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Sample records for 2-3 fold higher

  1. Folding paper-based lithium-ion batteries for higher areal energy densities.

    PubMed

    Cheng, Qian; Song, Zeming; Ma, Teng; Smith, Bethany B; Tang, Rui; Yu, Hongyu; Jiang, Hanqing; Chan, Candace K

    2013-10-01

    Paper folding techniques are used in order to compact a Li-ion battery and increase its energy per footprint area. Full cells were prepared using Li4Ti5O12 and LiCoO2 powders deposited onto current collectors consisting of paper coated with carbon nanotubes. Folded cells showed higher areal capacities compared to the planar versions with a 5 × 5 cell folded using the Miura-ori pattern displaying a ~14× increase in areal energy density. PMID:24059538

  2. The role of alphoid higher order repeats (HORs) in the centromere folding.

    PubMed

    Rosandić, Marija; Gluncić, Matko; Paar, Vladimir; Basar, Ivan

    2008-10-01

    Understanding the folding of centromere DNA in the maximally condensed methaphase chromosome remains a basic challenge in cell biology. We propose here a set of structural models with a graphical presentation of alphoid higher order repeat (HOR) distribution in the centromere folding, based on the assumption of encryption key for microtubule-centromere interaction which arises from chromosome-specific crystal-like structure of HORs. Specific HOR leads to a characteristic geometrical pattern which may be responsible for individual microtubule to recognize a specific structure of centromere in each chromosome. PMID:18625244

  3. Protein folds and protein folding

    PubMed Central

    Schaeffer, R. Dustin; Daggett, Valerie

    2011-01-01

    The classification of protein folds is necessarily based on the structural elements that distinguish domains. Classification of protein domains consists of two problems: the partition of structures into domains and the classification of domains into sets of similar structures (or folds). Although similar topologies may arise by convergent evolution, the similarity of their respective folding pathways is unknown. The discovery and the characterization of the majority of protein folds will be followed by a similar enumeration of available protein folding pathways. Consequently, understanding the intricacies of structural domains is necessary to understanding their collective folding pathways. We review the current state of the art in the field of protein domain classification and discuss methods for the systematic and comprehensive study of protein folding across protein fold space via atomistic molecular dynamics simulation. Finally, we discuss our large-scale Dynameomics project, which includes simulations of representatives of all autonomous protein folds. PMID:21051320

  4. Transtensional folding

    NASA Astrophysics Data System (ADS)

    Fossen, Haakon; Teyssier, Christian; Whitney, Donna L.

    2014-05-01

    For now three decades transpression has dominated the concepts that underlie oblique tectonics, but in more recent years transtension has garnered much interest as a simple model that can be applied to shallow and deep crustal tectonics. One fundamental aspect that distinguishes transtension from transpression is that material lines in transtension rotate toward the direction of oblique divergence. Another point that may be less intuitive when thinking of transtension is that while transtensional strain involves shortening in the vertical direction, one of the horizontal axes is also a shortening axis, whatever the angle of divergence. It is the combination of these two shortening axes that leads to constrictional finite strain in transtension. The existence of a horizontal shortening strain axis implies that transtension offers the potential for folds of horizontal layers to form and then rotate toward the direction of oblique divergence. An investigation of transtensional folding using 3D strain modeling reveals that folding is more likely for simple shear dominated transtension (large wrench component). Transtensional folds can only accumulate a fixed amount of horizontal shortening and tightness that are prescribed by the angle of oblique divergence, regardless of finite strain. Transtensional folds are characterized by hinge-parallel stretching that exceeds that expected from pure wrenching. In addition, the magnitude of hinge-parallel stretching always exceeds hinge-perpendicular shortening, causing constrictional fabrics and hinge-parallel boudinage to develop. Because the dominant vertical strain axis is shortening, transtensional fold growth is generally suppressed, but when folds do develop their limbs enter the field of shortening, resulting in possible fold interference patterns akin to cascading folds. Application of these transtensional folding principles to regions of oblique rifting (i.e. Gulf of California) or exhumation of deep crust (i.e. Western

  5. The Long-term Risk of Upper-extremity Lymphedema is Two-fold Higher in Breast Cancer Patients than in Melanoma Patients

    PubMed Central

    Voss, Rachel K.; Cromwell, Kate D.; Chiang, Yi-Ju; Armer, Jane M.; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Stewart, Bob R.; Shaitelman, Simona F.; Cormier, Janice N.

    2015-01-01

    Background and Objectives We assessed the cumulative incidence, symptoms, and risk factors for upper-extremity lymphedema in breast cancer and melanoma patients undergoing sentinel lymph node biopsy or axillary lymph node dissection. Methods Patients were recruited preoperatively (time 0) and assessed at 6, 12, and 18 months postoperatively. Limb volume change (LVC) was measured by perometry. Lymphedema was categorized as none, mild (LVC 5–9.9%), or moderate/severe (LVC≥10%). Symptoms were assessed with a validated lymphedema instrument. Longitudinal logistic regression analyses were conducted to identify risk factors associated with moderate/severe lymphedema. Results Among 205 breast cancer and 144 melanoma patients, the cumulative incidence of moderate/severe lymphedema at 18 months was 36.5% and 35.0, respectively. However, in adjusted analyses, factors associated with moderate/severe lymphedema were breast cancer (OR 2.0, p=0.03), body mass index ≥30 kg/m2 (OR 1.6, p=0.04), greater number of lymph nodes removed (OR 1.05, p<0.01), and longer interval since surgery (OR 2.33 at 18 months, p<0.01). Conclusions: Lymphedema incidence increased over time in both cohorts. However, the adjusted risk of moderate/severe lymphedema was two-fold higher in breast cancer patients. These results may be attributed to surgical treatment of the primary tumor in the breast and more frequent use of radiation. PMID:26477877

  6. The dexmedetomidine concentration required after remifentanil anesthesia is three-fold higher than that after fentanyl anesthesia or that for general sedation in the ICU

    PubMed Central

    Kunisawa, Takayuki; Fujimoto, Kazuhiro; Kurosawa, Atsushi; Nagashima, Michio; Matsui, Koji; Hayashi, Dai; Yamamoto, Kunihiko; Goto, Yuya; Akutsu, Hiroaki; Iwasaki, Hiroshi

    2014-01-01

    Purpose The general dexmedetomidine (DEX) concentration required for sedation of intensive care unit patients is considered to be approximately 0.7 ng/mL. However, higher DEX concentrations are considered to be required for sedation and/or pain management after major surgery using remifentanil. We determined the DEX concentration required after major surgery by using a target-controlled infusion (TCI) system for DEX. Methods Fourteen patients undergoing surgery for abdominal aortic aneurysms (AAA) were randomly, double-blindly assigned to two groups and underwent fentanyl- or remifentanil-based anesthetic management. DEX TCI was started at the time of closing the peritoneum and continued for 12 hours after stopping propofol administration (M0); DEX TCI was adjusted according to the sedation score and complaints of pain. The doses and concentrations of all anesthetics and postoperative conditions were investigated. Results Throughout the observation period, the predicted plasma concentration of DEX in the fentanyl group was stable at approximately 0.7 ng/mL. In contrast, the predicted plasma concentration of DEX in the remifentanil group rapidly increased and stabilized at approximately 2 ng/mL. The actual DEX concentration at 540 minutes after M0 showed a similar trend (0.54±0.14 [fentanyl] versus 1.57±0.39 ng/mL [remifentanil]). In the remifentanil group, the dopamine dose required and the duration of intubation decreased, and urine output increased; however, no other outcomes improved. Conclusion The DEX concentration required after AAA surgery with remifentanil was three-fold higher than that required after AAA surgery with fentanyl or the conventional DEX concentration for sedation. High DEX concentration after remifentanil affords some benefits in anesthetic management. PMID:25328395

  7. Issues/Higher Education/Institutional Research. NCAIR Proceedings. Fifth Annual Meeting of the North Carolina Association for Institutional Research (Asheville, North Carolina, November 2-3, 1977).

    ERIC Educational Resources Information Center

    Brown, Charles I., Ed.

    Proceedings from the fifth annual meeting of the North Carolina Association for Institutional Research (NCAIR) focus on issues affecting higher education and the relationship of these issues to the institutional research function. Included are general session addresses by Charles A. Lyons and Dick Robinson that discuss the implications of Judge…

  8. Photoelectron spectroscopy of higher bromine and iodine oxide anions: Electron affinities and electronic structures of BrO2,3 and IO2-4 radicals.

    SciTech Connect

    Wen, Hui; Hou, Gaolei; Huang, Wei; Govind, Niranjan; Wang, Xue B.

    2011-11-14

    This report details a photoelectron spectroscopy (PES) investigation on electron affinities (EAs) and electronic structures of several atmospherically relevant higher bromine and iodine oxide molecules in the gas phase. PES spectra of BrO{sub 2}{sup -} and IO{sub 2}{sup -} were recorded at 12 K and four photon energies--355 nm/3.496 eV, 266 nm/4.661 eV, 193 nm/6.424 eV, and 157 nm/7.867 eV--while BrO{sub 3}{sup -}, IO{sub 3}{sup -}, and IO{sub 4}{sup -} were studied at 193 and 157 nm only due to their expected high electron binding energies. Spectral features corresponding to transitions from the anion ground state to the ground and excited states of the neutral are unraveled and resolved for each species. For the first time, EAs of these bromine and iodine oxides are experimentally determined (except for IO{sub 2}) to be 2.515 {+-} 0.010 (BrO{sub 2}), 2.575 {+-} 0.010 (IO{sub 2}), 4.60 {+-} 0.05 (BrO{sub 3}), 4.70 {+-} 0.05 (IO{sub 3}), and 6.05 {+-} 0.05 eV (IO{sub 4}). Three low-lying excited states with their respective excitation energies are obtained for BrO{sub 2} [1.69 (A {sup 2}B2), 1.79 (B {sup 2}A{sub 1}), 1.99 eV (C {sup 2}A{sub 2})], BrO{sub 3} [0.7 (A {sup 2}A{sub 2}), 1.6 (B {sup 2}E), 3.1 eV (C {sup 2}E)], and IO{sub 3} [0.60 (A {sup 2}A{sub 2}), 1.20 (B {sup 2}E), {approx}3.0 eV (C {sup 2}E)], whereas six excited states of IO{sub 2} are determined with the respective excitation energies of 1.63 (A {sup 2}B{sub 2}), 1.73 (B {sup 2}A{sub 1}), 1.83 (C {sup 2}A{sub 2}), 4.23 (D {sup 2}A{sub 1}), 4.63 (E {sup 2}B{sub 2}), and 5.23 eV (F {sup 2}B{sub 1}). Periodate possesses a very high electron binding energy. Only one excited state feature with 0.95 eV excitation energy is shown in the 157 nm spectrum. The obtained EAs and low-lying excited state information are compared with available theoretical calculations and discussed with their atmospheric implications.

  9. Folding of proteins with diverse folds.

    PubMed

    Mohanty, Sandipan; Hansmann, Ulrich H E

    2006-11-15

    Using parallel tempering simulations with high statistics, we investigate the folding and thermodynamic properties of three small proteins with distinct native folds: the all-helical 1RIJ, the all-sheet beta3s, and BBA5, which has a mixed helix-sheet fold. In all three cases, simulations with our energy function find the native structures as global minima in free energy at experimentally relevant temperatures. However, the folding process strongly differs for the three molecules, indicating that the folding mechanism is correlated with the form of the native structure. PMID:16950845

  10. Structural Bridges through Fold Space

    PubMed Central

    Edwards, Hannah; Deane, Charlotte M.

    2015-01-01

    Several protein structure classification schemes exist that partition the protein universe into structural units called folds. Yet these schemes do not discuss how these units sit relative to each other in a global structure space. In this paper we construct networks that describe such global relationships between folds in the form of structural bridges. We generate these networks using four different structural alignment methods across multiple score thresholds. The networks constructed using the different methods remain a similar distance apart regardless of the probability threshold defining a structural bridge. This suggests that at least some structural bridges are method specific and that any attempt to build a picture of structural space should not be reliant on a single structural superposition method. Despite these differences all representations agree on an organisation of fold space into five principal community structures: all-α, all-β sandwiches, all-β barrels, α/β and α + β. We project estimated fold ages onto the networks and find that not only are the pairings of unconnected folds associated with higher age differences than bridged folds, but this difference increases with the number of networks displaying an edge. We also examine different centrality measures for folds within the networks and how these relate to fold age. While these measures interpret the central core of fold space in varied ways they all identify the disposition of ancestral folds to fall within this core and that of the more recently evolved structures to provide the peripheral landscape. These findings suggest that evolutionary information is encoded along these structural bridges. Finally, we identify four highly central pivotal folds representing dominant topological features which act as key attractors within our landscapes. PMID:26372166

  11. 2,3-Dichloropropanol

    Integrated Risk Information System (IRIS)

    2,3 - Dichloropropanol ; CASRN 616 - 23 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcino

  12. Let Them Fold

    ERIC Educational Resources Information Center

    Grant, Nicholas; Tobin, Alexander

    1972-01-01

    Directions are given for seven activities involving the folding of paper strips to illustrate geometric concepts. Properties of pentagons, triangles, hexagons, and Mobius bands resulting from the various foldings are discussed. (DT)

  13. Protein folding by motion planning

    NASA Astrophysics Data System (ADS)

    Thomas, Shawna; Song, Guang; Amato, Nancy M.

    2005-12-01

    We investigate a novel approach for studying protein folding that has evolved from robotics motion planning techniques called probabilistic roadmap methods (PRMs). Our focus is to study issues related to the folding process, such as the formation of secondary and tertiary structures, assuming we know the native fold. A feature of our PRM-based framework is that the large sets of folding pathways in the roadmaps it produces, in just a few hours on a desktop PC, provide global information about the protein's energy landscape. This is an advantage over other simulation methods such as molecular dynamics or Monte Carlo methods which require more computation and produce only a single trajectory in each run. In our initial studies, we obtained encouraging results for several small proteins. In this paper, we investigate more sophisticated techniques for analyzing the folding pathways in our roadmaps. In addition to more formally revalidating our previous results, we present a case study showing that our technique captures known folding differences between the structurally similar proteins G and L. This research was supported in part by NSF CAREER Award CCR-9624315, NSF Grants ACI-9872126, EIA-9975018, EIA-0103742, EIA-9805823, ACR-0113971, CCR-0113974, EIA-9810937, EIA-0079874 and the Texas Higher Education Coordinating Board grant ATP-000512-0261-2001. ST was supported in part by an NSF Graduate Research Fellowship. GS was supported in part by an IBM PhD Fellowship.

  14. Teaching polymers to fold

    SciTech Connect

    Judson, R.S. )

    1992-12-10

    A new method is presented for predicting folding pathways of polymers. The folding pathway is described as a generic program or sequence of logical steps of such a form that a computer can carry them out to produce a folded structure. A genetic (GA) is used to learn specific sequences or folding pathways that carry a denatured conformation into a target final conformation. The method is demonstrated on a model 2-dimensional polymer for which the global energy minimum is known. The GA learns a program that will fold a denatured polymer into its global energy minimum conformation. 27 refs., 4 figs.

  15. Mechanics of Curved Folds

    NASA Astrophysics Data System (ADS)

    Dias, Marcelo A.; Santangelo, Christian D.

    2011-03-01

    Despite an almost two thousand year history, origami, the art of folding paper, remains a challenge both artistically and scientifically. Traditionally, origami is practiced by folding along straight creases. A whole new set of shapes can be explored, however, if, instead of straight creases, one folds along arbitrary curves. We present a mechanical model for curved fold origami in which the energy of a plastically-deformed crease is balanced by the bending energy of developable regions on either side of the crease. Though geometry requires that a sheet buckle when folded along a closed curve, its shape depends on the elasticity of the sheet. NSF DMR-0846582.

  16. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2013-10-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold distribution procedure. The fold distribution provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of change in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Distribution, Proposal 13149, as Cycle 20.

  17. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2012-10-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold distribution procedure. The fold distribution provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of change in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Distribution, Proposal 12778, as Cycle 19.

  18. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2010-09-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Analysis {11863} during Cycle 17.

  19. STIS MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2011-10-01

    The performance of MAMA microchannel plates can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the STIS MAMA Fold Analysis, Proposal 12416, as Cycle 18.

  20. A galaxy of folds.

    PubMed

    Alva, Vikram; Remmert, Michael; Biegert, Andreas; Lupas, Andrei N; Söding, Johannes

    2010-01-01

    Many protein classification systems capture homologous relationships by grouping domains into families and superfamilies on the basis of sequence similarity. Superfamilies with similar 3D structures are further grouped into folds. In the absence of discernable sequence similarity, these structural similarities were long thought to have originated independently, by convergent evolution. However, the growth of databases and advances in sequence comparison methods have led to the discovery of many distant evolutionary relationships that transcend the boundaries of superfamilies and folds. To investigate the contributions of convergent versus divergent evolution in the origin of protein folds, we clustered representative domains of known structure by their sequence similarity, treating them as point masses in a virtual 2D space which attract or repel each other depending on their pairwise sequence similarities. As expected, families in the same superfamily form tight clusters. But often, superfamilies of the same fold are linked with each other, suggesting that the entire fold evolved from an ancient prototype. Strikingly, some links connect superfamilies with different folds. They arise from modular peptide fragments of between 20 and 40 residues that co-occur in the connected folds in disparate structural contexts. These may be descendants of an ancestral pool of peptide modules that evolved as cofactors in the RNA world and from which the first folded proteins arose by amplification and recombination. Our galaxy of folds summarizes, in a single image, most known and many yet undescribed homologous relationships between protein superfamilies, providing new insights into the evolution of protein domains. PMID:19937658

  1. Fast protein folding kinetics

    PubMed Central

    Gelman, Hannah; Gruebele, Martin

    2014-01-01

    Fast folding proteins have been a major focus of computational and experimental study because they are accessible to both techniques: they are small and fast enough to be reasonably simulated with current computational power, but have dynamics slow enough to be observed with specially developed experimental techniques. This coupled study of fast folding proteins has provided insight into the mechanisms which allow some proteins to find their native conformation well less than 1 ms and has uncovered examples of theoretically predicted phenomena such as downhill folding. The study of fast folders also informs our understanding of even “slow” folding processes: fast folders are small, relatively simple protein domains and the principles that govern their folding also govern the folding of more complex systems. This review summarizes the major theoretical and experimental techniques used to study fast folding proteins and provides an overview of the major findings of fast folding research. Finally, we examine the themes that have emerged from studying fast folders and briefly summarize their application to protein folding in general as well as some work that is left to do. PMID:24641816

  2. Multiply folded graphene

    NASA Astrophysics Data System (ADS)

    Kim, Kwanpyo; Lee, Zonghoon; Malone, Brad D.; Chan, Kevin T.; Alemán, Benjamín; Regan, William; Gannett, Will; Crommie, M. F.; Cohen, Marvin L.; Zettl, A.

    2011-06-01

    The folding of paper, hide, and woven fabric has been used for millennia to achieve enhanced articulation, curvature, and visual appeal for intrinsically flat, two-dimensional materials. For graphene, an ideal two-dimensional material, folding may transform it to complex shapes with new and distinct properties. Here, we present experimental results that folded structures in graphene, termed grafold, exist, and their formations can be controlled by introducing anisotropic surface curvature during graphene synthesis or transfer processes. Using pseudopotential-density-functional-theory calculations, we also show that double folding modifies the electronic band structure of graphene. Furthermore, we demonstrate the intercalation of C60 into the grafolds. Intercalation or functionalization of the chemically reactive folds further expands grafold's mechanical, chemical, optical, and electronic diversity.

  3. Folding of a miniprotein with mixed fold.

    PubMed

    Mohanty, Sandipan; Hansmann, U H E

    2007-07-21

    Using the 28 residue betabetaalpha protein FSD-EY as a target system, we examine correction terms for the ECEPP/3 force field. We find an increased probability of formation of the native state at low temperatures resulting from a reduced propensity to form alpha helices and increased formation of beta sheets. Our analysis of the observed folding events suggests that the C-terminal helix of FSD-EY is much more stable than the N-terminal beta hairpin and forms first. The hydrophobic groups of the helix provide a template which promotes the formation of the beta hairpin that is never observed to form without the helix. PMID:17655464

  4. Multiple folding pathways of proteins with shallow knots and co-translational folding

    NASA Astrophysics Data System (ADS)

    Chwastyk, Mateusz; Cieplak, Marek

    2015-07-01

    We study the folding process in the shallowly knotted protein MJ0366 within two variants of a structure-based model. We observe that the resulting topological pathways are much richer than identified in previous studies. In addition to the single knot-loop events, we find novel, and dominant, two-loop mechanisms. We demonstrate that folding takes place in a range of temperatures and the conditions of most successful folding are at temperatures which are higher than those required for the fastest folding. We also demonstrate that nascent conditions are more favorable to knotting than off-ribosome folding.

  5. Multiple folding pathways of proteins with shallow knots and co-translational folding.

    PubMed

    Chwastyk, Mateusz; Cieplak, Marek

    2015-07-28

    We study the folding process in the shallowly knotted protein MJ0366 within two variants of a structure-based model. We observe that the resulting topological pathways are much richer than identified in previous studies. In addition to the single knot-loop events, we find novel, and dominant, two-loop mechanisms. We demonstrate that folding takes place in a range of temperatures and the conditions of most successful folding are at temperatures which are higher than those required for the fastest folding. We also demonstrate that nascent conditions are more favorable to knotting than off-ribosome folding. PMID:26233164

  6. Stress and strain evolution of folding rocks

    NASA Astrophysics Data System (ADS)

    Llorens, Maria-Gema; Griera, Albert; Bons, Paul; Gomez-Rivas, Enrique; Weikusat, Ilka

    2015-04-01

    One of the main objectives of structural geology is to unravel rock deformation histories. Fold shapes can be used to estimate the orientation and amount of strain associated with folding. However, much more information on rheology and kinematics can potentially be extracted from fold geometries (Llorens et al., 2013a). We can study the development of folds, quantify the relationships between the different parameters that determine their geometries and estimate their mechanical evolution. This approach allows us to better understand and predict not only rock but also ice deformation. One of the main parameters in fold development is the viscosity contrast between the folding layer and the matrix in which it is embedded (m), since it determines the initial fold wavelength and the amplification rate of the developing folds. Moreover, non-linear viscous rheology influences fold geometry too (Llorens et al., 2013b). We present a series of 2-dimensional simulations of folding of viscous single layers in pure and simple shear. We vary different parameters in order to compare and determine their influence on the resulting fold patterns and the associated mechanical response of the material. To perform these simulations we use the software platform ELLE (www.elle.ws) with the non-linear viscous finite element code BASIL. The results show that layers thicken at the beginning of deformation in all simulations, and visible folds start earlier or later depending on the viscosity contrast. When folds start to nucleate the layer maximum shear strain decreases, moving away from the theoretical trend for homogeneous strain (no folding). This allows the accurate determination of the onset of folding. Maximum deviatoric stresses are higher in power-law than in linear-viscosity materials, and it is initially double in pure shear than in simple shear conditions. Therefore, folding a competent layer requires less work in simple than in pure shear. The maximum deviatoric stress

  7. Programmable matter by folding

    PubMed Central

    Hawkes, E.; An, B.; Benbernou, N. M.; Tanaka, H.; Kim, S.; Demaine, E. D.; Rus, D.; Wood, R. J.

    2010-01-01

    Programmable matter is a material whose properties can be programmed to achieve specific shapes or stiffnesses upon command. This concept requires constituent elements to interact and rearrange intelligently in order to meet the goal. This paper considers achieving programmable sheets that can form themselves in different shapes autonomously by folding. Past approaches to creating transforming machines have been limited by the small feature sizes, the large number of components, and the associated complexity of communication among the units. We seek to mitigate these difficulties through the unique concept of self-folding origami with universal crease patterns. This approach exploits a single sheet composed of interconnected triangular sections. The sheet is able to fold into a set of predetermined shapes using embedded actuation. To implement this self-folding origami concept, we have developed a scalable end-to-end planning and fabrication process. Given a set of desired objects, the system computes an optimized design for a single sheet and multiple controllers to achieve each of the desired objects. The material, called programmable matter by folding, is an example of a system capable of achieving multiple shapes for multiple functions. PMID:20616049

  8. Folding without charges

    PubMed Central

    Kurnik, Martin; Hedberg, Linda; Danielsson, Jens; Oliveberg, Mikael

    2012-01-01

    Surface charges of proteins have in several cases been found to function as “structural gatekeepers,” which avoid unwanted interactions by negative design, for example, in the control of protein aggregation and binding. The question is then if side-chain charges, due to their desolvation penalties, play a corresponding role in protein folding by avoiding competing, misfolded traps? To find out, we removed all 32 side-chain charges from the 101-residue protein S6 from Thermus thermophilus. The results show that the charge-depleted S6 variant not only retains its native structure and cooperative folding transition, but folds also faster than the wild-type protein. In addition, charge removal unleashes pronounced aggregation on longer timescales. S6 provides thus an example where the bias toward native contacts of a naturally evolved protein sequence is independent of charges, and point at a fundamental difference in the codes for folding and intermolecular interaction: specificity in folding is governed primarily by hydrophobic packing and hydrogen bonding, whereas solubility and binding relies critically on the interplay of side-chain charges. PMID:22454493

  9. Synthesizing folded band chaos.

    PubMed

    Corron, Ned J; Hayes, Scott T; Pethel, Shawn D; Blakely, Jonathan N

    2007-04-01

    A randomly driven linear filter that synthesizes Lorenz-like, reverse-time chaos is shown also to produce Rössler-like folded band wave forms when driven using a different encoding of the random source. The relationship between the topological entropy of the random source, dissipation in the linear filter, and the positive Lyapunov exponent for the reverse-time wave form is exposed. The two drive encodings are viewed as grammar restrictions on a more general encoding that produces a chaotic superset encompassing both the Lorenz butterfly and Rössler folded band paradigms of nonlinear dynamics. PMID:17500950

  10. Modelling of lateral fold growth and fold linkage: Applications to fold-and-thrust belt tectonics

    NASA Astrophysics Data System (ADS)

    Grasemann, Bernhard; Schmalholz, Stefan

    2013-04-01

    We use a finite element model to investigate the three-dimensional fold growth and interference of two initially isolated fold segments. The most critical parameter, which controls the fold linkage mode, is the phase difference between the laterally growing fold hinge lines: 1) "Linear-linkage" yields a sub-cylindrical fold with a saddle at the location where the two initial folds linked. 2) "Oblique-linkage" produces a curved fold resembling a Type II refold structure. 3) "Oblique-no-linkage" results in two curved folds with fold axes plunging in opposite directions. 4) "Linear-no-linkage" yields a fold train of two separate sub-cylindrical folds with fold axes plunging in opposite directions. The transition from linkage to no-linkage occurs when the fold separation between the initially isolated folds is slightly larger than one half of the low-amplitude fold wavelength. The model results compare well with previously published plasticine analogue models and can be directly applied to the investigation of fold growth history in fold-and-thust belts. An excellent natural example of lateral fold linkage is described from the Zagros fold-and-thrust belt in the Kurdistan Region of Iraq. The fold growth in this region is not controlled by major thrust faults but the shortening of the Paleozoic to Cenozoic passive margin sediments of the Arabian plate occurred mainly by detachment folding. The sub-cylindrical anticlines with hinge-parallel lengths of more than 50 km have not developed from single sub-cylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification and lateral fold growth. Linkage points are marked by geomorphological saddle points which are structurally the lowermost points of antiforms and points of principal curvatures with opposite sign. Linkage points can significantly influence the migration of mineral-rich fluids and hydrocarbons and are therefore of great economic importance.

  11. The uteroglobin fold.

    PubMed

    Callebaut, I; Poupon, A; Bally, R; Demaret, J P; Housset, D; Delettré, J; Hossenlopp, P; Mornon, J P

    2000-01-01

    Uteroglobin (UTG) forms a fascinating homodimeric structure that binds small- to medium-sized ligands through an internal hydrophobic cavity, located at the interface between the two monomers. Previous studies have shown that UTG fold is not limited to the UTG/CC10 family, whose sequence/structure relationships are highlighted here, but can be extended to the cap domain of Xanthobacter autotrophicus haloalkane dehalogenase. We show here that UTG fold is adopted by several other cap domains within the alpha/beta hydrolase family, making it a well-suited "geode" structure allowing it to sequester various hydrophobic molecules. Additionally, some data about a new crystal form of oxidized rabbit UTG are presented, completing previous structural studies, as well as results from molecular dynamics, suggesting an alternative way for the ligand to reach the internal cavity. PMID:11193783

  12. The protein folding network

    NASA Astrophysics Data System (ADS)

    Rao, Francesco; Caflisch, Amedeo

    2004-03-01

    Networks are everywhere. The conformation space of a 20-residue antiparallel beta-sheet peptide [1], sampled by molecular dynamics simulations, is mapped to a network. Conformations are nodes of the network, and the transitions between them are links. As previously found for the World-Wide Web as well as for social and biological networks , the conformation space contains highly connected hubs like the native state which is the most populated free energy basin. Furthermore, the network shows a hierarchical modularity [2] which is consistent with the funnel mechanism of folding [3] and is not observed for a random heteropolymer lacking a native state. Here we show that the conformation space network describes the free energy landscape without requiring projections into arbitrarily chosen reaction coordinates. The network analysis provides a basis for understanding the heterogeneity of the folding transition state and the existence of multiple pathways. [1] P. Ferrara and A. Caflisch, Folding simulations of a three-stranded antiparallel beta-sheet peptide, PNAS 97, 10780-10785 (2000). [2] Ravasz, E. and Barabási, A. L. Hierarchical organization in complex networks. Phys. Rev. E 67, 026112 (2003). [3] Dill, K. and Chan, H From Levinthal to pathways to funnels. Nature Struct. Biol. 4, 10-19 (1997)

  13. Ab initio RNA folding

    NASA Astrophysics Data System (ADS)

    Cragnolini, Tristan; Derreumaux, Philippe; Pasquali, Samuela

    2015-06-01

    RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, the experimental determination of RNA structures through x-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, the need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties, when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.

  14. Chirality and protein folding

    NASA Astrophysics Data System (ADS)

    Kwiecinska, Joanna I.; Cieplak, Marek

    2005-05-01

    There are several simple criteria of folding to a native state in model proteins. One of them involves crossing of a threshold value of the root mean square deviation distance away from the native state. Another checks whether all native contacts are established, i.e. whether the interacting amino acids come closer than some characteristic distance. We use Go-like models of proteins and show that such simple criteria may prompt one to declare folding even though fragments of the resulting conformations have a wrong sense of chirality. We propose that a better condition of folding should augment the simple criteria with the requirement that most of the local values of the chirality should be nearly native. The kinetic discrepancy between the simple and compound criteria can be substantially reduced in the Go-like models by providing the Hamiltonian with a term which favours native values of the local chirality. We study the effects of this term as a function of its amplitude and compare it to other models such as ones with side groups and ones with angle-dependent potentials.

  15. Folding within seconds

    NASA Astrophysics Data System (ADS)

    Kenkmann, Thomas

    2002-03-01

    Hypervelocity impacts of cosmic projectiles larger than ˜200 m diameter are capable of forming complex craters on Earth. At these craters, shock loading, shock damage, and excavation flow are followed by a gravity-driven collapse of the deep transient cavity. Such impact structures are characterized by a central uplift, a flat crater floor, and a terraced crater rim. Collapse-induced deformation features, like folds and brittle fault zones, have many similarities to tectonic structures. Typical deformation patterns of complex terrestrial impact craters of 5 15 km diameter are compiled and analyzed with respect to their kinematic development. Unlike their tectonic counterparts, deformation structures are always the result of non-plane-strain deformation and are formed in a single event that takes place in seconds to minutes. To understand the high-strain-rate processes, the microstructure of an impact-induced fold of the Crooked Creek impact crater (˜7 km diameter), Missouri, United States, is investigated in detail. A period of 20 30 s at the most is determined for the collapse phase of this crater. The gross plastic deformation behavior of the fold is achieved by localized brittle deformation along millimeter- to centimeter-spaced fault zones, forming a network of veins. Shock damage has fractured ˜40% of grain boundaries. The onset of collapse and associated deformation started in rocks with a reduced cohesion and is friction controlled.

  16. Ab initio RNA folding.

    PubMed

    Cragnolini, Tristan; Derreumaux, Philippe; Pasquali, Samuela

    2015-06-17

    RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, the experimental determination of RNA structures through x-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, the need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties, when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding. PMID:25993396

  17. Folded waveguide coupler

    DOEpatents

    Owens, Thomas L.

    1988-03-01

    A resonant cavity waveguide coupler for ICRH of a magnetically confined plasma. The coupler consists of a series of inter-leaved metallic vanes disposed withn an enclosure analogous to a very wide, simple rectangular waveguide that has been "folded" several times. At the mouth of the coupler, a polarizing plate is provided which has coupling apertures aligned with selected folds of the waveguide through which rf waves are launched with magnetic fields of the waves aligned in parallel with the magnetic fields confining the plasma being heated to provide coupling to the fast magnetosonic wave within the plasma in the frequency usage of from about 50-200 mHz. A shorting plate terminates the back of the cavity at a distance approximately equal to one-half the guide wavelength from the mouth of the coupler to ensure that the electric field of the waves launched through the polarizing plate apertures are small while the magnetic field is near a maximum. Power is fed into the coupler folded cavity by means of an input coaxial line feed arrangement at a point which provides an impedance match between the cavity and the coaxial input line.

  18. Kinematics of constant arc length folding for different fold shapes

    NASA Astrophysics Data System (ADS)

    Ghassemi, Mohammad R.; Schmalholz, Stefan M.; Ghassemi, Ali R.

    2010-06-01

    Basic mathematical functions are applied for the two-dimensional geometrical and kinematical analysis of different fold shapes. Relationships between different fold parameters are established and related to the bulk shortening taking place during folding under upper crustal conditions. The bulk shortening taking place during constant arc length folding is mathematically related to the bulk shortening during homogenous pure shear using a particular aspect ratio, which is for folding the ratio of amplitude to half wavelength and for pure shear the ratio of vertical to horizontal length of the deformed, initially square body. The evolution of the fold aspect ratio with bulk shortening is similar for a wide range of fold shapes and indicates that the fold aspect ratio allows a good estimate of the bulk shortening. The change of the geometry of individual layers across a multilayer sequence in disharmonic folding indicates a specific kinematics of multilayer folding, referred to here as "wrap folding", which does not require significant flexural slip nor flexural flow. The kinematic analysis indicates that there is a critical value for constant arc length folding between shortening values of 30-40% (depending on the fold geometry). For shortening values smaller than the critical value limb rotation and fold amplitude growth are dominating. For shortening larger than this value, faulting, boudinage and foliation development are likely the dominating deformation process during continued shortening. The kinematical analysis of constant arc length folding can be used for estimating the bulk shortening taking place during multilayer folding which is an important component of the deformation of crustal rocks during the early history of shortening. The bulk shortening is estimated for a natural, multilayer detachment fold and the shortening estimates based on the kinematic analysis are compared and supported by numerical finite element simulations of multilayer detachment

  19. Information from folds: A review

    NASA Astrophysics Data System (ADS)

    Hudleston, Peter J.; Treagus, Susan H.

    2010-12-01

    Folds are spectacular geological structures that are seen in layered rock on many different scales. To mark 30 years of the Journal of Structural Geology, we review the information that can be gained from studies of folds in theory, experiment and nature. We first review theoretical considerations and modeling, from classical approaches to current developments. The subject is dominated by single-layer fold theory, with the assumption of perfect layer-parallel shortening, but we also review multilayer fold theory and modeling, and folding of layers that are oblique to principal stresses and strains. This work demonstrates that viscosity ratio, degree of non-linearity of the flow law, anisotropy, and the thickness and spacing distribution of layers of different competence are all important in determining the nature and strength of the folding instability. Theory and modeling provide the basis for obtaining rheological information from natural folds, through analysis of wavelength/thickness ratios of single layer folds, and fold shapes. They also provide a basis for estimating the bulk strain from folded layers. Information about folding mechanisms can be obtained by analysis of cleavage and fabric patterns in folded rocks, and the history of deformation can be revealed by understanding how asymmetry can develop in folds, by how folds develop in shear zones, and how folds develop in more complex three-dimensional deformations.

  20. Peptide folding simulations.

    PubMed

    Gnanakaran, S; Nymeyer, Hugh; Portman, John; Sanbonmatsu, Kevin Y; García, Angel E

    2003-04-01

    Developments in the design of small peptides that mimic proteins in complexity, recent advances in nanosecond time-resolved spectroscopy methods to study peptides and the development of modern, highly parallel simulation algorithms have come together to give us a detailed picture of peptide folding dynamics. Two newly implemented simulation techniques, parallel replica dynamics and replica exchange molecular dynamics, can now describe directly from simulations the kinetics and thermodynamics of peptide formation, respectively. Given these developments, the simulation community now has the tools to verify and validate simulation protocols and models (forcefields). PMID:12727509

  1. Structural Characteristics of Novel Protein Folds

    PubMed Central

    Fernandez-Fuentes, Narcis; Dybas, Joseph M.; Fiser, Andras

    2010-01-01

    Folds are the basic building blocks of protein structures. Understanding the emergence of novel protein folds is an important step towards understanding the rules governing the evolution of protein structure and function and for developing tools for protein structure modeling and design. We explored the frequency of occurrences of an exhaustively classified library of supersecondary structural elements (Smotifs), in protein structures, in order to identify features that would define a fold as novel compared to previously known structures. We found that a surprisingly small set of Smotifs is sufficient to describe all known folds. Furthermore, novel folds do not require novel Smotifs, but rather are a new combination of existing ones. Novel folds can be typified by the inclusion of a relatively higher number of rarely occurring Smotifs in their structures and, to a lesser extent, by a novel topological combination of commonly occurring Smotifs. When investigating the structural features of Smotifs, we found that the top 10% of most frequent ones have a higher fraction of internal contacts, while some of the most rare motifs are larger, and contain a longer loop region. PMID:20421995

  2. Folds on Europa

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This image, acquired by NASA's Galileo spacecraft on September 26, 1998, shows features on the surface of Jupiter's moon Europa that a scientific report published today interprets as signs of compressive folding.

    The imaged area is in the Astypalaea Linea region of Europa's southern hemisphere, seen with low-angle sunshine coming from the upper right. North is toward the top.

    Astypalaea Linea is the smooth, gray area that stretches from north to south across the image mosaic. It is thought to have formed by a combination of pulling apart and sliding of the icy surface. The telltale fold features are within the smoother portions of the surface between the more dominant ridges, which are attributed to upwelling of material through surface ice. In the smooth areas, the surface has gentle swells and dips, which show most clearly in the version on the right, processed to accentuate broader-scale shapes. For example, a dip about 15 kilometers (about 10 miles) wide cuts diagonally across the northern half of the largest smooth area, and a rise runs parallel to that in the southern half of the smooth area. closeup detail

    Louise M. Prockter, at Johns Hopkins University, and Robert T. Pappalardo, at Brown University, report in the journal Science today that those rises, or anticlines, and dips, or synclines, appear to be the result of compression causing the crust to fold.

    Additional evidence comes from smaller features more visible in the version on the left, covering the same area. At the crest of the gentle rise in the largest smooth area are small fractures that could be caused by the stretching stress of bending the surface layer upwards. Similarly, at the bottom of the adjacent dip are small, wrinkle-like ridges that could be caused by stress from bending the surface layer downwards.

    The Jet Propulsion Laboratory, Pasadena, Calif., manages the Galileo mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California

  3. Cellular folding pathway of a metastable serpin.

    PubMed

    Chandrasekhar, Kshama; Ke, Haiping; Wang, Ning; Goodwin, Theresa; Gierasch, Lila M; Gershenson, Anne; Hebert, Daniel N

    2016-06-01

    Although proteins generally fold to their thermodynamically most stable state, some metastable proteins populate higher free energy states. Conformational changes from metastable higher free energy states to lower free energy states with greater stability can then generate the work required to perform physiologically important functions. However, how metastable proteins fold to these higher free energy states in the cell and avoid more stable but inactive conformations is poorly understood. The serpin family of metastable protease inhibitors uses large conformational changes that are downhill in free energy to inhibit target proteases by pulling apart the protease active site. The serpin antithrombin III (ATIII) targets thrombin and other proteases involved in blood coagulation, and ATIII misfolding can thus lead to thrombosis and other diseases. ATIII has three disulfide bonds, two near the N terminus and one near the C terminus. Our studies of ATIII in-cell folding reveal a surprising, biased order of disulfide bond formation, with early formation of the C-terminal disulfide, before formation of the N-terminal disulfides, critical for folding to the active, metastable state. Early folding of the predominantly β-sheet ATIII domain in this two-domain protein constrains the reactive center loop (RCL), which contains the protease-binding site, ensuring that the RCL remains accessible. N-linked glycans and carbohydrate-binding molecular chaperones contribute to the efficient folding and secretion of functional ATIII. The inability of a number of disease-associated ATIII variants to navigate the folding reaction helps to explain their disease phenotypes. PMID:27222580

  4. Analysis of High-Fold Gamma Data

    SciTech Connect

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

    1998-08-10

    Historically, {gamma}-{gamma} and {gamma}-{gamma}-{gamma} 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 higher efficiencies, and detect an many as 15 or 20 {gamma} 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.

  5. Protein folding. Translational tuning optimizes nascent protein folding in cells.

    PubMed

    Kim, Soo Jung; Yoon, Jae Seok; Shishido, Hideki; Yang, Zhongying; Rooney, LeeAnn A; Barral, Jose M; Skach, William R

    2015-04-24

    In cells, biosynthetic machinery coordinates protein synthesis and folding to optimize efficiency and minimize off-pathway outcomes. However, it has been difficult to delineate experimentally the mechanisms responsible. Using fluorescence resonance energy transfer, we studied cotranslational folding of the first nucleotide-binding domain from the cystic fibrosis transmembrane conductance regulator. During synthesis, folding occurred discretely via sequential compaction of N-terminal, α-helical, and α/β-core subdomains. Moreover, the timing of these events was critical; premature α-subdomain folding prevented subsequent core formation. This process was facilitated by modulating intrinsic folding propensity in three distinct ways: delaying α-subdomain compaction, facilitating β-strand intercalation, and optimizing translation kinetics via codon usage. Thus, de novo folding is translationally tuned by an integrated cellular response that shapes the cotranslational folding landscape at critical stages of synthesis. PMID:25908822

  6. Probes for narcotic receptor mediated phenomena 49. N-substituted rac-cis-4a-arylalkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.

    PubMed

    Iyer, Malliga R; Rothman, Richard B; Dersch, Christina M; Jacobson, Arthur E; Rice, Kenner C

    2015-03-01

    Racemic N-substituted -1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols containing cis-4a-aralkyl groups were explored as probes for opioid receptors. Specifically cis-4a-phenylpropyl, -phenylbutyl, and-phenylpentyl groups coupled with widely varied substituents on the nitrogen atom were synthesized and their pharmacological profiles at opioid receptors examined. The study yielded compounds with good affinity and moderate to potent antagonist activity at the μ- and δ-opioid receptors, and agonist activity at the κ-opioid receptor. An N-allyl substituent in the C4a phenylpropyl series induced 6-fold higher affinity at δ-than μ-receptors, while an N-CPM substituent in the C4a (CH2)3Ph series led to a compound with high δ-affinity and potent δ-antagonist activity. PMID:25599950

  7. How the genome folds

    NASA Astrophysics Data System (ADS)

    Lieberman Aiden, Erez

    2012-02-01

    I describe Hi-C, a novel technology for probing the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. Working with collaborators at the Broad Institute and UMass Medical School, we used Hi-C to construct spatial proximity maps of the human genome at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

  8. Protein folding in the ER.

    SciTech Connect

    Stevens, F. J.; Argon, Y.; Biosciences Division; Univ. of Chicago

    1999-10-01

    The endoplasmic reticulum (ER) is a major protein folding compartment for secreted, plasma membrane and organelle proteins. Each of these newly-synthesized polypeptides folds in a deterministic process, affected by the unique conditions that exist in the ER. An understanding of protein folding in the ER is a fundamental biomolecular challenge at two levels. The first level addresses how the amino acid sequence programs that polypeptide to efficiently arrive at a particular fold out of a multitude of alternatives, and how different sequences obtain similar folds. At the second level are the issues introduced by folding not in the cytosol, but in the ER, including the risk of aggregation in a molecularly crowded environment, accommodation of post-translational modifications and the compatibility with subsequent intracellular trafficking. This review discusses both the physicochemical and cell biological constraints of folding, which are the challenges that the ER molecular chaperones help overcome.

  9. 1,2,3-Trichloropropane

    Integrated Risk Information System (IRIS)

    1,2,3 - Trichloropropane ; CASRN 96 - 18 - 4 Human health assessment information on a chemical substance is included in IRIS only after a comprehensive review of toxicity data by U.S . EPA health scientists from several program offices , regional offices , and the Office of Research and Development

  10. 3D fold growth rates in transpressional tectonic settings

    NASA Astrophysics Data System (ADS)

    Frehner, Marcel

    2015-04-01

    Geological folds are inherently three-dimensional (3D) structures; hence, they also grow in 3D. In this study, fold growth in all three dimensions is quantified numerically using a finite-element algorithm for simulating deformation of Newtonian media in 3D. The presented study is an extension and generalization of the work presented in Frehner (2014), which only considered unidirectional layer-parallel compression. In contrast, the full range from strike slip settings (i.e., simple shear) to unidirectional layer-parallel compression is considered here by varying the convergence angle of the boundary conditions; hence the results are applicable to general transpressional tectonic settings. Only upright symmetrical single-layer fold structures are considered. The horizontal higher-viscous layer exhibits an initial point-like perturbation. Due to the mixed pure- and simple shear boundary conditions a mechanical buckling instability grows from this perturbation in all three dimensions, described by: Fold amplification (vertical growth): Fold amplification describes the growth from a fold shape with low limb-dip angle to a shape with higher limb-dip angle. Fold elongation (growth parallel to fold axis): Fold elongation describes the growth from a dome-shaped (3D) structure to a more cylindrical fold (2D). Sequential fold growth (growth perpendicular to fold axial plane): Sequential fold growth describes the growth of secondary (and further) folds adjacent to the initial isolated fold. The term 'lateral fold growth' is used as an umbrella term for both fold elongation and sequential fold growth. In addition, the orientation of the fold axis is tracked as a function of the convergence angle. Even though the absolute values of all three growth rates are markedly reduced with increasing simple-shear component at the boundaries, the general pattern of the quantified fold growth under the studied general-shear boundary conditions is surprisingly similar to the end

  11. Computational analysis of hydrogenated graphyne folding

    NASA Astrophysics Data System (ADS)

    Lenear, Christopher; Becton, Matthew; Wang, Xianqiao

    2016-02-01

    This letter employs molecular mechanics simulations to analyze the geometric changes of foreign-atom-doped graphyne. Simulation results show that higher the density of dopant and the greater area covered by the dopant correlates to a greater folding angle of the graphyne sheet. Compared to graphene, graphyne folding could prove to be more effective for various nanodevices based on its unique band gap, especially when doped, and its tunable interactions with and absorption of foreign molecules. Therefore, our findings may offer unique perspectives into the development of novel graphyne-based nanodevices and stimulate the community's research interest in graphene-related origami.

  12. Evolutionary optimization of protein folding.

    PubMed

    Debès, Cédric; Wang, Minglei; Caetano-Anollés, Gustavo; Gräter, Frauke

    2013-01-01

    Nature has shaped the make up of proteins since their appearance, [Formula: see text]3.8 billion years ago. However, the fundamental drivers of structural change responsible for the extraordinary diversity of proteins have yet to be elucidated. Here we explore if protein evolution affects folding speed. We estimated folding times for the present-day catalog of protein domains directly from their size-modified contact order. These values were mapped onto an evolutionary timeline of domain appearance derived from a phylogenomic analysis of protein domains in 989 fully-sequenced genomes. Our results show a clear overall increase of folding speed during evolution, with known ultra-fast downhill folders appearing rather late in the timeline. Remarkably, folding optimization depends on secondary structure. While alpha-folds showed a tendency to fold faster throughout evolution, beta-folds exhibited a trend of folding time increase during the last [Formula: see text]1.5 billion years that began during the "big bang" of domain combinations. As a consequence, these domain structures are on average slow folders today. Our results suggest that fast and efficient folding of domains shaped the universe of protein structure. This finding supports the hypothesis that optimization of the kinetic and thermodynamic accessibility of the native fold reduces protein aggregation propensities that hamper cellular functions. PMID:23341762

  13. Isoform diversity in the Arp2/3 complex determines actin filament dynamics.

    PubMed

    Abella, Jasmine V G; Galloni, Chiara; Pernier, Julien; Barry, David J; Kjær, Svend; Carlier, Marie-France; Way, Michael

    2016-01-01

    The Arp2/3 complex consists of seven evolutionarily conserved subunits (Arp2, Arp3 and ARPC1-5) and plays an essential role in generating branched actin filament networks during many different cellular processes. In mammals, however, the ARPC1 and ARPC5 subunits are each encoded by two isoforms that are 67% identical. This raises the possibility that Arp2/3 complexes with different properties may exist.  We found that Arp2/3 complexes containing ARPC1B and ARPC5L are significantly better at promoting actin assembly than those with ARPC1A and ARPC5, both in cells and in vitro. Branched actin networks induced by complexes containing ARPC1B or ARPC5L are also disassembled ∼2-fold slower than those formed by their counterparts. This difference reflects the ability of cortactin to stabilize ARPC1B- and ARPC5L- but not ARPC1A- and ARPC5-containing complexes against coronin-mediated disassembly. Our observations demonstrate that the Arp2/3 complex in higher eukaryotes is actually a family of complexes with different properties. PMID:26655834

  14. Graphene folding on flat substrates

    SciTech Connect

    Chen, Xiaoming; Zhao, Yadong; Ke, Changhong; Zhang, Liuyang; Wang, Xianqiao

    2014-10-28

    We present a combined experimental-theoretical study of graphene folding on flat substrates. The structure and deformation of the folded graphene sheet are experimentally characterized by atomic force microscopy. The local graphene folding behaviors are interpreted based on nonlinear continuum mechanics modeling and molecular dynamics simulations. Our study on self-folding of a trilayer graphene sheet reports a bending stiffness of about 6.57 eV, which is about four times the reported values for monolayer graphene. Our results reveal that an intriguing free sliding phenomenon occurs at the interlayer van der Waals interfaces during the graphene folding process. This work demonstrates that it is a plausible venue to quantify the bending stiffness of graphene based on its self-folding conformation on flat substrates. The findings reported in this work are useful to a better understanding of the mechanical properties of graphene and in the pursuit of its applications.

  15. COS NUV MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2010-09-01

    The performance of the MAMA microchannel plate can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the COS MAMA Fold Analysis {11891} during Cycle 17.

  16. COS NUV MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2012-10-01

    The performance of the MAMA microchannel plate can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the COS MAMA Fold Analysis {12723} during Cycle 19.

  17. Limited cooperativity in protein folding.

    PubMed

    Muñoz, Victor; Campos, Luis A; Sadqi, Mourad

    2016-02-01

    Theory and simulations predict that the structural concert of protein folding reactions is relatively low. Experimentally, folding cooperativity has been difficult to study, but in recent years we have witnessed major advances. New analytical procedures in terms of conformational ensembles rather than discrete states, experimental techniques with improved time, structural, or single-molecule resolution, and combined thermodynamic and kinetic analysis of fast folding have contributed to demonstrate a general scenario of limited cooperativity in folding. Gradual structural disorder is already apparent on the unfolded and native states of slow, two-state folding proteins, and it greatly increases in magnitude for fast folding domains. These results demonstrate a direct link between how fast a single-domain protein folds and unfolds, and how cooperative (or structurally diverse) is its equilibrium unfolding process. Reducing cooperativity also destabilizes the native structure because it affects unfolding more than folding. We can thus define a continuous cooperativity scale that goes from the 'pliable' two-state character of slow folders to the gradual unfolding of one-state downhill, and eventually to intrinsically disordered proteins. The connection between gradual unfolding and intrinsic disorder is appealing because it suggests a conformational rheostat mechanism to explain the allosteric effects of folding coupled to binding. PMID:26845039

  18. Compact intermediates in RNA folding

    SciTech Connect

    Woodson, S.A.

    2011-12-14

    Large noncoding RNAs fold into their biologically functional structures via compact yet disordered intermediates, which couple the stable secondary structure of the RNA with the emerging tertiary fold. The specificity of the collapse transition, which coincides with the assembly of helical domains, depends on RNA sequence and counterions. It determines the specificity of the folding pathways and the magnitude of the free energy barriers to the ensuing search for the native conformation. By coupling helix assembly with nascent tertiary interactions, compact folding intermediates in RNA also play a crucial role in ligand binding and RNA-protein recognition.

  19. Paradoxical Vocal Fold Movement (PVFM)

    MedlinePlus

    ... Careers Certification Publications Events Advocacy Continuing Education Practice Management Research Home / Information for the Public / Speech, Language and Swallowing / Disorders and Diseases Paradoxical Vocal Fold ...

  20. Folding superfunnel to describe cooperative folding of interacting proteins.

    PubMed

    Smeller, László

    2016-07-01

    This paper proposes a generalization of the well-known folding funnel concept of proteins. In the funnel model the polypeptide chain is treated as an individual object not interacting with other proteins. Since biological systems are considerably crowded, protein-protein interaction is a fundamental feature during the life cycle of proteins. The folding superfunnel proposed here describes the folding process of interacting proteins in various situations. The first example discussed is the folding of the freshly synthesized protein with the aid of chaperones. Another important aspect of protein-protein interactions is the folding of the recently characterized intrinsically disordered proteins, where binding to target proteins plays a crucial role in the completion of the folding process. The third scenario where the folding superfunnel is used is the formation of aggregates from destabilized proteins, which is an important factor in case of several conformational diseases. The folding superfunnel constructed here with the minimal assumption about the interaction potential explains all three cases mentioned above. Proteins 2016; 84:1009-1016. © 2016 Wiley Periodicals, Inc. PMID:27090200

  1. Understanding the folding rates and folding nuclei of globular proteins.

    PubMed

    Finkelstein, Alexei V; Ivankov, Dmitry N; Garbuzynskiy, Sergiy O; Galzitskaya, Oxana V

    2007-12-01

    The first part of this paper contains an overview of protein structures, their spontaneous formation ("folding"), and the thermodynamic and kinetic aspects of this phenomenon, as revealed by in vitro experiments. It is stressed that universal features of folding are observed near the point of thermodynamic equilibrium between the native and denatured states of the protein. Here the "two-state" ("denatured state" <--> "native state") transition proceeds without accumulation of metastable intermediates, but includes only the unstable "transition state". This state, which is the most unstable in the folding pathway, and its structured core (a "nucleus") are distinguished by their essential influence on the folding/unfolding kinetics. In the second part of the paper, a theory of protein folding rates and related phenomena is presented. First, it is shown that the protein size determines the range of a protein's folding rates in the vicinity of the point of thermodynamic equilibrium between the native and denatured states of the protein. Then, we present methods for calculating folding and unfolding rates of globular proteins from their sizes, stabilities and either 3D structures or amino acid sequences. Finally, we show that the same theory outlines the location of the protein folding nucleus (i.e., the structured part of the transition state) in reasonable agreement with experimental data. PMID:18220841

  2. Characterization and evolution of vertebrate indoleamine 2, 3-dioxygenases IDOs from monotremes and marsupials.

    PubMed

    Yuasa, Hajime J; Ball, Helen J; Ho, Yuen Fern; Austin, Christopher J D; Whittington, Camilla M; Belov, Katherine; Maghzal, Ghassan J; Jermiin, Lars S; Hunt, Nicholas H

    2009-06-01

    Indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that catalyze the first step in tryptophan catabolism via the kynurenine pathway. TDO is widely distributed in both eukaryotes and bacteria. In contrast, IDO has been found only in mammals and yeast. In 2007, a third enzyme, indoleamine 2,3-dioxygenase-2 (IDO2), was discovered. IDO2 is found not only in mammals but also in lower vertebrates. Interestingly, the Km value of IDO2 for L-Trp was 500-1000 fold higher than that of IDO1. In this study, we isolated both IDO1 and IDO2 cDNA from a monotreme, the platypus (Ornithorhynchus anatinus), and a marsupial, the gray short-tailed opossum (Monodelphis domestica). We characterized the recombinant proteins and those of other known IDO1/IDO2 in intact cells and a cell-free system. It was found that methylene blue may not be suitable reductant for IDO2, hence resulting in an underestimation of recombinant IDO2 activity. In intact cells, the Km value of IDO2 for L-Trp was estimated to be much higher than that of IDO1 and this high Km value appears to have been conserved during the evolution of IDO2. The protein encoded by the ancestor gene of IDO1 and IDO2 is likely to have had properties more similar to present day IDO2 than to IDO1. PMID:19402226

  3. Shear properties of vocal fold mucosal tissues and their effect on vocal fold oscillation

    NASA Astrophysics Data System (ADS)

    Chan, Roger Wai Kai

    Viscoelastic shear properties of vocal fold mucosal tissues and phonosurgical biomaterials were measured with a parallel-plate rotational rheometer. Elastic, viscous and damping properties were quantified as a function of frequency (0.01 Hz to 15 Hz) for human vocal fold mucosal tissues (N = 15), implantable biomaterials commonly used in the treatment of vocal fold paralysis (Teflon, gelatin, and collagen) (the non-mucosal group), and biomaterials currently or potentially useful in the treatment of vocal fold mucosal defects (adipose tissue or fat, hyaluronic acid, and fibronectin) (the mucosal group). It was found that intersubject differences as large as an order of magnitude were often observed for the shear properties of vocal fold mucosal tissues, part of which may be age- and gender-related. Shear properties of the non-mucosal group biomaterials were often much higher than those of the mucosal group biomaterials, which were relatively close to the shear properties of mucosal tissues. Viscoelastic and rheological modeling showed that shear properties of human vocal fold mucosa may be described by a quasi-linear viscoelastic theory and a statistical network theory, based upon which extrapolations to audio frequencies were possible. A theory of small-amplitude vocal fold oscillation was revisited to describe the effects of tissue shear properties on vocal fold oscillation and phonation threshold pressure, a measure of the 'ease' of phonation and an objective indication of vocal function. It was found that phonation threshold pressure is directly related to the viscous shear modulus or the 'effective damping modulus', a concept proposed to quantify the effective amount of damping in vocal fold oscillation. The mucosal group biomaterials were incorporated into the artificial vocal fold mucosa of a physical model in order to empirically assess their effects on phonation threshold pressure. Results showed that higher threshold pressures were consistently observed

  4. Pseudoknots in RNA folding landscapes

    PubMed Central

    Kucharík, Marcel; Hofacker, Ivo L.; Stadler, Peter F.; Qin, Jing

    2016-01-01

    Motivation: The function of an RNA molecule is not only linked to its native structure, which is usually taken to be the ground state of its folding landscape, but also in many cases crucially depends on the details of the folding pathways such as stable folding intermediates or the timing of the folding process itself. To model and understand these processes, it is necessary to go beyond ground state structures. The study of rugged RNA folding landscapes holds the key to answer these questions. Efficient coarse-graining methods are required to reduce the intractably vast energy landscapes into condensed representations such as barrier trees or basin hopping graphs (BHG) that convey an approximate but comprehensive picture of the folding kinetics. So far, exact and heuristic coarse-graining methods have been mostly restricted to the pseudoknot-free secondary structures. Pseudoknots, which are common motifs and have been repeatedly hypothesized to play an important role in guiding folding trajectories, were usually excluded. Results: We generalize the BHG framework to include pseudoknotted RNA structures and systematically study the differences in predicted folding behavior depending on whether pseudoknotted structures are allowed to occur as folding intermediates or not. We observe that RNAs with pseudoknotted ground state structures tend to have more pseudoknotted folding intermediates than RNAs with pseudoknot-free ground state structures. The occurrence and influence of pseudoknotted intermediates on the folding pathway, however, appear to depend very strongly on the individual RNAs so that no general rule can be inferred. Availability and implementation: The algorithms described here are implemented in C++ as standalone programs. Its source code and Supplemental material can be freely downloaded from http://www.tbi.univie.ac.at/bhg.html. Contact: qin@bioinf.uni-leipzig.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID

  5. Destruction of 2,2`,3 - trichlorobiphenyl in aqueous solution by hydrous pyrolysis/oxidation (HPO)

    SciTech Connect

    Leif, R.N.; Knauss, K.G.; Mew, D.A.; Aines, R.D.

    1997-11-25

    Aqueous, low-temperature oxidation rates for the polychlorinated biphenyl (PCB) congener 2,2`,3-trichlorobiphenyl have been measured in aqueous phosphate-buffered solutions using Dickson-type reaction vessels. Concentrations of the target compounds were determined by gas chromatography and compound identification was verified by gas chromatography - mass spectrometry. The reaction temperatures ranged from 131 {degrees}C to 165{degrees}C and the activation energy for the destruction of 2,2`,3-trichlorobiphenyl was estimated to be 134 kJ/mole. In a low concentration experiment (approximately 500 ng/g starting concentration), 2,2`,3-trichlorobiphenyl concentration reached non-detect in two days at 135{degrees}C. In a much higher concentration experiment (approximately 24,000 mg/g initial loading), nearly 40% of the initial 2,2`,3-trichlorobiphenyl concentration, or about 10,000 ng/g was destroyed at 161{degrees}C in 18 days. The 2,2`, 3-trichlorobiphenyl concentration of 24,000 ng/g measured at 131{degrees}C represents a greater than 100 fold increase in the aqueous solubility compared to the value of 200 ng/g at 20{degrees}C reported by Mackay et al. During the experiments the reacted portion of the 2,2`, 3-trichlorobiphenyl was completely mineralized, as indicated by a stoichiometric production of inorganic carbon and chloride ion, and no intermediates amenable to gas chromatography were observed during the HPO experiments. These preliminary experiments indicate that hydrous pyrolysis/oxidation (HPO) may be a useful alternative method for remediating soil and groundwater contaminated with PCBs.

  6. COS NUV MAMA Fold Distribution

    NASA Astrophysics Data System (ADS)

    Wheeler, Thomas

    2013-10-01

    The performance of the MAMA microchannel plate can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as Cycle 20 proposal 13128.

  7. Problem Solving through Paper Folding

    ERIC Educational Resources Information Center

    Wares, Arsalan

    2014-01-01

    The purpose of this article is to describe a couple of challenging mathematical problems that involve paper folding. These problem-solving tasks can be used to foster geometric and algebraic thinking among students. The context of paper folding makes some of the abstract mathematical ideas involved relatively concrete. When implemented…

  8. How do chaperonins fold protein?

    PubMed Central

    Motojima, Fumihiro

    2015-01-01

    Protein folding is a biological process that is essential for the proper functioning of proteins in all living organisms. In cells, many proteins require the assistance of molecular chaperones for their folding. Chaperonins belong to a class of molecular chaperones that have been extensively studied. However, the mechanism by which a chaperonin mediates the folding of proteins is still controversial. Denatured proteins are folded in the closed chaperonin cage, leading to the assumption that denatured proteins are completely encapsulated inside the chaperonin cage. In contrast to the assumption, we recently found that denatured protein interacts with hydrophobic residues at the subunit interfaces of the chaperonin, and partially protrude out of the cage. In this review, we will explain our recent results and introduce our model for the mechanism by which chaperonins accelerate protein folding, in view of recent findings.

  9. Effects of Knots on Protein Folding Properties

    PubMed Central

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

    2013-01-01

    This work explores the impact of knots, knot depth and motif of the threading terminus in protein folding properties (kinetics, thermodynamics and mechanism) via extensive Monte Carlo simulations of lattice models. A knotted backbone has no effect on protein thermodynamic stability but it may affect key aspects of folding kinetics. In this regard, we found clear evidence for a functional advantage of knots: knots enhance kinetic stability because a knotted protein unfolds at a distinctively slower rate than its unknotted counterpart. However, an increase in knot deepness does not necessarily lead to more effective changes in folding properties. In this regard, a terminus with a non-trivial conformation (e.g. hairpin) can have a more dramatic effect in enhancing kinetic stability than knot depth. Nevertheless, our results suggest that the probability of the denatured ensemble to keep knotted is higher for proteins with deeper knots, indicating that knot depth plays a role in determining the topology of the denatured state. Refolding simulations starting from denatured knotted conformations show that not every knot is able to nucleate folding and further indicate that the formation of the knotting loop is a key event in the folding of knotted trefoils. They also show that there are specific native contacts within the knotted core that are crucial to keep a native knotting loop in denatured conformations which otherwise have no detectable structure. The study of the knotting mechanism reveals that the threading of the knotting loop generally occurs towards late folding in conformations that exhibit a significant degree of structural consolidation. PMID:24023962

  10. Fast events in protein folding

    SciTech Connect

    Woodruff, W.; Callender, R.; Causgrove, T.; Dyer, R.; Williams, S.

    1996-04-01

    The primary objective of this work was to develop a molecular understanding of how proteins achieve their native three-dimensional (folded) structures. This requires the identification and characterization of intermediates in the protein folding process on all relevant timescales, from picoseconds to seconds. The short timescale events in protein folding have been entirely unknown. Prior to this work, state-of-the-art experimental approaches were limited to milliseconds or longer, when much of the folding process is already over. The gap between theory and experiment is enormous: current theoretical and computational methods cannot realistically model folding processes with lifetimes longer than one nanosecond. This unique approach to employ laser pump-probe techniques that combine novel methods of laser flash photolysis with time-resolved vibrational spectroscopic probes of protein transients. In this scheme, a short (picosecond to nanosecond) laser photolysis pulse was used to produce an instantaneous pH or temperature jump, thereby initiating a protein folding or unfolding reaction. Structure-specific, time-resolved vibrational probes were then used to identify and characterize protein folding intermediates.

  11. Fog spontaneously folds mosquito wings

    NASA Astrophysics Data System (ADS)

    Dickerson, Andrew K.; Liu, Xing; Zhu, Ting; Hu, David L.

    2015-02-01

    The flexibility of insect wings confers aerodynamic benefits, but can also present a hazard if exposed to fog or dew. Fog can cause water to accumulate on wings, bending them into tight taco shapes and rendering them useless for flight. In this combined experimental and theoretical study, we use high-speed video to film the spontaneous folding of isolated mosquito wings due to the evaporation of a water drop. We predict shapes of the deformed wing using two-dimensional elastica theory, considering both surface tension and Laplace pressure. We also recommend fold-resistant geometries for the wings of flapping micro-aerial vehicles. Our work reveals the mechanism of insect wing folding and provides a framework for further study of capillarity-driven folding in both natural and biomimetic systems at small scales.

  12. Rapid compaction during RNA folding

    NASA Astrophysics Data System (ADS)

    Russell, Rick; Millett, Ian S.; Tate, Mark W.; Kwok, Lisa W.; Nakatani, Bradley; Gruner, Sol M.; Mochrie, Simon G. J.; Pande, Vijay; Doniach, Sebastian; Herschlag, Daniel; Pollack, Lois

    2002-04-01

    We have used small angle x-ray scattering and computer simulations with a coarse-grained model to provide a time-resolved picture of the global folding process of the Tetrahymena group I RNA over a time window of more than five orders of magnitude. A substantial phase of compaction is observed on the low millisecond timescale, and the overall compaction and global shape changes are largely complete within one second, earlier than any known tertiary contacts are formed. This finding indicates that the RNA forms a nonspecifically collapsed intermediate and then searches for its tertiary contacts within a highly restricted subset of conformational space. The collapsed intermediate early in folding of this RNA is grossly akin to molten globule intermediates in protein folding.

  13. Rapid folding of DNA into nanoscale shapes at constant temperature.

    PubMed

    Sobczak, Jean-Philippe J; Martin, Thomas G; Gerling, Thomas; Dietz, Hendrik

    2012-12-14

    We demonstrate that, at constant temperature, hundreds of DNA strands can cooperatively fold a long template DNA strand within minutes into complex nanoscale objects. Folding occurred out of equilibrium along nucleation-driven pathways at temperatures that could be influenced by the choice of sequences, strand lengths, and chain topology. Unfolding occurred in apparent equilibrium at higher temperatures than those for folding. Folding at optimized constant temperatures enabled the rapid production of three-dimensional DNA objects with yields that approached 100%. The results point to similarities with protein folding in spite of chemical and structural differences. The possibility for rapid and high-yield assembly will enable DNA nanotechnology for practical applications. PMID:23239734

  14. Polymer principles and protein folding.

    PubMed Central

    Dill, K. A.

    1999-01-01

    This paper surveys the emerging role of statistical mechanics and polymer theory in protein folding. In the polymer perspective, the folding code is more a solvation code than a code of local phipsi propensities. The polymer perspective resolves two classic puzzles: (1) the Blind Watchmaker's Paradox that biological proteins could not have originated from random sequences, and (2) Levinthal's Paradox that the folded state of a protein cannot be found by random search. Both paradoxes are traditionally framed in terms of random unguided searches through vast spaces, and vastness is equated with impossibility. But both processes are partly guided. The searches are more akin to balls rolling down funnels than balls rolling aimlessly on flat surfaces. In both cases, the vastness of the search is largely irrelevant to the search time and success. These ideas are captured by energy and fitness landscapes. Energy landscapes give a language for bridging between microscopics and macroscopics, for relating folding kinetics to equilibrium fluctuations, and for developing new and faster computational search strategies. PMID:10386867

  15. Osmolyte solutions and protein folding

    PubMed Central

    Hu, Char Y; Roesgen, Joerg

    2009-01-01

    In this brief review we discuss the evolution of recent thought regarding the role and mechanism of osmolytes with respect to protein stability. Osmolytes are naturally occurring intracellular compounds that change the protein folding landscape. Contributions from experiments are considered in the context of current theory and simulation results. PMID:19960095

  16. Predicting RNA pseudoknot folding thermodynamics.

    PubMed

    Cao, Song; Chen, Shi-Jie

    2006-01-01

    Based on the experimentally determined atomic coordinates for RNA helices and the self-avoiding walks of the P (phosphate) and C4 (carbon) atoms in the diamond lattice for the polynucleotide loop conformations, we derive a set of conformational entropy parameters for RNA pseudoknots. Based on the entropy parameters, we develop a folding thermodynamics model that enables us to compute the sequence-specific RNA pseudoknot folding free energy landscape and thermodynamics. The model is validated through extensive experimental tests both for the native structures and for the folding thermodynamics. The model predicts strong sequence-dependent helix-loop competitions in the pseudoknot stability and the resultant conformational switches between different hairpin and pseudoknot structures. For instance, for the pseudoknot domain of human telomerase RNA, a native-like and a misfolded hairpin intermediates are found to coexist on the (equilibrium) folding pathways, and the interplay between the stabilities of these intermediates causes the conformational switch that may underlie a human telomerase disease. PMID:16709732

  17. Is Protein Folding Sub-Diffusive?

    PubMed Central

    Krivov, Sergei V.

    2010-01-01

    Protein folding dynamics is often described as diffusion on a free energy surface considered as a function of one or few reaction coordinates. However, a growing number of experiments and models show that, when projected onto a reaction coordinate, protein dynamics is sub-diffusive. This raises the question as to whether the conventionally used diffusive description of the dynamics is adequate. Here, we numerically construct the optimum reaction coordinate for a long equilibrium folding trajectory of a Go model of a -repressor protein. The trajectory projected onto this coordinate exhibits diffusive dynamics, while the dynamics of the same trajectory projected onto a sub-optimal reaction coordinate is sub-diffusive. We show that the higher the (cut-based) free energy profile for the putative reaction coordinate, the more diffusive the dynamics become when projected on this coordinate. The results suggest that whether the projected dynamics is diffusive or sub-diffusive depends on the chosen reaction coordinate. Protein folding can be described as diffusion on the free energy surface as function of the optimum reaction coordinate. And conversely, the conventional reaction coordinates, even though they might be based on physical intuition, are often sub-optimal and, hence, show sub-diffusive dynamics. PMID:20862361

  18. Homogeneous Crystal Nucleation: To Fold or Not to Fold?

    NASA Astrophysics Data System (ADS)

    Crist, Buckley

    2007-03-01

    Recent simulations and related theories have addressed interesting aspects of homogeneous nucleation of polymer crystals in very dilute solutions; embryos and very small crystals are composed of folded chains. At the same time there has been renewed activity with experimental studies of homogeneous nucleation in molten polymers, either with dispersed droplets or with microphase-separated block copolymers. Compared to dilute solutions, melts offer enhanced possibilities for nucleation by fringed micelle structures with stems from different chains. Basal or ``end'' surface energy is estimated for unfolded and folded chain nuclei and employed with classical nucleation theory to distinguish between nucleation rates in the two cases. The effect of chain length on the nucleation barrier offers a way to test model predictions.

  19. 11 CFR 2.3 - General rules.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... this part. (b) Except as provided in 11 CFR 2.4, every portion of every Commission meeting shall be... 11 Federal Elections 1 2011-01-01 2011-01-01 false General rules. 2.3 Section 2.3 Federal Elections FEDERAL ELECTION COMMISSION SUNSHINE REGULATIONS; MEETINGS § 2.3 General rules. (a)...

  20. 36 CFR 2.3 - Fishing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Fishing. 2.3 Section 2.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.3 Fishing. (a) Except in designated areas or as provided in this section, fishing shall be in accordance with...

  1. 36 CFR 2.3 - Fishing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Fishing. 2.3 Section 2.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.3 Fishing. (a) Except in designated areas or as provided in this section, fishing shall be in accordance with...

  2. 36 CFR 2.3 - Fishing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Fishing. 2.3 Section 2.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.3 Fishing. (a) Except in designated areas or as provided in this section, fishing shall be in accordance with...

  3. 36 CFR 2.3 - Fishing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Fishing. 2.3 Section 2.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.3 Fishing. (a) Except in designated areas or as provided in this section, fishing shall be in accordance with...

  4. 36 CFR 2.3 - Fishing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Fishing. 2.3 Section 2.3 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.3 Fishing. (a) Except in designated areas or as provided in this section, fishing shall be in accordance with...

  5. 43 CFR 5511.2-3 - Permits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Permits. 5511.2-3 Section 5511.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR FOREST MANAGEMENT (5000) FREE USE OF TIMBER Free Use Regulations § 5511.2-3 Permits. (a) Application for permit. Before timber...

  6. 45 CFR 1206.2-3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Definitions. 1206.2-3 Section 1206.2-3 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE GRANTS AND CONTRACTS-SUSPENSION AND TERMINATION AND DENIAL OF APPLICATION FOR REFUNDING Denial of Application for Refunding § 1206.2-3...

  7. Characterization and evolution of vertebrate indoleamine 2, 3-dioxygenases IDOs from monotremes and marsupials.

    PubMed

    Yuasa, Hajime J; Ball, Helen J; Ho, Yuen Fern; Austin, Christopher J D; Whittington, Camilla M; Belov, Katherine; Maghzal, Ghassan J; Jermiin, Lars S; Hunt, Nicholas H

    2009-06-01

    Indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that catalyze the first step in tryptophan catabolism via the kynurenine pathway. TDO is widely distributed in both eukaryotes and bacteria. In contrast, IDO has been found only in mammals and yeast. In 2007, a third enzyme, indoleamine 2,3-dioxygenase-2 (IDO2), was discovered. IDO2 is found not only in mammals but also in lower vertebrates. Interestingly, the K(m) value of IDO2 for L-Trp was 500-1000 fold higher than that of IDO1. In this study, we isolated both IDO1 and IDO2 cDNA from a monotreme, the platypus (Ornithorhynchus anatinus), and a marsupial, the gray short-tailed opossum (Monodelphis domestica). We characterized the recombinant proteins and those of other known IDO1/IDO2 in intact cells and a cell-free system. It was found that methylene blue may not be suitable reductant for IDO2, hence resulting in an underestimation of recombinant IDO2 activity. In intact cells, the K(m) value of IDO2 for L-Trp was estimated to be much higher than that of IDO1 and this high K(m) value appears to have been conserved during the evolution of IDO2. The protein encoded by the ancestor gene of IDO1 and IDO2 is likely to have had properties more similar to present day IDO2 than to IDO1. PMID:19416693

  8. Plastic folding of buckling structures.

    PubMed

    Colin, Jérôme; Coupeau, Christophe; Grilhé, Jean

    2007-07-27

    Atomic force microscopy observations of the free surface of gold thin films deposited on silicon substrates have evidenced the buckling of the films and the formation of blister patterns undergoing plastic folding. The classical elastic buckling and plastic deformation of the films are analyzed in the framework of the Föppl-Von Kármán theory of thin plates introducing the notion of low-angle tilt boundaries and dislocation distributions to describe this folding effect. It is demonstrated that, in agreement with elementary plasticity of bent crystals, the presence of such tilt-boundaries results in the formation of buckling patterns of lower energy than "classical" elastic blisters. PMID:17678376

  9. Quantitative Morphology of Epithelial Folds.

    PubMed

    Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož

    2016-01-01

    The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429

  10. Folded supersymmetry with a twist

    NASA Astrophysics Data System (ADS)

    Cohen, Timothy; Craig, Nathaniel; Lou, Hou Keong; Pinner, David

    2016-03-01

    Folded supersymmetry ( f-SUSY) stabilizes the weak scale against radiative corrections from the top sector via scalar partners whose gauge quantum numbers differ from their Standard Model counterparts. This non-trivial pairing of states can be realized in extra-dimensional theories with appropriate supersymmetry-breaking boundary conditions. We present a class of calculable f-SUSY models that are parametrized by a non-trivial twist in 5D boundary conditions and can accommodate the observed Higgs mass and couplings. Although the distinctive phenomenology associated with the novel folded states should provide strong evidence for this mechanism, the most stringent constraints are currently placed by conventional supersymmetry searches. These models remain minimally fine-tuned in light of LHC8 data and provide a range of both standard and exotic signatures accessible at LHC13.

  11. Folding and assembly of proteorhodopsin.

    PubMed

    Klyszejko, Adriana L; Shastri, Sarika; Mari, Stefania A; Grubmüller, Helmut; Muller, Daniel J; Glaubitz, Clemens

    2008-02-01

    Proteorhodopsins (PRs), the recently discovered light-driven proton pumps, play a major role in supplying energy for microbial organisms of oceans. In contrast to PR, rhodopsins found in Archaea and Eukarya are structurally well characterized. Using single-molecule microscopy and spectroscopy, we observed the oligomeric assembly of native PR molecules and detected their folding in the membrane. PR showed unfolding patterns identical with those of bacteriorhodopsin and halorhodopsin, indicating that PR folds similarly to archaeal rhodopsins. Surprisingly, PR predominantly assembles into hexameric oligomers, with a smaller fraction assembling into pentamers. Within these oligomers, PR arranged into radial assemblies. We suggest that this structural assembly of PR may have functional implications. PMID:18155728

  12. Evolutionary Strategies for Protein Folding

    NASA Astrophysics Data System (ADS)

    Murthy Gopal, Srinivasa; Wenzel, Wolfgang

    2006-03-01

    The free energy approach for predicting the protein tertiary structure describes the native state of a protein as the global minimum of an appropriate free-energy forcefield. The low-energy region of the free-energy landscape of a protein is extremely rugged. Efficient optimization methods must therefore speed up the search for the global optimum by avoiding high energy transition states, adapt large scale moves or accept unphysical intermediates. Here we investigate an evolutionary strategies(ES) for optimizing a protein conformation in our all-atom free-energy force field([1],[2]). A set of random conformations is evolved using an ES to get a diverse population containing low energy structure. The ES is shown to balance energy improvement and yet maintain diversity in structures. The ES is implemented as a master-client model for distributed computing. Starting from random structures and by using this optimization technique, we were able to fold a 20 amino-acid helical protein and 16 amino-acid beta hairpin[3]. We compare ES to basin hopping method. [1]T. Herges and W. Wenzel,Biophys.J. 87,3100(2004) [2] A. Verma and W. Wenzel Stabilization and folding of beta-sheet and alpha-helical proteins in an all-atom free energy model(submitted)(2005) [3] S. M. Gopal and W. Wenzel Evolutionary Strategies for Protein Folding (in preparation)

  13. Ventricular-Fold Dynamics in Human Phonation

    ERIC Educational Resources Information Center

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

    2014-01-01

    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 ventricular-fold oscillations could be sustained by aerodynamic coupling with the vocal folds. Method: A 72-sample…

  14. Protein folding in a force clamp

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Szymczak, P.

    2006-05-01

    Kinetics of folding of a protein held in a force clamp are compared to an unconstrained folding. The comparison is made within a simple topology-based dynamical model of ubiquitin. We demonstrate that the experimentally observed variations in the end-to-end distance reflect microscopic events during folding. However, the folding scenarios in and out of the force clamp are distinct.

  15. Quantifying the similarities within fold space.

    PubMed

    Harrison, Andrew; Pearl, Frances; Mott, Richard; Thornton, Janet; Orengo, Christine

    2002-11-01

    We have used GRATH, a graph-based structure comparison algorithm, to map the similarities between the different folds observed in the CATH domain structure database. Statistical analysis of the distributions of the fold similarities has allowed us to assess the significance for any similarity. Therefore we have examined whether it is best to represent folds as discrete entities or whether, in fact, a more accurate model would be a continuum wherein folds overlap via common motifs. To do this we have introduced a new statistical measure of fold similarity, termed gregariousness. For a particular fold, gregariousness measures how many other folds have a significant structural overlap with that fold, typically comprising 40% or more of the larger structure. Gregarious folds often contain commonly occurring super-secondary structural motifs, such as beta-meanders, greek keys, alpha-beta plait motifs or alpha-hairpins, which are matching similar motifs in other folds. Apart from one example, all the most gregarious folds matching 20% or more of the other folds in the database, are alpha-beta proteins. They also occur in highly populated architectural regions of fold space, adopting sandwich-like arrangements containing two or more layers of alpha-helices and beta-strands.Domains that exhibit a low gregariousness, are those that have very distinctive folds, with few common motifs or motifs that are packed in unusual arrangements. Most of the superhelices exhibit low gregariousness despite containing some commonly occurring super-secondary structural motifs. In these folds, these common motifs are combined in an unusual way and represent a small proportion of the fold (<10%). Our results suggest that fold space may be considered as continuous for some architectural arrangements (e.g. alpha-beta sandwiches), in that super-secondary motifs can be used to link neighbouring fold groups. However, in other regions of fold space much more discrete topologies are observed with

  16. Folded MEMS approach to NMRG

    NASA Astrophysics Data System (ADS)

    Gundeti, Venu Madhav

    Atomic gyroscopes have a potential for good performance advantages and several attempts are being made to miniaturize them. This thesis describes the efforts made in implementing a Folded MEMS based NMRG. The micro implementations of all the essential components for NMRG (Nuclear Magnetic Resonance Gyroscope) are described in detail in regards to their design, fabrication, and characterization. A set of micro-scale Helmholtz coils are described and the homogeneity of the generated magnetic field is analyzed for different designs of heaters. The dielectric mirrors and metallic mirrors are compared in terms of reflectivity and polarization change up on reflection. A pyramid shaped folded backbone structure is designed, fabricated, and assembled along with all the required components. A novel double-folded structure 1/4th the size of original version is fabricated and assembled. Design and modeling details of a 5 layered shield with shielding factor > 106 and total volume of around 90 cc are also presented. A table top setup for characterization of atomic vapor cell is described in detail. A micro vapor cell based Rb magnetometer with a sensitivity of 108 pT/√Hz is demonstrated. The challenges due to DC heating are addressed and mitigated using an AC heater. Several experiments related to measuring the relaxation time of Xe are provided along with results. For Xe131, relaxation times of T1 = 23.78 sec, T2 = 18.06 sec and for Xe129, T1 = 21.65 sec and T2 = 20.45 sec are reported.

  17. All-or-none folding of a polymer in confinement

    NASA Astrophysics Data System (ADS)

    Taylor, Mark

    A flexible homopolymer chain with sufficiently short-range interactions undergoes a discontinuous transition from an expanded coil to a compact crystallite analogous to the all-or-none folding transition exhibited by fast-folding proteins. One anticipates that geometric confinement will reduce the entropy of the unfolded chain, thereby stabilizing the folded state and shifting the transition to higher temperature. In this work we study a flexible square-well N-mer chain (monomer diameter d) located between two hard walls forming a slit-like pore (width W) with the chain end-tethered to one wall. We carry out Monte simulations with Wang-Landau sampling to construct the single-chain density of states and use both microcanonical and canonical analyses to characterize phase transitions. When the slit width is similar to the size of the folded chain we observe a modest stabilization effect. Further reduction of the slit width geometrically prohibits the chain from folding into the free-chain ground state. However, a discontinuous all-or-none folding transition still occurs to a flattened crystallite that spans the pore. All-or-none folding persists even to the limit of a very narrow pore (W d) where the ground-state structure is a quasi-two-dimensional crystal. Funding: NSF DMR-1204747.

  18. Paradoxic vocal fold movement disorder.

    PubMed

    Matrka, Laura

    2014-02-01

    Paradoxical Vocal Fold Movement Disorder (PVFMD) is a cause of dyspnea that can mimic or occur alongside asthma or other pulmonary disease. Treatment with Laryngeal Control Therapy is very effective once the entity is properly diagnosed and contributing comorbidities are managed appropriately. In understanding the etiology of PVFMD, focus has broadened beyond psychiatric factors alone to include the spectrum of laryngeal irritants (laryngopharyngeal reflux, allergic and sinus disease, sicca, and possibly obstructive sleep apnea). The following is a discussion of the history, terminology, epidemiology, diagnosis, comorbid conditions, and treatment of this entity. PMID:24286687

  19. Hydrodynamic interactions in protein folding

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Niewieczerzał, Szymon

    2009-03-01

    We incorporate hydrodynamic interactions (HIs) in a coarse-grained and structure-based model of proteins by employing the Rotne-Prager hydrodynamic tensor. We study several small proteins and demonstrate that HIs facilitate folding. We also study HIV-1 protease and show that HIs make the flap closing dynamics faster. The HIs are found to affect time correlation functions in the vicinity of the native state even though they have no impact on same time characteristics of the structure fluctuations around the native state.

  20. Hydrodynamic interactions in protein folding.

    PubMed

    Cieplak, Marek; Niewieczerzał, Szymon

    2009-03-28

    We incorporate hydrodynamic interactions (HIs) in a coarse-grained and structure-based model of proteins by employing the Rotne-Prager hydrodynamic tensor. We study several small proteins and demonstrate that HIs facilitate folding. We also study HIV-1 protease and show that HIs make the flap closing dynamics faster. The HIs are found to affect time correlation functions in the vicinity of the native state even though they have no impact on same time characteristics of the structure fluctuations around the native state. PMID:19334888

  1. Hydrogen Bonds in Polymer Folding

    NASA Astrophysics Data System (ADS)

    Borg, Jesper; Jensen, Mogens H.; Sneppen, Kim; Tiana, Guido

    2001-02-01

    We studied the thermodynamics of a homopolymeric chain with both van der Waals and directed hydrogen bond interaction. The effect of hydrogen bonds is to reduce dramatically the entropy of low-lying states and to give rise to long-range order and to conformations displaying secondary structures. For compact polymers a transition is found between helix-rich states and low-entropy sheet-dominated states. The consequences of this transition for protein folding and, in particular, for the problem of prions are discussed.

  2. Chaperonin-mediated Protein Folding

    PubMed Central

    Horwich, Arthur L.

    2013-01-01

    We have been studying chaperonins these past twenty years through an initial discovery of an action in protein folding, analysis of structure, and elucidation of mechanism. Some of the highlights of these studies were presented recently upon sharing the honor of the 2013 Herbert Tabor Award with my early collaborator, Ulrich Hartl, at the annual meeting of the American Society for Biochemistry and Molecular Biology in Boston. Here, some of the major findings are recounted, particularly recognizing my collaborators, describing how I met them and how our great times together propelled our thinking and experiments. PMID:23803606

  3. Improving protein fold recognition by random forest

    PubMed Central

    2014-01-01

    Background Recognizing the correct structural fold among known template protein structures for a target protein (i.e. fold recognition) is essential for template-based protein structure modeling. Since the fold recognition problem can be defined as a binary classification problem of predicting whether or not the unknown fold of a target protein is similar to an already known template protein structure in a library, machine learning methods have been effectively applied to tackle this problem. In our work, we developed RF-Fold that uses random forest - one of the most powerful and scalable machine learning classification methods - to recognize protein folds. Results RF-Fold consists of hundreds of decision trees that can be trained efficiently on very large datasets to make accurate predictions on a highly imbalanced dataset. We evaluated RF-Fold on the standard Lindahl's benchmark dataset comprised of 976 × 975 target-template protein pairs through cross-validation. Compared with 17 different fold recognition methods, the performance of RF-Fold is generally comparable to the best performance in fold recognition of different difficulty ranging from the easiest family level, the medium-hard superfamily level, and to the hardest fold level. Based on the top-one template protein ranked by RF-Fold, the correct recognition rate is 84.5%, 63.4%, and 40.8% at family, superfamily, and fold levels, respectively. Based on the top-five template protein folds ranked by RF-Fold, the correct recognition rate increases to 91.5%, 79.3% and 58.3% at family, superfamily, and fold levels. Conclusions The good performance achieved by the RF-Fold demonstrates the random forest's effectiveness for protein fold recognition. PMID:25350499

  4. Structure based prediction of protein folding intermediates.

    PubMed

    Xie, D; Freire, E

    1994-09-01

    The complete unfolding of a protein involves the disruption of non-covalent intramolecular interactions within the protein and the subsequent hydration of the backbone and amino acid side-chains. The magnitude of the thermodynamic parameters associated with this process is known accurately for a growing number of globular proteins for which high-resolution structures are also available. The existence of this database of structural and thermodynamic information has facilitated the development of statistical procedures aimed at quantifying the relationships existing between protein structure and the thermodynamic parameters of folding/unfolding. Under some conditions proteins do not unfold completely, giving rise to states (commonly known as molten globules) in which the molecule retains some secondary structure and remains in a compact configuration after denaturation. This phenomenon is reflected in the thermodynamics of the process. Depending on the nature of the residual structure that exists after denaturation, the observed enthalpy, entropy and heat capacity changes will deviate in a particular and predictable way from the values expected for complete unfolding. For several proteins, these deviations have been shown to exhibit similar characteristics, suggesting that their equilibrium folding intermediates exhibit some common structural features. Employing empirically derived structure-energetic relationships, it is possible to identify in the native structure of the protein those regions with the higher probability of being structured in equilibrium partly folded states. In this work, a thermodynamic search algorithm aimed at identifying the structural determinants of the molten globule state has been applied to six globular proteins; alpha-lactalbumin, barnase, IIIGlc, interleukin-1 beta, phage T4 lysozyme and phage 434 repressor. Remarkably, the structural features of the predicted equilibrium intermediates coincide to a large extent with the known

  5. Soliton instability and fold formation in laterally compressed graphene

    NASA Astrophysics Data System (ADS)

    Libério de Lima, Amauri; Müssnich, Lucas A. M.; Manhabosco, Taíse M.; Chacham, Hélio; Batista, Ronaldo J. C.; Barros de Oliveira, Alan

    2015-01-01

    We investigate—through simulations and analytical calculations—the consequences of uniaxial lateral compression applied to the upper layer of multilayer graphene. The simulations of compressed graphene show that strains larger than 2.8% induce soliton-like deformations that further develop into large, mobile folds. Such folds were indeed experimentally observed in graphene and other solid lubricants two-dimensional (2D) materials. Interestingly, in the soliton-fold regime, the shear stress decreases with the strain s, initially as {{s}-2/3} and rapidly going to zero. Such instability is consistent with the recently observed negative dynamic compressibility of 2D materials. We also predict that the curvatures of the soliton-folds are given by {{r}c}=δ \\sqrt{β /2α }, where 1≤slant δ ≤slant 2, and β and α are respectively related to the layer bending modulus and to the interlayer binding energy of the material. This finding might allow experimental estimates of the β /α ratio of 2D materials from fold morphology.

  6. Soliton instability and fold formation in laterally compressed graphene.

    PubMed

    de Lima, Amauri Libério; Müssnich, Lucas A M; Manhabosco, Taíse M; Chacham, Hélio; Batista, Ronaldo J C; de Oliveira, Alan Barros

    2015-01-30

    We investigate-through simulations and analytical calculations-the consequences of uniaxial lateral compression applied to the upper layer of multilayer graphene. The simulations of compressed graphene show that strains larger than 2.8% induce soliton-like deformations that further develop into large, mobile folds. Such folds were indeed experimentally observed in graphene and other solid lubricants two-dimensional (2D) materials. Interestingly, in the soliton-fold regime, the shear stress decreases with the strain s, initially as s(-2/3) and rapidly going to zero. Such instability is consistent with the recently observed negative dynamic compressibility of 2D materials. We also predict that the curvatures of the soliton-folds are given by r(c) = δ√(β/2α) where 1 ≤ δ ≤ 2 and β and α are respectively related to the layer bending modulus and to the interlayer binding energy of the material. This finding might allow experimental estimates of the β/α ratio of 2D materials from fold morphology. PMID:25566691

  7. Learning Protein Folding Energy Functions

    PubMed Central

    Guan, Wei; Ozakin, Arkadas; Gray, Alexander; Borreguero, Jose; Pandit, Shashi; Jagielska, Anna; Wroblewska, Liliana; Skolnick, Jeffrey

    2014-01-01

    A critical open problem in ab initio protein folding is protein energy function design, which pertains to defining the energy of protein conformations in a way that makes folding most efficient and reliable. In this paper, we address this issue as a weight optimization problem and utilize a machine learning approach, learning-to-rank, to solve this problem. We investigate the ranking-via-classification approach, especially the RankingSVM method and compare it with the state-of-the-art approach to the problem using the MINUIT optimization package. To maintain the physicality of the results, we impose non-negativity constraints on the weights. For this we develop two efficient non-negative support vector machine (NNSVM) methods, derived from L2-norm SVM and L1-norm SVMs, respectively. We demonstrate an energy function which maintains the correct ordering with respect to structure dissimilarity to the native state more often, is more efficient and reliable for learning on large protein sets, and is qualitatively superior to the current state-of-the-art energy function. PMID:25311546

  8. 43 CFR 3105.2-3 - Requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Requirements. 3105.2-3 Section 3105.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Cooperative Conservation...

  9. 43 CFR 3105.2-3 - Requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Requirements. 3105.2-3 Section 3105.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Cooperative Conservation...

  10. 43 CFR 3105.2-3 - Requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Requirements. 3105.2-3 Section 3105.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Cooperative Conservation...

  11. 43 CFR 3105.2-3 - Requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Requirements. 3105.2-3 Section 3105.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Cooperative Conservation...

  12. Six-fold coordinated carbon dioxide VI

    SciTech Connect

    Iota, Valentin; Yoo, Choong-Shik; Klepeis, Jae-Hyun; Jenei, Zsolt; Evans, William; Cynn, Hyunchae

    2008-06-16

    Under standard conditions, carbon dioxide (CO{sub 2}) is a simple molecular gas and an important atmospheric constituent, whereas silicon dioxide (SiO{sub 2}) is a covalent solid, and one of the fundamental minerals of the planet. The remarkable dissimilarity between these two group IV oxides is diminished at higher pressures and temperatures as CO{sub 2} transforms to a series of solid phases, from simple molecular to a fully covalent extended-solid V, structurally analogous to SiO{sub 2} tridymite. Here, we present the discovery of an extended-solid phase of CO{sub 2}: a six-fold coordinated stishovite-like phase VI, obtained by isothermal compression of associated CO{sub 2}-II above 50 GPa at 530-650 K. Together with the previously reported CO{sub 2}-V and a-carbonia, this extended phase indicates a fundamental similarity between CO{sub 2} (a prototypical molecular solid) and SiO{sub 2} (one of Earth's fundamental building blocks). We present a phase diagram with a limited stability domain for molecular CO{sub 2}-I, and suggest that the conversion to extended-network solids above 40-50 GPa occurs via intermediate phases II, III and IV. The crystal structure of phase VI suggests strong disorder along the c axis in stishovite-like P4{sub 2}/mnm, with carbon atoms manifesting an average six-fold coordination within the framework of sp{sup 3} hybridization.

  13. Kinematics and thermodynamics of a folding heteropolymer.

    PubMed Central

    Fukugita, M; Lancaster, D; Mitchard, M G

    1993-01-01

    In order to elucidate the folding dynamics of protein, we have carried out numerical simulations of a heteropolymer model of self-interacting random chains. We find that folding propensity depends strongly on sequence and that both folding and nonfolding sequences exist. Furthermore we show that folding is a two-step process: the transition from coil state to unique folded state takes place through a globule phase. In addition to the continuous coil-globule transition, there exists an abrupt transition that separates the unique folded state from the globule state and ensures the stability of the native state. PMID:8327518

  14. Cell Transfection with a β-Cyclodextrin-PEI-Propane-1,2,3-Triol Nanopolymer

    PubMed Central

    Lai, Wing-Fu; Jung, Han-Sung

    2014-01-01

    Successful gene therapy necessitates safe and efficient gene transfer. This article describes the use of a cationic polymer, which was synthesized by cross-linking low molecular weight branched poly(ethylenimine) (PEI) with both β-cyclodextrin and propane-1,2,3-triol, for efficient and safe non-viral gene delivery. Experimentation demonstrated that the polymer had a pH buffering capacity and DNA condensing ability comparable to those of PEI 25 kDa. In B16-F0 cells, the polymer increased the transfection efficiency of naked DNA by 700-fold and yielded better transfection efficiencies than Fugene HD (threefold higher) and PEI 25 kDa (fivefold higher). The high transfection efficiency of the polymer was not affected by the presence of serum during transfection. In addition to B16-F0 cells, the polymer enabled efficient transfection of HepG2 and U87 cells with low cytotoxicity. Our results indicated that our polymer is a safe and efficient transfection reagent that warrants further development for in vitro, in vivo and clinical applications. PMID:24956480

  15. Protein folding in the endoplasmic reticulum: lessons from the human chorionic gonadotropin beta subunit.

    PubMed Central

    Ruddon, R. W.; Sherman, S. A.; Bedows, E.

    1996-01-01

    There have been few studies of protein folding in the endoplasmic reticulum of intact mammalian cells. In the one case where the in vivo and in vitro folding pathways of a mammalian secretory protein have been compared, the folding of the human chorionic gonadotropin beta subunit (hCG-beta), the order of formation of the detected folding intermediates is the same. The rate and efficiency with which multidomain proteins such as hCG-beta fold to native structure in intact cells is higher than in vitro, although intracellular rates of folding of the beta subunit can be approached in vitro in the presence of an optimal redox potential and protein disulfide isomerase. Understanding how proteins fold in vivo may provide a new way to diagnose and treat human illnesses that occur due to folding defects. PMID:8844836

  16. Protein folding in a force-clamp

    NASA Astrophysics Data System (ADS)

    Cieplak, Marek; Szymczak, Piotr

    2006-03-01

    Kinetics of folding of a protein held in a force-clamp are compared to an unconstrained folding. The comparison is made within a simple topology-based dynamical model of ubiquitin. We demonstrate that the experimentally observed rapid changes in the end-to-end distance mirror microscopic events during folding. However, the folding scenarios in and out of the force-clamp are distinct.

  17. Synthesis and evaluation of N-(2,3-dihydroxypropyl)-PEIs as efficient vectors for nucleic acids.

    PubMed

    Tripathi, Sushil K; Yadav, Santosh; Gupta, Kailash C; Kumar, Pradeep

    2012-04-01

    Branched polyethylenimine (bPEI, 25 kDa) has been widely used as an efficient delivery vector for nucleic acids in vitro. However, its charge-associated toxicity has limited its in vivo applications. In an attempt to control its toxicity, it was reacted with varying amounts of glycidol (2,3-epoxy-1-propanol) to obtain a small series of hydrophilic polymers, 2,3-dihydroxypropyl-grafted-polyethylenimines (DHP-g-P). The resulting polymers were characterized by (1)H-NMR and subjected to interaction with negatively charged pDNA, which yielded complexes in the size range of ~171-190 nm with a zeta potential of ∼+33-39 mV. Acid-base titration revealed no effect of substitution on the buffering capacity of the modified polymers. Grafting of 2,3-dihydroxypropyl groups on bPEI significantly improved the cell viability (i.e. almost non-toxic) as well as the DNA release properties of these modified polymers compared to native bPEI. Formation of a relatively loose DHP-g-P25/pDNA complex (the best working system in terms of transfection efficiency) resulted in the efficient nuclear release of pDNA for transcription, a prerequisite for efficient transfection. Subsequently, upon evaluation of their ability to transfer nucleic acids in vitro, the DHP-g-P/pDNA complexes exhibited higher gene transfection efficiency with one of the formulations, DHP-g-P25/DNA complex, displaying ~2.7 folds higher GFP expression than bPEI and ~2.3-3.5 folds higher than the selected commercial transfection reagents used in this study. Further to quantify the extent of GFP positive cells, FACS analysis was performed, which revealed DHP-g-P25/DNA mediated gene expression in ~51% cells outcompeting bPEI, Superfect™, Fugene™ and Lipofectamine™. Sequential delivery of GFP-specific siRNA resulted in ~78% suppression of the target gene compared to ~49% achieved by Fugene™. All these results demonstrate the potential of these polymers for in vivo gene delivery. PMID:22419101

  18. Extracting Information from Folds in Rocks.

    ERIC Educational Resources Information Center

    Hudleston, Peter John

    1986-01-01

    Describes the three processes of folding in rocks: buckling, bending, and passive folding. Discusses how geometrical properties and strain distributions help to identify which processes produce natural folds, and also provides information about the mechanical properties of rocks, and the sense of shear in shear zones. (TW)

  19. Folded Symplectic Toric Four-Manifolds

    ERIC Educational Resources Information Center

    Lee, Christopher R.

    2009-01-01

    A folded symplectic form on an even-dimensional manifold is a closed two-form that degenerates in a suitably controlled way along a smooth hypersurface. When a torus having half the dimension of the manifold acts in a way preserving the folded symplectic form and admitting a moment map, the manifold is called a folded symplectic toric manifold.…

  20. Dynamics of Folds in the Plane

    ERIC Educational Resources Information Center

    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…

  1. HPF Implementation of NPB2.3

    NASA Technical Reports Server (NTRS)

    Frumkin, Michael; Jin, Hao-Qiang; Yan, Jerry; Saini, Subhash (Technical Monitor)

    1998-01-01

    We present the HPF implementation of BT, SP, LU, FT, and MG of NPB2.3-serial benchmark set, The implementation is based on HPF performance model of the benchmark specific operations with distributed arrays. We present profiling and performance data on SGI origin 2000 and compare the results with NPB2.3. We discuss advantages and limitations of HPF and pghpf compiler.

  2. Enhanced protein fold recognition using a structural alphabet.

    PubMed

    Deschavanne, Patrick; Tufféry, Pierre

    2009-07-01

    Fold recognition from sequence can be an important step in protein structure and function prediction. Many methods have tackled this goal. Most of them, based on sequence alignment, fail for sequences of low similarity. Alignment-free approaches can provide an efficient alternative. For such approaches, the identification of efficient fold discriminatory features is critical. We propose a new fold recognition approach that relies on the encoding of the local structure of proteins using a Hidden Markov Model Structural Alphabet. This encoding provides a 1D description of the conformation of complete proteins structures, including loops. At the fold level, compared with the classical secondary structure helix, strand, and coil states, such encoding is expected to provide the means of a better discrimination between loop conformations, hence providing better fold identification. Compared with previous related approaches, this supplement of information results in significant improvement. When combining this information with supplementary information of secondary structure and residue burial, we obtain a fold recognition accuracy of 78% for 27 protein families, that is, 8% higher than the best available method so far, and of 68% for 60 families. Corresponding scores at the class level are of 92% and 90% indicating that mispredictions are mostly within structural classes. PMID:19089985

  3. Folding of viscous sheets and filaments

    NASA Astrophysics Data System (ADS)

    Skorobogatiy, M.; Mahadevan, L.

    2000-12-01

    We consider the nonlinear folding behavior of a viscous filament or a sheet under the influence of an external force such as gravity. Everyday examples of this phenomenon are provided by the periodic folding of a sheet of honey as it impinges on toast, or the folding of a stream of shampoo as it falls on one's hand. To understand the evolution of a fold, we formulate and solve a free-boundary problem for the phenomenon, give scaling laws for the size of the folds and the frequency with which they are laid out, and verify these experimentally.

  4. Understanding Protein Non-Folding

    PubMed Central

    Uversky, Vladimir N.; Dunker, A. Keith

    2010-01-01

    This review describes the family of intrinsically disordered proteins, members of which fail to form rigid 3-D structures under physiological conditions, either along their entire lengths or only in localized regions. Instead, these intriguing proteins/regions exist as dynamic ensembles within which atom positions and backbone Ramachandran angles exhibit extreme temporal fluctuations without specific equilibrium values. Many of these intrinsically disordered proteins are known to carry out important biological functions which, in fact, depend on the absence of specific 3-D structure. The existence of such proteins does not fit the prevailing structure-function paradigm, which states that unique 3-D structure is a prerequisite to function. Thus, the protein structure-function paradigm has to be expanded to include intrinsically disordered proteins and alternative relationships among protein sequence, structure, and function. This shift in the paradigm represents a major breakthrough for biochemistry, biophysics and molecular biology, as it opens new levels of understanding with regard to the complex life of proteins. This review will try to answer the following questions: How were intrinsically disordered proteins discovered? Why don't these proteins fold? What is so special about intrinsic disorder? What are the functional advantages of disordered proteins/regions? What is the functional repertoire of these proteins? What are the relationships between intrinsically disordered proteins and human diseases? PMID:20117254

  5. Folded waveguide cavity coupler for ICRF heating

    SciTech Connect

    Owens, T.L.

    1986-01-01

    This paper introduces a new type of waveguide coupler for ion cyclotron range of frequencies (ICRF) heating which is an adaptation of a concept known as a ''folded waveguide'' reported by Barrow and Schaevitz in connection with low-frequency waveguide transmission systems. The basic idea involves ''folding'' a simple rectangular waveguide to form a more compact structure. Cutoff for the folded waveguide occurs when one-half of a free-space wavelength equals the path length around the ''folds'' of the structure. By adding a large number of folds, the path length around the folds can be made large, leading to very low cutoff frequencies relative to those for simple rectangular waveguides having comparable outside dimensions. Folded waveguide couplers are practical for frequencies as low as 60 MHz for some ports found on present-day experients.

  6. Six-fold Coordinated Carbon Dioxide VI

    SciTech Connect

    Iota, V; Yoo, C; Klepeis, J; Jenei, Z

    2006-03-01

    Under standard conditions, carbon dioxide (CO{sub 2}) is a simple molecular gas and an important atmospheric constituent while silicon dioxide (SiO{sub 2}) is a covalent solid, and represents one of the fundamental minerals of the planet. The remarkable dissimilarity between these two group IV oxides is diminished at higher pressures and temperatures as CO{sub 2} transforms to a series of solid phases, from simple molecular to a fully covalent extended-solid V, structurally analogous to SiO{sub 2} tridymite. Here, we present the discovery of a new extended-solid phase of carbon dioxide (CO{sub 2}): a six-fold coordinated stishovite-like phase VI, obtained by isothermal compression of associated CO{sub 2}-II above 50GPa at 530-650K. Together with the previously reported CO{sub 2}-V and a-carbonia, this new extended phase indicates a fundamental similarity between CO{sub 2}--a prototypical molecular solid, and SiO{sub 2}--one of Earth's fundamental building blocks. The phase diagram suggests a limited stability domain for molecular CO{sub 2}-I, and proposes that the conversion to extended-network solids above 40-50 GPa occurs via intermediate phases II, III, and IV. The crystal structure of phase VI suggests strong disorder along the caxis in stishovite-like P4{sub 2}/mnm, with carbon atoms manifesting an average six-fold coordination within the framework of sp{sup 3} hybridization.

  7. Six-fold coordinated carbon dioxide VI.

    PubMed

    Iota, Valentin; Yoo, Choong-Shik; Klepeis, Jae-Hyun; Jenei, Zsolt; Evans, William; Cynn, Hyunchae

    2007-01-01

    Under standard conditions, carbon dioxide (CO2) is a simple molecular gas and an important atmospheric constituent, whereas silicon dioxide (SiO2) is a covalent solid, and one of the fundamental minerals of the planet. The remarkable dissimilarity between these two group IV oxides is diminished at higher pressures and temperatures as CO2 transforms to a series of solid phases, from simple molecular to a fully covalent extended-solid V, structurally analogous to SiO2 tridymite. Here, we present the discovery of an extended-solid phase of CO2: a six-fold coordinated stishovite-like phase VI, obtained by isothermal compression of associated CO2-II (refs 1,2) above 50 GPa at 530-650 K. Together with the previously reported CO2-V (refs 3-5) and a-carbonia, this extended phase indicates a fundamental similarity between CO2 (a prototypical molecular solid) and SiO2 (one of Earth's fundamental building blocks). We present a phase diagram with a limited stability domain for molecular CO2-I, and suggest that the conversion to extended-network solids above 40-50 GPa occurs via intermediate phases II (refs 1,2), III (refs 7,8) and IV (refs 9,10). The crystal structure of phase VI suggests strong disorder along the c axis in stishovite-like P42/mnm, with carbon atoms manifesting an average six-fold coordination within the framework of sp3 hybridization. PMID:17160005

  8. [Management of T1a vocal fold carcinoma].

    PubMed

    Reiter, R; Brosch, S; Smith, E; Pickhard, A

    2013-12-01

    About 2/3 of the larynx carcinomas affect the vocal chords. The main risk factor is smoking. Carcinomas in this localisation often arise from leukoplakias with dysplasia. A typical symptom is dysphonia. Arrest of vibration in microlaryngostroboscopy is a hint that a carcinoma could be present. Transoral laser cordectomy or radiotherapy show equivalent oncological results and results in quality of voice in the treatment of vocal fold carcinoma (T1a). As lymph node and distant metastasis are very rare, follow-up can concentrate on microlaryngoscopy. In case of a suspicious area on the vocal fold, biopsy of the affected tissue is needed to plan correct treatment. The prognosis of the T1 vocal chord carcinoma is quite good with a 5-year survival rate of almost 100%. PMID:23929210

  9. Fabrication of ten-fold photonic quasicrystalline structures

    SciTech Connect

    Sun, XiaoHong Wu, YuLong; Liu, Wen; Liu, Wei; Han, Juan; Jiang, Lei

    2015-05-15

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

  10. The energy landscape for folding and function

    NASA Astrophysics Data System (ADS)

    Onuchic, Jose

    2006-03-01

    Globally the energy landscape of a folding protein resembles a partially rough funnel. The local roughness of the funnel reflects transient trapping of the protein configurations in local free energy minima. The kinetics of folding is best considered as a progressive organization of an ensemble of partially folded structures through which the protein passes through on its way to the folded structure. The folding mechanisms for several fast-folding proteins can be described using an energy landscape theory to set up the correspondence with simulations of protein minimalist models. Using these simulations together with analytical theory, we can learn about good (minimally frustrated) folding sequences and non-folding (frustrated) sequences. An important idea that emerges from this theory is that subtle features of the protein landscape can profoundly affect the apparent mechanism of folding. Experiments on the dependence of the folding/unfolding times, and the stability of these proteins to denaturant concentration and site-directed mutagenesis, and on the early events of folding allow to infer the global characteristics of the landscape. In addition to need to minimize energetic frustration, the topology of the native fold also plays a major role in the folding mechanism. Some folding motifs are easier to design than others suggesting the possibility that evolution not only selected sequences with sufficiently small energetic frustration but also selected more easily designable native structures. Several proteins (such as CI2 and SH3) have sufficiently reduced energetic frustration) that much of the heterogeneity observed in their transition state ensemble (TSE) is determined by topology. Topological effects go beyond the structure of the TSE. The overall structure of the on-route and off-route (traps) intermediates for the folding of more complex proteins is also influenced by topology. Utilizing this theoretical framework, simulations of minimalist models and

  11. Asymmetric hindwing foldings in rove beetles

    PubMed Central

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

    2014-01-01

    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. PMID:25368178

  12. Kinetic partitioning mechanism of HDV ribozyme folding

    NASA Astrophysics Data System (ADS)

    Chen, Jiawen; Gong, Sha; Wang, Yujie; Zhang, Wenbing

    2014-01-01

    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.

  13. Kinetic partitioning mechanism of HDV ribozyme folding

    SciTech Connect

    Chen, Jiawen; Gong, Sha; Wang, Yujie; Zhang, Wenbing

    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.

  14. Reduced alphabet for protein folding prediction.

    PubMed

    Huang, Jitao T; Wang, Titi; Huang, Shanran R; Li, Xin

    2015-04-01

    What are the key building blocks that would have been needed to construct complex protein folds? This is an important issue for understanding protein folding mechanism and guiding de novo protein design. Twenty naturally occurring amino acids and eight secondary structures consist of a 28-letter alphabet to determine folding kinetics and mechanism. Here we predict folding kinetic rates of proteins from many reduced alphabets. We find that a reduced alphabet of 10 letters achieves good correlation with folding rates, close to the one achieved by full 28-letter alphabet. Many other reduced alphabets are not significantly correlated to folding rates. The finding suggests that not all amino acids and secondary structures are equally important for protein folding. The foldable sequence of a protein could be designed using at least 10 folding units, which can either promote or inhibit protein folding. Reducing alphabet cardinality without losing key folding kinetic information opens the door to potentially faster machine learning and data mining applications in protein structure prediction, sequence alignment and protein design. PMID:25641420

  15. Viscoelastic properties of the false vocal fold

    NASA Astrophysics Data System (ADS)

    Chan, Roger W.

    2001-05-01

    The biomechanical properties of vocal fold tissues have been the focus of many previous studies, as vocal fold viscoelasticity critically dictates the acoustics and biomechanics of phonation. However, not much is known about the viscoelastic response of the ventricular fold or false vocal fold. It has been shown both clinically and in computer simulations that the false vocal fold may contribute significantly to the aerodynamics and sound generation processes of human voice production, with or without flow-induced oscillation of the false fold. To better understand the potential role of the false fold in phonation, this paper reports some preliminary measurements on the linear and nonlinear viscoelastic behavior of false vocal fold tissues. Linear viscoelastic shear properties of human false fold tissue samples were measured by a high-frequency controlled-strain rheometer as a function of frequency, and passive uniaxial tensile stress-strain response of the tissue samples was measured by a muscle lever system as a function of strain and loading rate. Elastic moduli (Young's modulus and shear modulus) of the false fold tissues were calculated from the measured data. [Work supported by NIH.

  16. Some aspects of vocal fold bowing.

    PubMed

    Tanaka, S; Hirano, M; Chijiwa, K

    1994-05-01

    Bowing of the vocal fold frequently occurs in patients with vocal fold paralysis (VFP), those with sulcus vocalis, and those who have had laser surgery. Additionally, there are vocal folds that present bowing with no noticeable organic lesion. For the purpose of investigating the causes and mechanisms of vocal fold bowing, consecutive fiberscopic videorecordings of 127 patients with VFP, 33 with sulcus vocalis, 33 with laser surgery, and 33 with dysphonia having no clinically noticeable organic lesion were reviewed. Sixty-nine percent of the paralyzed vocal folds had bowing, and the occurrence of bowing was significantly related to the activity of the thyroarytenoid muscle as measured by electromyography. The cricothyroid activity had no significant relationship to vocal fold bowing. All vocal folds with sulcus presented with bowing. Thirty-five percent of the vocal folds that had had laser surgery had bowing. The extent of tissue removal was closely related to the occurrence of bowing. Twelve cases with no organic lesion had vocal fold bowing. Of these 12 patients, 8 were male and 9 were older than 60 years. Some aging process in the mucosa was presumed to be the cause of the bowing in this age group of patients without clinically noticeable organic lesions. Causes of vocal fold bowing in the younger group of patients without organic lesions were not determined in this study. PMID:8179251

  17. Asymmetric hindwing foldings in rove beetles.

    PubMed

    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. PMID:25368178

  18. Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds: Evidence for Autoinflammation.

    PubMed

    Marzano, Angelo V; Tavecchio, Simona; Berti, Emilio; Gelmetti, Carlo; Cugno, Massimo

    2015-12-01

    Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1β, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P = 0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P = 0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P = 0.010), CXCL 16 (P = 0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P = 0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P = 0.010) and MMP-9 (P = 0.003) were increased. APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component. PMID:26683967

  19. Protein folding at atomic resolution: analysis of autonomously folding supersecondary structure motifs by nuclear magnetic resonance.

    PubMed

    Sborgi, Lorenzo; Verma, Abhinav; Sadqi, Mourad; de Alba, Eva; Muñoz, Victor

    2013-01-01

    The study of protein folding has been conventionally hampered by the assumption that all single-domain proteins fold by an all-or-none process (two-state folding) that makes it impossible to resolve folding mechanisms experimentally. Here we describe an experimental method for the thermodynamic analysis of protein folding at atomic resolution using nuclear magnetic resonance (NMR). The method is specifically developed for the study of small proteins that fold autonomously into basic supersecondary structure motifs, and that do so in the sub-millisecond timescale (folding archetypes). From the NMR experiments we obtain hundreds of atomic unfolding curves that are subsequently analyzed leading to the determination of the characteristic network of folding interactions. The application of this approach to a comprehensive catalog of elementary folding archetypes holds the promise of becoming the first experimental approach capable of unraveling the basic rules connecting protein structure and folding mechanism. PMID:22987355

  20. Assessment of optimized Markov models in protein fold classification.

    PubMed

    Lampros, Christos; Simos, Thomas; Exarchos, Themis P; Exarchos, Konstantinos P; Papaloukas, Costas; Fotiadis, Dimitrios I

    2014-08-01

    Protein fold classification is a challenging task strongly associated with the determination of proteins' structure. In this work, we tested an optimization strategy on a Markov chain and a recently introduced Hidden Markov Model (HMM) with reduced state-space topology. The proteins with unknown structure were scored against both these models. Then the derived scores were optimized following a local optimization method. The Protein Data Bank (PDB) and the annotation of the Structural Classification of Proteins (SCOP) database were used for the evaluation of the proposed methodology. The results demonstrated that the fold classification accuracy of the optimized HMM was substantially higher compared to that of the Markov chain or the reduced state-space HMM approaches. The proposed methodology achieved an accuracy of 41.4% on fold classification, while Sequence Alignment and Modeling (SAM), which was used for comparison, reached an accuracy of 38%. PMID:25152041

  1. Protein Folding in Confined and Crowded Environments

    PubMed Central

    Zhou, Huan-Xiang

    2007-01-01

    Confinement and crowding are two major factors that can potentially impact protein folding in cellular environments. Theories based on considerations of excluded volumes predict disparate effects on protein folding stability for confinement and crowding: confinement can stabilize proteins by over 10kBT but crowding has a very modest effect on stability. On the other hand, confinement and crowding are both predicted to favor conformations of the unfolded state which are compact, and consequently may increase the folding rate. These predictions are largely borne out by experimental studies of protein folding under confined and crowded conditions in the test tube. Protein folding in cellular environments is further complicated by interactions with surrounding surfaces and other factors. Concerted theoretical modeling and test-tube and in vivo experiments promise to elucidate the complexity of protein folding in cellular environments. PMID:17719556

  2. Folding with thermal-mechanical feedback: Discussion

    NASA Astrophysics Data System (ADS)

    Treagus, Susan H.; Hudleston, Peter J.

    2009-07-01

    A recent paper in this Journal by Bruce Hobbs, Klaus Regenauer-Lieb and Alison Ord [Hobbs, B., Regenauer-Lieb, K., Ord, A., 2008. Folding with thermal-mechanical feedback. Journal of Structural Geology 30, 1572-1592] presents an alternative theory to the traditional Biot-Ramberg theory for folding of viscous rocks that involves non-equilibrium thermodynamics and thermal-mechanical feedback. The authors convey a strong message throughout their paper that the folds produced by this theoretical and numerical modelling are geologically realistic and provide a better explanation for many natural folds than the traditional theory. They promise the same approach for boudinage, and present this folding paper as part of a "unified framework for rock deformation processes". Readers of the Journal of Structural Geology might be led to conclude that this paper provides a good alternative model for folding of rocks. Our discussion will disagree, on four counts.

  3. Hierarchical classification of protein folds using a novel ensemble classifier.

    PubMed

    Lin, Chen; Zou, Ying; Qin, Ji; Liu, Xiangrong; Jiang, Yi; Ke, Caihuan; Zou, Quan

    2013-01-01

    The analysis of biological information from protein sequences is important for the study of cellular functions and interactions, and protein fold recognition plays a key role in the prediction of protein structures. Unfortunately, the prediction of protein fold patterns is challenging due to the existence of compound protein structures. Here, we processed the latest release of the Structural Classification of Proteins (SCOP, version 1.75) database and exploited novel techniques to impressively increase the accuracy of protein fold classification. The techniques proposed in this paper include ensemble classifying and a hierarchical framework, in the first layer of which similar or redundant sequences were deleted in two manners; a set of base classifiers, fused by various selection strategies, divides the input into seven classes; in the second layer of which, an analogous ensemble method is adopted to predict all protein folds. To our knowledge, it is the first time all protein folds can be intelligently detected hierarchically. Compared with prior studies, our experimental results demonstrated the efficiency and effectiveness of our proposed method, which achieved a success rate of 74.21%, which is much higher than results obtained with previous methods (ranging from 45.6% to 70.5%). When applied to the second layer of classification, the prediction accuracy was in the range between 23.13% and 46.05%. This value, which may not be remarkably high, is scientifically admirable and encouraging as compared to the relatively low counts of proteins from most fold recognition programs. The web server Hierarchical Protein Fold Prediction (HPFP) is available at http://datamining.xmu.edu.cn/software/hpfp. PMID:23437146

  4. Hierarchical Classification of Protein Folds Using a Novel Ensemble Classifier

    PubMed Central

    Qin, Ji; Liu, Xiangrong; Jiang, Yi; Ke, Caihuan; Zou, Quan

    2013-01-01

    The analysis of biological information from protein sequences is important for the study of cellular functions and interactions, and protein fold recognition plays a key role in the prediction of protein structures. Unfortunately, the prediction of protein fold patterns is challenging due to the existence of compound protein structures. Here, we processed the latest release of the Structural Classification of Proteins (SCOP, version 1.75) database and exploited novel techniques to impressively increase the accuracy of protein fold classification. The techniques proposed in this paper include ensemble classifying and a hierarchical framework, in the first layer of which similar or redundant sequences were deleted in two manners; a set of base classifiers, fused by various selection strategies, divides the input into seven classes; in the second layer of which, an analogous ensemble method is adopted to predict all protein folds. To our knowledge, it is the first time all protein folds can be intelligently detected hierarchically. Compared with prior studies, our experimental results demonstrated the efficiency and effectiveness of our proposed method, which achieved a success rate of 74.21%, which is much higher than results obtained with previous methods (ranging from 45.6% to 70.5%). When applied to the second layer of classification, the prediction accuracy was in the range between 23.13% and 46.05%. This value, which may not be remarkably high, is scientifically admirable and encouraging as compared to the relatively low counts of proteins from most fold recognition programs. The web server Hierarchical Protein Fold Prediction (HPFP) is available at http://datamining.xmu.edu.cn/software/hpfp. PMID:23437146

  5. 2,3,4,6-Tetrachlorophenol

    Integrated Risk Information System (IRIS)

    2,3,4,6 - Tetrachlorophenol ; CASRN 58 - 90 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncar

  6. 2,3-Dihydrobiflavone from Ginkgo biloba.

    PubMed

    Krauze-Baranowska, M; Sowiński, P

    1999-06-01

    From the yellow leaves of Ginkgo biloba 2,3-dihydrosciadopitysin (5,5'',7''-trihydroxy-7,4',4'''-trimethoxy-3',8''-flavanone/flavone) was isolated as a mixture of two diastereomers. Its structure was elucidated employing 2D NMR techniques. PMID:17260276

  7. 1,2,3-triazolium ionic liquids

    SciTech Connect

    Luebke, David; Nulwala, Hunaid; Tang, Chau

    2014-12-09

    The present invention relates to compositions of matter that are ionic liquids, the compositions comprising substituted 1,2,3-triazolium cations combined with any anion. Compositions of the invention should be useful in the separation of gases and, perhaps, as catalysts for many reactions.

  8. Occupancy of pramipexole (Sifrol) at cerebral dopamine D2/3 receptors in Parkinson's disease patients.

    PubMed

    Deutschländer, Angela; la Fougère, Christian; Boetzel, Kai; Albert, Nathalie L; Gildehaus, Franz-Josef; Bartenstein, Peter; Xiong, Guoming; Cumming, Paul

    2016-01-01

    Whereas positron emission tomography (PET) with the antagonist ligand [(18)F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [(18)F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d.), and again at a later date, after withholding pramipexole 48-72 h (OFF-Sifrol); in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01) occupancy at [(18)F]fallypride binding sites in globus pallidus (8%) thalamus (9%) and substantia nigra (19%), as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum. PMID:27408789

  9. Acquired retinal folds in the cat.

    PubMed

    MacMillan, A D

    1976-06-01

    Retinal folds were found in 5 cats. The apparent cause of the folding was varied: in 1 cat the folds appeared after a localized retinal detachment; in 2 cats the condition accompanied other intraocular abnormalities associated with feline infectious peritonitis; 1 cat had active keratitis, and the retinal changes were thought to have been injury related; and 1 cat, bilaterally affected, had chronic glomerulonephritis. PMID:945253

  10. [Design of a medical folding fridge].

    PubMed

    Sun, Jianjun; Wei, Jiancang; Wu, Taihu; Meng, Xingju

    2011-07-01

    This article introduces a design of a medical folding fridge, which consists of three major components, base, folding frame and insulated cover. The base has a cooling system. The frame and cover are expanded during normal use and folded during storage or transportation. The device is compact, durable, transportable and well environmental adaptable. The system design is proved proper and the temperature inside is reliable. It is very suitable for temperature sensitive supplies stored in the medical emergency field. PMID:22097750

  11. Dependence of Internal Friction on Folding Mechanism

    PubMed Central

    2016-01-01

    An outstanding challenge in protein folding is understanding the origin of “internal friction” in folding dynamics, experimentally identified from the dependence of folding rates on solvent viscosity. A possible origin suggested by simulation is the crossing of local torsion barriers. However, it was unclear why internal friction varied from protein to protein or for different folding barriers of the same protein. Using all-atom simulations with variable solvent viscosity, in conjunction with transition-path sampling to obtain reaction rates and analysis via Markov state models, we are able to determine the internal friction in the folding of several peptides and miniproteins. In agreement with experiment, we find that the folding events with greatest internal friction are those that mainly involve helix formation, while hairpin formation exhibits little or no evidence of friction. Via a careful analysis of folding transition paths, we show that internal friction arises when torsion angle changes are an important part of the folding mechanism near the folding free energy barrier. These results suggest an explanation for the variation of internal friction effects from protein to protein and across the energy landscape of the same protein. PMID:25721133

  12. COS Side 2 NUV MAMA Fold Test

    NASA Astrophysics Data System (ADS)

    Bacinski, John

    2013-10-01

    The performance of the MAMA microchannel plate can be monitored using a MAMA fold analysis procedure. The fold analysis provides a measurement of the distribution of charge cloud sizes incident upon the anode giving some measure of changes in the pulse-height distribution of the MCP and, therefore, MCP gain. This proposal executes the same steps as the COS MAMA Fold Analysis {13128} during Cycle 20.This proposal is an exact duplication of nominal COS MAMA Fold Analysis {proposal 13128, Cycle 20}. Any changes 13128 or subsequent cycle submissions should be reflected in this proposal and vice versa.

  13. Protein Folding and Self-Organized Criticality

    NASA Astrophysics Data System (ADS)

    Bajracharya, Arun; Murray, Joelle

    Proteins are known to fold into tertiary structures that determine their functionality in living organisms. However, the complex dynamics of protein folding and the way they consistently fold into the same structures is not fully understood. Self-organized criticality (SOC) has provided a framework for understanding complex systems in various systems (earthquakes, forest fires, financial markets, and epidemics) through scale invariance and the associated power law behavior. In this research, we use a simple hydrophobic-polar lattice-bound computational model to investigate self-organized criticality as a possible mechanism for generating complexity in protein folding.

  14. AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist

    PubMed Central

    Gever, Joel R; Soto, Rothschild; Henningsen, Robert A; Martin, Renee S; Hackos, David H; Panicker, Sandip; Rubas, Werner; Oglesby, Ian B; Dillon, Michael P; Milla, Marcos E; Burnstock, Geoffrey; Ford, Anthony PDW

    2010-01-01

    Background and purpose: Purinoceptors containing the P2X3 subunit (P2X3 homotrimeric and P2X2/3 heterotrimeric) are members of the P2X family of ion channels gated by ATP and may participate in primary afferent sensitization in a variety of pain-related diseases. The current work describes the in vitro pharmacological characteristics of AF-353, a novel, orally bioavailable, highly potent and selective P2X3/P2X2/3 receptor antagonist. Experimental approach: The antagonistic potencies (pIC50) of AF-353 for rat and human P2X3 and human P2X2/3 receptors were determined using methods of radioligand binding, intracellular calcium flux and whole cell voltage-clamp electrophysiology. Key results: The pIC50 estimates for these receptors ranged from 7.3 to 8.5, while concentrations 300-fold higher had little or no effect on other P2X channels or on an assortment of receptors, enzymes and transporter proteins. In contrast to A-317491 and TNP-ATP, competition binding and intracellular calcium flux experiments suggested that AF-353 inhibits activation by ATP in a non-competitive fashion. Favourable pharmacokinetic parameters were observed in rat, with good oral bioavailability (%F = 32.9), reasonable half-life (t1/2 = 1.63 h) and plasma-free fraction (98.2% protein bound). Conclusions and implications: The combination of a favourable pharmacokinetic profile with the antagonist potency and selectivity for P2X3 and P2X2/3 receptors suggests that AF-353 is an excellent in vivo tool compound for study of these channels in animal models and demonstrates the feasibility of identifying and optimizing molecules into potential clinical candidates, and, ultimately, into a novel class of therapeutics for the treatment of pain-related disorders. PMID:20590629

  15. Retinal and Choroidal Folds in Papilledema

    PubMed Central

    Sibony, Patrick A.; Kupersmith, Mark J.; Feldon, Steven E.; Wang, Jui-Kai; Garvin, Mona

    2015-01-01

    Purpose To determine the frequency, patterns, associations, and biomechanical implications of retinal and choroidal folds in papilledema due to idiopathic intracranial hypertension (IIH). Methods Retinal and choroidal folds were studied in patients enrolled in the IIH Treatment Trial using fundus photography (n = 165 study eyes) and spectral-domain optical coherence tomography (SD-OCT; n = 125). We examined the association between folds and peripapillary shape, retinal nerve fiber layer (RNFL) thickness, disc volume, Frisén grade, acuity, perimetric mean deviation, intraocular pressure, intracranial pressure, and refractive error. Results We identified three types of folds in IIH patients with papilledema: peripapillary wrinkles (PPW), retinal folds (RF), and choroidal folds (CF). Frequency, with photos, was 26%, 19%, and 1%, respectively; SD-OCT frequency was 46%, 47%, and 10%. At least one type of fold was present in 41% of patients with photos and 73% with SD-OCT. Spectral-domain OCT was more sensitive. Structural parameters related to the severity of papilledema were associated with PPW and RF, whereas anterior deformation of the peripapillary RPE/basement membrane layer was associated with CF and RF. Folds were not associated with vision loss at baseline. Conclusions Folds in papilledema are biomechanical signs of stress/strain on the optic nerve head and load-bearing structures induced by intracranial hypertension. Folds are best imaged with SD-OCT. The patterns of retinal and choroidal folds are the products of a complex interplay between the degree of papilledema and anterior deformation of the load-bearing structures (sclera and possibly the lamina cribrosa), both modulated by structural geometry and material properties of the optic nerve head. (ClinicalTrials.gov number, NCT01003639.) PMID:26335066

  16. Guiding the folding pathway of DNA origami

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

    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

  17. Indoleamine 2,3-dioxygenase vaccination

    PubMed Central

    Andersen, Mads Hald; Svane, Inge Marie

    2015-01-01

    Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. Remarkably, we discovered IDO-specific T cells that can influence adaptive immune reactions in patients with cancer. Further, a recent phase I clinical trial demonstrated long-lasting disease stabilization without toxicity in patients with non-small-cell lung cancer (NSCLC) who were vaccinated with an IDO-derived HLA-A2-restricted epitope. PMID:25949864

  18. Energy Landscapes and Solved Protein Folding Problems

    NASA Astrophysics Data System (ADS)

    Wolynes, Peter

    2004-03-01

    Peter G. Wolynes Center for Theoretical Biological Physics Department of Chemistry and Biochemistry and Physics University of California, San Diego La Jolla, CA 92093-0371 Fifteen years ago, how proteins folded into organized structures on the basis of their sequence was a great mystery. By characterizing the energy landscapes of proteins with tools from the statistical mechanics of disordered systems like spin glasses, a "new view' of the folding process became possible. Energy landscape theory provided an incentive to pursue heroic new experiments and to carry out difficult computer simulations addressing protein folding mechanisms. Many aspects of folding kinetics revealed by these studies can be quantitatively understood using the simple idea that the topography of the energy landscape is that of a "rugged funnel". Energy landscape theory provided a quantitative means of characterizing which amino acid sequences can rapidly fold. Algorithms based on energy landscape theory have been used to successfully design novel sequences that fold to a given structure in the laboratory. Energy landscape ideas have begun to transform the prediction of protein structure from sequence data from being an art to being a science. The success of energy landscape- based algorithms in predicting protein structure from sequence will be highlighted. While there is still much to learn about folding mechanisms and much work to do achieving universally reliable structure prediction, many parts of what used to be called "the protein folding problem" can now be considered solved.

  19. Stochastic Resonance in Protein Folding Dynamics.

    PubMed

    Davtyan, Aram; Platkov, Max; Gruebele, Martin; Papoian, Garegin A

    2016-05-01

    Although protein folding reactions are usually studied under static external conditions, it is likely that proteins fold in a locally fluctuating cellular environment in vivo. To mimic such behavior in in vitro experiments, the local temperature of the solvent can be modulated either harmonically or using correlated noise. In this study, coarse-grained molecular simulations are used to investigate these possibilities, and it is found that both periodic and correlated random fluctuations of the environment can indeed accelerate folding kinetics if the characteristic frequencies of the applied fluctuations are commensurate with the internal timescale of the folding reaction; this is consistent with the phenomenon of stochastic resonance observed in many other condensed-matter processes. To test this theoretical prediction, the folding dynamics of phosphoglycerate kinase under harmonic temperature fluctuations are experimentally probed using Förster resonance energy transfer fluorescence measurements. To analyze these experiments, a combination of theoretical approaches is developed, including stochastic simulations of folding kinetics and an analytical mean-field kinetic theory. The experimental observations are consistent with the theoretical predictions of stochastic resonance in phosphoglycerate kinase folding. When combined with an alternative experiment on the protein VlsE using a power spectrum analysis, elaborated in Dave et al., ChemPhysChem 2016, 10.1002/cphc.201501041, the overall data overwhelmingly point to the experimental confirmation of stochastic resonance in protein folding dynamics. PMID:26992148

  20. Protein folding: When ribosomes pick the structure

    NASA Astrophysics Data System (ADS)

    Sivertsson, Elin M.; Itzhaki, Laura S.

    2014-05-01

    Anfinsen's principle tells us that the folded structure of a protein is determined solely by its sequence. Now, it has been shown that the rate at which a polypeptide chain is synthesized in the cell can affect which of two alternative folded structures it adopts.

  1. Folding Polyominoes from One Level to Two

    ERIC Educational Resources Information Center

    Frederickson, Greg N.

    2011-01-01

    For any given polyomino, is it possible to cut it into pieces and then hinge the pieces, so that the polyomino folds up into a similar version of itself but two levels thick? While we don't know how to do this for every polyomino, the article does show how to cut, hinge, and fold polyominoes from several infinite classes, providing an…

  2. Truss Structure Could Be Folded For Transport

    NASA Technical Reports Server (NTRS)

    Theer, Douglas S.

    1996-01-01

    Proposed truss structure comprises cubical bays and folded for compactness during transport. When folded, truss 1/25.6 as long as when fully extended. Conceived for transport and deployment in outerspace, suitable for terrestrial structures that must be transported compactly and erected quickly.

  3. A Canonical Biomechanical Vocal Fold Model

    PubMed Central

    Bhattacharya, Pinaki; Siegmund, Thomas H.

    2012-01-01

    Summary The present article aimed at constructing a canonical geometry of the human vocal fold (VF) from subject-specific image slice data. A computer-aided design approach automated the model construction. A subject-specific geometry available in literature, three abstractions (which successively diminished in geometric detail) derived from it, and a widely used quasi two-dimensional VF model geometry were used to create computational models. The first three natural frequencies of the models were used to characterize their mechanical response. These frequencies were determined for a representative range of tissue biomechanical properties, accounting for underlying VF histology. Compared with the subject-specific geometry model (baseline), a higher degree of abstraction was found to always correspond to a larger deviation in model frequency (up to 50% in the relevant range of tissue biomechanical properties). The model we deemed canonical was optimally abstracted, in that it significantly simplified the VF geometry compared with the baseline geometry but can be recalibrated in a consistent manner to match the baseline response. Models providing only a marginally higher degree of abstraction were found to have significant deviation in predicted frequency response. The quasi two-dimensional model presented an extreme situation: it could not be recalibrated for its frequency response to match the subject-specific model. This deficiency was attributed to complex support conditions at anterior-posterior extremities of the VFs, accentuated by further issues introduced through the tissue biomechanical properties. In creating canonical models by leveraging advances in clinical imaging techniques, the automated design procedure makes VF modeling based on subject-specific geometry more realizable. PMID:22209063

  4. Cooperative Tertiary Interaction Network Guides RNA Folding

    SciTech Connect

    Behrouzi, Reza; Roh, Joon Ho; Kilburn, Duncan; Briber, R.M.; Woodson, Sarah A.

    2013-04-08

    Noncoding RNAs form unique 3D structures, which perform many regulatory functions. To understand how RNAs fold uniquely despite a small number of tertiary interaction motifs, we mutated the major tertiary interactions in a group I ribozyme by single-base substitutions. The resulting perturbations to the folding energy landscape were measured using SAXS, ribozyme activity, hydroxyl radical footprinting, and native PAGE. Double- and triple-mutant cycles show that most tertiary interactions have a small effect on the stability of the native state. Instead, the formation of core and peripheral structural motifs is cooperatively linked in near-native folding intermediates, and this cooperativity depends on the native helix orientation. The emergence of a cooperative interaction network at an early stage of folding suppresses nonnative structures and guides the search for the native state. We suggest that cooperativity in noncoding RNAs arose from natural selection of architectures conducive to forming a unique, stable fold.

  5. Molecular gymnastics: serpin structure, folding and misfolding.

    PubMed

    Whisstock, James C; Bottomley, Stephen P

    2006-12-01

    The native state of serpins represents a long-lived intermediate or metastable structure on the serpin folding pathway. Upon interaction with a protease, the serpin trap is sprung and the molecule continues to fold into a more stable conformation. However, thermodynamic stability can also be achieved through alternative, unproductive folding pathways that result in the formation of inactive conformations. Our increasing understanding of the mechanism of protease inhibition and the dynamics of native serpin structures has begun to reveal how evolution has harnessed the actual process of protein folding (rather than the final folded outcome) to elegantly achieve function. The cost of using metastability for function, however, is an increased propensity for misfolding. PMID:17079131

  6. Protein folding at single-molecule resolution

    PubMed Central

    Ferreon, Allan Chris M.; Deniz, Ashok A.

    2011-01-01

    The protein folding reaction carries great significance for cellular function and hence continues to be the research focus of a large interdisciplinary protein science community. Single-molecule methods are providing new and powerful tools for dissecting the mechanisms of this complex process by virtue of their ability to provide views of protein structure and dynamics without associated ensemble averaging. This review briefly introduces common FRET and force methods, and then explores several areas of protein folding where single-molecule experiments have yielded insights. These include exciting new information about folding landscapes, dynamics, intermediates, unfolded ensembles, intrinsically disordered proteins, assisted folding and biomechanical unfolding. Emerging and future work is expected to include advances in single-molecule techniques aimed at such investigations, and increasing work on more complex systems from both the physics and biology standpoints, including folding and dynamics of systems of interacting proteins and of proteins in cells and organisms. PMID:21303706

  7. Fan-fold shielded electrical leads

    DOEpatents

    Rohatgi, Rajeev R.; Cowan, Thomas E.

    1996-01-01

    Fan-folded electrical leads made from copper cladded Kapton, for example, with the copper cladding on one side serving as a ground plane and the copper cladding on the other side being etched to form the leads. The Kapton is fan folded with the leads located at the bottom of the fan-folds. Electrical connections are made by partially opening the folds of the fan and soldering, for example, the connections directly to the ground plane and/or the lead. The fan folded arrangement produces a number of advantages, such as electrically shielding the leads from the environment, is totally non-magnetic, and has a very low thermal conductivity, while being easy to fabricate.

  8. Visualizing chaperone-assisted protein folding.

    PubMed

    Horowitz, Scott; Salmon, Loïc; Koldewey, Philipp; Ahlstrom, Logan S; Martin, Raoul; Quan, Shu; Afonine, Pavel V; van den Bedem, Henry; Wang, Lili; Xu, Qingping; Trievel, Raymond C; Brooks, Charles L; Bardwell, James C A

    2016-07-01

    Challenges in determining the structures of heterogeneous and dynamic protein complexes have greatly hampered past efforts to obtain a mechanistic understanding of many important biological processes. One such process is chaperone-assisted protein folding. Obtaining structural ensembles of chaperone-substrate complexes would ultimately reveal how chaperones help proteins fold into their native state. To address this problem, we devised a new structural biology approach based on X-ray crystallography, termed residual electron and anomalous density (READ). READ enabled us to visualize even sparsely populated conformations of the substrate protein immunity protein 7 (Im7) in complex with the Escherichia coli chaperone Spy, and to capture a series of snapshots depicting the various folding states of Im7 bound to Spy. The ensemble shows that Spy-associated Im7 samples conformations ranging from unfolded to partially folded to native-like states and reveals how a substrate can explore its folding landscape while being bound to a chaperone. PMID:27239796

  9. Similarities between protein folding and granular jamming

    PubMed Central

    Jose, Prasanth P; Andricioaei, Ioan

    2012-01-01

    Grains and glasses, widely different materials, arrest their motions upon decreasing temperature and external load, respectively, in common ways, leading to a universal jamming phase diagram conjecture. However, unified theories are lacking, mainly because of the disparate nature of the particle interactions. Here we demonstrate that folded proteins exhibit signatures common to both glassiness and jamming by using temperature- and force-unfolding molecular dynamics simulations. Upon folding, proteins develop a peak in the interatomic force distributions that falls on a universal curve with experimentally measured forces on jammed grains and droplets. Dynamical signatures are found as a dramatic slowdown of stress relaxation upon folding. Together with granular similarities, folding is tied not just to the jamming transition, but a more nuanced picture of anisotropy, preparation protocol and internal interactions emerges. Results have implications for designing stable polymers and can open avenues to link protein folding to jamming theory. PMID:23093180

  10. Single-molecule Studies of Riboswitch Folding

    PubMed Central

    Savinov, Andrew; Perez, Christian F.; Block, Steven M.

    2014-01-01

    The folding dynamics of riboswitches are central to their ability to modulate gene expression in response to environmental cues. In most cases, a structural competition between the formation of a ligand-binding aptamer and an expression platform (or some other competing off-state) determines the regulatory outcome. Here, we review single-molecule studies of riboswitch folding and function, predominantly carried out using single-molecule FRET or optical trapping approaches. Recent results have supplied new insights into riboswitch folding energy landscapes, the mechanisms of ligand binding, the roles played by divalent ions, the applicability of hierarchical folding models, and kinetic vs. thermodynamic control schemes. We anticipate that future work, based on improved data sets and potentially combining multiple experimental techniques, will enable the development of more complete models for complex RNA folding processes. PMID:24727093

  11. Protein folding on the ribosome studied using NMR spectroscopy

    PubMed Central

    Waudby, Christopher A.; Launay, Hélène; Cabrita, Lisa D.; Christodoulou, John

    2013-01-01

    NMR spectroscopy is a powerful tool for the investigation of protein folding and misfolding, providing a characterization of molecular structure, dynamics and exchange processes, across a very wide range of timescales and with near atomic resolution. In recent years NMR methods have also been developed to study protein folding as it might occur within the cell, in a de novo manner, by observing the folding of nascent polypeptides in the process of emerging from the ribosome during synthesis. Despite the 2.3 MDa molecular weight of the bacterial 70S ribosome, many nascent polypeptides, and some ribosomal proteins, have sufficient local flexibility that sharp resonances may be observed in solution-state NMR spectra. In providing information on dynamic regions of the structure, NMR spectroscopy is therefore highly complementary to alternative methods such as X-ray crystallography and cryo-electron microscopy, which have successfully characterized the rigid core of the ribosome particle. However, the low working concentrations and limited sample stability associated with ribosome–nascent chain complexes means that such studies still present significant technical challenges to the NMR spectroscopist. This review will discuss the progress that has been made in this area, surveying all NMR studies that have been published to date, and with a particular focus on strategies for improving experimental sensitivity. PMID:24083462

  12. Fold interaction and wavelength selection in 3D models of multilayer detachment folding

    NASA Astrophysics Data System (ADS)

    Fernandez, Naiara; Kaus, Boris J. P.

    2014-09-01

    Many fold-and-thrust belts are dominated by folding and exhibit a fairly regular fold-spacing. Yet, in map-view, the aspect ratio of doubly-plunging anticlines varies considerably from very elongated, and sometimes slightly curved, cylindrical folds to nearly circular, dome-like structures. In addition, the fold spacing often varies significantly around an average value. So far, it remains unclear whether these features are consistent with a folding instability. Therefore, we here study the dynamics of multilayer detachment folding, process by which shortening can be accommodated in thin-skinned fold-and-thrust belts. We start by analysing the physics of this process by using both a semi-analytical thick plate theory and numerical simulations. Results show that several different folding modes occur, about half of which are affected by gravity and have a wavelength that depends on the background deformation rate. Non-dimensional expressions are derived that predict the dominant wavelength and growth rate of each of these folding modes and mechanical phase diagrams are presented that illustrate the applicability of each of the modes. Next, we perform 3D simulations and compare the results with those of 2D models and analytical theory. Both 2D and 3D numerical simulations have wavelengths that are in good agreement with the analytical predictions. In the high-resolution 3D simulations the lateral growth of folds is studied, in particular with respect to fold segment interactions and evolution of fold width-length aspect ratio. The numerical simulations show a number of similarities with the Fars region of the Zagros fold-and-thrust belt including a large range of fold aspect ratio and a normally distributed fold wavelength around a dominant one.

  13. Folding kinematics expressed in fracture patterns: An example from the Anti-Atlas fold belt, Morocco

    NASA Astrophysics Data System (ADS)

    Ismat, Zeshan

    2008-11-01

    The Anti-Atlas fold belt, Morocco, formed during the same Variscan collisional event that produced the Valley-and-Ridge fold-thrust belt of the Appalachian mountains. Both are external belts of the Appalachian-Ouachita-Mauritanides chain and at the map scale have very similar topographic expressions. The Anti-Atlas, however, consists of map-scale folds that are buckle-related, detachment folds, whereas the Valley-and-Ridge folds developed in response to imbricate thrusting. For this reason, the Anti-Atlas is referred to as a fold belt rather than a fold-thrust belt. This paper examines Variscan folding processes in the Anti-Atlas Mountains. Folding in some layers occurred by sliding along a penetrative network of mesoscale fractures, i.e. cataclastic flow, during buckling. Layer-parallel shortening fractures were reactivated in the later stages of folding to accommodate limb rotation. Although 'boutonnieres', i.e. basement uplifts, punctuate the fold belt, the fracture patterns indicate that the uplifts failed to provide any 'bending' component. Folding is also interpreted to occur under low to moderate confining pressures because the fracture network includes conjugate shear fractures with very small (˜20°) dihedral angles.

  14. SO(2, 3) noncommutative gravity model

    NASA Astrophysics Data System (ADS)

    Dimitrijević, M.; Radovanović, V.

    2014-12-01

    In this paper the noncommutative gravity is treated as a gauge theory of the non-commutative SO(2, 3)★ group, while the noncommutativity is canonical. The Seiberg-Witten (SW) map is used to express noncommutative fields in terms of the corresponding commutative fields. The commutative limit of the model is the Einstein-Hilbert action plus the cosmological term and the topological Gauss-Bonnet term. We calculate the second order correction to this model and obtain terms that are zeroth, first, ... and fourth power of the curvature tensor. Finally, we discuss physical consequences of those correction terms in the limit of big cosmological constant.

  15. Quantification of a Helical Origami Fold

    NASA Astrophysics Data System (ADS)

    Dai, Eric; Han, Xiaomin; Chen, Zi

    2015-03-01

    Origami, the Japanese art of paper folding, is traditionally viewed as an amusing pastime and medium of artistic expression. However, in recent years, origami has served as a source of inspiration for innovations in science and engineering. Here, we present the geometric and mechanical properties of a twisting origami fold. The origami structure created by the fold exhibits several interesting properties, including rigid foldibility, local bistability and finely tunable helical coiling, with control over pitch, radius and handedness of the helix. In addition, the pattern generated by the fold closely mimics the twist buckling patterns shown by thin materials, for example, a mobius strip. We use six parameters of the twisting origami pattern to generate a fully tunable graphical model of the fold. Finally, we present a mathematical model of the local bistability of the twisting origami fold. Our study elucidates the mechanisms behind the helical coiling and local bistability of the twisting origami fold, with potential applications in robotics and deployable structures. Acknowledgment to Branco Weiss Fellowship for funding.

  16. The nature of protein folding pathways.

    PubMed

    Englander, S Walter; Mayne, Leland

    2014-11-11

    How do proteins fold, and why do they fold in that way? This Perspective integrates earlier and more recent advances over the 50-y history of the protein folding problem, emphasizing unambiguously clear structural information. Experimental results show that, contrary to prior belief, proteins are multistate rather than two-state objects. They are composed of separately cooperative foldon building blocks that can be seen to repeatedly unfold and refold as units even under native conditions. Similarly, foldons are lost as units when proteins are destabilized to produce partially unfolded equilibrium molten globules. In kinetic folding, the inherently cooperative nature of foldons predisposes the thermally driven amino acid-level search to form an initial foldon and subsequent foldons in later assisted searches. The small size of foldon units, ∼ 20 residues, resolves the Levinthal time-scale search problem. These microscopic-level search processes can be identified with the disordered multitrack search envisioned in the "new view" model for protein folding. Emergent macroscopic foldon-foldon interactions then collectively provide the structural guidance and free energy bias for the ordered addition of foldons in a stepwise pathway that sequentially builds the native protein. These conclusions reconcile the seemingly opposed new view and defined pathway models; the two models account for different stages of the protein folding process. Additionally, these observations answer the "how" and the "why" questions. The protein folding pathway depends on the same foldon units and foldon-foldon interactions that construct the native structure. PMID:25326421

  17. Folding Elastic Thermal Surface - FETS

    NASA Technical Reports Server (NTRS)

    Urquiza, Eugenio; Zhang, Burt X.; Thelen, Michael P.; Rodriquez, Jose I.; Pellegrino, Sergio

    2013-01-01

    the FETS is also self-locking so the panels stay in a rigid and extended configuration after deployment. This unexpected benefit makes the tape-spring hinge design of the FETS a light, simple, reliable, compact, non-outgassing hinge, spring, and latch. While tape-spring hinges are not novel, they have never been used to deploy passive unfolding thermal surfaces (radiator panels, covers, sun shades, or IR thermal shields). Furthermore, because this technology is compact, it has minimal impact on the launch envelope and mass specifications. FETS enhances the performance of hosted payload instruments where the science data is limited by dark noise. Incorporating FETS into a thermal control system increases radiator area, which lowers the optical detector temperature. This results in higher SNR (signal-to-noise ratio) and improved science data.

  18. Aeroelastic and Flight Dynamics Analysis of Folding Wing Systems

    NASA Astrophysics Data System (ADS)

    Wang, Ivan

    This dissertation explores the aeroelastic stability of a folding wing using both theoretical and experimental methods. The theoretical model is based on the existing clamped-wing aeroelastic model that uses beam theory structural dynamics and strip theory aerodynamics. A higher-fidelity theoretical model was created by adding several improvements to the existing model, namely a structural model that uses ANSYS for individual wing segment modes and an unsteady vortex lattice aerodynamic model. The comparison with the lower-fidelity model shows that the higher-fidelity model typical provides better agreement between theory and experiment, but the predicted system behavior in general does not change, reinforcing the effectiveness of the low-fidelity model for preliminary design of folding wings. The present work also conducted more detailed aeroelastic analyses of three-segment folding wings, and in particular considers the Lockheed-type configurations to understand the existence of sudden changes in predicted aeroelastic behavior with varying fold angle for certain configurations. These phenomena were observed in carefully conducted experiments, and nonlinearities---structural and geometry---were shown to suppress the phenomena. Next, new experimental models with better manufacturing tolerances are designed to be tested in the Duke University Wind Tunnel. The testing focused on various configurations of three-segment folding wings in order to obtain higher quality data. Next, the theoretical model was further improved by adding aircraft longitudinal degrees of freedom such that the aeroelastic model may predict the instabilities for the entire aircraft and not just a clamped wing. The theoretical results show that the flutter instabilities typically occur at a higher air speed due to greater frequency separation between modes for the aircraft system than a clamped wing system, but the divergence instabilities occur at a lower air speed. Lastly, additional

  19. Folding pathways of the Tetrahymena ribozyme

    PubMed Central

    Mitchell, David; Russell, Rick

    2014-01-01

    Like many structured RNAs, the Tetrahymena group I intron ribozyme folds through multiple pathways and intermediates. Under standard conditions in vitro, a small fraction reaches the native state (N) with kobs ≈ 0.6 min–1, while the remainder forms a long-lived misfolded conformation (M) thought to differ in topology. These alternative outcomes reflect a pathway that branches late in folding, after disruption of a trapped intermediate (Itrap). Here, we use catalytic activity to probe the folding transitions from Itrap to the native and misfolded states. We show that mutations predicted to weaken the core helix P3 do not increase the rate of folding from Itrap but they increase the fraction that reaches the native state rather than forming the misfolded state. Thus, P3 is disrupted during folding to the native state but not to the misfolded state, and P3 disruption occurs after the rate-limiting step. Interestingly, P3-strengthening mutants also increase native folding. Additional experiments show that these mutants are rapidly committed to folding to the native state, although they reach the native state with approximately the same rate constant as the wild-type ribozyme (~1 min–1). Thus, the P3-strengthening mutants populate a distinct pathway that includes at least one intermediate but avoids the M state, most likely because P3 and the correct topology are formed early. Our results highlight multiple pathways in RNA folding and illustrate how kinetic competitions between rapid events can have long-lasting effects because the ‘choice’ is enforced by energy barriers that grow larger as folding progresses. PMID:24747051

  20. Osteochondrodysplasia in three Scottish Fold cats.

    PubMed

    Chang, Jinhwa; Jung, Joohyun; Oh, Sunkyoung; Lee, Sungok; Kim, Gyeongmin; Kim, Haksang; Kweon, Ohkyeong; Yoon, Junghee; Choi, Mincheol

    2007-09-01

    This report explains typical radiographic features of Scottish Fold osteochondrodysplasia. Three Scottish Fold cats suffering from lameness were referred to the Veterinary Medical Teaching Hospital, Seoul National University, Korea. Based on the breed predisposition, history, clinical signs, physical examination, and radiographic findings, Scottish Fold osteochondrodysplasia was confirmed in three cases. Radiographic changes mainly included exostosis and secondary arthritis around affected joint lesions, and defective conformation in the phalanges and caudal vertebrae. The oral chondroprotective agents such as glucosamine and chondroitin sulfate make the patients alleviate their pain without adverse effects. PMID:17679781

  1. Mechanical Models of Fault-Related Folding

    SciTech Connect

    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).

  2. Network measures for protein folding state discrimination

    PubMed Central

    Menichetti, Giulia; Fariselli, Piero; Remondini, Daniel

    2016-01-01

    Proteins fold using a two-state or multi-state kinetic mechanisms, but up to now there is not a first-principle model to explain this different behavior. We exploit the network properties of protein structures by introducing novel observables to address the problem of classifying the different types of folding kinetics. These observables display a plain physical meaning, in terms of vibrational modes, possible configurations compatible with the native protein structure, and folding cooperativity. The relevance of these observables is supported by a classification performance up to 90%, even with simple classifiers such as discriminant analysis. PMID:27464796

  3. Protein Folding and Unfolding Under Force

    PubMed Central

    Jagannathan, Bharat; Marqusee, Susan

    2014-01-01

    The recent revolution in optics and instrumentation has enabled the study of protein folding using extremely low mechanical forces as the denaturant. This exciting development has led to the observation of the protein folding process at single molecule resolution and its response to mechanical force. Here, we describe the principles and experimental details of force spectroscopy on proteins, with a focus on the optical tweezers instrument. Several recent results will be discussed to highlight the importance of this technique in addressing a variety of questions in the protein folding field. PMID:23784721

  4. Probing the physical determinants of thermal expansion of folded proteins.

    PubMed

    Dellarole, Mariano; Kobayashi, Kei; Rouget, Jean-Baptiste; Caro, José Alfredo; Roche, Julien; Islam, Mohammad M; Garcia-Moreno E, Bertrand; Kuroda, Yutaka; Royer, Catherine A

    2013-10-24

    The magnitude and sign of the volume change upon protein unfolding are strongly dependent on temperature. This temperature dependence reflects differences in the thermal expansivity of the folded and unfolded states. The factors that determine protein molar expansivities and the large differences in thermal expansivity for proteins of similar molar volume are not well understood. Model compound studies have suggested that a major contribution is made by differences in the molar volume of water molecules as they transfer from the protein surface to the bulk upon heating. The expansion of internal solvent-excluded voids upon heating is another possible contributing factor. Here, the contribution from hydration density to the molar thermal expansivity of a protein was examined by comparing bovine pancreatic trypsin inhibitor and variants with alanine substitutions at or near the protein-water interface. Variants of two of these proteins with an additional mutation that unfolded them under native conditions were also examined. A modest decrease in thermal expansivity was observed in both the folded and unfolded states for the alanine variants compared with the parent protein, revealing that large changes can be made to the external polarity of a protein without causing large ensuing changes in thermal expansivity. This modest effect is not surprising, given the small molar volume of the alanine residue. Contributions of the expansion of the internal void volume were probed by measuring the thermal expansion for cavity-containing variants of a highly stable form of staphylococcal nuclease. Significantly larger (2-3-fold) molar expansivities were found for these cavity-containing proteins relative to the reference protein. Taken together, these results suggest that a key determinant of the thermal expansivities of folded proteins lies in the expansion of internal solvent-excluded voids. PMID:23646824

  5. Influence of glycosaminoglycan identity on vocal fold fibroblast behavior.

    PubMed

    Jimenez-Vergara, Andrea Carolina; Munoz-Pinto, Dany J; Becerra-Bayona, Silvia; Wang, Bo; Iacob, Alexandra; Hahn, Mariah S

    2011-11-01

    Poly(ethylene glycol) (PEG) hydrogels have recently begun to be studied for the treatment of scarred vocal fold lamina propria due, in part, to their tunable mechanical properties, resistance to fibroblast-mediated contraction, and ability to be polymerized in situ. However, pure PEG gels lack intrinsic biochemical signals to guide cell behavior and generally fail to mimic the frequency-dependent viscoelastic response critical to normal superficial lamina propria function. Recent results suggest that incorporation of viscoelastic bioactive substances, such as glycosaminoglycans (GAGs), into PEG networks may allow these gels to more closely approach the mechanical responses of normal vocal fold lamina propria while also stimulating desired vocal fold fibroblast behaviors. Although a number of vocal fold studies have examined the influence of hyaluronan (HA) on implant mechanics and vocal fold fibroblast responses, the effects of other GAG types have been relatively unexplored. This is significant, since recent studies have suggested that chondroitin sulfate C (CSC) and heparan sulfate (HS) are substantially altered in scarred lamina propria. The present study was therefore designed to evaluate the effects of CSC and HS incorporation on the mechanical response of PEG gels and vocal fold fibroblast behavior relative to HA. As with PEG-HA, the viscoelasticity of PEG-CSC and PEG-HS gels more closely approached that of the normal vocal fold lamina propria than pure PEG hydrogels. In addition, collagen I deposition and fibronectin production were significantly higher in CSC than in HA gels, and levels of the myofibroblast marker smooth muscle α-actin (SM α-actin) were greater in CSC and HS gels than in HA gels. Since collagen I, fibronectin, and SM α-actin are generally elevated in scarred lamina propria these results suggest that CSC and HS may be undesirable for vocal fold implants relative to HA. Investigation of various signaling intermediates indicated that

  6. Identification of 2,3-dimethyl-2,3-diisobutyl succinonitrile in laser printer emissions.

    PubMed

    Barrero-Moreno, Josefa M; Tirendi, Salvatore; Reniero, Fabiano; Giordano, Giuseppe; Kotzias, Dimitrios

    2008-01-01

    2,3-Dimethyl-2,3-diisobutyl succinonitrile was identified as the main volatile organic compound (>90%) emitted from laser printers during the printing process. Experiments were carried out in a large environmental chamber of 30 m3, where the printers were placed and working simulating 'real office setting' conditions. Air samples were taken on Tenax TA adsorbent cartridges in the vicinity of the printers and further analyzed by thermal desorption gas chromatography/mass spectrometry (TDGC/MS). The structure of the compound has been determined and is presented in this study. Additional data obtained by nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, and liquid chromatography/tandem mass spectrometry (LC/MS/MS) support the proposed structure, with no reported CAS number, as 2,3-dimethyl-2,3-diisobutyl succinonitrile. It is a byproduct of the thermal decomposition of 2,2'-azobis(2,4-dimethyl valeronitrile), a commercially available free radical polymerization initiator used in polymerization processes during the manufacture of the toners. By means of head-space GC/MS, 15 toners used in black & white and colour printers have been investigated. Six of them contained 2,3-dimethyl-2,3-diisobutyl succinonitrile, which has also been detected in the respective processed paper. PMID:18205250

  7. Folded waveguide coupler for ion cyclotron heating

    SciTech Connect

    Owens, T.L.; Chen, G.L.

    1986-01-01

    A new type of waveguide coupler for plasma heating in the ion cyclotron range of frequencies is described. The coupler consists of a series of interleaved metallic vanes within a rectangular enclosure analogous to a wide rectangular waveguide that has been ''folded'' several times. At the mouth of the coupler, a plate is attached which contains coupling apertures in each fold or every other fold of the waveguide, depending upon the wavenumber spectrum desired. This plate serves primarily as a wave field polarizer that converts coupler fields to the polarization of the fast magnetosonic wave within the plasma. Theoretical estimates indicate that the folded waveguide is capable of high-efficiency, multimegawatt operation into a plasma. Bench tests have verified the predicted field structure within the waveguide in preparation for high-power tests on the Radio Frequency Test Facility at the Oak Ridge National Laboratory.

  8. Topology Explains Why Automobile Sunshades Fold Oddly

    ERIC Educational Resources Information Center

    Feist, Curtis; Naimi, Ramin

    2009-01-01

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

  9. Unexplained Profound Hypoglycemia After Vocal Fold Lipoinjection.

    PubMed

    Modanlou, Shohreh; Marie Giglio, Nicole; Carroll, Thomas; Pancaro, Carlo

    2016-02-01

    Vocal fold injection is used for the management of glottal incompetence from various causes. The procedure is well tolerated and has few reported complications. We present a case of a 66-year-old man with long-lasting hoarseness secondary to vocal fold atrophy, who underwent an uneventful bilateral vocal fold injection with autologous fat. While in the recovery area, he experienced profuse sweating approximately 30 minutes after the surgical procedure. His blood glucose value was measured at 24 mg/dL, and plasmatic insulin level was 246 mU/L. To our knowledge, this is the first reported case of a systemic side effect after vocal fold lipoinjection. PMID:26491839

  10. Frustration in Condensed Matter and Protein Folding

    NASA Astrophysics Data System (ADS)

    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.

  11. Monster Mash: Protein Folding Gone Wrong

    MedlinePlus

    ... Articles | Inside Life Science Home Page Monster Mash: Protein Folding Gone Wrong By Joseph Piergrossi Posted October 31, 2013 In this image, globs of misfolded proteins called amyloid plaques (blobs) are found outside neurons ( ...

  12. Self-folding miniature elastic electric devices

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    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.

  13. Statistical properties of a folded elastic rod

    NASA Astrophysics Data System (ADS)

    Bayart, Elsa; Deboeuf, Stéphanie; Boué, Laurent; Corson, Francis; Boudaoud, Arezki; Adda-Bedia, Mokhtar

    2010-03-01

    A large variety of elastic structures naturally seem to be confined into environments too small to accommodate them; the geometry of folded structures span a wide range of length-scales. The elastic properties of these confined systems are further constrained by self-avoidance as well as by the dimensionality of both structures and container. To mimic crumpled paper, we devised an experimental setup to study the packing of a dimensional elastic object in 2D geometries: an elastic rod is folded at the center of a circular Hele-Shaw cell by a centripetal force. The initial configuration of the rod and the acceleration of the rotating disk allow to span different final folded configurations while the final rotation speed controls the packing intensity. Using image analysis we measure geometrical and mechanical properties of the folded configurations, focusing on length, curvature and energy distributions.

  14. Cotranslational folding of deeply knotted proteins

    NASA Astrophysics Data System (ADS)

    Chwastyk, Mateusz; Cieplak, Marek

    2015-09-01

    Proper folding of deeply knotted proteins has a very low success rate even in structure-based models which favor formation of the native contacts but have no topological bias. By employing a structure-based model, we demonstrate that cotranslational folding on a model ribosome may enhance the odds to form trefoil knots for protein YibK without any need to introduce any non-native contacts. The ribosome is represented by a repulsive wall that keeps elongating the protein. On-ribosome folding proceeds through a a slipknot conformation. We elucidate the mechanics and energetics of its formation. We show that the knotting probability in on-ribosome folding is a function of temperature and that there is an optimal temperature for the process. Our model often leads to the establishment of the native contacts without formation of the knot.

  15. Cotranslational folding of deeply knotted proteins.

    PubMed

    Chwastyk, Mateusz; Cieplak, Marek

    2015-09-01

    Proper folding of deeply knotted proteins has a very low success rate even in structure-based models which favor formation of the native contacts but have no topological bias. By employing a structure-based model, we demonstrate that cotranslational folding on a model ribosome may enhance the odds to form trefoil knots for protein YibK without any need to introduce any non-native contacts. The ribosome is represented by a repulsive wall that keeps elongating the protein. On-ribosome folding proceeds through a a slipknot conformation. We elucidate the mechanics and energetics of its formation. We show that the knotting probability in on-ribosome folding is a function of temperature and that there is an optimal temperature for the process. Our model often leads to the establishment of the native contacts without formation of the knot. PMID:26292194

  16. Reinke Edema: Watch For Vocal Fold Cysts.

    PubMed

    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. PMID:26080256

  17. Folded Resonant Horns for Power Ultrasonic Applications

    NASA Technical Reports Server (NTRS)

    Sherrit, Stewart; Askins, Stephen; Gradziel, Michael; Bao, Xiaoqi; Chang, Zensheu; Dolgin, Benjamin; Bar-Cohen, Yoseph; Peterson, Tom

    2003-01-01

    Folded horns have been conceived as alternatives to straight horns used as resonators and strain amplifiers in power ultrasonic systems. Such systems are used for cleaning, welding, soldering, cutting, and drilling in a variety of industries. In addition, several previous NASA Tech Briefs articles have described instrumented drilling, coring, and burrowing machines that utilize combinations of sonic and ultrasonic vibrational actuation. The main advantage of a folded horn, relative to a straight horn of the same resonance frequency, is that the folded horn can be made shorter (that is, its greatest linear dimension measured from the outside can be made smaller). Alternatively, for a given length, the resonance frequency can be reduced. Hence, the folded-horn concept affords an additional degree of design freedom for reducing the length of an ultrasonic power system that includes a horn.

  18. Kinetic Analysis of Protein Folding Lattice Models

    NASA Astrophysics Data System (ADS)

    Chen, Hu; Zhou, Xin; Liaw, Chih Young; Koh, Chan Ghee

    Based on two-dimensional square lattice models of proteins, the relation between folding time and temperature is studied by Monte Carlo simulation. The results can be represented by a kinetic model with three states — random coil, molten globule, and native state. The folding process is composed of nonspecific collapse and final searching for the native state. At high temperature, it is easy to escape from local traps in the folding process. With decreasing temperature, because of the trapping in local traps, the final searching speed decreases. Then the folding shows chevron rollover. Through the analysis of the fitted parameters of the kinetic model, it is found that the main difference between the energy landscapes of the HP model and the Go model is that the number of local minima of the Go model is less than that of the HP model.

  19. Dew-driven folding of insect wings

    NASA Astrophysics Data System (ADS)

    Dickerson, Andrew; Beadles, Sam; Clement, Courtney; Hu, David

    2013-11-01

    Small insect wings fold into tacos when exposed to dewfall or fog for extended times. Such shapes are tightly held together and require great force or long evaporation times for the wings to unfold. In this experimental investigation, we use time-lapse and high-speed videography on a mosquito wing exposed to fog to characterize the folding process from a flat wing to a taco. We observe a taco is formed through a series of processes involving wing bending, unbending, and subsequent tight folding of the wing following the sliding of the drop off the wing. We use a simplified 2D model to determine the forces coalescing drops exert on the wing, and present folding-resistant design suggestions for micro-aerial vehicle wings.

  20. The 2.3-Angstrom Structure of Porcine Circovirus 2

    SciTech Connect

    Khayat, Reza; Brunn, Nicholas; Speir, Jeffrey A.; Hardham, John M.; Ankenbauer, Robert G.; Schneemann, Anette; Johnson, John E.

    2012-10-25

    Porcine circovirus 2 (PCV2) is a T = 1 nonenveloped icosahedral virus that has had severe impact on the swine industry. Here we report the crystal structure of an N-terminally truncated PCV2 virus-like particle at 2.3-{angstrom} resolution, and the cryo-electron microscopy (cryo-EM) image reconstruction of a full-length PCV2 virus-like particle at 9.6-{angstrom} resolution. This is the first atomic structure of a circovirus. The crystal structure revealed that the capsid protein fold is a canonical viral jelly roll. The loops connecting the strands of the jelly roll define the limited features of the surface. Sulfate ions interacting with the surface and electrostatic potential calculations strongly suggest a heparan sulfate binding site that allows PCV2 to gain entry into the cell. The crystal structure also allowed previously determined epitopes of the capsid to be visualized. The cryo-EM image reconstruction showed that the location of the N terminus, absent in the crystal structure, is inside the capsid. As the N terminus was previously shown to be antigenic, it may externalize through viral 'breathing'.

  1. Folding funnels, binding funnels, and protein function.

    PubMed Central

    Tsai, C. J.; Kumar, S.; Ma, B.; Nussinov, R.

    1999-01-01

    Folding funnels have been the focus of considerable attention during the last few years. These have mostly been discussed in the general context of the theory of protein folding. Here we extend the utility of the concept of folding funnels, relating them to biological mechanisms and function. In particular, here we describe the shape of the funnels in light of protein synthesis and folding; flexibility, conformational diversity, and binding mechanisms; and the associated binding funnels, illustrating the multiple routes and the range of complexed conformers. Specifically, the walls of the folding funnels, their crevices, and bumps are related to the complexity of protein folding, and hence to sequential vs. nonsequential folding. Whereas the former is more frequently observed in eukaryotic proteins, where the rate of protein synthesis is slower, the latter is more frequent in prokaryotes, with faster translation rates. The bottoms of the funnels reflect the extent of the flexibility of the proteins. Rugged floors imply a range of conformational isomers, which may be close on the energy landscape. Rather than undergoing an induced fit binding mechanism, the conformational ensembles around the rugged bottoms argue that the conformers, which are most complementary to the ligand, will bind to it with the equilibrium shifting in their favor. Furthermore, depending on the extent of the ruggedness, or of the smoothness with only a few minima, we may infer nonspecific, broad range vs. specific binding. In particular, folding and binding are similar processes, with similar underlying principles. Hence, the shape of the folding funnel of the monomer enables making reasonable guesses regarding the shape of the corresponding binding funnel. Proteins having a broad range of binding, such as proteolytic enzymes or relatively nonspecific endonucleases, may be expected to have not only rugged floors in their folding funnels, but their binding funnels will also behave similarly

  2. [Surgery of benign vocal fold lesions].

    PubMed

    Olthoff, A

    2016-09-01

    Surgical treatment of benign vocal fold lesions can be indicated for clinical or functional reasons. The principles of phonosurgery have to be maintained in either case. The appropriate phonosurgical technique depends on the type of vocal fold lesion. Depending on the findings, phonosurgery aims to maintain or improve voice quality. The evaluation of clinical and functional results includes indirect laryngoscopy, videostroboscopy, and voice analysis. PMID:27552826

  3. Protein folding and misfolding: mechanism and principles.

    PubMed

    Englander, S Walter; Mayne, Leland; Krishna, Mallela M G

    2007-11-01

    Two fundamentally different views of how proteins fold are now being debated. Do proteins fold through multiple unpredictable routes directed only by the energetically downhill nature of the folding landscape or do they fold through specific intermediates in a defined pathway that systematically puts predetermined pieces of the target native protein into place? It has now become possible to determine the structure of protein folding intermediates, evaluate their equilibrium and kinetic parameters, and establish their pathway relationships. Results obtained for many proteins have serendipitously revealed a new dimension of protein structure. Cooperative structural units of the native protein, called foldons, unfold and refold repeatedly even under native conditions. Much evidence obtained by hydrogen exchange and other methods now indicates that cooperative foldon units and not individual amino acids account for the unit steps in protein folding pathways. The formation of foldons and their ordered pathway assembly systematically puts native-like foldon building blocks into place, guided by a sequential stabilization mechanism in which prior native-like structure templates the formation of incoming foldons with complementary structure. Thus the same propensities and interactions that specify the final native state, encoded in the amino-acid sequence of every protein, determine the pathway for getting there. Experimental observations that have been interpreted differently, in terms of multiple independent pathways, appear to be due to chance misfolding errors that cause different population fractions to block at different pathway points, populate different pathway intermediates, and fold at different rates. This paper summarizes the experimental basis for these three determining principles and their consequences. Cooperative native-like foldon units and the sequential stabilization process together generate predetermined stepwise pathways. Optional misfolding errors

  4. Protein folding, protein homeostasis, and cancer

    PubMed Central

    Van Drie, John H.

    2011-01-01

    Proteins fold into their functional 3-dimensional structures from a linear amino acid sequence. In vitro this process is spontaneous; while in vivo it is orchestrated by a specialized set of proteins, called chaperones. Protein folding is an ongoing cellular process, as cellular proteins constantly undergo synthesis and degradation. Here emerging links between this process and cancer are reviewed. This perspective both yields insights into the current struggle to develop novel cancer chemotherapeutics and has implications for future chemotherapy discovery. PMID:21272445

  5. Folding thermodynamics of pseudoknotted chain conformations

    NASA Astrophysics Data System (ADS)

    Kopeikin, Zoia; Chen, Shi-Jie

    2006-04-01

    We develop a statistical mechanical framework for the folding thermodynamics of pseudoknotted structures. As applications of the theory, we investigate the folding stability and the free energy landscapes for both the thermal and the mechanical unfolding of pseudoknotted chains. For the mechanical unfolding process, we predict the force-extension curves, from which we can obtain the information about structural transitions in the unfolding process. In general, a pseudoknotted structure unfolds through multiple structural transitions. The interplay between the helix stems and the loops plays an important role in the folding stability of pseudoknots. For instance, variations in loop sizes can lead to the destabilization of some intermediate states and change the (equilibrium) folding pathways (e.g., two helix stems unfold either cooperatively or sequentially). In both thermal and mechanical unfolding, depending on the nucleotide sequence, misfolded intermediate states can emerge in the folding process. In addition, thermal and mechanical unfoldings often have different (equilibrium) pathways. For example, for certain sequences, the misfolded intermediates, which generally have longer tails, can fold, unfold, and refold again in the pulling process, which means that these intermediates can switch between two different average end-end extensions.

  6. "Wet" Versus "Dry" Folding of Polyproline

    NASA Astrophysics Data System (ADS)

    Shi, Liuqing; Holliday, Alison E.; Bohrer, Brian C.; Kim, Doyong; Servage, Kelly A.; Russell, David H.; Clemmer, David E.

    2016-06-01

    When the all- cis polyproline-I helix (PPI, favored in 1-propanol) of polyproline-13 is introduced into water, it folds into the all- trans polyproline-II (PPII) helix through at least six intermediates [Shi, L., Holliday, A.E., Shi, H., Zhu, F., Ewing, M.A., Russell, D.H., Clemmer, D.E.: Characterizing intermediates along the transition from PPI to PPII using ion mobility-mass spectrometry. J. Am. Chem. Soc. 136, 12702-12711 (2014)]. Here, we show that the solvent-free intermediates refold into the all- cis PPI helix with high (>90%) efficiency. Moreover, in the absence of solvent, each intermediate appears to utilize the same small set of pathways observed for the solution-phase PPII → PPI transition upon immersion of PPIIaq in 1-propanol. That folding in solution (under conditions where water is displaced by propanol) and folding in vacuo (where energy required for folding is provided by collisional activation) occur along the same pathway is remarkable. Implicit in this statement is that 1-propanol mimics a "dry" environment, similar to the gas phase. We note that intermediates with structures that are similar to PPIIaq can form PPII under the most gentle activation conditions—indicating that some transitions observed in water (i.e. , "we t" folding, are accessible (albeit inefficient) in vacuo. Lastly, these "dry" folding experiments show that PPI (all cis) is favored under "dry" conditions, which underscores the role of water as the major factor promoting preference for trans proline.

  7. Protein Folding and Misfolding on Surfaces

    PubMed Central

    Stefani, Massimo

    2008-01-01

    Protein folding, misfolding and aggregation, as well as the way misfolded and aggregated proteins affects cell viability are emerging as key themes in molecular and structural biology and in molecular medicine. Recent advances in the knowledge of the biophysical basis of protein folding have led to propose the energy landscape theory which provides a consistent framework to better understand how a protein folds rapidly and efficiently to the compact, biologically active structure. The increased knowledge on protein folding has highlighted its strict relation to protein misfolding and aggregation, either process being in close competition with the other, both relying on the same physicochemical basis. The theory has also provided information to better understand the structural and environmental factors affecting protein folding resulting in protein misfolding and aggregation into ordered or disordered polymeric assemblies. Among these, particular importance is given to the effects of surfaces. The latter, in some cases make possible rapid and efficient protein folding but most often recruit proteins/peptides increasing their local concentration thus favouring misfolding and accelerating the rate of nucleation. It is also emerging that surfaces can modify the path of protein misfolding and aggregation generating oligomers and polymers structurally different from those arising in the bulk solution and endowed with different physical properties and cytotoxicities. PMID:19330090

  8. Folding of non-Euclidean curved shells

    NASA Astrophysics Data System (ADS)

    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.

  9. Characteristics of tropopause folds over Arctic latitudes

    NASA Astrophysics Data System (ADS)

    Rao, T. Narayana; Kirkwood, S.

    2005-09-01

    Characteristics of tropopause folds over Arctic latitudes have been studied using VHF radar measurements supplemented by balloon measurements. The variation of the radar parameters during the passage of tropopause folds is discussed in detail. To our knowledge, these observations constitute the first spaced antenna (SA) radar measurements during the passage of tropopause folds. This allows us to compare the parameters detectable using this mode with those observed using other configurations, such as the Doppler beam swinging (DBS) technique. In general, the structural characteristics, such as the slope of folds, seem to be similar at Arctic latitudes to that at midlatitudes; however, the height of the tropopause and the axis of the jet stream (and hence the folding) are found to be lower by 1-2 km than their counterparts in midlatitudes. In the case studies the radar-derived parameters, such as the signal-to-noise ratio (SNR) and vertical shear of horizontal wind, clearly show the upper-air frontal zone. The frontal circulation, conceived from vertical velocity, including the warm conveyer belt flow and the dry intrusion, is clearly visible in the first case, whereas it is masked by high-amplitude mountain lee waves in the second case. Further, the frontal zone seems to be acting as a critical layer to mountain lee wave activity by absorbing/filtering the wave activity. The aspect angles derived from the present analysis agree well with those estimated by vertical beam spectral width but are small in comparison with those estimated by the power ratio method. The mean full correlation analysis (FCA) turbulent velocity is estimated using the ESRAD data obtained during the passage of 15 tropopause folds. The mean eddy diffusion coefficients, Kz, near the tropopause and in the upper portion of the fold, where strong turbulence is seen in case studies, are found to be 3.54 and 6.4 m2 s-1, respectively. Utilizing the mean Kz and the mean ozone gradient (obtained from

  10. Folding patterns and shape optimization using SMA-based self-folding laminates

    NASA Astrophysics Data System (ADS)

    Peraza-Hernandez, Edwin A.; Frei, Katherine R.; Hartl, Darren J.; Lagoudas, Dimitris C.

    2014-03-01

    Origami engineering, a discipline encompassing the creation of practical three-dimensional structures from two- dimensional entities via folding operations, has the potential to impact multiple fields of manufacturing and design. In some circumstances, it may be practical to have self-folding capabilities instead of creating folds by external manipulations (as in morphing structures in outer space or on the ocean floor). This paper considers the use of a self-folding laminate composite consisting of two outer layers of thermally actuated shape memory alloy (SMA) wire meshes separated by an inner compliant insulating layer. Methods for designing folding patterns and determining temperature fields to obtain desired shapes and behaviors are proposed. Sheets composed of the self-folding laminate are modeled via finite element analysis (FEA) and the proposed methods are implemented to test their capabilities. One method uses a previously developed and freely available software called Freeform Origami for folding pattern design. The second method entails the use of optimization to determine the localized activation temperatures required to obtain desired shapes or to perform specific functions. The proposed methods are demonstrated to be applicable for the design of folding patterns and determination of activation temperatures for the self-folding laminate by showing successful examples of their implementation. This exploratory study provides new tools that can be integrated into the design framework of self-folding origami structures.

  11. Structural and enzyme activity studies demonstrate that aryl substituted 2,3-butadienamine analogs inactivate Arthrobacter globiformis amine oxidase (AGAO) by chemical derivatization of the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor.

    PubMed

    Ernberg, Karin; Zhong, Bo; Ko, Kristin; Miller, Larry; Nguyen, Yen Hoang le; Sayre, Lawrence M; Guss, J Mitchell; Lee, Irene

    2011-05-01

    Copper amine oxidases (CAOs) are a family of redox active enzymes containing a 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor generated from post translational modification of an active site tyrosine residue. The Arthrobacter globiformis amine oxidase (AGAO) has been widely used as a model to guide the design and development of selective inhibitors of CAOs. In this study, two aryl 2,3-butadienamine analogs, racemic 5-phenoxy-2,3-pentadienylamine (POPDA) and racemic 6-phenyl-2,3-hexadienylamine (PHDA), were synthesized and evaluated as mechanism-based inactivators of AGAO. Crystal structures show that both compounds form a covalent adduct with the amino group of the substrate-reduced TPQ, and that the chemical structures of the rac-PHDA and rac-POPDA modified TPQ differ by the allenic carbon that is attached to the cofactor. A chemical mechanism accounting for the formation of the respective TPQ derivative is proposed. Under steady-state conditions, no recovery of enzyme activity is detected when AGAO pre-treated with rac-PHDA or rac-POPDA is diluted with excess amount of the benzylamine substrate (100-fold K(m)). Comparing the IC(50) values further reveals that the phenoxy substituent in POPDA offers an approximately 4-fold increase in inhibition potency, which can be attributed to a favourable binding interaction between the oxygen atom in the phenoxy group and the active site of AGAO as revealed by crystallographic studies. This hypothesis is corroborated by the observed >3-fold higher partition ratio of PHDA compared to POPDA. Taken together, the results presented in this study reveal the mechanism by which aryl 2,3-butadienamines act as mechanism-based inhibitors of AGAO, and the potency of enzyme inactivation could be fine-tuned by optimizing binding interaction between the aryl substituent and the enzyme active site. PMID:21215824

  12. The nature of protein folding pathways

    PubMed Central

    Englander, S. Walter; Mayne, Leland

    2014-01-01

    How do proteins fold, and why do they fold in that way? This Perspective integrates earlier and more recent advances over the 50-y history of the protein folding problem, emphasizing unambiguously clear structural information. Experimental results show that, contrary to prior belief, proteins are multistate rather than two-state objects. They are composed of separately cooperative foldon building blocks that can be seen to repeatedly unfold and refold as units even under native conditions. Similarly, foldons are lost as units when proteins are destabilized to produce partially unfolded equilibrium molten globules. In kinetic folding, the inherently cooperative nature of foldons predisposes the thermally driven amino acid-level search to form an initial foldon and subsequent foldons in later assisted searches. The small size of foldon units, ∼20 residues, resolves the Levinthal time-scale search problem. These microscopic-level search processes can be identified with the disordered multitrack search envisioned in the “new view” model for protein folding. Emergent macroscopic foldon–foldon interactions then collectively provide the structural guidance and free energy bias for the ordered addition of foldons in a stepwise pathway that sequentially builds the native protein. These conclusions reconcile the seemingly opposed new view and defined pathway models; the two models account for different stages of the protein folding process. Additionally, these observations answer the “how” and the “why” questions. The protein folding pathway depends on the same foldon units and foldon–foldon interactions that construct the native structure. PMID:25326421

  13. Cross folding in southern Bighorn basin

    SciTech Connect

    Gubbels, T.L.

    1986-08-01

    Analysis of Landsat Thematic Mapper imagery coupled with surface structural investigations of well-exposed folds in the southern Bighorn basin have revealed two northwest-trending folds that have been refolded. The eastern boundary of the Owl Creek Mountains is characterized by a well-defined alignment of folds that extend north-northwest from the Owl Creek thrust front. Bridger monocline, Wildhorse Butte anticline, and Red Hole anticline lie along this trend. Initial Laramide folding, probably during latest Cretaceous time, resulted in a single, continuous, north-northwest-trending anticline with a southwestward vergence. This anticline was progressively unfolded from south to north as the Owl Creek Range was thrust southward over the Wind River basin in earliest Eocene time; scissors-like vertical motion along this flexure rotated the axial surface of the early formed Bridger anticline, resulting in a monocline with a reversed vergence (northeastward). Formation of the Thermopolis/East Warm Springs anticline parallel to the north flank of the range accompanied thrusting and effectively refolded the northern end of the Wildhorse Butte anticline along an east-west axis. Faulting of the oversteepened south limb of the Red Hole cross fold was contemporaneous with folding. Cross-cutting fold axes in this area and the Mud Creek area to the west are best explained by a counterclockwise change in stress direction during the latest phase of the Laramide orogeny. Vertical movement along the eastern side of the Owl Creek Range results from differential motion in the hanging wall of the crystalline thrust sheet.

  14. Safrole-2',3'-oxide induces cytotoxic and genotoxic effects in HepG2 cells and in mice.

    PubMed

    Chiang, Su-yin; Lee, Pei-yi; Lai, Ming-tsung; Shen, Li-ching; Chung, Wen-sheng; Huang, Hui-fen; Wu, Kuen-yuh; Wu, Hsiu-ching

    2011-12-24

    Safrole-2',3'-oxide (SAFO) is a reactive electrophilic metabolite of the hepatocarcinogen safrole, the main component of sassafras oil. Safrole occurs naturally in a variety of spices and herbs, including the commonly used Chinese medicine Xi xin (Asari Radix et Rhizoma) and Dong quai (Angelica sinensis). SAFO is the most mutagenic metabolite of safrole tested in the Ames test. However, little or no data are available on the genotoxicity of SAFO in mammalian systems. In this study, we investigated the cytotoxicity and genotoxicity of SAFO in human HepG2 cells and male FVB mice. Using MTT assay, SAFO exhibited a dose- and time-dependent cytotoxic effect in HepG2 cells with TC(50) values of 361.9μM and 193.2μM after 24 and 48h exposure, respectively. In addition, treatment with SAFO at doses of 125μM and higher for 24h in HepG2 cells resulted in a 5.1-79.6-fold increase in mean Comet tail moment by the alkaline Comet assay and a 2.6-7.8-fold increase in the frequency of micronucleated binucleated cells by the cytokinesis-block micronucleus assay. Furthermore, repeated intraperitoneal administration of SAFO (15, 30, 45, and 60mg/kg) to mice every other day for a total of twelve doses caused a significant dose-dependent increase in mean Comet tail moment in peripheral blood leukocytes (13.3-43.4-fold) and in the frequency of micronucleated reticulocytes (1.5-5.8-fold). Repeated administration of SAFO (60mg/kg) to mice caused liver lesions manifested as a rim of ballooning degeneration of hepatocytes immediately surrounding the central vein. Our data clearly demonstrate that SAFO significantly induced cytotoxicity, DNA strand breaks, micronuclei formation both in human cells in vitro and in mice. More studies are needed to explore the role SAFO plays in safrole-induced genotoxicity. PMID:21986196

  15. Erythrocyte 2,3-diphosphoglycerate and adenosine-triphosphate in cretins living at high altitude.

    PubMed

    Adams, W H

    1976-01-01

    A comparison of concentrations of 2,3-diphosphoglycerate (2,3-DPG) and adenosine-triphosphate (ATP) in the red cells of cretins and normal controls living at 3,700 m in the Nepal Himalayas has shown that 2,3-DPG and ATP levels were higher in the cretins. A negative correlation between hemoglobin and 2.3-DPG level was found. Chronic hypoxia appears to have provided the additional stress required to differentiate the significance of thyroid hormone deficiency in producing anemia from its effect on 2,3-DPG levels. If thyroid hormone is in fact one regulator of 2,3-DPG, the anemia of hypothyroidism appears to be more significant. This also suggest that the anemia of hypothyroidism, is at least in part, "pathologic" as opposed to "adaptive". PMID:822672

  16. How Quickly Can a β-Hairpin Fold from Its Transition State?

    PubMed Central

    2015-01-01

    Understanding the structural nature of the free energy bottleneck(s) encountered in protein folding is essential to elucidating the underlying dynamics and mechanism. For this reason, several techniques, including Φ-value analysis, have previously been developed to infer the structural characteristics of such high free-energy or transition states. Herein we propose that one (or few) appropriately placed backbone and/or side chain cross-linkers, such as disulfides, could be used to populate a thermodynamically accessible conformational state that mimics the folding transition state. Specifically, we test this hypothesis on a model β-hairpin, Trpzip4, as its folding mechanism has been extensively studied and is well understood. Our results show that cross-linking the two β-strands near the turn region increases the folding rate by an order of magnitude, to about (500 ns)−1, whereas cross-linking the termini results in a hyperstable β-hairpin that has essentially the same folding rate as the uncross-linked peptide. Taken together, these findings suggest that cross-linking is not only a useful strategy to manipulate folding free energy barriers, as shown in other studies, but also, in some cases, it can be used to stabilize a folding transition state analogue and allow for direct assessment of the folding process on the downhill side of the free energy barrier. The calculated free energy landscape of the cross-linked Trpzip4 also supports this picture. An empirical analysis further suggests, when folding of β-hairpins does not involve a significant free energy barrier, the folding time (τ) follows a power law dependence on the number of hydrogen bonds to be formed (nH), namely, τ = τ0nHα, with τ0 = 20 ns and α = 2.3. PMID:24611730

  17. Estimation of vocal fold plane in 3D CT images for diagnosis of vocal fold abnormalities.

    PubMed

    Hewavitharanage, Sajini; Gubbi, Jayavardhana; Thyagarajan, Dominic; Lau, Ken; Palaniswami, Marimuthu

    2015-01-01

    Vocal folds are the key body structures that are responsible for phonation and regulating air movement into and out of lungs. Various vocal fold disorders may seriously impact the quality of life. When diagnosing vocal fold disorders, CT of the neck is the commonly used imaging method. However, vocal folds do not align with the normal axial plane of a neck and the plane containing vocal cords and arytenoids does vary during phonation. It is therefore important to generate an algorithm for detecting the actual plane containing vocal folds. In this paper, we propose a method to automatically estimate the vocal fold plane using vertebral column and anterior commissure localization. Gray-level thresholding, connected component analysis, rule based segmentation and unsupervised k-means clustering were used in the proposed algorithm. The anterior commissure segmentation method achieved an accuracy of 85%, a good estimate of the expert assessment. PMID:26736949

  18. Viral infections of the folds (intertriginous areas).

    PubMed

    Adışen, Esra; Önder, Meltem

    2015-01-01

    Viruses are considered intracellular obligates with a nucleic acid, either RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for the cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Though the cutaneous manifestations of viral infections are closely related to the type and the transmission route of the virus, viral skin diseases may occur in almost any part of the body. In addition to friction caused by skin-to-skin touch, skin folds are warm and moist areas of the skin that have limited air circulation. These features provide a fertile breeding ground for many kinds of microorganisms, including bacteria and fungi. In contrast to specific bacterial and fungal agents that have an affinity for the skin folds, except for viral diseases of the anogenital area, which have well-known presentations, viral skin infections that have a special affinity to the skin folds are not known. Many viral exanthems may affect the skin folds during the course of the infection, but here we focus only on the ones that usually affect the fold areas and also on the less well-known conditions or recently described associations. PMID:26051057

  19. Protein Folding and Mechanisms of Proteostasis

    PubMed Central

    Díaz-Villanueva, José Fernando; Díaz-Molina, Raúl; García-González, Victor

    2015-01-01

    Highly sophisticated mechanisms that modulate protein structure and function, which involve synthesis and degradation, have evolved to maintain cellular homeostasis. Perturbations in these mechanisms can lead to protein dysfunction as well as deleterious cell processes. Therefore in recent years the etiology of a great number of diseases has been attributed to failures in mechanisms that modulate protein structure. Interconnections among metabolic and cell signaling pathways are critical for homeostasis to converge on mechanisms associated with protein folding as well as for the preservation of the native structure of proteins. For instance, imbalances in secretory protein synthesis pathways lead to a condition known as endoplasmic reticulum (ER) stress which elicits the adaptive unfolded protein response (UPR). Therefore, taking this into consideration, a key part of this paper is developed around the protein folding phenomenon, and cellular mechanisms which support this pivotal condition. We provide an overview of chaperone protein function, UPR via, spatial compartmentalization of protein folding, proteasome role, autophagy, as well as the intertwining between these processes. Several diseases are known to have a molecular etiology in the malfunction of mechanisms responsible for protein folding and in the shielding of native structure, phenomena which ultimately lead to misfolded protein accumulation. This review centers on our current knowledge about pathways that modulate protein folding, and cell responses involved in protein homeostasis. PMID:26225966

  20. Petrofabric test of viscous folding theory

    NASA Astrophysics Data System (ADS)

    Onasch, Charles M.

    1984-06-01

    Compression and extension axes are deduced from quartz deformation lamellae in a quartzite and a graywacke folded into an asymetrical syncline. Deformation lamellae fabrics in the two sandstones are distinctly different. In the graywacke, regardless of bedding orientation or position on the fold, compression axes are normal or nearly normal to the axial planar rough cleavage. Extension axes generally lie in the cleavage plane, parallel to dip. In most quartzite samples, compression axes are parallel or subparallel to bedding, at high angles to the fold axis and extension axes are normal to bedding. Two samples from the very base of the formation indicate compression parallel to the fold axis with extension parallel to bedding, at high angles to the fold axis. One of these two shows both patterns. The lamellae fabric geometry in these two samples suggests the presence of a neutral surface in the quartzite. The lamellae-derived compression and extension axes are in good agreement with the buckling behavior of a viscous layer (quartzite) embedded in a less viscous medium (graywacke and shale below and shale and carbonate above).

  1. Protein Folding and Mechanisms of Proteostasis.

    PubMed

    Díaz-Villanueva, José Fernando; Díaz-Molina, Raúl; García-González, Victor

    2015-01-01

    Highly sophisticated mechanisms that modulate protein structure and function, which involve synthesis and degradation, have evolved to maintain cellular homeostasis. Perturbations in these mechanisms can lead to protein dysfunction as well as deleterious cell processes. Therefore in recent years the etiology of a great number of diseases has been attributed to failures in mechanisms that modulate protein structure. Interconnections among metabolic and cell signaling pathways are critical for homeostasis to converge on mechanisms associated with protein folding as well as for the preservation of the native structure of proteins. For instance, imbalances in secretory protein synthesis pathways lead to a condition known as endoplasmic reticulum (ER) stress which elicits the adaptive unfolded protein response (UPR). Therefore, taking this into consideration, a key part of this paper is developed around the protein folding phenomenon, and cellular mechanisms which support this pivotal condition. We provide an overview of chaperone protein function, UPR via, spatial compartmentalization of protein folding, proteasome role, autophagy, as well as the intertwining between these processes. Several diseases are known to have a molecular etiology in the malfunction of mechanisms responsible for protein folding and in the shielding of native structure, phenomena which ultimately lead to misfolded protein accumulation. This review centers on our current knowledge about pathways that modulate protein folding, and cell responses involved in protein homeostasis. PMID:26225966

  2. Towards a systematic classification of protein folds

    NASA Astrophysics Data System (ADS)

    Lindgård, Per-Anker; Bohr, Henrik

    1997-10-01

    A lattice model Hamiltonian is suggested for protein structures that can explain the division into structural fold classes during the folding process. Proteins are described by chains of secondary structure elements, with the hinges in between being the important degrees of freedom. The protein structures are given a unique name, which simultaneously represent a linear string of physical coupling constants describing hinge spin interactions. We have defined a metric and a precise distance measure between the fold classes. An automated procedure is constructed in which any protein structure in the usual protein data base coordinate format can be transformed into the proposed chain representation. Taking into account hydrophobic forces we have found a mechanism for the formation of domains with a unique fold containing predicted magic numbers \\{4,6,9,12,16,18,...\\} of secondary structures and multiples of these domains. It is shown that the same magic numbers are robust and occur as well for packing on other nonclosed packed lattices. We have performed a statistical analysis of available protein structures and found agreement with the predicted preferred abundances of proteins with a predicted magic number of secondary structures. Thermodynamic arguments for the increased abundance and a phase diagram for the folding scenario are given. This includes an intermediate high symmetry phase, the parent structures, between the molten globule and the native states. We have made an exhaustive enumeration of dense lattice animals on a cubic lattice for acceptance number Z=4 and Z=5 up to 36 vertices.

  3. Proteopedia: Rossmann Fold: A Beta-Alpha-Beta Fold at Dinucleotide Binding Sites

    ERIC Educational Resources Information Center

    Hanukoglu, Israel

    2015-01-01

    The Rossmann fold is one of the most common and widely distributed super-secondary structures. It is composed of a series of alternating beta strand (ß) and alpha helical (a) segments wherein the ß-strands are hydrogen bonded forming a ß-sheet. The initial beta-alpha-beta (ßaß) fold is the most conserved segment of Rossmann folds. As this segment…

  4. Competition between surface adsorption and folding of fibril-forming polypeptides

    NASA Astrophysics Data System (ADS)

    Ni, Ran; Kleijn, J. Mieke; Abeln, Sanne; Cohen Stuart, Martien A.; Bolhuis, Peter G.

    2015-02-01

    Self-assembly of polypeptides into fibrillar structures can be initiated by planar surfaces that interact favorably with certain residues. Using a coarse-grained model, we systematically studied the folding and adsorption behavior of a β -roll forming polypeptide. We find that there are two different folding pathways depending on the temperature: (i) at low temperature, the polypeptide folds in solution into a β -roll before adsorbing onto the attractive surface; (ii) at higher temperature, the polypeptide first adsorbs in a disordered state and folds while on the surface. The folding temperature increases with increasing attraction as the folded β -roll is stabilized by the surface. Surprisingly, further increasing the attraction lowers the folding temperature again, as strong attraction also stabilizes the adsorbed disordered state, which competes with folding of the polypeptide. Our results suggest that to enhance the folding, one should use a weakly attractive surface. They also explain the recent experimental observation of the nonmonotonic effect of charge on the fibril formation on an oppositely charged surface [C. Charbonneau et al., ACS Nano 8, 2328 (2014), 10.1021/nn405799t].

  5. Influence of the ventricular folds on a voice source with specified vocal fold motion1

    PubMed Central

    McGowan, Richard S.; Howe, Michael S.

    2010-01-01

    The unsteady drag on the vocal folds is the major source of sound during voiced speech. The drag force is caused by vortex shedding from the vocal folds. The influence of the ventricular folds (i.e., the “false” vocal folds that protrude into the vocal tract a short distance downstream of the glottis) on the drag and the voice source are examined in this paper by means of a theoretical model involving vortex sheets in a two-dimensional geometry. The effect of the ventricular folds on the output acoustic pressure is found to be small when the movement of the vocal folds is prescribed. It is argued that the effect remains small when fluid-structure interactions account for vocal fold movement. These conclusions can be justified mathematically when the characteristic time scale for change in the velocity of the glottal jet is large compared to the time it takes for a vortex disturbance to be convected through the vocal fold and ventricular fold region. PMID:20329852

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

    NASA Astrophysics Data System (ADS)

    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

  7. Proteins with Highly Similar Native Folds Can Show Vastly Dissimilar Folding Behavior When Desolvated**

    PubMed Central

    Schennach, Moritz; Breuker, Kathrin

    2014-01-01

    Proteins can be exposed to vastly different environments such as the cytosol or membranes, but the delicate balance between external factors and intrinsic determinants of protein structure, stability, and folding is only poorly understood. Here we used electron capture dissociation to study horse and tuna heart Cytochromes c in the complete absence of solvent. The significantly different stability of their highly similar native folds after transfer into the gas phase, and their strikingly different folding behavior in the gas phase, can be rationalized on the basis of electrostatic interactions such as salt bridges. In the absence of hydrophobic bonding, protein folding is far slower and more complex than in solution. PMID:24259450

  8. Stretching and folding in finite time.

    PubMed

    Ma, Tian; Ouellette, Nicholas T; Bollt, Erik M

    2016-02-01

    Complex flows mix efficiently, and this process can be understood by considering the stretching and folding of material volumes. Although many metrics have been devised to characterize stretching, fewer are able to capture folding in a quantitative way in spatiotemporally variable flows. Here, we extend our previous methods based on the finite-time curving of fluid-element trajectories to nonzero scales and show that this finite-scale finite-time curvature contains information about both stretching and folding. We compare this metric to the more commonly used finite-time Lyapunov exponent and illustrate our methods using experimental flow-field data from a quasi-two-dimensional laboratory flow. Our new analysis tools add to the growing set of Lagrangian methods for characterizing mixing in complex, aperiodic fluid flows. PMID:26931593

  9. Stretching and folding in finite time

    NASA Astrophysics Data System (ADS)

    Ma, Tian; Ouellette, Nicholas T.; Bollt, Erik M.

    2016-02-01

    Complex flows mix efficiently, and this process can be understood by considering the stretching and folding of material volumes. Although many metrics have been devised to characterize stretching, fewer are able to capture folding in a quantitative way in spatiotemporally variable flows. Here, we extend our previous methods based on the finite-time curving of fluid-element trajectories to nonzero scales and show that this finite-scale finite-time curvature contains information about both stretching and folding. We compare this metric to the more commonly used finite-time Lyapunov exponent and illustrate our methods using experimental flow-field data from a quasi-two-dimensional laboratory flow. Our new analysis tools add to the growing set of Lagrangian methods for characterizing mixing in complex, aperiodic fluid flows.

  10. Thermal stability of idealized folded carbyne loops.

    PubMed

    Cranford, Steven W

    2013-01-01

    Self-unfolding items provide a practical convenience, wherein ring-like frames are contorted into a state of equilibrium and subsequently  pop up' or deploy when perturbed from a folded structure. Can the same process be exploited at the molecular scale? At the limiting scale is a closed chain of single atoms, used here to investigate the limits of stability of such folded ring structures via full atomistic molecular dynamics. Carbyne is a one-dimensional carbon allotrope composed of sp-hybridized carbon atoms. Here, we explore the stability of idealized carbyne loops as a function of chain length, curvature, and temperature, and delineate an effective phase diagram between folded and unfolded states. We find that while overall curvature is reduced, in addition to torsional and self-adhesive energy barriers, a local increase in curvature results in the largest impedance to unfolding. PMID:24252156

  11. Exact folded-band chaotic oscillator.

    PubMed

    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. PMID:22757520

  12. Computing folding pathways between RNA secondary structures.

    PubMed

    Dotu, Ivan; Lorenz, William A; Van Hentenryck, Pascal; Clote, Peter

    2010-03-01

    Given an RNA sequence and two designated secondary structures A, B, we describe a new algorithm that computes a nearly optimal folding pathway from A to B. The algorithm, RNAtabupath, employs a tabu semi-greedy heuristic, known to be an effective search strategy in combinatorial optimization. Folding pathways, sometimes called routes or trajectories, are computed by RNAtabupath in a fraction of the time required by the barriers program of Vienna RNA Package. We benchmark RNAtabupath with other algorithms to compute low energy folding pathways between experimentally known structures of several conformational switches. The RNApathfinder web server, source code for algorithms to compute and analyze pathways and supplementary data are available at http://bioinformatics.bc.edu/clotelab/RNApathfinder. PMID:20044352

  13. Microbial Manipulation of the Amyloid Fold

    PubMed Central

    DePas, William H.

    2012-01-01

    Microbial biofilms are encased in a protein, DNA and polysaccharide matrix that protects the community, promotes interactions with the environment, and helps cells to adhere together. The protein component of these matrices is often a remarkably stable, β-sheet-rich polymer called amyloid. Amyloids form ordered, self-templating fibers that are highly aggregative, making them a valuable biofilm component. Some eukaryotic proteins inappropriately adopt the amyloid fold and these misfolded protein aggregates disrupt normal cellular proteostasis, which can cause significant cytotoxicity. Indeed, until recently amyloids were considered solely the result of protein misfolding. However, research over the past decade has revealed how various organisms have capitalized on the amyloid fold by developing sophisticated biogenesis pathways that coordinate gene expression, protein folding, and secretion so that amyloid-related toxicities are minimized. How microbes manipulate amyloids, by augmenting their advantageous properties and by reducing their undesirable properties, will be the subject of this review. PMID:23108148

  14. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Gregory, Dennis E.

    Decisions made by federal and state courts during 1983 concerning higher education are reported in this chapter. Issues of employment and the treatment of students underlay the bulk of the litigation. Specific topics addressed in these and other cases included federal authority to enforce regulations against age discrimination and to revoke an…

  15. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    Litigation in 1987 was very brisk with an increase in the number of higher education cases reviewed. Cases discussed in this chapter are organized under four major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining and denial of employee benefits; (3)…

  16. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Finnegan, Dorothy E.

    The higher education case law in 1988 is extensive. Cases discussed in this chapter are organized under five major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining, and denial of employee benefits; (3) students, involving admissions, financial aid, First…

  17. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    This eighth chapter of "The Yearbook of School Law, 1986" summarizes and analyzes over 330 state and federal court cases litigated in 1985 in which institutions of higher education were involved. Among the topics examined were relationships between postsecondary institutions and various governmental agencies; discrimination in the employment of…

  18. "Wet" Versus "Dry" Folding of Polyproline

    NASA Astrophysics Data System (ADS)

    Shi, Liuqing; Holliday, Alison E.; Bohrer, Brian C.; Kim, Doyong; Servage, Kelly A.; Russell, David H.; Clemmer, David E.

    2016-04-01

    When the all-cis polyproline-I helix (PPI, favored in 1-propanol) of polyproline-13 is introduced into water, it folds into the all-trans polyproline-II (PPII) helix through at least six intermediates [Shi, L., Holliday, A.E., Shi, H., Zhu, F., Ewing, M.A., Russell, D.H., Clemmer, D.E.: Characterizing intermediates along the transition from PPI to PPII using ion mobility-mass spectrometry. J. Am. Chem. Soc. 136, 12702-12711 (2014)]. Here, we show that the solvent-free intermediates refold into the all-cis PPI helix with high (>90%) efficiency. Moreover, in the absence of solvent, each intermediate appears to utilize the same small set of pathways observed for the solution-phase PPII → PPI transition upon immersion of PPIIaq in 1-propanol. That folding in solution (under conditions where water is displaced by propanol) and folding in vacuo (where energy required for folding is provided by collisional activation) occur along the same pathway is remarkable. Implicit in this statement is that 1-propanol mimics a "dry" environment, similar to the gas phase. We note that intermediates with structures that are similar to PPIIaq can form PPII under the most gentle activation conditions—indicating that some transitions observed in water (i.e., "wet" folding, are accessible (albeit inefficient) in vacuo. Lastly, these "dry" folding experiments show that PPI (all cis) is favored under "dry" conditions, which underscores the role of water as the major factor promoting preference for trans proline.

  19. Fast gravitational wave radiometry using data folding

    NASA Astrophysics Data System (ADS)

    Ain, Anirban; Dalvi, Prathamesh; Mitra, Sanjit

    2015-07-01

    Gravitational waves (GWs) from the early universe and unresolved astrophysical sources are expected to create a stochastic GW background (SGWB). The GW radiometer algorithm is well suited to probe such a background using data from ground-based laser interferometric detectors. Radiometer analysis can be performed in different bases, e.g., isotropic, pixel or spherical harmonic. Each of these analyses possesses a common temporal symmetry which we exploit here to fold the whole data set for every detector pair, typically a few hundred to a thousand days of data, to only one sidereal day, without any compromise in precision. We develop the algebra and a software pipeline needed to fold data, accounting for the effect of overlapping windows and nonstationary noise. We implement this on LIGO's fifth science run data and validate it by performing a standard anisotropic SGWB search on both folded and unfolded data. Folded data not only leads to orders of magnitude reduction in computation cost, but it results in a conveniently small data volume of few gigabytes, making it possible to perform an actual analysis on a personal computer, as well as easy movement of data. A few important analyses, yet unaccomplished due to computational limitations, will now become feasible. Folded data, being independent of the radiometer basis, will also be useful in reducing processing redundancies in multiple searches and provide a common ground for mutual consistency checks. Most importantly, folded data will allow vast amount of experimentation with existing searches and provide substantial help in developing new strategies to find unknown sources.

  20. Understanding protein folding: small proteins in silico.

    PubMed

    Zimmermann, Olav; Hansmann, Ulrich H E

    2008-01-01

    Recent improvements in methodology and increased computer power now allow atomistic computer simulations of protein folding. We briefly review several advanced Monte Carlo algorithms that have contributed to this development. Details of folding simulations of three designed mini proteins are shown. Adding global translations and rotations has allowed us to handle multiple chains and to simulate the aggregation of six beta-amyloid fragments. In a different line of research we have developed several algorithms to predict local features from sequence. In an outlook we sketch how such biasing could extend the application spectrum of Monte Carlo simulations to structure prediction of larger proteins. PMID:18036571

  1. Extramedullary plasmacytoma of the true vocal fold.

    PubMed

    De Zoysa, Nilantha; Sandler, Belinda; Amonoo-Kuofi, Kwame; Swamy, Rajiv; Kothari, Prasad; Mochloulis, George

    2012-08-01

    We report a rare case of extramedullary plasmacytoma (EMP) of the true vocal fold. Our patient, a 62-year-old woman, presented with dysphonia. On workup, fiberoptic laryngoscopy detected a lesion arising from the anterior half of her left true vocal fold. No evidence of other pathology was noted. The patient underwent radical radiotherapy, and the lesion resolved. Follow-up revealed no sign of recurrence. A type of myeloma, EMP is rare, especially in the larynx. To the best of our knowledge, our patient represents the sixth case of glottic EMP to be reported in the literature. PMID:22930090

  2. Circular permutant GFP insertion folding reporters

    SciTech Connect

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2013-04-16

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  3. Circular permutant GFP insertion folding reporters

    DOEpatents

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2008-06-24

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  4. Circular permutant GFP insertion folding reporters

    DOEpatents

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2011-06-14

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  5. Circular permutant GFP insertion folding reporters

    DOEpatents

    Waldo, Geoffrey S; Cabantous, Stephanie

    2013-02-12

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  6. Control of folding by gravity and matrix thickness: Implications for large-scale folding

    NASA Astrophysics Data System (ADS)

    Schmalholz, S. M.; Podladchikov, Y. Y.; Burg, J.-P.

    2002-01-01

    We show that folding of a non-Newtonian layer resting on a homogeneous Newtonian matrix with finite thickness under influence of gravity can occur by three modes: (1) matrix-controlled folding, dependent on the effective viscosity contrast between layer and matrix, (2) gravity-controlled folding, dependent on the Argand number (the ratio of the stress caused by gravity to the stress caused by shortening), and (3) detachment folding, dependent on the ratio of matrix thickness to layer thickness. We construct a phase diagram that defines the transitions between each of the three folding modes. Our priority is transparency of the analytical derivations (e.g., thin-plate versus thick-plate approximations), which permits complete classification of the folding modes involving a minimum number of dimensionless parameters. Accuracy and sensitivity of the analytical results to model assumptions are investigated. In particular, depth dependence of matrix rheology is only important for folding over a narrow range of material parameters. In contrast, strong depth dependence of the viscosity of the folding layer limits applicability of ductile rheology and leads to a viscoelastic transition. Our theory is applied to estimate the effective thickness of the folded central Asian upper crust using the ratio of topographic wavelength to Moho depth. Phase diagrams based on geometrical parameters show that gravity does not significantly control folding in the Jura and the Zagros Mountains but does control folding in central Asia. Applicability conditions of viscous and thin sheet models for large-scale lithospheric deformation, derived in terms of the Argand number, have implications for the plate-like style of planetary tectonics.

  7. Regulation of cerebral cortex size and folding by expansion of basal progenitors

    PubMed Central

    Nonaka-Kinoshita, Miki; Reillo, Isabel; Artegiani, Benedetta; Ángeles Martínez-Martínez, Maria; Nelson, Mark; Borrell, Víctor; Calegari, Federico

    2013-01-01

    Size and folding of the cerebral cortex increased massively during mammalian evolution leading to the current diversity of brain morphologies. Various subtypes of neural stem and progenitor cells have been proposed to contribute differently in regulating thickness or folding of the cerebral cortex during development, but their specific roles have not been demonstrated. We report that the controlled expansion of unipotent basal progenitors in mouse embryos led to megalencephaly, with increased surface area of the cerebral cortex, but not to cortical folding. In contrast, expansion of multipotent basal progenitors in the naturally gyrencephalic ferret was sufficient to drive the formation of additional folds and fissures. In both models, changes occurred while preserving a structurally normal, six-layered cortex. Our results are the first experimental demonstration of specific and distinct roles for basal progenitor subtypes in regulating cerebral cortex size and folding during development underlying the superior intellectual capability acquired by higher mammals during evolution. PMID:23624932

  8. De Novo Evolutionary Emergence of a Symmetrical Protein Is Shaped by Folding Constraints.

    PubMed

    Smock, Robert G; Yadid, Itamar; Dym, Orly; Clarke, Jane; Tawfik, Dan S

    2016-01-28

    Molecular evolution has focused on the divergence of molecular functions, yet we know little about how structurally distinct protein folds emerge de novo. We characterized the evolutionary trajectories and selection forces underlying emergence of β-propeller proteins, a globular and symmetric fold group with diverse functions. The identification of short propeller-like motifs (<50 amino acids) in natural genomes indicated that they expanded via tandem duplications to form extant propellers. We phylogenetically reconstructed 47-residue ancestral motifs that form five-bladed lectin propellers via oligomeric assembly. We demonstrate a functional trajectory of tandem duplications of these motifs leading to monomeric lectins. Foldability, i.e., higher efficiency of folding, was the main parameter leading to improved functionality along the entire evolutionary trajectory. However, folding constraints changed along the trajectory: initially, conflicts between monomer folding and oligomer assembly dominated, whereas subsequently, upon tandem duplication, tradeoffs between monomer stability and foldability took precedence. PMID:26806127

  9. De Novo Evolutionary Emergence of a Symmetrical Protein Is Shaped by Folding Constraints

    PubMed Central

    Smock, Robert G.; Yadid, Itamar; Dym, Orly; Clarke, Jane; Tawfik, Dan S.

    2016-01-01

    Summary Molecular evolution has focused on the divergence of molecular functions, yet we know little about how structurally distinct protein folds emerge de novo. We characterized the evolutionary trajectories and selection forces underlying emergence of β-propeller proteins, a globular and symmetric fold group with diverse functions. The identification of short propeller-like motifs (<50 amino acids) in natural genomes indicated that they expanded via tandem duplications to form extant propellers. We phylogenetically reconstructed 47-residue ancestral motifs that form five-bladed lectin propellers via oligomeric assembly. We demonstrate a functional trajectory of tandem duplications of these motifs leading to monomeric lectins. Foldability, i.e., higher efficiency of folding, was the main parameter leading to improved functionality along the entire evolutionary trajectory. However, folding constraints changed along the trajectory: initially, conflicts between monomer folding and oligomer assembly dominated, whereas subsequently, upon tandem duplication, tradeoffs between monomer stability and foldability took precedence. PMID:26806127

  10. Nomenclature proposal to describe vocal fold motion impairment.

    PubMed

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

    2016-08-01

    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 impairment. Overarching terms of vocal fold immobility and hypomobility are rigorously defined. This includes assessment techniques and inclusion and exclusion criteria for determining vocal fold immobility and hypomobility. In addition, criteria for use of the following terms have been outlined in detail: vocal fold paralysis, vocal fold paresis, vocal fold immobility/hypomobility associated with mechanical impairment of the crico-arytenoid joint and vocal fold immobility/hypomobility related to laryngeal malignant disease. This represents the first rigorously defined vocal fold motion impairment nomenclature system. This provides detailed definitions to the terms vocal fold paralysis and vocal fold paresis. PMID:26036851

  11. Protein GB1 Folding and Assembly from Structural Elements

    PubMed Central

    Bauer, Mikael C.; Xue, Wei-Feng; Linse, Sara

    2009-01-01

    Folding of the Protein G B1 domain (PGB1) shifts with increasing salt concentration from a cooperative assembly of inherently unstructured subdomains to an assembly of partly pre-folded structures. The salt-dependence of pre-folding contributes to the stability minimum observed at physiological salt conditions. Our conclusions are based on a study in which the reconstitution of PGB1 from two fragments was studied as a function of salt concentrations and temperature using circular dichroism spectroscopy. Salt was found to induce an increase in β-hairpin structure for the C-terminal fragment (residues 41 – 56), whereas no major salt effect on structure was observed for the isolated N-terminal fragment (residues 1 – 41). In line with the increasing evidence on the interrelation between fragment complementation and stability of the corresponding intact protein, we also find that salt effects on reconstitution can be predicted from salt dependence of the stability of the intact protein. Our data show that our variant (which has the mutations T2Q, N8D, N37D and reconstitutes in a manner similar to the wild type) displays the lowest equilibrium association constant around physiological salt concentration, with higher affinity observed both at lower and higher salt concentration. This corroborates the salt effects on the stability towards denaturation of the intact protein, for which the stability at physiological salt is lower compared to both lower and higher salt concentrations. Hence we conclude that reconstitution reports on molecular factors that govern the native states of proteins. PMID:19468325

  12. The geometry and topology of natural sheath folds: a new tool for structural analysis

    NASA Astrophysics Data System (ADS)

    Alsop, G. I.; Holdsworth, R. E.

    2004-09-01

    Curvilinear sheath folds are classically depicted as displaying symmetrical geometries about two orthogonal mirror planes centred along the (X-Y) axial surface and the (X-Z) medial (culmination/depression) surface which bisects the fold nose. However, 10,000 geometric analyses of minor folds and fabrics formed during ductile thrusting in the Caledonides of northern Scotland reveals that major dome and basin sheath folds can display distinct and predictable asymmetries across both axial and medial surfaces. The strain is typically heterogeneous so that structural fabrics and younging evidence are preserved within sheath folds at varying stages of development. This allows an analysis of the evolution of such structures from 'tongue' folds to more extreme 'tubular' forms. Geometric relationships between measured orientations of fold hinges, axial planes, extension lineations and foliations are compared on fabric topology plots (FTPs), which provide an effective tool for monitoring planar and linear fabric rotations with increasing progressive non-coaxial deformation. They consistently display systematic variation from regions of lower to higher strain on passing from upper to lower fold limbs across major axial surfaces, and on crossing medial surfaces from short to long hinge-line segments. Axial and medial surfaces effectively therefore divide major sheath folds into quadrants with different amounts, senses and combinations of planar and linear fabric rotation within each domain. Such heterogeneous deformation implies that models of intense non-coaxial deformation uniformly affecting pre-existing folds may overestimate bulk displacement and shear strain. Variable fold hinge-line rotation about medial surfaces also provides an effective mechanism for the closure of major sheaths, which may otherwise project for unfeasible distances in the X direction. Bedding/cleavage intersections are developed at greater angles to the transport direction than fold hinges which they

  13. Self-folding graphene-polymer bilayers

    NASA Astrophysics Data System (ADS)

    Deng, Tao; Yoon, ChangKyu; Jin, Qianru; Li, Mingen; Liu, Zewen; Gracias, David H.

    2015-05-01

    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.

  14. Folded-path optical analysis gas cell

    DOEpatents

    Carangelo, R.M.; Wright, D.D.

    1995-08-08

    A folded-path gas cell employs an elliptical concave mirror in confronting relationship to two substantially spherical concave mirrors. At least one of the spherical mirrors, and usually both, are formed with an added cylindrical component to increase orthogonal foci coincidence and thereby to increase the radiation energy throughput characteristic of the cell. 10 figs.

  15. Folded cavity design for a ruby resonator

    NASA Technical Reports Server (NTRS)

    Arunkumar, K. A.; Trolinger, James D.

    1988-01-01

    A folded cavity laser resonator operating in the TEM(00) mode has been built and tested. The new oscillator configuration leads to an increase in efficiency and to better line narrowing due to the increased number of passes through the laser rod and tuning elements, respectively. The modification is shown to lead to cavity ruggedization.

  16. Folding and faulting of an elastic continuum

    PubMed Central

    Gourgiotis, Panos A.

    2016-01-01

    Folding is a process in which bending is localized at sharp edges separated by almost undeformed elements. This process is rarely encountered in Nature, although some exceptions can be found in unusual layered rock formations (called ‘chevrons’) and seashell patterns (for instance Lopha cristagalli). In mechanics, the bending of a three-dimensional elastic solid is common (for example, in bulk wave propagation), but folding is usually not achieved. In this article, the route leading to folding is shown for an elastic solid obeying the couple-stress theory with an extreme anisotropy. This result is obtained with a perturbation technique, which involves the derivation of new two-dimensional Green's functions for applied concentrated force and moment. While the former perturbation reveals folding, the latter shows that a material in an extreme anisotropic state is also prone to a faulting instability, in which a displacement step of finite size emerges. Another failure mechanism, namely the formation of dilation/compaction bands, is also highlighted. Finally, a geophysical application to the mechanics of chevron formation shows how the proposed approach may explain the formation of natural structures. PMID:27118925

  17. Sheath fold morphology in simple shear

    NASA Astrophysics Data System (ADS)

    Reber, Jacqueline E.; Dabrowski, Marcin; Galland, Olivier; Schmid, Daniel W.

    2013-08-01

    Sheath folds are highly non-cylindrical structures often associated with shear zones. We investigate the formation of sheath folds around a weak inclusion acting as a slip surface in simple shear by means of an analytical model. We present results for different slip surface orientations and shapes. Cross-sections perpendicular to the shear direction through the sheath fold display closed contours, so called eye-structures. The aspect ratio of the outermost closed contour is strongly dependent on the initial slip surface configuration. The center of the eye-structure is subject to change in height with respect to the upper edge of the outermost closed contour for different cross-sections perpendicular to the shear direction. This results in a large variability in layer thickness across the sheath fold length, questioning the usefulness of eye-structures as shear sense indicators. The location of the center of the eye structure is largely invariant to the initial configurations of the slip surface as well as to strain. The values of the aspect ratios of the closed contours within the eye-pattern are dependent on the strain and the cross-section location. The ratio (R') of the aspect ratios of the outermost closed contour (Ryz) and the innermost closed contour (Ry'z') shows values above and below 1. R' shows dependence on the slip surface shape and orientation but not on the number of involved contours. Using R' measurements to deduce the bulk strain type may be erroneous.

  18. Folded-path optical analysis gas cell

    DOEpatents

    Carangelo, Robert M.; Wright, David D.

    1995-01-01

    A folded-path gas cell employs an elliptical concave mirror in confronting relationship to two substantially spherical concave mirrors. At least one of the spherical mirrors, and usually both, are formed with an added cylindrical component to increase orthogonal focii coincidence and thereby to increase the radiation energy throughput characteristic of the cell.

  19. Force-extension behavior of folding polymers

    NASA Astrophysics Data System (ADS)

    Cocco, S.; Marko, J. F.; Monasson, R.; Sarkar, A.; Yan, J.

    2003-03-01

    The elastic response of flexible polymers made of elements which can be either folded or unfolded, having different lengths in these two states, is discussed. These situations are common for biopolymers as a result of folding interactions intrinsic to the monomers, or as a result of binding of other smaller molecules along the polymer length. Using simple flexible-chain models, we show that even when the energy ɛ associated with maintaining the folded state is comparable to k_B T, the elastic response of such a chain can mimic usual polymer linear elasticity, but with a force scale enhanced above that expected from the flexibility of the chain backbone. We discuss recent experiments on single-stranded DNA, chromatin fiber and double-stranded DNA with proteins weakly absorbed along its length which show this effect. Effects of polymer semiflexiblity and torsional stiffness relevant to experiments on proteins binding to dsDNA are analyzed. We finally discuss the competition between electrostatic self-repulsion and folding interactions responsible for the complex elastic response of single-stranded DNA.

  20. Coiling and Folding of Viscoelastic Jets

    NASA Astrophysics Data System (ADS)

    Majmudar, Trushant; Varagnat, Matthieu; McKinley, Gareth

    2007-11-01

    The study of fluid jets impacting on a flat surface has industrial applications in many areas, including processing of foods and consumer goods, bottle filling, and polymer melt processing. Previous studies have focused primarily on purely viscous, Newtonian fluids, which exhibit a number of different dynamical regimes including dripping, steady jetting, folding, and steady coiling. Here we add another dimension to the problem by focusing on mobile (low viscosity) viscoelastic fluids, with the study of two wormlike-micellar fluids, a cetylpyridinum-salicylic acid salt (CPyCl/NaSal) solution, and an industrially relevant shampoo base. We investigate the effects of viscosity and elasticity on the dynamics of axi-symmetric jets. The viscoelasticity of the fluids is systematically controlled by varying the concentration of salt counterions. Experimental methods include shear and extensional rheology measurements to characterize the fluids, and high-speed digital video imaging. In addition to the regimes observed in purely viscous systems, we also find a novel regime in which the elastic jet buckles and folds on itself, and alternates between coiling and folding behavior. We suggest phase diagrams and scaling laws for the coiling and folding frequencies through a systematic exploration of the experimental parameter space (height of fall, imposed flow rate, elasticity of the solution).

  1. Fast phase randomization via two-folds

    PubMed Central

    Jeffrey, M. R.

    2016-01-01

    A two-fold is a singular point on the discontinuity surface of a piecewise-smooth vector field, at which the vector field is tangent to the discontinuity surface on both sides. If an orbit passes through an invisible two-fold (also known as a Teixeira singularity) before settling to regular periodic motion, then the phase of that motion cannot be determined from initial conditions, and, in the presence of small noise, the asymptotic phase of a large number of sample solutions is highly random. In this paper, we show how the probability distribution of the asymptotic phase depends on the global nonlinear dynamics. We also show how the phase of a smooth oscillator can be randomized by applying a simple discontinuous control law that generates an invisible two-fold. We propose that such a control law can be used to desynchronize a collection of oscillators, and that this manner of phase randomization is fast compared with existing methods (which use fixed points as phase singularities), because there is no slowing of the dynamics near a two-fold. PMID:27118901

  2. Self-folding graphene-polymer bilayers

    SciTech Connect

    Deng, Tao; Yoon, ChangKyu; Jin, Qianru; Li, Mingen; Liu, Zewen; Gracias, David H.

    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.

  3. Fold in Origami and Unfold Math

    ERIC Educational Resources Information Center

    Georgeson, Joseph

    2011-01-01

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

  4. Oxidative folding of peptides with cystine-knot architectures: kinetic studies and optimization of folding conditions.

    PubMed

    Reinwarth, Michael; Glotzbach, Bernhard; Tomaszowski, Michael; Fabritz, Sebastian; Avrutina, Olga; Kolmar, Harald

    2013-01-01

    Bioactive peptides often contain several disulfide bonds that provide the main contribution to conformational rigidity and structural, thermal, or biological stability. Among them, cystine-knot peptides-commonly named "knottins"-make up a subclass with several thousand natural members. Hence, they are considered promising frameworks for peptide-based pharmaceuticals. Although cystine-knot peptides are available through chemical and recombinant synthetic routes, oxidative folding to afford the bioactive isomers still remains a crucial step. We therefore investigated the oxidative folding of ten protease-inhibiting peptides from two knottin families, as well as that of an HIV entry inhibitor and of aprotinin, under two conventional sets of folding conditions and by a newly developed procedure. Kinetic studies identified folding conditions that resulted in correctly folded miniproteins with high rates of conversion even for highly hydrophobic and aggregation-prone peptides in concentrated solutions. PMID:23229141

  5. 1,2,3-Triazoles as inhibitors of indoleamine 2,3-dioxygenase 2 (IDO2).

    PubMed

    Röhrig, Ute F; Majjigapu, Somi Reddy; Caldelari, Daniela; Dilek, Nahzli; Reichenbach, Patrick; Ascencao, Kelly; Irving, Melita; Coukos, George; Vogel, Pierre; Zoete, Vincent; Michielin, Olivier

    2016-09-01

    Indoleamine 2,3-dioxygenase 2 (IDO2) is a potential therapeutic target for the treatment of diseases that involve immune escape such as cancer. In contrast to IDO1, only a very limited number of inhibitors have been described for IDO2 due to inherent difficulties in expressing and purifying a functionally active, soluble form of the enzyme. Starting from our previously discovered highly efficient 4-aryl-1,2,3-triazole IDO1 inhibitor scaffold, we used computational structure-based methods to design inhibitors of IDO2 which we then tested in cellular assays. Our approach yielded low molecular weight inhibitors of IDO2, the most active displaying an IC50 value of 51μM for mIDO2, and twofold selectivity over hIDO1. These compounds could be useful as molecular probes to investigate the biological role of IDO2, and could inspire the design of new IDO2 inhibitors. PMID:27469130

  6. Protein folding guides disulfide bond formation

    PubMed Central

    Qin, Meng; Wang, Wei; Thirumalai, D.

    2015-01-01

    The Anfinsen principle that the protein sequence uniquely determines its structure is based on experiments on oxidative refolding of a protein with disulfide bonds. The problem of how protein folding drives disulfide bond formation is poorly understood. Here, we have solved this long-standing problem by creating a general method for implementing the chemistry of disulfide bond formation and rupture in coarse-grained molecular simulations. As a case study, we investigate the oxidative folding of bovine pancreatic trypsin inhibitor (BPTI). After confirming the experimental findings that the multiple routes to the folded state contain a network of states dominated by native disulfides, we show that the entropically unfavorable native single disulfide [14–38] between Cys14 and Cys38 forms only after polypeptide chain collapse and complete structuring of the central core of the protein containing an antiparallel β-sheet. Subsequent assembly, resulting in native two-disulfide bonds and the folded state, involves substantial unfolding of the protein and transient population of nonnative structures. The rate of [14–38] formation increases as the β-sheet stability increases. The flux to the native state, through a network of kinetically connected native-like intermediates, changes dramatically by altering the redox conditions. Disulfide bond formation between Cys residues not present in the native state are relevant only on the time scale of collapse of BPTI. The finding that formation of specific collapsed native-like structures guides efficient folding is applicable to a broad class of single-domain proteins, including enzyme-catalyzed disulfide proteins. PMID:26297249

  7. Folding of Layers of Finite Length

    NASA Astrophysics Data System (ADS)

    Schmid, D. W.; Podladchikov, Yu. Yu.; Marques, F.

    All existing folding theories assume that the layers are infinitely long or, which is mathematically equivalent, that the compression is directly applied to the lateral boundaries. These assumptions are not always justified for natural geological sys- tems. In fact we can observe that on all scales, from veins to sub-ducting slabs, the layers are of finite length and that there are no distinct, rigid walls pushing the lay- ers from the side. Using the method of Muskhelishvili we have derived the complete two-dimensional solution of an elliptic object embedded in a matrix and subject to far field boundary conditions; pure shear, simple shear and arbitrary combinations thereof. The rheology of the matrix is viscous, the layer may behave either elastically or viscous. Using the values from this background state analysis, stress, pressure and strain rate, we performed the classical linear stability analysis to examine the mech- anism of folding in the described setup. The resulting expressions maximum growth rates and dominant wavelengths are applicable to general geological systems; in the limit of an infinite aspect ratio of the layer the classical expressions of Biot are ob- tained for all other cases new expressions result. Our main results are: 1. Folding of finite length layers is controlled by the ratio of aspect ratio to competence contrast. 2. The described setup explains why in nature only folds can be observed with a rela- tively small wavelength to thickness ratio, suggesting small viscosity contrast 3. The problem of the unknown compressive stress value for the elastic layer is solved. 4. For finite length elastic layers the dominant wavelength selection shows a cubic, instead of square, root dependence. 5. A complete table, describing the folding in all the possible limits is presented and the applicability to natural systems discussed. All the presented results were checked numerically and/or with analogue models.

  8. Generation of buckle folds in Naga fold thrust belt, north-east India

    NASA Astrophysics Data System (ADS)

    Saha, B.; Dietl, C.

    2009-04-01

    Naga fold thrust belt (NFTB), India, formed as a result of northward migration of the Indian plate initiated in Eocene and its subsequent collision with the Burmese plate during Oligocene. The NW-SE oriented compression generated a spectrum of structures; among them, we intend to focus on the folds- varying from gentle to tight asymmetric in geometry. Large recumbent folds are often associated with thrusting. Buckle folds forming under shallow crustal conditions are frequently reported from NFTB. Buckle folding occurs mainly within sandstones with intercalated shale layers which are in the study area typical for the Barail, Surma and Tipam Groups. We have tried to explain the controlling factors behind the variation of the buckle fold shapes and their varying wavelengths throughout the fold thrust belt with the aid of analogue (sand box) modelling. It is undoubted that competence contrast along with the layer parallel compressive stress are the major influencing factors in generation of buckle folds. Schmalholz and Podladchikov (1999) and Jeng et al. (2002) have shown that when low strain rate and low temperature are applicable, not only the viscosity contrast, but also the elasticity contrast govern the geometry of the developing buckle folds. Rocks deforming under high temperature and high pressure deform in pure viscous manner, whereas, rocks undergoing less confining stress and less temperature, are subjected to pure elastic deformation. However, they are the end members, and most of the deformations are a combination of these two end members, i.e. of viscoelastic nature. Our models are made up of sieved sand (0.5 mm grain size) and mica layers (1-5 mm) This interlayering imparts a mechanical anisotropy in the model. Mica is not a pure viscous material, rather it displays more elastic behaviour. The mica layers in the model produce bedding parallel slip during shortening through internal reorganization of the individual mica crystals leading to the thickening

  9. Structural Basis and Biological Consequences for JNK2/3 Isoform Selective Aminopyrazoles

    PubMed Central

    Park, HaJeung; Iqbal, Sarah; Hernandez, Pamela; Mora, Rudy; Zheng, Ke; Feng, Yangbo; LoGrasso, Philip

    2015-01-01

    Three JNK isoforms, JNK1, JNK2, and JNK3 have been reported and unique biological function has been ascribed to each. It is unknown if selective inhibition of these isoforms would confer therapeutic or safety benefit. To probe JNK isoform function we designed JNK2/3 inhibitors that have >30-fold selectivity over JNK1. Utilizing site-directed mutagenesis and x-ray crystallography we identified L144 in JNK3 as a key residue for selectivity. To test whether JNK2/3 selective inhibitors protect human dopaminergic neurons against neurotoxin-induced mitochondrial dysfunction, we monitored reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP). The results showed that JNK2/3 selective inhibitors protected against 6-hydroxydopamine-induced ROS generation and MMP depolarization. These results suggest that it was possible to develop JNK2/3 selective inhibitors and that residues in hydrophobic pocket I were responsible for selectivity. Moreover, the findings also suggest that inhibition of JNK2/3 likely contributed to protecting mitochondrial function and prevented ultimate cell death. PMID:25623238

  10. Structure of Human Phosphopantothenoylcysteine Synthetase at 2.3 Å Resolution

    SciTech Connect

    Manoj, N.; Strauss, E.; Begley, T.P.; Ealick, S.E.

    2010-12-01

    The structure of human phosphopantothenoylcysteine (PPC) synthetase was determined at 2.3 {angstrom} resolution. PPC synthetase is a dimer with identical monomers. Some features of the monomer fold resemble a group of NAD-dependent enzymes, while other features resemble the ribokinase fold. The ATP, phosphopantothenate, and cysteine binding sites were deduced from modeling studies. Highly conserved ATP binding residues include Gly43, Ser61, Gly63, Gly66, Phe230, and Asn258. Highly conserved phosphopantothenate binding residues include Asn59, Ala179, Ala180, and Asp183 from one monomer and Arg55 from the adjacent monomer. The structure predicts a ping pong mechanism with initial formation of an acyladenylate intermediate, followed by release of pyrophosphate and attack by cysteine to form the final products PPC and AMP.

  11. Start2Fold: a database of hydrogen/deuterium exchange data on protein folding and stability

    PubMed Central

    Pancsa, Rita; Varadi, Mihaly; Tompa, Peter; Vranken, Wim F.

    2016-01-01

    Proteins fulfil a wide range of tasks in cells; understanding how they fold into complex three-dimensional (3D) structures and how these structures remain stable while retaining sufficient dynamics for functionality is essential for the interpretation of overall protein behaviour. Since the 1950's, solvent exchange-based methods have been the most powerful experimental means to obtain information on the folding and stability of proteins. Considerable expertise and care were required to obtain the resulting datasets, which, despite their importance and intrinsic value, have never been collected, curated and classified. Start2Fold is an openly accessible database (http://start2fold.eu) of carefully curated hydrogen/deuterium exchange (HDX) data extracted from the literature that is open for new submissions from the community. The database entries contain (i) information on the proteins investigated and the underlying experimental procedures and (ii) the classification of the residues based on their exchange protection levels, also allowing for the instant visualization of the relevant residue groups on the 3D structures of the corresponding proteins. By providing a clear hierarchical framework for the easy sharing, comparison and (re-)interpretation of HDX data, Start2Fold intends to promote a better understanding of how the protein sequence encodes folding and structure as well as the development of new computational methods predicting protein folding and stability. PMID:26582925

  12. Vocal fold and ventricular fold vibration in period-doubling phonation: physiological description and aerodynamic modeling.

    PubMed

    Bailly, Lucie; Henrich, Nathalie; Pelorson, Xavier

    2010-05-01

    Occurrences of period-doubling are found in human phonation, in particular for pathological and some singing phonations such as Sardinian A Tenore Bassu vocal performance. The combined vibration of the vocal folds and the ventricular folds has been observed during the production of such low pitch bass-type sound. The present study aims to characterize the physiological correlates of this acoustical production and to provide a better understanding of the physical interaction between ventricular fold vibration and vocal fold self-sustained oscillation. The vibratory properties of the vocal folds and the ventricular folds during phonation produced by a professional singer are analyzed by means of acoustical and electroglottographic signals and by synchronized glottal images obtained by high-speed cinematography. The periodic variation in glottal cycle duration and the effect of ventricular fold closing on glottal closing time are demonstrated. Using the detected glottal and ventricular areas, the aerodynamic behavior of the laryngeal system is simulated using a simplified physical modeling previously validated in vitro using a larynx replica. An estimate of the ventricular aperture extracted from the in vivo data allows a theoretical prediction of the glottal aperture. The in vivo measurements of the glottal aperture are then compared to the simulated estimations. PMID:21117769

  13. Microfluidic Mixers for Studying Protein Folding

    PubMed Central

    Waldauer, Steven A.; Wu, Ling; Yao, Shuhuai; Bakajin, Olgica; Lapidus, Lisa J.

    2012-01-01

    The process by which a protein folds into its native conformation is highly relevant to biology and human health yet still poorly understood. One reason for this is that folding takes place over a wide range of timescales, from nanoseconds to seconds or longer, depending on the protein1. Conventional stopped-flow mixers have allowed measurement of folding kinetics starting at about 1 ms. We have recently developed a microfluidic mixer that dilutes denaturant ~100-fold in ~8 μs2. Unlike a stopped-flow mixer, this mixer operates in the laminar flow regime in which turbulence does not occur. The absence of turbulence allows precise numeric simulation of all flows within the mixer with excellent agreement to experiment3-4. Laminar flow is achieved for Reynolds numbers Re ≤100. For aqueous solutions, this requires micron scale geometries. We use a hard substrate, such as silicon or fused silica, to make channels 5-10 μm wide and 10 μm deep (See Figure 1). The smallest dimensions, at the entrance to the mixing region, are on the order of 1 μm in size. The chip is sealed with a thin glass or fused silica coverslip for optical access. Typical total linear flow rates are ~1 m/s, yielding Re~10, but the protein consumption is only ~0.5 nL/s or 1.8 μL/hr. Protein concentration depends on the detection method: For tryptophan fluorescence the typical concentration is 100 μM (for 1 Trp/protein) and for FRET the typical concentration is ~100 nM. The folding process is initiated by rapid dilution of denaturant from 6 M to 0.06 M guanidine hydrochloride. The protein in high denaturant flows down a central channel and is met on either side at the mixing region by buffer without denaturant moving ~100 times faster (see Figure 2). This geometry causes rapid constriction of the protein flow into a narrow jet ~100 nm wide. Diffusion of the light denaturant molecules is very rapid, while diffusion of the heavy protein molecules is much slower, diffusing less than 1 μm in 1 ms

  14. Crystalline 1H-1,2,3-triazol-5-ylidenes

    DOEpatents

    Bertrand, Guy; Gulsado-Barrios, Gregorio; Bouffard, Jean; Donnadieu, Bruno

    2016-08-02

    The present invention provides novel and stable crystalline 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of making 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of using 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes in catalytic reactions.

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

    NASA Astrophysics Data System (ADS)

    Pappu, Rohit V.; Nussinov, Ruth

    2009-03-01

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

  16. Predictive Computational Modeling of Chromatin Folding

    NASA Astrophysics Data System (ADS)

    di Pierro, Miichele; Zhang, Bin; Wolynes, Peter J.; Onuchic, Jose N.

    In vivo, the human genome folds into well-determined and conserved three-dimensional structures. The mechanism driving the folding process remains unknown. We report a theoretical model (MiChroM) for chromatin derived by using the maximum entropy principle. The proposed model allows Molecular Dynamics simulations of the genome using as input the classification of loci into chromatin types and the presence of binding sites of loop forming protein CTCF. The model was trained to reproduce the Hi-C map of chromosome 10 of human lymphoblastoid cells. With no additional tuning the model was able to predict accurately the Hi-C maps of chromosomes 1-22 for the same cell line. Simulations show unknotted chromosomes, phase separation of chromatin types and a preference of chromatin of type A to sit at the periphery of the chromosomes.

  17. Folded membrane dialyzer with mechanically sealed edges

    DOEpatents

    Markley, Finley W.

    1976-01-01

    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.

  18. Dynamic Coupling between Folding, Binding and Function

    NASA Astrophysics Data System (ADS)

    Wolynes, Peter G.

    2003-03-01

    Elementary presentations of biophysics suggest a clear separation between the events of protein folding and function. The situation is much more interesting and complex. Many proteins in the cell are unfolded until called upon to interact with targets. Why? Energy landscape theory suggest some interesting kinetic advantages and possible explanations concerning the promiscuity of protein-protein interactions. This will be discussed in the context of protein DNA recognition. The energy landscapes for binding surfaces show interesting systematic differences from those of protein interiors. Energy landscape ideas also raise the prospect that folded proteins partially unfold during their function. I will illustrate this with a specific example of large scale conformation change in a kinase.

  19. RNA Hairpin Folding in the Crowded Cell.

    PubMed

    Gao, Mimi; Gnutt, David; Orban, Axel; Appel, Bettina; Righetti, Francesco; Winter, Roland; Narberhaus, Franz; Müller, Sabine; Ebbinghaus, Simon

    2016-02-24

    Precise secondary and tertiary structure formation is critically important for the cellular functionality of ribonucleic acids (RNAs). RNA folding studies were mainly conducted in vitro, without the possibility of validating these experiments inside cells. Here, we directly resolve the folding stability of a hairpin-structured RNA inside live mammalian cells. We find that the stability inside the cell is comparable to that in dilute physiological buffer. On the contrary, the addition of in vitro artificial crowding agents, with the exception of high-molecular-weight PEG, leads to a destabilization of the hairpin structure through surface interactions and reduction in water activity. We further show that RNA stability is highly variable within cell populations as well as within subcellular regions of the cytosol and nucleus. We conclude that inside cells the RNA is subject to (localized) stabilizing and destabilizing effects that lead to an on average only marginal modulation compared to diluted buffer. PMID:26833452

  20. Elastic models of vocal fold tissues.

    PubMed

    Alipour-Haghighi, F; Titze, I R

    1991-09-01

    Elastic properties of canine vocal fold tissue (muscle and mucosa) were obtained through a series of experiments conducted in vitro and were modeled mathematically. The elastic properties play a significant role in quantitative analysis of vocal fold vibrations and theory of pitch control. Samples of vocalis muscle and mucosa were dissected and prepared from dog larynges a few minutes premortem and kept in a Krebs solution at a temperature of 37 +/- 1 degrees C and a pH of 7.4 +/- 0.05. Samples of muscle tissue and mucosa were stretched and released in a slow, sinusoidal fashion. Force and displacement of the samples were measured with a dual-servo system (ergometer). After digitization, stress-strain data for samples of muscle tissue and cover tissue were averaged. The stress-strain data were then fitted numerically by polynomial and exponential models. PMID:1939897

  1. Ca-Dependent Folding of Human Calumenin

    PubMed Central

    Mazzorana, Marco; Hussain, Rohanah; Sorensen, Thomas

    2016-01-01

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

  2. Chevron folding patterns and heteroclinic orbits

    NASA Astrophysics Data System (ADS)

    Budd, Christopher J.; Chakhchoukh, Amine N.; Dodwell, Timothy J.; Kuske, Rachel

    2016-09-01

    We present a model of multilayer folding in which layers with bending stiffness EI are separated by a very stiff elastic medium of elasticity k2 and subject to a horizontal load P. By using a dynamical system analysis of the resulting fourth order equation, we show that as the end shortening per unit length E is increased, then if k2 is large there is a smooth transition from small amplitude sinusoidal solutions at moderate values of P to larger amplitude chevron folds, with straight limbs separated by regions of high curvature when P is large. The chevron solutions take the form of near heteroclinic connections in the phase-plane. By means of this analysis, values for P and the slope of the limbs are calculated in terms of E and k2.

  3. RNA Hairpin Folding in the Crowded Cell

    PubMed Central

    Gao, Mimi; Gnutt, David; Orban, Axel; Appel, Bettina; Righetti, Francesco; Winter, Roland; Narberhaus, Franz; Müller, Sabine

    2016-01-01

    Abstract Precise secondary and tertiary structure formation is critically important for the cellular functionality of ribonucleic acids (RNAs). RNA folding studies were mainly conducted in vitro, without the possibility of validating these experiments inside cells. Here, we directly resolve the folding stability of a hairpin‐structured RNA inside live mammalian cells. We find that the stability inside the cell is comparable to that in dilute physiological buffer. On the contrary, the addition of in vitro artificial crowding agents, with the exception of high‐molecular‐weight PEG, leads to a destabilization of the hairpin structure through surface interactions and reduction in water activity. We further show that RNA stability is highly variable within cell populations as well as within subcellular regions of the cytosol and nucleus. We conclude that inside cells the RNA is subject to (localized) stabilizing and destabilizing effects that lead to an on average only marginal modulation compared to diluted buffer. PMID:26833452

  4. Recognizing the fold of a protein structure.

    PubMed

    Harrison, Andrew; Pearl, Frances; Sillitoe, Ian; Slidel, Tim; Mott, Richard; Thornton, Janet; Orengo, Christine

    2003-09-22

    This paper reports a graph-theoretic program, GRATH, that rapidly, and accurately, matches a novel structure against a library of domain structures to find the most similar ones. GRATH generates distributions of scores by comparing the novel domain against the different types of folds that have been classified previously in the CATH database of structural domains. GRATH uses a measure of similarity that details the geometric information, number of secondary structures and number of residues within secondary structures, that any two protein structures share. Although GRATH builds on well established approaches for secondary structure comparison, a novel scoring scheme has been introduced to allow ranking of any matches identified by the algorithm. More importantly, we have benchmarked the algorithm using a large dataset of 1702 non-redundant structures from the CATH database which have already been classified into fold groups, with manual validation. This has facilitated introduction of further constraints, optimization of parameters and identification of reliable thresholds for fold identification. Following these benchmarking trials, the correct fold can be identified with the top score with a frequency of 90%. It is identified within the ten most likely assignments with a frequency of 98%. GRATH has been implemented to use via a server (http://www.biochem.ucl.ac.uk/cgi-bin/cath/Grath.pl). GRATH's speed and accuracy means that it can be used as a reliable front-end filter for the more accurate, but computationally expensive, residue based structure comparison algorithm SSAP, currently used to classify domain structures in the CATH database. With an increasing number of structures being solved by the structural genomics initiatives, the GRATH server also provides an essential resource for determining whether newly determined structures are related to any known structures from which functional properties may be inferred. PMID:14512345

  5. Chen’s Double Eyelid Fold Ratio

    PubMed Central

    Chen, Chen-Chia; Tai, Hao-Chih

    2016-01-01

    Background: Double eyelidplasty can construct palpebral folds and enhance beauty perception for Asians with single eyelids. A new palpebral parameter for the quantitative interpretation of surgical outcomes is proposed on the basis of a photometric study of the altered proportions of Asian eyes after double eyelid operation. Methods: A total of 100 Asian adults with single upper eyelids who were satisfied with the enlarged eyes by operation were included in the study. A retrospective measurement of palpebral parameters in the frontal profile both preoperatively and 6 months postoperatively was performed. The proportions of various parameters in the eyebrow–eye aesthetic unit were calculated and analyzed. Results: Double eyelidplasty can augment the vertical dimension of palpebral fissure by 27.9% increase on average. The vertical ratio of palpebral fissure to the eyebrow–eye unit is augmented by 34.4% increase. The vertical ratio of the subunit below double eyelid fold peak to the unit is augmented by 82.6% increase. Conclusions: Double eyelidplasty can substantially enlarge the vertical dimensions of the eyes of Asians with single eyelids. The eyes are perceived to be larger because of the visually assimilated illusion of the superimposed eyelid fold and the relative proportions of the eyebrow–eye unit. The authors propose using a vertical ratio of the subunit below double eyelid fold peak in the eyebrow–eye unit to measure the visually perceived proportion of the eye in the unit. This ratio can be applied clinically for a quantitative evaluation of the surgical outcome after double eyelidplasty. PMID:27200243

  6. Coherent topological phenomena in protein folding.

    PubMed

    Bohr, H; Brunak, S; Bohr, J

    1997-01-01

    A theory is presented for coherent topological phenomena in protein dynamics with implications for protein folding and stability. We discuss the relationship to the writhing number used in knot diagrams of DNA. The winding state defines a long-range order along the backbone of a protein with long-range excitations, 'wring' modes, that play an important role in protein denaturation and stability. Energy can be pumped into these excitations, either thermally or by an external force. PMID:9218961

  7. Folded fibre bus interconnects with distributed amplification

    NASA Astrophysics Data System (ADS)

    Lorenzo, Raul Hernandez; Urquhart, Paul; Lopez-Amo, Manuel

    1998-06-01

    An optical fibre network for application as an interconnect within major nodes is investigated theoretically. The network is configured as a folded bus in which the spine consists of erbium doped fibre to overcome the power division at the couplers. It is argued that high received powers with a narrow dynamic range can be obtained simultaneously with bit rates in the order of 10 Gbit/s and bit error rates of 10 -12 or less.

  8. Protein Folding Stages and Universal Exponents

    NASA Astrophysics Data System (ADS)

    Huang, Kerson

    We propose three stages in protein folding, based on physical arguements involving the interplay between the hydrophobic effect and hydrogen bonding, and computer simulations using the CSAW (conditioned self-avoiding walk) model. These stages are characterized by universal exponents ν = 3/5, 3/7, 2/5 in the power law R ~ Nν, where R is the radius of gyration and N is the number of residues. They correspond to the experimentally observed stages: unfolded, preglobule, molten globule.

  9. Protein Folding Stages and Universal Exponents

    NASA Astrophysics Data System (ADS)

    Huang, Kerson

    2011-11-01

    We propose three stages in protein folding, based on physical arguements involving the interplay between the hydrophobic effect and hydrogen bonding, and computer simulations using the CSAW (conditioned self-avoiding walk) model. These stages are characterized by universal exponents ν = 3/5, 3/7, 2/5 in the power law R ˜ Nν, where R is the radius of gyration and N is the number of residues. They correspond to the experimentally observed stages: unfolded, preglobule, molten globule.

  10. A Simple Model for Protein Folding

    NASA Astrophysics Data System (ADS)

    Henry, Eric R.; Eaton, William A.

    We describe a simple Ising-like statistical mechanical model for folding proteins based on the α-carbon contact map of the native structure. In this model residues can adopt two microscopic states corresponding to the native and non-native conformations. In order to exactly enumerate the large number of possible configurations, structure is considered to grow as continuous sequences of native residues, with no more than two sequences in each molecule. Inter-residue contacts can only form within each sequence and between residues of the two native sequences. As structure grows there is a tradeoff between the stabilizing effect of inter-residue contacts and the entropy losses from ordering residues in their native conformation and from forming a disordered loop to connect two continuous sequences. Folding kinetics are calculated from the dynamics on the free energy profile, as in Kramers' reaction rate theory. Although non-native interactions responsible for roughness in the energy landscape are not explicitly considered in the model, they are implicitly included by determining the absolute rates for motion on the free energy profile. With the exception of α-helical proteins, the kinetic progress curves exhibit single exponential time courses, consistent with two state behavior, as observed experimentally. The calculated folding rates are in remarkably good agreement with the measured values for the 25 two-state proteins investigated, with a correlation coefficient of 0.8. With its coarse-grained description of both the energy and entropy, and only three independently adjustable parameters, the model may be regarded as the simplest possible analytical model of protein folding capable of predicting experimental properties of specific proteins.

  11. Iontophoresis across the proximal nail fold to target drugs to the nail matrix.

    PubMed

    Manda, Prashanth; Sammeta, Srinivasa M; Repka, Michael A; Murthy, S Narasimha

    2012-07-01

    The main objective of the present study was to investigate the plausibility of iontophoretic delivery of drugs to the nail matrix via proximal nail fold. The in vitro drug transport studies were performed in Franz diffusion cells across folded epidermis, which is used as a model for the proximal nail fold. The amount of drug transported into the receiver compartment following iontophoresis for 3 h at 0.5 mA/cm(2) was 150-fold higher than the control (0.008 ± 0.002 μg/cm(2)). The amount of drug present in the skin after iontophoresis (0.45 ± 0.12 μg/mg) was approximately fivefold higher as compared with that of the control (0.08 ± 0.01 μg/mg). Iontophoresis of terbinafine across the proximal nail fold was assessed using excised cadaver toe model as well. A custom-designed foam-pad-type patch system was used for iontophoresis in cadaver toes. The amount of the drug delivered into the nail matrix following iontophoresis for 3 h was significantly higher than the minimum inhibition concentration of terbinafine. However, on the contrary, passive delivery for about 24 h did not result in any detectable drug levels in the nail matrix. Iontophoresis across the proximal nail fold could be developed as a potential method to target drugs to nail matrix. PMID:22487899

  12. Evolution of the beta-propeller fold.

    PubMed

    Chaudhuri, Indronil; Söding, Johannes; Lupas, Andrei N

    2008-05-01

    beta-Propellers are toroidal folds, in which repeated, four-stranded beta-meanders are arranged in a circular and slightly tilted fashion, like the blades of a propeller. They are found in all domains of life, with a strong preponderance among eukaryotes. Propellers show considerable sequence diversity and are classified into six separate structural groups by the SCOP and CATH databases. Despite this diversity, they often show similarities across groups, not only in structure but also in sequence, raising the possibility of a common origin. In agreement with this hypothesis, most propellers group together in a cluster map of all-beta folds generated by sequence similarity, because of numerous pairwise matches, many of which are individually nonsignificant. In total, 45 of 60 propellers in the SCOP25 database, covering four SCOP folds, are clustered in this group and analysis with sensitive sequence comparison methods shows that they are similar at a level indicative of homology. Two mechanisms appear to contribute to the evolution of beta-propellers: amplification from single blades and subsequent functional differentiation. The observation of propellers with nearly identical blades in genomic sequences show that these mechanisms are still operating today. PMID:17979191

  13. Cellular pathways controlling integron cassette site folding.

    PubMed

    Loot, Céline; Bikard, David; Rachlin, Anna; Mazel, Didier

    2010-08-01

    By mobilizing small DNA units, integrons have a major function in the dissemination of antibiotic resistance among bacteria. The acquisition of gene cassettes occurs by recombination between the attI and attC sites catalysed by the IntI1 integron integrase. These recombination reactions use an unconventional mechanism involving a folded single-stranded attC site. We show that cellular bacterial processes delivering ssDNA, such as conjugation and replication, favour proper folding of the attC site. By developing a very sensitive in vivo assay, we also provide evidence that attC sites can recombine as cruciform structures by extrusion from double-stranded DNA. Moreover, we show an influence of DNA superhelicity on attC site extrusion in vitro and in vivo. We show that the proper folding of the attC site depends on both the propensity to form non-recombinogenic structures and the length of their variable terminal structures. These results draw the network of cell processes that regulate integron recombination. PMID:20628355

  14. Trp-Cage Folding on Organic Surfaces.

    PubMed

    Levine, Zachary A; Fischer, Sean A; Shea, Joan-Emma; Pfaendtner, Jim

    2015-08-20

    Trp-cage is an artificial miniprotein that is small, stable, and fast folding due to concerted hydrophobic shielding of a Trp residue by polyproline helices. Simulations have extensively characterized Trp-cage; however, the interactions of Trp-cage with organic surfaces (e.g., membranes) and their effect on protein conformation are largely unknown. To better understand these interactions we utilized a combination of replica-exchange molecular dynamics (REMD) and metadynamics (MetaD), to investigate Trp-cage folding on self-assembled monolayers (SAMs). We found that, with REMD and MetaD, Trp-cage strongly binds to neutral CH3 surfaces (-25kT) and moderately adsorbs to anionic COOH interfaces (-7.6kT), with hydrophobic interactions driving CH3 adhesion and electrostatic attractions driving COOH adhesion. Similar to solid-state surfaces, SAMs facilitate a number of intermediate Trp-cage conformations between folded and unfolded states. Regarding Trp-cage's aromatic groups in neutral CH3 systems, Tyr becomes oriented parallel to the surface in order to maximize hydrophobic interactions while Trp remains caged perpendicular to the surface; however, Trp can reorient itself parallel to the interface as the miniprotein more closely binds to the surface. In contrast, Tyr and Trp are both repelled from COOH surfaces, though the Trp-cage still adheres to the anionic interface via Lys and its N-terminated Asn residue. PMID:26207727

  15. Inframammary Fold Reconstruction: A Biomechanical Analysis

    PubMed Central

    Schell, Julia; Uener, Jens; Prescher, Andreas; Scaal, Martin; Puppe, Julian; Warm, Mathias

    2016-01-01

    Background: Inframammary fold reconstruction has scarcely been evaluated in literature. No biomechanical analyses have been performed comparing different reconstructive methods. This evaluation compares the gold-standard suture reconstruction with an intrarib anchor system (Micro BioComposite SutureTak, Arthrex). Methods: Three analysis groups were compared including 8 Sawbone blocks, 22 embalmed cadaver, and 27 regular cadaver specimens (N = 57). Transient mechanical analysis was performed at 5 N/s using an Instron 5565 test frame. Results: Ultimate load favored the anchor system (compared with the gold-standard suture) by a factor of 9.8 (P < 0.0001) for the regular cadaver group and a factor of 1.7 (P < 0.038) for the embalmed cadaver group. A similar statistically significant benefit was shown for stiffness and load at 2-mm displacement. Conclusions: This analysis showed an anchor system to be the biomechanically superior fixation method in terms of ultimate load, fixation stiffness, and displacement at failure when compared with the gold-standard suture method in inframammary fold reconstruction. Because of superior stability in every aspect, an anchor system may be considered for inframammary fold reconstruction. PMID:27257564

  16. Evolution of a protein folding nucleus.

    PubMed

    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. PMID:26610273

  17. RNA folding pathways in stop motion.

    PubMed

    Bottaro, Sandro; Gil-Ley, Alejandro; Bussi, Giovanni

    2016-07-01

    We introduce a method for predicting RNA folding pathways, with an application to the most important RNA tetraloops. The method is based on the idea that ensembles of three-dimensional fragments extracted from high-resolution crystal structures are heterogeneous enough to describe metastable as well as intermediate states. These ensembles are first validated by performing a quantitative comparison against available solution nuclear magnetic resonance (NMR) data of a set of RNA tetranucleotides. Notably, the agreement is better with respect to the one obtained by comparing NMR with extensive all-atom molecular dynamics simulations. We then propose a procedure based on diffusion maps and Markov models that makes it possible to obtain reaction pathways and their relative probabilities from fragment ensembles. This approach is applied to study the helix-to-loop folding pathway of all the tetraloops from the GNRA and UNCG families. The results give detailed insights into the folding mechanism that are compatible with available experimental data and clarify the role of intermediate states observed in previous simulation studies. The method is computationally inexpensive and can be used to study arbitrary conformational transitions. PMID:27091499

  18. Computing the conformational entropy for RNA folds

    NASA Astrophysics Data System (ADS)

    Liu, Liang; Chen, Shi-Jie

    2010-06-01

    We develop a polymer physics-based method to compute the conformational entropy for RNA tertiary folds, namely, conformations consisting of multiple helices connected through (cross-linked) loops. The theory is based on a virtual bond conformational model for the nucleotide chain. A key issue in the calculation of the entropy is how to treat the excluded volume interactions. The weak excluded volume interference between the different loops leads to the decomposition of the whole structure into a number of three-body building blocks, each consisting of a loop and two helices connected to the two ends of the loop. The simple construct of the three-body system allows an accurate computation for the conformational entropy for each building block. The assembly of the building blocks gives the entropy of the whole structure. This approach enables treatment of molten globule-like folds (partially unfolded tertiary structures) for RNAs. Extensive tests against experiments and exact computer enumerations indicate that the method can give accurate results for the entropy. The method developed here provides a solid first step toward a systematic development of a theory for the entropy and free energy landscape for complex tertiary folds for RNAs and proteins.

  19. Fold assisted transport in graphene systems

    NASA Astrophysics Data System (ADS)

    Carrillo-Bastos, Ramon; Faria, Daiara; Jiang, Yuhang; Mao, Jinhai; Li, Guohong; Andrei, Eva Y.; Latge, Andrea; Sandler, Nancy

    Sasaki pointed out that a constant uniaxial strain applied along the zigzag direction in graphene causes localized states, akin to edge states in nanoribbons. These states are dispersionless and can carry ballistic transport. Recent experiments reported the presence of ballistic channels in graphene grown on SiC characterized with STM spectroscopy. In this work, we show that out-of plane deformations in the form of folds produce states as those predicted by Sasaki. Using tight-binding calculations and recursive Green's function methods, we obtain conductance, density of states (DOS), local density of states, and band structure (BS) for graphene nanoribbons with zigzag termination. Regions with enhanced DOS are identified in the deformed area corresponding to states in new flattened bands in the BS and new ballistic channels in the conductance. Adjusting the fold parameters, desired properties of these states can be tailored. Our results show that folds could serve as pathways for electronic transport and open the possibility of circuitry design within a simple graphene membrane. Support: DOE-FG02-99ER45742, NSF-DMR 1207108 and 1508325.

  20. RNA folding pathways in stop motion

    PubMed Central

    Bottaro, Sandro; Gil-Ley, Alejandro; Bussi, Giovanni

    2016-01-01

    We introduce a method for predicting RNA folding pathways, with an application to the most important RNA tetraloops. The method is based on the idea that ensembles of three-dimensional fragments extracted from high-resolution crystal structures are heterogeneous enough to describe metastable as well as intermediate states. These ensembles are first validated by performing a quantitative comparison against available solution nuclear magnetic resonance (NMR) data of a set of RNA tetranucleotides. Notably, the agreement is better with respect to the one obtained by comparing NMR with extensive all-atom molecular dynamics simulations. We then propose a procedure based on diffusion maps and Markov models that makes it possible to obtain reaction pathways and their relative probabilities from fragment ensembles. This approach is applied to study the helix-to-loop folding pathway of all the tetraloops from the GNRA and UNCG families. The results give detailed insights into the folding mechanism that are compatible with available experimental data and clarify the role of intermediate states observed in previous simulation studies. The method is computationally inexpensive and can be used to study arbitrary conformational transitions. PMID:27091499

  1. Embryo toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the wood duck (Aix sponsa)

    USGS Publications Warehouse

    Augspurger, T.P.; Tillitt, D.E.; Bursian, S.J.; Fitzgerald, S.D.; Hinton, D.E.; Di Giulio, R.T.

    2008-01-01

    We examined the sensitivity of the wood duck (Aix sponsa) embryo to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by injecting the toxicant into their eggs. Six groups of wood duck eggs (n = 35 to 211 per trial) were injected with 0 to 4600 pg TCDD/g egg between 2003 and 2005. Injections were made into yolk prior to incubation, and eggs were subsequently incubated and assessed weekly for mortality. Significant TCDD-induced mortality was not observed through day 25 (90% of incubation). Liver, heart, eye, and brain histology were generally unremarkable. Hepatic ethoxyresorufin-O-deethylase activity, a biomarker of dioxin-like compound exposure, was induced by 12-fold in the 4600 pg/g treatment relative to controls. The median lethal dose for chicken (Gallus domesticus) eggs we dosed identically to wood duck eggs was about 100 pg/g, similar to other assessments of chickens. Among dioxin-like compound embryo lethality data for 15 avian genera, the wood duck 4600 pg/g no-observed-effect level ranks near the middle. Because no higher doses were tested, wood ducks may be like other waterfowl (order Anseriformes), which are comparatively tolerant to embryo mortality from polychlorinated dibenzo-p-dioxins and dibenzofurans when exposed by egg injection. ?? 2008 US Government.

  2. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on development of anuran amphibians

    SciTech Connect

    Jung, R.E.; Walker, M.K.

    1997-02-01

    The authors exposed anuran eggs and tadpoles to vehicle control (0.7% acetone) or waterborne [{sup 3}H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 24 h and subsequently raised them in clean water. Neither American toads nor green frogs exhibited TCDD-related mortality, but leopard frogs showed significantly increased mortality over controls. Eggs and tadpoles eliminated TCDD relatively quickly compared with published data for other vertebrates, with t{sub {1/2}} of 1 to 5 d (American toad), 2 to 7 d (leopard frog), and 4 to 6 d (green frog). Elimination rates were slowest for tadpoles fed nothing, fastest for those fed a low-fat diet, and intermediate for those fed a high-fat diet. Although not significant, American toads exposed to {ge}0.03 {micro}g TCDD/L appeared to metamorphose earlier, and those exposed to higher TCDD treatments appeared to metamorphose at a larger body mass than controls. Comparisons of these results with studies of fish early life stages suggest that anuran eggs and tadpoles eliminate TCDD more rapidly and are 100- to 1,000-fold less sensitive to its deleterious effects during development. These differences may be related to differences in metabolic rate, patterns of lipid storage and utilization, and aryl hydrocarbon receptor binding and signal transduction.

  3. Embryo toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the wood duck (Aix sponsa).

    PubMed

    Augspurger, T P; Tillitt, D E; Bursian, S J; Fitzgerald, S D; Hinton, D E; Di Giulio, R T

    2008-11-01

    We examined the sensitivity of the wood duck (Aix sponsa) embryo to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by injecting the toxicant into their eggs. Six groups of wood duck eggs (n = 35 to 211 per trial) were injected with 0 to 4600 pg TCDD/g egg between 2003 and 2005. Injections were made into yolk prior to incubation, and eggs were subsequently incubated and assessed weekly for mortality. Significant TCDD-induced mortality was not observed through day 25 (90% of incubation). Liver, heart, eye, and brain histology were generally unremarkable. Hepatic ethoxyresorufin-O-deethylase activity, a biomarker of dioxin-like compound exposure, was induced by 12-fold in the 4600 pg/g treatment relative to controls. The median lethal dose for chicken (Gallus domesticus) eggs we dosed identically to wood duck eggs was about 100 pg/g, similar to other assessments of chickens. Among dioxin-like compound embryo lethality data for 15 avian genera, the wood duck 4600 pg/g no-observed-effect level ranks near the middle. Because no higher doses were tested, wood ducks may be like other waterfowl (order Anseriformes), which are comparatively tolerant to embryo mortality from polychlorinated dibenzo-p-dioxins and dibenzofurans when exposed by egg injection. PMID:18704254

  4. Purification of a vitamin K epoxide reductase that catalyzes conversion of vitamin K 2,3-epoxide to 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone.

    PubMed Central

    Mukharji, I; Silverman, R B

    1985-01-01

    An enzyme from bovine liver microsomes that catalyzes the reduction of vitamin K 2,3-epoxide to 2- and 3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone was purified 1152-fold to apparent homogeneity. Microsomes were solubilized with 3-[3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), and the enzyme was purified by chromatography on PBE-94 ion exchanger, hydroxylapatite, and DEAE-cellulose, and then gel filtration on Sephacryl S-200. The homogeneity of the final preparation was established by polyacrylamide slab gel electrophoresis in the presence of sodium dodecyl sulfate. The molecular weight of the native enzyme is 25,000 and that of denatured enzyme is 12,400, which suggests that the enzyme is a dimer with identical subunits. No chromophoric cofactors are associated with the enzyme. Dithiothreitol and CHAPS are essential for activity, but high concentrations of glycerol reduces the activity. The enzyme is not inhibited by warfarin, a potent inhibitor of the vitamin K epoxide reductase, which catalyzes the conversion of vitamin K 2,3-epoxide to vitamin K. Evidence is presented indicating that the purified enzyme is not simply a fragment of the warfarin-sensitive vitamin K epoxide reductase. Images PMID:3857611

  5. Fragmentation pathways of 2,3-dimethyl-2,3-dinitrobutane cations in the gas phase.

    PubMed

    Paine, Martin R L; Kirk, Benjamin B; Ellis-Steinborner, Simon; Blanksby, Stephen J

    2009-09-01

    2,3-Dimethyl-2,3-dinitrobutane (DMNB) is an explosive taggant added to plastic explosives during manufacture making them more susceptible to vapour-phase detection systems. In this study, the formation and detection of gas-phase [M+H](+), [M+Li](+), [M+NH(4)](+) and [M+Na](+) adducts of DMNB was achieved using electrospray ionisation on a triple quadrupole mass spectrometer. The [M+H](+) ion abundance was found to have a strong dependence on ion source temperature, decreasing markedly at source temperatures above 50 degrees C. In contrast, the [M+Na](+) ion demonstrated increasing ion abundance at source temperatures up to 105 degrees C. The relative susceptibility of DMNB adduct ions toward dissociation was investigated by collision-induced dissociation. Probable structures of product ions and mechanisms for unimolecular dissociation have been inferred based on fragmentation patterns from tandem mass (MS/MS) spectra of source-formed ions of normal and isotopically labelled DMNB, and quantum chemical calculations. Both thermal and collisional activation studies suggest that the [M+Na](+) adduct ions are significantly more stable toward dissociation than their protonated analogues and, as a consequence, the former provide attractive targets for detection by contemporary rapid screening methods such as desorption electrospray ionisation mass spectrometry. PMID:19670345

  6. Engineering of cofactor regeneration enhances (2S,3S)-2,3-butanediol production from diacetyl

    PubMed Central

    Wang, Yu; Li, Lixiang; Ma, Cuiqing; Gao, Chao; Tao, Fei; Xu, Ping

    2013-01-01

    (2S,3S)-2,3-Butanediol ((2S,3S)-2,3-BD) is a potentially valuable liquid fuel and an excellent building block in asymmetric synthesis. In this study, cofactor engineering was applied to improve the efficiency of (2S,3S)-2,3-BD production and simplify the product purification. Two NADH regeneration enzymes, glucose dehydrogenase and formate dehydrogenase (FDH), were introduced into Escherichia coli with 2,3-BD dehydrogenase, respectively. Introduction of FDH resulted in higher (2S,3S)-2,3-BD concentration, productivity and yield from diacetyl, and large increase in the intracellular NADH concentration. In fed-batch bioconversion, the final titer, productivity and yield of (2S,3S)-2,3-BD on diacetyl reached 31.7 g/L, 2.3 g/(L·h) and 89.8%, the highest level of (2S,3S)-2,3-BD production thus far. Moreover, cosubstrate formate was almost totally converted to carbon dioxide and no organic acids were produced. The biocatalytic process presented should be a promising route for biotechnological production of NADH-dependent microbial metabolites. PMID:24025762

  7. 3-Oxoisoxazole-2(3H)-carboxamides and isoxazol-3-yl carbamates: Resistance-breaking acetylcholinesterase inhibitors targeting the malaria mosquito, Anopheles gambiae

    PubMed Central

    Verma, Astha; Wong, Dawn M.; Islam, Rafique; Tong, Fan; Ghavami, Maryam; Mutunga, James M.; Slebodnick, Carla; Li, Jianyong; Viayna, Elisabet; Lam, Polo C.-H.; Totrov, Maxim M.; Bloomquist, Jeffrey R.; Carlier, Paul R.

    2015-01-01

    To identify potential selective and resistance-breaking mosquitocides against the African malaria vector Anopheles gambiae, we investigated the acetylcholinesterase (AChE) inhibitory and mosquitocidal properties of isoxazol-3-yl dimethylcarbamates (15), and the corresponding 3-oxoisoxazole-2(3H)-dimethylcarboxamide isomers (14). In both series, compounds were found with excellent contact toxicity to wild-type susceptible (G3) strain and multiply resistant (Akron) strain mosquitoes that carry the G119S resistance mutation of AChE. Compounds possessing good to excellent toxicity to Akron strain mosquitoes inhibit the G119S mutant of An. gambiae AChE (AgAChE) with ki values at least 10- to 600-fold higher than that of propoxur, a compound that does not kill Akron mosquitoes at the highest concentration tested. On average, inactivation of WT AgAChE by dimethylcarboxamides 14 was 10-20 fold faster than that of the corresponding isoxazol-3-yl dimethylcarbamates 15. X-ray crystallography of dimethylcarboxamide 14d provided insight into that reactivity, a finding that may explain the inhibitory power of structurally-related inhibitors of hormone-sensitive lipase. Finally, human/An. gambiae AChE inhibition selectivities of these compounds were low, suggesting the need for additional structural modification. PMID:25684426

  8. Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Neurotoxicity with Blood-Brain Barrier Monoamine Oxidase Activity

    NASA Astrophysics Data System (ADS)

    Kalaria, Rajesh N.; Mitchell, Mary Jo; Harik, Sami I.

    1987-05-01

    Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and subhuman primates, but not in rats and many other laboratory animals; mice are intermediate in their susceptibility. Since MPTP causes selective dopaminergic neurotoxicity when infused directly into rat substantia nigra, we hypothesized that systemic MPTP may be metabolized by monoamine oxidase and/or other enzymes in rat brain capillaries and possibly other peripheral organs and thus prevented from reaching its neuronal sites of toxicity. We tested this hypothesis by assessing monoamine oxidase in isolated cerebral microvessels of humans, rats, and mice by measuring the specific binding of [3H]pargyline, an irreversible monoamine oxidase inhibitor, and by estimating the rates of MPTP and benzylamine oxidation. [3H]Pargyline binding to rat cerebral microvessels was about 10-fold higher than to human or mouse microvessels. Also, MPTP oxidation by rat brain microvessels was about 30-fold greater than by human microvessels; mouse microvessels yielded intermediate values. These results may explain, at least in part, the marked species differences in susceptibility to systemic MPTP. They also suggest the potential importance of ``enzyme barriers'' at the blood-brain interface that can metabolize toxins not excluded by structural barriers, and may provide biological bases for developing therapeutic strategies for the prevention of MPTP-induced neurotoxicity and other neurotoxic conditions including, possibly, Parkinson disease.

  9. A Rat Excised Larynx Model of Vocal Fold Scar

    ERIC Educational Resources Information Center

    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…

  10. Conjugate-shear folding: A model for the relationships between foliations, folds and shear zones

    NASA Astrophysics Data System (ADS)

    Aerden, Domingo G. A. M.; Sayab, Mohammad; Bouybaouene, Mohamed L.

    2010-08-01

    Microstructural mapping of whole thin sections cut from two samples of micaschist containing cm-scale folds plus garnet porphyroblasts has provided new insight in the relationships between folding, shearing and foliation development. The garnets exhibit coherent inclusion-trail patterns that place important constraints on the kinematic development of both samples, which are shown to be representative of coaxial versus non-coaxial deformation in rocks containing a pre-existing schistosity. A comparison of crenulations-cleavages geometries in both samples and a review of the geometry of natural and experimental multilayer folds leads to the conclusion that folding involves conjugate shearing at different scales. At microscopic scales, crenulation cleavages nucleate as conjugate-kink or shear instabilities and develop further as a function of the macroscopic partitioning of deformation. In fold-hinge domains, bulk-coaxial deformation results in equal development of conjugate crenulations that progressively coalescence into symmetrical crenulation patterns so that, macroscopically, parallelism is achieved between foliation, fold-axial planes and long axes of strain ellipses. Fold-limb domains represent a system of conjugate-shear zones where single sets of crenulation instabilities with synthetic shearing component preferentially develop producing oblique relationships between the aforementioned elements. Cleavage fanning is inferred as a direct consequence of this conjugate-shear origin of folds. The model implies that crenulation cleavages and S-C fabrics in shear zones form by analogous processes, in both cases involving a component of shearing along foliation planes. The development of conjugate sets of foliation planes surrounding porphyroblasts during early, relatively coaxial stages of deformation explains continued "gyrostatic" behaviour during more advanced non-coaxial stages, as indicated by consistently oriented inclusion trails in the studied samples.

  11. Folding of a single polygrain layer

    NASA Astrophysics Data System (ADS)

    Adamuszek, Marta; Dabrowski, Marcin

    2013-04-01

    Shortening of a mechanically layered rock in the direction parallel to the layering leads to the formation of buckle folds. Simultaneously, the rock microstructure undergoes modification due to changes in geometry and arrangement of the minerals leading to the development of the shape preferred orientation (SPO) and mechanical anisotropy. The progressive deformation influences the effective mechanical properties, which may affect the evolution of the folds. The mechanical anisotropy is considered to have a first-order effect on the fold growth, thus its evolution is potentially a crucial factor in folding process. In contrast to the previous studies, where the anisotropy is often considered as a prescribed (or inherited) property, we treat the anisotropy as a parameter that develops and evolves during deformation. In our numerical model, we study a polygrain, two-phase medium consisting of an effectively strong layer embedded in a weaker matrix. Both the layer and the matrix comprise the same material types but in different proportions. The layer and the matrix are initially mechanically isotropic. The viscosity of individual grains is isotropic, thus the role of the crystallographic orientation is not taken into account. The recrystallization and pressure solution processes are neglected. We investigate the influence of 1) the viscosity ratio between the mineral phases and 2) the effective viscosity ratio between the layer and the matrix on the development and evolution of anisotropy and folding. The complex, polygrain structure is represented using Voronoi polygons, which are then discretized with an unstructured mesh using Triangle software developed by Shewchuk (2007) and then used for the finite element approximations. We solve the incompressible Stokes equations under zero gravity using the finite element method (FEM) solver MILAMIN (Dabrowski et al., 2008). The normal components of the velocity vectors are prescribed at the boundaries according to a pure

  12. 4 CFR 2.3 - GAO Personnel Appeals Board.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 4 Accounts 1 2011-01-01 2011-01-01 false GAO Personnel Appeals Board. 2.3 Section 2.3 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM PURPOSE AND GENERAL PROVISION § 2.3 GAO Personnel Appeals Board. The Government Accountability Office Personnel Appeals Board is established by 31 U.S.C....

  13. 4 CFR 2.3 - GAO Personnel Appeals Board.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false GAO Personnel Appeals Board. 2.3 Section 2.3 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM PURPOSE AND GENERAL PROVISION § 2.3 GAO Personnel Appeals Board. The Government Accountability Office Personnel Appeals Board is established by 31 U.S.C....

  14. 43 CFR 3107.2-3 - Leases capable of production.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Leases capable of production. 3107.2-3 Section 3107.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL AND GAS LEASING Continuation, Extension or Renewal § 3107.2-3 Leases capable...

  15. 43 CFR 2920.2-3 - Other land use proposals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Other land use proposals. 2920.2-3 Section 2920.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND..., Permits and Easements: General Provisions § 2920.2-3 Other land use proposals. (a) A proposal for a...

  16. 43 CFR 2920.2-3 - Other land use proposals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Other land use proposals. 2920.2-3 Section 2920.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND..., Permits and Easements: General Provisions § 2920.2-3 Other land use proposals. (a) A proposal for a...

  17. 43 CFR 2920.2-3 - Other land use proposals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Other land use proposals. 2920.2-3 Section 2920.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND..., Permits and Easements: General Provisions § 2920.2-3 Other land use proposals. (a) A proposal for a...

  18. 43 CFR 2920.2-3 - Other land use proposals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Other land use proposals. 2920.2-3 Section 2920.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND..., Permits and Easements: General Provisions § 2920.2-3 Other land use proposals. (a) A proposal for a...

  19. 22 CFR 2.3 - Notification of foreign officials.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Notification of foreign officials. 2.3 Section 2.3 Foreign Relations DEPARTMENT OF STATE GENERAL PROTECTION OF FOREIGN DIGNITARIES AND OTHER OFFICIAL PERSONNEL § 2.3 Notification of foreign officials. (a) Any notification of a foreign official...

  20. 10 CFR 960.5-2-3 - Meteorology.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Meteorology. 960.5-2-3 Section 960.5-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Preclosure Radiological Safety § 960.5-2-3 Meteorology. (a)...

  1. 10 CFR 960.5-2-3 - Meteorology.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Meteorology. 960.5-2-3 Section 960.5-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Preclosure Radiological Safety § 960.5-2-3 Meteorology. (a)...

  2. 10 CFR 960.5-2-3 - Meteorology.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Meteorology. 960.5-2-3 Section 960.5-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Preclosure Radiological Safety § 960.5-2-3 Meteorology. (a)...

  3. 10 CFR 960.5-2-3 - Meteorology.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Meteorology. 960.5-2-3 Section 960.5-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Preclosure Radiological Safety § 960.5-2-3 Meteorology. (a)...

  4. 10 CFR 960.5-2-3 - Meteorology.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Meteorology. 960.5-2-3 Section 960.5-2-3 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Preclosure Guidelines Preclosure Radiological Safety § 960.5-2-3 Meteorology. (a)...

  5. 17 CFR 2.3 - Prohibitions against misuse of seal.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... seal. 2.3 Section 2.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION OFFICIAL SEAL § 2.3 Prohibitions against misuse of seal. (a) Fraudulently or wrongfully affixing or impressing the Seal to or upon any certificate, instrument, document or paper or with knowledge of its...

  6. 17 CFR 2.3 - Prohibitions against misuse of seal.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... seal. 2.3 Section 2.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION OFFICIAL SEAL § 2.3 Prohibitions against misuse of seal. (a) Fraudulently or wrongfully affixing or impressing the Seal to or upon any certificate, instrument, document or paper or with knowledge of its...

  7. 17 CFR 2.3 - Prohibitions against misuse of seal.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... seal. 2.3 Section 2.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION OFFICIAL SEAL § 2.3 Prohibitions against misuse of seal. (a) Fraudulently or wrongfully affixing or impressing the Seal to or upon any certificate, instrument, document or paper or with knowledge of its...

  8. 17 CFR 2.3 - Prohibitions against misuse of seal.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... seal. 2.3 Section 2.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION OFFICIAL SEAL § 2.3 Prohibitions against misuse of seal. (a) Fraudulently or wrongfully affixing or impressing the Seal to or upon any certificate, instrument, document or paper or with knowledge of its...

  9. 17 CFR 2.3 - Prohibitions against misuse of seal.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... seal. 2.3 Section 2.3 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION OFFICIAL SEAL § 2.3 Prohibitions against misuse of seal. (a) Fraudulently or wrongfully affixing or impressing the Seal to or upon any certificate, instrument, document or paper or with knowledge of its...

  10. 28 CFR 2.3 - Same: Narcotic Addict Rehabilitation Act.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Same: Narcotic Addict Rehabilitation Act. 2.3 Section 2.3 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND... § 2.3 Same: Narcotic Addict Rehabilitation Act. A Federal prisoner committed under the Narcotic...

  11. 28 CFR 2.3 - Same: Narcotic Addict Rehabilitation Act.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Same: Narcotic Addict Rehabilitation Act. 2.3 Section 2.3 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND... § 2.3 Same: Narcotic Addict Rehabilitation Act. A Federal prisoner committed under the Narcotic...

  12. 28 CFR 2.3 - Same: Narcotic Addict Rehabilitation Act.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Same: Narcotic Addict Rehabilitation Act. 2.3 Section 2.3 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND... § 2.3 Same: Narcotic Addict Rehabilitation Act. A Federal prisoner committed under the Narcotic...

  13. 28 CFR 2.3 - Same: Narcotic Addict Rehabilitation Act.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Same: Narcotic Addict Rehabilitation Act. 2.3 Section 2.3 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND... § 2.3 Same: Narcotic Addict Rehabilitation Act. A Federal prisoner committed under the Narcotic...

  14. 28 CFR 2.3 - Same: Narcotic Addict Rehabilitation Act.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Same: Narcotic Addict Rehabilitation Act. 2.3 Section 2.3 Judicial Administration DEPARTMENT OF JUSTICE PAROLE, RELEASE, SUPERVISION AND... § 2.3 Same: Narcotic Addict Rehabilitation Act. A Federal prisoner committed under the Narcotic...

  15. 4 CFR 2.3 - GAO Personnel Appeals Board.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 4 Accounts 1 2012-01-01 2012-01-01 false GAO Personnel Appeals Board. 2.3 Section 2.3 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM PURPOSE AND GENERAL PROVISION § 2.3 GAO Personnel Appeals Board. The Government Accountability Office Personnel Appeals Board is established by 31 U.S.C....

  16. 16 CFR 2.3 - Policy as to private controversies.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Policy as to private controversies. 2.3 Section 2.3 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE NONADJUDICATIVE PROCEDURES Inquiries; Investigations; Compulsory Processes § 2.3 Policy as to...

  17. 43 CFR 8365.2-3 - Occupancy and use.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Occupancy and use. 8365.2-3 Section 8365.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RECREATION PROGRAMS VISITOR SERVICES Rules of Conduct § 8365.2-3 Occupancy and...

  18. 43 CFR 8365.2-3 - Occupancy and use.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Occupancy and use. 8365.2-3 Section 8365.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RECREATION PROGRAMS VISITOR SERVICES Rules of Conduct § 8365.2-3 Occupancy and...

  19. Folding of β-barrel membrane proteins in lipid bilayers - Unassisted and assisted folding and insertion.

    PubMed

    Kleinschmidt, Jörg H

    2015-09-01

    In cells, β-barrel membrane proteins are transported in unfolded form to an outer membrane into which they fold and insert. Model systems have been established to investigate the mechanisms of insertion and folding of these versatile proteins into detergent micelles, lipid bilayers and even synthetic amphipathic polymers. In these experiments, insertion into lipid membranes is initiated from unfolded forms that do not display residual β-sheet secondary structure. These studies therefore have allowed the investigation of membrane protein folding and insertion in great detail. Folding of β-barrel membrane proteins into lipid bilayers has been monitored from unfolded forms by dilution of chaotropic denaturants that keep the protein unfolded as well as from unfolded forms present in complexes with molecular chaperones from cells. This review is aimed to provide an overview of the principles and mechanisms observed for the folding of β-barrel transmembrane proteins into lipid bilayers, the importance of lipid-protein interactions and the function of molecular chaperones and folding assistants. This article is part of a Special Issue entitled: Lipid-protein interactions. PMID:25983306

  20. Influence of surface processes and initial topography on lateral fold growth and fold linkage mode

    NASA Astrophysics Data System (ADS)

    Collignon, M.; Fernandez, N.; Kaus, B. J. P.

    2015-08-01

    Elongation of randomly distributed fold segments and their potential linkage are important for hydrocarbon exploration because it can greatly influence the morphology of the reservoir and both migration and accumulation of hydrocarbons in antiformal traps. Here we study the effects of surface processes and the presence of a topographic slope on the different linkage modes that can occur, and how these parameters affect the required horizontal offset for perturbations to link. The proposed numerical model represents a sedimentary cover detached over a much weaker basal décollement layer. The upper surface is modified by mass redistribution, which is achieved by a combination of fluvial and hillslope processes. Several series of simulations were performed: (1) without surface processes or regional slope, (2) with regional slope only, (3) with fluvial incision and hillslope processes, and (4) with hillslope processes only. Model results show that the presence of a regional slope reduces the critical distance required for the transition between linkage and no linkage modes, whereas erosion and redeposition of sediments, on the contrary, increase this distance. The location of the saddle point, where fold segments link, and its vertical distance to the crests of the anticlines are different compared to the case without erosion or initial topographic slope, which potentially can affect the morphology of hydrocarbon traps. Moreover, both erosion and redeposition of sediments enhance the fold elongation (growth along the fold axis), once the erosion velocity exceeds the folding velocity. Model results have been compared to the Zagros Fold Belt.

  1. Mechanical Regulation of Three-Dimensional Epithelial Fold Pattern Formation in the Mouse Oviduct.

    PubMed

    Koyama, Hiroshi; Shi, Dongbo; Suzuki, Makoto; Ueno, Naoto; Uemura, Tadashi; Fujimori, Toshihiko

    2016-08-01

    Epithelia exhibit various three-dimensional morphologies linked to organ function in animals. However, the mechanisms of three-dimensional morphogenesis remain elusive. The luminal epithelium of the mouse oviduct forms well-aligned straight folds along the longitudinal direction of the tubes. Disruption of the Celsr1 gene, a planar cell polarity-related gene, causes ectopically branched folds. Here, we evaluated the mechanical contributions of the epithelium to the fold pattern formation. In the mutant oviduct, the epithelium was more intricate along the longitudinal direction than in the wild-type, suggesting a higher ratio of the longitudinal length of the epithelial layer to that of the surrounding smooth muscle (SM) layer (L-Epi/SM ratio). Our mathematical modeling and computational simulations suggested that the L-Epi/SM ratio could explain the differences in fold branching between the two genotypes. Longitudinal epithelial tensions were increased in well-aligned folds compared with those in disorganized folds both in the simulations and in experimental estimations. Artificially increasing the epithelial tensions suppressed the branching in simulations, suggesting that the epithelial tensions can regulate fold patterning. The epithelial tensions could be explained by the combination of line tensions along the epithelial cell-cell boundaries with the polarized cell arrays observed in vivo. These results suggest that the fold pattern is associated with the polarized cell array through the longitudinal epithelial tension. Further simulations indicated that the L-Epi/SM ratio could contribute to fold pattern diversity, suggesting that the L-Epi/SM ratio is a critical parameter in the fold patterning in tubular organs. PMID:27508448

  2. Mechanical restoration of large-scale folded multilayers using the finite element method: Application to the Zagros Simply Folded Belt, N-Iraq

    NASA Astrophysics Data System (ADS)

    Frehner, Marcel; Reif, Daniel; Grasemann, Bernhard

    2010-05-01

    and digital elevation models using the dip-domain method for balancing the cross-section. The lithology consists of Cretaceous to Cenozoic sediments. Massive carbonate rock units act as the competent layers compared to the incompetent behavior of siltstone, claystone and marl layers. We show the first results of the mechanical restoration of the Zagros cross-section and we discuss advantages and disadvantages, as well as some technical aspects of the applied method. First results indicate that a shortening of at least 50% was necessary to create the present-day folded cross-section. This value is higher than estimates of the amount of shortening solely based on kinematic or geometric restoration. One particular problem that is discussed is the presence of (unnaturally) sharp edges in a balanced cross-section produced using the dip-domain method, which need to be eliminated for mechanical restoration calculations to get reasonable results.

  3. Deep crustal structures of the Cape Fold Belt, South Africa

    NASA Astrophysics Data System (ADS)

    Weckmann, U.; Ritter, O.; Chen, X.; Tietze, K.; de Wit, M.

    2010-12-01

    Magnetotelluric (MT) soundings along a 100 km segment of the Inkaba yeAfrica Agulhas-Karoo transect through the Cape Fold Belt, South Africa, yield its first electrical conductivity image on a crustal scale. The Cape Fold Belt (CFB) plays an important role to understand the inversion tectonic setting within the accretionary history along the paleo-pacific margin of Gondwana. The MT profile crosses the Swartberg and Outeniqua (Langeberg) mountain ranges, as well as the Oudtshoorn Basin and the Kango and Kaaimans tectonic inliers. Two-dimensional (2D) inversion models of the MT data show generally good correlation with surface geology. We resolve the resistive roots of the both mountain ranges, to depths of approximately 5 and 10 km, respectively. By contrast, the adjacent Kango and Kaaimans inliers are imaged as shallow wedges partly overlain by sediments of the Oudtshoorn Basin and the Pletmos Basin, respectively. The Kango fault has a shallow southward dip, in contrast to more sub-vertical structures south of the Oudtshoorn basin. Based on the conductivity section we estimate the thickness of the Oudtshoorn basin to 2-3 km. A massive conductivity anomaly at a depth of 3-4 km is located in a synclinorium between the anticlinoria of Table Mountain Group rocks in the Swartberg and Outeniqua ranges. From the conductivity image alone we can neither confirm nor rule out the existence of a mega-detachment in the middle crust, as previously suggested. However, if the Kango Fault is rooted in a detachment zone, it is at upper crustal levels.

  4. Representations of the POINCARÉ Group from Positive Energy Representations of SO(2,3)

    NASA Astrophysics Data System (ADS)

    Moylan, P.

    2004-10-01

    We describe representations of the simply connected covering group of the Poincaré group, {˜ {B}}, which are associated with certain positive energy representations of SO0(2, 3), the simply connected cover of SO0(2, 3). The translation generators of these representations of {˜ {B}} can be viewed as solutions of certain algebraic equations with coefficients from a commutative algebraic extension of the skew field of {˜ {B}}. These representations of {˜ {B}} depend upon a parameter λ that is essentially the reciprocal of the radius of anti-deSitter space, and they go over into the Segal-Inönü-Wigner contractions of the corresponding representations of SO0(2, 3) as λ → 0. Explicit results are given for the Di and Rac representations and the representations of SO0(2, 3) which extend to massless, unitary irreducible representations of SU(2, 2), the four-fold cover of the conformal group of Minkowski space-time.

  5. Structure of the catalytic domain of the hepatitis C virus NS2-3 protease

    SciTech Connect

    Lorenz,I.; Marcotrigiano, J.; Dentzer, T.; Rice, C.

    2006-01-01

    Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 Angstroms resolution. The structure reveals a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design.

  6. Spectroscopic identification of higher-order rare gas-dihalogen complexes with different geometries: He(2,3)...Br(2) and He(2,3)...ICl.

    PubMed

    Boucher, David S; Darr, Joshua P; Strasfeld, David B; Loomis, Richard A

    2008-12-25

    Rovibronic transitions of multiple conformers of the He(2)...(79)Br(2)(X, v'' = 0), He(3)...(79)Br(2)(X, v'' = 0), He(2)...I(35)Cl(X, v'' = 0), and He(3)...I(35)Cl(X, v'' = 0) complexes stabilized in a pulsed, supersonic expansion are observed in action spectra recorded in the B-X region of the dihalogens. In addition to features associated with He(2)...(79)Br(2) and He(2)...I(35)Cl complexes with the rare gas atoms localized in the toroidal potential well lying in a plane perpendicular to the dihalogen bond, those associated with a ground-state conformer that has one He atom localized in the toroidal potential and the other He atom localized in the linear well at the end of the dihalogen moiety are also identified. Transitions of at least three conformers of the He(3)...Br(2) complex and two conformers of the He(3)...ICl complex are also observed. The relative populations of the different conformers are found to depend on where along the supersonic expansion the spectra are recorded, and thus on the local temperature regime sampled. The He(2)...(79)Br(2) and He(2)...I(35)Cl conformers with one He atom in each well are found to be the more stable conformers. PMID:19053811

  7. Fault-related fold styles and progressions in fold-thrust belts: Insights from sandbox modeling

    NASA Astrophysics Data System (ADS)

    Yan, Dan-Ping; Xu, Yan-Bo; Dong, Zhou-Bin; Qiu, Liang; Zhang, Sen; Wells, Michael

    2016-03-01

    Fault-related folds of variable structural styles and assemblages commonly coexist in orogenic belts with competent-incompetent interlayered sequences. Despite their commonality, the kinematic evolution of these structural styles and assemblages are often loosely constrained because multiple solutions exist in their structural progression during tectonic restoration. We use a sandbox modeling instrument with a particle image velocimetry monitor to test four designed sandbox models with multilayer competent-incompetent materials. Test results reveal that decollement folds initiate along selected incompetent layers with decreasing velocity difference and constant vorticity difference between the hanging wall and footwall of the initial fault tips. The decollement folds are progressively converted to fault-propagation folds and fault-bend folds through development of fault ramps breaking across competent layers and are followed by propagation into fault flats within an upper incompetent layer. Thick-skinned thrust is produced by initiating a decollement fault within the metamorphic basement. Progressive thrusting and uplifting of the thick-skinned thrust trigger initiation of the uppermost incompetent decollement with formation of a decollement fold and subsequent converting to fault-propagation and fault-bend folds, which combine together to form imbricate thrust. Breakouts at the base of the early formed fault ramps along the lowest incompetent layers, which may correspond to basement-cover contacts, domes the upmost decollement and imbricate thrusts to form passive roof duplexes and constitute the thin-skinned thrust belt. Structural styles and assemblages in each of tectonic stages are similar to that in the representative orogenic belts in the South China, Southern Appalachians, and Alpine orogenic belts.

  8. The role of ascorbate in protein folding.

    PubMed

    Szarka, András; Lőrincz, Tamás

    2014-05-01

    Ascorbate was linked to protein folding a long time ago. At the first level of this connection, it had been shown that ascorbate functions as an essential cofactor in the hydroxylation enzymes involved in collagen synthesis. Although the hydroxylation reactions catalyzed by the members of the prolyl 4-hydroxylase family are considered to be ascorbate dependent, the hydroxylation of proline alone does not need ascorbate. Prolyl 4-hydroxylases participate in two catalytic reactions: one in which proline residues are hydroxylated, while 2-oxoglutarate is decarboxylated and molecular oxygen is consumed. This reaction is ascorbate independent. However, in another reaction, prolyl 4-hydroxylases catalyze the decarboxylation of 2-oxoglutarate uncoupled from proline hydroxylation but still needing molecular oxygen. At this time, ferrous iron is oxidized and the protein is rendered catalytically inactive until reduced by ascorbate. At the second level of the connection, the oxidation and the oxidized form of ascorbate, dehydroascorbate, is involved in the formation of disulfide bonds of secretory proteins. The significance of the dehydroascorbate reductase activity of protein disulfide isomerase was debated because protein disulfide isomerase as a dehydroascorbate reductase was found to be too slow to be the major route for the reduction of dehydroascorbate (and formation of disulfides) in the endoplasmic reticulum lumen. However, very recently, low tissue ascorbate levels and a noncanonical scurvy were observed in endoplasmic reticulum thiol oxidase- and peroxiredoxin 4-compromised mice. This novel observation implies that ascorbate may be involved in oxidative protein folding and creates a link between the disulfide bond formation (oxidative protein folding) and hydroxylation. PMID:24150425

  9. An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals

    PubMed Central

    Toda, Tomohisa; Shinmyo, Yohei; Dinh Duong, Tung Anh; Masuda, Kosuke; Kawasaki, Hiroshi

    2016-01-01

    Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain. PMID:27403992

  10. An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals.

    PubMed

    Toda, Tomohisa; Shinmyo, Yohei; Dinh Duong, Tung Anh; Masuda, Kosuke; Kawasaki, Hiroshi

    2016-01-01

    Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain. PMID:27403992

  11. Enhanced production of (R,R)-2,3-butanediol by metabolically engineered Klebsiella oxytoca.

    PubMed

    Park, Jong Myoung; Rathnasingh, Chelladurai; Song, Hyohak

    2015-10-01

    Microbial fermentation produces a racemic mixture of 2,3-butanediol ((R,R)-BD, (S,S)-BD, and meso-BD), and the compositions and physiochemical properties vary from microorganism to microorganism. Although the meso form is much more difficult to transport and store because of its higher freezing point than those of the optically active forms, most microorganisms capable of producing 2,3-BD mainly yield meso-2,3-BD. Thus, we developed a metabolically engineered (R,R)-2,3-BD overproducing strain using a Klebsiella oxytoca ΔldhA ΔpflB strain, which shows an outstanding 2,3-BD production performance with more than 90 % of the meso form. A budC gene encoding 2,3-BD dehydrogenase in the K. oxytoca ΔldhA ΔpflB strain was replaced with an exogenous gene encoding (R,R)-2,3-BD dehydrogenase from Paenibacillus polymyxa (K. oxytoca ΔldhA ΔpflB ΔbudC::PBDH strain), and then its expression level was further amplified with using a pBBR1MCS plasmid. The fed-batch fermentation of the K. oxytoca ΔldhA ΔpflB ΔbudC::PBDH (pBBR-PBDH) strain with intermittent glucose feeding allowed the production of 106.7 g/L of (R,R)-2,3-BD [meso-2,3-BD, 9.3 g/L], with a yield of 0.40 g/g and a productivity of 3.1 g/L/h, which should be useful for the industrial application of 2,3-BD. PMID:26275527

  12. Protein-facilitated ribozyme folding and catalysis.

    PubMed

    Zingler, Nora; Solem, Amanda; Pyle, Anna Marie

    2008-01-01

    In vivo, large RNAs rely on proteins to fold to their native conformation. In the case of the S. cerevisiae group II intron ai5 gamma, the DEAD-box protein Mss116 has been shown to promote the formation of the catalytically active structure. However, it is a matter of debate whether it does this by stabilizing on-pathway intermediates or by disrupting misfolded structures. Here we present the available experimental evidence to distinguish between those mechanisms and discuss the possible interpretations. PMID:18776256

  13. Foldons as independently folding units of proteins

    NASA Astrophysics Data System (ADS)

    Panchenko, Anna R.; Luthey-Schulten, Zaida; Wolynes, Peter G.

    1997-02-01

    Independently folding units of proteins, foldons, have been identified by maxima in a scan of the ratio of an energetic stability gap to the energy variance of that segment's molten globule states, reflecting the requirement of minimal frustration. Foldon boundaries, unlike structural domains, depend on the sequence of the protein. Therefore, domains defined by purely structural criteria and the foldons of a given protein may differ in size and structure. The predicted foldons have been compared to the exons and structural modules. Statistical analysis indicates a strong correlation between the energetically determined foldons and Go's geometrically defined structural modules. There is only a weak correlation of foldons to exons.

  14. Folding of the hammerhead ribozyme: Pyrrolo-cytosine fluorescence separates core folding from global folding and reveals a pH-dependent conformational change

    PubMed Central

    Buskiewicz, Iwona A.; Burke, John M.

    2012-01-01

    The catalytic activity of the hammerhead ribozyme is limited by its ability to fold into the native tertiary structure. Analysis of folding has been hampered by a lack of assays that can independently monitor the environment of nucleobases throughout the ribozyme–substrate complex in real time. Here, we report the development and application of a new folding assay in which we use pyrrolo-cytosine (pyC) fluorescence to (1) probe active-site formation, (2) examine the ability of peripheral ribozyme domains to support native folding, (3) identify a pH-dependent conformational change within the ribozyme, and (4) explore its influence on the equilibrium between the folded and unfolded core of the hammerhead ribozyme. We conclude that the natural ribozyme folds in two distinct noncooperative steps and the pH-dependent correlation between core folding and activity is linked to formation of the G8-C3 base pair. PMID:22274955

  15. Structure of a Folding Intermediate Reveals the Interplay Between Core and Peripheral Elements in RNA Folding

    SciTech Connect

    Baird, Nathan J.; Westhof, Eric; Qin, Hong; Pan, Tao; Sosnick, Tobin R.

    2010-07-13

    Though the molecular architecture of many native RNA structures has been characterized, the structures of folding intermediates are poorly defined. Here, we present a nucleotide-level model of a highly structured equilibrium folding intermediate of the specificity domain of the Bacillus subtilis RNase P RNA, obtained using chemical and nuclease mapping, circular dichroism spectroscopy, small-angle X-ray scattering and molecular modeling. The crystal structure indicates that the 154 nucleotide specificity domain is composed of several secondary and tertiary structural modules. The structure of the intermediate contains modules composed of secondary structures and short-range tertiary interactions, implying a sequential order of tertiary structure formation during folding. The intermediate lacks the native core and several long-range interactions among peripheral regions, such as a GAAA tetraloop and its receptor. Folding to the native structure requires the local rearrangement of a T-loop in the core in concert with the formation of the GAAA tetraloop-receptor interaction. The interplay of core and peripheral structure formation rationalizes the high degree of cooperativity observed in the folding transition leading to the native structure.

  16. Scaled-up in vitro experiments of vocal fold paralysis

    NASA Astrophysics Data System (ADS)

    Peterson, Keith; Wei, Timothy; Krane, Michael

    2006-11-01

    Vocal fold paralysis is the inability of either one, or both vocal folds to open and close properly. Digital Particle Image Velocimetry (DPIV) measurements were taken to further understand the consequences paralyzed vocal folds have on the fluid dynamics downstream of the vocal folds during human phonation. The experiments were taken in a free-stream water tunnel using a simplified scaled-up model of human vocal folds. The Reynolds and Strouhal numbers ranged from 4500 to 10000, and 0.01 to 0.04, respectively. Various configuration setups were tested to emulate several types of vocal fold paralyses. These configurations include unilateral vocal fold immobility (UVFI), bilateral vocal fold immobility (BVFI) and the vocal folds operating at different oscillating frequencies. Data from these different conditions will be compared with an eye toward understanding the critical dynamics associated with this class of disease.

  17. The folding of knotted proteins: insights from lattice simulations.

    PubMed

    Faísca, Patrícia F N; Travasso, Rui D M; Charters, Tiago; Nunes, Ana; Cieplak, Marek

    2010-01-01

    We carry out systematic Monte Carlo simulations of Gō lattice proteins to investigate and compare the folding processes of two model proteins whose native structures differ from each other due to the presence of a trefoil knot located near the terminus of one of the protein chains. We show that the folding time of the knotted fold is larger than that of the unknotted protein and that this difference in folding time is particularly striking in the temperature region below the optimal folding temperature. Both proteins display similar folding transition temperatures, which is indicative of similar thermal stabilities. By using the folding probability reaction coordinate as an estimator of folding progression we have found out that the formation of the knot is mainly a late folding event in our shallow knot system. PMID:20130340

  18. The folding of knotted proteins: insights from lattice simulations

    NASA Astrophysics Data System (ADS)

    Faísca, Patrícia F. N.; Travasso, Rui D. M.; Charters, Tiago; Nunes, Ana; Cieplak, Marek

    2010-03-01

    We carry out systematic Monte Carlo simulations of Gō lattice proteins to investigate and compare the folding processes of two model proteins whose native structures differ from each other due to the presence of a trefoil knot located near the terminus of one of the protein chains. We show that the folding time of the knotted fold is larger than that of the unknotted protein and that this difference in folding time is particularly striking in the temperature region below the optimal folding temperature. Both proteins display similar folding transition temperatures, which is indicative of similar thermal stabilities. By using the folding probability reaction coordinate as an estimator of folding progression we have found out that the formation of the knot is mainly a late folding event in our shallow knot system.

  19. Equation to Line the Borders of the Folding-Unfolding Transition Diagram of Lysozyme.

    PubMed

    Mohammad, Mohammad Amin; Grimsey, Ian M; Forbes, Robert T

    2016-07-21

    It is important for the formulators of biopharmaceuticals to predict the folding-unfolding transition of proteins. This enables them to process proteins under predetermined conditions, without denaturation. Depending on the apparent denaturation temperature (Tm) of lysozyme, we have derived an equation describing its folding-unfolding transition diagram. According to the water content and temperature, this diagram was divided into three different areas, namely, the area of the water-folded lysozyme phase, the area of the water-folded lysozyme phase and the bulk water phase, and the area of the denatured lysozyme phase. The water content controlled the appearance and intensity of the Raman band at ∼1787 cm(-1) when lysozyme powders were thermally denatured at temperatures higher than Tm. PMID:27341101

  20. Mesozoic folds, fossil fields, and future finds ( )

    SciTech Connect

    Newman, G.W.; Witter, G.G.

    1988-02-01

    Drilling and surface geologic mapping have shown that pre-Tertiary, post-Triassic folds and upthrusted anticlines in an eastern Nevada fold-belt have accumulated major oil columns. This Mesozoic foldbelt involves a Cambrian through Triassic section, which has hundreds of feet of porosity in Ordovician sandstones, Silurian and Devonian carbonates, and Mississippian sandstones. In addition to the Devonian Pilot and Mississippian Chainman shales, source rocks are found in Cambrian and Ordovician shales and in some Paleozoic carbonates. The occurrence of live and dead oil shows in hundreds of vertical feet of porosity in wells drilled on several of these Mesozoic structures is interpreted as evidence that these structures were giant oil fields prior to being breached by Tertiary Basin and Range extensional faulting, which allowed vertical hydrocarbon leakage. Noting that undrilled Mesozoic structures still exist in the foldbelt and noting that natural processes are seldom 100% efficient - including, probably, the disruptive effects of Basin and range extensional faulting - the authors suggest that there is a very good chance of finding one or more giant fields in the remaining structures of this foldbelt.

  1. The folding landscape of the epigenome

    NASA Astrophysics Data System (ADS)

    Olarte-Plata, Juan D.; Haddad, Noelle; Vaillant, Cédric; Jost, Daniel

    2016-04-01

    The role of the spatial organization of chromatin in gene regulation is a long-standing but still open question. Experimentally it has been shown that the genome is segmented into epigenomic chromatin domains that are organized into hierarchical sub-nuclear spatial compartments. However, whether this non-random spatial organization only reflects or indeed contributes—and how—to the regulation of genome function remains to be elucidated. To address this question, we recently proposed a quantitative description of the folding properties of the fly genome as a function of its epigenomic landscape using a polymer model with epigenomic-driven attractions. We propose in this article, to characterize more deeply the physical properties of the 3D epigenome folding. Using an efficient lattice version of the original block copolymer model, we study the structural and dynamical properties of chromatin and show that the size of epigenomic domains and asymmetries in sizes and in interaction strengths play a critical role in the chromatin organization. Finally, we discuss the biological implications of our findings. In particular, our predictions are quantitatively compatible with experimental data and suggest a different mean of self-interaction in euchromatin versus heterochromatin domains.

  2. Fungal infections of the folds (intertriginous areas).

    PubMed

    Metin, Ahmet; Dilek, Nursel; Demirseven, Duriye Deniz

    2015-01-01

    Superficial fungal infections are widespread, regardless of age and gender, in populations all around the world and may affect the skin and skin appendages. Although there are thousands of fungal infections from various genera and families in nature, those that are pathogenic for humans and nesting in skin folds are limited in number. The prevalence and distribution of these fungi vary according to the patients and certain environmental factors. Because the areas including the lids, external auditory canal, behind the ears, navel, inguinal region, and axillae, also called flexures, are underventilated and moist areas exposed to friction, they are especially sensitive to fungal infections. Fungi can both directly invade the skin, leading to infections, and indirectly stimulate immune mechanisms due to tissue interaction and their antigenic character and contribute to the development or exacerbation of secondary bacterial infections, seborrheic dermatitis, atopic dermatitis, and psoriasis. Superficial fungal infections can be classified and studied as dermatophyte infections, candidal infections, Malassezia infections, and other superficial infections independently from the involved skin fold areas. PMID:26051058

  3. 2,3-Dideoxyglucosides of selected terpene phenols and alcohols as potent antifungal compounds.

    PubMed

    James Bound, D; Murthy, Pushpa S; Srinivas, P

    2016-11-01

    The antifungal activities of novel 2,3-unsaturated and 2,3-dideoxy 1-O-glucosides of carvacrol, thymol, and perillyl alcohol were tested against Aspergillus flavus, Aspergillus ochraceus, Fusarium oxysporum, Saccharomyces cerevisiae and Candida albicans. In the agar well diffusion tests, zones of inhibition for the derivatives of carvacrol, thymol and perillyl alcohol were higher (15-30mm) in the case of filamentous fungi than those for the parent compounds. Their MIC and MFC values indicated that the 2,3-unsaturated and 2,3-dideoxy 1-O-glucosides of carvacrol and thymol exhibited more fungicidal activity than the other compounds. Further, the 2,3-dideoxyglucosides of carvacrol and thymol, exhibited antitoxigenic effects against A. ochraceus and A. flavus and inhibited the production of ochratoxin and aflatoxin-B2. Propidium iodide influx assay demonstrated the lysis of C. albicans cells by carvacrol and its 2,3-unsaturated 1-O-glucoside and the loss of the membrane integrity. These new 2,3-dideoxyglucosides can be useful as antifungal agents and condiments in foods. PMID:27211660

  4. Identification of Selective Inhibitors of the Potassium Channel Kv1.1–1.2(3) by High-Throughput Virtual Screening and Automated Patch Clamp

    PubMed Central

    Wacker, Sören J; Jurkowski, Wiktor; Simmons, Katie J; Fishwick, Colin W G; Johnson, A Peter; Madge, David; Lindahl, Erik; Rolland, Jean-Francois; de Groot, Bert L

    2012-01-01

    Abstract Two voltage-dependent potassium channels, Kv1.1 (KCNA1) and Kv1.2 (KCNA2), are found to co-localize at the juxtaparanodal region of axons throughout the nervous system and are known to co-assemble in heteromultimeric channels, most likely in the form of the concatemer Kv1.1–1.2(3). Loss of the myelin sheath, as is observed in multiple sclerosis, uncovers the juxtaparanodal region of nodes of Ranvier in myelinated axons leading to potassium conductance, resulting in loss of nerve conduction. The selective blocking of these Kv channels is therefore a promising approach to restore nerve conduction and function. In the present study, we searched for novel inhibitors of Kv1.1–1.2(3) by combining a virtual screening protocol and electrophysiological measurements on a concatemer Kv1.1–1.2(3) stably expressed in Chinese hamster ovary K1 (CHO-K1) cells. The combined use of four popular virtual screening approaches (eHiTS, FlexX, Glide, and Autodock-Vina) led to the identification of several compounds as potential inhibitors of the Kv1.1–1.2(3) channel. From 89 electrophysiologically evaluated compounds, 14 novel compounds were found to inhibit the current carried by Kv1.1–1.2(3) channels by more than 80 % at 10 μM. Accordingly, the IC50 values calculated from concentration–response curve titrations ranged from 0.6 to 6 μM. Two of these compounds exhibited at least 30-fold higher potency in inhibition of Kv1.1–1.2(3) than they showed in inhibition of a set of cardiac ion channels (hERG, Nav1.5, and Cav1.2), resulting in a profile of selectivity and cardiac safety. The results presented herein provide a promising basis for the development of novel selective ion channel inhibitors, with a dramatically lower demand in terms of experimental time, effort, and cost than a sole high-throughput screening approach of large compound libraries. PMID:22473914

  5. CoinFold: a web server for protein contact prediction and contact-assisted protein folding.

    PubMed

    Wang, Sheng; Li, Wei; Zhang, Renyu; Liu, Shiwang; Xu, Jinbo

    2016-07-01

    CoinFold (http://raptorx2.uchicago.edu/ContactMap/) is a web server for protein contact prediction and contact-assisted de novo structure prediction. CoinFold predicts contacts by integrating joint multi-family evolutionary coupling (EC) analysis and supervised machine learning. This joint EC analysis is unique in that it not only uses residue coevolution information in the target protein family, but also that in the related families which may have divergent sequences but similar folds. The supervised learning further improves contact prediction accuracy by making use of sequence profile, contact (distance) potential and other information. Finally, this server predicts tertiary structure of a sequence by feeding its predicted contacts and secondary structure to the CNS suite. Tested on the CASP and CAMEO targets, this server shows significant advantages over existing ones of similar category in both contact and tertiary structure prediction. PMID:27112569

  6. High power folded waveguide millimeter-wave gyro-TWT

    SciTech Connect

    Choi, J.J.; Ganguly, A.K.; Armstrong, C.M.

    1994-12-31

    Investigations on a periodic TE serpentine waveguide gyro-TWT are underway at NRL. A high power axis-encircling electron beam interacts with a fundamental TE waveguide mode when it passes through an oversized beam tunnel hole in the narrow wall of the H-plane bend rectangular serpentine waveguide. Potential advantages of the circuit configuration include: easy fabrication, fundamental forward space harmonic operation, large beam tunnel suitable for high power application, natural separation of beam and rf, and simplicity of coupling. To avoid bandwidth reduction due to closely spaced stop-bands and large gap detuning angle, a double rigid TE folded waveguide structure is proposed. To utilize the entire bandwidth, it is necessary to suppress gyro-BWO oscillation at the higher space harmonics. Linear theory predicts that oscillation takes place at {approximately} 7 cm near the stop-band frequency. Therefore, a multi-stage configuration is required to saturate the device without oscillations. An experiment is underway at NRL to verify the negative mass instability in both fast and slow wave regions in a transverse folded waveguide structure and to investigate the basic circuit stability characteristics. Design parameters of the amplifier, large signal simulations using a MAGIC code and cold-test results of the circuit components will be presented.

  7. Predictive energy landscapes for folding membrane protein assemblies

    NASA Astrophysics Data System (ADS)

    Truong, Ha H.; Kim, Bobby L.; Schafer, Nicholas P.; Wolynes, Peter G.

    2015-12-01

    We study the energy landscapes for membrane protein oligomerization using the Associative memory, Water mediated, Structure and Energy Model with an implicit membrane potential (AWSEM-membrane), a coarse-grained molecular dynamics model previously optimized under the assumption that the energy landscapes for folding α-helical membrane protein monomers are funneled once their native topology within the membrane is established. In this study we show that the AWSEM-membrane force field is able to sample near native binding interfaces of several oligomeric systems. By predicting candidate structures using simulated annealing, we further show that degeneracies in predicting structures of membrane protein monomers are generally resolved in the folding of the higher order assemblies as is the case in the assemblies of both nicotinic acetylcholine receptor and V-type Na+-ATPase dimers. The physics of the phenomenon resembles domain swapping, which is consistent with the landscape following the principle of minimal frustration. We revisit also the classic Khorana study of the reconstitution of bacteriorhodopsin from its fragments, which is the close analogue of the early Anfinsen experiment on globular proteins. Here, we show the retinal cofactor likely plays a major role in selecting the final functional assembly.

  8. Nonlinear theory of slow cyclotron wave interaction in folded waveguide

    SciTech Connect

    Ganguly, A.K.; Choi, J.J.

    1995-12-31

    A three-dimensional non-linear theory is presented for the generation of broadband radiation from slow cyclotron wave interaction in a folded waveguide. The serpentine structure is formed by folding a rectangular waveguide so that the orientation of the magnetic changes (H-plane bend) instead of the conventional E-plane bend configuration where the orientation of the electric field changes. The H-plane bend structure can use larger beam tunnel without distorting the rf field structure and generate higher output power. Numerical results will be shown for the TE{sub 10} mode propagation in an unridged and a double ridged waveguide. For a 61.5 kV, 3 A beam with {alpha}=1.0 and {Delta}v{sub z}/v{sub z}=0, calculations show an efficiency of 25% with 20% bandwidth and an efficiency of 35% at 10% bandwidth. The efficiency and bandwidth is relatively unchanged up to a beam axial velocity spread of 2%. The bandwidth can be further increased by mode coalescing techniques. Multistage operation is necessary to avoid backward wave oscillation.

  9. THE INFLUENCE OF FOLD AND FRACTURE DEVELOPMENT ON RESERVOIR BEHAVIOR OF THE LISBURNE GROUP OF NORTHERN ALASKA

    SciTech Connect

    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

  10. Synthesis and bioactivity of 2',3'-benzoabscisic acid analogs.

    PubMed

    Han, Xiaoqiang; Wan, Chuan; Li, Xiuyun; Li, Hong; Yang, Dongyan; Du, Shijie; Xiao, Yumei; Qin, Zhaohai

    2015-06-01

    2',3'-Benzoabscisic acid 4a is significantly more active than (±)-ABA and can be potentially used as a plant growth regulator for agriculture. In this study, six 4a analogs were designed and synthesized. Bioassay showed that 4a displayed greater activity than (±)-ABA and the six analogs produced less inhibition than 4a itself. Specially, some analogs displayed markedly different activities to different physiological and biochemical process, which were largely different from ABA and 4a. Compared to (±)-ABA, 4b and 4c were more effective germination inhibitors for lettuce, but less effective inhibitors for rice elongation. Five-membered analog 5 was higher or slightly weaker in inhibiting Arabidopsis seed germination and rice elongation, respectively, but at least 10 times less effective than (±)-ABA in lettuce seed germination. Dual acid 6 and alkyne acid 20 nearly produced no inhibitory activity for Arabidopsis seed germination, but displayed excellent activity in inhibiting rice seedling growth. The preference of the analogs to different physiology process indicated that they might provide a strategy to develop novel ABA agonists or antagonist and be used as probe to investigate the function of different ABA receptors. PMID:25913114

  11. Polymer Uncrossing and Knotting in Protein Folding, and Their Role in Minimal Folding Pathways

    PubMed Central

    Mohazab, Ali R.; Plotkin, Steven S.

    2013-01-01

    We introduce a method for calculating the extent to which chain non-crossing is important in the most efficient, optimal trajectories or pathways for a protein to fold. This involves recording all unphysical crossing events of a ghost chain, and calculating the minimal uncrossing cost that would have been required to avoid such events. A depth-first tree search algorithm is applied to find minimal transformations to fold , , , and knotted proteins. In all cases, the extra uncrossing/non-crossing distance is a small fraction of the total distance travelled by a ghost chain. Different structural classes may be distinguished by the amount of extra uncrossing distance, and the effectiveness of such discrimination is compared with other order parameters. It was seen that non-crossing distance over chain length provided the best discrimination between structural and kinetic classes. The scaling of non-crossing distance with chain length implies an inevitable crossover to entanglement-dominated folding mechanisms for sufficiently long chains. We further quantify the minimal folding pathways by collecting the sequence of uncrossing moves, which generally involve leg, loop, and elbow-like uncrossing moves, and rendering the collection of these moves over the unfolded ensemble as a multiple-transformation “alignment”. The consensus minimal pathway is constructed and shown schematically for representative cases of an , , and knotted protein. An overlap parameter is defined between pathways; we find that proteins have minimal overlap indicating diverse folding pathways, knotted proteins are highly constrained to follow a dominant pathway, and proteins are somewhere in between. Thus we have shown how topological chain constraints can induce dominant pathway mechanisms in protein folding. PMID:23365638

  12. Oral and vocal fold diadochokinesis in dysphonic women

    PubMed Central

    LOUZADA, Talita; BERALDINELLE, Roberta; BERRETIN-FELIX, Giédre; BRASOLOTTO, Alcione Ghedini

    2011-01-01

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

  13. Condensed phase preparation of 2,3-pentanedione

    DOEpatents

    Miller, Dennis J.; Perry, Scott M.; Fanson, Paul T.; Jackson, James E.

    1998-01-01

    A condensed phase process for the preparation of purified 2,3-pentanedione from lactic acid and an alkali metal lactate is described. The process uses elevated temperatures between about 200.degree. to 360.degree. C. for heating a reaction mixture of lactic acid and an alkali metal lactate to produce the 2,3-pentanedione in a reaction vessel. The 2,3-pentanedione produced is vaporized from the reaction vessel and condensed with water.

  14. Condensed phase preparation of 2,3-pentanedione

    DOEpatents

    Miller, D.J.; Perry, S.M.; Fanson, P.T.; Jackson, J.E.

    1998-11-03

    A condensed phase process for the preparation of purified 2,3-pentanedione from lactic acid and an alkali metal lactate is described. The process uses elevated temperatures between about 200 to 360 C for heating a reaction mixture of lactic acid and an alkali metal lactate to produce the 2,3-pentanedione in a reaction vessel. The 2,3-pentanedione produced is vaporized from the reaction vessel and condensed with water. 5 figs.

  15. 42 CFR 2.3 - Purpose and effect.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... criminal penalty (a fine—see 42 U.S.C. 290ee-3(f), 42 U.S.C. 290dd-3(f) and 42 CFR 2.4) for violating the... 42 Public Health 1 2011-10-01 2011-10-01 false Purpose and effect. 2.3 Section 2.3 Public Health... ALCOHOL AND DRUG ABUSE PATIENT RECORDS Introduction § 2.3 Purpose and effect. (a) Purpose. Under...

  16. 42 CFR 2.3 - Purpose and effect.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ALCOHOL AND DRUG ABUSE PATIENT RECORDS Introduction § 2.3 Purpose and effect. (a) Purpose. Under the... criminal penalty (a fine—see 42 U.S.C. 290ee-3(f), 42 U.S.C. 290dd-3(f) and 42 CFR 2.4) for violating the... 42 Public Health 1 2010-10-01 2010-10-01 false Purpose and effect. 2.3 Section 2.3 Public...

  17. Amino-substituted 1,8-naphthyridines and pyrido[2,3-d]pyrimidines: new compounds with affinity for A1- and A2-adenosine receptors.

    PubMed

    Müller, C E; Grahner, B; Heber, D

    1994-12-01

    Two novel classes of adenosine receptor (AR) antagonists, 4-amino-1,8-naphthyridines and 5-aminopyrido[2,3-d]pyrimidines, have been identified and investigated in radioligand binding assays. The compounds exhibit affinities for A1 and A2a AR of rat brain in the micromolar range. 1,8-Naphthyridines are non-selective, or somewhat selective for either A1- or A2 AR. Pyrido[2,3-d]pyrimidines are several-fold selective for A1 AR, the most potent and selective compound being 5-n-butylamino-1,3-dimethyl-1,2,3,4-tetrahydropyrido-[2,3-d]pyr imi dine-2,4-dione (12) with a Ki value of 1.8 microM at A1 AR and greater than 10-fold A1-selectivity. PMID:7838877

  18. Cenozoic detachment folding in the southern Tianshan foreland, NW China: Shortening distances and rates

    NASA Astrophysics Data System (ADS)

    Tian, Zhonghua; Sun, Jimin; Windley, Brian F.; Zhang, Zhiliang; Gong, Zhijun; Lin, Xu; Xiao, Wenjiao

    2016-03-01

    Intracontinental foreland basins with fold-and-thrust belts on the southern periphery of the Tianshan orogenic belt in China resulted from still-active contractional deformation ultimately cased by the India-Asia collision. To quantify the amounts of shortening distance and the rates of deformation, and to decipher the architectural framework, we mapped the stratigraphy and structure of four anticlines in the Kuqa and Baicheng foreland thrust belts in the central southern Tianshan. In the Baicheng foreland thrust belts, Lower Cretaceous Baxigai and Bashijiqike Formations located in the core of the Kumugeliemu anticline are overlain by the Paleocene to Eocene Kumugeliemu Formation, above which are conformable Oligocene through Pleistocene sediments. A disharmonic transition from parallel to unconformable bedding at the boundary of the Miocene Kangcun and Pliocene Kuqa Formations suggests a change from pre-detachment folded strata to beds deposited on top of a growing anticline. Most of the anticlines have steep limbs (70-90°) and are box to isoclinal folds, suggestive of detachment folding or faulted detachment folding (faults that transect a fold core or limb). Shortening estimates calculated from the cross-sections by the Excess area method indicate that the total shortening for the Kelasu, Kuchetawu, Kezile and Yaken sections are 6.3 km, 6.4 km, 5.8 km and 0.6 km, respectively, and the respective depths of the detachment zones are (2.3 km and 6.9 km), 2.3 km, 2.5 km and 3.4 km. Time estimates derived from a paleomagnetic study indicate that the transition to syn-folding strata occurred at ∼6.5 Ma at the Kuchetawu section along the Kuqa river. In addition, according to our field observations and previous sedimentary rate studies, the initial time of folding of the Yaken anticline was at 0.15-0.21 Ma. Therefore, the average shortening rate that began at ∼6 Ma was ∼2 mm/a for the Kelasu, Kuchetawu and Kezile sections. At 0.15-0.21 Ma, the average shortening

  19. Improving Protein Fold Recognition by Deep Learning Networks

    PubMed Central

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

    2015-01-01

    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. PMID:26634993

  20. The folding of an ``average'' beta trefoil protein.

    NASA Astrophysics Data System (ADS)

    Gosavi, Shachi; Jennings, Pat; Onuchic, Jose

    2007-03-01

    The beta-trefoil fold is characterized by twelve beta strands folded into three similar beta-beta-beta-loop-beta (trefoil) units. The overall fold has pseudo-threefold symmetry and consists of a six stranded-barrel, capped by a triangular hairpin triplet. The loops connecting the beta-strands vary in length and structure. It is these loops that give the fold its varied binding capability and the binding sites lie in different parts of the fold. The beta-trefoil proteins have little sequence similarity (sometimes less than 17%) and bind a range of molecules, including other proteins, DNA, membranes and carbohydrates. Protein folding experiments have been performed on four of the beta trefoils, namely, interleukin-1 (IL1B), acidic and basic fibroblast growth factors (FGF-1 and FGF-2) and hisactophilin (HIS). These experiments indicate that the proteins fold by different routes. Folding simulations of the proteins identify the possible folding routes and also show that the shapes of the barriers are different for the different proteins. In this work, we design a model protein which contains only the core fold elements of the beta-trefoil fold. We compare the folding of this ``average'' protein to the folding of His, FGF and IL1B and make some connections with function.

  1. Improving Protein Fold Recognition by Deep Learning Networks.

    PubMed

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

    2015-01-01

    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. PMID:26634993

  2. Improving Protein Fold Recognition by Deep Learning Networks

    NASA Astrophysics Data System (ADS)

    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.

  3. Geomechanical Modeling in Fold-and-Thrust Belts Systems

    NASA Astrophysics Data System (ADS)

    Gao, B.; Flemings, P. B.

    2015-12-01

    We present a large-strain poro-mechanical model to investigate the evolution of stress and strain in fold and thrust belt systems. We impose horizontal shortening in the model and observe that a tapered wedge develops. Inside the accretionary wedge, the horizontal effective stress increases to about 2.3 times the vertical effective stress. The maximum principle stress direction rotates gradually from the initial vertical direction to the horizontal direction as the sediment gets closer to the backstop. We use stress paths to illustrate how the stresses evolve during the thrust loading. We find the sediment stress path starts from uniaxial condition and moves towards critical state condition. We categorize the thrust belt into 3 zones according to their stress conditions from the backstop to the farfield: critical state region, transition region, and uniaxial region. We show that the sediments within the accretionary wedge are at critical state, which indicate they lost their strength to resist deformation. The sediment porosity decreases dramatically within the wedge due to high mean effective and differential stress. We built the model in finite element program Elfen. The sediments are modeled as poro-elastoplastic materials with a critical state soil model. Overall, our results provide insights of stress and porosity evolution in compressional regimes and can assist field stress and pressure predictions.

  4. The Fluid Memory of Clays in Faults and Folds

    NASA Astrophysics Data System (ADS)

    van der Pluijm, B.; Fitz-Diaz, E.; Haines, S. H.

    2013-12-01

    Constraining fluid sources is key to understanding crustal-scale fluid circulation, rock mechanics, mineral reactions and the origin of economic deposits. The role of meteoric fluids in exhumed fault rocks has been proposed in a few recent studies, notably in mylonites in low-angle normal fault (LANF) systems. However, the extent of meteoric influx and fluid pathways, and a mechanism for infiltration of surface waters up to 10+km depth remains mostly unknown. The occurrence of clay neomineralization in fault rocks and folds has the potential to resolve this question, as clay (trans)formation preserves host fluid information in its isotopic signatures, particularly H. New stable isotope studies of clays in normal faults and folds in the SW US and Mexico show major meteoric input, based on which we propose a mechanism for downward fluid infiltration and upper-crustal circulation. We obtained paired δ18O and δ2H (‰ wrt SMOW) isotopic measurements from neo-formed clays in fault gouge that formed above major LANF detachments in the SW US, which show that clays in brittle fault rocks formed from exchange with pristine to only weakly evolved meteoric fluids. Illite δ18O measurements range from -2.0‰ to +11.5‰, while illite δ2H measurements range from -142‰ to -107‰. Smectite δ18O values are +3.6‰ to 17.9‰, while smectite δ2H measurements are -147‰ to -95‰. The isotopic signature of clays at multiple depths in LANFs indicates that crustal-scale normal fault systems are highly permeable over geologic time scales, and that they are dominated by downward fluid flow of surface waters, instead of buoyancy-driven flow from deeper levels. Clay grain size fractions from folded rocks of the Mexican fold-thrust belt containing chlorite and smectite show very low values in δ2H (-75.9 to -53.9‰), while samples containing illite and kaolinite or pure illite show slightly higher δ2H values (-33.1 to -50.1‰). In these samples the discriminating potential of

  5. Higher Spin Holography

    NASA Astrophysics Data System (ADS)

    Chang, Chi-Ming

    This dissertation splits into two distinct halves. The first half is devoted to the study of the holography of higher spin gauge theory in AdS 3. We present a conjecture that the holographic dual of W N minimal model in a 't Hooft-like large N limit is an unusual "semi-local" higher spin gauge theory on AdS3 x 1. At each point on the S1 lives a copy of three-dimensional Vasiliev theory, that contains an infinite tower of higher spin gauge fields coupled to a single massive complex scalar propagating in AdS3. The Vasiliev theories at different points on the S1 are correlated only through the AdS3 boundary conditions on the massive scalars. All but one single tower of higher spin symmetries are broken by the boundary conditions. This conjecture is checked by comparing tree-level two- and three-point functions, and also one-loop partition functions on both side of the duality. The second half focuses on the holography of higher spin gauge theory in AdS 4. We demonstrate that a supersymmetric and parity violating version of Vasiliev's higher spin gauge theory in AdS4 admits boundary conditions that preserve N = 0,1,2,3,4 or 6 supersymmetries. In particular, we argue that the Vasiliev theory with U( M) Chan-Paton and N = 6 boundary condition is holographically dual to the 2+1 dimensional U(N) k x U(M) -k ABJ theory in the limit of large N, k and finite M. In this system all bulk higher spin fields transform in the adjoint of the U(M) gauge group, whose bulk t'Hooft coupling is M/N. Our picture suggests that the supersymmetric Vasiliev theory can be obtained as a limit of type IIA string theory in AdS4 x CP3, and that the non-Abelian Vasiliev theory at strong bulk 't Hooft coupling smoothly turn into a string field theory. The fundamental string is a singlet bound state of Vasiliev's higher spin particles held together by U(M) gauge interactions.

  6. Remote control over folding by light.

    PubMed

    Yu, Zhilin; Hecht, Stefan

    2016-05-10

    Integrating stimulus-responsive components into macromolecular architectures is a versatile strategy to create smart materials that can be controlled by external stimuli and even adapt to their environment. Helical foldamers, which are omnipresent in Nature and display well-defined yet dynamic structures, serve as an ideal platform to integrate photoswitches to modulate their conformations by light. This feature article summarizes the development of photoswitchable foldamers, focussing on various design approaches that incorporate the photoswitches either at the side chains, as tethered loops, or directly in the main chain. Based on the emerging insight into the folding-switching relationship more advanced molecular designs should enable the development of photoresponsive foldamers with high sensitivity to control and power functional macromolecular and supramolecular systems. PMID:27021403

  7. Mesozoic folds, fossil fields, and future finds

    SciTech Connect

    Newman, G.W.; Witter, G.G.

    1988-01-01

    Drilling and surface geologic mapping have shown that pre-Tertiary, post-Triassic folds and upthrusted anticlines in an eastern Nevada foldbelt have accumulated major oil columns. This Mesozoic foldbelt involves a Cambrian through Triassic section, which has hundreds of feet of porosity in Ordovician sandstones, Silurian and Devonian carbonates, and Mississippian sandstones. In addition to the Devonian Pilot and Mississippian Chainman Shales, source rocks are found in Cambrian and Ordovician shales and in some Paleozoic carbonates. The occurrence of live and dead oil shows in hundreds of vertical feet of porosity in wells drilled on several of these Mesozoic structures is interpreted as evidence that these structures were giant oil fields prior to being breached by Tertiary Basin and Range extensional faulting, which allowed vertical hydrocarbon leakage.

  8. Quirky collider signals of folded supersymmetry

    NASA Astrophysics Data System (ADS)

    Burdman, Gustavo; Chacko, Z.; Goh, Hock-Seng; Harnik, Roni; Krenke, Christopher A.

    2008-10-01

    We investigate the collider signals associated with scalar quirks (squirks) in folded supersymmetric models. As opposed to regular superpartners in supersymmetric models these particles are uncolored, but are instead charged under a new confining group, leading to radically different collider signals. Because of the new strong dynamics, squirks that are pair produced do not hadronize separately, but rather form a highly excited bound state. The excited squirkonium loses energy to radiation before annihilating back into standard model particles. We calculate the branching fractions into various channels for this process, which is prompt on collider time scales. The most promising annihilation channel for discovery is W+photon which dominates for squirkonium near its ground state. We demonstrate the feasibility of the LHC search, showing that the mass peak is visible above the SM continuum background and estimate the discovery reach.

  9. Universality Classes in Folding Times of Proteins

    PubMed Central

    Cieplak, Marek; Hoang, Trinh Xuan

    2003-01-01

    Molecular dynamics simulations in simplified models allow one to study the scaling properties of folding times for many proteins together under a controlled setting. We consider three variants of the Go models with different contact potentials and demonstrate scaling described by power laws and no correlation with the relative contact order parameter. We demonstrate existence of at least three kinetic universality classes that are correlated with the types of structure: the α-, α-β-, and β- proteins have the scaling exponents of ∼1.7, 2.5, and 3.2, respectively. The three classes merge into one when the contact range is truncated at a reasonable value. We elucidate the role of the potential associated with the chirality of a protein. PMID:12524300

  10. Macromolecular crowding increases structural content of folded proteins.

    PubMed

    Perham, Michael; Stagg, Loren; Wittung-Stafshede, Pernilla

    2007-10-30

    Here we show that increased amount of secondary structure is acquired in the folded states of two structurally-different proteins (alpha-helical VlsE and alpha/beta flavodoxin) in the presence of macromolecular crowding agents. The structural content of flavodoxin and VlsE is enhanced by 33% and 70%, respectively, in 400 mg/ml Ficoll 70 (pH 7, 20 degrees C) and correlates with higher protein-thermal stability. In the same Ficoll range, there are only small effects on the unfolded-state structures of the proteins. This is the first in vitro assessment of crowding effects on the native-state structures at physiological conditions. Our findings imply that for proteins with low intrinsic stability, the functional structures in vivo may differ from those observed in dilute buffers. PMID:17919600

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

    PubMed

    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. PMID:23700314

  12. Diagnostic and therapeutic pitfalls in benign vocal fold diseases

    PubMed Central

    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

  13. Parasitic folds with wrong vergence: How pre-existing geometrical asymmetries can be inherited during multilayer buckle folding

    NASA Astrophysics Data System (ADS)

    Frehner, Marcel; Schmid, Timothy

    2016-06-01

    Parasitic folds are typical structures in geological multilayer folds; they are characterized by a small wavelength and are situated within folds with larger wavelength. Parasitic folds exhibit a characteristic asymmetry (or vergence) reflecting their structural relationship to the larger-scale fold. Here we investigate if a pre-existing geometrical asymmetry (e.g., from sedimentary structures or folds from a previous tectonic event) can be inherited during buckle folding to form parasitic folds with wrong vergence. We conduct 2D finite-element simulations of multilayer folding using Newtonian materials. The applied model setup comprises a thin layer exhibiting the pre-existing geometrical asymmetry sandwiched between two thicker layers, all intercalated with a lower-viscosity matrix and subjected to layer-parallel shortening. When the two outer thick layers buckle and amplify, two processes work against the asymmetry: layer-perpendicular flattening between the two thick layers and the rotational component of flexural flow folding. Both processes promote de-amplification and unfolding of the pre-existing asymmetry. We discuss how the efficiency of de-amplification is controlled by the larger-scale fold amplification and conclude that pre-existing asymmetries that are open and/or exhibit low amplitude are prone to de-amplification and may disappear during buckling of the multilayer system. Large-amplitude and/or tight to isoclinal folds may be inherited and develop type 3 fold interference patterns.

  14. Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

    SciTech Connect

    Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L. . E-mail: leonguo@ha.mc.ntu.edu.tw

    2007-05-15

    Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification.

  15. Robustness of downhill folding: guidelines for the analysis of equilibrium folding experiments on small proteins.

    PubMed

    Naganathan, Athi N; Perez-Jimenez, Raúl; Sanchez-Ruiz, Jose M; Muñoz, Victor

    2005-05-24

    Previously, we identified the protein BBL as a downhill folder. This conclusion was based on the statistical mechanical analysis of equilibrium experiments performed in two variants of BBL, one with a fluorescent label at the N-terminus, and another one labeled at both ends. A recent report has claimed that our results are an artifact of label-induced aggregation and that BBL with no fluorescent labels and a longer N-terminal tail folds in a two-state fashion. Here, we show that singly and doubly labeled BBL do not aggregate, unfold reversibly, and have the same thermodynamic properties when studied under appropriate experimental conditions (e.g., our original conditions (1)). With an elementary analysis of the available data on the nonlabeled BBL (2), we also show that this slightly more stable BBL variant is not a two-state folder. We discuss the problems that led to its previous misclassification and how they can be avoided. Finally, we investigate the equilibrium unfolding of the singly labeled BBL with both ends protected by acetylation and amidation. This variant has the same thermodynamic stability of the nonlabeled BBL and displays all the equilibrium signatures of downhill folding. From all these observations, we conclude that fluorescent labels do not perturb the thermodynamic properties of BBL, which consistently folds downhill regardless of its stability and specific protein tails. The work on BBL illustrates the shortcomings of applying conventional procedures intended to distinguish between two-state and three-state folding models to small fast-folding proteins. PMID:15895987

  16. RNAiFOLD: a constraint programming algorithm for RNA inverse folding and molecular design.

    PubMed

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

    2013-04-01

    Synthetic biology is a rapidly emerging discipline with long-term ramifications that range from single-molecule detection within cells to the creation of synthetic genomes and novel life forms. Truly phenomenal results have been obtained by pioneering groups--for instance, the combinatorial synthesis of genetic networks, genome synthesis using BioBricks, and hybridization chain reaction (HCR), in which stable DNA monomers assemble only upon exposure to a target DNA fragment, biomolecular self-assembly pathways, etc. Such work strongly suggests that nanotechnology and synthetic biology together seem poised to constitute the most transformative development of the 21st century. In this paper, we present a Constraint Programming (CP) approach to solve the RNA inverse folding problem. Given a target RNA secondary structure, we determine an RNA sequence which folds into the target structure; i.e. whose minimum free energy structure is the target structure. Our approach represents a step forward in RNA design--we produce the first complete RNA inverse folding approach which allows for the specification of a wide range of design constraints. We also introduce a Large Neighborhood Search approach which allows us to tackle larger instances at the cost of losing completeness, while retaining the advantages of meeting design constraints (motif, GC-content, etc.). Results demonstrate that our software, RNAiFold, performs as well or better than all state-of-the-art approaches; nevertheless, our approach is unique in terms of completeness, flexibility, and the support of various design constraints. The algorithms presented in this paper are publicly available via the interactive webserver http://bioinformatics.bc.edu/clotelab/RNAiFold; additionally, the source code can be downloaded from that site. PMID:23600819

  17. 43 CFR 3712.2-3 - Contents of published notice.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Contents of published notice. 3712.2-3 Section 3712.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) PUBLIC LAW 167; ACT OF JULY 23,...

  18. 43 CFR 3107.2-3 - Leases capable of production.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... or Renewal § 3107.2-3 Leases capable of production. No lease for lands on which there is a well... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Leases capable of production. 3107.2-3... same, unless the lessee fails to place the lease in production within a period of not less than 60...

  19. 43 CFR 3107.2-3 - Leases capable of production.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... or Renewal § 3107.2-3 Leases capable of production. No lease for lands on which there is a well... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Leases capable of production. 3107.2-3... same, unless the lessee fails to place the lease in production within a period of not less than 60...

  20. 43 CFR 3107.2-3 - Leases capable of production.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... or Renewal § 3107.2-3 Leases capable of production. No lease for lands on which there is a well... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Leases capable of production. 3107.2-3... same, unless the lessee fails to place the lease in production within a period of not less than 60...

  1. 16 CFR 2.3 - Policy as to private controversies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... other action when the alleged violation of law is merely a matter of private controversy and does not... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Policy as to private controversies. 2.3... NONADJUDICATIVE PROCEDURES Inquiries; Investigations; Compulsory Processes § 2.3 Policy as to...

  2. 43 CFR 3453.2-3 - Filing location and fee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... leased lands proposed for transfer (see 43 CFR subpart 1821). Each instrument of transfer shall be... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Filing location and fee. 3453.2-3 Section 3453.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF...

  3. 43 CFR 4110.2-3 - Transfer of grazing preference.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Transfer of grazing preference. 4110.2-3 Section 4110.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... improvements authorized on public lands under § 4120.3 and maintained in conjunction with the...

  4. 43 CFR 4110.2-3 - Transfer of grazing preference.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Transfer of grazing preference. 4110.2-3 Section 4110.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... improvements authorized on public lands under § 4120.3 and maintained in conjunction with the...

  5. 43 CFR 4110.2-3 - Transfer of grazing preference.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Transfer of grazing preference. 4110.2-3 Section 4110.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... improvements authorized on public lands under § 4120.3 and maintained in conjunction with the...

  6. 43 CFR 4110.2-3 - Transfer of grazing preference.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Transfer of grazing preference. 4110.2-3 Section 4110.2-3 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND... improvements authorized on public lands under § 4120.3 and maintained in conjunction with the...

  7. 32 CFR 2.3 - Regulatory relief for participating programs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....3 Section 2.3 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE ACQUISITION PILOT PROGRAM POLICY § 2.3 Regulatory relief for participating programs. (a) A program participating in... the Component, or the DoD Component Acquisition Executive. 1 Copies of this Department of...

  8. 32 CFR 2.3 - Regulatory relief for participating programs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....3 Section 2.3 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE ACQUISITION PILOT PROGRAM POLICY § 2.3 Regulatory relief for participating programs. (a) A program participating in... the Component, or the DoD Component Acquisition Executive. 1 Copies of this Department of...

  9. 40 CFR 35.909 - Step 2+3 grants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Step 2+3 grants. 35.909 Section 35.909 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works-Clean Water Act § 35.909 Step 2+3 grants. (a) Authority. The Regional...

  10. 43 CFR 3410.2-3 - Surface management agency.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Surface management agency. 3410.2-3... § 3410.2-3 Surface management agency. The authorized officer may issue an exploration license covering lands the surface of which is under the jurisdiction of any Federal agency other than the Bureau of...

  11. 76 FR 50438 - Folded Self-Mailers and Unenveloped Mailpieces

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-15

    ... 111 Folded Self-Mailers and Unenveloped Mailpieces AGENCY: Postal Service TM . ACTION: Proposed rule..., Domestic Mail Manual (DMM ) 201.3.14 to provide standards for creating folded self-mailers (FSM) and other.... Folded self-mailer maximum dimensions and weights are now proposed to align with other unenveloped...

  12. Technique to achieve the symmetry of the new inframammary fold.

    PubMed

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

    2014-08-01

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

  13. SIRT1, 2, 3 protect mouse oocytes from postovulatory aging

    PubMed Central

    Zhang, Teng; Zhou, Yang; Li, Li; Wang, Hong-Hui; Ma, Xue-Shan; Qian, Wei-Ping; Shen, Wei; Schatten, Heide; Sun, Qing-Yuan

    2016-01-01

    The quality of metaphase II oocytes will undergo a time-dependent deterioration following ovulation as the result of the oocyte aging process. In this study, we determined that the expression of sirtuin family members (SIRT1, 2, 3) was dramatically reduced in mouse oocytes aged in vivo or in vitro. Increased intracellular ROS was observed when SIRT1, 2, 3 activity was inhibited. Increased frequency of spindle defects and disturbed distribution of mitochondria were also observed in MII oocytes aged in vitro after treatment with Nicotinamide (NAM), indicating that inhibition of SIRT1, 2, 3 may accelerate postovulatory oocyte aging. Interestingly, when MII oocytes were exposed to caffeine, the decline of SIRT1, 2, 3 mRNA levels was delayed and the aging-associated defective phenotypes could be improved. The results suggest that the SIRT1, 2, 3 pathway may play a potential protective role against postovulatory oocyte aging by controlling ROS generation. PMID:26974211

  14. Characterization of the vocal fold vertical stiffness in a canine model

    PubMed Central

    Oren, Liran; Dembinski, Doug; Gutmark, Ephraim; Khosla, Sid

    2014-01-01

    Objectives/Hypothesis Characterizing the vertical stiffness gradient that exists between the superior and inferior aspects of the medial surface of the vocal fold. Characterization of this stiffness gradient could elucidate the mechanism behind the divergent glottal shape observed during closing. Study Design Basic science. Methods Indentation testing of the folds was done in a canine model. Stress-strain curves are generated using a customized load-cell and the differential Young's modulus is calculated as a function of strain. Results Results from 11 larynges show that stress increases as a function of strain more rapidly in the inferior aspect of the fold. The calculations for local Young's modulus show that at high strain values a stiffness gradient is formed between the superior and inferior aspects of the fold. Conclusions For small strain values, which are observed at low subglottal pressures, the stiffness of the tissue is similar in both the superior and inferior aspects of the vocal fold. Consequently, the lateral force that is applied by the glottal flow at both aspects results in almost identical displacements, yielding no divergence angle. Conversely, at higher strain values, which are measured in high subglottal pressure, the inferior aspect of the vocal fold is much stiffer than the superior edge; thus any lateral force that is applied at both aspects will result in a much greater displacement of the superior edge, yielding a large divergence angle. The increased stiffness observed at the inferior edge could be due to the proximity of the conus elasticus. PMID:24495431

  15. The role of transverse drainage in the development of foreland folds

    SciTech Connect

    Mussuridis, A.; Slingerland, R.; Furlong, K.P. )

    1992-01-01

    It is a fact of some consequence that transverse streams in active fold and thrust belts often lie atop the culminations of the principal anticlines. The conventional explanation for this association is discordant superposition of transverse subsequent streams. Here the authors present the alternative hypothesis that antecedent transverse rivers maintain their courses during deformation, thereby effecting greater denudation rates in their vicinity. These higher rates unload fault bends and thrust tips, thus facilitating local fold growth. To test this hypothesis, a two-dimensional finite element program (TECTON) is employed to assess the effects of mass removal on the growth and propagation of folds in the Zagros foreland of Iran. The model encompasses a varying lithology, in accordance with the local stratigraphic column. A single thrust sheet with a ramp dipping at 30[degree], represents the main Zagros thrust. The author applies a horizontal pressure force of 3.8 [times] 10[sup 11] Pascals and simulate weathering by applying upward directed forces equal to the weight of material eroded off during a timestep. Results show that increased denudation of an emerging range not only enhances fold growth, but also facilitates propagation of the buckle folds. This arises because the total work performed in the development of a duplex fold is dominated by the work needed to move thrust slices up-section against the force of gravity. They therefore hypothesize that mass unloading in the very early stages of an orogen can plan an important role in the overall development of the mountain belt.

  16. Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists.

    PubMed

    Pereira, Nuno A L; Sureda, Francesc X; Pérez, Maria; Amat, Mercedes; Santos, Maria M M

    2016-01-01

    Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl d-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i) a stereoselective cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic δ-oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson's disease). This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors. PMID:27509489

  17. Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding

    NASA Astrophysics Data System (ADS)

    Nissley, Daniel A.; Sharma, Ajeet K.; Ahmed, Nabeel; Friedrich, Ulrike A.; Kramer, Günter; Bukau, Bernd; O'Brien, Edward P.

    2016-02-01

    The rates at which domains fold and codons are translated are important factors in determining whether a nascent protein will co-translationally fold and function or misfold and malfunction. Here we develop a chemical kinetic model that calculates a protein domain's co-translational folding curve during synthesis using only the domain's bulk folding and unfolding rates and codon translation rates. We show that this model accurately predicts the course of co-translational folding measured in vivo for four different protein molecules. We then make predictions for a number of different proteins in yeast and find that synonymous codon substitutions, which change translation-elongation rates, can switch some protein domains from folding post-translationally to folding co-translationally--a result consistent with previous experimental studies. Our approach explains essential features of co-translational folding curves and predicts how varying the translation rate at different codon positions along a transcript's coding sequence affects this self-assembly process.

  18. The Skp chaperone helps fold soluble proteins in vitro by inhibiting aggregation.

    PubMed

    Entzminger, Kevin C; Chang, Christine; Myhre, Ryan O; McCallum, Katie C; Maynard, Jennifer A

    2012-06-19

    The periplasmic seventeen kilodalton protein (Skp) chaperone has been characterized primarily for its role in outer membrane protein (OMP) biogenesis, during which the jellyfish-like trimeric protein encapsulates partially folded OMPs, protecting them from the aqueous environment until delivery to the BAM outer membrane protein insertion complex. However, Skp is increasingly recognized as a chaperone that also assists in folding soluble proteins in the bacterial periplasm. In this capacity, Skp coexpression increases the active yields of many recombinant proteins and bacterial virulence factors. Using a panel of single-chain antibodies and a single-chain T-cell receptor (collectively termed scFvs) possessing varying stabilities and biophysical characteristics, we performed in vivo expression and in vitro folding and aggregation assays in the presence or absence of Skp. For Skp-sensitive scFvs, the presence of Skp during in vitro refolding assays reduced aggregation but did not alter the observed folding rates, resulting in a higher overall yield of active protein. Of the proteins analyzed, Skp sensitivity in all assays correlated with the presence of folding intermediates, as observed with urea denaturation studies. These results are consistent with Skp acting as a holdase, sequestering partially folded intermediates and thereby preventing aggregation. Because not all soluble proteins are sensitive to Skp coexpression, we hypothesize that the presence of a long-lived protein folding intermediate renders a protein sensitive to Skp. Improved understanding of the bacterial periplasmic protein folding machinery may assist in high-level recombinant protein expression and may help identify novel approaches to block bacterial virulence. PMID:22650963

  19. Tropopause Folds: Global Climatology and their Impact on Extreme Weather Events

    NASA Astrophysics Data System (ADS)

    Skerlak, B.; Sprenger, M.; Pfahl, S.; Wernli, H.

    2014-12-01

    Folded structures in the tropopause, so-called tropopause folds, are intimately linked to upper-level frontogenesis and jet-stream dynamics. They play an important role for stratosphere-troposphere exchange, the dynamical coupling of upper- and lower troposphere, and can be important for generating severe weather events. Together with the filamentation and roll-up of streamers and the formation of cut-off lows, tropopause folds are a prime example for the complex dynamical structure of the UTLS on time scales from hours to days. For case studies, in-situ data or detailed manual analysis of model output often allow for an unambiguous identification of the tropopause. Obtaining a global, long-term perspective of this phenomenon, however, requires an automated and objective identification method. We present an elaborated three-dimensional labelling algorithm, based on an isosurface of potential vorticity (PV), that allows to objectively separate stratospheric and tropospheric air in complex situations in polar regions and in situations with diabatically and/or frictionally generated PV anomalies typically found near extratropical cyclones. We apply this algorithm to the ERA-Interim reanalysis data set from 1979 to 2012 to compile a robust global climatology of tropopause folds. We present geographical and seasonal distributions of fold frequencies for three classes of folds as defined by their vertical extent (shallow, medium and deep). Typical synoptic situations associated with deep tropopause folds like cyclonically curved jets are discussed and we investigate their potential impact on extreme weather events. For example, the frequency of wind speed extremes at 700 hPa is in many areas significantly higher if a tropopause fold is present.

  20. Influence of supraglottal structures on the glottal jet exiting a two-layer synthetic, self-oscillating vocal fold model

    PubMed Central

    Drechsel, James S.; Thomson, Scott L.

    2008-01-01

    A synthetic two-layer, self-oscillating, life-size vocal fold model was used to study the influence of the vocal tract and false folds on the glottal jet. The model vibrated at frequencies, pressures, flow rates, and amplitudes consistent with human phonation, although some differences in behavior between the model and the human vocal folds are noted. High-speed images of model motion and flow visualization were acquired. Phase-locked ensemble-averaged glottal jet velocity measurements using particle image velocimetry (PIV) were acquired with and without an idealized vocal tract, with and without false folds. PIV data were obtained with varying degrees of lateral asymmetric model positioning. Glottal jet velocity magnitudes were consistent with those measured using excised larynges. A starting vortex was observed in all test cases. The false folds interfered with the starting vortex, and in some cases vortex shedding from the false folds was observed. In asymmetric cases without false folds, the glottal jet tended to skew toward the nearest wall; with the false folds, the opposite trend was observed. rms velocity calculations showed the jet shear layer and laminar core. The rms velocities were higher in the vocal tract cases compared to the open jet and false fold cases. PMID:18537394

  1. Statics, metastable states, and barriers in protein folding: A replica variational approach

    NASA Astrophysics Data System (ADS)

    Takada, Shoji; Wolynes, Peter G.

    1997-04-01

    Protein folding is analyzed using a replica variational formalism to investigate some free energy landscape characteristics relevant for dynamics. A random contact interaction model that satisfies the minimum frustration principle is used to describe the coil-globule transition (characterized by TCG), glass transitions (by TA and TK), and folding transition (by TF). Trapping on the free energy landscape is characterized by two characteristic temperatures, one dynamic (TA) and the other static [TK (TA>TK)], which are similar to those found in mean field theories of the Potts glass. (i) Above TA, the free energy landscape is monotonous and the polymer is melted both dynamically and statically. (ii) Between TA and TK, the melted phase is still dominant thermodynamically, but frozen metastable states, exponentially large in number, appear. (iii) A few lowest minima become thermodynamically dominant below TK, where the polymer is totally frozen. In the temperature range between TA and TK, barriers between metastable states are shown to grow with decreasing temperature, suggesting super-Arrhenius behavior in a sufficiently large system. Due to evolutionary constraints on fast folding, the folding temperature TF is expected to be higher than TK, but may or may not be higher than TA. Diverse scenarios of the folding kinetics are discussed based on phase diagrams that take into account the dynamical transition, as well as the static ones.

  2. Fold-preserving electronic cleansing using a reconstruction model integrating material fractions and structural responses.

    PubMed

    Lee, Hyunna; Kim, Bohyoung; Lee, Jeongjin; Kim, Se Hyung; Shin, Yeong-Gil; Kim, Tae-Gong

    2013-06-01

    In this paper, we propose an electronic cleansing method using a novel reconstruction model for removing tagged materials (TMs) in computed tomography (CT) images. To address the partial volume (PV) and pseudoenhancement (PEH) effects concurrently, material fractions and structural responses are integrated into a single reconstruction model. In our approach, colonic components including air, TM, an interface layer between air and TM, and an interface layer between soft-tissue (ST) and TM (IL ST/TM ) are first segmented. For each voxel in IL ST/TM, the material fractions of ST and TM are derived using a two-material transition model, and the structural response to identify the folds submerged in the TM is calculated by the rut-enhancement function based on the eigenvalue signatures of the Hessian matrix. Then, the CT density value of each voxel in IL ST/TM is reconstructed based on both the material fractions and structural responses. The material fractions remove the aliasing artifacts caused by a PV effect in IL ST/TM effectively while the structural responses avoid the erroneous cleansing of the submerged folds caused by the PEH effect. Experimental results using ten clinical datasets demonstrated that the proposed method showed higher cleansing quality and better preservation of submerged folds than the previous method, which was validated by the higher mean density values and fold preservation rates for manually segmented fold regions. PMID:23335656

  3. Heavy smokers have higher bcl-2 mutation frequency and risk for lymphoma than non-smokers

    SciTech Connect

    Liu, Y.; Cortopassi, G.A.; Bell, D.A.

    1994-09-01

    Early detection of cells carrying somatic mutations at oncogenic loci could prove useful for identifying individuals at high risk for cancer and permit intervention prior to the onset of clinically recognizable disease. We have determined the frequency of rare t(14;18)(q32;q21) translocations at the bcl-2 proto-oncogene locus in the peripheral blood of 85 smokers and 35 nonsmokers using a sensitive nested PCR assay. The identical translocation occurs in 85% of follicular lymphoma tumors, and about 50% of all non-Hodgkin`s Lymphoma. Smokers with the highest exposure had a 3.6-fold higher mutation frequency relative to the nonsmokers. Logistic regression analysis showed that of the variables tested (age, race, sex, current smoking, years of smoking, and pack-years), the cumulative smoking measure (pack-years) was the best predictor of t(14;18) frequency (p=0.004). These observations are consistent with two recent epidemiological studies showing 2.3-fold and 3.8-fold increased risk for Non-Hodgkins lymphoma among heavy smokers. The results support the hypothesis that smokers have an increased burden of lymphocytes bearing bcl-2 mutations which raises their individual risk for future lymphoid tumors. We speculate that the increased frequency of oncogenic translocations in smokers may result either from the mutagenic or antigenic activity of cigarette smoke.

  4. Reductions in Red Blood Cell 2,3-Diphosphoglycerate Concentration during Continuous Renal Replacment Therapy

    PubMed Central

    Brugnara, Carlo; Betensky, Rebecca A.; Waikar, Sushrut S.

    2015-01-01

    Background and objectives Hypophosphatemia is a frequent complication during continuous renal replacement therapy (CRRT), a dialytic technique used to treat AKI in critically ill patients. This study sought to confirm that phosphate depletion during CRRT may decrease red blood cell (RBC) concentration of 2,3-diphosphoglycerate (2,3-DPG), a crucial allosteric effector of hemoglobin’s (Hgb’s) affinity for oxygen, thereby leading to impaired oxygen delivery to peripheral tissues. Design, setting, participants, & measurements Phosphate mass balance studies were performed in 20 patients with severe AKI through collection of CRRT effluent. RBC concentrations of 2,3-DPG, venous blood gas pH, and oxygen partial pressure required for 50% hemoglobin saturation (P50) were measured at CRRT initiation and days 2, 4, and 7. Similar measurements were obtained on days 0 and 2 in a reference group of 10 postsurgical patients, most of whom did not have AKI. Associations of 2,3-DPG with laboratory parameters and clinical outcomes were examined using mixed-effects and Cox regression models. Results Mean 2,3-DPG levels decreased from a mean (±SD) of 13.4±3.4 µmol/g Hgb to 11.0±3.1 µmol/g Hgb after 2 days of CRRT (P<0.001). Mean hemoglobin saturation P50 levels decreased from 29.7±4.4 mmHg to 26.7±4.0 mmHg (P<0.001). No significant change was seen in the reference group. 2,3-DPG levels after 2 days of CRRT were not significantly lower than those in the reference group on day 2. Among patients receiving CRRT, 2,3-DPG decreased by 0.53 µmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68 µmol/g Hgb; P<0.001). Greater reductions in 2,3-DPG were associated with higher risk for death (hazard ratio, 1.43; 95% confidence interval, 1.09 to 1.88; P=0.01). Conclusions CRRT-induced phosphate depletion is associated with measurable reductions in RBC 2,3-DPG concentration and a shift in the O2:Hgb affinity curve even in the absence of overt hypophosphatemia. 2,3

  5. Nicotinic acid metabolism. 2,3-Dimethylmalate lyase.

    PubMed

    Pirzer, P; Lill, U; Eggerer, H

    1979-12-01

    1) A new enzyme, 2,3-dimethylmalate lyase, was purified from Clostridium barkeri to about 80% homogeneity. Some of the properties of the enzyme are described. 2) It is shown that the 2,3-dimethylmalic acid (m.p. 143 degrees C) described in the literature represents only one racemic pair. This pair is not attacked by 2,3-dimethylmalate lyase. 3) The isolation of both racemic pairs of 2,3-dimethylmalic acid is described. Half of one pair, m.p. 104-106 degrees C, was converted to propionate and pyruvate by 2,3-dimethylmalate lyase. 4) In combination with earlier work performed by E.R. Stadtman and coworkers the results given under points 1--3 establish 2,3-dimethylmalate as an intermediate in the degradation of nicotinic acid by C. barkeri. 5) Experimental evidence indicates the 2,3-dimethylmalate lyase is no acyl-S-enzyme and that it is different in this respect as well as in quaternary structure from the apparently related enzymes citrate lyase and citramalate lyase. PMID:527937

  6. Fluorination of 1,2,3,4- and 1,2,3,5-tetrahalobenzenes with potassium fluoride in dimethyl sulfone

    USGS Publications Warehouse

    Finger, G.C.; Dickerson, D.R.; Shiley, R.H.

    1972-01-01

    1,2,3,4-Tetrachlorobenzene, 1,2,3,5-tetrachlorobenzene, 2,4,6-trichlorofluorobenzene, and 2,6-dichloro-1,4-difluorobenzene were fluorinated with potassium fluoride and potassium fluoride-cesium fluoride mixtures in dimethyl sulfone. By varying the concentration, temperature and reaction time, the degree of fluorination could be controlled to some extent. The optimum conditions for producing mono-, di- and tri-fluoro-substituted chlorobenzenes and trace amounts of tetrafluorobenzene from the corresponding tetrachlorobenzenes are given. 1,2,3,5-Tetrafluorobenzene was obtained in 44.8% yield from 2,6-dichloro-1,4-difluorobenzene. 1,2,3,4-Tetrafluorobenzene was obtained in only trace amounts from 1,2,3,4-tetrachlorobenzene. A total of 24 new chlorofluorobenzenes and intermediates are described. Fluorination with potassium fluoride and certain other metal fluorides was also investigated. ?? 1972.

  7. Pemphigus vegetans of the folds (intertriginous areas).

    PubMed

    Ruocco, Vincenzo; Ruocco, Eleonora; Caccavale, Stefano; Gambardella, Alessio; Lo Schiavo, Ada

    2015-01-01

    Pemphigus vegetans (P Veg), the rarest form of pemphigus, is thought to be a variant of pemphigus vulgaris (PV). Classically, two subtypes of P Veg are recognized: (1) Neumann P Veg, which usually begins as PV with vesicles and bullae that rupture to form hypertrophic granulating erosions, then evolving into vegetating exuding masses; (2) Hallopeau P Veg, initially characterized by pustular lesions that, after rupturing, merge and gradually evolve into vegetating erosions with a centrifugal expansion. The disease typically affects the big folds (axillary, inframammary, inguinocrural, intergluteal), where semiocclusion, maceration, and mixed infections continuously incite exudation and granulation tissue formation (wet P Veg). In nonintertriginous locations, the vegetating buttons can dry out to change into warty, fissured, painful, seborrheic keratosis-like lesions (dry P Veg). Histologic examination indicates hyperplastic epidermis with intramalpighian leukocyte microabscesses and indistinct traits of suprabasal acantholysis. Immunofluorescence findings are similar to those of PV. Diagnosis is straightforward when PV lesions coexist. Difficulties can arise in cases with nonflexural location. Cytology (Tzanck test), histology, immunofluorescence, and ELISA search for anti-desmoglein antibodies are the diagnostic laboratory tools. Systemic treatment is similar to that for PV, high-dose steroids being the first choice therapy. Immunosuppressive agents and etretinate may allow a steroid-sparing effect. Topical treatment is aimed at countering the granulation tissue formation by means of several strategies (sublesional steroid injection, application of medicated gauzes in the involved flexures, chemical cautery or surgical excision of vegetating lesions). PMID:26051064

  8. Bioengineered vocal fold mucosa for voice restoration.

    PubMed

    Ling, Changying; Li, Qiyao; Brown, Matthew E; Kishimoto, Yo; Toya, Yutaka; Devine, Erin E; Choi, Kyeong-Ok; Nishimoto, Kohei; Norman, Ian G; Tsegyal, Tenzin; Jiang, Jack J; Burlingham, William J; Gunasekaran, Sundaram; Smith, Lloyd M; Frey, Brian L; Welham, Nathan V

    2015-11-18

    Patients with voice impairment caused by advanced vocal fold (VF) fibrosis or tissue loss have few treatment options. A transplantable, bioengineered VF mucosa would address the individual and societal costs of voice-related communication loss. Such a tissue must be biomechanically capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration and physiologically capable of maintaining a barrier against the airway lumen. We isolated primary human VF fibroblasts and epithelial cells and cocultured them under organotypic conditions. The resulting engineered mucosae showed morphologic features of native tissue, proteome-level evidence of mucosal morphogenesis and emerging extracellular matrix complexity, and rudimentary barrier function in vitro. When grafted into canine larynges ex vivo, the mucosae generated vibratory behavior and acoustic output that were indistinguishable from those of native VF tissue. When grafted into humanized mice in vivo, the mucosae survived and were well tolerated by the human adaptive immune system. This tissue engineering approach has the potential to restore voice function in patients with otherwise untreatable VF mucosal disease. PMID:26582902

  9. Folding and Aggregation of Mucin Domains.

    NASA Astrophysics Data System (ADS)

    Urbanc, Brigita; Bansil, Rama; Turner, Bradley

    2007-03-01

    Mucin glycoproteins consist of tandem repeating glycosylated regions flanked by non-repetitive protein domains with little glycosylation. These non-repetitive domains are involved in polymerization of mucin via disulfide bonds and play an important role in the pH dependent gelation of gastric mucin, which is essential to protecting the stomach from autodigestion. We have examined the folding and aggregation of the non-repetitive sequence of von Willebrand factor vWF-C1 domain (67 amino acids) and PGM 2X (242 amino acids) using Discrete Molecular Dynamics (four-bead protein model with hydrogen bonding and amino acid-specific hydrophobic/hydrophilic and electrostatic interactions of side chains). Simulations of vWF C1 show 4-6 β-strands separated by turns/loops with more loops at lower pH. A simulation of several vWF C1 proteins at low pH shows aggregates still with a high content of β-strands and enhanced turn/loop regions. For the PGM 2X simulation the contact map shows several salt bridges enclosing hairpin turns. The implications of these simulations for describing the aggregation/gelation of PGM will be discussed.

  10. Diaper (napkin) dermatitis: A fold (intertriginous) dermatosis.

    PubMed

    Tüzün, Yalçın; Wolf, Ronni; Bağlam, Süleyman; Engin, Burhan

    2015-01-01

    Diaper (napkin) dermatitis is an acutely presenting inflammatory irritant contact dermatitis of the diaper region. It is one of the most common dermatologic diseases in infants and children. In the past, the disease was thought to be caused by ammonia; however, a number of factors, such as friction, wetness, inappropriate skin care, microorganisms, antibiotics, and nutritional defects, are important. Diaper dermatitis commonly affects the lower parts of the abdomen, thighs, and diaper area. Involvement of skin fold regions is typical with diaper dermatitis. At the early stages of the disease, only dryness is observed in the affected area. At later stages, erythematous maceration and edema can be seen. Secondary candidal and bacterial infections can complicate the dermatitis. In the differential diagnosis of the disease, allergic contact dermatitis, intertrigo, psoriasis, atopic and seborrheic dermatitis, and the other diseases should be considered. Causes of the disease should be determined and eliminated primarily. Families need to be informed about the importance of a clean, dry diaper area and the frequency of diaper changes. The use of superabsorbent disposable diapers has decreased the incidence of the disease. Soap and alcohol-containing products should be avoided in cleaning the area. In some cases, corticosteroids and antifungal agents can be administered. If necessary, antibacterial agents and calcineurin inhibitors can also be beneficial. PMID:26051065

  11. Protein-Folding Landscapes in Multi-Chain Systems

    SciTech Connect

    Cellmer, Troy; Bratko, Dusan; Prausnitz, John M.; Blanch, Harvey

    2005-06-20

    Computational studies of proteins have significantly improved our understanding of protein folding. These studies are normally carried out using chains in isolation. However, in many systems of practical interest, proteins fold in the presence of other molecules. To obtain insight into folding in such situations, we compare the thermodynamics of folding for a Miyazawa-Jernigan model 64-mer in isolation to results obtained in the presence of additional chains. The melting temperature falls as the chain concentration increases. In multi-chain systems, free-energy landscapes for folding show an increased preference for misfolded states. Misfolding is accompanied by an increase in inter-protein interactions; however, near the folding temperature, the transition from folded chains to misfolded and associated chains isentropically driven. A majority of the most probable inter-protein contacts are also native contacts, suggesting that native topology plays a role in early stages of aggregation.

  12. Designing pH induced fold switch in proteins

    NASA Astrophysics Data System (ADS)

    Baruah, Anupaul; Biswas, Parbati

    2015-05-01

    This work investigates the computational design of a pH induced protein fold switch based on a self-consistent mean-field approach by identifying the ensemble averaged characteristics of sequences that encode a fold switch. The primary challenge to balance the alternative sets of interactions present in both target structures is overcome by simultaneously optimizing two foldability criteria corresponding to two target structures. The change in pH is modeled by altering the residual charge on the amino acids. The energy landscape of the fold switch protein is found to be double funneled. The fold switch sequences stabilize the interactions of the sites with similar relative surface accessibility in both target structures. Fold switch sequences have low sequence complexity and hence lower sequence entropy. The pH induced fold switch is mediated by attractive electrostatic interactions rather than hydrophobic-hydrophobic contacts. This study may provide valuable insights to the design of fold switch proteins.

  13. Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

    NASA Astrophysics Data System (ADS)

    Toto, Angelo; Camilloni, Carlo; Giri, Rajanish; Brunori, Maurizio; Vendruscolo, Michele; Gianni, Stefano

    2016-02-01

    Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions.

  14. Design principles for rapid folding of knotted DNA nanostructures.

    PubMed

    Kočar, Vid; Schreck, John S; Čeru, Slavko; Gradišar, Helena; Bašić, Nino; Pisanski, Tomaž; Doye, Jonathan P K; Jerala, Roman

    2016-01-01

    Knots are some of the most remarkable topological features in nature. Self-assembly of knotted polymers without breaking or forming covalent bonds is challenging, as the chain needs to be threaded through previously formed loops in an exactly defined order. Here we describe principles to guide the folding of highly knotted single-chain DNA nanostructures as demonstrated on a nano-sized square pyramid. Folding of knots is encoded by the arrangement of modules of different stability based on derived topological and kinetic rules. Among DNA designs composed of the same modules and encoding the same topology, only the one with the folding pathway designed according to the 'free-end' rule folds efficiently into the target structure. Besides high folding yield on slow annealing, this design also folds rapidly on temperature quenching and dilution from chemical denaturant. This strategy could be used to design folding of other knotted programmable polymers such as RNA or proteins. PMID:26887681

  15. Cotranslational protein folding on the ribosome monitored in real time.

    PubMed

    Holtkamp, Wolf; Kokic, Goran; Jäger, Marcus; Mittelstaet, Joerg; Komar, Anton A; Rodnina, Marina V

    2015-11-27

    Protein domains can fold into stable tertiary structures while they are synthesized on the ribosome. We used a high-performance, reconstituted in vitro translation system to investigate the folding of a small five-helix protein domain-the N-terminal domain of Escherichia coli N5-glutamine methyltransferase HemK-in real time. Our observations show that cotranslational folding of the protein, which folds autonomously and rapidly in solution, proceeds through a compact, non-native conformation that forms within the peptide tunnel of the ribosome. The compact state rearranges into a native-like structure immediately after the full domain sequence has emerged from the ribosome. Both folding transitions are rate-limited by translation, allowing for quasi-equilibrium sampling of the conformational space restricted by the ribosome. Cotranslational folding may be typical of small, intrinsically rapidly folding protein domains. PMID:26612953

  16. Design principles for rapid folding of knotted DNA nanostructures

    PubMed Central

    Kočar, Vid; Schreck, John S.; Čeru, Slavko; Gradišar, Helena; Bašić, Nino; Pisanski, Tomaž; Doye, Jonathan P. K.; Jerala, Roman

    2016-01-01

    Knots are some of the most remarkable topological features in nature. Self-assembly of knotted polymers without breaking or forming covalent bonds is challenging, as the chain needs to be threaded through previously formed loops in an exactly defined order. Here we describe principles to guide the folding of highly knotted single-chain DNA nanostructures as demonstrated on a nano-sized square pyramid. Folding of knots is encoded by the arrangement of modules of different stability based on derived topological and kinetic rules. Among DNA designs composed of the same modules and encoding the same topology, only the one with the folding pathway designed according to the ‘free-end' rule folds efficiently into the target structure. Besides high folding yield on slow annealing, this design also folds rapidly on temperature quenching and dilution from chemical denaturant. This strategy could be used to design folding of other knotted programmable polymers such as RNA or proteins. PMID:26887681

  17. Sequential Folding using Light-activated Polystyrene Sheet

    PubMed Central

    Lee, Yonghee; Lee, Hyeok; Hwang, Taesoon; Lee, Jong-Gu; Cho, Maenghyo

    2015-01-01

    A pre-strained polystyrene (PS) polymer sheet is deformed when it approaches the glass transition state as a result of light absorption. By controlling the light absorption of the polymer sheet, non-contact sequential folding can be accomplished. Line patterns of different transparencies and shapes are used to control the light absorption. The line pattern shape is closely related to the folding angle and folding start time. The relation between the line pattern design and folding performance was evaluated experimentally to develop a technique for folding PS sheets. The results show that sequential folding of PS sheets can be accomplished by changing the degree of transparency of the line pattern. Using the technique developed in this study, self-folding origami structures with complicated shapes can be designed and manufactured. PMID:26559611

  18. Prediction of protein folding rates from simplified secondary structure alphabet.

    PubMed

    Huang, Jitao T; Wang, Titi; Huang, Shanran R; Li, Xin

    2015-10-21

    Protein folding is a very complicated and highly cooperative dynamic process. However, the folding kinetics is likely to depend more on a few key structural features. Here we find that secondary structures can determine folding rates of only large, multi-state folding proteins and fails to predict those for small, two-state proteins. The importance of secondary structures for protein folding is ordered as: extended β strand > α helix > bend > turn > undefined secondary structure>310 helix > isolated β strand > π helix. Only the first three secondary structures, extended β strand, α helix and bend, can achieve a good correlation with folding rates. This suggests that the rate-limiting step of protein folding would depend upon the formation of regular secondary structures and the buckling of chain. The reduced secondary structure alphabet provides a simplified description for the machine learning applications in protein design. PMID:26247139

  19. Pseudomonas sp. CL7 from Sludge Removed 2,3,4,6-Tetrachlorophenol in Vivo and in Vitro Condition.

    PubMed

    Karn, Santosh Kumar; Reddy, M Sudhakara; Chakrabarti, Swapan Kumar

    2016-04-01

    The present research focused on 2,3,4,6-Tetrachlorophenol (2,3,4,6-TeCP) mineralizing bacterium from the sludge of pulp and paper industry and identified as Pseudomonas sp. CL7 by 16s rRNA gene sequences analysis. This isolate degraded 2,3,4,6-TeCP as indicated by stoichiometric release of chloride and biomass formation. High pressure liquid chromatography (HPLC) analysis showed that Pseudomonas sp. (CL7) was able to mineralize a higher concentration of 2,3,4,6-TeCP (600 mg/l or 2.5 mM) than any previously reported 2,3,4,6-TeCP degrading bacteria. As the concentration of 2,3,4,6-TeCP increased from 50 (0.21 mM) to 600 mg/l (2.5 mM), the reduction in the cell growth was observed and the 2,3,4,6-TeCP degradation was more than 85% in all the concentrations in the present study. CL7 was able to remove 100% of 2,3,4,6-TeCP from the sludge (in Vitro condition) when supplemented with 100 mg/l (0.42 mM) of 2,3,4,6-TeCP and grown for two weeks. This study showed that CL7 can be used for bioremediation of 2,3,4,6-TeCP. PMID:27131053

  20. The geometry and kinematics of flow perturbation folds

    NASA Astrophysics Data System (ADS)

    Alsop, G. I.; Holdsworth, R. E.

    2002-05-01

    Minor folds formed synchronous with ductile deformation in high strain zones can preserve a record of the scale and kinematics of heterogeneous flow. Using structures associated with WNW-directed Caledonian thrusting in N Scotland, we show that localised perturbations in flow resulted in the generation of predominantly cylindrical minor folds with hinges lying at low angles to the transport direction. These define a series of larger-scale fold culminations (reflecting 'surging flow') or depressions (reflecting 'slackening flow') that are bisected by transport-parallel culmination and depression surfaces. The fold patterns suggest a dominance of layer-normal differential shearing due to gradients in shear strain normal to transport. Culmination surfaces are marked by along-strike reversals in the polarity of structural facing and vergence of minor folds which, contrary to classic fold patterns, define reverse asymmetric relationships. Culmination surfaces separate folding in to clockwise (Z folds) and anticlockwise (S folds) domains relative to the transport lineation. The dip of fold axial planes systematically increases as their strike becomes sub-parallel to transport resulting in a 3D statistical fanning arrangement centred about the transport direction. Thus, mean S- and Z-fold axial planes intersect precisely parallel to the transport lineation and potentially provide a means of determining transport directions in cases where lineations are poorly preserved. Culminations display convergent fold patterns with fold hinges becoming sub-parallel to transport towards the culmination surface and underlying detachment, whilst axial planes define overall concave up listric geometries which are bisected by the culmination surface. Thus, around culminations and depressions there are ordered, scale-independent relationships between transport direction, shear sense, fold facing, vergence and hinge/axial plane orientations. The techniques described here can be applied and

  1. Vergence and facing patterns in large-scale sheath folds

    NASA Astrophysics Data System (ADS)

    Alsop, G. I.; Holdsworth, R. E.

    1999-10-01

    The careful geometric analysis of minor structural detail elucidates the relationships and evolution of associated large-scale curvilinear hinge geometries, developed during WNW-directed Caledonian thrusting exposed in Neoproterozoic Moine psammites of the Moine Nappe. Reversals in the polarity of structural facing associated with minor folding, mark the position of major sheath folds which parallel transport. Upwardly convex sheaths (closing in the direction of thrust transport) cored by older gneissose basement inliers are termed culminations, whilst those opening in the transport direction (and cored by Moine psammites) are termed depressions. Sheath folds are bisected by transport parallel and foliation normal (culmination/depression) surfaces which separate not only the reversals in facing, but also delineate zones of minor fold hinge obliquity into clockwise and anticlockwise domains relative to the transport direction. The sense of obliquity of minor Z and S folds is thus dependent on position with respect to the surfaces of culmination and depression and not the fold axial surfaces. Surfaces of culmination and depression may be superimposed on original overturned antiformal and synformal folds to produce a variety of dome (culmination on antiform), saddle (depression on antiform), inverted saddle (culmination on synform) and basin (depression on synform) configurations. The curvilinear hinges of minor folds may also be asymmetrical about the transport direction and within the plane of the regional foliation to define patterns of fold hinge-line vergence. Classical concepts of fold limb vergence may thus relate to larger antiformal and synformal hinges, whilst the fold hinge-line vergence defines major curvilinear hinges associated with culminations and depressions. Major sheath folds may therefore be interpreted in terms of both minor fold hinge-line and limb vergence, coupled with fold axis obliquity and reversals in the polarity of structural facing. The

  2. Enhanced solubilization of arsenic and 2,3,4,6 tetrachlorophenol from soils by a cyclodextrin derivative.

    PubMed

    Chatain, V; Hanna, K; de Brauer, C; Bayard, R; Germain, P

    2004-10-01

    The application of extracting aqueous solutions with cyclodextrins in several soil remediation technologies has been increasingly studied but little is known about their removal capacities toward the inorganic species. Herein, the effectiveness of cyclodextrins (CDs) in extracting arsenic, copper, and iron from a mining soil is presented. In a preliminary test of four types of CD aqueous solutions, only the addition of carboxylmethyl-beta-cyclodextrin CMCD (a cyclodextrin derivative) led to a significant enhancement in arsenic removal. An increase in the concentration of copper and iron in the leachates was also observed with CMCD. Kinetic study of arsenic release was carried out at two temperatures (20 and 35 degrees C). The arsenic concentration in the leachates increases with increasing cyclodextrin concentration. At an 80 mM CMCD concentration, arsenic, copper, and iron released in filtrates were about 20-, 1,000-, and 4,000-fold greater, respectively, than that obtained using deionized water. In the soil system, the CMCD capacity removal was found to be higher for cations than for arsenic. Because the tetrachlorophenol can co-occur with arsenic and copper in several contaminated sites, its solubilization by CMCD was also investigated. Extraction experiments were performed to extract 2,3,4,6 tetrachlorophenol (TeCP) in spiked soil with CMCD. The results of batch experiments have shown that CMCD could significantly increase the TeCP extraction from soil. CD sorption on soils as quantified by a fluorescence technique was low, indicating no significant loss of CD during the leaching experiments. The use of CMCD as a flushing agent to enhance the removal of both inorganic and organic pollutants from mixed-contaminated soils appears as a promising remediation method. PMID:15312736

  3. Ferromagnetism in Cu 3-thiosemicarbazone- 2,3-dioxoindole complexes

    NASA Astrophysics Data System (ADS)

    Zentková, M.; Kováč, J.; Zentko, A.; Košturiak, A.

    1991-12-01

    We report evidence for ferromagnetic ordering in Cu-chelates of 3-thiosemicarbazone-2,3-dioxoindole (isatine). It has been found that the Curie temperature is 16.8 K and is independent of the Cu content.

  4. Dielectric properties of polyfunctional alcohols: 2,3-butanediol

    NASA Astrophysics Data System (ADS)

    Zhuravlev, V. I.

    2016-08-01

    Using a variety theoretical approaches within the Debye, Davidson-Cole, and Forsman models, and an approach based on the Dissado-Hill theory, dielectric spectra of 2,3-butanediol in the temperature range of 298 to 423 K are analyzed. It is shown that the dielectric spectra of 2,3-butanediole are described by the Davidson-Cole equation, and the βDC parameter depends strongly on temperature. The spectrum of dielectric relaxation of 2,3-butanediol within the Debye theory is presented as the sum of two areas of dispersion, and conclusions are drawn regarding possible mechanisms of dispersion responsible for the obtained fields. The relaxation times of 2,3-butanediol, calculated using different equations describing the nonlinear behavior of relaxation times, are compared. The dipole moments of clusters are obtained for the first time using the Dissado-Hill cluster model, and a preliminary analysis of them is performed.

  5. 43 CFR 2916.2-3 - Renewal of leases.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., DEPARTMENT OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) LEASES Alaska Fur Farm § 2916.2-3 Renewal of... preference right to a renewal. The timely filing of an application will, however authorize the exclusive...

  6. 43 CFR 2916.2-3 - Renewal of leases.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) LEASES Alaska Fur Farm § 2916.2-3 Renewal of... preference right to a renewal. The timely filing of an application will, however authorize the exclusive...

  7. 43 CFR 2916.2-3 - Renewal of leases.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., DEPARTMENT OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) LEASES Alaska Fur Farm § 2916.2-3 Renewal of... preference right to a renewal. The timely filing of an application will, however authorize the exclusive...

  8. 43 CFR 2916.2-3 - Renewal of leases.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF THE INTERIOR LAND RESOURCE MANAGEMENT (2000) LEASES Alaska Fur Farm § 2916.2-3 Renewal of... preference right to a renewal. The timely filing of an application will, however authorize the exclusive...

  9. 34. DETAILS OF CAISSON FOR PIERS 2, 3, 4 AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. DETAILS OF CAISSON FOR PIERS 2, 3, 4 AND 5 TO BE BUILT ON SOIL OVERBURDEN - East Bloomsburg Bridge, Spanning Susquehanna River at Pennsylvania Route 487 (Legislative Route 283), Bloomsburg, Columbia County, PA

  10. Asymmetric Organocatalytic Wittig [2,3]-Rearrangement of Oxindoles.

    PubMed

    Ošeka, Maksim; Kimm, Mariliis; Kaabel, Sandra; Järving, Ivar; Rissanen, Kari; Kanger, Tõnis

    2016-03-18

    A highly enantioselective organocatalytic [2,3]-rearrangement of oxindole derivatives is presented. The reaction was catalyzed by squaramide, and this provides access to 3-hydroxy 3-substituted oxindoles in high enantiomeric purities. PMID:26937554

  11. 2,3-Butanediol Metabolism in the Acetogen Acetobacterium woodii.

    PubMed

    Hess, Verena; Oyrik, Olga; Trifunović, Dragan; Müller, Volker

    2015-07-01

    The acetogenic bacterium Acetobacterium woodii is able to reduce CO2 to acetate via the Wood-Ljungdahl pathway. Only recently we demonstrated that degradation of 1,2-propanediol by A. woodii was not dependent on acetogenesis, but that it is disproportionated to propanol and propionate. Here, we analyzed the metabolism of A. woodii on another diol, 2,3-butanediol. Experiments with growing and resting cells, metabolite analysis and enzymatic measurements revealed that 2,3-butanediol is oxidized in an NAD(+)-dependent manner to acetate via the intermediates acetoin, acetaldehyde, and acetyl coenzyme A. Ethanol was not detected as an end product, either in growing cultures or in cell suspensions. Apparently, all reducing equivalents originating from the oxidation of 2,3-butanediol were funneled into the Wood-Ljungdahl pathway to reduce CO2 to another acetate. Thus, the metabolism of 2,3-butanediol requires the Wood-Ljungdahl pathway. PMID:25934628

  12. 2,3-Butanediol Metabolism in the Acetogen Acetobacterium woodii

    PubMed Central

    Hess, Verena; Oyrik, Olga; Trifunović, Dragan

    2015-01-01

    The acetogenic bacterium Acetobacterium woodii is able to reduce CO2 to acetate via the Wood-Ljungdahl pathway. Only recently we demonstrated that degradation of 1,2-propanediol by A. woodii was not dependent on acetogenesis, but that it is disproportionated to propanol and propionate. Here, we analyzed the metabolism of A. woodii on another diol, 2,3-butanediol. Experiments with growing and resting cells, metabolite analysis and enzymatic measurements revealed that 2,3-butanediol is oxidized in an NAD+-dependent manner to acetate via the intermediates acetoin, acetaldehyde, and acetyl coenzyme A. Ethanol was not detected as an end product, either in growing cultures or in cell suspensions. Apparently, all reducing equivalents originating from the oxidation of 2,3-butanediol were funneled into the Wood-Ljungdahl pathway to reduce CO2 to another acetate. Thus, the metabolism of 2,3-butanediol requires the Wood-Ljungdahl pathway. PMID:25934628

  13. VIEW OF APALACHICOLA RIVER BRIDGE SPANS 2, 3, AND 4, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF APALACHICOLA RIVER BRIDGE SPANS 2, 3, AND 4, EAST SIDE, FROM CENTER OF RIVER, FACING WEST - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  14. VIEW OF APALACHICOLA RIVER BRIDGE SPANS 2, 3, 4, AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF APALACHICOLA RIVER BRIDGE SPANS 2, 3, 4, AND 5, EAST SIDE, FROM NORTH SHORE OF RIVER (CALHOUN COUNTY SIDE), FACING SOUTH - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  15. VIEW OF APALACHICOLA RIVER BRIDGE SPANS 1, 2, 3, 4, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF APALACHICOLA RIVER BRIDGE SPANS 1, 2, 3, 4, AND 5, EAST SIDE, FROM SOUTH SHORE OF RIVER (LIBERTY COUNTY SIDE), FACING WEST - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  16. ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 AND 6, APALACHICOLA RIVER BRIDGE, SHEET 5505 TO 8-M1 - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  17. VIEW OF APALACHICOLA RIVER BRIDGE SPANS 2, 3, AND 4, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF APALACHICOLA RIVER BRIDGE SPANS 2, 3, AND 4, WEST SIDE, FROM CENTER OF RIVER, FACING EAST - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  18. CRISPR/Cas9 genome editing throws descriptive 3-D genome folding studies for a loop.

    PubMed

    Beagan, Jonathan A; Phillips-Cremins, Jennifer E

    2016-07-01

    CRISPR/Cas9 genome editing studies have recently shed new light into the causal link between the linear DNA sequence and 3-D chromatin architecture. Here we describe current models for the folding of genomes into a nested hierarchy of higher-order structures and discuss new insights into the organizing principles governing genome folding at each length scale. WIREs Syst Biol Med 2016, 8:286-299. doi: 10.1002/wsbm.1338 For further resources related to this article, please visit the WIREs website. PMID:27265842

  19. A Computational Study of the Effect of False Vocal Folds on Glottal Flow and Vocal Fold Vibration During Phonation

    PubMed Central

    Zheng, Xudong; Bielamowicz, Steve; Luo, Haoxiang; Mittal, Rajat

    2010-01-01

    The false vocal folds are believed to be components of the acoustic filter that is responsible for shaping the voice. However, the effects of false vocal folds on the vocal fold vibration and the glottal aerodynamic during phonation remain unclear. This effect has implications for computational modeling of phonation as well as for understanding laryngeal pathologies such as glottal incompetence resulting from unilateral vocal fold paralysis. In this study, a high fidelity, two-dimensional computational model, which combines an immersed boundary method for the airflow and a continuum, finite-element method for the vocal folds, is used to examine the effect of the false vocal folds on flow-induced vibration (FIV) of the true vocal folds and the dynamics of the glottal jet. The model is notionally based on a laryngeal CT scan and employs realistic flow conditions and tissue properties. Results show that the false vocal folds potentially have a significant impact on phonation. The false vocal folds reduce the glottal flow impedance and increase the amplitude as well as the mean glottal jet velocity. The false vocal folds also enhance the intensity of the monopole acoustic sources in the glottis. A mechanism for reduction in flow impedance due to the false vocal folds is proposed. PMID:19142730

  20. A computational study of the effect of false vocal folds on glottal flow and vocal fold vibration during phonation.

    PubMed

    Zheng, Xudong; Bielamowicz, Steve; Luo, Haoxiang; Mittal, Rajat

    2009-03-01

    The false vocal folds are believed to be components of the acoustic filter that is responsible for shaping the voice. However, the effects of false vocal folds on the vocal fold vibration and the glottal aerodynamic during phonation remain unclear. This effect has implications for computational modeling of phonation as well as for understanding laryngeal pathologies such as glottal incompetence resulting from unilateral vocal fold paralysis. In this study, a high fidelity, two-dimensional computational model, which combines an immersed boundary method for the airflow and a continuum, finite-element method for the vocal folds, is used to examine the effect of the false vocal folds on flow-induced vibration (FIV) of the true vocal folds and the dynamics of the glottal jet. The model is notionally based on a laryngeal CT scan and employs realistic flow conditions and tissue properties. Results show that the false vocal folds potentially have a significant impact on phonation. The false vocal folds reduce the glottal flow impedance and increase the amplitude as well as the mean glottal jet velocity. The false vocal folds also enhance the intensity of the monopole acoustic sources in the glottis. A mechanism for reduction in flow impedance due to the false vocal folds is proposed. PMID:19142730

  1. Structure of EvaA: a paradigm for sugar 2,3-dehydratases.

    PubMed

    Kubiak, Rachel L; Thoden, James B; Holden, Hazel M

    2013-03-26

    Unusual deoxysugars found appended to natural products often provide or enhance the pharmacokinetic activities of the parent compound. The preferred carbohydrate donors for the biosynthesis of such glycosylated natural products are the dTDP-linked sugars. Many of the biologically relevant dTDP-deoxysugars are constructed around the 2,6-dideoxyhexoses or the 2,3(4),6-trideoxyhexoses. A key step in the biosynthesis of these sugars is the removal of the hexose C-2' hydroxyl group and the oxidation of the C-3' hydroxyl group to a carbonyl moiety. Enzymes that catalyze these reactions are referred to as 2,3-dehydratases and have been, for the most part, largely uncharacterized. Here we report the first structural analysis of a sugar 2,3-dehydratase. For this investigation, the enzyme, EvaA, was cloned from Amycolatopsis orientalis, and the structure was solved and refined to a nominal resolution of 1.7 Å. On the basis of the resulting model, it is clear that EvaA belongs to the large Nudix hydrolase superfamily and is most similar to GDP-mannose hydrolase. Each subunit of the EvaA dimer folds into two domains that clearly arose via gene duplication. Two dTDP-sugar binding pockets, A and B, are present in each EvaA subunit. On the basis of site-directed mutagenesis experiments and activity assays, it appears that pocket A functions as the active site and pocket B is simply a remnant left behind from the gene duplication event. As 2,3-dehydration is crucial for the biosynthesis of many unusual deoxysugars, this investigation provides key structural insight into this widely conserved reaction. PMID:23473392

  2. Fold assessment for comparative protein structure modeling.

    PubMed

    Melo, Francisco; Sali, Andrej

    2007-11-01

    Accurate and automated assessment of both geometrical errors and incompleteness of comparative protein structure models is necessary for an adequate use of the models. Here, we describe a composite score for discriminating between models with the correct and incorrect fold. To find an accurate composite score, we designed and applied a genetic algorithm method that searched for a most informative subset of 21 input model features as well as their optimized nonlinear transformation into the composite score. The 21 input features included various statistical potential scores, stereochemistry quality descriptors, sequence alignment scores, geometrical descriptors, and measures of protein packing. The optimized composite score was found to depend on (1) a statistical potential z-score for residue accessibilities and distances, (2) model compactness, and (3) percentage sequence identity of the alignment used to build the model. The accuracy of the composite score was compared with the accuracy of assessment by single and combined features as well as by other commonly used assessment methods. The testing set was representative of models produced by automated comparative modeling on a genomic scale. The composite score performed better than any other tested score in terms of the maximum correct classification rate (i.e., 3.3% false positives and 2.5% false negatives) as well as the sensitivity and specificity across the whole range of thresholds. The composite score was implemented in our program MODELLER-8 and was used to assess models in the MODBASE database that contains comparative models for domains in approximately 1.3 million protein sequences. PMID:17905832

  3. Fracture patterns in synclinal folds, Miaofengshan, Beijing

    NASA Astrophysics Data System (ADS)

    Liu, X. Z.; Liao, Z.; Reches, Z.

    2014-12-01

    The anticlinal bends are of interest for the oil/gas exploration and drilling designs as they are structural traps associated with high intensity of natural fractures due to bending curvature extension. However, some petroliferous areas with proven oil reserves were identified in synclinal structures, e.g. Songliao, Ordos and Bohai Bay Basins, northeast China, Bonaparte Basin, Australia, and Santa Maria Valley field, California. We analyze the fractures in synclines that are expected to carry curvature related fractures similarly to anticlines. The analysis is conducted on a 500m long and ~300 tall exposure of a folded sequence of dolomite and limestone layers at Miaofengshan, Beijing. Two general fracture groups are recognized: (1) layer crossing joints that are sub-parallel to the syncline axial surface; and (2) a distinct system of extension veins, which are joints filled with secondary calcite, that was found only in two layers of 0.8 and 2.2 m thick. These veins are layer-bound, they are up to 5 cm wide, and their width tapers toward the top and bottom of the host layers. Most of them are oriented normal to the bedding surfaces and radially with respect to the syncline shape. We recognized two phases of secondary mineralization that indicate layer-parallel extension of 5% or more. Apparently, these veins developed by bending extension of the most brittle layers whereas the more ductile layers above and below extended quasi-continuously. The analysis suggests that synclinal fracturing should be considered as possible mechanism for exploration of unconventional.

  4. 10 CFR 2.3 - Resolution of conflict.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Resolution of conflict. 2.3 Section 2.3 Energy NUCLEAR... Resolution of conflict. (a) In any conflict between a general rule in subpart C of this part and a special... not apply to hearings in 10 CFR parts 4, 9, 10, 11, 12, 13, 15, 16, and subparts H and I of 10...

  5. 10 CFR 2.3 - Resolution of conflict.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... not apply to hearings in 10 CFR parts 4, 9, 10, 11, 12, 13, 15, 16, and subparts H and I of 10 CFR... 10 Energy 1 2010-01-01 2010-01-01 false Resolution of conflict. 2.3 Section 2.3 Energy NUCLEAR... Resolution of conflict. (a) In any conflict between a general rule in subpart C of this part and a...

  6. 2.3.1 Biological Effects of Ionizing Radiations

    NASA Astrophysics Data System (ADS)

    Kaul, A.

    This document is part of Subvolume A 'Fundamentals and Data in Radiobiology, Radiation Biophysics, Dosimetry and Medical Radiological Protection' of Volume 7 'Medical Radiological Physics' of Landolt-Börnstein - Group VIII 'Advanced Materials and Technologies'. It contains the Subsection '2.3.1 Biological Effects of Ionizing Radiations' of the Section '2.3 Biological Effects' of the Chapter '2 Radiation and Biological Effects' with the comtents:

  7. Renewable Gasoline, Solvents, and Fuel Additives from 2,3-Butanediol.

    PubMed

    Harvey, Benjamin G; Merriman, Walter W; Quintana, Roxanne L

    2016-07-21

    2,3-Butanediol (2,3-BD) is a renewable alcohol that can be prepared in high yield from biomass sugars. 2,3-BD was selectively dehydrated in a solvent-free process to a complex mixture of 2-ethyl-2,4,5-trimethyl-1,3-dioxolanes and 4,5-dimethyl-2isopropyl dioxolanes with the heterogeneous acid catalyst Amberlyst-15. The purified dioxolane mixture exhibited an anti-knock index of 90.5, comparable to high octane gasoline, and a volumetric net heat of combustion 34 % higher than ethanol. The solubility of the dioxolane mixture in water was only 0.8 g per 100 mL, nearly an order of magnitude lower than the common gasoline oxygenate methyl tert-butyl ether. The dioxolane mixture has potential applications as a sustainable gasoline blending component, diesel oxygenate, and industrial solvent. PMID:27304610

  8. Influence of intensity loss in the cavity of a folded Fabry-Perot interferometer on interferometric signals

    SciTech Connect

    Shyu, Lih-Horng; Chang, Chung-Ping; Wang, Yung-Cheng

    2011-06-15

    Fabry-Perot interferometer is often used for the micro-displacement, because of its common optical path structure being insensitive to the environmental disturbances. Recently, the folded Fabry-Perot interferometer has been investigated for displacement measurements in large ranges. The advantages of a folded Fabry-Perot interferometer are insensitive to the tilt angle and higher optical resolution. But the design of the optical cavity has become more and more complicated. For this reason, the intensity loss in the cavity will be an important parameter for the distribution of the interferometric intensity. To obtain a more accurate result of such interferometer utilized for displacement measurements, the intensity loss of the cavity in the fabricated folded Fabry-Perot interferometer and the modified equation of the folded Fabry-Perot interferometer will be described. According to the theoretical and experimental results, the presented model is available for the analysis of displacement measurements by a folded Fabry-Perot interferometer.

  9. Carbon Solubility of Molten Sulfides at 2-3 GPa

    NASA Astrophysics Data System (ADS)

    Zhang, Z.; Hirschmann, M. M.

    2012-12-01

    Sulfide is molten through much of Earth's upper mantle and so could have an important influence on geochemical and geophysical properties. For example, liquid sulfide could dissolve appreciable carbon, and thereby be a significant sink for reduced carbon in the mantle and perhaps be associated with carbon transport, including diamond precipitation. Here we present experimental data on the phase relations and carbon solubility of sulfides at 2-3 GPa in graphite capsules. Carbon was analyzed by EMPA using an LDE2 crystal and a 10 kV, 80 nA beam, and secondary steel and carbide standards. Repeated analyses of 99.995 wt% Fe indicate a C blank of 0.47 ± 0.12 wt.% (n=38), which was subtracted from the analyses. The limit of detection is therefore likely near 0.1-0.15 wt.%, but we take a more conservative value of 0.27 wt.%, which is the concentration in NIST C1248 steel, the lowest standard for which we unambiguously measure C. FeS monosulfide melts coexist with crystalline sulfide at 2GPa and 1100°C, and at 3GPa and 1200°C, respectively. Lower temperatures are subsolidus and higher temperatures produce only liquids (+graphite). For Fe-S liquids at 2GPa,1500-1600°C and 3GPa, 1600°C, at low bulk S content (5-10 wt.%), a carbide melt coexists with the sulfide. More sulfur-rich bulk compositions produce two immiscible liquids which are approximately (Fe~93%S2~3%C2~4%) and (Fe~70%S~30%)., but Ni addition diminishes the miscibility gap. Carbon solubility in (Fe0.5,Ni0.5)-S liquids diminishes with decreasing metal/sulfide ratio; up to 10 wt.% S, solubility is 2 wt.% C, but diminishes to <1 wt.% at 15 wt% S and is below detection at >20 wt.% S. At 2GPa and 1600°C, other graphite-saturated monosulfide compositions, (Fe1-x,Nix)S (x=0.33,0.50,0.67), FeCuS2 NiS, CuS, and CoS, dissolve less C than detection limit. We detect <0.5 wt.% C in Ni metal and Cu metal in graphite-saturated compositions. In the shallow mantle, where sulfide liquid approximates monosulfide stoichiometry

  10. Impact of structure space continuity on protein fold classification

    PubMed Central

    Xu, Jinrui; Zhang, Jianzhi

    2016-01-01

    Protein structure classification hierarchically clusters domain structures based on structure and/or sequence similarities and plays important roles in the study of protein structure-function relationship and protein evolution. Among many classifications, SCOP and CATH are widely viewed as the gold standards. Fold classification is of special interest because this is the lowest level of classification that does not depend on protein sequence similarity. The current fold classifications such as those in SCOP and CATH are controversial because they implicitly assume that folds are discrete islands in the structure space, whereas increasing evidence suggests significant similarities among folds and supports a continuous fold space. Although this problem is widely recognized, its impact on fold classification has not been quantitatively evaluated. Here we develop a likelihood method to classify a domain into the existing folds of CATH or SCOP using both query-fold structure similarities and within-fold structure heterogeneities. The new classification differs from the original classification for 3.4–12% of domains, depending on factors such as the structure similarity score and original classification scheme used. Because these factors differ for different biological purposes, our results indicate that the importance of considering structure space continuity in fold classification depends on the specific question asked. PMID:27006112

  11. Examination of postmortem retinal folds: A non-invasive study.

    PubMed

    Oshima, Toru; Yoshikawa, Hiroshi; Ohtani, Maki; Mimasaka, Sohtaro

    2015-02-01

    The postmortem retinal fold has been previously documented, but its mechanism of formation is not known. All previous studies of the fold involved invasive techniques and the postmortem ocular fundus has yet to be non-invasively examined. Our study used the non-invasive techniques of monocular indirect ophthalmoscopy and ocular echography to examine 79 postmortem eyes of 42 bodies. We examined whether the postmortem retinal fold was associated with postmortem time, position, and/or age. Age was significantly associated with postmortem retinal fold formation (Mann-Whitney U test, P = 0.013), which led us to examine the effect of posterior vitreous detachment (PVD) on retinal folds. The absence of a PVD was statistically associated with the presence of a retinal fold (Fisher's exact test, P < 0.0001). Interestingly, the presence of a PVD was also significantly correlated with retinal fold height (Mann-Whitney U test, P < 0.0001). Therefore, we hypothesized that retinal folds result from postmortem vitreoretinal traction caused by eyeball flaccidity. We also believe that the loss of retinochoroidal hydrostatic pressure plays a role. It is important that forensic pathologists not confuse a postmortem retinal fold with traumatic retinal detachment or perimacular retinal folds caused by child abuse. When child abuse is suspected, forensic pathologists should perform enucleation and a subsequent histological examination for confirmation. PMID:25623189

  12. Mutational Effects on the Folding Dynamics of a Minimized Hairpin‡

    PubMed Central

    Scian, Michele; Shu, Irene; Olsen, Katherine A.; Hassam, Khalil; Andersen, Niels H.

    2013-01-01

    The fold stabilities and folding dynamics of a series of mutants of a model hairpin, KTW-NPATGK-WTE (HP7), are reported. The parent system and the corresponding DPATGK loop species display sub-μs folding time constants. The mutational studies revealed that ultrafast folding requires both some pre-structuring of the loop and a favorable interaction between the chain termini at the transition state. In the case of YY-DPETGT-WY, another sub-μs folding species [Davis, C. M.; Xiao, S.; Raleigh, D. P.; Dyer, R. B. (2012) J. Am. Chem. Soc. 134, 14476–14482], a hydrophobic cluster provides the latter. In the case of HP7, the Coulombic interaction between the terminal NH3+ and CO2− units provides this; a C-terminal Glu to amidated Ala mutation results in a 5-fold folding rate retardation. The effects of mutations within the reversing loop indicate the balance between loop flexibility (favoring fast conformational searching) and turn-formation in the unfolded state is a major factor in determining the folding dynamics. The –NAAAKX- loops examined display no detectable turn formation propensity in other hairpin constructs, but do result in stable analogs of HP7. Peptide KTW-NAAAKK-WTE displays the same fold stability as HP7 but both the folding and unfolding time constants are greater by a factor of 20. PMID:23521619

  13. Mutational effects on the folding dynamics of a minimized hairpin.

    PubMed

    Scian, Michele; Shu, Irene; Olsen, Katherine A; Hassam, Khalil; Andersen, Niels H

    2013-04-16

    The fold stabilities and folding dynamics of a series of mutants of a model hairpin, KTW-NPATGK-WTE (HP7), are reported. The parent system and the corresponding DPATGK loop species display submicrosecond folding time constants. The mutational studies revealed that ultrafast folding requires both some prestructuring of the loop and a favorable interaction between the chain termini in the transition state. In the case of YY-DPETGT-WY, another submicrosecond folding species [Davis, C. M., Xiao, S., Raleigh, D. P., and Dyer, R. B. (2012) J. Am. Chem. Soc. 134, 14476-14482], a hydrophobic cluster provides the latter. In the case of HP7, the Coulombic interaction between the terminal NH3(+) and CO2(-) units provides this; a C-terminal Glu to amidated Ala mutation results in a 5-fold retardation of the folding rate. The effects of mutations within the reversing loop indicate the balance between loop flexibility (favoring fast conformational searching) and turn formation in the unfolded state is a major factor in determining the folding dynamics. The -NAAAKX- loops examined display no detectable turn formation propensity in other hairpin constructs but do result in stable analogues of HP7. Peptide KTW-NAAAKK-WTE displays the same fold stability as HP7, but both the folding and unfolding time constants are greater by a factor of 20. PMID:23521619

  14. Exploring the protein funnel energy landscape for folding and function

    NASA Astrophysics Data System (ADS)

    Onuchic, Jose

    2005-03-01

    Globally the energy landscape of a folding protein resembles a partially rough funnel. Using minimalist model simulations together with analytical theory, we learn about good (minimally frustrated) folding sequences and non-folding (frustrated) sequences In addition to the need to minimize energetic frustration, the fold topology also plays a major role in the folding mechanism. Some folding motifs are easier to design than others, suggesting the possibility that evolution not only selected sequences with sufficiently small energetic frustration but also more easily designable native structures. We have demonstrated for several proteins (such as CI2 and SH3) that they are sufficiently well designed (i.e., reduced energetic frustration) that much of the heterogeneity observed in their transition state ensemble (TSE) is determined by topology. Topological effects go beyond the TSE. The overall structure of the on-route and off-route (traps) intermediates for the folding of more complex proteins and protein dimers is also strongly influenced by topology.this theoretical framework, simulations of minimalist models and their connections to more computationally-expensive all-atom simulations, we are now in the process of obtaining a quantitative understanding of the folding problem, which allows for a direct comparison to a new generation of folding experiments. Connections between the folding landscape and protein function will also be discussed.

  15. Detachment folds versus thrust-folds: numerical modelling and applications to the Swiss Jura Mountains and the Canadian Foothills

    NASA Astrophysics Data System (ADS)

    Humair, Florian; Bauville, Arthur; Epard, Jean-Luc; Schmalholz, Stefan

    2016-04-01

    The Jura Mountains and the Foothills of the Canadian Rockies fold-and-thrust belts are classical examples of thin-skinned belts where folds develop over weak detachment horizons. They offer the possibility to observe and measure strain in folds. In these two belts, a large spectrum of fold geometries is expressed, from symmetric box-fold or pop-up structures to asymmetric thrust-related folds. In this study, we focus on the quantification and prediction of the brittle strain distribution in folds as a function of the fold geometry. Fold geometry is considered as a continuum between two end-member structural styles: symmetric detachment folds and asymmetric foreland-vergent thrust-folds. We performed two-dimensional numerical simulations of visco-plastic detachment folding. The models are used (1) to systematically examine the influence of different initial parameters on the resulting geometry and style of folding and (2) to quantify the local strain pattern through time. The different parameters tested are the following: presence and size of initial geometrical perturbation at the detachment-sediment interface, rheology of the detachment (frictional vs. viscous), additional detachment layer within the series and overbunden thickness. Results of single detachment layer models show that the asymmetry of folds is primarily controlled by the height of the initial geometrical perturbation, regardless to the rheology of the detachment (frictional vs. viscous). Additional detachment interlayer within the series decreases the brittle strain within the stiff layers and favours more rounded anticlines geometry. The models were then adapted to the Swiss Jura and the Canadian Foothills settings. Compared to field observations and cross-sections of existing fault-related anticlines, the proposed simulations agree with the first order geometry and the development of associated localized zones of brittle deformation.

  16. Proteome folding kinetics is limited by protein halflife.

    PubMed

    Zou, Taisong; Williams, Nickolas; Ozkan, S Banu; Ghosh, Kingshuk

    2014-01-01

    How heterogeneous are proteome folding timescales and what physical principles, if any, dictate its limits? We answer this by predicting copy number weighted folding speed distribution - using the native topology - for E.coli and Yeast proteome. E.coli and Yeast proteomes yield very similar distributions with average folding times of 100 milliseconds and 170 milliseconds, respectively. The topology-based folding time distribution is well described by a diffusion-drift mutation model on a flat-fitness landscape in free energy barrier between two boundaries: i) the lowest barrier height determined by the upper limit of folding speed and ii) the highest barrier height governed by the lower speed limit of folding. While the fastest time scale of the distribution is near the experimentally measured speed limit of 1 microsecond (typical of barrier-less folders), we find the slowest folding time to be around seconds ([Formula: see text]8 seconds for Yeast distribution), approximately an order of magnitude less than the fastest halflife (approximately 2 minutes) in the Yeast proteome. This separation of timescale implies even the fastest degrading protein will have moderately high (96%) probability of folding before degradation. The overall agreement with the flat-fitness landscape model further hints that proteome folding times did not undergo additional major selection pressures - to make proteins fold faster - other than the primary requirement to "sufficiently beat the clock" against its lifetime. Direct comparison between the predicted folding time and experimentally measured halflife further shows 99% of the proteome have a folding time less than their corresponding lifetime. These two findings together suggest that proteome folding kinetics may be bounded by protein halflife. PMID:25393560

  17. Naphtho[2,3-c][1,2,5]thiadiazole and 2H-Naphtho[2,3-d][1,2,3]triazole-Containing D-A-π-A Conjugated Organic Dyes for Dye-Sensitized Solar Cells.

    PubMed

    Yen, Yung-Sheng; Ni, Jen-Shyang; Hung, Wei-I; Hsu, Chih-Yu; Chou, Hsien-Hsin; Lin, Jiann-T Suen

    2016-03-01

    Dipolar dyes comprising an arylamine as the electron donor, a cyanoacrylic acid as electron acceptor, and an electron deficient naphtho[2,3-c][1,2,5]thiadiazole (NTD) or naphtho[2,3-d][1,2,3]triazole (NTz) entity in the conjugated spacer, were developed and used as the sensitizers in dye-sensitized solar cells (DSSCs). The introduction of the NTD unit into the molecular frame distinctly narrows the HOMO/LUMO gap with electronic absorption extending to >650 nm. However, significant charge trapping and dye aggregation were found in these dyes. Under standard global AM 1.5 G illumination, the best cell photovoltaic performance achieved 6.37 and 7.53% (∼94% relative to N719-based standard cell) without and with chenodeoxycholic acid (CDCA) coadsorbent, respectively. Without CDCA, the NTz dyes have higher power conversion efficiency (7.23%) than NTD dyes due to less charge trapping, dye aggregation, and better dark current suppression. PMID:26891701

  18. Fast folding of a prototypic polypeptide: the immunoglobulin binding domain of streptococcal protein G.

    PubMed

    Kuszewski, J; Clore, G M; Gronenborn, A M

    1994-11-01

    The folding of the small (56 residues) highly stable B1 immunoglobulin binding domain (GB1) of streptococcal protein G has been investigated by quenched-flow deuterium-hydrogen exchange. This system represents a paradigm for the study of protein folding because it exhibits no complicating features superimposed upon the intrinsic properties of the polypeptide chain. Collapse to a semicompact state exhibiting partial order, reflected in protection factors for ND-NH exchange up to 10-fold higher than that expected for a random coil, occurs within the dead time (< or = 1 ms) of the quenched flow apparatus. This is followed by the formation of the fully native state, as monitored by the fractional proton occupancy of 26 backbone amide groups spread throughout the protein, in a single rapid concerted step with a half-life of 5.2 ms at 5 degrees C. PMID:7703841

  19. Experimental study of the aeroacoustic-aeroelastic behavior of model vocal folds

    NASA Astrophysics Data System (ADS)

    Campo, Elizabeth; Camarena, Ernesto; Krane, Michael

    2010-11-01

    The effect of vocal fold body stiffness and bilateral asymmetry was studied using a life-size physical model of the human airway using interchangeable silicone rubber models of the human vocal folds. The two layer vocal fold models are comprised of an inner body layer and an outside cover layer. The following measures were used to assess the effect of body stiffness and asymmetry: radiated sound power, phonation threshold pressure and aeroacoustic source strengths. Results obtained from the human airway model compared favorably with behavior observed in human subjects. Furthermore, the results reveal that the asymmetric cases required a higher subglottal pressure to initiate phonation and radiated less intense sound, in comparison to the symmetrical configuration.

  20. Structural proteomics of minimal organisms: conservation ofprotein fold usage and evolutionary implications

    SciTech Connect

    Chandonia, John-Marc; Kim, Sung-Hou

    2006-03-15

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

  1. Optimization and scale-up of 2,3-butanediol production by Bacillus amyloliquefaciens B10-127.

    PubMed

    Yang, Taowei; Zhang, Xian; Rao, Zhiming; Gu, Shenghui; Xia, Haifeng; Xu, Zhenghong

    2012-04-01

    The effects of culture conditions on 2,3-butanediol (2,3-BD) production and its possible scale-up have been studied. A newly isolated Bacillus amyloliquefaciens B10-127, belonged to GRAS microorganisms and showed a remarkable 2,3-BD producing potency, was used for this experiment. Corn steep liquor, soybean meal and ammonium citrate were found to be the key factors in the fermentation according to the results obtained from the Plackett-Burman experimental design. The optimal concentration range of the three factors was examined by the steepest ascent path, and their optimal concentration were further optimized via response surface methodological approach and determined to be 31.9, 22.0 and 5.58 g/l, respectively. The concentration of the obtained 2,3-BD increased significantly with optimized medium (62.7 g/l) when compared with unoptimized medium (45.7 g/l) and the 2,3-BD productivity was about 2.4-fold (The fermentation time was shorten from 72 to 42 h). To observe scale-up effects, batch fermentation was carried out at various working volumes. At a working volume of 20.0 l, the final 2,3-BD concentration and yield were 61.4 and 0.38 g/g at 36 h with a 2,3-BD productivity of 1.71 g/l h. This result shows similar amount of 2,3-BD obtained in lab-scale fermentation, and it is possible to scale up to larger fermentors without major problems. PMID:22805938

  2. Very Short Peptides with Stable Folds

    PubMed Central

    Eidenschink, Lisa; Kier, Brandon L.; Huggins, Kelly N. L.; Andersen, Niels H.

    2008-01-01

    By combining a favorable turn sequence with a turn flanking Trp/Trp interaction and a C-terminal H-bonding interaction between a backbone amide and an i - 2 Trp ring, a particularly stable (ΔGU > 7 kJ/mol) truncated hairpin, Ac-WI-(D-Pro-D-Asn)-KWTG-NH2, results. In this construct and others with a W-(4-residue turn)-W motif in severely truncated hairpins, the C-terminal Trp is the edge residue in a well-defined face-to-edge (FtE) aryl/aryl interaction. Longer hairpins and those with six-residue turns retain the reversed “edge-to-face” Trp/Trp geometry first observed for the trpzip peptides. Mutational studies suggest that the W-(4-residue turn)-W interaction provides at least 3 kJ/mol of stabilization in excess of that due to the greater β-propensity of Trp. The β-propensity of Trp is context dependent; but, for the systems studied, always greater than that of Thr (by 0.4 - 4.7 kJ/mol). At non-H-bonded positions remote from the turn, two alternative edge-to-face geometries are observed and there is no evidence of additional stabilization due to the Trp/Trp interaction. The NMR structuring shift diagnostics of edge-to-face Trp/Trp, Trp/Lys π-cation, and Trp/Gly-HN interactions have been defined. The latter can give rise to > 3 ppm upfield shifts for the Gly-HN in -WXnG- units both in turns (n = 2) and at the C-termini (n = 1) of hairpins. Terminal YTG units result in somewhat smaller shifts (extrapolated to 2 ppm for 100% folding). In peptides with both the EtF and FtE W/W interaction geometries, Trp to Tyr mutations indicate that Trp is the preferred “face” residue in aryl/aryl pairings, presumably due to its greater π basicity. PMID:18831035

  3. Prions and protein-folding diseases.

    PubMed

    Norrby, E

    2011-07-01

    Prions represent a group of proteins with a unique capacity to fold into different conformations. One isoform is rich in beta-pleated sheets and can aggregate into amyloid that may be pathogenic. This abnormal form propagates itself by imposing its confirmation on the homologous normal host cell protein. Pathogenic prions have been shown to cause lethal neurodegenerative diseases in humans and animals. These diseases are sometimes infectious and hence referred to as transmissible spongiform encephalopathies. In the present review, the remarkable evolution of the heterodox prion concept is summarized. The origin of this phenomenon is based on information transfer between homologous proteins, without the involvement of nucleic acid-encoded mechanisms. Historically, kuru and Creutzfeldt-Jakob disease (CJD) were the first infectious prion diseases to be identified in man. It was their relationship to scrapie in sheep and experimental rodents that allowed an unravelling of the particular molecular mechanism that underlie the disease process. Transmission between humans has been documented to have occurred in particular contexts, including ritual cannibalism, iatrogenic transmission because of pituitary gland-derived growth hormone or the use in neurosurgical procedures of dura mater from cadavers, and the temporary use of a prion-contaminated protein-rich feed for cows. The latter caused a major outbreak of bovine spongiform encephalopathy, which spread to man by human consumption of contaminated meat, causing approximately 200 cases of variant CJD. All these epidemics now appear to be over because of measures taken to curtail further spread of prions. Recent studies have shown that the mechanism of protein aggregation may apply to a wider range of diseases in and possibly also outside the brain, some of which are relatively common such as Alzheimer's and Parkinson's diseases. Furthermore, it has become apparent that the phenomenon of prion aggregation may have a wider

  4. Method for preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline from 1,2,3,4-tetrahydroquinoline

    DOEpatents

    Field, George; Hammond, Peter R.

    1994-01-01

    Methods for the efficient preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline include a first method in which the acylation of m-aminophenol obtains a lactam which is reduced to give the desired quinoline and a second method in which tetrahydroquinoline is nitrated and hydrogenated and then hydrolyzed to obtain the desire quinoline. 7-hydroxy-1,2,3,4-tetrahydroquinoline is used in the efficient synthesis of four lasing dyes of the rhodamine class.

  5. Method for preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline from 1,2,3,4-tetrahydroquinoline

    DOEpatents

    Field, G.; Hammond, P.R.

    1994-02-01

    Methods for the efficient preparation of 7-hydroxy-1,2,3,4-tetrahydroquinoline include a first method in which the acylation of m-aminophenol obtains a lactam which is reduced to give the desired quinoline and a second method in which tetrahydroquinoline is nitrated and hydrogenated and then hydrolyzed to obtain the desire quinoline. 7-hydroxy-1,2,3,4-tetrahydroquinoline is used in the efficient synthesis of four lasing dyes of the rhodamine class.

  6. Structure-Based Prediction of Protein-Folding Transition Paths.

    PubMed

    Jacobs, William M; Shakhnovich, Eugene I

    2016-09-01

    We propose a general theory to describe the distribution of protein-folding transition paths. We show that transition paths follow a predictable sequence of high-free-energy transient states that are separated by free-energy barriers. Each transient state corresponds to the assembly of one or more discrete, cooperative units, which are determined directly from the native structure. We show that the transition state on a folding pathway is reached when a small number of critical contacts are formed between a specific set of substructures, after which folding proceeds downhill in free energy. This approach suggests a natural resolution for distinguishing parallel folding pathways and provides a simple means to predict the rate-limiting step in a folding reaction. Our theory identifies a common folding mechanism for proteins with diverse native structures and establishes general principles for the self-assembly of polymers with specific interactions. PMID:27602721

  7. Late Quaternary folding of coral reef terraces, Barbados

    NASA Astrophysics Data System (ADS)

    Taylor, Frederick W.; Mann, Paul

    1991-02-01

    Uplifted late Ouaternary coral reefs on the island of Barbados record folding of the emergent crest of the Lesser Antilles accretionary prism (Barbados Ridge complex) since ca. 1 Ma. Three northeast striking folds are defined by systematic changes in altitudes in the crest of First High Cliff, a mostly constructional reef terrace about 125 ka, and Second High Cliff, a partially erosional reef terrace about 500 ka. The folds have wavelengths of 6 to 8 km and fold axes extend about 10 km. The largest anticline rises to the northeast, where it has been breached by erosion exposing highly deformed Eocene to lower Miocene rocks of the Scotland District. Uplift rates based on heights of the last interglacial First High Cliff range from 0.07 to 0.44 mm/yr. Quaternary folding on Barbados indicates that the crest of the accretionary prism continues to be an active fold belt undergoing northwestsoutheast shortening.

  8. Single molecule fluorescence experiments determine protein folding transition path times

    PubMed Central

    Chung, Hoi Sung; McHale, Kevin; Louis, John M.; Eaton, William A.

    2013-01-01

    The transition path is the tiny fraction of an equilibrium molecular trajectory when a transition occurs by crossing the free-energy barrier between two states. It is a single-molecule property that contains all the mechanistic information on how a process occurs. As a step toward observing transition paths in protein folding we determined the average transition-path time for a fast- and a slow-folding protein from a photon-by-photon analysis of fluorescence trajectories in single-molecule Förster-resonance-energy-transfer experiments. While the folding rate coefficients differ by a factor of 10,000, the transition-path times differ by less than a factor of 5, showing that a fast-and a slow-folding protein take almost the same time to fold when folding actually happens. A very simple model based on energy landscape theory can explain this result. PMID:22363011

  9. Cotranslational Protein Folding inside the Ribosome Exit Tunnel.

    PubMed

    Nilsson, Ola B; Hedman, Rickard; Marino, Jacopo; Wickles, Stephan; Bischoff, Lukas; Johansson, Magnus; Müller-Lucks, Annika; Trovato, Fabio; Puglisi, Joseph D; O'Brien, Edward P; Beckmann, Roland; von Heijne, Gunnar

    2015-09-01

    At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins. PMID:26321634

  10. Accordian-folded boot shield for flexible swivel connection

    DOEpatents

    Hoh, Joseph C.

    1986-01-01

    A flexible swivel boot connector for connecting a first boot shield section to a second boot shield section, both first and second boot sections having openings therethrough, the second boot section having at least two adjacent accordian folds at the end having the opening, the second boot section being positioned through the opening of the first boot section such that a first of the accordian folds is within the first boot section and a second of the accordian folds is outside of the first boot, includes first and second annular discs, the first disc being positioned within and across the first accordian fold, the second disc being positioned within and across the second accordian fold, such that the first boot section is moveably and rigidly connected between the first and second accordian folds of the second boot section.

  11. Cotranslational Protein Folding inside the Ribosome Exit Tunnel

    PubMed Central

    Nilsson, Ola B.; Hedman, Rickard; Marino, Jacopo; Wickles, Stephan; Bischoff, Lukas; Johansson, Magnus; Müller-Lucks, Annika; Trovato, Fabio; Puglisi, Joseph D.; O’Brien, Edward P.; Beckmann, Roland; von Heijne, Gunnar

    2015-01-01

    Summary At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins. PMID:26321634

  12. Microbial production of 2,3-butanediol from Jerusalem artichoke tubers by Klebsiella pneumoniae.

    PubMed

    Sun, Li-Hui; Wang, Xu-Dong; Dai, Jian-Ying; Xiu, Zhi-Long

    2009-04-01

    2,3-Butanediol is one of the promising bulk chemicals with wide applications. Its fermentative production has attracted great interest due to the high end concentration. However, large-scale production of 2,3-butanediol requires low-cost substrate and efficient fermentation process. In the present study, 2,3-butanediol production by Klebsiella pneumoniae from Jerusalem artichoke tubers was successfully performed, and various technologies, including separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF), were investigated. The concentration of target products reached 81.59 and 91.63 g/l, respectively after 40 h in batch and fed-batch SSF processes. Comparing with fed-batch SHF, the fed-batch SSF provided 30.3% higher concentration and 83.2% higher productivity of target products. The results showed that Jerusalem artichoke tuber is a favorable substrate for 2,3-butanediol production, and the application of fed-batch SSF for its conversion can result in a more cost-effective process. PMID:19122999

  13. Folding-promoted methylation of a helical DMAP analogue.

    PubMed

    Heemstra, Jennifer M; Moore, Jeffrey S

    2004-02-18

    The methylation rate for a series of pyridine-containing phenylene ethynylene oligomers shows a nonlinear dependence on chain length, with a significant rate enhancement observed for oligomers that adopt a folded, helical conformation. The folded structure provides a microenvironment that lowers the energy barrier for the methylation reaction. Of these noncovalent interactions, the largest stabilization may arise from binding of methyl iodide in the hydrophobic cavity of the folded oligomer, in close proximity to the pyridine nucleophile. PMID:14871092

  14. Kink folding in an extended terrane: Tortilla Mountains, southeastern Arizona

    NASA Astrophysics Data System (ADS)

    Naruk, Stephen J.; Bykerk-Kauffman, Ann; Currier-Lewis, Debra; Davis, George H.; Faulds, James E.; Lewis, Scott W.

    1986-12-01

    Structural analysis of early Miocene metre-scale kink folds in southeastern Arizona shows that they formed in an extensional stress field and that they record horizontal extension. The folds represent a previously unrecognized style of extensional fold. *Present addresses: Faulds—Department of Geology, University of New Mexico, Albuquerque, New Mexico 87131; Currier-Lewis and Lewis—Calpine Energy Corporation, San Jose, California 95110

  15. Crowders perturb the entropy of RNA energy landscapes to favour folding

    PubMed Central

    Kilburn, Duncan; Roh, Joon Ho; Behrouzi, Reza; Briber, Robert M.; Woodson, Sarah A.

    2013-01-01

    Biological macromolecules have evolved to fold and operate in the crowded environment of the cell. We have shown previously that molecular crowding stabilizes folded RNA structures. Here we report SAXS measurements on a 64 kDa bacterial group I ribozyme in the presence of mono- and divalent ions and PEG crowders of different molecular weight. These experiments show that crowders always stabilize the folded RNA, but this stabilization is weaker in NaCl solutions than MgCl2 solutions. Additionally, we find that RNAs with the same global structure, parameterized by Rg, have different scattering functions depending upon the ratio of electrostatic and entropic stabilization by ions and crowders, respectively. We quantify this difference using the scattering length per scattering volume and find that this ratio is larger for RNAs that fold in lower ionic strength solutions due to the higher crowder content. We conclude that lower RNA flexibility, or reduced configurational entropy, widens the free energy gap between the unfolded and folded RNA in crowded MgCl2 solutions. PMID:23773075

  16. Gradual Folding of an Off-Pathway Molten Globule Detected at the Single-Molecule Level.

    PubMed

    Lindhoud, Simon; Pirchi, Menahem; Westphal, Adrie H; Haran, Gilad; van Mierlo, Carlo P M

    2015-09-25

    Molten globules (MGs) are compact, partially folded intermediates that are transiently present during folding of many proteins. These intermediates reside on or off the folding pathway to native protein. Conformational evolution during folding of off-pathway MGs is largely unexplored. Here, we characterize the denaturant-dependent structure of apoflavodoxin's off-pathway MG. Using single-molecule fluorescence resonance energy transfer (smFRET), we follow conversion of unfolded species into MG down to denaturant concentrations that favor formation of native protein. Under strongly denaturing conditions, fluorescence resonance energy transfer histograms show a single peak, arising from unfolded protein. The smFRET efficiency distribution shifts to higher value upon decreasing denaturant concentration because the MG folds. Strikingly, upon approaching native conditions, the fluorescence resonance energy transfer efficiency of the MG rises above that of native protein. Thus, smFRET exposes the misfolded nature of apoflavodoxin's off-pathway MG. We show that conversion of unfolded into MG protein is a gradual, second-order-like process that simultaneously involves separate regions within the polypeptide. PMID:26163276

  17. Enhanced production of 2,3-butanediol from sugarcane molasses.

    PubMed

    Dai, Jian-Ying; Zhao, Pan; Cheng, Xiao-Long; Xiu, Zhi-Long

    2015-03-01

    2,3-Butanediol has been known as a platform green chemical, and the production cost is the key problem for its large-scale production in which the carbon source occupies a major part. Sugarcane molasses is a by-product of sugar industry and considered as a cheap carbon source for biorefinery. In this paper, the fermentation of 2,3-butanediol with sugarcane molasses was studied by reducing the medium ingredients and operation steps. The fermentation medium was optimized by response surface methodology, and 2,3-butanediol production was explored under the deficiency of sterilization, molasses acidification, and organic nitrogen source. Based on these experiments, the fermentation medium with sugarcane molasses as carbon source was simplified to five ingredients, and the steps of molasses acidification and medium sterilization were reduced; thus, the cost was reduced and the production of 2,3-butanediol was enhanced. Under fed-batch fermentation, 99.5 g/L of 2,3-butanediol and acetoin was obtained at 60 h with a yield of 0.39 g/g sugar. PMID:25586489

  18. Folded inflatable protective device and method for making same

    DOEpatents

    Behr, V.L.; Nelsen, J.M.; Gwinn, K.W.

    1998-10-20

    An apparatus and method are disclosed for making an inflatable protective device made of lightweight material that can withstand the initial stress from inflation and enhance radial inflation. The device includes a cushion and an inflator port. The invention further includes several stacks of folded cushion material including a combination of full-width stacks and half-width stacks: a first full-width stack defined by one or more fan folds in a first lateral half of the cushion wherein the folds are substantially centered above a first center line and are substantially over the inflator port; a second full-width stack defined by one or more fan folds in a second lateral half of the cushion wherein the folds are substantially centered above the first center line and substantially over the inflator port in the first full-width stack; a first half-width stack defined by a plurality of fan folds in the bottom of the cushion where neither edge of each fold extends substantially over the second center line; and a second half-width stack defined by a plurality of fan folds in the top of the cushion wherein neither edge of each fold extends substantially over the second center line. 22 figs.

  19. Folded inflatable protective device and method for making same

    DOEpatents

    Behr, Vance L.; Nelsen, James M.; Gwinn, Kenneth W.

    1998-01-01

    An apparatus and method for making an inflatable protective device made of lightweight material that can withstand the initial stress from inflation and enhance radial inflation. The device includes a cushion and an inflator port. The invention further includes several stacks of folded cushion material including a combination of full-width stacks and half-width stacks: a first full-width stack defined by one or more fan folds in a first lateral half of the cushion wherein the folds are substantially centered above a first center line and are substantially over the inflator port; a second full-width stack defined by one or more fan folds in a second lateral half of the cushion wherein the folds are substantially centered above the first center line and substantially over the inflator port in the first full-width stack; a first half-width stack defined by a plurality of fan folds in the bottom of the cushion where neither edge of each fold extends substantially over the second center line; and a second half-width stack defined by a plurality of fan folds in the top of the cushion wherein neither edge of each fold extends substantially over the second center line.

  20. Improved Method of Design for Folding Inflatable Shells

    NASA Technical Reports Server (NTRS)

    Johnson, Christopher J.

    2009-01-01

    An improved method of designing complexly shaped inflatable shells to be assembled from gores was conceived for original application to the inflatable outer shell of a developmental habitable spacecraft module having a cylindrical mid-length section with toroidal end caps. The method is also applicable to inflatable shells of various shapes for terrestrial use. The method addresses problems associated with the assembly, folding, transport, and deployment of inflatable shells that may comprise multiple layers and have complex shapes that can include such doubly curved surfaces as toroids and spheres. One particularly difficult problem is that of mathematically defining fold lines on a gore pattern in a double- curvature region. Moreover, because the fold lines in a double-curvature region tend to be curved, there is a practical problem of how to implement the folds. Another problem is that of modifying the basic gore shapes and sizes for the various layers so that when they are folded as part of the integral structure, they do not mechanically interfere with each other at the fold lines. Heretofore, it has been a common practice to design an inflatable shell to be assembled in the deployed configuration, without regard for the need to fold it into compact form. Typically, the result has been that folding has been a difficult, time-consuming process resulting in a An improved method of designing complexly shaped inflatable shells to be assembled from gores was conceived for original application to the inflatable outer shell of a developmental habitable spacecraft module having a cylindrical mid-length section with toroidal end caps. The method is also applicable to inflatable shells of various shapes for terrestrial use. The method addresses problems associated with the assembly, folding, transport, and deployment of inflatable shells that may comprise multiple layers and have complex shapes that can include such doubly curved surfaces as toroids and spheres. One