Miura-type transformations for lattice equations and Lie group actions associated with Darboux-Lax representations

NASA Astrophysics Data System (ADS)

Berkeley, George; Igonin, Sergei

2016-07-01

Miura-type transformations (MTs) are an essential tool in the theory of integrable nonlinear partial differential and difference equations. We present a geometric method to construct MTs for differential-difference (lattice) equations from Darboux-Lax representations (DLRs) of such equations. The method is applicable to parameter-dependent DLRs satisfying certain conditions. We construct MTs and modified lattice equations from invariants of some Lie group actions on manifolds associated with such DLRs. Using this construction, from a given suitable DLR one can obtain many MTs of different orders. The main idea behind this method is closely related to the results of Drinfeld and Sokolov on MTs for the partial differential KdV equation. Considered examples include the Volterra, Narita-Itoh-Bogoyavlensky, Toda, and Adler-Postnikov lattices. Some of the constructed MTs and modified lattice equations seem to be new.

Darboux transformation of the coupled nonisospectral Gross-Pitaevskii system and its multi-component generalization

NASA Astrophysics Data System (ADS)

Xu, Tao; Chen, Yong

2018-04-01

In this paper, we extend the one-component Gross-Pitaevskii (GP) equation to the two-component coupled GP system including damping term, linear and parabolic density profiles. The Lax pair with nonisospectral parameter and infinitely-many conservation laws of this coupled GP system are presented. Actually, the Darboux transformation (DT) for this kind of nonautonomous system is essentially different from the autonomous case. Consequently, we construct the DT of the coupled GP equations, besides, nonautonomous multi-solitons, one-breather and the first-order rogue wave are also obtained. Various kinds of one-soliton solution are constructed, which include stationary one-soliton and nonautonomous one-soliton propagating along the negative (positive) direction of x-axis. The interaction of two solitons and two-soliton bound state are demonstrated respectively. We get the nonautonomous one-breather on a curved background and this background is completely controlled by the parameter β. Using a limiting process, the nonautonomous first-order rogue wave can be obtained. Furthermore, some dynamic structures of these analytical solutions are discussed in detail. In addition, the multi-component generalization of GP equations are given, then the corresponding Lax pair and DT are also constructed.

Dark and bright solitons for the two-dimensional complex modified Korteweg-de Vries and Maxwell-Bloch system with time-dependent coefficient

NASA Astrophysics Data System (ADS)

Shaikhova, G.; Ozat, N.; Yesmakhanova, K.; Bekova, G.

2018-02-01

In this work, we present Lax pair for two-dimensional complex modified Korteweg-de Vries and Maxwell-Bloch (cmKdV-MB) system with the time-dependent coefficient. Dark and bright soliton solutions for the cmKdV-MB system with variable coefficient are received by Darboux transformation. Moreover, the determinant representation of the one-fold and two-fold Darboux transformation for the cmKdV-MB system with time-dependent coefficient is presented.

Three-wave resonant interactions: Multi-dark-dark-dark solitons, breathers, rogue waves, and their interactions and dynamics

NASA Astrophysics Data System (ADS)

Zhang, Guoqiang; Yan, Zhenya; Wen, Xiao-Yong

2018-03-01

We investigate three-wave resonant interactions through both the generalized Darboux transformation method and numerical simulations. Firstly, we derive a simple multi-dark-dark-dark-soliton formula through the generalized Darboux transformation. Secondly, we use the matrix analysis method to avoid the singularity of transformed potential functions and to find the general nonsingular breather solutions. Moreover, through a limit process, we deduce the general rogue wave solutions and give a classification by their dynamics including bright, dark, four-petals, and two-peaks rogue waves. Ever since the coexistence of dark soliton and rogue wave in non-zero background, their interactions naturally become a quite appealing topic. Based on the N-fold Darboux transformation, we can derive the explicit solutions to depict their interactions. Finally, by performing extensive numerical simulations we can predict whether these dark solitons and rogue waves are stable enough to propagate. These results can be available for several physical subjects such as fluid dynamics, nonlinear optics, solid state physics, and plasma physics.

Darboux transformation and solitons for an integrable nonautonomous nonlinear integro-differential Schrödinger equation

NASA Astrophysics Data System (ADS)

Yong, Xuelin; Fan, Yajing; Huang, Yehui; Ma, Wen-Xiu; Tian, Jing

2017-10-01

By modifying the scheme for an isospectral problem, the non-isospectral Ablowitz-Kaup-Newell-Segur (AKNS) hierarchy is constructed via allowing the time varying spectrum. In this paper, we consider an integrable nonautonomous nonlinear integro-differential Schrödinger equation discussed before in “Multi-soliton management by the integrable nonautonomous nonlinear integro-differential Schrödinger equation” [Y. J. Zhang, D. Zhao and H. G. Luo, Ann. Phys. 350 (2014) 112]. We first analyze the integrability conditions and identify the model. Second, we modify the existing Darboux transformation (DT) for such a non-isospectral problem. Third, the nonautonomous soliton solutions are obtained via the resulting DT and basic properties of these solutions in the inhomogeneous media are discussed graphically to illustrate the influences of the variable coefficients. In the process, a technique by selecting appropriate spectral parameters instead of the variable inhomogeneities is employed to realize a different type of one-soliton management. Several novel optical solitons are constructed and their features are shown by some specific figures. In addition, four kinds of the special localized two-soliton solutions are obtained. The solitonic excitations localized both in space and time, which exhibit the feature of the so-called rogue waves but with a zero background, are discussed.

Higher-order rational solitons and rogue-like wave solutions of the (2 + 1)-dimensional nonlinear fluid mechanics equations

NASA Astrophysics Data System (ADS)

Wen, Xiao-Yong; Yan, Zhenya

2017-02-01

The novel generalized perturbation (n, M)-fold Darboux transformations (DTs) are reported for the (2 + 1)-dimensional Kadomtsev-Petviashvili (KP) equation and its extension by using the Taylor expansion of the Darboux matrix. The generalized perturbation (1 , N - 1) -fold DTs are used to find their higher-order rational solitons and rogue wave solutions in terms of determinants. The dynamics behaviors of these rogue waves are discussed in detail for different parameters and time, which display the interesting RW and soliton structures including the triangle, pentagon, heptagon profiles, etc. Moreover, we find that a new phenomenon that the parameter (a) can control the wave structures of the KP equation from the higher-order rogue waves (a ≠ 0) into higher-order rational solitons (a = 0) in (x, t)-space with y = const . These results may predict the corresponding dynamical phenomena in the models of fluid mechanics and other physically relevant systems.

Structural perturbations on huntingtin N17 domain during its folding on 2D-nanomaterials

NASA Astrophysics Data System (ADS)

Zhang, Leili; Feng, Mei; Zhou, Ruhong; Luan, Binquan

2017-09-01

A globular protein’s folded structure in its physiological environment is largely determined by its amino acid sequence. Recently, newly discovered transformer proteins as well as intrinsically disordered proteins may adopt the folding-upon-binding mechanism where their secondary structures are highly dependent on their binding partners. Due to the various applications of nanomaterials in biological sensors and potential wearable devices, it is important to discover possible conformational changes of proteins on nanomaterials. Here, through molecular dynamics simulations, we show that the first 17 residues of the huntingtin protein (HTT-N17) exhibit appreciable differences during its folding on 2D-nanomaterials, such as graphene and MoS2 nanosheets. Namely, the protein is disordered on the graphene surface but is helical on the MoS2 surface. Despite that the amphiphilic environment at the nanosheet-water interface promotes the folding of the amphipathic proteins (such as HTT-N17), competitions between protein-nanosheet and intra-protein interactions yield very different protein conformations. Therefore, as engineered binding partners, nanomaterials might significantly affect the structures of adsorbed proteins.

Intuitionistic fuzzy n-fold KU-ideal of KU-algebra

NASA Astrophysics Data System (ADS)

Mostafa, Samy M.; Kareem, Fatema F.

2018-05-01

In this paper, we apply the notion of intuitionistic fuzzy n-fold KU-ideal of KU-algebra. Some types of ideals such as intuitionistic fuzzy KU-ideal, intuitionistic fuzzy closed ideal and intuitionistic fuzzy n-fold KU-ideal are studied. Also, the relations between intuitionistic fuzzy n-fold KU-ideal and intuitionistic fuzzy KU-ideal are discussed. Furthermore, a few results of intuitionistic fuzzy n-fold KU-ideals of a KU-algebra under homomorphism are discussed.

Dynamics and elastic interactions of the discrete multi-dark soliton solutions for the Kaup-Newell lattice equation

NASA Astrophysics Data System (ADS)

Liu, Nan; Wen, Xiao-Yong

2018-03-01

Under consideration in this paper is the Kaup-Newell (KN) lattice equation which is an integrable discretization of the KN equation. Infinitely, many conservation laws and discrete N-fold Darboux transformation (DT) for this system are constructed and established based on its Lax representation. Via the resulting N-fold DT, the discrete multi-dark soliton solutions in terms of determinants are derived from non-vanishing background. Propagation and elastic interaction structures of such solitons are shown graphically. Overtaking interaction phenomena between/among the two, three and four solitons are discussed. Numerical simulations are used to explore their dynamical behaviors of such multi-dark solitons. Numerical results show that their evolutions are stable against a small noise. Results in this paper might be helpful for understanding the propagation of nonlinear Alfvén waves in plasmas.

Oxidative Folding and N-terminal Cyclization of Onconase+

PubMed Central

Welker, Ervin; Hathaway, Laura; Xu, Guoqiang; Narayan, Mahesh; Pradeep, Lovy; Shin, Hang-Cheol; Scheraga, Harold A.

2008-01-01

Cyclization of the N-terminal glutamine residue to pyroglutamic acid in onconase, an anti-cancer chemotherapeutic agent, increases the activity and stability of the protein. Here, we examine the correlated effects of the folding/unfolding process and the formation of this N-terminal pyroglutamic acid. The results in this study indicate that cyclization of the N-terminal glutamine has no significant effect on the rate of either reductive unfolding or oxidative folding of the protein. Both the cyclized and uncyclized proteins seem to follow the same oxidative folding pathways; however, cyclization altered the relative flux of the protein in these two pathways by increasing the rate of formation of a kinetically trapped intermediate. Glutaminyl cyclase (QC) catalyzed the cyclization of the unfolded, reduced protein, but had no effect on the disulfide-intact, uncyclized, folded protein. The structured intermediates of uncyclized onconase were also resistant to QC-catalysis, consistent with their having a native-like fold. These observations suggest that, in vivo, cyclization takes place during the initial stages of oxidative folding, specifically, before the formation of structured intermediates. The competition between oxidative folding and QC-mediated cyclization suggests that QC-catalyzed cyclization of the N-terminal glutamine in onconase occurs in the endoplasmic reticulum, probably co-translationally. PMID:17439243

Determination of elementary first integrals of a generalized Raychaudhuri equation by the Darboux integrability method

NASA Astrophysics Data System (ADS)

Choudhury, A. Ghose; Guha, Partha; Khanra, Barun

2009-10-01

The Darboux integrability method is particularly useful to determine first integrals of nonplanar autonomous systems of ordinary differential equations, whose associated vector fields are polynomials. In particular, we obtain first integrals for a variant of the generalized Raychaudhuri equation, which has appeared in string inspired modern cosmology.

On Darboux's approach to R-separability of variables. Classification of conformally flat 4-dimensional binary metrics

NASA Astrophysics Data System (ADS)

Szereszewski, A.; Sym, A.

2015-09-01

The standard method of separation of variables in PDEs called the Stäckel-Robertson-Eisenhart (SRE) approach originated in the papers by Robertson (1928 Math. Ann. 98 749-52) and Eisenhart (1934 Ann. Math. 35 284-305) on separability of variables in the Schrödinger equation defined on a pseudo-Riemannian space equipped with orthogonal coordinates, which in turn were based on the purely classical mechanics results by Paul Stäckel (1891, Habilitation Thesis, Halle). These still fundamental results have been further extended in diverse directions by e.g. Havas (1975 J. Math. Phys. 16 1461-8 J. Math. Phys. 16 2476-89) or Koornwinder (1980 Lecture Notes in Mathematics 810 (Berlin: Springer) pp 240-63). The involved separability is always ordinary (factor R = 1) and regular (maximum number of independent parameters in separation equations). A different approach to separation of variables was initiated by Gaston Darboux (1878 Ann. Sci. E.N.S. 7 275-348) which has been almost completely forgotten in today’s research on the subject. Darboux’s paper was devoted to the so-called R-separability of variables in the standard Laplace equation. At the outset he did not make any specific assumption about the separation equations (this is in sharp contrast to the SRE approach). After impressive calculations Darboux obtained a complete solution of the problem. He found not only eleven cases of ordinary separability Eisenhart (1934 Ann. Math. 35 284-305) but also Darboux-Moutard-cyclidic metrics (Bôcher 1894 Ueber die Reihenentwickelungen der Potentialtheorie (Leipzig: Teubner)) and non-regularly separable Dupin-cyclidic metrics as well. In our previous paper Darboux’s approach was extended to the case of the stationary Schrödinger equation on Riemannian spaces admitting orthogonal coordinates. In particular the class of isothermic metrics was defined (isothermicity of the metric is a necessary condition for its R-separability). An important sub-class of isothermic metrics

Non-polynomial extensions of solvable potentials à la Abraham-Moses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Odake, Satoru; Sasaki, Ryu; Center for Theoretical Sciences, National Taiwan University, Taipei 10617, Taiwan

2013-10-15

Abraham-Moses transformations, besides Darboux transformations, are well-known procedures to generate extensions of solvable potentials in one-dimensional quantum mechanics. Here we present the explicit forms of infinitely many seed solutions for adding eigenstates at arbitrary real energy through the Abraham-Moses transformations for typical solvable potentials, e.g., the radial oscillator, the Darboux-Pöschl-Teller, and some others. These seed solutions are simple generalisations of the virtual state wavefunctions, which are obtained from the eigenfunctions by discrete symmetries of the potentials. The virtual state wavefunctions have been an essential ingredient for constructing multi-indexed Laguerre and Jacobi polynomials through multiple Darboux-Crum transformations. In contrast to themore » Darboux transformations, the virtual state wavefunctions generate non-polynomial extensions of solvable potentials through the Abraham-Moses transformations.« less

Elliptic Euler-Poisson-Darboux equation, critical points and integrable systems

NASA Astrophysics Data System (ADS)

Konopelchenko, B. G.; Ortenzi, G.

2013-12-01

The structure and properties of families of critical points for classes of functions W(z,{\\overline{z}}) obeying the elliptic Euler-Poisson-Darboux equation E(1/2, 1/2) are studied. General variational and differential equations governing the dependence of critical points in variational (deformation) parameters are found. Explicit examples of the corresponding integrable quasi-linear differential systems and hierarchies are presented. There are the extended dispersionless Toda/nonlinear Schrödinger hierarchies, the ‘inverse’ hierarchy and equations associated with the real-analytic Eisenstein series E(\\beta ,{\\overline{\\beta }};1/2) among them. The specific bi-Hamiltonian structure of these equations is also discussed.

The Euler-Poisson-Darboux equation for relativists

NASA Astrophysics Data System (ADS)

Stewart, John M.

2009-09-01

The Euler-Poisson-Darboux (EPD) equation is the simplest linear hyperbolic equation in two independent variables whose coefficients exhibit singularities, and as such must be of interest as a paradigm to relativists. Sadly it receives scant treatment in the textbooks. The first half of this review is didactic in nature. It discusses in the simplest terms possible the nature of solutions of the EPD equation for the timelike and spacelike singularity cases. Also covered is the Riemann representation of solutions of the characteristic initial value problem, which is hard to find in the literature. The second half examines a few of the possible applications, ranging from explicit computation of the leading terms in the far-field backscatter from predominantly outgoing radiation in a Schwarzschild space-time, to computing explicitly the leading terms in the matter-induced singularities in plane symmetric space-times. There are of course many other applications and the aim of this article is to encourage relativists to investigate this underrated paradigm.

Finding higher order Darboux polynomials for a family of rational first order ordinary differential equations

NASA Astrophysics Data System (ADS)

Avellar, J.; Claudino, A. L. G. C.; Duarte, L. G. S.; da Mota, L. A. C. P.

2015-10-01

For the Darbouxian methods we are studying here, in order to solve first order rational ordinary differential equations (1ODEs), the most costly (computationally) step is the finding of the needed Darboux polynomials. This can be so grave that it can render the whole approach unpractical. Hereby we introduce a simple heuristics to speed up this process for a class of 1ODEs.

The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.

PubMed

Friberg, Anders; Thumann, Sybille; Hennig, Janosch; Zou, Peijian; Nössner, Elfriede; Ling, Paul D; Sattler, Michael; Kempkes, Bettina

2015-05-01

Epstein-Barr virus (EBV) is a γ-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2) is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END) domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four β-strands and an α-helix which form a parallel dimer by interaction of two β-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the α-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics.

Non-contact radio frequency shielding and wave guiding by multi-folded transformation optics method

PubMed Central

Madni, Hamza Ahmad; Zheng, Bin; Yang, Yihao; Wang, Huaping; Zhang, Xianmin; Yin, Wenyan; Li, Erping; Chen, Hongsheng

2016-01-01

Compared with conventional radio frequency (RF) shielding methods in which the conductive coating material encloses the circuits design and the leakage problem occurs due to the gap in such conductive material, non-contact RF shielding at a distance is very promising but still impossible to achieve so far. In this paper, a multi-folded transformation optics method is proposed to design a non-contact device for RF shielding. This “open-shielded” device can shield any object at a distance from the electromagnetic waves at the operating frequency, while the object is still physically open to the outer space. Based on this, an open-carpet cloak is proposed and the functionality of the open-carpet cloak is demonstrated. Furthermore, we investigate a scheme of non-contact wave guiding to remotely control the propagation of surface waves over any obstacles. The flexibilities of such multi-folded transformation optics method demonstrate the powerfulness of the method in the design of novel remote devices with impressive new functionalities. PMID:27841358

Notes on S-folds and {N} = 3 theories

NASA Astrophysics Data System (ADS)

Agarwal, Prarit; Amariti, Antonio

2016-09-01

We consider D3 branes in presence of an S-fold plane. The latter is a non-perturbative object, arising from the combined projection of an S-duality twist and a discrete orbifold of the R-symmetry group. This construction naively gives rise to 4d {N} = 3 SCFTs. Nevertheless it has been observed that in some cases supersymmetry is enhanced to {N} = 4. In this paper we study the explicit counting of degrees of freedom arising from vector multiplets associated to strings suspended between the D3 branes probing the S-fold. We propose that, for trivial discrete torsion, there is no vector multiplet associated to (1, 0) strings stretched between a brane and its image. We then focus on the case of rank 2 {N} = 3 theory that enhances to SU(3) {N} = 4 SYM, explicitly spelling out the isomorphism between the BPS-spectrum of the manifestly {N} = 3 theory and that of three D3 branes in flat spacetime. Subsequently, we consider 3-pronged strings in these setups and show how wall-crossing in the S-fold background implies wall crossing in the flat geometry. This can be considered a consistency check of the conjectured SUSY enhancement. We also find that the above isomorphism implies that a (1, 0) string, suspended between a brane and its image in the S-fold, corresponds to a 3-string junction in the flat geometry. This is in agreement with our claim on the absence of a vector multiplet associated to such (1, 0) strings. This is because the 3-string junction in flat geometry gives rise to a 1/4-th BPS multiplet of the {N} = 4 algebra. Such multiplets always include particles with spin > 1 as opposed to a vector multiplet which is restricted by the requirement that the spins must be ≤ 1.

Language study on Spliced Semigraph using Folding techniques

NASA Astrophysics Data System (ADS)

Thiagarajan, K.; Padmashree, J.

2018-04-01

In this paper, we proposed algorithm to identify cut vertices and cut edges for n-Cut Spliced Semigraph and splicing the n-Cut Spliced Semigraph using cut vertices else cut edges or combination of cut vertex and cut edge and applying sequence of folding to the spliced semigraph to obtain the semigraph quadruple η(S)=(2, 1, 1, 1). We observed that the splicing and folding using both cut vertices and cut edges is applicable only for n-Cut Spliced Semigraph where n > 2. Also, we transformed the spliced semigraph into tree structure and studied the language for the semigraph with n+2 vertices and n+1 semivertices using Depth First Edge Sequence algorithm and obtain the language structure with sequence of alphabet ‘a’ and ‘b’.

Hamiltonian structure and Darboux theorem for families of generalized Lotka-Volterra systems

NASA Astrophysics Data System (ADS)

Hernández-Bermejo, Benito; Fairén, Víctor

1998-11-01

This work is devoted to the establishment of a Poisson structure for a format of equations known as generalized Lotka-Volterra systems. These equations, which include the classical Lotka-Volterra systems as a particular case, have been deeply studied in the literature. They have been shown to constitute a whole hierarchy of systems, the characterization of which is made in the context of simple algebra. Our main result is to show that this algebraic structure is completely translatable into the Poisson domain. Important Poisson structures features, such as the symplectic foliation and the Darboux canonical representation, rise as a result of rather simple matrix manipulations.

Integrable discretisations for a class of nonlinear Schrödinger equations on Grassmann algebras

NASA Astrophysics Data System (ADS)

Grahovski, Georgi G.; Mikhailov, Alexander V.

2013-12-01

Integrable discretisations for a class of coupled (super) nonlinear Schrödinger (NLS) type of equations are presented. The class corresponds to a Lax operator with entries in a Grassmann algebra. Elementary Darboux transformations are constructed. As a result, Grassmann generalisations of the Toda lattice and the NLS dressing chain are obtained. The compatibility (Bianchi commutativity) of these Darboux transformations leads to integrable Grassmann generalisations of the difference Toda and NLS equations. The resulting systems will have discrete Lax representations provided by the set of two consistent elementary Darboux transformations. For the two discrete systems obtained, initial value and initial-boundary problems are formulated.

A discriminative method for protein remote homology detection and fold recognition combining Top-n-grams and latent semantic analysis.

PubMed

Liu, Bin; Wang, Xiaolong; Lin, Lei; Dong, Qiwen; Wang, Xuan

2008-12-01

Protein remote homology detection and fold recognition are central problems in bioinformatics. Currently, discriminative methods based on support vector machine (SVM) are the most effective and accurate methods for solving these problems. A key step to improve the performance of the SVM-based methods is to find a suitable representation of protein sequences. In this paper, a novel building block of proteins called Top-n-grams is presented, which contains the evolutionary information extracted from the protein sequence frequency profiles. The protein sequence frequency profiles are calculated from the multiple sequence alignments outputted by PSI-BLAST and converted into Top-n-grams. The protein sequences are transformed into fixed-dimension feature vectors by the occurrence times of each Top-n-gram. The training vectors are evaluated by SVM to train classifiers which are then used to classify the test protein sequences. We demonstrate that the prediction performance of remote homology detection and fold recognition can be improved by combining Top-n-grams and latent semantic analysis (LSA), which is an efficient feature extraction technique from natural language processing. When tested on superfamily and fold benchmarks, the method combining Top-n-grams and LSA gives significantly better results compared to related methods. The method based on Top-n-grams significantly outperforms the methods based on many other building blocks including N-grams, patterns, motifs and binary profiles. Therefore, Top-n-gram is a good building block of the protein sequences and can be widely used in many tasks of the computational biology, such as the sequence alignment, the prediction of domain boundary, the designation of knowledge-based potentials and the prediction of protein binding sites.

High-order rogue wave solutions of the classical massive Thirring model equations

NASA Astrophysics Data System (ADS)

Guo, Lijuan; Wang, Lihong; Cheng, Yi; He, Jingsong

2017-11-01

The nth-order solutions of the classical massive Thirring model (MTM) equations are derived by using the n-fold Darboux transformation. These solutions are expressed by the ratios of the two determinants consisted of 2n eigenfunctions under the reduction conditions. Using this method, rogue waves are constructed explicitly up to the third-order. Three patterns, i.e., fundamental, triangular and circular patterns, of the rogue waves are discussed. The parameter μ in the MTM model plays the role of the mass in the relativistic field theory while in optics it is related to the medium periodic constant, which also results in a significant rotation and a remarkable lengthening of the first-order rogue wave. These results provide new opportunities to observe rouge waves by using a combination of electromagnetically induced transparency and the Bragg scattering four-wave mixing because of large amplitudes.

Highly effective action from large N gauge fields

NASA Astrophysics Data System (ADS)

Yang, Hyun Seok

2014-10-01

Recently Schwarz put forward a conjecture that the world-volume action of a probe D3-brane in an AdS5×S5 background of type IIB superstring theory can be reinterpreted as the highly effective action (HEA) of four-dimensional N =4 superconformal field theory on the Coulomb branch. We argue that the HEA can be derived from the noncommutative (NC) field theory representation of the AdS/CFT correspondence and the Seiberg-Witten (SW) map defining a spacetime field redefinition between ordinary and NC gauge fields. It is based only on the well-known facts that the master fields of large N matrices are higher-dimensional NC U(1) gauge fields and the SW map is a local coordinate transformation eliminating U(1) gauge fields known as the Darboux theorem in symplectic geometry.

Modulational instability and dynamics of implicit higher-order rogue wave solutions for the Kundu equation

NASA Astrophysics Data System (ADS)

Wen, Xiao-Yong; Zhang, Guoqiang

2018-01-01

Under investigation in this paper is the Kundu equation, which may be used to describe the propagation process of ultrashort optical pulses in nonlinear optics. The modulational instability of the plane-wave for the possible reason of the formation of the rogue wave (RW) is studied for the system. Based on our proposed generalized perturbation (n,N - n)-fold Darboux transformation (DT), some new higher-order implicit RW solutions in terms of determinants are obtained by means of the generalized perturbation (1,N - 1)-fold DT, when choosing different special parameters, these results will reduce to the RW solutions of the Kaup-Newell (KN) equation, Chen-Lee-Liu (CLL) equation and Gerjikov-Ivanov (GI) equation, respectively. The relevant wave structures are shown graphically, which display abundant interesting wave structures. The dynamical behaviors and propagation stability of the first-order and second-order RW solutions are discussed by using numerical simulations, the higher-order nonlinear terms for the Kundu equation have an impact on the propagation instability of the RW. The method can also be extended to find the higher-order RW or rational solutions of other integrable nonlinear equations.

Large-scale chromosome folding versus genomic DNA sequences: A discrete double Fourier transform technique.

PubMed

Chechetkin, V R; Lobzin, V V

2017-08-07

Using state-of-the-art techniques combining imaging methods and high-throughput genomic mapping tools leaded to the significant progress in detailing chromosome architecture of various organisms. However, a gap still remains between the rapidly growing structural data on the chromosome folding and the large-scale genome organization. Could a part of information on the chromosome folding be obtained directly from underlying genomic DNA sequences abundantly stored in the databanks? To answer this question, we developed an original discrete double Fourier transform (DDFT). DDFT serves for the detection of large-scale genome regularities associated with domains/units at the different levels of hierarchical chromosome folding. The method is versatile and can be applied to both genomic DNA sequences and corresponding physico-chemical parameters such as base-pairing free energy. The latter characteristic is closely related to the replication and transcription and can also be used for the assessment of temperature or supercoiling effects on the chromosome folding. We tested the method on the genome of E. coli K-12 and found good correspondence with the annotated domains/units established experimentally. As a brief illustration of further abilities of DDFT, the study of large-scale genome organization for bacteriophage PHIX174 and bacterium Caulobacter crescentus was also added. The combined experimental, modeling, and bioinformatic DDFT analysis should yield more complete knowledge on the chromosome architecture and genome organization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protein Folding Mechanism of the Dimeric AmphiphysinII/Bin1 N-BAR Domain

PubMed Central

Gruber, Tobias; Balbach, Jochen

2015-01-01

The human AmphyphisinII/Bin1 N-BAR domain belongs to the BAR domain superfamily, whose members sense and generate membrane curvatures. The N-BAR domain is a 57 kDa homodimeric protein comprising a six helix bundle. Here we report the protein folding mechanism of this protein as a representative of this protein superfamily. The concentration dependent thermodynamic stability was studied by urea equilibrium transition curves followed by fluorescence and far-UV CD spectroscopy. Kinetic unfolding and refolding experiments, including rapid double and triple mixing techniques, allowed to unravel the complex folding behavior of N-BAR. The equilibrium unfolding transition curve can be described by a two-state process, while the folding kinetics show four refolding phases, an additional burst reaction and two unfolding phases. All fast refolding phases show a rollover in the chevron plot but only one of these phases depends on the protein concentration reporting the dimerization step. Secondary structure formation occurs during the three fast refolding phases. The slowest phase can be assigned to a proline isomerization. All kinetic experiments were also followed by fluorescence anisotropy detection to verify the assignment of the dimerization step to the respective folding phase. Based on these experiments we propose for N-BAR two parallel folding pathways towards the homodimeric native state depending on the proline conformation in the unfolded state. PMID:26368922

Ultrathin thermoresponsive self-folding 3D graphene

PubMed Central

Xu, Weinan; Qin, Zhao; Chen, Chun-Teh; Kwag, Hye Rin; Ma, Qinli; Sarkar, Anjishnu; Buehler, Markus J.; Gracias, David H.

2017-01-01

Graphene and other two-dimensional materials have unique physical and chemical properties of broad relevance. It has been suggested that the transformation of these atomically planar materials to three-dimensional (3D) geometries by bending, wrinkling, or folding could significantly alter their properties and lead to novel structures and devices with compact form factors, but strategies to enable this shape change remain limited. We report a benign thermally responsive method to fold and unfold monolayer graphene into predesigned, ordered 3D structures. The methodology involves the surface functionalization of monolayer graphene using ultrathin noncovalently bonded mussel-inspired polydopamine and thermoresponsive poly(N-isopropylacrylamide) brushes. The functionalized graphene is micropatterned and self-folds into ordered 3D structures with reversible deformation under a full control by temperature. The structures are characterized using spectroscopy and microscopy, and self-folding is rationalized using a multiscale molecular dynamics model. Our work demonstrates the potential to design and fabricate ordered 3D graphene structures with predictable shape and dynamics. We highlight applicability by encapsulating live cells and creating nonlinear resistor and creased transistor devices. PMID:28989963

Fast quantum nD Fourier and radon transforms

NASA Astrophysics Data System (ADS)

Labunets, Valeri G.; Labunets-Rundblad, Ekaterina V.; Astola, Jaakko T.

2001-07-01

Fast Classical and quantum algorithms are introduced for a wide class of non-separable nD discrete unitary K- transforms(DKT)KNn. They require a number of 1D DKT Kn smaller than in the Cooley-Tukey radix-p FFT-type approach. The method utilizes a decomposition of the nDK- transform into a product of original nD discrete Radon Transform and of a family parallel/independ 1DK-transforms. If the nDK-transform has a separable kernel, that again in this case our approach leads to decrease of multiplicative complexity by factor of n compared to the tow/column separable Cooley-Tukey p-radix approach.

Exact solution of the generalized Peierls equation for arbitrary n-fold screw dislocation

NASA Astrophysics Data System (ADS)

Wang, Shaofeng; Hu, Xiangsheng

2018-05-01

The exact solution of the generalized Peierls equation is presented and proved for arbitrary n-fold screw dislocation. The displacement field, stress field and the energy of the n-fold dislocation are also evaluated explicitly. It is found that the solution defined on each individual fold is given by the tail cut from the original Peierls solution. In viewpoint of energetics, a screw dislocation has a tendency to spread the distribution on all possible slip planes which are contained in the dislocation line zone. Based on the exact solution, the approximated solution of the improved Peierls equation is proposed for the modified γ-surface.

N-Soliton Solution and Soliton Resonances for the (2+1)-Dimensional Inhomogeneous Gardner Equation

NASA Astrophysics Data System (ADS)

Wang, Xin; Geng, Xian-Guo

2017-08-01

We derive the Lax pair and Darboux transformation for the (2+1)-dimensional inhomogeneous Gardner equation via the two-singular manifold method from Painlevé analysis. N-soliton solution in a compact determinant representation of Grammian type is presented. As an application, dynamic properties of the bright and dark soliton solutions under periodic and parabolic oscillations up to second order are shown. Resonant behaviors of two bright and two dark solitons are studied, and asymptotic analysis of the corresponding resonant bright and dark two-soliton solutions are performed, respectively. Supported by National Natural Science Foundation of China under Grant No. 11331008 and China Postdoctoral Science Foundation Funded Sixtieth Batches (2016M602252)

Inhibitory effects of hepatocyte growth factor and interleukin-6 on transforming growth factor-beta1 mediated vocal fold fibroblast-myofibroblast differentiation.

PubMed

Vyas, Bimal; Ishikawa, Keiko; Duflo, Suzy; Chen, Xia; Thibeault, Susan L

2010-05-01

The role of myofibroblasts in vocal fold scarring has not been extensively studied, partly because of the lack of a robust in vitro model. The objective of this investigation was to develop and characterize a myofibroblast in vitro model that could be utilized to investigate the molecular mechanism of myofibroblast differentiation and function in injured vocal fold tissue. Differentiation of human primary vocal fold fibroblasts (hVFFs) to myofibroblasts was stimulated with 5, 10, or 20 ng/mL of recombinant transforming growth factor-beta1 (TGF-beta1). Cultures were analyzed by immunofluorescence and Western blotting, with an alpha-smooth muscle actin (alpha-SMA) antibody used as a myofibroblast marker. Normal rabbit vocal folds were treated with 10 ng/mL of TGF-beta1 for 7 days for in vivo corroboration. The effects of interleukin-6 (IL-6) and hepatocyte growth factor (HGF) on myofibroblast differentiation were studied with Western blots. The hVFFs demonstrated positive alpha-SMA labeling in cells stimulated by 10 and 20 ng/mL TGF-beta1, indicating that hVFFs were capable of differentiation to myofibroblasts. Transforming growth factor-beta1 induced the largest increase in alpha-SMA at 10 ng/mL on day 5 of treatment. Both HGF and IL-6 suppressed the expression of TGF-beta1-induced alpha-SMA. Our work characterizes a useful in vitro model of TGF-beta1-mediated vocal fold fibroblast-myofibroblast differentiation. The extent of differentiation appears to be attenuated by HGF, suggesting a potential mechanism to support prior work indicating that HGF plays a protective role in reducing scar formation in vocal fold injuries. Paradoxically, IL-6, which has been shown to play a profibrotic role in dermal studies, also attenuated the TGF-beta1 response.

On a Class of Hairy Square Barriers and Gamow Vectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandez-Garcia, N.

The second order Darboux-Gamow transformation is applied to deform square one dimensional barriers in non-relativistic quantum mechanics. The initial and the new 'hairy' potentials have the same transmission probabilities (for the appropriate parameters). In general, new Gamow vectors are constructed as Darboux deformations of the initial ones.

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

On the continuum limit for a semidiscrete Hirota equation

PubMed Central

Pickering, Andrew; Zhao, Hai-qiong

2016-01-01

In this paper, we propose a new semidiscrete Hirota equation which yields the Hirota equation in the continuum limit. We focus on the topic of how the discrete space step δ affects the simulation for the soliton solution to the Hirota equation. The Darboux transformation and explicit solution for the semidiscrete Hirota equation are constructed. We show that the continuum limit for the semidiscrete Hirota equation, including the Lax pair, the Darboux transformation and the explicit solution, yields the corresponding results for the Hirota equation as δ→0. PMID:27956884

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

Programmable matter by folding.

PubMed

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

2010-07-13

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.

Simple triple-state polymer actuators with controllable folding characteristics

NASA Astrophysics Data System (ADS)

Chen, Shuyang; Li, Jing; Fang, Lichen; Zhu, Zeyu; Kang, Sung Hoon

2017-03-01

Driven by the interests in self-folding, there have been studies developing artificial self-folding structures at different length scales based on various polymer actuators that can realize dual-state actuation. However, their unidirectional nature limits the applicability of the actuators for a wide range of multi-state self-folding behaviors. In addition, complex fabrication and programming procedures hinder broad applications of existing polymer actuators. Moreover, few of the existing polymer actuators are able to show the self-folding behaviors with the precise control of curvature and force. To address these issues, we report an easy-to-fabricate triple-state actuator with controllable folding behaviors based on bilayer polymer composites with different glass transition temperatures. Initially, the fabricated actuator is in the flat state, and it can sequentially self-fold to angled folding states of opposite directions as it is heated up. Based on an analytical model and measured partial recovery behaviors of polymers, we can accurately control the folding characteristics (curvature and force) for the rational design. To demonstrate an application of our triple-state actuator, we have developed a self-folding transformer robot which self-folds from a two-dimensional sheet into a three-dimensional boat-like configuration and transforms from the boat shape to a car shape with the increase in the temperature applied to the actuator. Our findings offer a simple approach to generate multiple configurations from a single system by harnessing behaviors of polymers with the rational design.

Beam-folding ultraviolet-visible Fourier transform spectrometry and underwater cytometry for in situ measurement of marine phytoplankton

NASA Astrophysics Data System (ADS)

Wang, Xuzhu

The system complexity and hence high cost needed for generating the high-resolution and precise position-sampling triggers over very long distances is one of main hindrances to the popularization of the UV-visible Fourier transform spectrometer (FTS). In part one of this thesis, the specially designed beam-folding and improved beam-folding methods to optically subdivide the laser fringes are presented. The Near-UV to Near-infrared FTSs based on 4-fold beam-folding systems were developed. The experimental results have demonstrated that these techniques are promising methods to produce the high-resolution and high-precision sampling triggers of scanning mechanism of UV-visible FTSs without the need for complicated optics, sophisticated detector electronics and high-stability motion control systems. The FTS based on the beam-folding technique can reach a spectral resolution of ˜4 cm-1 (0.1nm) in the visible wavelengths; The FTS based on the improved beam-folding technique can achieve a spectral resolution of ˜0.28 cm-1 (0.01nm) in the visible wavelengths. In the improved beam-folding FTS, The adoption of retroreflectors and the symmetrical arrangement of two back-to back interferometers produced much higher performance than that of the beam-folding FTS employing prism mirrors. The replacement of prism mirrors by retroreflectors and the symmetrical optical arrangement maintain the FTS in perfect optical alignment during scanning process by keeping all beams parallel with the incident beams. The vertex of the movable retroreflector in the measurement interferometer is arranged very close to the midpoint of the vertices of the movable retroreflectors in the tracking interferometer so that the optical symmetrical axes for both interferometers always keep in line with each other. That is, the change of the OPD of the tracking interferometer always remains synchronous to that of the OPD of the measurement interferometer even for any moving misalignments, making the FTS

N-glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic.

PubMed

Glozman, Rina; Okiyoneda, Tsukasa; Mulvihill, Cory M; Rini, James M; Barriere, Herve; Lukacs, Gergely L

2009-03-23

N-glycosylation, a common cotranslational modification, is thought to be critical for plasma membrane expression of glycoproteins by enhancing protein folding, trafficking, and stability through targeting them to the ER folding cycles via lectin-like chaperones. In this study, we show that N-glycans, specifically core glycans, enhance the productive folding and conformational stability of a polytopic membrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR), independently of lectin-like chaperones. Defective N-glycosylation reduces cell surface expression by impairing both early secretory and endocytic traffic of CFTR. Conformational destabilization of the glycan-deficient CFTR induces ubiquitination, leading to rapid elimination from the cell surface. Ubiquitinated CFTR is directed to lysosomal degradation instead of endocytic recycling in early endosomes mediated by ubiquitin-binding endosomal sorting complex required for transport (ESCRT) adaptors Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) and TSG101. These results suggest that cotranslational N-glycosylation can exert a chaperone-independent profolding change in the energetic of CFTR in vivo as well as outline a paradigm for the peripheral trafficking defect of membrane proteins with impaired glycosylation.

Modulational instability, beak-shaped rogue waves, multi-dark-dark solitons and dynamics in pair-transition-coupled nonlinear Schrödinger equations.

PubMed

Zhang, Guoqiang; Yan, Zhenya; Wen, Xiao-Yong

2017-07-01

The integrable coupled nonlinear Schrödinger equations with four-wave mixing are investigated. We first explore the conditions for modulational instability of continuous waves of this system. Secondly, based on the generalized N -fold Darboux transformation (DT), beak-shaped higher-order rogue waves (RWs) and beak-shaped higher-order rogue wave pairs are derived for the coupled model with attractive interaction in terms of simple determinants. Moreover, we derive the simple multi-dark-dark and kink-shaped multi-dark-dark solitons for the coupled model with repulsive interaction through the generalizing DT. We explore their dynamics and classifications by different kinds of spatial-temporal distribution structures including triangular, pentagonal, 'claw-like' and heptagonal patterns. Finally, we perform the numerical simulations to predict that some dark solitons and RWs are stable enough to develop within a short time. The results would enrich our understanding on nonlinear excitations in many coupled nonlinear wave systems with transition coupling effects.

Integrable equations of the infinite nonlinear Schrödinger equation hierarchy with time variable coefficients.

PubMed

Kedziora, D J; Ankiewicz, A; Chowdury, A; Akhmediev, N

2015-10-01

We present an infinite nonlinear Schrödinger equation hierarchy of integrable equations, together with the recurrence relations defining it. To demonstrate integrability, we present the Lax pairs for the whole hierarchy, specify its Darboux transformations and provide several examples of solutions. These resulting wavefunctions are given in exact analytical form. We then show that the Lax pair and Darboux transformation formalisms still apply in this scheme when the coefficients in the hierarchy depend on the propagation variable (e.g., time). This extension thus allows for the construction of complicated solutions within a greatly diversified domain of generalised nonlinear systems.

N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma.

PubMed

Li, Jiang-Hua; Huang, Wan; Lin, Peng; Wu, Bo; Fu, Zhi-Guang; Shen, Hao-Miao; Jing, Lin; Liu, Zhen-Yu; Zhou, Yang; Meng, Yao; Xu, Bao-Qing; Chen, Zhi-Nan; Jiang, Jian-Li

2016-11-21

Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer, is a transmembrane glycoprotein that mediates oncogenic processes partly through N-glycosylation modifications. N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation. However, the role that site-specific glycosylation of CD147 plays in its defective function in hepatocellular carcinomacells needs to be determined. Here, we demonstrate that the modification of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma (HCC) invasion and migration. After the removal of N-glycans at Asn152, CD147 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated endoplasmic reticulum-associated degradation (ERAD). Furthermore, N-linked glycans at Asn152 were required for CD147 to acquire and maintain proper folding in the ER. Moreover, N-linked glycans at Asn152 functioned as a recognition motif that was directly mediated by the CNX quality control system. Two phases in the retention-based ER chaperones system drove ER-localized CD147 trafficking to degradation. Deletion of N-linked glycosylation at Asn152 on CD147 significantly suppressed in situ tumour metastasis. These data could potentially shed light on the molecular regulation of CD147 through glycosylation and provide a valuable means of developing drugs that target N-glycans at Asn152 on CD147.

N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma

PubMed Central

Li, Jiang-Hua; Huang, Wan; Lin, Peng; Wu, Bo; Fu, Zhi-Guang; Shen, Hao-Miao; Jing, Lin; Liu, Zhen-Yu; Zhou, Yang; Meng, Yao; Xu, Bao-Qing; Chen, Zhi-Nan; Jiang, Jian-Li

2016-01-01

Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer, is a transmembrane glycoprotein that mediates oncogenic processes partly through N-glycosylation modifications. N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation. However, the role that site-specific glycosylation of CD147 plays in its defective function in hepatocellular carcinomacells needs to be determined. Here, we demonstrate that the modification of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma (HCC) invasion and migration. After the removal of N-glycans at Asn152, CD147 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated endoplasmic reticulum-associated degradation (ERAD). Furthermore, N-linked glycans at Asn152 were required for CD147 to acquire and maintain proper folding in the ER. Moreover, N-linked glycans at Asn152 functioned as a recognition motif that was directly mediated by the CNX quality control system. Two phases in the retention-based ER chaperones system drove ER-localized CD147 trafficking to degradation. Deletion of N-linked glycosylation at Asn152 on CD147 significantly suppressed in situ tumour metastasis. These data could potentially shed light on the molecular regulation of CD147 through glycosylation and provide a valuable means of developing drugs that target N-glycans at Asn152 on CD147. PMID:27869218

Identification of Metabolites in the Normal Ovary and Their Transformation in Primary and Metastatic Ovarian Cancer

PubMed Central

Fong, Miranda Y.; McDunn, Jonathan; Kakar, Sham S.

2011-01-01

In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids—such as carnitine (1.79 fold in EOC, p<0.001; 1.88 fold in MOC, p<0.001), acetylcarnitine (1.75 fold in EOC, p<0.001; 2.39 fold in MOC, p<0.001), and butyrylcarnitine (3.62 fold, p<0.0094 in EOC; 7.88 fold, p<0.001 in MOC). There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098) and phenyllactate (195.45 fold; p<0.0023) in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316) and in MOC (2.25 fold, p<0.001) and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients. PMID:21625518

Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.

PubMed

Fong, Miranda Y; McDunn, Jonathan; Kakar, Sham S

2011-01-01

In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids--such as carnitine (1.79 fold in EOC, p<0.001; 1.88 fold in MOC, p<0.001), acetylcarnitine (1.75 fold in EOC, p<0.001; 2.39 fold in MOC, p<0.001), and butyrylcarnitine (3.62 fold, p<0.0094 in EOC; 7.88 fold, p<0.001 in MOC). There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098) and phenyllactate (195.45 fold; p<0.0023) in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316) and in MOC (2.25 fold, p<0.001) and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients.

Conceptual Transformation and Cognitive Processes in Origami Paper Folding

ERIC Educational Resources Information Center

Tenbrink, Thora; Taylor, Holly A.

2015-01-01

Research on problem solving typically does not address tasks that involve following detailed and/or illustrated step-by-step instructions. Such tasks are not seen as cognitively challenging problems to be solved. In this paper, we challenge this assumption by analyzing verbal protocols collected during an Origami folding task. Participants…

Morphology and crystallographic orientation relationship in isothermally transformed Fe–N austenite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiao, Dongling, E-mail: dljiao@scut.edu.cn; Luo, Chengping; Liu, Jiangwen

2014-02-15

The 225 °C isothermal transformation of a high-nitrogen austenite with Fe–2.71 wt.% N was investigated by means of electron microscopy. It was found that the transformation products were composed of ultrafine α-Fe and γ′-Fe{sub 4}N plus retained austenite γ, which were in two types of morphologies, namely, (i) with the retained austenite patches dispersed among the (α-Fe + γ′-Fe{sub 4}N) packets and (ii) with the ultrafine α-Fe and γ/γ′-Fe{sub 4}N laths interwoven with each other within a single bainitic packet. A cube–cube orientation relationship between the γ (austenite) and γ′-Fe{sub 4}N, and a near Greninger–Troiano (G–T) one between the γmore » (austenite) and the bainitic α-ferrite were detected. The morphology, orientation relationship and high hardness (> 1000 HV) of the transformation products indicated that the isothermal transformation of the high nitrogen austenite was analogous to a bainitic one. - Highlights: • Isothermal transformation products consisted of nano-sized α-Fe + γ′ + γ (retained). • The hardness of transformation product exceeded 1000 HV. • The α-Fe and γ/γ′-Fe{sub 4}N kept a near G-T OR in the grain interior.« less

Requirement for the SnoN oncoprotein in transforming growth factor beta-induced oncogenic transformation of fibroblast cells.

PubMed

Zhu, Qingwei; Pearson-White, Sonia; Luo, Kunxin

2005-12-01

Transforming growth factor beta (TGF-beta) was originally identified by virtue of its ability to induce transformation of the AKR-2B and NRK fibroblasts but was later found to be a potent inhibitor of the growth of epithelial, endothelial, and lymphoid cells. Although the growth-inhibitory pathway of TGF-beta mediated by the Smad proteins is well studied, the signaling pathway leading to the transforming activity of TGF-beta in fibroblasts is not well understood. Here we show that SnoN, a member of the Ski family of oncoproteins, is required for TGF-beta-induced proliferation and transformation of AKR-2B and NRK fibroblasts. TGF-beta induces upregulation of snoN expression in both epithelial cells and fibroblasts through a common Smad-dependent mechanism. However, a strong and prolonged activation of snoN transcription that lasts for 8 to 24 h is detected only in these two fibroblast lines. This prolonged induction is mediated by Smad2 and appears to play an important role in the transformation of both AKR-2B and NRK cells. Reduction of snoN expression by small interfering RNA or shortening of the duration of snoN induction by a pharmacological inhibitor impaired TGF-beta-induced anchorage-independent growth of AKR-2B cells. Interestingly, Smad2 and Smad3 play opposite roles in regulating snoN expression in both fibroblasts and epithelial cells. The Smad2/Smad4 complex activates snoN transcription by direct binding to the TGF-beta-responsive element in the snoN promoter, while the Smad3/Smad4 complex inhibits it through a novel Smad inhibitory site. Mutations of Smad4 that render it defective in heterodimerization with Smad3, which are found in many human cancers, convert the activity of Smad3 on the snoN promoter from inhibitory to stimulatory, resulting in increased snoN expression in cancer cells. Thus, we demonstrate a novel role of SnoN in the transforming activity of TGF-beta in fibroblasts and also uncovered a mechanism for the elevated SnoN expression in

In vitro folding of inclusion body proteins.

PubMed

Rudolph, R; Lilie, H

1996-01-01

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

Nonlinear integrable model of Frenkel-like excitations on a ribbon of triangular lattice

NASA Astrophysics Data System (ADS)

Vakhnenko, Oleksiy O.

2015-03-01

Following the considerable progress in nanoribbon technology, we propose to model the nonlinear Frenkel-like excitations on a triangular-lattice ribbon by the integrable nonlinear ladder system with the background-controlled intersite resonant coupling. The system of interest arises as a proper reduction of first general semidiscrete integrable system from an infinite hierarchy. The most significant local conservation laws related to the first general integrable system are found explicitly in the framework of generalized recursive approach. The obtained general local densities are equally applicable to any general semidiscrete integrable system from the respective infinite hierarchy. Using the recovered second densities, the Hamiltonian formulation of integrable nonlinear ladder system with background-controlled intersite resonant coupling is presented. In doing so, the relevant Poisson structure turns out to be essentially nontrivial. The Darboux transformation scheme as applied to the first general semidiscrete system is developed and the key role of Bäcklund transformation in justification of its self-consistency is pointed out. The spectral properties of Darboux matrix allow to restore the whole Darboux matrix thus ensuring generation one more soliton as compared with a priori known seed solution of integrable nonlinear system. The power of Darboux-dressing method is explicitly demonstrated in generating the multicomponent one-soliton solution to the integrable nonlinear ladder system with background-controlled intersite resonant coupling.

Circular permutation of a WW domain: Folding still occurs after excising the turn of the folding-nucleating hairpin

PubMed Central

Kier, Brandon L.; Anderson, Jordan M.; Andersen, Niels H.

2014-01-01

A hyperstable Pin1 WW domain has been circularly permuted via excision of the fold-nucleating turn; it still folds to form the native three-strand sheet and hydrophobic core features. Multiprobe folding dynamics studies of the normal and circularly permuted sequences, as well as their constituent hairpin fragments and comparable-length β-strand-loop-β-strand models, indicate 2-state folding for all topologies. N-terminal hairpin formation is the fold nucleating event for the wild-type sequence; the slower folding circular permutant has a more distributed folding transition state. PMID:24350581

Discrete rational and breather solution in the spatial discrete complex modified Korteweg-de Vries equation and continuous counterparts.

PubMed

Zhao, Hai-Qiong; Yu, Guo-Fu

2017-04-01

In this paper, a spatial discrete complex modified Korteweg-de Vries equation is investigated. The Lax pair, conservation laws, Darboux transformations, and breather and rational wave solutions to the semi-discrete system are presented. The distinguished feature of the model is that the discrete rational solution can possess new W-shape rational periodic-solitary waves that were not reported before. In addition, the first-order rogue waves reach peak amplitudes which are at least three times of the background amplitude, whereas their continuous counterparts are exactly three times the constant background. Finally, the integrability of the discrete system, including Lax pair, conservation laws, Darboux transformations, and explicit solutions, yields the counterparts of the continuous system in the continuum limit.

Spherical aberration correction with an in-lens N-fold symmetric line currents model.

PubMed

Hoque, Shahedul; Ito, Hiroyuki; Nishi, Ryuji

2018-04-01

In our previous works, we have proposed N-SYLC (N-fold symmetric line currents) models for aberration correction. In this paper, we propose "in-lens N-SYLC" model, where N-SYLC overlaps rotationally symmetric lens. Such overlap is possible because N-SYLC is free of magnetic materials. We analytically prove that, if certain parameters of the model are optimized, an in-lens 3-SYLC (N = 3) doublet can correct 3rd order spherical aberration. By computer simulation, we show that the required excitation current for correction is less than 0.25 AT for beam energy 5 keV, and the beam size after correction is smaller than 1 nm at the corrector image plane for initial slope less than 4 mrad. Copyright © 2018 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Karaaǧaç, Serdal; Koral, Hayrettin

2017-04-01

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

Nonlinear tunneling of optical soliton in 3 coupled NLS equation with symbolic computation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mani Rajan, M.S., E-mail: senthilmanirajanofc@gmail.com; Mahalingam, A.; Uthayakumar, A.

We investigated the soliton solution for N coupled nonlinear Schrödinger (CNLS) equations. These equations are coupled due to the cross-phase-modulation (CPM). Lax pair of this system is obtained via the Ablowitz–Kaup–Newell–Segur (AKNS) scheme and the corresponding Darboux transformation is constructed to derive the soliton solution. One and two soliton solutions are generated. Using two soliton solutions of 3 CNLS equation, nonlinear tunneling of soliton for both with and without exponential background has been discussed. Finally cascade compression of optical soliton through multi-nonlinear barrier has been discussed. The obtained results may have promising applications in all-optical devices based on optical solitons,more » study of soliton propagation in birefringence fiber systems and optical soliton with distributed dispersion and nonlinearity management. -- Highlights: •We consider the nonlinear tunneling of soliton in birefringence fiber. •3-coupled NLS (CNLS) equation with variable coefficients is considered. •Two soliton solutions are obtained via Darboux transformation using constructed Lax pair. •Soliton tunneling through dispersion barrier and well are investigated. •Finally, cascade compression of soliton has been achieved.« less

Tracing changes in soil N transformations to explain the doubling of N2O emissions under elevated CO2 in the Giessen FACE

NASA Astrophysics Data System (ADS)

Moser, Gerald; Brenzinger, Kristof; Gorenflo, Andre; Clough, Tim; Braker, Gesche; Müller, Christoph

2017-04-01

To reduce the emissions of greenhouse gases (CO2, CH4 & N2O) it is important to quantify main sources and identify the respective ecosystem processes. While the main sources of N2O emissions in agro-ecosystems under current conditions are well known, the influence of a projected higher level of CO2 on the main ecosystem processes responsible for N2O emissions has not been investigated in detail. A major result of the Giessen FACE in a managed temperate grassland was that a +20% CO2 level caused a positive feedback due to increased emissions of N2O to 221% related to control condition. To be able to trace the sources of additional N2O emissions a 15N tracing study was conducted. We measured the N2O emission and its 15N signature, together with the 15N signature of soil and plant samples. The results were analyzed using a 15N tracing model which quantified the main changes in N transformation rates under elevated CO2. Directly after 15N fertilizer application a much higher dynamic of N transformations was observed than in the long run. Absolute mineralisation and DNRA rates were lower under elevated CO2 in the short term but higher in the long term. During the one year study period beginning with the 15N labelling a 1.8-fold increase of N2O emissions occurred under elevated CO2. The source of increased N2O was associated with NO3- in the first weeks after 15N application. Elevated CO2 affected denitrification rates, which resulted in increased N2O emissions due to a change of gene transcription rates (nosZ/(nirK+nirS)) and resulting enzyme activity (see: Brenzinger et al.). Here we show that the reported enhanced N2O emissions for the first 8 FACE years do prevail even in the long-term (> 15 years). The effect of elevated CO2 on N2O production/emission can be explained by altered activity ratios within a stable microbial community.

Bianchi's Bäcklund transformation for higher dimensional quadrics

NASA Astrophysics Data System (ADS)

Dincă, Ion I.

2016-12-01

We provide a generalization of Bianchi's Bäcklund transformation from 2-dimensional quadrics to higher dimensional quadrics (which is also a generalization of Tenenblat-Terng's Bäcklund transformation of isometric deformations of Hn(R) in R 2 n - 1 to general quadrics). Our investigation is the higher dimensional version of Bianchi's main three theorems on the theory of isometric deformations of quadrics and Bianchi's treatment of the Bäcklund transformation for diagonal paraboloids via conjugate systems. It became the driving force which led to the flourishing of the classical differential geometry in the second half of the XIX th century and its profound study by illustrious geometers led to interesting results. Today it is still an open problem in its full generality, but basic familiar results like the Gauß-Bonnet fundamental theorem of surfaces and the Codazzi-Mainardi equations (independently discovered also by Peterson) were first communicated to the French Academy of Sciences. A list (most likely incomplete) of the winners of the prize includes Bianchi, Bonnet, Guichard, Weingarten.Up to 1899 isometric deformations of the (pseudo-)sphere and isotropic quadrics without center (from a metric point of view they can be considered as metrically degenerate quadrics without center) together with their Bäcklund transformation and the complementary transformation of isometric deformations of surfaces of revolution were investigated by geometers such as Bäcklund, Bianchi, Bonnet, Darboux, Goursat, Hazzidakis, Lie, Weingarten, etc.In 1899 Guichard discovered that when quadrics with(out) center and of revolution around the focal axis roll on their isometric deformations their foci describe constant mean curvature (minimal) surfaces (and Bianchi proved the converse: all constant mean curvature (minimal) surfaces can be realized in this way).With Guichard's result the race to find the isometric

Bifurcation of self-folded polygonal bilayers

NASA Astrophysics Data System (ADS)

Abdullah, Arif M.; Braun, Paul V.; Hsia, K. Jimmy

2017-09-01

Motivated by the self-assembly of natural systems, researchers have investigated the stimulus-responsive curving of thin-shell structures, which is also known as self-folding. Self-folding strategies not only offer possibilities to realize complicated shapes but also promise actuation at small length scales. Biaxial mismatch strain driven self-folding bilayers demonstrate bifurcation of equilibrium shapes (from quasi-axisymmetric doubly curved to approximately singly curved) during their stimulus-responsive morphing behavior. Being a structurally instable, bifurcation could be used to tune the self-folding behavior, and hence, a detailed understanding of this phenomenon is appealing from both fundamental and practical perspectives. In this work, we investigated the bifurcation behavior of self-folding bilayer polygons. For the mechanistic understanding, we developed finite element models of planar bilayers (consisting of a stimulus-responsive and a passive layer of material) that transform into 3D curved configurations. Our experiments with cross-linked Polydimethylsiloxane samples that change shapes in organic solvents confirmed our model predictions. Finally, we explored a design scheme to generate gripper-like architectures by avoiding the bifurcation of stimulus-responsive bilayers. Our research contributes to the broad field of self-assembly as the findings could motivate functional devices across multiple disciplines such as robotics, artificial muscles, therapeutic cargos, and reconfigurable biomedical devices.

Cause of vocal fold scar.

PubMed

Allen, Jacqui

2010-12-01

The prolonged debilitation, loss of income, and decrement in quality of life caused by vocal fold scar is exacerbated by our inability to successfully treat this difficult problem. As technology focuses on developing innovative treatments, we need to fully appreciate and understand the mechanisms giving rise to glottal scar, on both a macroscopic and microscopic level. This review examines recent literature pertaining to the gross and molecular mechanisms which give rise to vocal fold scar. Mechanisms of vocal fold scar production have been examined in both macroscopic and microscopic detail. Trauma and injury involving any aspect of the lamina propria, particularly the deeper layers, may result in epithelial tethering and scar formation. At the molecular level, early inflammatory cytokines activate and recruit fibroblasts which then drive the fibrotic cascade. Transforming growth factor-β enhances fibrosis and is balanced by tissue matrix metalloproteinases and hepatocyte growth factor activity. Molecular signaling offers novel opportunities to intervene in scar formation. New work investigating the cause of vocal fold scar identifies complex molecular processes leading to fibrosis in the lamina propria. Improved mechanistic understanding offers insight into prevention strategies and possible targets for antifibrotic therapies that may help prevent or treat this debilitating condition.

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.

n-SIFT: n-dimensional scale invariant feature transform.

PubMed

Cheung, Warren; Hamarneh, Ghassan

2009-09-01

We propose the n-dimensional scale invariant feature transform (n-SIFT) method for extracting and matching salient features from scalar images of arbitrary dimensionality, and compare this method's performance to other related features. The proposed features extend the concepts used for 2-D scalar images in the computer vision SIFT technique for extracting and matching distinctive scale invariant features. We apply the features to images of arbitrary dimensionality through the use of hyperspherical coordinates for gradients and multidimensional histograms to create the feature vectors. We analyze the performance of a fully automated multimodal medical image matching technique based on these features, and successfully apply the technique to determine accurate feature point correspondence between pairs of 3-D MRI images and dynamic 3D + time CT data.

Inhibition delay increases neural network capacity through Stirling transform.

PubMed

Nogaret, Alain; King, Alastair

2018-03-01

Inhibitory neural networks are found to encode high volumes of information through delayed inhibition. We show that inhibition delay increases storage capacity through a Stirling transform of the minimum capacity which stabilizes locally coherent oscillations. We obtain both the exact and asymptotic formulas for the total number of dynamic attractors. Our results predict a (ln2)^{-N}-fold increase in capacity for an N-neuron network and demonstrate high-density associative memories which host a maximum number of oscillations in analog neural devices.

Inhibition delay increases neural network capacity through Stirling transform

NASA Astrophysics Data System (ADS)

Nogaret, Alain; King, Alastair

2018-03-01

Inhibitory neural networks are found to encode high volumes of information through delayed inhibition. We show that inhibition delay increases storage capacity through a Stirling transform of the minimum capacity which stabilizes locally coherent oscillations. We obtain both the exact and asymptotic formulas for the total number of dynamic attractors. Our results predict a (ln2) -N-fold increase in capacity for an N -neuron network and demonstrate high-density associative memories which host a maximum number of oscillations in analog neural devices.

RNAslider: a faster engine for consecutive windows folding and its application to the analysis of genomic folding asymmetry.

PubMed

Horesh, Yair; Wexler, Ydo; Lebenthal, Ilana; Ziv-Ukelson, Michal; Unger, Ron

2009-03-04

Scanning large genomes with a sliding window in search of locally stable RNA structures is a well motivated problem in bioinformatics. Given a predefined window size L and an RNA sequence S of size N (L < N), the consecutive windows folding problem is to compute the minimal free energy (MFE) for the folding of each of the L-sized substrings of S. The consecutive windows folding problem can be naively solved in O(NL3) by applying any of the classical cubic-time RNA folding algorithms to each of the N-L windows of size L. Recently an O(NL2) solution for this problem has been described. Here, we describe and implement an O(NLpsi(L)) engine for the consecutive windows folding problem, where psi(L) is shown to converge to O(1) under the assumption of a standard probabilistic polymer folding model, yielding an O(L) speedup which is experimentally confirmed. Using this tool, we note an intriguing directionality (5'-3' vs. 3'-5') folding bias, i.e. that the minimal free energy (MFE) of folding is higher in the native direction of the DNA than in the reverse direction of various genomic regions in several organisms including regions of the genomes that do not encode proteins or ncRNA. This bias largely emerges from the genomic dinucleotide bias which affects the MFE, however we see some variations in the folding bias in the different genomic regions when normalized to the dinucleotide bias. We also present results from calculating the MFE landscape of a mouse chromosome 1, characterizing the MFE of the long ncRNA molecules that reside in this chromosome. The efficient consecutive windows folding engine described in this paper allows for genome wide scans for ncRNA molecules as well as large-scale statistics. This is implemented here as a software tool, called RNAslider, and applied to the scanning of long chromosomes, leading to the observation of features that are visible only on a large scale.

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

There are a large number of numerical finite element studies concerned with modeling the evolution of folded geological layers through time. This body of research includes many aspects of folding and many different approaches, such as two- and three-dimensional studies, single-layer folding, detachment folding, development of chevron folds, Newtonian, power-law viscous and more complex rheologies, influence of anisotropy, pure-shear, simple-shear and other boundary conditions and so forth. In recent years, studies of multilayer folding emerged, thanks to more advanced mesh generator software and increased computational power. Common to all of these studies is the fact that they consider a forward directed time evolution, as in nature. Very few studies use the finite element method for reverse-time simulations. In such studies, folded geological layers are taken as initial conditions for the numerical simulation. The folding process is reversed by changing the signs of the boundary conditions that supposedly drove the folding process. In such studies, the geometry of the geological layers before the folding process is searched and the amount of shortening necessary for the final folded geometry can be calculated. In contrast to a kinematic or geometric fold restoration procedure, the described approach takes the mechanical behavior of the geological layers into account, such as rheology and the relative strength of the individual layers. This approach is therefore called mechanical restoration of folds. In this study, the concept of mechanical restoration is applied to a two-dimensional 50km long NE-SW-cross-section through the Zagros Simply Folded Belt in Iraqi Kurdistan, NE from the city of Erbil. The Simply Folded Belt is dominated by gentle to open folding and faults are either absent or record only minor offset. Therefore, this region is ideal for testing the concept of mechanical restoration. The profile used is constructed from structural field measurements

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

PubMed

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

2018-04-04

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Xianguo; Li, Ruomeng, E-mail: li_ruomeng@163.com

A Darboux transformation for the Drinfeld–Sokolov–Satsuma–Hirota system of coupled equations is constructed with the aid of gauge transformations between the Lax pairs. As an application, several types of solutions of the Drinfeld–Sokolov–Satsuma–Hirota system are obtained, including soliton solutions, periodic solutions, rational solutions and others.

Adenovirus fibre shaft sequences fold into the native triple beta-spiral fold when N-terminally fused to the bacteriophage T4 fibritin foldon trimerisation motif.

PubMed

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

2004-09-03

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

Comparison of fault-related folding algorithms to restore a fold-and-thrust-belt

NASA Astrophysics Data System (ADS)

Brandes, Christian; Tanner, David

2017-04-01

Fault-related folding means the contemporaneous evolution of folds as a consequence of fault movement. It is a common deformation process in the upper crust that occurs worldwide in accretionary wedges, fold-and-thrust belts, and intra-plate settings, in either strike-slip, compressional, or extensional regimes. Over the last 30 years different algorithms have been developed to simulate the kinematic evolution of fault-related folds. All these models of fault-related folding include similar simplifications and limitations and use the same kinematic behaviour throughout the model (Brandes & Tanner, 2014). We used a natural example of fault-related folding from the Limón fold-and-thrust belt in eastern Costa Rica to test two different algorithms and to compare the resulting geometries. A thrust fault and its hanging-wall anticline were restored using both the trishear method (Allmendinger, 1998; Zehnder & Allmendinger, 2000) and the fault-parallel flow approach (Ziesch et al. 2014); both methods are widely used in academia and industry. The resulting hanging-wall folds above the thrust fault are restored in substantially different fashions. This is largely a function of the propagation-to-slip ratio of the thrust, which controls the geometry of the related anticline. Understanding the controlling factors for anticline evolution is important for the evaluation of potential hydrocarbon reservoirs and the characterization of fault processes. References: Allmendinger, R.W., 1998. Inverse and forward numerical modeling of trishear fault propagation folds. Tectonics, 17, 640-656. Brandes, C., Tanner, D.C. 2014. Fault-related folding: a review of kinematic models and their application. Earth Science Reviews, 138, 352-370. Zehnder, A.T., Allmendinger, R.W., 2000. Velocity field for the trishear model. Journal of Structural Geology, 22, 1009-1014. Ziesch, J., Tanner, D.C., Krawczyk, C.M. 2014. Strain associated with the fault-parallel flow algorithm during kinematic fault

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.

There and back again: Two views on the protein folding puzzle

NASA Astrophysics Data System (ADS)

Finkelstein, Alexei V.; Badretdin, Azat J.; Galzitskaya, Oxana V.; Ivankov, Dmitry N.; Bogatyreva, Natalya S.; Garbuzynskiy, Sergiy O.

2017-07-01

The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured folding times of single-domain globular proteins range from microseconds to hours: the difference (10-11 orders of magnitude) is the same as that between the life span of a mosquito and the age of the universe. This review describes physical theories of rates of overcoming the free-energy barrier separating the natively folded (N) and unfolded (U) states of protein chains in both directions: ;U-to-N; and ;N-to-U;. In the theory of protein folding rates a special role is played by the point of thermodynamic (and kinetic) equilibrium between the native and unfolded state of the chain; here, the theory obtains the simplest form. Paradoxically, a theoretical estimate of the folding time is easier to get from consideration of protein unfolding (the ;N-to-U; transition) rather than folding, because it is easier to outline a good unfolding pathway of any structure than a good folding pathway that leads to the stable fold, which is yet unknown to the folding protein chain. And since the rates of direct and reverse reactions are equal at the equilibrium point (as follows from the physical ;detailed balance; principle), the estimated folding time can be derived from the estimated unfolding time. Theoretical analysis of the ;N-to-U; transition outlines the range of protein folding rates in a good agreement with experiment. Theoretical analysis of folding (the ;U-to-N; transition), performed at the level of formation and assembly of protein secondary structures, outlines the upper limit of protein folding times (i.e., of the time of search for the most stable fold). Both theories come to essentially the same results; this is not a surprise, because they describe overcoming one and the same free-energy barrier, although the way to the top of this barrier from the side of the unfolded state is very different from the way from the

Single Folding Optical Potential for Elastic Scattering of Protons from 14N and 16O in a Wide Range of Energies

NASA Astrophysics Data System (ADS)

Hamada, Sh.

2018-03-01

Available experimental data for protons elastically scattered from 14N and 16O target nuclei are reanalyzed within the framework of single folding optical potential (SFOP) model. In this model, the real part of the potential is derived on the basis of single folding potential. The renormalization factor N r is extracted for the two aforementioned nuclear systems. Theoretical calculations fairly reproduce the experimental data in the whole angular range. Energy dependence of real and imaginary volume integrals as well as reaction cross sections are discussed.

Equilibrium thermodynamics and folding kinetics of a short, fast-folding, beta-hairpin.

PubMed

Jimenez-Cruz, Camilo A; Garcia, Angel E

2014-04-14

Equilibrium thermodynamics of a short beta-hairpin are studied using unbiased all-atom replica exchange molecular dynamics simulations in explicit solvent. An exploratory analysis of the free energy landscape of the system is provided in terms of various structural characteristics, for both the folded and unfolded ensembles. We find that the favorable interactions between the ends introduced by the tryptophan cap, along with the flexibility of the turn region, explain the remarkable stability of the folded state. Charging of the N termini results in effective roughening of the free energy landscape and stabilization of non-native contacts. Folding-unfolding dynamics are further discussed using a set of 2413 independent molecular dynamics simulations, 2 ns to 20 ns long, at the melting temperature of the beta-hairpin. A novel method for the construction of Markov models consisting of an iterative refinement of the discretization in reduced dimensionality is presented and used to generate a detailed kinetic network of the system. The hairpin is found to fold heterogeneously on sub-microsecond timescales, with the relative position of the tryptophan side chains driving the selection of the specific pathway.

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

The Complexity of Folding Self-Folding Origami

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

Computation of the three-dimensional medial surface dynamics of the vocal folds.

PubMed

Döllinger, Michael; Berry, David A

2006-01-01

To increase our understanding of pathological and healthy voice production, quantitative measurement of the medial surface dynamics of the vocal folds is significant, albeit rarely performed because of the inaccessibility of the vocal folds. Using an excised hemilarynx methodology, a new calibration technique, herein referred to as the linear approximate (LA) method, was introduced to compute the three-dimensional coordinates of fleshpoints along the entire medial surface of the vocal fold. The results were compared with results from the direct linear transform. An associated error estimation was presented, demonstrating the improved accuracy of the new method. A test on real data was reported including computation of quantitative measurements of vocal fold dynamics.

M≡E and M=E Complexes of Iron and Cobalt that Emphasize Three-fold Symmetry (E = O, N, NR)

PubMed Central

Saouma, Caroline T.; Peters, Jonas C.

2011-01-01

Mid-to-late transition metal complexes that feature terminal, multiply bonded ligands such as oxos, imides, and nitrides have been invoked as intermediates in several catalytic transformations of synthetic and biological significance. Until about ten years ago, isolable examples of such species were virtually unknown. Over the past decade or so, numerous chemically well-defined examples of such species have been discovered. In this context, the presentreview summarizes the development of 4- and 5-coordinate Fe(E) and Co(E) species under local three-fold symmetry. PMID:21625302

There and back again: Two views on the protein folding puzzle.

PubMed

Finkelstein, Alexei V; Badretdin, Azat J; Galzitskaya, Oxana V; Ivankov, Dmitry N; Bogatyreva, Natalya S; Garbuzynskiy, Sergiy O

2017-07-01

The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured folding times of single-domain globular proteins range from microseconds to hours: the difference (10-11 orders of magnitude) is the same as that between the life span of a mosquito and the age of the universe. This review describes physical theories of rates of overcoming the free-energy barrier separating the natively folded (N) and unfolded (U) states of protein chains in both directions: "U-to-N" and "N-to-U". In the theory of protein folding rates a special role is played by the point of thermodynamic (and kinetic) equilibrium between the native and unfolded state of the chain; here, the theory obtains the simplest form. Paradoxically, a theoretical estimate of the folding time is easier to get from consideration of protein unfolding (the "N-to-U" transition) rather than folding, because it is easier to outline a good unfolding pathway of any structure than a good folding pathway that leads to the stable fold, which is yet unknown to the folding protein chain. And since the rates of direct and reverse reactions are equal at the equilibrium point (as follows from the physical "detailed balance" principle), the estimated folding time can be derived from the estimated unfolding time. Theoretical analysis of the "N-to-U" transition outlines the range of protein folding rates in a good agreement with experiment. Theoretical analysis of folding (the "U-to-N" transition), performed at the level of formation and assembly of protein secondary structures, outlines the upper limit of protein folding times (i.e., of the time of search for the most stable fold). Both theories come to essentially the same results; this is not a surprise, because they describe overcoming one and the same free-energy barrier, although the way to the top of this barrier from the side of the unfolded state is very different from the way from the

Growth and stress-induced transformation of zinc blende AlN layers in Al-AlN-TiN multilayers

DOE PAGES

Li, Nan; Yadav, Satyesh K.; Wang, Jian; ...

2015-12-18

We report that AlN nanolayers in sputter deposited {111}Al/AlN/TiN multilayers exhibit the metastable zinc-blende-structure (z-AlN). Based on density function theory calculations, the growth of the z-AlN is ascribed to the kinetically and energetically favored nitridation of the deposited aluminium layer. In situ nanoindentation of the as-deposited {111}Al/AlN/TiN multilayers in a high-resolution transmission electron microscope revealed the z-AlN to wurzite AlN phase transformation through collective glide of Shockley partial dislocations on every two {111} planes of the z-AlN.

Synergism of herpes simplex virus and tobacco-specific N'-nitrosamines in cell transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, N.H.; Dokko, H.; Li, S.L.

1991-03-01

Previous studies indicate that herpes simplex virus (HSV) enhances the carcinogenic activity of smokeless tobacco and tobacco-related chemical carcinogens in animals. Since tobacco-specific N'-nitrosamines (TSNAs) such as N'-nitrosonornicotine (NNN) and 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major chemical carcinogens of smokeless tobacco and are known to be responsible for the development of oral cancers in smokeless tobacco users, the combined effects of TSNAs and HSV in cell transformation were investigated. Exposure of cells to NNN or NNK followed by virus infection resulted in a significant enhancement of transformation frequency when compared with that observed with chemical carcinogens or virus alone. This study suggestsmore » that TSNAs and HSV can interact together and show synergism in cell transformation.« less

General n-dimensional quadrature transform and its application to interferogram demodulation.

PubMed

Servin, Manuel; Quiroga, Juan Antonio; Marroquin, Jose Luis

2003-05-01

Quadrature operators are useful for obtaining the modulating phase phi in interferometry and temporal signals in electrical communications. In carrier-frequency interferometry and electrical communications, one uses the Hilbert transform to obtain the quadrature of the signal. In these cases the Hilbert transform gives the desired quadrature because the modulating phase is monotonically increasing. We propose an n-dimensional quadrature operator that transforms cos(phi) into -sin(phi) regardless of the frequency spectrum of the signal. With the quadrature of the phase-modulated signal, one can easily calculate the value of phi over all the domain of interest. Our quadrature operator is composed of two n-dimensional vector fields: One is related to the gradient of the image normalized with respect to local frequency magnitude, and the other is related to the sign of the local frequency of the signal. The inner product of these two vector fields gives us the desired quadrature signal. This quadrature operator is derived in the image space by use of differential vector calculus and in the frequency domain by use of a n-dimensional generalization of the Hilbert transform. A robust numerical algorithm is given to find the modulating phase of two-dimensional single-image closed-fringe interferograms by use of the ideas put forward.

How cooperative are protein folding and unfolding transitions?

PubMed Central

Malhotra, Pooja

2016-01-01

Abstract A thermodynamically and kinetically simple picture of protein folding envisages only two states, native (N) and unfolded (U), separated by a single activation free energy barrier, and interconverting by cooperative two‐state transitions. The folding/unfolding transitions of many proteins occur, however, in multiple discrete steps associated with the formation of intermediates, which is indicative of reduced cooperativity. Furthermore, much advancement in experimental and computational approaches has demonstrated entirely non‐cooperative (gradual) transitions via a continuum of states and a multitude of small energetic barriers between the N and U states of some proteins. These findings have been instrumental towards providing a structural rationale for cooperative versus noncooperative transitions, based on the coupling between interaction networks in proteins. The cooperativity inherent in a folding/unfolding reaction appears to be context dependent, and can be tuned via experimental conditions which change the stabilities of N and U. The evolution of cooperativity in protein folding transitions is linked closely to the evolution of function as well as the aggregation propensity of the protein. A large activation energy barrier in a fully cooperative transition can provide the kinetic control required to prevent the accumulation of partially unfolded forms, which may promote aggregation. Nevertheless, increasing evidence for barrier‐less “downhill” folding, as well as for continuous “uphill” unfolding transitions, indicate that gradual non‐cooperative processes may be ubiquitous features on the free energy landscape of protein folding. PMID:27522064

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

PubMed Central

Prentiss, Michael C.; Wales, David J.; Wolynes, Peter G.

2010-01-01

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N or C terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N terminus portion of the knot and a rate-determining step where the C terminus is incorporated. The low-lying minima with the N terminus knotted and the C terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N and C termini into the knot occurs late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly. PMID:20617197

Three dimensional simulations of viscous folding in diverging microchannels

NASA Astrophysics Data System (ADS)

Xu, Bingrui; Chergui, Jalel; Shin, Seungwon; Juric, Damir

2016-11-01

Three dimensional simulations on the viscous folding in diverging microchannels reported by Cubaud and Mason are performed using the parallel code BLUE for multi-phase flows. The more viscous liquid L1 is injected into the channel from the center inlet, and the less viscous liquid L2 from two side inlets. Liquid L1 takes the form of a thin filament due to hydrodynamic focusing in the long channel that leads to the diverging region. The thread then becomes unstable to a folding instability, due to the longitudinal compressive stress applied to it by the diverging flow of liquid L2. We performed a parameter study in which the flow rate ratio, the viscosity ratio, the Reynolds number, and the shape of the channel were varied relative to a reference model. In our simulations, the cross section of the thread produced by focusing is elliptical rather than circular. The initial folding axis can be either parallel or perpendicular to the narrow dimension of the chamber. In the former case, the folding slowly transforms via twisting to perpendicular folding, or it may remain parallel. The direction of folding onset is determined by the velocity profile and the elliptical shape of the thread cross section in the channel that feeds the diverging part of the cell.

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

PubMed

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

2017-05-30

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

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

PubMed Central

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

2017-01-01

Ladybird beetles are high-mobility insects and explore broad areas by switching between walking and flying. Their excellent wing transformation systems enabling this lifestyle are expected to provide large potential for engineering applications. However, the mechanism behind the folding of their hindwings remains unclear. The reason is that ladybird beetles close the elytra ahead of wing folding, preventing the observation of detailed processes occurring under the elytra. In the present study, artificial transparent elytra were transplanted on living ladybird beetles, thereby enabling us to observe the detailed wing-folding processes. The result revealed that in addition to the abdominal movements mentioned in previous studies, the edge and ventral surface of the elytra, as well as characteristic shaped veins, play important roles in wing folding. The structures of the wing frames enabling this folding process and detailed 3D shape of the hindwing were investigated using microcomputed tomography. The results showed that the tape spring-like elastic frame plays an important role in the wing transformation mechanism. Compared with other beetles, hindwings in ladybird beetles are characterized by two seemingly incompatible properties: (i) the wing rigidity with relatively thick veins and (ii) the compactness in stored shapes with complex crease patterns. The detailed wing-folding process revealed in this study is expected to facilitate understanding of the naturally optimized system in this excellent deployable structure. PMID:28507159

Development of a High-Efficiency Transformation Method and Implementation of Rational Metabolic Engineering for the Industrial Butanol Hyperproducer Clostridium saccharoperbutylacetonicum Strain N1-4

PubMed Central

Herman, Nicolaus A.; Li, Jeffrey; Bedi, Ripika; Turchi, Barbara; Liu, Xiaoji

2016-01-01

ABSTRACT While a majority of academic studies concerning acetone, butanol, and ethanol (ABE) production by Clostridium have focused on Clostridium acetobutylicum, other members of this genus have proven to be effective industrial workhorses despite the inability to perform genetic manipulations on many of these strains. To further improve the industrial performance of these strains in areas such as substrate usage, solvent production, and end product versatility, transformation methods and genetic tools are needed to overcome the genetic intractability displayed by these species. In this study, we present the development of a high-efficiency transformation method for the industrial butanol hyperproducer Clostridium saccharoperbutylacetonicum strain N1-4 (HMT) ATCC 27021. Following initial failures, we found that the key to creating a successful transformation method was the identification of three distinct colony morphologies (types S, R, and I), which displayed significant differences in transformability. Working with the readily transformable type I cells (transformation efficiency, 1.1 × 106 CFU/μg DNA), we performed targeted gene deletions in C. saccharoperbutylacetonicum N1-4 using a homologous recombination-mediated allelic exchange method. Using plasmid-based gene overexpression and targeted knockouts of key genes in the native acetone-butanol-ethanol (ABE) metabolic pathway, we successfully implemented rational metabolic engineering strategies, yielding in the best case an engineered strain (Clostridium saccharoperbutylacetonicum strain N1-4/pWIS13) displaying an 18% increase in butanol titers and 30% increase in total ABE titer (0.35 g ABE/g sucrose) in batch fermentations. Additionally, two engineered strains overexpressing aldehyde/alcohol dehydrogenases (encoded by adh11 and adh5) displayed 8.5- and 11.8-fold increases (respectively) in batch ethanol production. IMPORTANCE This paper presents the first steps toward advanced genetic engineering of the

Development of a High-Efficiency Transformation Method and Implementation of Rational Metabolic Engineering for the Industrial Butanol Hyperproducer Clostridium saccharoperbutylacetonicum Strain N1-4.

PubMed

Herman, Nicolaus A; Li, Jeffrey; Bedi, Ripika; Turchi, Barbara; Liu, Xiaoji; Miller, Michael J; Zhang, Wenjun

2017-01-15

While a majority of academic studies concerning acetone, butanol, and ethanol (ABE) production by Clostridium have focused on Clostridium acetobutylicum, other members of this genus have proven to be effective industrial workhorses despite the inability to perform genetic manipulations on many of these strains. To further improve the industrial performance of these strains in areas such as substrate usage, solvent production, and end product versatility, transformation methods and genetic tools are needed to overcome the genetic intractability displayed by these species. In this study, we present the development of a high-efficiency transformation method for the industrial butanol hyperproducer Clostridium saccharoperbutylacetonicum strain N1-4 (HMT) ATCC 27021. Following initial failures, we found that the key to creating a successful transformation method was the identification of three distinct colony morphologies (types S, R, and I), which displayed significant differences in transformability. Working with the readily transformable type I cells (transformation efficiency, 1.1 × 10 6 CFU/μg DNA), we performed targeted gene deletions in C. saccharoperbutylacetonicum N1-4 using a homologous recombination-mediated allelic exchange method. Using plasmid-based gene overexpression and targeted knockouts of key genes in the native acetone-butanol-ethanol (ABE) metabolic pathway, we successfully implemented rational metabolic engineering strategies, yielding in the best case an engineered strain (Clostridium saccharoperbutylacetonicum strain N1-4/pWIS13) displaying an 18% increase in butanol titers and 30% increase in total ABE titer (0.35 g ABE/g sucrose) in batch fermentations. Additionally, two engineered strains overexpressing aldehyde/alcohol dehydrogenases (encoded by adh11 and adh5) displayed 8.5- and 11.8-fold increases (respectively) in batch ethanol production. This paper presents the first steps toward advanced genetic engineering of the industrial butanol

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

Efficient Plastid Transformation in Arabidopsis.

PubMed

Yu, Qiguo; Lutz, Kerry Ann; Maliga, Pal

2017-09-01

Plastid transformation is routine in tobacco ( Nicotiana tabacum ) but 100-fold less frequent in Arabidopsis ( Arabidopsis thaliana ), preventing its use in plastid biology. A recent study revealed that null mutations in ACC2 , encoding a plastid-targeted acetyl-coenzyme A carboxylase, cause hypersensitivity to spectinomycin. We hypothesized that plastid transformation efficiency should increase in the acc2 background, because when ACC2 is absent, fatty acid biosynthesis becomes dependent on translation of the plastid-encoded ACC β-carboxylase subunit. We bombarded ACC2 -defective Arabidopsis leaves with a vector carrying a selectable spectinomycin resistance ( aadA ) gene and gfp , encoding the green fluorescence protein GFP. Spectinomycin-resistant clones were identified as green cell clusters on a spectinomycin medium. Plastid transformation was confirmed by GFP accumulation from the second open reading frame of a polycistronic messenger RNA, which would not be translated in the cytoplasm. We obtained one to two plastid transformation events per bombarded sample in spectinomycin-hypersensitive Slavice and Columbia acc2 knockout backgrounds, an approximately 100-fold enhanced plastid transformation frequency. Slavice and Columbia are accessions in which plant regeneration is uncharacterized or difficult to obtain. A practical system for Arabidopsis plastid transformation will be obtained by creating an ACC2 null background in a regenerable Arabidopsis accession. The recognition that the duplicated ACCase in Arabidopsis is an impediment to plastid transformation provides a rational template to implement plastid transformation in related recalcitrant crops. © 2017 American Society of Plant Biologists. All Rights Reserved.

Aromatic thiol-mediated cleavage of N-O bonds enables chemical ubiquitylation of folded proteins

NASA Astrophysics Data System (ADS)

Weller, Caroline E.; Dhall, Abhinav; Ding, Feizhi; Linares, Edlaine; Whedon, Samuel D.; Senger, Nicholas A.; Tyson, Elizabeth L.; Bagert, John D.; Li, Xiaosong; Augusto, Ohara; Chatterjee, Champak

2016-09-01

Access to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N-O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N-O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins.

Factors affecting the efficient transformation of Colletotrichum species

USGS Publications Warehouse

Redman, Regina S.; Rodriguez, Rusty J.

1994-01-01

Factors affecting the efficient transformation of Colletotrichum species. Experimental Mycology, 18, 230-246. Twelve isolates representing four species of Colletotrichum were transformed either by enhanced protoplast, restriction enzyme-mediated integration (REMI), or electroporation-mediated protocols. The enhanced protoplast transformation protocol resulted in 100- and 50-fold increases in the transformation efficiencies of Colletotrichum lindemuthianum and C. magna , respectively. REMI transformation involved the use of Hin dIII and vector DNA linearized with HindIII to increase the number of integration events and potential gene disruptions in the fungal genome. Combining the enhanced protoplast and the REMI protocols resulted in a 22-fold increase in the number of hygromycin/nystatin-resistant mutants in C. lindemuthianum . Electroporation-mediated transformation was performed on mycelial fragments and spores of four Colletotrichum species, resulting in efficiencies of up to 1000 transformants/μg DNA. The pHA1.3 vector which confers hygromycin resistance contains telomeric sequences from Fusarium oxysporum , transforms by autonomous replication and genomic integration, and was essential for elevated transformation efficiencies of 100 to 10,000 transformants/μg DNA. Modifications of pHA1.3 occurred during bacterial amplification and post fungal transformation resulting in plasmids capable of significantly elevated transformation efficiencies in C. lindemuthianum.

Exact analytical modeling of lightwave propagation in planar media with arbitrarily graded index profiles

NASA Astrophysics Data System (ADS)

Krapez, J.-C.

2018-02-01

Applying the Darboux transformation in the optical-depth space allows building infinite chains of exact analytical solutions of the electromagnetic (EM) fields in planar 1D-graded dielectrics. As a matter of fact, infinite chains of solvable admittance profiles (e.g. refractive-index profiles, in the case of non-magnetic materials), together with the related EM fields are simultaneously and recursively obtained. The whole procedure has received the name "PROFIDT method" for PROperty and FIeld Darboux Transformation method. By repeating the Darboux transformations we can find out progressively more complex profiles and their EM solutions. An alternative is to stop after the first step and settle for a particular class of four-parameter admittance profiles that were dubbed of "sech(ξ)-type". These profiles are highly flexible. For this reason, they can be used as elementary bricks for building and modeling profiles of arbitrary shape. In addition, the corresponding transfer matrix involves only elementary functions. The sub-class of "sech(ξ)-type" profiles with horizontal end-slopes (S-shaped function) is particularly interesting: these can be used for high-level modeling of piecewise-sigmoidal refractive-index profiles encountered in various photonic devices such as matchinglayers, antireflection layers, rugate filters, chirped mirrors and photonic crystals. These simple analytical tools also allow exploring the fascinating properties of a new kind of structure, namely smooth quasicrystals. They can also be applied to model propagation of other types of waves in graded media such as acoustic waves and electric waves in tapered transmission lines.

Radiation Fibrosis of the Vocal Fold: From Man to Mouse

PubMed Central

Johns, Michael M.; Kolachala, Vasantha; Berg, Eric; Muller, Susan; Creighton, Frances X.; Branski, Ryan C.

2013-01-01

Objectives To characterize fundamental late tissue effects in the human vocal fold following radiation therapy. To develop a murine model of radiation fibrosis to ultimately develop both treatment and prevention paradigms. Design Translational study using archived human and fresh murine irradiated vocal fold tissue. Methods 1) Irradiated vocal fold tissue from patients undergoing laryngectomy for loss of function from radiation fibrosis were identified from pathology archives. Histomorphometry, immunohistochemistry, and whole-genome microarray as well as real-time transcriptional analyses was performed. 2) Focused radiation to the head and neck was delivered to mice in a survival fashion. One month following radiation, vocal fold tissue was analyzed with histomorphometry, immunohistochemistry, and real-time PCR transcriptional analysis for selected markers of fibrosis. Results Human irradiated vocal folds demonstrated increased collagen transcription with increased deposition and disorganization of collagen in both the thyroarytenoid muscle and the superficial lamina propria. Fibronectin were increased in the superficial lamina propria. Laminin decreased in the thyroarytenoid muscle. Whole genome microarray analysis demonstrated increased transcription of markers for fibrosis, oxidative stress, inflammation, glycosaminoglycan production and apoptosis. Irradiated murine vocal folds demonstrated increases in collagen and fibronectin transcription and deposition in the lamina propria. Transforming growth factor (TGF)-β increased in the lamina propria. Conclusion Human irradiated vocal folds demonstrate molecular changes leading to fibrosis that underlie loss of vocal fold pliability that occurs in patients following laryngeal irradiation. Irradiated murine tissue demonstrates similar findings, and this mouse model may have utility in creating prevention and treatment strategies for vocal fold radiation fibrosis. PMID:23242839

Surface folding in metals: a mechanism for delamination wear in sliding

PubMed Central

Mahato, Anirban; Guo, Yang; Sundaram, Narayan K.; Chandrasekar, Srinivasan

2014-01-01

Using high-resolution, in situ imaging of a hard, wedge-shaped model asperity sliding against a metal surface, we demonstrate a new mechanism for particle formation and delamination wear. Damage to the residual surface is caused by the occurrence of folds on the free surface of the prow-shaped region ahead of the wedge. This damage manifests itself as shallow crack-like features and surface tears, which are inclined at very acute angles to the surface. The transformation of folds into cracks, tears and particles is directly captured. Notably, a single sliding pass is sufficient to damage the surface, and subsequent passes result in the generation of platelet-like wear particles. Tracking the folding process at every stage from surface bumps to folds to cracks/tears/particles ensures that there is no ambiguity in capturing the mechanism of wear. Because fold formation and consequent delamination are quite general, our findings have broad applicability beyond wear itself, including implications for design of surface generation and conditioning processes. PMID:25197251

Reduction of estrogen-induced transformation of mouse mammary epithelial cells by N-acetylcysteine

PubMed Central

Venugopal, Divya; Zahid, Muhammad; Mailander, Paula C; Meza, Jane L.; Rogan, Eleanor G.; Cavalieri, Ercole L.; Chakravarti, Dhrubajyoti

2009-01-01

A growing number of studies indicate that breast cancer initiation is related to abnormal estrogen oxidation to form an excess of estrogen-3,4-quinones, which react with DNA to form depurinating adducts and induce mutations. This mechanism is often called estrogen genotoxicity. 4-catechol estrogens, precursors of the estrogen-3,4-quinones, were previously shown to account for most of the transforming and tumorigenic activity. We examined whether estrogen-induced transformation can be reduced by inhibiting the oxidation of a 4-catechol estrogen to its quinone. We demonstrate that E6 cells (a normal mouse epithelial cell line) can be transformed by a single treatment with a catechol estrogen or its quinone. The transforming activities of 4-hydroxyestradiol and estradiol-3,4-quinone were comparable. N-acetylcysteine, a common antioxidant, inhibited the oxidation of 4-hydroxyestradiol to the quinone and consequent formation of DNA adducts. It also drastically reduced estrogen-induced transformation of E6 cells. These results strongly implicate estrogen genotoxicity in mammary cell transformation. Since N-acetylcysteine is well-tolerated in clinical studies, it may be a promising candidate for breast cancer prevention. PMID:18226522

Hamiltonian theory of guiding-center motion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Littlejohn, R.G.

1980-05-01

A Hamiltonian treatment of the guiding center problem is given which employs noncanonical coordinates in phase space. Separation of the unperturbed system from the perturbation is achieved by using a coordinate transformation suggested by a theorem of Darboux. As a model to illustrate the method, motion in the magnetic field B=B(x,y)z is studied. Lie transforms are used to carry out the perturbation expansion.

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

PubMed

Saha, Mitul; Morais, Marc C

2012-12-15

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

Folding 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. © 2016 Wiley Periodicals, Inc.

Co-Translational Folding Trajectory of the HemK Helical Domain.

PubMed

Mercier, Evan; Rodnina, Marina V

2018-06-26

Protein folding begins co-translationally within the restricted space of the peptide exit tunnel of the ribosome. We have already shown that the N-terminal α-helical domain of the universally conserved N 5 -glutamine methyltransferase HemK is compacted within the exit tunnel and rearranges into the native fold upon emerging from the ribosome. However, the exact folding pathway of the domain remained unclear. Here we analyzed the rapid kinetics of translation and folding monitored by fluorescence resonance energy transfer and photoinduced electron transfer using global fitting to a model for synthesis of the 112-amino acid HemK fragment. Our results suggest that the co-translational folding trajectory of HemK starts within the tunnel and passes through four kinetically distinct folding intermediates that may represent sequential docking of helices to a growing compact core. The kinetics of the process is defined entirely by translation. The results show how analysis of ensemble kinetic data can be used to dissect complex trajectories of rapid conformational rearrangements in multicomponent systems.

Dark-dark solitons for a coupled variable-coefficient higher-order nonlinear Schrödinger system in an inhomogeneous optical fiber

NASA Astrophysics Data System (ADS)

Li, Ming-Zhen; Tian, Bo; Qu, Qi-Xing; Chai, Han-Peng; Liu, Lei; Du, Zhong

2017-12-01

In this paper, under investigation is a coupled variable-coefficient higher-order nonlinear Schrödinger system, which describes the simultaneous propagation of optical pulses in an inhomogeneous optical fiber. Based on the Lax pair and binary Darboux transformation, we present the nondegenerate N-dark-dark soliton solutions. With the graphical simulation, soliton propagation and interaction are discussed with the group velocity dispersion and fourth-order dispersion effects, which affect the velocity but have no effect on the amplitude. Linear, parabolic and periodic one dark-dark solitons are displayed. Interactions between the two solitons are presented as well, which are all elastic.

Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops

PubMed Central

Paslawski, Wojciech; Lillelund, Ove K.; Kristensen, Julie Veje; Schafer, Nicholas P.; Baker, Rosanna P.; Urban, Sinisa; Otzen, Daniel E.

2015-01-01

Despite the ubiquity of helical membrane proteins in nature and their pharmacological importance, the mechanisms guiding their folding remain unclear. We performed kinetic folding and unfolding experiments on 69 mutants (engineered every 2–3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli. The only clustering of significantly positive ϕ-values occurs at the cytosolic termini of transmembrane helices 1 and 2, which we identify as a compact nucleus. The three loops flanking these helices show a preponderance of negative ϕ-values, which are sometimes taken to be indicative of nonnative interactions in the transition state. Mutations in transmembrane helices 3–6 yielded predominantly ϕ-values near zero, indicating that this part of the protein has denatured-state–level structure in the transition state. We propose that loops 1–3 undergo conformational rearrangements to position the folding nucleus correctly, which then drives folding of the rest of the domain. A compact N-terminal nucleus is consistent with the vectorial nature of cotranslational membrane insertion found in vivo. The origin of the interactions in the transition state that lead to a large number of negative ϕ-values remains to be elucidated. PMID:26056273

Extreme Folding

NASA Astrophysics Data System (ADS)

Demaine, Erik

2012-02-01

Our understanding of the mathematics and algorithms behind paper folding, and geometric folding in general, has increased dramatically over the past several years. These developments have found a surprisingly broad range of applications. In the art of origami, it has helped spur the technical origami revolution. In engineering and science, it has helped solve problems in areas such as manufacturing, robotics, graphics, and protein folding. On the recreational side, it has led to new kinds of folding puzzles and magic. I will give an overview of the mathematics and algorithms of folding, with a focus on new mathematics and sculpture.

The dynamics of folding instability in a constrained Cosserat medium

NASA Astrophysics Data System (ADS)

Gourgiotis, Panos A.; Bigoni, Davide

2017-04-01

Different from Cauchy elastic materials, generalized continua, and in particular constrained Cosserat materials, can be designed to possess extreme (near a failure of ellipticity) orthotropy properties and in this way to model folding in a three-dimensional solid. Following this approach, folding, which is a narrow zone of highly localized bending, spontaneously emerges as a deformation pattern occurring in a strongly anisotropic solid. How this peculiar pattern interacts with wave propagation in the time-harmonic domain is revealed through the derivation of an antiplane, infinite-body Green's function, which opens the way to integral techniques for anisotropic constrained Cosserat continua. Viewed as a perturbing agent, the Green's function shows that folding, emerging near a steadily pulsating source in the limit of failure of ellipticity, is transformed into a disturbance with wavefronts parallel to the folding itself. The results of the presented study introduce the possibility of exploiting constrained Cosserat solids for propagating waves in materials displaying origami patterns of deformation. This article is part of the themed issue 'Patterning through instabilities in complex media: theory and applications.'

Dcm methylation is detrimental to plasmid transformation in Clostridium thermocellum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guss, Adam M; Olson, Daniel G.; Caiazza, Nicky

2012-01-01

BACKGROUND: Industrial production of biofuels and other products by cellulolytic microorganisms is of interest but hindered by the nascent state of genetic tools. Although a genetic system for Clostridium thermocellum DSM1313 has recently been developed, available methods achieve relatively low efficiency and similar plasmids can transform C. thermocellum at dramatically different efficiencies. RESULTS: We report an increase in transformation efficiency of C. thermocellum for a variety of plasmids by using DNA that has been methylated by Escherichia coli Dam but not Dcm methylases. When isolated from a dam+ dcm+ E. coli strain, pAMG206 transforms C. thermocellum 100-fold better than themore » similar plasmid pAMG205, which contains an additional Dcm methylation site in the pyrF gene. Upon removal of Dcm methylation, transformation with pAMG206 showed a four- to seven-fold increase in efficiency; however, transformation efficiency of pAMG205 increased 500-fold. Removal of the Dcm methylation site from the pAM205 pyrF gene via silent mutation resulted in increased transformation efficiencies equivalent to that of pAMG206. Upon proper methylation, transformation efficiency of plasmids bearing the pMK3 and pB6A origins of replication increased ca. three orders of magnitude. CONCLUSION: E. coli Dcm methylation decreases transformation efficiency in C. thermocellum DSM1313. The use of properly methylated plasmid DNA should facilitate genetic manipulation of this industrially relevant bacterium.« less

Symptomatic unilateral vocal fold paralysis following cardiothoracic surgery.

PubMed

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

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

Classification for animal vocal fold surgery: resection margins impact histological outcomes of vocal fold injury.

PubMed

Imaizumi, Mitsuyoshi; Thibeault, Susan L; Leydon, Ciara

2014-11-01

Extent of vocal fold injury impacts the nature and timing of wound healing and voice outcomes. However, depth and extent of the lesion created to study wound healing in animal models vary across studies, likely contributing to different outcomes. Our goal was to create a surgery classification system to enable comparison of postoperative outcomes across animal vocal fold wound-healing studies. Prospective, controlled animal study. Rats underwent one of three types of unilateral vocal fold surgeries classified by depth and length of resection. The surgeries were: for subepithelial injury, resection of epithelium and superficial layer of the lamina propria at the midmembranous portion of the vocal fold; for transmucosal injury, resection of epithelium and lamina propria; and for transmuscular injury, resection of epithelium, lamina propria, and superficial portion of the vocalis muscle. Wound healing was evaluated histologically at various time points up to 35 days postinjury. Complete healing occurred by 14 days postsurgery for subepithelial injury, and by day 35 for transmucosal injury. Injury remained present at day 35 for transmuscular injury. Timing and completeness of healing varied by extent and depth of resection. Scarless healing occurred rapidly following subepithelial injury, whereas scarring was observed at 5 weeks after transmuscular injury. The proposed classification system may facilitate comparison of surgical outcomes across vocal fold wound-healing studies. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Swelling-Induced Folding in Confined Nanoscale Responsive Polymer Gels

DTIC Science & Technology

2010-03-16

transformations leading to micrometer scale lenticular surface structures due to strong shear forces at the filmsubstrate interface. The growth of the...observed here. To further understand the origin of the observed lenticular folding patterns, we considered how the con- ditions for buckling patterns in...periodic- ity of 900 nm) exhibited organized lenticular structures popping up from nanoimprinted film similar to that ob- served in a uniform flat

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

PubMed

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

2015-01-01

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

How Does Your Protein Fold? Elucidating the Apomyoglobin Folding Pathway

PubMed Central

Dyson, H. Jane; Wright, Peter E.

2017-01-01

Conspectus Although each type of protein fold and in some cases individual proteins within a fold classification can have very different mechanisms of folding, the underlying biophysical and biochemical principles that operate to cause a linear polypeptide chain to fold into a globular structure must be the same. In an aqueous solution, the protein takes up the thermodynamically most stable structure, but the pathway along which the polypeptide proceeds in order to reach that structure is a function of the amino acid sequence, which must be the final determining factor, not only in shaping the final folded structure, but in dictating the folding pathway. A number of groups have focused on a single protein or group of proteins, to determine in detail the factors that influence the rate and mechanism of folding in a defined system, with the hope that hypothesis-driven experiments can elucidate the underlying principles governing the folding process. Our research group has focused on the folding of the globin family of proteins, and in particular on the monomeric protein apomyoglobin. Apomyoglobin (apoMb) folds relatively slowly (~2 seconds) via an ensemble of obligatory intermediates that form rapidly after the initiation of folding. The folding pathway can be dissected using rapid-mixing techniques, which can probe processes in the millisecond time range. Stopped-flow measurements detected by circular dichroism (CD) or fluorescence spectroscopy give information on the rates of folding events. Quench-flow experiments utilize the differential rates of hydrogen-deuterium exchange of amide protons protected in parts of the structure that are folded early; protection of amides can be detected by mass spectrometry or proton nuclear magnetic resonance spectroscopy (NMR). In addition, apoMb forms an intermediate at equilibrium at pH ~ 4, which is sufficiently stable for it to be structurally characterized by solution methods such as CD, fluorescence and NMR spectroscopies

Radiometric Dating of Folds: A new approach to determine the timing of deformation at shallow-crustal conditions, with examples from the Mexican Fold-Thrust Belt

NASA Astrophysics Data System (ADS)

Fitz Diaz, E.; van der Pluijm, B. A.

2012-12-01

We are developing a robust method to obtain absolute ages of folds that were formed at shallow crustal conditions. The method takes advantage of illite neocrystallization in folded, clay-bearing layers and the ability to obtain accurate retention and total gas ages from small size fractions using encapsulated Ar analysis, analogous to prior work on fault gouge dating. We illustrate our approach in folded Cretaceous shale-bentonitic layers that are interbedded with carbonates of the Zimapán and the Tampico-Misantla cretaceous basins in central-eastern Mexico. Basinal carbonates were buried by syntectonic turbidites and inverted during the formation of the Mexican Fold-Thrust in the Late Cretaceous. Results were obtained from four chevron folds that are representative of different stages of deformation, burial/temperature conditions and location within this thin-skinned orogenic wedge: two from the Zimapán Basin (Folds 1 and 2) in the west and two from the Tampico-Misantla Basin (Folds 3 and 4) in the east. Mineralogic compositions and variations in illite-polytypes, crystallite-size (CS) and Ar/Ar ages were obtained from size fractions in limbs and hinges of folded layers. Ar retention ages produce a folding age of ~81 Ma for Fold 1 and ~69 Ma for Fold 2, which are fully consistent with stratigraphic limits from syn-orogenic turbidities and observed overprinting events in the Mexican Fold-Thrust Belt. The total gas age of Fold 3, on the easternmost margin of the Tampico-Misantla Basin is similar to that of Fold 2, indicating that the second event is regional in scale. In addition to presenting a new, reliable method to constrain the timing of local deformation, we interpret folding and associated clay neo-mineralization in terms of the regional burial history, and localization and propagation of deformation within a heterogeneous orogenic wedge involving progressive deformation of two basins separated by a platform block.

Aerobic and anaerobic nitrogen transformation processes in N2-fixing cyanobacterial aggregates.

PubMed

Klawonn, Isabell; Bonaglia, Stefano; Brüchert, Volker; Ploug, Helle

2015-06-01

Colonies of N(2)-fixing cyanobacteria are key players in supplying new nitrogen to the ocean, but the biological fate of this fixed nitrogen remains poorly constrained. Here, we report on aerobic and anaerobic microbial nitrogen transformation processes that co-occur within millimetre-sized cyanobacterial aggregates (Nodularia spumigena) collected in aerated surface waters in the Baltic Sea. Microelectrode profiles showed steep oxygen gradients inside the aggregates and the potential for nitrous oxide production in the aggregates' anoxic centres. (15)N-isotope labelling experiments and nutrient analyses revealed that N(2) fixation, ammonification, nitrification, nitrate reduction to ammonium, denitrification and possibly anaerobic ammonium oxidation (anammox) can co-occur within these consortia. Thus, N. spumigena aggregates are potential sites of nitrogen gain, recycling and loss. Rates of nitrate reduction to ammonium and N(2) were limited by low internal nitrification rates and low concentrations of nitrate in the ambient water. Presumably, patterns of N-transformation processes similar to those observed in this study arise also in other phytoplankton colonies, marine snow and fecal pellets. Anoxic microniches, as a pre-condition for anaerobic nitrogen transformations, may occur within large aggregates (⩾1 mm) even when suspended in fully oxygenated waters, whereas anoxia in small aggregates (<1 to ⩾0.1 mm) may only arise in low-oxygenated waters (⩽25 μM). We propose that the net effect of aggregates on nitrogen loss is negligible in NO(3)(-)-depleted, fully oxygenated (surface) waters. In NO(3)(-)-enriched (>1.5 μM), O(2)-depleted water layers, for example, in the chemocline of the Baltic Sea or the oceanic mesopelagic zone, aggregates may promote N-recycling and -loss processes.

Biochemical basis of vocal fold mobilization after microflap surgery in a rabbit model.

PubMed

Mitchell, Joshua R; Kojima, Tsuyoshi; Wu, Hongmei; Garrett, C Gaelyn; Rousseau, Bernard

2014-02-01

To investigate phonation-related extracellular matrix (ECM) changes in the vocal fold lamina propria after microflap surgery using an in vivo rabbit phonation model. Prospective animal study. Twenty-four New Zealand White rabbits were used in this study. Quantitative polymerase chain reaction and immunohistochemistry were used to investigate alterations in vocal fold ECM proinflammatory and profibrotic gene, and protein expression from a control group of animals receiving a microflap without phonation and a separate group of animals receiving experimentally induced phonation on postmicroflap days 0, 3, and 7. IHC demonstrated the highest concentration of CD45 in vocal folds on postoperative day 0. Staining for CD45 was absent by postoperative day 7, with no differences in CD45 staining between groups. Fibronectin gene expression increased significantly on postoperative day 3 in the control and experimentally induced phonation groups, with maximal staining of fibronectin around the microflap incision on postoperative day 7. No alterations in cyclooxygenase-2, interleukin-1β, and transforming growth factor-β1 gene expression were observed between groups. Results of the present study revealed an acute inflammatory response in the vocal fold at the time of microflap (day 0) and up to 3 days post-microflap. By post-operative day 3, staining of CD45 positive cells decreased, with essentially no evidence of inflammation by post-operative day 7. With the end of the acute inflammatory response occurring around day 3, these data may provide support for mobilizing tissue after inflammation has subsided and the process of active tissue remodeling has ensued (days 3-7). N/A. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

TRANSFORMATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

LACKS,S.A.

2003-10-09

Transformation, which alters the genetic makeup of an individual, is a concept that intrigues the human imagination. In Streptococcus pneumoniae such transformation was first demonstrated. Perhaps our fascination with genetics derived from our ancestors observing their own progeny, with its retention and assortment of parental traits, but such interest must have been accelerated after the dawn of agriculture. It was in pea plants that Gregor Mendel in the late 1800s examined inherited traits and found them to be determined by physical elements, or genes, passed from parents to progeny. In our day, the material basis of these genetic determinants wasmore » revealed to be DNA by the lowly bacteria, in particular, the pneumococcus. For this species, transformation by free DNA is a sexual process that enables cells to sport new combinations of genes and traits. Genetic transformation of the type found in S. pneumoniae occurs naturally in many species of bacteria (70), but, initially only a few other transformable species were found, namely, Haemophilus influenzae, Neisseria meningitides, Neisseria gonorrheae, and Bacillus subtilis (96). Natural transformation, which requires a set of genes evolved for the purpose, contrasts with artificial transformation, which is accomplished by shocking cells either electrically, as in electroporation, or by ionic and temperature shifts. Although such artificial treatments can introduce very small amounts of DNA into virtually any type of cell, the amounts introduced by natural transformation are a million-fold greater, and S. pneumoniae can take up as much as 10% of its cellular DNA content (40).« less

Elliptic CY3folds and non-perturbative modular transformation

NASA Astrophysics Data System (ADS)

Iqbal, Amer; Shabbir, Khurram

2016-03-01

We study the refined topological string partition function of a class of toric elliptically fibered Calabi-Yau threefolds. These Calabi-Yau threefolds give rise to five dimensional quiver gauge theories and are dual to configurations of M5-M2-branes. We determine the Gopakumar-Vafa invariants for these threefolds and show that the genus g free energy is given by the weight 2 g Eisenstein series. We also show that although the free energy at all genera are modular invariant, the full partition function satisfies the non-perturbative modular transformation property discussed by Lockhart and Vafa in arXiv:1210.5909 and therefore the modularity of free energy is up to non-perturbative corrections.

Discrete Haar transform and protein structure.

PubMed

Morosetti, S

1997-12-01

The discrete Haar transform of the sequence of the backbone dihedral angles (phi and psi) was performed over a set of X-ray protein structures of high resolution from the Brookhaven Protein Data Bank. Afterwards, the new dihedral angles were calculated by the inverse transform, using a growing number of Haar functions, from the lower to the higher degree. New structures were obtained using these dihedral angles, with standard values for bond lengths and angles, and with omega = 0 degree. The reconstructed structures were compared with the experimental ones, and analyzed by visual inspection and statistical analysis. When half of the Haar coefficients were used, all the reconstructed structures were not yet collapsed to a tertiary folding, but they showed yet realized most of the secondary motifs. These results indicate a substantial separation of structural information in the space of Haar transform, with the secondary structural information mainly present in the Haar coefficients of lower degrees, and the tertiary one present in the higher degree coefficients. Because of this separation, the representation of the folded structures in the space of Haar transform seems a promising candidate to encompass the problem of premature convergence in genetic algorithms.

Natural triple beta-stranded fibrous folds.

PubMed

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

2006-01-01

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

Seismic Expression of Fault Related Folding in Southeastern Turkey

NASA Astrophysics Data System (ADS)

Beauchamp, W.; McDonald, D.

2009-12-01

Weldon Beauchamp, and David McDonald,TransAtlantic Petroleum Corp. 5910 N. Central Expressway, Suite 1755, Dallas, TX 75206 weldon@tapcor.com, 214-395-7125 The Zagros fold belt extends northwest from Iran and Iraq into southeastern Turkey. Large scale fault related folds control the topography of this region and the path of the Tigris river. Large surface anticlines in the Zagros Mountains provide traps for giant oil and gas fields in Iran and Iraq. Similar scale folds extend into southeast Turkey. These southward verging fault related folds are believed to detach in the Paleozoic. Borehole data, surface geological maps, satellite data and digital topographic models were used to create models to constrain structure at depth. Structural modeling of these folds was used to design, acquire and process seismic reflection data in the region. The seismic reflection data confirmed the presence of asymmetrical, south verging complex fault related folding. Faults related to these folds detach in the Lower Ordovician to Cambrian age shales. These folds are believed to form doubly plunging structures that fold Tertiary through Paleozoic age rocks forming multiple levels of possible hydrocarbon entrapment.

Aerobic and anaerobic nitrogen transformation processes in N2-fixing cyanobacterial aggregates

PubMed Central

Klawonn, Isabell; Bonaglia, Stefano; Brüchert, Volker; Ploug, Helle

2015-01-01

Colonies of N2-fixing cyanobacteria are key players in supplying new nitrogen to the ocean, but the biological fate of this fixed nitrogen remains poorly constrained. Here, we report on aerobic and anaerobic microbial nitrogen transformation processes that co-occur within millimetre-sized cyanobacterial aggregates (Nodularia spumigena) collected in aerated surface waters in the Baltic Sea. Microelectrode profiles showed steep oxygen gradients inside the aggregates and the potential for nitrous oxide production in the aggregates' anoxic centres. 15N-isotope labelling experiments and nutrient analyses revealed that N2 fixation, ammonification, nitrification, nitrate reduction to ammonium, denitrification and possibly anaerobic ammonium oxidation (anammox) can co-occur within these consortia. Thus, N. spumigena aggregates are potential sites of nitrogen gain, recycling and loss. Rates of nitrate reduction to ammonium and N2 were limited by low internal nitrification rates and low concentrations of nitrate in the ambient water. Presumably, patterns of N-transformation processes similar to those observed in this study arise also in other phytoplankton colonies, marine snow and fecal pellets. Anoxic microniches, as a pre-condition for anaerobic nitrogen transformations, may occur within large aggregates (⩾1 mm) even when suspended in fully oxygenated waters, whereas anoxia in small aggregates (<1 to ⩾0.1 mm) may only arise in low-oxygenated waters (⩽25 μM). We propose that the net effect of aggregates on nitrogen loss is negligible in NO3−-depleted, fully oxygenated (surface) waters. In NO3−-enriched (>1.5 μM), O2-depleted water layers, for example, in the chemocline of the Baltic Sea or the oceanic mesopelagic zone, aggregates may promote N-recycling and -loss processes. PMID:25575306

GROSS N TRANSFORMATION RATES AND MICROBIAL POPULATION DYNAMICS UNDER FIELD AND LABORATORY CONDITIONS FROM TWO DIFFERENT ECOSYSTEMS

EPA Science Inventory

Change of soil and environmental conditions can influence microbial activities and subsequent soil nitrogen (N) transformation processes. The objective of this study was to compare gross N transformation rates between field and laboratory incubation conditions using an old-field...

High-resolution Fourier-transform extreme ultraviolet photoabsorption spectroscopy of 14N15N

NASA Astrophysics Data System (ADS)

Heays, A. N.; Dickenson, G. D.; Salumbides, E. J.; de Oliveira, N.; Joyeux, D.; Nahon, L.; Lewis, B. R.; Ubachs, W.

2011-12-01

The first comprehensive high-resolution photoabsorption spectrum of 14N15N has been recorded using the Fourier-transform spectrometer attached to the Desirs beamline at the Soleil synchrotron. Observations are made in the extreme ultraviolet and span 100 000-109 000 cm-1 (100-91.7 nm). The observed absorption lines have been assigned to 25 bands and reduced to a set of transition energies, f values, and linewidths. This analysis has verified the predictions of a theoretical model of N2 that simulates its photoabsorption and photodissociation cross section by solution of an isotopomer independent formulation of the coupled-channel Schrödinger equation. The mass dependence of predissociation linewidths and oscillator strengths is clearly evident and many local perturbations of transition energies, strengths, and widths within individual rotational series have been observed.

Apico-basal forces exerted by apoptotic cells drive epithelium folding.

PubMed

Monier, Bruno; Gettings, Melanie; Gay, Guillaume; Mangeat, Thomas; Schott, Sonia; Guarner, Ana; Suzanne, Magali

2015-02-12

Epithelium folding is a basic morphogenetic event that is essential in transforming simple two-dimensional epithelial sheets into three-dimensional structures in both vertebrates and invertebrates. Folding has been shown to rely on apical constriction. The resulting cell-shape changes depend either on adherens junction basal shift or on a redistribution of myosin II, which could be driven by mechanical signals. Yet the initial cellular mechanisms that trigger and coordinate cell remodelling remain largely unknown. Here we unravel the active role of apoptotic cells in initiating morphogenesis, thus revealing a novel mechanism of epithelium folding. We show that, in a live developing tissue, apoptotic cells exert a transient pulling force upon the apical surface of the epithelium through a highly dynamic apico-basal myosin II cable. The apoptotic cells then induce a non-autonomous increase in tissue tension together with cortical myosin II apical stabilization in the surrounding tissue, eventually resulting in epithelium folding. Together our results, supported by a theoretical biophysical three-dimensional model, identify an apoptotic myosin-II-dependent signal as the initial signal leading to cell reorganization and tissue folding. This work further reveals that, far from being passively eliminated as generally assumed (for example, during digit individualization), apoptotic cells actively influence their surroundings and trigger tissue remodelling through regulation of tissue tension.

Structure, Folding Dynamics, and Amyloidogenesis of D76N β2-Microglobulin

PubMed Central

Mangione, P. Patrizia; Esposito, Gennaro; Relini, Annalisa; Raimondi, Sara; Porcari, Riccardo; Giorgetti, Sofia; Corazza, Alessandra; Fogolari, Federico; Penco, Amanda; Goto, Yuji; Lee, Young-Ho; Yagi, Hisashi; Cecconi, Ciro; Naqvi, Mohsin M.; Gillmore, Julian D.; Hawkins, Philip N.; Chiti, Fabrizio; Rolandi, Ranieri; Taylor, Graham W.; Pepys, Mark B.; Stoppini, Monica; Bellotti, Vittorio

2013-01-01

Systemic amyloidosis is a fatal disease caused by misfolding of native globular proteins, which then aggregate extracellularly as insoluble fibrils, damaging the structure and function of affected organs. The formation of amyloid fibrils in vivo is poorly understood. We recently identified the first naturally occurring structural variant, D76N, of human β2-microglobulin (β2m), the ubiquitous light chain of class I major histocompatibility antigens, as the amyloid fibril protein in a family with a new phenotype of late onset fatal hereditary systemic amyloidosis. Here we show that, uniquely, D76N β2m readily forms amyloid fibrils in vitro under physiological extracellular conditions. The globular native fold transition to the fibrillar state is primed by exposure to a hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild type β2m is recruited by the variant into amyloid fibrils in vitro but is absent from amyloid deposited in vivo. This may be because, as we show here, such recruitment is inhibited by chaperone activity. Our results suggest general mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a previously obscure process. Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition. PMID:24014031

Cortical thickness and folding deficits in conduct-disordered adolescents

PubMed Central

Hyatt, Christopher J.; Haney-Caron, Emily; Stevens, Michael C.

2012-01-01

Background Studies of pediatric conduct disorder (CD) have described frontal and temporal lobe structural abnormalities that parallel findings in antisocial adults. The purpose of this study was to examine previously unexplored cortical thickness and folding as markers for brain abnormalities in “pure CD”-diagnosed adolescents. Based on current fronto-temporal theories, we hypothesized that CD youth would have thinner cortex or less cortical folding in temporal and frontal lobes than control subjects. Methods We obtained T1-weighted brain structure images from n=24 control and n=19 CD participants aged 12–18 years, matched by overall gender and age. We measured group differences in cortical thickness and local gyrification index (regional cortical folding measure) using surface-based morphometry with clusterwise correction for multiple comparisons. Results CD participants, when compared with controls, showed both reduced cortical thickness and folding. Thinner cortex was located primarily in posterior brain regions, including left superior temporal and parietal lobes, temporoparietal junction and paracentral lobule, right superior temporal and parietal lobes, temporoparietal junction and precuneus. Folding deficits were located mainly in anterior brain regions and included left insula, ventro- and dorsomedial prefrontal, anterior cingulate and orbitofrontal cortices, temporal lobe, right superior frontal and parietal lobes and paracentral lobule. Conclusions Our findings generally agree with previous CD volumetric studies, but here show the unique contributions of cortical thickness and folding to gray matter reductions in pure CD in different brain regions. PMID:22209639

High-Resolution Mapping of a Repeat Protein Folding Free Energy Landscape.

PubMed

Fossat, Martin J; Dao, Thuy P; Jenkins, Kelly; Dellarole, Mariano; Yang, Yinshan; McCallum, Scott A; Garcia, Angel E; Barrick, Doug; Roumestand, Christian; Royer, Catherine A

2016-12-06

A complete description of the pathways and mechanisms of protein folding requires a detailed structural and energetic characterization of the conformational ensemble along the entire folding reaction coordinate. Simulations can provide this level of insight for small proteins. In contrast, with the exception of hydrogen exchange, which does not monitor folding directly, experimental studies of protein folding have not yielded such structural and energetic detail. NMR can provide residue specific atomic level structural information, but its implementation in protein folding studies using chemical or temperature perturbation is problematic. Here we present a highly detailed structural and energetic map of the entire folding landscape of the leucine-rich repeat protein, pp32 (Anp32), obtained by combining pressure-dependent site-specific 1 H- 15 N HSQC data with coarse-grained molecular dynamics simulations. The results obtained using this equilibrium approach demonstrate that the main barrier to folding of pp32 is quite broad and lies near the unfolded state, with structure apparent only in the C-terminal region. Significant deviation from two-state unfolding under pressure reveals an intermediate on the folded side of the main barrier in which the N-terminal region is disordered. A nonlinear temperature dependence of the population of this intermediate suggests a large heat capacity change associated with its formation. The combination of pressure, which favors the population of folding intermediates relative to chemical denaturants; NMR, which allows their observation; and constrained structure-based simulations yield unparalleled insight into protein folding mechanisms. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Measurement of the viscoelastic properties of the vocal folds.

PubMed

Wiikmann, Christian; da Silva, Marcelo Alves; Arêas, Elizabeth Pinheiro Gomes; Tsuji, Domingos Hiroshi; Sennes, Luiz Ubirajara

2009-06-01

Studies of the viscoelastic properties of the vocal folds are normally performed with rheometers that use parallel plates whose interplate space is usually arbitrarily assigned a fixed value. In tissues subject to variation of thickness between samples, fixed gaps could result in different compressions, compromising the comparison among them. We performed an experimental study to determine whether different compressions can lead to different results in measurements of dynamic viscosity (DV) of vocal fold samples. We measured the DV of vocal fold samples of 10 larynges of cadavers under 3 different compression levels, corresponding to 0.2, 0.5, and 10 N on an 8-mm-diameter parallel-plate rheometer. The DV directly varied with compression. We observed statistically significant differences between the results of 0.2 and 10 N (p = 0.0396) and 0.5 and 10 N (p = 0.0442). The study demonstrated that the level of compression influences the DV measure and suggests that a defined compression level should be used in rheometric studies of biological tissues.

The topomer-sampling model of protein folding

PubMed Central

Debe, Derek A.; Carlson, Matt J.; Goddard, William A.

1999-01-01

Clearly, a protein cannot sample all of its conformations (e.g., ≈3100 ≈ 1048 for a 100 residue protein) on an in vivo folding timescale (<1 s). To investigate how the conformational dynamics of a protein can accommodate subsecond folding time scales, we introduce the concept of the native topomer, which is the set of all structures similar to the native structure (obtainable from the native structure through local backbone coordinate transformations that do not disrupt the covalent bonding of the peptide backbone). We have developed a computational procedure for estimating the number of distinct topomers required to span all conformations (compact and semicompact) for a polypeptide of a given length. For 100 residues, we find ≈3 × 107 distinct topomers. Based on the distance calculated between different topomers, we estimate that a 100-residue polypeptide diffusively samples one topomer every ≈3 ns. Hence, a 100-residue protein can find its native topomer by random sampling in just ≈100 ms. These results suggest that subsecond folding of modest-sized, single-domain proteins can be accomplished by a two-stage process of (i) topomer diffusion: random, diffusive sampling of the 3 × 107 distinct topomers to find the native topomer (≈0.1 s), followed by (ii) intratopomer ordering: nonrandom, local conformational rearrangements within the native topomer to settle into the precise native state. PMID:10077555

Time and space integrating acousto-optic folded spectrum processing for SETI

NASA Technical Reports Server (NTRS)

Wagner, K.; Psaltis, D.

1986-01-01

Time and space integrating folded spectrum techniques utilizing acousto-optic devices (AOD) as 1-D input transducers are investigated for a potential application as wideband, high resolution, large processing gain spectrum analyzers in the search for extra-terrestrial intelligence (SETI) program. The space integrating Fourier transform performed by a lens channels the coarse spectral components diffracted from an AOD onto an array of time integrating narrowband fine resolution spectrum analyzers. The pulsing action of a laser diode samples the interferometrically detected output, aliasing the fine resolution components to baseband, as required for the subsequent charge coupled devices (CCD) processing. The raster scan mechanism incorporated into the readout of the CCD detector array is used to unfold the 2-D transform, reproducing the desired high resolution Fourier transform of the input signal.

Effect of growth factors on hyaluronan production by canine vocal fold fibroblasts.

PubMed

Hirano, Shigeru; Bless, Diane M; Heisey, Dennis; Ford, Charles N

2003-07-01

Hyaluronan (HYA) is considered to be a crucial factor in scarless wound healing and in maintaining tissue viscosity of the vocal fold lamina propria. In this study focusing on the effects of growth factors, we examined how HYA is produced and controlled in canine cultured vocal fold fibroblasts. Fibroblasts were taken from the lamina propria of the vocal folds of 8 dogs and cultured with and without growth factors. The production of HYA in the supernatant culture was quantitatively examined by enzyme-linked immunosorbent assay. Hepatocyte growth factor, epidermal growth factor, basic fibroblast growth factor, and transforming growth factor beta1 all stimulated HYA synthesis from vocal fold fibroblasts. These effects differed with the concentration of growth factors and the incubation period. We also examined how frequently the growth factors had to be administered in order to maintain appropriate levels of HYA. A single administration was sufficient to maintain appropriate HYA levels for at least 7 days. The present studies have demonstrated positive effects of growth factors in stimulating HYA production. Further in vivo study is needed to clarify the usefulness of these growth factors in the management of vocal fold scarring.

Selected mode of dendritic growth with n-fold symmetry in the presence of a forced flow

NASA Astrophysics Data System (ADS)

Alexandrov, D. V.; Galenko, P. K.

2017-07-01

The effect of n-fold crystal symmetry is investigated for a two-dimensional stable dendritic growth in the presence of a forced convective flow. We consider dendritic growth in a one-component undercooled liquid. The theory is developed for the parabolic solid-liquid surface of dendrite growing at arbitrary growth Péclet numbers keeping in mind small anisotropies of surface energy and growth kinetics. The selection criterion determining the stable growth velocity of the dendritic tip and its stable tip diameter is found on the basis of solvability analysis. The obtained criterion includes previously developed theories of thermally and kinetically controlled dendritic growth with convection for the case of four-fold crystal symmetry. The obtained nonlinear system of equations (representing the selection criterion and undercooling balance) for the determination of dendrite tip velocity and dendrite tip diameter is analytically solved in a parametric form. These exact solutions clearly demonstrate a transition between thermally and kinetically controlled growth regimes. In addition, we show that the dendrites with larger crystal symmetry grow faster than those with smaller symmetry.

Transformation of hydrazinium azide to molecular N8 at 40 GPa

NASA Astrophysics Data System (ADS)

Duwal, Sakun; Ryu, Young-Jay; Kim, Minseob; Yoo, Choong-Shik; Bang, Sora; Kim, Kyungtae; Hur, Nam Hwi

2018-04-01

Hydrazinium azide (HA) has been investigated at high pressures to 68 GPa using confocal micro-Raman spectroscopy and synchrotron powder x-ray diffraction. The results show that HA undergoes structural phase transitions from solid HA-I to HA-II at 13 GPa, associated with the strengthening of hydrogen bonding, and then to N8 at 40 GPa. The transformation of HA to recently predicted N8 (N≡N+—N-—N=N—-N—+N≡N) is evident by the emergence of new peaks at 2384 cm-1, 1665 cm-1, and 1165 cm-1, arising from the terminal N≡N stretching, the central N=N stretching, and the N—N stretching, respectively. However, upon decompression, N8 decomposes to ɛ-N2 below 25 GPa, but the remnant can be seen as low as 3 GPa.

Predicting repeat protein folding kinetics from an experimentally determined folding energy landscape

PubMed Central

Street, Timothy O; Barrick, Doug

2009-01-01

The Notch ankyrin domain is a repeat protein whose folding has been characterized through equilibrium and kinetic measurements. In previous work, equilibrium folding free energies of truncated constructs were used to generate an experimentally determined folding energy landscape (Mello and Barrick, Proc Natl Acad Sci USA 2004;101:14102–14107). Here, this folding energy landscape is used to parameterize a kinetic model in which local transition probabilities between partly folded states are based on energy values from the landscape. The landscape-based model correctly predicts highly diverse experimentally determined folding kinetics of the Notch ankyrin domain and sequence variants. These predictions include monophasic folding and biphasic unfolding, curvature in the unfolding limb of the chevron plot, population of a transient unfolding intermediate, relative folding rates of 19 variants spanning three orders of magnitude, and a change in the folding pathway that results from C-terminal stabilization. These findings indicate that the folding pathway(s) of the Notch ankyrin domain are thermodynamically selected: the primary determinants of kinetic behavior can be simply deduced from the local stability of individual repeats. PMID:19177351

Fracture patterns in the Zagros fold-and-thrust belt, Kurdistan Region of Iraq

NASA Astrophysics Data System (ADS)

Reif, Daniel; Decker, Kurt; Grasemann, Bernhard; Peresson, Herwig

2012-11-01

Fracture data have been collected in the Kurdistan Region of Iraq, which is a poorly accessible and unexplored area of the Zagros. Pre to early folding NE-SW striking extensional fractures and NW-SE striking contractive elements represent the older set affecting the exposed multilayer of the area. These latter structures are early syn-folding and followed by folding-related mesostructural assemblages, which include elements striking parallel to the axial trend of major folds (longitudinal fractures). Bedding perpendicular joints and veins, and extensional faults belonging to this second fracture set are located in the outer arc of exposed anticlines, whilst longitudinal reverse faults locate in the inner arcs. Consistently, these elements are associated with syn-folding tangential longitudinal strain. The younger two sets are related to E-W extension and NNE-SSW to N-S shortening, frequently displaying reactivation of the older sets. The last shortening event, which is described along the entire Zagros Belt, probably relates with the onset of N-S compression induced by the northward movement of the Arabian plate relative to the Eurasian Plate. In comparison between the inferred palaeostrain directions and the kinematics of recent GPS measurements, we conclude that the N-S compression and the partitioning into NW-SE trending folds and NW to N trending strike-slip faults likely remained unchanged throughout the Neogene tectonic history of the investigated area.

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

Domains of Pyrococcus furiosus L-asparaginase fold sequentially and assemble through strong intersubunit associative forces.

PubMed

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

2015-05-01

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

Folding pathway of a multidomain protein depends on its topology of domain connectivity

PubMed Central

Inanami, Takashi; Terada, Tomoki P.; Sasai, Masaki

2014-01-01

How do the folding mechanisms of multidomain proteins depend on protein topology? We addressed this question by developing an Ising-like structure-based model and applying it for the analysis of free-energy landscapes and folding kinetics of an example protein, Escherichia coli dihydrofolate reductase (DHFR). DHFR has two domains, one comprising discontinuous N- and C-terminal parts and the other comprising a continuous middle part of the chain. The simulated folding pathway of DHFR is a sequential process during which the continuous domain folds first, followed by the discontinuous domain, thereby avoiding the rapid decrease in conformation entropy caused by the association of the N- and C-terminal parts during the early phase of folding. Our simulated results consistently explain the observed experimental data on folding kinetics and predict an off-pathway structural fluctuation at equilibrium. For a circular permutant for which the topological complexity of wild-type DHFR is resolved, the balance between energy and entropy is modulated, resulting in the coexistence of the two folding pathways. This coexistence of pathways should account for the experimentally observed complex folding behavior of the circular permutant. PMID:25267632

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

PubMed

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

2018-04-27

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

Semiempirical prediction of protein folds

NASA Astrophysics Data System (ADS)

Fernández, Ariel; Colubri, Andrés; Appignanesi, Gustavo

2001-08-01

We introduce a semiempirical approach to predict ab initio expeditious pathways and native backbone geometries of proteins that fold under in vitro renaturation conditions. The algorithm is engineered to incorporate a discrete codification of local steric hindrances that constrain the movements of the peptide backbone throughout the folding process. Thus, the torsional state of the chain is assumed to be conditioned by the fact that hopping from one basin of attraction to another in the Ramachandran map (local potential energy surface) of each residue is energetically more costly than the search for a specific (Φ, Ψ) torsional state within a single basin. A combinatorial procedure is introduced to evaluate coarsely defined torsional states of the chain defined ``modulo basins'' and translate them into meaningful patterns of long range interactions. Thus, an algorithm for structure prediction is designed based on the fact that local contributions to the potential energy may be subsumed into time-evolving conformational constraints defining sets of restricted backbone geometries whereupon the patterns of nonbonded interactions are constructed. The predictive power of the algorithm is assessed by (a) computing ab initio folding pathways for mammalian ubiquitin that ultimately yield a stable structural pattern reproducing all of its native features, (b) determining the nucleating event that triggers the hydrophobic collapse of the chain, and (c) comparing coarse predictions of the stable folds of moderately large proteins (N~100) with structural information extracted from the protein data bank.

Folding Beauties

ERIC Educational Resources Information Center

Berman, Leah Wrenn

2006-01-01

This article has its genesis in an MAA mini-course on origami, where a way to get a parabola by folding paper was presented. This article discusses the methods and mathematics of other curves obtained by paper-folding.

Soil N transformations and its controlling factors in temperate grasslands in China: A study from 15N tracing experiment to literature synthesis

NASA Astrophysics Data System (ADS)

Wang, Jing; Wang, Liang; Feng, Xiaojuan; Hu, Huifeng; Cai, Zucong; Müller, Christoph; Zhang, Jinbo

2016-12-01

Temperate grasslands in arid and semiarid regions cover about 40% of the total land area in China. So far, only a few studies have studied the N transformations in these important ecosystems. In the present study, soil gross N transformation rates in Inner Mongolia temperate grasslands in China were determined using a 15N tracing experiment and combined with a literature synthesis to identify the soil N transformation characteristics and their controlling factors in a global perspective. Our results showed that the rates of gross N mineralization and immobilization NH4+ were significantly lower, while autotrophic nitrification rates were significantly higher in Chinese temperate grassland soils compared to other regions in the world. In particular, the primary mineral N consumption processes, i.e., immobilization of NO3- and NH4+, and dissimilatory nitrate reduction to ammonium, were on average much lower in temperate grassland soils in China, compared to other temperate grassland regions. The reduced heterotrophic activity and microbial growth associated with lower soil organic carbon and arid climate (e.g., mean annual precipitation) were identified as the main factors regulating soil N cycling in the studied regions in China. To restrict NO3- accumulation and associated high risks of N losses in these arid and semiarid ecosystems in China, it is important to develop the regimes of soil organic C and water management that promote the retention of N in these grassland ecosystems.

Characterization of the first true coaxial 18-fold segmented n-type prototype HPGe detector for the GERDA project

NASA Astrophysics Data System (ADS)

Abt, I.; Caldwell, A.; Gutknecht, D.; Kröninger, K.; Lampert, M.; Liu, X.; Majorovits, B.; Quirion, D.; Stelzer, F.; Wendling, P.

2007-07-01

The first true coaxial 18-fold segmented n-type HPGe prototype detector produced by Canberra-France for the GERDA neutrinoless double beta-decay project was tested both at Canberra-France and at the Max-Planck-Institut für Physik in Munich. The main characteristics of the detector are given and measurements concerning detector properties are described. A novel method to establish contacts between the crystal and a Kapton cable is presented.

Synthetic oligorotaxanes exert high forces when folding under mechanical load

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Influence of Biochar on C and N Transformation in Soil and Their Impact on Greenhouse Gas Emissions

NASA Astrophysics Data System (ADS)

Chintala, R.; Schumacher, T. E.; Kumar, S.; Clay, D. E.; Malo, D. D.

2014-12-01

The capacity of pyrogenic biochar to mitigate soil surface exchange of greenhouse gases (GHG) is dependent on the influence of biochar on physiochemical transformations of C and N in soils. Incorporated biochar amendments are hypothesized to interfere with transformations of C and N as a result of the unique recalcitrant chemical structure and surface complexity of biochars. The nature of interference by biochar with C and N transformations are assumed to be dynamic not only due to their highly variable amphilicity inherited from feedstock source and controlled pyrolytic processing parameters but also to variation in soil factors. Experiments comprised of laboratory and field studies were designed to gain insight into the priming effect of incorporated non-native biochar materials on the transformations of C and N species in the soil. Molecular structure and surface functionality of plant based biochar materials produced from carbon optimized gasification of corn stover (Zea mays L.), Ponderosa pine (Pinus ponderosa Lawson and C. Lawson) wood residue, and switchgrass (Panicum virgatum L.) were studied in the laboratory using NMR and SEM-EdX. Biochar materials were found to be highly hydrophobic (low H/C values) with high aromaticity. The surface morphology of all the biochar materials was highly heterogeneous and pore size ranged from 1-22µm with the faces and edges of ordered sheets. In the field study, all the three biochar types were applied at a 1% (w/w) rate to a Maddock soil (Sandy, Mixed, Frigid Entic Hapludolls) located in an eroded upper landscape position and a Brookings soil (Fine-Silty, Mixed, Superactive, Frigid Pachic Hapludolls) located in a depositional landscape position. The crop rotation is a corn (Zea mays L.) followed by soybean (Glycine max L.). The priming effect of biochars on the transformations of C and N is determined by measuring the changes in soil C (total organic carbon, microbial biomass C, hydrolyzable C, and δ 13C) and N pools

Global analysis of protein folding using massively parallel design, synthesis and testing

PubMed Central

Rocklin, Gabriel J.; Chidyausiku, Tamuka M.; Goreshnik, Inna; Ford, Alex; Houliston, Scott; Lemak, Alexander; Carter, Lauren; Ravichandran, Rashmi; Mulligan, Vikram K.; Chevalier, Aaron; Arrowsmith, Cheryl H.; Baker, David

2017-01-01

Proteins fold into unique native structures stabilized by thousands of weak interactions that collectively overcome the entropic cost of folding. Though these forces are “encoded” in the thousands of known protein structures, “decoding” them is challenging due to the complexity of natural proteins that have evolved for function, not stability. Here we combine computational protein design, next-generation gene synthesis, and a high-throughput protease susceptibility assay to measure folding and stability for over 15,000 de novo designed miniproteins, 1,000 natural proteins, 10,000 point-mutants, and 30,000 negative control sequences, identifying over 2,500 new stable designed proteins in four basic folds. This scale—three orders of magnitude greater than that of previous studies of design or folding—enabled us to systematically examine how sequence determines folding and stability in uncharted protein space. Iteration between design and experiment increased the design success rate from 6% to 47%, produced stable proteins unlike those found in nature for topologies where design was initially unsuccessful, and revealed subtle contributions to stability as designs became increasingly optimized. Our approach achieves the long-standing goal of a tight feedback cycle between computation and experiment, and promises to transform computational protein design into a data-driven science. PMID:28706065

The transforming activity of Ski and SnoN is dependent on their ability to repress the activity of Smad proteins.

PubMed

He, Jun; Tegen, Sarah B; Krawitz, Ariel R; Martin, G Steven; Luo, Kunxin

2003-08-15

The regulation of cell growth and differentiation by transforming growth factor-beta (TGF-beta) is mediated by the Smad proteins. In the nucleus, the Smad proteins are negatively regulated by two closely related nuclear proto-oncoproteins, Ski and SnoN. When overexpressed, Ski and SnoN induce oncogenic transformation of chicken embryo fibroblasts. However, the mechanism of transformation by Ski and SnoN has not been defined. We have previously reported that Ski and SnoN interact directly with Smad2, Smad3, and Smad4 and repress their ability to activate TGF-beta target genes through multiple mechanisms. Because Smad proteins are tumor suppressors, we hypothesized that the ability of Ski and SnoN to inactivate Smad function may be responsible for their transforming activity. Here, we show that the receptor regulated Smad proteins (Smad2 and Smad3) and common mediator Smad (Smad4) bind to different regions in Ski and SnoN. Mutation of both regions, but not each region alone, markedly impaired the ability of Ski and SnoN to repress TGF-beta-induced transcriptional activation and cell cycle arrest. Moreover, when expressed in chicken embryo fibroblasts, mutant Ski or SnoN defective in binding to the Smad proteins failed to induce oncogenic transformation. These results suggest that the ability of Ski and SnoN to repress the growth inhibitory function of the Smad proteins is required for their transforming activity. This may account for the resistance to TGF-beta-induced growth arrest in some human cancer cell lines that express high levels of Ski or SnoN.

Context-dependent effects of asparagine glycosylation on Pin WW folding kinetics and thermodynamics.

PubMed

Price, Joshua L; Shental-Bechor, Dalit; Dhar, Apratim; Turner, Maurice J; Powers, Evan T; Gruebele, Martin; Levy, Yaakov; Kelly, Jeffery W

2010-11-03

Asparagine glycosylation is one of the most common and important post-translational modifications of proteins in eukaryotic cells. N-glycosylation occurs when a triantennary glycan precursor is transferred en bloc to a nascent polypeptide (harboring the N-X-T/S sequon) as the peptide is cotranslationally translocated into the endoplasmic reticulum (ER). In addition to facilitating binding interactions with components of the ER proteostasis network, N-glycans can also have intrinsic effects on protein folding by directly altering the folding energy landscape. Previous work from our laboratories (Hanson et al. Proc. Natl. Acad. Sci. U.S.A. 2009, 109, 3131-3136; Shental-Bechor, D.; Levy, Y. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 8256-8261) suggested that the three sugar residues closest to the protein are sufficient for accelerating protein folding and stabilizing the resulting structure in vitro; even a monosaccharide can have a dramatic effect. The highly conserved nature of these three proximal sugars in N-glycans led us to speculate that introducing an N-glycosylation site into a protein that is not normally glycosylated would stabilize the protein and increase its folding rate in a manner that does not depend on the presence of specific stabilizing protein-saccharide interactions. Here, we test this hypothesis experimentally and computationally by incorporating an N-linked GlcNAc residue at various positions within the Pin WW domain, a small β-sheet-rich protein. The results show that an increased folding rate and enhanced thermodynamic stability are not general, context-independent consequences of N-glycosylation. Comparison between computational predictions and experimental observations suggests that generic glycan-based excluded volume effects are responsible for the destabilizing effect of glycosylation at highly structured positions. However, this reasoning does not adequately explain the observed destabilizing effect of glycosylation within flexible

Paper Folding Fractions

ERIC Educational Resources Information Center

Pagni, David

2007-01-01

In this article, the author presents a paper folding activity that can be used for teaching fractions. This activity can be used to describe areas of folded polygons in terms of a standard unit of measure. A paper folding fractions worksheet and its corresponding solutions are also presented in this article. (Contains 2 figures.)

Effects of a mutation on the folding mechanism of a beta-hairpin.

PubMed

Juraszek, Jarek; Bolhuis, Peter G

2009-12-17

The folding mechanism of a protein is determined by its primary sequence. Yet, how the mechanism is changed by a mutation is still poorly understood, even for basic secondary structures such as beta-hairpins. We perform an extensive simulation study of the effects of mutating the GB1 beta-hairpin into Trpzip4 (Y5W, F12W, V14W) on the folding mechanism. While Trpzip4 has a much more stable native state due to very strong hydrophobic interactions of the side chains, its folding rate does not differ significantly from the wild type beta-hairpin. We sample the free-energy landscapes of both hairpins with Replica Exchange Molecular Dynamics (REMD) and identify the four (meta)stable states (U, H, F, and N). Using Transition Path Sampling (TPS), we then harvest ensembles of unbiased pathways between the H and F states and between the F and N states to investigate the unbiased folding mechanisms. In both hairpins, the hydrophobic collapse (U-H) is followed by the middle hydrogen bond formation (H-F), and finally a closing of the strands in a zipper-like fashion (F-N). For the Trpzip4, the path ensembles indicate that the final F-N step is much more difficult than for GB1 and involves partial unfolding, rezipping of hydrogen bonds, and rearrangement of the Trp-14 side chain. For the rate-limiting (H-F) step, the path ensembles show that in GB1 desolvation and strand closure go hand in hand, while in Trpzip4 desolvation is decoupled from strand closure. Nevertheless, likelihood maximization shows that the reaction coordinate for both hairpins remains the interstrand distance. We conclude that the folding mechanism of both hairpins is a combination of hydrophobic collapse and zipping of hydrogen bonds but that the zipper mechanism is more visible in Trpzip4. A major difference between the two hairpins is that in the transition state of the rate-limiting step for Trpzip4 one tryptophan is exposed to the solvent due to steric hindrance, making the folding mechanism more complex

Protein collapse is encoded in the folded state architecture.

PubMed

Samanta, Himadri S; Zhuravlev, Pavel I; Hinczewski, Michael; Hori, Naoto; Chakrabarti, Shaon; Thirumalai, D

2017-05-21

Folded states of single domain globular proteins are compact with high packing density. The radius of gyration, R g , of both the folded and unfolded states increase as N ν where N is the number of amino acids in the protein. The values of the Flory exponent ν are, respectively, ≈⅓ and ≈0.6 in the folded and unfolded states, coinciding with those for homopolymers. However, the extent of compaction of the unfolded state of a protein under low denaturant concentration (collapsibility), conditions favoring the formation of the folded state, is unknown. We develop a theory that uses the contact map of proteins as input to quantitatively assess collapsibility of proteins. Although collapsibility is universal, the propensity to be compact depends on the protein architecture. Application of the theory to over two thousand proteins shows that collapsibility depends not only on N but also on the contact map reflecting the native structure. A major prediction of the theory is that β-sheet proteins are far more collapsible than structures dominated by α-helices. The theory and the accompanying simulations, validating the theoretical predictions, provide insights into the differing conclusions reached using different experimental probes assessing the extent of compaction of proteins. By calculating the criterion for collapsibility as a function of protein length we provide quantitative insights into the reasons why single domain proteins are small and the physical reasons for the origin of multi-domain proteins. Collapsibility of non-coding RNA molecules is similar β-sheet proteins structures adding support to "Compactness Selection Hypothesis".

Topological Constraints and Their Conformational Entropic Penalties on RNA Folds.

PubMed

Mak, Chi H; Phan, Ethan N H

2018-05-08

Functional RNAs can fold into intricate structures using a number of different secondary and tertiary structural motifs. Many factors contribute to the overall free energy of the target fold. This study aims at quantifying the entropic costs coming from the loss of conformational freedom when the sugar-phosphate backbone is subjected to constraints imposed by secondary and tertiary contacts. Motivated by insights from topology theory, we design a diagrammatic scheme to represent different types of RNA structures so that constraints associated with a folded structure may be segregated into mutually independent subsets, enabling the total conformational entropy loss to be easily calculated as a sum of independent terms. We used high-throughput Monte Carlo simulations to simulate large ensembles of single-stranded RNA sequences in solution to validate the assumptions behind our diagrammatic scheme, examining the entropic costs for hairpin initiation and formation of many multiway junctions. Our diagrammatic scheme aids in the factorization of secondary/tertiary constraints into distinct topological classes and facilitates the discovery of interrelationships among multiple constraints on RNA folds. This perspective, which to our knowledge is novel, leads to useful insights into the inner workings of some functional RNA sequences, demonstrating how they might operate by transforming their structures among different topological classes. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Optimal fold symmetry of LH2 rings on a photosynthetic membrane

PubMed Central

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

2013-01-01

An intriguing observation of photosynthetic light-harvesting systems is the N-fold symmetry of light-harvesting complex 2 (LH2) of purple bacteria. We calculate the optimal rotational configuration of N-fold rings on a hexagonal lattice and establish two related mechanisms for the promotion of maximum excitation energy transfer (EET). (i) For certain fold numbers, there exist optimal basis cells with rotational symmetry, extendable to the entire lattice for the global optimization of the EET network. (ii) The type of basis cell can reduce or remove the frustration of EET rates across the photosynthetic network. We find that the existence of a basis cell and its type are directly related to the number of matching points S between the fold symmetry and the hexagonal lattice. The two complementary mechanisms provide selection criteria for the fold number and identify groups of consecutive numbers. Remarkably, one such group consists of the naturally occurring 8-, 9-, and 10-fold rings. By considering the inter-ring distance and EET rate, we demonstrate that this group can achieve minimal rotational sensitivity in addition to an optimal packing density, achieving robust and efficient EET. This corroborates our findings i and ii and, through their direct relation to S, suggests the design principle of matching the internal symmetry with the lattice order. PMID:23650366

Optimal fold symmetry of LH2 rings on a photosynthetic membrane.

PubMed

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

2013-05-21

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

Cyclic Adenosine Monophosphate Regulation of Ion Transport in Porcine Vocal Fold Mucosae

PubMed Central

Sivasankar, Mahalakshmi; Nofziger, Charity; Blazer-Yost, Bonnie

2012-01-01

Objectives/Hypothesis Cyclic adenosine monophosphate (cAMP) is an important biological molecule that regulates ion transport and inflammatory responses in epithelial tissue. The present study examined whether the adenylyl cyclase activator, forskolin, would increase cAMP concentration in porcine vocal fold mucosa and whether the effects of increased cAMP would be manifested as a functional increase in transepithelial ion transport. Additionally, changes in cAMP concentrations following exposure to an inflammatory mediator, tumor necrosis factor-α (TNFα) were investigated. Study Design In vitro experimental design with matched treatment and control groups. Methods Porcine vocal fold mucosae (N = 30) and tracheal mucosae (N = 20) were exposed to forskolin, TNFα, or vehicle (dimethyl sulfoxide) treatment. cAMP concentrations were determined with enzyme-linked immunosorbent assay. Ion transport was measured using electrophysiological techniques. Results Thirty minute exposure to forskolin significantly increased cAMP concentration and ion transport in porcine vocal fold and tracheal mucosae. However, 30-minute and 2-hour exposure to TNFα did not significantly alter cAMP concentration. Conclusions We demonstrate that forskolin-sensitive adenylyl cyclase is present in vocal fold mucosa, and further, that the product, cAMP increases vocal fold ion transport. The results presented here contribute to our understanding of the intracellular mechanisms underlying vocal fold ion transport. As ion transport is important for maintaining superficial vocal fold hydration, data demonstrating forskolin-stimulated ion transport in vocal fold mucosa suggest opportunities for developing pharmacological treatments that increase surface hydration. PMID:18596479

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

Epithelial sheet folding induces lumen formation by Madin-Darby canine kidney cells in a collagen gel.

PubMed

Ishida, Sumire; Tanaka, Ryosuke; Yamaguchi, Naoya; Ogata, Genki; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

2014-01-01

Lumen formation is important for morphogenesis; however, an unanswered question is whether it involves the collective migration of epithelial cells. Here, using a collagen gel overlay culture method, we show that Madin-Darby canine kidney cells migrated collectively and formed a luminal structure in a collagen gel. Immediately after the collagen gel overlay, an epithelial sheet folded from the periphery, migrated inwardly, and formed a luminal structure. The inhibition of integrin-β1 or Rac1 activity decreased the migration rate of the peripheral cells after the sheets folded. Moreover, lumen formation was perturbed by disruption of apical-basolateral polarity induced by transforming growth factor-β1. These results indicate that cell migration and cell polarity play an important role in folding. To further explore epithelial sheet folding, we developed a computer-simulated mechanical model based on the rigidity of the extracellular matrix. It indicated a soft substrate is required for the folding movement.

FROM FOLDING THEORIES TO FOLDING PROTEINS: A Review and Assessment of Simulation Studies of Protein Folding and Unfolding

NASA Astrophysics Data System (ADS)

Shea, Joan-Emma; Brooks, Charles L., III

2001-10-01

Beginning with simplified lattice and continuum "minimalist" models and progressing to detailed atomic models, simulation studies have augmented and directed development of the modern landscape perspective of protein folding. In this review we discuss aspects of detailed atomic simulation methods applied to studies of protein folding free energy surfaces, using biased-sampling free energy methods and temperature-induced protein unfolding. We review studies from each on systems of particular experimental interest and assess the strengths and weaknesses of each approach in the context of "exact" results for both free energies and kinetics of a minimalist model for a beta-barrel protein. We illustrate in detail how each approach is implemented and discuss analysis methods that have been developed as components of these studies. We describe key insights into the relationship between protein topology and the folding mechanism emerging from folding free energy surface calculations. We further describe the determination of detailed "pathways" and models of folding transition states that have resulted from unfolding studies. Our assessment of the two methods suggests that both can provide, often complementary, details of folding mechanism and thermodynamics, but this success relies on (a) adequate sampling of diverse conformational regions for the biased-sampling free energy approach and (b) many trajectories at multiple temperatures for unfolding studies. Furthermore, we find that temperature-induced unfolding provides representatives of folding trajectories only when the topology and sequence (energy) provide a relatively funneled landscape and "off-pathway" intermediates do not exist.

Dark and antidark soliton interactions in the nonlocal nonlinear Schrödinger equation with the self-induced parity-time-symmetric potential.

PubMed

Li, Min; Xu, Tao

2015-03-01

Via the Nth Darboux transformation, a chain of nonsingular localized-wave solutions is derived for a nonlocal nonlinear Schrödinger equation with the self-induced parity-time (PT) -symmetric potential. It is found that the Nth iterated solution in general exhibits a variety of elastic interactions among 2N solitons on a continuous-wave background and each interacting soliton could be the dark or antidark type. The interactions with an arbitrary odd number of solitons can also be obtained under different degenerate conditions. With N=1 and 2, the two-soliton and four-soliton interactions and their various degenerate cases are discussed in the asymptotic analysis. Numerical simulations are performed to support the analytical results, and the stability analysis indicates that the PT-symmetry breaking can also destroy the stability of the soliton interactions.

Superfast algorithms of multidimensional discrete k-wave transforms and Volterra filtering based on superfast radon transform

NASA Astrophysics Data System (ADS)

Labunets, Valeri G.; Labunets-Rundblad, Ekaterina V.; Astola, Jaakko T.

2001-12-01

Fast algorithms for a wide class of non-separable n-dimensional (nD) discrete unitary K-transforms (DKT) are introduced. They need less 1D DKTs than in the case of the classical radix-2 FFT-type approach. The method utilizes a decomposition of the nD K-transform into the product of a new nD discrete Radon transform and of a set of parallel/independ 1D K-transforms. If the nD K-transform has a separable kernel (e.g., the case of the discrete Fourier transform) our approach leads to decrease of multiplicative complexity by the factor of n comparing to the classical row/column separable approach. It is well known that an n-th order Volterra filter of one dimensional signal can be evaluated by an appropriate nD linear convolution. This work describes new superfast algorithm for Volterra filtering. New approach is based on the superfast discrete Radon and Nussbaumer polynomial transforms.

Effect of Nitrogen on Transformation Behaviors and Microstructure of V-N Microalloyed Steel

NASA Astrophysics Data System (ADS)

Zhao, Baochun; Zhao, Tan; Li, Guiyan; Lu, Qiang

Multi-pass deformation simulation tests were performed on V-N microalloyed steels with different nitrogen addition by using a Gleeble-3800 thermo-mechanical simulator and the corresponding continuous cooling transformation (CCT) diagrams were determined by thermal dilation method and metallographic method. The deformed austenite transformation behavior and resultant microstructure of the tested steels were studied. Furthermore, the effect of nitrogen addition on the transformation behavior and microstructure evolution was analyzed. The results show that the transformed microstructures in the three tested steels are ferrite, pearlite and bainite respectively while the transformation temperatures are not the same. For the two tested steel with higher nitrogen additions, higher ferrite start temperature and critical cooling rates are observed. Furthermore, an increase in nitrogen addition leads to increasing quantities of ferrite and the transformed ferrite is smaller in size. The hardness test results reveal that the hardness number increases with increasing nitrogen addition at low cooling rate while the value tends to be smaller due to increasing nitrogen addition at high cooling rate. Therefore, the hardness number of the steel with high nitrogen addition is not so sensitive to cooling rate as that of the steel with low nitrogen addition.

Protein folding by NMR.

PubMed

Zhuravleva, Anastasia; Korzhnev, Dmitry M

2017-05-01

Protein folding is a highly complex process proceeding through a number of disordered and partially folded nonnative states with various degrees of structural organization. These transiently and sparsely populated species on the protein folding energy landscape play crucial roles in driving folding toward the native conformation, yet some of these nonnative states may also serve as precursors for protein misfolding and aggregation associated with a range of devastating diseases, including neuro-degeneration, diabetes and cancer. Therefore, in vivo protein folding is often reshaped co- and post-translationally through interactions with the ribosome, molecular chaperones and/or other cellular components. Owing to developments in instrumentation and methodology, solution NMR spectroscopy has emerged as the central experimental approach for the detailed characterization of the complex protein folding processes in vitro and in vivo. NMR relaxation dispersion and saturation transfer methods provide the means for a detailed characterization of protein folding kinetics and thermodynamics under native-like conditions, as well as modeling high-resolution structures of weakly populated short-lived conformational states on the protein folding energy landscape. Continuing development of isotope labeling strategies and NMR methods to probe high molecular weight protein assemblies, along with advances of in-cell NMR, have recently allowed protein folding to be studied in the context of ribosome-nascent chain complexes and molecular chaperones, and even inside living cells. Here we review solution NMR approaches to investigate the protein folding energy landscape, and discuss selected applications of NMR methodology to studying protein folding in vitro and in vivo. Together, these examples highlight a vast potential of solution NMR in providing atomistic insights into molecular mechanisms of protein folding and homeostasis in health and disease. Copyright © 2016 Elsevier B.V. All

Work Done by Titin Protein Folding Assists Muscle Contraction.

PubMed

Rivas-Pardo, Jaime Andrés; Eckels, Edward C; Popa, Ionel; Kosuri, Pallav; Linke, Wolfgang A; Fernández, Julio M

2016-02-16

Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that stepwise unfolding/folding of titin immunoglobulin (Ig) domains occurs in the elastic I band region of intact myofibrils at physiological sarcomere lengths and forces of 6-8 pN. We use single-molecule techniques to demonstrate that unfolded titin Ig domains undergo a spontaneous stepwise folding contraction at forces below 10 pN, delivering up to 105 zJ of additional contractile energy, which is larger than the mechanical energy delivered by the power stroke of a myosin motor. Thus, it appears inescapable that folding of titin Ig domains is an important, but as yet unrecognized, contributor to the force generated by a contracting muscle. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Role of the Simian Virus 5 Fusion Protein N-Terminal Coiled-Coil Domain in Folding and Promotion of Membrane Fusion

PubMed Central

West, Dava S.; Sheehan, Michael S.; Segeleon, Patrick K.; Dutch, Rebecca Ellis

2005-01-01

Formation of a six-helix bundle comprised of three C-terminal heptad repeat regions in antiparallel orientation in the grooves of an N-terminal coiled-coil is critical for promotion of membrane fusion by paramyxovirus fusion (F) proteins. We have examined the effect of mutations in four residues of the N-terminal heptad repeat in the simian virus 5 (SV5) F protein on protein folding, transport, and fusogenic activity. The residues chosen have previously been shown from study of isolated peptides to have differing effects on stability of the N-terminal coiled-coil and six-helix bundle (R. E. Dutch, G. P. Leser, and R. A. Lamb, Virology 254:147-159, 1999). The mutant V154M showed reduced proteolytic cleavage and surface expression, indicating a defect in intracellular transport, though this mutation had no effect when studied in isolated peptides. The mutation I137M, previously shown to lower thermostability of the six-helix bundle, resulted in an F protein which was properly processed and transported to the cell surface but which had reduced fusogenic activity. Finally, mutations at L140M and L161M, previously shown to disrupt α-helix formation of isolated N-1 peptides but not to affect six-helix bundle formation, resulted in F proteins that were properly processed. Interestingly, the L161M mutant showed increased syncytium formation and promoted fusion at lower temperatures than the wild-type F protein. These results indicate that interactions separate from formation of an N-terminal coiled-coil or six-helix bundle are important in the initial folding and transport of the SV5 F protein and that mutations that destabilize the N-terminal coiled-coil can result in stimulation of membrane fusion. PMID:15650180

Acid or erythromycin stress significantly improves transformation efficiency through regulating expression of DNA binding proteins in Lactococcus lactis F44.

PubMed

Wang, Binbin; Zhang, Huawei; Liang, Dongmei; Hao, Panlong; Li, Yanni; Qiao, Jianjun

2017-12-01

Lactococcus lactis is a gram-positive bacterium used extensively in the dairy industry and food fermentation, and its biological characteristics are usually improved through genetic manipulation. However, poor transformation efficiency was the main restriction factor for the construction of engineered strains. In this study, the transformation efficiency of L. lactis F44 showed a 56.1-fold increase in acid condition (pH 5.0); meanwhile, erythromycin stress (0.04 μg/mL) promoted the transformation efficiency more significantly (76.9-fold). Notably, the transformation efficiency of F44e (L. lactis F44 harboring empty pLEB124) increased up to 149.1-fold under the synergistic stresses of acid and erythromycin. In addition, the gene expression of some DNA binding proteins (DprA, RadA, RadC, RecA, RecQ, and SsbA) changed correspondingly. Especially for radA, 25.1-fold improvement was detected when F44e was exposed to pH 5.0. Overexpression of some DNA binding proteins could improve the transformation efficiency. The results suggested that acid or erythromycin stress could improve the transformation efficiency of L. lactis through regulating gene expression of DNA binding proteins. We have proposed a simple but promising strategy for improving the transformation efficiency of L. lactis and other hard-transformed microorganisms. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Robustness of atomistic Gō models in predicting native-like folding intermediates

NASA Astrophysics Data System (ADS)

Estácio, S. G.; Fernandes, C. S.; Krobath, H.; Faísca, P. F. N.; Shakhnovich, E. I.

2012-08-01

Gō models are exceedingly popular tools in computer simulations of protein folding. These models are native-centric, i.e., they are directly constructed from the protein's native structure. Therefore, it is important to understand up to which extent the atomistic details of the native structure dictate the folding behavior exhibited by Gō models. Here we address this challenge by performing exhaustive discrete molecular dynamics simulations of a Gō potential combined with a full atomistic protein representation. In particular, we investigate the robustness of this particular type of Gō models in predicting the existence of intermediate states in protein folding. We focus on the N47G mutational form of the Spc-SH3 folding domain (x-ray structure) and compare its folding pathway with that of alternative native structures produced in silico. Our methodological strategy comprises equilibrium folding simulations, structural clustering, and principal component analysis.

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

PubMed

Wang, Moye; Hu, Jie; Zhang, Zhuqing

2016-04-26

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

Fourier transform microwave spectroscopy of Ac-Ser-NH2: the role of side chain interactions in peptide folding.

PubMed

Cabezas, Carlos; Robben, Martinus A T; Rijs, Anouk M; Peña, Isabel; Alonso, J L

2015-08-21

Serine capped dipeptide N-acetyl-l-serinamide (Ac-Ser-NH2) has been investigated using Fourier transform microwave spectroscopic techniques combined with laser ablation sources. Spectral signatures originating from one dominant species have been detected in the supersonic expansion. Rotational and nuclear quadrupole coupling constants of the two (14)N nuclei have been used in the characterization of a C/γ-turn structure, which is stabilized by a CO∙∙∙HN intramolecular hydrogen bond closing a seven-membered ring. Two extra hydrogen bonds involving the polar side chain (-CH2OH) further stabilize the structure. The non-observation of C5 species, attributed to the presence of the polar side chain, is in contrast with the previous gas phase observation of the related dipeptides containing glycine or alanine residues. The A-E splitting pattern arising from the internal rotation of the methyl group has been analyzed and the internal rotation barrier has been determined.

Naturally occurring soil salinity does not reduce N-transforming enzymes or organisms

USDA-ARS?s Scientific Manuscript database

Soil salinity can negatively affect plant production and important biogeochemical cycles which are mainly carried out by soil microbes. The objective of this study was to contribute new information on soil biological N transformations by examining the impact primary salinity reduction has on a) the ...

A simple method for astigmatic compensation of folded resonator without Brewster window.

PubMed

Qiao, Wen; Xiaojun, Zhang; Yonggang, Wang; Liqun, Sun; Hanben, Niu

2014-02-10

A folded resonator requires an oblique angle of incidence on the folded curved mirror, which introduces astigmatic distortions that limit the performance of the lasers. We present a simple method to compensate the astigmatism of folded resonator without Brewster windows for the first time to the best of our knowledge. Based on the theory of the propagation and transformation of Gaussian beams, the method is both effective and reliable. Theoretical results show that the folded resonator can be compensated astigmatism completely when the following two conditions are fulfilled. Firstly, when the Gaussian beam with a determined size beam waist is obliquely incident on an off-axis concave mirror, two new Gaussian beam respectively in the tangential and sagittal planes are formed. Another off-axis concave mirror is located at another intersection point of the two new Gaussian beams. Secondly, adjusting the incident angle of the second concave mirror or its focal length can make the above two Gaussian beam coincide in the image plane of the second concave mirror, which compensates the astigmatic aberration completely. A side-pumped continues-wave (CW) passively mode locked Nd:YAG laser was taken as an example of the astigmatically compensated folded resonators. The experimental results show good agreement with the theoretical predictions. This method can be used effectively to design astigmatically compensated cavities resonator of high-performance lasers.

Application of motion analysis in the study of the effect of botulinum toxin to rat vocal folds

NASA Astrophysics Data System (ADS)

Saadah, Abdul K.; Galatsanos, Nikolas P.; Inagi, K.; Bless, D.

1997-05-01

In the past we have proposed a system that measures the deformations of the vocal folds from videostroboscopic images of the larynx, in that system: (1) we extract the boundaries of the vocal folds, (2) we register elastically the vocal fold boundaries in successive frames. This yields the displacement vector field (DVF) between adjacent frames, and (3) we fit using a least-squares approach an affine transformation model to succinctly describe the deformations between adjacent frames. In this paper, we present as an example of the capabilities of this system, an initial study of the deformation changes in rat vocal folds pre and post injection with Botulinum toxin. For this application the generated DVF was segmented into right DVF and left DVF and the deformation of each segment is studied separately.

Transformation of Escherichia coli with large DNA molecules by electroporation.

PubMed Central

Sheng, Y; Mancino, V; Birren, B

1995-01-01

We have examined bacterial electroporation with a specific interest in the transformation of large DNA, i.e. molecules > 100 kb. We have used DNA from bacterial artificial chromosomes (BACs) ranging from 7 to 240 kb, as well as BAC ligation mixes containing a range o different sized molecules. The efficiency of electroporation with large DNA is strongly dependent on the strain of Escherichia coli used; strains which offer comparable efficiencies for 7 kb molecules differ in their uptake of 240 kb DNA by as much as 30-fold. Even with a host strain that transforms relatively well with large DNA, transformation efficiency drops dramatically with increasing size of the DNA. Molecules of 240 kb transform approximately 30-fold less well, on a molar basis, than molecules of 80 kb. Maximum transformation of large DNA occurs with different voltage gradients and with different time constants than are optimal for smaller DNA. This provides the opportunity to increase the yield of transformants which have taken up large DNA relative to the number incorporating smaller molecules. We have demonstrated that conditions may be selected which increase the average size of BAC clones generated by electroporation and compare the overall efficiency of each of the conditions tested. Images PMID:7596828

Balancing cross-sections combining field work and remote sensing data using LithoTect software in the Zagros fold-and-thrust belt, N Iraq.

NASA Astrophysics Data System (ADS)

Reif, Daniel; Grasemann, Bernhard; Lockhart, Duncan

2010-05-01

The Zagros fold-and-thrust belt has formed in detached Phanerozoic sedimentary cover rocks above a shortened crystalline Precambrian basement and evolved through the Late Cretaceous to Miocene collision between the Arabian and Eurasian plate, during which the Neotethys oceanic basin was closed. Deformation is partitioned in SW directed folding and thrusting of the sediments and NW-SE to N-S trending dextral strike slip faults. The sub-cylindrical doubly-plunging fold trains with wavelengths of 5 - 10 km host more than half of the world's hydrocarbon reserves in mostly anticlinal traps. Generally the Zagros is divided into three NW-SE striking tectonic units: the Zagros Imbricate Zone, the Zagros Simply Folded Belt and the Zagros Foredeep. This work presents a balanced cross-section through the Simply Folded Belt, NE of the city of Erbil (Kurdistan, Iraq). The regional stratigraphy comprises mainly Cretaceous to Cenozoic folded sediments consisting of massive, carbonate rocks (limestones, dolomites), reacting as competent layers during folding compared to the incompetent behavior of interlayered siltstones, claystones and marls. Although the overall security situation in Kurdistan is much better than in the rest of Iraq, structural field mapping was restricted to asphalt streets, mainly because of the contamination of the area with landmines and unexploded ordnance. In order to extend the structural measurements statistically over the investigated area, we used a newly developed software tool (www.terramath.com) for interactive structural mapping of spatial orientations (i.e. dip direction and dip angles) of the sedimentary beddings from digital elevation models. Structural field data and computed measurements where integrated and projected in NE-SW striking balanced cross-sections perpendicular to the regional trend of the fold axes. We used the software LithoTect (www.geologicsystems.com) for the restoration of the cross-sections. Depending on the interpretation

Folding mechanism of β-hairpin trpzip2: heterogeneity, transition state and folding pathways.

PubMed

Xiao, Yi; Chen, Changjun; He, Yi

2009-06-22

We review the studies on the folding mechanism of the beta-hairpin tryptophan zipper 2 (trpzip2) and present some additional computational results to refine the picture of folding heterogeneity and pathways. We show that trpzip2 can have a two-state or a multi-state folding pattern, depending on whether it folds within the native basin or through local state basins on the high-dimensional free energy surface; Trpzip2 can fold along different pathways according to the packing order of tryptophan pairs. We also point out some important problems related to the folding mechanism of trpzip2 that still need clarification, e.g., a wide distribution of the computed conformations for the transition state ensemble.

Quasideterminant solutions of the extended noncommutative Kadomtsev-Petviashvili hierarchy

NASA Astrophysics Data System (ADS)

Wu, Hongxia; Liu, Jingxin; Li, Chunxia

2017-07-01

We construct a nonauto Darboux transformation for the extended noncommutative Kadomtsev-Petviashvili (ncKP) hierarchy and consequently derive its quasi-Wronskian solution. We also obtain the quasi-Wronskian solution of the ncKP equation with self-consistent sources (ncKPESCS) as a by-product. Finally, we use the direct verification method to prove the quasi-Wronskian solution of the ncKPESCS.

Kink detachment fold in the southwest Montana fold and thrust belt

NASA Astrophysics Data System (ADS)

Mitchell, Michael M.; Woodward, Nicholas B.

1988-02-01

The Hossfeldt anticline in the southwest Montana thrust belt is characterized by a kink geometry and probably overlies a thrust detachment at depth. The mesofabric distribution in the limbs documents that the eastern overturned limb has undergone most of the rotation and internal deformation during folding, leaving the gently dipping western limb virtually undeformed. The anticline exhibits unique mesofabrics in its hinge region that require a pinned anticlinal hinge during its evolution. The half-wavelength of the Hossfeldt anticline-Eustis syncline pair coincides with that predicted from buckling theory, if one considers the massive carbonates of the Paleozoic section as a competent beam. Although the geometry and mesofabric distribution of the Hossfeldt anticline satisfy the geometric requirements of either a fault-propagation fold or a detachment kink fold, the buckling wavelength strongly suggests that its origin was as a kink-buckle fold above a flat detachment rather than as a fault-propagation fold above a thrust ramp.

Signal Transduction by a Fungal NOD-Like Receptor Based on Propagation of a Prion Amyloid Fold

PubMed Central

Daskalov, Asen; Habenstein, Birgit; Martinez, Denis; Debets, Alfons J. M.; Sabaté, Raimon; Loquet, Antoine; Saupe, Sven J.

2015-01-01

In the fungus Podospora anserina, the [Het-s] prion induces programmed cell death by activating the HET-S pore-forming protein. The HET-s β-solenoid prion fold serves as a template for converting the HET-S prion-forming domain into the same fold. This conversion, in turn, activates the HET-S pore-forming domain. The gene immediately adjacent to het-S encodes NWD2, a Nod-like receptor (NLR) with an N-terminal motif similar to the elementary repeat unit of the β-solenoid fold. NLRs are immune receptors controlling cell death and host defense processes in animals, plants and fungi. We have proposed that, analogously to [Het-s], NWD2 can activate the HET-S pore-forming protein by converting its prion-forming region into the β-solenoid fold. Here, we analyze the ability of NWD2 to induce formation of the β-solenoid prion fold. We show that artificial NWD2 variants induce formation of the [Het-s] prion, specifically in presence of their cognate ligands. The N-terminal motif is responsible for this prion induction, and mutations predicted to affect the β-solenoid fold abolish templating activity. In vitro, the N-terminal motif assembles into infectious prion amyloids that display a structure resembling the β-solenoid fold. In vivo, the assembled form of the NWD2 N-terminal region activates the HET-S pore-forming protein. This study documenting the role of the β-solenoid fold in fungal NLR function further highlights the general importance of amyloid and prion-like signaling in immunity-related cell fate pathways. PMID:25671553

Agrobacterium-mediated transformation in Alpinia galanga (Linn.) Willd. for enhanced acetoxychavicol acetate production.

PubMed

Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Mangamoori, Lakshmi Narasu; Giri, Archana

2012-09-01

Agrobacterium-mediated transformations ensure elevated amounts of secondary metabolite accumulation with genetic and biosynthetic stability. In the present study, Alpinia galanga rich in bioactive compounds was genetically transformed using different strains of Agrobacterium rhizogenes viz. LBA 9402, A(4), 532, 2364 and PRTGus. Even though a higher growth rate was obtained with the LBA 9402 strain, maximum acetoxychavicol acetate accumulation (ACA) was seen in the PRTGus transformant. PRTGus root line has shown 10.1 fold higher ACA content in comparison to the control roots. The lowest ACA production was shown by the A(4) transformant (4.9 fold). The quantification of ACA in the transformed roots was carried out by using HPLC, which was found to be in the order of PRTGus > LBA 9402 > 2364 > 532 > A(4). The fast growth rate of hairy roots, genetic stability and their ability to synthesize more than one metabolite offer a promising system for the production of valuable secondary metabolites.

Interactions of non-detergent sulfobetaines with early folding intermediates facilitate in vitro protein renaturation.

PubMed

Vuillard, L; Rabilloud, T; Goldberg, M E

1998-08-15

Non-detergent sulfobetaines (NDSB) are a family of solubilizing and stabilizing agents for proteins. In a previous study [Goldberg, M. E., Expert-Bezancon, N., Vuillard, L. & Rabilloud, T. (1996) Folding & Design 1, 21-27] we showed that the amount of active protein recovered in in vitro folding experiments could be significantly increased by some NDSBS. In this work we investigated the mechanisms by which these molecules facilitate protein renaturation. Stopped-flow and manual-mixing fluorescence and enzyme activity measurements were used to compare the kinetics of protein folding in the presence and absence of N-phenyl-methyl-N,N-dimethylammonium-propane-sulfonate (NDSB 256). Hen lysozyme and the beta2 subunit of Escherichia coli tryptophan synthase were chosen as model systems since their folding pathways had been previously investigated in detail. It is shown that, massive aggregation of tryptophan synthase occurs within less than 2.5 s after dilution in the renaturation buffer, but can be prevented by NDSB 256; only very early folding phases (such as the formation of a loosely packed hydrophobic core able to bind 8-anilino-1-naphthalenesulphonic acid, and the initial burying of tryptophan 177) are significantly altered by NDSB 256; none of the later phases is affected. Furthermore, NDSB 256 did not significantly affect any of the kinetic phases observed during the refolding of denatured lysozyme retaining intact disulphide bonds. This shows that NDSB 256 only interferes with very early steps in the folding process and acts by limiting the abortive interactions that could lead to the formation of inactive aggregates.

Force generation by titin folding.

PubMed

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

2017-07-01

Titin is a giant protein that provides elasticity to muscle. As the sarcomere is stretched, titin extends hierarchically according to the mechanics of its segments. Whether titin's globular domains unfold during this process and how such unfolded domains might contribute to muscle contractility are strongly debated. To explore the force-dependent folding mechanisms, here we manipulated skeletal-muscle titin molecules with high-resolution optical tweezers. In force-clamp mode, after quenching the force (<10 pN), extension fluctuated without resolvable discrete events. In position-clamp experiments, the time-dependent force trace contained rapid fluctuations and a gradual increase of average force, indicating that titin can develop force via dynamic transitions between its structural states en route to the native conformation. In 4 M urea, which destabilizes H-bonds hence the consolidated native domain structure, the net force increase disappeared but the fluctuations persisted. Thus, whereas net force generation is caused by the ensemble folding of the elastically-coupled domains, force fluctuations arise due to a dynamic equilibrium between unfolded and molten-globule states. Monte-Carlo simulations incorporating a compact molten-globule intermediate in the folding landscape recovered all features of our nanomechanics results. The ensemble molten-globule dynamics delivers significant added contractility that may assist sarcomere mechanics, and it may reduce the dissipative energy loss associated with titin unfolding/refolding during muscle contraction/relaxation cycles. © 2017 The Protein Society.

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.

Defocusing complex short-pulse equation and its multi-dark-soliton solution.

PubMed

Feng, Bao-Feng; Ling, Liming; Zhu, Zuonong

2016-05-01

In this paper, we propose a complex short-pulse equation of both focusing and defocusing types, which governs the propagation of ultrashort pulses in nonlinear optical fibers. It can be viewed as an analog of the nonlinear Schrödinger (NLS) equation in the ultrashort-pulse regime. Furthermore, we construct the multi-dark-soliton solution for the defocusing complex short-pulse equation through the Darboux transformation and reciprocal (hodograph) transformation. One- and two-dark-soliton solutions are given explicitly, whose properties and dynamics are analyzed and illustrated.

Bidirectional solitons on water.

PubMed

Zhang, Jin E; Li, Yishen

2003-01-01

A theory of bidirectional solitons on water is developed by using an integrable Boussinesq surface-variable equation. We present an explicit transformation between the system and a member of the Ablowitz-Kaup-Newell-Segur system, and derive an exact multisoliton solution by using a Darboux transformation. The phase shifts and the maximum wave heights during the interaction are studied for two-soliton overtaking and head-on collisions. They agree with the Korteweg-de Vries solution for overtaking collision and the perturbation solution for head-on collision.

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

PubMed Central

Wang, Moye; Hu, Jie; Zhang, Zhuqing

2016-01-01

As they are not subjected to natural selection process, de novo designed proteins usually fold in a manner different from natural proteins. Recently, a de novo designed mini-protein DS119, with a βαβ motif and 36 amino acids, has folded unusually slowly in experiments, and transient dimers have been detected in the folding process. Here, by means of all-atom replica exchange molecular dynamics (REMD) simulations, several comparably stable intermediate states were observed on the folding free-energy landscape of DS119. Conventional molecular dynamics (CMD) simulations showed that when two unfolded DS119 proteins bound together, most binding sites of dimeric aggregates were located at the N-terminal segment, especially residues 5–10, which were supposed to form β-sheet with its own C-terminal segment. Furthermore, a large percentage of individual proteins in the dimeric aggregates adopted conformations similar to those in the intermediate states observed in REMD simulations. These results indicate that, during the folding process, DS119 can easily become trapped in intermediate states. Then, with diffusion, a transient dimer would be formed and stabilized with the binding interface located at N-terminals. This means that it could not quickly fold to the native structure. The complicated folding manner of DS119 implies the important influence of natural selection on protein-folding kinetics, and more improvement should be achieved in rational protein design. PMID:27128902

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

PubMed

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

2017-12-01

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

Accurate template-based modeling in CASP12 using the IntFOLD4-TS, ModFOLD6, and ReFOLD methods.

PubMed

McGuffin, Liam J; Shuid, Ahmad N; Kempster, Robert; Maghrabi, Ali H A; Nealon, John O; Salehe, Bajuna R; Atkins, Jennifer D; Roche, Daniel B

2018-03-01

Our aim in CASP12 was to improve our Template-Based Modeling (TBM) methods through better model selection, accuracy self-estimate (ASE) scores and refinement. To meet this aim, we developed two new automated methods, which we used to score, rank, and improve upon the provided server models. Firstly, the ModFOLD6_rank method, for improved global Quality Assessment (QA), model ranking and the detection of local errors. Secondly, the ReFOLD method for fixing errors through iterative QA guided refinement. For our automated predictions we developed the IntFOLD4-TS protocol, which integrates the ModFOLD6_rank method for scoring the multiple-template models that were generated using a number of alternative sequence-structure alignments. Overall, our selection of top models and ASE scores using ModFOLD6_rank was an improvement on our previous approaches. In addition, it was worthwhile attempting to repair the detected errors in the top selected models using ReFOLD, which gave us an overall gain in performance. According to the assessors' formula, the IntFOLD4 server ranked 3rd/5th (average Z-score > 0.0/-2.0) on the server only targets, and our manual predictions (McGuffin group) ranked 1st/2nd (average Z-score > -2.0/0.0) compared to all other groups. © 2017 Wiley Periodicals, Inc.

Resolution and some properties of enzymes involved in enantioselective transformation of 1,3-dichloro-2-propanol to (R)-3-chloro-1,2-propanediol by Corynebacterium sp. strain N-1074.

PubMed Central

Nakamura, T; Nagasawa, T; Yu, F; Watanabe, I; Yamada, H

1992-01-01

During the course of the transformation of 1,3-dichloro-2-propanol (DCP) into (R)-3-chloro-1,2-propanediol [(R)-MCP] with the cell extract of Corynebacterium sp. strain N-1074, epichlorohydrin (ECH) was transiently formed. The cell extract was fractionated into two DCP-dechlorinating activities (fractions Ia and Ib) and two ECH-hydrolyzing activities (fractions IIa and IIb) by TSKgel DEAE-5PW column chromatography. Fractions Ia and Ib catalyzed the interconversion of DCP to ECH, and fractions IIa and IIb catalyzed the transformation of ECH into MCP. Fractions Ia and IIa showed only low enantioselectivity for each reaction, whereas fractions Ib and IIb exhibited considerable enantioselectivity, yielding R-rich ECH and MCP, respectively. Enzymes Ia and Ib were isolated from fractions Ia and Ib, respectively. Enzyme Ia had a molecular mass of about 108 kDa and consisted of four subunits identical in molecular mass (about 28 kDa). Enzyme Ib was a protein of 115 kDa, composed of two different polypeptides (about 35 and 32 kDa). The specific activity of enzyme Ib for DCP was about 30-fold higher than that of enzyme Ia. Both enzymes catalyzed the transformation of several halohydrins into the corresponding epoxides with liberation of halides and its reverse reaction. Their substrate specificities and immunological properties differed from each other. Enzyme Ia seemed to be halohydrin hydrogen-halide-lyase which was already purified from Escherichia coli carrying a gene from Corynebacterium sp. strain N-1074. Images PMID:1447132

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

PubMed

Parida, Laxmi; Zhou, Ruhong

2005-06-01

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

Dock 'n roll: folding of a silk-inspired polypeptide into an amyloid-like beta solenoid.

PubMed

Zhao, Binwu; Cohen Stuart, Martien A; Hall, Carol K

2016-04-20

Polypeptides containing the motif ((GA)mGX)n occur in silk and have a strong tendency to self-assemble. For example, polypeptides containing (GAGAGAGX)n, where X = G or H have been observed to form filaments; similar sequences but with X = Q have been used in the design of coat proteins (capsids) for artificial viruses. The structure of the (GAGAGAGX)m filaments has been proposed to be a stack of peptides in a β roll structure with the hydrophobic side chains pointing outwards (hydrophobic shell). Another possible configuration, a β roll or β solenoid structure which has its hydrophobic side chains buried inside (hydrophobic core) was, however, overlooked. We perform ground state analysis as well as atomic-level molecular dynamics simulations, both on single molecules and on two-molecule stacks of the silk-inspired sequence (GAGAGAGQ)10, to decide whether the hydrophobic core or the hydrophobic shell configuration is the most stable one. We find that a stack of two hydrophobic core molecules is energetically more favorable than a stack of two hydrophobic shell molecules. A shell molecule initially placed in a perfect β roll structure tends to rotate its strands, breaking in-plane hydrogen bonds and forming out-of-plane hydrogen bonds, while a core molecule stays in the β roll structure. The hydrophobic shell structure has type II' β turns whereas the core configuration has type II β turns; only the latter secondary structure agrees well with solid-state NMR experiments on a similar sequence (GA)15. We also observe that the core stack has a higher number of intra-molecular hydrogen bonds and a higher number of hydrogen bonds between stack and water than the shell stack. Hence, we conclude that the hydrophobic core configuration is the most likely structure. In the stacked state, each peptide has more intra-molecular hydrogen bonds than a single folded molecule, which suggests that stacking provides the extra stability needed for molecules to reach the folded

Vocal fold ion transport and mucin expression following acrolein exposure

PubMed Central

Levendoski, Elizabeth Erickson; Sivasankar, M. Preeti

2014-01-01

The vocal fold epithelium is exposed to inhaled particulates including pollutants during breathing in everyday environments. Yet, our understanding of the effects of pollutants on vocal fold epithelial function is extremely limited. The objective of this study was to investigate the effect of the pollutant acrolein on two vocal fold epithelial mechanisms: ion transport and mucin synthesis. These mechanisms were chosen as each plays a critical role in vocal defense and in maintaining surface hydration which is necessary for optimal voice production. Healthy, native porcine vocal folds (N=85) were excised and exposed to an acrolein or sham challenge. A 60 minute acrolein, but not sham challenge significantly reduced ion transport and inhibited cyclic adenosine monophosphate-dependent increases in ion transport. Decreases in ion transport were associated with reduced sodium absorption. Within the same timeline, no significant acrolein-induced changes in mucin gene or protein expression were observed. These results improve our understanding of the effects of acrolein on key vocal fold epithelial functions and inform the development of future investigations that seek to elucidate the impact of a wide range of pollutant exposures on vocal fold health. PMID:24648011

PREFACE: Nonlinearity and Geometry: connections with integrability Nonlinearity and Geometry: connections with integrability

NASA Astrophysics Data System (ADS)

Cieslinski, Jan L.; Ferapontov, Eugene V.; Kitaev, Alexander V.; Nimmo, Jonathan J. C.

2009-10-01

equations. Some integrable systems still await successful application of the twistor approach. This review, although concerned with advanced differential geometry, is quite elementary and self-contained. F Nijhoff, J Atkinson and J Hietarinta review the construction of soliton solutions for the KdV type lattice equations and derive N-soliton solutions for all lattice equations in the Adler-Bobenko-Suris list except for the generic elliptic case. The same problem is addressed in the contribution by J Hietarinta and D J Zhang based on the more traditional direct Hirota method. This leads to Casoratians and bilinear difference equations. Regular contributions include the following. H Baran and M Marvan launch a project to classify integrable classes of surfaces based on a novel deformation procedure of the equations of the embedding. This leads to a remarkable new integrable equation describing a class of Weingarten surfaces which seems to be overlooked in the literature. A Doliwa shows that the τ-function of the quadrilateral lattice can be identified with the Fredholm determinant of the integral equation inverting the nonlocal problem. This result is expected because its continuous counterpart (the case of conjugate nets, Darboux equations and the multicomponent KP hierarchy) is already known. Here one can find an explicit proof. P Gaillard and V B Matveev consider special reductions of the generic Darboux-Crum dressing procedure, leading to new formulas for Darboux-Pöschl-Teller potentials, their difference deformations and the related eigenfunctions. A Gouberman and K Leschke develop the theory of (generalized) Darboux transformations for conformal immersions of a Riemann surface into the 4-sphere. Applying this construction to the Clifford torus, they obtain a family of Willmore tori parametrized by Pythagorean triples. V Kiselev and J W van de Leur construct compatible nontrivial finite deformations of the Lie algebra structure in the symmetry algebra of the 3

Effects of N-glycan precursor length diversity on quality control of protein folding and on protein glycosylation

PubMed Central

Samuelson, John; Robbins, Phillips W.

2014-01-01

Asparagine-linked glycans (N-glycans) of medically important protists have much to tell us about the evolution of N-glycosylation and of N-glycan-dependent quality control (N-glycan QC) of protein folding in the endoplasmic reticulum. While host N-glycans are built upon a dolichol-pyrophosphate-linked precursor with 14 sugars (Glc3Man9GlcNAc2), protist N-glycan precursors vary from Glc3Man9GlcNAc2 (Acanthamoeba) to Man9GlcNAc2 (Trypanosoma) to Glc3Man5GlcNAc2 (Toxoplasma) to Man5GlcNAc2 (Entamoeba, Trichomonas, and Eimeria) to GlcNAc2 (Plasmodium and Giardia) to zero (Theileria). As related organisms have differing N-glycan lengths (e.g. Toxoplasma, Eimeria, Plasmodium, and Theileria), the present N-glycan variation is based upon secondary loss of Alg genes, which encode enzymes that add sugars to the N-glycan precursor. An N-glycan precursor with Man5GlcNAc2 is necessary but not sufficient for N-glycan QC, which is predicted by the presence of the UDP-glucose:glucosyltransferase (UGGT) plus calreticulin and/or calnexin. As many parasites lack glucose in their N-glycan precursor, UGGT product may be identified by inhibition of glucosidase II. The presence of an armless calnexin in Toxoplasma suggests secondary loss of N-glycan QC from coccidia. Positive selection for N-glycan sites occurs in secreted proteins of organisms with NG-QC and is based upon an increased likelihood of threonine but not serine in the second position versus asparagine. In contrast, there appears to be selection against N-glycan length in Plasmodium and N-glycan site density in Toxoplasma. Finally, there is suggestive evidence for N-glycan-dependent ERAD in Trichomonas, which glycosylates and degrades the exogenous reporter mutant carboxypeptidase Y (CPY*). PMID:25475176

Structural evolution of the J-fold; a multi-scalar approach to modeling kinematic fold evolution in the Cordilleran fold-thrust belt, southwestern Montana

NASA Astrophysics Data System (ADS)

Wallace, James W.

The Highway 2 structural complex (HW2SC) is part of the North American western Cordilleran fold-and-thrust belt that extends from northern Wyoming into northwestern Canada. More precisely, the HW2SC is located on the southeastern margin of the Helena salient in what is known as the southwest Montana transverse zone. Based on the location of the HW2SC it appears to have formed as footwall deformation associated with displacement along the southwestern Montana transverse zone. The most prominent structural feature in the HW2SC is the Late-Cretaceous "J-fold", a east-west trending, muliti-hinged, northeast plunging anticline with an associated northeast plunging syncline. The purpose of this study is to provide insight into whether the geometries of thrust-related folds correlate to particular mechanical responses taking place within the folded sedimentary sequences. This is accomplished by conducting a multifaceted examination of the J-fold using high-resolution terrestrial laser scanning combined with detailed field measurements of kinematic indicators, and petrographic analysis of microstructures in thin section. Based on the findings of this study four specific conclusions about the kinematic and mechanical evolution of the J-fold can be made: 1) the J-fold kinematically behaves as a fault-bend fold throughout its structural evolution; 2) the J-fold enjoyed two stages of fault-bend folding deformation that produced its present day geometry; 3) the J-fold has been tectonically thinned by >50% in the Permian Phosphoria and Jurassic Ellis-Rierdon formations located in the Overturned forelimb; and finally 4) the J-fold is mechanically accommodating the thinning in the Overturned forelimb by pressure solution and dissolution of chert grains in the Permian Phosphoria formation and by faulting and shearing in the Jurassic Ellis-Rierdon formation.

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.

Breathers and rogue waves in a Heisenberg ferromagnetic spin chain or an alpha helical protein

NASA Astrophysics Data System (ADS)

Yang, Jin-Wei; Gao, Yi-Tian; Su, Chuan-Qi; Wang, Qi-Min; Lan, Zhong-Zhou

2017-07-01

In this paper, a fourth-order variable-coefficient nonlinear Schrödinger equation for a one-dimensional continuum anisotropic Heisenberg ferromagnetic spin chain or an alpha helical protein has been investigated. Breathers and rogue waves are constructed via the Darboux transformation and generalized Darboux transformation, respectively. Results of the breathers and rogue waves are presented: (1) The first- and second-order Akhmediev breathers and Kuznetsov-Ma solitons are presented with different values of variable coefficients which are related to the energy transfer or higher-order excitations and interactions in the helical protein, or related to the spin excitations resulting from the lowest order continuum approximation and octupole-dipole interaction in a Heisenberg ferromagnetic spin chain, and the nonlinear periodic breathers resulting from the Akhmediev breathers are studied as well; (2) For the first- and second-order rogue waves, we find that they can be split into many similar components when the variable coefficients are polynomial functions of time; (3) Rogue waves can also be split when the variable coefficients are hyperbolic secant functions of time, but the profile of each component in such a case is different.

ABC of ladder operators for rationally extended quantum harmonic oscillator systems

NASA Astrophysics Data System (ADS)

Cariñena, José F.; Plyushchay, Mikhail S.

2017-07-01

The problem of construction of ladder operators for rationally extended quantum harmonic oscillator (REQHO) systems of a general form is investigated in the light of existence of different schemes of the Darboux-Crum-Krein-Adler transformations by which such systems can be generated from the quantum harmonic oscillator. Any REQHO system is characterized by the number of separated states in its spectrum, the number of ‘valence bands’ in which the separated states are organized, and by the total number of the missing energy levels and their position. All these peculiarities of a REQHO system are shown to be detected and reflected by a trinity (A^+/- , B^+/- , C^+/-) of the basic (primary) lowering and raising ladder operators related between themselves by certain algebraic identities with coefficients polynomially-dependent on the Hamiltonian. We show that all the secondary, higher-order ladder operators are obtainable by a composition of the basic ladder operators of the trinity which form the set of the spectrum-generating operators. Each trinity, in turn, can be constructed from the intertwining operators of the two complementary minimal schemes of the Darboux-Crum-Krein-Adler transformations.

Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium.

PubMed

Pelch, Katherine E; Tokar, Erik J; Merrick, B Alex; Waalkes, Michael P

2015-08-01

Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10μM Cd for 11weeks (CTPE) or 5μM iAs for 29weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (>25-fold) and S100P (>40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (>15-fold) and NTM (>1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status. Published by Elsevier Inc.

Dynamics of folding: Impact of fault bend folds on earthquake cycles

NASA Astrophysics Data System (ADS)

Sathiakumar, S.; Barbot, S.; Hubbard, J.

2017-12-01

Earthquakes in subduction zones and subaerial convergent margins are some of the largest in the world. So far, forecasts of future earthquakes have primarily relied on assessing past earthquakes to look for seismic gaps and slip deficits. However, the roles of fault geometry and off-fault plasticity are typically overlooked. We use structural geology (fault-bend folding theory) to inform fault modeling in order to better understand how deformation is accommodated on the geological time scale and through the earthquake cycle. Fault bends in megathrusts, like those proposed for the Nepal Himalaya, will induce folding of the upper plate. This introduces changes in the slip rate on different fault segments, and therefore on the loading rate at the plate interface, profoundly affecting the pattern of earthquake cycles. We develop numerical simulations of slip evolution under rate-and-state friction and show that this effect introduces segmentation of the earthquake cycle. In crustal dynamics, it is challenging to describe the dynamics of fault-bend folds, because the deformation is accommodated by small amounts of slip parallel to bedding planes ("flexural slip"), localized on axial surface, i.e. folding axes pinned to fault bends. We use dislocation theory to describe the dynamics of folding along these axial surfaces, using analytic solutions that provide displacement and stress kernels to simulate the temporal evolution of folding and assess the effects of folding on earthquake cycles. Studies of the 2015 Gorkha earthquake, Nepal, have shown that fault geometry can affect earthquake segmentation. Here, we show that in addition to the fault geometry, the actual geology of the rocks in the hanging wall of the fault also affect critical parameters, including the loading rate on parts of the fault, based on fault-bend folding theory. Because loading velocity controls the recurrence time of earthquakes, these two effects together are likely to have a strong impact on the

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…

Experimental validation of ultra-thin metalenses for N-beam emissions based on transformation optics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Kuang, E-mail: zhangkuang@hit.edu.cn; State Key Laboratory of Millimeter Waves, Nanjing 210096; Ding, Xumin

2016-02-01

A general design of metalenses for N-beam emissions is proposed based on transformation optics. A linear mapping function is adopted to achieve the homogeneous characterization of the transforming medium, which is therefore easy to be achieved compared with previous designs limited by inhomogeneity based on transformation optics. To verify the theoretical design, a four-beam antenna constructed with ultrathin, homogenous, and uniaxial anisotropic metalens is designed, fabricated, and measured. It is shown that the realized gain of the four-beam antenna is increased by 6 dB compared with the single dipole source, while working frequency and relative bandwidth are kept unchanged. The measuredmore » far-field pattern verifies theoretical design procedure.« less

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

Nonlinear viscoelastic characterization of human vocal fold tissues under large-amplitude oscillatory shear (LAOS)

PubMed Central

Chan, Roger W.

2018-01-01

Viscoelastic shear properties of human vocal fold tissues were previously quantified by the shear moduli (G′ and G″). Yet these small-strain linear measures were unable to describe any nonlinear tissue behavior. This study attempted to characterize the nonlinear viscoelastic response of the vocal fold lamina propria under large-amplitude oscillatory shear (LAOS) with a stress decomposition approach. Human vocal fold cover and vocal ligament specimens from eight subjects were subjected to LAOS rheometric testing with a simple-shear rheometer. The empirical total stress response was decomposed into elastic and viscous stress components, based on odd-integer harmonic decomposition approach with Fourier transform. Nonlinear viscoelastic measures derived from the decomposition were plotted in Pipkin space and as rheological fingerprints to observe the onset of nonlinearity and the type of nonlinear behavior. Results showed that both the vocal fold cover and the vocal ligament experienced intercycle strain softening, intracycle strain stiffening, as well as shear thinning both intercycle and intracycle. The vocal ligament appeared to demonstrate an earlier onset of nonlinearity at phonatory frequencies, and higher sensitivity to changes in frequency and strain. In summary, the stress decomposition approach provided much better insights into the nonlinear viscoelastic behavior of the vocal fold lamina propria than the traditional linear measures. PMID:29780189

Nonlinear viscoelastic characterization of human vocal fold tissues under large-amplitude oscillatory shear (LAOS).

PubMed

Chan, Roger W

2018-05-01

Viscoelastic shear properties of human vocal fold tissues were previously quantified by the shear moduli ( G' and G″ ). Yet these small-strain linear measures were unable to describe any nonlinear tissue behavior. This study attempted to characterize the nonlinear viscoelastic response of the vocal fold lamina propria under large-amplitude oscillatory shear (LAOS) with a stress decomposition approach. Human vocal fold cover and vocal ligament specimens from eight subjects were subjected to LAOS rheometric testing with a simple-shear rheometer. The empirical total stress response was decomposed into elastic and viscous stress components, based on odd-integer harmonic decomposition approach with Fourier transform. Nonlinear viscoelastic measures derived from the decomposition were plotted in Pipkin space and as rheological fingerprints to observe the onset of nonlinearity and the type of nonlinear behavior. Results showed that both the vocal fold cover and the vocal ligament experienced intercycle strain softening, intracycle strain stiffening, as well as shear thinning both intercycle and intracycle. The vocal ligament appeared to demonstrate an earlier onset of nonlinearity at phonatory frequencies, and higher sensitivity to changes in frequency and strain. In summary, the stress decomposition approach provided much better insights into the nonlinear viscoelastic behavior of the vocal fold lamina propria than the traditional linear measures.

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

PubMed

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

2016-11-01

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

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

USGS Publications Warehouse

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

2008-01-01

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

The IntFOLD server: an integrated web resource for protein fold recognition, 3D model quality assessment, intrinsic disorder prediction, domain prediction and ligand binding site prediction.

PubMed

Roche, Daniel B; Buenavista, Maria T; Tetchner, Stuart J; McGuffin, Liam J

2011-07-01

The IntFOLD server is a novel independent server that integrates several cutting edge methods for the prediction of structure and function from sequence. Our guiding principles behind the server development were as follows: (i) to provide a simple unified resource that makes our prediction software accessible to all and (ii) to produce integrated output for predictions that can be easily interpreted. The output for predictions is presented as a simple table that summarizes all results graphically via plots and annotated 3D models. The raw machine readable data files for each set of predictions are also provided for developers, which comply with the Critical Assessment of Methods for Protein Structure Prediction (CASP) data standards. The server comprises an integrated suite of five novel methods: nFOLD4, for tertiary structure prediction; ModFOLD 3.0, for model quality assessment; DISOclust 2.0, for disorder prediction; DomFOLD 2.0 for domain prediction; and FunFOLD 1.0, for ligand binding site prediction. Predictions from the IntFOLD server were found to be competitive in several categories in the recent CASP9 experiment. The IntFOLD server is available at the following web site: http://www.reading.ac.uk/bioinf/IntFOLD/.

Folding associated with extensional faulting: Sheep Range detachment, southern Nevada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guth, P.L.

1985-01-01

The Sheep Range detachment is a major Miocene extensional fault system of the Great Basin. Its major faults have a scoop shape, with straight, N-S traces extending 15-30 km and then abruptly turning to strike E-W. Tertiary deformation involved simultaneous normal faulting, sedimentation, landsliding, and strike-slip faulting. Folds occur in two settings: landslide blocks and drag along major faults. Folds occur in landslide blocks and beneath them. Most folds within landslide blocks are tight anticlines, with limbs dipping 40-60 degrees. Brecciation of the folds and landslide blocks suggests brittle deformation. Near Quijinump Canyon in the Sheep Range, at least threemore » landslide blocks (up to 500 by 1500 m) slid into a small Tertiary basin. Tertiary limestone beneath the Paleozoic blocks was isoclinally folded. Westward dips reveal drag folds along major normal faults, as regional dips are consistently to the east. The Chowderhead anticline is the largest drag fold, along an extensional fault that offsets Ordovician units 8 km. East-dipping Ordovician and Silurian rocks in the Desert Range form the hanging wall. East-dipping Cambrian and Ordovician units in the East Desert Range form the foot wall and east limb of the anticline. Caught along the fault plane, the anticline's west-dipping west limb contains mostly Cambrian units.« less

NoFold: RNA structure clustering without folding or alignment.

PubMed

Middleton, Sarah A; Kim, Junhyong

2014-11-01

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

Dynamics of protein folding: probing the kinetic network of folding-unfolding transitions with experiment and theory.

PubMed

Buchner, Ginka S; Murphy, Ronan D; Buchete, Nicolae-Viorel; Kubelka, Jan

2011-08-01

The problem of spontaneous folding of amino acid chains into highly organized, biologically functional three-dimensional protein structures continues to challenge the modern science. Understanding how proteins fold requires characterization of the underlying energy landscapes as well as the dynamics of the polypeptide chains in all stages of the folding process. In recent years, important advances toward these goals have been achieved owing to the rapidly growing interdisciplinary interest and significant progress in both experimental techniques and theoretical methods. Improvements in the experimental time resolution led to determination of the timescales of the important elementary events in folding, such as formation of secondary structure and tertiary contacts. Sensitive single molecule methods made possible probing the distributions of the unfolded and folded states and following the folding reaction of individual protein molecules. Discovery of proteins that fold in microseconds opened the possibility of atomic-level theoretical simulations of folding and their direct comparisons with experimental data, as well as of direct experimental observation of the barrier-less folding transition. The ultra-fast folding also brought new questions, concerning the intrinsic limits of the folding rates and experimental signatures of barrier-less "downhill" folding. These problems will require novel approaches for even more detailed experimental investigations of the folding dynamics as well as for the analysis of the folding kinetic data. For theoretical simulations of folding, a main challenge is how to extract the relevant information from overwhelmingly detailed atomistic trajectories. New theoretical methods have been devised to allow a systematic approach towards a quantitative analysis of the kinetic network of folding-unfolding transitions between various configuration states of a protein, revealing the transition states and the associated folding pathways at

Twisted rogue-wave pairs in the Sasa-Satsuma equation.

PubMed

Chen, Shihua

2013-08-01

Exact explicit rogue wave solutions of the Sasa-Satsuma equation are obtained by use of a Darboux transformation. In addition to the double-peak structure and an analog of the Peregrine soliton, the rogue wave can exhibit an intriguing twisted rogue-wave pair that involves four well-defined zero-amplitude points. This exotic structure may enrich our understanding on the nature of rogue waves.

Atomic-level description of ubiquitin folding

PubMed Central

Piana, Stefano; Lindorff-Larsen, Kresten; Shaw, David E.

2013-01-01

Equilibrium molecular dynamics simulations, in which proteins spontaneously and repeatedly fold and unfold, have recently been used to help elucidate the mechanistic principles that underlie the folding of fast-folding proteins. The extent to which the conclusions drawn from the analysis of such proteins, which fold on the microsecond timescale, apply to the millisecond or slower folding of naturally occurring proteins is, however, unclear. As a first attempt to address this outstanding issue, we examine here the folding of ubiquitin, a 76-residue-long protein found in all eukaryotes that is known experimentally to fold on a millisecond timescale. Ubiquitin folding has been the subject of many experimental studies, but its slow folding rate has made it difficult to observe and characterize the folding process through all-atom molecular dynamics simulations. Here we determine the mechanism, thermodynamics, and kinetics of ubiquitin folding through equilibrium atomistic simulations. The picture emerging from the simulations is in agreement with a view of ubiquitin folding suggested from previous experiments. Our findings related to the folding of ubiquitin are also consistent, for the most part, with the folding principles derived from the simulation of fast-folding proteins, suggesting that these principles may be applicable to a wider range of proteins. PMID:23503848

Deformation and kinematics of the central Kirthar Fold Belt, Pakistan

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

A new feature constituting approach to detection of vocal fold pathology

NASA Astrophysics Data System (ADS)

Hariharan, M.; Polat, Kemal; Yaacob, Sazali

2014-08-01

In the last two decades, non-invasive methods through acoustic analysis of voice signal have been proved to be excellent and reliable tool to diagnose vocal fold pathologies. This paper proposes a new feature vector based on the wavelet packet transform and singular value decomposition for the detection of vocal fold pathology. k-means clustering based feature weighting is proposed to increase the distinguishing performance of the proposed features. In this work, two databases Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database and MAPACI speech pathology database are used. Four different supervised classifiers such as k-nearest neighbour (k-NN), least-square support vector machine, probabilistic neural network and general regression neural network are employed for testing the proposed features. The experimental results uncover that the proposed features give very promising classification accuracy of 100% for both MEEI database and MAPACI speech pathology database.

Models of fold-related hysteresis

NASA Astrophysics Data System (ADS)

Shtern, Vladimir

2018-05-01

Hysteresis is a strongly nonlinear physics phenomenon observed in many fluid mechanics flows. This paper composes evolution equations of the minimal nonlinearity and dimension which describe three hysteresis kinds related to a fold catastrophe formed by (i) two fold bifurcations, (ii) fold and transcritical bifurcations, and (iii) fold and subcritical bifurcations.

Mechanisms of flexural flow folding of competent single-layers as evidenced by folded fibrous dolomite veins

NASA Astrophysics Data System (ADS)

Torremans, Koen; Muchez, Philippe; Sintubin, Manuel

2014-12-01

Flexural flow is thought unlikely to occur in naturally deformed, competent isotropic single-layers. In this study we discuss a particular case of folded bedding-parallel fibrous dolomite veins in shale, in which the internal strain pattern and microstructural deformation features provide new insights in the mechanisms enabling flexural flow folding. Strain in the pre-folding veins is accommodated by two main mechanisms: intracrystalline deformation by bending and intergranular deformation with bookshelf rotation of dolomite fibres. The initially orthogonal dolomite fibres allowed a reconstruction of the strain distribution across the folded veins. This analysis shows that the planar mechanical anisotropy created by the fibres causes the veins to approximate flexural flow. During folding, synkinematic veins overgrow the pre-folding fibrous dolomite veins. Microstructures and dolomite growth morphologies reflect growth during progressive fold evolution, with evidence for flexural slip at fold lock-up. Homogeneous flattening, as evidenced by disjunctive axial-planar cleavage, subsequently modified these folds from class 1B to 1C folds. Our study shows that the internal vein fabric has a first-order influence on folding kinematics. Moreover, the fibrous dolomite veins show high viscosity contrasts with the shale matrix, essential in creating transient permeability for subsequent mineralising stages in the later synkinematic veins during progressive folding.

Baecklund transformations of Toda chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreev, V.A.

Baecklund transformations of the nonperiodic Toda chains corresponding to the algebras A/sub n/, B/sub n/, C/sub n/, G/sub 2/ and the periodic Toda chains corresponding to the algebras A/sub n/ and C/sub n/ are constructed. Baecklund transformations of matrix Toda chains are also considered.

Ab initio RNA folding by discrete molecular dynamics: From structure prediction to folding mechanisms

PubMed Central

Ding, Feng; Sharma, Shantanu; Chalasani, Poornima; Demidov, Vadim V.; Broude, Natalia E.; Dokholyan, Nikolay V.

2008-01-01

RNA molecules with novel functions have revived interest in the accurate prediction of RNA three-dimensional (3D) structure and folding dynamics. However, existing methods are inefficient in automated 3D structure prediction. Here, we report a robust computational approach for rapid folding of RNA molecules. We develop a simplified RNA model for discrete molecular dynamics (DMD) simulations, incorporating base-pairing and base-stacking interactions. We demonstrate correct folding of 150 structurally diverse RNA sequences. The majority of DMD-predicted 3D structures have <4 Å deviations from experimental structures. The secondary structures corresponding to the predicted 3D structures consist of 94% native base-pair interactions. Folding thermodynamics and kinetics of tRNAPhe, pseudoknots, and mRNA fragments in DMD simulations are in agreement with previous experimental findings. Folding of RNA molecules features transient, non-native conformations, suggesting non-hierarchical RNA folding. Our method allows rapid conformational sampling of RNA folding, with computational time increasing linearly with RNA length. We envision this approach as a promising tool for RNA structural and functional analyses. PMID:18456842

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

PubMed

Arviv, Oshrit; Levy, Yaakov

2012-12-01

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

Folding of polyglutamine chains

NASA Astrophysics Data System (ADS)

Chopra, Manan; Reddy, Allam S.; Abbott, N. L.; de Pablo, J. J.

2008-10-01

Long polyglutamine chains have been associated with a number of neurodegenerative diseases. These include Huntington's disease, where expanded polyglutamine (PolyQ) sequences longer than 36 residues are correlated with the onset of symptoms. In this paper we study the folding pathway of a 54-residue PolyQ chain into a β-helical structure. Transition path sampling Monte Carlo simulations are used to generate unbiased reactive pathways between unfolded configurations and the folded β-helical structure of the polyglutamine chain. The folding process is examined in both explicit water and an implicit solvent. Both models reveal that the formation of a few critical contacts is necessary and sufficient for the molecule to fold. Once the primary contacts are formed, the fate of the protein is sealed and it is largely committed to fold. We find that, consistent with emerging hypotheses about PolyQ aggregation, a stable β-helical structure could serve as the nucleus for subsequent polymerization of amyloid fibrils. Our results indicate that PolyQ sequences shorter than 36 residues cannot form that nucleus, and it is also shown that specific mutations inferred from an analysis of the simulated folding pathway exacerbate its stability.

Structural Bridges through Fold Space.

PubMed

Edwards, Hannah; Deane, Charlotte M

2015-09-01

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.

Microstructures and Continuous Cooling Transformation of CGHAZ in E36 Class V-N-Ti, V-Ti and Nb-Ti Shipbuilding Steels

NASA Astrophysics Data System (ADS)

Shi, Zhongran; Wang, Ruizhen; Wang, Qingfeng; Su, Hang; Chai, Feng; Yang, Caifu

For the purpose of obtaining the optimal microstructures and mechanical properties of the CGHAZ under high input welding, continuous cooling transformation diagrams of the coarse grain heat-affected zone (CGHAZ) and the corresponding microstructures were investigated for a E36 class V-N-Ti, V-Ti, and Nb-Ti shipbuilding steels. The results indicated that the CGHAZ continuous transformation behaviors of Nb-Ti and V-Ti steel were similar, but the V-retard phenomenon was not as apparent as that of Nb. In addition, the cooling rate of ferrite transformation of V-Ti steel was higher than that of Nb-Ti steel. The nitrogen addition in the V-Ti steel enhanced the ferrite transformation, since that increasing the nitrogen could obtain fine (Ti, V)(C, N) particles and refine the original austenite size, which can promote the ferrite nucleation. The bainite transformation range of V-N-Ti steel was obviously lower than that of Nb-Ti, V-Ti steel at the t8/5≥100s.

Chrestenson transform FPGA embedded factorizations.

PubMed

Corinthios, Michael J

2016-01-01

Chrestenson generalized Walsh transform factorizations for parallel processing imbedded implementations on field programmable gate arrays are presented. This general base transform, sometimes referred to as the Discrete Chrestenson transform, has received special attention in recent years. In fact, the Discrete Fourier transform and Walsh-Hadamard transform are but special cases of the Chrestenson generalized Walsh transform. Rotations of a base-p hypercube, where p is an arbitrary integer, are shown to produce dynamic contention-free memory allocation, in processor architecture. The approach is illustrated by factorizations involving the processing of matrices of the transform which are function of four variables. Parallel operations are implemented matrix multiplications. Each matrix, of dimension N × N, where N = p (n) , n integer, has a structure that depends on a variable parameter k that denotes the iteration number in the factorization process. The level of parallelism, in the form of M = p (m) processors can be chosen arbitrarily by varying m between zero to its maximum value of n - 1. The result is an equation describing the generalised parallelism factorization as a function of the four variables n, p, k and m. Applications of the approach are shown in relation to configuring field programmable gate arrays for digital signal processing applications.

Fast Unitary Transforms - Benefits and Restrictions.

DTIC Science & Technology

1980-04-01

transformation kernel, and u assumes values in the range 0, 1, ... , N-i. Similarly, the inverse transform is given by the relation N-1 f(x) E T(u)h(x...function to obtain T(u,v). Similar comments hold for the inverse transform if h(x,y,u,v) is separable. If the kernel g(xy,u,v) is separable and symmetric...the forward transform can be used directly to obtain the inverse transform simply by multiplying the result of the algorithm by N. 12 The forward and

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

PubMed Central

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

2016-01-01

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

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

PubMed

Bartlett, R S; Guille, J T; Chen, X; Christensen, M B; Wang, S F; Thibeault, S L

2016-10-01

Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (RT-PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]β1, alpha smooth muscle actin, interleukin-1β, interleukin-17β and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC-treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Policy Intensions and the Folds of the Self

ERIC Educational Resources Information Center

Webb, P. Taylor; Gulson, Kalervo N.

2013-01-01

In this essay, P. Taylor Webb and Kalervo N. Gulson argue that educational policy is a spatial process and that implementation processes in particular produce crucial emergent geographies for policy research. Webb and Gulson describe how emergent geographies are produced when policy "folds" actors through senses and enactments of policy. The idea…

The Pilin N-terminal Domain Maintains Neisseria gonorrhoeae Transformation Competence during Pilus Phase Variation

PubMed Central

2016-01-01

The obligate human pathogen Neisseria gonorrhoeae is the sole aetiologic agent of the sexually transmitted infection, gonorrhea. Required for gonococcal infection, Type IV pili (Tfp) mediate many functions including adherence, twitching motility, defense against neutrophil killing, and natural transformation. Critical for immune escape, the gonococcal Tfp undergoes antigenic variation, a recombination event at the pilE locus that varies the surface exposed residues of the major pilus subunit PilE (pilin) in the pilus fiber. This programmed recombination system has the potential to produce thousands of pilin variants and can produce strains with unproductive pilin molecules that are completely unable to form Tfp. Saturating mutagenesis of the 3’ third of the pilE gene identified 68 unique single nucleotide mutations that each resulted in an underpiliated colony morphology. Notably, all isolates, including those with undetectable levels of pilin protein and no observable surface-exposed pili, retained an intermediate level of transformation competence not exhibited in ΔpilE strains. Site-directed, nonsense mutations revealed that only the first 38 amino acids of the mature pilin N-terminus (the N-terminal domain or Ntd) are required for transformation competence, and microscopy, ELISAs and pilus purification demonstrate that extended Tfp are not required for competence. Transformation in strains producing only the pilin Ntd has the same genetic determinants as wild-type transformation. The Ntd corresponds to the alternative product of S-pilin cleavage, a specific proteolysis unique to pathogenic Neisseria. Mutation of the S-pilin cleavage site demonstrated that S-pilin cleavage mediated release of the Ntd is required for competence when a strain produces unproductive pilin molecules that cannot assemble into a Tfp through mutation or antigenic variation. We conclude that S-pilin cleavage evolved as a mechanism to maintain competence in nonpiliated antigenic

Laplace transforms of the Hulthén Green's function and their application to potential scattering

NASA Astrophysics Data System (ADS)

Laha, U.; Ray, S.; Panda, S.; Bhoi, J.

2017-10-01

We derive closed-form representations for the single and double Laplace transforms of the Hulthén Green's function of the outgoing wave multiplied by the Yamaguchi potential and write them in the maximally reduced form. We use the expression for the double transform to compute the low-energy phase shifts for the elastic scattering in the systems α-nucleon, α-He3, and α-H3. The calculation results agree well with the experimental data.

Dock ’n Roll: Folding of a Silk-Inspired Polypeptide into an Amyloid-like Beta Solenoid

PubMed Central

Zhao, Binwu; Cohen Stuart, Martien A.; Hall, Carol K.

2016-01-01

Polypeptides containing the motif ((GA)mGX)n occur in silk (we refer to them as ‘silk-like’) and have a strong tendency to self-assemble. For example, polypeptides containing (GAGAGAGX)n, where X = G or H have been observed to form filaments; similar sequences but with X = Q have been used in the design of coat proteins (capsids) for artificial viruses. The structure of the (GAGAGAGX)m filaments has been proposed to be a stack of peptides in a β roll structure with the hydrophobic side chains pointing outwards (hydrophobic shell). Another possible configuration, a β roll or β solenoid structure which has its hydrophobic side chains buried inside (hydrophobic core) was, however, overlooked. We perform ground state analysis as well as atomic-level molecular dynamics simulations, both on single molecules and on two-molecule stacks of the silk-inspired sequence (GAGAGAGQ)10, to decide whether the hydrophobic core or the hydrophobic shell configuration is the most stable one. We find that a stack of two hydrophobic core molecules is energetically more favorable than a stack of two shell molecules. A shell molecule initially placed in a perfect β roll structure tends to rotate its strands, breaking in-plane hydrogen bonds and forming out-of-plane hydrogen bonds, while a core molecule stays in the β roll structure. The hydrophobic shell structure has type II’ β turns whereas the core configuration has type II β turns; only the latter secondary structure agrees well with solid-state NMR experiments on a similar sequence (GA)15. We also observe that the core stack has a higher number of intra-molecular hydrogen bonds and a higher number of hydrogen bonds between stack and water than the shell stack. Hence, we conclude that the hydrophobic core configuration is the most likely structure. In the stacked state, each peptide has more intra-molecular hydrogen bonds than a single folded molecule, which suggests that stacking provides the extra stability needed for

Analysis of plasma membrane Ca(2+)-ATPase expression in control and SV40-transformed human fibroblasts.

PubMed

Reisner, P D; Brandt, P C; Vanaman, T C

1997-01-01

It has been long known that neoplastic transformation is accompanied by a lowered requirement for extracellular Ca2+ for growth. The studies presented here demonstrate that human fibroblastic cell lines produce the two commonly found 'housekeeping' isoforms of the plasma membrane Ca(2+)-ATPase (PMCA), PMCA1b and 4b, and at the expression of both is demonstrably lower in cell lines neoplastically transformed by SV40 than in the corresponding parental cell lines. Western blot analyses of lysates from control (GM00037) and SV40-transformed (GM00637) skin fibroblasts revealed a 138 kDa PMCA whose level was significantly lower in the SV40-transformed cells relative to either total cellular protein or alpha-tubulin. Similar analyses of plasma membrane preparations from control WI-38) and SV40-transformed (WI-38VA13) lung fibroblasts revealed 3-4-fold lower levels of PMCA in the SV40-transformed cells. Competitive ELISAs performed on detergent solubilized plasma membrane preparations indicated at least 3-4-fold lower levels of PMCA in the SV40-transformed cell lines compared to controls. Reverse transcriptase coupled-PCR analyses showed that PMCA1b and PMCA4b were the only isoforms expressed in all four cell lines. The PMCA4b mRNA level detected by Northern analysis also was substantially lower in SV40 transformed skin fibroblasts than in non-transformed fibroblasts. Quantitative RT-PCR analyses showed levels of PMCA1b and 4b mRNAs to be 5 and 10-fold lower, respectively, in GM00637 than in GM00037 when the levels of PCR products were normalized to glyceraldehyde-3-phosphate dehydrogenase (G3PDH) mRNA. These results demonstrate that the expression of these distinct PMCA genes is substantially lower in SV40 transformed human skin and lung fibroblasts and may be coordinately regulated in these cells.

Incremental fold tests of remagnetized carbonate rocks

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Mapping the energy landscape for second-stage folding of a single membrane protein

PubMed Central

Min, Duyoung; Jefferson, Robert E; Bowie, James U; Yoon, Tae-Young

2016-01-01

Membrane proteins are designed to fold and function in a lipid membrane, yet folding experiments within a native membrane environment are challenging to design. Here we show that single-molecule forced unfolding experiments can be adapted to study helical membrane protein folding under native-like bicelle conditions. Applying force using magnetic tweezers, we find that a transmembrane helix protein, Escherichia coli rhomboid protease GlpG, unfolds in a highly cooperative manner, largely unraveling as one physical unit in response to mechanical tension above 25 pN. Considerable hysteresis is observed, with refolding occurring only at forces below 5 pN. Characterizing the energy landscape reveals only modest thermodynamic stability (ΔG = 6.5 kBT) but a large unfolding barrier (21.3 kBT) that can maintain the protein in a folded state for long periods of time (t1/2 ~3.5 h). The observed energy landscape may have evolved to limit the existence of troublesome partially unfolded states and impart rigidity to the structure. PMID:26479439

The fast-folding HP35 double mutant has a substantially reduced primary folding free energy barrier

NASA Astrophysics Data System (ADS)

Lei, Hongxing; Deng, Xiaojian; Wang, Zhixiang; Duan, Yong

2008-10-01

The LYS24/29NLE double mutant of villin headpiece subdomain (HP35) is the fastest folding protein known so far with a folding time constant of 0.6μs. In this work, the folding mechanism of the mutant has been investigated by both conventional and replica exchange molecular dynamics (CMD and REMD) simulations with AMBER FF03 force field and a generalized-Born solvation model. Direct comparison to the ab initio folding of the wild type HP35 enabled a close examination on the mutational effect on the folding process. The mutant folded to the native state, as demonstrated by the 0.50Å Cα-root mean square deviation (RMSD) sampled in both CMD and REMD simulations and the high population of the folded conformation compared with the denatured conformations. Consistent with experiments, the significantly reduced primary folding free energy barrier makes the mutant closer to a downhill folder than the wild type HP35 that directly leads to the faster transition and higher melting temperature. However, unlike the proposed downhill folding which envisages a smooth shift between unfolded and folded states without transition barrier, we observed a well-defined folding transition that was consistent with experiments. Further examination of the secondary structures revealed that the two mutated residues have higher intrinsic helical preference that facilitated the formation of both helix III and the intermediate state which contains the folded segment helix II/III. Other factors contributing to the faster folding include the more favorable electrostatic interactions in the transition state with the removal of the charged NH3+ groups from LYS. In addition, both transition state ensemble and denatured state ensemble are shifted in the mutant.

Connectivity-driven white matter scaling and folding in primate cerebral cortex

PubMed Central

Herculano-Houzel, Suzana; Mota, Bruno; Kaas, Jon H.

2010-01-01

Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across species with its number of nonneuronal cells, which is expected to be proportional to the total length of myelinated axons in the white matter. This result implies that the average axonal cross-section area in the white matter, a, does not scale significantly with the number of neurons in the gray matter, N. The surface area of the white matter increases with N0.87, not N1.0. Because this surface can be defined as the product of N, a, and the fraction n of cortical neurons connected through the white matter, we deduce that connectivity decreases in larger cerebral cortices as a slowly diminishing fraction of neurons, which varies with N−0.16, sends myelinated axons into the white matter. Decreased connectivity is compatible with previous suggestions that neurons in the cerebral cortex are connected as a small-world network and should slow down the increase in global conduction delay in cortices with larger numbers of neurons. Further, a simple model shows that connectivity and cortical folding are directly related across species. We offer a white matter-based mechanism to account for increased cortical folding across species, which we propose to be driven by connectivity-related tension in the white matter, pulling down on the gray matter. PMID:20956290

Effects of a classroom intervention with spatial play materials on children's object and viewer transformation abilities.

PubMed

Vander Heyden, Karin M; Huizinga, Mariette; Jolles, Jelle

2017-02-01

Children practice their spatial skills when playing with spatial toys, such as construction materials, board games, and puzzles. Sex and SES differences are observed in the engagement in such spatial play activities at home, which relate to individual differences in spatial performance. The current study investigated the effects of explicitly providing spatial play activities in the school setting on different types of spatial ability. We presented 8- to 10-year-old children with a short and easy-to-adopt classroom intervention comprising a set of different spatial play materials. The design involved a pretest-posttest comparison between the intervention group (n = 70) and a control group without intervention (n = 70). Effects were examined on object transformation ability (i.e., a paper-and-pencil mental rotation and paper folding task) and viewer transformation ability (i.e., a hands-on 3D spatial perspective-taking task). Results showed specific effects: there were no differences between the intervention and control group in progress on the two object transformation tasks. Substantial improvements were found for the intervention group compared to the control group on the viewer transformation task. Training progress was not related to sex and socioeconomic background of the child. These findings support the value of spatial play in the classroom for the spatial development of children between 8 and 10 years of age. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Congenital hypothyroidism mutations affect common folding and trafficking in the α/β-hydrolase fold proteins

PubMed Central

De Jaco, Antonella; Dubi, Noga; Camp, Shelley; Taylor, Palmer

2017-01-01

The α/β-hydrolase fold superfamily of proteins is composed of structurally related members that, despite great diversity in their catalytic, recognition, adhesion and chaperone functions, share a common fold governed by homologous residues and conserved disulfide bridges. Non-synonymous single nucleotide polymorphisms within the α/β-hydrolase fold domain in various family members have been found for congenital endocrine, metabolic and nervous system disorders. By examining the amino acid sequence from the various proteins, mutations were found to be prevalent in conserved residues within the α/β-hydrolase fold of the homologous proteins. This is the case for the thyroglobulin mutations linked to congenital hypothyroidism. To address whether correct folding of the common domain is required for protein export, we inserted the thyroglobulin mutations at homologous positions in two correlated but simpler α/β-hydrolase fold proteins known to be exported to the cell surface: neuroligin3 and acetylcholinesterase. Here we show that these mutations in the cholinesterase homologous region alter the folding properties of the α/β-hydrolase fold domain, which are reflected in defects in protein trafficking, folding and function, and ultimately result in retention of the partially processed proteins in the endoplasmic reticulum. Accordingly, mutations at conserved residues may be transferred amongst homologous proteins to produce common processing defects despite disparate functions, protein complexity and tissue-specific expression of the homologous proteins. More importantly, a similar assembly of the α/β-hydrolase fold domain tertiary structure among homologous members of the superfamily is required for correct trafficking of the proteins to their final destination. PMID:23035660

A Simulated Intermediate State for Folding and Aggregation Provides Insights into ΔN6 β2-Microglobulin Amyloidogenic Behavior

PubMed Central

Estácio, Sílvia G.; Krobath, Heinrich; Vila-Viçosa, Diogo; Machuqueiro, Miguel; Shakhnovich, Eugene I.; Faísca, Patrícia F. N.

2014-01-01

A major component of ex vivo amyloid plaques of patients with dialysis-related amyloidosis (DRA) is a cleaved variant of β2-microglobulin (ΔN6) lacking the first six N-terminal residues. Here we perform a computational study on ΔN6, which provides clues to understand the amyloidogenicity of the full-length β2-microglobulin. Contrary to the wild-type form, ΔN6 is able to efficiently nucleate fibrillogenesis in vitro at physiological pH. This behavior is enhanced by a mild acidification of the medium such as that occurring in the synovial fluid of DRA patients. Results reported in this work, based on molecular simulations, indicate that deletion of the N-terminal hexapeptide triggers the formation of an intermediate state for folding and aggregation with an unstructured strand A and a native-like core. Strand A plays a pivotal role in aggregation by acting as a sticky hook in dimer assembly. This study further predicts that the detachment of strand A from the core is maximized at pH 6.2 resulting into higher aggregation efficiency. The structural mapping of the dimerization interface suggests that Tyr10, His13, Phe30 and His84 are hot-spot residues in ΔN6 amyloidogenesis. PMID:24809460

In silico study of amyloid -protein folding and oligomerization

NASA Astrophysics Data System (ADS)

Urbanc, B.; Cruz, L.; Yun, S.; Buldyrev, S. V.; Bitan, G.; Teplow, D. B.; Stanley, H. E.

2004-12-01

Experimental findings suggest that oligomeric forms of the amyloid protein (A) play a critical role in Alzheimer's disease. Thus, elucidating their structure and the mechanisms of their formation is critical for developing therapeutic agents. We use discrete molecular dynamics simulations and a four-bead protein model to study oligomerization of two predominant alloforms, A40 and A42, at the atomic level. The four-bead model incorporates backbone hydrogen-bond interactions and amino acid-specific interactions mediated through hydrophobic and hydrophilic elements of the side chains. During the simulations we observe monomer folding and aggregation of monomers into oligomers of variable sizes. A40 forms significantly more dimers than A42, whereas pentamers are significantly more abundant in A42 relative to A40. Structure analysis reveals a turn centered at Gly-37-Gly-38 that is present in a folded A42 monomer but not in a folded A40 monomer and is associated with the first contacts that form during monomer folding. Our results suggest that this turn plays an important role in A42 pentamer formation. A pentamers have a globular structure comprising hydrophobic residues within the pentamer's core and hydrophilic N-terminal residues at the surface of the pentamer. The N termini of A40 pentamers are more spatially restricted than A42 pentamers. A40 pentamers form a -strand structure involving Ala-2-Phe-4, which is absent in A42 pentamers. These structural differences imply a different degree of hydrophobic core exposure between pentamers of the two alloforms, with the hydrophobic core of the Aβ42 pentamer being more exposed and thus more prone to form larger oligomers.

How a Spatial Arrangement of Secondary Structure Elements Is Dispersed in the Universe of Protein Folds

PubMed Central

Minami, Shintaro; Sawada, Kengo; Chikenji, George

2014-01-01

It has been known that topologically different proteins of the same class sometimes share the same spatial arrangement of secondary structure elements (SSEs). However, the frequency by which topologically different structures share the same spatial arrangement of SSEs is unclear. It is important to estimate this frequency because it provides both a deeper understanding of the geometry of protein folds and a valuable suggestion for predicting protein structures with novel folds. Here we clarified the frequency with which protein folds share the same SSE packing arrangement with other folds, the types of spatial arrangement of SSEs that are frequently observed across different folds, and the diversity of protein folds that share the same spatial arrangement of SSEs with a given fold, using a protein structure alignment program MICAN, which we have been developing. By performing comprehensive structural comparison of SCOP fold representatives, we found that approximately 80% of protein folds share the same spatial arrangement of SSEs with other folds. We also observed that many protein pairs that share the same spatial arrangement of SSEs belong to the different classes, often with an opposing N- to C-terminal direction of the polypeptide chain. The most frequently observed spatial arrangement of SSEs was the 2-layer α/β packing arrangement and it was dispersed among as many as 27% of SCOP fold representatives. These results suggest that the same spatial arrangements of SSEs are adopted by a wide variety of different folds and that the spatial arrangement of SSEs is highly robust against the N- to C-terminal direction of the polypeptide chain. PMID:25243952

Spanning the scales of mechanical metamaterials using time domain simulations in transformed crystals, graphene flakes and structured soils

NASA Astrophysics Data System (ADS)

Aznavourian, Ronald; Puvirajesinghe, Tania M.; Brûlé, Stéphane; Enoch, Stefan; Guenneau, Sébastien

2017-11-01

We begin with a brief historical survey of discoveries of quasi-crystals and graphene, and then introduce the concept of transformation crystallography, which consists of the application of geometric transforms to periodic structures. We consider motifs with three-fold, four-fold and six-fold symmetries according to the crystallographic restriction theorem. Furthermore, we define motifs with five-fold symmetry such as quasi-crystals generated by a cut-and-projection method from periodic structures in higher-dimensional space. We analyze elastic wave propagation in the transformed crystals and (Penrose-type) quasi-crystals with the finite difference time domain freeware SimSonic. We consider geometric transforms underpinning the design of seismic cloaks with square, circular, elliptical and peanut shapes in the context of honeycomb crystals that can be viewed as scaled-up versions of graphene. Interestingly, the use of morphing techniques leads to the design of cloaks with interpolated geometries reminiscent of Victor Vasarely’s artwork. Employing the case of transformed graphene-like (honeycomb) structures allows one to draw useful analogies between large-scale seismic metamaterials such as soils structured with columns of concrete or grout with soil and nanoscale biochemical metamaterials. We further identify similarities in designs of cloaks for elastodynamic and hydrodynamic waves and cloaks for diffusion (heat or mass) processes, as these are underpinned by geometric transforms. Experimental data extracted from field test analysis of soil structured with boreholes demonstrates the application of crystallography to large scale phononic crystals, coined as seismic metamaterials, as they might exhibit low frequency stop bands. This brings us to the outlook of mechanical metamaterials, with control of phonon emission in graphene through extreme anisotropy, attenuation of vibrations of suspension bridges via low frequency stop bands and the concept of transformed

Multi-component Wronskian solution to the Kadomtsev-Petviashvili equation

NASA Astrophysics Data System (ADS)

Xu, Tao; Sun, Fu-Wei; Zhang, Yi; Li, Juan

2014-01-01

It is known that the Kadomtsev-Petviashvili (KP) equation can be decomposed into the first two members of the coupled Ablowitz-Kaup-Newell-Segur (AKNS) hierarchy by the binary non-linearization of Lax pairs. In this paper, we construct the N-th iterated Darboux transformation (DT) for the second- and third-order m-coupled AKNS systems. By using together the N-th iterated DT and Cramer's rule, we find that the KPII equation has the unreduced multi-component Wronskian solution and the KPI equation admits a reduced multi-component Wronskian solution. In particular, based on the unreduced and reduced two-component Wronskians, we obtain two families of fully-resonant line-soliton solutions which contain arbitrary numbers of asymptotic solitons as y → ∓∞ to the KPII equation, and the ordinary N-soliton solution to the KPI equation. In addition, we find that the KPI line solitons propagating in parallel can exhibit the bound state at the moment of collision.

Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR?

PubMed

Illingworth, Christopher J R; Parkes, Kevin E; Snell, Christopher R; Mullineaux, Philip M; Reynolds, Christopher A

2008-03-01

Methods to determine periodicity in protein sequences are useful for inferring function. Fourier transformation is one approach but care is required to ensure the periodicity is genuine. Here we have shown that empirically-derived statistical tables can be used as a measure of significance. Genuine protein sequences data rather than randomly generated sequences were used as the statistical backdrop. The method has been applied to G-protein coupled receptor (GPCR) sequences, by Fourier transformation of hydrophobicity values, codon frequencies and the extent of over-representation of codon pairs; the latter being related to translational step times. Genuine periodicity was observed in the hydrophobicity whereas the apparent periodicity (as inferred from previously reported measures) in the translation step times was not validated statistically. GCR2 has recently been proposed as the plant GPCR receptor for the hormone abscisic acid. It has homology to the Lanthionine synthetase C-like family of proteins, an observation confirmed by fold recognition. Application of the Fourier transform algorithm to the GCR2 family revealed strongly predicted seven fold periodicity in hydrophobicity, suggesting why GCR2 has been reported to be a GPCR, despite negative indications in most transmembrane prediction algorithms. The underlying multiple sequence alignment, also required for the Fourier transform analysis of periodicity, indicated that the hydrophobic regions around the 7 GXXG motifs commence near the C-terminal end of each of the 7 inner helices of the alpha-toroid and continue to the N-terminal region of the helix. The results clearly explain why GCR2 has been understandably but erroneously predicted to be a GPCR.

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

Rogue periodic waves of the modified KdV equation

NASA Astrophysics Data System (ADS)

Chen, Jinbing; Pelinovsky, Dmitry E.

2018-05-01

Rogue periodic waves stand for rogue waves on a periodic background. Two families of travelling periodic waves of the modified Korteweg–de Vries (mKdV) equation in the focusing case are expressed by the Jacobian elliptic functions dn and cn. By using one-fold and two-fold Darboux transformations of the travelling periodic waves, we construct new explicit solutions for the mKdV equation. Since the dn-periodic wave is modulationally stable with respect to long-wave perturbations, the new solution constructed from the dn-periodic wave is a nonlinear superposition of an algebraically decaying soliton and the dn-periodic wave. On the other hand, since the cn-periodic wave is modulationally unstable with respect to long-wave perturbations, the new solution constructed from the cn-periodic wave is a rogue wave on the cn-periodic background, which generalizes the classical rogue wave (the so-called Peregrine’s breather) of the nonlinear Schrödinger equation. We compute the magnification factor for the rogue cn-periodic wave of the mKdV equation and show that it remains constant for all amplitudes. As a by-product of our work, we find explicit expressions for the periodic eigenfunctions of the spectral problem associated with the dn and cn periodic waves of the mKdV equation.

Effects of Phonation Time and Magnitude Dose on Vocal Fold Epithelial Genes, Barrier Integrity, and Function

PubMed Central

Kojima, Tsuyoshi; Valenzuela, Carla V.; Novaleski, Carolyn K.; Van Deusen, Mark; Mitchell, Joshua R.; Garrett, C. Gaelyn; Sivasankar, M. Preeti; Rousseau, Bernard

2014-01-01

Objective To investigate the effects of increasing time and magnitude doses of vibration exposure on transcription of the vocal fold's junctional proteins, structural alterations, and functional tissue outcomes. Study Design Animal study. Methods 100 New Zealand White breeder rabbits were studied. Dependent variables were measured in response to increasing time doses (30, 60, or 120 minutes) and magnitude doses (control, modal intensity, and raised intensity) of vibration exposure. Messenger RNA expression of occludin, zonula occluden-1 (ZO-1), E-cadherin, β-catenin, interleukin 1β (IL-1β), cyclooxygenase-2 (COX-2), transforming growth factor β-1 (TGFβ1), and fibronectin were measured. Tissue structural alterations were assessed using transmission electron microscopy (TEM). Transepithelial resistance was used to measure functional tissue outcomes. Results Occludin gene expression was downregulated in vocal folds exposed to 120 minute time doses of raised intensity phonation, relative to control, and modal intensity phonation. ZO-1 gene expression was upregulated following a 120 minute time dose of modal intensity phonation, compared to control, and downregulated after a 120 minute time dose of raised intensity phonation, compared to modal intensity phonation. E-cadherin gene expression was downregulated after a120 minute time dose of raised intensity phonation, compared to control and modal intensity phonation. TEM revealed extensive desquamation of the stratified squamous epithelial cells with increasing time and magnitude doses of vibration exposure. A general observation of lower transepithelial resistance measures was made in tissues exposed to raised intensity phonation, compared to all other groups. Conclusions This study provides evidence of vocal fold tissue responses to varying time and magnitude doses of vibration exposure. Level of Evidence N/A PMID:25073715

Fold pattern formation in 3D

NASA Astrophysics Data System (ADS)

Schmid, Daniel W.; Dabrowski, Marcin; Krotkiewski, Marcin

2010-05-01

The vast majority of studies concerned with folding focus on 2D and assume that the resulting fold structures are cylindrically extended in the out of place direction. This simplification is often justified as fold aspect ratios, length/width, are quite large. However, folds always exhibit finite aspect ratios and it is unclear what controls this (cf. Fletcher 1995). Surprisingly little is known about the fold pattern formation in 3D for different in-plane loading conditions. Even more complicated is the pattern formation when several folding events are superposed. Let us take the example of a plane strain pure shear superposed by the same kind of deformation but rotated by 90 degrees. The text book prediction for this event is the formation of an egg carton structure; relevant analogue models either agree and produce type 1 interference patterns or contradict and produce type 2. In order to map out 3D fold pattern formation we have performed a systematic parameter space investigation using BILAMIN, our efficient unstructured mesh finite element Stokes solver. BILAMIN is capable of solving problems with more than half a billion unknowns. This allows us to study fold patterns that emerge in randomly (red noise) perturbed layers. We classify the resulting structures with differential geometry tools. Our results show that there is a relationship between fold aspect ratio and in-plane loading conditions. We propose that this finding can be used to determine the complete parameter set potentially contained in the geometry of three dimensional folds: mechanical properties of natural rocks, maximum strain, and relative strength of the in-plane far-field load components. Furthermore, we show how folds in 3D amplify and that there is a second deformation mode, besides continuous amplification, where compression leads to a lateral rearrangement of blocks of folds. Finally, we demonstrate that the textbook prediction of egg carton shaped dome and basin structures resulting

Transformations of snow chemistry in the boreal forest: Accumulation and volatilization

USGS Publications Warehouse

Pomeroy, J.W.; Davies, T.D.; Jones, H.G.; Marsh, P.; Peters, N.E.; Tranter, M.

1999-01-01

This paper examines the processes and dynamics of ecologically-important inorganic chemical (primarily NO3-N) accumulation and loss in boreal forest snow during the cold winter period at a northern and southern location in the boreal forest of western Canada. Field observations from Inuvik, Northwest Territories and Waskesiu, Saskatchewan, Canada were used to link chemical transformations and physical processes in boreal forest snow. Data on the disposition and overwinter transformation of snow water equivalent, NO3-, SO42- and other major ions were examined. No evidence of enhanced dry deposition of chemical species to intercepted snow was found at either site except where high atmospheric aerosol concentrations prevailed. At Inuvik, concentrations of SO42- and Cl- were five to six times higher in intercepted snow than in surface snow away from the trees. SO4-S and Cl loads at Inuvik were correspondingly enhanced three-fold within the nearest 0.5 m to individual tree stems. Measurements of snow affected by canopy interception without rapid sublimation provided no evidence of ion volatilization from intercepted snow. Where intercepted snow sublimation rates were significant, ion loads in sub-canopy snow suggested that NO3- volatized with an efficiency of about 62% per snow mass sublimated. Extrapolating this measurement from Waskesiu to sublimation losses observed in other southern boreal environments suggests that 19-25% of snow inputs of NO3- can be lost during intercepted snow sublimation. The amount of N lost during sublimation may be large in high-snowfall, high N load southern boreal forests (Quebec) where 0.42 kg NO3-N ha-1 is estimated as a possible seasonal NO3- volatilization. The sensitivity of the N fluxes to climate and forest canopy variation and implications of the winter N losses for N budgets in the boreal forest are discussed.This paper examines the processes and dynamics of ecologically-important inorganic chemical (primarily NO3-N) accumulation

Periodic folding of viscous sheets

NASA Astrophysics Data System (ADS)

Ribe, Neil M.

2003-09-01

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

Fan-fold shielded electrical leads

DOEpatents

Rohatgi, R.R.; Cowan, T.E.

1996-06-11

Disclosed are 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. 3 figs.

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.

Pre-folding fracture development in the Lurestan region of the Zagros Fold and Thrust Belt: constraints from early fracture sets in the Shabazan and Asmari Formations

NASA Astrophysics Data System (ADS)

Corradetti, Amerigo; Tavani, Stefano; D'Assisi Tramparulo, Francesco; Prinzi, Ernesto Paolo; Vitale, Stefano; Parente, Mariano; Morsalnejad, Davoud; Mazzoli, Stefano

2017-04-01

In the Zagros Fold and Thrust Belt (FTB), the timing of fracture development with respect to folding is debated. Multiple fracture systems occur in the area. These include "typical" fracture systems that are oriented parallel and orthogonal to the NW-SE strike of the belt, as well as sets oriented N-S and E-W. The interpretation of the N-S and E-W sets is controversial. Despite the general consensus about the first-order relationship between these fractures and inherited N-S striking basement faults, their timing and kinematic significance is not yet fully understood. The ambiguous crosscutting/abutting relationships with the NE-SW and NW-SE sets, together with the difficulty of framing them into the classical scenario of fracturing in foreland basin systems, has led to the development of different hypotheses about the timing of N-S and E-W sets. For the generation of these structures, both pre- and syn-thrusting interpretations have been proposed. In this work, we report on the occurrence of bed-perpendicular fracture sets in the upper part of the Shabazan (Eocene) and in the Asmari (Oligo-Miocene) Formations of the Zagros FTB. These fractures have the peculiarity of being filled with karst material. Such filled fractures are preserved in beds showing variable angles of dip, ranging from horizontal to vertical. Their homogeneous distribution in variably dipping beds around folds undoubtedly point to an origin of these fracture sets predating the tilting of the strata in which they are contained. Therefore, fracture development and related infilling occurred at an early stage, in still flat lying strata, following the deposition of the top Shabazan and Asmari Formations. Such a deposition took place within the general framework of ongoing shortening in the Zagros. This process, occurring since the Late Cretaceous, progressively led to folding of the syn-orogenic Shabazan and Asmari Formations subsequently to the development of the studied filled fractures.

Endoluminal surface registration for CT colonography using haustral fold matching☆

PubMed Central

Hampshire, Thomas; Roth, Holger R.; Helbren, Emma; Plumb, Andrew; Boone, Darren; Slabaugh, Greg; Halligan, Steve; Hawkes, David J.

2013-01-01

Computed Tomographic (CT) colonography is a technique used for the detection of bowel cancer or potentially precancerous polyps. The procedure is performed routinely with the patient both prone and supine to differentiate fixed colonic pathology from mobile faecal residue. Matching corresponding locations is difficult and time consuming for radiologists due to colonic deformations that occur during patient repositioning. We propose a novel method to establish correspondence between the two acquisitions automatically. The problem is first simplified by detecting haustral folds using a graph cut method applied to a curvature-based metric applied to a surface mesh generated from segmentation of the colonic lumen. A virtual camera is used to create a set of images that provide a metric for matching pairs of folds between the prone and supine acquisitions. Image patches are generated at the fold positions using depth map renderings of the endoluminal surface and optimised by performing a virtual camera registration over a restricted set of degrees of freedom. The intensity difference between image pairs, along with additional neighbourhood information to enforce geometric constraints over a 2D parameterisation of the 3D space, are used as unary and pair-wise costs respectively, and included in a Markov Random Field (MRF) model to estimate the maximum a posteriori fold labelling assignment. The method achieved fold matching accuracy of 96.0% and 96.1% in patient cases with and without local colonic collapse. Moreover, it improved upon an existing surface-based registration algorithm by providing an initialisation. The set of landmark correspondences is used to non-rigidly transform a 2D source image derived from a conformal mapping process on the 3D endoluminal surface mesh. This achieves full surface correspondence between prone and supine views and can be further refined with an intensity based registration showing a statistically significant improvement (p < 0

Flexible Electronics-Based Transformers for Extreme Environments

NASA Technical Reports Server (NTRS)

Quadrelli, Marco B.; Stoica, Adrian; Ingham, Michel; Thakur, Anubhav

2015-01-01

This paper provides a survey of the use of modular multifunctional systems, called Flexible Transformers, to facilitate the exploration of extreme and previously inaccessible environments. A novel dynamics and control model of a modular algorithm for assembly, folding, and unfolding of these innovative structural systems is also described, together with the control model and the simulation results.

The role of the N-terminal tail for the oligomerization, folding and stability of human frataxin☆

PubMed Central

Faraj, Santiago E.; Venturutti, Leandro; Roman, Ernesto A.; Marino-Buslje, Cristina B.; Mignone, Astor; Tosatto, Silvio C.E.; Delfino, José M.; Santos, Javier

2013-01-01

The N-terminal stretch of human frataxin (hFXN) intermediate (residues 42–80) is not conserved throughout evolution and, under defined experimental conditions, behaves as a random-coil. Overexpression of hFXN56–210 in Escherichia coli yields a multimer, whereas the mature form of hFXN (hFXN81–210) is monomeric. Thus, cumulative experimental evidence points to the N-terminal moiety as an essential element for the assembly of a high molecular weight oligomer. The secondary structure propensity of peptide 56–81, the moiety putatively responsible for promoting protein–protein interactions, was also studied. Depending on the environment (TFE or SDS), this peptide adopts α-helical or β-strand structure. In this context, we explored the conformation and stability of hFXN56–210. The biophysical characterization by fluorescence, CD and SEC-FPLC shows that subunits are well folded, sharing similar stability to hFXN90–210. However, controlled proteolysis indicates that the N-terminal stretch is labile in the context of the multimer, whereas the FXN domain (residues 81–210) remains strongly resistant. In addition, guanidine hydrochloride at low concentration disrupts intermolecular interactions, shifting the ensemble toward the monomeric form. The conformational plasticity of the N-terminal tail might impart on hFXN the ability to act as a recognition signal as well as an oligomerization trigger. Understanding the fine-tuning of these activities and their resulting balance will bear direct relevance for ultimately comprehending hFXN function. PMID:23951553

A Note on ;New Hierarchies of Integrable Lattice Equations and Associated Properties: Darboux Transformation Conservation Laws and Integrable Coupling; [Rep. Math. Phys. 67 (2011), 259

NASA Astrophysics Data System (ADS)

Xu, Xi-Xiang

2016-12-01

We prove that two new hierarchies of integrable lattice equations in [Rep. Math. Phys.67 (2011), 259] can be respectively changed into the famous relativistic Toda lattice hierarchies in the polynomial and the rational forms by means of a simple transformation.

Generation of higher-order rogue waves from multibreathers by double degeneracy in an optical fiber.

PubMed

Wang, Lihong; He, Jingsong; Xu, Hui; Wang, Ji; Porsezian, Kuppuswamy

2017-04-01

In this paper, we construct a special kind of breather solution of the nonlinear Schrödinger (NLS) equation, the so-called breather-positon (b-positon for short), which can be obtained by taking the limit λ_{j}→λ_{1} of the Lax pair eigenvalues in the order-n periodic solution, which is generated by the n-fold Darboux transformation from a special "seed" solution-plane wave. Further, an order-n b-positon gives an order-n rogue wave under a limit λ_{1}→λ_{0}. Here, λ_{0} is a special eigenvalue in a breather of the NLS equation such that its period goes to infinity. Several analytical plots of order-2 breather confirm visually this double degeneration. The last limit in this double degeneration can be realized approximately in an optical fiber governed by the NLS equation, in which an injected initial ideal pulse is created by a frequency comb system and a programable optical filter (wave shaper) according to the profile of an analytical form of the b-positon at a certain position z_{0}. We also suggest a new way to observe higher-order rogue waves generation in an optical fiber, namely, measure the patterns at the central region of the higher-order b-positon generated by above ideal initial pulses when λ_{1} is very close to the λ_{0}. The excellent agreement between the numerical solutions generated from initial ideal inputs with a low signal-to-noise ratio and analytical solutions of order-2 b-positon supports strongly this way in a realistic optical fiber system. Our results also show the validity of the generating mechanism of a higher-order rogue waves from a multibreathers through the double degeneration.

Energy landscape of knotted protein folding

PubMed Central

Sułkowska, Joanna I.; Noel, Jeffrey K.; Onuchic, Jose N.

2012-01-01

Recent experiments have conclusively shown that proteins are able to fold from an unknotted, denatured polypeptide to the knotted, native state without the aid of chaperones. These experiments are consistent with a growing body of theoretical work showing that a funneled, minimally frustrated energy landscape is sufficient to fold small proteins with complex topologies. Here, we present a theoretical investigation of the folding of a knotted protein, 2ouf, engineered in the laboratory by a domain fusion that mimics an evolutionary pathway for knotted proteins. Unlike a previously studied knotted protein of similar length, we see reversible folding/knotting and a surprising lack of deep topological traps with a coarse-grained structure-based model. Our main interest is to investigate how evolution might further select the geometry and stiffness of the threading region of the newly fused protein. We compare the folding of the wild-type protein to several mutants. Similarly to the wild-type protein, all mutants show robust and reversible folding, and knotting coincides with the transition state ensemble. As observed experimentally, our simulations show that the knotted protein folds about ten times slower than an unknotted construct with an identical contact map. Simulated folding kinetics reflect the experimentally observed rollover in the folding limbs of chevron plots. Successful folding of the knotted protein is restricted to a narrow range of temperature as compared to the unknotted protein and fits of the kinetic folding data below folding temperature suggest slow, nondiffusive dynamics for the knotted protein. PMID:22891304

Impacts of insect biological control on soil N transformations in Tamarix-invaded ecosystems in the Great Basin

USDA-ARS?s Scientific Manuscript database

Understanding the impacts of insect biological control of Tamarix spp. on soil nitrogen (N) transformations is important because changes to N supply could alter plant community succession. We investigated short-term and longer-term impacts of herbivory by the northern tamarisk beetle (Diorhabda cari...

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.

[Transverse folding and the evolution of hind wings in beetles (Insecta, Coleoptera)].

PubMed

Fedorenko, D N

2013-01-01

Strong intensification of the protective function of the fore wing in Coleoptera has made their flight apparatus a posteromotoric one and invited an apparatus responsible for folding the hindwings beneath the elytra to develop. Folding apparatus could hardly develop without higher deformability of veins or their parts, which diminished strength properties of the wing support. The effect was stressed by folds that intersected veins. Organization of the folds into a system confined this negative influence to a few wing regions and some veinal sections. This having happened, wing support and folding pattern evolved interrelated, the former into being more flexible, with no or minimum loss of rigidity, and the latter towards being less harmful for the supporting elements, especially axial ones. Monofunctionality, together with very simple structure and little specialization of constituent parts, made the folding pattern very labile during evolution. The folding pattern evolved more rapidly than wing venation, thus defining transformations of the latter. Evolutionary conservatism of wing venation stemmed from that many veins were strongly specialized in performing two conflicting functions. An adaptive compromise was necessary for the conflict to be solved, which determined the wing to orthogenetic development. The main evolutionary trends for wing venation and folding pattern were those towards simplification and a higher complexity, respectively. The beetle wing has passed through two main evolutionary stages. Among them, the first resulted in the development of the "Archostemata" wing type, the second started from the "cantharoid" structural plan. The main evolutionary factors were the infancies of wing posteromotorism at the first stage while the wing strongly influenced by size evolution, with the main trend towards miniaturization, at the second. The archostematan and "cantharoid" morphofunctional wing types differ fundamentally. In the wing of the former kind

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

NASA Astrophysics Data System (ADS)

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

2010-05-01

The Zagros fold and thrust belt is a seismically active orogen, where actual kinematic models based on GPS networks suggest a north-south shortening between Arabian and Eurasian in the order of 1.5-2.5 cm/yr. Most of this deformation is partitioned in south-southwest oriented folding and thrusting with northwest-southeast to north-south trending dextral strike slip faults. The Zagros fold and thrust belt is of great economic interest because it has been estimated that this area contains about 15% of the global recoverable hydrocarbons. Whereas the SE parts of the Zagros have been investigated by detailed geological studies, the NW extent being part of the Republic of Iraq have experienced considerably less attention. In this study we combine field work and remote sensing techniques in order to investigate the interaction of erosion and fold growth in the area NE of Erbil (Kurdistan, Iraq). In particular we focus on the interaction of the transient development of drainage patterns along growing antiforms, which directly reflects the kinematics of progressive fold growth. Detailed geomorphological studies of the Bana Bawi-, Permam- and Safeen fold trains show that these anticlines have not developed from subcylindrical embryonic folds but they have merged from different fold segments that joined laterally during fold amplification. This fold segments with length between 5 and 25 km have been detected by mapping ancient and modern river courses that initially cut the nose of growing folds and eventually got defeated leaving behind a wind gap. Fold segments, propagating in different directions force rivers to join resulting in steep gorges, which dissect the merging fold noses. Along rapidly lateral growing folds (e.g. at the SE end of the Bana Bawi Anticline) we observed "curved wind gaps", a new type of abandoned river course, where form of the wind gap mimics a formed nose of a growing antiform. The inherited curved segments of uplifted curved river courses strongly

Fold-up concrete construction.

DOT National Transportation Integrated Search

1975-01-01

The fold-up method of concrete construction is a relatively new method of precasting a variety of structural shapes on a single flat surface and then folding portions up to form a three-dimensional shape. Structural members as beams, girders, columns...

Note: Simple 100 Hz N2 laser with longitudinal discharge tube and high-voltage power supply using neon sign transformer.

PubMed

Uno, K; Jitsuno, T

2017-12-01

We developed a longitudinally excited N 2 laser with a simple driver circuit and a simple power supply. The N 2 laser consisted of a 20 cm-long glass tube with an inner diameter of 2.5 mm, a normal stable resonator formed by flat mirrors, a variable transformer, a neon sign transformer, a spark gap, and a 200 pF capacitance. The N 2 laser produced a laser pulse with an energy of 379 nJ and a pulse width of 7.5 ns at a repetition rate of 100 Hz. The laser beam was circular and had a Gaussian profile with a correlation factor of 0.992 93.

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

PubMed Central

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

2016-01-01

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. PMID:26887592

Single-molecule studies highlight conformational heterogeneity in the early folding steps of a large ribozyme

PubMed Central

Xie, Zheng; Srividya, Narayanan; Sosnick, Tobin R.; Pan, Tao; Scherer, Norbert F.

2004-01-01

The equilibrium folding of the catalytic domain of Bacillus subtilis RNase P RNA is investigated by single-molecule fluorescence resonance energy transfer (FRET). Previous ensemble studies of this 255-nucleotide ribozyme described the equilibrium folding with two transitions, U-to-Ieq-to-N, and focused on the Ieq-to-N transition. The present study focuses on the U-to-Ieq transition. Comparative ensemble measurements of the ribozyme construct labeled with fluorescein at the 5′ end and Cy3 at the 3′ end show that modifications required for labeling do not interfere with folding and help to define the Mg2+ concentration range for the U-to-Ieq transition. Histogram analysis of the Mg2+-dependent single-molecule FRET efficiency reveals two previously undetermined folding intermediates. The single-molecule FRET trajectories exhibit non-two-state and nonergodic behaviors at intermediate Mg2+ concentrations on the time scale of seconds. The trajectories at intermediate Mg2+ concentrations are classified into five classes based on three FRET levels and their dynamics of interconversion within the measured time range. This heterogeneity, together with the observation of “nonsudden jump” FRET transitions, indicates that the early folding steps of this ribozyme involve a series of intermediates with different degrees of kinetic isolation and that folding occurs under kinetic control and involves many “local” conformational switches. A free energy contour is constructed to illustrate the complex folding surface. PMID:14704266

Extant fold-switching proteins are widespread.

PubMed

Porter, Lauren L; Looger, Loren L

2018-06-05

A central tenet of biology is that globular proteins have a unique 3D structure under physiological conditions. Recent work has challenged this notion by demonstrating that some proteins switch folds, a process that involves remodeling of secondary structure in response to a few mutations (evolved fold switchers) or cellular stimuli (extant fold switchers). To date, extant fold switchers have been viewed as rare byproducts of evolution, but their frequency has been neither quantified nor estimated. By systematically and exhaustively searching the Protein Data Bank (PDB), we found ∼100 extant fold-switching proteins. Furthermore, we gathered multiple lines of evidence suggesting that these proteins are widespread in nature. Based on these lines of evidence, we hypothesized that the frequency of extant fold-switching proteins may be underrepresented by the structures in the PDB. Thus, we sought to identify other putative extant fold switchers with only one solved conformation. To do this, we identified two characteristic features of our ∼100 extant fold-switching proteins, incorrect secondary structure predictions and likely independent folding cooperativity, and searched the PDB for other proteins with similar features. Reassuringly, this method identified dozens of other proteins in the literature with indication of a structural change but only one solved conformation in the PDB. Thus, we used it to estimate that 0.5-4% of PDB proteins switch folds. These results demonstrate that extant fold-switching proteins are likely more common than the PDB reflects, which has implications for cell biology, genomics, and human health. Copyright © 2018 the Author(s). Published by PNAS.

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…

Folding and unfolding phylogenetic trees and networks.

PubMed

Huber, Katharina T; Moulton, Vincent; Steel, Mike; Wu, Taoyang

2016-12-01

Phylogenetic networks are rooted, labelled directed acyclic graphswhich are commonly used to represent reticulate evolution. There is a close relationship between phylogenetic networks and multi-labelled trees (MUL-trees). Indeed, any phylogenetic network N can be "unfolded" to obtain a MUL-tree U(N) and, conversely, a MUL-tree T can in certain circumstances be "folded" to obtain aphylogenetic network F(T) that exhibits T. In this paper, we study properties of the operations U and F in more detail. In particular, we introduce the class of stable networks, phylogenetic networks N for which F(U(N)) is isomorphic to N, characterise such networks, and show that they are related to the well-known class of tree-sibling networks. We also explore how the concept of displaying a tree in a network N can be related to displaying the tree in the MUL-tree U(N). To do this, we develop aphylogenetic analogue of graph fibrations. This allows us to view U(N) as the analogue of the universal cover of a digraph, and to establish a close connection between displaying trees in U(N) and reconciling phylogenetic trees with networks.

High-efficiency Agrobacterium rhizogenes-mediated transformation of heat inducible sHSP18.2-GUS in Nicotiana tabacum.

PubMed

Chen, Shih-Cheng; Liu, Hui-Wen; Lee, Kung-Ta; Yamakawa, Takashi

2007-01-01

The chimerical gene, Arabidopsis thaliana sHSP18.2 promoter fused to E. coli gusA gene, was Agrobacterium rhizogenes-mediated transformed into Nicotiana tabacum as a heat-regulatable model, and the thermo-inducible expression of GUS activity in N. tabacum transgenic hairy roots was profiled. An activation of A. rhizogenes with acetosyringone (AS) before cocultured with tobacco's leaf disc strongly promoted transgenic hairy roots formation. Transgenic hairy roots formation efficiency of A. rhizogenes precultured with 200 microM AS supplementation was 3.1-fold and 7.5-fold, respectively, compared to the formation efficiency obtained with and without AS supplementation in coculture. Transgenic hairy roots transformed with different AS concentration exhibited a similar pattern of thermo-inducibility after 10 min to 3 h heat treatments detected by GUS expression. The peak of expressed GUS specific activity, 399,530 pmol MUG per mg total protein per min, of the transgenic hairy roots was observed at 48 h after 3 h of 42 degrees C heat treatment, and the expressed GUS specific activity was 7-26 times more than that reported in A. thaliana, tobacco BY-2 cells and Nicotiana plumbaginifolia. Interference caused by AS supplementation on the growth of transgenic hairy roots, time-course of GUS expression and its expression level were not observed.

Effects of N and B on continuous cooling transformation diagrams of Mo-V-Ti micro-alloyed steels

NASA Astrophysics Data System (ADS)

Yuhui, Wang; Bo, Liao; Ligang, Liu; Xianfeng, Li; Hang, Su; Caifu, Yang; Qingfeng, Wang

2012-05-01

Effects of the single addition of nitrogen (N) and boron (B) and the combined addition of N and B on continuous cooling transformation (CCT) diagrams and properties of the three Mo-V-Ti micro-alloyed steels were investigated by means of a combined method of dilatometry and metallography. Microstructures observed in continuous cooled specimens were composed of pearlite (P), quasi-polygonal ferrite (QPF), granular bainite (GB), acicular ferrite (AF), lath-like bainite (LB) and martensite (M) depending on the cooling rates and transformation temperatures. Single addition of 12 ppm B effectively reduced the formation of QPF and broadened the cooling rate region for LB and M. Added N makes the action of B invalid and the QPF region was prominently broadened, and even though the cooling rate is higher than 50°C s-1, it cannot obtain full bainite.

Rough energy landscapes in protein folding: dimeric E. coli Trp repressor folds through three parallel channels.

PubMed

Gloss, L M; Simler, B R; Matthews, C R

2001-10-05

The folding mechanism of the dimeric Escherichia coli Trp repressor (TR) is a kinetically complex process that involves three distinguishable stages of development. Following the formation of a partially folded, monomeric ensemble of species, within 5 ms, folding to the native dimer is controlled by three kinetic phases. The rate-limiting step in each phase is either a non-proline isomerization reaction or a dimerization reaction, depending on the final denaturant concentration. Two approaches have been employed to test the previously proposed folding mechanism of TR through three parallel channels: (1) unfolding double-jump experiments demonstrate that all three folding channels lead directly to native dimer; and (2) the differential stabilization of the transition state for the final step in folding and the native dimer, by the addition of salt, shows that all three channels involve isomerization of a dimeric species. A refined model for the folding of Trp repressor is presented, in which all three channels involve a rapid dimerization reaction between partially folded monomers followed by the isomerization of the dimeric intermediates to yield native dimer. The ensemble of partially folded monomers can be captured at equilibrium by low pH; one-dimensional proton NMR spectra at pH 2.5 demonstrate that monomers exist in two distinct, slowly interconverting conformations. These data provide a potential structural explanation for the three-channel folding mechanism of TR: random association of two different monomeric forms, which are distinguished by alternative packing modes of the core dimerization domain and the DNA-binding, helix-turn-helix, domain. One, perhaps both, of these packing modes contains non-native contacts. Copyright 2001 Academic Press.

Protein folding on Biosensor tips: Folding of Maltodextrin glucosidase monitored by its interactions with GroEL

PubMed Central

Pastor, Ashutosh; Singh, Amit K.; Fisher, Mark T.; Chaudhuri, Tapan K.

2016-01-01

Protein folding has been extensively studied for past four decades by employing solution based experiments such as solubility, enzymatic activity, secondary structure analysis, and analytical methods like FRET, NMR and HD exchange. However, for rapid analysis of the folding process, solution based approaches are often plagued with aggregation side reactions resulting in poor yields. In this work we demonstrate that a Bio-Layer Interferometry (BLI) chaperonin detection system can be potentially applied to identify superior refolding conditions for denatured proteins. The degree of immobilized protein folding as a function of time can be detected by monitoring the binding of the high-affinity nucleotide-free form of the chaperonin GroEL. GroEL preferentially interacts with proteins that have hydrophobic surfaces exposed in their unfolded or partially folded form so a decrease in GroEL binding can be correlated with burial of hydrophobic surfaces as folding progresses. The magnitude of GroEL binding to the protein immobilized on Bio-layer interferometry biosensor inversely reflects the extent of protein folding and hydrophobic residue burial. We demonstrate conditions where accelerated folding can be observed for the aggregation prone protein Maltodextrin glucosidase (MalZ). Superior immobilized folding conditions identified on the Bio-layer interferometry biosensor surface were reproduced on Ni-NTA sepharose bead surfaces and resulted in significant improvement in folding yields of released MalZ (measured by enzymatic activity) compared to bulk refolding conditions in solution. PMID:27367928

Reversible Aggregation Plays a Crucial Role on the Folding Landscape of p53 Core Domain

PubMed Central

Ishimaru, Daniella; Lima, Luis M. T. R.; Maia, Lenize F.; Lopez, Priscila M.; Ano Bom, Ana P.; Valente, Ana P.; Silva, Jerson L.

2004-01-01

The role of tumor suppressor protein p53 in cell cycle control depends on its flexible and partially unstructured conformation, which makes it crucial to understand its folding landscape. Here we report an intermediate structure of the core domain of the tumor suppressor protein p53 (p53C) during equilibrium and kinetic folding/unfolding transitions induced by guanidinium chloride. This partially folded structure was undetectable when investigated by intrinsic fluorescence. Indeed, the fluorescence data showed a simple two-state transition. On the other hand, analysis of far ultraviolet circular dichroism in 1.0 M guanidinium chloride demonstrated a high content of secondary structure, and the use of an extrinsic fluorescent probe, 4,4′-dianilino-1,1′ binaphthyl-5,5′-disulfonic acid, indicated an increase in exposure of the hydrophobic core at 1 M guanidinium chloride. This partially folded conformation of p53C was plagued by aggregation, as suggested by one-dimensional NMR and demonstrated by light-scattering and gel-filtration chromatography. Dissociation by high pressure of these aggregates reveals the reversibility of the process and that the aggregates have water-excluded cavities. Kinetic measurements show that the intermediate formed in a parallel reaction between unfolded and folded structures and that it is under fine energetic control. They are not only crucial to the folding pathway of p53C but may explain as well the vulnerability of p53C to undergo departure of the native to an inactive state, which makes the cell susceptible to malignant transformation. PMID:15298872

Structure of the N-terminal domain of the protein Expansion: an ‘Expansion’ to the Smad MH2 fold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beich-Frandsen, Mads; Aragón, Eric; Llimargas, Marta

2015-04-01

Expansion is a modular protein that is conserved in protostomes. The first structure of the N-terminal domain of Expansion has been determined at 1.6 Å resolution and the new Nα-MH2 domain was found to belong to the Smad/FHA superfamily of structures. Gene-expression changes observed in Drosophila embryos after inducing the transcription factor Tramtrack led to the identification of the protein Expansion. Expansion contains an N-terminal domain similar in sequence to the MH2 domain characteristic of Smad proteins, which are the central mediators of the effects of the TGF-β signalling pathway. Apart from Smads and Expansion, no other type of proteinmore » belonging to the known kingdoms of life contains MH2 domains. To compare the Expansion and Smad MH2 domains, the crystal structure of the Expansion domain was determined at 1.6 Å resolution, the first structure of a non-Smad MH2 domain to be characterized to date. The structure displays the main features of the canonical MH2 fold with two main differences: the addition of an α-helical region and the remodelling of a protein-interaction site that is conserved in the MH2 domain of Smads. Owing to these differences, to the new domain was referred to as Nα-MH2. Despite the presence of the Nα-MH2 domain, Expansion does not participate in TGF-β signalling; instead, it is required for other activities specific to the protostome phyla. Based on the structural similarities to the MH2 fold, it is proposed that the Nα-MH2 domain should be classified as a new member of the Smad/FHA superfamily.« less

Spherical images and inextensible curved folding

NASA Astrophysics Data System (ADS)

Seffen, Keith A.

2018-02-01

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

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.

Deciding Full Branching Time Logic by Program Transformation

NASA Astrophysics Data System (ADS)

Pettorossi, Alberto; Proietti, Maurizio; Senni, Valerio

We present a method based on logic program transformation, for verifying Computation Tree Logic (CTL*) properties of finite state reactive systems. The finite state systems and the CTL* properties we want to verify, are encoded as logic programs on infinite lists. Our verification method consists of two steps. In the first step we transform the logic program that encodes the given system and the given property, into a monadic ω -program, that is, a stratified program defining nullary or unary predicates on infinite lists. This transformation is performed by applying unfold/fold rules that preserve the perfect model of the initial program. In the second step we verify the property of interest by using a proof method for monadic ω-programs.

The work of titin protein folding as a major driver in muscle contraction

PubMed Central

Eckels, Edward C.; Tapia-Rojo, Rafael; Rivas-Pardo, Jamie Andrés; Fernández, Julio M.

2018-01-01

Single molecule atomic force microscopy and magnetic tweezers experiments have demonstrated that titin Ig domains are capable of folding against a pulling force, generating mechanical work which exceeds that produced by a myosin motor. We hypothesize that upon muscle activation, formation of actomyosin crossbridges reduces the force on titin causing entropic recoil of the titin polymer and triggering the folding of the titin Ig domains. In the physiological force range of 4–15 pN under which titin operates in muscle, the folding contraction of a single Ig domain can generate 200% of the work of entropic recoil, and occurs at forces which exceed the maximum stalling force of single myosin motors. Thus titin operates like a mechanical battery storing elastic energy efficiently by unfolding Ig domains, and delivering the charge back by folding when the motors are activated during a contraction. We advance the hypothesis that titin folding and myosin activation act as inextricable partners during muscle contraction. PMID:29433413

Numerical modeling of fold-and-thrust belts: Applications to Kuqa foreland fold belt, China

NASA Astrophysics Data System (ADS)

Yin, H.; Morgan, J. K.; Zhang, J.; Wang, Z.

2009-12-01

We constructed discrete element models to simulate the evolution of fold-and-thrust belts. The impact of rock competence and decollement strength on the geometric pattern and deformation mechanics of fold-and-thrust belts has been investigated. The models reproduced some characteristic features of fold-and-thrust belts, such as faulted detachment folds, pop-ups, far-traveled thrust sheets, passive-roof duplexes, and back thrusts. In general, deformation propagates farther above a weak decollement than above a strong decollement. Our model results confirm that fold-and-thrust belts with strong frictional decollements develop relatively steep and narrow wedges formed by closely spaced imbricate thrust slices, whereas fold belts with weak decollements form wide low-taper wedges composed of faulted detachment folds, pop-ups, and back thrusts. Far-traveled thrust sheets and passive-roof duplexes are observed in the model with a strong lower decollement and a weak upper detachment. Model results also indicate that the thickness of the weak layer is critical. If it is thick enough, it acts as a ductile layer that is able to flow under differential stress, which helps to partition deformation above and below it. The discrete element modeling results were used to interpret the evolution of Kuqa Cenozoic fold-and-thrust belt along northern Tarim basin, China. Seismic and well data show that the widely distributed Paleogene rock salt has a significant impact on the deformation in this area. Structures beneath salt are closely spaced imbricate thrust and passive-roof duplex systems. Deformation above salt propagates much farther than below the salt. Faults above salt are relatively wide spaced. A huge controversy over the Kuqa fold-and-thrust belt is whether it is thin-skinned or thick-skinned. With the insights from DEM results, we suggest that Kuqa structures are mostly thin-skinned with Paleogene salt as decollement, except for the rear part near the backstop, where the

Kink-style detachment folding in Bachu fold belt of central Tarim Basin, China: geometry and seismic interpretation

NASA Astrophysics Data System (ADS)

Bo, Zhang; Jinjiang, Zhang; Shuyu, Yan; Jiang, Liu; Jinhai, Zhang; Zhongpei, Zhang

2010-05-01

The phenomenon of Kink banding is well known throughout the engineering and geophysical sciences. Associated with layered structures compressed in a layer-parallel direction, it arises for example in stratified geological systems under tectonic compression. Our work documented it is also possible to develop super large-scale kink-bands in sedimentary sequences. We interpret the Bachu fold uplift belt of the central Tarim basin in western China to be composed of detachment folds flanked by megascopic-scale kink-bands. Those previous principal fold models for the Bachu uplift belt incorporated components of large-scale thrust faulting, such as the imbricate fault-related fold model and the high-angle, reverse-faulted detachment fold model. Based on our observations in the outcrops and on the two-dimension seismic profiles, we interpret that first-order structures in the region are kink-band style detachment folds to accommodate regional shortening, and thrust faulting can be a second-order deformation style occurring on the limb of the detachment folds or at the cores of some folds to accommodate the further strain of these folds. The belt mainly consists of detachment folds overlying a ductile decollement layer. The crests of the detachment folds are bounded by large-scale kink-bands, which are zones of angularly folded strata. These low-signal-tonoise, low-reflectivity zones observed on seismic profiles across the Bachu belt are poorly imaged sections, which resulted from steeply dipping bedding in the kink-bands. The substantial width (beyond 200m) of these low-reflectivity zones, their sub-parallel edges in cross section, and their orientations at a high angle to layering between 50 and 60 degrees, as well as their conjugate geometry, support a kink-band interpretation. The kink-band interpretation model is based on the Maximum Effective Moment Criteria for continuous deformation, rather than Mohr-Column Criteria for brittle fracture. Seismic modeling is done to

Stable transformation of Pleurotus ostreatus to hygromycin B resistance using Lentinus edodes GPD expression signals.

PubMed

Irie, T; Honda, Y; Hirano, T; Sato, T; Enei, H; Watanabe, T; Kuwahara, M

2001-09-01

It was reported that Pleurotus ostreatus was transformed unstably using recombinant plasmids containing a hygromycin B phosphotransferase gene (hph) under the control of Aspergillus nidulans expression signals, and that the plasmids were maintained extrachromosomally in the transformants. Here we report a stable and integrative transformation of the fungus to hygromycin B resistance, using a recombinant hph fused with Lentinus edodes glyceraldehyde-3-phosphate dehydrogenase expression signals. Restriction-enzyme-mediated integration (REMI) was also tried and increased the transformation efficiency about ten-fold.

Modulation of frustration in folding by sequence permutation.

PubMed

Nobrega, R Paul; Arora, Karunesh; Kathuria, Sagar V; Graceffa, Rita; Barrea, Raul A; Guo, Liang; Chakravarthy, Srinivas; Bilsel, Osman; Irving, Thomas C; Brooks, Charles L; Matthews, C Robert

2014-07-22

Folding of globular proteins can be envisioned as the contraction of a random coil unfolded state toward the native state on an energy surface rough with local minima trapping frustrated species. These substructures impede productive folding and can serve as nucleation sites for aggregation reactions. However, little is known about the relationship between frustration and its underlying sequence determinants. Chemotaxis response regulator Y (CheY), a 129-amino acid bacterial protein, has been shown previously to populate an off-pathway kinetic trap in the microsecond time range. The frustration has been ascribed to premature docking of the N- and C-terminal subdomains or, alternatively, to the formation of an unproductive local-in-sequence cluster of branched aliphatic side chains, isoleucine, leucine, and valine (ILV). The roles of the subdomains and ILV clusters in frustration were tested by altering the sequence connectivity using circular permutations. Surprisingly, the stability and buried surface area of the intermediate could be increased or decreased depending on the location of the termini. Comparison with the results of small-angle X-ray-scattering experiments and simulations points to the accelerated formation of a more compact, on-pathway species for the more stable intermediate. The effect of chain connectivity in modulating the structures and stabilities of the early kinetic traps in CheY is better understood in terms of the ILV cluster model. However, the subdomain model captures the requirement for an intact N-terminal domain to access the native conformation. Chain entropy and aliphatic-rich sequences play crucial roles in biasing the early events leading to frustration in the folding of CheY.

Folding cooperativity in a three-stranded beta-sheet model.

PubMed

Roe, Daniel R; Hornak, Viktor; Simmerling, Carlos

2005-09-16

The thermodynamic behavior of a previously designed three-stranded beta-sheet was studied via several microseconds of standard and replica exchange molecular dynamics simulations. The system is shown to populate at least four thermodynamic minima, including two partially folded states in which only a single hairpin is formed. Simulated melting curves show different profiles for the C and N-terminal hairpins, consistent with differences in secondary structure content in published NMR and CD/FTIR measurements, which probed different regions of the chain. Individual beta-hairpins that comprise the three-stranded beta-sheet are observed to form cooperatively. Partial folding cooperativity between the component hairpins is observed, and good agreement between calculated and experimental values quantifying this cooperativity is obtained when similar analysis techniques are used. However, the structural detail in the ensemble of conformations sampled in the simulations permits a more direct analysis of this cooperativity than has been performed on the basis of experimental data. The results indicate the actual folding cooperativity perpendicular to strand direction is significantly larger than the lower bound obtained previously.

Folding cooperativity in a 3-stranded β-sheet model

PubMed Central

Roe, Daniel R.; Hornak, Viktor

2015-01-01

Summary The thermodynamic behavior of a previously designed three-stranded β-sheet was studied via several µs of standard and replica exchange molecular dynamics simulations. The system is shown to populate at least four thermodynamic minima, including 2 partially folded states in which only a single hairpin is formed. Simulated melting curves show different profiles for the C and N-terminal hairpins, consistent with differences in secondary structure content in published NMR and CD/FTIR measurements, which probed different regions of the chain. Individual β-hairpins that comprise the 3-stranded β-sheet are observed to form cooperatively. Partial folding cooperativity between the component hairpins is observed, and good agreement between calculated and experimental values quantifying this cooperativity is obtained when similar analysis techniques are used. However, the structural detail in the ensemble of conformations sampled in the simulations permits a more direct analysis of this cooperatively than has been performed based on experimental data. The results indicate the actual folding cooperativity perpendicular to strand direction is significantly larger than the lower bound obtained previously. PMID:16095612

Enhancement of SV40 transformation by treatment of C3H2K cells with uv light and caffeine. I. Combined effect of uv light and caffeine. [Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ide, T.; Anzai, K.; Andoh, T.

1975-08-01

Treatment of cultured mouse cells, C3H2K, with uv light and/or caffeine enhanced the frequency of SV40-induced transformation. This enhancement depends upon the doses of uv and caffeine and the mode of combination of these agents. Irradiation of cells with increasing doses of uv just before infection resulted in approximately 2-fold enhancement of the transformation frequency up to a dose of 90 ergs/mm/sup 2/ and 3.3-fold at 150 ergs/mm/sup 2/. Addition of 1 mM caffeine to the medium for 4 days subsequent to infection brought about a 2-fold enhancement. When cells were irradiated and treated with 1 mM caffeine, the enhancementmore » was approximately 4-fold up to a uv dose of 90 ergs/mm/sup 2/ and 5.9-fold at 150 ergs/mm/sup 2/. When 0.1 to 4 mM caffeine was added for 4 days postinfection, the absolute number of transformations increased, and an enhancement ratio of 1.3 to 6.8 resulted. After the addition of the same increasing doses of caffeine to uv-irradiated cells (75 ergs/mm/sup 2/), the enhancement of transformation frequency was even higher ranging 2.0 to 13.3. The transformation frequencies thus obtained by the double treatment were always higher than those predicted if uv and caffeine acted additively. The transformation frequency was little affected by the addition of dibutyrylcyclic AMP and theophylline.« less

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.

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

PubMed

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

2016-11-23

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

Discovering Cortical Folding Patterns in Neonatal Cortical Surfaces Using Large-Scale Dataset

PubMed Central

Meng, Yu; Li, Gang; Wang, Li; Lin, Weili; Gilmore, John H.

2017-01-01

The cortical folding of the human brain is highly complex and variable across individuals. Mining the major patterns of cortical folding from modern large-scale neuroimaging datasets is of great importance in advancing techniques for neuroimaging analysis and understanding the inter-individual variations of cortical folding and its relationship with cognitive function and disorders. As the primary cortical folding is genetically influenced and has been established at term birth, neonates with the minimal exposure to the complicated postnatal environmental influence are the ideal candidates for understanding the major patterns of cortical folding. In this paper, for the first time, we propose a novel method for discovering the major patterns of cortical folding in a large-scale dataset of neonatal brain MR images (N = 677). In our method, first, cortical folding is characterized by the distribution of sulcal pits, which are the locally deepest points in cortical sulci. Because deep sulcal pits are genetically related, relatively consistent across individuals, and also stable during brain development, they are well suitable for representing and characterizing cortical folding. Then, the similarities between sulcal pit distributions of any two subjects are measured from spatial, geometrical, and topological points of view. Next, these different measurements are adaptively fused together using a similarity network fusion technique, to preserve their common information and also catch their complementary information. Finally, leveraging the fused similarity measurements, a hierarchical affinity propagation algorithm is used to group similar sulcal folding patterns together. The proposed method has been applied to 677 neonatal brains (the largest neonatal dataset to our knowledge) in the central sulcus, superior temporal sulcus, and cingulate sulcus, and revealed multiple distinct and meaningful folding patterns in each region. PMID:28229131

Folding of a detachment and fault - Modified detachment folding along a lateral ramp, southwestern Montana, USA

NASA Astrophysics Data System (ADS)

Schmidt, Christopher; Whisner, S. Christopher; Whisner, Jennifer B.

2014-12-01

The inversion of the Middle Proterozoic Belt sedimentary basin during Late Cretaceous thrusting in Montana produced a large eastwardly-convex salient, the southern boundary of which is a 200 km-long oblique to lateral ramp subtended by a detachment between the Belt rocks and Archean basement. A 10 km-long lateral ramp segment exposes the upper levels of the detachment where hanging wall Belt rocks have moved out over the Paleozoic and Mesozoic section. The hanging wall structure consists of a train of high amplitude, faulted, asymmetrical detachment folds. Initial west-east shortening produced layer parallel shortening fabrics and dominantly strike slip faulting followed by symmetrical detachment folding. 'Lock-up' of movement on the detachment surface produced regional simple shear and caused the detachment folds to become asymmetrical and faulted. Folding of the detachment surface after lock-up modified the easternmost detachment folds further into a southeast-verging, overturned fold pair with a ramp-related fault along the base of the stretched mutual limb.

Visualizing chaperone-assisted protein folding

DOE PAGES

Horowitz, Scott; Salmon, Loïc; Koldewey, Philipp; ...

2016-05-30

We present that 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 chaperonemore » 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.« less

Role for ion transport in porcine vocal fold epithelial defense to acid challenge.

PubMed

Erickson-Levendoski, Elizabeth; Sivasankar, M Preeti

2012-02-01

The vocal fold epithelium is routinely exposed to gastric contents, including acid and pepsin, during laryngopharyngeal reflux events. The epithelium may possess intrinsic defenses to reflux. The first objective of the current study was to examine whether vocal fold epithelial ion transport is one potential mechanism of defense to gastric contents. The second objective was to determine whether ion transport in response to gastric contents is associated with the secretion of bicarbonate. Prospective design in excised porcine larynges. Laboratory. Porcine vocal folds (N = 56) were exposed on the luminal surface to acid, pepsin, or sham challenges. Ion transport at baseline and following challenge exposure was measured using electrophysiological techniques. To examine specific ion transport mechanisms, vocal folds were pretreated with either a sodium channel blocker or bicarbonate channel blocker. Within 60 seconds of acid but not pepsin exposure, there was a significant increase in ion transport. This rapid increase in ion transport was transient and related to bicarbonate secretion. The current data suggest that porcine vocal folds immediately increase bicarbonate secretion following exposure to acid. Bicarbonate secretion may act to neutralize acid. These findings contribute to the identification of the mechanisms underlying vocal fold defense to reflux and offer implications for the development of treatments for reflux-induced vocal fold injury.

Impacts of insect biological control on soil N transformations in Tamarix-invaded ecosystems in the Great Basin, USA

USDA-ARS?s Scientific Manuscript database

Understanding the impacts of insect biological control of Tamarix spp. on soil nitrogen (N) transformations is important because changes to N supply could alter plant community succession. We investigated short-term and longer-term impacts of herbivory by the northern tamarisk beetle (Diorhabda cari...

Episodic Rifting Events Within the Tjörnes Fracture Zone, an Onshore-Offshore Ridge-Transform in N-Iceland

NASA Astrophysics Data System (ADS)

Brandsdottir, B.; Magnusdottir, S.; Karson, J. A.; Detrick, R. S.; Driscoll, N. W.

2015-12-01

The multi-branched plate boundary across Iceland is made up of divergent and oblique rifts, and transform zones, characterized by entwined extensional and transform tectonics. The Tjörnes Fracture Zone (TFZ), located on the coast and offshore Northern Iceland, is a complex transform linking the northern rift zone (NVZ) on land with the Kolbeinsey Ridge offshore. Extension across TFZ is partitioned across three N-S trending rift basins; Eyjafjarðaráll, Skjálfandadjúp (SB) and Öxarfjörður and three WNW-NW oriented seismic lineaments; the Grímsey Oblique Rift, Húsavík-Flatey Faults (HFFs) and Dalvík Lineament. We compile the tectonic framework of the TFZ ridge-transform from aerial photos, satellite images, multibeam bathymetry and high-resolution seismic reflection data (Chirp). The rift basins are made up of normal faults with vertical displacements of up to 50-60 m, and post-glacial sediments of variable thickness. The SB comprises N5°W obliquely trending, eastward dipping normal faults as well as N10°E striking, westward dipping faults oriented roughly perpendicular to the N104°E spreading direction, indicative of early stages of rifting. Correlation of Chirp reflection data and tephrachronology from a sediment core within SB reveal major rifting episodes between 10-12.1 kyrs BP activating the whole basin, followed by smaller-scale fault movements throughout Holocene. Onshore faults have the same orientations as those mapped offshore and provide a basis for the interpretation of the kinematics of the faults throughout the region. These include transform parallel right-lateral, strike-slip faults separating domains dominated by spreading parallel left-lateral bookshelf faults. Shearing is most prominent along the HFFs, a system of right-lateral strike-slip faults with vertical displacement up to 15 m. Vertical fault movements reflect increased tectonic activity during early postglacial time coinciding with isostatic rebound enhancing volcanism within

Tracking polypeptide folds on the free energy surface: effects of the chain length and sequence.

PubMed

Brukhno, Andrey V; Ricchiuto, Piero; Auer, Stefan

2012-07-26

Characterization of the folding transition in polypeptides and assessing the thermodynamic stability of their structured folds are of primary importance for approaching the problem of protein folding. We use molecular dynamics simulations for a coarse grained polypeptide model in order to (1) obtain the equilibrium conformation diagram of homopolypeptides in a broad range of the chain lengths, N = 10, ..., 100, and temperatures, T (in a multicanonical ensemble), and (2) determine free energy profiles (FEPs) projected onto an optimal, so-called "natural", reaction coordinate that preserves the height of barriers and the diffusion coefficients on the underlying free energy hyper-surface. We then address the following fundamental questions. (i) How well does a kinetically determined free energy landscape of a single chain represent the polypeptide equilibrium (ensemble) behavior? In particular, under which conditions might the correspondence be lost, and what are the possible implications for the folding processes? (ii) How does the free energy landscape depend on the chain length (homopolypeptides) and the monomer interaction sequence (heteropolypeptides)? Our data reveal that at low T values equilibrium structures adopted by relatively short homopolypeptides (N < 60) are dominated by α-helical folds which correspond to the primary and secondary minima of the FEP. In contrast, longer homopolypeptides (N > 70), upon quasi-equilibrium cooling, fold preferentially in β-bundles with small helical portions, while the FEPs exhibit no distinct global minima. Moreover, subject to the choice of the initial configuration, at sufficiently low T, essentially metastable structures can be found and prevail far from the true thermodynamic equilibrium. We also show that, by sequence-enabling the polypeptide model, it is possible to restrict the chain to a very specific part of the configuration space, which results in substantial simplification and smoothing of the free energy

The role of allergy in the etiology of Reinke's edema on vocal folds.

PubMed

Kravos, Alenka; Zupevc, Avgust; Cizmarevic, Bogdan; Hocevar-Boltezar, Irena

2010-05-01

To identify the role of allergy in the occurrence of Reinke's edema on vocal folds. This was a prospective study in patients with Reinke's edema on vocal folds (n = 80) and a control group of patients without Reinke's edema (n = 80). All the patients were examined by the same ENT specialist at an ENT outpatient center in the period 2001-2003. The control group comprised 80 successive patients from the same clinic who were willing to cooperate in the study and were not already being treated for allergic disease by any specialist other than an ENT specialist. Patients from both groups were examined by rigid laryngoscope, skin prick allergic testing (type I allergy) and laboratory determination of serum thyroid-stimulating hormone level. The prevalence of allergy was not significantly different between the two groups: 20.0% in the patients with Reinke's edema and 23.8% in the control group (P = 0.576). No significant difference was detected in the prevalence of allergy when comparing patients with recurrent Reinke's edema after previous surgical treatment (n = 10) with patients with a first occurrence (n = 70) (P = 1.000). However, we found significantly more type I allergy in the patients with Reinke's edema and chronic hyperplastic rhinitis than in the patients with Reinke's edema without chronic hyperplastic rhinitis. All other risk factors (reflux of gastric content to the larynx, vocal abuse or misuse, unfavorable microclimate conditions at work, thyroid diseases) appeared significantly more often in the group with Reinke's edema on vocal folds than in the control group. Type I allergy is not a crucial factor in the pathogenesis of Reinke's edema on vocal folds or in recurrence of the disease after surgical treatment.

Competing Pathways and Multiple Folding Nuclei in a Large Multidomain Protein, Luciferase.

PubMed

Scholl, Zackary N; Yang, Weitao; Marszalek, Piotr E

2017-05-09

Proteins obtain their final functional configuration through incremental folding with many intermediate steps in the folding pathway. If known, these intermediate steps could be valuable new targets for designing therapeutics and the sequence of events could elucidate the mechanism of refolding. However, determining these intermediate steps is hardly an easy feat, and has been elusive for most proteins, especially large, multidomain proteins. Here, we effectively map part of the folding pathway for the model large multidomain protein, Luciferase, by combining single-molecule force-spectroscopy experiments and coarse-grained simulation. Single-molecule refolding experiments reveal the initial nucleation of folding while simulations corroborate these stable core structures of Luciferase, and indicate the relative propensities for each to propagate to the final folded native state. Both experimental refolding and Monte Carlo simulations of Markov state models generated from simulation reveal that Luciferase most often folds along a pathway originating from the nucleation of the N-terminal domain, and that this pathway is the least likely to form nonnative structures. We then engineer truncated variants of Luciferase whose sequences corresponded to the putative structure from simulation and we use atomic force spectroscopy to determine their unfolding and stability. These experimental results corroborate the structures predicted from the folding simulation and strongly suggest that they are intermediates along the folding pathway. Taken together, our results suggest that initial Luciferase refolding occurs along a vectorial pathway and also suggest a mechanism that chaperones may exploit to prevent misfolding. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

High-efficiency Agrobacterium-mediated transformation of Norway spruce (Picea abies) and loblolly pine (Pinus taeda)

NASA Technical Reports Server (NTRS)

Wenck, A. R.; Quinn, M.; Whetten, R. W.; Pullman, G.; Sederoff, R.; Brown, C. S. (Principal Investigator)

1999-01-01

Agrobacterium-mediated gene transfer is the method of choice for many plant biotechnology laboratories; however, large-scale use of this organism in conifer transformation has been limited by difficult propagation of explant material, selection efficiencies and low transformation frequency. We have analyzed co-cultivation conditions and different disarmed strains of Agrobacterium to improve transformation. Additional copies of virulence genes were added to three common disarmed strains. These extra virulence genes included either a constitutively active virG or extra copies of virG and virB, both from pTiBo542. In experiments with Norway spruce, we increased transformation efficiencies 1000-fold from initial experiments where little or no transient expression was detected. Over 100 transformed lines expressing the marker gene beta-glucuronidase (GUS) were generated from rapidly dividing embryogenic suspension-cultured cells co-cultivated with Agrobacterium. GUS activity was used to monitor transient expression and to further test lines selected on kanamycin-containing medium. In loblolly pine, transient expression increased 10-fold utilizing modified Agrobacterium strains. Agrobacterium-mediated gene transfer is a useful technique for large-scale generation of transgenic Norway spruce and may prove useful for other conifer species.

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.

Ridge-transform interaction and seismic behavior within the Tjörnes Fracture Zone, N-Iceland

NASA Astrophysics Data System (ADS)

Brandsdottir, B.; Magnusdottir, S.; Einarsson, P.; Gudmundsson, G.; Detrick, R. S.; Driscoll, N. W.

2013-12-01

High-resolution multibeam bathymetry and chirp profiling data have provided a new perspective on the structure and neotectonics of the onland-offshore Húsavík-Flatey Fault System (HFF) within the Tjörnes Fracture Zone (TFZ), N-Iceland. The TFZ comprises a broad right lateral transform zone made up of three major N-S striking extensional basins and three WNW-striking seismic lineaments, the dextral HFF, the Grímsey Oblique Rift Zone (GRZ) and the Dalvík Fault System (DF). The HFF connects the North Iceland Rift Zone (NIRZ) with the Eyjafjardaráll extensional basin (EB), the magma starved southern extension of the Kolbeinsey Ridge (KR) whereas the GRZ constitutes the offshore extension of the NIRZ with the KR. The HFF has an overall trend of N65°W and can be traced 75-80 km from its eastern junction with the NIRZ, across the Skjálfandi Bay and into the Eyjafjardaráll basin. Four pull-apart basins characterize the HFF, the largest at its intersection with the EB. En echelon arrays of conjugate strike-slip faults intersect the main HFF at angles of N20°-30°W and N20°E. Some can be traced onto land where they exhibit complicated flower patterns. Within the Skjálfandi Bay, the HFF is divided into two main branches, separated by a 70 m high N-S aligned push-up ridge and several smaller, sub-parallel WNW-trending faults. Individual fault strands have vertical displacement from 0-15 m. Large earthquakes occurred along the HFF in 1755, 1867, 1872 and 1884, the GRZ in 1884-1885 and 1910 and on the DF in 1838, 1934 and 1963. Some were destructive. A dextral transform offshore N-Iceland was initially based on diffuse earthquake epicenters and the M7, 1963 Skagafjördur earthquake. Data from the analog Iceland seismic network, established in the early 1970s, showed the TFZ microseismicity to be too diffuse to be associated with a simple oceanic transform fault. Recent seismicity within the TFZ consists of frequent earthquake swarms, lasting days or weeks with a

A stoichiometry driven universal spatial organization of backbones of folded proteins: are there Chargaff's rules for protein folding?

PubMed

Mittal, A; Jayaram, B; Shenoy, Sandhya; Bawa, Tejdeep Singh

2010-10-01

Protein folding is at least a six decade old problem, since the times of Pauling and Anfinsen. However, rules of protein folding remain elusive till date. In this work, rigorous analyses of several thousand crystal structures of folded proteins reveal a surprisingly simple unifying principle of backbone organization in protein folding. We find that protein folding is a direct consequence of a narrow band of stoichiometric occurrences of amino-acids in primary sequences, regardless of the size and the fold of a protein. We observe that "preferential interactions" between amino-acids do not drive protein folding, contrary to all prevalent views. We dedicate our discovery to the seminal contribution of Chargaff which was one of the major keys to elucidation of the stoichiometry-driven spatially organized double helical structure of DNA.

Improved FFT-based numerical inversion of Laplace transforms via fast Hartley transform algorithm

NASA Technical Reports Server (NTRS)

Hwang, Chyi; Lu, Ming-Jeng; Shieh, Leang S.

1991-01-01

The disadvantages of numerical inversion of the Laplace transform via the conventional fast Fourier transform (FFT) are identified and an improved method is presented to remedy them. The improved method is based on introducing a new integration step length Delta(omega) = pi/mT for trapezoidal-rule approximation of the Bromwich integral, in which a new parameter, m, is introduced for controlling the accuracy of the numerical integration. Naturally, this method leads to multiple sets of complex FFT computations. A new inversion formula is derived such that N equally spaced samples of the inverse Laplace transform function can be obtained by (m/2) + 1 sets of N-point complex FFT computations or by m sets of real fast Hartley transform (FHT) computations.

Parallel and pipeline computation of fast unitary transforms

NASA Technical Reports Server (NTRS)

Fino, B. J.; Algazi, V. R.

1975-01-01

The letter discusses the parallel and pipeline organization of fast-unitary-transform algorithms such as the fast Fourier transform, and points out the efficiency of a combined parallel-pipeline processor of a transform such as the Haar transform, in which (2 to the n-th power) -1 hardware 'butterflies' generate a transform of order 2 to the n-th power every computation cycle.

The oxidoreductase ERp57 efficiently reduces partially folded in preference to fully folded MHC class I molecules

PubMed Central

Antoniou, Antony N.; Ford, Stuart; Alphey, Magnus; Osborne, Andrew; Elliott, Tim; Powis, Simon J.

2002-01-01

The oxidoreductase ERp57 is an integral component of the peptide loading complex of major histocompatibility complex (MHC) class I molecules, formed during their chaperone-assisted assembly in the endoplasmic reticulum. Misfolded MHC class I molecules or those denied suitable peptides are retrotranslocated and degraded in the cytosol. The presence of ERp57 during class I assembly suggests it may be involved in the reduction of intrachain disulfides prior to retrotranslocation. We have studied the ability of ERp57 to reduce MHC class I molecules in vitro. Recombinant ERp57 specifically reduced partially folded MHC class I molecules, whereas it had little or no effect on folded and peptide-loaded MHC class I molecules. Reductase activity was associated with cysteines at positions 56 and 405 of ERp57, the N-terminal residues of the active CXXC motifs. Our data suggest that the reductase activity of ERp57 may be involved during the unfolding of MHC class I molecules, leading to targeting for degradation. PMID:12032078

Folding Automaton for Trees

NASA Astrophysics Data System (ADS)

Subashini, N.; Thiagarajan, K.

2018-04-01

In this paper we observed the definition of folding technique in graph theory and we derived the corresponding automaton for trees. Also derived some propositions on symmetrical structure tree, non-symmetrical structure tree, point symmetrical structure tree, edge symmetrical structure tree along with finite number of points. This approach provides to derive one edge after n’ number of foldings.

Optical methods for measuring DNA folding

NASA Astrophysics Data System (ADS)

Smith, Adam D.; Ukogu, Obinna A.; Devenica, Luka M.; White, Elizabeth D.; Carter, Ashley R.

2017-03-01

One of the most important biological processes is the dynamic folding and unfolding of deoxyribonucleic acid (DNA). The folding process is crucial for DNA to fit within the boundaries of the cell, while the unfolding process is essential for DNA replication and transcription. To accommodate both processes, the cell employs a highly active folding mechanism that has been the subject of intense study over the last few decades. Still, many open questions remain. What are the pathways for folding or unfolding? How does the folding equilibrium shift? And, what is the energy landscape for a particular process? Here, we review these emerging questions and the in vitro, optical methods that have provided answers, introducing the topic for those physicists seeking to step into biology. Specifically, we discuss two iconic experiments for DNA folding, the tethered particle motion (TPM) experiment and the optical tweezers experiment.

Evolution of the Chos Malal and Agrio fold and thrust belts, Andes of Neuquén: Insights from structural analysis and apatite fission track dating

NASA Astrophysics Data System (ADS)

Rojas Vera, E. A.; Mescua, J.; Folguera, A.; Becker, T. P.; Sagripanti, L.; Fennell, L.; Orts, D.; Ramos, V. A.

2015-12-01

The Chos Malal and Agrio fold and thrust belts are located in the western part of the Neuquén basin, an Andean retroarc basin of central-western Argentina. Both belts show evidence of tectonic inversion at the western part during Late Cretaceous times. The eastern part is dominated by late Miocene deformation which also partially reactivated the western structures. This work focuses on the study of the regional structure and the deformational event that shaped the relief of this part of the Andes. Based on new field work and structural data and previously published works a detailed map of the central part of the Neuquén basin is presented. Three regional structural cross sections were surveyed and balanced using the 2d Move™ software. In order to define a more accurate uplift history, new apatite fission track analyses were carried on selected structures. These data was used for new thermal history modeling of the inner part of the Agrio and Chos Malal fold and thrust belts. The results of the fission track analyses improve the knowledge of how these fold and thrust belts have grown trough time. Two main deformational events are defined in Late Cretaceous to Paleocene and Late Miocene times. Based on this regional structural analysis and the fission track data the precise location of the orogenic front for the Late Cretaceous-Paleocene times is reconstructed and it is proposed a structural evolution of this segment of the Andes. This new exhumation data show how the Late Cretaceous to Paleocene event was a continuous and uninterrupted deformational event.

Vector breather-to-soliton transitions and nonlinear wave interactions induced by higher-order effects in an erbium-doped fiber

NASA Astrophysics Data System (ADS)

Sun, Wen-Rong; Wang, Lei; Xie, Xi-Yang

2018-06-01

Vector breather-to-soliton transitions for the higher-order nonlinear Schrödinger-Maxwell-Bloch (NLS-MB) system with sextic terms are investigated. The Lax pair and Darboux transformation (DT) of such system are constructed. With the DT, analytic vector breather solutions up to the second order are obtained. With appropriate choices of the spectra parameters, vector breather-to-soliton transitions happen. Interaction mechanisms of vector nonlinear waves (breather-soliton or soliton-soliton interactions) are displayed.

Current treatment of vocal fold scarring.

PubMed

Hirano, Shigeru

2005-06-01

Vocal fold scarring still remains a therapeutic challenge, with the most problematic issue being the histologic changes that are primarily responsible for altering the viscoelasticity of the vocal fold mucosa. Optimal treatment for vocal fold scarring has not yet been established. To restore or regenerate damaged vocal folds, it is important to investigate the changes to the layer structure of the lamina propria. Tissue engineering and regenerative medicine may provide new strategies for the prevention and treatment of vocal fold scarring. Recent developments in this field are reviewed in the present article. Histologic studies have revealed that hyaluronic acid, fibronectin, decorin, and various other extracellular matrix components, as well as collagen, may contribute to determining the vibratory properties of the vocal fold mucosa. Changes of these molecules are thought to affect the viscoelasticity of the scarred vocal folds. Based on such histologic findings, innovative approaches have been developed, including administration of hyaluronic acid into injured or scarred vocal folds. Other strategies that have recently shown advances include growth factor therapy and cell therapy using stem cells or mature fibroblasts. The effects of these new treatments have not fully been confirmed clinically, but there seems to be great therapeutic potential in such regenerative medical strategies. Recent research has revealed the detailed histologic and rheologic changes related to vocal fold scarring. Based on these findings, various new therapeutic strategies have been developed in animal models using tissue engineering and regenerative medicine. However, no clinical trials have been performed, and more studies are necessary to establish the optimum modality.

Kinetic Folding Mechanism of Erythropoietin

PubMed Central

Banks, Douglas D.; Scavezze, Joanna L.; Siska, Christine C.

2009-01-01

This report describes what to our knowledge is the first kinetic folding studies of erythropoietin, a glycosylated four-helical bundle cytokine responsible for the regulation of red blood cell production. Kinetic responses for folding and unfolding reactions initiated by manual mixing were monitored by far-ultraviolet circular dichroism and fluorescence spectroscopy, and folding reactions initiated by stopped-flow mixing were monitored by fluorescence. The urea concentration dependence of the observed kinetics were best described by a three-state model with a transiently populated intermediate species that is on-pathway and obligatory. This folding scheme was further supported by the excellent agreement between the free energy of unfolding and m-value calculated from the microscopic rate constants derived from this model and these parameters determined from separate equilibrium unfolding experiments. Compared to the kinetics of other members of the four-helical bundle cytokine family, erythropoietin folding and unfolding reactions were slower and less susceptible to aggregation. We tentatively attribute these slower rates and protection from association events to the large amount of carbohydrate attached to erythropoietin at four sites. PMID:19450492

Meta-analysis of published transcriptional and translational fold changes reveals a preference for low-fold inductions.

PubMed

Wren, Jonathan D; Conway, Tyrrell

2006-01-01

The goals of this study were to gain a better quantitative understanding of the dynamic range of transcriptional and translational response observed in biological systems and to examine the reporting of regulatory events for trends and biases. A straightforward pattern-matching routine extracted 3,408 independent observations regarding transcriptional fold-changes and 1,125 regarding translational fold-changes from over 15 million MEDLINE abstracts. Approximately 95% of reported changes were > or =2-fold. Further, the historical trend of reporting individual fold-changes is declining in favor of high-throughput methods for transcription but not translation. Where it was possible to compare the average fold-changes in transcription and translation for the same gene/product (203 examples), approximately 53% were a < or =2-fold difference, suggesting a loose tendency for the two to be coupled in magnitude. We found also that approximately three-fourths of reported regulatory events have been at the transcriptional level. The frequency distribution appears to be normally distributed and peaks near 2-fold, suggesting that nature selects for a low-energy solution to regulatory responses. Because high-throughput technologies ordinarily sacrifice measurement quality for quantity, this also suggests that many regulatory events may not be reliably detectable by such technologies. Text mining of regulatory events and responses provides additional information incorporable into microarray analysis, such as prior fold-change observations and flagging genes that are regulated post-transcription. All extracted regulation and response patterns can be downloaded at the following website: www.ou.edu/microarray/ oumcf/Meta_analysis.xls.

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.

Direct folding simulation of helical proteins using an effective polarizable bond force field.

PubMed

Duan, Lili; Zhu, Tong; Ji, Changge; Zhang, Qinggang; Zhang, John Z H

2017-06-14

We report a direct folding study of seven helical proteins (, Trpcage, , C34, N36, , ) ranging from 17 to 53 amino acids through standard molecular dynamics simulations using a recently developed polarizable force field-Effective Polarizable Bond (EPB) method. The backbone RMSDs, radius of gyrations, native contacts and native helix content are in good agreement with the experimental results. Cluster analysis has also verified that these folded structures with the highest population are in good agreement with their corresponding native structures for these proteins. In addition, the free energy landscape of seven proteins in the two dimensional space comprised of RMSD and radius of gyration proved that these folded structures are indeed of the lowest energy conformations. However, when the corresponding simulations were performed using the standard (nonpolarizable) AMBER force fields, no stable folded structures were observed for these proteins. Comparison of the simulation results based on a polarizable EPB force field and a nonpolarizable AMBER force field clearly demonstrates the importance of polarization in the folding of stable helical structures.

Repairing the vibratory vocal fold.

PubMed

Long, Jennifer L

2018-01-01

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

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)

Equilibrium folding of pro-HlyA from Escherichia coli reveals a stable calcium ion dependent folding intermediate.

PubMed

Thomas, Sabrina; Bakkes, Patrick J; Smits, Sander H J; Schmitt, Lutz

2014-09-01

HlyA from Escherichia coli is a member of the repeats in toxin (RTX) protein family, produced by a wide range of Gram-negative bacteria and secreted by a dedicated Type 1 Secretion System (T1SS). RTX proteins are thought to be secreted in an unfolded conformation and to fold upon secretion by Ca(2+) binding. However, the exact mechanism of secretion, ion binding and folding to the correct native state remains largely unknown. In this study we provide an easy protocol for high-level pro-HlyA purification from E. coli. Equilibrium folding studies, using intrinsic tryptophan fluorescence, revealed the well-known fact that Ca(2+) is essential for stability as well as correct folding of the whole protein. In the absence of Ca(2+), pro-HlyA adopts a non-native conformation. Such molecules could however be rescued by Ca(2+) addition, indicating that these are not dead-end species and that Ca(2+) drives pro-HlyA folding. More importantly, pro-HlyA unfolded via a two-state mechanism, whereas folding was a three-state process. The latter is indicative of the presence of a stable folding intermediate. Analysis of deletion and Trp mutants revealed that the first folding transition, at 6-7M urea, relates to Ca(2+) dependent structural changes at the extreme C-terminus of pro-HlyA, sensed exclusively by Trp914. Since all Trp residues of HlyA are located outside the RTX domain, our results demonstrate that Ca(2+) induced folding is not restricted to the RTX domain. Taken together, Ca(2+) binding to the pro-HlyA RTX domain is required to drive the folding of the entire protein to its native conformation. Copyright © 2014 Elsevier B.V. All rights reserved.

Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

PubMed

Shih, Ying-Chun; Chen, Chao-Ling; Zhang, Yan; Mellor, Rebecca L; Kanter, Evelyn M; Fang, Yun; Wang, Hua-Chi; Hung, Chen-Ting; Nong, Jing-Yi; Chen, Hui-Ju; Lee, Tzu-Han; Tseng, Yi-Shuan; Chen, Chiung-Nien; Wu, Chau-Chung; Lin, Shuei-Liong; Yamada, Kathryn A; Nerbonne, Jeanne M; Yang, Kai-Chien

2018-04-13

Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics. Exploiting coexpression gene network analysis on RNA sequencing data from failing human heart, we identified TXNDC5 (thioredoxin domain containing 5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum protein, as a potential novel mediator of cardiac fibrosis, and we completed experiments to test this hypothesis directly. The objective of this study was to determine the functional role of TXNDC5 in the pathogenesis of cardiac fibrosis. RNA sequencing and Western blot analyses revealed that TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles and in hypertrophied/failing mouse left ventricle. In addition, cardiac TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor β1 and ECM proteins in vivo. TXNDC5 mRNA and protein were increased in human CF (hCF) under transforming growth factor β1 stimulation in vitro. Knockdown of TXNDC5 attenuated transforming growth factor β1-induced hCF activation and ECM protein upregulation independent of SMAD3 (SMAD family member 3), whereas increasing expression of TXNDC5 triggered hCF activation and proliferation and increased ECM protein production. Further experiments showed that TXNDC5, a protein disulfide isomerase, facilitated ECM protein folding and that depletion of TXNDC5 led to ECM protein misfolding and degradation in CF. In addition, TXNDC5 promotes hCF activation and proliferation by enhancing c-Jun N-terminal kinase activity via increased reactive oxygen species, derived from NAD(P)H oxidase 4

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

Role for Ion Transport in Porcine Vocal Fold Epithelial Defense to Acid Challenge

PubMed Central

Erickson-Levendoski, Elizabeth; Sivasankar, M. Preeti

2012-01-01

Objective The vocal fold epithelium is routinely exposed to gastric contents, including acid and pepsin, during laryngopharyngeal reflux events. The epithelium may possess intrinsic defenses to reflux. The first objective of the current study was to examine whether vocal fold epithelial ion transport is one potential mechanism of defense to gastric contents. The second objective was to determine whether ion transport in response to gastric contents is associated with the secretion of bicarbonate. Study Design Prospective design in excised porcine larynges. Setting Laboratory. Subjects and Methods Porcine vocal folds (N = 56) were exposed on the luminal surface to acid, pepsin, or sham challenges. Ion transport at baseline and following challenge exposure was measured using electrophysiological techniques. To examine specific ion transport mechanisms, vocal folds were pretreated with either a sodium channel blocker or bicarbonate channel blocker. Results Within 60 seconds of acid but not pepsin exposure, there was a significant increase in ion transport. This rapid increase in ion transport was transient and related to bicarbonate secretion. Conclusion The current data suggest that porcine vocal folds immediately increase bicarbonate secretion following exposure to acid. Bicarbonate secretion may act to neutralize acid. These findings contribute to the identification of the mechanisms underlying vocal fold defense to reflux and offer implications for the development of treatments for reflux-induced vocal fold injury. PMID:22086905

Cooperativity and modularity in protein folding

PubMed Central

Sasai, Masaki; Chikenji, George; Terada, Tomoki P.

2016-01-01

A simple statistical mechanical model proposed by Wako and Saitô has explained the aspects of protein folding surprisingly well. This model was systematically applied to multiple proteins by Muñoz and Eaton and has since been referred to as the Wako-Saitô-Muñoz-Eaton (WSME) model. The success of the WSME model in explaining the folding of many proteins has verified the hypothesis that the folding is dominated by native interactions, which makes the energy landscape globally biased toward native conformation. Using the WSME and other related models, Saitô emphasized the importance of the hierarchical pathway in protein folding; folding starts with the creation of contiguous segments having a native-like configuration and proceeds as growth and coalescence of these segments. The Φ-values calculated for barnase with the WSME model suggested that segments contributing to the folding nucleus are similar to the structural modules defined by the pattern of native atomic contacts. The WSME model was extended to explain folding of multi-domain proteins having a complex topology, which opened the way to comprehensively understanding the folding process of multi-domain proteins. The WSME model was also extended to describe allosteric transitions, indicating that the allosteric structural movement does not occur as a deterministic sequential change between two conformations but as a stochastic diffusive motion over the dynamically changing energy landscape. Statistical mechanical viewpoint on folding, as highlighted by the WSME model, has been renovated in the context of modern methods and ideas, and will continue to provide insights on equilibrium and dynamical features of proteins. PMID:28409080

Thermodynamic properties of an extremely rapid protein folding reaction.

PubMed

Schindler, T; Schmid, F X

1996-12-24

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

Self-folding origami at any energy scale

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Generalized Kustaanheimo-Stiefel transformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Komarov, L.I.; Van Hoang, L.

1994-10-01

A theory is given for the construction of generalized Kustaanheimo-Stiefel (KS) transformations for dimensions q+1 (q=2{sup h}, h=0, 1, 2,...) of the Kepler problem, and the following proposition is proved: A connection between the Kepler problem in a real space of dimension q+1 and the problem of an isotropic harmonic oscillator in a real space dimension N exists and can be established by means of generalized KS transformations in the cases in which N=2q and q=2{sup h} (h=0, 1, 2,...). A simple graphical prescription for constructing generalized KS transformations that realize this connection is proposed.

Anatomy and Histology of an Epicanthal Fold.

PubMed

Park, Jae Woo; Hwang, Kun

2016-06-01

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

Dynamics of the Smooth Positons of the Wadati-Konno-Ichikawa Equation

NASA Astrophysics Data System (ADS)

Wang, Gai-Hua; Zhang, Yong-Shuai; He, Jing-Song

2018-03-01

We discuss a modified Wadati-Konno-Ichikawa (mWKI) equation, which is equivalent to the WKI equation by a hodograph transformation. The explicit formula of degenerated solution of mWKI equation is provided by using degenerate Darboux transformation with respect to the eigenvalues, which yields two kinds of smooth solutions possessing the vanishing and nonvanishing boundary conditions respectively. In particular, a method for the decomposition of modulus square is operated to the positon solution, and the approximate orbits before and after collision of positon solutions are displayed explicitly. Supported by the National Natural Science Foundation of China under Grant No. 11671219, the K. C. Wong Magna Fund in Ningbo University

Replica exchange molecular dynamics simulation of structure variation from α/4β-fold to 3α-fold protein.

PubMed

Lazim, Raudah; Mei, Ye; Zhang, Dawei

2012-03-01

Replica exchange molecular dynamics (REMD) simulation provides an efficient conformational sampling tool for the study of protein folding. In this study, we explore the mechanism directing the structure variation from α/4β-fold protein to 3α-fold protein after mutation by conducting REMD simulation on 42 replicas with temperatures ranging from 270 K to 710 K. The simulation began from a protein possessing the primary structure of GA88 but the tertiary structure of GB88, two G proteins with "high sequence identity." Albeit the large Cα-root mean square deviation (RMSD) of the folded protein (4.34 Å at 270 K and 4.75 Å at 304 K), a variation in tertiary structure was observed. Together with the analysis of secondary structure assignment, cluster analysis and principal component, it provides insights to the folding and unfolding pathway of 3α-fold protein and α/4β-fold protein respectively paving the way toward the understanding of the ongoings during conformational variation.

Refolding of urea-denatured α-chymotrypsin by protein-folding liquid chromatography.

PubMed

Congyu, Ke; Wujuan, Sun; Qunzheng, Zhang; Xindu, Geng

2013-04-01

An approach for re-folding denatured proteins during proteome research by protein folding liquid chromatography (PFLC) is presented. Standard protein, α-chymotrypsin (α-Chy), was selected as a model protein and hydrophobic interaction chromatography was performed as a typical PFLC; the three different α-Chy states - urea-denatured (U state), its folded intermediates (M state) and nature state (N state) - were studied during protein folding. Based on the test by matrix-assisted laser desorption/ionization time of flight mass spectrometry and bioactivity, only one stable M state of the α-Chy was identified and then it was prepared for further investigation. The specific bioactivity of the refolded α-Chy was found to be higher than that of commercial α-Chy as the urea concentration in the sample solution ranged from 1.0 to 3.0 m; the highest specific bioactivity at urea concentration was 1.0 m, indicating the possibility for re-folding some proteins that have partially or completely lost their bioactivity, as a dilute urea solution was employed for dissolving the sample. The experiment showed that the peak height of its M state increased with increasing urea concentration, and correspondingly decreased in the amount of the refolded α-Chy. When the urea concentration reached 6.0 m, the unfolded α-Chy could not be refolded at all. Copyright © 2012 John Wiley & Sons, Ltd.

The review on tessellation origami inspired folded structure

NASA Astrophysics Data System (ADS)

Chu, Chai Chen; Keong, Choong Kok

2017-10-01

Existence of folds enhances the load carrying capacity of a folded structure which makes it suitable to be used for application where large open space is required such as large span roof structures and façade. Folded structure is closely related to origami especially the tessellation origami. Tessellation origami provides a folded configuration with facetted surface as a result from repeated folding pattern. Besides that, tessellation origami has flexible folding mechanism that produced a variety of 3-dimensional folded configurations. Despite the direct relationship between fold in origami and folded structure, the idea of origami inspired folded structure is not properly reviewed in the relevant engineering field. Hence, this paper aims to present the current studies from related discipline which has direct relation with application of tessellation origami in folded structure. First, tessellation origami is properly introduced and defined. Then, the review covers the topic on the origami tessellation design suitable for folded structure, its modeling and simulation method, and existing studies and applications of origami as folded structure is presented. The paper also includes the discussion on the current issues related to each topic.

Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins

PubMed Central

Calosci, Nicoletta; Chi, Celestine N.; Richter, Barbara; Camilloni, Carlo; Engström, Åke; Eklund, Lars; Travaglini-Allocatelli, Carlo; Gianni, Stefano; Vendruscolo, Michele; Jemth, Per

2008-01-01

The energy landscape theory provides a general framework for describing protein folding reactions. Because a large number of studies, however, have focused on two-state proteins with single well-defined folding pathways and without detectable intermediates, the extent to which free energy landscapes are shaped up by the native topology at the early stages of the folding process has not been fully characterized experimentally. To this end, we have investigated the folding mechanisms of two homologous three-state proteins, PTP-BL PDZ2 and PSD-95 PDZ3, and compared the early and late transition states on their folding pathways. Through a combination of Φ value analysis and molecular dynamics simulations we obtained atomic-level structures of the transition states of these homologous three-state proteins and found that the late transition states are much more structurally similar than the early ones. Our findings thus reveal that, while the native state topology defines essentially in a unique way the late stages of folding, it leaves significant freedom to the early events, a result that reflects the funneling of the free energy landscape toward the native state. PMID:19033470

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

Dependence of internal friction on folding mechanism.

PubMed

Zheng, Wenwei; De Sancho, David; Hoppe, Travis; Best, Robert B

2015-03-11

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.

Dynamic Folding Pathway Models of the Trp-Cage Protein

PubMed Central

Kim, Seung-Yeon

2013-01-01

Using action-derived molecular dynamics (ADMD), we study the dynamic folding pathway models of the Trp-cage protein by providing its sequential conformational changes from its initial disordered structure to the final native structure at atomic details. We find that the numbers of native contacts and native hydrogen bonds are highly correlated, implying that the native structure of Trp-cage is achieved through the concurrent formations of native contacts and native hydrogen bonds. In early stage, an unfolded state appears with partially formed native contacts (~40%) and native hydrogen bonds (~30%). Afterward, the folding is initiated by the contact of the side chain of Tyr3 with that of Trp6, together with the formation of the N-terminal α-helix. Then, the C-terminal polyproline structure docks onto the Trp6 and Tyr3 rings, resulting in the formations of the hydrophobic core of Trp-cage and its near-native state. Finally, the slow adjustment processes of the near-native states into the native structure are dominant in later stage. The ADMD results are in agreement with those of the experimental folding studies on Trp-cage and consistent with most of other computational studies. PMID:23865078

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.

A new model for approximating RNA folding trajectories and population kinetics

NASA Astrophysics Data System (ADS)

Kirkpatrick, Bonnie; Hajiaghayi, Monir; Condon, Anne

2013-01-01

RNA participates both in functional aspects of the cell and in gene regulation. The interactions of these molecules are mediated by their secondary structure which can be viewed as a planar circle graph with arcs for all the chemical bonds between pairs of bases in the RNA sequence. The problem of predicting RNA secondary structure, specifically the chemically most probable structure, has many useful and efficient algorithms. This leaves RNA folding, the problem of predicting the dynamic behavior of RNA structure over time, as the main open problem. RNA folding is important for functional understanding because some RNA molecules change secondary structure in response to interactions with the environment. The full RNA folding model on at most O(3n) secondary structures is the gold standard. We present a new subset approximation model for the full model, give methods to analyze its accuracy and discuss the relative merits of our model as compared with a pre-existing subset approximation. The main advantage of our model is that it generates Monte Carlo folding pathways with the same probabilities with which they are generated under the full model. The pre-existing subset approximation does not have this property.

Effect of double-fold surgery on spontaneous resolution of Graves' upper eyelid retraction.

PubMed

Kim, Dong Kyu; Choi, Moonjung; Yoon, Jin Sook

2015-02-01

To investigate the effect of previous incisional double-fold surgery on spontaneous resolution of eyelid retraction caused by Graves orbitopathy (GO) in Asian individuals. Retrospective review of medical records. Patients (N = 30; 39 eyes) with eyelid retraction associated with GO with symptom duration of less than 6 months. Patients who visited the Ophthalmology Department of Severance Hospital, Yonsei University, between January 2010 and December 2011, followed up for more than 6 months and in a euthyroid state with antithyroid drug treatment were included. Patients treated with steroids or who underwent surgery during follow-up were excluded. Upper scleral show was measured as the distance between the central upper lid margin and limbus at initial presentation and after 6 months. Comparative analysis was performed between the 2 groups delineated by history (n = 12; 16 eyes), or lack thereof (n = 18; 23 eyes), of incisional double-fold surgery before onset of GO symptoms and signs. Patient demographics and initial upper scleral show were not significantly different between groups. In both groups, upper scleral show significantly decreased at 6 months of follow-up (p < 0.001 in both groups); however, improvement of upper scleral show was significantly reduced in patients who had undergone previous double-fold surgery (0.8 ± 0.5 mm) than in nonsurgical patients (1.8 ± 0.5 mm; p < 0.001). Graves eyelid retraction resolves spontaneously over time, albeit not completely. Previous double-fold surgery hinders the degree of spontaneous resolution, probably because of the fibrosis and cicatrization between the skin, the subcutaneous layer, and the levator complex. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Self-Folded Gripper-Like Architectures from Stimuli-Responsive Bilayers.

PubMed

Abdullah, Arif M; Li, Xiuling; Braun, Paul V; Rogers, John A; Hsia, K Jimmy

2018-06-19

Self-folding microgrippers are an emerging class of smart structures that have widespread applications in medicine and micro/nanomanipulation. To achieve their functionalities, these architectures rely on spatially patterned hinges to transform into 3D configurations in response to an external stimulus. Incorporating hinges into the devices requires the processing of multiple layers which eventually increases the fabrication costs and actuation complexities. The goal of this work is to demonstrate that it is possible to achieve gripper-like configurations in an on-demand manner from simple planar bilayers that do not require hinges for their actuation. Finite element modeling of bilayers is performed to understand the mechanics behind their stimuli-responsive shape transformation behavior. The model predictions are then experimentally validated and axisymmetric gripper-like shapes are realized using millimeter-scale poly(dimethylsiloxane) bilayers that undergo differential swelling in organic solvents. Owing to the nature of the computational scheme which is independent of length scales and material properties, the guidelines reported here would be applicable to a diverse array of gripping systems and functional devices. Thus, this work not only demonstrates a simple route to fabricate functional microgrippers but also contributes to self-assembly in general. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effective Potentials for Folding Proteins

NASA Astrophysics Data System (ADS)

Chen, Nan-Yow; Su, Zheng-Yao; Mou, Chung-Yu

2006-02-01

A coarse-grained off-lattice model that is not biased in any way to the native state is proposed to fold proteins. To predict the native structure in a reasonable time, the model has included the essential effects of water in an effective potential. Two new ingredients, the dipole-dipole interaction and the local hydrophobic interaction, are introduced and are shown to be as crucial as the hydrogen bonding. The model allows successful folding of the wild-type sequence of protein G and may have provided important hints to the study of protein folding.

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.

Investigation of RNA Hairpin Loop Folding with Time-Resolved Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Stancik, Aaron Lee

Ribonucleic acids (RNAs) are a group of functional biopolymers central to the molecular underpinnings of life. To complete the many processes they mediate, RNAs must fold into precise three-dimensional structures. Hairpin loops are the most ubiquitous and basic structural elements present in all folded RNAs, and are the foundation upon which all complex tertiary structures are built. A hairpin loop forms when a single stranded RNA molecule folds back on itself creating a helical stem of paired bases capped by a loop. This work investigates the formation of UNCG hairpin loops with the sequence 5'-GC(UNCG)GC-3' (N = A, U, G, or C) using both equilibrium infrared (IR) and time-resolved IR spectroscopy. Equilibrium IR melting data were used to determine thermodynamic parameters. Melting temperatures ranged from 50 to 60°C, and enthalpies of unfolding were on the order of 100 kJ/mol. In the time-resolved work, temperature jumps of up to 20°C at 2.5°C increments were obtained with transient relaxation kinetics spanning nanoseconds to hundreds of microseconds. The relaxation kinetics for all of the oligomers studied were fit to first or second order exponentials. Multiple vibrational transitions were probed on each oligomer for fully folded and partially denatured structures. In the time-resolved limit, in contrast to equilibrium melting, RNA does not fold according to two-state behavior. These results are some of the first to show that RNA hairpins fold according to a rugged energy landscape, which contradicts their relatively simple nature. In addition, this work has proven that time-resolved IR spectroscopy is a powerful and novel tool for investigating the earliest events of RNA folding, the formation of the hairpin loop.

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.

Improving Protein Fold Recognition by Deep Learning Networks.

PubMed

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

2015-12-04

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

Cyclooxygenase-2 expression and clinical parameters in laryngeal squamous cell carcinoma, vocal fold nodule, and laryngeal atypical hyperplasia.

PubMed

Sayar, Cağdaş; Sayar, Hamide; Özdemir, Süleyman; Selçuk, Tahsin; Görgülü, Orhan; Akbaş, Yücel; Kemal Olgun, Mustafa

2013-01-01

The diagnostic role of cyclooxygenase-2 (COX-2) expression in laryngeal atypical hyperplasia, vocal fold nodule, and laryngeal squamous cell carcinoma was examined. Specimens obtained from patients diagnosed with vocal fold nodule (n = 35), atypical hyperplasia (n = 35), laryngeal squamous cell carcinoma (n = 35), and clinical parameters were evaluated retrospectively. Although no staining was observed in patients with vocal fold nodules, staining was noted in laryngeal atypical hyperplasia and squamous cell carcinoma. The percentage of COX-2 staining was the highest in the carcinoma group. It was determined that COX-2 staining was significantly associated with laryngeal squamous cell carcinoma. It should be noted that overexpression of COX-2, a potentially important factor in the evolution of carcinogenesis in precancerous lesions, might be an indicator of the development of carcinoma. Copyright © 2012 Wiley Periodicals, Inc.

A computational model of cerebral cortex folding.

PubMed

Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Stephen Miller, L; Liu, Tianming

2010-05-21

The geometric complexity and variability of the human cerebral cortex have long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3D geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: (1) Mechanical constraints of the skull regulate the cortical folding process. (2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. (3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. (4) The cortical folding pattern is dependent on the initial geometry of the cortex. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Study of protein folding under native conditions by rapidly switching the hydrostatic pressure inside an NMR sample cell

PubMed Central

Charlier, Cyril; Alderson, T. Reid; Courtney, Joseph M.; Ying, Jinfa; Anfinrud, Philip

2018-01-01

In general, small proteins rapidly fold on the timescale of milliseconds or less. For proteins with a substantial volume difference between the folded and unfolded states, their thermodynamic equilibrium can be altered by varying the hydrostatic pressure. Using a pressure-sensitized mutant of ubiquitin, we demonstrate that rapidly switching the pressure within an NMR sample cell enables study of the unfolded protein under native conditions and, vice versa, study of the native protein under denaturing conditions. This approach makes it possible to record 2D and 3D NMR spectra of the unfolded protein at atmospheric pressure, providing residue-specific information on the folding process. 15N and 13C chemical shifts measured immediately after dropping the pressure from 2.5 kbar (favoring unfolding) to 1 bar (native) are close to the random-coil chemical shifts observed for a large, disordered peptide fragment of the protein. However, 15N relaxation data show evidence for rapid exchange, on a ∼100-μs timescale, between the unfolded state and unstable, structured states that can be considered as failed folding events. The NMR data also provide direct evidence for parallel folding pathways, with approximately one-half of the protein molecules efficiently folding through an on-pathway kinetic intermediate, whereas the other half fold in a single step. At protein concentrations above ∼300 μM, oligomeric off-pathway intermediates compete with folding of the native state. PMID:29666248

Effect of prescribed fire on soil properties and N transformation in two vegetation types in South China.

PubMed

Wang, Faming; Li, Jian; Zou, Bi; Xu, Xin; Li, Zhian

2013-06-01

Prescribed fire is a common site preparation practice in forest management in southern China. However, the effect of fire on soil properties and N transformations is still poorly understood in this region. In this study, soil properties and N transformations in burned and unburned site of two vegetation types (Eucalyptus plantation and shrubland) were compared in rainy and dry seasons after 2 years' prescribed fire. Soil pH and soil NH4-N were all higher in the burned site compared to the unburned control. Furthermore, burned sites had 30-40 % lower of soil total phosphorus than conspecific unburned sites. There was no difference in soil organic matter, total N, soil exchangeable cations, available P or NO3-N. Nitrogen mineralization rate of 0-5 cm soil in the unburned site ranged from 8.24 to 11.6 mg N kg(-1) soil month(-1) in the rainy season, compared to a lower level of 4.82-5.25 mg N kg(-1) soil month(-1) in the burned sites. In contrast, 0-5 cm layer nitrification rate was overall 2.47 mg N kg(-1) soil month(-1) in the rainy season, and was not significantly affected by burning. The reduced understory vegetation coverage after burning may be responsible for the higher soil NH4-N in the burned site. This study highlights that a better understanding the effect of prescribed burning on soil nutrients cycling would provide a critical foundation for management decision and be beneficial to afforestation in southern China.

Pulsed dye laser-induced inflammatory response and extracellular matrix turnover in rat vocal folds and vocal fold fibroblasts.

PubMed

Lin, Ya; Yamashita, Masaru; Zhang, Jingxian; Ling, Changying; Welham, Nathan V

2009-10-01

Disruption of the vocal fold extracellular matrix (ECM) can induce a profound and refractory dysphonia. Pulsed dye laser (PDL) irradiation has shown early promise as a treatment modality for disordered ECM in patients with chronic vocal fold scar; however, there are limited data addressing the mechanism by which this laser energy might induce cellular and extracellular changes in vocal fold tissues. In this study, we examined the inflammatory and ECM modulating effects of PDL irradiation on normal vocal fold tissues and cultured vocal fold fibroblasts (VFFs). We evaluated the effects of 585 nm PDL irradiation on inflammatory cytokine and collagen/collagenase gene transcription in normal rat vocal folds in vivo (3-168 hours following delivery of approximately 39.46 J/cm(2) fluence) and VFFs in vitro (3-72 hours following delivery of 4.82 or 9.64 J/cm(2) fluence). We also examined morphological vocal fold tissue changes 3 hours, 1 week, and 1 month post-irradiation. PDL irradiation altered inflammatory cytokine and procollagen/collagenase expression at the transcript level, both in vitro and in vivo. Additionally, PDL irradiation induced an inflammatory repair process in vivo that was completed by 1 month with preservation of normal tissue morphology. PDL irradiation can modulate ECM turnover in phenotypically normal vocal folds. Additional work is required to determine if these findings extend to disordered ECM, such as is seen in vocal fold scar. Lasers Surg. Med. 41:585-594, 2009. (c) 2009 Wiley-Liss, Inc.

Methods for performing fast discrete curvelet transforms of data

DOEpatents

Candes, Emmanuel; Donoho, David; Demanet, Laurent

2010-11-23

Fast digital implementations of the second generation curvelet transform for use in data processing are disclosed. One such digital transformation is based on unequally-spaced fast Fourier transforms (USFFT) while another is based on the wrapping of specially selected Fourier samples. Both digital transformations return a table of digital curvelet coefficients indexed by a scale parameter, an orientation parameter, and a spatial location parameter. Both implementations are fast in the sense that they run in about O(n.sup.2 log n) flops for n by n Cartesian arrays or about O(N log N) flops for Cartesian arrays of size N=n.sup.3; in addition, they are also invertible, with rapid inversion algorithms of about the same complexity.

Transformation optics beyond the manipulation of light trajectories

PubMed Central

Ginis, Vincent; Tassin, Philippe

2015-01-01

Since its inception in 2006, transformation optics has become an established tool to understand and design electromagnetic systems. It provides a geometrical perspective into the properties of light waves without the need for a ray approximation. Most studies have focused on modifying the trajectories of light rays, e.g. beam benders, lenses, invisibility cloaks, etc. In this contribution, we explore transformation optics beyond the manipulation of light trajectories. With a few well-chosen examples, we demonstrate that transformation optics can be used to manipulate electromagnetic fields up to an unprecedented level. In the first example, we introduce an electromagnetic cavity that allows for deep subwavelength confinement of light. The cavity is designed with transformation optics even though the concept of trajectory ceases to have any meaning in a structure as small as this cavity. In the second example, we show that the properties of Cherenkov light emitted in a transformation-optical material can be understood and modified from simple geometric considerations. Finally, we show that optical forces—a quadratic function of the fields—follow the rules of transformation optics too. By applying a folded coordinate transformation to a pair of waveguides, optical forces can be enhanced just as if the waveguides were closer together. With these examples, we open up an entirely new spectrum of devices that can be conceived using transformation optics. PMID:26217057

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

PubMed Central

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

2007-01-01

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

Dynamics of one-state downhill protein folding.

PubMed

Li, Peng; Oliva, Fabiana Y; Naganathan, Athi N; Muñoz, Victor

2009-01-06

The small helical protein BBL has been shown to fold and unfold in the absence of a free energy barrier according to a battery of quantitative criteria in equilibrium experiments, including probe-dependent equilibrium unfolding, complex coupling between denaturing agents, characteristic DSC thermogram, gradual melting of secondary structure, and heterogeneous atom-by-atom unfolding behaviors spanning the entire unfolding process. Here, we present the results of nanosecond T-jump experiments probing backbone structure by IR and end-to-end distance by FRET. The folding dynamics observed with these two probes are both exponential with common relaxation times but have large differences in amplitude following their probe-dependent equilibrium unfolding. The quantitative analysis of amplitude and relaxation time data for both probes shows that BBL folding dynamics are fully consistent with the one-state folding scenario and incompatible with alternative models involving one or several barrier crossing events. At 333 K, the relaxation time for BBL is 1.3 micros, in agreement with previous folding speed limit estimates. However, late folding events at room temperature are an order of magnitude slower (20 micros), indicating a relatively rough underlying energy landscape. Our results in BBL expose the dynamic features of one-state folding and chart the intrinsic time-scales for conformational motions along the folding process. Interestingly, the simple self-averaging folding dynamics of BBL are the exact dynamic properties required in molecular rheostats, thus supporting a biological role for one-state folding.

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.

How Fast is Collapse of Proteins During Folding?

NASA Astrophysics Data System (ADS)

Chahine, J.; Onuchic, J. N.; Socci, N. D.

1998-03-01

Recent experiments in fast folding proteins are now starting to address the question of how fast is collapse relative to the total folding time. Using minimalist models, we are able to investigate the way in which different scenarios of folding can arise depending on the interplay between the collapse order parameter and the order parameter sensitive to specific tertiary contacts. Most of our earlier studies have focused on the limit that collapse is very fast compared to the total folding time. In this work we focus on the opposite limit, i.e., at the folding temperature, collapse and folding occurs simultaneously. The folding mechanism becomes very different in this limit. Particularly, the non-specific collapse transition, that occurs at temperatures higher than the folding temperature for the fast collapse limit, now occurs between the folding and the glass temperature. We show how this transition can be identified and its consequences for the folding kinetics.

Ultrafast hydrogen exchange reveals specific structural events during the initial stages of folding of cytochrome c.

PubMed

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

2014-01-15

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

Pharmacological chaperones facilitate the post-ER transport of recombinant N370S mutant β-glucocerebrosidase in plant cells: Evidence that N370S is a folding mutant

PubMed Central

Babajani, Gholamreza; Tropak, Michael B.; Mahuran, Don J.; Kermode, Allison R.

2012-01-01

Gaucher disease is a prevalent lysosomal storage disease in which affected individuals inherit mutations in the gene (GBA1) encoding lysosomal acid β-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45). One of the most prevalent disease-causing mutations in humans is a N370S missense mutation in the GCase protein. As part of a larger endeavor to study the fate of mutant human proteins expressed in plant cells, the N370S mutant protein along with the wild-type- (WT)-GCase, both equipped with a signal peptide, were synthesized in transgenic tobacco BY2 cells, which do not possess lysosomes. The enzymatic activity of plant-recombinant N370S GCase lines was significantly lower (by 81–95%) than that of the WT-GCase lines. In contrast to the WT-GCase protein, which was efficiently secreted from tobacco BY2 cells, and detected in large amounts in the culture medium, only a small proportion of the N370S GCase was secreted. Pharmacological chaperones such as N-(n-nonyl) deoxynojirimycin and ambroxol increased the steady-state mutant protein levels both inside the plant cells and in the culture medium. These findings contradict the assertion that small molecule chaperones increase N370S GCase activity (as assayed in treated patient cell lysates) by stabilizing the enzyme in the lysosome, and suggest that the mutant protein is impaired in its ability to obtain its functional folded conformation, which is a requirement for exiting the lumen of the ER. PMID:22592100

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…

Effects of long-acting beta adrenergic agonists on vocal fold ion transport.

PubMed

Sivasankar, Mahalakshmi; Blazer-Yost, Bonnie

2009-03-01

Inhaled medications prescribed for the hypersensitive airway typically combine corticosteroids and long-acting beta2 adrenergic agonists (LABAs). The phonatory side effects of these combination treatments are widely recognized. However, there is limited understanding of the physiological changes induced by these medications that underlie the phonatory side effects. The objective of this study was to investigate the distinct effects of corticosteroids and LABAs on vocal fold mucosal physiology. Understanding the physiological changes to the vocal folds after corticosteroid and LABA treatments is necessary to prevent the prevalent vocal decrement associated with these medications. Experimental in vitro design with treatment and control groups. Native porcine vocal fold mucosae (N = 38) were exposed to corticosteroid or LABA treatments. Ion transport was measured continuously at baseline and after treatment. To quantify the nature of ion transport, vocal folds were also treated with chloride and sodium channel inhibitors. Corticosteroid treatment did not alter ion transport. Conversely, exposure to LABAs significantly increased ion transport. This increase in ion transport was transient, observed immediately after treatment in all tissue and associated with increased chloride secretion. The distinct effects of corticosteroids and LABAs on vocal fold physiology have not been examined to date. This study demonstrates that short-term treatment with LABAs, but not corticosteroids, significantly increases ion transport. These findings suggest that one underlying physiological mechanism for phonatory changes associated with inhaled treatments may be related to acute alterations in vocal fold ion transport and surface hydration.

Origami-Inspired Folding of Thick, Rigid Panels

NASA Technical Reports Server (NTRS)

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

2014-01-01

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

Effects of myclobutanil on soil microbial biomass, respiration, and soil nitrogen transformations.

PubMed

Ju, Chao; Xu, Jun; Wu, Xiaohu; Dong, Fengshou; Liu, Xingang; Zheng, Yongquan

2016-01-01

A 3-month-long experiment was conducted to ascertain the effects of different concentrations of myclobutanil (0.4 mg kg(-1) soil [T1]; 1.2 mg kg(-1) soil [T3]; and 4 mg kg(-1) soil [T10]) on soil microbial biomass, respiration, and soil nitrogen transformations using two typical agricultural soils (Henan fluvo-aquic soil and Shanxi cinnamon soil). Soil was sampled after 7, 15, 30, 60, and 90 days of incubation to determine myclobutanil concentration and microbial parameters: soil basal respiration (RB), microbial biomass carbon (MBC) and nitrogen (MBN), NO(-)3-N and NH(+)4-N concentrations, and gene abundance of total bacteria, N2-fixing bacteria, fungi, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB). The half-lives of the different doses of myclobutanil varied from 20.3 to 69.3 d in the Henan soil and from 99 to 138.6 d in the Shanxi soil. In the Henan soil, the three treatments caused different degrees of short-term inhibition of RB and MBC, NH(+)4-N, and gene abundance of total bacteria, fungi, N2-fixing bacteria, AOA, and AOB, with the exception of a brief increase in NO(-)3-N content during the T10 treatment. The MBN (immobilized nitrogen) was not affected. In the Shanxi soil, MBC, the populations of total bacteria, fungi, and N2-fixing bacteria, and NH(+)4-N concentration were not significantly affected by myclobutanil. The RB and MBN were decreased transitorily in the T10 treatment. The NO(-)3-N concentrations and the abundance of both AOA and AOB were erratically stimulated by myclobutanil. Regardless of whether stimulation or suppression occurred, the effects of myclobutanil on the two soil types were short term. In summary, myclobutanil had no long-term negative effects on the soil microbial biomass, respiration, and soil nitrogen transformations in the two types of soil, even at 10-fold the recommended dosage. Copyright © 2015 Elsevier Ltd. All rights reserved.

Folding and translocation of the undecamer of poly-L-leucine across the water-hexane interface. A molecular dynamics study

NASA Technical Reports Server (NTRS)

Chipot, C.; Pohorille, A.

1998-01-01

The undecamer of poly-L-leucine at the water-hexane interface is studied by molecular dynamics simulations. This represents a simple model relevant to folding and insertion of hydrophobic peptides into membranes. The peptide, initially placed in a random coil conformation on the aqueous side of the system, rapidly translocates toward the hexane phase and undergoes interfacial folding into an alpha-helix in the subsequent 36 ns. Folding is nonsequential and highly dynamic. The initially formed helical segment at the N-terminus of the undecamer becomes transiently broken and, subsequently, reforms before the remainder of the peptide folds from the C-terminus. The formation of intramolecular hydrogen bonds during the folding of the peptide is preceded by a dehydration of the participating polar groups, as they become immersed in hexane. Folding proceeds through a short-lived intermediate, a 3(10)-helix, which rapidly interconverts to an alpha-helix. Both helices contribute to the equilibrium ensemble of folded structures. The helical peptide is largely buried in hexane, yet remains adsorbed at the interface. Its preferred orientation is parallel to the interface, although the perpendicular arrangement with the N-terminus immersed in hexane is only slightly less favorable. In contrast, the reversed orientation is highly unfavorable, because it would require dehydration of C-terminus carbonyl groups that do not participate in intramolecular hydrogen bonding. For the same reason, the transfer of the undecamer from the interface to the bulk hexane is also unfavorable. The results suggest that hydrophobic peptides fold in the interfacial region and, simultaneously, translocate into the nonpolar side of the interface. It is further implied that peptide insertion into the membrane is accomplished by rotating from the parallel to the perpendicular orientation, most likely in such a way that the N-terminus penetrates the bilayer.

Accelerated molecular dynamics simulations of protein folding.

PubMed

Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

2015-07-30

Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

Frnakenstein: multiple target inverse RNA folding.

PubMed

Lyngsø, Rune B; Anderson, James W J; Sizikova, Elena; Badugu, Amarendra; Hyland, Tomas; Hein, Jotun

2012-10-09

RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are

Frnakenstein: multiple target inverse RNA folding

PubMed Central

2012-01-01

Background RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. Results In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Conclusions Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures

Magnetic characterisation of folded aeolian sandstones: Interpretation of magnetic fabrics in diamagnetic rocks

NASA Astrophysics Data System (ADS)

Callot, J.-P.; Robion, P.; Sassi, W.; Guiton, M. L. E.; Faure, J.-L.; Daniel, J.-M.; Mengus, J.-M.; Schmitz, J.

2010-12-01

This study provides an original example of exploitation of Anisotropy of Magnetic Susceptibility (AMS) for rocks with weak magnetic susceptibility. Within the upper Weber Sandstone at Split Mountain, Utah, 430 cores from 31 sites were collected for magnetic characterization. The magnetic susceptibility ranges from -10 to 10 μSI, indicating a mostly diamagnetic matrix, with degree of anisotropy up to 1.6. Specific treatment of magnetic susceptibility allows using diamagnetic data. The fabrics are fairly clustered and triaxial. Sedimentary magnetic fabrics show a foliation plane parallel to the lamina of the sand dunes, without defined lineation. Apart from sedimentary fabrics (< 30%), most of the sites display intermediate to tectonic fabrics related to variable degree of strain (> 70%). Magnetic fabric patterns averaged for sites distributed on the anticline are well defined in sub-groups related to the major structural domains of the anticline. The fracture network at Split Mountain is composed of a dominant N120 set and a secondary N035 set. A scenario of strain record is proposed based on the correlation of (1) fracture sets orientation, (2) diagenetic cementation, (3) paleostresses and (4) distribution of magnetic susceptibility anisotropy. Following the Sevier orogeny and N120 fracture set emplacement, the N035 fracture network and AMS signal were recorded during the Laramide Layer Parallel Shortening phase, with local deviation along pre-existing structures, and recorded a partitioning of the strain during early folding, with a maximum horizontal stress axis perpendicular to the fold bounding faults within the fold.

Folding thermodynamics of pseudoknotted chain conformations

PubMed Central

Kopeikin, Zoia; Chen, Shi-Jie

2008-01-01

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. PMID:16674261

Vocal fold hemorrhage: factors predicting recurrence.

PubMed

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

2014-01-01

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

Geometric U-folds in four dimensions

NASA Astrophysics Data System (ADS)

Lazaroiu, C. I.; Shahbazi, C. S.

2018-01-01

We describe a general construction of geometric U-folds compatible with a non-trivial extension of the global formulation of four-dimensional extended supergravity on a differentiable spin manifold. The topology of geometric U-folds depends on certain flat fiber bundles which encode how supergravity fields are globally glued together. We show that smooth non-trivial U-folds of this type can exist only in theories where both the scalar and space-time manifolds have non-trivial fundamental group and in addition the scalar map of the solution is homotopically non-trivial. Consistency with string theory requires smooth geometric U-folds to be glued using subgroups of the effective discrete U-duality group, implying that the fundamental group of the scalar manifold of such solutions must be a subgroup of the latter. We construct simple examples of geometric U-folds in a generalization of the axion-dilaton model of \

Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice.

PubMed

Prakash, Thazha P; Graham, Mark J; Yu, Jinghua; Carty, Rick; Low, Audrey; Chappell, Alfred; Schmidt, Karsten; Zhao, Chenguang; Aghajan, Mariam; Murray, Heather F; Riney, Stan; Booten, Sheri L; Murray, Susan F; Gaus, Hans; Crosby, Jeff; Lima, Walt F; Guo, Shuling; Monia, Brett P; Swayze, Eric E; Seth, Punit P

2014-07-01

Triantennary N-acetyl galactosamine (GalNAc, GN3: ), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances the potency of second-generation gapmer antisense oligonucleotides (ASOs) 6-10-fold in mouse liver. When combined with next-generation ASO designs comprised of short S-cEt (S-2'-O-Et-2',4'-bridged nucleic acid) gapmer ASOs, ∼ 60-fold enhancement in potency relative to the parent MOE (2'-O-methoxyethyl RNA) ASO was observed. GN3: -conjugated ASOs showed high affinity for mouse ASGPR, which results in enhanced ASO delivery to hepatocytes versus non-parenchymal cells. After internalization into cells, the GN3: -ASO conjugate is metabolized to liberate the parent ASO in the liver. No metabolism of the GN3: -ASO conjugate was detected in plasma suggesting that GN3: acts as a hepatocyte targeting prodrug that is detached from the ASO by metabolism after internalization into the liver. GalNAc conjugation also enhanced potency and duration of the effect of two ASOs targeting human apolipoprotein C-III and human transthyretin (TTR) in transgenic mice. The unconjugated ASOs are currently in late stage clinical trials for the treatment of familial chylomicronemia and TTR-mediated polyneuropathy. The ability to translate these observations in humans offers the potential to improve therapeutic index, reduce cost of therapy and support a monthly dosing schedule for therapeutic suppression of gene expression in the liver using ASOs. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

Guiding the folding pathway of DNA origami.

PubMed

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

2015-09-03

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

A new approach to geometrical measurements in an animal model of vocal fold scar.

PubMed

Jabbour, Noel; Krishna, Priya D; Osborne, James; Rosen, Clark A

2009-01-01

A standard method for quantifying the geometric properties of vocal folds has not been widely adopted. An ideal method of geometrical measurement should effectively quantify the dimensions of the medial vibratory portion of the vocal fold, should be easily performed, should yield consistent results, and should be readily available at little to no cost. We have developed a new approach for geometrical measurements to meet these goals. The objective of this study is to describe this new approach and to assess its effectiveness in a canine model of vocal fold scar. One hundred thirty-five mid-membranous coronal sections of vocal folds from 10 canines (five with unilateral surgical scarring) were examined by light microscopy; digital images were captured. ImageJ was used to measure a variety of described parameters. Comparison between scarred vocal folds and control vocal folds was made. At least 20% of the slides for each vocal fold were randomly selected (n=42) for repeat measurements of interrater and intrarater reliability. A statistically significant difference between scarred and control vocal folds was obtained for horizontal distance (P<0.001), vertical distance (P=0.005), area (P<0.001), mean optical density (OD) (P<0.001), and OD at defined points along the length of the vocal fold (P< or =0.009). Reliability calculations for intrarater and interrater measurements ranged from r=0.845 to r=0.994 and from r=0.734 to r=0.976, respectively. The proposed approach for geometrical measurements meets the intended objectives in a canine model of vocal fold scar. Future work is needed to apply this approach to other model systems.

A rabbit vocal fold laser scarring model for testing lamina propria tissue engineering therapies

PubMed Central

Mau, Ted; Du, Mindy; Xu, Chet C.

2015-01-01

Objectives/Hypothesis To develop a vocal fold scarring model using an ablative laser in the rabbit as a platform for testing bioengineered therapies for missing or damaged lamina propria. Study Design Prospective controlled animal study. Methods An optimal laser energy level was first determined by assessing the depths of vocal fold injury created by a Holmium:YAG laser at various energy levels on fresh cadaveric rabbit larynges. The selected energy level was then used to create controlled unilateral injuries in vocal folds of New Zealand white rabbits, with the contralateral folds serving as uninjured controls. After 4 weeks, the larynges were harvested and subjected to excised-larynx phonation with high-speed imaging and immunohistochemical staining for collagen types I and III, elastin, and hyaluronic acid (HA) with quantitative histological analysis. Results 1.8 joules produced full-thickness injury of the lamina propria without extensive muscle injury. After 4 weeks, the injured vocal folds vibrated with reduced amplitude (P = 0.036) in excised-larynx phonation compared to normal vocal folds. The injured vocal folds contained a higher relative density of collagen type I (P = 0.004), higher elastin (P = 0.022), and lower HA (P = 0.030) compared to normal controls. Collagen type III was unchanged. Conclusions With its potential for higher precision of injury, this laser vocal fold scarring model may serve as an alternative to scarring produced by cold instruments for studying the effects of vocal fold lamina propria bioengineered therapies. Level of Evidence N/A. PMID:24715695

Predicting RNA pseudoknot folding thermodynamics

PubMed Central

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

The mechanism of folding robustness revealed by the crystal structure of extra-superfolder GFP.

PubMed

Choi, Jae Young; Jang, Tae-Ho; Park, Hyun Ho

2017-01-01

Stability of green fluorescent protein (GFP) is sometimes important for a proper practical application of this protein. Random mutagenesis and targeted mutagenesis have been used to create better-folded variants of GFP, including recently reported extra-superfolder GFP. Our aim was to determine the crystal structure of extra-superfolder GFP, which is more robustly folded and stable than GFP and superfolder GFP. The structural and structure-based mutagenesis analyses revealed that some of the mutations that created extra-superfolder GFP (F46L, E126K, N149K, and S208L) contribute to folding robustness by stabilizing extra-superfolder GFP with various noncovalent bonds. © 2016 Federation of European Biochemical Societies.

The PYRIN domain: A member of the death domain-fold superfamily

PubMed Central

Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.

2001-01-01

PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682

Rapid measurement of 3J(H N-H alpha) and 3J(N-H beta) coupling constants in polypeptides.

PubMed

Barnwal, Ravi Pratap; Rout, Ashok K; Chary, Kandala V R; Atreya, Hanudatta S

2007-12-01

We present two NMR experiments, (3,2)D HNHA and (3,2)D HNHB, for rapid and accurate measurement of 3J(H N-H alpha) and 3J(N-H beta) coupling constants in polypeptides based on the principle of G-matrix Fourier transform NMR spectroscopy and quantitative J-correlation. These experiments, which facilitate fast acquisition of three-dimensional data with high spectral/digital resolution and chemical shift dispersion, will provide renewed opportunities to utilize them for sequence specific resonance assignments, estimation/characterization of secondary structure with/without prior knowledge of resonance assignments, stereospecific assignment of prochiral groups and 3D structure determination, refinement and validation. Taken together, these experiments have a wide range of applications from structural genomics projects to studying structure and folding in polypeptides.

Mechanically controlling the reversible phase transformation from zinc blende to wurtzite in AlN

DOE PAGES

Li, Zhen; Yadav, Satyesh; Chen, Youxing; ...

2017-04-10

III–V and other binary octet semiconductors often take two phase forms—wurtzite (wz) and zinc blende (zb) crystal structures—with distinct functional performance at room temperature. Here, we investigate how to control the synthesized phase structure to either wz or zb phase by tuning the interfacial strain by taking AlN as a representative III–V compound. Furthermore, by applying in situ mechanical tests at atomic scale in a transmission electron microscope, we observed the reversible phase transformation from zb to wz, and characterized the transition path—the collective glide of Shockley partials on every two {111} planes of the zb AlN.

Differences Between a Single- and a Double-Folding Nucleus-^{9}Be Optical Potential

NASA Astrophysics Data System (ADS)

Bonaccorso, A.; Carstoiu, F.; Charity, R. J.; Kumar, R.; Salvioni, G.

2016-05-01

We have recently constructed two very successful n-^9Be optical potentials (Bonaccorso and Charity in Phys Rev C89:024619, 2014). One by the Dispersive Optical Model (DOM) method and the other (AB) fully phenomenological. The two potentials have strong surface terms in common for both the real and the imaginary parts. This feature makes them particularly suitable to build a single-folded (light-) nucleus-^9Be optical potential by using ab-initio projectile densities such as those obtained with the VMC method (Wiringa http://www.phy.anl.gov/theory/research/density/). On the other hand, a VMC density together with experimental nucleon-nucleon cross-sections can be used also to obtain a neutron and/or proton-^9Be imaginary folding potential. We will use here an ab-initio VMC density (Wiringa http://www.phy.anl.gov/theory/research/density/) to obtain both a n-^9Be single-folded potential and a nucleus-nucleus double-folded potential. In this work we report on the cases of ^8B, ^8Li and ^8C projectiles. Our approach could be the basis for a systematic study of optical potentials for light exotic nuclei scattering on such light targets. Some of the projectiles studied are cores of other exotic nuclei for which neutron knockout has been used to extract spectroscopic information. For those cases, our study will serve to make a quantitative assessment of the core-target part of the reaction description, in particular its localization.

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

PubMed

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

2018-04-24

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

General mechanism of two-state protein folding kinetics.

PubMed

Rollins, Geoffrey C; Dill, Ken A

2014-08-13

We describe here a general model of the kinetic mechanism of protein folding. In the Foldon Funnel Model, proteins fold in units of secondary structures, which form sequentially along the folding pathway, stabilized by tertiary interactions. The model predicts that the free energy landscape has a volcano shape, rather than a simple funnel, that folding is two-state (single-exponential) when secondary structures are intrinsically unstable, and that each structure along the folding path is a transition state for the previous structure. It shows how sequential pathways are consistent with multiple stochastic routes on funnel landscapes, and it gives good agreement with the 9 order of magnitude dependence of folding rates on protein size for a set of 93 proteins, at the same time it is consistent with the near independence of folding equilibrium constant on size. This model gives estimates of folding rates of proteomes, leading to a median folding time in Escherichia coli of about 5 s.

General Mechanism of Two-State Protein Folding Kinetics

PubMed Central

Rollins, Geoffrey C.; Dill, Ken A.

2016-01-01

We describe here a general model of the kinetic mechanism of protein folding. In the Foldon Funnel Model, proteins fold in units of secondary structures, which form sequentially along the folding pathway, stabilized by tertiary interactions. The model predicts that the free energy landscape has a volcano shape, rather than a simple funnel, that folding is two-state (single-exponential) when secondary structures are intrinsically unstable, and that each structure along the folding path is a transition state for the previous structure. It shows how sequential pathways are consistent with multiple stochastic routes on funnel landscapes, and it gives good agreement with the 9 order of magnitude dependence of folding rates on protein size for a set of 93 proteins, at the same time it is consistent with the near independence of folding equilibrium constant on size. This model gives estimates of folding rates of proteomes, leading to a median folding time in Escherichia coli of about 5 s. PMID:25056406

Vocal Fold Surface Hydration: A review

PubMed Central

Leydon, Ciara; Sivasankar, Mahalakshmi; Falciglia, Danielle Lodewyck; Atkins, Christopher; Fisher, Kimberly V.

2009-01-01

Vocal fold surface liquid homeostasis contributes to optimal vocal physiology. In this paper we review emerging evidence that vocal fold surface liquid is maintained in part by salt and water fluxes across the epithelium. Based on recent immunolocalization and electrophysiological findings, we describe a transcellular pathway as one mechanism for regulating superficial vocal fold hydration. We propose that the pathway includes the sodium-potassium pump, sodium-potassium-chloride cotransporter, epithelial sodium channels, cystic fibrosis transmembrane regulator chloride channels, and aquaporin water channels. By integrating knowledge of the regulating mechanisms underlying ion and fluid transport with observations from hydration challenges and treatments using in vitro and in vivo studies, we provide a theoretical basis for understanding how environmental and behavioral challenges and clinical interventions may modify vocal fold surface liquid composition. We present converging evidence that clinical protocols directed at facilitating vocal fold epithelial ion and fluid transport may benefit healthy speakers, those with voice disorders, and those at risk for voice disorders. PMID:19111440

Viscoelasticity of rabbit vocal folds after injection augmentation.

PubMed

Dahlqvist, Ake; Gärskog, Ola; Laurent, Claude; Hertegård, Stellan; Ambrosio, Luigi; Borzacchiello, Assunta

2004-01-01

Vocal fold function is related to the viscoelasticity of the vocal fold tissue. Augmentation substances used for injection treatment of voice insufficiency may alter the viscoelastic properties of vocal folds and their vibratory capacity. The objective was to compare the mechanical properties (viscoelasticity) of various injectable substances and the viscoelasticity of rabbit vocal folds, 6 months after injection with one of these substances. Animal model. Cross-linked collagen (Zyplast), double cross-linked hyaluronan (hylan B gel), dextranomers in hyaluronan (DHIA), and polytetrafluoroethylene (Teflon) were injected into rabbit vocal folds. Six months after the injection, the animals were killed and the right- and left-side vocal folds were removed. Dynamic viscosity of the injected substances and the vocal folds was measured with a Bohlin parallel-plate rheometer during small-amplitude oscillation. All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Hylan B gel and DiHA showed the lowest dynamic viscosity values, and vocal folds injected with these substances also showed the lowest dynamic viscosity (similar to noninjected control samples). Teflon (and vocal folds injected with Teflon) showed the highest dynamic viscosity values, followed by the collagen samples. Substances with low viscoelasticity alter the mechanical properties of the vocal fold to a lesser degree than substances with a high viscoelasticity. The data indicated that hylan B gel and DiHA render the most natural viscoelastic properties to the vocal folds. These substances seem to be appropriate for preserving or restoring the vibratory capacity of the vocal folds when glottal insufficiency is treated with augmentative injections.

Muscular anatomy of the human ventricular folds.

PubMed

Moon, Jerald; Alipour, Fariborz

2013-09-01

Our purpose in this study was to better understand the muscular anatomy of the ventricular folds in order to help improve biomechanical modeling of phonation and to better understand the role of these muscles during phonatory and nonphonatory tasks. Four human larynges were decalcified, sectioned coronally from posterior to anterior by a CryoJane tape transfer system, and stained with Masson's trichrome. The total and relative areas of muscles observed in each section were calculated and used for characterizing the muscle distribution within the ventricular folds. The ventricular folds contained anteriorly coursing thyroarytenoid and ventricularis muscle fibers that were in the lower half of the ventricular fold posteriorly, and some ventricularis muscle was evident in the upper and lateral portions of the fold more anteriorly. Very little muscle tissue was observed in the medial half of the fold, and the anterior half of the ventricular fold was largely devoid of any muscle tissue. All 4 larynges contained muscle bundles that coursed superiorly and medially through the upper half of the fold, toward the lateral margin of the epiglottis. Although variability of expression was evident, a well-defined thyroarytenoid muscle was readily apparent lateral to the arytenoid cartilage in all specimens.

Exact folded-band chaotic oscillator.

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.

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…

Protein Folding Using a Vortex Fluidic Device.

PubMed

Britton, Joshua; Smith, Joshua N; Raston, Colin L; Weiss, Gregory A

2017-01-01

Essentially all biochemistry and most molecular biology experiments require recombinant proteins. However, large, hydrophobic proteins typically aggregate into insoluble and misfolded species, and are directed into inclusion bodies. Current techniques to fold proteins recovered from inclusion bodies rely on denaturation followed by dialysis or rapid dilution. Such approaches can be time consuming, wasteful, and inefficient. Here, we describe rapid protein folding using a vortex fluidic device (VFD). This process uses mechanical energy introduced into thin films to rapidly and efficiently fold proteins. With the VFD in continuous flow mode, large volumes of protein solution can be processed per day with 100-fold reductions in both folding times and buffer volumes.

Rational Degenerations of M-Curves, Totally Positive Grassmannians and KP2-Solitons

NASA Astrophysics Data System (ADS)

Abenda, Simonetta; Grinevich, Petr G.

2018-03-01

We establish a new connection between the theory of totally positive Grassmannians and the theory of M-curves using the finite-gap theory for solitons of the KP equation. Here and in the following KP equation denotes the Kadomtsev-Petviashvili 2 equation [see (1)], which is the first flow from the KP hierarchy. We also assume that all KP times are real. We associate to any point of the real totally positive Grassmannian Gr^{tp} (N,M) a reducible curve which is a rational degeneration of an M-curve of minimal genus {g=N(M-N)} , and we reconstruct the real algebraic-geometric data á la Krichever for the underlying real bounded multiline KP soliton solutions. From this construction, it follows that these multiline solitons can be explicitly obtained by degenerating regular real finite-gap solutions corresponding to smooth M-curves. In our approach, we rule the addition of each new rational component to the spectral curve via an elementary Darboux transformation which corresponds to a section of a specific projection Gr^{tp} (r+1,M-N+r+1)\\mapsto Gr^{tp} (r,M-N+r).

Loss of N-Cadherin Expression in Tumor Transplants Produced From As+3- and Cd+2-Transformed Human Urothelial (UROtsa) Cell Lines.

PubMed

Sandquist, Elizabeth J; Somji, Seema; Dunlevy, Jane R; Garrett, Scott H; Zhou, Xu Dong; Slusser-Nore, Andrea; Sens, Donald A

2016-01-01

Epithelial to mesenchymal transition is a process in which a cell experiences a loss of epithelial cell characteristics and acquires a more mesenchymal cell phenotype. In cancer, epithelial to mesenchymal transition has been proposed to play an important role during specific stages of tumor progression. The role epithelial to mesenchymal transition and mesenchymal to epithelial transition might play in toxicant-induced urothelial cancer is unknown. Real-time PCR, Western blotting, immuno-histochemistry and immuno-fluorescence were used to determine the expression of E- and N-cadherin in the UROtsa parent, the As+3- and Cd+2-transformed cell lines, the spheroids isolated from these cell lines as well as the tumor heterotransplants that were produced by the injection of the transformed cells into immune compromised mice. This study showed that N-cadherin expression was increased in 6 As+3- and 7 Cd+2- transformed cell lines generated from human urothelial cells (UROtsa). The expression varied within each cell line, with 10% to 95% of the cells expressing N-cadherin. Tumors produced from these cell lines showed no expression of the N-cadherin protein. Spheroids which are made up of putative cancer initiating cells produced from these cell lines showed only background expression of N-cadherin mRNA, increased expression of aldehyde dehydrogenase 1 mRNA and produced tumors which did not express N-cadherin. There was no change in the expression of E-cadherin in the tumors, and the tumors formed by all the As+3 and Cd+2-transformed cell lines and cancer initiating cells stained intensely and uniformly for E-cadherin. The finding that the cells expressing N-cadherin gave rise to tumors with no expression of N-cadherin is in agreement with the classical view of epithelial to mesenchymal transition. Epithelial to mesenchymal transition and N-cadherin are associated with dissemination and not with the ability to establish new tumor growth. Mesenchymal to epithelial transition

Viscoelastic properties of rabbit vocal folds after augmentation.

PubMed

Hertegård, Stellan; Dahlqvist, Ake; Laurent, Claude; Borzacchiello, Assunta; Ambrosio, Luigi

2003-03-01

Vocal fold function is closely related to tissue viscoelasticity. Augmentation substances may alter the viscoelastic properties of vocal fold tissues and hence their vibratory capacity. We sought to investigate the viscoelastic properties of rabbit vocal folds in vitro after injections of various augmentation substances. Polytetrafluoroethylene (Teflon), cross-linked collagen (Zyplast), and cross-linked hyaluronan, hylan b gel (Hylaform) were injected into the lamina propria and the thyroarytenoid muscle of rabbit vocal folds. Dynamic viscosity of the injected vocal fold as a function of frequency was measured with a Bohlin parallel-plate rheometer during small-amplitude oscillation. All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Vocal fold samples injected with hylan b gel showed the lowest dynamic viscosity, quite close to noninjected control samples. Vocal folds injected with polytetrafluoroethylene showed the highest dynamic viscosity followed by the collagen samples. The data indicated that hylan b gel in short-term renders the most natural viscoelastic properties to the vocal fold among the substances tested. This is of importance to restore/preserve the vibratory capacity of the vocal folds when glottal insufficiency is treated with injections.

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies

PubMed Central

Wingstrand, Vibe Lindeblad; Jensen, David H.; Bork, Kristian; Sebbesen, Lars; Balle, Jesper; Fischer-Nielsen, Anne; von Buchwald, Christian

2016-01-01