonlinear mapping in spatial tasks as well as in cooperative and social functions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Coxiella burnetii Nine Mile II proteins modulate gene expression of monocytic host cells during infection

    Directory of Open Access Journals (Sweden)

    Shaw Edward I

    2010-09-01

    Full Text Available Abstract Background Coxiella burnetii is an intracellular bacterial pathogen that causes acute and chronic disease in humans. Bacterial replication occurs within enlarged parasitophorous vacuoles (PV of eukaryotic cells, the biogenesis and maintenance of which is dependent on C. burnetii protein synthesis. These observations suggest that C. burnetii actively subverts host cell processes, however little is known about the cellular biology mechanisms manipulated by the pathogen during infection. Here, we examined host cell gene expression changes specifically induced by C. burnetii proteins during infection. Results We have identified 36 host cell genes that are specifically regulated when de novo C. burnetii protein synthesis occurs during infection using comparative microarray analysis. Two parallel sets of infected and uninfected THP-1 cells were grown for 48 h followed by the addition of chloramphenicol (CAM to 10 μg/ml in one set. Total RNA was harvested at 72 hpi from all conditions, and microarrays performed using Phalanx Human OneArray™ slides. A total of 784 (mock treated and 901 (CAM treated THP-1 genes were up or down regulated ≥2 fold in the C. burnetii infected vs. uninfected cell sets, respectively. Comparisons between the complementary data sets (using >0 fold, eliminated the common gene expression changes. A stringent comparison (≥2 fold between the separate microarrays revealed 36 host cell genes modulated by C. burnetii protein synthesis. Ontological analysis of these genes identified the innate immune response, cell death and proliferation, vesicle trafficking and development, lipid homeostasis, and cytoskeletal organization as predominant cellular functions modulated by C. burnetii protein synthesis. Conclusions Collectively, these data indicate that C. burnetii proteins actively regulate the expression of specific host cell genes and pathways. This is in addition to host cell genes that respond to the presence of the

  13. 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.

  14. Structural, micro-structural and kinematic analyses of channel flow in the Karmostaj salt diapir in the Zagros foreland folded belt, Fars province, Iran

    Science.gov (United States)

    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

  15. Physics of protein folding

    Science.gov (United States)

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

    2004-04-01

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

  16. Collapsible Photovoltaic Module for a Large-Scale Solar Power Plant

    DEFF Research Database (Denmark)

    2014-01-01

    An elongate photovoltaic (PV) module for use in a solar energy conversion plant for the production of electricity from incident light, the PV-module comprising a top portion with a support panel (G) carrying on a front side a plurality of electrically connected PV cells (D), and a transparent...... protective layer (A) sealed to the support panel (G) so as to encapsulate the PV-cells (D) between the support panel (G) and the protective layer (A), wherein prior to installation of the PV-module at the deployment site a collapsible portion of the PV-module is configured to be collapsible in a longitudinal...... direction by folding and/or rolling, wherein the collapsible portion includes at least the top portion, wherein the PV-module further comprises one or more integrated ballast chambers (I) in a bottom portion of the PV-module arranged on a rear side of the support panel (G), wherein said integrated ballast...

  17. 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.

  18. 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.

  19. 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

  20. Optimization of Modulator and Circuits for Low Power Continuous-Time Delta-Sigma ADC

    DEFF Research Database (Denmark)

    Marker-Villumsen, Niels; Bruun, Erik

    2014-01-01

    This paper presents a new optimization method for achieving a minimum current consumption in a continuous-time Delta-Sigma analog-to-digital converter (ADC). The method is applied to a continuous-time modulator realised with active-RC integrators and with a folded-cascode operational transconduc...... levels are swept. Based on the results of the circuit analysis, for each modulator combination the summed current consumption of the 1st integrator and quantizer of the ADC is determined. By also sweeping the partitioning of the noise power for the different circuit parts, the optimum modulator...

  1. A promising new mechanism of ionizing radiation detection for positron emission tomography: Modulation of optical properties

    OpenAIRE

    Tao, Li; Daghighian, Henry M.; Levin, Craig S.

    2016-01-01

    Using conventional scintillation detection, the fundamental limit in positron emission tomography (PET) time resolution is strongly dependent on the inherent temporal variances generated during the scintillation process, yielding an intrinsic physical limit for the coincidence time resolution of around 100 ps. On the other hand, modulation mechanisms of the optical properties of a material exploited in the optical telecommunications industry can be orders of magnitude faster. In this paper we...

  2. 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.

  3. Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats

    Science.gov (United States)

    Guo, Zhi-Ling; Li, Min; Longhurst, John C.

    2013-01-01

    Electroacupuncture (EA) at P5–P6 acupoints overlying the median nerves typically reduces sympathoexcitatory blood pressure (BP) reflex responses in eucapnic rats. Gastric distention in hypercapnic acidotic rats, by activating both vagal and sympathetic afferents, decreases heart rate (HR) and BP through actions in the rostral ventrolateral medulla (rVLM) and nucleus ambiguus (NAmb), leading to sympathetic withdrawal and parasympathetic activation, respectively. A GABAA mechanism in the rVLM mediates the decreased sympathetic outflow. The present study investigated the hypothesis that EA modulates gastric distention-induced hemodynamic depressor and bradycardia responses through nuclei that process parasympathetic and sympathetic outflow. Anesthetized hypercapnic acidotic rats manifested repeatable decreases in BP and HR with gastric distention every 10 min. Bilateral EA at P5–P6 for 30 min reversed the hypotensive response from −26 ± 3 to −6 ± 1 mmHg and the bradycardia from −35 ± 11 to −10 ± 3 beats/min for a period that lasted more than 70 min. Immunohistochemistry and in situ hybridization to detect c-Fos protein and GAD 67 mRNA expression showed that GABAergic caudal ventral lateral medulla (cVLM) neurons were activated by EA. Glutamatergic antagonism of cVLM neurons with kynurenic acid reversed the actions of EA. Gabazine used to block GABAA receptors microinjected into the rVLM or cVLM reversed EA's action on both the reflex depressor and bradycardia responses. EA modulation of the decreased HR was inhibited by microinjection of gabazine into the NAmb. Thus, EA through GABAA receptor mechanisms in the rVLM, cVLM, and NAmb modulates gastric distention-induced reflex sympathoinhibition and vagal excitation. PMID:23302958

  4. 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.

  5. Folding in and out: passive morphing in flapping wings.

    Science.gov (United States)

    Stowers, Amanda K; Lentink, David

    2015-03-25

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

  6. Folding and fracturing of rock adjacent to salt diapirs

    Science.gov (United States)

    Rowan, Mark G.

    2017-04-01

    When John Ramsay wrote his groundbreaking book in 1967, deformation around salt diapirs was not something he covered. At the time, most geologists considered diapirs to form due to density inversion, rising through thick overlying strata due to buoyancy. In doing so, salt was thought to shove aside the younger rocks, shearing and fracturing them in drag folds and supposedly producing "salt gouge". Even after it was realized that the majority of diapirs spend most of their history growing at or just beneath the surface, the relative rise of salt and sinking of minibasins were (and are) still thought by many to be accommodated in part by shear and fracturing of rocks in a collar zone around the salt. There are two arguments against this model. The first is mechanical: whereas halite behaves as a viscous fluid, even young sediment deforms as a brittle material with layer anisotropy. Thus, the salt-sediment interface is the outer margin of an intrasalt shear zone caused by viscous drag against the diapir margin. The velocity of salt flow decreases dramatically toward the edge of the diapir, so that the outermost salt effectively doesn't move. Hence, no shear or fracturing is expected in surrounding strata. The second and more important argument is that empirical field data do not support the idea of drag folds and associated deformation. Certainly, strata are typically folded and thinned adjacent to diapirs. However, stratal upturn is generated by monoclinal drape folding of the diapir roof over the edge of the rising salt, and thinning is caused by deposition onto the bathymetric highs formed by the diapirs, often supplemented by roof erosion and slumping. Halokinetic sequences observed in numerous salt basins (e.g., Paradox Basin, La Popa Basin, Spanish Pyrenees, Sivas Basin, Zagros Mountains, Kuqa Basin) contain no diapir-parallel shear zones and minimal thinning and fracturing caused by diapir rise. Even megaflaps, in which strata extend for kilometers up the sides

  7. Mechanical design of the folded waveguide for PBX-M and TFTR

    International Nuclear Information System (INIS)

    Fogelman, C.H.; Bigelow, T.S.; Yugo, J.J.

    1995-01-01

    The folded waveguide (FWG) antenna is an advanced Cyclotron Range of Frequencies launcher being designed at Oak Ridge National Laboratory in collaboration with Princeton Plasma Physics Laboratory. The FWG offers a drastic increase in radio frequency (RF) power density over typical loop antennas. It also results in internal electric fields of much lower magnitude near the plasma. It is scheduled for installation on either the Tokamak Fusion Test Reactor (TFTR) or the Princeton Beta Experiment-Modified (PBX-M) tokamak in January 1996. The design objective is to provide an FWG that can withstand the thermal loads and disruption scenarios and meet the space constants of both machines. The design is also intended to be prototypical for the International Thermonuclear Experimental Reactor (ITER). The FWG is fully retractable, and maintenance operations can be performed while the vessel remains under vacuum. The FWG can operate in fast-wave mode, or it can be retracted, rotated 90 degrees, and reengaged for the ion-Bernstein wave launch. The polarizing plate completely covers the front of the antenna, except for slots cut at every other gap between with plates of other configurations such as a 0-π dipole plate

  8. 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.

  9. 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...

  10. Design and simulation of origami structures with smooth folds.

    Science.gov (United States)

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

    2017-04-01

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

  11. Melody discrimination and protein fold classification

    Directory of Open Access Journals (Sweden)

    Robert P. Bywater

    2016-10-01

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

  12. 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....

  13. 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.

  14. 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.

  15. Interleukin-1β modulates endochondral ossification by human adult bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    M Mumme

    2012-09-01

    Full Text Available Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1β (IL-1β on the main events of endochondral bone formation by human bone marrow mesenchymal stromal cells (BM-MSC, namely cell proliferation, differentiation and maturation/remodelling of the resulting hypertrophic cartilage. Low doses of IL-1β (50 pg/mL enhanced colony-forming units-fibroblastic (CFU-f and -osteoblastic (CFU-o number (up to 1.5-fold and size (1.2-fold in the absence of further supplements and glycosaminoglycan accumulation (1.4-fold upon BM-MSC chondrogenic induction. In osteogenically cultured BM-MSC, IL-1β enhanced calcium deposition (62.2-fold and BMP-2 mRNA expression by differential activation of NF-κB and ERK signalling. IL-1β-treatment of BM-MSC generated cartilage resulted in higher production of MMP-13 (14.0-fold in vitro, mirrored by an increased accumulation of the cryptic cleaved fragment of aggrecan, and more efficient cartilage remodelling/resorption after 5 weeks in vivo (i.e., more TRAP positive cells and bone marrow, less cartilaginous areas, resulting in the formation of mature bone and bone marrow after 12 weeks. In conclusion, IL-1β finely modulates early and late events of the endochondral bone formation by BM-MSC. Controlling the inflammatory environment could enhance the success of therapeutic approaches for the treatment of fractures by resident MSC and as well as improve the engineering of implantable tissues.

  16. 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.

  17. 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.

  18. 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...

  19. Hydroxypropyl-sulfobutyl-β-cyclodextrin improves the oral bioavailability of edaravone by modulating drug efflux pump of enterocytes.

    Science.gov (United States)

    Rong, Wen-Ting; Lu, Ya-Peng; Tao, Qing; Guo, Miao; Lu, Yu; Ren, Yong; Yu, Shu-Qin

    2014-02-01

    The objective of the study was to evaluate the effect of hydroxypropyl-sulfobutyl-β-cyclodextrin (HP-SBE-βCD) on the bioavailability and intestinal absorption of edaravone, and identify its mechanism of action. We devised HP-SBE-βCD as a carrier and modulator of P-glycoprotein (Pgp) efflux pump, and edaravone as a model drug, and prepared edaravone/HP-SBE-βCD inclusion complex. HP-SBE-βCD improved the water solubility and enhanced the bioavailability of edaravone by 10.3-fold in rats. Then, in situ single-pass intestinal perfusion showed that HP-SBE-βCD had an effect of improving the permeability and inhibiting the efflux of edaravone. Furthermore, the effects of HP-SBE-βCD on Pgp were achieved through interfering with the lipid raft and depleting the cholesterol of enterocytes membrane. From the results, we presented the novel mechanisms. First, edaravone/HP-SBE-βCD had a lower release from the inclusion compound to protect edaravone from the low pH of the stomach. Then, HP-SBE-βCD modulated the membrane microenvironment of intestinal absorption epithelial cells. At last, the result was that HP-SBE-βCD enhanced the absorption of edaravone by interfering with Pgp. In conclusion, HP-SBE-βCD improves the bioavailability of drug not only because of its enhancing water solubility of the drug, but also because it modulates the Pgp-mediated efflux from enterocytes. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Multi-stability in folded shells: non-Euclidean origami

    Science.gov (United States)

    Evans, Arthur

    2015-03-01

    Both natural and man-made structures benefit from having multiple mechanically stable states, from the quick snapping motion of hummingbird beaks to micro-textured surfaces with tunable roughness. Rather than discuss special fabrication techniques for creating bi-stability through material anisotropy, in this talk I will present several examples of how folding a structure can modify the energy landscape and thus lead to multiple stable states. Using ideas from origami and differential geometry, I will discuss how deforming a non-Euclidean surface can be done either continuously or discontinuously, and explore the effects that global constraints have on the ultimate stability of the surface.

  1. Growth Mechanism of Pumpkin-Shaped Vaterite Hierarchical Structures

    Science.gov (United States)

    Ma, Guobin; Xu, Yifei; Wang, Mu

    2015-03-01

    CaCO3-based biominerals possess sophisticated hierarchical structures and promising mechanical properties. Recent researches imply that vaterite may play an important role in formation of CaCO3-based biominerals. However, as a less common polymorph of CaCO3, the growth mechanism of vaterite remains not very clear. Here we report the growth of a pumpkin-shaped vaterite hierarchical structure with a six-fold symmetrical axis and lamellar microstructure. We demonstrate that the growth is controlled by supersaturation and the intrinsic crystallographic anisotropy of vaterite. For the scenario of high supersaturation, the nucleation rate is higher than the lateral extension rate, favoring the ``double-leaf'' spherulitic growth. Meanwhile, nucleation occurs preferentially in as determined by the crystalline structure of vaterite, modulating the grown products with a hexagonal symmetry. The results are beneficial for an in-depth understanding of the biomineralization of CaCO3. The growth mechanism may also be applicable to interpret the formation of similar hierarchical structures of other materials. The authors gratefully acknowledge the financial support from National Science Foundation of China (Grant Nos. 51172104 and 50972057) and National Key Basic Research Program of China (Grant No. 2010CB630705).

  2. 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...

  3. 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.

  4. Hypercapnic acidosis modulates inflammation, lung mechanics, and edema in the isolated perfused lung.

    Science.gov (United States)

    De Smet, Hilde R; Bersten, Andrew D; Barr, Heather A; Doyle, Ian R

    2007-12-01

    Low tidal volume (V(T)) ventilation strategies may be associated with permissive hypercapnia, which has been shown by ex vivo and in vivo studies to have protective effects. We hypothesized that hypercapnic acidosis may be synergistic with low V(T) ventilation; therefore, we studied the effects of hypercapnia and V(T) on unstimulated and lipopolysaccharide-stimulated isolated perfused lungs. Isolated perfused rat lungs were ventilated for 2 hours with low (7 mL/kg) or moderately high (20 mL/kg) V(T) and 5% or 20% CO(2), with lipopolysaccharide or saline added to the perfusate. Hypercapnia resulted in reduced pulmonary edema, lung stiffness, tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the lavage and perfusate. The moderately high V(T) did not cause lung injury but increased lavage IL-6 and perfusate IL-6 as well as TNF-alpha. Pulmonary edema and respiratory mechanics improved, possibly as a result of a stretch-induced increase in surfactant turnover. Lipopolysaccharide did not induce significant lung injury. We conclude that hypercapnia exerts a protective effect by modulating inflammation, lung mechanics, and edema. The moderately high V(T) used in this study stimulated inflammation but paradoxically improved edema and lung mechanics with an associated increase in surfactant release.

  5. 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.

  6. 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

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

    Science.gov (United States)

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

    2016-09-01

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

  8. Characterization of fold defects in AZ91D and AE42 magnesium alloy permanent mold castings

    International Nuclear Information System (INIS)

    Bichler, L.; Ravindran, C.

    2010-01-01

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

  9. 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

  10. 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

  11. Hardness and Elastic Modulus on Six-Fold Symmetry Gold Nanoparticles

    Science.gov (United States)

    Ramos, Manuel; Ortiz-Jordan, Luis; Hurtado-Macias, Abel; Flores, Sergio; Elizalde-Galindo, José T.; Rocha, Carmen; Torres, Brenda; Zarei-Chaleshtori, Maryam; Chianelli, Russell R.

    2013-01-01

    The chemical synthesis of gold nanoparticles (NP) by using gold (III) chloride trihydrate (HAuCl∙3H2O) and sodium citrate as a reducing agent in aqueous conditions at 100 °C is presented here. Gold nanoparticles areformed by a galvanic replacement mechanism as described by Lee and Messiel. Morphology of gold-NP was analyzed by way of high-resolution transmission electron microscopy; results indicate a six-fold icosahedral symmetry with an average size distribution of 22 nm. In order to understand the mechanical behaviors, like hardness and elastic moduli, gold-NP were subjected to nanoindentation measurements—obtaining a hardness value of 1.72 GPa and elastic modulus of 100 GPa in a 3–5 nm of displacement at the nanoparticle’s surface. PMID:28809302

  12. 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...

  13. Indirect and two fold measurements in quantum mechanics

    International Nuclear Information System (INIS)

    Fer, Francis

    1981-01-01

    Keeping strictly in the positivist, probabilistic and hilbertian frame of quantum mechanics, the author develops a criticism of the accepted theory of indirect and twofold measurements. He shows that this theory cannot logically derive from the usual axiomatics, namely from the so-called reduction-of-state axiom. He proposes a modified statement (already used sometimes) of this axiom, which leads to a reliable theory of indirect and twofold measurements. The results are particularly: a) that a measurement made on a sub-system does not modify the mathematical representation of the complementary system, nor its prior probability distributions; b) that measurement is nothing else than an information which enables to correct the probabilities of further measurements according to the classical rules of the calculus of probabilities [fr

  14. Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

    Science.gov (United States)

    Chang, Joseph; Yung, Katherine C

    2014-11-01

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

  15. 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.

  16. Erythrocyte Saturation with IgG Is Required for Inducing Antibody-Mediated Immune Suppression and Impacts Both Erythrocyte Clearance and Antigen-Modulation Mechanisms.

    Science.gov (United States)

    Cruz-Leal, Yoelys; Marjoram, Danielle; Lazarus, Alan H

    2018-02-15

    Anti-D prevents hemolytic disease of the fetus and newborn, and this mechanism has been referred to as Ab-mediated immune suppression (AMIS). Anti-D, as well as other polyclonal AMIS-inducing Abs, most often induce both epitope masking and erythrocyte clearance mechanisms. We have previously observed that some Abs that successfully induce AMIS effects could be split into those that mediate epitope masking versus those that induce erythrocyte clearance, allowing the ability to analyze these mechanisms separately. In addition, AMIS-inducing activity has recently been shown to induce Ag modulation (Ag loss from the erythrocyte surface). To assess these mechanisms, we immunized mice with transgenic murine RBCs expressing a single Ag protein comprising a recombinant Ag composed of hen egg lysozyme, OVA sequences comprising aa 251-349, and the human Duffy transmembrane protein (HOD-Ag) with serial doses of polyclonal anti-OVA IgG as the AMIS-inducing Ab. The anti-OVA Ab induced AMIS in the absence of apparent epitope masking. AMIS occurred only when the erythrocytes appeared saturated with IgG. This Ab was capable of inducing HOD-RBC clearance, as well as loss of the OVA epitope at doses of Ab that caused AMIS effects. HOD-RBCs also lost reactivity with Abs specific for the hen egg lysozyme and Duffy portions of the Ag consistent with the initiation of Ag modulation and/or trogocytosis mechanisms. These data support the concept that an AMIS-inducing Ab that does not cause epitope masking can induce AMIS effects in a manner consistent with RBC clearance and/or Ag modulation. Copyright © 2018 by The American Association of Immunologists, Inc.

  17. 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.

  18. Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Ken Soderstrom

    2017-10-01

    Full Text Available Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

  19. Nested folded-beam suspensions with low longitudinal stiffness for comb-drive actuators

    International Nuclear Information System (INIS)

    Hou, Max T; Huang, Ming-Xian; Chang, Chao-Min

    2014-01-01

    Nested folded-beam suspensions with a low longitudinal spring constant and a high lateral spring constant have been used in comb-drive actuators. In the new design, every two flexible beams and two stiff members form a parallelogram flexure, which is considered as an ‘element’ of the nested folded-beam suspension. A set of these flexures of increasing size were placed one outside another to compose a nested structure. In this way, a serial mechanical connection between adjacent parallelogram flexures was formed; thus, a longer output stroke was obtained by combining the stroke displacements of all flexures in an additive fashion. The designed suspensions were theoretically analyzed and numerically simulated. Furthermore, comb-drive actuators with conventional and new suspensions were fabricated and tested to verify the predicted function. In the testing cases, the longitudinal spring constants of suspensions with two (conventional), three and four parallelogram flexures on each side were measured as 2.77, 1.75 and 1.36 N m −1 . The ratio among these three values was approximately 6:4:3, which is consistent with the theoretical predictions and simulation results. Microfabricated folded beams in series were achieved. (paper)

  20. Mechanisms of masked evaluative priming: task sets modulate behavioral and electrophysiological priming for picture and words differentially.

    Science.gov (United States)

    Kiefer, Markus; Liegel, Nathalie; Zovko, Monika; Wentura, Dirk

    2017-04-01

    Research with the evaluative priming paradigm has shown that affective evaluation processes reliably influence cognition and behavior, even when triggered outside awareness. However, the precise mechanisms underlying such subliminal evaluative priming effects, response activation vs semantic processing, are matter of a debate. In this study, we determined the relative contribution of semantic processing and response activation to masked evaluative priming with pictures and words. To this end, we investigated the modulation of masked pictorial vs verbal priming by previously activated perceptual vs semantic task sets and assessed the electrophysiological correlates of priming using event-related potential (ERP) recordings. Behavioral and electrophysiological effects showed a differential modulation of pictorial and verbal subliminal priming by previously activated task sets: Pictorial priming was only observed during the perceptual but not during the semantic task set. Verbal priming, in contrast, was found when either task set was activated. Furthermore, only verbal priming was associated with a modulation of the N400 ERP component, an index of semantic processing, whereas a priming-related modulation of earlier ERPs, indexing visuo-motor S-R activation, was found for both picture and words. The results thus demonstrate that different neuro-cognitive processes contribute to unconscious evaluative priming depending on the stimulus format. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  1. 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

  2. Modulation in vitro and in vivo of cytotoxicity but not cellular levels of doxorubicin by the calmodulin inhibitor trifluoperazine is dependent on the level of resistance.

    Science.gov (United States)

    Ganapathi, R.; Schmidt, H.; Grabowski, D.; Melia, M.; Ratliff, N.

    1988-01-01

    The role of the calmodulin inhibitor trifluoperazine (TFP) in modulating the cellular levels and cytotoxicity in vitro and antitumour effects in vivo of doxorubicin (DOX), was evaluated in progressively DOX-resistant (5- to 40-fold) sublines of B16-BL6 mouse melanoma. In parental-sensitive B16-BL6 cells treated for 3 h, the IC50 of DOX was 0.1 microgram ml-1, and a less than 2-fold enhancement in DOX cell kill in the presence of a noncytotoxic concentration of 5 microM TFP was observed. However, in the DOX-resistant sublines, the IC50 was 0.7 to 5.0 micrograms ml-1 DOX in the absence of 5 microM TFP and 0.3 to 0.7 microgram ml-1 DOX in the presence of 5 microM TFP. The 2- to 7.5-fold decrease in the IC50 of DOX in the presence of 5 microM TFP, was dependent on the level of DOX-resistance in the various sublines. Compared to parental-sensitive cells, a 2-fold decrease in DOX-accumulation was evident only in the 40-fold DOX-resistant subline. Further, maximal enhancement (50%) of cellular DOX accumulation in the presence of 5 microM TFP was observed only in the 40-fold resistant cells treated with 5.0 micrograms ml-1 DOX. Retention of DOX in the 40-fold resistant subline was only 20% lower than similarly treated sensitive cells, and the inclusion of TFP increased DOX retention less than 10-15%. Antitumour studies in mice with experimental pulmonary metastases revealed that although DOX and DOX plus TFP had similar antitumour activity with the parental sensitive B16-BL6 cells, the combination of DOX plus TFP was significantly more effective than DOX alone with the DOX-resistant sublines. No overt toxicity was observed in normal mice treated with doses of TFP, DOX or DOX plus TFP used for in vivo chemotherapy studies. Results from this study suggest that gross cellular DOX levels do not appear to correlate with the magnitude of resistance, and the effects of TFP in modulating DOX resistance is possibly due to mechanisms other than mere alterations in cellular drug

  3. 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.

  4. 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.

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

    Science.gov (United States)

    Kokado, Akihiro; Yamaji, Atsushi; Sato, Katsushi

    2017-04-01

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

  6. Phorbol diesters and transferrin modulate lymphoblastoid cell transferrin receptor expression by two different mechanisms

    International Nuclear Information System (INIS)

    Alcantara, O.; Phillips, J.L.; Boldt, D.H.

    1986-01-01

    Expression of transferrin receptors (TfR) by activated lymphocytes is necessary for lymphocyte DNA synthesis and proliferation. Regulation of TfR expression, therefore, is a mechanism by which the lymphocyte's proliferative potential may be directed and controlled. The authors studied mechanisms by which lymphoblastoid cells modulate TfR expression during treatment with phorbol diesters or iron transferrin (FeTf), agents which cause downregulation of cell surface TfR. Phorbol diester-induced TfR downregulation occurred rapidly, being detectable at 2 min and reaching maximal decreases of 50% by 15 min. It was inhibited by cold but not by agents that destabilize cytoskeletal elements. Furthermore, this downregulation was reversed rapidly by washing or by treatment with the membrane interactive agent, chlorpromazine. In contrast, FeTf-induced TfR downregulation occurred slowly. Decreased expression of TfR was detectable only after 15 min and maximal downregulation was achieved after 60 min. Although FeTf-induced downregulation also was inhibited by cold, it was inhibited in addition by a group of microtubule destabilizing agents (colchicine, vinblastine, podophyllotoxin) or cytochalasin B, a microfilament inhibitor. Furthermore, FeTf-induced downregulation was not reversed readily by washing or by treatment with chlorpromazine. Phorbol diesters cause TfR downregulation by a cytoskeleton-independent mechanism. These data indicate that TfR expression is regulated by two independent mechanisms in lymphoblastoid cells, and they provide the possibility that downregulation of TfR by different mechanisms may result in different effects in these cells

  7. 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

  8. Mechanisms of mechanical strain memory in airway smooth muscle.

    Science.gov (United States)

    Kim, Hak Rim; Hai, Chi-Ming

    2005-10-01

    We evaluated the hypothesis that mechanical deformation of airway smooth muscle induces structural remodeling of airway smooth muscle cells, thereby modulating mechanical performance in subsequent contractions. This hypothesis implied that past experience of mechanical deformation was retained (or "memorized") as structural changes in airway smooth muscle cells, which modulated the cell's subsequent contractile responses. We termed this phenomenon mechanical strain memory. Preshortening has been found to induce attenuation of both force and isotonic shortening velocity in cholinergic receptor-activated airway smooth muscle. Rapid stretching of cholinergic receptor-activated airway smooth muscle from an initial length to a final length resulted in post-stretch force and myosin light chain phosphorylation that correlated significantly with initial length. Thus post-stretch muscle strips appeared to retain memory of the initial length prior to rapid stretch (mechanical strain memory). Cytoskeletal recruitment of actin- and integrin-binding proteins and Erk 1/2 MAPK appeared to be important mechanisms of mechanical strain memory. Sinusoidal length oscillation led to force attenuation during oscillation and in subsequent contractions in intact airway smooth muscle, and p38 MAPK appeared to be an important mechanism. In contrast, application of local mechanical strain to cultured airway smooth muscle cells induced local actin polymerization and cytoskeletal stiffening. It is conceivable that deep inspiration-induced bronchoprotection may be a manifestation of mechanical strain memory such that mechanical deformation from past breathing cycles modulated the mechanical performance of airway smooth muscle in subsequent cycles in a continuous and dynamic manner.

  9. 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.

  10. 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…

  11. 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)

  12. 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.

  13. 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.

  14. 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.

  15. Why and how does native topology dictate the folding speed of a protein?

    Science.gov (United States)

    Rustad, Mark; Ghosh, Kingshuk

    2012-11-01

    , we find our new topology based metric (combining ACO, COC1, and COC2) scales as N0.54, N being the number of amino acids in a protein. This is in remarkable agreement with a previous argument based on random systems that predict protein folding speed depends on exp (- N0.5). The first principle calculation presented here provides deeper insights to the role of topology in protein folding and unifies many parallel arguments, seemingly disconnected, demonstrating the existence of universal mechanism in protein folding kinetics that can be understood from simple polymer physics based principles.

  16. 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.

  17. Mounting support for a photovoltaic module

    Science.gov (United States)

    Brandt, Gregory Michael; Barsun, Stephan K.; Coleman, Nathaniel T.; Zhou, Yin

    2013-03-26

    A mounting support for a photovoltaic module is described. The mounting support includes a foundation having an integrated wire-way ledge portion. A photovoltaic module support mechanism is coupled with the foundation.

  18. 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

  19. 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

  20. Targeting the OB-Folds of Replication Protein A with Small Molecules

    Directory of Open Access Journals (Sweden)

    Victor J. Anciano Granadillo

    2010-01-01

    Full Text Available Replication protein A (RPA is the main eukaryotic single-strand (ss DNA-binding protein involved in DNA replication and repair. We have identified and developed two classes of small molecule inhibitors (SMIs that show in vitro inhibition of the RPA-DNA interaction. We present further characterization of these SMIs with respect to their target binding, mechanism of action, and specificity. Both reversible and irreversible modes of inhibition are observed for the different classes of SMIs with one class found to specifically interact with DNA-binding domains A and B (DBD-A/B of RPA. In comparison with other oligonucleotide/oligosaccharide binding-fold (OB-fold containing ssDNA-binding proteins, one class of SMIs displayed specificity for the RPA protein. Together these data demonstrate that the specific targeting of a protein-DNA interaction can be exploited towards interrogating the cellular activity of RPA as well as increasing the efficacy of DNA-damaging chemotherapeutics used in cancer treatment.

  1. Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

    Science.gov (United States)

    Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

    2012-12-01

    The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

  2. 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

  3. Effect of modulation periods on the microstructure and mechanical properties of DLC/TiC multilayer films deposited by filtered cathodic vacuum arc method

    International Nuclear Information System (INIS)

    Xu, Zhaoying; Sun, H.; Leng, Y.X.; Li, Xueyuan; Yang, Wenmao; Huang, N.

    2015-01-01

    Highlights: • DLC/TiC multilayer films with different modulation periods at same modulation ratio 1:1 were deposited by FCVA. • The residual stress of DLC/TiC multilayer films decreases with the modulation periods decrease. • The hardness of the multilayer DLC films decreases with modulation periods increasing. - Abstract: The high stress of diamond-like carbon (DLC) film limits its thickness and adhesion on substrate. Multilayer structure is one approach to overcome this disadvantage. In this paper, the DLC/TiC multilayer films with different modulation periods (80 nm, 106 nm or 160 nm) at same modulation ratio of 1:1 were deposited on Si(1 0 0) wafer and Ti-6Al-4V substrate by filtered cathodic vacuum arc (FCVA) technology. X-ray diffraction (XRD), transmission electron microscopy (TEM), nanoindention and wear test were employed to investigate the effect of modulation periods on the microstructure and mechanical properties of the multilayer films. The results showed that the residual stress of the DLC/TiC multilayer films could be effectively reduced and the residual stress decreased with the modulation periods decreasing. The hardness of the DLC/TiC multilayer films increased with modulation periods decreasing. The DLC/TiC multilayer film with modulation period of 106 nm had the best wear resistance due to the good combination of hardness, ductility and low compressive stress

  4. 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.

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

    Science.gov (United States)

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

    2013-09-01

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

  6. The effects of mechanical loading on tendons--an in vivo and in vitro model study.

    Directory of Open Access Journals (Sweden)

    Jianying Zhang

    Full Text Available Mechanical loading constantly acts on tendons, and a better understanding of its effects on the tendons is essential to gain more insights into tendon patho-physiology. This study aims to investigate tendon mechanobiological responses through the use of mouse treadmill running as an in vivo model and mechanical stretching of tendon cells as an in vitro model. In the in vivo study, mice underwent moderate treadmill running (MTR and intensive treadmill running (ITR regimens. Treadmill running elevated the expression of mechanical growth factors (MGF and enhanced the proliferative potential of tendon stem cells (TSCs in both patellar and Achilles tendons. In both tendons, MTR upregulated tenocyte-related genes: collagen type I (Coll. I ∼10 fold and tenomodulin (∼3-4 fold, but did not affect non-tenocyte-related genes: LPL (adipocyte, Sox9 (chondrocyte, Runx2 and Osterix (both osteocyte. However, ITR upregulated both tenocyte (Coll. I ∼7-11 fold; tenomodulin ∼4-5 fold and non-tenocyte-related genes (∼3-8 fold. In the in vitro study, TSCs and tenocytes were stretched to 4% and 8% using a custom made mechanical loading system. Low mechanical stretching (4% of TSCs from both patellar and Achilles tendons increased the expression of only the tenocyte-related genes (Coll. I ∼5-6 fold; tenomodulin ∼6-13 fold, but high mechanical stretching (8% increased the expression of both tenocyte (Coll. I ∼28-50 fold; tenomodulin ∼14-48 fold and non-tenocyte-related genes (2-5-fold. However, in tenocytes, non-tenocyte related gene expression was not altered by the application of either low or high mechanical stretching. These findings indicate that appropriate mechanical loading could be beneficial to tendons because of their potential to induce anabolic changes in tendon cells. However, while excessive mechanical loading caused anabolic changes in tendons, it also induced differentiation of TSCs into non-tenocytes, which may lead to the development

  7. 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.

  8. 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

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

    Science.gov (United States)

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

    2015-04-01

    Salt structures have been identified as a potential target for hydrocarbon, CO2, or radioactive waste storage. The most suitable locations for magazines are considered in the thick and relatively homogeneous rock salt layers. However, salt structures often consist of the evaporite sequence including rock salt intercalated with other rock types e.g.: anhydrite, gypsum, potassium and magnesium salt, calcite, dolomite, or shale. The presence of such heterogeneities causes a serious disturbance in the structure management. Detailed analysis of the internal architecture and internal dynamics of the salt structure are crucial for evaluating them as suitable repositories and also their long-term stability. The goal of this study is to analyse the influence of the presence of anhydrite layers on the internal dynamics of salt structures. Anhydrite is a common rock in evaporite sequences. Its physical and mechanical properties strongly differ from the properties of rock salt. The density of anhydrite is much higher than the density of salt, thus anhydrite is likely to sink in salt causing the disturbance of the surrounding structures. This suggestion was the starting point to the discussion about the long-term stability of the magazines in salt structures [1]. However, the other important parameter that has to be taken into account is the viscosity of anhydrite. The high viscosity ratio between salt and anhydrite can restrain the layer from sinking. The rheological behaviour of anhydrite has been studied in laboratory experiments [2], but the results only provide information about the short-term behaviour. The long-term behaviour can be best predicted using indirect methods e.g. based on the analysis of natural structures that developed over geological time scale. One of the most promising are fold structures, the shape of which is very sensitive to the rheological parameters of the deforming materials. Folds can develop in mechanically stratified materials during layer

  10. 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

  11. Inverse folding of RNA pseudoknot structures

    Directory of Open Access Journals (Sweden)

    Li Linda YM

    2010-06-01

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

  12. Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.

    Science.gov (United States)

    Borelli, C; Becker, B; Thude, S; Fehrenbacher, B; Isermann, D

    2017-12-01

    Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis. We analyzed the effect of DRG on the expression of KLK5, LL-37, PAR2, and VEGF in an in vitro skin model of human reconstituted epidermis. The expression of CAMP (LL-37 gene, fold change -4.19 [±0.11]), VEGFA (fold change -2.55 [±0.12]) and PAR2 (-1.33 [±0.12]) was reduced, KLK5 expression increased (fold change 2.06 (±0.08)) after 18 h of treatment with DRG in comparison to treatment with the matrix gel only. The reduction in CAMP expression was significant (P<.01). The protein expression of all four inflammatory markers was markedly reduced after 18 hours of DRG treatment in comparison to baseline (0 hour), by measure of fluorescence intensity. We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable. © 2017 Wiley Periodicals, Inc.

  13. Uses of four-fold coaxial corrugated piping in low temperature technology

    Energy Technology Data Exchange (ETDEWEB)

    Beck, A; Rohner, P [Kabel- und Metallwerke Gutehoffnungshuette A.G., Hannover (Germany, F.R.)

    1978-06-01

    The increasing uses of superconducting equipment in various areas of research and technology, including even medicine, create an increasing demand for suitable transfer lines for liquid helium which still remains practically the only suitable coolant. This paper reports on flexible four-fold coaxial corrugated piping lines which can combine a forword flow and a return flow channel for the coolant and which can be designed for various operating conditions. The mechanical and thermal properties of such piping lines are discussed.

  14. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P)*

    Science.gov (United States)

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-01

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. PMID:26645686

  15. 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.

  16. Antifungal amphiphilic aminoglycoside K20: bioactivities and mechanism of action

    Directory of Open Access Journals (Sweden)

    Sanjib K. Shrestha

    2014-12-01

    Full Text Available K20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin A. Reported here are investigations of K20’s antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. In vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were determined. Effects on Cryptococcus neoformans H-99 infectivity were determined with a preventive murine lung infection model. The antifungal mechanism of action was studied using intact fungal cells, yeast lipid mutants, and small unilamellar lipid vesicles. K20 exhibited broad-spectrum in vitro antifungal activities but not antibacterial activities. Pulmonary, single dose-administration of K20 reduced C. neoformans lung infection rates 4-fold compared to controls. Hemolysis and half-maximal cytotoxicities of mammalian cells occurred at concentrations that were 10 to 32-fold higher than fungicidal MICs. With fluorescein isothiocyanate, 20 to 25 mg/L K20 caused staining of >95% of C. neoformans and Fusarium graminearum cells and at 31.3 mg/L caused rapid leakage (30 to 80% in 15 min of calcein from preloaded small unilamellar lipid vesicles. K20 appears to be a broad-spectrum fungicide, capable of reducing the infectivity of C. neoformans, and exhibits low hemolytic activity and mammalian cell toxicity. It perturbs the plasma membrane by mechanisms that are lipid modulated. K20 is a novel amphiphilic aminoglycoside amenable to scalable production and a potential lead antifungal for therapeutic and crop protection applications.

  17. 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.

  18. 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

  19. Endogenous angiotensin II modulates nNOS expression in renovascular hypertension

    Directory of Open Access Journals (Sweden)

    T.M.C. Pereira

    2009-07-01

    Full Text Available Nitric oxide (NO influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS. Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight divided into 2K1C (N = 19 and sham-operated (N = 19 groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9 was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan (10 mg·kg-1·day-1; N = 5 or the superoxide scavenger tempol (0.2 mmol·kg-1·day-1; N = 5, which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.

  20. 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.

  1. 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.

  2. Bilingualism modulates dual mechanisms of cognitive control: Evidence from ERPs.

    Science.gov (United States)

    Morales, Julia; Yudes, Carolina; Gómez-Ariza, Carlos J; Bajo, M Teresa

    2015-01-01

    Recent behavioral findings with the AX-Continous Performance Task (AX-CPT; Morales et al., 2013) show that bilinguals only outperform monolinguals under conditions that require the highest adjustment between monitoring (proactive) and inhibitory (reactive) control, which supports the idea that bilingualism modulates the coordination of different control mechanisms. In an ERP experiment we aimed to further investigate the role that bilingualism plays in the dynamic combination of proactive and reactive control in the AX-CPT. Our results strongly indicate that bilingualism facilitates an effective adjustment between both components of cognitive control. First, we replicated previous behavioral results. Second, ERP components indicated that bilingualism influences the conflict monitoring, response inhibition and error monitoring components of control (as indexed by the N2 and P3a elicited by the probe and the error-related negativity following incorrect responses, respectively). Thus, bilinguals exerted higher reactive control than monolinguals but only when they needed to overcome the competing cue-information. These findings join others in suggesting that a better understanding of the cognitive benefits of bilingualism may require consideration of a multi-component perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. 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

  4. 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…

  5. 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

  6. Kinematics of tectonic fracture development during regional folding in sandstones of the Kamlial Formation, Khushalgarh, northern Pakistan

    International Nuclear Information System (INIS)

    Sayab, M.

    2005-01-01

    Systematic relationships between the fracture orientation and fold geometry in sedimentary rocks have been used to explain the development of synfolding fractures. Based on field observations at the Khushalgarh syncline, located east of the Kohat Plateau, we proposed that the orientation of fractures was influenced dominantly by two tectonic fracture sets, that is, the NE-SW and NW-SE. The NE-SW fracture set dominantly formed as mode 1 (tensile), where as, the NW-SE fracture set developed as mode 11 (shear) conjugate fractures. The NE-SW trending fractures follow the axis of the syncline, whereas, the NW-SE fracture about crosscuts the fold axis. Most of the NE-SW fractures abut against the NW-SW fracture set. Based on the orientation and crosscutting relationship, their modes in response to stress, we conclude that the NE-SW trending fractures formed early than those of NW-SE fracture set. Though, both the fracture sets are formed during the folding, we suggest that they were not formed at the same time. Their crosscutting relationship suggests that they developed sequentially rather than synchronously. Our interpretations support the laboratory-based models where only one fracture orientation (or set of fractures with one orientation) form in response to single stress. However, as the stress distribution in folded strata changes over time new fractures of distinct orientations can form during or late in the folding history. We conclude that the sandstone units underwent bedding-parallel extension during folding, where bedding is stretched to accommodate extension. Parallel to the fold axis orientation. Bending of the limbs is a likely mechanism for the development of observed NE-SW trending fractures during folding, whereas the NW-SE fractures developed late in the folded history. (author)

  7. 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...

  8. Deformation and kinematics of the central Kirthar Fold Belt, Pakistan

    Science.gov (United States)

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

    2017-04-01

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

  9. Mechanisms of P-Glycoprotein Modulation by Semen Strychni Combined with Radix Paeoniae Alba

    Directory of Open Access Journals (Sweden)

    Li-Li Liu

    2017-01-01

    Full Text Available Semen Strychni has been extensively used as a Chinese herb, but its therapeutic window is narrowed by the strong toxicity of the compound, which limits its effectiveness. Radix Paeoniae Alba has been reported to reduce the toxic effects and increase the therapeutic effects of Semen Strychni, but the underlying mechanism remains unknown. This research aimed to explore the mechanism through which P-glycoprotein (P-gp is modulated by Semen Strychni combined with Radix Paeoniae Alba in vitro. An MTT assay was used to study cytotoxicity in an MDCK-MDR1 cell model. Rh123 efflux and accumulation were measured to assess P-gp function. The expression levels of MDR1 mRNA and P-gp protein in MDCK-MDR1 cells were investigated. A P-gp ATPase activity assay kit was applied to detect the effect on P-gp ATPase activity. Semen Strychni combined with Radix Paeoniae Alba could induce P-gp-mediated drug transport by inhibiting brucine and strychnine transport in MDCK-MDR1 cells, enhancing the P-gp efflux function, upregulating the P-gp expression and MDR1 mRNA levels, and stimulating P-gp ATPase activity.

  10. 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.

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

    Science.gov (United States)

    Ruh, Jonas B.; Gerya, Taras

    2015-04-01

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

  12. Elucidating PID Degradation Mechanisms and In Situ Dark I-V Monitoring for Modeling Degradation Rate in CdTe Thin-Film Modules

    DEFF Research Database (Denmark)

    Hacke, Peter; Spataru, Sergiu; Johnston, Steve

    2016-01-01

    A progression of potential-induced degradation (PID) mechanisms are observed in CdTe modules, including shunting/junction degradation and two different manifestations of series resistance depending on the stress level and water ingress. The dark I-V method for in-situ characterization of Pmax bas...

  13. Single-molecule folding mechanisms of the apo- and Mg2+-bound states of human neuronal calcium sensor-1

    DEFF Research Database (Denmark)

    Naqvi, Mohsin M; Heiðarsson, Pétur Orri; Otazo, Mariela R

    2015-01-01

    , at least transiently, at resting Ca(2+) conditions. Here, we used optical tweezers to study the folding behavior of individual NCS-1 molecules in the presence of Mg(2+) and in the absence of divalent ions. Under tension, the Mg(2+)-bound state of NCS-1 unfolds and refolds in a three-state process...... in a variety of cellular processes in which it has been linked to a number of disorders such as schizophrenia and autism. Despite extensive studies on the Ca(2+)-activated state of NCS proteins, little is known about the conformational dynamics of the Mg(2+)-bound and apo states, both of which are populated...... by populating one intermediate state consisting of a folded C-domain and an unfolded N-domain. The interconversion at equilibrium between the different molecular states populated by NCS-1 was monitored in real time through constant-force measurements and the energy landscapes underlying the observed transitions...

  14. 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....

  15. 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 ...

  16. An efficient and low resistant circumferential overlap trisection helical baffle heat exchanger with folded baffles

    International Nuclear Information System (INIS)

    Dong, Cong; Li, Dongshuang; Zheng, Youqu; Li, Guoneng; Suo, Yange; Chen, Yaping

    2016-01-01

    Highlights: • The novel cothHXf with circumferential overlap and folded baffles is first proposed. • The key sections of cylindrical and dumbbell are constructed to analyze local flow field characteristics. • The restricted leakage, easier to install and low resistant characteristics are emphasized. • The enhanced heat transfer mechanism of Dean Vortex secondary flow is analyzed. • A variety of comprehensive efficiency assessments are used. - Abstract: An efficient and low resistant circumferential overlap trisection helical baffle shell-and-tube heat exchanger with folded baffles (cothHXf) is presented. It is a modified trisection helical baffle heat exchanger with folded helical baffles for setting rods-and-spanning sleeves. It not only inherits all the merits of circumferential overlap helical baffle scheme, but also adds many additional advantages, such as supporting the inclined baffles with the least rods, simplifying the manufacturing process of spanning tubes and effectively inhibiting the reverse leakage at triangular areas between adjacent baffles. The improved flow characteristic and heat transfer enhancement mechanism of this heat exchanger were numerically investigated in comparison with conventional segmental baffles shell-and-tube heat exchanger (segHX). The flow fields within triangular area of adjacent baffles and nearby regions were depicted. The impacts of the folded baffles on shell-side helical flow, secondary vortex flow, and leakage pattern were analyzed. The distribution configurations of fields of velocity, pressure, temperature and local heat flow rate were revealed. The results show that the heat transfer performance and comprehensive performance evaluation indexes of the cothHXf are much better than those of the segHX while the pressure drop of the cothHXf is much lower than that of the segHX. The numerical simulation results of vivid distributions of flow and thermal fields of the cothHXf can provide theoretical basis for an

  17. Enhanced photoelastic modulation in silica phononic crystal cavities

    Science.gov (United States)

    Kim, Ingi; Iwamoto, Satoshi; Arakawa, Yasuhiko

    2018-04-01

    The enhanced photoelastic modulation in quasi-one-dimensional (1D) phononic crystal (PnC) cavities made of fused silica is experimentally demonstrated. A confined acoustic wave in the cavity can induce a large birefringence through the photoelastic effect and enable larger optical modulation amplitude at the same acoustic power. We observe a phase retardation of ∼26 mrad of light passing through the cavity when the exciting acoustic frequency is tuned to the cavity mode resonance of ∼500 kHz at 2.5 V. In the present experiment, a 16-fold enhancement of retardation in the PnC cavity is demonstrated compared with that in a bar-shaped silica structure. Spatially resolved optical retardation measurement reveals that the large retardation is realized only around the cavity reflecting the localized nature of the acoustic cavity mode. The enhanced interactions between acoustic waves and light can be utilized to improve the performance of acousto-optic devices such as photoelastic modulators.

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

    Science.gov (United States)

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

    2017-02-01

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

  19. 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.

  20. 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.

  1. Antimicrobial and modulation effects of selected Ghanaian ...

    African Journals Online (AJOL)

    The ethanol extracts of the three plants studied here are good modulators as they reduced the MIC of ciprofloxacin and ketoconazole by factors that are comparable to that of reserpine. However the exact compounds and their exact mechanism of modulation require further investigation. Keywords: Anti-infective, modulation, ...

  2. Structure and Mechanism of the S Component of a Bacterial ECF Transporter

    Energy Technology Data Exchange (ETDEWEB)

    P Zhang; J Wang; Y Shi

    2011-12-31

    The energy-coupling factor (ECF) transporters, responsible for vitamin uptake in prokaryotes, are a unique family of membrane transporters. Each ECF transporter contains a membrane-embedded, substrate-binding protein (known as the S component), an energy-coupling module that comprises two ATP-binding proteins (known as the A and A' components) and a transmembrane protein (known as the T component). The structure and transport mechanism of the ECF family remain unknown. Here we report the crystal structure of RibU, the S component of the ECF-type riboflavin transporter from Staphylococcus aureus at 3.6-{angstrom} resolution. RibU contains six transmembrane segments, adopts a previously unreported transporter fold and contains a riboflavin molecule bound to the L1 loop and the periplasmic portion of transmembrane segments 4-6. Structural analysis reveals the essential ligand-binding residues, identifies the putative transport path and, with sequence alignment, uncovers conserved structural features and suggests potential mechanisms of action among the ECF transporters.

  3. Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic atypicality.

    Science.gov (United States)

    Heresco-Levy, Uriel

    2003-10-01

    The neurotransmission mediated by the excitatory amino acids (EAA) glutamate (GLU) and aspartate is of interest to the pharmacotherapy of psychosis due to its role in neurodevelopment and neurotoxicity, its complex interactions with dopaminergic and other neurotransmitter systems and its pivotal importance in recent models of schizophrenia. Accumulating evidence indicates that modulation of glutamatergic neurotransmission may play an important role in the mechanisms of action of atypical antipsychotic drugs. The principles of the phencyclidine (PCP) model of schizophrenia suggest that conventional neuroleptics cannot counteract all aspects of schizophrenia symptomatology, while a more favorable outcome, including anti-negative and cognitive symptoms effects, would be expected with the use of treatment modalities targeting glutamatergic neurotransmission. Clozapine and other presently used atypical antipsychotics differ from conventional neuroleptics in the way they affect various aspects of glutamatergic receptors function. In this context, a specific hypothesis suggesting an agonistic role of clozapine at the N-methyl-D-aspartate (NMDA) subtype of GLU receptors has been postulated. Furthermore, the results of the first generation of clinical trials with glycine (GLY) site agonists of the NMDA receptor in schizophrenia suggest that this type of compounds (1) have efficacy and side effects profiles different than those of conventional neuroleptics and (2) differ in their synergic effects when used in addition to conventional neuroleptics versus clozapine and possibly additional atypical antipsychotics. These findings (1) bring further support to the hypothesis that glutamatergic effects may play an important role in the mechanism of action of atypical antipsychotics, (2) help explain the unique clinical profile of clozapine, and (3) suggest that GLY site agonists of the NMDA receptor may represent a new class of atypical antipsychotic medication. Future research in

  4. 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

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

    Science.gov (United States)

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

    2017-01-01

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

  6. Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Humberto Nicastro

    2012-01-01

    Full Text Available Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs, especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

  7. Mechanism of Folding and Activation of Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P).

    Science.gov (United States)

    da Palma, Joel Ramos; Cendron, Laura; Seidah, Nabil Georges; Pasquato, Antonella; Kunz, Stefan

    2016-01-29

    The proprotein convertase subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is implicated in lipid homeostasis, the unfolded protein response, and lysosome biogenesis. The protease is further hijacked by highly pathogenic emerging viruses for the processing of their envelope glycoproteins. Zymogen activation of SKI-1/S1P requires removal of an N-terminal prodomain, by a multistep process, generating the mature enzyme. Here, we uncover a modular structure of the human SKI-1/S1P prodomain and define its function in folding and activation. We provide evidence that the N-terminal AB fragment of the prodomain represents an autonomous structural and functional unit that is necessary and sufficient for folding and partial activation. In contrast, the C-terminal BC fragment lacks a defined structure but is crucial for autoprocessing and full catalytic activity. Phylogenetic analysis revealed that the sequence of the AB domain is highly conserved, whereas the BC fragment shows considerable variation and seems even absent in some species. Notably, SKI-1/S1P of arthropods, like the fruit fly Drosophila melanogaster, contains a shorter prodomain comprised of full-length AB and truncated BC regions. Swapping the prodomain fragments between fly and human resulted in a fully mature and active SKI-1/S1P chimera. Our study suggests that primordial SKI-1/S1P likely contained a simpler prodomain consisting of the highly conserved AB fragment that represents an independent folding unit. The BC region appears as a later evolutionary acquisition, possibly allowing more subtle fine-tuning of the maturation process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. 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

  9. Age and gender differences in mechanically induced intraoral temporal summation and conditioned pain modulation in healthy subjects.

    Science.gov (United States)

    Khan, Junad; Korczeniewska, Olga; Benoliel, Rafael; Kalladka, Mythili; Eliav, Eli; Nasri-Heir, Cibelle

    2018-04-13

    The aim of this study was to investigate intraoral temporal summation (TS) and conditioned pain modulation (CPM) and compare the outcome with TS and CPM induced in the forearm. In addition, we aimed to study the effect of age and gender on intraoral and forearm TS and CPM. Mechanical stimulation was induced with # 5.46 von Frey filament applying 26 grams of force. A single stimulus, followed by a train of 30 successive stimuli, was applied intraorally and to the dominant forearm. CPM was assessed with the TS test as the painful stimulus and with immersion of the nondominant hand in a hot water bath as the conditioning stimulus. Gender was significantly associated with TS but not with CPM measures. Females had significantly lower mean TS measured in the face and in the dominant forearm compared with males. Age was significantly associated with CPM, but not with TS measures. In both sites examined, older patients had significantly lower mean CPM compared with younger patients. Mechanical TM elicited in the oral cavity can be used as test stimulus for CPM testing. Intraoral modulation, both TS and CPM, has an extent similar to that of the standard cutaneous extremity. TS was lower in females, and CPM was reduced with age. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Controlled Folding, Motional, and Constitutional Dynamic Processes of Polyheterocyclic Molecular Strands.

    Science.gov (United States)

    Barboiu, Mihail; Stadler, Adrian-Mihail; Lehn, Jean-Marie

    2016-03-18

    General design principles have been developed for the control of the structural features of polyheterocyclic strands and their effector-modulated shape changes. Induced defined molecular motions permit designed enforcement of helical as well as linear molecular shapes. The ability of such molecular strands to bind metal cations allows the generation of coiling/uncoiling processes between helically folded and extended linear states. Large molecular motions are produced on coordination of metal ions, which may be made reversible by competition with an ancillary complexing agent and fueled by sequential acid/base neutralization energy. The introduction of hydrazone units into the strands confers upon them constitutional dynamics, whereby interconversion between different strand compositions is achieved through component exchange. These features have relevance for nanomechanical devices. We present a morphological and functional analysis of such systems developed in our laboratories. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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

  12. Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

    International Nuclear Information System (INIS)

    Gracia, Tannia; Hilscherova, Klara; Jones, Paul D.; Newsted, John L.; Higley, Eric B.; Zhang, Xiaowei; Hecker, Markus; Murphy, Margaret B.; Yu, Richard M.K.; Lam, Paul K.S.; Wu, Rudolf S.S.; Giesy, John P.

    2007-01-01

    The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different

  13. Construction and performance of the ATLAS silicon microstrip barrel modules

    International Nuclear Information System (INIS)

    Kondo, T.; Apsimon, R.; Beck, G.A.; Bell, P.; Brenner, R.; Bruckman de Renstrom, P.; Carter, A.A.; Carter, J.R.; Charlton, D.; Dabrowski, W.; Dorholt, O.; Ekelof, T.; Eklund, L.; Gibson, M.; Gadomski, S.; Grillo, A.; Grosse-Knetter, J.; Haber, C.; Hara, K.; Hill, J.C.; Ikegami, Y.; Iwata, Y.; Johansen, L.G.; Kohriki, T.; Macpherson, A.; McMahon, S.; Moorhead, G.; Morin, J.; Morris, J.; Morrissey, M.; Nagai, K.; Nakano, I.; Pater, J.; Pernegger, H.; Perrin, E.; Phillips, P.; Robinson, D.; Skubic, B.; Spencer, N.; Stapnes, S.; Stugu, B.; Takashima, R.; Terada, S.; Tyndel, M.; Ujiie, N.; Unno, Y.; Vos, M.

    2002-01-01

    The ATLAS Semiconductor Tracker (SCT) consists of four barrel cylinders and 18 end-cap disks. This paper describes the SCT modules of the barrel region, of which more than 2000 are about to be constructed. The module design is fixed. Its design concept is given together with the electrical, thermal and mechanical specifications. The pre-series production of the barrel modules is underway using mass-production procedures and jigs. The pre-series modules have given satisfactory performances on noise, noise occupancy, electrical as well as mechanical and thermal properties. In addition, irradiated modules were demonstrated to work successfully. Also first results from a 10-module system test are given

  14. Oscillator, neutron modulator

    International Nuclear Information System (INIS)

    Agaisse, R.; Leguen, R.; Ombredane, D.

    1960-01-01

    The authors present a mechanical device and an electronic control circuit which have been designed to sinusoidally modulate the reactivity of the Proserpine atomic pile. The mechanical device comprises an oscillator and a mechanism assembly. The oscillator is made of cadmium blades which generate the reactivity oscillation. The mechanism assembly comprises a pulse generator for cycle splitting, a gearbox and an engine. The electronic device comprises or performs pulse detection, an on-off device, cycle pulse shaping, phase separation, a dephasing amplifier, electronic switches, counting scales, and control devices. All these elements are briefly presented

  15. The natural history of biocatalytic mechanisms.

    Science.gov (United States)

    Nath, Neetika; Mitchell, John B O; Caetano-Anollés, Gustavo

    2014-05-01

    Phylogenomic analysis of the occurrence and abundance of protein domains in proteomes has recently showed that the α/β architecture is probably the oldest fold design. This holds important implications for the origins of biochemistry. Here we explore structure-function relationships addressing the use of chemical mechanisms by ancestral enzymes. We test the hypothesis that the oldest folds used the most mechanisms. We start by tracing biocatalytic mechanisms operating in metabolic enzymes along a phylogenetic timeline of the first appearance of homologous superfamilies of protein domain structures from CATH. A total of 335 enzyme reactions were retrieved from MACiE and were mapped over fold age. We define a mechanistic step type as one of the 51 mechanistic annotations given in MACiE, and each step of each of the 335 mechanisms was described using one or more of these annotations. We find that the first two folds, the P-loop containing nucleotide triphosphate hydrolase and the NAD(P)-binding Rossmann-like homologous superfamilies, were α/β architectures responsible for introducing 35% (18/51) of the known mechanistic step types. We find that these two oldest structures in the phylogenomic analysis of protein domains introduced many mechanistic step types that were later combinatorially spread in catalytic history. The most common mechanistic step types included fundamental building blocks of enzyme chemistry: "Proton transfer," "Bimolecular nucleophilic addition," "Bimolecular nucleophilic substitution," and "Unimolecular elimination by the conjugate base." They were associated with the most ancestral fold structure typical of P-loop containing nucleotide triphosphate hydrolases. Over half of the mechanistic step types were introduced in the evolutionary timeline before the appearance of structures specific to diversified organisms, during a period of architectural diversification. The other half unfolded gradually after organismal diversification and during a

  16. 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

  17. 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 ...

  18. 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.

  19. Energy-efficient WDM-OFDM-PON employing shared OFDM modulation modules in optical line terminal.

    Science.gov (United States)

    Hu, Xiaofeng; Zhang, Liang; Cao, Pan; Wang, Kongtao; Su, Yikai

    2012-03-26

    We propose and experimentally demonstrate a scheme to improve the energy efficiency of wavelength division multiplexing - orthogonal frequency division multiplexing - passive optical networks (WDM-OFDM-PONs). By using an N × M opto-mechanic switch in optical line terminal (OLT), an OFDM modulation module is shared by several channels to deliver data to multiple users with low traffic demands during non-peak hours of the day, thus greatly reducing the number of operating devices and minimizing the energy consumption of the OLT. An experiment utilizing one OFDM modulation module to serve three optical network units (ONUs) in a WDM-OFDM-PON is performed to verify the feasibility of our proposal. Theoretical analysis and numerical calculation show that the proposed scheme can achieve a saving of 23.6% in the energy consumption of the OFDM modulation modules compared to conventional WDM-OFDM-PON.

  20. 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...

  1. 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)

  2. 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...

  3. Selective estrogen receptor modulators (SERMs): Mechanisms of anticarcinogenesis and drug resistance

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Joan S. [Fox Chase Cancer Center, Alfred G. Knudson Chair of Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111 (United States); Jordan, V. Craig [Fox Chase Cancer Center, Alfred G. Knudson Chair of Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111 (United States)]. E-mail: v.craig.jordan@fccc.edu

    2005-12-11

    Despite the beneficial effects of estrogens in women's health, there is a plethora of evidence that suggest an important role for these hormones, particularly 17{beta}-estradiol (E{sub 2}), in the development and progression of breast cancer. Most estrogenic responses are mediated by estrogen receptors (ERs), either ER{alpha} or ER{beta}, which are members of the nuclear receptor superfamily of ligand-dependent transcription factors. Selective estrogen receptor modulators (SERMs) are ER ligands that in some tissues (i.e. bone and cardiovascular system) act like estrogens but block estrogen action in others. Tamoxifen is the first SERM that has been successfully tested for the prevention of breast cancer in high-risk women and is currently approved for the endocrine treatment of all stages of ER-positive breast cancer. Raloxifene, a newer SERM originally developed for osteoporosis, also appears to have preventive effect on breast cancer incidence. Numerous studies have examined the molecular mechanisms for the tissue selective action of SERMs, and collectively they indicate that different ER ligands induce distinct conformational changes in the receptor that influence its ability to interact with coregulatory proteins (i.e. coactivators and corepressors) critical for the regulation of target gene transcription. The relative expression of coactivators and corepressors, and the nature of the ER and its target gene promoter also affect SERM biocharacter. This review summarizes the therapeutic application of SERMs in medicine; particularly breast cancer, and highlights the emerging understanding of the mechanism of action of SERMs in select target tissues, and the inevitable development of resistance.

  4. 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.

  5. 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.

  6. Fiscal 1999 achievement report on research and development project on intellectual infrastructure creation and utilization technologies. Development of efficient protein expression system (Development of efficient protein expression system utilizing protein folding mechanism of hyperthermophilic bacteria); 1999 nendo kokoritsu tanpakushitsu hatsugen system no kaihatsu seika hokokusho. Chokonetsukin no tanpakushitsu oritatami kiko wo riyoshita kokoritsu tanpakushitsu hatsugen system no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    Efforts were exerted to achieve efficient expression of proteins of hyperthermophilic bacteria, hyperthermophilic archaeabacteria in particular, using a heterogene expression system in which Escherichia coli was the host. In an effort to search for genes related to protein folding and to elucidate the mechanism of folding, chaperonin and prefoldin subunit genes, out of various factors participating in protein folding in hyperthermophilic archaeabacteria, were cloned, and expressed in Escherichia coli. As a system for analyzing protein folding reaction, an experimental system was established on a substrate comprising isopropyl malate dehydrogenase, citrate synthase, glucose dehydrogenase, and a green fluorescent protein. Studies were further conducted to elucidate the mechanism of expression of enzyme genes in Escherichia coli for the establishment of a mass production method for useful enzymes. Also carried out was the research and development of an element technology evaluation system involving protein expression. (NEDO)

  7. 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.

  8. 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.

  9. WRAP Module 1 waste characterization plan

    International Nuclear Information System (INIS)

    Mayancsik, B.A.

    1995-01-01

    The purpose of this document is to present the characterization methodology for waste generated, processed, or otherwise the responsibility of the Waste Receiving and Processing (WRAP) Module 1 facility. The scope of this document includes all solid low level waste (LLW), transuranic (TRU), mixed waste (MW), and dangerous waste. This document is not meant to be all-inclusive of the waste processed or generated within WRAP Module 1, but to present a methodology for characterization. As other streams are identified, the method of characterization will be consistent with the other streams identified in this plan. The WRAP Module 1 facility is located in the 200 West Area of the Hanford Site. The facility's function is two-fold. The first is to verify/characterize, treat and repackage contact handled (CH) waste currently in retrievable storage in the LLW Burial Grounds, Hanford Central Waste Complex, and the Transuranic Storage and Assay Facility (TRUSAF). The second is to verify newly generated CH TRU waste and LLW, including MW. The WRAP Module 1 facility provides NDE and NDA of the waste for both drums and boxes. The NDE is used to identify the physical contents of the waste containers to support waste characterization and processing, verification, or certification. The NDA results determine the radioactive content and distribution of the waste

  10. 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.

  11. Light-harvesting complex gene expression is controlled by both transcriptional and post-transcriptional mechanisms during photoacclimation in Chlamydomonas reinhardtii

    CERN Document Server

    Durnford Dion, G; McKim, Sarah M; Sarchfield, Michelle L

    2003-01-01

    To compensate for increases in photon flux density (PFD), photosynthetic organisms possess mechanisms for reversibly modulating their photosynthetic apparatus to minimize photodamage. The photoacclimation response in Chlamydomonas reinhardtii was assessed following a 10-fold increase in PFD over 24h. In addition to a 50% reduction in the amount of chlorophyll and light-harvesting complexes (LHC) per cell, the expression of genes encoding polypeptides of the light-harvesting antenna were also affected. The abundance of Lhcb (a LHCH gene), Lhcb4 (a CP29-like gene), and Lhca (a LHCI gene) transcripts were reduced by 65 to 80%, within 1-2 h; however, the RNA levels of all three genes recovered to their low-light (LL) concentrations within 6-8 h. To determine the role of transcript turnover in this transient decline in abundance, the stability of all transcripts was measured. Although there was no change in the Lhcb or Lhca transcript turnover time, the Lhcb4 mRNA stability decreased 2.5-fold immediately following...

  12. Shape morphing Kirigami mechanical metamaterials.

    Science.gov (United States)

    Neville, Robin M; Scarpa, Fabrizio; Pirrera, Alberto

    2016-08-05

    Mechanical metamaterials exhibit unusual properties through the shape and movement of their engineered subunits. This work presents a new investigation of the Poisson's ratios of a family of cellular metamaterials based on Kirigami design principles. Kirigami is the art of cutting and folding paper to obtain 3D shapes. This technique allows us to create cellular structures with engineered cuts and folds that produce large shape and volume changes, and with extremely directional, tuneable mechanical properties. We demonstrate how to produce these structures from flat sheets of composite materials. By a combination of analytical models and numerical simulations we show how these Kirigami cellular metamaterials can change their deformation characteristics. We also demonstrate the potential of using these classes of mechanical metamaterials for shape change applications like morphing structures.

  13. Evolution of a protein folding nucleus.

    Science.gov (United States)

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

    2016-07-01

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

  14. 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%.

  15. 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.

  16. 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.

  17. 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.

  18. Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies.

    Science.gov (United States)

    Tipton, Thomas R W; Roghanian, Ali; Oldham, Robert J; Carter, Matthew J; Cox, Kerry L; Mockridge, C Ian; French, Ruth R; Dahal, Lekh N; Duriez, Patrick J; Hargreaves, Philip G; Cragg, Mark S; Beers, Stephen A

    2015-03-19

    Following the success of rituximab, 2 other anti-CD20 monoclonal antibodies (mAbs), ofatumumab and obinutuzumab, have entered clinical use. Ofatumumab has enhanced capacity for complement-dependent cytotoxicity, whereas obinutuzumab, a type II mAb, lacks the ability to redistribute into lipid rafts and is glycoengineered for augmented antibody-dependent cellular cytotoxicity (ADCC). We previously showed that type I mAbs such as rituximab have a propensity to undergo enhanced antigenic modulation compared with type II. Here we assessed the key effector mechanisms affected, comparing type I and II antibodies of various isotypes in ADCC and antibody-dependent cellular-phagocytosis (ADCP) assays. Rituximab and ofatumumab depleted both normal and leukemic human CD20-expressing B cells in the mouse less effectively than glycoengineered and wild-type forms of obinutuzumab, particularly when human immunoglobulin G1 (hIgG1) mAbs were compared. In contrast to mouse IgG2a, hIgG1 mAbs were ineffective in ADCC assays with murine natural killer cells as effectors, whereas ADCP was equivalent for mouse IgG2a and hIgG1. However, rituximab's ability to elicit both ADCC and ADCP was reduced by antigenic modulation, whereas type II antibodies remained unaffected. These data demonstrate that ADCP and ADCC are impaired by antigenic modulation and that ADCP is the main effector function employed in vivo. © 2015 by The American Society of Hematology.

  19. 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.

  20. Electric field modulated conduction mechanism in Al/BaTiO3/La0.67Sr0.33MnO3 heterostructures

    KAUST Repository

    Zheng, Dongxing; Li, Dong; Gong, Junlu; Jin, Chao; Li, Peng; Zhang, Xixiang; Bai, Haili

    2017-01-01

    Mediating a metastable state is a promising way to achieve a giant modulation of physical properties in artificial heterostructures. A metastable state La0.67Sr0.33MnO3 (LSMO) layer suffering tensile strain was grown on MgO substrates. Incorporating with the ferroelectric BaTiO3 (BTO) layer, an accumulation or depletion state controlled by electric fields can be formed at the BTO/LSMO interface, which drives a switching of the conduction mechanism between space charge limited conduction and Poole-Frenkel emission, corresponding to the low and high resistance states. Our results lighten an effective way for electric-field modulated resistance states in multiferroic magnetoelectric devices.

  1. Electric field modulated conduction mechanism in Al/BaTiO3/La0.67Sr0.33MnO3 heterostructures

    KAUST Repository

    Zheng, Dongxing

    2017-08-08

    Mediating a metastable state is a promising way to achieve a giant modulation of physical properties in artificial heterostructures. A metastable state La0.67Sr0.33MnO3 (LSMO) layer suffering tensile strain was grown on MgO substrates. Incorporating with the ferroelectric BaTiO3 (BTO) layer, an accumulation or depletion state controlled by electric fields can be formed at the BTO/LSMO interface, which drives a switching of the conduction mechanism between space charge limited conduction and Poole-Frenkel emission, corresponding to the low and high resistance states. Our results lighten an effective way for electric-field modulated resistance states in multiferroic magnetoelectric devices.

  2. The 27 February 1997 Sibi double-earthquake (Mw 6.9, 6.7) in the Sulaiman range of Pakistan - implications for the tectonics of fold-and-thrust belts and for earthquake triggering mechanisms

    Science.gov (United States)

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

    2011-12-01

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

  3. Mechanical tolerances study through simulations and experimental characterization for a 1000X micro-concentrator CPV module

    Science.gov (United States)

    Ritou, Arnaud; Voarino, Philippe; Goubault, Baptiste; David, Nadine; Bernardis, Sarah; Raccurt, Olivier; Baudrit, Mathieu

    2017-09-01

    Existing CPV technology markets are not compliant with a standard configuration. Concentrations vary from several suns to more than 1000 suns and the optical technology used could be very different. Nowadays, the market trends are moving toward more and more compact optical systems in order to exploit the Light Emitting Diode (LED) like approach. The aim is to increase the optical efficiency by using an ultra-short focal distance and to improve thermal management. Moreover the efficiency to weight ratio is increasing and the solar cell size becomes sub-millimetric. With these conditions, more stringent mechanical tolerances are essential to ensure an optimum optical alignment between cells and optics. A new process of micro-concentrator manufacturing is developed in this work. This process enables manufacturing and auto-alignment of Primary Optical Elements (POE) with Secondary Optical Elements (SOE) and solar cells with respect to certain mechanical tolerances. A 1000X micro-concentrator is manufactured with 0.6 x 0.6 mm² triple-junction cells and molded silicone optics. Mechanical alignment defects are studied by ray-tracing simulations and a prototype is characterized with respect to its mechanical behavior. An efficiency of 33.4% is measured with a Cell-to-Module ratio of 77.8%.

  4. The thermo-mechanical design of the water cooled PB-17Li test blanket module for ITER

    International Nuclear Information System (INIS)

    Nardi, C.; Palmieri, A.; Pinna, T.; Porfini, M.T.; Rapisarda, M.; Roccella, M.; Futterer, M.; Lucca, F.

    1998-01-01

    The Water Cooled Lithium Lead (WCLL) blanket is one of the two European concepts to be further developed. A Test Blanket Module (TBM) representative of the DEMO blanket shall be tested in ITER. This paper reports on the activities related to the thermo-mechanical design analysis, taking into account the electromagnetic and neutronic loads in normal and off normal conditions. These loads were applied to a finite elements model of the structure, and the structural response was compared to the allowable value, dependent on the operating conditions. Besides the loads assumed by the design specifications (pressure, temperature, etc), electro-mechanical and thermal loads have been evaluated. A model of the TBM has been performed to compute the loads related to the electromagnetic effects of a centered plasma disruption. The thermal loads have been evaluated considering the heat deposition from the plasma and from the neutrons. The neutronic analysis has been carried out also in order to evaluate the shielding characteristics of the TBM. Taking into account the thermal and mechanical loads a fracture mechanics analysis has been carried out. From this analysis the J Ic parameter was evaluated at the crack tip and compared with the allowable value. The work carried out showed that the TBM present design fulfills ITER normal operation requirements. (authors)

  5. Observation of modulation speed enhancement, frequency modulation suppression, and phase noise reduction by detuned loading in a coupled-cavity semiconductor laser

    OpenAIRE

    Vahala, Kerry; Paslaski, Joel; Yariv, Amnon

    1985-01-01

    Simultaneous direct modulation response enhancement, phase noise (linewidth) reduction, and frequency modulation suppression are produced in a coupled-cavity semiconductor laser by the detuned loading mechanism.

  6. 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.

  7. 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

  8. 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.

  9. Report on the SCT Forward Electrical Module Program

    CERN Document Server

    Benes, J; Feld, L; Hornung, M; Joos, D; Ketterer, C; Kodys, P; Kubik, P; Ludwig, J; Modesto, P; Rieth, G; Runge, K; Smith, T; Snow, S W; Taylor, G; Webel, M

    1999-01-01

    IN THE CONTEXT OF THE ATLAS SCT FORWARD HYBRID PROGRAM, THREEELECTRICAL DETECTOR MODULES HAVE BEEN BUILT. THIS NOTE DESCRIBES THEASSEMBLY AND SUMMARISES THE MECHANICAL AND ELECTRICAL PROPERTIES OFTHESE MODULES. SOME COMMENTS ON THE SPECIAL REQUIREMENTS OF THEPRODUCTION OF A REAL MODULE AS COMPARED TO DUMMY MODULES ARE GIVEN.A LIST OF OPEN QUESTIONS ARISING FROM THIS ASSEMBLY RUN IS APPENDED.

  10. Sulfated glycosaminoglycans in human vocal fold lamina propria

    Directory of Open Access Journals (Sweden)

    Sung Woo Park

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

  11. 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)

  12. Development of mechanical analysis module for simulation of SFR fuel rod behavior using finite element method

    International Nuclear Information System (INIS)

    Shin, Andong; Jeong, Hyedong; Suh, Namduk; Kim, Hyochan; Yang, Yongsik

    2014-01-01

    if the characteristics of 'analytical model' are simple and fast running time, there are some limitations which can disturb the detailed modeling of nature. For instance, contact force between cracked slug and cladding shows much larger than non-cracked one due to the high stress concentration at crack tip. The analytical model cannot simulate the cracked slug model. To resolve the limitations, the finite element method (FEM) has been introduced to simulate the mechanical behavior of fuel rod. The ALFUS code adopts FEM modeling to solve mechanical behavior of fuel rod. In this work, 2D FEM model, so called 'NUFORM2D', has been developed to simulate mechanical behavior of fuel and cladding in SFR. The model will be integrated into audit code system. To evaluate the developed model, a code-to-code benchmark was performed using the commercial FE package (ANSYS). The project for the new fuel performance code development has been launched to evaluate the integrity and safety of SFR fuel in regulation aspects. Based on survey of the previous SFR fuel code system, the mechanical analysis module of the previous code should be improved to resolve limitations. This work develops the advanced mechanical analysis model of SFR fuel rod using finite element method, which is well matured in the mechanical field. The module has been implemented by FORTRAN77 to be called by main program

  13. Development of mechanical analysis module for simulation of SFR fuel rod behavior using finite element method

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Andong; Jeong, Hyedong; Suh, Namduk [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Kim, Hyochan; Yang, Yongsik [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    if the characteristics of 'analytical model' are simple and fast running time, there are some limitations which can disturb the detailed modeling of nature. For instance, contact force between cracked slug and cladding shows much larger than non-cracked one due to the high stress concentration at crack tip. The analytical model cannot simulate the cracked slug model. To resolve the limitations, the finite element method (FEM) has been introduced to simulate the mechanical behavior of fuel rod. The ALFUS code adopts FEM modeling to solve mechanical behavior of fuel rod. In this work, 2D FEM model, so called 'NUFORM2D', has been developed to simulate mechanical behavior of fuel and cladding in SFR. The model will be integrated into audit code system. To evaluate the developed model, a code-to-code benchmark was performed using the commercial FE package (ANSYS). The project for the new fuel performance code development has been launched to evaluate the integrity and safety of SFR fuel in regulation aspects. Based on survey of the previous SFR fuel code system, the mechanical analysis module of the previous code should be improved to resolve limitations. This work develops the advanced mechanical analysis model of SFR fuel rod using finite element method, which is well matured in the mechanical field. The module has been implemented by FORTRAN77 to be called by main program.

  14. 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...

  15. 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...

  16. On the origins of the weak folding cooperativity of a designed ββα ultrafast protein FSD-1.

    Science.gov (United States)

    Wu, Chun; Shea, Joan-Emma

    2010-11-18

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

  17. Light intensity modulation in phototherapy

    Science.gov (United States)

    Lukyanovich, P. A.; Zon, B. A.; Kunin, A. A.; Pankova, S. N.

    2015-04-01

    A hypothesis that blocking ATP synthesis is one of the main causes of the stimulating effect is considered based on analysis of the primary photostimulation mechanisms. The light radiation intensity modulation is substantiated and the estimates of such modulation parameters are made. An explanation is offered to the stimulation efficiency decrease phenomenon at the increase of the radiation dose during the therapy. The results of clinical research of the medical treatment in preventive dentistry are presented depending on the spectrum and parameters of the light flux modulation.

  18. Neural mechanisms by which attention modulates the comparison of remembered and perceptual representations.

    Directory of Open Access Journals (Sweden)

    Bo-Cheng Kuo

    Full Text Available Attention is important for effectively comparing incoming perceptual information with the contents of visual short-term memory (VSTM, such that any differences can be detected. However, how attentional mechanisms operate upon these comparison processes remains largely unknown. Here we investigate the underlying neural mechanisms by which attention modulates the comparisons between VSTM and perceptual representations using functional magnetic resonance imaging (fMRI. Participants performed a cued change detection task. Spatial cues were presented to orient their attention either to the location of an item in VSTM prior to its comparison (retro-cues, or simultaneously (simultaneous-cues with the probe array. A no-cue condition was also included. When attention cannot be effectively deployed in advance (i.e. following the simultaneous-cues, we observed a distributed and extensive activation pattern in the prefrontal and parietal cortices in support of successful change detection. This was not the case when participants can deploy their attention in advance (i.e. following the retro-cues. The region-of-interest analyses confirmed that neural responses for successful change detection versus correct rejection in the visual and parietal regions were significantly different for simultaneous-cues compared to retro-cues. Importantly, we found enhanced functional connectivity between prefrontal and parietal cortices when detecting changes on the simultaneous-cue trials. Moreover, we demonstrated a close relationship between this functional connectivity and d' scores. Together, our findings elucidate the attentional and neural mechanisms by which items held in VSTM are compared with incoming perceptual information.

  19. The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

    Science.gov (United States)

    Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

    2006-01-15

    The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate

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

    Science.gov (United States)

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

    2018-03-27

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