Geometrically engineering the standard model: Locally unfolding three families out of E8

International Nuclear Information System (INIS)

Bourjaily, Jacob L.

2007-01-01

This paper extends and builds upon the results of [J. L. Bourjaily, arXiv:0704.0444.], in which we described how to use the tools of geometrical engineering to deform geometrically engineered grand unified models into ones with lower symmetry. This top-down unfolding has the advantage that the relative positions of singularities giving rise to the many 'low-energy' matter fields are related by only a few parameters which deform the geometry of the unified model. And because the relative positions of singularities are necessary to compute the superpotential, for example, this is a framework in which the arbitrariness of geometrically engineered models can be greatly reduced. In [J. L. Bourjaily, arXiv:0704.0444.], this picture was made concrete for the case of deforming the representations of an SU 5 model into their standard model content. In this paper we continue that discussion to show how a geometrically engineered 16 of SO 10 can be unfolded into the standard model, and how the three families of the standard model uniquely emerge from the unfolding of a single, isolated E 8 singularity

Network Unfolding Map by Vertex-Edge Dynamics Modeling.

Science.gov (United States)

Verri, Filipe Alves Neto; Urio, Paulo Roberto; Zhao, Liang

2018-02-01

The emergence of collective dynamics in neural networks is a mechanism of the animal and human brain for information processing. In this paper, we develop a computational technique using distributed processing elements in a complex network, which are called particles, to solve semisupervised learning problems. Three actions govern the particles' dynamics: generation, walking, and absorption. Labeled vertices generate new particles that compete against rival particles for edge domination. Active particles randomly walk in the network until they are absorbed by either a rival vertex or an edge currently dominated by rival particles. The result from the model evolution consists of sets of edges arranged by the label dominance. Each set tends to form a connected subnetwork to represent a data class. Although the intrinsic dynamics of the model is a stochastic one, we prove that there exists a deterministic version with largely reduced computational complexity; specifically, with linear growth. Furthermore, the edge domination process corresponds to an unfolding map in such way that edges "stretch" and "shrink" according to the vertex-edge dynamics. Consequently, the unfolding effect summarizes the relevant relationships between vertices and the uncovered data classes. The proposed model captures important details of connectivity patterns over the vertex-edge dynamics evolution, in contrast to the previous approaches, which focused on only vertex or only edge dynamics. Computer simulations reveal that the new model can identify nonlinear features in both real and artificial data, including boundaries between distinct classes and overlapping structures of data.

Mechanics of collective unfolding

Science.gov (United States)

Caruel, M.; Allain, J.-M.; Truskinovsky, L.

2015-03-01

Mechanically induced unfolding of passive crosslinkers is a fundamental biological phenomenon encountered across the scales from individual macro-molecules to cytoskeletal actin networks. In this paper we study a conceptual model of athermal load-induced unfolding and use a minimalistic setting allowing one to emphasize the role of long-range interactions while maintaining full analytical transparency. Our model can be viewed as a description of a parallel bundle of N bistable units confined between two shared rigid backbones that are loaded through a series spring. We show that the ground states in this model correspond to synchronized, single phase configurations where all individual units are either folded or unfolded. We then study the fine structure of the wiggly energy landscape along the reaction coordinate linking the two coherent states and describing the optimal mechanism of cooperative unfolding. Quite remarkably, our study shows the fundamental difference in the size and the structure of the folding-unfolding energy barriers in the hard (fixed displacements) and soft (fixed forces) loading devices which persists in the continuum limit. We argue that both, the synchronization and the non-equivalence of the mechanical responses in hard and soft devices, have their origin in the dominance of long-range interactions. We then apply our minimal model to skeletal muscles where the power-stroke in acto-myosin crossbridges can be interpreted as passive folding. A quantitative analysis of the muscle model shows that the relative rigidity of myosin backbone provides the long-range interaction mechanism allowing the system to effectively synchronize the power-stroke in individual crossbridges even in the presence of thermal fluctuations. In view of the prototypical nature of the proposed model, our general conclusions pertain to a variety of other biological systems where elastic interactions are mediated by effective backbones.

Thermal unfolding of barstar and the properties of interfacial water around the unfolded forms

Energy Technology Data Exchange (ETDEWEB)

Pal, Somedatta; Bandyopadhyay, Sanjoy, E-mail: sanjoy@chem.iitkgp.ernet.in [Molecular Modeling Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur - 721302 (India)

2013-12-21

Identification of the intermediates along the folding-unfolding pathways and probing their interactions with surrounding solvent are two important but relatively unexplored issues in protein folding. In this work, we have carried out atomistic molecular dynamics simulations to study the thermal unfolding of barstar in aqueous solution from its folded native form at two different temperatures (400 K and 450 K). The calculations at 400 K reveal partial unfolding of two α-helices (helix-1 and helix-2) and their interconnecting loop. At 450 K, on the other hand, the entire protein attains an expanded flexible conformation due to disruption of a large fraction of tertiary contacts and breaking of almost all the secondary structures. These two disordered structures obtained at such high temperatures are then studied around room temperature to probe their influence on the properties of surrounding solvent. It is found that though the unfolding of the protein in general leads to increasingly hydrated interface, but new structural motifs with locally dehydrated interface may also form during the structural transition. Additionally, independent of the conformational state of the protein, its influence on surrounding solvent has been found to be restricted to the first hydration layer.

Thermal dissociation and unfolding of insulin

DEFF Research Database (Denmark)

Huus, Kasper; Havelund, Svend; Olsen, Helle B

2005-01-01

The thermal stability of human insulin was studied by differential scanning microcalorimetry and near-UV circular dichroism as a function of zinc/protein ratio, to elucidate the dissociation and unfolding processes of insulin in different association states. Zinc-free insulin, which is primarily...... dimeric at room temperature, unfolded at approximately 70 degrees C. The two monomeric insulin mutants Asp(B28) and Asp(B9),Glu(B27) unfolded at higher temperatures, but with enthalpies of unfolding that were approximately 30% smaller. Small amounts of zinc caused a biphasic thermal denaturation pattern...... of insulin. The biphasic denaturation is caused by a redistribution of zinc ions during the heating process and results in two distinct transitions with T(m)'s of approximately 70 and approximately 87 degrees C corresponding to monomer/dimer and hexamer, respectively. At high zinc concentrations (>or=5 Zn(2...

Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.

Science.gov (United States)

Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J

2018-05-25

Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Defining a methodology for benchmarking spectrum unfolding codes

International Nuclear Information System (INIS)

Meyer, W.; Kirmser, P.G.; Miller, W.H.; Hu, K.K.

1976-01-01

It has long been recognized that different neutron spectrum unfolding codes will produce significantly different results when unfolding the same measured data. In reviewing the results of such analyses it has been difficult to determine which result if any is the best representation of what was measured by the spectrometer detector. A proposal to develop a benchmarking procedure for spectrum unfolding codes is presented. The objective of the procedure will be to begin to develop a methodology and a set of data with a well established and documented result that could be used to benchmark and standardize the various unfolding methods and codes. It is further recognized that development of such a benchmark must involve a consensus of the technical community interested in neutron spectrum unfolding

Cotranslocational processing of the protein substrate calmodulin by an AAA+ unfoldase occurs via unfolding and refolding intermediates.

Science.gov (United States)

Augustyniak, Rafal; Kay, Lewis E

2018-05-22

Protein remodeling by AAA+ enzymes is central for maintaining proteostasis in a living cell. However, a detailed structural description of how this is accomplished at the level of the substrate molecules that are acted upon is lacking. Here, we combine chemical cross-linking and methyl transverse relaxation-optimized NMR spectroscopy to study, at atomic resolution, the stepwise unfolding and subsequent refolding of the two-domain substrate calmodulin by the VAT AAA+ unfoldase from Thermoplasma acidophilum By engineering intermolecular disulphide bridges between the substrate and VAT we trap the substrate at different stages of translocation, allowing structural studies throughout the translocation process. Our results show that VAT initiates substrate translocation by pulling on intrinsically unstructured N or C termini of substrate molecules without showing specificity for a particular amino acid sequence. Although the B1 domain of protein G is shown to unfold cooperatively, translocation of calmodulin leads to the formation of intermediates, and these differ on an individual domain level in a manner that depends on whether pulling is from the N or C terminus. The approach presented generates an atomic resolution picture of substrate unfolding and subsequent refolding by unfoldases that can be quite different from results obtained via in vitro denaturation experiments.

Uncertainty analysis of dosimetry spectrum unfolding

International Nuclear Information System (INIS)

Perey, F.G.

1977-01-01

The propagation of uncertainties in the input data is analyzed for the usual dosimetry unfolding solution. A new formulation of the dosimetry unfolding problem is proposed in which the most likely value of the spectrum is obtained. The relationship of this solution to the usual one is discussed

Unfolding four-helix bundles

Science.gov (United States)

Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

2011-03-01

A geometrical model has been developed to describe the early stages of unfolding of cytochromes c‧ and c-b562 . Calculations are based on a step-wise extension of the polypeptide chain subject to the constraint that the spatial relationship among the residues of each triplet is fixed by the native-state crystallographic data. The response of each protein to these structural perturbations allows the evolution of each of the four helices in these two proteins to be differentiated. It is found that the two external helices in c‧ unfold before its two internal helices, whereas exactly the opposite behaviour is demonstrated by c-b562 . Each of these cytochromes has an extended, internal, non-helical ('turning') region that initially lags behind the most labile helix but then, at a certain stage (identified for each cytochrome), unravels before any of the four helices present in the native structure. It is believed that these predictions will be useful in guiding future experimental studies on the unfolding of these two cytochromes.

UNFOLDED REGULAR AND SEMI-REGULAR POLYHEDRA

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IONIŢĂ Elena

2015-06-01

Full Text Available This paper proposes a presentation unfolding regular and semi-regular polyhedra. Regular polyhedra are convex polyhedra whose faces are regular and equal polygons, with the same number of sides, and whose polyhedral angles are also regular and equal. Semi-regular polyhedra are convex polyhedra with regular polygon faces, several types and equal solid angles of the same type. A net of a polyhedron is a collection of edges in the plane which are the unfolded edges of the solid. Modeling and unfolding Platonic and Arhimediene polyhedra will be using 3dsMAX program. This paper is intended as an example of descriptive geometry applications.

Unfolding Simulations of Holomyoglobin from Four Mammals: Identification of Intermediates and β-Sheet Formation from Partially Unfolded States

DEFF Research Database (Denmark)

Dasmeh, Pouria; Kepp, Kasper Planeta

2013-01-01

simulations of holoMb and the first comparative study of unfolding of protein orthologs from different species (sperm whale, pig, horse, and harbor seal). We also provide new interpretations of experimental mean molecular ellipticities of myoglobin intermediates, notably correcting for random coil and number...... of helices in intermediates. The simulated holoproteins at 310 K displayed structures and dynamics in agreement with crystal structures (Rg ,1.48–1.51 nm, helicity ,75%). At 400 K, heme was not lost, but some helix loss was observed in pig and horse, suggesting that these helices are less stable......Myoglobin (Mb) is a centrally important, widely studied mammalian protein. While much work has investigated multi-step unfolding of apoMb using acid or denaturant, holomyoglobin unfolding is poorly understood despite its biological relevance. We present here the first systematic unfolding...

Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites.

Science.gov (United States)

Elam, W Austin; Schrank, Travis P; Campagnolo, Andrew J; Hilser, Vincent J

2013-04-01

Intrinsically disordered (ID) proteins function in the absence of a unique stable structure and appear to challenge the classic structure-function paradigm. The extent to which ID proteins take advantage of subtle conformational biases to perform functions, and whether signals for such mechanism can be identified in proteome-wide studies is not well understood. Of particular interest is the polyproline II (PII) conformation, suggested to be highly populated in unfolded proteins. We experimentally determine a complete calorimetric propensity scale for the PII conformation. Projection of the scale into representative eukaryotic proteomes reveals significant PII bias in regions coding for ID proteins. Importantly, enrichment of PII in ID proteins, or protein segments, is also captured by other PII scales, indicating that this enrichment is robustly encoded and universally detectable regardless of the method of PII propensity determination. Gene ontology (GO) terms obtained using our PII scale and other scales demonstrate a consensus for molecular functions performed by high PII proteins across the proteome. Perhaps the most striking result of the GO analysis is conserved enrichment (P ontology reveals an enrichment of PII bias near disordered phosphorylation sites that is conserved throughout eukaryotes. Copyright © 2013 The Protein Society.

Experience with using unfolding procedures in ATLAS

CERN Document Server

Biondi, Silvia; The ATLAS collaboration

2016-01-01

In ATLAS, several unfolding methods are used to correct experimental measurements for detector effects, like acceptance and resolution. These methods use as input the raw experimental distributions, as well as Monte Carlo simulation for the description of the detector effects. The systematic uncertainties associated to the various unfolding methods are evaluated. The statistical and systematic uncertainties affecting the raw measurements and/or the simulation are propagated through the unfolding procedure. The resulting corrected measurements with their uncertainties can be directly compared with the corresponding theoretical predictions.

Salt bridge as a gatekeeper against partial unfolding.

Science.gov (United States)

Hinzman, Mark W; Essex, Morgan E; Park, Chiwook

2016-05-01

Salt bridges are frequently observed in protein structures. Because the energetic contribution of salt bridges is strongly dependent on the environmental context, salt bridges are believed to contribute to the structural specificity rather than the stability. To test the role of salt bridges in enhancing structural specificity, we investigated the contribution of a salt bridge to the energetics of native-state partial unfolding in a cysteine-free version of Escherichia coli ribonuclease H (RNase H*). Thermolysin cleaves a protruding loop of RNase H(*) through transient partial unfolding under native conditions. Lys86 and Asp108 in RNase H(*) form a partially buried salt bridge that tethers the protruding loop. Investigation of the global stability of K86Q/D108N RNase H(*) showed that the salt bridge does not significantly contribute to the global stability. However, K86Q/D108N RNase H(*) is greatly more susceptible to proteolysis by thermolysin than wild-type RNase H(*) is. The free energy for partial unfolding determined by native-state proteolysis indicates that the salt bridge significantly increases the energy for partial unfolding by destabilizing the partially unfolded form. Double mutant cycles with single and double mutations of the salt bridge suggest that the partially unfolded form is destabilized due to a significant decrease in the interaction energy between Lys86 and Asp108 upon partial unfolding. This study demonstrates that, even in the case that a salt bridge does not contribute to the global stability, the salt bridge may function as a gatekeeper against partial unfolding that disturbs the optimal geometry of the salt bridge. © 2016 The Protein Society.

Applied multidimensional scaling and unfolding

CERN Document Server

Borg, Ingwer; Mair, Patrick

2018-01-01

This book introduces multidimensional scaling (MDS) and unfolding as data analysis techniques for applied researchers. MDS is used for the analysis of proximity data on a set of objects, representing the data as distances between points in a geometric space (usually of two dimensions). Unfolding is a related method that maps preference data (typically evaluative ratings of different persons on a set of objects) as distances between two sets of points (representing the persons and the objects, resp.). This second edition has been completely revised to reflect new developments and the coverage of unfolding has also been substantially expanded. Intended for applied researchers whose main interests are in using these methods as tools for building substantive theories, it discusses numerous applications (classical and recent), highlights practical issues (such as evaluating model fit), presents ways to enforce theoretical expectations for the scaling solutions, and addresses the typical mistakes that MDS/unfoldin...

A broadband gamma-ray spectrometry using novel unfolding algorithms for characterization of laser wakefield-generated betatron radiation

Energy Technology Data Exchange (ETDEWEB)

Jeon, Jong Ho, E-mail: jhjeon07@ibs.re.kr; Nakajima, Kazuhisa, E-mail: naka115@dia-net.ne.jp; Pathak, Vishwa Bandhu; Cho, Myung Hoon; Yoo, Byung Ju; Shin, Kang Woo [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 500-712 (Korea, Republic of); Kim, Hyung Taek; Sung, Jae Hee; Lee, Seung Ku; Choi, Il Woo [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 500-712 (Korea, Republic of); Advanced Photonics Research Institute, GIST, Gwangju 500-712 (Korea, Republic of); Rhee, Yong Joo [Nuclear Data Center, Korea Atomic Energy Research Institute, Daejeon 305-353 (Korea, Republic of); Shin, Jung Hun; Jo, Sung Ha [Advanced Photonics Research Institute, GIST, Gwangju 500-712 (Korea, Republic of); Hojbota, Calin; Cho, Byeoung Ick; Nam, Chang Hee [Center for Relativistic Laser Science, Institute for Basic Science (IBS), Gwangju 500-712 (Korea, Republic of); Department of Physics and Photon Science, GIST, Gwangju 500-712 (Korea, Republic of)

2015-12-15

We present a high-flux, broadband gamma-ray spectrometry capable of characterizing the betatron radiation spectrum over the photon energy range from 10 keV to 20 MeV with respect to the peak photon energy, spectral bandwidth, and unique discrimination from background radiations, using a differential filtering spectrometer and the unfolding procedure based on the Monte Carlo code GEANT4. These properties are experimentally verified by measuring betatron radiation from a cm-scale laser wakefield accelerator (LWFA) driven by a 1-PW laser, using a differential filtering spectrometer consisting of a 15-filter and image plate stack. The gamma-ray spectra were derived by unfolding the photostimulated luminescence (PSL) values recorded on the image plates, using the spectrometer response matrix modeled with the Monte Carlo code GEANT4. The accuracy of unfolded betatron radiation spectra was assessed by unfolding the test PSL data simulated with GEANT4, showing an ambiguity of less than 20% and clear discrimination from the background radiation with less than 10%. The spectral analysis of betatron radiation from laser wakefield-accelerated electron beams with energies up to 3 GeV revealed radiation spectra characterized by synchrotron radiation with the critical photon energy up to 7 MeV. The gamma-ray spectrometer and unfolding method presented here facilitate an in-depth understanding of betatron radiation from LWFA process and a novel radiation source of high-quality photon beams in the MeV regime.

Experience with using unfolding procedures in ATLAS

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00407321; The ATLAS collaboration

2016-01-01

In the ATLAS experiment, several unfolding methods are used to correct experimental measurements for detector effects, like acceptance and resolution. These methods use as input the raw experimental distributions, as well as Monte Carlo simulation for the description of the detector effects. The systematic uncertainties associated to the various unfolding methods are evaluated. The statistical and systematic uncertainties affecting the raw measurements and/or the simulation are propagated through the unfolding procedure. The resulting corrected measurements with their uncertainties can be directly compared with the corresponding theoretical predictions.

Osmolyte Effects on the Unfolding Pathway of β-Lactoglobulin

International Nuclear Information System (INIS)

Meng Wei; Pan Hai; Qin Meng; Cao Yi; Wang Wei

2013-01-01

There are large amounts of osmolytes inside cells, which impact many physiological processes by complicated mechanisms. The osmolyte effects on the stability and folding of proteins have been studied in detail using simple two-state folding proteins. However, many important functional proteins fold in complex pathways involving various intermediates. Little is known about the osmolyte effects on the folding and unfolding of these proteins. It is noted that β-lactoglobulin (BLG) is an example of such proteins, whose unfolding involves an obvious intermediate state. Using equilibrium chemical denaturation and stopped-flow kinetics, we investigate the unfolding of BLG in the presence of different osmolytes, e.g., glycerol, ethylene glycol (EG) and poly(ethylene glycol)400 (PEG400). It is found that all these osmolytes can stabilize the unfolding intermediate by modulating the relative unfolding kinetics of the native and the intermediate states. The stabilization effects are similar for EG and PEG400 but distinct for glycerol. Since the unfolding intermediates of many proteins are directly related to protein misfolding diseases, evaluation of the osmolyte effects for the unfolding of these proteins in vitro should be beneficial for the understanding of the occurrence of the related diseases in vivo

Neutron spectrum unfolding: Pt. 2

International Nuclear Information System (INIS)

Matiullah; Wiyaja, D.S.; Berzonis, M.A.; Bondars, H.; Lapenas, A.A.; Kudo, K.; Majeed, A.; Durrani, S.A.

1991-01-01

In Part I of this paper, we described the use of the computer code SAIPS in neutron spectrum unfolding. Here in Part II, we present our experimental work carried out to study the shape of the neutron spectrum in different experimental channels of a 5 MW light-water cooled and moderated research reactor. The spectral neutron flux was determined using various fission foils (placed in close contact with mica track detectors) and activation detectors. From the measured activities, the neutron spectrum was unfolded by SAIPS. (author)

Optimization of expression and purification of human mortalin (Hsp70): Folding/unfolding analysis

Science.gov (United States)

Khan, Mohd Shahnawaz; Ahmed, Anwar; Tabrez, Shams; Islam, Badar ul; Rabbani, Nayyar; Malik, Ajamaluddin; Ismael, Mohamad A.; Alsenaidy, Mohammad A.; Alsenaidy, Abdulrahman M.

2017-12-01

Human mortalin is a Hsp70 mitochondrial protein that plays an essential role in the biogenesis of mitochondria. The deregulation of mortalin expression and its functions could lead to several age-associated disorders and some types of cancers. In the present study, we optimized the expression and purification of recombinant human mortalin by the use of two-step chromatography. Low temperature (18 °C) and 0.5 mM (IPTG) was required for optimum mortalin expression. Chaperone activity of mortalin was assessed by the citrate synthase and insulin protection assay, which suggested their protective role in mitochondria. Folding and unfolding assessments of mortalin were carried out in the presence of guanidine hydrochloride (GdnHCl) by intrinsic fluorescence measurement, ANS (8-analino 1-nephthlene sulfonic acid) binding and CD (circular dichroism) analysis. Under denaturing conditions, mortalin showed decrease in tryptophan fluorescence intensity along with a red shift of 11 nm. Moreover, ANS binding studies illustrated decrease in hydrophobicity. CD measurement of mortalin showed a predominant helical structure. However, the secondary structure was lost at low concentration of GdnHCl (1 M). We present a simple and robust method to produce soluble mortalin and warranted that chaperones are also susceptible to unfolding and futile to maintain protein homeostasis.

A genetic algorithm based method for neutron spectrum unfolding

International Nuclear Information System (INIS)

Suman, Vitisha; Sarkar, P.K.

2013-03-01

An approach to neutron spectrum unfolding based on a stochastic evolutionary search mechanism - Genetic Algorithm (GA) is presented. It is tested to unfold a set of simulated spectra, the unfolded spectra is compared to the output of a standard code FERDOR. The method was then applied to a set of measured pulse height spectrum of neutrons from the AmBe source as well as of emitted neutrons from Li(p,n) and Ag(C,n) nuclear reactions carried out in the accelerator environment. The unfolded spectra compared to the output of FERDOR show good agreement in the case of AmBe spectra and Li(p,n) spectra. In the case of Ag(C,n) spectra GA method results in some fluctuations. Necessity of carrying out smoothening of the obtained solution is also studied, which leads to approximation of the solution yielding an appropriate solution finally. Few smoothing techniques like second difference smoothing, Monte Carlo averaging, combination of both and gaussian based smoothing methods are also studied. Unfolded results obtained after inclusion of the smoothening criteria are in close agreement with the output obtained from the FERDOR code. The present method is also tested on a set of underdetermined problems, the outputs of which is compared to the unfolded spectra obtained from the FERDOR applied to a completely determined problem, shows a good match. The distribution of the unfolded spectra is also studied. Uncertainty propagation in the unfolded spectra due to the errors present in the measurement as well as the response function is also carried out. The method appears to be promising for unfolding the completely determined as well as underdetermined problems. It also has provisions to carry out the uncertainty analysis. (author)

Iterative nonlinear unfolding code: TWOGO

International Nuclear Information System (INIS)

Hajnal, F.

1981-03-01

a new iterative unfolding code, TWOGO, was developed to analyze Bonner sphere neutron measurements. The code includes two different unfolding schemes which alternate on successive iterations. The iterative process can be terminated either when the ratio of the coefficient of variations in terms of the measured and calculated responses is unity, or when the percentage difference between the measured and evaluated sphere responses is less than the average measurement error. The code was extensively tested with various known spectra and real multisphere neutron measurements which were performed inside the containments of pressurized water reactors

Branches of Triangulated Origami Near the Unfolded State

Directory of Open Access Journals (Sweden)

Bryan Gin-ge Chen

2018-02-01

Full Text Available Origami structures are characterized by a network of folds and vertices joining unbendable plates. For applications to mechanical design and self-folding structures, it is essential to understand the interplay between the set of folds in the unfolded origami and the possible 3D folded configurations. When deforming a structure that has been folded, one can often linearize the geometric constraints, but the degeneracy of the unfolded state makes a linear approach impossible there. We derive a theory for the second-order infinitesimal rigidity of an initially unfolded triangulated origami structure and use it to study the set of nearly unfolded configurations of origami with four boundary vertices. We find that locally, this set consists of a number of distinct “branches” which intersect at the unfolded state, and that the number of these branches is exponential in the number of vertices. We find numerical and analytical evidence that suggests that the branches are characterized by choosing each internal vertex to either “pop up” or “pop down.” The large number of pathways along which one can fold an initially unfolded origami structure strongly indicates that a generic structure is likely to become trapped in a “misfolded” state. Thus, new techniques for creating self-folding origami are likely necessary; controlling the popping state of the vertices may be one possibility.

Branches of Triangulated Origami Near the Unfolded State

Science.gov (United States)

Chen, Bryan Gin-ge; Santangelo, Christian D.

2018-01-01

Origami structures are characterized by a network of folds and vertices joining unbendable plates. For applications to mechanical design and self-folding structures, it is essential to understand the interplay between the set of folds in the unfolded origami and the possible 3D folded configurations. When deforming a structure that has been folded, one can often linearize the geometric constraints, but the degeneracy of the unfolded state makes a linear approach impossible there. We derive a theory for the second-order infinitesimal rigidity of an initially unfolded triangulated origami structure and use it to study the set of nearly unfolded configurations of origami with four boundary vertices. We find that locally, this set consists of a number of distinct "branches" which intersect at the unfolded state, and that the number of these branches is exponential in the number of vertices. We find numerical and analytical evidence that suggests that the branches are characterized by choosing each internal vertex to either "pop up" or "pop down." The large number of pathways along which one can fold an initially unfolded origami structure strongly indicates that a generic structure is likely to become trapped in a "misfolded" state. Thus, new techniques for creating self-folding origami are likely necessary; controlling the popping state of the vertices may be one possibility.

Evolution and thermodynamics of the slow unfolding of hyperstable monomeric proteins

Directory of Open Access Journals (Sweden)

Koga Yuichi

2010-07-01

Full Text Available Abstract Background The unfolding speed of some hyperthermophilic proteins is dramatically lower than that of their mesostable homologs. Ribonuclease HII from the hyperthermophilic archaeon Thermococcus kodakaraensis (Tk-RNase HII is stabilized by its remarkably slow unfolding rate, whereas RNase HI from the thermophilic bacterium Thermus thermophilus (Tt-RNase HI unfolds rapidly, comparable with to that of RNase HI from Escherichia coli (Ec-RNase HI. Results To clarify whether the difference in the unfolding rate is due to differences in the types of RNase H or differences in proteins from archaea and bacteria, we examined the equilibrium stability and unfolding reaction of RNases HII from the hyperthermophilic bacteria Thermotoga maritima (Tm-RNase HII and Aquifex aeolicus (Aa-RNase HII and RNase HI from the hyperthermophilic archaeon Sulfolobus tokodaii (Sto-RNase HI. These proteins from hyperthermophiles are more stable than Ec-RNase HI over all the temperature ranges examined. The observed unfolding speeds of all hyperstable proteins at the different denaturant concentrations studied are much lower than those of Ec-RNase HI, which is in accordance with the familiar slow unfolding of hyperstable proteins. However, the unfolding rate constants of these RNases H in water are dispersed, and the unfolding rate constant of thermophilic archaeal proteins is lower than that of thermophilic bacterial proteins. Conclusions These results suggest that the nature of slow unfolding of thermophilic proteins is determined by the evolutionary history of the organisms involved. The unfolding rate constants in water are related to the amount of buried hydrophobic residues in the tertiary structure.

Direct ubiquitin independent recognition and degradation of a folded protein by the eukaryotic proteasomes-origin of intrinsic degradation signals.

Directory of Open Access Journals (Sweden)

Amit Kumar Singh Gautam

Full Text Available Eukaryotic 26S proteasomes are structurally organized to recognize, unfold and degrade globular proteins. However, all existing model substrates of the 26S proteasome in addition to ubiquitin or adaptor proteins require unstructured regions in the form of fusion tags for efficient degradation. We report for the first time that purified 26S proteasome can directly recognize and degrade apomyoglobin, a globular protein, in the absence of ubiquitin, extrinsic degradation tags or adaptor proteins. Despite a high affinity interaction, absence of a ligand and presence of only helices/loops that follow the degradation signal, apomyoglobin is degraded slowly by the proteasome. A short floppy F-helix exposed upon ligand removal and in conformational equilibrium with a disordered structure is mandatory for recognition and initiation of degradation. Holomyoglobin, in which the helix is buried, is neither recognized nor degraded. Exposure of the floppy F-helix seems to sensitize the proteasome and primes the substrate for degradation. Using peptide panning and competition experiments we speculate that initial encounters through the floppy helix and additional strong interactions with N-terminal helices anchors apomyoglobin to the proteasome. Stabilizing helical structure in the floppy F-helix slows down degradation. Destabilization of adjacent helices accelerates degradation. Unfolding seems to follow the mechanism of helix unraveling rather than global unfolding. Our findings while confirming the requirement for unstructured regions in degradation offers the following new insights: a origin and identification of an intrinsic degradation signal in the substrate, b identification of sequences in the native substrate that are likely to be responsible for direct interactions with the proteasome, and c identification of critical rate limiting steps like exposure of the intrinsic degron and destabilization of an unfolding intermediate that are presumably

The structural basis of urea-induced protein unfolding in β-catenin

Science.gov (United States)

Wang, Chao; Chen, Zhongzhou; Hong, Xia; Ning, Fangkun; Liu, Haolin; Zang, Jianye; Yan, Xiaoxue; Kemp, Jennifer; Musselman, Catherine A.; Kutateladze, Tatinna G.; Zhao, Rui; Jiang, Chengyu; Zhang, Gongyi

2014-01-01

Although urea and guanidine hydrochloride are commonly used to denature proteins, the molecular underpinnings of this process have remained unclear for a century. To address this question, crystal structures of β-catenin were determined at various urea concentrations. These structures contained at least 105 unique positions that were occupied by urea molecules, each of which interacted with the protein primarily via hydrogen bonds. Hydrogen-bond competition experiments showed that the denaturing effects of urea were neutralized when polyethylene glycol was added to the solution. These data suggest that urea primarily causes proteins to unfold by competing and disrupting hydrogen bonds in proteins. Moreover, circular-dichroism spectra and nuclear magnetic resonance (NMR) analysis revealed that a similar mechanism caused protein denaturation in the absence of urea at pH levels greater than 12. Taken together, the results led to the conclusion that the disruption of hydrogen bonds is a general mechanism of unfolding induced by urea, high pH and potentially other denaturing agents such as guanidine hydrochloride. Traditionally, the disruption of hydrophobic inter­actions instead of hydrogen bonds has been thought to be the most important cause of protein denaturation. PMID:25372676

[Comparison of Physico-chemical Aspects between E. coli and Human Dihydrofolate Reductase: an Equilibrium Unfolding Study].

Science.gov (United States)

Thapliyal, Charu; Jain, Neha; Chaudhuri, Pratima

2015-01-01

A protein, differing in origin, may exhibit variable physicochemical behaviour, difference in sequence homology, fold and function. Thus studying structure-function relationship of proteins from altered sources is meaningful in the sense that it may give rise to comparative aspects of their sequence-structure-function relationship. Dihydrofolate reductase is an enzyme involved in cell cycle regulation. It is a significant enzyme as.a target for developing anticancer drugs. Hence, detailed understanding of structure-function relationships of wide variants of the enzyme dihydrofolate reductase would be important for developing an inhibitor or an antagonist against the enzyme involved in the cellular developmental processes. In this communication, we have reported the comparative structure-function relationship between E. coli and human dihydrofolate reductase. The differences in the unfolding behaviour of these two proteins have been investigated to understand various properties of these two proteins like relative' stability differences and variation in conformational changes under identical denaturing conditions. The equilibrium unfolding mechanism of dihydrofolate reductase proteins using guanidine hydrochloride as a denaturant in the presence of various types of osmolytes has been monitored using loss in enzymatic activity, intrinsic tryptophan fluorescence and an extrinsic fluorophore 8-anilino-1-naphthalene-sulfonic acid as probes. It has been observed that osmolytes, such as 1M sucrose, and 30% glycerol, provided enhanced stability to both variants of dihydrofolate reductase. Their level of stabilisation has been observed to be dependent on intrinsic protein stability. It was observed that 100 mM proline does not show any 'significant stabilisation to either of dihydrofolate reductases. In the present study, it has been observed that the human protein is relatively less stable than the E.coli counterpart.

NEUPAC, Experimental Neutron Spectra Unfolding with Sensitivities

International Nuclear Information System (INIS)

Sasaki, Makoto; Nakazawa, Masaharu

1986-01-01

1 - Description of problem or function: The code is able to determine the integral quantities and their sensitivities, together with an estimate of the unfolded spectrum and integral quantities. The code also performs a chi-square test of the input/output data, and contains many options for the calculational routines. 2 - Method of solution: The code is based on the J1-type unfolding method, and the estimated neutron flux spectrum is obtained as its solution. 3 - Restrictions on the complexity of the problem: The maximum number of energy groups used for unfolding is 620. The maximum number of reaction rates and the window functions given as input is 20. The total storage requirement depends on the amount of input data

Unfolding studies of the cysteine protease baupain, a papain-like enzyme from leaves of Bauhinia forficata: effect of pH, guanidine hydrochloride and temperature.

Science.gov (United States)

Silva-Lucca, Rosemeire A; Andrade, Sheila S; Ferreira, Rodrigo Silva; Sampaio, Misako U; Oliva, Maria Luiza V

2013-12-24

Baupain belongs to the α+β class of proteins with a secondary structure-content of 44% α-helix, 16% β-sheet and 12% β-turn. The structural transition induced by pH was found to be noncooperative, with no important differences observed in the pH range from 3.0 to 10.5. At pH 2.0 the protein presented substantial non-native structure with strong ANS binding. Guanidine hydrochloride (GdnHCl)-induced unfolding did not change the protein structure significantly until 4.0 M, indicating the high rigidity of the molecule. The unfolding was cooperative, as seen by the sigmoidal transition curves with midpoints at 4.7±0.2 M and 5.0±0.2 M GdnHCl, as measured by CD and fluorescence spectroscopy. A red shift of 7 nm in intrinsic fluorescence was observed with 6.0 M GdnHCl. Temperature-induced unfolding of baupain was incomplete, and at least 35% of the native structure of the protein was retained, even at high temperature (90 °C). Baupain showed characteristics of a molten globule state, due to preferential ANS binding at pH 2.0 in comparison to the native form (pH 7.0) and completely unfolded (6.0 M GdnHCl) state. Combined with information about N-terminal sequence similarity, these results allow us to include baupain in the papain superfamily.

History, rare, and multiple events of mechanical unfolding of repeat proteins

Science.gov (United States)

Sumbul, Fidan; Marchesi, Arin; Rico, Felix

2018-03-01

Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

Unfolding methods in high-energy physics experiments

International Nuclear Information System (INIS)

Blobel, V.

1985-01-01

Distributions measured in high-energy physics experiments are often distorted or transformed by limited acceptance and finite resolution of the detectors. The unfolding of measured distributions is an important, but due to inherent instabilities a very difficult problem. Methods for unfolding, applicable for the analysis of high-energy physics experiments, and their properties are discussed. An introduction is given to the method of regularization. (orig.)

Unfolding methods in high-energy physics experiments

International Nuclear Information System (INIS)

Blobel, V.

1984-12-01

Distributions measured in high-energy physics experiments are often distorted or transformed by limited acceptance and finite resolution of the detectors. The unfolding of measured distributions is an important, but due to inherent instabilities a very difficult problem. Methods for unfolding, applicable for the analysis of high-energy physics experiments, and their properties are discussed. An introduction is given to the method of regularization. (orig.)

Concepts of intrinsic safety

International Nuclear Information System (INIS)

Anon.

1985-01-01

A newly introduced Japanese reactor concept, ISER (Intrinsically Safe and Economical Reactor), is intended to be a reference intrinsically safe light water reactor. ISER is designed similarly to PIUS but with greater economy in mind such that any utility in any country can choose it for its power system. Social assimilation and acceptability in the Asia Pacific Region including the United States are the keys to the ISER with the hope of dramatic reductions of social costs due to safeguards, reliability, financiability, and infrastructure building, particularly in the third world, as well as reactor safety itself. In this respect and others, the ISER proposal is different from other vendor-proposed reactor concepts and is unique

NMR of unfolded proteins

Indian Academy of Sciences (India)

Unknown

2005-01-03

Jan 3, 2005 ... covering all the systems, so far discovered.5,7,8,12. With the increasing ... Structural investigations on proteins by NMR are, currently ... rapid analysis of unfolded proteins. ...... and hence help in design of drugs against them.

Catalogue to select the initial guess spectrum during unfolding

CERN Document Server

Vega-Carrillo, H R

2002-01-01

A new method to select the initial guess spectrum is presented. Neutron spectra unfolded from Bonner sphere data are dependent on the initial guess spectrum used in the unfolding code. The method is based on a catalogue of detector count rates calculated from a set of reported neutron spectra. The spectra of three isotopic neutron sources sup 2 sup 5 sup 2 Cf, sup 2 sup 3 sup 9 PuBe and sup 2 sup 5 sup 2 Cf/D sub 2 O, were measured to test the method. The unfolding was carried out using the three initial guess options included in the BUNKIUT code. Neutron spectra were also calculated using MCNP code. Unfolded spectra were compared with those calculated; in all the cases our method gives the best results.

OPERATOR NORM INEQUALITIES BETWEEN TENSOR UNFOLDINGS ON THE PARTITION LATTICE.

Science.gov (United States)

Wang, Miaoyan; Duc, Khanh Dao; Fischer, Jonathan; Song, Yun S

2017-05-01

Interest in higher-order tensors has recently surged in data-intensive fields, with a wide range of applications including image processing, blind source separation, community detection, and feature extraction. A common paradigm in tensor-related algorithms advocates unfolding (or flattening) the tensor into a matrix and applying classical methods developed for matrices. Despite the popularity of such techniques, how the functional properties of a tensor changes upon unfolding is currently not well understood. In contrast to the body of existing work which has focused almost exclusively on matricizations, we here consider all possible unfoldings of an order- k tensor, which are in one-to-one correspondence with the set of partitions of {1, …, k }. We derive general inequalities between the l p -norms of arbitrary unfoldings defined on the partition lattice. In particular, we demonstrate how the spectral norm ( p = 2) of a tensor is bounded by that of its unfoldings, and obtain an improved upper bound on the ratio of the Frobenius norm to the spectral norm of an arbitrary tensor. For specially-structured tensors satisfying a generalized definition of orthogonal decomposability, we prove that the spectral norm remains invariant under specific subsets of unfolding operations.

Review of unfolding methods for neutron flux dosimetry

International Nuclear Information System (INIS)

Stallmann, F.W.; Kam, F.B.K.

1975-01-01

The primary method in reactor dosimetry is the foil activation technique. To translate the activation measurements into neutron fluxes, a special data processing technique called unfolding is needed. Some general observations about the problems and the reliability of this approach to reactor dosimetry are presented. Current unfolding methods are reviewed. 12 references. (auth)

Deep Unfolding for Topic Models.

Science.gov (United States)

Chien, Jen-Tzung; Lee, Chao-Hsi

2018-02-01

Deep unfolding provides an approach to integrate the probabilistic generative models and the deterministic neural networks. Such an approach is benefited by deep representation, easy interpretation, flexible learning and stochastic modeling. This study develops the unsupervised and supervised learning of deep unfolded topic models for document representation and classification. Conventionally, the unsupervised and supervised topic models are inferred via the variational inference algorithm where the model parameters are estimated by maximizing the lower bound of logarithm of marginal likelihood using input documents without and with class labels, respectively. The representation capability or classification accuracy is constrained by the variational lower bound and the tied model parameters across inference procedure. This paper aims to relax these constraints by directly maximizing the end performance criterion and continuously untying the parameters in learning process via deep unfolding inference (DUI). The inference procedure is treated as the layer-wise learning in a deep neural network. The end performance is iteratively improved by using the estimated topic parameters according to the exponentiated updates. Deep learning of topic models is therefore implemented through a back-propagation procedure. Experimental results show the merits of DUI with increasing number of layers compared with variational inference in unsupervised as well as supervised topic models.

Influence of cross-section structure on unfolded neutron spectra

International Nuclear Information System (INIS)

Ertek, C.; Vlasov, M.F.; Cross, B.; Smith, P.M.

1979-01-01

The influence of cross-section structure on neutron spectra unfolded by multiple foil activation technique, SAND-II case, has been studied. For three reactions with evident structure in neutron cross-section above threshold: 27Al(n,α)24Na, 31P(n,p)31Si and 32S(n,p)32P, two remarkably different sets of evaluated data were selected from the available evaluations; one set of data was ''smooth'', the structure having been averaged over by a smooth curve; the other set was ''sharp'' with structure given in detail. These data were used in unfolding procedure together with other reactions, the same in both cases (as well as input spectra and measured reaction rates). It was found that during unfolding calculations less iteration steps were needed to unfold the neutron flux spectrum with the set of ''sharp'' data. In case of ''smooth'' data it was difficult to obtain an agreement between measured and calculated activity values even by increasing the number of iteration steps. Contrary to expectations, considerable deformation of unfolded neutron flux spectrum has been observed in the case of the ''smooth'' data set. (author)

Protein unfolding versus β-sheet separation in spider silk nanocrystals

International Nuclear Information System (INIS)

Alam, Parvez

2014-01-01

In this communication a mechanism for spider silk strain hardening is proposed. Shear failure of β-sheet nanocrystals is the first failure mode that gives rise to the creation of smaller nanocrystals, which are of higher strength and stiffness. β-sheet unfolding requires more energy than nanocrystal separation in a shear mode of failure. As a result, unfolding occurs after the nanocrystals separate in shear. β-sheet unfolding yields a secondary strain hardening effect once the β-sheet conformation is geometrically stable and acts like a unidirectional fibre in a fibre reinforced composite. The mechanism suggested herein is based on molecular dynamics calculations of residual inter-β-sheet separation strengths against residual intra-β-sheet unfolding strengths. (paper)

Unfolding Studies of the Cysteine Protease Baupain, a Papain-Like Enzyme from Leaves of Bauhinia forficata: Effect of pH, Guanidine Hydrochloride and Temperature

Directory of Open Access Journals (Sweden)

Rosemeire A. Silva-Lucca

2013-12-01

Full Text Available Baupain belongs to the α+β class of proteins with a secondary structure-content of 44% α-helix, 16% β-sheet and 12% β-turn. The structural transition induced by pH was found to be noncooperative, with no important differences observed in the pH range from 3.0 to 10.5. At pH 2.0 the protein presented substantial non-native structure with strong ANS binding. Guanidine hydrochloride (GdnHCl-induced unfolding did not change the protein structure significantly until 4.0 M, indicating the high rigidity of the molecule. The unfolding was cooperative, as seen by the sigmoidal transition curves with midpoints at 4.7 ± 0.2 M and 5.0 ± 0.2 M GdnHCl, as measured by CD and fluorescence spectroscopy. A red shift of 7 nm in intrinsic fluorescence was observed with 6.0 M GdnHCl. Temperature-induced unfolding of baupain was incomplete, and at least 35% of the native structure of the protein was retained, even at high temperature (90 °C. Baupain showed characteristics of a molten globule state, due to preferential ANS binding at pH 2.0 in comparison to the native form (pH 7.0 and completely unfolded (6.0 M GdnHCl state. Combined with information about N-terminal sequence similarity, these results allow us to include baupain in the papain superfamily.

Comparison of intra-organellar chaperone capacity for dealing with stress-induced protein unfolding.

Science.gov (United States)

Hageman, Jurre; Vos, Michel J; van Waarde, Maria A W H; Kampinga, Harm H

2007-11-23

Molecular chaperones are essential for cells to prevent that partially unfolded proteins form non-functional, toxic aggregates. This requirement is increased when cells experience protein unfolding stresses and such could affect all compartments in the eukaryotic cell. Whether all organelles are equipped with comparable chaperone capacities is largely unknown, mainly due to the lack of suitable reporters that allow such a comparison. Here we describe the development of fluorescent luciferase reporters that are sorted to various cellular locations (nucleus, cytoplasm, endoplasmic reticulum, and peroxisomes) and that differ minimally in their intrinsic thermal stability properties. When heating living cells, the rate of inactivation was most rapid for the nuclear-targeted luciferase, indicating that the nucleus is the most sensitive organelle toward heat-induced denaturing stress. Post-heat re-activation, however, occurred at equal kinetics irrespective of luciferase localization. Also, induction of thermotolerance by a priming heat treatment, that coordinately up-regulates all heat-inducible chaperones, resulted in a transient heat resistance of the luciferase in all organelles in a comparable manner. Overexpression of the main heat-inducible Hsp70 family member, HspA1A, protected only the cytosolic and nuclear, but not the other luciferases. Together, our data suggest that in each compartment investigated, including the peroxisome in which so far no chaperones could be detected, chaperone machines are present and can be induced with activities similar to those present in the cytosolic/nuclear compartment.

Unfolding of cytochrome c immobilized on self-assembled monolayers. An electrochemical study

International Nuclear Information System (INIS)

Monari, Stefano; Ranieri, Antonio; Bortolotti, Carlo Augusto; Peressini, Silvia; Tavagnacco, Claudio; Borsari, Marco

2011-01-01

Highlights: → Denaturation involves intermediate and partially unfolded forms. → An unfolded species displaying the haem with Fe coordinated by two His is observed. → Under unfolding conditions the nature of the SAM influences conformation of protein. → Concentration of the unfolding agent affects redox properties of immobilized protein. - Abstract: The electron transfer (ET) process of progressively unfolded bovine cytochrome c immobilized on different self-assembled monolayers (SAMs) was investigated. Insight is gained on the role of the SAM surface on the functionality of the partially unfolded and non-native forms of the adsorbed protein. Direct electrochemical measurements were performed on cytochrome c adsorbed on mercaptopyridine (MP) and mixed 11-mercapto-1-undecanoic acid/11-mercapto-1-undecanol (MUA/MU) at varying temperature, in the presence of urea as unfolding agent. Under strongly unfolding conditions, a non-native form of cytochrome c, in which the methionine ligand is replaced by a histidine, was observed on both MP and MUA/MU SAMs. The E o ' of the native form, in which the haem is axially coordinated by methionine and histidine, slightly shifts to negative values upon increasing urea concentration. However, the non-native bis-histidinate species shows a much lower E o ' value (by approximately 0.4 V) which is by far enthalpic in origin and largely determined by axial ligand swapping. Analysis of the reduction enthalpies and entropies and of the ET rate constants indicate that the nature of the SAM (hydrophilic or anionic) results in changes in the conformational rearrangement of the cytochrome c under unfolding conditions.

Unfolding of cytochrome c immobilized on self-assembled monolayers. An electrochemical study

Energy Technology Data Exchange (ETDEWEB)

Monari, Stefano; Ranieri, Antonio; Bortolotti, Carlo Augusto; Peressini, Silvia [Department of Chemistry, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena (Italy); Tavagnacco, Claudio [Department of Chemistry, University of Trieste, via Giorgieri 1, 34127 Trieste (Italy); Borsari, Marco, E-mail: marco.borsari@unimore.it [Department of Chemistry, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena (Italy)

2011-08-01

Highlights: > Denaturation involves intermediate and partially unfolded forms. > An unfolded species displaying the haem with Fe coordinated by two His is observed. > Under unfolding conditions the nature of the SAM influences conformation of protein. > Concentration of the unfolding agent affects redox properties of immobilized protein. - Abstract: The electron transfer (ET) process of progressively unfolded bovine cytochrome c immobilized on different self-assembled monolayers (SAMs) was investigated. Insight is gained on the role of the SAM surface on the functionality of the partially unfolded and non-native forms of the adsorbed protein. Direct electrochemical measurements were performed on cytochrome c adsorbed on mercaptopyridine (MP) and mixed 11-mercapto-1-undecanoic acid/11-mercapto-1-undecanol (MUA/MU) at varying temperature, in the presence of urea as unfolding agent. Under strongly unfolding conditions, a non-native form of cytochrome c, in which the methionine ligand is replaced by a histidine, was observed on both MP and MUA/MU SAMs. The E{sup o}' of the native form, in which the haem is axially coordinated by methionine and histidine, slightly shifts to negative values upon increasing urea concentration. However, the non-native bis-histidinate species shows a much lower E{sup o}' value (by approximately 0.4 V) which is by far enthalpic in origin and largely determined by axial ligand swapping. Analysis of the reduction enthalpies and entropies and of the ET rate constants indicate that the nature of the SAM (hydrophilic or anionic) results in changes in the conformational rearrangement of the cytochrome c under unfolding conditions.

Geometrical analysis of cytochrome c unfolding

Science.gov (United States)

Urie, Kristopher G.; Pletneva, Ekaterina; Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

2011-01-01

A geometrical model has been developed to study the unfolding of iso-1 cytochrome c. The model draws on the crystallographic data reported for this protein. These data were used to calculate the distance between specific residues in the folded state, and in a sequence of extended states defined by n = 3, 5, 7, 9, 11, 13, and 15 residue units. Exact calculations carried out for each of the 103 residues in the polypeptide chain demonstrate that different regions of the chain have different unfolding histories. Regions where there is a persistence of compact structures can be identified, and this geometrical characterization is fully consistent with analyses of time-resolved fluorescence energy-transfer (TrFET) data using dansyl-derivatized cysteine side-chain probes at positions 39, 50, 66, 85, and 99. The calculations were carried out assuming that different regions of the polypeptide chain unfold synchronously. To test this assumption, lattice Monte Carlo simulations were performed to study systematically the possible importance of asynchronicity. Calculations show that small departures from synchronous dynamics can arise if displacements of residues in the main body of the chain are much more sluggish than near-terminal residues.

Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange: THERMODYNAMIC STABILITY CORRELATES WITH RATES OF UNFOLDING RATHER THAN FOLDING.

Science.gov (United States)

Shah, Riddhi; Ohashi, Tomoo; Erickson, Harold P; Oas, Terrence G

2017-01-20

Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. FNIII domains are one of the most common protein folds and are present in 2% of animal proteins. FNIII domains are ideal for this study because they have an identical seven-strand β-sandwich structure, but they vary widely in sequence and thermodynamic stability. We assayed thermodynamic stability of each domain by equilibrium denaturation in urea. We then assayed the kinetics of domain opening and closing by a technique known as thiol exchange. For this we introduced a buried Cys at the identical location in each FNIII domain and measured the kinetics of labeling with DTNB over a range of urea concentrations. A global fit of the kinetics data gave the kinetics of spontaneous unfolding and refolding in zero urea. We found that the folding rates were relatively similar, ∼0.1-1 s -1 , for the different domains. The unfolding rates varied widely and correlated with thermodynamic stability. Our study is the first to address this question using a set of domains that are structurally homologous but evolved with widely varying sequence identity and thermodynamic stability. These data add new evidence that thermodynamic stability correlates primarily with unfolding rate rather than folding rate. The study also has implications for the question of whether opening of FNIII domains contributes to the stretching of fibronectin matrix fibrils. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Solving inverse problems with the unfolding program TRUEE: Examples in astroparticle physics

International Nuclear Information System (INIS)

Milke, N.; Doert, M.; Klepser, S.; Mazin, D.; Blobel, V.; Rhode, W.

2013-01-01

The unfolding program TRUEE is a software package for the numerical solution of inverse problems. The algorithm was first applied in the FORTRAN 77 program RUN. RUN is an event-based unfolding algorithm which makes use of the Tikhonov regularization. It has been tested and compared to different unfolding applications and stood out with notably stable results and reliable error estimation. TRUEE is a conversion of RUN to C++, which works within the powerful ROOT framework. The program has been extended for more user-friendliness and delivers unfolding results which are identical to RUN. Beside the simplicity of the installation of the software and the generation of graphics, there are new functions, which facilitate the choice of unfolding parameters and observables for the user. In this paper, we introduce the new unfolding program and present its performance by applying it to two exemplary data sets from astroparticle physics, taken with the MAGIC telescopes and the IceCube neutrino detector, respectively.

Reversible Unfolding of Rhomboid Intramembrane Proteases.

Science.gov (United States)

Panigrahi, Rashmi; Arutyunova, Elena; Panwar, Pankaj; Gimpl, Katharina; Keller, Sandro; Lemieux, M Joanne

2016-03-29

Denaturant-induced unfolding of helical membrane proteins provides insights into their mechanism of folding and domain organization, which take place in the chemically heterogeneous, anisotropic environment of a lipid membrane. Rhomboid proteases are intramembrane proteases that play key roles in various diseases. Crystal structures have revealed a compact helical bundle with a buried active site, which requires conformational changes for the cleavage of transmembrane substrates. A dimeric form of the rhomboid protease has been shown to be important for activity. In this study, we examine the mechanism of refolding for two distinct rhomboids to gain insight into their secondary structure-activity relationships. Although helicity is largely abolished in the unfolded states of both proteins, unfolding is completely reversible for HiGlpG but only partially reversible for PsAarA. Refolding of both proteins results in reassociation of the dimer, with a 90% regain of catalytic activity for HiGlpG but only a 70% regain for PsAarA. For both proteins, a broad, gradual transition from the native, folded state to the denatured, partly unfolded state was revealed with the aid of circular dichroism spectroscopy as a function of denaturant concentration, thus arguing against a classical two-state model as found for many globular soluble proteins. Thermal denaturation has irreversible destabilizing effects on both proteins, yet reveals important functional details regarding substrate accessibility to the buried active site. This concerted biophysical and functional analysis demonstrates that HiGlpG, with a simple six-transmembrane-segment organization, is more robust than PsAarA, which has seven predicted transmembrane segments, thus rendering HiGlpG amenable to in vitro studies of membrane-protein folding. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

[Partially unfolded state of lysozyme with a developed secondary structure in dimethylsulfoxide].

Science.gov (United States)

Timchenko, A A; Kirkitadze, M D; Prokhorov, D A; Potekhin, S A; Serdiuk, I N

1996-06-01

The conformation of a chicken egg lysozyme molecule (dimensions, stoichiometry of its associates, and the degree of helicity) in DMSO was studied by small-angle neutron scattering, dynamic light scattering, and optical rotatory dispersion in the visible region of the spectrum. At high DMSO concentrations (70%), the protein was shown to exist as a dimer. The monomer molecules in the dimer adopt a partially unfolded conformation, with dimensions substantially greater than those in the native state and a high content of secondary structure (the degree of helicity is close to that of native lysozyme). This approach provides a unique possibility to assess the compactness of molecules in associates, which may be very useful in studying protein self-organization.

Dry molten globule intermediates and the mechanism of protein unfolding.

Science.gov (United States)

Baldwin, Robert L; Frieden, Carl; Rose, George D

2010-10-01

New experimental results show that either gain or loss of close packing can be observed as a discrete step in protein folding or unfolding reactions. This finding poses a significant challenge to the conventional two-state model of protein folding. Results of interest involve dry molten globule (DMG) intermediates, an expanded form of the protein that lacks appreciable solvent. When an unfolding protein expands to the DMG state, side chains unlock and gain conformational entropy, while liquid-like van der Waals interactions persist. Four unrelated proteins are now known to form DMGs as the first step of unfolding, suggesting that such an intermediate may well be commonplace in both folding and unfolding. Data from the literature show that peptide amide protons are protected in the DMG, indicating that backbone structure is intact despite loss of side-chain close packing. Other complementary evidence shows that secondary structure formation provides a major source of compaction during folding. In our model, the major free-energy barrier separating unfolded from native states usually occurs during the transition between the unfolded state and the DMG. The absence of close packing at this barrier provides an explanation for why phi-values, derived from a Brønsted-Leffler plot, depend primarily on structure at the mutational site and not on specific side-chain interactions. The conventional two-state folding model breaks down when there are DMG intermediates, a realization that has major implications for future experimental work on the mechanism of protein folding. 2010 Wiley-Liss, Inc.

Distribution, transition and thermodynamic stability of protein conformations in the denaturant-induced unfolding of proteins.

Science.gov (United States)

Bian, Liujiao; Ji, Xu

2014-01-01

Extensive and intensive studies on the unfolding of proteins require appropriate theoretical model and parameter to clearly illustrate the feature and characteristic of the unfolding system. Over the past several decades, four approaches have been proposed to describe the interaction between proteins and denaturants, but some ambiguity and deviations usually occur in the explanation of the experimental data. In this work, a theoretical model was presented to show the dependency of the residual activity ratio of the proteins on the molar denaturant concentration. Through the characteristic unfolding parameters ki and Δmi in this model, the distribution, transition and thermodynamic stability of protein conformations during the unfolding process can be quantitatively described. This model was tested with the two-state unfolding of bovine heart cytochrome c and the three-state unfolding of hen egg white lysozyme induced by both guanidine hydrochloride and urea, the four-state unfolding of bovine carbonic anhydrase b induced by guanidine hydrochloride and the unfolding of some other proteins induced by denaturants. The results illustrated that this model could be used accurately to reveal the distribution and transition of protein conformations in the presence of different concentrations of denaturants and to evaluate the unfolding tendency and thermodynamic stability of different conformations. In most denaturant-induced unfolding of proteins, the unfolding became increasingly hard in next transition step and the proteins became more unstable as they attained next successive stable conformation. This work presents a useful method for people to study the unfolding of proteins and may be used to describe the unfolding and refolding of other biopolymers induced by denaturants, inducers, etc.

[Unfolding item response model using best-worst scaling].

Science.gov (United States)

Ikehara, Kazuya

2015-02-01

In attitude measurement and sensory tests, the unfolding model is typically used. In this model, response probability is formulated by the distance between the person and the stimulus. In this study, we proposed an unfolding item response model using best-worst scaling (BWU model), in which a person chooses the best and worst stimulus among repeatedly presented subsets of stimuli. We also formulated an unfolding model using best scaling (BU model), and compared the accuracy of estimates between the BU and BWU models. A simulation experiment showed that the BWU modell performed much better than the BU model in terms of bias and root mean square errors of estimates. With reference to Usami (2011), the proposed models were apllied to actual data to measure attitudes toward tardiness. Results indicated high similarity between stimuli estimates generated with the proposed models and those of Usami (2011).

Application of long-range order to predict unfolding rates of two-state proteins.

Science.gov (United States)

Harihar, B; Selvaraj, S

2011-03-01

Predicting the experimental unfolding rates of two-state proteins and models describing the unfolding rates of these proteins is quite limited because of the complexity present in the unfolding mechanism and the lack of experimental unfolding data compared with folding data. In this work, 25 two-state proteins characterized by Maxwell et al. (Protein Sci 2005;14:602–616) using a consensus set of experimental conditions were taken, and the parameter long-range order (LRO) derived from their three-dimensional structures were related with their experimental unfolding rates ln(k(u)). From the total data set of 30 proteins used by Maxwell et al. (Protein Sci 2005;14:602–616), five slow-unfolding proteins with very low unfolding rates were considered to be outliers and were not included in our data set. Except all beta structural class, LRO of both the all-alpha and mixed-class proteins showed a strong inverse correlation of r = -0.99 and -0.88, respectively, with experimental ln(k(u)). LRO shows a correlation of -0.62 with experimental ln(k(u)) for all-beta proteins. For predicting the unfolding rates, a simple statistical method has been used and linear regression equations were developed for individual structural classes of proteins using LRO, and the results obtained showed a better agreement with experimental results. Copyright © 2010 Wiley-Liss, Inc.

Regularization and error assignment to unfolded distributions

CERN Document Server

Zech, Gunter

2011-01-01

The commonly used approach to present unfolded data only in graphical formwith the diagonal error depending on the regularization strength is unsatisfac-tory. It does not permit the adjustment of parameters of theories, the exclusionof theories that are admitted by the observed data and does not allow the com-bination of data from different experiments. We propose fixing the regulariza-tion strength by a p-value criterion, indicating the experimental uncertaintiesindependent of the regularization and publishing the unfolded data in additionwithout regularization. These considerations are illustrated with three differentunfolding and smoothing approaches applied to a toy example.

Experimental parameterization of an energy function for the simulation of unfolded proteins

DEFF Research Database (Denmark)

Norgaard, A.B.; Ferkinghoff-Borg, Jesper; Lindorff-Larsen, K.

2008-01-01

The determination of conformational preferences in unfolded and disordered proteins is an important challenge in structural biology. We here describe an algorithm to optimize energy functions for the simulation of unfolded proteins. The procedure is based on the maximum likelihood principle and e...... and can be applied to a range of experimental data and energy functions including the force fields used in molecular dynamics simulations.......The determination of conformational preferences in unfolded and disordered proteins is an important challenge in structural biology. We here describe an algorithm to optimize energy functions for the simulation of unfolded proteins. The procedure is based on the maximum likelihood principle...

The unfolding effects on the protein hydration shell and partial molar volume: a computational study.

Science.gov (United States)

Del Galdo, Sara; Amadei, Andrea

2016-10-12

In this paper we apply the computational analysis recently proposed by our group to characterize the solvation properties of a native protein in aqueous solution, and to four model aqueous solutions of globular proteins in their unfolded states thus characterizing the protein unfolded state hydration shell and quantitatively evaluating the protein unfolded state partial molar volumes. Moreover, by using both the native and unfolded protein partial molar volumes, we obtain the corresponding variations (unfolding partial molar volumes) to be compared with the available experimental estimates. We also reconstruct the temperature and pressure dependence of the unfolding partial molar volume of Myoglobin dissecting the structural and hydration effects involved in the process.

Conformational dynamics of a protein in the folded and the unfolded state

Energy Technology Data Exchange (ETDEWEB)

Fitter, Joerg

2003-08-01

In a quasielastic neutron scattering experiment, the picosecond dynamics of {alpha}-amylase was investigated for the folded and the unfolded state of the protein. In order to ensure a reasonable interpretation of the internal protein dynamics, the protein was measured in D{sub 2}O-buffer solution. The much higher structural flexibility of the pH induced unfolded state as compared to the native folded state was quantified using a simple analytical model, describing a local diffusion inside a sphere. In terms of this model the conformational volume, which is explored mainly by confined protein side-chain movements, is parameterized by the radius of a sphere (folded state, r=1.2 A; unfolded state, 1.8 A). Differences in conformational dynamics between the folded and the unfolded state of a protein are of fundamental interest in the field of protein science, because they are assumed to play an important role for the thermodynamics of folding/unfolding transition and for protein stability.

Unfolding code for neutron spectrometry based on neural nets technology

International Nuclear Information System (INIS)

Ortiz R, J. M.; Vega C, H. R.

2012-10-01

The most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Novel methods based on Artificial Neural Networks have been widely investigated. In this work, a neutron spectrum unfolding code based on neural nets technology is presented. This unfolding code called Neutron Spectrometry and Dosimetry by means of Artificial Neural Networks was designed in a graphical interface under LabVIEW programming environment. The core of the code is an embedded neural network architecture, previously optimized by the R obust Design of Artificial Neural Networks Methodology . The main features of the code are: is easy to use, friendly and intuitive to the user. This code was designed for a Bonner Sphere System based on a 6 Lil(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. The main feature of the code is that as entrance data, only seven rate counts measurement with a Bonner spheres spectrometer are required for simultaneously unfold the 60 energy bins of the neutron spectrum and to calculate 15 dosimetric quantities, for radiation protection porpoises. This code generates a full report in html format with all relevant information. (Author)

A neutron spectrum unfolding computer code based on artificial neural networks

International Nuclear Information System (INIS)

Ortiz-Rodríguez, J.M.; Reyes Alfaro, A.; Reyes Haro, A.; Cervantes Viramontes, J.M.; Vega-Carrillo, H.R.

2014-01-01

The Bonner Spheres Spectrometer consists of a thermal neutron sensor placed at the center of a number of moderating polyethylene spheres of different diameters. From the measured readings, information can be derived about the spectrum of the neutron field where measurements were made. Disadvantages of the Bonner system are the weight associated with each sphere and the need to sequentially irradiate the spheres, requiring long exposure periods. Provided a well-established response matrix and adequate irradiation conditions, the most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Novel methods based on Artificial Intelligence, mainly Artificial Neural Networks, have been widely investigated. In this work, a neutron spectrum unfolding code based on neural nets technology is presented. This code is called Neutron Spectrometry and Dosimetry with Artificial Neural networks unfolding code that was designed in a graphical interface. The core of the code is an embedded neural network architecture previously optimized using the robust design of artificial neural networks methodology. The main features of the code are: easy to use, friendly and intuitive to the user. This code was designed for a Bonner Sphere System based on a 6 LiI(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. The main feature of the code is that as entrance data, for unfolding the neutron spectrum, only seven rate counts measured with seven Bonner spheres are required; simultaneously the code calculates 15 dosimetric quantities as well as the total flux for radiation protection purposes. This code generates a full report with all information of the unfolding

Unfolding neutron spectra obtained from BS–TLD system using genetic algorithm

International Nuclear Information System (INIS)

Santos, J.A.L.; Silva, E.R.; Ferreira, T.A.E; Vilela, E.C.

2012-01-01

Due to the variability of neutron spectrum within the same environment, it is essential that the spectral distribution as a function of energy should be characterized. The precise information allows radiological quantities establishment related to that spectrum, but it is necessary that a spectrometric system covers a large interval of energy and an unfolding process is appropriate. This paper proposes use of a technique of Artificial Intelligence (AI) called genetic algorithm (GA), which uses bio-inspired mathematical models with the implementation of a specific matrix to unfolding data obtained from a combination of TLDs embedded in a BS system to characterize the neutron spectrum as a function of energy. The results obtained with this method were in accordance with reference spectra, thus enabling this technique to unfold neutron spectra with the BS–TLD system. - Highlights: ► The unfolding code used the artificial intelligence technique called genetic algorithms. ► A response matrix specific to the unfolding data obtained with the BS–TLD system is used by the AGLN. ► The observed results demonstrate the potential use of genetic algorithms in solving complex nuclear problems.

Unfolding in particle physics: A window on solving inverse problems

International Nuclear Information System (INIS)

Spano, F.

2013-01-01

Unfolding is the ensemble of techniques aimed at resolving inverse, ill-posed problems. A pedagogical introduction to the origin and main problems related to unfolding is presented and used as the the stepping stone towards the illustration of some of the most common techniques that are currently used in particle physics experiments. (authors)

Refining the intrinsic chimera flap: a review.

Science.gov (United States)

Agarwal, Jayant P; Agarwal, Shailesh; Adler, Neta; Gottlieb, Lawrence J

2009-10-01

Reconstruction of complex tissue deficiencies in which each missing component is in a different spatial relationship to each other can be particularly challenging, especially in patients with limited recipient vessels. The chimera flap design is uniquely suited to reconstruct these deformities. Chimera flaps have been previously defined in many ways with 2 main categories: prefabricated or intrinsic. Herein we attempt to clarify the definition of a true intrinsic chimeric flap and provide examples of how these constructs provide a method for reconstruction of complex defects. The versatility of the intrinsic chimera flap and its procurement from 7 different vascular systems is described. A clarification of the definition of a true intrinsic chimera flap is described. In addition, construction of flaps from the lateral femoral circumflex, deep circumflex iliac, inferior gluteal, peroneal, subscapular, thoracodorsal, and radial arterial systems is described to showcase the versatility of these chimera flaps. A true intrinsic chimera flap must consist of more than a single tissue type. Each of the tissue components receives its blood flow from separate vascular branches or perforators that are connected to a single vascular source. These vascular branches must be of appropriate length to allow for insetting with 3-dimensional spatial freedom. There are a multitude of sites from which true intrinsic chimera flaps may be harvested.

Declining global warming effects on the phenology of spring leaf unfolding.

Science.gov (United States)

Fu, Yongshuo H; Zhao, Hongfang; Piao, Shilong; Peaucelle, Marc; Peng, Shushi; Zhou, Guiyun; Ciais, Philippe; Huang, Mengtian; Menzel, Annette; Peñuelas, Josep; Song, Yang; Vitasse, Yann; Zeng, Zhenzhong; Janssens, Ivan A

2015-10-01

Earlier spring leaf unfolding is a frequently observed response of plants to climate warming. Many deciduous tree species require chilling for dormancy release, and warming-related reductions in chilling may counteract the advance of leaf unfolding in response to warming. Empirical evidence for this, however, is limited to saplings or twigs in climate-controlled chambers. Using long-term in situ observations of leaf unfolding for seven dominant European tree species at 1,245 sites, here we show that the apparent response of leaf unfolding to climate warming (ST, expressed in days advance of leaf unfolding per °C warming) has significantly decreased from 1980 to 2013 in all monitored tree species. Averaged across all species and sites, ST decreased by 40% from 4.0 ± 1.8 days °C(-1) during 1980-1994 to 2.3 ± 1.6 days °C(-1) during 1999-2013. The declining ST was also simulated by chilling-based phenology models, albeit with a weaker decline (24-30%) than observed in situ. The reduction in ST is likely to be partly attributable to reduced chilling. Nonetheless, other mechanisms may also have a role, such as 'photoperiod limitation' mechanisms that may become ultimately limiting when leaf unfolding dates occur too early in the season. Our results provide empirical evidence for a declining ST, but also suggest that the predicted strong winter warming in the future may further reduce ST and therefore result in a slowdown in the advance of tree spring phenology.

Unfolding code for neutron spectrometry based on neural nets technology

Energy Technology Data Exchange (ETDEWEB)

Ortiz R, J. M.; Vega C, H. R., E-mail: morvymm@yahoo.com.mx [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica, Apdo. Postal 336, 98000 Zacatecas (Mexico)

2012-10-15

The most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Novel methods based on Artificial Neural Networks have been widely investigated. In this work, a neutron spectrum unfolding code based on neural nets technology is presented. This unfolding code called Neutron Spectrometry and Dosimetry by means of Artificial Neural Networks was designed in a graphical interface under LabVIEW programming environment. The core of the code is an embedded neural network architecture, previously optimized by the {sup R}obust Design of Artificial Neural Networks Methodology{sup .} The main features of the code are: is easy to use, friendly and intuitive to the user. This code was designed for a Bonner Sphere System based on a {sup 6}Lil(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. The main feature of the code is that as entrance data, only seven rate counts measurement with a Bonner spheres spectrometer are required for simultaneously unfold the 60 energy bins of the neutron spectrum and to calculate 15 dosimetric quantities, for radiation protection porpoises. This code generates a full report in html format with all relevant information. (Author)

An Extended Guinier Analysis for Intrinsically Disordered Proteins.

Science.gov (United States)

Zheng, Wenwei; Best, Robert B

2018-03-21

Guinier analysis allows model-free determination of the radius of gyration (R g ) of a biomolecule from X-ray or neutron scattering data, in the limit of very small scattering angles. Its range of validity is well understood for globular proteins, but is known to be more restricted for unfolded or intrinsically disordered proteins (IDPs). We have used ensembles of disordered structures from molecular dynamics simulations to investigate which structural properties cause deviations from the Guinier approximation at small scattering angles. We find that the deviation from the Guinier approximation is correlated with the polymer scaling exponent ν describing the unfolded ensemble. We therefore introduce an empirical, ν-dependent, higher-order correction term, to augment the standard Guinier analysis. We test the new fitting scheme using all-atom simulation data for several IDPs and experimental data for both an IDP and a destabilized mutant of a folded protein. In all cases tested, we achieve an accuracy of the inferred R g within ∼3% of the true R g . The method is straightforward to implement and extends the range of validity to a maximum qR g of ∼2 versus ∼1.1 for Guinier analysis. Compared with the Guinier or Debye approaches, our method allows data from wider angles with lower noise to be used to analyze scattering data accurately. In addition to R g , our fitting scheme also yields estimates of the scaling exponent ν in excellent agreement with the reference ν determined from the underlying molecular ensemble. Published by Elsevier Ltd.

UMG 3.3, Analysis of data measured with spectrometers using unfolding techniques

International Nuclear Information System (INIS)

Reginatto, Marcel; Wiegel, Burkhard; Zimbal, Andreas; Langner, Frank

2004-01-01

1 - Description of program or function: UMG (Unfolding with MAXED and GRAVEL) is a package of seven programs written for the analysis of data measured with spectrometers that require the use of unfolding techniques. The program MAXED applies the maximum entropy principle to the unfolding problem, and the program GRAVEL uses a modified SAND-II algorithm to do the unfolding. There are two versions of each: MXD F C33 and GRV F C33 for 'few-channel' unfolding (e.g., Bonner sphere spectrometers) and MXD M C33 and GRV M C33 for 'multi-channel' unfolding (e.g., NE-213). The program IQU can be used to calculate integral quantities for both MAXED and GRAVEL solution spectra and, in the case of MAXED solutions, it can also be used to calculate the uncertainty in these values as well as the uncertainty in the solution spectrum. The uncertainty calculation is handled in the following way: given a solution spectrum generated by MAXED, the program IQU considers variations in the measured data and in the default spectrum and uses standard Methods to do sensitivity analysis and uncertainty propagation. There are two versions: IQU F C33 for 'few-channel' unfolding and IQU M C33 for 'multi-channel' unfolding. The program UMGPlot can be used to display the results from the unfolding programs MAXED and GRAVEL in graphical form in a quick and easy way. 2 - Methods: MAXED is based on the maximum entropy principle. The solution to the unfolding problem is obtained by maximisation of the relative entropy (used here in the form due to Skilling, which is a generalisation of the usual expression to distributions that are not necessarily normalized) subject to constraints imposed by the measurements. This approach permits the inclusion of prior information in a well-defined and mathematically consistent way, and it leads to a solution spectrum that is a non-negative function which can be written in closed form. This last feature permits the use of standard Methods for sensitivity analysis and

Blimp-1 controls plasma cell function through regulation of immunoglobulin secretion and the unfolded protein response

Science.gov (United States)

Tellier, Julie; Shi, Wei; Minnich, Martina; Liao, Yang; Crawford, Simon; Smyth, Gordon K; Kallies, Axel; Busslinger, Meinrad; Nutt, Stephen L

2015-01-01

Plasma cell differentiation requires silencing of B cell transcription, while establishing antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for plasma cell generation, however their function in mature plasma cells has remained elusive. We have found that while IRF4 was essential for plasma cell survival, Blimp-1 was dispensable. Blimp-1-deficient plasma cells retained their transcriptional identity, but lost the ability to secrete antibody. Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap of Blimp-1 and XBP-1 function was restricted to the UPR, with Blimp-1 uniquely regulating mTOR activity and plasma cell size. Thus, Blimp-1 is required for the unique physiological capacity of plasma cells that enables the secretion of protective antibody. PMID:26779600

Decoding Structural Properties of a Partially Unfolded Protein Substrate: En Route to Chaperone Binding.

Science.gov (United States)

Nagpal, Suhani; Tiwari, Satyam; Mapa, Koyeli; Thukral, Lipi

2015-01-01

Many proteins comprising of complex topologies require molecular chaperones to achieve their unique three-dimensional folded structure. The E.coli chaperone, GroEL binds with a large number of unfolded and partially folded proteins, to facilitate proper folding and prevent misfolding and aggregation. Although the major structural components of GroEL are well defined, scaffolds of the non-native substrates that determine chaperone-mediated folding have been difficult to recognize. Here we performed all-atomistic and replica-exchange molecular dynamics simulations to dissect non-native ensemble of an obligate GroEL folder, DapA. Thermodynamics analyses of unfolding simulations revealed populated intermediates with distinct structural characteristics. We found that surface exposed hydrophobic patches are significantly increased, primarily contributed from native and non-native β-sheet elements. We validate the structural properties of these conformers using experimental data, including circular dichroism (CD), 1-anilinonaphthalene-8-sulfonic acid (ANS) binding measurements and previously reported hydrogen-deutrium exchange coupled to mass spectrometry (HDX-MS). Further, we constructed network graphs to elucidate long-range intra-protein connectivity of native and intermediate topologies, demonstrating regions that serve as central "hubs". Overall, our results implicate that genomic variations (or mutations) in the distinct regions of protein structures might disrupt these topological signatures disabling chaperone-mediated folding, leading to formation of aggregates.

Microscopic dynamics of water around unfolded structures of barstar at room temperature

Energy Technology Data Exchange (ETDEWEB)

Pal, Somedatta; Chakraborty, Kaushik; Khatua, Prabir; Bandyopadhyay, Sanjoy, E-mail: sanjoy@chem.iitkgp.ernet.in [Molecular Modeling Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India)

2015-02-07

The breaking of the native structure of a protein and its influences on the dynamic response of the surrounding solvent is an important issue in protein folding. In this work, we have carried out atomistic molecular dynamics simulations to unfold the protein barstar at two different temperatures (400 K and 450 K). The two unfolded forms obtained at such high temperatures are further studied at room temperature to explore the effects of nonuniform unfolding of the protein secondary structures along two different pathways on the microscopic dynamical properties of the surface water molecules. It is demonstrated that though the structural transition of the protein in general results in less restricted water motions around its segments, but there are evidences of formation of new conformational motifs upon unfolding with increasingly confined environment around them, thereby resulting in further restricted water mobility in their hydration layers. Moreover, it is noticed that the effects of nonuniform unfolding of the protein segments on the relaxation times of the protein–water (PW) and the water–water (WW) hydrogen bonds are correlated with hindered hydration water motions. However, the kinetics of breaking and reformation of such hydrogen bonds are found to be influenced differently at the interface. It is observed that while the effects of unfolding on the PW hydrogen bond kinetics seem to be minimum, but the kinetics involving the WW hydrogen bonds around the protein segments exhibit noticeably heterogeneous characteristics. We believe that this is an important observation, which can provide valuable insights on the origin of heterogeneous influence of unfolding of a protein on the microscopic properties of its hydration water.

Unfolded equations for massive higher spin supermultiplets in AdS{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Buchbinder, I.L. [Department of Theoretical Physics, Tomsk State Pedagogical University,60 Kievskaya Str., Tomsk, 634061 (Russian Federation); National Research Tomsk State University,36 Lenina Ave., Tomsk, 634050 (Russian Federation); Snegirev, T.V. [Department of Theoretical Physics, Tomsk State Pedagogical University,60 Kievskaya Str., Tomsk, 634061 (Russian Federation); Department of Higher Mathematics and Mathematical Physics,National Research Tomsk Polytechnic University, 30 Lenina Ave., Tomsk, 634050 (Russian Federation); Zinoviev, Yu.M. [Department of Theoretical Physics,Institute for High Energy Physics of National Research Center “Kurchatov Institute”, 1 Pobedy Str., Protvino, Moscow Region, 142280 (Russian Federation)

2016-08-10

In this paper we give an explicit construction of unfolded equations for massive higher spin supermultiplets of the minimal (1,0) supersymmetry in AdS{sub 3} space. For that purpose we use an unfolded formulation for massive bosonic and fermionic higher spins and find supertransformations leaving appropriate set of unfolded equations invariant. We provide two general supermultiplets (s,s+1/2) and (s,s−1/2) with arbitrary integer s, as well as a number of lower spin examples.

On unfolding counting-rate spectra of recoil-proton neutron detectors

International Nuclear Information System (INIS)

Yeivin, Yehuda

1983-01-01

This note proposes a possible scheme for unfolding recoil-proton neutron detector data, in which at first the undistorted proton source spectrum is derived. The main argument in favour of this scheme is that, compared with the conventional scheme, it necessitates somewhat weaker assumptions with respect to the unknown spectrum above the detector's upper energy cutoff, and would therefore be more reliable. We also demonstrate a simple, elementary proof of the wall effect correction for spherical detectors, and, in order to gain insight of the potential merits of the proposed unfolding scheme, illustrate our main argument by considering a hypothetic linear range-energy relation, in which case complete unfolding becomes possible with no assumptions at all on the proton spectrum above the cutoff energy. (author)

A neutron spectrum unfolding computer code based on artificial neural networks

Science.gov (United States)

Ortiz-Rodríguez, J. M.; Reyes Alfaro, A.; Reyes Haro, A.; Cervantes Viramontes, J. M.; Vega-Carrillo, H. R.

2014-02-01

The Bonner Spheres Spectrometer consists of a thermal neutron sensor placed at the center of a number of moderating polyethylene spheres of different diameters. From the measured readings, information can be derived about the spectrum of the neutron field where measurements were made. Disadvantages of the Bonner system are the weight associated with each sphere and the need to sequentially irradiate the spheres, requiring long exposure periods. Provided a well-established response matrix and adequate irradiation conditions, the most delicate part of neutron spectrometry, is the unfolding process. The derivation of the spectral information is not simple because the unknown is not given directly as a result of the measurements. The drawbacks associated with traditional unfolding procedures have motivated the need of complementary approaches. Novel methods based on Artificial Intelligence, mainly Artificial Neural Networks, have been widely investigated. In this work, a neutron spectrum unfolding code based on neural nets technology is presented. This code is called Neutron Spectrometry and Dosimetry with Artificial Neural networks unfolding code that was designed in a graphical interface. The core of the code is an embedded neural network architecture previously optimized using the robust design of artificial neural networks methodology. The main features of the code are: easy to use, friendly and intuitive to the user. This code was designed for a Bonner Sphere System based on a 6LiI(Eu) neutron detector and a response matrix expressed in 60 energy bins taken from an International Atomic Energy Agency compilation. The main feature of the code is that as entrance data, for unfolding the neutron spectrum, only seven rate counts measured with seven Bonner spheres are required; simultaneously the code calculates 15 dosimetric quantities as well as the total flux for radiation protection purposes. This code generates a full report with all information of the unfolding in

The construction of periodic unfolding operators on some compact Riemannian manifolds

DEFF Research Database (Denmark)

Dobberschütz, Sören; Böhm, Michael

2014-01-01

The notion of periodic unfolding has become a standard tool in the theory of periodic homogenization. However, all the results obtained so far are only applicable to the "flat" Euclidean space R n. In this paper, we present a generalization of the method of periodic unfolding applicable to struct...

RPA-mediated unfolding of systematically varying G-quadruplex structures.

Science.gov (United States)

Ray, Sujay; Qureshi, Mohammad H; Malcolm, Dominic W; Budhathoki, Jagat B; Celik, Uğur; Balci, Hamza

2013-05-21

G-quadruplex (GQ) is a noncanonical nucleic acid structure that is formed by guanine rich sequences. Unless it is destabilized by proteins such as replication protein A (RPA), GQ could interfere with DNA metabolic functions, such as replication or repair. We studied RPA-mediated GQ unfolding using single-molecule FRET on two groups of GQ structures that have different loop lengths and different numbers of G-tetrad layers. We observed a linear increase in the steady-state stability of the GQ against RPA-mediated unfolding with increasing number of layers or decreasing loop length. The stability demonstrated by different GQ structures varied by at least three orders of magnitude. Those with shorter loops (less than three nucleotides long) or a greater number of layers (more than three layers) maintained a significant folded population even at physiological RPA concentration (≈1 μM), raising the possibility of physiological viability of such GQ structures. Finally, we measured the transition time between the start and end of the RPA-mediated GQ unfolding process to be 0.35 ± 0.10 s for all GQ constructs we studied, despite significant differences in their steady-state stabilities. We propose a two-step RPA-mediated GQ unfolding mechanism that is consistent with our observations. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

NSDUAZ unfolding package for neutron spectrometry and dosimetry with Bonner spheres

Energy Technology Data Exchange (ETDEWEB)

Vega C, H. R.; Martinez B, M. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Ortiz R, J. M., E-mail: fermineutron@yahoo.com [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica, Av. Ramon Lopez Velarde 801, Col. Centro, 98000 Zacatecas (Mexico)

2011-10-15

NSDUAZ (Neutron Spectrometry and Dosimetry for the Universidad Autonoma de Zacatecas) is a user friendly neutron unfolding package for Bonner sphere spectrometer with {sup 6}Lil(Eu) developed under Lab View environment. Unfolding is carried out using a recursive iterative procedure with the SPUNIT algorithm, where the starting spectrum is obtained from a library initial guess spectrum to start the iterations, the package include a statistical procedure based on the count rates relative to the count rate in the 8 inches-diameter sphere to select the initial spectrum. Neutron spectrum is unfolded in 32 energy groups ranging from 10{sup -8} up to 231.2 MeV. (Author)

Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin.

Directory of Open Access Journals (Sweden)

Vasyl V Mykuliak

2018-04-01

Full Text Available Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins.

Spectrum unfolding in X-ray spectrometry using the maximum entropy method

International Nuclear Information System (INIS)

Fernandez, Jorge E.; Scot, Viviana; Di Giulio, Eugenio

2014-01-01

The solution of the unfolding problem is an ever-present issue in X-ray spectrometry. The maximum entropy technique solves this problem by taking advantage of some known a priori physical information and by ensuring an outcome with only positive values. This method is implemented in MAXED (MAXimum Entropy Deconvolution), a software code contained in the package UMG (Unfolding with MAXED and GRAVEL) developed at PTB and distributed by NEA Data Bank. This package contains also the code GRAVEL (used to estimate the precision of the solution). This article introduces the new code UMESTRAT (Unfolding Maximum Entropy STRATegy) which applies a semi-automatic strategy to solve the unfolding problem by using a suitable combination of MAXED and GRAVEL for applications in X-ray spectrometry. Some examples of the use of UMESTRAT are shown, demonstrating its capability to remove detector artifacts from the measured spectrum consistently with the model used for the detector response function (DRF). - Highlights: ► A new strategy to solve the unfolding problem in X-ray spectrometry is presented. ► The presented strategy uses a suitable combination of the codes MAXED and GRAVEL. ► The applied strategy provides additional information on the Detector Response Function. ► The code UMESTRAT is developed to apply this new strategy in a semi-automatic mode

Genetic algorithms - A new technique for solving the neutron spectrum unfolding problem

International Nuclear Information System (INIS)

Freeman, David W.; Edwards, D. Ray; Bolon, Albert E.

1999-01-01

A new technique utilizing genetic algorithms has been applied to the Bonner sphere neutron spectrum unfolding problem. Genetic algorithms are part of a relatively new field of 'evolutionary' solution techniques that mimic living systems with computer-simulated 'chromosome' solutions. Solutions mate and mutate to create better solutions. Several benchmark problems, considered representative of radiation protection environments, have been evaluated using the newly developed UMRGA code which implements the genetic algorithm unfolding technique. The results are compared with results from other well-established unfolding codes. The genetic algorithm technique works remarkably well and produces solutions with relatively high spectral qualities. UMRGA appears to be a superior technique in the absence of a priori data - it does not rely on 'lucky' guesses of input spectra. Calculated personnel doses associated with the unfolded spectra match benchmark values within a few percent

Immobilized unfolded cytochrome c acts as a catalyst for dioxygen reduction.

Science.gov (United States)

Tavagnacco, Claudio; Monari, Stefano; Ranieri, Antonio; Bortolotti, Carlo Augusto; Peressini, Silvia; Borsari, Marco

2011-10-21

Unfolding turns immobilized cytochrome c into a His-His ligated form endowed with catalytic activity towards O(2), which is absent in the native protein. Dioxygen could be used by naturally occurring unfolded cytochrome c as a substrate for the production of partially reduced oxygen species (PROS) contributing to the cell oxidative stress.

Application of LEPRICON methodology to the unfolding of neutron fluxes in the Arkansas Nuclear One-Unit 1 reactor

International Nuclear Information System (INIS)

Maerker, R.E.; Broadhead, B.L.; Williams, M.L.

1985-01-01

The LEPRICON (Least-squares EPRI CONsolidation) methodology has been gradually developed over the past few years. The system predicts the absolute neutron fluence levels as a function of energy at specified locations within the pressure vessel of an LWR from the analysis of dosimetry measurements performed at some other readily accessible surveillance location(s). LEPRICON is unique in the field of few-group spectral unfolding in that (1) it solves the extrapolation problem necessitated by the ex-situ measurements; (2) it has the capability of simultaneously unfolding a large number of spectral fluences; (3) it has the capability of simultaneously analyzing a series of benchmark experiments, along with measurements performed in an LWR; (4) it provides state-of-the-art methods for calculating the surveillance dosimeter activities and pressure vessel spectral fluences; (5) it incorporates the basic sensitivity and covariance information necessary for estimates of the uncertainties in the original calculated quantities; and (6) it produces adjustments to the calculated quantities with uncertainties that can be significantly reduced from the original values

The effect of a DeltaK280 mutation on the unfolded state of a microtubule-binding repeat in Tau.

Directory of Open Access Journals (Sweden)

Austin Huang

Full Text Available Tau is a natively unfolded protein that forms intracellular aggregates in the brains of patients with Alzheimer's disease. To decipher the mechanism underlying the formation of tau aggregates, we developed a novel approach for constructing models of natively unfolded proteins. The method, energy-minima mapping and weighting (EMW, samples local energy minima of subsequences within a natively unfolded protein and then constructs ensembles from these energetically favorable conformations that are consistent with a given set of experimental data. A unique feature of the method is that it does not strive to generate a single ensemble that represents the unfolded state. Instead we construct a number of candidate ensembles, each of which agrees with a given set of experimental constraints, and focus our analysis on local structural features that are present in all of the independently generated ensembles. Using EMW we generated ensembles that are consistent with chemical shift measurements obtained on tau constructs. Thirty models were constructed for the second microtubule binding repeat (MTBR2 in wild-type (WT tau and a DeltaK280 mutant, which is found in some forms of frontotemporal dementia. By focusing on structural features that are preserved across all ensembles, we find that the aggregation-initiating sequence, PHF6*, prefers an extended conformation in both the WT and DeltaK280 sequences. In addition, we find that residue K280 can adopt a loop/turn conformation in WT MTBR2 and that deletion of this residue, which can adopt nonextended states, leads to an increase in locally extended conformations near the C-terminus of PHF6*. As an increased preference for extended states near the C-terminus of PHF6* may facilitate the propagation of beta-structure downstream from PHF6*, these results explain how a deletion at position 280 can promote the formation of tau aggregates.

Proving the correctness of unfold/fold program transformations using bisimulation

DEFF Research Database (Denmark)

Hamilton, Geoff W.; Jones, Neil

2011-01-01

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

The unfolded protein response has a protective role in yeast models of classic galactosemia

Directory of Open Access Journals (Sweden)

Evandro A. De-Souza

2014-01-01

Full Text Available Classic galactosemia is a human autosomal recessive disorder caused by mutations in the GALT gene (GAL7 in yeast, which encodes the enzyme galactose-1-phosphate uridyltransferase. Here we show that the unfolded protein response pathway is triggered by galactose in two yeast models of galactosemia: lithium-treated cells and the gal7Δ mutant. The synthesis of galactose-1-phosphate is essential to trigger the unfolded protein response under these conditions because the deletion of the galactokinase-encoding gene GAL1 completely abolishes unfolded protein response activation and galactose toxicity. Impairment of the unfolded protein response in both yeast models makes cells even more sensitive to galactose, unmasking its cytotoxic effect. These results indicate that endoplasmic reticulum stress is induced under galactosemic conditions and underscores the importance of the unfolded protein response pathway to cellular adaptation in these models of classic galactosemia.

Non-leftmost Unfolding in Partial Evaluation of Logic Programs with Impure Predicates

DEFF Research Database (Denmark)

Albert, Elvira; Puebla, German; Gallagher, John Patrick

2006-01-01

-leftmost unfolding steps can result in incorrect results since the independence of the computation rule no longer holds in the presence of impure predicates. Existing proposals allow non-leftmost unfolding steps, but at the cost of accuracy: bindings and failure are not propagated backwards to predicates which...

Probing force-induced unfolding intermediates of a single staphylococcal nuclease molecule and the effect of ligand binding

International Nuclear Information System (INIS)

Ishii, Takaaki; Murayama, Yoshihiro; Katano, Atsuto; Maki, Kosuke; Kuwajima, Kunihiro; Sano, Masaki

2008-01-01

Single-molecule manipulation techniques have given experimental access to unfolding intermediates of proteins that are inaccessible in conventional experiments. A detailed characterization of the intermediates is a challenging problem that provides new possibilities for directly probing the energy landscape of proteins. We investigated single-molecule mechanical unfolding of a small globular protein, staphylococcal nuclease (SNase), using atomic force microscopy. The unfolding trajectories of the protein displayed sub-molecular and stochastic behavior with typical lengths corresponding to the size of the unfolded substructures. Our results support the view that the single protein unfolds along multiple pathways as suggested in recent theoretical studies. Moreover, we found the drastic change, caused by the ligand and inhibitor bindings, in the mechanical unfolding dynamics

Individual globular domains and domain unfolding visualized in overstretched titin molecules with atomic force microscopy.

Directory of Open Access Journals (Sweden)

Zsolt Mártonfalvi

Full Text Available Titin is a giant elastomeric protein responsible for the generation of passive muscle force. Mechanical force unfolds titin's globular domains, but the exact structure of the overstretched titin molecule is not known. Here we analyzed, by using high-resolution atomic force microscopy, the structure of titin molecules overstretched with receding meniscus. The axial contour of the molecules was interrupted by topographical gaps with a mean width of 27.7 nm that corresponds well to the length of an unfolded globular (immunoglobulin and fibronectin domain. The wide gap-width distribution suggests, however, that additional mechanisms such as partial domain unfolding and the unfolding of neighboring domain multimers may also be present. In the folded regions we resolved globules with an average spacing of 5.9 nm, which is consistent with a titin chain composed globular domains with extended interdomain linker regions. Topographical analysis allowed us to allocate the most distal unfolded titin region to the kinase domain, suggesting that this domain systematically unfolds when the molecule is exposed to overstretching forces. The observations support the prediction that upon the action of stretching forces the N-terminal ß-sheet of the titin kinase unfolds, thus exposing the enzyme's ATP-binding site and hence contributing to the molecule's mechanosensory function.

Decoding Structural Properties of a Partially Unfolded Protein Substrate: En Route to Chaperone Binding

Science.gov (United States)

Nagpal, Suhani; Tiwari, Satyam; Mapa, Koyeli; Thukral, Lipi

2015-01-01

Many proteins comprising of complex topologies require molecular chaperones to achieve their unique three-dimensional folded structure. The E.coli chaperone, GroEL binds with a large number of unfolded and partially folded proteins, to facilitate proper folding and prevent misfolding and aggregation. Although the major structural components of GroEL are well defined, scaffolds of the non-native substrates that determine chaperone-mediated folding have been difficult to recognize. Here we performed all-atomistic and replica-exchange molecular dynamics simulations to dissect non-native ensemble of an obligate GroEL folder, DapA. Thermodynamics analyses of unfolding simulations revealed populated intermediates with distinct structural characteristics. We found that surface exposed hydrophobic patches are significantly increased, primarily contributed from native and non-native β-sheet elements. We validate the structural properties of these conformers using experimental data, including circular dichroism (CD), 1-anilinonaphthalene-8-sulfonic acid (ANS) binding measurements and previously reported hydrogen-deutrium exchange coupled to mass spectrometry (HDX-MS). Further, we constructed network graphs to elucidate long-range intra-protein connectivity of native and intermediate topologies, demonstrating regions that serve as central “hubs”. Overall, our results implicate that genomic variations (or mutations) in the distinct regions of protein structures might disrupt these topological signatures disabling chaperone-mediated folding, leading to formation of aggregates. PMID:26394388

Towards data warehousing and mining of protein unfolding simulation data.

Science.gov (United States)

Berrar, Daniel; Stahl, Frederic; Silva, Candida; Rodrigues, J Rui; Brito, Rui M M; Dubitzky, Werner

2005-10-01

The prediction of protein structure and the precise understanding of protein folding and unfolding processes remains one of the greatest challenges in structural biology and bioinformatics. Computer simulations based on molecular dynamics (MD) are at the forefront of the effort to gain a deeper understanding of these complex processes. Currently, these MD simulations are usually on the order of tens of nanoseconds, generate a large amount of conformational data and are computationally expensive. More and more groups run such simulations and generate a myriad of data, which raises new challenges in managing and analyzing these data. Because the vast range of proteins researchers want to study and simulate, the computational effort needed to generate data, the large data volumes involved, and the different types of analyses scientists need to perform, it is desirable to provide a public repository allowing researchers to pool and share protein unfolding data. To adequately organize, manage, and analyze the data generated by unfolding simulation studies, we designed a data warehouse system that is embedded in a grid environment to facilitate the seamless sharing of available computer resources and thus enable many groups to share complex molecular dynamics simulations on a more regular basis. To gain insight into the conformational fluctuations and stability of the monomeric forms of the amyloidogenic protein transthyretin (TTR), molecular dynamics unfolding simulations of the monomer of human TTR have been conducted. Trajectory data and meta-data of the wild-type (WT) protein and the highly amyloidogenic variant L55P-TTR represent the test case for the data warehouse. Web and grid services, especially pre-defined data mining services that can run on or 'near' the data repository of the data warehouse, are likely to play a pivotal role in the analysis of molecular dynamics unfolding data.

Complete all-atom hydrodynamics of protein unfolding in uniform flow

International Nuclear Information System (INIS)

Wang, Guan M; Sandberg, William C

2010-01-01

The unfolding dynamics of a protein, ubiquitin, pinned in several uniform flows, was studied at low and high flow rates in an all-atom style through a non-equilibrium molecular dynamics approach with explicit water molecules included. Atomic hydrodynamic force components on individual amino acids, as a function of time, due to the collisional interactions with the flowing water molecules were calculated explicitly. The protein conformational change in response to those time-varying forces was computed completely at the high flow rate up to nanosecond until the fully stretched state was reached. The end-to-end length of the single ubiquitin protein molecule at high flow rate is smoothly increasing. The step-like jumps between metastable states that describe the μm ms -1 scale force pulling experiments conducted on polyubiquitins at low flow rates, are not seen at the high flow speeds necessary to computationally probe the ns nm -1 scale regime. No unfolding was observed in the low flow rate atomic computations at nanosecond scale while partial and complete unfolding was observed in the coarse-grained low flow rate computations at microsecond scale. Examination of the all-atom computation of the time variation of the hydrodynamic forces on, and the velocity components of, the protein molecule unveiled to some extent the details of the complexity of the hydrodynamic friction variation in the nm ns -1 regime of high rate flow-driven protein unfolding. This demonstrates quantitatively that all-atom computations are more suitable than the Langevin equation or Brownian dynamics methods for probing the interaction dynamics and resulting conformational dynamics of protein unfolding in strong flows on nm ns -1 time/length scales while the reverse is true for investigation of slow, diffusively driven systems.

A novel neutron energy spectrum unfolding code using particle swarm optimization

International Nuclear Information System (INIS)

Shahabinejad, H.; Sohrabpour, M.

2017-01-01

A novel neutron Spectrum Deconvolution using Particle Swarm Optimization (SDPSO) code has been developed to unfold the neutron spectrum from a pulse height distribution and a response matrix. The Particle Swarm Optimization (PSO) imitates the bird flocks social behavior to solve complex optimization problems. The results of the SDPSO code have been compared with those of the standard spectra and recently published Two-steps Genetic Algorithm Spectrum Unfolding (TGASU) code. The TGASU code have been previously compared with the other codes such as MAXED, GRAVEL, FERDOR and GAMCD and shown to be more accurate than the previous codes. The results of the SDPSO code have been demonstrated to match well with those of the TGASU code for both under determined and over-determined problems. In addition the SDPSO has been shown to be nearly two times faster than the TGASU code. - Highlights: • Introducing a novel method for neutron spectrum unfolding. • Implementation of a particle swarm optimization code for neutron unfolding. • Comparing results of the PSO code with those of recently published TGASU code. • Match results of the PSO code with those of TGASU code. • Greater convergence rate of implemented PSO code than TGASU code.

Intrinsic disorder in Viral Proteins Genome-Linked: experimental and predictive analyses

Directory of Open Access Journals (Sweden)

Van Dorsselaer Alain

2009-02-01

Full Text Available Abstract Background VPgs are viral proteins linked to the 5' end of some viral genomes. Interactions between several VPgs and eukaryotic translation initiation factors eIF4Es are critical for plant infection. However, VPgs are not restricted to phytoviruses, being also involved in genome replication and protein translation of several animal viruses. To date, structural data are still limited to small picornaviral VPgs. Recently three phytoviral VPgs were shown to be natively unfolded proteins. Results In this paper, we report the bacterial expression, purification and biochemical characterization of two phytoviral VPgs, namely the VPgs of Rice yellow mottle virus (RYMV, genus Sobemovirus and Lettuce mosaic virus (LMV, genus Potyvirus. Using far-UV circular dichroism and size exclusion chromatography, we show that RYMV and LMV VPgs are predominantly or partly unstructured in solution, respectively. Using several disorder predictors, we show that both proteins are predicted to possess disordered regions. We next extend theses results to 14 VPgs representative of the viral diversity. Disordered regions were predicted in all VPg sequences whatever the genus and the family. Conclusion Based on these results, we propose that intrinsic disorder is a common feature of VPgs. The functional role of intrinsic disorder is discussed in light of the biological roles of VPgs.

Unique structural modulation of a non-native substrate by cochaperone DnaJ.

Science.gov (United States)

Tiwari, Satyam; Kumar, Vignesh; Jayaraj, Gopal Gunanathan; Maiti, Souvik; Mapa, Koyeli

2013-02-12

The role of bacterial DnaJ protein as a cochaperone of DnaK is strongly appreciated. Although DnaJ unaccompanied by DnaK can bind unfolded as well as native substrate proteins, its role as an individual chaperone remains elusive. In this study, we demonstrate that DnaJ binds a model non-native substrate with a low nanomolar dissociation constant and, more importantly, modulates the structure of its non-native state. The structural modulation achieved by DnaJ is different compared to that achieved by the DnaK-DnaJ complex. The nature of structural modulation exerted by DnaJ is suggestive of a unique unfolding activity on the non-native substrate by the chaperone. Furthermore, we demonstrate that the zinc binding motif along with the C-terminal substrate binding domain of DnaJ is necessary and sufficient for binding and the subsequent binding-induced structural alterations of the non-native substrate. We hypothesize that this hitherto unknown structural alteration of non-native states by DnaJ might be important for its chaperoning activity by removing kinetic traps of the folding intermediates.

Unfolding Semantics of the Untyped λ-Calculus with lectrec-Calculus with letrec

NARCIS (Netherlands)

Rochel, J.

2016-01-01

We investigate the relationship between finite terms in lambda-letrec, the lambda calculus with letrec, and the infinite lambda terms they express. We say that a lambda-letrec term expresses a lambda term if the latter can be obtained as an infinite unfolding of the former. Unfolding is the process

Mapping of unfolding states of integral helical membrane proteins by GPS-NMR and scattering techniques

DEFF Research Database (Denmark)

Calcutta, Antonello; Jessen, Christian M; Behrens, Manja Annette

2012-01-01

induced by unfolding of an integral membrane protein, namely TFE-induced unfolding of KcsA solubilized by the n-dodecyl ß-d-maltoside (DDM) surfactant is investigated by the recently introduced GPS-NMR (Global Protein folding State mapping by multivariate NMR) (Malmendal et al., PlosONE 5, e10262 (2010......)) along with dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). GPS-NMR is used as a tool for fast analysis of the protein unfolding processes upon external perturbation, and DLS and SAXS are used for further structural characterization of the unfolding states. The combination allows...

Bosonic Fradkin-Tseytlin equations unfolded

Energy Technology Data Exchange (ETDEWEB)

Shaynkman, O.V. [I.E.Tamm Theory Department, Lebedev Physical Institute,Leninski prospect 53, 119991, Moscow (Russian Federation)

2016-12-22

We test infinite-dimensional extension of algebra su(k,k) proposed by Fradkin and Linetsky as the candidate for conformal higher spin algebra. Adjoint and twisted-adjoint representations of su(k,k) on the space of this algebra are carefully explored. For k=2 corresponding unfolded system is analyzed and it is shown to encode Fradkin-Tseytlin equations for the set of all integer spins 1,2,… with infinite multiplicity.

TFE-induced local unfolding and fibrillation of SOD1: bridging the experiment and simulation studies.

Science.gov (United States)

Kumar, Vijay; Prakash, Amresh; Pandey, Preeti; Lynn, Andrew M; Hassan, Md Imtaiyaz

2018-05-18

Misfolding and aggregation of Cu, Zn Superoxide dismutase (SOD1) is involved in the neurodegenerative disease, amyotrophic lateral sclerosis. Many studies have shown that metal-depleted, monomeric form of SOD1 displays substantial local unfolding dynamics and is the precursor for aggregation. Here, we have studied the structure and dynamics of different apo monomeric SOD1 variants associated with unfolding and aggregation in aqueous trifluoroethanol (TFE) through experiments and simulation. TFE induces partially unfolded β-sheet-rich extended conformations in these SOD1 variants, which subsequently develops aggregates with fibril-like characteristics. Fibrillation was achieved more easily in disulfide-reduced monomeric SOD1 when compared with wild-type and mutant monomeric SOD1. At higher concentrations of TFE, a native-like structure with the increase in α-helical content was observed. The molecular dynamics simulation results illustrate distinct structural dynamics for different regions of SOD1 variants and show uniform local unfolding of β-strands. The strands protected by the zinc-binding and electrostatic loops were found to unfold first in 20% (v/v) TFE, leading to a partial unfolding of β-strands 4, 5, and 6 which are prone to aggregation. Our results thus shed light on the role of local unfolding and conformational dynamics in SOD1 misfolding and aggregation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Comparison of intra-organellar chaperone capacity for dealing with stress-induced protein unfolding

NARCIS (Netherlands)

Hageman, Jurre; Vos, Michel J.; van Waarde, Maria A. W. H.; Kampinga, Harm H.

2007-01-01

Molecular chaperones are essential for cells to prevent that partially unfolded proteins form non-functional, toxic aggregates. This requirement is increased when cells experience protein unfolding stresses and such could affect all compartments in the eukaryotic cell. Whether all organelles are

Comparison of neutron spectrum unfolding codes

International Nuclear Information System (INIS)

Zijp, W.

1979-02-01

This final report contains a set of four ECN-reports. The first is dealing with the comparison of the neutron spectrum unfolding codes CRYSTAL BALL, RFSP-JUL, SAND II and STAY'SL. The other three present the results of calculations about the influence of statistical weights in CRYSTAL BALL, SAND II and RFSP-JUL

Moessbauer spectroscopic evidence on the heme binding to the proximal histidine in unfolded carbonmonoxy myoglobin by guanidine hydrochloride

Energy Technology Data Exchange (ETDEWEB)

Harami, Taikan, E-mail: harami.taikan@jaea.go.jp [Japan Atomic Energy Agency (Japan); Kitao, Shinji; Kobayashi, Yasuhiro [Kyoto University, Research Reactor Institute (Japan); Mitsui, Takaya [Japan Atomic Energy Agency (Japan)

2008-01-15

The unfolded heme structure in myoglobin is controversial because of no chance of direct X-ray structure analyses. The unfolding of carbonmonoxy myoglobin (MbCO) by guanidine hydrochloride (GdnHCl) was studied by the Moessbauer spectroscopy. The spectra show the presence of a sort of spectrum in the unfolded MbCO, independent on the concentration of GdnHCl from 1 to 6 M and the increase of the fraction of unfolded MbCO, depending on the GdnHCl concentration. The isomer shift of the iron of heme in the unfolded MbCO was identified to be different from that of the native MbCO as the globin structure in Mb collapses under the unfolded conditions. This result and the existing related Moessbauer data proved that the heme in the unfolded MbCO may remain coordinated to the proximal histidine.

BONDI-97 A novel neutron energy spectrum unfolding tool using a genetic algorithm

CERN Document Server

Mukherjee, B

1999-01-01

The neutron spectrum unfolding procedure using the count rate data obtained from a set of Bonner sphere neutron detectors requires the solution of the Fredholm integral equation of the first kind by using complex mathematical methods. This paper reports a new approach for the unfolding of neutron spectra using the Genetic Algorithm tool BONDI-97 (BOnner sphere Neutron DIfferentiation). The BONDI-97 was used as the input for Genetic Algorithm engine EVOLVER to search for a globally optimised solution vector from a population of randomly generated solutions. This solution vector corresponds to the unfolded neutron energy spectrum. The Genetic Algorithm engine emulates the Darwinian 'Survival of the Fittest' strategy, the key ingredient of the 'Theory of Evolution'. The spectra of sup 2 sup 4 sup 1 Am/Be (alpha,n) and sup 2 sup 3 sup 9 Pu/Be (alpha,n) neutron sources were unfolded using the BONDI-97 tool. (author)

Unique Features of Halophilic Proteins.

Science.gov (United States)

Arakawa, Tsutomu; Yamaguchi, Rui; Tokunaga, Hiroko; Tokunaga, Masao

2017-01-01

Proteins from moderate and extreme halophiles have unique characteristics. They are highly acidic and hydrophilic, similar to intrinsically disordered proteins. These characteristics make the halophilic proteins soluble in water and fold reversibly. In addition to reversible folding, the rate of refolding of halophilic proteins from denatured structure is generally slow, often taking several days, for example, for extremely halophilic proteins. This slow folding rate makes the halophilic proteins a novel model system for folding mechanism analysis. High solubility and reversible folding also make the halophilic proteins excellent fusion partners for soluble expression of recombinant proteins.

The criteria for selecting a method for unfolding neutron spectra based on the information entropy theory

International Nuclear Information System (INIS)

Zhu, Qingjun; Song, Fengquan; Ren, Jie; Chen, Xueyong; Zhou, Bin

2014-01-01

To further expand the application of an artificial neural network in the field of neutron spectrometry, the criteria for choosing between an artificial neural network and the maximum entropy method for the purpose of unfolding neutron spectra was presented. The counts of the Bonner spheres for IAEA neutron spectra were used as a database, and the artificial neural network and the maximum entropy method were used to unfold neutron spectra; the mean squares of the spectra were defined as the differences between the desired and unfolded spectra. After the information entropy of each spectrum was calculated using information entropy theory, the relationship between the mean squares of the spectra and the information entropy was acquired. Useful information from the information entropy guided the selection of unfolding methods. Due to the importance of the information entropy, the method for predicting the information entropy using the Bonner spheres' counts was established. The criteria based on the information entropy theory can be used to choose between the artificial neural network and the maximum entropy method unfolding methods. The application of an artificial neural network to unfold neutron spectra was expanded. - Highlights: • Two neutron spectra unfolding methods, ANN and MEM, were compared. • The spectrum's entropy offers useful information for selecting unfolding methods. • For the spectrum with low entropy, the ANN was generally better than MEM. • The spectrum's entropy was predicted based on the Bonner spheres' counts

FERD and FERDOR type unfolding codes

International Nuclear Information System (INIS)

Burrus, W.R.

1976-01-01

FERD and FERDO are unfolding codes which were developed at the Neutron Physics Division of Oak Ridge National Laboratory in 1965 and 1966. FERDO variants such as FERDOR and FORIST have been widely used, and many useful supplementary procedures have been developed for neutron and gamma-ray spectroscopy and other diverse applications. Algorithms for the codes are discussed

Development of the unfolding procedures in fast neutron scintillation spectrometry; Razvoj unfolding procedura u scintilacionoj spektrometriji brzih neutrona

Energy Technology Data Exchange (ETDEWEB)

Marinkovic, P [Elektrotehnicki fakultet, Belgrade (Yugoslavia)

1988-07-01

Two unfolding procedures have been developed for obtaining fast neutron spectrum from proton-recoil spectrum assigned for spectrometry with organic scintillators. First is the method of differentiation of proton-recoil spectrum, and the second is the method based on solution of integral equation of Fredholm of first kind. (author)

Unfolding the phenomenon of inter-rater agreement

DEFF Research Database (Denmark)

Slaug, Bjørn; Schilling, Oliver; Helle, Tina

2011-01-01

Objective: The overall objective was to unfold the phenomenon of inter-rater agreement: to identify potential sources of variation in agreement data and to explore how they can be statistically accounted for. The ultimate aim was to propose recommendations for in-depth examination of agreement, i...

Sequence-dependent unfolding kinetics of DNA hairpins studied by nanopore force spectroscopy

International Nuclear Information System (INIS)

Renner, Stephan; Bessonov, Andrey; Simmel, Friedrich C; Gerland, Ulrich

2010-01-01

Nanopore force spectroscopy is used to study the unzipping kinetics of two DNA hairpin molecules with a 12 base pair long stem containing two contiguous stretches of six GC and six AT base pairs in interchanged order. Even though the thermodynamic stabilities of the two structures are nearly the same, they differ greatly in their unzipping kinetics. When the GC segment has to be broken before the AT segment, the unfolding rate is orders of magnitude smaller than in the opposite case. We also investigated hairpins with stem regions consisting only of AT or GC base pairs. The pure AT hairpins translocate much faster than the other hairpins, whereas the pure GC hairpins translocate on similar timescales to the hairpins with only an initial GC segment. For each hairpin, nanopore force spectroscopy is performed for different loading rates and the resulting unzipping distributions are mathematically transformed to a master curve that yields the unfolding rate as a function of applied voltage. This is compared with a stochastic model of the unfolding process for the two sequences for different voltages. The results can be rationalized in terms of the different natures of the free energy landscapes for the unfolding process.

Highly Perturbed pKa Values in the Unfolded State of Hen Egg White Lysozyme

OpenAIRE

Bradley, John; O'Meara, Fergal; Farrell, Damien; Nielsen, Jens Erik

2012-01-01

The majority of pKa values in protein unfolded states are close to the amino acid model pKa values, thus reflecting the weak intramolecular interactions present in the unfolded ensemble of most proteins. We have carried out thermal denaturation measurements on the WT and eight mutants of HEWL from pH 1.5 to pH 11.0 to examine the unfolded state pKa values and the pH dependence of protein stability for this enzyme. The availability of accurate pKa values for the folded state of HEWL and separa...

Neutron spectra unfolding in Bonner spheres spectrometry using neural networks

International Nuclear Information System (INIS)

Kardan, M.R.; Setayeshi, S.; Koohi-Fayegh, R.; Ghiassi-Nejad, M.

2003-01-01

The neural network method has been used for the unfolding of neutron spectra in neutron spectrometry by Bonner spheres. A back propagation algorithm was used for training of neural networks 4mm x 4 mm bare LiI(Eu) and in a polyethylene sphere set: 2, 3, 4, 5, 6, 7, 8, 10, 12, 18 inch diameter have been used for unfolding of neutron spectra. Neural networks were trained by 199 sets of neutron spectra, which were subdivided into 6, 8, 10, 12, 15 and 20 energy bins and for each of them an appropriate neural network was designed and trained. The validation was performed by the 21 sets of neutron spectra. A neural network with 10 energy bins which had a mean value of error of 6% for dose equivalent estimation of spectra in the validation set showed the best results. The obtained results show that neural networks can be applied as an effective method for unfolding neutron spectra especially when the main target is neutron dosimetry. (author)

Prediction and analysis of structure, stability and unfolding of thermolysin-like proteases

Science.gov (United States)

Vriend, Gert; Eijsink, Vincent

1993-08-01

Bacillus neutral proteases (NPs) form a group of well-characterized homologous enzymes, that exhibit large differences in thermostability. The three-dimensional (3D) structures of several of these enzymes have been modelled on the basis of the crystal structures of the NPs of B. thermoproteolyticus (thermolysin) and B. cercus. Several new techniques have been developed to improve the model-building procedures. Also a model-building by mutagenesis' strategy was used, in which mutants were designed just to shed light on parts of the structures that were particularly hard to model. The NP models have been used for the prediction of site-directed mutations aimed at improving the thermostability of the enzymes. Predictions were made using several novel computational techniques, such as position-specific rotamer searching, packing quality analysis and property-profile database searches. Many stabilizing mutations were predicted and produced: improvement of hydrogen bonding, exclusion of buried water molecules, capping helices, improvement of hydrophobic interactions and entropic stabilization have been applied successfully. At elevated temperatures NPs are irreversibly inactivated as a result of autolysis. It has been shown that this denaturation process is independent of the protease activity and concentration and that the inactivation follows first-order kinetics. From this it has been conjectured that local unfolding of (surface) loops, which renders the protein susceptible to autolysis, is the rate-limiting step. Despite the particular nature of the thermal denaturation process, normal rules for protein stability can be applied to NPs. However, rather than stabilizing the whole protein against global unfolding, only a small region has to be protected against local unfolding. In contrast to proteins in general, mutational effects in proteases are not additive and their magnitude is strongly dependent on the location of the mutation. Mutations that alter the stability

Motional properties of unfolded ubiquitin: a model for a random coil protein

Energy Technology Data Exchange (ETDEWEB)

Wirmer, Julia [Johann Wolfgang GoeUniversityFrankfurt, Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (Germany); Peti, Wolfgang [Brown University, Department of Molecular Pharmacology, Physiology and Biotechnology (United States); Schwalbe, Harald [Johann Wolfgang GoeUniversityFrankfurt, Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (Germany)], E-mail: schwalbe@nmr.uni-frankfurt.de

2006-07-15

The characterization of unfolded states of proteins has recently attracted considerable interest, as the residual structure present in these states may play a crucial role in determining their folding and misfolding behavior. Here, we investigated the dynamics in the denatured state of ubiquitin in 8 M urea at pH2. Under these conditions, ubiquitin does not have any detectable local residual structure, and uniform {sup 15}N relaxation rates along the sequence indicate the absence of motional restrictions caused by residual secondary structure and/or long-range interactions. A comparison of different models to predict relaxation data in unfolded proteins suggests that the subnanosecond dynamics in unfolded states depend on segmental motions only and do not show a dependence on the residue type but for proline and glycine residues.

An unfolding method for high energy physics experiments

International Nuclear Information System (INIS)

Blobel, V.

2002-06-01

Finite detector resolution and limited acceptance require one to apply unfolding methods in high energy physics experiments. Information on the detector resolution is usually given by a set of Monte Carlo events. Based on the experience with a widely used unfolding program (RUN) a modified method has been developed. The first step of the method is a maximum likelihood fit of the Monte Carlo distributions to the measured distribution in one, two or three dimensions; the finite statistics of the Monte Carlo events is taken into account by the use of Barlow's method with a new method of solution. A clustering method is used before combining bins in sparsely populated areas. In the second step a regularization is applied to the solution, which introduces only a small bias. The regularization parameter is determined from the data after a diagonalization and rotation procedure. (orig.)

FERDO/FERD, Unfolding of Pulse-Height Spectrometer Spectra

International Nuclear Information System (INIS)

Rust, B.W.; Ingersoll, D.T.; Burrus, W.R.

1985-01-01

1 - Description of problem or function: FERDO and FERD are unfolding codes which can be used to correct observed pulse-height distributions for the non-ideal response of a pulse-height spectrometer or to solve poorly conditioned linear equations. 2 - Method of solution: It is assumed that the response of the spectrometer is given by Ax = b, where A is the spectrometer response function matrix, x is the unknown spectrum, and b is the pulse-height distribution. FERDO does not resolve directly for x but instead solves for p = Wx, where W is a 'window function matrix'. Typically, W is the resolution function of an ideal spectrometer which has a single Gaussian response. The effective resolution of the unfolding solution may be varied by the choice of W. Confidence intervals are found for each element of the solution p

Reversibility and two state behaviour in the thermal unfolding of oligomeric TIM barrel proteins.

Science.gov (United States)

Romero-Romero, Sergio; Costas, Miguel; Rodríguez-Romero, Adela; Alejandro Fernández-Velasco, D

2015-08-28

Temperature is one of the main variables that modulate protein function and stability. Thermodynamic studies of oligomeric proteins, the dominant protein natural form, have been often hampered because irreversible aggregation and/or slow reactions are common. There are no reports on the reversible equilibrium thermal unfolding of proteins composed of (β/α)8 barrel subunits, albeit this "TIM barrel" topology is one of the most abundant and versatile in nature. We studied the eponymous TIM barrel, triosephosphate isomerase (TIM), belonging to five species of different bacterial taxa. All of them were found to be catalytically efficient dimers. The three-dimensional structure of four enzymes was solved at high/medium resolution. Irreversibility and kinetic control were observed in the thermal unfolding of two TIMs, while for the other three the thermal unfolding was found to follow a two-state equilibrium reversible process. Shifts in the global stability curves of these three proteins are related to the organismal temperature range of optimal growth and modulated by variations in maximum stability temperature and in the enthalpy change at that temperature. Reversibility appears to correlate with the low isoelectric point, the absence of a residual structure in the unfolded state, small cavity volume in the native state, low conformational stability and a low melting temperature. Furthermore, the strong coupling between dimer dissociation and monomer unfolding may reduce aggregation and favour reversibility. It is therefore very thought-provoking to find that a common topological ensemble, such as the TIM barrel, can unfold/refold in the Anfinsen way, i.e. without the help of the cellular machinery.

Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved beta(2)-microglobulin

DEFF Research Database (Denmark)

Heegaard, N.H.H.; Jørgensen, T.J.D.; Rozlosnik, N.

2005-01-01

. Using amide hydrogen/deuterium exchange monitored by mass spectrometry, we show that Delta K58-beta(2)m has increased unfolding rates compared to wt-beta(2)m and that unfolding is highly temperature dependent. The unfolding rate is I order of magnitude faster in Delta K58-beta(2)M than in wt-beta(2)m...... in the circulation of dialysis patients. This beta(2)M variant, Delta K58-beta(2)m, is a disulfide-linked two-chain molecule consisting of amino acid residues 1-57 and 59-99 of intact beta(2)m, and we here demonstrate and characterize its decreased conformational stability as compared to wild-type (wt) beta(2)M...

THE SURFACE-MEDIATED UNFOLDING KINETICS OF GLOBULAR PROTEINS IS DEPENDENT ON MOLECULAR WEIGHT AND TEMPERATURE

Energy Technology Data Exchange (ETDEWEB)

Patananan, A.N.; Goheen, S.C.

2008-01-01

The adsorption and unfolding pathways of proteins on rigid surfaces are essential in numerous complex processes associated with biomedical engineering, nanotechnology, and chromatography. It is now well accepted that the kinetics of unfolding are characterized by chemical and physical interactions dependent on protein deformability and structure, as well as environmental pH, temperature, and surface chemistry. Although this fundamental process has broad implications in medicine and industry, little is known about the mechanism because of the atomic lengths and rapid time scales involved. Therefore, the unfolding kinetics of myoglobin, β-glucosidase, and ovalbumin were investigated by adsorbing the globular proteins to non-porous cationic polymer beads. The protein fractions were adsorbed at different residence times (0, 9, 10, 20, and 30 min) at near-physiological conditions using a gradient elution system similar to that in high-performance liquid chromatography. The elution profi les and retention times were obtained by ultraviolet/visible spectrophotometry. A decrease in recovery was observed with time for almost all proteins and was attributed to irreversible protein unfolding on the non-porous surfaces. These data, and those of previous studies, fi t a positively increasing linear trend between percent unfolding after a fi xed (9 min) residence time (71.8%, 31.1%, and 32.1% of myoglobin, β-glucosidase, and ovalbumin, respectively) and molecular weight. Of all the proteins examined so far, only myoglobin deviated from this trend with higher than predicted unfolding rates. Myoglobin also exhibited an increase in retention time over a wide temperature range (0°C and 55°C, 4.39 min and 5.74 min, respectively) whereas ovalbumin and β-glucosidase did not. Further studies using a larger set of proteins are required to better understand the physiological and physiochemical implications of protein unfolding kinetics. This study confi rms that surface

Unfolding Green Defense

DEFF Research Database (Denmark)

Larsen, Kristian Knus

2015-01-01

In recent years, many states have developed and implemented green solutions for defense. Building on these initiatives NATO formulated the NATO Green Defence Framework in 2014. The framework provides a broad basis for cooperation within the Alliance on green solutions for defense. This report aims...... to inform and support the further development of green solutions by unfolding how green technologies and green strategies have been developed and used to handle current security challenges. The report, initially, focuses on the security challenges that are being linked to green defense, namely fuel...... consumption in military operations, defense expenditure, energy security, and global climate change. The report then proceeds to introduce the NATO Green Defence Framework before exploring specific current uses of green technologies and green strategies for defense. The report concludes that a number...

An approach to unfold the response of a multi-element system using an artificial neural network

International Nuclear Information System (INIS)

Cordes, E.; Fehrenbacher, G.; Schuetz, R.; Sprunck, M.; Hahn, K.; Hofmann, R.; Wahl, W.

1998-01-01

An unfolding procedure is proposed which aims at obtaining spectral information of a neutron radiation field by the analysis of the response of a multi-element system consisting of converter type semiconductors. For the unfolding procedure an artificial neural network (feed forward network), trained by the back-propagation method, was used. The response functions of the single elements to neutron radiation were calculated by application of a computational model for an energy range from 10 -2 eV to 10 MeV. The training of the artificial neural network was based on the computation of responses of a six-element system for a set of 300 neutron spectra and the application of the back-propagation method. The validation was performed by the unfolding of 100 computed responses. Two unfolding examples were pointed out for the determination of the neutron spectra. The spectra resulting from the unfolding procedure agree well with the original spectra used for the response computation

Considerably Unfolded Transthyretin Monomers Preceed and Exchange with Dynamically Structured Amyloid Protofibrils

DEFF Research Database (Denmark)

Groenning, Minna; Campos, Raul I; Hirschberg, Daniel

2015-01-01

describe an unexpectedly dynamic TTR protofibril structure which exchanges protomers with highly unfolded monomers in solution. The protofibrils only grow to an approximate final size of 2,900 kDa and a length of 70 nm and a comparative HXMS analysis of native and aggregated samples revealed a much higher...... average solvent exposure of TTR upon fibrillation. With SAXS, we reveal the continuous presence of a considerably unfolded TTR monomer throughout the fibrillation process, and show that a considerable fraction of the fibrillating protein remains in solution even at a late maturation state. Together......, these data reveal that the fibrillar state interchanges with the solution state. Accordingly, we suggest that TTR fibrillation proceeds via addition of considerably unfolded monomers, and the continuous presence of amyloidogenic structures near the protofibril surface offers a plausible explanation...

Joint mapping of genes and conditions via multidimensional unfolding analysis

Directory of Open Access Journals (Sweden)

Engelen Kristof

2007-06-01

Full Text Available Abstract Background Microarray compendia profile the expression of genes in a number of experimental conditions. Such data compendia are useful not only to group genes and conditions based on their similarity in overall expression over profiles but also to gain information on more subtle relations between genes and conditions. Getting a clear visual overview of all these patterns in a single easy-to-grasp representation is a useful preliminary analysis step: We propose to use for this purpose an advanced exploratory method, called multidimensional unfolding. Results We present a novel algorithm for multidimensional unfolding that overcomes both general problems and problems that are specific for the analysis of gene expression data sets. Applying the algorithm to two publicly available microarray compendia illustrates its power as a tool for exploratory data analysis: The unfolding analysis of a first data set resulted in a two-dimensional representation which clearly reveals temporal regulation patterns for the genes and a meaningful structure for the time points, while the analysis of a second data set showed the algorithm's ability to go beyond a mere identification of those genes that discriminate between different patient or tissue types. Conclusion Multidimensional unfolding offers a useful tool for preliminary explorations of microarray data: By relying on an easy-to-grasp low-dimensional geometric framework, relations among genes, among conditions and between genes and conditions are simultaneously represented in an accessible way which may reveal interesting patterns in the data. An additional advantage of the method is that it can be applied to the raw data without necessitating the choice of suitable genewise transformations of the data.

Characterization and error analysis of an N×N unfolding procedure applied to filtered, photoelectric x-ray detector arrays. II. Error analysis and generalization

Directory of Open Access Journals (Sweden)

D. L. Fehl

2010-12-01

Full Text Available A five-channel, filtered-x-ray-detector (XRD array has been used to measure time-dependent, soft-x-ray flux emitted by z-pinch plasmas at the Z pulsed-power accelerator (Sandia National Laboratories, Albuquerque, New Mexico, USA. The preceding, companion paper [D. L. Fehl et al., Phys. Rev. ST Accel. Beams 13, 120402 (2010PRABFM1098-4402] describes an algorithm for spectral reconstructions (unfolds and spectrally integrated flux estimates from data obtained by this instrument. The unfolded spectrum S_{unfold}(E,t is based on (N=5 first-order B-splines (histograms in contiguous unfold bins j=1,…,N; the recovered x-ray flux F_{unfold}(t is estimated as ∫S_{unfold}(E,tdE, where E is x-ray energy and t is time. This paper adds two major improvements to the preceding unfold analysis: (a Error analysis.—Both data noise and response-function uncertainties are propagated into S_{unfold}(E,t and F_{unfold}(t. Noise factors ν are derived from simulations to quantify algorithm-induced changes in the noise-to-signal ratio (NSR for S_{unfold} in each unfold bin j and for F_{unfold} (ν≡NSR_{output}/NSR_{input}: for S_{unfold}, 1≲ν_{j}≲30, an outcome that is strongly spectrally dependent; for F_{unfold}, 0.6≲ν_{F}≲1, a result that is less spectrally sensitive and corroborated independently. For nominal z-pinch experiments, the combined uncertainty (noise and calibrations in F_{unfold}(t at peak is estimated to be ∼15%. (b Generalization of the unfold method.—Spectral sensitivities (called here passband functions are constructed for S_{unfold} and F_{unfold}. Predicting how the unfold algorithm reconstructs arbitrary spectra is thereby reduced to quadratures. These tools allow one to understand and quantitatively predict algorithmic distortions (including negative artifacts, to identify potentially troublesome spectra, and to design more useful response functions.

Computational design and biophysical characterization of aggregation-resistant point mutations for γD crystallin illustrate a balance of conformational stability and intrinsic aggregation propensity.

Science.gov (United States)

Sahin, Erinc; Jordan, Jacob L; Spatara, Michelle L; Naranjo, Andrea; Costanzo, Joseph A; Weiss, William F; Robinson, Anne Skaja; Fernandez, Erik J; Roberts, Christopher J

2011-02-08

γD crystallin is a natively monomeric eye-lens protein that is associated with hereditary juvenile cataract formation. It is an attractive model system as a multidomain Greek-key protein that aggregates through partially folded intermediates. Point mutations M69Q and S130P were used to test (1) whether the protein-design algorithm RosettaDesign would successfully predict mutants that are resistant to aggregation when combined with informatic sequence-based predictors of peptide aggregation propensity and (2) how the mutations affected relative unfolding free energies (ΔΔG(un)) and intrinsic aggregation propensity (IAP). M69Q was predicted to have ΔΔG(un) ≫ 0, without significantly affecting IAP. S130P was predicted to have ΔΔG(un) ∼ 0 but with reduced IAP. The stability, conformation, and aggregation kinetics in acidic solution were experimentally characterized and compared for the variants and wild-type (WT) protein using circular dichroism and intrinsic fluorescence spectroscopy, calorimetric and chemical unfolding, thioflavin-T binding, chromatography, static laser light scattering, and kinetic modeling. Monomer secondary and tertiary structures of both variants were indistinguishable from WT, while ΔΔG(un) > 0 for M69Q and ΔΔG(un) < 0 for S130P. Surprisingly, despite being the least conformationally stable, S130P was the most resistant to aggregation, indicating a significant decrease of its IAP compared to WT and M69Q.

Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

Science.gov (United States)

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

2016-04-05

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

Aging in the Male Face: Intrinsic and Extrinsic Factors.

Science.gov (United States)

Keaney, Terrence C

2016-07-01

Gender is one of the most significant factors that influence facial anatomy and behavior, both key factors in the aging process. To review male facial anatomy, physiology, and behavior and how it contributes to sexual dimorphism in facial aging. A MEDLINE search was performed for publications on gender differences in facial anatomy, aging, cutaneous physiology, and behavior. There are differences in both intrinsic and extrinsic aging factors in men. Men have a thicker epidermis and dermis with more active cutaneous appendages including hair growth. Male skin has a reduced antioxidant capacity and increased ultraviolet-induced immunosuppression. The male face is larger and has a unique square shape with less subcutaneous soft tissue, especially at the medial cheek. Men are also more prone to smoking and exhibiting poor sun-protective behavior. The differences in intrinsic and extrinsic aging factors contribute to poor facial aging in men. Men develop more severe rhytides in a unique pattern, show increased periocular aging changes, and are more prone to hair loss. This review provides insight into the factors contributing to accelerated male facial aging. Understanding gender differences in aging will help physicians tailor cosmetic treatments for men and minimize extrinsic aging factors.

Measurement of the unfolded protein response (UPR) in monocytes.

LENUS (Irish Health Repository)

Carroll, Tomás P

2011-01-01

In mammalian cells, the primary function of the endoplasmic reticulum (ER) is to synthesize and assemble membrane and secreted proteins. As the main site of protein folding and posttranslational modification in the cell, the ER operates a highly conserved quality control system to ensure only correctly assembled proteins exit the ER and misfolded and unfolded proteins are retained for disposal. Any disruption in the equilibrium of the ER engages a multifaceted intracellular signaling pathway termed the unfolded protein response (UPR) to restore normal conditions in the cell. A variety of pathological conditions can induce activation of the UPR, including neurodegenerative disorders such as Parkinson\\'s disease, metabolic disorders such as atherosclerosis, and conformational disorders such as cystic fibrosis. Conformational disorders are characterized by mutations that modify the final structure of a protein and any cells that express abnormal protein risk functional impairment. The monocyte is an important and long-lived immune cell and acts as a key immunological orchestrator, dictating the intensity and duration of the host immune response. Monocytes expressing misfolded or unfolded protein may exhibit UPR activation and this can compromise the host immune system. Here, we describe in detail methods and protocols for the examination of UPR activation in peripheral blood monocytes. This guide should provide new investigators to the field with a broad understanding of the tools required to investigate the UPR in the monocyte.

Measurement of the unfolded protein response (UPR) in monocytes.

LENUS (Irish Health Repository)

Carroll, Tomas P

2012-02-01

In mammalian cells, the primary function of the endoplasmic reticulum (ER) is to synthesize and assemble membrane and secreted proteins. As the main site of protein folding and posttranslational modification in the cell, the ER operates a highly conserved quality control system to ensure only correctly assembled proteins exit the ER and misfolded and unfolded proteins are retained for disposal. Any disruption in the equilibrium of the ER engages a multifaceted intracellular signaling pathway termed the unfolded protein response (UPR) to restore normal conditions in the cell. A variety of pathological conditions can induce activation of the UPR, including neurodegenerative disorders such as Parkinson\\'s disease, metabolic disorders such as atherosclerosis, and conformational disorders such as cystic fibrosis. Conformational disorders are characterized by mutations that modify the final structure of a protein and any cells that express abnormal protein risk functional impairment. The monocyte is an important and long-lived immune cell and acts as a key immunological orchestrator, dictating the intensity and duration of the host immune response. Monocytes expressing misfolded or unfolded protein may exhibit UPR activation and this can compromise the host immune system. Here, we describe in detail methods and protocols for the examination of UPR activation in peripheral blood monocytes. This guide should provide new investigators to the field with a broad understanding of the tools required to investigate the UPR in the monocyte.

Dante-unfolding code for energy spectra evaluation

International Nuclear Information System (INIS)

Petilli, M.

1979-01-01

The code DANTE, using the last square method in unfolding for dosimetry purpose, solves the neutron spectra evaluation problem starting by activity measurements. The code DANTE introduced for the first time the correlation between available data by mean of flux and activity variance-covariance matrices and the error propagation. In the present report the solution method is detailed described

A high-resolution neutron spectra unfolding method using the Genetic Algorithm technique

CERN Document Server

Mukherjee, B

2002-01-01

The Bonner sphere spectrometers (BSS) are commonly used to determine the neutron spectra within various nuclear facilities. Sophisticated mathematical tools are used to unfold the neutron energy distribution from the output data of the BSS. This paper highlights a novel high-resolution neutron spectra-unfolding method using the Genetic Algorithm (GA) technique. The GA imitates the biological evolution process prevailing in the nature to solve complex optimisation problems. The GA method was utilised to evaluate the neutron energy distribution, average energy, fluence and equivalent dose rates at important work places of a DIDO class research reactor and a high-energy superconducting heavy ion cyclotron. The spectrometer was calibrated with a sup 2 sup 4 sup 1 Am/Be (alpha,n) neutron standard source. The results of the GA method agreed satisfactorily with the results obtained by using the well-known BUNKI neutron spectra unfolding code.

Microsecond simulations of the folding/unfolding thermodynamics of the Trp-cage mini protein

Science.gov (United States)

Day, Ryan; Paschek, Dietmar; Garcia, Angel E.

2012-01-01

We study the unbiased folding/unfolding thermodynamics of the Trp-cage miniprotein using detailed molecular dynamics simulations of an all-atom model of the protein in explicit solvent, using the Amberff99SB force field. Replica-exchange molecular dynamics (REMD) simulations are used to sample the protein ensembles over a broad range of temperatures covering the folded and unfolded states, and at two densities. The obtained ensembles are shown to reach equilibrium in the 1 μs per replica timescale. The total simulation time employed in the calculations exceeds 100 μs. Ensemble averages of the fraction folded, pressure, and energy differences between the folded and unfolded states as a function of temperature are used to model the free energy of the folding transition, ΔG(P,T), over the whole region of temperature and pressures sampled in the simulations. The ΔG(P,T) diagram describes an ellipse over the range of temperatures and pressures sampled, predicting that the system can undergo pressure induced unfolding and cold denaturation at low temperatures and high pressures, and unfolding at low pressures and high temperatures. The calculated free energy function exhibits remarkably good agreement with the experimental folding transition temperature (Tf = 321 K), free energy and specific heat changes. However, changes in enthalpy and entropy are significantly different than the experimental values. We speculate that these differences may be due to the simplicity of the semi-empirical force field used in the simulations and that more elaborate force fields may be required to describe appropriately the thermodynamics of proteins. PMID:20408169

A highly compliant protein native state with a spontaneous-like mechanical unfolding pathway

DEFF Research Database (Denmark)

Heiðarsson, Pétur Orri; Valpapuram, Immanuel; Camilloni, Carlo

2012-01-01

The mechanical properties of proteins and their force-induced structural changes play key roles in many biological processes. Previous studies have shown that natively folded proteins are brittle under tension, unfolding after small mechanical deformations, while partially folded intermediate...... states, such as molten globules, are compliant and can deform elastically a great amount before crossing the transition state barrier. Moreover, under tension proteins appear to unfold through a different sequence of events than during spontaneous unfolding. Here, we describe the response to force...... of the four-α-helix acyl-CoA binding protein (ACBP) in the low-force regime using optical tweezers and ratcheted molecular dynamics simulations. The results of our studies reveal an unprecedented mechanical behavior of a natively folded protein. ACBP displays an atypical compliance along two nearly orthogonal...

Unfolding neutron spectra with BS-TLD system using genetic algorithms

Energy Technology Data Exchange (ETDEWEB)

Santos, Joelan A.L., E-mail: jasantos@cnen.gov.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Silva, Everton R. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Centro de Informatica; Ferreira, Tiago A.E. [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil). Dept. de Estatistica e Informatica; Fonseca, Evaldo S. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Vilela, Eudice C., E-mail: ecvilela@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

2011-07-01

Due to the variability of neutron spectrum within the same environment, it is essential that the spectral distribution as function of energy to be characterized. To perform this task, the neutron spectrometer has a primary role in determining the neutron flux ({Phi}{sub E}(E)). Precise information allows radiological quantities establishment related to that spectrum but it is necessary, however, a series of steps with a spectrometric system that can cover a large interval of energy and whose answer is isotropic. The most widely used for accomplishing this task is the spectrometric Bonner spheres system. One of the biggest problems related to neutron spectrometry is the process of data analysis, known as unfolding. Most of the work undertaken to implement new techniques of this process, using data obtained with the scintillator {sup 6}LiI(I). However, characteristics related to the dead time make it not be so effective when used in high flow neutron fields. An alternative to this problem is the use of thermoluminescent detectors (TLD), but the codes used do not provide a more specific response matrix to unfolding the information obtained through these materials, which makes the development of a specific response matrix important to adequately characterize the response obtained by them. This paper proposes using a technique of artificial intelligence called genetic algorithm, which uses bio-inspired mathematical models and through the implementation of a specific matrix to unfolding data obtained from a combination of TLDs embedded in a system of Bonner spheres, such as thermal neutron detectors, to characterize the neutron spectrum as a function of energy. The results obtained with this method were in accordance with reference spectra, thus enables of this technique to unfolding neutrons spectra with BS-TLD system. (author)

Unfolding neutron spectra with BS-TLD system using genetic algorithms

International Nuclear Information System (INIS)

Santos, Joelan A.L.; Silva, Everton R.; Vilela, Eudice C.

2011-01-01

Due to the variability of neutron spectrum within the same environment, it is essential that the spectral distribution as function of energy to be characterized. To perform this task, the neutron spectrometer has a primary role in determining the neutron flux (Φ E (E)). Precise information allows radiological quantities establishment related to that spectrum but it is necessary, however, a series of steps with a spectrometric system that can cover a large interval of energy and whose answer is isotropic. The most widely used for accomplishing this task is the spectrometric Bonner spheres system. One of the biggest problems related to neutron spectrometry is the process of data analysis, known as unfolding. Most of the work undertaken to implement new techniques of this process, using data obtained with the scintillator 6 LiI(I). However, characteristics related to the dead time make it not be so effective when used in high flow neutron fields. An alternative to this problem is the use of thermoluminescent detectors (TLD), but the codes used do not provide a more specific response matrix to unfolding the information obtained through these materials, which makes the development of a specific response matrix important to adequately characterize the response obtained by them. This paper proposes using a technique of artificial intelligence called genetic algorithm, which uses bio-inspired mathematical models and through the implementation of a specific matrix to unfolding data obtained from a combination of TLDs embedded in a system of Bonner spheres, such as thermal neutron detectors, to characterize the neutron spectrum as a function of energy. The results obtained with this method were in accordance with reference spectra, thus enables of this technique to unfolding neutrons spectra with BS-TLD system. (author)

Thermal, chemical and pH induced unfolding of turmeric root lectin: modes of denaturation.

Directory of Open Access Journals (Sweden)

Himadri Biswas

Full Text Available Curcuma longa rhizome lectin, of non-seed origin having antifungal, antibacterial and α-glucosidase inhibitory activities, forms a homodimer with high thermal stability as well as acid tolerance. Size exclusion chromatography and dynamic light scattering show it to be a dimer at pH 7, but it converts to a monomer near pH 2. Circular dichroism spectra and fluorescence emission maxima are virtually indistinguishable from pH 7 to 2, indicating secondary and tertiary structures remain the same in dimer and monomer within experimental error. The tryptophan environment as probed by acrylamide quenching data yielded very similar data at pH 2 and pH 7, implying very similar folding for monomer and dimer. Differential scanning calorimetry shows a transition at 350.3 K for dimer and at 327.0 K for monomer. Thermal unfolding and chemical unfolding induced by guanidinium chloride for dimer are both reversible and can be described by two-state models. The temperatures and the denaturant concentrations at which one-half of the protein molecules are unfolded, are protein concentration-dependent for dimer but protein concentration-independent for monomer. The free energy of unfolding at 298 K was found to be 5.23 Kcal mol-1 and 14.90 Kcal mol-1 for the monomer and dimer respectively. The value of change in excess heat capacity upon protein denaturation (ΔCp is 3.42 Kcal mol-1 K-1 for dimer. The small ΔCp for unfolding of CLA reflects a buried hydrophobic core in the folded dimeric protein. These unfolding experiments, temperature dependent circular dichroism and dynamic light scattering for the dimer at pH 7 indicate its higher stability than for the monomer at pH 2. This difference in stability of dimeric and monomeric forms highlights the contribution of inter-subunit interactions in the former.

Relatedness Need Satisfaction, Intrinsic Motivation, and Engagement in Secondary School Physical Education

Science.gov (United States)

Xiang, Ping; Agbuga, Bülent; Liu, Jiling; McBride, Ron E.

2017-01-01

Purpose: Using self-determination theory, this study examined unique contributions of relatedness need satisfaction (to both teachers and peers) to intrinsic motivation and engagement (behavioral, cognitive, and emotional) over and above those of autonomy need satisfaction and competence need satisfaction among Turkish students in secondary school…

UNFOLDINGS OF THE CYLINDRICA L SURFACES USED IN THE INDUSTRIAL INSTALLATIONS

Directory of Open Access Journals (Sweden)

VASILE GHEORGHITA

2013-02-01

Full Text Available The connections in the construction of the various industrial installations: pipes, boilers, joints elements and fittings have a cylindrical configuration, or similar cylindrical shape. The execution and their installation require knowledge of the unfolding and intersection curves, which compose them. The graphical solving of the problems of tech nical representation has enabled the formation of abstract geometric of the pieces forms and the ability to see into space. The paper proposes to establish the unfolding of a connection, used in the industrial equipments, by the classical method of the des criptive geometry and mathematics, using appropriate software

Stable intermediates determine proteins' primary unfolding sites in the presence of surfactants

DEFF Research Database (Denmark)

Petersen, Steen Vang; Andersen, Kell kleiner; Enghild, Jan J.

2009-01-01

Despite detailed knowledge of the overall structural changes and stoichiometries of surfactant binding, little is known about which protein regions constitute the preferred sites of attack for initial unfolding. Here we have exposed three proteins to limited proteolysis at anionic (SDS) and catio......Despite detailed knowledge of the overall structural changes and stoichiometries of surfactant binding, little is known about which protein regions constitute the preferred sites of attack for initial unfolding. Here we have exposed three proteins to limited proteolysis at anionic (SDS......) and cationic (DTAC) surfactant concentrations corresponding to specific conformational transitions, using the surfactant-robust broad-specificity proteases Savinase and Alcalase. Cleavage sites are identified by SDS-PAGE and N-terminal sequencing. We observe well-defined cleavage fragments, which suggest......, cleavage sites can be rationalized from the structure of the protein's folding transition state and the position of loops in the native state. Nevertheless, they are more sensitive to choice of surfactant and protease, probably reflecting a heterogeneous and fluctuating ensemble of partially unfolded...

Time-dependent, x-ray spectral unfolds and brightness temperatures for intense Li+ ion beam-driven hohlraums

International Nuclear Information System (INIS)

Fehl, D.L.; Chandler, G.A.; Biggs, F.; Dukart, R.J.; Moats, A.R.; Leeper, R.J.

1996-01-01

X-ray-producing hohlraums are being studied as indirect drives for Inertial Confinement Fusion targets. In a 1994 target series on the PBFAII accelerator, cylindrical hohlraum targets were heated by an intense Li + ion beam and viewed by an array of 13 time-resolved, filtered x-ray detectors (XRDs). The UFO unfold code and its suite of auxiliary functions were used extensively in obtaining time- resolved x-ray spectra and radiation temperatures from this diagnostic. UFO was also used to obtain fitted response functions from calibration data, to simulate data from blackbody x-ray spectra of interest, to determine the suitability of various unfolding parameters (e.g., energy domain, energy partition, smoothing conditions, and basis functions), to interpolate the XRD signal traces, and to unfold experimental data. The simulation capabilities of the code were useful in understanding an anomalous feature in the unfolded spectra at low photon energies (≤ 100 eV). Uncertainties in the differential and energy-integrated unfolded spectra were estimated from uncertainties in the data. The time-history of the radiation temperature agreed well with independent calculations of the wall temperature in the hohlraum

Time-dependent, x-ray spectral unfolds and brightness temperatures for intense Li+ ion beam-driven hohlraums

International Nuclear Information System (INIS)

Fehl, D.L.; Chandler, G.A.; Biggs, F.; Dukart, R.J.; Moats, A.R.; Leeper, R.J.

1997-01-01

X-ray-producing hohlraums are being studied as indirect drives for inertial confinement fusion targets. In a 1994 target series on the PBFAII accelerator, cylindrical hohlraum targets were heated by an intense Li + ion beam and viewed by an array of 13 time-resolved, filtered x-ray detectors (XRDs). The unfold operator (UFO) code and its suite of auxiliary functions were used extensively in obtaining time-resolved x-ray spectra and radiation temperatures from this diagnostic. The UFO was also used to obtain fitted response functions from calibration data, to simulate data from blackbody x-ray spectra of interest, to determine the suitability of various unfolding parameters (e.g., energy domain, energy partition, smoothing conditions, and basis functions), to interpolate the XRD signal traces, and to unfold experimental data. The simulation capabilities of the code were useful in understanding an anomalous feature in the unfolded spectra at low photon energies (≤100 eV). Uncertainties in the differential and energy-integrated unfolded spectra were estimated from uncertainties in the data. The time endash history of the radiation temperature agreed well with independent calculations of the wall temperature in the hohlraum. copyright 1997 American Institute of Physics

PPARγ Ligand-Induced Unfolded Protein Responses in Monocytes

African Journals Online (AJOL)

High levels of oxLDL lead to cell dysfunction and apoptosis, a phenomenon known as lipotoxicity. Disturbing endoplasmic reticulum (ER) function results in ER stress and unfolded protein response (UPR), which tends to restore ER homeostasis but switches to apoptosis when ER stress is prolonged. In the present study the ...

PPARγ Ligand-Induced Unfolded Protein Responses in Monocytes ...

African Journals Online (AJOL)

acer

Disturbing endoplasmic reticulum (ER) function results in ER stress and unfolded protein response. (UPR), which tends to ... in mnocyte/macrophage cell lines as evident of the activation/up-regulation of ER stress/UPR genes. Cholesterol does not seem to exert ... inflammation (Tiwari et al., 2008). One prominent feature of ...

Extrinsic vs Intrinsic Motivations for Tax Compliance. Evidence from a Randomized Field Experiment in Germany

OpenAIRE

Dwenger, Nadja; Kleven, Henrik; Rasul, Imran; Rincke, Johannes

2014-01-01

Is tax compliance driven only by extrinsic motivations such as deterrence and tax policy or is there also a role for intrinsic motivations such as morals, norms and psychology? Agents may comply based on moral sentiments, social norms, guilt and shame (Andreoni et al. 1998), all of which are non-deterrence driven reasons for compliance. The importance of such intrinsically motivated compliance is hard to study empirically and therefore the least understood. This study uses a unique setting fo...

Identification of an Unfolding Intermediate for a DNA Lesion Bypass Polymerase

Science.gov (United States)

Sherrer, Shanen M.; Maxwell, Brian A.; Pack, Lindsey R.; Fiala, Kevin A.; Fowler, Jason D.; Zhang, Jun; Suo, Zucai

2012-01-01

Sulfolobus solfataricusDNA Polymerase IV (Dpo4), a prototype Y-family DNA polymerase, has been well characterized biochemically and biophysically at 37 °C or lower temperatures. However, the physiological temperature of the hyperthermophile S. solfataricus is approximately 80 °C. With such a large discrepancy in temperature, the in vivo relevance of these in vitro studies of Dpo4 has been questioned. Here, we employed circular dichroism spectroscopy and fluorescence-based thermal scanning to investigate the secondary structural changes of Dpo4 over a temperature range from 26 to 119 °C. Dpo4 was shown to display a high melting temperature characteristic of hyperthermophiles. Unexpectedly, the Little Finger domain of Dpo4, which is only found in the Y-family DNA polymerases, was shown to be more thermostable than the polymerase core. More interestingly, Dpo4 exhibited a three-state cooperative unfolding profile with an unfolding intermediate. The linker region between the Little Finger and Thumb domains of Dpo4 was found to be a source of structural instability. Through site-directed mutagenesis, the interactions between the residues in the linker region and the Palm domain were identified to play a critical role in the formation of the unfolding intermediate. Notably, the secondary structure of Dpo4 was not altered when the temperature was increased from 26 to 87.5 °C. Thus, in addition to providing structural insights into the thermal stability and an unfolding intermediate of Dpo4, our work also validated the relevance of the in vitro studies of Dpo4 performed at temperatures significantly lower than 80 °C. PMID:22667759

β-sheet-like formation during the mechanical unfolding of prion protein

Science.gov (United States)

Tao, Weiwei; Yoon, Gwonchan; Cao, Penghui; Eom, Kilho; Park, Harold S.

2015-09-01

Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrPC, whose misfolded form PrPSc can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded β-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the β-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220.

β-sheet-like formation during the mechanical unfolding of prion protein

Energy Technology Data Exchange (ETDEWEB)

Tao, Weiwei; Cao, Penghui; Park, Harold S., E-mail: parkhs@bu.edu [Department of Mechanical Engineering, Boston University, Boston, Massachusetts 02215 (United States); Yoon, Gwonchan [Department of Mechanical Engineering, Boston University, Boston, Massachusetts 02215 (United States); Department of Mechanical Engineering, Korea University, Seoul 136-701 (Korea, Republic of); Eom, Kilho [Biomechanics Laboratory, College of Sport Science, Sungkyunkwan University, Suwon 16419 (Korea, Republic of)

2015-09-28

Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrP{sup C}, whose misfolded form PrP{sup Sc} can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded β-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the β-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220.

β-sheet-like formation during the mechanical unfolding of prion protein

International Nuclear Information System (INIS)

Tao, Weiwei; Cao, Penghui; Park, Harold S.; Yoon, Gwonchan; Eom, Kilho

2015-01-01

Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrP C , whose misfolded form PrP Sc can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded β-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the β-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220

Development of unfolding method to obtain pin-wise source strength distribution from PWR spent fuel assembly measurement

International Nuclear Information System (INIS)

Sitompul, Yos Panagaman; Shin, Hee-Sung; Park, Se-Hwan; Oh, Jong Myeong; Seo, Hee; Kim, Ho Dong

2013-01-01

An unfolding method has been developed to obtain a pin-wise source strength distribution of a 14 × 14 pressurized water reactor (PWR) spent fuel assembly. Sixteen measured gamma dose rates at 16 control rod guide tubes of an assembly are unfolded to 179 pin-wise source strengths of the assembly. The method calculates and optimizes five coefficients of the quadratic fitting function for X-Y source strength distribution, iteratively. The pin-wise source strengths are obtained at the sixth iteration, with a maximum difference between two sequential iterations of about 0.2%. The relative distribution of pin-wise source strength from the unfolding is checked using a comparison with the design code (Westinghouse APA code). The result shows that the relative distribution from the unfolding and design code is consistent within a 5% difference. The absolute value of the pin-wise source strength is also checked by reproducing the dose rates at the measurement points. The result shows that the pin-wise source strengths from the unfolding reproduce the dose rates within a 2% difference. (author)

Neutron response matrix for unfolding NE-213 measurements to 21 MeV

International Nuclear Information System (INIS)

Ingersoll, D.T.; Wehring, B.W.; Johnson, R.H.

1976-01-01

A neutron response matrix from measured neutron responses of NE-213 in the energy range of 0.2 to 22 MeV is presented. An interpolation scheme was used to construct an 81-column matrix from the data of Verbinski, Burrus, Love, Zobel, and Hill. As a test of the new response matrix, the Cf-252 neutron spectrum was measured and unfolded using the new response matrix and the FORIST unfolding code. The spectrum agrees well with previous measurements at lower energies, while providing new information above 8 MeV

Plant transducers of the endoplasmic reticulum unfolded protein response

KAUST Repository

Iwata, Yuji; Koizumi, Nozomu

2012-01-01

The unfolded protein response (UPR) activates a set of genes to overcome accumulation of unfolded proteins in the endoplasmic reticulum (ER), a condition termed ER stress, and constitutes an essential part of ER protein quality control that ensures efficient maturation of secretory and membrane proteins in eukaryotes. Recent studies on Arabidopsis and rice identified the signaling pathway in which the ER membrane-localized ribonuclease IRE1 (inositol-requiring enzyme 1) catalyzes unconventional cytoplasmic splicing of mRNA, thereby producing the active transcription factor Arabidopsis bZIP60 (basic leucine zipper 60) and its ortholog in rice. Here we review recent findings identifying the molecular components of the plant UPR, including IRE1/bZIP60 and the membrane-bound transcription factors bZIP17 and bZIP28, and implicating its importance in several physiological phenomena such as pathogen response. © 2012 Elsevier Ltd.

Plant transducers of the endoplasmic reticulum unfolded protein response

KAUST Repository

Iwata, Yuji

2012-12-01

The unfolded protein response (UPR) activates a set of genes to overcome accumulation of unfolded proteins in the endoplasmic reticulum (ER), a condition termed ER stress, and constitutes an essential part of ER protein quality control that ensures efficient maturation of secretory and membrane proteins in eukaryotes. Recent studies on Arabidopsis and rice identified the signaling pathway in which the ER membrane-localized ribonuclease IRE1 (inositol-requiring enzyme 1) catalyzes unconventional cytoplasmic splicing of mRNA, thereby producing the active transcription factor Arabidopsis bZIP60 (basic leucine zipper 60) and its ortholog in rice. Here we review recent findings identifying the molecular components of the plant UPR, including IRE1/bZIP60 and the membrane-bound transcription factors bZIP17 and bZIP28, and implicating its importance in several physiological phenomena such as pathogen response. © 2012 Elsevier Ltd.

Detection and characterization of partially unfolded oligomers of the SH3 domain of α-Spectrin

NARCIS (Netherlands)

Casares, S.; Sadqi, M.; López-Mayorga, O.; Conejero-Lara, F.; van Nuland, N.A.J.

2004-01-01

For the purpose of equilibrium and kinetic folding-unfolding studies, the SH3 domain of α-spectrin (spc-SH3) has long been considered a classic two-state folding protein. In this work we have indeed observed that the thermal unfolding curves of spc-SH3 measured at pH 3.0 by differential scanning

An Intrinsic Algorithm for Parallel Poisson Disk Sampling on Arbitrary Surfaces.

Science.gov (United States)

Ying, Xiang; Xin, Shi-Qing; Sun, Qian; He, Ying

2013-03-08

Poisson disk sampling plays an important role in a variety of visual computing, due to its useful statistical property in distribution and the absence of aliasing artifacts. While many effective techniques have been proposed to generate Poisson disk distribution in Euclidean space, relatively few work has been reported to the surface counterpart. This paper presents an intrinsic algorithm for parallel Poisson disk sampling on arbitrary surfaces. We propose a new technique for parallelizing the dart throwing. Rather than the conventional approaches that explicitly partition the spatial domain to generate the samples in parallel, our approach assigns each sample candidate a random and unique priority that is unbiased with regard to the distribution. Hence, multiple threads can process the candidates simultaneously and resolve conflicts by checking the given priority values. It is worth noting that our algorithm is accurate as the generated Poisson disks are uniformly and randomly distributed without bias. Our method is intrinsic in that all the computations are based on the intrinsic metric and are independent of the embedding space. This intrinsic feature allows us to generate Poisson disk distributions on arbitrary surfaces. Furthermore, by manipulating the spatially varying density function, we can obtain adaptive sampling easily.

Model based rib-cage unfolding for trauma CT

Science.gov (United States)

von Berg, Jens; Klinder, Tobias; Lorenz, Cristian

2018-03-01

A CT rib-cage unfolding method is proposed that does not require to determine rib centerlines but determines the visceral cavity surface by model base segmentation. Image intensities are sampled across this surface that is flattened using a model based 3D thin-plate-spline registration. An average rib centerline model projected onto this surface serves as a reference system for registration. The flattening registration is designed so that ribs similar to the centerline model are mapped onto parallel lines preserving their relative length. Ribs deviating from this model appear deviating from straight parallel ribs in the unfolded view, accordingly. As the mapping is continuous also the details in intercostal space and those adjacent to the ribs are rendered well. The most beneficial application area is Trauma CT where a fast detection of rib fractures is a crucial task. Specifically in trauma, automatic rib centerline detection may not be guaranteed due to fractures and dislocations. The application by visual assessment on the large public LIDC data base of lung CT proved general feasibility of this early work.

The Unfolded Protein Response in Homeostasis and Modulation of Mammalian Immune Cells.

Science.gov (United States)

Martins, Ana Sofia; Alves, Inês; Helguero, Luisa; Domingues, Maria Rosário; Neves, Bruno Miguel

2016-11-01

The endoplasmic reticulum (ER) plays important roles in eukaryotic protein folding and lipid biosynthesis. Several exogenous and endogenous cellular sources of stress can perturb ER homeostasis leading to the accumulation of unfolded proteins in the lumen. Unfolded protein accumulation triggers a signal-transduction cascade known as the unfolded protein response (UPR), an adaptive mechanism which aims to protect cells from protein aggregates and to restore ER functions. Further to this protective mechanism, in immune cells, UPR molecular effectors have been shown to participate in a wide range of biological processes such as cell differentiation, survival and immunoglobulin and cytokine production. Recent findings also highlight the involvement of the UPR machinery in the maturational program and antigen presentation capacities of dendritic cells. UPR is therefore a key element in immune system homeostasis with direct implications on both adaptive and innate immune responses. The present review summarizes the knowledge on the emerging roles of UPR signaling cascades in mammalian immune cells as well as the consequences of their dysregulation in relation to the pathogenesis of several diseases.

Unfolding a molecular trefoil derived from a zwitterionic metallopeptide to form self-assembled nanostructures

KAUST Repository

Zhang, Ye; Zhou, Ning; Shi, Junfeng; Pochapsky, Susan Sondej; Pochapsky, Thomas C.; Zhang, Bei; Zhang, Xixiang; Xu, Bing

2015-01-01

While used extensively by nature to control the geometry of protein structures, and dynamics of proteins, such as self-organization, hydration forces and ionic interactions received less attention for controlling the behaviour of small molecules. Here we describe the synthesis and characterization of a novel zwitterionic metallopeptide consisting of a cationic core and three distal anionic groups linked by self-assembling peptide motifs. 2D NMR spectra, total correlated spectroscopy and nuclear Overhauser effect spectroscopy, show that the molecule exhibits a three-fold rotational symmetry and adopts a folded conformation in dimethyl sulfoxide due to Coulombic forces. When hydrated in water, the molecule unfolds to act as a self-assembling building block of supramolecular nanostructures. By combining ionic interactions with the unique geometry from metal complex and hydrophobic interactions from simple peptides, we demonstrate a new and effective way to design molecules for smart materials through mimicking a sophisticated biofunctional system using a conformational switch.

Unfolding a molecular trefoil derived from a zwitterionic metallopeptide to form self-assembled nanostructures

KAUST Repository

Zhang, Ye

2015-02-19

While used extensively by nature to control the geometry of protein structures, and dynamics of proteins, such as self-organization, hydration forces and ionic interactions received less attention for controlling the behaviour of small molecules. Here we describe the synthesis and characterization of a novel zwitterionic metallopeptide consisting of a cationic core and three distal anionic groups linked by self-assembling peptide motifs. 2D NMR spectra, total correlated spectroscopy and nuclear Overhauser effect spectroscopy, show that the molecule exhibits a three-fold rotational symmetry and adopts a folded conformation in dimethyl sulfoxide due to Coulombic forces. When hydrated in water, the molecule unfolds to act as a self-assembling building block of supramolecular nanostructures. By combining ionic interactions with the unique geometry from metal complex and hydrophobic interactions from simple peptides, we demonstrate a new and effective way to design molecules for smart materials through mimicking a sophisticated biofunctional system using a conformational switch.

Clinical evaluation of coronary territory map by using unfolded map of Tl-201 myocardial SPECT

International Nuclear Information System (INIS)

Uehara, Toshiisa; Nishimura, Tsunehiko; Katafuchi, Tetsuro; Yamagami, Hidetoshi; Kumita, Shinichirou; Hayashida, Kohei; Hayashi, Makoto

1990-01-01

Coronary territory map was developed on unfolded map of exercise Tl-201 myocardial SPECT. Each coronary territory was determined by summing the each unfolded map of 54 cases of single vessel disease respectively, and standardizing with normal pattern obtained from normal patients. The diagnostic accuracy of coronary territory map to identify the diseased coronary artery was analyzed in 104 clinical cases and was compared with that of planar and SPECT visual diagnosis, simple unfolded map (raw map) and extent and severity map. The results were as follows. (1) Territory map showed excellent diagnostic accuracy in single or double vessel disease, especially in diagnosis of left circumflex coronary artery lesion. (2) In triple vessel disease, the diagnostic accuracy of territory map or other unfolded maps was 30% at best, and was inferior to planar or SPECT visual analysis. The cause of this inferiority seemed that the quantitatively analyzed map had no information about the degree of Tl-uptake into lung or myocardium, which give useful information in visual diagnosis. (3) The diagnostic agreement ratio in two observers was the highest in territory map diagnosis, so that the territory map diagnosis seemed to be the most objective one. (4) The unfolded map diagnosis with apical display obtained from long-axis tomogram was useful to diagnose left anteior descending coronary (LAD) lesion, which improve not only the sensitivity of LAD but also specificity of right coronary artery single vessel disease. (author)

Inter-regulation of the unfolded protein response and auxin signaling

Czech Academy of Sciences Publication Activity Database

Chen, Y.N.; Aung, K.; Rolčík, Jakub; Walicki, K.; Friml, J.; Brandizzi, F.

2014-01-01

Roč. 77, č. 1 (2014), s. 97-107 ISSN 0960-7412 Institutional support: RVO:61389030 Keywords : endoplasmic reticulum stress * unfolded protein response * auxin response Subject RIV: ED - Physiology Impact factor: 5.972, year: 2014

Performance of artificial neural networks and genetical evolved artificial neural networks unfolding techniques

International Nuclear Information System (INIS)

Ortiz R, J. M.; Martinez B, M. R.; Vega C, H. R.; Gallego D, E.; Lorente F, A.; Mendez V, R.; Los Arcos M, J. M.; Guerrero A, J. E.

2011-01-01

With the Bonner spheres spectrometer neutron spectrum is obtained through an unfolding procedure. Monte Carlo methods, Regularization, Parametrization, Least-squares, and Maximum Entropy are some of the techniques utilized for unfolding. In the last decade methods based on Artificial Intelligence Technology have been used. Approaches based on Genetic Algorithms and Artificial Neural Networks (Ann) have been developed in order to overcome the drawbacks of previous techniques. Nevertheless the advantages of Ann still it has some drawbacks mainly in the design process of the network, vg the optimum selection of the architectural and learning Ann parameters. In recent years the use of hybrid technologies, combining Ann and genetic algorithms, has been utilized to. In this work, several Ann topologies were trained and tested using Ann and Genetically Evolved Artificial Neural Networks in the aim to unfold neutron spectra using the count rates of a Bonner sphere spectrometer. Here, a comparative study of both procedures has been carried out. (Author)

Contribution of long-range interactions to the secondary structure of an unfolded globin.

Science.gov (United States)

Fedyukina, Daria V; Rajagopalan, Senapathy; Sekhar, Ashok; Fulmer, Eric C; Eun, Ye-Jin; Cavagnero, Silvia

2010-09-08

This work explores the effect of long-range tertiary contacts on the distribution of residual secondary structure in the unfolded state of an alpha-helical protein. N-terminal fragments of increasing length, in conjunction with multidimensional nuclear magnetic resonance, were employed. A protein representative of the ubiquitous globin fold was chosen as the model system. We found that, while most of the detectable alpha-helical population in the unfolded ensemble does not depend on the presence of the C-terminal region (corresponding to the native G and H helices), specific N-to-C long-range contacts between the H and A-B-C regions enhance the helical secondary structure content of the N terminus (A-B-C regions). The simple approach introduced here, based on the evaluation of N-terminal polypeptide fragments of increasing length, is of general applicability to identify the influence of long-range interactions in unfolded proteins. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Characteristics of SiC neutron sensor spectrum unfolding process based on Bayesian inference

Energy Technology Data Exchange (ETDEWEB)

Cetnar, Jerzy; Krolikowski, Igor [Faculty of Energy and Fuels AGH - University of Science and Technology, Al. Mickiewicza 30, 30-059 Krakow (Poland); Ottaviani, L. [IM2NP, UMR CNRS 7334, Aix-Marseille University, Case 231 -13397 Marseille Cedex 20 (France); Lyoussi, A. [CEA, DEN, DER, Instrumentation Sensors and Dosimetry Laboratory, Cadarache, F-13108 St-Paul-Lez-Durance (France)

2015-07-01

This paper deals with SiC detector signal interpretation in neutron radiation measurements in mixed neutron gamma radiation fields, which is called the detector inverse problem or the spectrum unfolding, and it aims in finding a representation of the primary radiation, based on the measured detector signals. In our novel methodology we resort to Bayesian inference approach. In the developed procedure the resultant spectra is unfolded form detector channels reading, where the estimated neutron fluence in a group structure is obtained with its statistical characteristic comprising of standard deviation and correlation matrix. In the paper we present results of unfolding process for case of D-T neutron source in neutron moderating environment. Discussions of statistical properties of obtained results are presented as well as of the physical meaning of obtained correlation matrix of estimated group fluence. The presented works has been carried out within the I-SMART project, which is part of the KIC InnoEnergy R and D program. (authors)

RDANN a new methodology to solve the neutron spectra unfolding problem

Energy Technology Data Exchange (ETDEWEB)

Ortiz R, J.M.; Martinez B, M.R.; Vega C, H.R. [UAZ, Av. Ramon Lopez Velarde No. 801, 98000 Zacatecas (Mexico)

2006-07-01

The optimization processes known as Taguchi method and DOE methodology are applied to the design, training and testing of Artificial Neural Networks in the neutron spectrometry field, which offer potential benefits in the evaluation of the behavior of the net as well as the ability to examine the interaction of the weights and neurons inside the same one. In this work, the Robust Design of Artificial Neural Networks methodology is used to solve the neutron spectra unfolding problem, designing, training and testing an ANN using a set of 187 neutron spectra compiled by the International Atomic Energy Agency, to obtain the better neutron spectra unfolded from the Bonner spheres spectrometer's count rates. (Author)

RDANN a new methodology to solve the neutron spectra unfolding problem

International Nuclear Information System (INIS)

Ortiz R, J.M.; Martinez B, M.R.; Vega C, H.R.

2006-01-01

The optimization processes known as Taguchi method and DOE methodology are applied to the design, training and testing of Artificial Neural Networks in the neutron spectrometry field, which offer potential benefits in the evaluation of the behavior of the net as well as the ability to examine the interaction of the weights and neurons inside the same one. In this work, the Robust Design of Artificial Neural Networks methodology is used to solve the neutron spectra unfolding problem, designing, training and testing an ANN using a set of 187 neutron spectra compiled by the International Atomic Energy Agency, to obtain the better neutron spectra unfolded from the Bonner spheres spectrometer's count rates. (Author)

Learning to learn - intrinsic plasticity as a metaplasticity mechanism for memory formation.

Science.gov (United States)

Sehgal, Megha; Song, Chenghui; Ehlers, Vanessa L; Moyer, James R

2013-10-01

"Use it or lose it" is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder. With the advancing age of our population, understanding how use-dependent plasticity changes across the lifespan may also help to promote healthy brain aging. A common misconception is that such experience-dependent plasticity (e.g., associative learning) is synonymous with synaptic plasticity. Other forms of plasticity also play a critical role in shaping adaptive changes within the nervous system, including intrinsic plasticity - a change in the intrinsic excitability of a neuron. Intrinsic plasticity can result from a change in the number, distribution or activity of various ion channels located throughout the neuron. Here, we review evidence that intrinsic plasticity is an important and evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts as a metaplasticity mechanism by lowering the threshold for synaptic changes. Thus, learning-related intrinsic changes can facilitate future synaptic plasticity and learning. Such intrinsic changes can impact the allocation of a memory trace within a brain structure, and when compromised, can contribute to cognitive decline during the aging process. This unique role of intrinsic excitability can provide insight into how memories are formed and, more interestingly, how neurons that participate in a memory trace are selected. Most importantly, modulation of intrinsic excitability can allow for regulation of learning ability - this can prevent or provide treatment for cognitive decline not only in patients with clinical disorders but

Effective electrochemical method for investigation of hemoglobin unfolding based on the redox property of heme groups at glassy carbon electrodes.

Science.gov (United States)

Li, Xianchan; Zheng, Wei; Zhang, Limin; Yu, Ping; Lin, Yuqing; Su, Lei; Mao, Lanqun

2009-10-15

This study demonstrates a facile and effective electrochemical method for investigation of hemoglobin (Hb) unfolding based on the electrochemical redox property of heme groups in Hb at bare glassy carbon (GC) electrodes. In the native state, the heme groups are deeply buried in the hydrophobic pockets of Hb with a five-coordinate high-spin complex and thus show a poor electrochemical property at bare GC electrodes. Upon the unfolding of Hb induced by the denaturant of guanidine hydrochloride (GdnHCl), the fifth coordinative bond between the heme groups and the residue of the polypeptides (His-F8) is broken, and as a result, the heme groups initially buried deeply in the hydrophobic pockets dissociate from the polypeptide chains and are reduced electrochemically at GC electrodes, which can be used to probe the unfolding of Hb. The results on the GdnHCl-induced Hb unfolding obtained with the electrochemical method described here well coincide with those studied with other methods, such as UV-vis spectroscopy, fluorescence, and circular dichroism. The application of the as-established electrochemical method is illustrated to study the kinetics of GdnHCl-induced Hb unfolding, the GdnHCl-induced unfolding of another kind of hemoprotein, catalase, and the pH-induced Hb unfolding/refolding.

Unfolding intermediates of the mutant His-107-Tyr of human ...

Indian Academy of Sciences (India)

Srabani Taraphder

We present in this article a detailed analysis of representative structures and proton transfer activity of .... cal molecular dynamics simulations to identify potential unfolding ... clustering parameters to carry out K-means cluster- ing of different ...

Neutron spectrum unfolding using genetic algorithm in a Monte Carlo simulation

Energy Technology Data Exchange (ETDEWEB)

Suman, Vitisha [Health Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Sarkar, P.K., E-mail: pksarkar02@gmail.com [Manipal Centre for Natural Sciences, Manipal University, Manipal 576104 (India)

2014-02-11

A spectrum unfolding technique GAMCD (Genetic Algorithm and Monte Carlo based spectrum Deconvolution) has been developed using the genetic algorithm methodology within the framework of Monte Carlo simulations. Each Monte Carlo history starts with initial solution vectors (population) as randomly generated points in the hyper dimensional solution space that are related to the measured data by the response matrix of the detection system. The transition of the solution points in the solution space from one generation to another are governed by the genetic algorithm methodology using the techniques of cross-over (mating) and mutation in a probabilistic manner adding new solution points to the population. The population size is kept constant by discarding solutions having lesser fitness values (larger differences between measured and calculated results). Solutions having the highest fitness value at the end of each Monte Carlo history are averaged over all histories to obtain the final spectral solution. The present method shows promising results in neutron spectrum unfolding for both under-determined and over-determined problems with simulated test data as well as measured data when compared with some existing unfolding codes. An attractive advantage of the present method is the independence of the final spectra from the initial guess spectra.

Neutron spectrum unfolding using genetic algorithm in a Monte Carlo simulation

International Nuclear Information System (INIS)

Suman, Vitisha; Sarkar, P.K.

2014-01-01

A spectrum unfolding technique GAMCD (Genetic Algorithm and Monte Carlo based spectrum Deconvolution) has been developed using the genetic algorithm methodology within the framework of Monte Carlo simulations. Each Monte Carlo history starts with initial solution vectors (population) as randomly generated points in the hyper dimensional solution space that are related to the measured data by the response matrix of the detection system. The transition of the solution points in the solution space from one generation to another are governed by the genetic algorithm methodology using the techniques of cross-over (mating) and mutation in a probabilistic manner adding new solution points to the population. The population size is kept constant by discarding solutions having lesser fitness values (larger differences between measured and calculated results). Solutions having the highest fitness value at the end of each Monte Carlo history are averaged over all histories to obtain the final spectral solution. The present method shows promising results in neutron spectrum unfolding for both under-determined and over-determined problems with simulated test data as well as measured data when compared with some existing unfolding codes. An attractive advantage of the present method is the independence of the final spectra from the initial guess spectra

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-01-21

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

A method for unfolding high-energy scintillation gamma-ray spectra up to 8 MeV

International Nuclear Information System (INIS)

Dymke, N.; Hofmann, B.

1982-01-01

In unfolding a high-energy scintillation gamma-ray spectrum up to 8 MeV with the help of a response matrix, the means of linear algebra fail if the matrix is ill conditioned. In such cases, unfolding could be accomplished by means of a mathematical method based on a priori knowledge of the photon spectrum to be expected. The method which belongs to the class of regularization techniques was tested on in-situ gamma-ray spectra of 16 N recorded in a nuclear power plant near the primary circuit, using an 1.5 x 1.5 in. NaI(Tl) scintillation detector. For one regularized unfolding the results were presented in the form of an energy and a dose-rate spectrum. (author)

Inter-subject Functional Correlation Reveal a Hierarchical Organization of Extrinsic and Intrinsic Systems in the Brain.

Science.gov (United States)

Ren, Yudan; Nguyen, Vinh Thai; Guo, Lei; Guo, Christine Cong

2017-09-07

The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.

Intrinsic motivation and extrinsic incentives jointly predict performance: a 40-year meta-analysis.

Science.gov (United States)

Cerasoli, Christopher P; Nicklin, Jessica M; Ford, Michael T

2014-07-01

More than 4 decades of research and 9 meta-analyses have focused on the undermining effect: namely, the debate over whether the provision of extrinsic incentives erodes intrinsic motivation. This review and meta-analysis builds on such previous reviews by focusing on the interrelationship among intrinsic motivation, extrinsic incentives, and performance, with reference to 2 moderators: performance type (quality vs. quantity) and incentive contingency (directly performance-salient vs. indirectly performance-salient), which have not been systematically reviewed to date. Based on random-effects meta-analytic methods, findings from school, work, and physical domains (k = 183, N = 212,468) indicate that intrinsic motivation is a medium to strong predictor of performance (ρ = .21-45). The importance of intrinsic motivation to performance remained in place whether incentives were presented. In addition, incentive salience influenced the predictive validity of intrinsic motivation for performance: In a "crowding out" fashion, intrinsic motivation was less important to performance when incentives were directly tied to performance and was more important when incentives were indirectly tied to performance. Considered simultaneously through meta-analytic regression, intrinsic motivation predicted more unique variance in quality of performance, whereas incentives were a better predictor of quantity of performance. With respect to performance, incentives and intrinsic motivation are not necessarily antagonistic and are best considered simultaneously. Future research should consider using nonperformance criteria (e.g., well-being, job satisfaction) as well as applying the percent-of-maximum-possible (POMP) method in meta-analyses. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The Unfolding MD Simulations of Cyclophilin: Analyzed by Surface Contact Networks and Their Associated Metrics

Science.gov (United States)

Roy, Sourav; Basu, Sankar; Dasgupta, Dipak; Bhattacharyya, Dhananjay; Banerjee, Rahul

2015-01-01

Currently, considerable interest exists with regard to the dissociation of close packed aminoacids within proteins, in the course of unfolding, which could result in either wet or dry moltenglobules. The progressive disjuncture of residues constituting the hydrophobic core ofcyclophilin from L. donovani (LdCyp) has been studied during the thermal unfolding of the molecule, by molecular dynamics simulations. LdCyp has been represented as a surface contactnetwork (SCN) based on the surface complementarity (Sm) of interacting residues within themolecular interior. The application of Sm to side chain packing within proteins make it a very sensitive indicator of subtle perturbations in packing, in the thermal unfolding of the protein. Network based metrics have been defined to track the sequential changes in the disintegration ofthe SCN spanning the hydrophobic core of LdCyp and these metrics prove to be highly sensitive compared to traditional metrics in indicating the increased conformational (and dynamical) flexibility in the network. These metrics have been applied to suggest criteria distinguishing DMG, WMG and transition state ensembles and to identify key residues involved in crucial conformational/topological events during the unfolding process. PMID:26545107

Heat, Acid and Chemically Induced Unfolding Pathways, Conformational Stability and Structure-Function Relationship in Wheat α-Amylase.

Directory of Open Access Journals (Sweden)

Kritika Singh

Full Text Available Wheat α-amylase, a multi-domain protein with immense industrial applications, belongs to α+β class of proteins with native molecular mass of 32 kDa. In the present study, the pathways leading to denaturation and the relevant unfolded states of this multi-domain, robust enzyme from wheat were discerned under the influence of temperature, pH and chemical denaturants. The structural and functional aspects along with thermodynamic parameters for α-amylase unfolding were probed and analyzed using fluorescence, circular dichroism and enzyme assay methods. The enzyme exhibited remarkable stability up to 70°C with tendency to aggregate at higher temperature. Acid induced unfolding was also incomplete with respect to the structural content of the enzyme. Strong ANS binding at pH 2.0 suggested the existence of a partially unfolded intermediate state. The enzyme was structurally and functionally stable in the pH range 4.0-9.0 with 88% recovery of hydrolytic activity. Careful examination of biophysical properties of intermediate states populated in urea and GdHCl induced denaturation suggests that α-amylase unfolding undergoes irreversible and non-coincidental cooperative transitions, as opposed to previous reports of two-state unfolding. Our investigation highlights several structural features of the enzyme in relation to its catalytic activity. Since, α-amylase has been comprehensively exploited for use in a range of starch-based industries, in addition to its physiological significance in plants and animals, knowledge regarding its stability and folding aspects will promote its biotechnological applications.

Accuracy of unfolded map method for determining the left ventricular border. Evaluation of the cut-off value from autopsy finding

International Nuclear Information System (INIS)

Sugibayashi, Keiichi; Abe, Yoshiteru; Suga, Yutaka

1996-01-01

To improve the quantification of the left ventricular surface area (LVSA) by unfolded map method, we evaluated the cut-off value for determining the left ventricular border. The LVSA measured by unfolded map was compared with those measured using myocardial phantom and autopsy findings. The relative error (RE) was calculated as difference between LVSA in phantom and area of unfolded map. In phantom study, the cut-off value was calculated as 73.3±0.5% when the RE was zero. In autopsy study, the cut-off value was 74.0±7.2%. The area of unfolded map had good correlation with LVSA at autopsy when the cut-off value was 74% (r=0.83, p<0.003). The diameter of left ventricle at autopsy was compared with that of beating heart obtained by two-dimensional echocardiography, because the area of unfolded map was greater than LVSA at autopsy. The ratio of LVSA at autopsy to beating heart was calculated as 1.37. The suitable cut-off value was evaluated as 55.6% when the unfolded map area obtained by autopsy was increased 1.37 magnifications. There was a good correlation between LVSA of unfolded map (cut-off=56%) and the LVSA at autopsy (r=0.90, p<0.001). These results suggest that the cut-off value for determining the left ventricular border in vivo is 56%. (author)

Intrinsic Stability of the Smallest Possible Silver Nanotube

Science.gov (United States)

Autreto, P. A. S.; Lagos, M. J.; Sato, F.; Bettini, J.; Rocha, A. R.; Rodrigues, V.; Ugarte, D.; Galvao, D. S.

2011-02-01

Recently, Lagos et al. [Nature Nanotech. 4, 149 (2009)1748-338710.1038/nnano.2008.414] reported the discovery of the smallest possible Ag nanotube with a square cross section. Ab initio density functional theory calculations strongly support that the stability of these hollow structures is structurally intrinsic and not the result of contamination by light atoms. We also report the first experimental observation of the theoretically predicted corrugation of the hollow structure. Quantum conductance calculations predict a unique signature of 3.6G0 for this new family of nanotubes.

Participatory role of zinc in structural and functional characterization of bioremediase: a unique thermostable microbial silica leaching protein.

Science.gov (United States)

Chowdhury, Trinath; Sarkar, Manas; Chaudhuri, Biswadeep; Chattopadhyay, Brajadulal; Halder, Umesh Chandra

2015-07-01

A unique protein, bioremediase (UniProt Knowledgebase Accession No.: P86277), isolated from a hot spring bacterium BKH1 (GenBank Accession No.: FJ177512), has shown to exhibit silica leaching activity when incorporated to prepare bio-concrete material. Matrix-assisted laser desorption ionization mass spectrometry analysis suggests that bioremediase is 78% homologous to bovine carbonic anhydrase II though it does not exhibit carbonic anhydrase-like activity. Bioinformatics study is performed for understanding the various physical and chemical parameters of the protein which predicts the involvement of zinc encircled by three histidine residues (His94, His96 and His119) at the active site of the protein. Isothermal titration calorimetric-based thermodynamic study on diethyl pyrocarbonate-modified protein recognizes the presence of Zn(2+) in the enzyme moiety. Exothermic to endothermic transition as observed during titration of the protein with Zn(2+) discloses that there are at least two binding sites for zinc within the protein moiety. Addition of Zn(2+) regains the activity of EDTA chelated bioremediase confirming the presence of extra binding site of Zn(2+) in the protein moiety. Revival of folding pattern of completely unfolded urea-treated protein by Zn(2+) explains the participatory role of zinc in structural stability of the protein. Restoration of the λ max in intrinsic fluorescence emission study of the urea-treated protein by Zn(2+) similarly confirms the involvement of Zn in the refolding of the protein. The utility of bioremediase for silica nanoparticles preparation is observed by field emission scanning electron microscopy.

Directional Unfolded Source Term (DUST) for Compton Cameras.

Energy Technology Data Exchange (ETDEWEB)

Mitchell, Dean J.; Mitchell, Dean J.; Horne, Steven M.; O' Brien, Sean; Thoreson, Gregory G

2018-03-01

A Directional Unfolded Source Term (DUST) algorithm was developed to enable improved spectral analysis capabilities using data collected by Compton cameras. Achieving this objective required modification of the detector response function in the Gamma Detector Response and Analysis Software (GADRAS). Experimental data that were collected in support of this work include measurements of calibration sources at a range of separation distances and cylindrical depleted uranium castings.

Structural changes during the unfolding of Bovine serum albumin

Indian Academy of Sciences (India)

The native form of serum albumin is the most important soluble protein in the body plasma. In order to investigate the structural changes of Bovine serum albumin (BSA) during its unfolding in the presence of urea, a small-angle neutron scattering (SANS) study was performed. The scattering curves of dilute solutions of BSA ...

Learning to learn – intrinsic plasticity as a metaplasticity mechanism for memory formation

Science.gov (United States)

Sehgal, Megha; Song, Chenghui; Ehlers, Vanessa L.; Moyer, James R.

2013-01-01

“Use it or lose it” is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder. With the advancing age of our population, understanding how use-dependent plasticity changes across the lifespan may also help to promote healthy brain aging. A common misconception is that such experience-dependent plasticity (e.g., associative learning) is synonymous with synaptic plasticity. Other forms of plasticity also play a critical role in shaping adaptive changes within the nervous system, including intrinsic plasticity – a change in the intrinsic excitability of a neuron. Intrinsic plasticity can result from a change in the number, distribution or activity of various ion channels located throughout the neuron. Here, we review evidence that intrinsic plasticity is an important and evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts as a metaplasticity mechanism by lowering the threshold for synaptic changes. Thus, learning-related intrinsic changes can facilitate future synaptic plasticity and learning. Such intrinsic changes can impact the allocation of a memory trace within a brain structure, and when compromised, can contribute to cognitive decline during the aging process. This unique role of intrinsic excitability can provide insight into how memories are formed and, more interestingly, how neurons that participate in a memory trace are selected. Most importantly, modulation of intrinsic excitability can allow for regulation of learning ability – this can prevent or provide treatment for cognitive decline not only in patients with clinical

High-energy intermediates in protein unfolding characterized by thiol labeling under nativelike conditions.

Science.gov (United States)

Malhotra, Pooja; Udgaonkar, Jayant B

2014-06-10

A protein unfolding reaction usually appears to be so dominated by a large free energy barrier that identifying and characterizing high-energy intermediates and, hence, dissecting the unfolding reaction into multiple structural transitions have proven to be a challenge. In particular, it has been difficult to identify any detected high-energy intermediate with the dry (DMG) and wet (WMG) molten globules that have been implicated in the unfolding reactions of at least some proteins. In this study, a native-state thiol labeling methodology was used to identify high-energy intermediates, as well as to delineate the barriers to the disruption of side chain packing interactions and to site-specific solvent exposure in different regions of the small protein, single-chain monellin (MNEI). Labeling studies of four single-cysteine-containing variants of MNEI have identified three high-energy intermediates, populated to very low extents under nativelike conditions. A significant dispersion in the opening rates of the cysteine side chains has allowed multiple steps, leading to the loss of side chain packing, to be resolved temporally. A detailed structural analysis of the positions of the four cysteine residue positions, which are buried to different depths within the protein, has suggested a direct correlation with the structure of a DMG, detected in previous studies. It is observed that side chain packing within the core of the protein is maintained, while that at the surface is disrupted, in the DMG. The core of the protein becomes solvent-exposed only in a WMG populated after the rate-limiting step of unfolding at high denaturant concentrations.

Improved spectral data unfolding for radiochromic film imaging spectroscopy of laser-accelerated proton beams

Energy Technology Data Exchange (ETDEWEB)

Schollmeier, M.; Geissel, M.; Sefkow, A. B. [Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States); Flippo, K. A. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

2014-04-15

An improved method to unfold the space-resolved proton energy distribution function of laser-accelerated proton beams using a layered, radiochromic film (RCF) detector stack has been developed. The method takes into account the reduced RCF response near the Bragg peak due to a high linear energy transfer (LET). This LET dependence of the active RCF layer has been measured, and published data have been re-interpreted to find a nonlinear saturation scaling of the RCF response with stopping power. Accounting for the LET effect increased the integrated particle yield by 25% after data unfolding. An iterative, analytical, space-resolved deconvolution of the RCF response functions from the measured dose was developed that does not rely on fitting. After the particle number unfold, three-dimensional interpolation is performed to determine the spatial proton beam distribution for proton energies in-between the RCF data points. Here, image morphing has been implemented as a novel interpolation method that takes into account the energy-dependent, changing beam topology.

Nonintegrability of the unfolding of the fold-Hopf bifurcation

Science.gov (United States)

Yagasaki, Kazuyuki

2018-02-01

We consider the unfolding of the codimension-two fold-Hopf bifurcation and prove its meromorphic nonintegrability in the meaning of Bogoyavlenskij for almost all parameter values. Our proof is based on a generalized version of the Morales-Ramis-Simó theory for non-Hamiltonian systems and related variational equations up to second order are used.

Descriptive and Computer Aided Drawing Perspective on an Unfolded Polyhedral Projection Surface

Science.gov (United States)

Dzwierzynska, Jolanta

2017-10-01

The aim of the herby study is to develop a method of direct and practical mapping of perspective on an unfolded prism polyhedral projection surface. The considered perspective representation is a rectilinear central projection onto a surface composed of several flat elements. In the paper two descriptive methods of drawing perspective are presented: direct and indirect. The graphical mapping of the effects of the representation is realized directly on the unfolded flat projection surface. That is due to the projective and graphical connection between points displayed on the polyhedral background and their counterparts received on the unfolded flat surface. For a significant improvement of the construction of line, analytical algorithms are formulated. They draw a perspective image of a segment of line passing through two different points determined by their coordinates in a spatial coordinate system of axis x, y, z. Compared to other perspective construction methods that use information about points, for computer vision and the computer aided design, our algorithms utilize data about lines, which are applied very often in architectural forms. Possibility of drawing lines in the considered perspective enables drawing an edge perspective image of an architectural object. The application of the changeable base elements of perspective as a horizon height and a station point location enable drawing perspective image from different viewing positions. The analytical algorithms for drawing perspective images are formulated in Mathcad software, however, they can be implemented in the majority of computer graphical packages, which can make drawing perspective more efficient and easier. The representation presented in the paper and the way of its direct mapping on the flat unfolded projection surface can find application in presentation of architectural space in advertisement and art.

Unfolding and smoothing applied to the quality enhancement of neutron tomographic images

International Nuclear Information System (INIS)

Almeida, Gevaldo L. de; Silvani, Maria I.; Lopes, Ricardo T.

2008-01-01

Resolution and contrast are the major parameters defining the quality of a computer-aided tomographic image. These parameters depend upon several features of the image acquisition system, such as detector resolution, geometrical arrangement of the source-object-detector, beam divergence, source strength, detector efficiency and counting time. Roughly, the detector finite resolution is the main source of systematic errors affecting the separation power of the image acquisition system, while the electronic noise and statistical fluctuation are responsible for the data dispersion, which spoils the contrast. An algorithm has been developed in this work aiming at the improvement of the image quality through the minimization of both types of errors. The systematic ones are reduced by a mathematical unfolding of the position spectra - used as projections to reconstruct the 2D-images - using the Line Spread Function - LSF of the neutron tomographic system. The principle behind this technique is that every single channel contains information about all channels of the spectrum, but it is concealed due to the automatic integration carried out by the detector. Therefore, knowing the shape of this curve, it is possible to retrieve the original spectra. These spectra are unfortunately corrupted by the unavoidable statistical fluctuation, and by oscillations arising from the unfolding process, which strongly affects the quality of the final unfolded image. In order to reduce this impact, the spectra have been filtered by a Fourier transform technique or smoothed with a least square fitting procedure. The algorithm has been applied to spectra of some test-bodies generated by an earlier developed tomographic simulator, which reproduces the spectra furnished by a thermal neutron tomographic system employing a position sensitive detector. The obtained results have shown that the unfolded spectra produce final images capable to resolve features otherwise not achievable with the

An Auto sequence Code to Integrate a Neutron Unfolding Code with thePC-MCA Accuspec

International Nuclear Information System (INIS)

Darsono

2000-01-01

In a neutron spectrometry using proton recoil method, the neutronunfolding code is needed to unfold the measured proton spectrum to become theneutron spectrum. The process of the unfolding neutron in the existingneutron spectrometry which was successfully installed last year was doneseparately. This manuscript reports that the auto sequence code to integratethe neutron unfolding code UNFSPEC.EXE with the software facility of thePC-MCA Accuspec has been made and run successfully so that the new neutronspectrometry become compact. The auto sequence code was written based on therules in application program facility of PC-MCA Accuspec and then it wascompiled using AC-EXE. Result of the test of the auto sequence code showedthat for binning width 20, 30, and 40 giving a little different spectrumshape. The binning width around 30 gives a better spectrum in mean of givingsmall error compared to the others. (author)

Unfolding measurement of the atmospheric muon neutrino spectrum using IceCube

Energy Technology Data Exchange (ETDEWEB)

Boerner, Mathis; Ruhe, Tim; Meier, Maximilian; Schlunder, Philipp; Menne, Thorben; Fuchs, Tomasz [Dept. of Physics, Technical University of Dortmund, 44227 Dortmund (Germany); Collaboration: IceCube-Collaboration

2016-07-01

IceCube is a cubic kilometer neutrino observatory located at the geographic South Pole. With its huge volume, the detector is well suited for measurements of the atmospheric muon neutrino energy spectrum. Over the last years, several unfolding analyses for single years were able to provide model independent measurements for the northern hemisphere in an energy region between 200 GeV and 3.2 PeV. In this talk, the extension of the analyses to four additional years of data is presented. With this significant enlargement of the data basis, it is possible to reanalyze the full northern hemisphere with smaller statistical errors. Moreover, the spectrum can be unfolded in several small zenith bands. Measurements of the energy spectrum for different zenith regions provide further information on the composition and the shape of the flux.

Situated peer coaching and unfolding cases in the fundamentals skills laboratory.

Science.gov (United States)

Himes, Deborah O; Ravert, Patricia K

2012-09-03

Using unfolding case studies and situated peer coaching for the Fundamentals Skills Laboratory provides students with individualized feedback and creates a realistic clinical learning experience. A quasi-experimental design with pre- and post-intervention data was used to evaluate changes in student ratings of the course. An instrument was used to examine students' self-ratings and student comments about each lab. We found that students' ratings of the lab remained high with the new method and self-evaluations of their performance were higher as the semester progressed. Students appreciated the personalized feedback associated with peer coaching and demonstrated strong motivation and self-regulation in learning. By participating in unfolding case studies with situated peer coaching, students focus on safety issues, practice collaborative communication, and critical thinking in addition to performing psychomotor skills.

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

Science.gov (United States)

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

2016-07-01

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

Strong intrinsic motivation

OpenAIRE

Dessi, Roberta; Rustichini, Aldo

2015-01-01

A large literature in psychology, and more recently in economics, has argued that monetary rewards can reduce intrinsic motivation. We investigate whether the negative impact persists when intrinsic motivation is strong, and test this hypothesis experimentally focusing on the motivation to undertake interesting and challenging tasks, informative about individual ability. We find that this type of task can generate strong intrinsic motivation, that is impervious to the effect of monetary incen...

Intrinsic Motivation.

Science.gov (United States)

Deci, Edward L.

The paper draws together a wide variety of research which relates to the topic of intrinsic motivation; intrinsically motivated activities are defined as those which a person does for no apparent reward except the activity itself or the feelings which result from the activity. Most of this research was not originally reported within the framework…

The secondary structure and the thermal unfolding parameters of the S-layer protein from Lactobacillus salivarius.

Science.gov (United States)

Lighezan, Liliana; Georgieva, Ralitsa; Neagu, Adrian

2016-09-01

Surface layer (S-layer) proteins have been identified in the cell envelope of many organisms, such as bacteria and archaea. They self-assemble, forming monomolecular crystalline arrays. Isolated S-layer proteins are able to recrystallize into regular lattices, which proved useful in biotechnology. Here we investigate the structure and thermal unfolding of the S-layer protein isolated from Lactobacillus salivarius 16 strain of human origin. Using circular dichroism (CD) spectroscopy, and the software CDSSTR from DICHROWEB, CONTINLL from CDPro, as well as CDNN, we assess the fractions of the protein's secondary structural elements at temperatures ranging between 10 and 90 °C, and predict the tertiary class of the protein. To study the thermal unfolding of the protein, we analyze the temperature dependence of the CD signal in the far- and near-UV domains. Fitting the experimental data by two- and three-state models of thermal unfolding, we infer the midpoint temperatures, the temperature dependence of the changes in Gibbs free energy, enthalpy, and entropy of the unfolding transitions in standard conditions, and the temperature dependence of the equilibrium constant. We also estimate the changes in heat capacity at constant pressure in standard conditions. The results indicate that the thermal unfolding of the S-layer protein from L. salivarius is highly cooperative, since changes in the secondary and tertiary structures occur simultaneously. The thermodynamic analysis predicts a "cold" transition, at about -3 °C, of both the secondary and tertiary structures. Our findings may be important for the use of S-layer proteins in biotechnology and in biomedical applications.

Intrinsic contractures of the hand.

Science.gov (United States)

Paksima, Nader; Besh, Basil R

2012-02-01

Contractures of the intrinsic muscles of the fingers disrupt the delicate and complex balance of intrinsic and extrinsic muscles, which allows the hand to be so versatile and functional. The loss of muscle function primarily affects the interphalangeal joints but also may affect etacarpophalangeal joints. The resulting clinical picture is often termed, intrinsic contracture or intrinsic-plus hand. Disruption of the balance between intrinsic and extrinsic muscles has many causes and may be secondary to changes within the intrinsic musculature or the tendon unit. This article reviews diagnosis, etiology, and treatment algorithms in the management of intrinsic contractures of the fingers. Copyright © 2012 Elsevier Inc. All rights reserved.

Amyloid protein unfolding and insertion kinetics on neuronal membrane mimics

Science.gov (United States)

Qiu, Liming; Buie, Creighton; Vaughn, Mark; Cheng, Kwan

2010-03-01

Atomistic details of beta-amyloid (Aβ ) protein unfolding and lipid interaction kinetics mediated by the neuronal membrane surface are important for developing new therapeutic strategies to prevent and cure Alzheimer's disease. Using all-atom MD simulations, we explored the early unfolding and insertion kinetics of 40 and 42 residue long Aβ in binary lipid mixtures with and without cholesterol that mimic the cholesterol-depleted and cholesterol-enriched lipid nanodomains of neurons. The protein conformational transition kinetics was evaluated from the secondary structure profile versus simulation time plot. The extent of membrane disruption was examined by the calculated order parameters of lipid acyl chains and cholesterol fused rings as well as the density profiles of water and lipid headgroups at defined regions across the lipid bilayer from our simulations. Our results revealed that both the cholesterol content and the length of the protein affect the protein-insertion and membrane stability in our model lipid bilayer systems.

Characterization and error analysis of an N×N unfolding procedure applied to filtered, photoelectric x-ray detector arrays. I. Formulation and testing

Directory of Open Access Journals (Sweden)

D. L. Fehl

2010-12-01

Full Text Available An algorithm for spectral reconstructions (unfolds and spectrally integrated flux estimates from data obtained by a five-channel, filtered x-ray-detector array (XRD is described in detail and characterized. This diagnostic is a broad-channel spectrometer, used primarily to measure time-dependent soft x-ray flux emitted by z-pinch plasmas at the Z pulsed-power accelerator (Sandia National Laboratories, Albuquerque, New Mexico, USA, and serves as both a plasma probe and a gauge of accelerator performance. The unfold method, suitable for online analysis, arises naturally from general assumptions about the x-ray source and spectral properties of the channel responses; a priori constraints control the ill-posed nature of the inversion. The unfolded spectrum is not assumed to be Planckian. This study is divided into two consecutive papers. This paper considers three major issues: (a Formulation of the unfold method.—The mathematical background, assumptions, and procedures leading to the algorithm are described: the spectral reconstruction S_{unfold}(E,t—five histogram x-ray bins j over the x-ray interval, 137≤E≤2300  eV at each time step t—depends on the shape and overlap of the calibrated channel responses and on the maximum electrical power delivered to the plasma. The x-ray flux F_{unfold} is estimated as ∫S_{unfold}(E,tdE. (b Validation with simulations.—Tests of the unfold algorithm with known static and time-varying spectra are described. These spectra included—but were not limited to—Planckian spectra S_{bb}(E,T (25≤T≤250  eV, from which noise-free channel data were simulated and unfolded. For Planckian simulations with 125≤T≤250  eV and typical responses, the binwise unfold values S_{j} and the corresponding binwise averages ⟨S_{bb}⟩_{j} agreed to ∼20%, except where S_{bb}≪max⁡{S_{bb}}. Occasionally, unfold values S_{j}≲0 (artifacts were encountered. The algorithm recovered ≳90% of the x

Direct Evidence of Intrinsic Blue Fluorescence from Oligomeric Interfaces of Human Serum Albumin.

Science.gov (United States)

Bhattacharya, Arpan; Bhowmik, Soumitra; Singh, Amit K; Kodgire, Prashant; Das, Apurba K; Mukherjee, Tushar Kanti

2017-10-10

The molecular origin behind the concentration-dependent intrinsic blue fluorescence of human serum albumin (HSA) is not known yet. This unusual blue fluorescence is believed to be a characteristic feature of amyloid-like fibrils of protein/peptide and originates due to the delocalization of peptide bond electrons through the extended hydrogen bond networks of cross-β-sheet structure. Herein, by combining the results of spectroscopy, size exclusion chromatography, native gel electrophoresis, and confocal microscopy, we have shown that the intrinsic blue fluorescence of HSA exclusively originates from oligomeric interfaces devoid of any amyloid-like fibrillar structure. Our study suggests that this low energy fluorescence band is not due to any particular residue/sequence, but rather it is a common feature of self-assembled peptide bonds. The present findings of intrinsic blue fluorescence from oligomeric interfaces pave the way for future applications of this unique visual phenomenon for early stage detection of various protein aggregation related human diseases.

Predictors of natively unfolded proteins: unanimous consensus score to detect a twilight zone between order and disorder in generic datasets

Directory of Open Access Journals (Sweden)

Deiana Antonio

2010-04-01

Full Text Available Abstract Background Natively unfolded proteins lack a well defined three dimensional structure but have important biological functions, suggesting a re-assignment of the structure-function paradigm. To assess that a given protein is natively unfolded requires laborious experimental investigations, then reliable sequence-only methods for predicting whether a sequence corresponds to a folded or to an unfolded protein are of interest in fundamental and applicative studies. Many proteins have amino acidic compositions compatible both with the folded and unfolded status, and belong to a twilight zone between order and disorder. This makes difficult a dichotomic classification of protein sequences into folded and natively unfolded ones. In this work we propose an operational method to identify proteins belonging to the twilight zone by combining into a consensus score good performing single predictors of folding. Results In this methodological paper dichotomic folding indexes are considered: hydrophobicity-charge, mean packing, mean pairwise energy, Poodle-W and a new global index, that is called here gVSL2, based on the local disorder predictor VSL2. The performance of these indexes is evaluated on different datasets, in particular on a new dataset composed by 2369 folded and 81 natively unfolded proteins. Poodle-W, gVSL2 and mean pairwise energy have good performance and stability in all the datasets considered and are combined into a strictly unanimous combination score SSU, that leaves proteins unclassified when the consensus of all combined indexes is not reached. The unclassified proteins: i belong to an overlap region in the vector space of amino acidic compositions occupied by both folded and unfolded proteins; ii are composed by approximately the same number of order-promoting and disorder-promoting amino acids; iii have a mean flexibility intermediate between that of folded and that of unfolded proteins. Conclusions Our results show that

Spectrum unfolding by the least-squares methods

International Nuclear Information System (INIS)

Perey, F.G.

1977-01-01

The method of least squares is briefly reviewed, and the conditions under which it may be used are stated. From this analysis, a least-squares approach to the solution of the dosimetry neutron spectrum unfolding problem is introduced. The mathematical solution to this least-squares problem is derived from the general solution. The existence of this solution is analyzed in some detail. A chi 2 -test is derived for the consistency of the input data which does not require the solution to be obtained first. The fact that the problem is technically nonlinear, but should be treated in general as a linear one, is argued. Therefore, the solution should not be obtained by iteration. Two interpretations are made for the solution of the code STAY'SL, which solves this least-squares problem. The relationship of the solution to this least-squares problem to those obtained currently by other methods of solving the dosimetry neutron spectrum unfolding problem is extensively discussed. It is shown that the least-squares method does not require more input information than would be needed by current methods in order to estimate the uncertainties in their solutions. From this discussion it is concluded that the proposed least-squares method does provide the best complete solution, with uncertainties, to the problem as it is understood now. Finally, some implications of this method are mentioned regarding future work required in order to exploit its potential fully

The unfolding effects of transfer functions and processing of the pulse height distributions

Directory of Open Access Journals (Sweden)

Avdić Senada

2010-01-01

Full Text Available This paper deals with the improvements of the linear artificial neural network unfolding approach aimed at accurately determining the incident neutron spectrum. The effects of the transfer functions and pre-processing of the simulated pulse height distributions from liquid scintillation detectors on the artificial neural networks performance have been studied. A better energy resolution and higher reliability of the linear artificial neural network technique have been achieved after implementation of the results of this study. The optimized structure of the network was used to unfold both monoenergetic and continuous neutron energy spectra, such as the spectra of 252Cf and 241Am-Be sources, traditionally used in the nuclear safeguards experiments. We have demonstrated that the artificial neural network energy resolution of 0.1 MeV is comparable with the one obtained by the reference maximum likelihood expectation-maximization method which was implemented by using the one step late algorithm. Although the maximum likelihood algorithm provides the unfolded results of higher accuracy, especially for continuous neutron sources, the artificial neural network approach with the improved performances is more suitable for fast and robust determination of the neutron spectra with sufficient accuracy.

Guanidinium chloride induction of partial unfolding in amide proton exchange in RNase A.

Science.gov (United States)

Mayo, S L; Baldwin, R L

1993-11-05

Amide (NH) proton exchange rates were measured in 0.0 to 0.7 M guanidinium chloride (GdmCl) for 23 slowly exchanging peptide NH protons of ribonuclease A (RNase A) at pH* 5.5 (uncorrected pH measured in D2O), 34 degrees C. The purpose was to find out whether GdmCl induces exchange through binding to exchange intermediates that are partly or wholly unfolded. It was predicted that, when the logarithm of the exchange rate is plotted as a function of the molarity of GdmCl, the slope should be a measure of the amount of buried surface area exposed to GdmCl in the exchange intermediate. The results indicate that these concentrations of GdmCl do induce exchange by means of a partial unfolding mechanism for all 23 protons; this implies that exchange reactions can be used to study the unfolding and stability of local regions. Of the 23 protons, nine also show a second mechanism of exchange at lower concentrations of GdmCl, a mechanism that is nearly independent of GdmCl concentration and is termed "limited structural fluctuation."

Energy spectra unfolding of fast neutron sources using the group method of data handling and decision tree algorithms

Energy Technology Data Exchange (ETDEWEB)

Hosseini, Seyed Abolfazl, E-mail: sahosseini@sharif.edu [Department of Energy Engineering, Sharif University of Technology, Tehran 8639-11365 (Iran, Islamic Republic of); Afrakoti, Iman Esmaili Paeen [Faculty of Engineering & Technology, University of Mazandaran, Pasdaran Street, P.O. Box: 416, Babolsar 47415 (Iran, Islamic Republic of)

2017-04-11

Accurate unfolding of the energy spectrum of a neutron source gives important information about unknown neutron sources. The obtained information is useful in many areas like nuclear safeguards, nuclear nonproliferation, and homeland security. In the present study, the energy spectrum of a poly-energetic fast neutron source is reconstructed using the developed computational codes based on the Group Method of Data Handling (GMDH) and Decision Tree (DT) algorithms. The neutron pulse height distribution (neutron response function) in the considered NE-213 liquid organic scintillator has been simulated using the developed MCNPX-ESUT computational code (MCNPX-Energy engineering of Sharif University of Technology). The developed computational codes based on the GMDH and DT algorithms use some data for training, testing and validation steps. In order to prepare the required data, 4000 randomly generated energy spectra distributed over 52 bins are used. The randomly generated energy spectra and the simulated neutron pulse height distributions by MCNPX-ESUT for each energy spectrum are used as the output and input data. Since there is no need to solve the inverse problem with an ill-conditioned response matrix, the unfolded energy spectrum has the highest accuracy. The {sup 241}Am-{sup 9}Be and {sup 252}Cf neutron sources are used in the validation step of the calculation. The unfolded energy spectra for the used fast neutron sources have an excellent agreement with the reference ones. Also, the accuracy of the unfolded energy spectra obtained using the GMDH is slightly better than those obtained from the DT. The results obtained in the present study have good accuracy in comparison with the previously published paper based on the logsig and tansig transfer functions. - Highlights: • The neutron pulse height distribution was simulated using MCNPX-ESUT. • The energy spectrum of the neutron source was unfolded using GMDH. • The energy spectrum of the neutron source was

Intrinsic and extrinsic mortality reunited

DEFF Research Database (Denmark)

Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P

2015-01-01

Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However......, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well...... as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic...

An intrinsic algorithm for parallel Poisson disk sampling on arbitrary surfaces.

Science.gov (United States)

Ying, Xiang; Xin, Shi-Qing; Sun, Qian; He, Ying

2013-09-01

Poisson disk sampling has excellent spatial and spectral properties, and plays an important role in a variety of visual computing. Although many promising algorithms have been proposed for multidimensional sampling in euclidean space, very few studies have been reported with regard to the problem of generating Poisson disks on surfaces due to the complicated nature of the surface. This paper presents an intrinsic algorithm for parallel Poisson disk sampling on arbitrary surfaces. In sharp contrast to the conventional parallel approaches, our method neither partitions the given surface into small patches nor uses any spatial data structure to maintain the voids in the sampling domain. Instead, our approach assigns each sample candidate a random and unique priority that is unbiased with regard to the distribution. Hence, multiple threads can process the candidates simultaneously and resolve conflicts by checking the given priority values. Our algorithm guarantees that the generated Poisson disks are uniformly and randomly distributed without bias. It is worth noting that our method is intrinsic and independent of the embedding space. This intrinsic feature allows us to generate Poisson disk patterns on arbitrary surfaces in IR(n). To our knowledge, this is the first intrinsic, parallel, and accurate algorithm for surface Poisson disk sampling. Furthermore, by manipulating the spatially varying density function, we can obtain adaptive sampling easily.

Intrinsic Religiosity and Hypertension Among Older North American Seventh-Day Adventists.

Science.gov (United States)

Charlemagne-Badal, Sherma J; Lee, Jerry W

2016-04-01

A unique lifestyle based on religious beliefs has been associated with longevity among North American Seventh-day Adventists (SDAs); however, little is known about how religion is directly associated with hypertension in this group. Identifying and understanding the relationship between hypertension and its predictors is important because hypertension is responsible for half of all cardiovascular-related deaths and one in every seven deaths in the USA. The relationship between intrinsic religiosity and hypertension is examined. Cross-sectional data from the Biopsychosocial Religion and Health Study (N = 9581) were used. The relationship between intrinsic religiosity and hypertension when controlling for demographics, lifestyle variables, and church attendance was examined using binary logistic regression. While lifestyle factors such as vegetarian diet and regular exercise were important predictors of reduced rates of hypertension, even after controlling for these, intrinsic religiosity was just as strongly related to lower hypertension rates as the lifestyle factors. This study is the first to examine the relationship between intrinsic religiosity and hypertension among North American SDAs and demonstrates that in addition to the positive effects of lifestyle choices on health noted in the group, religion may offer direct salutary effects on hypertension. This finding is particularly important because it suggests that religiosity and not just lifestyle is related to lower risk of hypertension, a leading cause of death in the USA.

Redox Thermodynamics of Cytochromes c Subjected to Urea Induced Unfolding

NARCIS (Netherlands)

Monari, S.; Ranieri, A.; Di Rocco, G.; van der Zwan, G.; Peressini, S.; Tavagnacco, C.; Millo, D.; Borsari, M.

2009-01-01

The thermodynamics of the electron transfer (ET) process for beef heart and yeast cytochromes c and the Lys72Ala/Lys73Ala/Lys79Ala mutant of the latter species subjected to progressive urea-induced unfolding was determined electrochemically. The results indicate the presence of at least three

A linear iterative unfolding method

International Nuclear Information System (INIS)

László, András

2012-01-01

A frequently faced task in experimental physics is to measure the probability distribution of some quantity. Often this quantity to be measured is smeared by a non-ideal detector response or by some physical process. The procedure of removing this smearing effect from the measured distribution is called unfolding, and is a delicate problem in signal processing, due to the well-known numerical ill behavior of this task. Various methods were invented which, given some assumptions on the initial probability distribution, try to regularize the unfolding problem. Most of these methods definitely introduce bias into the estimate of the initial probability distribution. We propose a linear iterative method (motivated by the Neumann series / Landweber iteration known in functional analysis), which has the advantage that no assumptions on the initial probability distribution is needed, and the only regularization parameter is the stopping order of the iteration, which can be used to choose the best compromise between the introduced bias and the propagated statistical and systematic errors. The method is consistent: 'binwise' convergence to the initial probability distribution is proved in absence of measurement errors under a quite general condition on the response function. This condition holds for practical applications such as convolutions, calorimeter response functions, momentum reconstruction response functions based on tracking in magnetic field etc. In presence of measurement errors, explicit formulae for the propagation of the three important error terms is provided: bias error (distance from the unknown to-be-reconstructed initial distribution at a finite iteration order), statistical error, and systematic error. A trade-off between these three error terms can be used to define an optimal iteration stopping criterion, and the errors can be estimated there. We provide a numerical C library for the implementation of the method, which incorporates automatic

NEWSPEC: A computer code to unfold neutron spectra from Bonner sphere data

International Nuclear Information System (INIS)

Lemley, E.C.; West, L.

1996-01-01

A new computer code, NEWSPEC, is in development at the University of Arkansas. The NEWSPEC code allows a user to unfold, fold, rebin, display, and manipulate neutron spectra as applied to Bonner sphere measurements. The SPUNIT unfolding algorithm, a new rebinning algorithm, and the graphical capabilities of Microsoft (MS) Windows and MS Excel are utilized to perform these operations. The computer platform for NEWSPEC is a personal computer (PC) running MS Windows 3.x or Win95, while the code is written in MS Visual Basic (VB) and MS VB for Applications (VBA) under Excel. One of the most useful attributes of the NEWSPEC software is the link to Excel allowing additional manipulation of program output or creation of program input

Complex Cloud and Radiative Processes Unfolding at the Earth's Terminator: A Unique Perspective from the Proposed Deep Space Gateway

Science.gov (United States)

Davis, A. B.; Marshak, A.

2018-02-01

The Deep Space Gateway offers a unique vantage for Earth observation using reflected sunlight: day/night or night/day terminators slowly marching across the disc. It's an opportunity to improve our understanding of clouds at that key moment in their daily cycle.

Common features in the unfolding and misfolding of PDZ domains and beyond: the modulatory effect of domain swapping and extra-elements.

Science.gov (United States)

Murciano-Calles, Javier; Güell-Bosch, Jofre; Villegas, Sandra; Martinez, Jose C

2016-01-12

PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbin PDZ domain. Results showed that all domains passed through a common intermediate, which populated upon unfolding, and that this in turn drove the misfolding towards worm-like fibrillar structures. Thus, the unfolding/misfolding behaviour appears to be shared within these domains. We have also analyzed how this landscape can be modified upon the inclusion of extra-elements, as it is in the nNOS PDZ domain, or the organization of swapped species, as happens in the second PDZ domain of the ZO2 protein. Although the intermediates still formed upon thermal unfolding, the misfolding was prevented to varying degrees.

High-Temperature unfolding of a trp-Cage mini-protein: a molecular dynamics simulation study

Directory of Open Access Journals (Sweden)

Seshasayee Aswin Sai Narain

2005-03-01

Full Text Available Abstract Background Trp cage is a recently-constructed fast-folding miniprotein. It consists of a short helix, a 3,10 helix and a C-terminal poly-proline that packs against a Trp in the alpha helix. It is known to fold within 4 ns. Results High-temperature unfolding molecular dynamics simulations of the Trp cage miniprotein have been carried out in explicit water using the OPLS-AA force-field incorporated in the program GROMACS. The radius of gyration (Rg and Root Mean Square Deviation (RMSD have been used as order parameters to follow the unfolding process. Distributions of Rg were used to identify ensembles. Conclusion Three ensembles could be identified. While the native-state ensemble shows an Rg distribution that is slightly skewed, the second ensemble, which is presumably the Transition State Ensemble (TSE, shows an excellent fit. The denatured ensemble shows large fluctuations, but a Gaussian curve could be fitted. This means that the unfolding process is two-state. Representative structures from each of these ensembles are presented here.

Intrinsic and extrinsic mortality reunited.

Science.gov (United States)

Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P; van Bodegom, David; Westendorp, Rudi G J

2015-07-01

Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic stressors in the causation of aging leads to the recognition that aging is not inevitable, but malleable through the environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic coarse-graining fills the gap between atomistic simulations and experimental investigations of mechanical unfolding

Science.gov (United States)

Knoch, Fabian; Schäfer, Ken; Diezemann, Gregor; Speck, Thomas

2018-01-01

We present a dynamic coarse-graining technique that allows one to simulate the mechanical unfolding of biomolecules or molecular complexes on experimentally relevant time scales. It is based on Markov state models (MSMs), which we construct from molecular dynamics simulations using the pulling coordinate as an order parameter. We obtain a sequence of MSMs as a function of the discretized pulling coordinate, and the pulling process is modeled by switching among the MSMs according to the protocol applied to unfold the complex. This way we cover seven orders of magnitude in pulling speed. In the region of rapid pulling, we additionally perform steered molecular dynamics simulations and find excellent agreement between the results of the fully atomistic and the dynamically coarse-grained simulations. Our technique allows the determination of the rates of mechanical unfolding in a dynamical range from approximately 10-8/ns to 1/ns thus reaching experimentally accessible time regimes without abandoning atomistic resolution.

A neutron spectrum unfolding code based on iterative procedures

International Nuclear Information System (INIS)

Ortiz R, J. M.; Vega C, H. R.

2012-10-01

In this work, the version 3.0 of the neutron spectrum unfolding code called Neutron Spectrometry and Dosimetry from Universidad Autonoma de Zacatecas (NSDUAZ), is presented. This code was designed in a graphical interface under the LabVIEW programming environment and it is based on the iterative SPUNIT iterative algorithm, using as entrance data, only the rate counts obtained with 7 Bonner spheres based on a 6 Lil(Eu) neutron detector. The main features of the code are: it is intuitive and friendly to the user; it has a programming routine which automatically selects the initial guess spectrum by using a set of neutron spectra compiled by the International Atomic Energy Agency. Besides the neutron spectrum, this code calculates the total flux, the mean energy, H(10), h(10), 15 dosimetric quantities for radiation protection porpoises and 7 survey meter responses, in four energy grids, based on the International Atomic Energy Agency compilation. This code generates a full report in html format with all relevant information. In this work, the neutron spectrum of a 241 AmBe neutron source on air, located at 150 cm from detector, is unfolded. (Author)

Antibody-Unfolding and Metastable-State Binding in Force Spectroscopy and Recognition Imaging

Science.gov (United States)

Kaur, Parminder; Qiang-Fu; Fuhrmann, Alexander; Ros, Robert; Kutner, Linda Obenauer; Schneeweis, Lumelle A.; Navoa, Ryman; Steger, Kirby; Xie, Lei; Yonan, Christopher; Abraham, Ralph; Grace, Michael J.; Lindsay, Stuart

2011-01-01

Force spectroscopy and recognition imaging are important techniques for characterizing and mapping molecular interactions. In both cases, an antibody is pulled away from its target in times that are much less than the normal residence time of the antibody on its target. The distribution of pulling lengths in force spectroscopy shows the development of additional peaks at high loading rates, indicating that part of the antibody frequently unfolds. This propensity to unfold is reversible, indicating that exposure to high loading rates induces a structural transition to a metastable state. Weakened interactions of the antibody in this metastable state could account for reduced specificity in recognition imaging where the loading rates are always high. The much weaker interaction between the partially unfolded antibody and target, while still specific (as shown by control experiments), results in unbinding on millisecond timescales, giving rise to rapid switching noise in the recognition images. At the lower loading rates used in force spectroscopy, we still find discrepancies between the binding kinetics determined by force spectroscopy and those determined by surface plasmon resonance—possibly a consequence of the short tethers used in recognition imaging. Recognition imaging is nonetheless a powerful tool for interpreting complex atomic force microscopy images, so long as specificity is calibrated in situ, and not inferred from equilibrium binding kinetics. PMID:21190677

Intrinsic-density functionals

International Nuclear Information System (INIS)

Engel, J.

2007-01-01

The Hohenberg-Kohn theorem and Kohn-Sham procedure are extended to functionals of the localized intrinsic density of a self-bound system such as a nucleus. After defining the intrinsic-density functional, we modify the usual Kohn-Sham procedure slightly to evaluate the mean-field approximation to the functional, and carefully describe the construction of the leading corrections for a system of fermions in one dimension with a spin-degeneracy equal to the number of particles N. Despite the fact that the corrections are complicated and nonlocal, we are able to construct a local Skyrme-like intrinsic-density functional that, while different from the exact functional, shares with it a minimum value equal to the exact ground-state energy at the exact ground-state intrinsic density, to next-to-leading order in 1/N. We briefly discuss implications for real Skyrme functionals

Application of unfolding transformation in the random matrix theory to analyze in vivo neuronal spike firing during awake and anesthetized conditions

Directory of Open Access Journals (Sweden)

Risako Kato

2018-03-01

Full Text Available General anesthetics decrease the frequency and density of spike firing. This effect makes it difficult to detect spike regularity. To overcome this problem, we developed a method utilizing the unfolding transformation which analyzes the energy level statistics in the random matrix theory. We regarded the energy axis as time axis of neuron spike and analyzed the time series of cortical neural firing in vivo. Unfolding transformation detected regularities of neural firing while changes in firing densities were associated with pentobarbital. We found that unfolding transformation enables us to compare firing regularity between awake and anesthetic conditions on a universal scale. Keywords: Unfolding transformation, Spike-timing, Regularity

Inclusive neutral current ep cross sections with HERA II and two-dimensional unfolding

International Nuclear Information System (INIS)

Fischer, David-Johannes

2011-06-01

In this thesis, the inclusive neutral current ep → eX cross section at small e - scattering angles has been measured using the electromagnetic SpaCal calorimeter in the backward region of the H1 detector. This calorimeter constructed of lead and scintillating fiber was designed to measure the scattered electron with high resolution in both energy and polar angle. The analysis comprises the kinematic range of 0.06 e 2 e 2 2 for the squared momentum exchange. The data sample consists of positron proton collisions of the years 2006 and 2007, adding up to an integrated luminosity of ∝141 pb -1 . Due to the high luminosity of the HERA II run phase the accuracy is no longer limited by the data statistics but rather by the detector resolution and systematics. The migration becomes increasingly influential; an effect which leads to distortions of the measured distribution as well as to statistical correlations between adjacent data points. At this stage, the correction of detector effects as well as the precise determination of statistical correlations become important features of a rigorous error treatment. In this analysis two-dimensional unfolding has been applied. This is a novel approach to H1 inclusive cross section measurements, which are usually based on a bin-by-bin efficiency correction (bin-by-bin method). With unfolding, the detector effect to the measurements is modelled by a linear transformation (''response matrix'') which is used to correct any distortion of the data. The inclusion of off-diagonal elements results in a coherent assessment of the statistical uncertainties and correlations. The model dependence can be optimally evaluated. In this context, the bin-by-bin method can be viewed as an approximation based on a diagonal response matrix. In a scenario of limited detector resolution, the unfolded data distributions will typically exhibit strong fluctuations and correlations between the data points. This issue can be addressed by smoothing

Inclusive neutral current ep cross sections with HERA II and two-dimensional unfolding

Energy Technology Data Exchange (ETDEWEB)

Fischer, David-Johannes

2011-06-15

In this thesis, the inclusive neutral current ep {yields} eX cross section at small e{sup -} scattering angles has been measured using the electromagnetic SpaCal calorimeter in the backward region of the H1 detector. This calorimeter constructed of lead and scintillating fiber was designed to measure the scattered electron with high resolution in both energy and polar angle. The analysis comprises the kinematic range of 0.06 < y{sub e} < 0.6 for the inelasticity and 14 GeV{sup 2} < Q{sub e}{sup 2} < 110 GeV{sup 2} for the squared momentum exchange. The data sample consists of positron proton collisions of the years 2006 and 2007, adding up to an integrated luminosity of {proportional_to}141 pb{sup -1}. Due to the high luminosity of the HERA II run phase the accuracy is no longer limited by the data statistics but rather by the detector resolution and systematics. The migration becomes increasingly influential; an effect which leads to distortions of the measured distribution as well as to statistical correlations between adjacent data points. At this stage, the correction of detector effects as well as the precise determination of statistical correlations become important features of a rigorous error treatment. In this analysis two-dimensional unfolding has been applied. This is a novel approach to H1 inclusive cross section measurements, which are usually based on a bin-by-bin efficiency correction (bin-by-bin method). With unfolding, the detector effect to the measurements is modelled by a linear transformation (''response matrix'') which is used to correct any distortion of the data. The inclusion of off-diagonal elements results in a coherent assessment of the statistical uncertainties and correlations. The model dependence can be optimally evaluated. In this context, the bin-by-bin method can be viewed as an approximation based on a diagonal response matrix. In a scenario of limited detector resolution, the unfolded data distributions will

Unfolded protein response and activated degradative pathways regulation in GNE myopathy.

Directory of Open Access Journals (Sweden)

Honghao Li

Full Text Available Although intracellular beta amyloid (Aβ accumulation is known as an early upstream event in the degenerative course of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE myopathy, the process by which Aβdeposits initiate various degradative pathways, and their relationship have not been fully clarified. We studied the possible secondary responses after amyloid beta precursor protein (AβPP deposition including unfolded protein response (UPR, ubiquitin proteasome system (UPS activation and its correlation with autophagy system. Eight GNE myopathy patients and five individuals with normal muscle morphology were included in this study. We performed immunofluorescence and immunoblotting to investigate the expression of AβPP, phosphorylated tau (p-tau and endoplasmic reticulum molecular chaperones. Proteasome activities were measured by cleavage of fluorogenic substrates. The expression of proteasome subunits and linkers between proteasomal and autophagy systems were also evaluated by immunoblotting and relative quantitative real-time RT-PCR. Four molecular chaperones, glucose-regulated protein 94 (GRP94, glucose-regulated protein 78 (GRP78, calreticulin and calnexin and valosin containing protein (VCP were highly expressed in GNE myopathy. 20S proteasome subunits, three main proteasome proteolytic activities, and the factors linking UPS and autophagy system were also increased. Our study suggests that AβPP deposition results in endoplasmic reticulum stress (ERS and highly expressed VCP deliver unfolded proteins from endoplasmic reticulum to proteosomal system which is activated in endoplasmic reticulum associated degradation (ERAD in GNE myopathy. Excessive ubiquitinated unfolded proteins are exported by proteins that connect UPS and autophagy to autophagy system, which is activated as an alternative pathway for degradation.

Solvent Effects on Protein Folding/Unfolding

Science.gov (United States)

García, A. E.; Hillson, N.; Onuchic, J. N.

Pressure effects on the hydrophobic potential of mean force led Hummer et al. to postulate a model for pressure denaturation of proteins in which denaturation occurs by means of water penetration into the protein interior, rather than by exposing the protein hydrophobic core to the solvent --- commonly used to describe temperature denaturation. We study the effects of pressure in protein folding/unfolding kinetics in an off-lattice minimalist model of a protein in which pressure effects have been incorporated by means of the pair-wise potential of mean force of hydrophobic groups in water. We show that pressure slows down the kinetics of folding by decreasing the reconfigurational diffusion coefficient and moves the location of the folding transition state.

Kinetics of protein unfolding at interfaces

International Nuclear Information System (INIS)

Yano, Yohko F

2012-01-01

The conformation of protein molecules is determined by a balance of various forces, including van der Waals attraction, electrostatic interaction, hydrogen bonding, and conformational entropy. When protein molecules encounter an interface, they are often adsorbed on the interface. The conformation of an adsorbed protein molecule strongly depends on the interaction between the protein and the interface. Recent time-resolved investigations have revealed that protein conformation changes during the adsorption process due to the protein-protein interaction increasing with increasing interface coverage. External conditions also affect the protein conformation. This review considers recent dynamic observations of protein adsorption at various interfaces and their implications for the kinetics of protein unfolding at interfaces. (topical review)

Combining short- and long-range fluorescence reporters with simulations to explore the intramolecular dynamics of an intrinsically disordered protein

Science.gov (United States)

Zosel, Franziska; Haenni, Dominik; Soranno, Andrea; Nettels, Daniel; Schuler, Benjamin

2017-10-01

Intrinsically disordered proteins (IDPs) are increasingly recognized as a class of molecules that can exert essential biological functions even in the absence of a well-defined three-dimensional structure. Understanding the conformational distributions and dynamics of these highly flexible proteins is thus essential for explaining the molecular mechanisms underlying their function. Single-molecule fluorescence spectroscopy in combination with Förster resonance energy transfer (FRET) is a powerful tool for probing intramolecular distances and the rapid long-range distance dynamics in IDPs. To complement the information from FRET, we combine it with photoinduced electron transfer (PET) quenching to monitor local loop-closure kinetics at the same time and in the same molecule. Here we employed this combination to investigate the intrinsically disordered N-terminal domain of HIV-1 integrase. The results show that both long-range dynamics and loop closure kinetics on the sub-microsecond time scale can be obtained reliably from a single set of measurements by the analysis with a comprehensive model of the underlying photon statistics including both FRET and PET. A more detailed molecular interpretation of the results is enabled by direct comparison with a recent extensive atomistic molecular dynamics simulation of integrase. The simulations are in good agreement with experiment and can explain the deviation from simple models of chain dynamics by the formation of persistent local secondary structure. The results illustrate the power of a close combination of single-molecule spectroscopy and simulations for advancing our understanding of the dynamics and detailed mechanisms in unfolded and intrinsically disordered proteins.

Multistage unfolding of an SH3 domain: an initial urea-filled dry molten globule precedes a wet molten globule with non-native structure.

Science.gov (United States)

Dasgupta, Amrita; Udgaonkar, Jayant B; Das, Payel

2014-06-19

The unfolding of the SH3 domain of the PI3 kinase in aqueous urea has been studied using a synergistic experiment-simulation approach. The experimental observation of a transient wet molten globule intermediate, IU, with an unusual non-native burial of the sole Trp residue, W53, provides the benchmark for the unfolding simulations performed (eight in total, each at least 0.5 μs long). The simulations reveal that the partially unfolded IU ensemble is preceded by an early native-like molten globule intermediate ensemble I*. In the very initial stage of unfolding, dry globule conformations with the protein core filled with urea instead of water are transiently observed within the I* ensemble. Water penetration into the urea-filled core of dry globule conformations is frequently accompanied by very transient burial of W53. Later during gradual unfolding, W53 is seen to again become transiently buried in the IU ensemble for a much longer time. In the structurally heterogeneous IU ensemble, conformational flexibility of the C-terminal β-strands enables W53 burial by the formation of non-native, tertiary contacts with hydrophobic residues, which could serve to protect the protein from aggregation during unfolding.

Simulation study on unfolding methods for diagnostic X-rays and mixed gamma rays

International Nuclear Information System (INIS)

Hashimoto, Makoto; Ohtaka, Masahiko; Ara, Kuniaki; Kanno, Ikuo; Imamura, Ryo; Mikami, Kenta; Nomiya, Seiichiro; Onabe, Hideaki

2009-01-01

A photon detector operating in current mode that can sense X-ray energy distribution has been reported. This detector consists of a row of several segment detectors. The energy distribution is derived using an unfolding technique. In this paper, comparisons of the unfolding techniques among error reduction, spectrum surveillance, and neural network methods are discussed through simulation studies on the detection of diagnostic X-rays and gamma rays emitted by a mixture of 137 Cs and 60 Co. For diagnostic X-ray measurement, the spectrum surveillance and neural network methods appeared promising, while the error reduction method yielded poor results. However, in the case of measuring mixtures of gamma rays, the error reduction method was both sufficient and effective. (author)

Evaluation of spectral unfolding techniques for neutron spectroscopy

International Nuclear Information System (INIS)

Sunden, Erik Andersson; Conroy, S.; Ericsson, G.; Johnson, M. Gatu; Giacomelli, L.; Hellesen, C.; Hjalmarsson, A.; Ronchi, E.; Sjoestrand, H.; Weiszflog, M.; Kaellne, J.; Gorini, G.; Tardocchi, M.

2008-01-01

The precision of the JET installations of MAXED, GRAVEL and the L-curve version of MAXED has been evaluated by using synthetic neutron spectra. We have determined the number of counts needed for the detector systems NE213 and MPR to get an error below 10% of the MAXED unfolded neutron spectra is determined to be ∼10 6 and ∼10 4 , respectively. For GRAVEL the same number is ∼10 7 and ∼3·10 4 for NE213 and MPR, respectively

Urea-temperature phase diagrams capture the thermodynamics of denatured state expansion that accompany protein unfolding

Science.gov (United States)

Tischer, Alexander; Auton, Matthew

2013-01-01

We have analyzed the thermodynamic properties of the von Willebrand factor (VWF) A3 domain using urea-induced unfolding at variable temperature and thermal unfolding at variable urea concentrations to generate a phase diagram that quantitatively describes the equilibrium between native and denatured states. From this analysis, we were able to determine consistent thermodynamic parameters with various spectroscopic and calorimetric methods that define the urea–temperature parameter plane from cold denaturation to heat denaturation. Urea and thermal denaturation are experimentally reversible and independent of the thermal scan rate indicating that all transitions are at equilibrium and the van't Hoff and calorimetric enthalpies obtained from analysis of individual thermal transitions are equivalent demonstrating two-state character. Global analysis of the urea–temperature phase diagram results in a significantly higher enthalpy of unfolding than obtained from analysis of individual thermal transitions and significant cross correlations describing the urea dependence of and that define a complex temperature dependence of the m-value. Circular dichroism (CD) spectroscopy illustrates a large increase in secondary structure content of the urea-denatured state as temperature increases and a loss of secondary structure in the thermally denatured state upon addition of urea. These structural changes in the denatured ensemble make up ∼40% of the total ellipticity change indicating a highly compact thermally denatured state. The difference between the thermodynamic parameters obtained from phase diagram analysis and those obtained from analysis of individual thermal transitions illustrates that phase diagrams capture both contributions to unfolding and denatured state expansion and by comparison are able to decipher these contributions. PMID:23813497

Thermal- and urea-induced unfolding processes of glutathione S-transferase by molecular dynamics simulation.

Science.gov (United States)

Li, Jiahuang; Chen, Yuan; Yang, Jie; Hua, Zichun

2015-05-01

The Schistosoma juponicum 26 kDa glutathione S-transferase (sj26GST) consists of the N-terminal domain (N-domain), containing three alpha-helices (named H1-H3) and four anti-parallel beta-strands (S1-S4), and the C-terminal domain (C-domain), comprising five alpha-helices (named H4-H8). In present work, molecular dynamics simulations and fluorescence spectroscopic were used to gain insights into the unfolding process of sj26GST. The molecular dynamics simulations on sj26GST subunit both in water and in 8 M urea were carried out at 300 K, 400 K and 500 K, respectively. Spectroscopic measurements were employed to monitor structural changes. Molecular dynamics simulations of sj26GST subunit induced by urea and temperature showed that the initial unfolding step of sj26GST both in water and urea occurred on N-domain, involving the disruption of helices H2, H3 and strands S3 and S4, whereas H6 was the last region exposed to solution and was the last helix to unfold. Moreover, simulations analyses combining with fluorescence and circular dichroism spectra indicated that N-domain could not fold independent, suggesting that correct folding of N-domain depended on its interactions with C-domain. We further proposed that the folding of GSTs could begin with the hydrophobic collapse of C-domain whose H4, H5, H6 and H7 could move close to each other and form a hydrophobic core, especially H6 wrapped in the hydrophobic center and beginning spontaneous formation of the helix. S3, S4, H3, and H2 could form in the wake of the interaction between C-domain and N-domain. The paper can offer insights into the molecular mechanism of GSTs unfolding. © 2014 Wiley Periodicals, Inc.

Influence of the initial guess spectrum in the unfolding of Bss data obtained inside a bunker of a PET cyclotron

Energy Technology Data Exchange (ETDEWEB)

Benavente C, J. A.; Lacerda, M. A. S.; Guimaraes, A. M.; Da Silva, T. A. [Universidade Federal de Minas Gerais, Departamento de Engenharia Nuclear, Programa de Pos-graduacao em Ciencias e Tecnicas Nucleares, Pte. Antonio Carlos 6627, Belo Horizonte 31270-901, Minas Gerais (Brazil); Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98060 Zacatecas, Zac. (Mexico)

2015-10-15

In a cyclotron facility is strongly advised the use of spectrometry techniques to support workplace neutron dosimetry. Bonner sphere spectrometer (Bss) is the most used for radiation protection applications. Bss data must be unfolded to determine the spectral particle fluence. Some computer codes have been utilized for this purpose. These codes allow unfolding the spectrum from the Bss count rates through different algorithms. Some iterative routines need an initial guess spectrum to start the unfolding. The adequate choice of this initial spectrum is a critical part of the process and can affect the final solution. In this work, we evaluate the influence of the initial guess spectrum in the unfolding of Bss data obtained in four points inside the bunker of a PET cyclotron. The measurements were done utilizing a modified Bss system with thermoluminescent detectors (TLDs). Codes BUNKIUT and NSDUAZ were utilized to unfold the Bss data. For the NSDUAZ the starting spectrum is automatically obtained from a library initial guess spectra. For the BUNKIUT code were utilized two different initial guess spectra: (a) a Maxwellian spectrum with temperature of 1.4 MeV and shape factor of 0.1, created with the MAXIET algorithm and; (b) the spectra obtained through simulation with the MCNPX code version 2.7. Spectra obtained with both unfold codes and with the different initial guess spectra presented epithermal and thermal neutrons due to room-return effects. However, the contribution of the fast neutron to the total fluence were quite different for the different cases studied. These differences highlight the importance of an appropriate choice of an initial guess spectra for the quality of the results. (Author)

Influence of the initial guess spectrum in the unfolding of Bss data obtained inside a bunker of a PET cyclotron

International Nuclear Information System (INIS)

Benavente C, J. A.; Lacerda, M. A. S.; Guimaraes, A. M.; Da Silva, T. A.; Vega C, H. R.

2015-10-01

In a cyclotron facility is strongly advised the use of spectrometry techniques to support workplace neutron dosimetry. Bonner sphere spectrometer (Bss) is the most used for radiation protection applications. Bss data must be unfolded to determine the spectral particle fluence. Some computer codes have been utilized for this purpose. These codes allow unfolding the spectrum from the Bss count rates through different algorithms. Some iterative routines need an initial guess spectrum to start the unfolding. The adequate choice of this initial spectrum is a critical part of the process and can affect the final solution. In this work, we evaluate the influence of the initial guess spectrum in the unfolding of Bss data obtained in four points inside the bunker of a PET cyclotron. The measurements were done utilizing a modified Bss system with thermoluminescent detectors (TLDs). Codes BUNKIUT and NSDUAZ were utilized to unfold the Bss data. For the NSDUAZ the starting spectrum is automatically obtained from a library initial guess spectra. For the BUNKIUT code were utilized two different initial guess spectra: (a) a Maxwellian spectrum with temperature of 1.4 MeV and shape factor of 0.1, created with the MAXIET algorithm and; (b) the spectra obtained through simulation with the MCNPX code version 2.7. Spectra obtained with both unfold codes and with the different initial guess spectra presented epithermal and thermal neutrons due to room-return effects. However, the contribution of the fast neutron to the total fluence were quite different for the different cases studied. These differences highlight the importance of an appropriate choice of an initial guess spectra for the quality of the results. (Author)

Exploring the Unfolding Pathway of Maltose Binding Proteins: An Integrated Computational Approach

KAUST Repository

Guardiani, Carlo; Marino, Daniele Di; Tramontano, Anna; Chinappi, Mauro; Cecconi, Fabio

2014-01-01

© 2014 American Chemical Society. Recent single-molecule force spectroscopy experiments on the Maltose Binding Proteins (MBPs) identified four stable structural units, termed unfoldons, that resist mechanical stress and determine the intermediates of the unfolding pathway. In this work, we analyze the topological origin and the dynamical role of the unfoldons using an integrated approach which combines a graph-theoretical analysis of the interaction network of the MBP native-state with steered molecular dynamics simulations. The topological analysis of the native state, while revealing the structural nature of the unfoldons, provides a framework to interpret the MBP mechanical unfolding pathway. Indeed, the experimental pathway can be effectively predicted by means of molecular dynamics simulations with a simple topology-based and low-resolution model of the MBP. The results obtained from the coarse-grained approach are confirmed and further refined by all-atom molecular dynamics.

Exploring the Unfolding Pathway of Maltose Binding Proteins: An Integrated Computational Approach

KAUST Repository

Guardiani, Carlo

2014-09-09

© 2014 American Chemical Society. Recent single-molecule force spectroscopy experiments on the Maltose Binding Proteins (MBPs) identified four stable structural units, termed unfoldons, that resist mechanical stress and determine the intermediates of the unfolding pathway. In this work, we analyze the topological origin and the dynamical role of the unfoldons using an integrated approach which combines a graph-theoretical analysis of the interaction network of the MBP native-state with steered molecular dynamics simulations. The topological analysis of the native state, while revealing the structural nature of the unfoldons, provides a framework to interpret the MBP mechanical unfolding pathway. Indeed, the experimental pathway can be effectively predicted by means of molecular dynamics simulations with a simple topology-based and low-resolution model of the MBP. The results obtained from the coarse-grained approach are confirmed and further refined by all-atom molecular dynamics.

Constrained Unfolding of a Helical Peptide: Implicit versus Explicit Solvents.

Directory of Open Access Journals (Sweden)

Hailey R Bureau

Full Text Available Steered Molecular Dynamics (SMD has been seen to provide the potential of mean force (PMF along a peptide unfolding pathway effectively but at significant computational cost, particularly in all-atom solvents. Adaptive steered molecular dynamics (ASMD has been seen to provide a significant computational advantage by limiting the spread of the trajectories in a staged approach. The contraction of the trajectories at the end of each stage can be performed by taking a structure whose nonequilibrium work is closest to the Jarzynski average (in naive ASMD or by relaxing the trajectories under a no-work condition (in full-relaxation ASMD--namely, FR-ASMD. Both approaches have been used to determine the energetics and hydrogen-bonding structure along the pathway for unfolding of a benchmark peptide initially constrained as an α-helix in a water environment. The energetics are quite different to those in vacuum, but are found to be similar between implicit and explicit solvents. Surprisingly, the hydrogen-bonding pathways are also similar in the implicit and explicit solvents despite the fact that the solvent contact plays an important role in opening the helix.

Unfolding of hemoglobin variants--insights from urea gradient gel electrophoresis photon correlation spectroscopy and zeta potential measurements

International Nuclear Information System (INIS)

Bhattacharya, Jaydeep; GhoshMoulick, Ranjita; Choudhuri, Utpal; Chakrabarty, Prantar; Bhattacharya, Pranab K.; Lahiri, Prabir; Chakraborti, Bikas; Dasgupta, Anjan Kr.

2004-01-01

The unfolding pattern of crystal human hemoglobin and variants of hemoglobin obtained from hemolysate were studied using transverse urea gradient gel electrophoresis (TUGGE). A smooth sigmoid like increase of electrophoretic mobility was observed with increasing urea concentrations. A decrease in electrophoretic mobility resulted, if the protein was unfolded with guanidium hydrochloride (GdnHCl). The anomaly was resolved after the Stoke's radii (obtained using the photon correlation spectroscopy) and zeta potential (measured using laser Doppler velocimetry) measurements were made at different denaturant concentrations. Addition of denaturant led to formation of extended structure, irrespective of the nature of the denaturant, as indicated by increase in Stoke's radii in both cases (urea and GdnHCl). The unexpected increase in electrophoretic mobility in case of urea could be explained in terms of a critical redistribution of negative charge at intermediate stages of the unfolding process. In case of GdnHCl, the higher ionic strength masked the charge effect. The mobility, being solely dependent on size, decreased at higher denaturant concentration. Incidentally, folding loci of other hemoglobin variants (e.g. HbE) or that of post-translationally modified hemoglobin (e.g. HbA1c) could be determined by studying the charge distribution and hydrodynamic radius at varying denaturing stress and in each case the gel migration profile could be approximately scaled by the ratio of charge and hydrodynamic diameter of the protein. While unfolding induced charge effect was most pronounced in HbA0 (and crystal ferrous hemoglobin), the unfolding induced aggregation (manifested by the increase in Stoke's radii) was predominantly observed in the variant forms HbE and HbA1c. Representing the proteins by a plot, in which charge and hydrodynamic diameter are on independent axes, may be a useful way of characterizing protein variants having similar migration profiles on native gels

A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

Science.gov (United States)

Noël, Emily S.; Verhoeven, Manon; Lagendijk, Anne Karine; Tessadori, Federico; Smith, Kelly; Choorapoikayil, Suma; den Hertog, Jeroen; Bakkers, Jeroen

2013-11-01

Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

Experience – Information – Image: A Historiography of Unfolding. Arab Cinema as Example

Directory of Open Access Journals (Sweden)

Laura U. Marks

2011-04-01

Many artworks can be illuminated by this process. My examples will be drawn from contemporary Arab cinema. In the heavily politicized Arab milieu, the Image world is constructed as a selective unfolding of only those aspects of Experience that are deemed to be useful or profitable. Some Arab filmmakers, rather than deconstruct the resulting ideological images, prefer to carry out their own unfoldings:  explicating hitherto latent events, knowledges, and sensations. Thus what official history deems merely personal, absurd, micro-events, or no events at all, becomes the stuff of a rich alternative historiography. This process characterizes the work of, among others, Joana Hadjithomas and Khalil Joreige, Nisrine Khodr, Mohammed Soueid, and Akram Zaatari (Lebanon, Azza El-Hassan, Elia Suleiman, and Sobhi Al-Zobaidi (Palestine, and Mohamad Khan (Egypt.

Characteristic Investigation of Unfolded Neutron Spectra with Different Priori Information and Gamma Radiation Interference

International Nuclear Information System (INIS)

Kim, Bong Hwan

2006-01-01

Neutron field spectrometry using multi spheres such as Bonner Spheres (BS) has been almost essential in radiation protection dosimetry for a long time at workplace in spite of poor energy resolution because it is not asking the fine energy resolution but requiring easy operation and measurement performance over a wide range of energy interested. KAERI has developed and used extended BS system based on a LiI(Eu) scintillator as the representative neutron spectrometry system for workplace monitoring as well as for the quantification of neutron calibration fields such as those recommended by ISO 8529. Major topics in using BS are how close the unfolded spectra is the real one and to minimize the interference of gamma radiation in neutron/gamma mixed fields in case of active instrument such as a BS with a LiI(Eu) scintillator. The former is related with choosing a priori information when unfolding the measured data and the latter is depend on how to discriminate it in intense gamma radiation fields. Influence of a priori information in unfolding and effect of counting loss due to pile-up of signals for the KAERI BS system were investigated analyzing the spectral measurement results of Scattered Neutron Calibration Fields (SNCF)

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

Science.gov (United States)

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

2014-11-07

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

[Effects of redox state of disulfide bonds on the intrinsic fluorescence and denaturation of Trx-fused gibberellin-induced cysteine-rich protein from Gymnadnia conopsea].

Science.gov (United States)

Zhang, Teng; Feng, Juan; Li, Yang; Chen, Rui; Tang, Li-Xia; Pang, Xiao-Feng; Ren, Zheng-Long

2010-02-01

In the present paper, thioredoxin-fused gibberellin-induced cysteine-rich protein from Gymnadnia conopsea, desigated as Trx-GcGASA and expressed prokaryotically, was purified and identified by using Ni(2+) -NTA affinity chromatography column and SDS-PAGE, and then its intrinsic fluorescence was investigated in the absence and presence of dithiothreitol (DTT), oxidized glutathione (GSSG), peroxide and guanidine hydrochloride (GdnHCl) by means of steady-state fluorescence spectroscopic methods. It was found that (1) at the neutral pH Trx-GcGASA had maximum fluorescence emission at 305 nm following excitation at different wavelengths varying from 250 to 280 nm, which was ascribed to the fluorescence emission from tyrosine residues. (2) The reduction of disulphide bonds lead to the changes in the relative fluorescence intensity between tyrosine and tryptophan residues from 0.7 to 1.8. (3) Both Tyr and Trp residues underwent 12%-21% decrease in fluorescence intensity with the addition of 0.5 mmol x L(-1) GSSG or 5 mmol x L(-1) peroxide. The latter was roughly consistent with the antioxidative activity reported in vivo. (4) No matter whether 1 mmol x L(-1) DTT was absent or present, the fusion protein could not be fully unfolded with lambda(max) Trx-GcGASA experienced GdnHCl-induced denaturation process, and the unfolding equilibrium curve could be well fitted by using two-state model, giving the Gibbs free energy change (deltaG) of 3.7 kJ x mol(-1). However, it was not the case for reduced Trx-GcGASA protein. The aforementioned experimental results will not only provide some guides to investigate the effects of fusion partner Trx on the unfolding thermodynamics, kinetics and refolding process of Trx-GcGASA, but also will be useful for further studies on the strucuture of GA-induced cysteine-rich protein with the help of spectroscopic methods.

THE INTRINSIC EXPLANATORY VALUE OF SOCIAL CONSTRUCTIVISM IN INTERNATIONAL RELATIONS THEORY

Directory of Open Access Journals (Sweden)

Ts. V. Karkalanov

2016-01-01

Full Text Available Why has constructivism emerged as an important force in the field of international relations and politics in the end of the 20th century? Why constructivism and not any other theoretical approach? The constructivist perspective of international relations appeared as a counterbalance to rationalism that was entrenched in US Political Science throughout the last decades. Analyzing the contemporary state of world affairs through the prism of social constructivism provides us with a unique understanding of how intersubjective perceptions lead to unique epistemic interpretations of reality, which form the ideological framework within which social constructs are being generated. Constructivism succeeds not only in identifying the motives behind the behavior of international actors, but also in unfolding the mechanism through which those motives are being envisaged and accepted through the process of social construction – here lies the greatest value of the constructivist approach in IR theory. Culture formation, nation building, imagined communities, security complexes – the constructivist approach remains an invaluable tool in the arsenal of political analysts, seeking to understand how culture, history, social order, religion, and language project their infl uence on the international arena and ultimately: why international players behave the way they do?

Unfolding of a Temperature-Sensitive Domain Controls Voltage-Gated Channel Activation.

Science.gov (United States)

Arrigoni, Cristina; Rohaim, Ahmed; Shaya, David; Findeisen, Felix; Stein, Richard A; Nurva, Shailika Reddy; Mishra, Smriti; Mchaourab, Hassane S; Minor, Daniel L

2016-02-25

Voltage-gated ion channels (VGICs) are outfitted with diverse cytoplasmic domains that impact function. To examine how such elements may affect VGIC behavior, we addressed how the bacterial voltage-gated sodium channel (BacNa(V)) C-terminal cytoplasmic domain (CTD) affects function. Our studies show that the BacNa(V) CTD exerts a profound influence on gating through a temperature-dependent unfolding transition in a discrete cytoplasmic domain, the neck domain, proximal to the pore. Structural and functional studies establish that the BacNa(V) CTD comprises a bi-partite four-helix bundle that bears an unusual hydrophilic core whose integrity is central to the unfolding mechanism and that couples directly to the channel activation gate. Together, our findings define a general principle for how the widespread four-helix bundle cytoplasmic domain architecture can control VGIC responses, uncover a mechanism underlying the diverse BacNa(V) voltage dependencies, and demonstrate that a discrete domain can encode the temperature-dependent response of a channel. Copyright © 2016 Elsevier Inc. All rights reserved.

Understanding how biodiversity unfolds through time under neutral theory.

Science.gov (United States)

Missa, Olivier; Dytham, Calvin; Morlon, Hélène

2016-04-05

Theoretical predictions for biodiversity patterns are typically derived under the assumption that ecological systems have reached a dynamic equilibrium. Yet, there is increasing evidence that various aspects of ecological systems, including (but not limited to) species richness, are not at equilibrium. Here, we use simulations to analyse how biodiversity patterns unfold through time. In particular, we focus on the relative time required for various biodiversity patterns (macroecological or phylogenetic) to reach equilibrium. We simulate spatially explicit metacommunities according to the Neutral Theory of Biodiversity (NTB) under three modes of speciation, which differ in how evenly a parent species is split between its two daughter species. We find that species richness stabilizes first, followed by species area relationships (SAR) and finally species abundance distributions (SAD). The difference in timing of equilibrium between these different macroecological patterns is the largest when the split of individuals between sibling species at speciation is the most uneven. Phylogenetic patterns of biodiversity take even longer to stabilize (tens to hundreds of times longer than species richness) so that equilibrium predictions from neutral theory for these patterns are unlikely to be relevant. Our results suggest that it may be unwise to assume that biodiversity patterns are at equilibrium and provide a first step in studying how these patterns unfold through time. © 2016 The Author(s).

Identification of pitfalls in the analysis of heat capacity changes of β-lactoglobulin A

NARCIS (Netherlands)

Teeffelen, A.M.M. van; Meinders, M.B.J.; Jongh, H.H.J. de

2005-01-01

Information on changes in heat capacity (ΔCp) of proteins upon unfolding is used frequently in literature to understand possible follow-up reactions of protein denaturation, like their aggregation propensity. This thermodynamic property is intrinsic to the protein's architecture and unfolding and

First results of Minimum Fisher Regularisation as unfolding method for JET NE213 liquid scintillator neutron spectrometry

International Nuclear Information System (INIS)

Mlynar, Jan; Adams, John M.; Bertalot, Luciano; Conroy, Sean

2005-01-01

At JET, the NE213 liquid scintillator is being validated as a diagnostic tool for spectral measurements of neutrons emitted from the plasma. Neutron spectra have to be unfolded from the measured pulse-height spectra, which is an ill-conditioned problem. Therefore, use of two independent unfolding methods allows for less ambiguity on the interpretation of the data. In parallel to the routine algorithm MAXED based on the Maximum Entropy method, the Minimum Fisher Regularisation (MFR) method has been introduced at JET. The MFR method, known from two-dimensional tomography applications, has proved to provide a new transparent tool to validate the JET neutron spectra measured with the NE213 liquid scintillators. In this article, the MFR method applicable to spectra unfolding is briefly explained. After a mention of MFR tests on phantom spectra experimental neutron spectra are presented that were obtained by applying MFR to NE213 data in selected JET experiments. The results tend to confirm MAXED observations

A generator for unique quantum random numbers based on vacuum states

DEFF Research Database (Denmark)

Gabriel, C.; Wittmann, C.; Sych, D.

2010-01-01

the purity of a continuous-variable quantum vacuum state to generate unique random numbers. We use the intrinsic randomness in measuring the quadratures of a mode in the lowest energy vacuum state, which cannot be correlated to any other state. The simplicity of our source, combined with its verifiably......Random numbers are a valuable component in diverse applications that range from simulations(1) over gambling to cryptography(2,3). The quest for true randomness in these applications has engendered a large variety of different proposals for producing random numbers based on the foundational...... unpredictability of quantum mechanics(4-11). However, most approaches do not consider that a potential adversary could have knowledge about the generated numbers, so the numbers are not verifiably random and unique(12-15). Here we present a simple experimental setup based on homodyne measurements that uses...

Genome-Wide Prediction of Intrinsic Disorder; Sequence Alignment of Intrinsically Disordered Proteins

Science.gov (United States)

Midic, Uros

2012-01-01

Intrinsic disorder (ID) is defined as a lack of stable tertiary and/or secondary structure under physiological conditions in vitro. Intrinsically disordered proteins (IDPs) are highly abundant in nature. IDPs possess a number of crucial biological functions, being involved in regulation, recognition, signaling and control, e.g. their functional…

Major Intrinsic Proteins in Biomimetic Membranes

DEFF Research Database (Denmark)

Helix Nielsen, Claus

2010-01-01

or as sensor devices based on e.g., the selective permeation of metalloids. In principle a MIP based membrane sensor/separation device requires the supporting biomimetic matrix to be virtually impermeable to anything but water or the solute in question. In practice, however, a biomimetic support matrix....../separation technology, a unique class of membrane transport proteins is especially interesting the major intrinsic proteins (MIPs). Generally, MIPs conduct water molecules and selected solutes in and out of the cell while preventing the passage of other solutes, a property critical for the conservation of the cells...... internal pH and salt concentration. Also known as water channels or aquaporins they are highly efficient membrane pore proteins some of which are capable of transporting water at very high rates up to 109 molecules per second. Some MIPs transport other small, uncharged solutes, such as glycerol and other...

A simple rescue maneuver for unfolding and centering a tightly rolled graft in Descemet membrane endothelial keratoplasty

Directory of Open Access Journals (Sweden)

Droutsas K

2014-10-01

Full Text Available Konstantinos Droutsas,1,2 Thomas Bertelmann,1 Frank M Schroeder,1 Dimitrios Papaconstantinou,2 Walter Sekundo1 1Department of Ophthalmology, Philipps University, Marburg, Germany; 2First Department of Ophthalmology, University of Athens, Medical School of Athens, Athens, Greece Abstract: A 74-year-old man underwent Descemet membrane endothelial keratoplasty (DMEK for endothelial decompensation due to Fuchs endothelial dystrophy. After descemetorhexis, the DMEK graft was inserted into the anterior chamber. However, unfolding of the graft was not possible as the graft was very tightly rolled together and the anterior chamber deep. After placing a 30G-cannula connected to an air-filled syringe inside the roll's lumen, a small air bubble was injected, which allowed the roll to open up, until it assumed a “taco” configuration around the bubble. Then, the graft was centered by pressing the posterior part of the roll against, and sweeping it over the iris. In the present case a “tight” DMEK roll was successfully unfolded by injection of a single air bubble into the roll’s lumen and centered by a “sweeping” the partialy unfolded graft over the iris. This technique allowed a controlled unfolding and centering of the DMEK graft with limited trauma to the donor endothelium and may be applied in cases where other less traumatic maneuvers are not successful. Keywords: Fuchs endothelial dystrophy, surgical technique, endothelial keratoplasty

Warhead verification as inverse problem: Applications of neutron spectrum unfolding from organic-scintillator measurements

Science.gov (United States)

Lawrence, Chris C.; Febbraro, Michael; Flaska, Marek; Pozzi, Sara A.; Becchetti, F. D.

2016-08-01

Verification of future warhead-dismantlement treaties will require detection of certain warhead attributes without the disclosure of sensitive design information, and this presents an unusual measurement challenge. Neutron spectroscopy—commonly eschewed as an ill-posed inverse problem—may hold special advantages for warhead verification by virtue of its insensitivity to certain neutron-source parameters like plutonium isotopics. In this article, we investigate the usefulness of unfolded neutron spectra obtained from organic-scintillator data for verifying a particular treaty-relevant warhead attribute: the presence of high-explosive and neutron-reflecting materials. Toward this end, several improvements on current unfolding capabilities are demonstrated: deuterated detectors are shown to have superior response-matrix condition to that of standard hydrogen-base scintintillators; a novel data-discretization scheme is proposed which removes important detector nonlinearities; and a technique is described for re-parameterizing the unfolding problem in order to constrain the parameter space of solutions sought, sidestepping the inverse problem altogether. These improvements are demonstrated with trial measurements and verified using accelerator-based time-of-flight calculation of reference spectra. Then, a demonstration is presented in which the elemental compositions of low-Z neutron-attenuating materials are estimated to within 10%. These techniques could have direct application in verifying the presence of high-explosive materials in a neutron-emitting test item, as well as other for treaty verification challenges.

Uncertainties related to numerical methods for neutron spectra unfolding

International Nuclear Information System (INIS)

Glodic, S.; Ninkovic, M.; Adarougi, N.A.

1987-10-01

One of the often used techniques for neutron detection in radiation protection utilities is the Bonner multisphere spectrometer. Besides its advantages and universal applicability for evaluating integral parameters of neutron fields in health physics practices, the outstanding problems of the method are data analysis and the accuracy of the results. This paper briefly discusses some numerical problems related to neutron spectra unfolding, such as uncertainty of the response matrix as a source of error, and the possibility of real time data reduction using spectrometers. (author)

Intrinsic magnetism and spontaneous band gap opening in bilayer silicene and germanene.

Science.gov (United States)

Wang, Xinquan; Wu, Zhigang

2017-01-18

It has been long sought to create magnetism out of simple non-magnetic materials, such as silicon and germanium. Here we show that intrinsic magnetism exists in bilayer silicene and germanene with no need to cut, etch, or dope. Unlike bilayer graphene, strong covalent interlayer bonding formed in bilayer silicene and germanene breaks the original π-bonding network of each layer, leaving the unbonded electrons unpaired and localized to carry magnetic moments. These magnetic moments then couple ferromagnetically within each layer while antiferromagnetically across two layers, giving rise to an infinite magnetic sheet with structural integrity and magnetic homogeneity. Furthermore, this unique magnetic ordering results in fundamental band gaps of 0.55 eV and 0.32 eV for bilayer silicene and germanene, respectively. The integration of intrinsic magnetism and spontaneous band gap opening makes bilayer silicene and germanene attractive for future nanoelectronics as well as spin-based computation and data storage.

Inactivation and unfolding of protein tyrosine phosphatase from Thermus thermophilus HB27 during urea and guanidine hydrochloride denaturation.

Directory of Open Access Journals (Sweden)

Yejing Wang

Full Text Available The effects of urea and guanidine hydrochloride (GdnHCl on the activity, conformation and unfolding process of protein tyrosine phosphatase (PTPase, a thermostable low molecular weight protein from Thermus thermophilus HB27, have been studied. Enzymatic activity assays showed both urea and GdnHCl resulted in the inactivation of PTPase in a concentration and time-dependent manner. Inactivation kinetics analysis suggested that the inactivation of PTPase induced by urea and GdnHCl were both monophasic and reversible processes, and the effects of urea and GdnHCl on PTPase were similar to that of mixed-type reversible inhibitors. Far-ultraviolet (UV circular dichroism (CD, Tryptophan and 1-anilinonaphthalene -8-sulfonic acid (ANS fluorescence spectral analyses indicated the existence of a partially active and an inactive molten globule-like intermediate during the unfolding processes induced by urea and GdnHCl, respectively. Based on the sequence alignment and the homolog Tt1001 protein structure, we discussed the possible conformational transitions of PTPase induced by urea and GdnHCl and compared the conformations of these unfolding intermediates with the transient states in bovine PTPase and its complex structures in detail. Our results may be able to provide some valuable clues to reveal the relationship between the structure and enzymatic activity, and the unfolding pathway and mechanism of PTPase.

Unfolding of hemoglobin variants--insights from urea gradient gel electrophoresis photon correlation spectroscopy and zeta potential measurements

Energy Technology Data Exchange (ETDEWEB)

Bhattacharya, Jaydeep; GhoshMoulick, Ranjita; Choudhuri, Utpal; Chakrabarty, Prantar; Bhattacharya, Pranab K.; Lahiri, Prabir; Chakraborti, Bikas; Dasgupta, Anjan Kr

2004-09-27

The unfolding pattern of crystal human hemoglobin and variants of hemoglobin obtained from hemolysate were studied using transverse urea gradient gel electrophoresis (TUGGE). A smooth sigmoid like increase of electrophoretic mobility was observed with increasing urea concentrations. A decrease in electrophoretic mobility resulted, if the protein was unfolded with guanidium hydrochloride (GdnHCl). The anomaly was resolved after the Stoke's radii (obtained using the photon correlation spectroscopy) and zeta potential (measured using laser Doppler velocimetry) measurements were made at different denaturant concentrations. Addition of denaturant led to formation of extended structure, irrespective of the nature of the denaturant, as indicated by increase in Stoke's radii in both cases (urea and GdnHCl). The unexpected increase in electrophoretic mobility in case of urea could be explained in terms of a critical redistribution of negative charge at intermediate stages of the unfolding process. In case of GdnHCl, the higher ionic strength masked the charge effect. The mobility, being solely dependent on size, decreased at higher denaturant concentration. Incidentally, folding loci of other hemoglobin variants (e.g. HbE) or that of post-translationally modified hemoglobin (e.g. HbA1c) could be determined by studying the charge distribution and hydrodynamic radius at varying denaturing stress and in each case the gel migration profile could be approximately scaled by the ratio of charge and hydrodynamic diameter of the protein. While unfolding induced charge effect was most pronounced in HbA0 (and crystal ferrous hemoglobin), the unfolding induced aggregation (manifested by the increase in Stoke's radii) was predominantly observed in the variant forms HbE and HbA1c. Representing the proteins by a plot, in which charge and hydrodynamic diameter are on independent axes, may be a useful way of characterizing protein variants having similar migration profiles on

Induction of the unfolded protein response by constitutive G-protein signaling in rod photoreceptor cells.

Science.gov (United States)

Wang, Tian; Chen, Jeannie

2014-10-17

Phototransduction is a G-protein signal transduction cascade that converts photon absorption to a change in current at the plasma membrane. Certain genetic mutations affecting the proteins in the phototransduction cascade cause blinding disorders in humans. Some of these mutations serve as a genetic source of "equivalent light" that activates the cascade, whereas other mutations lead to amplification of the light response. How constitutive phototransduction causes photoreceptor cell death is poorly understood. We showed that persistent G-protein signaling, which occurs in rod arrestin and rhodopsin kinase knock-out mice, caused a rapid and specific induction of the PERK pathway of the unfolded protein response. These changes were not observed in the cGMP-gated channel knock-out rods, an equivalent light condition that mimics light-stimulated channel closure. Thus transducin signaling, but not channel closure, triggers rapid cell death in light damage caused by constitutive phototransduction. Additionally, we show that in the albino light damage model cell death was not associated with increase in global protein ubiquitination or unfolded protein response induction. Taken together, these observations provide novel mechanistic insights into the cell death pathway caused by constitutive phototransduction and identify the unfolded protein response as a potential target for therapeutic intervention. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantifying the topography of the intrinsic energy landscape of flexible biomolecular recognition

Science.gov (United States)

Chu, Xiakun; Gan, Linfeng; Wang, Erkang; Wang, Jin

2013-01-01

Biomolecular functions are determined by their interactions with other molecules. Biomolecular recognition is often flexible and associated with large conformational changes involving both binding and folding. However, the global and physical understanding for the process is still challenging. Here, we quantified the intrinsic energy landscapes of flexible biomolecular recognition in terms of binding–folding dynamics for 15 homodimers by exploring the underlying density of states, using a structure-based model both with and without considering energetic roughness. By quantifying three individual effective intrinsic energy landscapes (one for interfacial binding, two for monomeric folding), the association mechanisms for flexible recognition of 15 homodimers can be classified into two-state cooperative “coupled binding–folding” and three-state noncooperative “folding prior to binding” scenarios. We found that the association mechanism of flexible biomolecular recognition relies on the interplay between the underlying effective intrinsic binding and folding energy landscapes. By quantifying the whole global intrinsic binding–folding energy landscapes, we found strong correlations between the landscape topography measure Λ (dimensionless ratio of energy gap versus roughness modulated by the configurational entropy) and the ratio of the thermodynamic stable temperature versus trapping temperature, as well as between Λ and binding kinetics. Therefore, the global energy landscape topography determines the binding–folding thermodynamics and kinetics, crucial for the feasibility and efficiency of realizing biomolecular function. We also found “U-shape” temperature-dependent kinetic behavior and a dynamical cross-over temperature for dividing exponential and nonexponential kinetics for two-state homodimers. Our study provides a unique way to bridge the gap between theory and experiments. PMID:23754431

Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

Science.gov (United States)

Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

2013-06-14

The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

Characterization and error analysis of an N×N unfolding procedure applied to filtered, photoelectric x-ray detector arrays. I. Formulation and testing

Science.gov (United States)

Fehl, D. L.; Chandler, G. A.; Stygar, W. A.; Olson, R. E.; Ruiz, C. L.; Hohlfelder, J. J.; Mix, L. P.; Biggs, F.; Berninger, M.; Frederickson, P. O.; Frederickson, R.

2010-12-01

An algorithm for spectral reconstructions (unfolds) and spectrally integrated flux estimates from data obtained by a five-channel, filtered x-ray-detector array (XRD) is described in detail and characterized. This diagnostic is a broad-channel spectrometer, used primarily to measure time-dependent soft x-ray flux emitted by z-pinch plasmas at the Z pulsed-power accelerator (Sandia National Laboratories, Albuquerque, New Mexico, USA), and serves as both a plasma probe and a gauge of accelerator performance. The unfold method, suitable for online analysis, arises naturally from general assumptions about the x-ray source and spectral properties of the channel responses; a priori constraints control the ill-posed nature of the inversion. The unfolded spectrum is not assumed to be Planckian. This study is divided into two consecutive papers. This paper considers three major issues: (a) Formulation of the unfold method.—The mathematical background, assumptions, and procedures leading to the algorithm are described: the spectral reconstruction Sunfold(E,t)—five histogram x-ray bins j over the x-ray interval, 137≤E≤2300eV at each time step t—depends on the shape and overlap of the calibrated channel responses and on the maximum electrical power delivered to the plasma. The x-ray flux Funfold is estimated as ∫Sunfold(E,t)dE. (b) Validation with simulations.—Tests of the unfold algorithm with known static and time-varying spectra are described. These spectra included—but were not limited to—Planckian spectra Sbb(E,T) (25≤T≤250eV), from which noise-free channel data were simulated and unfolded. For Planckian simulations with 125≤T≤250eV and typical responses, the binwise unfold values Sj and the corresponding binwise averages ⟨Sbb⟩j agreed to ˜20%, except where Sbb≪max⁡{Sbb}. Occasionally, unfold values Sj≲0 (artifacts) were encountered. The algorithm recovered ≳90% of the x-ray flux over the wider range, 75≤T≤250eV. For lower T, the

Intrinsic Orbital Angular Momentum States of Neutrons

Science.gov (United States)

Cappelletti, Ronald L.; Jach, Terrence; Vinson, John

2018-03-01

It has been shown that single-particle wave functions, of both photons and electrons, can be created with a phase vortex, i.e., an intrinsic orbital angular momentum (OAM). A recent experiment has claimed similar success using neutrons [C. W. Clark et al., Nature, 525, 504 (2015), 10.1038/nature15265]. We show that their results are insufficient to unambiguously demonstrate OAM, and they can be fully explained as phase contrast interference patterns. Furthermore, given the small transverse coherence length of the neutrons in the original experiment, the probability that any neutron was placed in an OAM state is vanishingly small. We highlight the importance of the relative size of the coherence length, which presents a unique challenge for neutron experiments compared to electron or photon work, and we suggest improvements for the creation of neutron OAM states.

Neutron spectrum unfolding using computer code SAIPS

International Nuclear Information System (INIS)

Karim, S.

1999-01-01

The main objective of this project was to study the neutron energy spectrum at rabbit station-1 in Pakistan Research Reactor (PARR-I). To do so, multiple foils activation method was used to get the saturated activities. The computer code SAIPS was used to unfold the neutron spectra from the measured reaction rates. Of the three built in codes in SAIPS, only SANDI and WINDOWS were used. Contribution of thermal part of the spectra was observed to be higher than the fast one. It was found that the WINDOWS gave smooth spectra while SANDII spectra have violet oscillations in the resonance region. The uncertainties in the WINDOWS results are higher than those of SANDII. The results show reasonable agreement with the published results. (author)

Digital force-feedback for protein unfolding experiments using atomic force microscopy

Science.gov (United States)

Bippes, Christian A.; Janovjak, Harald; Kedrov, Alexej; Muller, Daniel J.

2007-01-01

Since its invention in the 1990s single-molecule force spectroscopy has been increasingly applied to study protein (un-)folding, cell adhesion, and ligand-receptor interactions. In most force spectroscopy studies, the cantilever of an atomic force microscope (AFM) is separated from a surface at a constant velocity, thus applying an increasing force to folded bio-molecules or bio-molecular bonds. Recently, Fernandez and co-workers introduced the so-called force-clamp technique. Single proteins were subjected to a defined constant force allowing their life times and life time distributions to be directly measured. Up to now, the force-clamping was performed by analogue PID controllers, which require complex additional hardware and might make it difficult to combine the force-feedback with other modes such as constant velocity. These points may be limiting the applicability and versatility of this technique. Here we present a simple, fast, and all-digital (software-based) PID controller that yields response times of a few milliseconds in combination with a commercial AFM. We demonstrate the performance of our feedback loop by force-clamp unfolding of single Ig27 domains of titin and the membrane proteins bacteriorhodopsin (BR) and the sodium/proton antiporter NhaA.

Methods for monitoring endoplasmic reticulum stress and the unfolded protein response.

LENUS (Irish Health Repository)

Samali, Afshin

2010-01-01

The endoplasmic reticulum (ER) is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR). The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. We would like to emphasize that no individual assay is guaranteed to be the most appropriate one in every situation and strongly recommend the use of multiple assays to verify UPR activation.

Digital force-feedback for protein unfolding experiments using atomic force microscopy

International Nuclear Information System (INIS)

Bippes, Christian A; Janovjak, Harald; Kedrov, Alexej; Muller, Daniel J

2007-01-01

Since its invention in the 1990s single-molecule force spectroscopy has been increasingly applied to study protein (un-)folding, cell adhesion, and ligand-receptor interactions. In most force spectroscopy studies, the cantilever of an atomic force microscope (AFM) is separated from a surface at a constant velocity, thus applying an increasing force to folded bio-molecules or bio-molecular bonds. Recently, Fernandez and co-workers introduced the so-called force-clamp technique. Single proteins were subjected to a defined constant force allowing their life times and life time distributions to be directly measured. Up to now, the force-clamping was performed by analogue PID controllers, which require complex additional hardware and might make it difficult to combine the force-feedback with other modes such as constant velocity. These points may be limiting the applicability and versatility of this technique. Here we present a simple, fast, and all-digital (software-based) PID controller that yields response times of a few milliseconds in combination with a commercial AFM. We demonstrate the performance of our feedback loop by force-clamp unfolding of single Ig27 domains of titin and the membrane proteins bacteriorhodopsin (BR) and the sodium/proton antiporter NhaA

Methods for Monitoring Endoplasmic Reticulum Stress and the Unfolded Protein Response

Directory of Open Access Journals (Sweden)

Afshin Samali

2010-01-01

Full Text Available The endoplasmic reticulum (ER is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR. The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. We would like to emphasize that no individual assay is guaranteed to be the most appropriate one in every situation and strongly recommend the use of multiple assays to verify UPR activation.

Thick-foils activation technique for neutron spectrum unfolding with the MINUIT routine-Comparison with GEANT4 simulations

Science.gov (United States)

Vagena, E.; Theodorou, K.; Stoulos, S.

2018-04-01

Neutron activation technique has been applied using a proposed set of twelve thick metal foils (Au, As, Cd, In, Ir, Er, Mn, Ni, Se, Sm, W, Zn) for off-site measurements to obtain the neutron spectrum over a wide energy range (from thermal up to a few MeV) in intense neutron-gamma mixed fields such as around medical Linacs. The unfolding procedure takes into account the activation rates measured using thirteen (n , γ) and two (n , p) reactions without imposing a guess solution-spectrum. The MINUIT minimization routine unfolds a neutron spectrum that is dominated by fast neutrons (70%) peaking at 0.3 MeV, while the thermal peak corresponds to the 15% of the total neutron fluence equal to the epithermal-resonances area. The comparison of the unfolded neutron spectrum against the simulated one with the GEANT4 Monte-Carlo code shows a reasonable agreement within the measurement uncertainties. Therefore, the proposed set of activation thick-foils could be a useful tool in order to determine low flux neutrons spectrum in intense mixed field.

Intrinsic Chevrolets at the SSC

International Nuclear Information System (INIS)

Brodsky, S.J.; Collins, J.C.; Ellis, S.D.; Gunion, J.F.; Mueller, A.H.

1984-01-01

The possibility of the production at high energy of heavy quarks, supersymmetric particles and other large mass colored systems via the intrinsic twist-six components in the proton wave function is discussed. While the existing data do not rule out the possible relevance of intrinsic charm production at present energies, the extrapolation of such intrinsic contributions to very high masses and energies suggests that they will not play an important role at the SSC

The Effect of Intrinsic Motivation on the Affect and Evaluation of the Creative Process among Fine Arts Students

Science.gov (United States)

Stanko-Kaczmarek, Maja

2012-01-01

The main aim of this study was to gain a deeper understanding of the effect of intrinsic motivation on affect, subjective evaluation, and the creative process of young artists. Relations between motivation, affect, and evaluation were treated as a dynamic process and measured several times. The unique contribution of this study is that it…

Unfolding education for sustainable development as didactic thinking and practice

DEFF Research Database (Denmark)

Madsen, Katrine Dahl

2013-01-01

This article’s primary objective is to unfold how teachers translate education for sustainable development (ESD) in a school context. The article argues that exploring tensions, ruptures and openings apparent in this meeting is crucial for the development of existing teaching practices in relatio...... the analytical foundation; thus it is the practices as seen from the ‘inside’. Furthermore, ESD practices are considered in a broader societal perspective, pointing to the critical power of the practice lens....

STRUCTURAL ANALYSIS, GEOMETRY AND STATICS OF A COACH UNFOLDING MECHANISM

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Ovidiu ANTONESCU

2016-05-01

Full Text Available Starting from the constructive scheme of the mechanism, the kinematic scheme is drawn in three distinct positions (folded, middle and unfolded. By means of this scheme the mobility of the mechanism is calculated and the structural-topological formula of it is obtained. In the last section of the paper an algorithm of geometric calculus has been elaborated, starting from a kinematic link articulated to the base, element which is considered the driving component.

The Role of E27-K31 and E56-K10 Salt-Bridge Pairs in the Unfolding Mechanism of the B1 Domain of Protein G

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Tony Ibnu Sumaryada

2018-02-01

Full Text Available Molecular dynamics simulations of the B1 fragment of protein G (56 residues have been performed at 325, 350, 375, 400, 450 and 500 K for 10 ns. An analysis of its structural and energetic parameters has indicated that the unfolding process of the GB1 protein begins at 900 ps of a 500-K simulation. The unfolding process is initiated when hydrogen bonds in the hydrophobic core region are broken; it continues with the α-helix transformation into coils and turns and ends with the destruction of the β-hairpins. These unfolding events are consistent with the hybrid model of the protein folding/unfolding mechanism, which is a compromise between the hydrophobic core collapse model and the zipper model. Salt-bridge pairs were found to play an important role in the unfolding process by maintaining the integrity of the tertiary structure of the protein. The breaking (or disappearance of the salt-bridge pairs E27–K31 (in the α-helix and E56–K10 (connecting β4 and β1 has resulted in the destruction of secondary structures and indicates the beginning of the unfolding process. Our results also suggest that the unfolding process in this simulation was not a complete denaturation of the protein because some β-hairpins remained

Intrinsic work function of molecular films

International Nuclear Information System (INIS)

Ivančo, Ján

2012-01-01

The electronic properties of molecular films are analysed with the consideration of the molecular orientation. The study demonstrates that surfaces of electroactive oligomeric molecular films can be classified—analogously to the elemental surfaces—by their intrinsic work functions. The intrinsic work function of molecular films is correlated with their ionisation energies; again, the behaviour is analogous to the correlation existing between the first ionisation energy of elements and the work function of the corresponding elemental surfaces. The proposed intrinsic work-function concept suggests that the mechanism for the energy-level alignment at the interfaces associated with molecular films is virtually controlled by work functions of materials brought into the contact. - Highlights: ► Molecular films exhibit their own (intrinsic) work function. ► Intrinsic work function is correlated with ionisation energy of molecular films. ► Intrinsic work function determines dipole at interface with a particular surface. ► Surface vacuum-level change upon film growth does not relate to interfacial dipole.

Solvent-Exposed Salt Bridges Influence the Kinetics of α-Helix Folding and Unfolding.

Science.gov (United States)

Meuzelaar, Heleen; Tros, Martijn; Huerta-Viga, Adriana; van Dijk, Chris N; Vreede, Jocelyne; Woutersen, Sander

2014-03-06

Salt bridges are known to play an essential role in the thermodynamic stability of the folded conformation of many proteins, but their influence on the kinetics of folding remains largely unknown. Here, we investigate the effect of Glu-Arg salt bridges on the kinetics of α-helix folding using temperature-jump transient-infrared spectroscopy and steady-state UV circular dichroism. We find that geometrically optimized salt bridges (Glu - and Arg + are spaced four peptide units apart, and the Glu/Arg order is such that the side-chain rotameric preferences favor salt-bridge formation) significantly speed up folding and slow down unfolding, whereas salt bridges with unfavorable geometry slow down folding and slightly speed up unfolding. Our observations suggest a possible explanation for the surprising fact that many biologically active proteins contain salt bridges that do not stabilize the native conformation: these salt bridges might have a kinetic rather than a thermodynamic function.

On the unfolding of the fundamental region in integrals of modular invariant amplitudes

International Nuclear Information System (INIS)

Trapletti, Michele

2003-01-01

We study generic one-loop (string) amplitudes where an integration over the fundamental region F of the modular group is needed. We show how the known lattice-reduction technique used to unfold F to a more suitable region S can be modified to rearrange generic modular invariant amplitudes. The main aim is to unfold F to the strip and, at the same time, to simplify the form of the integrand when it is a sum over a finite number of terms, like in one-loop amplitudes for closed strings compactified on orbifolds. We give a general formula and a recipe to compute modular invariant amplitudes. As an application of the technique we compute the one-loop vacuum energy ρ n for a generic Z n freely acting orbifold, generalizing the result that this energy is less than zero and drives the system to a tachyonic divergence, and that ρ n m if n>m. (author)

Intrinsically Disordered Proteins in a Physics-Based World

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Jianhan Chen

2010-12-01

Full Text Available Intrinsically disordered proteins (IDPs are a newly recognized class of functional proteins that rely on a lack of stable structure for function. They are highly prevalent in biology, play fundamental roles, and are extensively involved in human diseases. For signaling and regulation, IDPs often fold into stable structures upon binding to specific targets. The mechanisms of these coupled binding and folding processes are of significant importance because they underlie the organization of regulatory networks that dictate various aspects of cellular decision-making. This review first discusses the challenge in detailed experimental characterization of these heterogeneous and dynamics proteins and the unique and exciting opportunity for physics-based modeling to make crucial contributions, and then summarizes key lessons from recent de novo simulations of the structure and interactions of several regulatory IDPs.

Lactococcus lactis, an alternative system for functional expression of peripheral and intrinsic Arabidopsis membrane proteins.

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Annie Frelet-Barrand

Full Text Available BACKGROUND: Despite their functional and biotechnological importance, the study of membrane proteins remains difficult due to their hydrophobicity and their low natural abundance in cells. Furthermore, into established heterologous systems, these proteins are frequently only produced at very low levels, toxic and mis- or unfolded. Lactococcus lactis, a gram-positive lactic bacterium, has been traditionally used in food fermentations. This expression system is also widely used in biotechnology for large-scale production of heterologous proteins. Various expression vectors, based either on constitutive or inducible promoters, are available for this system. While previously used to produce bacterial and eukaryotic membrane proteins, the ability of this system to produce plant membrane proteins was until now not tested. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work was to test the expression, in Lactococcus lactis, of either peripheral or intrinsic Arabidopsis membrane proteins that could not be produced, or in too low amount, using more classical heterologous expression systems. In an effort to easily transfer genes from Gateway-based Arabidopsis cDNA libraries to the L. lactis expression vector pNZ8148, we first established a cloning strategy compatible with Gateway entry vectors. Interestingly, the six tested Arabidopsis membrane proteins could be produced, in Lactococcus lactis, at levels compatible with further biochemical analyses. We then successfully developed solubilization and purification processes for three of these proteins. Finally, we questioned the functionality of a peripheral and an intrinsic membrane protein, and demonstrated that both proteins were active when produced in this system. CONCLUSIONS/SIGNIFICANCE: Altogether, these data suggest that Lactococcus lactis might be an attractive system for the efficient and functional production of difficult plant membrane proteins.

Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

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Jody Groenendyk

Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins.

Science.gov (United States)

Uversky, Vladimir N

2016-03-25

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Symmetries of collective models in intrinsic frame

International Nuclear Information System (INIS)

Gozdz, A.; Pedrak, A.; Szulerecka, A.; Dobrowolski, A.; Dudek, J.

2013-01-01

In the paper a very general definition of intrinsic frame, by means of group theoretical methods, is introduced. It allows to analyze nuclear properties which are invariant in respect to the group which defines the intrinsic frame. For example, nuclear shape is a well determined feature in the intrinsic frame defined by the Euclidean group. It is shown that using of intrinsic frame gives an opportunity to consider intrinsic nuclear symmetries which are independent of symmetries observed in the laboratory frame. An importance of the notion of partial symmetries is emphasized. (author)

Evaluating the performance of two neutron spectrum unfolding codes based on iterative procedures and artificial neural networks

International Nuclear Information System (INIS)

Ortiz-Rodríguez, J. M.; Reyes Alfaro, A.; Reyes Haro, A.; Solís Sánches, L. O.; Miranda, R. Castañeda; Cervantes Viramontes, J. M.; Vega-Carrillo, H. R.

2013-01-01

In this work the performance of two neutron spectrum unfolding codes based on iterative procedures and artificial neural networks is evaluated. The first one code based on traditional iterative procedures and called Neutron spectrometry and dosimetry from the Universidad Autonoma de Zacatecas (NSDUAZ) use the SPUNIT iterative algorithm and was designed to unfold neutron spectrum and calculate 15 dosimetric quantities and 7 IAEA survey meters. The main feature of this code is the automated selection of the initial guess spectrum trough a compendium of neutron spectrum compiled by the IAEA. The second one code known as Neutron spectrometry and dosimetry with artificial neural networks (NDSann) is a code designed using neural nets technology. The artificial intelligence approach of neural net does not solve mathematical equations. By using the knowledge stored at synaptic weights on a neural net properly trained, the code is capable to unfold neutron spectrum and to simultaneously calculate 15 dosimetric quantities, needing as entrance data, only the rate counts measured with a Bonner spheres system. Similarities of both NSDUAZ and NSDann codes are: they follow the same easy and intuitive user's philosophy and were designed in a graphical interface under the LabVIEW programming environment. Both codes unfold the neutron spectrum expressed in 60 energy bins, calculate 15 dosimetric quantities and generate a full report in HTML format. Differences of these codes are: NSDUAZ code was designed using classical iterative approaches and needs an initial guess spectrum in order to initiate the iterative procedure. In NSDUAZ, a programming routine was designed to calculate 7 IAEA instrument survey meters using the fluence-dose conversion coefficients. NSDann code use artificial neural networks for solving the ill-conditioned equation system of neutron spectrometry problem through synaptic weights of a properly trained neural network. Contrary to iterative procedures, in neural

Evaluating the performance of two neutron spectrum unfolding codes based on iterative procedures and artificial neural networks

Science.gov (United States)

Ortiz-Rodríguez, J. M.; Reyes Alfaro, A.; Reyes Haro, A.; Solís Sánches, L. O.; Miranda, R. Castañeda; Cervantes Viramontes, J. M.; Vega-Carrillo, H. R.

2013-07-01

In this work the performance of two neutron spectrum unfolding codes based on iterative procedures and artificial neural networks is evaluated. The first one code based on traditional iterative procedures and called Neutron spectrometry and dosimetry from the Universidad Autonoma de Zacatecas (NSDUAZ) use the SPUNIT iterative algorithm and was designed to unfold neutron spectrum and calculate 15 dosimetric quantities and 7 IAEA survey meters. The main feature of this code is the automated selection of the initial guess spectrum trough a compendium of neutron spectrum compiled by the IAEA. The second one code known as Neutron spectrometry and dosimetry with artificial neural networks (NDSann) is a code designed using neural nets technology. The artificial intelligence approach of neural net does not solve mathematical equations. By using the knowledge stored at synaptic weights on a neural net properly trained, the code is capable to unfold neutron spectrum and to simultaneously calculate 15 dosimetric quantities, needing as entrance data, only the rate counts measured with a Bonner spheres system. Similarities of both NSDUAZ and NSDann codes are: they follow the same easy and intuitive user's philosophy and were designed in a graphical interface under the LabVIEW programming environment. Both codes unfold the neutron spectrum expressed in 60 energy bins, calculate 15 dosimetric quantities and generate a full report in HTML format. Differences of these codes are: NSDUAZ code was designed using classical iterative approaches and needs an initial guess spectrum in order to initiate the iterative procedure. In NSDUAZ, a programming routine was designed to calculate 7 IAEA instrument survey meters using the fluence-dose conversion coefficients. NSDann code use artificial neural networks for solving the ill-conditioned equation system of neutron spectrometry problem through synaptic weights of a properly trained neural network. Contrary to iterative procedures, in neural

Evaluating the performance of two neutron spectrum unfolding codes based on iterative procedures and artificial neural networks

Energy Technology Data Exchange (ETDEWEB)

Ortiz-Rodriguez, J. M.; Reyes Alfaro, A.; Reyes Haro, A.; Solis Sanches, L. O.; Miranda, R. Castaneda; Cervantes Viramontes, J. M. [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica. Av. Ramon Lopez Velarde 801. Col. Centro Zacatecas, Zac (Mexico); Vega-Carrillo, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica. Av. Ramon Lopez Velarde 801. Col. Centro Zacatecas, Zac., Mexico. and Unidad Academica de Estudios Nucleares. C. Cip (Mexico)

2013-07-03

In this work the performance of two neutron spectrum unfolding codes based on iterative procedures and artificial neural networks is evaluated. The first one code based on traditional iterative procedures and called Neutron spectrometry and dosimetry from the Universidad Autonoma de Zacatecas (NSDUAZ) use the SPUNIT iterative algorithm and was designed to unfold neutron spectrum and calculate 15 dosimetric quantities and 7 IAEA survey meters. The main feature of this code is the automated selection of the initial guess spectrum trough a compendium of neutron spectrum compiled by the IAEA. The second one code known as Neutron spectrometry and dosimetry with artificial neural networks (NDSann) is a code designed using neural nets technology. The artificial intelligence approach of neural net does not solve mathematical equations. By using the knowledge stored at synaptic weights on a neural net properly trained, the code is capable to unfold neutron spectrum and to simultaneously calculate 15 dosimetric quantities, needing as entrance data, only the rate counts measured with a Bonner spheres system. Similarities of both NSDUAZ and NSDann codes are: they follow the same easy and intuitive user's philosophy and were designed in a graphical interface under the LabVIEW programming environment. Both codes unfold the neutron spectrum expressed in 60 energy bins, calculate 15 dosimetric quantities and generate a full report in HTML format. Differences of these codes are: NSDUAZ code was designed using classical iterative approaches and needs an initial guess spectrum in order to initiate the iterative procedure. In NSDUAZ, a programming routine was designed to calculate 7 IAEA instrument survey meters using the fluence-dose conversion coefficients. NSDann code use artificial neural networks for solving the ill-conditioned equation system of neutron spectrometry problem through synaptic weights of a properly trained neural network. Contrary to iterative procedures, in

The effects of crowding agents Dextran-70k and PEG-8k on actin structure and unfolding reaction

Science.gov (United States)

Gagarskaia, Iuliia A.; Povarova, Olga I.; Uversky, Vladimir N.; Kuznetsova, Irina M.; Turoverov, Konstantin K.

2017-07-01

Recently, an increasing number of studies on proteins' structure, stability and folding are trying to bring the experimental conditions closer to those existing in a living cell, namely to the conditions of macromolecular crowding. In vitro such conditions are typically imitated by the ;inert; highly water-soluble polymers with different hydrodynamic dimensions. In this work, the effects of crowded milieu on the structure and conformational stability of actin, which is a key component of the muscle contraction system, was examined. The crowded milieu was simulated by high concentrations of PEG-8k or Dextran-70k. It was revealed that both crowding agents decelerated but not inhibited actin unfolding and made a compact state of inactivated actin thermodynamically more favorable in comparison with the unfolded state. At the same time, the high viscosity of the solution of crowding agents slowed down all processes and especially inactivated actin formation, since it involves the interaction of 14-16 partially unfolded actin molecules. The effects of crowding agent were larger when its hydrodynamic dimensions were closer to the size of globular actin.

Unfolding of neutron spectra from Godiva type critical assemblies

International Nuclear Information System (INIS)

Harvey, J.T.; Meason, J.L.; Wright, H.L.

1976-01-01

The results from three experiments conducted at the White Sands Missile Range Fast Burst Reactor Facility are discussed. The experiments were designed to measure the ''free-field'' neutron leakage spectrum and the neutron spectra from mildly perturbed environments. SAND-II was used to calculate the neutron spectrum utilizing several different trial input spectra for each experiment. Comparisons are made between the unfolded neutron spectrum for each trial input on the basis of the following parameters: average neutron energy (above 10 KeV), integral fluence (above 10 KeV), spectral index and the hardness parameter, phi/sub eq//phi

Unfolding neutron spectra from simulated response of thermoluminescence dosimeters inside a polyethylene sphere using GRNN neural network

Science.gov (United States)

Lotfalizadeh, F.; Faghihi, R.; Bahadorzadeh, B.; Sina, S.

2017-07-01

Neutron spectrometry using a single-sphere containing dosimeters has been developed recently, as an effective replacement for Bonner sphere spectrometry. The aim of this study is unfolding the neutron energy spectra using GRNN artificial neural network, from the response of thermoluminescence dosimeters, TLDs, located inside a polyethylene sphere. The spectrometer was simulated using MCNP5. TLD-600 and TLD-700 dosimeters were simulated at different positions in all directions. Then the GRNN was used for neutron spectra prediction, using the TLDs' readings. Comparison of spectra predicted by the network with the real spectra, show that the single-sphere dosimeter is an effective instrument in unfolding neutron spectra.

Conformational fluctuation dynamics of domain I of human serum albumin in the course of chemically and thermally induced unfolding using fluorescence correlation spectroscopy.

Science.gov (United States)

Yadav, Rajeev; Sengupta, Bhaswati; Sen, Pratik

2014-05-22

The present study elucidates the involvement of conformational fluctuation dynamics during chemically and thermally induced unfolding of human serum albumin (HSA) by fluorescence correlation spectroscopic (FCS) study, time-resolved fluorescence measurements, and circular dichroism (CD) spectroscopic methods. Two fluorescent probes, tetramethylrhodamine-5-maleimide (TMR) and N-(7-dimethylamino-4-methylcoumarin-3-yl) iodoacetamide (DACIA) were used to selectively label the domain I of HSA through the reaction with cys-34 for these studies. The guanidine hydrochloride (GnHCl) induced global structural change of HSA is monitored through its hydrodynamic radius (r(H)) and CD response, which is found to be two step in nature. In FCS experiment, along with the diffusion time component we have observed an exponential relaxation time component (τ(R)) that has been ascribed to the concerted chain dynamics of HSA. Unlike in the global structural change, we found that the τ(R) value changes in a different manner in the course of the unfolding. The dependence of τ(R) on the concentration of GnHCl was best fitted with a four state model, indicating the involvement of two intermediate states during the unfolding process, which were not observed through the CD response and r(H) data. The fluorescence lifetime measurement also supports our observation of intermediate states during the unfolding of HSA. However, no such intermediate states were observed during thermally induced unfolding of HSA.

Redox Thermodynamics of Cytochromes c Subjected to Urea Induced Unfolding

OpenAIRE

Monari, S.; Ranieri, A.; Di Rocco, G.; van der Zwan, G.; Peressini, S.; Tavagnacco, C.; Millo, D.; Borsari, M.

2009-01-01

The thermodynamics of the electron transfer (ET) process for beef heart and yeast cytochromes c and the Lys72Ala/Lys73Ala/Lys79Ala mutant of the latter species subjected to progressive urea-induced unfolding was determined electrochemically. The results indicate the presence of at least three protein forms which were assigned to a low-temperature and a high-temperature His-Met intermediate species and a bis-histidinate form (although the presence of a His-Lys form cannot be excluded). The muc...

Seeking Educational Quality in the Unfolding of Classroom Discourse: A Focus on Microtransitions

Science.gov (United States)

Mameli, Consuelo; Molinari, Luisa

2014-01-01

In this paper, we argue the importance of conceptualizing educational quality as located in everyday talk, and to search for it in the unfolding of classroom discourse and interactions. More specifically, we argue that for the discursive classroom process to be qualitatively effective it should be open and accessible by a series of…

Whole genome expression profiling associates activation of unfolded protein response with impaired production and release of epinephrine after recurrent hypoglycemia.

Directory of Open Access Journals (Sweden)

Juhye Lena Kim

Full Text Available Recurrent hypoglycemia can occur as a major complication of insulin replacement therapy, limiting the long-term health benefits of intense glycemic control in type 1 and advanced type 2 diabetic patients. It impairs the normal counter-regulatory hormonal and behavioral responses to glucose deprivation, a phenomenon known as hypoglycemia associated autonomic failure (HAAF. The molecular mechanisms leading to defective counter-regulation are not completely understood. We hypothesized that both neuronal (excessive cholinergic signaling between the splanchnic nerve fibers and the adrenal medulla and humoral factors contribute to the impaired epinephrine production and release in HAAF. To gain further insight into the molecular mechanism(s mediating the blunted epinephrine responses following recurrent hypoglycemia, we utilized a global gene expression profiling approach. We characterized the transcriptomes during recurrent (defective counter-regulation model and acute hypoglycemia (normal counter-regulation group in the adrenal medulla of normal Sprague-Dawley rats. Based on comparison analysis of differentially expressed genes, a set of unique genes that are activated only at specific time points after recurrent hypoglycemia were revealed. A complementary bioinformatics analysis of the functional category, pathway, and integrated network indicated activation of the unfolded protein response. Furthermore, at least three additional pathways/interaction networks altered in the adrenal medulla following recurrent hypoglycemia were identified, which may contribute to the impaired epinephrine secretion in HAAF: greatly increased neuropeptide signaling (proenkephalin, neuropeptide Y, galanin; altered ion homeostasis (Na+, K+, Ca2+ and downregulation of genes involved in Ca2+-dependent exocytosis of secretory vesicles. Given the pleiotropic effects of the unfolded protein response in different organs, involved in maintaining glucose homeostasis, these

A VHDL Core for Intrinsic Evolution of Discrete Time Filters with Signal Feedback

Science.gov (United States)

Gwaltney, David A.; Dutton, Kenneth

2005-01-01

The design of an Evolvable Machine VHDL Core is presented, representing a discrete-time processing structure capable of supporting control system applications. This VHDL Core is implemented in an FPGA and is interfaced with an evolutionary algorithm implemented in firmware on a Digital Signal Processor (DSP) to create an evolvable system platform. The salient features of this architecture are presented. The capability to implement IIR filter structures is presented along with the results of the intrinsic evolution of a filter. The robustness of the evolved filter design is tested and its unique characteristics are described.

Intrinsic Time Quantum Geometrodynamics

OpenAIRE

Ita III, Eyo Eyo; Soo, Chopin; Yu, Hoi-Lai

2015-01-01

Quantum Geometrodynamics with intrinsic time development and momentric variables is presented. An underlying SU(3) group structure at each spatial point regulates the theory. The intrinsic time behavior of the theory is analyzed, together with its ground state and primordial quantum fluctuations. Cotton-York potential dominates at early times when the universe was small; the ground state naturally resolves Penrose's Weyl Curvature Hypothesis, and thermodynamic and gravitational `arrows of tim...

Spectrum unfolding, sensitivity analysis and propagation of uncertainties with the maximum entropy deconvolution code MAXED

CERN Document Server

Reginatto, M; Neumann, S

2002-01-01

MAXED was developed to apply the maximum entropy principle to the unfolding of neutron spectrometric measurements. The approach followed in MAXED has several features that make it attractive: it permits inclusion of a priori information in a well-defined and mathematically consistent way, the algorithm used to derive the solution spectrum is not ad hoc (it can be justified on the basis of arguments that originate in information theory), and the solution spectrum is a non-negative function that can be written in closed form. This last feature permits the use of standard methods for the sensitivity analysis and propagation of uncertainties of MAXED solution spectra. We illustrate its use with unfoldings of NE 213 scintillation detector measurements of photon calibration spectra, and of multisphere neutron spectrometer measurements of cosmic-ray induced neutrons at high altitude (approx 20 km) in the atmosphere.

Mechanism of Protein Denaturation: Partial Unfolding of the P22 Coat Protein I-Domain by Urea Binding

Science.gov (United States)

Newcomer, Rebecca L.; Fraser, LaTasha C.R.; Teschke, Carolyn M.; Alexandrescu, Andrei T.

2015-01-01

The I-domain is an insertion domain of the bacteriophage P22 coat protein that drives rapid folding and accounts for over half of the stability of the full-length protein. We sought to determine the role of hydrogen bonds (H-bonds) in the unfolding of the I-domain by examining 3JNC’ couplings transmitted through H-bonds, the temperature and urea-concentration dependence of 1HN and 15N chemical shifts, and native-state hydrogen exchange at urea concentrations where the domain is predominantly folded. The native-state hydrogen-exchange data suggest that the six-stranded β-barrel core of the I-domain is more stable against unfolding than a smaller subdomain comprised of a short α-helix and three-stranded β-sheet. H-bonds, separately determined from solvent protection and 3JNC’ H-bond couplings, are identified with an accuracy of 90% by 1HN temperature coefficients. The accuracy is improved to 95% when 15N temperature coefficients are also included. In contrast, the urea dependence of 1HN and 15N chemical shifts is unrelated to H-bonding. The protein segments with the largest chemical-shift changes in the presence of urea show curved or sigmoidal titration curves suggestive of direct urea binding. Nuclear Overhauser effects to urea for these segments are also consistent with specific urea-binding sites in the I-domain. Taken together, the results support a mechanism of urea unfolding in which denaturant binds to distinct sites in the I-domain. Disordered segments bind urea more readily than regions in stable secondary structure. The locations of the putative urea-binding sites correlate with the lower stability of the structure against solvent exchange, suggesting that partial unfolding of the structure is related to urea accessibility. PMID:26682823

Botulinum neurotoxin: unique folding of enzyme domain of the most-poisonous poison.

Science.gov (United States)

Kumar, Raj; Kukreja, Roshan V; Li, Li; Zhmurov, Artem; Kononova, Olga; Cai, Shuowei; Ahmed, Syed A; Barsegov, Valeri; Singh, Bal Ram

2014-01-01

Botulinum neurotoxin (BoNT), the most toxic substance known to mankind, is the first example of the fully active molten globule state. To understand its folding mechanism, we performed urea denaturation experiments and theoretical modeling using BoNT serotype A (BoNT/A). We found that the extent of BoNT/A denaturation from the native state (N) shows a nonmonotonic dependence on urea concentration indicating a unique multistep denaturation process, N → I1 [Formula: see text] I2 [Formula: see text] U, with two intermediate states I1 and I2. BoNT/A loses almost all its secondary structure in 3.75 M urea (I1), yet it displays a native-like secondary structure in 5 M urea (I2). This agrees with the results of theoretical modeling, which helped to determine the molecular basis of unique behavior of BoNT/A in solution. Except for I2, all the states revert back to full enzymatic activity for SNAP-25 including the unfolded state U stable in 7 M urea. Our results stress the importance of structural flexibility in the toxin's mechanism of survival and action, an unmatched evolutionary trait from billion-year-old bacteria, which also correlates with the long-lasting enzymatic activity of BoNT inside neuronal cells. BoNT/A provides a rich model to explore protein folding in relation to functional activity.

Unfolding of Vortices into Topological Stripes in a Multiferroic Material

Science.gov (United States)

Wang, X.; Mostovoy, M.; Han, M. G.; Horibe, Y.; Aoki, T.; Zhu, Y.; Cheong, S.-W.

2014-06-01

Multiferroic hexagonal RMnO3 (R =rare earths) crystals exhibit dense networks of vortex lines at which six domain walls merge. While the domain walls can be readily moved with an applied electric field, the vortex cores so far have been impossible to control. Our experiments demonstrate that shear strain induces a Magnus-type force pulling vortices and antivortices in opposite directions and unfolding them into a topological stripe domain state. We discuss the analogy between this effect and the current-driven dynamics of vortices in superconductors and superfluids.

Use of new threshold detector 199Hg(n,n')/sup 199m/Hg for neutron spectrum unfolding

International Nuclear Information System (INIS)

Sakurai, K.

1982-01-01

The nuclear data for the 199 Hg(n,n')/sup 199m/Hg reaction are reviewed and the data are used for neutron spectrum unfolding. The neutron spectrum of the YAYOI glory-hole is unfolded by SAND II with 10 nuclear reactions including the 199 Hg(n,n')/sup 199m/Hg reaction. The ratio of the measured reaction rate to the calculated reaction rate is about 1:1.1 for the guess spectrum. The 199 Hg(n,n')/sup 199m/Hg, 115 In(n,n')/sup 115m/In, 103 Rh(n,n')/sup 103m/Rh reactions should be useful threshold detectors for the neutron dosimetry with low level fast neutron flux

The intrinsic resistome of bacterial pathogens.

Science.gov (United States)

Olivares, Jorge; Bernardini, Alejandra; Garcia-Leon, Guillermo; Corona, Fernando; B Sanchez, Maria; Martinez, Jose L

2013-01-01

Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

The intrinsic resistome of bacterial pathogens

Directory of Open Access Journals (Sweden)

Jorge Andrés Olivares Pacheco

2013-04-01

Full Text Available Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally a low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyse recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

Incentives and intrinsic motivation in healthcare.

Science.gov (United States)

Berdud, Mikel; Cabasés, Juan M; Nieto, Jorge

It has been established in the literature that workers within public organisations are intrinsically motivated. This paper is an empirical study of the healthcare sector using methods of qualitative analysis research, which aims to answer the following hypotheses: 1) doctors are intrinsically motivated; 2) economic incentives and control policies may undermine doctors' intrinsic motivation; and 3) well-designed incentives may encourage doctors' intrinsic motivation. We conducted semi-structured interviews à-la-Bewley with 16 doctors from Navarre's Healthcare Service (Servicio Navarro de Salud-Osasunbidea), Spain. The questions were based on current theories of intrinsic motivation and incentives to test the hypotheses. Interviewees were allowed to respond openly without time constraints. Relevant information was selected, quantified and analysed by using the qualitative concepts of saturation and codification. The results seem to confirm the hypotheses. Evidence supporting hypotheses 1 and 2 was gathered from all interviewees, as well as indications of the validity of hypothesis 3 based on interviewees' proposals of incentives. The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Evaluation of a new neutron energy spectrum unfolding code based on an Adaptive Neuro-Fuzzy Inference System (ANFIS).

Science.gov (United States)

Hosseini, Seyed Abolfazl; Esmaili Paeen Afrakoti, Iman

2018-01-17

The purpose of the present study was to reconstruct the energy spectrum of a poly-energetic neutron source using an algorithm developed based on an Adaptive Neuro-Fuzzy Inference System (ANFIS). ANFIS is a kind of artificial neural network based on the Takagi-Sugeno fuzzy inference system. The ANFIS algorithm uses the advantages of both fuzzy inference systems and artificial neural networks to improve the effectiveness of algorithms in various applications such as modeling, control and classification. The neutron pulse height distributions used as input data in the training procedure for the ANFIS algorithm were obtained from the simulations performed by MCNPX-ESUT computational code (MCNPX-Energy engineering of Sharif University of Technology). Taking into account the normalization condition of each energy spectrum, 4300 neutron energy spectra were generated randomly. (The value in each bin was generated randomly, and finally a normalization of each generated energy spectrum was performed). The randomly generated neutron energy spectra were considered as output data of the developed ANFIS computational code in the training step. To calculate the neutron energy spectrum using conventional methods, an inverse problem with an approximately singular response matrix (with the determinant of the matrix close to zero) should be solved. The solution of the inverse problem using the conventional methods unfold neutron energy spectrum with low accuracy. Application of the iterative algorithms in the solution of such a problem, or utilizing the intelligent algorithms (in which there is no need to solve the problem), is usually preferred for unfolding of the energy spectrum. Therefore, the main reason for development of intelligent algorithms like ANFIS for unfolding of neutron energy spectra is to avoid solving the inverse problem. In the present study, the unfolded neutron energy spectra of 252Cf and 241Am-9Be neutron sources using the developed computational code were

Structural properties of the intrinsically disordered, multiple calcium ion-binding otolith matrix macromolecule-64 (OMM-64).

Science.gov (United States)

Poznar, Monika; Hołubowicz, Rafał; Wojtas, Magdalena; Gapiński, Jacek; Banachowicz, Ewa; Patkowski, Adam; Ożyhar, Andrzej; Dobryszycki, Piotr

2017-11-01

Fish otoliths are calcium carbonate biominerals that are involved in hearing and balance sensing. An organic matrix plays a crucial role in their formation. Otolith matrix macromolecule-64 (OMM-64) is a highly acidic, calcium-binding protein (CBP) found in rainbow trout otoliths. It is a component of high-molecular-weight aggregates, which influence the size, shape and polymorph of calcium carbonate in vitro. In this study, a protocol for the efficient expression and purification of OMM-64 was developed. For the first time, the complete structural characteristics of OMM-64 were described. Various biophysical methods were combined to show that OMM-64 occurs as an intrinsically disordered monomer. Under denaturing conditions (pH, temperature) OMM-64 exhibits folding propensity. It was determined that OMM-64 binds approximately 61 calcium ions with millimolar affinity. The folding-unfolding experiments showed that calcium ions induced the collapse of OMM-64. The effect of other counter ions present in trout endolymph on OMM-64 conformational changes was studied. The significance of disordered properties of OMM-64 and the possible function of this protein is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The force-sensing device region of α-catenin is an intrinsically disordered segment in the absence of intramolecular stabilization of the autoinhibitory form.

Science.gov (United States)

Hirano, Yoshinori; Amano, Yu; Yonemura, Shigenobu; Hakoshima, Toshio

2018-05-01

Mechanotransduction by α-catenin facilitates the force-dependent development of adherens junctions (AJs) by recruiting vinculin to reinforce actin anchoring of AJs. The α-catenin mechanotransducing action is facilitated by its force-sensing device region that autoinhibits the vinculin-binding site 1 (VBS1). Here, we report the high-resolution structure of the force-sensing device region of α-catenin, which shows the autoinhibited form comprised of helix bundles E, F and G. The cryptic VBS1 is embedded into helix bundle E stabilized by direct interactions with the autoinhibitory region forming helix bundles F and G. Our molecular dissection study showed that helix bundles F and G are stable in solution in each isolated form, whereas helix bundle E that contains VBS1 is unstable and intrinsically disordered in solution in the isolated form. We successfully identified key residues mediating the autoinhibition and produced mutated α-catenins that display variable force sensitivity and autoinhibition. Using these mutants, we demonstrate both in vitro and in vivo that, in the absence of this stabilization, the helix bundle containing VBS1 would adopt an unfolded form, thus exposing VBS for vinculin binding. We provide evidence for importance of mechanotransduction with the intrinsic force sensitivity for vinculin recruitment to adherens junctions of epithelial cell sheets with mutated α-catenins. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

The Neuroscience of Growth Mindset and Intrinsic Motivation.

Science.gov (United States)

Ng, Betsy

2018-01-26

Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.

Influence of Neutron Spectra Unfolding Method on Fast Neutron Dose Determination

International Nuclear Information System (INIS)

Marinkovic, P.

1991-01-01

Full text: Accuracy of knowing the fast neutron spectra has great influence on equivalent dose determination. In usual fast neutron spectrum measurements with scintillation detectors based on proton recoil, the main difficulty is confidence of unfolding method. In former ones variance of obtained result is usually great and negative values are possible too, which does means that we don't now exactly is obtained neutron spectrum real one. The new unfolding method based on Shanon's information theory, which gives non-negative spectrum and relative low variance, is obtained and appropriate numerical code for application in fast neutron spectrometry based on proton recoil is realized. In this method principle of maximum entropy and maximum likelihood are used together. Unknown group density distribution functions, which are considered as desired normalized mean neutron group flux, are constl u cted using only constrain of knowing mean value. Obtained distributions are consistent to available information (counts in NCA from proton recoil), while being maximally noncommittal with respect to all other unknown circumstances. For maximum likelihood principle, distribution functions around mean value of counts in the channels of MCA are taken to be Gauss function shape. Optimal non-negative solution is searched by means of Lagrange parameter method. Nonlinear system of equations, is solved using gradient and Newton iterative algorithm. Error covariance matrix is obtained too. (author)

The impact of urea-induced unfolding on the redox process of immobilised cytochrome c

NARCIS (Netherlands)

Monari, S.; Millo, D.; Ranieri, A.; di Rocco, G.; van der Zwan, G.; Gooijer, C.; Peressini, S.; Tavagnacco, C.; Hildebrandt, P.; Borsari, M.

2010-01-01

We have studied the effect of urea-induced unfolding on the electron transfer process of yeast iso-1-cytochrome c and its mutant K72AK73AK79A adsorbed on electrodes coated by mixed 11-mercapto-1-undecanoic acid/11-mercapto-1-undecanol self-assembled monolayers. Electrochemical measurements,

Molecular origin of urea driven hydrophobic polymer collapse and unfolding depending on side chain chemistry.

Science.gov (United States)

Nayar, Divya; Folberth, Angelina; van der Vegt, Nico F A

2017-07-19

Osmolytes affect hydrophobic collapse and protein folding equilibria. The underlying mechanisms are, however, not well understood. We report large-scale conformational sampling of two hydrophobic polymers with secondary and tertiary amide side chains using extensive molecular dynamics simulations. The calculated free energy of unfolding increases with urea for the secondary amide, yet decreases for the tertiary amide, in agreement with experiment. The underlying mechanism is rooted in opposing entropic driving forces: while urea screens the hydrophobic macromolecular interface and drives unfolding of the tertiary amide, urea's concomitant loss in configurational entropy drives collapse of the secondary amide. Only at sufficiently high urea concentrations bivalent urea hydrogen bonding interactions with the secondary amide lead to further stabilisation of its collapsed state. The observations provide a new angle on the interplay between side chain chemistry, urea hydrogen bonding, and the role of urea in attenuating or strengthening the hydrophobic effect.

The Neuroscience of Growth Mindset and Intrinsic Motivation

Directory of Open Access Journals (Sweden)

Betsy Ng

2018-01-01

Full Text Available Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.

Beyond the evoked/intrinsic neural process dichotomy

Directory of Open Access Journals (Sweden)

Taylor Bolt

2018-03-01

Full Text Available Contemporary functional neuroimaging research has increasingly focused on characterization of intrinsic or “spontaneous” brain activity. Analysis of intrinsic activity is often contrasted with analysis of task-evoked activity that has traditionally been the focus of cognitive neuroscience. But does this evoked/intrinsic dichotomy adequately characterize human brain function? Based on empirical data demonstrating a close functional interdependence between intrinsic and task-evoked activity, we argue that the dichotomy between intrinsic and task-evoked activity as unobserved contributions to brain activity is artificial. We present an alternative picture of brain function in which the brain’s spatiotemporal dynamics do not consist of separable intrinsic and task-evoked components, but reflect the enaction of a system of mutual constraints to move the brain into and out of task-appropriate functional configurations. According to this alternative picture, cognitive neuroscientists are tasked with describing both the temporal trajectory of brain activity patterns across time, and the modulation of this trajectory by task states, without separating this process into intrinsic and task-evoked components. We argue that this alternative picture of brain function is best captured in a novel explanatory framework called enabling constraint. Overall, these insights call for a reconceptualization of functional brain activity, and should drive future methodological and empirical efforts.

Acoustic resonance spectroscopy intrinsic seals

International Nuclear Information System (INIS)

Olinger, C.T.; Burr, T.; Vnuk, D.R.

1994-01-01

We have begun to quantify the ability of acoustic resonance spectroscopy (ARS) to detect the removal and replacement of the lid of a simulated special nuclear materials drum. Conceptually, the acoustic spectrum of a container establishcs a baseline fingerprint, which we refer to as an intrinsic seal, for the container. Simply removing and replacing the lid changes some of the resonant frequencies because it is impossible to exactly duplicate all of the stress patterns between the lid and container. Preliminary qualitative results suggested that the ARS intrinsic seal could discriminate between cases where a lid has or has not been removed. The present work is directed at quantifying the utility of the ARS intrinsic seal technique, including the technique's sensitivity to ''nuisance'' effects, such as temperature swings, movement of the container, and placement of the transducers. These early quantitative tests support the potential of the ARS intrinsic seal application, but also reveal a possible sensitivity to nuisance effects that could limit environments or conditions under which the technique is effective

STRANGE ATTRACTORS IN SYMMETRIC UNFOLDINGS OF A SINGULARITY WITH THREE-FOLD ZERO EIGENVALUE

Institute of Scientific and Technical Information of China (English)

Qinghua Zhou

2009-01-01

In this paper, we study the Sil'nikov heteroclinic bifurcations, which display strange attractors, for the symmetric versal unfoldings of the singularity at the origin with a nilpotent Linear part and 3-jet, using the normal form, the blow-up and the ge-neralized Mel'nikov methods of heteroclinic orbits to two hyperbolic or nonhyperbolic equilibria in a high-dimensional space.

The Unfolding of Value Sources During Online Business Model Transformation

Directory of Open Access Journals (Sweden)

Nadja Hoßbach

2016-12-01

Full Text Available Purpose: In the magazine publishing industry, viable online business models are still rare to absent. To prepare for the ‘digital future’ and safeguard their long-term survival, many publishers are currently in the process of transforming their online business model. Against this backdrop, this study aims to develop a deeper understanding of (1 how the different building blocks of an online business model are transformed over time and (2 how sources of value creation unfold during this transformation process. Methodology: To answer our research question, we conducted a longitudinal case study with a leading German business magazine publisher (called BIZ. Data was triangulated from multiple sources including interviews, internal documents, and direct observations. Findings: Based on our case study, we nd that BIZ used the transformation process to differentiate its online business model from its traditional print business model along several dimensions, and that BIZ’s online business model changed from an efficiency- to a complementarity- to a novelty-based model during this process. Research implications: Our findings suggest that different business model transformation phases relate to different value sources, questioning the appropriateness of value source-based approaches for classifying business models. Practical implications: The results of our case study highlight the need for online-offline business model differentiation and point to the important distinction between service and product differentiation. Originality: Our study contributes to the business model literature by applying a dynamic and holistic perspective on the link between online business model changes and unfolding value sources.

An alternatively spliced heat shock transcription factor, OsHSFA2dI, functions in the heat stress-induced unfolded protein response in rice.

Science.gov (United States)

Cheng, Q; Zhou, Y; Liu, Z; Zhang, L; Song, G; Guo, Z; Wang, W; Qu, X; Zhu, Y; Yang, D

2015-03-01

As sessile organisms, plants have evolved a wide range of defence pathways to cope with environmental stress such as heat shock. However, the molecular mechanism of these defence pathways remains unclear in rice. In this study, we found that OsHSFA2d, a heat shock transcriptional factor, encodes two main splice variant proteins, OsHSFA2dI and OsHSFA2dII in rice. Under normal conditions, OsHSFA2dII is the dominant but transcriptionally inactive spliced form. However, when the plant suffers heat stress, OsHSFA2d is alternatively spliced into a transcriptionally active form, OsHSFA2dI, which participates in the heat stress response (HSR). Further study found that this alternative splicing was induced by heat shock rather than photoperiod. We found that OsHSFA2dI is localised to the nucleus, whereas OsHSFA2dII is localised to the nucleus and cytoplasm. Moreover, expression of the unfolded protein response (UNFOLDED PROTEIN RESPONSE) sensors, OsIRE1, OsbZIP39/OsbZIP60 and the UNFOLDED PROTEIN RESPONSE marker OsBiP1, was up-regulated. Interestingly, OsbZIP50 was also alternatively spliced under heat stress, indicating that UNFOLDED PROTEIN RESPONSE signalling pathways were activated by heat stress to re-establish cellular protein homeostasis. We further demonstrated that OsHSFA2dI participated in the unfolded protein response by regulating expression of OsBiP1. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Unique Piezoelectric Properties of the Monoclinic Phase in Pb (Zr ,Ti )O3 Ceramics: Large Lattice Strain and Negligible Domain Switching

Science.gov (United States)

Fan, Longlong; Chen, Jun; Ren, Yang; Pan, Zhao; Zhang, Linxing; Xing, Xianran

2016-01-01

The origin of the excellent piezoelectric properties at the morphotropic phase boundary is generally attributed to the existence of a monoclinic phase in various piezoelectric systems. However, there exist no experimental studies that reveal the role of the monoclinic phase in the piezoelectric behavior in phase-pure ceramics. In this work, a single monoclinic phase has been identified in Pb (Zr ,Ti )O3 ceramics at room temperature by in situ high-energy synchrotron x-ray diffraction, and its response to electric field has been characterized for the first time. Unique piezoelectric properties of the monoclinic phase in terms of large intrinsic lattice strain and negligible domain switching have been observed. The extensional strain constant d33 and the transverse strain constant d31 are calculated to be 520 and -200 pm /V , respectively. These large piezoelectric coefficients are mainly due to the large intrinsic lattice strain, with very little extrinsic contribution from domain switching. The unique properties of the monoclinic phase provide new insights into the mechanisms responsible for the piezoelectric properties at the morphotropic phase boundary.

Unique Piezoelectric Properties of the Monoclinic Phase in Pb(Zr,Ti)O_{3} Ceramics: Large Lattice Strain and Negligible Domain Switching.

Science.gov (United States)

Fan, Longlong; Chen, Jun; Ren, Yang; Pan, Zhao; Zhang, Linxing; Xing, Xianran

2016-01-15

The origin of the excellent piezoelectric properties at the morphotropic phase boundary is generally attributed to the existence of a monoclinic phase in various piezoelectric systems. However, there exist no experimental studies that reveal the role of the monoclinic phase in the piezoelectric behavior in phase-pure ceramics. In this work, a single monoclinic phase has been identified in Pb(Zr,Ti)O_{3} ceramics at room temperature by in situ high-energy synchrotron x-ray diffraction, and its response to electric field has been characterized for the first time. Unique piezoelectric properties of the monoclinic phase in terms of large intrinsic lattice strain and negligible domain switching have been observed. The extensional strain constant d_{33} and the transverse strain constant d_{31} are calculated to be 520 and -200  pm/V, respectively. These large piezoelectric coefficients are mainly due to the large intrinsic lattice strain, with very little extrinsic contribution from domain switching. The unique properties of the monoclinic phase provide new insights into the mechanisms responsible for the piezoelectric properties at the morphotropic phase boundary.

Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride-induced unfolding of peptide deformylase.

Science.gov (United States)

Berg, Alexander K; Manokaran, Sumathra; Eiler, Daniel; Kooren, Joel; Mallik, Sanku; Srivastava, D K

2008-01-01

Peptide deformylase (PDF) catalyzes the removal of formyl group from the N-terminal methionine residues of nascent proteins in prokaryotes, and this enzyme is a high priority target for antibiotic design. In pursuit of delineating the structural-functional features of Escherichia coli PDF (EcPDF), we investigated the mechanistic pathway for the guanidinium chloride (GdmCl)-induced unfolding of the enzyme by monitoring the secondary structural changes via CD spectroscopy. The experimental data revealed that EcPDF is a highly stable enzyme, and it undergoes slow denaturation in the presence of varying concentrations of GdmCl. The most interesting aspect of these studies has been the abrupt reversal of the unfolding pathway at low to moderate concentrations of the denaturant, but not at high concentration. An energetic rationale for such an unprecedented feature in protein chemistry is offered.

Crowding out intrinsic motivation in the public sector

OpenAIRE

Georgellis, Y; Iossa, E; Tabvuma, V

2011-01-01

Employing intrinsically motivated individuals has been proposed as a means of improving public sector performance. In this article, we investigate whether intrinsic motivation affects the sorting of employees between the private and the public sectors, paying particular attention to whether extrinsic rewards crowd out intrinsic motivation. Using British longitudinal data, we find that individuals are attracted to the public sector by the intrinsic rather than the extrinsic rewards that the se...

Plutonium uniqueness

International Nuclear Information System (INIS)

Silver, G.L.

1984-01-01

A standard is suggested against which the putative uniqueness of plutonium may be tested. It is common folklore that plutonium is unique among the chemical elements because its four common oxidation states can coexist in the same solution. Whether this putative uniqueness appears only during transit to equilibrium, or only at equilibrium, or all of the time, is not generally made clear. But while the folklore may contain some truth, it cannot be put to test until some measure of 'uniqueness' is agreed upon so that quantitative comparisons are possible. One way of measuring uniqueness is as the magnitude of the product of the mole fractions of the element at equilibrium. A 'coexistence index' is defined and discussed. (author)

Oxygen sensing PLIM together with FLIM of intrinsic cellular fluorophores for metabolic mapping

Science.gov (United States)

Kalinina, Sviatlana; Schaefer, Patrick; Breymayer, Jasmin; Bisinger, Dominik; Chakrabortty, Sabyasachi; Rueck, Angelika

2018-02-01

Otical imaging techniques based on time correlated single photon counting (TCSPC) has found wide applications in medicine and biology. Non-invasive and information-rich fluorescence lifetime imaging microscopy (FLIM) is successfully used for monitoring fluorescent intrinsic metabolic coenzymes as NAD(P)H (nicotinamide adenine dinucleotide (phosphate)) and FAD+ (flavin adenine dinucleotide) in living cells and tissues. The ratio between proteinbound and free coenzymes gives an information about the balance between oxidative phosphorylation and glycolysis in the cells. The changes of the ratio reflects major cellular disorders. A correlation exists between metabolic activity, redox ratio and fluorescence lifetime during stem cell differentiation, neurodegenerative diseases, and carcinogenesis. A multichannel FLIM detection system was designed for monitoring the redox state of NAD(P)H and FAD+ and other intrinsic fluorophores as protoporphyrin IX. In addition, the unique upgrade is useful to perform FLIM and PLIM (phosphorescence lifetime imaging microscopy) simultaneously. PLIM is a promising method to investigate oxygen sensing in biomedical samples. In detail, the oxygen-dependent quenching of phosphorescence of some compounds as transition metal complexes enables measuring of oxygen partial pressure (pO2). Using a two-channel FLIM/PLIM system we monitored intrinsic pO2 by PLIM simultaneously with NAD(P)H by FLIM providing complex metabolic and redox imaging of living cells. Physico-chemical properties of oxygen sensitive probes define certain parameters including their localisation. We present results of some ruthenium based complexes including those specifically bound to mitochondria.

The l z ( p ) * Person-Fit Statistic in an Unfolding Model Context.

Science.gov (United States)

Tendeiro, Jorge N

2017-01-01

Although person-fit analysis has a long-standing tradition within item response theory, it has been applied in combination with dominance response models almost exclusively. In this article, a popular log likelihood-based parametric person-fit statistic under the framework of the generalized graded unfolding model is used. Results from a simulation study indicate that the person-fit statistic performed relatively well in detecting midpoint response style patterns and not so well in detecting extreme response style patterns.

Spectrum unfolding from activation measurements in a CTR-model blanket experiment

International Nuclear Information System (INIS)

Kuijpers, L.J.M.

1977-07-01

Neutron spectra in a lithium fusion reactor model blanket are determined experimentally by performing SAND II unfolding runs from measured activities. The principles of the iterative SAND II method are given and characteristics of the output are described. The spectra are calculated from available data with the aid of a Monte Carlo program, of which procedure numerical results are given. Both kinds of spectra are compared; when number of input data is varied or different cross section data sets are chosen, inconsistencies in activities or cross section data may be detected. (orig./WL) [de

Defining intrinsic vs. extrinsic atopic dermatitis.

Science.gov (United States)

Karimkhani, Chante; Silverberg, Jonathan I; Dellavalle, Robert P

2015-06-16

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by eczematous lesions, i.e. ill-demarcated erythematous patches and plaques. AD is commonly associated with elevated immunoglobulin E (IgE) and atopic disorders, such as asthma, hay fever, and food allergies. Rackemann and Mallory were some of the first to distinguish between asthma based on the presence ("extrinsic") or absence ("intrinsic") of allergy. This distinction has subsequently been applied to AD based on the presence ("extrinsic") or absence ("intrinsic") of increased IgE and atopic disease. Although the distinction between intrinsic and extrinsic AD is widely used, it remains controversial.

Intrinsic Tunneling in Phase Separated Manganites

Science.gov (United States)

Singh-Bhalla, G.; Selcuk, S.; Dhakal, T.; Biswas, A.; Hebard, A. F.

2009-02-01

We present evidence of direct electron tunneling across intrinsic insulating regions in submicrometer wide bridges of the phase-separated ferromagnet (La,Pr,Ca)MnO3. Upon cooling below the Curie temperature, a predominantly ferromagnetic supercooled state persists where tunneling across the intrinsic tunnel barriers (ITBs) results in metastable, temperature-independent, high-resistance plateaus over a large range of temperatures. Upon application of a magnetic field, our data reveal that the ITBs are extinguished resulting in sharp, colossal, low-field resistance drops. Our results compare well to theoretical predictions of magnetic domain walls coinciding with the intrinsic insulating phase.

Intrinsic-extrinsic factors in sport motivation.

Science.gov (United States)

Pedersen, Darhl M

2002-10-01

Participants were 83 students (36 men and 47 women). 10 intrinsic-extrinsic factors involved in sport motivation were obtained. The factors were generated from items obtained from the participants rather than items from the experimenter. This was done to avoid the possible influence of preconceptions on the part of the experimenter regarding what the final dimensions may be. Obtained motivational factors were Social Reinforcement, Fringe Benefits, Fame and Fortune, External Forces, Proving Oneself, Social Benefits, Mental Enrichment, Expression of Self, Sense of Accomplishment, and Self-enhancement. Each factor was referred to an intrinsic-extrinsic dimension to describe its relative position on that dimension. The order of the factors as listed indicates increasing intrinsic motivation. i.e., the first four factors were rated in the extrinsic range, whereas the remaining six were rated to be in the intrinsic range. Next, the participants rated the extent to which each of the various factors was involved in their decision to participate in sport activities. The pattern of use of the motivational factors was the same for both sexes except that men indicated greater use of the Fringe Benefits factor. Overall, the more intrinsic a sport motivation factor was rated, the more likely it was to be rated as a factor in actual sport participation.

Determination of the plastic deformation and residual stress tensor distribution using surface and bulk intrinsic magnetic properties

International Nuclear Information System (INIS)

Hristoforou, E.; Svec, P. Sr.

2015-01-01

We have developed an unique method to provide the stress calibration curve in steels: performing flaw-less welding in the under examination steel, we obtained to determine the level of the local plastic deformation and the residual stress tensors. These properties where measured using both the X-ray and the neutron diffraction techniques, concerning their surface and bulk stresses type II (intra-grain stresses) respectively, as well as the stress tensor type III by using the electron diffraction technique. Measuring the distribution of these residual stresses along the length of a welded sample or structure, resulted in determining the local stresses from the compressive to tensile yield point. Local measurement of the intrinsic surface and bulk magnetic property tensors allowed for the un-hysteretic correlation. The dependence of these local magnetic tensors with the above mentioned local stress tensors, resulting in a unique and almost un-hysteretic stress calibration curve of each grade of steel. This calibration integrated the steel's mechanical and thermal history, as well as the phase transformations and the presence of precipitations occurring during the welding process.Additionally to that, preliminary results in different grade of steels reveal the existence of a universal law concerning the dependence of magnetic and magnetostrictive properties of steels on their plastic deformation and residual stress state, as they have been accumulated due to their mechanical and thermal fatigue and history. This universality is based on the unique dependence of the intrinsic magnetic properties of steels normalized with a certain magnetoelastic factor, upon the plastic deformation or residual stress state, which, in terms, is normalized with their yield point of stress. (authors)

Experiences matter: Positive emotions facilitate intrinsic motivation

OpenAIRE

Løvoll, Helga Synnevåg; Røysamb, Espen; Vittersø, Joar

2017-01-01

This paper has two major aims. First, to investigate how positive emotions and intrinsic motivation affect each other over time. Second, to test the effect of positive emotions and intrinsic motivation on subsequent educational choices. Through two ordinary study semesters, 64 sport students in Norway reported on their intrinsic motivation for outdoor activities (twice) as well as positive emotions after two three-day outdoor events (four times). Next autumn, students study choice was collect...

Experiences matter: Positive emotions facilitate intrinsic motivation

OpenAIRE

Løvoll, Helga Synnevåg; Røysamb, Espen; Vittersø, Joar

2017-01-01

https://doi.org/10.1080/23311908.2017.1340083 This paper has two major aims. First, to investigate how positive emotions and intrinsic motivation affect each other over time. Second, to test the effect of positive emotions and intrinsic motivation on subsequent educational choices. Through two ordinary study semesters, 64 sport students in Norway reported on their intrinsic motivation for outdoor activities (twice) as well as positive emotions after two three-day outdoor e...

Intrinsic and extrinsic geometry of random surfaces

International Nuclear Information System (INIS)

Jonsson, T.

1992-01-01

We prove that the extrinsic Hausdorff dimension is always greater than or equal to the intrinsic Hausdorff dimension in models of triangulated random surfaces with action which is quadratic in the separation of vertices. We furthermore derive a few naive scaling relations which relate the intrinsic Hausdorff dimension to other critical exponents. These relations suggest that the intrinsic Hausdorff dimension is infinite if the susceptibility does not diverge at the critical point. (orig.)

Neutron spectra unfolding with maximum entropy and maximum likelihood

International Nuclear Information System (INIS)

Itoh, Shikoh; Tsunoda, Toshiharu

1989-01-01

A new unfolding theory has been established on the basis of the maximum entropy principle and the maximum likelihood method. This theory correctly embodies the Poisson statistics of neutron detection, and always brings a positive solution over the whole energy range. Moreover, the theory unifies both problems of overdetermined and of underdetermined. For the latter, the ambiguity in assigning a prior probability, i.e. the initial guess in the Bayesian sense, has become extinct by virtue of the principle. An approximate expression of the covariance matrix for the resultant spectra is also presented. An efficient algorithm to solve the nonlinear system, which appears in the present study, has been established. Results of computer simulation showed the effectiveness of the present theory. (author)

Intrinsic Motivation: An Overlooked Component for Student Success

Science.gov (United States)

Augustyniak, Robert A.; Ables, Adrienne Z.; Guilford, Philip; Lujan, Heidi L.; Cortright, Ronald N.; DiCarlo, Stephen E.

2016-01-01

Intrinsic motivation to learn involves engaging in learning opportunities because they are seen as enjoyable, interesting, or relevant to meeting one's core psychological needs. As a result, intrinsic motivation is associated with high levels of effort and task performance. Students with greater levels of intrinsic motivation demonstrate strong…

The value of nature: Economic, intrinsic, or both?

Science.gov (United States)

There has been a long standing argument that ecosystems have intrinsic value and therefore there is no need to put a price tag on Mother Nature. The concept of intrinsic value reflects the perspective that nature has value in its own right, independent of human uses. Intrinsic va...

Intrinsic and extrinsic motivation for smoking cessation.

Science.gov (United States)

Curry, S; Wagner, E H; Grothaus, L C

1990-06-01

An intrinsic-extrinsic model of motivation for smoking cessation was evaluated with 2 samples (ns = 1.217 and 151) of smokers who requested self-help materials for smoking cessation. Exploratory and confirmatory principal components analysis on a 36-item Reasons for Quitting (RFQ) scale supported the intrinsic-extrinsic motivation distinction. A 4-factor model, with 2 intrinsic dimensions (concerns about health and desire for self-control) and 2 extrinsic dimensions (immediate reinforcement and social influence), was defined by 20 of the 36 RFQ items. The 20-item measure demonstrated moderate to high levels of internal consistency and convergent and discriminant validity. Logistic regression analyses indicated that smokers with higher levels of intrinsic relative to extrinsic motivation were more likely to achieve abstinence from smoking.

Deuterium NMR, induced and intrinsic cholesteric lyomesophases

International Nuclear Information System (INIS)

Alcantara, M.R.

1982-01-01

Induced and intrinsic cholesteric lyotropic mesophases were studied. Induced cholesteric lyomesophases based on potassium laurate (KL) system, with small amounts of cholesterol added, were studied by deuterium NMR and by polarizing microscopy. Order profiles obtained from deuterium NMR of KL perdenderated chains in both induced cholesteric and normal mesophases were compared. The intrinsic cholesteric lyotropic mesophases were based on the amphiphile potassium N-lauroyl serinate (KLNS) in the resolved levo form. The study of the type I intrinsic cholesteric mesophase was made by optical microscopy under polarized light and the type II intrinsic cholesteric lyomesophase was characterized by deuterium NMR. The new texture was explained by the use of the theory of disclinations developed for thermotropic liquid crystals, specially for cholesteric type. (M.J.C.) [pt

Intrinsic bioremediation of landfills interim report

International Nuclear Information System (INIS)

Brigmon, R.L.; Fliermans, C.B.

1997-01-01

Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP)

Intrinsic bioremediation of landfills interim report

Energy Technology Data Exchange (ETDEWEB)

Brigmon, R.L. [Westinghouse Savannah River Company, Aiken, SC (United States); Fliermans, C.B.

1997-07-14

Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP).

Expressing intrinsic volumes as rotational integrals

DEFF Research Database (Denmark)

Auneau, Jeremy Michel; Jensen, Eva Bjørn Vedel

2010-01-01

A new rotational formula of Crofton type is derived for intrinsic volumes of a compact subset of positive reach. The formula provides a functional defined on the section of X with a j-dimensional linear subspace with rotational average equal to the intrinsic volumes of X. Simplified forms of the ...

Spatial cognition and science achievement: The contribution of intrinsic and extrinsic spatial skills from 7 to 11 years.

Science.gov (United States)

Hodgkiss, Alex; Gilligan, Katie A; Tolmie, Andrew K; Thomas, Michael S C; Farran, Emily K

2018-01-22

Prior longitudinal and correlational research with adults and adolescents indicates that spatial ability is a predictor of science learning and achievement. However, there is little research to date with primary-school aged children that addresses this relationship. Understanding this association has the potential to inform curriculum design and support the development of early interventions. This study examined the relationship between primary-school children's spatial skills and their science achievement. Children aged 7-11 years (N = 123) completed a battery of five spatial tasks, based on a model of spatial ability in which skills fall along two dimensions: intrinsic-extrinsic; static-dynamic. Participants also completed a curriculum-based science assessment. Controlling for verbal ability and age, mental folding (intrinsic-dynamic spatial ability), and spatial scaling (extrinsic-static spatial ability) each emerged as unique predictors of overall science scores, with mental folding a stronger predictor than spatial scaling. These spatial skills combined accounted for 8% of the variance in science scores. When considered by scientific discipline, mental folding uniquely predicted both physics and biology scores, and spatial scaling accounted for additional variance in biology and variance in chemistry scores. The children's embedded figures task (intrinsic-static spatial ability) only accounted for variance in chemistry scores. The patterns of association were consistent across the age range. Spatial skills, particularly mental folding, spatial scaling, and disembedding, are predictive of 7- to 11-year-olds' science achievement. These skills make a similar contribution to performance for each age group. © 2018 The Authors. British Journal of Education Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

CNA web server: rigidity theory-based thermal unfolding simulations of proteins for linking structure, (thermo-)stability, and function.

Science.gov (United States)

Krüger, Dennis M; Rathi, Prakash Chandra; Pfleger, Christopher; Gohlke, Holger

2013-07-01

The Constraint Network Analysis (CNA) web server provides a user-friendly interface to the CNA approach developed in our laboratory for linking results from rigidity analyses to biologically relevant characteristics of a biomolecular structure. The CNA web server provides a refined modeling of thermal unfolding simulations that considers the temperature dependence of hydrophobic tethers and computes a set of global and local indices for quantifying biomacromolecular stability. From the global indices, phase transition points are identified where the structure switches from a rigid to a floppy state; these phase transition points can be related to a protein's (thermo-)stability. Structural weak spots (unfolding nuclei) are automatically identified, too; this knowledge can be exploited in data-driven protein engineering. The local indices are useful in linking flexibility and function and to understand the impact of ligand binding on protein flexibility. The CNA web server robustly handles small-molecule ligands in general. To overcome issues of sensitivity with respect to the input structure, the CNA web server allows performing two ensemble-based variants of thermal unfolding simulations. The web server output is provided as raw data, plots and/or Jmol representations. The CNA web server, accessible at http://cpclab.uni-duesseldorf.de/cna or http://www.cnanalysis.de, is free and open to all users with no login requirement.

Identifying the neural substrates of intrinsic motivation during task performance.

Science.gov (United States)

Lee, Woogul; Reeve, Johnmarshall

2017-10-01

Intrinsic motivation is the inherent tendency to seek out novelty and challenge, to explore and investigate, and to stretch and extend one's capacities. When people imagine performing intrinsically motivating tasks, they show heightened anterior insular cortex (AIC) activity. To fully explain the neural system of intrinsic motivation, however, requires assessing neural activity while people actually perform intrinsically motivating tasks (i.e., while answering curiosity-inducing questions or solving competence-enabling anagrams). Using event-related functional magnetic resonance imaging, we found that the neural system of intrinsic motivation involves not only AIC activity, but also striatum activity and, further, AIC-striatum functional interactions. These findings suggest that subjective feelings of intrinsic satisfaction (associated with AIC activations), reward processing (associated with striatum activations), and their interactions underlie the actual experience of intrinsic motivation. These neural findings are consistent with the conceptualization of intrinsic motivation as the pursuit and satisfaction of subjective feelings (interest and enjoyment) as intrinsic rewards.

Intrinsically Disordered Side of the Zika Virus Proteome

Directory of Open Access Journals (Sweden)

Rajanish Giri

2016-11-01

Full Text Available Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766. Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the Flaviviridae family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of new disorder-based drugs.

Exploring the role of internal friction in the dynamics of unfolded proteins using simple polymer models

Science.gov (United States)

Cheng, Ryan R.; Hawk, Alexander T.; Makarov, Dmitrii E.

2013-02-01

Recent experiments showed that the reconfiguration dynamics of unfolded proteins are often adequately described by simple polymer models. In particular, the Rouse model with internal friction (RIF) captures internal friction effects as observed in single-molecule fluorescence correlation spectroscopy (FCS) studies of a number of proteins. Here we use RIF, and its non-free draining analog, Zimm model with internal friction, to explore the effect of internal friction on the rate with which intramolecular contacts can be formed within the unfolded chain. Unlike the reconfiguration times inferred from FCS experiments, which depend linearly on the solvent viscosity, the first passage times to form intramolecular contacts are shown to display a more complex viscosity dependence. We further describe scaling relationships obeyed by contact formation times in the limits of high and low internal friction. Our findings provide experimentally testable predictions that can serve as a framework for the analysis of future studies of contact formation in proteins.

An assay for serum vitamin-B12 and for intrinsic factor antibody type I by means of hog intrinsic factor

International Nuclear Information System (INIS)

Hudak, J.; Berger, Z.; Varga, L.

1980-01-01

A new radioassay method was elaborated for the determination of the plasma level of vitamin B 12 and of the intrinsic factor antibody type I. The assay applies vitamin-B 12 labelled with 58 Co, but replaces human intrinsic factor by hog intrinsic factor. 124 cases were investigated by both the original and this modified method, and the results were in very good agreement. (L.E.)

Guanidine hydrochloride denaturation of human serum albumin originates by local unfolding of some stable loops in domain III.

Science.gov (United States)

Ahmad, Basir; Ahmed, Md Zulfazal; Haq, Soghra Khatun; Khan, Rizwan Hasan

2005-06-15

The effect of guanidine hydrochloride (GnHCl) on the global stability of human serum albumin (HSA) has been studied by fluorescence and circular dichroism spectroscopic measurements. The differential stability of native conformation of three HSA domains were explored by using domain-specific ligands, hemin (domain I), chloroform (domain II), bilirubin (at domain I/domain II interface) and diazepam (domain III). GnHCl induced unfolding transition curves as monitored by probes for secondary and tertiary structures were cooperative but noncoincidental. A strong ANS binding to the protein was observed around 1.8 M GnHCl, suggesting existence of intermediate states in the unfolding pathway of HSA. A gradual decrease (in the GnHCl concentration range 0.0-1.8 M) in the binding of diazepam indicates that domain III is the most labile to GnHCl denaturation. A significant increase in the binding of bilirubin up to 1.4 M GnHCl and decrease thereafter leading to complete abolishment of bilirubin binding at around 2.0 M GnHCl suggest favorable rearrangement and separation of domains I and II at 1.4 and 2.0 M GnHCl concentration, respectively. Above 1.6 M GnHCl, decrease of the binding of hemin, a ligand for domain I, chloroform, which binds in domain II and lone tryptophanyl fluorescence (Trp-214 located in domain II) indicate that at higher concentration of GnHCl domains I and II start unfolding simultaneously but the stability of domain I (7.4 Kcal/mol) is much more than domain II (4.3 Kcal/mol). A pictorial model for the unfolding of HSA domains, consistent with all these results, has been formulated, suggesting that domain III is the most labile followed by domain II while domain I is the most stable. A molten globule like state of domain III around 1.8 M GnHCl has also been identified and characterized.

The Unfolded Protein Response and Cell Fate Control.

Science.gov (United States)

Hetz, Claudio; Papa, Feroz R

2018-01-18

The secretory capacity of a cell is constantly challenged by physiological demands and pathological perturbations. To adjust and match the protein-folding capacity of the endoplasmic reticulum (ER) to changing secretory needs, cells employ a dynamic intracellular signaling pathway known as the unfolded protein response (UPR). Homeostatic activation of the UPR enforces adaptive programs that modulate and augment key aspects of the entire secretory pathway, whereas maladaptive UPR outputs trigger apoptosis. Here, we discuss recent advances into how the UPR integrates information about the intensity and duration of ER stress stimuli in order to control cell fate. These findings are timely and significant because they inform an evolving mechanistic understanding of a wide variety of human diseases, including diabetes mellitus, neurodegeneration, and cancer, thus opening up the potential for new therapeutic modalities to treat these diverse diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Flavor Structure of Intrinsic Nucleon Sea

International Nuclear Information System (INIS)

Peng, Jen-Chieh; Chang, Wen-Chen; Cheng, Hai-Yang; Liu, Keh-Fei

2015-01-01

The concept of intrinsic charm suggested by Brodsky et al. is extended to lighter quarks. Extraction of the intrinsic ū, d-macron, and s-macron seas is obtained from an analysis of the d-macron − ū, s + s-macron, and ū + d-macron − s −s-macron distributions. The connection between the intrinsic/extrinsic seas and the connected/disconnected seas in lattice QCD is also examined. It is shown that the connected and disconnected components for the ū(x) + d-macron(x) sea can be separated. The striking x-dependence of the [s(x) + s-macron(x)]/[ū(x) + d-macron(x)] ratio is interpreted as an interplay between the connected and disconnected seas. (author)

Exploring the Intrinsic Motivation of Hedonic Information Systems Acceptance: Integrating Hedonic Theory and Flow with TAM

Science.gov (United States)

Wang, Zhihuan

Research on Information Systems (IS) acceptance is substantially focused on extrinsic motivation in workplaces, little is known about the underlying intrinsic motivations of Hedonic IS (HIS) acceptance. This paper proposes a hybrid HIS acceptance model which takes the unique characteristics of HIS and multiple identities of a HIS user into consideration by interacting Hedonic theory, Flow theory with Technology Acceptance Model (TAM). The model was empirically tested by a field survey. The result indicates that emotional responses, imaginal responses, and flow experience are three main contributions of HIS acceptance.

Thermal unfolding of a Ca- and Lanthanide-binding protein

Energy Technology Data Exchange (ETDEWEB)

Fahmy, Karim [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biophysics; Goettfert, M. [Technische Univ. Dresden (Germany); Knoeppel, J.

2017-06-01

The MIIA (metal ion-induced autocleavage)-domain of the protein Vic001052 from the pathogen Vibrio coralliilyticus, comprises 173 amino acids and exhibits Ca-dependent autoproteolytic activity. It shows homology to nodulation proteins which are secreted by Rhizobiacea into plant host cells where they exert Ca-dependent functions. We have studied the structural and energetic aspects of metal protein interactions of the MIIA domain which appear attractive for engineering metal-binding synthetic peptides. Using a non-cleavable MIIA domain construct, we detected very similar structural changes upon binding to Ca{sup 2+} and Eu{sup 3+}. The thermal denaturation of the Ca-bound state was studied by circular dichroism spectroscopy. The metal-bound folded state unfolds reversibly into an unstructured metal-free state similar to the metal-free state at room temperature.

DANTE, Activation Analysis Neutron Spectra Unfolding by Covariance Matrix Method

International Nuclear Information System (INIS)

Petilli, M.

1981-01-01

1 - Description of problem or function: The program evaluates activation measurements of reactor neutron spectra and unfolds the results for dosimetry purposes. Different evaluation options are foreseen: absolute or relative fluxes and different iteration algorithms. 2 - Method of solution: A least-square fit method is used. A correlation between available data and their uncertainties has been introduced by means of flux and activity variance-covariance matrices. Cross sections are assumed to be constant, i.e. with variance-covariance matrix equal to zero. The Lagrange multipliers method has been used for calculating the solution. 3 - Restrictions on the complexity of the problem: 9 activation experiments can be analyzed. 75 energy groups are accepted

Intrinsic neuromodulation: altering neuronal circuits from within.

Science.gov (United States)

Katz, P S; Frost, W N

1996-02-01

There are two sources of neuromodulation for neuronal circuits: extrinsic inputs and intrinsic components of the circuits themselves. Extrinsic neuromodulation is known to be pervasive in nervous systems, but intrinsic neuromodulation is less recognized, despite the fact that it has now been demonstrated in sensory and neuromuscular circuits and in central pattern generators. By its nature, intrinsic neuromodulation produces local changes in neuronal computation, whereas extrinsic neuromodulation can cause global changes, often affecting many circuits simultaneously. Studies in a number of systems are defining the different properties of these two forms of neuromodulation.

Acceptable solutions obtained by unfolding noisy data with a conjugate gradient technique

International Nuclear Information System (INIS)

Lang, D.W.

1976-01-01

A linear resolution function in a physical measurement leads to data values and standard deviations at, say, N points. It is noted that the associated resolution functions may require that a number n of particular linear combinations of the data values be each not significantly different from zero. One is left with at most N-n parameters to evaluate. If the resolution functions are reasonably behaved, one can show that one sensible way to describe the underlying spectrum treats it as a linear combination of the given resolution functions and includes all the significant information from the data. An iterative search for the best component available to minimize the chi-square of the next fit to the data leads to a conjugate gradient technique. Programs based on the technique have been successfully used to obtain neutron spectra as a function of energy; in raw data from a pulse height analysis of proton recoils in a proportional counter, and where the raw data are time of flight spectra from a time dependent pulse of known form. It is planned to incorporate these, together with working programs respectively for photonuclear analysis and to explore the impurity concentration profile in a surface, into a single ''work-bench'' type program. A suitably difficult model unfolding problem has been developed and used to show the strengths and weaknesses of a number of other methods that have been used for unfolding

Unfolding Visual Lexical Decision in Time

Science.gov (United States)

Barca, Laura; Pezzulo, Giovanni

2012-01-01

Visual lexical decision is a classical paradigm in psycholinguistics, and numerous studies have assessed the so-called “lexicality effect" (i.e., better performance with lexical than non-lexical stimuli). Far less is known about the dynamics of choice, because many studies measured overall reaction times, which are not informative about underlying processes. To unfold visual lexical decision in (over) time, we measured participants' hand movements toward one of two item alternatives by recording the streaming x,y coordinates of the computer mouse. Participants categorized four kinds of stimuli as “lexical" or “non-lexical:" high and low frequency words, pseudowords, and letter strings. Spatial attraction toward the opposite category was present for low frequency words and pseudowords. Increasing the ambiguity of the stimuli led to greater movement complexity and trajectory attraction to competitors, whereas no such effect was present for high frequency words and letter strings. Results fit well with dynamic models of perceptual decision-making, which describe the process as a competition between alternatives guided by the continuous accumulation of evidence. More broadly, our results point to a key role of statistical decision theory in studying linguistic processing in terms of dynamic and non-modular mechanisms. PMID:22563419

Neutron spectrum unfolding using neural networks

International Nuclear Information System (INIS)

Vega C, H.R.; Hernandez D, V.M.; Manzanares A, E.

2004-01-01

An artificial neural network has been designed to obtain the neutron spectra from the Bonner spheres spectrometer's count rates. The neural network was trained using a large set of neutron spectra compiled by the International Atomic Energy Agency. These include spectra from iso- topic neutron sources, reference and operational neutron spectra obtained from accelerators and nuclear reactors. The spectra were transformed from lethargy to energy distribution and were re-binned to 31 energy groups using the MCNP 4C code. Re-binned spectra and UTA4 matrix were used to calculate the expected count rates in Bonner spheres spectrometer. These count rates were used as input and correspondent spectrum was used as output during neural network training. The network has 7 input nodes, 56 neurons as hidden layer and 31 neurons in the output layer. After training the network was tested with the Bonner spheres count rates produced by twelve neutron spectra. The network allows unfolding the neutron spectrum from count rates measured with Bonner spheres. Good results are obtained when testing count rates belong to neutron spectra used during training, acceptable results are obtained for count rates obtained from actual neutron fields; however the network fails when count rates belong to monoenergetic neutron sources. (Author)

Unfolding Leonardo DA Vinci's Globe (ad 1504) to Reveal its Historical World Map

Science.gov (United States)

Verhoeven, G. J.; Missinne, S. J.

2017-08-01

This paper reports in detail on the image-based modelling and unwrapping approach used to create a two-dimensional projected map of an astonishing ostrich egg globe from AD 1504. This miniature egg globe is not only the oldest extant engraved globe, but it is also the oldest post-Columbian globe of the world and the first ever to depict Newfoundland and many other territories. The intention of digitally recording the surface geometry and colour of this unique artefact was to portray the original layout of the world map used by the Florentine Renaissance artist to make this globe. In addition, it was expected to substantiate iconographical details, which are hard to study at its scale of 1:80,000,000. The ostrich egg globe is the prototype of the Lenox Globe kept at the New York Public Library. The latter is very beneficial to examine how the egg globe looked like before being glued together at its equator. On the other hand, unfolding the map engraved in the ostrich egg halves enables a more detailed study of the remarkable details visible on both globes, since the engravings on the quasi-white egg surface are much easier to discern than those of the highly reflective red copper Lenox Globe. Finally, a detailed study of the unwrapped 3D surface is essential to learn more about the world vision of its creator and the incredible efforts that went into making this globe. Thanks to some particular pictographic details as well as the way in which the engravings are applied (by a left-handed person), the globe artist can be identified as Leonardo da Vinci.

Uncovering intrinsic modular organization of spontaneous brain activity in humans.

Directory of Open Access Journals (Sweden)

Yong He

Full Text Available The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz, spontaneous fluctuations of the blood oxygen level dependent (BOLD signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in

Elements of the Competitive Situation That Affect Intrinsic Motivation.

Science.gov (United States)

Reeve, Johnmarshall; Deci, Edward L.

1996-01-01

Explores the effects of three elements of the competitive situation (competitive set, competitive outcome, and interpersonal context) on intrinsic motivation in a sample of college students (n=100). Competitive outcome and interpersonal context affected intrinsic motivation: winning increased intrinsic motivation, while pressured interpersonal…

Unfolding and effective bandstructure calculations as discrete real- and reciprocal-space operations

Energy Technology Data Exchange (ETDEWEB)

Boykin, Timothy B., E-mail: boykin@ece.uah.edu [Department of Electrical and Computer Engineering, The University of Alabama in Huntsville, Huntsville, AL 35899 (United States); Ajoy, Arvind [School of Electrical and Computer Engineering, Cornell University, Ithaca, NY 14853 (United States); Ilatikhameneh, Hesameddin; Povolotskyi, Michael; Klimeck, Gerhard [Network for Computational Nanotechnology, School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN 47907 (United States)

2016-06-15

In recent years, alloy electronic structure calculations based on supercell Brillouin zone unfolding have become popular. There are a number of formulations of the method which on the surface might appear different. Here we show that a discrete real-space description, based on discrete Fourier transforms, is fully general. Furthermore, such an approach can more easily show the effects of alloy scattering. We present such a method for treating the random alloy problem. This treatment features straightforward mathematics and a transparent physical interpretation of the calculated effective (i.e., approximate) energy bands.

A radioisotope dilution assay for unlabelled vitamin B12-intrinsic factor complex employing the binding intrinsic factor antibody: probable evidence for two types of binding antibody

International Nuclear Information System (INIS)

Jacob, E.; O'Brien, H.A.W.; Mollin, D.L.

1977-01-01

A new radioisotope dilution assay for vitamin B 12 -intrinsic factor complex is described. The method is based on the use of the binding type intrinsic antibody (the binding reagent), which when combined with the intrinsic factor-vitamin B 12 complex (labelled ligand), is quantitatively adsorbed onto zirconium phosphate gel pH 6.25. The new assay has been shown to provide a measure of intrinsic factor comparable with other intrinsic factor assays, but it has the important advantage of being able to measure the unlabelled vitamin B 12 -intrinsic factor complex (unlabelled ligand), and will, therefore, be valuable in the study of physiological events in the gastrointestinal tract. During the study, it was found that there is some evidence for at least two types of binding intrinsic factor antibody: One which combines preferentially with the intrinsic factor-vitamin B 12 complex and one which combines equally well with this complex or with free intrinsic factor. (author)

Evolution PDEs with nonstandard growth conditions existence, uniqueness, localization, blow-up

CERN Document Server

Antontsev, Stanislav

2015-01-01

This monograph offers the reader a treatment of the theory of evolution PDEs with nonstandard growth conditions. This class includes parabolic and hyperbolic equations with variable or anisotropic nonlinear structure. We develop methods for the study of such equations and present a detailed account of recent results. An overview of other approaches to the study of PDEs of this kind is provided. The presentation is focused on the issues of existence and uniqueness of solutions in appropriate function spaces, and on the study of the specific qualitative properties of solutions, such as localization in space and time, extinction in a finite time and blow-up, or nonexistence of global in time solutions. Special attention is paid to the study of the properties intrinsic to solutions of equations with nonstandard growth.

Dysregulation of the unfolded protein response in db/db mice with diet induced steatohepatitis

OpenAIRE

Rinella, Mary E.; Siddiqui, M. Shaddab; Gardikiotes, Konstantina; Gottstein, Jeanne; Elias, Marc; Green, Richard M.

2011-01-01

In humans with non-alcoholic fatty liver, diabetes is associated with more advanced disease. We have previously shown that diabetic db/db mice are highly susceptible to methionine choline deficient diet (MCD) induced hepatic injury. Since activation of the unfolded protein response (UPR) is an important adaptive cellular mechanism in diabetes, obesity and fatty liver, we hypothesized that dysregulation of the UPR may partially explain how diabetes could promote liver injury.

Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity

OpenAIRE

Judith A. Smith; Judith A. Smith

2018-01-01

Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defen...

Statins inhibit protein lipidation and induce the unfolded protein response in the non-sterol producing nematode Caenorhabditis elegans

DEFF Research Database (Denmark)

Mörck, Catarina; Elmelund-Præstekær, Louise Cathrine Braun; Kurth, Caroline

2009-01-01

of lipid moieties for protein prenylation. The nematode Caenorhabditis elegans possesses a mevalonate pathway that lacks the branch leading to cholesterol synthesis, and thus represents an ideal organism to specifically study the noncholesterol roles of the pathway. Inhibiting HMG-CoA reductase in C....... elegans using statins or RNAi leads to developmental arrest and loss of membrane association of a GFP-based prenylation reporter. The unfolded protein response (UPR) is also strongly activated, suggesting that impaired prenylation of small GTPases leads to the accumulation of unfolded proteins and ER...... and fatty acid composition were unaffected in statin-treated worms, even though they showed reduced staining with Nile red. We conclude that inhibitors of HMG-CoA reductase or of farnesyl transferases induce the UPR by inhibiting the prenylation of M57.2 substrates, resulting in developmental arrest in C...

Predicting Intrinsic Motivation

Science.gov (United States)

Martens, Rob; Kirschner, Paul A.

2004-01-01

Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the…

Individualistic vs. Competitive Participation: The Effect on Intrinsic Motivation.

Science.gov (United States)

Jones, Brent M.; And Others

Studies investigating intrinsic motivation and competition have supported the view that competition decreases intrinsic motivation. More recent studies suggest that the specific outcome of a competition (a win or a loss) differentially affects intrinsic motivation by highlighting the informational rather than the controlling aspect of the reward…

A J-modulated protonless NMR experiment characterizes the conformational ensemble of the intrinsically disordered protein WIP

Energy Technology Data Exchange (ETDEWEB)

Rozentur-Shkop, Eva; Goobes, Gil; Chill, Jordan H., E-mail: Jordan.Chill@biu.ac.il [Bar Ilan University, Department of Chemistry (Israel)

2016-12-15

Intrinsically disordered proteins (IDPs) are multi-conformational polypeptides that lack a single stable three-dimensional structure. It has become increasingly clear that the versatile IDPs play key roles in a multitude of biological processes, and, given their flexible nature, NMR is a leading method to investigate IDP behavior on the molecular level. Here we present an IDP-tailored J-modulated experiment designed to monitor changes in the conformational ensemble characteristic of IDPs by accurately measuring backbone one- and two-bond J({sup 15}N,{sup 13}Cα) couplings. This concept was realized using a unidirectional (H)NCO {sup 13}C-detected experiment suitable for poor spectral dispersion and optimized for maximum coverage of amino acid types. To demonstrate the utility of this approach we applied it to the disordered actin-binding N-terminal domain of WASp interacting protein (WIP), a ubiquitous key modulator of cytoskeletal changes in a range of biological systems. One- and two-bond J({sup 15}N,{sup 13}Cα) couplings were acquired for WIP residues 2–65 at various temperatures, and in denaturing and crowding environments. Under native conditions fitted J-couplings identified in the WIP conformational ensemble a propensity for extended conformation at residues 16–23 and 45–60, and a helical tendency at residues 28–42. These findings are consistent with a previous study of the based upon chemical shift and RDC data and confirm that the WIP{sup 2–65} conformational ensemble is biased towards the structure assumed by this fragment in its actin-bound form. The effects of environmental changes upon this ensemble were readily apparent in the J-coupling data, which reflected a significant decrease in structural propensity at higher temperatures, in the presence of 8 M urea, and under the influence of a bacterial cell lysate. The latter suggests that crowding can cause protein unfolding through protein–protein interactions that stabilize the unfolded

Hidden Structural Codes in Protein Intrinsic Disorder.

Science.gov (United States)

Borkosky, Silvia S; Camporeale, Gabriela; Chemes, Lucía B; Risso, Marikena; Noval, María Gabriela; Sánchez, Ignacio E; Alonso, Leonardo G; de Prat Gay, Gonzalo

2017-10-17

Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble.

Intrinsic motivation and sportsmanship: mediating role of interpersonal relationships.

Science.gov (United States)

Núñez, Juan L; Martín-Albo, José; Navarro, José G; Sánchez, Juana M; González-Cutre, David

2009-06-01

This study analyzed the mediating role of interpersonal relations between intrinsic motivation and sportsmanship. Athletes (98 men, 97 women), ages 11 to 43 years, completed measures of intrinsic motivation toward sports, self-concept of social and family relations, and sportsmanship orientation. A structural equation model indicated that self-concept of interpersonal relations mediated the relation between intrinsic motivation and sportsmanship. Also, intrinsic motivation was directly and positively associated with self-concept of interpersonal relations, which, in turn, was positively and significantly related to sportsmanship. Variances explained by self-concept of interpersonal relations and by sportsmanship were 32 and 56%, respectively. The motivational interaction between the context of interpersonal relations and the sports context proposed in the hierarchical model of intrinsic and extrinsic motivation was discussed.

Unfolding of true distributions from experimental data distorted by detectors with finite resolutions

International Nuclear Information System (INIS)

Gagunashvili, N.D.

1993-01-01

A new procedure for unfolding the true distribution from experimental data distorted by a detector is proposed. For the given detector a result can be found by the least squares method, hence, without bias and involving minimal statistical errors. Stability of the result is achieved at the expense of its information content and/or using additional information on the shape of the distributions to be measured. The method may be applied for detectors with linear or nonlinear distortions. 8 refs.; 5 figs

Unfolding of Ubiquitin Studied by Picosecond Time-Resolved Fluorescence of the Tyrosine Residue

OpenAIRE

Noronha, Melinda; Lima, João C.; Bastos, Margarida; Santos, Helena; Maçanita, António L.

2004-01-01

The photophysics of the single tyrosine in bovine ubiquitin (UBQ) was studied by picosecond time-resolved fluorescence spectroscopy, as a function of pH and along thermal and chemical unfolding, with the following results: First, at room temperature (25°C) and below pH 1.5, native UBQ shows single-exponential decays. From pH 2 to 7, triple-exponential decays were observed and the three decay times were attributed to the presence of tyrosine, a tyrosine-carboxylate hydrogen-bonded complex, and...

i=0 (Information has no intrinsic meaning

Directory of Open Access Journals (Sweden)

F.J. Miller

2002-01-01

Full Text Available This paper was written mainly to help identify some contradictions that can be found in the notion of knowledge management though its application is wider-ranging. The author suggests that knowledge - that is to say 'what we know' - can scarcely be understood and managed even by ourselves, much less by means of sophisticated information and communications (ie groupware and shareware technologies. We have progressed from the industrial age through the information age into what is being promoted as the 'golden age' of knowledge and, in the process, we've been led to believe that information contains meaning - rather than just standing for, provoking or evoking meaning in others. The paper argues that unless we take the trouble to face and understand the significance and implications of i=0 (ie that information has no intrinsic meaning and that knowledge is the uniquely human capability of making meaning from information - ideally in face-to-face relationships with other human beings - we may never emerge into any 'golden' age at all! The consequences of i=0 for communications, learning, safety, quality, management (itself, and winning work are also discussed.

The Unfolded Protein Response in Chronic Obstructive Pulmonary Disease.

Science.gov (United States)

Kelsen, Steven G

2016-04-01

Accumulation of nonfunctional and potentially cytotoxic, misfolded proteins in chronic obstructive pulmonary disease (COPD) is believed to contribute to lung cell apoptosis, inflammation, and autophagy. Because of its fundamental role as a quality control system in protein metabolism, the "unfolded protein response" (UPR) is of potential importance in the pathogenesis of COPD. The UPR comprises a series of transcriptional, translational, and post-translational processes that decrease protein synthesis while enhancing protein folding capacity and protein degradation. Several studies have suggested that the UPR contributes to lung cell apoptosis and lung inflammation in at least some subjects with human COPD. However, information on the prevalence of the UPR in subjects with COPD, the lung cells that manifest a UPR, and the role of the UPR in the pathogenesis of COPD is extremely limited and requires additional study.

Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage

Directory of Open Access Journals (Sweden)

Cheng Ji

2015-06-01

Full Text Available Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.

Algebraic description of intrinsic modes in nuclei

International Nuclear Information System (INIS)

Leviatan, A.

1989-01-01

We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. 28 refs., 1 fig

Roles of endoplasmic reticulum stress and unfolded protein response associated genes in seed stratification and bud endodormancy during chilling accumulation in Prunus persica.

Directory of Open Access Journals (Sweden)

Xi Ling Fu

Full Text Available Dormancy mechanisms in seeds and buds arrest growth until environmental conditions are optimal for development. A genotype-specific period of chilling is usually required to release dormancy, but the underlying molecular mechanisms are still not fully understood. To discover transcriptional pathways associated with dormancy release common to seed stratification and bud endodormancy, we explored the chilling-dependent expression of 11 genes involved in endoplasmic reticulum stress and the unfolded protein response signal pathways. We propose that endoplasmic reticulum stress and the unfolded protein response impact on seed as well as bud germination and development by chilling-dependent mechanisms. The emerging discovery of similarities between seed stratification and bud endodormancy status indicate that these two processes are probably regulated by common endoplasmic reticulum stress and unfolded protein response signalling pathways. Clarification of regulatory pathways common to both seed and bud dormancy may enhance understanding of the mechanisms underlying dormancy and breeding programs may benefit from earlier prediction of chilling requirements for uniform blooming of novel genotypes of deciduous fruit tree species.

It's about time: Earlier rewards increase intrinsic motivation.

Science.gov (United States)

Woolley, Kaitlin; Fishbach, Ayelet

2018-06-01

Can immediate (vs. delayed) rewards increase intrinsic motivation? Prior research compared the presence versus absence of rewards. By contrast, this research compared immediate versus delayed rewards, predicting that more immediate rewards increase intrinsic motivation by creating a perceptual fusion between the activity and its goal (i.e., the reward). In support of the hypothesis, framing a reward from watching a news program as more immediate (vs. delayed) increased intrinsic motivation to watch the program (Study 1), and receiving more immediate bonus (vs. delayed, Study 2; and vs. delayed and no bonus, Study 3) increased intrinsic motivation in an experimental task. The effect of reward timing was mediated by the strength of the association between an activity and a reward, and was specific to intrinsic (vs. extrinsic) motivation-immediacy influenced the positive experience of an activity, but not perceived outcome importance (Study 4). In addition, the effect of the timing of rewards was independent of the effect of the magnitude of the rewards (Study 5). (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Photovoltaic device comprising compositionally graded intrinsic photoactive layer

Science.gov (United States)

Hoffbauer, Mark A; Williamson, Todd L

2013-04-30

Photovoltaic devices and methods of making photovoltaic devices comprising at least one compositionally graded photoactive layer, said method comprising providing a substrate; growing onto the substrate a uniform intrinsic photoactive layer having one surface disposed upon the substrate and an opposing second surface, said intrinsic photoactive layer consisting essentially of In.sub.1-xA.sub.xN,; wherein: i. 0.ltoreq.x.ltoreq.1; ii. A is gallium, aluminum, or combinations thereof; and iii. x is at least 0 on one surface of the intrinsic photoactive layer and is compositionally graded throughout the layer to reach a value of 1 or less on the opposing second surface of the layer; wherein said intrinsic photoactive layer is isothermally grown by means of energetic neutral atom beam lithography and epitaxy at a temperature of 600.degree. C. or less using neutral nitrogen atoms having a kinetic energy of from about 1.0 eV to about 5.0 eV, and wherein the intrinsic photoactive layer is grown at a rate of from about 5 nm/min to about 100 nm/min.

Management Control, Intrinsic Motivation and Creativity

DEFF Research Database (Denmark)

Godt Gregersen, Mikkel

This thesis consists of a cape and three papers. The overall research question is: How can intrinsic motivation and management control coexist in a creative environment and how can coordination be possible in such a context? The cape ties together the research done in the three papers....... It is divided into six sections. The first section introduces the concepts of intrinsic motivation, creativity and management control. This is followed by a section on management control in a creative context. These two sections frame the thesis and introduce the setting in which the research has been done...... of the conclusion is that intrinsic motivation and management control can coexist under the conditions that all three basic needs, i.e. autonomy, competence and relatedness, are supported. This can happen when control takes point of departure in the individual employee. The second part of the conclusion...

Folding and unfolding phylogenetic trees and networks.

Science.gov (United States)

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.

Fine-Tuned Intrinsically Ultramicroporous Polymers Redefine the Permeability/Selectivity Upper Bounds of Membrane-Based Air and Hydrogen Separations

KAUST Repository

Swaidan, Raja

2015-08-20

Intrinsically ultramicroporous (<7 Å) polymers represent a new paradigm in materials development for membrane-based gas separation. In particular, they demonstrate that uniting intrachain “rigidity”, the traditional design metric of highly permeable polymers of intrinsic microporosity (PIMs), with gas-sieving ultramicroporosity yields high-performance gas separation membranes. Highly ultramicroporous PIMs have redefined the state-of-the-art in large-scale air (e.g., O2/N2) and hydrogen recovery (e.g., H2/N2, H2/CH4) applications with unprecedented molecular sieving gas transport properties. Accordingly, presented herein are new 2015 permeability/selectivity “upper bounds” for large-scale commercial membrane-based air and hydrogen applications that accommodate the substantial performance enhancements of recent PIMs over preceding polymers. A subtle balance between intrachain rigidity and interchain spacing has been achieved in the amorphous microstructures of PIMs, fine-tuned using unique bridged-bicyclic building blocks (i.e., triptycene, ethanoanthracene and Tröger’s base) in both ladder and semiladder (e.g., polyimide) structures.

Intrinsic Losses Based on Information Geometry and Their Applications

Directory of Open Access Journals (Sweden)

Yao Rong

2017-08-01

Full Text Available One main interest of information geometry is to study the properties of statistical models that do not depend on the coordinate systems or model parametrization; thus, it may serve as an analytic tool for intrinsic inference in statistics. In this paper, under the framework of Riemannian geometry and dual geometry, we revisit two commonly-used intrinsic losses which are respectively given by the squared Rao distance and the symmetrized Kullback–Leibler divergence (or Jeffreys divergence. For an exponential family endowed with the Fisher metric and α -connections, the two loss functions are uniformly described as the energy difference along an α -geodesic path, for some α ∈ { − 1 , 0 , 1 } . Subsequently, the two intrinsic losses are utilized to develop Bayesian analyses of covariance matrix estimation and range-spread target detection. We provide an intrinsically unbiased covariance estimator, which is verified to be asymptotically efficient in terms of the intrinsic mean square error. The decision rules deduced by the intrinsic Bayesian criterion provide a geometrical justification for the constant false alarm rate detector based on generalized likelihood ratio principle.

Intrinsic and Extrinsic Neuromodulation of Olfactory Processing.

Science.gov (United States)

Lizbinski, Kristyn M; Dacks, Andrew M

2017-01-01

Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons that participate in network coding) or an extrinsic origin (i.e., neurons from independent networks). In this conceptual dichotomy, intrinsic sources of neuromodulation provide a "memory" by adjusting network dynamics based upon previous and ongoing activation of the network itself, while extrinsic neuromodulators provide the context of ongoing activity of other neural networks. Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. In this review, we discuss intrinsic and extrinsic modulation in the context of olfactory processing in invertebrate and vertebrate model systems. We begin by discussing presynaptic modulation of olfactory sensory neurons by local interneurons (LNs) as a mechanism for gain control based on ongoing network activation. We then discuss the cell-class specific effects of serotonergic centrifugal neurons on olfactory processing. Finally, we briefly discuss the integration of intrinsic and extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting global control over olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this review as the effects of both intrinsic and extrinsic modulation are generally non-uniform.

Some chaotic features of intrinsically coupled Josephson junctions

International Nuclear Information System (INIS)

Kolahchi, M.R.; Shukrinov, Yu.M.; Hamdipour, M.; Botha, A.E.; Suzuki, M.

2013-01-01

Highlights: ► Intrinsically coupled Josephson junctions model a high-T c superconductor. ► Intrinsically coupled Josephson junctions can act as a chaotic nonlinear system. ► Chaos could be due to resonance overlap. ► Avoiding parameters that lead to chaos is important for the design of resonators. -- Abstract: We look for chaos in an intrinsically coupled system of Josephson junctions. This study has direct applications for the high-T c resonators which require coherence amongst the junctions

The identification of unfolding facial expressions.

Science.gov (United States)

Fiorentini, Chiara; Schmidt, Susanna; Viviani, Paolo

2012-01-01

We asked whether the identification of emotional facial expressions (FEs) involves the simultaneous perception of the facial configuration or the detection of emotion-specific diagnostic cues. We recorded at high speed (500 frames s-1) the unfolding of the FE in five actors, each expressing six emotions (anger, surprise, happiness, disgust, fear, sadness). Recordings were coded every 10 frames (20 ms of real time) with the Facial Action Coding System (FACS, Ekman et al 2002, Salt Lake City, UT: Research Nexus eBook) to identify the facial actions contributing to each expression, and their intensity changes over time. Recordings were shown in slow motion (1/20 of recording speed) to one hundred observers in a forced-choice identification task. Participants were asked to identify the emotion during the presentation as soon as they felt confident to do so. Responses were recorded along with the associated response times (RTs). The RT probability density functions for both correct and incorrect responses were correlated with the facial activity during the presentation. There were systematic correlations between facial activities, response probabilities, and RT peaks, and significant differences in RT distributions for correct and incorrect answers. The results show that a reliable response is possible long before the full FE configuration is reached. This suggests that identification is reached by integrating in time individual diagnostic facial actions, and does not require perceiving the full apex configuration.

A multi-state coarse grained modeling approach for an intrinsically disordered peptide

Science.gov (United States)

Ramezanghorbani, Farhad; Dalgicdir, Cahit; Sayar, Mehmet

2017-09-01

Many proteins display a marginally stable tertiary structure, which can be altered via external stimuli. Since a majority of coarse grained (CG) models are aimed at structure prediction, their success for an intrinsically disordered peptide's conformational space with marginal stability and sensitivity to external stimuli cannot be taken for granted. In this study, by using the LKα 14 peptide as a test system, we demonstrate a bottom-up approach for constructing a multi-state CG model, which can capture the conformational behavior of this peptide in three distinct environments with a unique set of interaction parameters. LKα 14 is disordered in dilute solutions; however, it strictly adopts the α -helix conformation upon aggregation or when in contact with a hydrophobic/hydrophilic interface. Our bottom-up approach combines a generic base model, that is unbiased for any particular secondary structure, with nonbonded interactions which represent hydrogen bonds, electrostatics, and hydrophobic forces. We demonstrate that by using carefully designed all atom potential of mean force calculations from all three states of interest, one can get a balanced representation of the nonbonded interactions. Our CG model behaves intrinsically disordered in bulk water, folds into an α -helix in the presence of an interface or a neighboring peptide, and is stable as a tetrameric unit, successfully reproducing the all atom molecular dynamics simulations and experimental results.

Characterization of the intrinsic density profiles for liquid surfaces

International Nuclear Information System (INIS)

Chacon, Enrique; Tarazona, Pedro

2005-01-01

This paper presents recent advances in the characterization of the intrinsic structures in computer simulations of liquid surfaces. The use of operational definitions for the intrinsic surface, associated with each molecular configuration of a liquid slab, gives direct access to the intrinsic profile and to the wavevector dependent surface tension. However, the characteristics of these functions depend on the definition used for the intrinsic surface. We discuss the pathologies associated with a local Gibbs dividing surface definition, and consider the alternative definition of a minimal area surface, going though a set of surface pivots, self-consistently chosen to represent the first liquid layer

Bacteria, the endoplasmic reticulum and the unfolded protein response: friends or foes?

Science.gov (United States)

Celli, Jean; Tsolis, Renée M

2015-02-01

The unfolded protein response (UPR) is a cytoprotective response that is aimed at restoring cellular homeostasis following physiological stress exerted on the endoplasmic reticulum (ER), which also invokes innate immune signalling in response to invading microorganisms. Although it has been known for some time that the UPR is modulated by various viruses, recent evidence indicates that it also has multiple roles during bacterial infections. In this Review, we describe how bacteria interact with the ER, including how bacteria induce the UPR, how subversion of the UPR promotes bacterial proliferation and how the UPR contributes to innate immune responses against invading bacteria.

Tapping mode AFM study on the surface dynamics of a single glucose oxidase molecule on a Au(1 1 1) surface in water with implication for a surface-induced unfolding pathway

International Nuclear Information System (INIS)

Otsuka, Ichiro; Yaoita, Masashi; Higano, Michi; Nagashima, Seiiichi; Kataoka, Ryoichi

2004-01-01

We have investigated a surface-induced unfolding dynamics of a single glucose oxidase (GO) molecule on Au(1 1 1) in air-saturated water, using tapping mode atomic force microscopy (TMAFM). We followed the unfolding process by measuring the maximum height of a well-isolated GO molecule on a terrace near a step-edge of the surface as a function of contact time. We find three linear portions with two intersections in a power-law fit to the selected values of the observed heights. The kinetic TMAFM result implies that there exist at least two distinct dynamic regimes in the unfolding

Intrinsic colony conditions affect the provisioning and oviposition process in the stingless bee Melipona scutellaris.

Science.gov (United States)

Pereira, R A; Morais, M M; Nascimento, F S; Bego, L R

2009-01-01

The cell provisioning and oviposition process (POP) is a unique characteristic of stingless bees (Meliponini), in which coordinated interactions between workers and queen regulate the filling of brood cells with larval resources and subsequent egg laying. Environmental conditions seem to regulate reproduction in stingless bees; however, little is known about how the amount of food affects quantitative sequences of the process. We examined intrinsic variables by comparing three colonies in distinct conditions (strong, intermediate and weak state). We predicted that some of these variables are correlated with temporal events of POP in Melipona scutellaris colonies. The results demonstrated that the strong colony had shorter periods of POP.

Separating intrinsic from extrinsic fluctuations in dynamic biological systems.

Science.gov (United States)

Hilfinger, Andreas; Paulsson, Johan

2011-07-19

From molecules in cells to organisms in ecosystems, biological populations fluctuate due to the intrinsic randomness of individual events and the extrinsic influence of changing environments. The combined effect is often too complex for effective analysis, and many studies therefore make simplifying assumptions, for example ignoring either intrinsic or extrinsic effects to reduce the number of model assumptions. Here we mathematically demonstrate how two identical and independent reporters embedded in a shared fluctuating environment can be used to identify intrinsic and extrinsic noise terms, but also how these contributions are qualitatively and quantitatively different from what has been previously reported. Furthermore, we show for which classes of biological systems the noise contributions identified by dual-reporter methods correspond to the noise contributions predicted by correct stochastic models of either intrinsic or extrinsic mechanisms. We find that for broad classes of systems, the extrinsic noise from the dual-reporter method can be rigorously analyzed using models that ignore intrinsic stochasticity. In contrast, the intrinsic noise can be rigorously analyzed using models that ignore extrinsic stochasticity only under very special conditions that rarely hold in biology. Testing whether the conditions are met is rarely possible and the dual-reporter method may thus produce flawed conclusions about the properties of the system, particularly about the intrinsic noise. Our results contribute toward establishing a rigorous framework to analyze dynamically fluctuating biological systems.

Annotation of Selaginella moellendorffii major intrinsic proteins and the evolution of the protein family in terrestrial plants

Directory of Open Access Journals (Sweden)

Hanna Isa Anderberg

2012-02-01

Full Text Available Major intrinsic proteins (MIPs also called aquaporins form pores in membranes to facilitate the permeation of water and certain small polar solutes across membranes. MIPs are present in virtually every organism but are uniquely abundant in land plants. To elucidate the evolution and function of MIPs in terrestrial plants, the MIPs encoded in the genome of the spikemoss Selaginella moellendorffii were identified and analyzed. In total 19 MIPs were found in S. moellendorffii belonging to six of the seven MIP subfamilies previously identified in the moss Physcomitrella patens. Only three of the MIPs were classified as members of the conserved water specific plasma membrane intrinsic protein (PIP subfamily whereas almost half were found to belong to the diverse NOD26-like intrinsic protein (NIP subfamily permeating various solutes. The small number of PIPs in S. moellendorffii is striking compared to all other land plants and no other species has more NIPs than PIPs. Similar to moss, S. moellendorffii only has one type of tonoplast intrinsic protein (TIP. Based on ESTs from non-angiosperms we conclude that the specialized groups of TIPs present in higher plants are not found in primitive vascular plants but evolved later in a common ancestor of seed plants. We also note that the silicic acid permeable NIP2 group that has been reported from angiosperms appears at the same time. We suggest that the expansion of the number MIP isoforms in higher plants is primarily associated with an increase in the different types of specialized tissues rather than the emergence of vascular tissue per se and that the loss of subfamilies has been possible due to a functional overlap between some subfamilies.

Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis

DEFF Research Database (Denmark)

Martel, Britta Cathrina; Litman, Thomas; Hald, Andreas

2016-01-01

Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared...... with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among...... patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD....

Management Control, Intrinsic Motivation and Creativity

OpenAIRE

Gregersen, Mikkel Godt

2017-01-01

This thesis consists of a cape and three papers. The overall research question is: How can intrinsic motivation and management control coexist in a creative environment and how can coordination be possible in such a context? The cape ties together the research done in the three papers. It is divided into six sections. The first section introduces the concepts of intrinsic motivation, creativity and management control. This is followed by a section on management control in a ...

Tunicamycin-induced unfolded protein response in the developing mouse brain

International Nuclear Information System (INIS)

Wang, Haiping; Wang, Xin; Ke, Zun-Ji; Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

2015-01-01

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific

Tunicamycin-induced unfolded protein response in the developing mouse brain

Energy Technology Data Exchange (ETDEWEB)

Wang, Haiping; Wang, Xin [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-Ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203 (China); Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo; Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

2015-03-15

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.

UNFOLDING LEONARDO DA VINCI’S GLOBE (AD 1504 TO REVEAL ITS HISTORICAL WORLD MAP

Directory of Open Access Journals (Sweden)

G. J. Verhoeven

2017-08-01

Full Text Available This paper reports in detail on the image-based modelling and unwrapping approach used to create a two-dimensional projected map of an astonishing ostrich egg globe from AD 1504. This miniature egg globe is not only the oldest extant engraved globe, but it is also the oldest post-Columbian globe of the world and the first ever to depict Newfoundland and many other territories. The intention of digitally recording the surface geometry and colour of this unique artefact was to portray the original layout of the world map used by the Florentine Renaissance artist to make this globe. In addition, it was expected to substantiate iconographical details, which are hard to study at its scale of 1:80,000,000. The ostrich egg globe is the prototype of the Lenox Globe kept at the New York Public Library. The latter is very beneficial to examine how the egg globe looked like before being glued together at its equator. On the other hand, unfolding the map engraved in the ostrich egg halves enables a more detailed study of the remarkable details visible on both globes, since the engravings on the quasi-white egg surface are much easier to discern than those of the highly reflective red copper Lenox Globe. Finally, a detailed study of the unwrapped 3D surface is essential to learn more about the world vision of its creator and the incredible efforts that went into making this globe. Thanks to some particular pictographic details as well as the way in which the engravings are applied (by a left-handed person, the globe artist can be identified as Leonardo da Vinci.

Instability-induced ordering, universal unfolding and the role of gravity in granular Couette flow

Science.gov (United States)

Alam, Meheboob; Arakeri, V. H.; Nott, P. R.; Goddard, J. D.; Herrmann, H. J.

2005-01-01

Linear stability theory and bifurcation analysis are used to investigate the role of gravity in shear-band formation in granular Couette flow, considering a kinetic-theory rheological model. We show that the only possible state, at low shear rates, corresponds to a "plug" near the bottom wall, in which the particles are densely packed and the shear rate is close to zero, and a uniformly sheared dilute region above it. The origin of such plugged states is shown to be tied to the spontaneous symmetry-breaking instabilities of the gravity-free uniform shear flow, leading to the formation of ordered bands of alternating dilute and dense regions in the transverse direction, via an infinite hierarchy of pitchfork bifurcations. Gravity plays the role of an "imperfection", thus destroying the "perfect" bifurcation structure of uniform shear. The present bifurcation problem admits universal unfolding of pitchfork bifurcations which subsequently leads to the formation of a sequence of a countably infinite number of "isolas", with the solution structures being a modulated version of their gravity-free counterpart. While the solution with a plug near the bottom wall looks remarkably similar to the shear-banding phenomenon in dense slow granular Couette flows, a "floating" plug near the top wall is also a solution of these equations at high shear rates. A two-dimensional linear stability analysis suggests that these floating plugged states are unstable to long-wave travelling disturbances.The unique solution having a bottom plug can also be unstable to long waves, but remains stable at sufficiently low shear rates. The implications and realizability of the present results are discussed in the light of shear-cell experiments under "microgravity" conditions.

Political-pedagogical unfoldings of bilingualism for deaf people: reflexions and directing

Directory of Open Access Journals (Sweden)

Sueli Fernandes

2009-09-01

Full Text Available The article talks about bilingualism for deaf people, it’s implications in the educational process, as well as in some of the inclusive linguistic politics unfoldings proposed officially from the end of the decade of 1990 for this segment. The sociocultural and linguistic characteristics of the Brazilian deaf people communities are argued and also the importance of the same ones to be known and socially valued. Some lines of direction and challenges are pointed for the access and remaining of the deaf students in the school educational process. Finally, the text reflects about the bilingual education programs for deaf students, considering that these are complex, specially because it crosses economic ideological, cultural contradictory and heterogeneous interests.

A dynamic birth-death model via Intrinsic Linkage

Directory of Open Access Journals (Sweden)

Robert Schoen

2013-05-01

Full Text Available BACKGROUND Dynamic population models, or models with changing vital rates, are only beginning to receive serious attention from mathematical demographers. Despite considerable progress, there is still no general analytical solution for the size or composition of a population generated by an arbitrary sequence of vital rates. OBJECTIVE The paper introduces a new approach, Intrinsic Linkage, that in many cases can analytically determine the birth trajectory of a dynamic birth-death population. METHODS Intrinsic Linkage assumes a weighted linear relationship between (i the time trajectory of proportional increases in births in a population and (ii the trajectory of the intrinsic rates of growth of the projection matrices that move the population forward in time. Flexibility is provided through choice of the weighting parameter, w, that links these two trajectories. RESULTS New relationships are found linking implied intrinsic and observed population patterns of growth. Past experience is "forgotten" through a process of simple exponential decay. When the intrinsic growth rate trajectory follows a polynomial, exponential, or cyclical pattern, the population birth trajectory can be expressed analytically in closed form. Numerical illustrations provide population values and relationships in metastable and cyclically stable models. Plausible projection matrices are typically found for a broad range of values of w, although w appears to vary greatly over time in actual populations. CONCLUSIONS The Intrinsic Linkage approach extends current techniques for dynamic modeling, revealing new relationships between population structures and the changing vital rates that generate them.

Exploring the link between intrinsic motivation and quality

Science.gov (United States)

Christy, Steven M.

1992-12-01

This thesis proposes that it is workers' intrinsic motivation that leads them to produce quality work. It reviews two different types of evidence- expert opinion and empirical studies--to attempt to evaluate a link between intrinsic motivation and work quality. The thesis reviews the works of Total Quality writers and behavioral scientists for any connection they might have made between intrinsic motivation and quality. The thesis then looks at the works of Deming and his followers in an attempt to establish a match between Deming's motivational assumptions and the four task rewards in the Thomas/Tymon model of intrinsic motivation: choice, competence, meaningfulness, and progress. Based upon this analysis, it is proposed that the four Thomas/Tymon task rewards are a promising theoretical foundation for explaining the motivational basis of quality for workers in Total Quality organizations.

Emerging Role of the Unfolded Protein Response in Tumor Immunosurveillance.

Science.gov (United States)

Vanacker, Hélène; Vetters, Jessica; Moudombi, Lyvia; Caux, Christophe; Janssens, Sophie; Michallet, Marie-Cécile

2017-07-01

Disruption of endoplasmic reticulum (ER) homeostasis results in ER stress and activation of the unfolded protein response (UPR). This response alleviates cell stress, and is activated in both tumor cells and tumor infiltrating immune cells. The UPR plays a dual function in cancer biology, acting as a barrier to tumorigenesis at the premalignant stage, while fostering cancer maintenance in established tumors. In infiltrating immune cells, the UPR has been involved in both immunosurveillance and immunosuppressive functions. This review aims to decipher the role of the UPR at different stages of tumorigenesis and how the UPR shapes the balance between immunosurveillance and immune escape. This knowledge may improve existing UPR-targeted therapies and the design of novel strategies for cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Unfolding and Refolding Embodiment into the Landscape of Ubiquitous Computing

DEFF Research Database (Denmark)

Schick, Lea; Malmborg, Lone

2009-01-01

This paper advocates the future of the body as a distributed and shared embodiment; an unfolded body that doesn’t end at one's skin, but emerges as intercorporeality between bodies and the technological environment. Looking at new tendencies within interaction design and ubiquitous computing to see...... how these are to an increasing extent focusing on sociality, context-awareness, relations, affects, connectedness, and collectivity we will examine how these new technological movements can change our perception of embodiment towards a distributed and shared one. By examining interactive textiles...... as part of a future rising landscape of multi-sensory networks we will exemplify how the new technologies can shutter dichotomies and challenge traditional notions of embodiment and the subject. Finally, we show how this ‘new embodiment’ manifests Deleuze’s philosophy of the body as something unstable...

Personality traits associated with intrinsic academic motivation in medical students.

Science.gov (United States)

Tanaka, Masaaki; Mizuno, Kei; Fukuda, Sanae; Tajima, Seiki; Watanabe, Yasuyoshi

2009-04-01

Motivation is one of the most important psychological concepts in education and is related to academic outcomes in medical students. In this study, the relationships between personality traits and intrinsic academic motivation were examined in medical students. The study group consisted of 119 Year 2 medical students at Osaka City University Graduate School of Medicine. They completed questionnaires dealing with intrinsic academic motivation (the Intrinsic Motivation Scale toward Learning) and personality (the Temperament and Character Inventory [TCI]). On simple regression analyses, the TCI dimensions of persistence, self-directedness, co-operativeness and self-transcendence were positively associated with intrinsic academic motivation. On multiple regression analysis adjusted for age and gender, the TCI dimensions of persistence, self-directedness and self-transcendence were positively associated with intrinsic academic motivation. The temperament dimension of persistence and the character dimensions of self-directedness and self-transcendence are associated with intrinsic academic motivation in medical students.

On the potential of using peculiarities of the protein intrinsic disorder distribution in mitochondrial cytochrome b to identify the source of animal meats

Science.gov (United States)

Yacoub, Haitham A.; Sadek, Mahmoud A.; Uversky, Vladimir N.

2017-01-01

ABSTRACT This study was conducted to identify the source of animal meat based on the peculiarities of protein intrinsic disorder distribution in mitochondrial cytochrome b (mtCyt-b). The analysis revealed that animal and avian species can be discriminated based on the proportions of the two groups of residues, Leu+Ile, and Ser+Pro+Ala, in the amino acid sequences of their mtCyt-b. Although levels of the overall intrinsic disorder in mtCyt-b is not very high, the peculiarities of disorder distribution within the sequences of mtCyt-b from different species varies in a rather specific way. In fact, positions and intensities of disorder/flexibility “signals” in the corresponding disorder profiles are relatively unique for avian and animal species. Therefore, it is possible to devise a set of simple rules based on the peculiarities of disorder profiles of their mtCyt-b proteins to discriminate among species. This intrinsic disorder-based analysis represents a new technique that could be used to provide a promising solution for identification of the source of meats. PMID:28331777

Sources of intrinsic rotation in the low-flow ordering

International Nuclear Information System (INIS)

Parra, Felix I.; Barnes, Michael; Catto, Peter J.

2011-01-01

A low flow, δf gyrokinetic formulation to obtain the intrinsic rotation profiles is presented. The momentum conservation equation in the low-flow ordering contains new terms, neglected in previous first-principles formulations, that may explain the intrinsic rotation observed in tokamaks in the absence of external sources of momentum. The intrinsic rotation profile depends on the density and temperature profiles and on the up-down asymmetry.

Catalogue of response spectra for unfolding in situ gamma-ray pulse-height distributions

International Nuclear Information System (INIS)

Dymke, N.

1982-01-01

To unfold in situ gamma-ray pulse-height distributions by means of a response matrix technique, the matrix must be in keeping with the measurement geometry, detector size, and energy range to be covered by the measurements. A methodology has been described for determination of standard gamma-ray spectra needed in deriving response matrices and a spectrum catalogue compiled containing graphs and data for the 0-3 MeV (4 x 4 in. NaI(Tl)) and 0-8 MeV (1.5 x 1.5 in. NaI(Tl)) ranges. (author)

Study of chemically unfolded β-casein by means of small-angle neutron scattering

International Nuclear Information System (INIS)

Aschi, Adel; Gharbi, Abdelhafidh; Daoud, Mohamed; Douillard, Roger; Calmettes, Patrick

2007-01-01

β-casein is a flexible amphiphilic milk protein which forms an unfolded conformation in presence of very high denaturant concentrations. The structure of β-casein formed at the bulk was studied by small-angle neutron scattering (SANS). The value of the second virial coefficient of the protein solutions indicates that the interactions between the polypeptide chain and solvent are repulsive. The protein conformation is similar to an excluded volume chain. The corresponding values of the contour length, L, the statistical length, b and the apparent radius of the chain cross-section, R c are given

Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

Directory of Open Access Journals (Sweden)

Daniela Marasco

2015-04-01

Full Text Available Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs.

Cooperative motion of intrinsic and actuated semiflexible swimmers

NARCIS (Netherlands)

Llopis, I.; Pagonabarraga, I.; Lagomarsino, M.C.; Lowe, C.P.

2013-01-01

We examine the phenomenon of hydrodynamic-induced cooperativity for pairs of flagellated micro-organism swimmers, of which spermatozoa cells are an example. We consider semiflexible swimmers, where inextensible filaments are driven by an internal intrinsic force and torque-free mechanism (intrinsic

Intrinsic rotation produced by ion orbit loss and X-loss

Energy Technology Data Exchange (ETDEWEB)

Stacey, W. M. [Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); Boedo, J. A. [University of California - San Diego, San Diego, California 92093 (United States); Evans, T. E.; Groebner, R. J. [General Atomics, San Diego, California 92186 (United States); Grierson, B. A. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08453 (United States)

2012-11-15

A practical calculation model for the intrinsic rotation imparted to the edge plasma by the directionally preferential loss of ions on orbits that cross the last closed flux surface is presented and applied to calculate intrinsic rotation in several DIII-D [J. Luxon, Nucl. Fusion 42, 614 (2002)] discharges. The intrinsic rotation produced by ion loss is found to be sensitive to the edge temperature and radial electric field profiles, which has implications for driving intrinsic rotation in future large tokamaks.

Positioning the Intracellular Salt Potassium Glutamate in the Hofmeister Series by Chemical Unfolding Studies of NTL9.

Science.gov (United States)

Sengupta, Rituparna; Pantel, Adrian; Cheng, Xian; Shkel, Irina; Peran, Ivan; Stenzoski, Natalie; Raleigh, Daniel P; Record, M Thomas

2016-04-19

In vitro, replacing KCl with potassium glutamate (KGlu), the Escherichia coli cytoplasmic salt and osmolyte, stabilizes folded proteins and protein-nucleic acid complexes. To understand the chemical basis for these effects and rank Glu- in the Hofmeister anion series for protein unfolding, we quantify and interpret the strong stabilizing effect of KGlu on the ribosomal protein domain NTL9, relative to the effects of other stabilizers (KCl, KF, and K2SO4) and destabilizers (GuHCl and GuHSCN). GuHSCN titrations at 20 ° C, performed as a function of the concentration of KGlu or another salt and monitored by NTL9 fluorescence, are analyzed to obtain R-values quantifying the Hofmeister salt concentration (m3) dependence of the unfolding equilibrium constant K(obs) [r-value = −d ln K(obs)/dm3 = (1/RT) dΔG(obs) ° /dm3 = m-value/RT]. r-Values for both stabilizing K+ salts and destabilizing GuH+ salts are compared with predictions from model compound data. For two-salt mixtures, we find that contributions of stabilizing and destabilizing salts to observed r-values are additive and independent. At 20 ° C, we determine a KGlu r-value of 3.22 m(−1) and K2SO4, KF, KCl, GuHCl, and GuHSCN r-values of 5.38, 1.05, 0.64, −1.38, and −3.00 m(−1), respectively. The KGlu r-value represents a 25-fold (1.9 kcal) stabilization per molal KGlu added. KGlu is much more stabilizing than KF, and the stabilizing effect of KGlu is larger in magnitude than the destabilizing effect of GuHSCN. Interpretation of the data reveals good agreement between predicted and observed relative r-values and indicates the presence of significant residual structure in GuHSCN-unfolded NTL9 at 20 ° C.

Differential scanning microcalorimetry of intrinsically disordered proteins.

Science.gov (United States)

Permyakov, Sergei E

2012-01-01

Ultrasensitive differential scanning calorimetry (DSC) is an indispensable thermophysical technique enabling to get direct information on enthalpies accompanying heating/cooling of dilute biopolymer solutions. The thermal dependence of protein heat capacity extracted from DSC data is a valuable source of information on intrinsic disorder level of a protein. Application details and limitations of DSC technique in exploration of protein intrinsic disorder are described.

Quantitative assessment of the infarct size with the unfolded map method of sup 201 Tl myocardial SPECT in patient with acute myocardial infarction

Energy Technology Data Exchange (ETDEWEB)

Kubota, Masahiro (Sapporo Medical Coll. (Japan))

1992-03-01

The unfolded map method of {sup 201}Tl single photon emission computed tomography (SPECT) was evaluated as to the ability to quantify and the clinical reliability in estimation of infarct size. The following results were obtained from basic experiments using a thoracic phantom. The defect area estimated by the unfolded map method was well correlated with the real defect area, in spite of overestimation of the defect area, when the defect area was determined by an isocount method (below 80% of maximum count) (y=1.941 + 2.292x, r=0.971). The defect volume estimated by short-axis images of {sup 201}Tl SPECT was closely correlated with real defect volume in spite of overestimation of defect volume (y=0.762 + 2.156x, r=0.982). When the defect area was estimated by division of the defect volume by the mean myocardial compartment thickness, it was closely correlated with real defect area (y=0.946 + 1.232x, r=0.990). When the volume was calculated from the summation of voxels in the regions districted by isocount threshold level at each section of the {sup 99m}Tc SPECT, the optimal isocount threshold level (percentage to maximum count) was 55%. Then, the clinical reliability of the unfolded map method as infarct sizing was evaluated in 26 patients with acute myocardial infarction by comparing it with enzymatic method, Bull's eye method, and {sup 99m}Tc pyrophosphate (PYP) SPECT method. In 14 first attack patients without right ventricular infarction, infarct area (IA) of the unfolded map method correlated most closely with the accumulated creatine kinase MB isoenzyme release (CK-MBr) (r=0.897), compared with the extent score (ES) (r=0.853) and the severity score (SS) (r=0.871) of Bull's eye method and the infarct volume (IV) (r=0.595) of {sup 99m}Tc PYP SPECT. In conclusion, although the unfolded map method of {sup 201}Tl SPECT has the tendency for overestimating infarct size, it is accurate and clinically reliable in estimating infarct size. (author).

Functional Anthology of Intrinsic Disorder. III. Ligands, Postranslational Modifications and Diseases Associated with Intrinsically Disordered Proteins

Science.gov (United States)

Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

2008-01-01

Currently, the understanding of the relationships between function, amino acid sequence and protein structure continues to represent one of the major challenges of the modern protein science. As much as 50% of eukaryotic proteins are likely to contain functionally important long disordered regions. Many proteins are wholly disordered but still possess numerous biologically important functions. However, the number of experimentally confirmed disordered proteins with known biological functions is substantially smaller than their actual number in nature. Therefore, there is a crucial need for novel bioinformatics approaches that allow projection of the current knowledge from a few experimentally verified examples to much larger groups of known and potential proteins. The elaboration of a bioinformatics tool for the analysis of functional diversity of intrinsically disordered proteins and application of this data mining tool to >200,000 proteins from Swiss-Prot database, each annotated with at least one of the 875 functional keywords was described in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Using this tool, we have found that out of the 711 Swiss-Prot functional keywords associated with at least 20 proteins, 262 were strongly positively correlated with long intrinsically disordered regions, and 302 were strongly negatively correlated. Illustrative examples of functional disorder or order were found for the vast majority of keywords showing strongest positive or negative correlation with intrinsic disorder, respectively. Some 80 Swiss-Prot keywords associated with disorder- and order-driven biological processes and protein functions were described in the first paper (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic

Binding properties of a streptavidin layer formed on a biotinylated Langmuir–Schaefer film of unfolded protein

Energy Technology Data Exchange (ETDEWEB)

Furuno, Taiji, E-mail: t_furuno@a8.keio.jp

2016-04-01

A Langmuir monolayer of carbonic anhydrase (CA) unfolded at an air/water interface was transferred onto the hydrophobic surface of a silicon wafer by means of the Langmuir–Schaefer technique. The transferred CA film was biotinylated and was incubated in a streptavidin (SAv) solution to obtain a densely packed SAv layer by biotin–SAv linkage. Biotinylated proteins including ferritin, catalase, alcohol dehydrogenase, and carbonic anhydrase were incubated with the SAv layer and binding of these proteins was examined by atomic force microscopy. High-density binding of the biotinylated proteins was observed, whereas the amount of adsorbed non-biotinylated proteins was low or negligible. The SAv layer on the Langmuir–Schaefer film of unfolded protein could become a basic architecture for protein immobilization studies. - Highlights: • Langmuir–Schaefer film of carbonic anhydrase (LSF-CA) was biotinylated. • A densely packed streptavidin (SAv) layer was formed on the biotinylated LSF-CA. • Biotinylated proteins were bound to the SAv layer at high density. • Nonspecific adsorption of intact proteins to the SAv layer was weak. • Atomic force microscopy showed the binding of proteins at molecular resolution.

The intrinsic stochasticity of near-integrable Hamiltonian systems

Energy Technology Data Exchange (ETDEWEB)

Krlin, L [Ceskoslovenska Akademie Ved, Prague (Czechoslovakia). Ustav Fyziky Plazmatu

1989-09-01

Under certain conditions, the dynamics of near-integrable Hamiltonian systems appears to be stochastic. This stochasticity (intrinsic stochasticity, or deterministic chaos) is closely related to the Kolmogorov-Arnold-Moser (KAM) theorem of the stability of near-integrable multiperiodic Hamiltonian systems. The effect of the intrinsic stochasticity attracts still growing attention both in theory and in various applications in contemporary physics. The paper discusses the relation of the intrinsic stochasticity to the modern ergodic theory and to the KAM theorem, and describes some numerical experiments on related astrophysical and high-temperature plasma problems. Some open questions are mentioned in conclusion. (author).

Informationally administered reward enhances intrinsic motivation in schizophrenia.

Science.gov (United States)

Lee, Hyeon-Seung; Jang, Seon-Kyeong; Lee, Ga-Young; Park, Seon-Cheol; Medalia, Alice; Choi, Kee-Hong

2017-10-01

Even when individuals with schizophrenia have an intact ability to enjoy rewarding moments, the means to assist them to translate rewarding experiences into goal-directed behaviors is unclear. The present study sought to determine whether informationally administered rewards enhance intrinsic motivation to foster goal-directed behaviors in individuals with schizophrenia (SZ) and healthy controls (HCs). Eighty-four participants (SZ=43, HCs=41) were randomly assigned to conditions involving either a performance-contingent reward with an informationally administered reward or a task-contingent reward with no feedback. Participants were asked to play two cognitive games of equalized difficulty. Accuracy, self-reported intrinsic motivation, free-choice intrinsic motivation (i.e., game play during a free-choice observation period), and perceived competency were measured. Intrinsic motivation and perceived competency in the cognitive games were similar between the two participant groups. The informationally administered reward significantly enhanced self-reported intrinsic motivation and perceived competency in both the groups. The likelihood that individuals with schizophrenia would play the game during the free-choice observation period was four times greater in the informationally administered reward condition than that in the no-feedback condition. Our findings suggest that, in the context of cognitive remediation, individuals with schizophrenia would benefit from informationally administered rewards. Copyright © 2017 Elsevier B.V. All rights reserved.

Unfolded Protein Response Signaling and MAP Kinase Pathways Underlie Pathogenesis of Arsenic-induced Cutaneous Inflammation

OpenAIRE

Li, Changzhao; Xu, Jianmin; Li, Fugui; Chaudhary, Sandeep C.; Weng, Zhiping; Wen, Jianming; Elmets, Craig A.; Ahsan, Habibul; Athar, Mohammad

2011-01-01

Arsenic exposure through drinking water is a major global public health problem and is associated with an enhanced risk of various cancers including skin cancer. In human skin, arsenic induces precancerous melanosis and keratosis, which may progress to basal cell and squamous cell carcinoma. However, the mechanism by which these pathophysiological alterations occur remains elusive. In this study, we showed that sub-chronic arsenic exposure to SKH-1 mice induced unfolded protein response (UPR)...

The unfolded protein response is required for dendrite morphogenesis

Science.gov (United States)

Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

2015-01-01

Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.06963.001 PMID:26052671

The effects of extrinsic rewards on children's intrinsic motivation

OpenAIRE

大槻, 千秋

1981-01-01

An experiment was conducted with preschool children to test whether a person's intrinsic motivation in an activity may be decreased by extrinsic salient rewards in Japan like in America. Children solved some jigsaw puzzles and received assorted candies, then they were observed how long they did other jigsaw puzzles. The results showed that the effects of extrinsic rewards on intrinsic motivation in an activity varied with the subject's social background. In uptown children's intrinsic motivat...

Self-perception of intrinsic and extrinsic motivation.

Science.gov (United States)

Calder, B J; Staw, B M

1975-04-01

Self-perception theory predicts that intrinsic and extrinsic motivation do not combine additively but rather interact. To test this predicted interaction, intrinsic and extrinsic motivation were both manipulated as independent variables. The results revealed a significant interaction for task satisfaction and a trend for the interaction on a behavioral measure. These results are discussed in terms of a general approach to the self-perception of motivation.

Do people differentiate between intrinsic and extrinsic goals for physical activity?

Science.gov (United States)

McLachlan, Sarah; Hagger, Martin S

2011-04-01

The distinction between intrinsic and extrinsic goals, and between goal pursuit for intrinsically and extrinsically motivated reasons, is a central premise of self-determination theory. Proponents of the theory have proposed that the pursuit of intrinsic goals and intrinsically motivated goal striving each predict adaptive psychological and behavioral outcomes relative to the pursuit of extrinsic goals and extrinsically motivated goal striving. Despite evidence to support these predictions, research has not explored whether individuals naturally differentiate between intrinsic and extrinsic goals. Two studies tested whether people make this differentiation when recalling goals for leisure-time physical activity. Using memory-recall methods, participants in Study 1 were asked to freely generate physical activity goals. A subsample (N = 43) was asked to code their freely generated goals as intrinsic or extrinsic. In Study 2, participants were asked to recall intrinsic and extrinsic goals after making a decision regarding their future physical activity. Results of these studies revealed that individuals' goal generation and recall exhibited significant clustering by goal type. Participants encountered some difficulties when explicitly coding goals. Findings support self-determination theory and indicate that individuals discriminate between intrinsic and extrinsic goals.

Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

Energy Technology Data Exchange (ETDEWEB)

Li, Chunhua [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States); Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Su, Jiguo, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [College of Science, Yanshan University, Qinhuangdao 066004 (China); Zhang, Yang, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States)

2016-07-07

Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

Self-Determination Theory: Intrinsic Motivation and Behavioral Change.

Science.gov (United States)

Flannery, Marie

2017-03-01

Motivation is a central concept in behavioral change. This article reviews the self-determination theory with an emphasis on "intrinsic motivation," which is facilitated when three basic psychological needs (autonomy, competence, and relatedness) are met. Intrinsic motivation is associated with improved well-being and sustained behavioral change.

A model of intrinsic symmetry breaking

International Nuclear Information System (INIS)

Ge, Li; Li, Sheng; George, Thomas F.; Sun, Xin

2013-01-01

Different from the symmetry breaking associated with a phase transition, which occurs when the controlling parameter is manipulated across a critical point, the symmetry breaking presented in this Letter does not need parameter manipulation. Instead, the system itself suddenly undergoes symmetry breaking at a certain time during its evolution, which is intrinsic symmetry breaking. Through a polymer model, it is revealed that the origin of the intrinsic symmetry breaking is nonlinearity, which produces instability at the instance when the evolution crosses an inflexion point, where this instability breaks the original symmetry

Vesicle Encapsulation Studies Reveal that Single Molecule Ribozyme Heterogeneities Are Intrinsic

Science.gov (United States)

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

2004-01-01

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

Ethnic Stigma, Academic Anxiety, and Intrinsic Motivation in Middle Childhood

Science.gov (United States)

Gillen-O’Neel, Cari; Ruble, Diane N.; Fuligni, Andrew J.

2011-01-01

Previous research addressing the dynamics of stigma and academics has focused on African-American adolescents and adults. The present study examined stigma awareness, academic anxiety, and intrinsic motivation among 451 young (ages 6–11) and diverse (African-American, Chinese, Dominican, Russian, and European-American) students. Results indicated that ethnic-minority children reported higher stigma awareness than European-American children. For all children, stigma awareness was associated with higher academic anxiety and lower intrinsic motivation. Despite these associations, ethnic-minority children reported higher levels of intrinsic motivation than their European-American peers. A significant portion of the higher intrinsic motivation among Dominican students was associated with their higher levels of school belonging, suggesting that supportive school environments may be important sources of intrinsic motivation among some ethnic-minority children. PMID:21883152

Extrinsic and intrinsic regulation of axon regeneration at a crossroads.

Science.gov (United States)

Kaplan, Andrew; Ong Tone, Stephan; Fournier, Alyson E

2015-01-01

Repair of the injured spinal cord is a major challenge in medicine. The limited intrinsic regenerative response mounted by adult central nervous system (CNS) neurons is further hampered by astrogliosis, myelin debris and scar tissue that characterize the damaged CNS. Improved axon regeneration and recovery can be elicited by targeting extrinsic factors as well as by boosting neuron-intrinsic growth regulators. Our knowledge of the molecular basis of intrinsic and extrinsic regulators of regeneration has expanded rapidly, resulting in promising new targets to promote repair. Intriguingly certain neuron-intrinsic growth regulators are emerging as promising targets to both stimulate growth and relieve extrinsic inhibition of regeneration. This crossroads between the intrinsic and extrinsic aspects of spinal cord injury is a promising target for effective therapies for this unmet need.

Motivating crowding theory - opening the black box of intrinsic motivation

DEFF Research Database (Denmark)

Jacobsen, Christian Bøtcher

2010-01-01

Public employees work for many other reasons than because they are paid for it. In other words, intrinsic motivation is an important determinant for their performance. Nonetheless, public sector organizations increasingly rely on extrinsic motivation factors such as monetary incentives to motivate...... employees. Motivation crowding theory claims that this may be at the expense of intrinsic motivation, if the extrinsic motivation factor is perceived to be controlling. On the other hand, intrinsic motivation will be enhanced (crowded in), if the extrinsic motivation factor is perceived to be supportive......, monetary incentives are found to cause different crowding effects for these different types of intrinsic motivation. The results call for more theoretical work on the drivers of motivation crowding effects and for practitioners to pay more attention to what type of intrinsic motivation is at stake, when...

Intrinsic and extrinsic motivation for stereotypic and repetitive behavior.

Science.gov (United States)

Joosten, Annette V; Bundy, Anita C; Einfeld, Stewart L

2009-03-01

This study provides evidence for intrinsic and extrinsic motivators for stereotypical and repetitive behavior in children with autism and intellectual disability and children with intellectual disability alone. We modified the Motivation Assessment Scale (MAS) (1988b); dividing it into intrinsic and extrinsic measures and adding items to assess anxiety as an intrinsic motivator. Rasch analysis of data from 279 MASs (74 children) revealed that the items formed two unidimensional scales. Anxiety was a more likely intrinsic motivator than sensory seeking for children with dual diagnoses; the reverse was true for children with intellectual disability only. Escape and gaining a tangible object were the most common extrinsic motivators for those with dual diagnoses and attention and escape for children with intellectual disability.

Semantic Interoperable Electronic Patient Records: The Unfolding of Consensus based Archetypes.

Science.gov (United States)

Pedersen, Rune; Wynn, Rolf; Ellingsen, Gunnar

2015-01-01

This paper is a status report from a large-scale openEHR-based EPR project from the North Norway Regional Health Authority encouraged by the unfolding of a national repository for openEHR archetypes. Clinicians need to engage in, and be responsible for the production of archetypes. The consensus processes have so far been challenged by a low number of active clinicians, a lack of critical specialties to reach consensus, and a cumbersome review process (3 or 4 review rounds) for each archetype. The goal is to have several clinicians from each specialty as a backup if one is hampered to participate. Archetypes and their importance for structured data and sharing of information has to become more visible for the clinicians through more sharpened information practice.

Personalizing Sample Databases with Facebook Information to Increase Intrinsic Motivation

Science.gov (United States)

Marzo, Asier; Ardaiz, Oscar; Sanz de Acedo, María Teresa; Sanz de Acedo, María Luisa

2017-01-01

Motivation is fundamental for students to achieve successful and complete learning. Motivation can be extrinsic, i.e., driven by external rewards, or intrinsic, i.e., driven by internal factors. Intrinsic motivation is the most effective and must be inspired by the task at hand. Here, a novel strategy is presented to increase intrinsic motivation…

Easy and unambiguous sequential assignments of intrinsically disordered proteins by correlating the backbone 15N or 13C′ chemical shifts of multiple contiguous residues in highly resolved 3D spectra

International Nuclear Information System (INIS)

Yoshimura, Yuichi; Kulminskaya, Natalia V.; Mulder, Frans A. A.

2015-01-01

Sequential resonance assignment strategies are typically based on matching one or two chemical shifts of adjacent residues. However, resonance overlap often leads to ambiguity in resonance assignments in particular for intrinsically disordered proteins. We investigated the potential of establishing connectivity through the three-bond couplings between sequentially adjoining backbone carbonyl carbon nuclei, combined with semi-constant time chemical shift evolution, for resonance assignments of small folded and larger unfolded proteins. Extended sequential connectivity strongly lifts chemical shift degeneracy of the backbone nuclei in disordered proteins. We show here that 3D (H)N(COCO)NH and (HN)CO(CO)NH experiments with relaxation-optimized multiple pulse mixing correlate up to seven adjacent backbone amide nitrogen or carbonyl carbon nuclei, respectively, and connections across proline residues are also obtained straightforwardly. Multiple, recurrent long-range correlations with ultra-high resolution allow backbone 1 H N , 15 N H , and 13 C′ resonance assignments to be completed from a single pair of 3D experiments

A Unique ISR Program Determines Cellular Responses to Chronic Stress

Czech Academy of Sciences Publication Activity Database

Guan, B.J.; van Hoef, V.; Jobava, R.; Elroy-Stein, O.; Valášek, Leoš Shivaya; Cargnello, M.; Gao, X.H.; Krokowski, D.; Merrick, W.C.; Kimball, S.R.; Komar, A.A.; Koromilas, A.E.; Wynshaw-Boris, A.; Topisirovic, I.; Larsson, O.; Hatzoglou, M.

2017-01-01

Roč. 68, č. 5 (2017), s. 885-900 ISSN 1097-2765 R&D Projects: GA ČR(CZ) GA17-06238S EU Projects: Wellcome Trust(GB) 090812/B/09/A Institutional support: RVO:61388971 Keywords : UNFOLDED PROTEIN RESPONSE * EUKARYOTIC TRANSLATION INITIATION * ENDOPLASMIC-RETICULUM STRESS Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 14.714, year: 2016

Biomechanics and energetics of walking in powered ankle exoskeletons using myoelectric control versus mechanically intrinsic control.

Science.gov (United States)

Koller, Jeffrey R; Remy, C David; Ferris, Daniel P

2018-05-25

Controllers for assistive robotic devices can be divided into two main categories: controllers using neural signals and controllers using mechanically intrinsic signals. Both approaches are prevalent in research devices, but a direct comparison between the two could provide insight into their relative advantages and disadvantages. We studied subjects walking with robotic ankle exoskeletons using two different control modes: dynamic gain proportional myoelectric control based on soleus muscle activity (neural signal), and timing-based mechanically intrinsic control based on gait events (mechanically intrinsic signal). We hypothesized that subjects would have different measures of metabolic work rate between the two controllers as we predicted subjects would use each controller in a unique manner due to one being dependent on muscle recruitment and the other not. The two controllers had the same average actuation signal as we used the control signals from walking with the myoelectric controller to shape the mechanically intrinsic control signal. The difference being the myoelectric controller allowed step-to-step variation in the actuation signals controlled by the user's soleus muscle recruitment while the timing-based controller had the same actuation signal with each step regardless of muscle recruitment. We observed no statistically significant difference in metabolic work rate between the two controllers. Subjects walked with 11% less soleus activity during mid and late stance and significantly less peak soleus recruitment when using the timing-based controller than when using the myoelectric controller. While walking with the myoelectric controller, subjects walked with significantly higher average positive and negative total ankle power compared to walking with the timing-based controller. We interpret the reduced ankle power and muscle activity with the timing-based controller relative to the myoelectric controller to result from greater slacking effects

Intrinsic Density Matrices of the Nuclear Shell Model

International Nuclear Information System (INIS)

Deveikis, A.; Kamuntavichius, G.

1996-01-01

A new method for calculation of shell model intrinsic density matrices, defined as two-particle density matrices integrated over the centre-of-mass position vector of two last particles and complemented with isospin variables, has been developed. The intrinsic density matrices obtained are completely antisymmetric, translation-invariant, and do not employ a group-theoretical classification of antisymmetric states. They are used for exact realistic density matrix expansion within the framework of the reduced Hamiltonian method. The procedures based on precise arithmetic for calculation of the intrinsic density matrices that involve no numerical diagonalization or orthogonalization have been developed and implemented in the computer code. (author). 11 refs., 2 tabs

Changes in Intrinsic Motivation as a Function of Negative Feedback and Threats.

Science.gov (United States)

Deci, Edward L.; Cascio, Wayne F.

Recent studies have demonstrated that external rewards can affect intrinsic motivation to perform an activity. Money tends to decrease intrinsic motivation, whereas positive verbal reinforcements tend to increase intrinsic motivation. This paper presents evidence that negative feedback and threats of punishment also decrease intrinsic motivation.…

Palatalization and Intrinsic Prosodic Vowel Features in Russian

Science.gov (United States)

Ordin, Mikhail

2011-01-01

The presented study is aimed at investigating the interaction of palatalization and intrinsic prosodic features of the vowel in CVC (consonant+vowel+consonant) syllables in Russian. The universal nature of intrinsic prosodic vowel features was confirmed with the data from the Russian language. It was found that palatalization of the consonants…

Study of chemically unfolded {beta}-casein by means of small-angle neutron scattering

Energy Technology Data Exchange (ETDEWEB)

Aschi, Adel [Laboratoire de Physique de la Matiere Molle, Faculte des Sciences de Tunis, Campus Universitaire, 1060, Tunis (Tunisia)]. E-mail: aschi13@yahoo.fr; Gharbi, Abdelhafidh [Laboratoire de Physique de la Matiere Molle, Faculte des Sciences de Tunis, Campus Universitaire, 1060, Tunis (Tunisia); Daoud, Mohamed [Service de Physique de l' Etat Condense. CEA Saclay. 91191 Gif-sur-Yvette cedex (France); Douillard, Roger [Equipe de Biochimie des Macromolecules Vegetales, Centre de Recherche Agronomique, 2Esplanade R. Garros, BP 224, 51686 Reims cedex 2 (France); Calmettes, Patrick [Laboratoire Leon Brillouin, CEA Saclay, 91191 Gif-sur-Yvette cedex (France)

2007-01-01

{beta}-casein is a flexible amphiphilic milk protein which forms an unfolded conformation in presence of very high denaturant concentrations. The structure of {beta}-casein formed at the bulk was studied by small-angle neutron scattering (SANS). The value of the second virial coefficient of the protein solutions indicates that the interactions between the polypeptide chain and solvent are repulsive. The protein conformation is similar to an excluded volume chain. The corresponding values of the contour length, L, the statistical length, b and the apparent radius of the chain cross-section, R{sub c} are given.

Intrinsic respiratory gating in small-animal CT

International Nuclear Information System (INIS)

Bartling, Soenke H.; Dinkel, Julien; Kauczor, Hans-Ulrich; Stiller, Wolfram; Semmler, Wolfhard; Grasruck, Michael; Madisch, Ijad; Gupta, Rajiv; Kiessling, Fabian

2008-01-01

Gating in small-animal CT imaging can compensate artefacts caused by physiological motion during scanning. However, all published gating approaches for small animals rely on additional hardware to derive the gating signals. In contrast, in this study a novel method of intrinsic respiratory gating of rodents was developed and tested for mice (n=5), rats (n=5) and rabbits (n=2) in a flat-panel cone-beam CT system. In a consensus read image quality was compared with that of non-gated and retrospective extrinsically gated scans performed using a pneumatic cushion. In comparison to non-gated images, image quality improved significantly using intrinsic and extrinsic gating. Delineation of diaphragm and lung structure improved in all animals. Image quality of intrinsically gated CT was judged to be equivalent to extrinsically gated ones. Additionally 4D datasets were calculated using both gating methods. Values for expiratory, inspiratory and tidal lung volumes determined with the two gating methods were comparable and correlated well with values known from the literature. We could show that intrinsic respiratory gating in rodents makes additional gating hardware and preparatory efforts superfluous. This method improves image quality and allows derivation of functional data. Therefore it bears the potential to find wide applications in small-animal CT imaging. (orig.)

VELOCITY EVOLUTION AND THE INTRINSIC COLOR OF TYPE Ia SUPERNOVAE

International Nuclear Information System (INIS)

Foley, Ryan J.; Sanders, Nathan E.; Kirshner, Robert P.

2011-01-01

To understand how best to use observations of Type Ia supernovae (SNe Ia) to obtain precise and accurate distances, we investigate the relations between spectra of SNe Ia and their intrinsic colors. Using a sample of 1630 optical spectra of 255 SNe, based primarily on data from the CfA Supernova Program, we examine how the velocity evolution and line strengths of Si II λ6355 and Ca II H and K are related to the B – V color at peak brightness. We find that the maximum-light velocity of Si II λ6355 and Ca II H and K and the maximum-light pseudo-equivalent width of Si II λ6355 are correlated with intrinsic color, with intrinsic color having a linear relation with the Si II λ6355 measurements. Ca II H and K does not have a linear relation with intrinsic color, but lower-velocity SNe tend to be intrinsically bluer. Combining the spectroscopic measurements does not improve intrinsic color inference. The intrinsic color scatter is larger for higher-velocity SNe Ia—even after removing a linear trend with velocity—indicating that lower-velocity SNe Ia are more 'standard crayons'. Employing information derived from SN Ia spectra has the potential to improve the measurements of extragalactic distances and the cosmological properties inferred from them.

The unfolded protein response in melanocytes: activation in response to chemical stressors of the endoplasmic reticulum and tyrosinase misfolding.

Science.gov (United States)

Manga, Prashiela; Bis, Sabina; Knoll, Kristen; Perez, Beremis; Orlow, Seth J

2010-10-01

Accumulation of proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), comprising three signaling pathways initiated by Ire1, Perk and Atf6 respectively. Unfolded protein response activation was compared in chemically stressed murine wildtype melanocytes and mutant melanocytes that retain tyrosinase in the ER. Thapsigargin, an ER stressor, activated all pathways in wildtype melanocytes, triggering Caspase 12-mediated apoptosis at toxic doses. Albino melanocytes expressing mutant tyrosinase showed evidence of ER stress with increased Ire1 expression, but the downstream effector, Xbp1, was not activated even following thapsigargin treatment. Attenuation of Ire1 signaling was recapitulated in wildtype melanocytes treated with thapsigargin for 8 days, with diminished Xbp1 activation observed after 4 days. Atf6 was also activated in albino melanocytes, with no response to thapsigargin, while the Perk pathway was not activated and thapsigargin treatment elicited robust expression of the downstream effector CCAAT-enhancer-binding protein homologous protein. Thus, melanocytes adapt to ER stress by attenuating two UPR pathways.

Alpha-lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

Science.gov (United States)

Svensson, Malin; Fast, Jonas; Mossberg, Ann-Kristin; Düringer, Caroline; Gustafsson, Lotta; Hallgren, Oskar; Brooks, Charles L; Berliner, Lawrence; Linse, Sara; Svanborg, Catharina

2003-12-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex of human alpha-lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis-like mechanism. Previous studies have shown that a conformational change is required to form HAMLET from alpha-lactalbumin, and that a partially unfolded conformation is maintained in the HAMLET complex. This study examined if unfolding of alpha-lactalbumin is sufficient to induce cell death. We used the bovine alpha-lactalbumin Ca(2+) site mutant D87A, which is unable to bind Ca(2+), and thus remains partially unfolded regardless of solvent conditions. The D87A mutant protein was found to be inactive in the apoptosis assay, but could readily be converted to a HAMLET-like complex in the presence of oleic acid. BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) and D87A-BAMLET complexes were both able to kill tumor cells. This activity was independent of the Ca(2+)site, as HAMLET maintained a high affinity for Ca(2+) but D87A-BAMLET was active with no Ca(2+) bound. We conclude that partial unfolding of alpha-lactalbumin is necessary but not sufficient to trigger cell death, and that the activity of HAMLET is defined both by the protein and the lipid cofactor. Furthermore, a functional Ca(2+)-binding site is not required for conversion of alpha-lactalbumin to the active complex or to cause cell death. This suggests that the lipid cofactor stabilizes the altered fold without interfering with the Ca(2+)site.

Driving force behind adsorption-induced protein unfolding: a time-resolved X-ray reflectivity study on lysozyme adsorbed at an air/water interface.

Science.gov (United States)

Yano, Yohko F; Uruga, Tomoya; Tanida, Hajime; Toyokawa, Hidenori; Terada, Yasuko; Takagaki, Masafumi; Yamada, Hironari

2009-01-06

Time-resolved X-ray reflectivity measurements for lysozyme (LSZ) adsorbed at an air/water interface were performed to study the mechanism of adsorption-induced protein unfolding. The time dependence of the density profile at the air/water interface revealed that the molecular conformation changed significantly during adsorption. Taking into account previous work using Fourier transform infrared (FTIR) spectroscopy, we propose that the LSZ molecules initially adsorbed on the air/water interface have a flat unfolded structure, forming antiparallel beta-sheets as a result of hydrophobic interactions with the gas phase. In contrast, as adsorption continues, a second layer forms in which the molecules have a very loose structure having random coils as a result of hydrophilic interactions with the hydrophilic groups that protrude from the first layer.

Hemin and bile pigments are the secondary structure regulators of intrinsically disordered antimicrobial peptides.

Science.gov (United States)

Zsila, Ferenc; Juhász, Tünde; Bősze, Szilvia; Horváti, Kata; Beke-Somfai, Tamás

2018-02-01

The interaction of protoporphyrin compounds of human origin with the major bee venom component melittin (26 a.a., Z +6) and its hybrid derivative (CM15, 15 a.a., Z +6) were studied by a combination of various spectroscopic methods. Throughout a two-state, concentration-dependent process, hemin and its metabolites (biliverdin, bilirubin, bilirubin ditaurate) increase the parallel β-sheet content of the natively unfolded melittin, suggesting the oligomerization of the peptide chains. In contrast, α-helix promoting effect was observed with the also disordered but more cationic CM15. According to fluorescence quenching experiments, the sole Trp residue of melittin is the key player during the binding, in the vicinity of which the first pigment molecule is accommodated presumably making indole-porphyrin π-π stacking interaction. As circular dichroism titration data suggest, cooperative association of additional ligands subsequently occurs, resulting in multimeric complexes with an apparent dissociation constant ranged from 20 to 65 μM. Spectroscopic measurements conducted with the bilirubin catabolite urobilin and stercobilin refer to the requirement of intact dipyrrinone moieties for inducing secondary structure transformations. The binding topography of porphyrin rings on a model parallel β-sheet motif was evaluated by absorption spectroscopy and computational modeling showing a slipped-cofacial binding mode responsible for the red shift and hypochromism of the Soret band. Our results may aid to recognize porphyrin-responsive binding motifs of biologically relevant, intrinsically disordered peptides and proteins, where transient conformations play a vital role in their functions. © 2017 Wiley Periodicals, Inc.

Improvement of diagnostic confidence for detection of multiple myeloma involvement of the ribs by a new CT software generating rib unfolded images: Comparison with 5- and 1-mm axial images

Energy Technology Data Exchange (ETDEWEB)

Homann, Georg; Mustafa, Deedar Farhad; Nikolaou, Konstantin; Horger, Marius [Eberhard Karls University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Weisel, Katja [Eberhard Karls University Tuebingen, Department of Internal Medicine II, Tuebingen (Germany); Ditt, Hendrik [Healthcare Sector Imaging and Therapy Division, Siemens AG, Forchheim (Germany)

2015-04-02

To investigate the performance of a new CT software generating rib unfolded images for improved detection of rib osteolyses in patients with multiple myeloma. One hundred sixteen patients who underwent whole-body reduced-dose multidetector computed tomography (WBRD-MDCT) for multiple myeloma diagnosis and during follow-up were retrospectively evaluated. Nonenhanced CT scans with 5- and 1-mm slice thickness were interpreted by two readers with focus on detection of rib involvement (location, number, fracture). Image analysis of ''unfolded,'' 1-mm-based CT rib images was subsequently undertaken. We classified the number of lytic bone lesions into 0, 1, 2, <5, <10 and ≥10. For all three data sets the reading time was registered. An approximated sum of 6,727 myeloma-related rib lesions was found. On a patient-based analysis, CT (5 mm), CT (1 mm) and CT (1 mm ''unfolded rib'') yielded a sensitivity, specificity and accuracy of 79.7/94.7/87.1, 88.1/93/90.5 and 98.3/96.5/97.4, respectively. In a lesion-based analysis, the sensitivity, specificity and accuracy of the three evaluations were 69.7/87.2/70.5, 79.8/55.9/78 and 96.5/89.7/96.1. Mean reading time for 5 mm/1 mm axial images and unfolded images was 178.7/215.1/90.8 s, respectively. The generation of ''unfolded rib'' images improves detection of rib involvement in patients with multiple myeloma and significantly reduces reading time. (orig.)

Multiscale unfolding of real networks by geometric renormalization

Science.gov (United States)

García-Pérez, Guillermo; Boguñá, Marián; Serrano, M. Ángeles

2018-06-01

Symmetries in physical theories denote invariance under some transformation, such as self-similarity under a change of scale. The renormalization group provides a powerful framework to study these symmetries, leading to a better understanding of the universal properties of phase transitions. However, the small-world property of complex networks complicates application of the renormalization group by introducing correlations between coexisting scales. Here, we provide a framework for the investigation of complex networks at different resolutions. The approach is based on geometric representations, which have been shown to sustain network navigability and to reveal the mechanisms that govern network structure and evolution. We define a geometric renormalization group for networks by embedding them into an underlying hidden metric space. We find that real scale-free networks show geometric scaling under this renormalization group transformation. We unfold the networks in a self-similar multilayer shell that distinguishes the coexisting scales and their interactions. This in turn offers a basis for exploring critical phenomena and universality in complex networks. It also affords us immediate practical applications, including high-fidelity smaller-scale replicas of large networks and a multiscale navigation protocol in hyperbolic space, which betters those on single layers.

Unfolded Protein Response-regulated Drosophila Fic (dFic) Protein Reversibly AMPylates BiP Chaperone during Endoplasmic Reticulum Homeostasis*

Science.gov (United States)

Ham, Hyeilin; Woolery, Andrew R.; Tracy, Charles; Stenesen, Drew; Krämer, Helmut; Orth, Kim

2014-01-01

Drosophila Fic (dFic) mediates AMPylation, a covalent attachment of adenosine monophosphate (AMP) from ATP to hydroxyl side chains of protein substrates. Here, we identified the endoplasmic reticulum (ER) chaperone BiP as a substrate for dFic and mapped the modification site to Thr-366 within the ATPase domain. The level of AMPylated BiP in Drosophila S2 cells is high during homeostasis, whereas the level of AMPylated BiP decreases upon the accumulation of misfolded proteins in the ER. Both dFic and BiP are transcriptionally activated upon ER stress, supporting the role of dFic in the unfolded protein response pathway. The inactive conformation of BiP is the preferred substrate for dFic, thus endorsing a model whereby AMPylation regulates the function of BiP as a chaperone, allowing acute activation of BiP by deAMPylation during an ER stress response. These findings not only present the first substrate of eukaryotic AMPylator but also provide a target for regulating the unfolded protein response, an emerging avenue for cancer therapy. PMID:25395623

Kinematical tests for the intrinsic shapes of galaxies

International Nuclear Information System (INIS)

Capaccioli, M.; Fasano, G.

1984-01-01

Determining the intrinsic shape of elliptical galaxies has been an illusive enterprise, but one fundamental to the understanding of their internal dynamics and formation. Here the problem is approached dynamically; noting that the velocity dispersion is largest when sighted down the longest axis, the correlations are derived of velocity dispersion with observed eccentricity expected, after the known trend of velocity dispersion with luminosity is removed. Using a compilation of published data, the relation between luminosity and velocity dispersion is determined more accurately. The residuals are examined as a function of axis ratio in order to construct a test for the intrinsic shape of galaxies. The effects of projection are modelled and possible intrinsic variations are examined. (author)

The Mysterious Unfoldome: Structureless, Underappreciated, Yet Vital Part of Any Given Proteome

Directory of Open Access Journals (Sweden)

Vladimir N. Uversky

2010-01-01

Full Text Available Contrarily to the general believe, many biologically active proteins lack stable tertiary and/or secondary structure under physiological conditions in vitro. These intrinsically disordered proteins (IDPs are highly abundant in nature and many of them are associated with various human diseases. The functional repertoire of IDPs complements the functions of ordered proteins. Since IDPs constitute a significant portion of any given proteome, they can be combined in an unfoldome; which is a portion of the proteome including all IDPs (also known as natively unfolded proteins, therefore, unfoldome, and describing their functions, structures, interactions, evolution, and so forth. Amino acid sequence and compositions of IDPs are very different from those of ordered proteins, making possible reliable identification of IDPs at the proteome level by various computational means. Furthermore, IDPs possess a number of unique structural properties and are characterized by a peculiar conformational behavior, including their high stability against low pH and high temperature and their structural indifference toward the unfolding by strong denaturants. These peculiarities were shown to be useful for elaboration of the experimental techniques for the large-scale identification of IDPs in various organisms. Some of the computational and experimental tools for the unfoldome discovery are discussed in this review.

In-situ spectrometry of 137Cs in the soil by unfolding method

International Nuclear Information System (INIS)

Fueloep, M.; Ragan, P.; Krnac, S.

1995-01-01

This contribution is aimed to the possibility of improving the in-situ gamma spectrometry to be independent on a knowledge about a depth distribution of 137 Cs in soil and sufficiently sensitive for the measurement of the post-Chernobyl 137 Cs at present, as well. The depth distribution of 137 Cs averaged over a large area of soil is obtained by unfolding of the detector responses to primary and in soil forward scattered photons. The proposed method employs detector with and without collimator. The 137 Cs distributions obtained in-situ measurements are analysed, and comparisons are made to the results obtained with soil sampling and with standard in-situ spectrometry, as well. 5 figs., 1 tab., 4 refs

Do intrinsic and extrinsic motivation relate differently to employee outcomes?

OpenAIRE

Kuvaas, Bard; Buch, Robert; Weibel, Antoinette; Dysvik, Anders; Nerstad, Christina

2017-01-01

In most theories that address how individual financial incentives affect work performance, researchers have assumed that two types of motivation—intrinsic and extrinsic—mediate the relationship between incentives and performance. Empirically, however, extrinsic motivation is rarely investigated. To explore the predictive validity of these theories of intrinsic and extrinsic motivation in work settings, we tested how both intrinsic and extrinsic motivation affected supervisor-ra...

Loss of Subcellular Lipid Transport Due to ARV1 Deficiency Disrupts Organelle Homeostasis and Activates the Unfolded Protein Response*

Science.gov (United States)

Shechtman, Caryn F.; Henneberry, Annette L.; Seimon, Tracie A.; Tinkelenberg, Arthur H.; Wilcox, Lisa J.; Lee, Eunjee; Fazlollahi, Mina; Munkacsi, Andrew B.; Bussemaker, Harmen J.; Tabas, Ira; Sturley, Stephen L.

2011-01-01

The ARV1-encoded protein mediates sterol transport from the endoplasmic reticulum (ER) to the plasma membrane. Yeast ARV1 mutants accumulate multiple lipids in the ER and are sensitive to pharmacological modulators of both sterol and sphingolipid metabolism. Using fluorescent and electron microscopy, we demonstrate sterol accumulation, subcellular membrane expansion, elevated lipid droplet formation, and vacuolar fragmentation in ARV1 mutants. Motif-based regression analysis of ARV1 deletion transcription profiles indicates activation of Hac1p, an integral component of the unfolded protein response (UPR). Accordingly, we show constitutive splicing of HAC1 transcripts, induction of a UPR reporter, and elevated expression of UPR targets in ARV1 mutants. IRE1, encoding the unfolded protein sensor in the ER lumen, exhibits a lethal genetic interaction with ARV1, indicating a viability requirement for the UPR in cells lacking ARV1. Surprisingly, ARV1 mutants expressing a variant of Ire1p defective in sensing unfolded proteins are viable. Moreover, these strains also exhibit constitutive HAC1 splicing that interacts with DTT-mediated perturbation of protein folding. These data suggest that a component of UPR induction in arv1Δ strains is distinct from protein misfolding. Decreased ARV1 expression in murine macrophages also results in UPR induction, particularly up-regulation of activating transcription factor-4, CHOP (C/EBP homologous protein), and apoptosis. Cholesterol loading or inhibition of cholesterol esterification further elevated CHOP expression in ARV1 knockdown cells. Thus, loss or down-regulation of ARV1 disturbs membrane and lipid homeostasis, resulting in a disruption of ER integrity, one consequence of which is induction of the UPR. PMID:21266578

Intrinsically bent DNA in replication origins and gene promoters.

Science.gov (United States)

Gimenes, F; Takeda, K I; Fiorini, A; Gouveia, F S; Fernandez, M A

2008-06-24

Intrinsically bent DNA is an alternative conformation of the DNA molecule caused by the presence of dA/dT tracts, 2 to 6 bp long, in a helical turn phase DNA or with multiple intervals of 10 to 11 bp. Other than flexibility, intrinsic bending sites induce DNA curvature in particular chromosome regions such as replication origins and promoters. Intrinsically bent DNA sites are important in initiating DNA replication, and are sometimes found near to regions associated with the nuclear matrix. Many methods have been developed to localize bent sites, for example, circular permutation, computational analysis, and atomic force microscopy. This review discusses intrinsically bent DNA sites associated with replication origins and gene promoter regions in prokaryote and eukaryote cells. We also describe methods for identifying bent DNA sites for circular permutation and computational analysis.

Impacts of global warming on phenology of spring leaf unfolding remain stable in the long run.

Science.gov (United States)

Wang, Huanjiong; Rutishauser, This; Tao, Zexing; Zhong, Shuying; Ge, Quansheng; Dai, Junhu

2017-02-01

The impact of spring temperature forcing on the timing of leaf unfolding of plants (temperature sensitivity, S T ) is one important indicator of how and to what degree plant species track climate change. Fu et al. (Nature 526:104-107, 2015) found that S T has significantly decreased from the 1980-1994 to the 1999-2013 period for seven mid-latitude tree species in Europe. However, long-term changes in S T over the past 60 years are still not clear. Here, using in situ observations of leaf unfolding for seven dominant European tree species, we analyze the temporal change in S T over decadal time scales extending the data series back to 1951. Our results demonstrate that S T shows no statistically significant change within shifting 30-year windows from 1951 to 2013 and remains stable between 1951-1980 and 1984-2013 (3.6 versus 3.7 days °C -1 ). This result suggests that the significant decrease in S T over the past 33 years could not be sustained when examining the trends of phenological responses in the long run. Therefore, we could not conclude that tree spring phenology advances will slow down in the future, and the S T changes in warming scenarios are still uncertain.

Congenital hypertrophy of multiple intrinsic muscles of the foot.

Science.gov (United States)

Shiraishi, Tomohiro; Park, Susam; Niu, Atushi; Hasegawa, Hiromi

2014-12-01

Congenital hypertrophy of a single intrinsic muscle of the foot is rare, and as far as we know, only six cases have been reported. We describe a case of congenital anomaly that showed hypertrophy of multiple intrinsic muscles of the foot; the affected muscles were all the intrinsic muscles of the foot except the extensor digitorum brevis or extensor hallucis. Other tissues such as adipose tissue, nervous tissue, or osseous tissue showed no abnormalities. To reduce the volume of the foot we removed parts of the enlarged muscles.

mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt).

Science.gov (United States)

Kenny, Timothy C; Germain, Doris

2017-01-01

While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPR mt ) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPR mt has also been studied in the context of cancer. More recent work suggests that rather than a single mutation or alternation, specific combinatorial mtDNA landscapes able to activate the UPR mt may be those that are selected by metastatic cells, while mtDNA landscapes unable to activate the UPR mt do not. This review aims at offering an overview of the confusing literature on mtDNA mutations and metastasis and the more recent work on the UPR mt in this setting.

Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

Directory of Open Access Journals (Sweden)

Wouter Boomsma

2016-02-01

Full Text Available The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work

Unique Path Partitions

DEFF Research Database (Denmark)

Bessenrodt, Christine; Olsson, Jørn Børling; Sellers, James A.

2013-01-01

We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions.......We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions....

Respiratory epithelial cell responses to cigarette smoke: the unfolded protein response.

Science.gov (United States)

Kelsen, Steven G

2012-12-01

Cigarette smoking exposes the respiratory epithelium to highly toxic, reactive oxygen nitrogen species which damage lung proteins in the endoplasmic reticulum (ER), the cell organelle in which all secreted and membrane proteins are processed. Accumulation of damaged or misfolded proteins in the ER, a condition termed ER stress, activates a complex cellular process termed the unfolded protein responses (UPR). The UPR acts to restore cellular protein homeostasis by regulating all aspects of protein metabolism including: protein translation and syntheses; protein folding; and protein degradation. However, activation of the UPR may also induce signaling pathways which induce inflammation and cell apoptosis. This review discusses the role of UPR in the respiratory epithelial cell response to cigarette smoke and the pathogenesis of lung diseases like COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response

NARCIS (Netherlands)

Nagelkerke, A.; Bussink, J.; Mujcic, H.; Wouters, B.G.; Lehmann, S.A.; Sweep, F.C.; Span, P.N.

2013-01-01

ABSTRACT: INTRODUCTION: The hypoxia-inducible factor (HIF)-1 pathway can stimulate tumor cell migration and metastasis. Furthermore, hypoxic tumors are associated with a poor prognosis. Besides the HIF-1 pathway, the unfolded protein response (UPR) is also induced by hypoxic conditions. The PKR-like

The Emerging Neuroscience of Intrinsic Motivation: A New Frontier in Self-Determination Research

Science.gov (United States)

Di Domenico, Stefano I.; Ryan, Richard M.

2017-01-01

Intrinsic motivation refers to people’s spontaneous tendencies to be curious and interested, to seek out challenges and to exercise and develop their skills and knowledge, even in the absence of operationally separable rewards. Over the past four decades, experimental and field research guided by self-determination theory (SDT; Ryan and Deci, 2017) has found intrinsic motivation to predict enhanced learning, performance, creativity, optimal development and psychological wellness. Only recently, however, have studies begun to examine the neurobiological substrates of intrinsic motivation. In the present article, we trace the history of intrinsic motivation research, compare and contrast intrinsic motivation to closely related topics (flow, curiosity, trait plasticity), link intrinsic motivation to key findings in the comparative affective neurosciences, and review burgeoning neuroscience research on intrinsic motivation. We review converging evidence suggesting that intrinsically motivated exploratory and mastery behaviors are phylogenetically ancient tendencies that are subserved by dopaminergic systems. Studies also suggest that intrinsic motivation is associated with patterns of activity across large-scale neural networks, namely, those that support salience detection, attentional control and self-referential cognition. We suggest novel research directions and offer recommendations for the application of neuroscience methods in the study of intrinsic motivation. PMID:28392765

The Emerging Neuroscience of Intrinsic Motivation: A New Frontier in Self-Determination Research.

Science.gov (United States)

Di Domenico, Stefano I; Ryan, Richard M

2017-01-01

Intrinsic motivation refers to people's spontaneous tendencies to be curious and interested, to seek out challenges and to exercise and develop their skills and knowledge, even in the absence of operationally separable rewards. Over the past four decades, experimental and field research guided by self-determination theory (SDT; Ryan and Deci, 2017) has found intrinsic motivation to predict enhanced learning, performance, creativity, optimal development and psychological wellness. Only recently, however, have studies begun to examine the neurobiological substrates of intrinsic motivation. In the present article, we trace the history of intrinsic motivation research, compare and contrast intrinsic motivation to closely related topics (flow, curiosity, trait plasticity), link intrinsic motivation to key findings in the comparative affective neurosciences, and review burgeoning neuroscience research on intrinsic motivation. We review converging evidence suggesting that intrinsically motivated exploratory and mastery behaviors are phylogenetically ancient tendencies that are subserved by dopaminergic systems. Studies also suggest that intrinsic motivation is associated with patterns of activity across large-scale neural networks, namely, those that support salience detection, attentional control and self-referential cognition. We suggest novel research directions and offer recommendations for the application of neuroscience methods in the study of intrinsic motivation.

Discovery of Intrinsic Primitives on Triangle Meshes

KAUST Repository

Solomon, Justin

2011-04-01

The discovery of meaningful parts of a shape is required for many geometry processing applications, such as parameterization, shape correspondence, and animation. It is natural to consider primitives such as spheres, cylinders and cones as the building blocks of shapes, and thus to discover parts by fitting such primitives to a given surface. This approach, however, will break down if primitive parts have undergone almost-isometric deformations, as is the case, for example, for articulated human models. We suggest that parts can be discovered instead by finding intrinsic primitives, which we define as parts that posses an approximate intrinsic symmetry. We employ the recently-developed method of computing discrete approximate Killing vector fields (AKVFs) to discover intrinsic primitives by investigating the relationship between the AKVFs of a composite object and the AKVFs of its parts. We show how to leverage this relationship with a standard clustering method to extract k intrinsic primitives and remaining asymmetric parts of a shape for a given k. We demonstrate the value of this approach for identifying the prominent symmetry generators of the parts of a given shape. Additionally, we show how our method can be modified slightly to segment an entire surface without marking asymmetric connecting regions and compare this approach to state-of-the-art methods using the Princeton Segmentation Benchmark. © 2011 The Author(s).

Intrinsically radiolabelled [59Fe]-SPIONs for dual MRI/radionuclide detection

OpenAIRE

Hoffman, David; Sun, Minghao; Yang, Likun; McDonagh, Philip R; Corwin, Frank; Sundaresan, Gobalakrishnan; Wang, Li; Vijayaragavan, Vimalan; Thadigiri, Celina; Lamichhane, Narottam; Zweit, Jamal

2014-01-01

Towards the development of iron oxide nanoparticles with intrinsically incorporated radionuclides for dual Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) and more recently of Single Photon Emission Computed Tomography/Magnetic Resonance Imaging (SPECT/MRI), we have developed intrinsically radiolabeled [59Fe]-superparamagnetic iron oxide nanoparticles ([59Fe]-SPIONs) as a proof of concept for an intrinsic dual probe strategy. 59Fe was incorporated into Fe3O4 nanoparticle cry...

First Results of Minimum Fisher Regularisation as Unfolding Method for JET NE213 Liquid Scintillator Neutron Spectrometry

Czech Academy of Sciences Publication Activity Database

Mlynář, Jan; Adams, J. M.; Bertalot, L.; Conroy, S.

2005-01-01

Roč. 74, 1-4 (2005), s. 781-786 ISSN 0920-3796. [Symposium on Fusion Technology - SOFT/23rd./. Benátky, 20.9.2004-24.9.2004] Institutional research plan: CEZ:AV0Z20430508 Keywords : Tokamak * fusion * neutron diagnostic * spectrum unfolding * scintillator regularisation Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 0.981, year: 2005 http://soft2004.igi.cnr.it/

Genome-Wide Identification of Antimicrobial Intrinsic Resistance Determinants in Staphylococcus aureus

DEFF Research Database (Denmark)

Vestergaard, Martin; Leng, Bingfeng; Haaber, Jakob

2016-01-01

The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired resistance has received considerable attention, relatively little is known of intrinsic resistance that allows bacteria to naturally withstand antimicrobials. Gene products...... that confer intrinsic resistance to antimicrobial agents may be explored for alternative antimicrobial therapies, by potentiating the efficacy of existing antimicrobials. In this study, we identified the intrinsic resistome to a broad spectrum of antimicrobials in the human pathogen, Staphylococcus aureus. We...... with the atpA mutant compared to wild type cells with gentamicin at a clinically relevant concentration. Our results demonstrate that many gene products contribute to the intrinsic antimicrobial resistance of S. aureus. Knowledge of these intrinsic resistance determinants provides alternative targets...

Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation.

Directory of Open Access Journals (Sweden)

Todd J Cohen

Full Text Available Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer's disease (AD. Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies.

Unfolded protein response in filamentous fungi-implications in biotechnology.

Science.gov (United States)

Heimel, Kai

2015-01-01

The unfolded protein response (UPR) represents a mechanism to preserve endoplasmic reticulum (ER) homeostasis that is conserved in eukaryotes. ER stress caused by the accumulation of potentially toxic un- or misfolded proteins in the ER triggers UPR activation and the induction of genes important for protein folding in the ER, ER expansion, and transport from and to the ER. Along with this adaptation, the overall capacity for protein secretion is markedly increased by the UPR. In filamentous fungi, various approaches to employ the UPR for improved production of homologous and heterologous proteins have been investigated. As the effects on protein production were strongly dependent on the expressed protein, generally applicable strategies have to be developed. A combination of transcriptomic approaches monitoring secretion stress and basic research on the UPR mechanism provided novel and important insight into the complex regulatory cross-connections between UPR signalling, cellular physiology, and developmental processes. It will be discussed how this increasing knowledge on the UPR might stimulate the development of novel strategies for using the UPR as a tool in biotechnology.

Direct measurement of the intrinsic ankle stiffness during standing.

Science.gov (United States)

Vlutters, M; Boonstra, T A; Schouten, A C; van der Kooij, H

2015-05-01

Ankle stiffness contributes to standing balance, counteracting the destabilizing effect of gravity. The ankle stiffness together with the compliance between the foot and the support surface make up the ankle-foot stiffness, which is relevant to quiet standing. The contribution of the intrinsic ankle-foot stiffness to balance, and the ankle-foot stiffness amplitude dependency remain a topic of debate in the literature. We therefore developed an experimental protocol to directly measure the bilateral intrinsic ankle-foot stiffness during standing balance, and determine its amplitude dependency. By applying fast (40 ms) ramp-and-hold support surface rotations (0.005-0.08 rad) during standing, reflexive contributions could be excluded, and the amplitude dependency of the intrinsic ankle-foot stiffness was investigated. Results showed that reflexive activity could not have biased the torque used for estimating the intrinsic stiffness. Furthermore, subjects required less recovery action to restore balance after bilateral rotations in opposite directions compared to rotations in the same direction. The intrinsic ankle-foot stiffness appears insufficient to ensure balance, ranging from 0.93±0.09 to 0.44±0.06 (normalized to critical stiffness 'mgh'). This implies that changes in muscle activation are required to maintain balance. The non-linear stiffness decrease with increasing rotation amplitude supports the previous published research. With the proposed method reflexive effects can be ruled out from the measured torque without any model assumptions, allowing direct estimation of intrinsic stiffness during standing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Numerical analysis of intrinsic bistability and chromatic switching in Tm3+ single-doped systems under photon avalanche pumping scheme

International Nuclear Information System (INIS)

Li Li; Zhang Xinlu; Chen Lixue

2008-01-01

In this paper, we predict and numerically demonstrate the intrinsic intensity bistability, spectra bistability and chromatic switching of visible-infrared emission in Tm 3+ single-doped systems that are pumped by the photon avalanche scheme at 648 nm. Based on the coupled rate equation theory, the evolutions of the populations at various Tm 3+ energy levels, emission spectra and fluorescence intensity versus pump excitation are numerically investigated in detail. The results show that intrinsic optical bistability (IOB) associated with emission spectra and luminescence intensity takes place in the vicinity of the avalanche threshold (∼10 kW cm -2 ). When the pump excitation rises above the switching threshold (∼17.5 kW cm -2 ), the chromatic switching between the infrared (1716 nm) and the visible blue (452/469 nm) spectra can be performed. Moreover, the influences of system parameters on IOB and the origin of chromatic switching are discussed. These unique characteristics of Tm 3+ -doped systems would lead to the new possibility of the development of pump-controlled all-solid-state luminescence switches and optical bistability switches.

Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

DEFF Research Database (Denmark)

Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

2014-01-01

and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

Elderly Taiwanese's Intrinsic Risk Factors for Fall-related Injuries

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In-Fun Li

2016-09-01

Conclusion: Elderly Taiwanese inpatients with existing intrinsic conditions of cancer, vertigo, and lower leg weakness were at high risk of falling, resulting in severe injuries. Additional research including controlled trials is necessary to further identify treatable, causal intrinsic risk factors for this elderly group.

Uniqueness and non-uniqueness of semigroups generated by singular diffusion operators

CERN Document Server

Eberle, Andreas

1999-01-01

This book addresses both probabilists working on diffusion processes and analysts interested in linear parabolic partial differential equations with singular coefficients. The central question discussed is whether a given diffusion operator, i.e., a second order linear differential operator without zeroth order term, which is a priori defined on test functions over some (finite or infinite dimensional) state space only, uniquely determines a strongly continuous semigroup on a corresponding weighted Lp space. Particular emphasis is placed on phenomena causing non-uniqueness, as well as on the relation between different notions of uniqueness appearing in analytic and probabilistic contexts.

Physics of Intrinsic Rotation in Flux-Driven ITG Turbulence

International Nuclear Information System (INIS)

Ku, S.; Abiteboul, J.; Dimond, P.H.; Dif-Pradalier, G.; Kwon, J.M.; Sarazin, Y.; Hahm, T.S.; Garbet, X.; Chang, C.S.; Latu, G.; Yoon, E.S.; Ghendrih, Ph.; Yi, S.; Strugarek, A.; Solomon, W.; Grandgirard, V.

2012-01-01

Global, heat flux-driven ITG gyrokinetic simulations which manifest the formation of macroscopic, mean toroidal flow profiles with peak thermal Mach number 0.05, are reported. Both a particle-in-cell (XGC1p) and a semi-Lagrangian (GYSELA) approach are utilized without a priori assumptions of scale-separation between turbulence and mean fields. Flux-driven ITG simulations with different edge flow boundary conditions show in both approaches the development of net unidirectional intrinsic rotation in the co-current direction. Intrinsic torque is shown to scale approximately linearly with the inverse scale length of the ion temperature gradient. External momentum input is shown to effectively cancel the intrinsic rotation profile, thus confirming the existence of a local residual stress and intrinsic torque. Fluctuation intensity, intrinsic torque and mean flow are demonstrated to develop inwards from the boundary. The measured correlations between residual stress and two fluctuation spectrum symmetry breakers, namely E x B shear and intensity gradient, are similar. Avalanches of (positive) heat flux, which propagate either outwards or inwards, are correlated with avalanches of (negative) parallel momentum flux, so that outward transport of heat and inward transport of parallel momentum are correlated and mediated by avalanches. The probability distribution functions of the outward heat flux and the inward momentum flux show strong structural similarity

Investigation of intrinsic toroidal rotation scaling in KSTAR

Science.gov (United States)

Yoo, J. W.; Lee, S. G.; Ko, S. H.; Seol, J.; Lee, H. H.; Kim, J. H.

2017-07-01

The behaviors of an intrinsic toroidal rotation without any external momentum sources are investigated in KSTAR. In these experiments, pure ohmic discharges with a wide range of plasma parameters are carefully selected and analyzed to speculate an unrevealed origin of toroidal rotation excluding any unnecessary heating sources, magnetic perturbations, and strong magneto-hydrodynamic activities. The measured core toroidal rotation in KSTAR is mostly in the counter-current direction and its magnitude strongly depends on the ion temperature divided by plasma current (Ti/IP). Especially the core toroidal rotation in the steady-state is well fitted by Ti/IP scaling with a slope of ˜-23, and the possible explanation of the scaling is compared with various candidates. As a result, the calculated offset rotation could not explain the measured core toroidal rotation since KSTAR has an extremely low intrinsic error field. For the stability conditions for ion and electron turbulences, it is hard to determine a dominant turbulence mode in this study. In addition, the intrinsic toroidal rotation level in ITER is estimated based on the KSTAR scaling since the intrinsic rotation plays an important role in stabilizing resistive wall modes for future reference.

Intrinsically Passive Handling and Grasping

NARCIS (Netherlands)

Stramigioli, Stefano; Scherpen, Jacquelien M.A.; Khodabandehloo, Koorosh

2000-01-01

The paper presents a control philosophy called Intrinsically Passive Control, which has the feature to properly behave during interaction with any passive objects. The controlled robot will never become unstable due to the physical structure of the controller.

Frames of References – Art Museums as Unique Visual Media

Directory of Open Access Journals (Sweden)

Aneta Hristova

2015-10-01

Full Text Available The age old activity of collecting arts is not intrinsically dependent on the art museum as separate architectural type. How was the art museum as an independent structure conceptualized and why? What was the idea behind that concept? Was it created as a medium consciously and what kind of messages was it supposed to deliver? What kind of unique “textual” overlaps the various disciplines of archaeology, art history, politics, literature, science and architecture created in order to produce what we today recognize as art museum space? This study focuses on the crucial historical moments of the late 17th century when such questions were posed for the first time within the classical discourse of the French architectural theory which followed the consolidation of French absolutism and the foundation of the Royal academies of arts and sciences, until the mid 19th century when the answers to those questions were finally exemplified in built architecture. The study gives a comprehensive overview of the cultural context art museums as public institutions emerged from and became new spatial models for collective cultivation.

Disorder and defects are not intrinsic to boron carbide

Science.gov (United States)

Mondal, Swastik; Bykova, Elena; Dey, Somnath; Ali, Sk Imran; Dubrovinskaia, Natalia; Dubrovinsky, Leonid; Parakhonskiy, Gleb; van Smaalen, Sander

2016-01-01

A unique combination of useful properties in boron-carbide, such as extreme hardness, excellent fracture toughness, a low density, a high melting point, thermoelectricity, semi-conducting behavior, catalytic activity and a remarkably good chemical stability, makes it an ideal material for a wide range of technological applications. Explaining these properties in terms of chemical bonding has remained a major challenge in boron chemistry. Here we report the synthesis of fully ordered, stoichiometric boron-carbide B13C2 by high-pressure-high-temperature techniques. Our experimental electron-density study using high-resolution single-crystal synchrotron X-ray diffraction data conclusively demonstrates that disorder and defects are not intrinsic to boron carbide, contrary to what was hitherto supposed. A detailed analysis of the electron density distribution reveals charge transfer between structural units in B13C2 and a new type of electron-deficient bond with formally unpaired electrons on the C-B-C group in B13C2. Unprecedented bonding features contribute to the fundamental chemistry and materials science of boron compounds that is of great interest for understanding structure-property relationships and development of novel functional materials.

A series of intrinsically chiral gold nanocage structures.

Science.gov (United States)

Liu, X J; Hamilton, I P

2017-07-27

We present a series of intrinsically chiral gold nanocage structures, Au 9n+6 , which are stable for n ≥ 2. These structures consist of an Au 9n tube which is capped with Au 3 units at each end. Removing the Au 3 caps, we obtain a series of intrinsically chiral gold nanotube structures, Au 9n , which are stable for n ≥ 4. The intrinsic chirality of these structures results from the helicity of the gold strands which form the tube and not because an individual Au atom is a chiral center. The symmetry of these structures is C 3 and substructures of gold hexagons with a gold atom in the middle are particularly prominent. We focus on the properties of Au 42 (C 3 ) and Au 105 (C 3 ) which are the two smallest gold nanocage structures to be completely tiled by these Au 7 "golden-eye" substructures. Our main focus is on Au 42 (C 3 ) since gold clusters in the 40-50 atom regime are currently being investigated in gas phase experiments. We show that the intrinsically chiral Au 42 cage structure is energetically comparable with previously reported achiral cage and compact Au 42 structures. Cage structures are of particular interest because species can be encapsulated (and stabilized) inside the cage and we provide strong evidence that Au 6 @Au 42 (C 3 ) is the global minimum Au 48 structure. The intrinsically chiral gold nanocage structures, which exhibit a range of size-related properties, have potential applications in chiral catalysis and as components in nanostructured devices.

Who wants to work in a rural health post? The role of intrinsic motivation, rural background and faith-based institutions in Ethiopia and Rwanda.

Science.gov (United States)

Serneels, Pieter; Montalvo, Jose G; Pettersson, Gunilla; Lievens, Tomas; Butera, Jean Damascene; Kidanu, Aklilu

2010-05-01

To understand the factors influencing health workers' choice to work in rural areas as a basis for designing policies to redress geographic imbalances in health worker distribution. A cohort survey of 412 nursing and medical students in Rwanda provided unique contingent valuation data. Using these data, we performed a regression analysis to examine the determinants of future health workers' willingness to work in rural areas as measured by rural reservation wages. These data were also combined with those from an identical survey in Ethiopia to enable a two-country analysis. Health workers with higher intrinsic motivation - measured as the importance attached to helping the poor - as well as those who had grown up in a rural area and Adventists who had participated in a local bonding scheme were all significantly more willing to work in a rural area. The main result for intrinsic motivation in Rwanda was strikingly similar to the result obtained for Ethiopia and Rwanda combined. Intrinsic motivation and rural origin play an important role in health workers' decisions to work in a rural area, in addition to economic incentives, while faith-based institutions can also influence the decision.

Diffusion in Intrinsic and Highly Doped III-V Semiconductors

CERN Multimedia

Stolwijk, N

2002-01-01

%title\\\\ \\\\Diffusion plays a key role in the fabrication of semiconductor devices. The diffusion of atoms in crystals is mediated by intrinsic point defects. Investigations of the diffusion behaviour of self- and solute atoms on the Ga sublattice of gallium arsenide led to the conclusion that in intrinsic and n-type material charged Ga vacancies are involved in diffusion processes whereas in p-type material diffusion if governed by charged Ga self-interstitials. Concerning the As sublattice of gallium arsenide there is a severe lack of reliable diffusion data. The few available literature data on intrinsic GaAs are not mutually consistent. A systematic study of the doping dependence of diffusion is completely missing. The most basic diffusion process - self-diffusion of As and its temperature and doping dependence - is practically not known. For GaP a similar statement holds.\\\\ \\\\The aim of the present project is to perform a systematic diffusion study of As diffusion in intrinsic and doped GaAs and in GaP. P...

INTRINSIC AND EXTRINSIC MOTIVATION - AN INVESTIGATION OF PERFORMANCE CORRELATION

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Abrudan Maria-Madela

2011-07-01

Full Text Available A series of research untaken in the last decade have revealed some interesting aspects regarding the effects of different types of motivation on performance. Among the researchers who have shown interest in this field we can number: Richard Ryan, Edward Deci, Sam Glucksberg, Dan Ariely, Robert Eisenhower, Linda Shanock, analysts from London School of Economics, and others. Their findings suggest that extrinsic incentives may have a negative impact on overall performance, but a general agreement in this respect has not been reached. In this paper we intend to shed some light upon the relationship between intrinsic and extrinsic motivation and performance. Experts define intrinsic motivation as being the execution of a task or activity because of the inherent satisfaction arising from it rather than due to some separate outcome. In contrast with intrinsic motivation, we speak of extrinsic motivation whenever an activity is done in order to attain some separable outcome. With the purpose of contributing to the clarification of the links between concepts, we initiated and conducted an explanatory research. The research is based on the analysis of the relations between the results obtained by third year students and their predominant type of motivation. For this, we formulated and tested four work hypotheses using a combination of quantitative methods (investigation and qualitative methods (focus group. After the validation of the questionnaires, the respondents were divided into four categories: intrinsically motivated, extrinsically motivated, both intrinsically and extrinsically motivated and unmotivated. To analyze the collected data, we made use of Excel and SPSS. Some of the primary conclusions of the research are as follows: as the average increases, the percent of individuals having both extrinsic and intrinsic motivation is decreasing; the highest percentage of unmotivated students is concentrated in the highest average category; Female

Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins.

Science.gov (United States)

Xie, Hongbo; Vucetic, Slobodan; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Obradovic, Zoran; Uversky, Vladimir N

2007-05-01

Currently, the understanding of the relationships between function, amino acid sequence, and protein structure continues to represent one of the major challenges of the modern protein science. As many as 50% of eukaryotic proteins are likely to contain functionally important long disordered regions. Many proteins are wholly disordered but still possess numerous biologically important functions. However, the number of experimentally confirmed disordered proteins with known biological functions is substantially smaller than their actual number in nature. Therefore, there is a crucial need for novel bionformatics approaches that allow projection of the current knowledge from a few experimentally verified examples to much larger groups of known and potential proteins. The elaboration of a bioinformatics tool for the analysis of functional diversity of intrinsically disordered proteins and application of this data mining tool to >200 000 proteins from the Swiss-Prot database, each annotated with at least one of the 875 functional keywords, was described in the first paper of this series (Xie, H.; Vucetic, S.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V.N. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 2007, 5, 1882-1898). Using this tool, we have found that out of the 710 Swiss-Prot functional keywords associated with at least 20 proteins, 262 were strongly positively correlated with long intrinsically disordered regions, and 302 were strongly negatively correlated. Illustrative examples of functional disorder or order were found for the vast majority of keywords showing strongest positive or negative correlation with intrinsic disorder, respectively. Some 80 Swiss-Prot keywords associated with disorder- and order-driven biological processes and protein functions were described in the first paper (see above). The second paper of the series was

Intrinsic Risk Factors of Falls in Elderly

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Yasmin Amatullah

2016-09-01

Full Text Available Background: Falls are common geriatric problems. The risk factors of falls are the intrinsic and extrinsic risk factors. Studies on falls are scarcely conducted in Indonesia, especially in Bandung. Therefore, this study was conducted to identify the intrinsic risk factors of falls among elderly. Methods: A descriptive study was carried out from August to October 2013 at the Geriatric Clinic of Dr. Hasan Sadikin General Hospital Bandung. Fifty three participants were selected according to the inclusion and exclusion criteria using consecutive sampling. The determined variables in this study were classification of the risk of falls, demographic profile, history of falls, disease, and medications. After the selection, the participants were tested by Timed up-and-go test (TUGT. Moreover, an interview and analysis of medical records were carried out to discover the risk factors of falls. The collected data were analyzed and presented in the form of percentages shown in tables. Results: From 53 patients, women (35.66% were considered to have higher risk of fall than men (18.34%. The majority of patients (66% with the risk of fall were from the age group 60–74 years. The major diseases suffered by patients were hypertension, osteoarthritis and diabetes mellitus. Drugs that were widely used were antihypertensive drugs; analgesic and antipyretic drugs and antidiabetic drugs. Conclusions: There are various intrinsic risk factors of falls in elderly and each of the elderly has more than one intrinsic risk factor of falls.

College Student Intrinsic and/or Extrinsic Motivation and Learning.

Science.gov (United States)

Lin, Yi-Guang; McKeachie, Wilbert J.

This paper investigates the joint effects of intrinsic and extrinsic goals on college students' learning in an introductory psychology course, a biology course, and several social science courses. The study questioned whether higher levels of motivation lead to better student performance. College students were surveyed using the Intrinsic Goal…