Communication: Role of explicit water models in the helix folding/unfolding processes

Science.gov (United States)

Palazzesi, Ferruccio; Salvalaglio, Matteo; Barducci, Alessandro; Parrinello, Michele

2016-09-01

In the last years, it has become evident that computer simulations can assume a relevant role in modelling protein dynamical motions for their ability to provide a full atomistic image of the processes under investigation. The ability of the current protein force-fields in reproducing the correct thermodynamics and kinetics systems behaviour is thus an essential ingredient to improve our understanding of many relevant biological functionalities. In this work, employing the last developments of the metadynamics framework, we compare the ability of state-of-the-art all-atom empirical functions and water models to consistently reproduce the folding and unfolding of a helix turn motif in a model peptide. This theoretical study puts in evidence that the choice of the water models can influence the thermodynamic and the kinetics of the system under investigation, and for this reason cannot be considered trivial.

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 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...

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.

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

Becoming a Peroxidase: Cardiolipin-Induced Unfolding of Cytochrome c

Science.gov (United States)

Muenzner, Julia; Toffey, Jason R.; Hong, Yuning; Pletneva, Ekaterina V.

2014-01-01

Interactions of cytochrome c (cyt c) with a unique mitochondrial glycerophospholipid cardiolipin (CL) are relevant for the protein’s function in oxidative phosphorylation and apoptosis. Binding to CL-containing membranes promotes cyt c unfolding and dramatically enhances the protein’s peroxidase activity, which is critical in early stages of apoptosis. We have employed a collection of seven dansyl variants of horse heart cyt c to probe the sequence of steps in this functional transformation. Kinetic measurements have unraveled four distinct processes during CL-induced cyt c unfolding: rapid protein binding to CL liposomes; rearrangements of protein substructures with small unfolding energies; partial insertion of the protein into the lipid bilayer; and extensive protein restructuring leading to “open” extended structures. While early rearrangements depend on a hierarchy of foldons in the native structure, the later process of large-scale unfolding is influenced by protein interactions with the membrane surface. The opening of the cyt c structure exposes the heme group, which enhances the protein’s peroxidase activity and also frees the C-terminal helix to aid in the translocation of the protein through CL membranes. PMID:23713573

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...

Active mechanics in living oocytes reveal molecular-scale force kinetics

Science.gov (United States)

Ahmed, Wylie; Fodor, Etienne; Almonacid, Maria; Bussonnier, Matthias; Verlhac, Marie-Helene; Gov, Nir; Visco, Paolo; van Wijland, Frederic; Betz, Timo

Unlike traditional materials, living cells actively generate forces at the molecular scale that change their structure and mechanical properties. This nonequilibrium activity is essential for cellular function, and drives processes such as cell division. Single molecule studies have uncovered the detailed force kinetics of isolated motor proteins in-vitro, however their behavior in-vivo has been elusive due to the complex environment inside the cell. Here, we quantify active forces and intracellular mechanics in living oocytes using in-vivo optical trapping and laser interferometry of endogenous vesicles. We integrate an experimental and theoretical framework to connect mesoscopic measurements of nonequilibrium properties to the underlying molecular- scale force kinetics. Our results show that force generation by myosin-V drives the cytoplasmic-skeleton out-of-equilibrium (at frequencies below 300 Hz) and actively softens the environment. In vivo myosin-V activity generates a force of F ~ 0 . 4 pN, with a power-stroke of length Δx ~ 20 nm and duration τ ~ 300 μs, that drives vesicle motion at vv ~ 320 nm/s. This framework is widely applicable to characterize living cells and other soft active materials.

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

Ground reaction forces and knee kinetics during single and repeated badminton lunges.

Science.gov (United States)

Lam, Wing Kai; Ding, Rui; Qu, Yi

2017-03-01

Repeated movement (RM) lunge that frequently executed in badminton might be used for footwear evaluation. This study examined the influence of single movement (SM) and RM lunges on the ground reaction forces (GRFs) and knee kinetics during the braking phase of a badminton lunge step. Thirteen male university badminton players performed left-forward lunges in both SM and RM sessions. Force platform and motion capturing system were used to measure GRFs and knee kinetics variables. Paired t-test was performed to determine any significant differences between SM and RM lunges regarding mean and coefficient of variation (CV) in each variable. The kinetics results indicated that compared to SM lunges, the RM lunges had shorter contact time and generated smaller maximum loading rate of impact force, peak knee anterior-posterior force, and peak knee sagittal moment but generated larger peak horizontal resultant forces (Ps < 0.05). Additionally, the RM lunges had lower CV for peak knee medial-lateral and vertical forces (Ps < 0.05). These results suggested that the RM testing protocols had a distinct loading response and adaptation pattern during lunge and that the RM protocol showed higher within-trial reliability, which may be beneficial for the knee joint loading evaluation under different interventions.

Force generation by titin folding.

Science.gov (United States)

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

2017-07-01

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

Verification of unfold error estimates in the unfold operator code

International Nuclear Information System (INIS)

Fehl, D.L.; Biggs, F.

1997-01-01

Spectral unfolding is an inverse mathematical operation that attempts to obtain spectral source information from a set of response functions and data measurements. Several unfold algorithms have appeared over the past 30 years; among them is the unfold operator (UFO) code written at Sandia National Laboratories. In addition to an unfolded spectrum, the UFO code also estimates the unfold uncertainty (error) induced by estimated random uncertainties in the data. In UFO the unfold uncertainty is obtained from the error matrix. This built-in estimate has now been compared to error estimates obtained by running the code in a Monte Carlo fashion with prescribed data distributions (Gaussian deviates). In the test problem studied, data were simulated from an arbitrarily chosen blackbody spectrum (10 keV) and a set of overlapping response functions. The data were assumed to have an imprecision of 5% (standard deviation). One hundred random data sets were generated. The built-in estimate of unfold uncertainty agreed with the Monte Carlo estimate to within the statistical resolution of this relatively small sample size (95% confidence level). A possible 10% bias between the two methods was unresolved. The Monte Carlo technique is also useful in underdetermined problems, for which the error matrix method does not apply. UFO has been applied to the diagnosis of low energy x rays emitted by Z-pinch and ion-beam driven hohlraums. copyright 1997 American Institute of Physics

BUMS--Bonner sphere Unfolding Made Simple an HTML based multisphere neutron spectrometer unfolding package

CERN Document Server

Sweezy, J; Veinot, K

2002-01-01

A new multisphere neutron spectrometer unfolding package, Bonner sphere Unfolding Made Simple (BUMS) has been developed that uses an HTML interface to simplify data input and code execution for the novice and the advanced user. This new unfolding package combines the unfolding algorithms contained in other popular unfolding codes under one easy to use interface. The interface makes use of web browsing software to provide a graphical user interface to the unfolding algorithms. BUMS integrates the SPUNIT, BON, MAXIET, and SAND-II unfolding algorithms into a single package. This package also includes a library of 14 response matrices, 58 starting spectra, and 24 dose and detector responses. BUMS has several improvements beyond the addition of unfolding algorithms. It has the ability to search for the most appropriate starting spectra. Also, plots of the unfolded neutron spectra are automatically generated. The BUMS package runs via a web server and may be accessed by any computer with access to the Internet at h...

BUMS--Bonner sphere Unfolding Made Simple: an HTML based multisphere neutron spectrometer unfolding package

International Nuclear Information System (INIS)

Sweezy, Jeremy; Hertel, Nolan; Veinot, Ken

2002-01-01

A new multisphere neutron spectrometer unfolding package, Bonner sphere Unfolding Made Simple (BUMS) has been developed that uses an HTML interface to simplify data input and code execution for the novice and the advanced user. This new unfolding package combines the unfolding algorithms contained in other popular unfolding codes under one easy to use interface. The interface makes use of web browsing software to provide a graphical user interface to the unfolding algorithms. BUMS integrates the SPUNIT, BON, MAXIET, and SAND-II unfolding algorithms into a single package. This package also includes a library of 14 response matrices, 58 starting spectra, and 24 dose and detector responses. BUMS has several improvements beyond the addition of unfolding algorithms. It has the ability to search for the most appropriate starting spectra. Also, plots of the unfolded neutron spectra are automatically generated. The BUMS package runs via a web server and may be accessed by any computer with access to the Internet at http://nukeisit.gatech.edu/bums

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle.

Science.gov (United States)

Stehle, Robert; Tesi, Chiara

2017-08-01

A basic goal in muscle research is to understand how the cyclic ATPase activity of cross-bridges is converted into mechanical force. A direct approach to study the chemo-mechanical coupling between P i release and the force-generating step is provided by the kinetics of force response induced by a rapid change in [P i ]. Classical studies on fibres using caged-P i discovered that rapid increases in [P i ] induce fast force decays dependent on final [P i ] whose kinetics were interpreted to probe a fast force-generating step prior to P i release. However, this hypothesis was called into question by studies on skeletal and cardiac myofibrils subjected to P i jumps in both directions (increases and decreases in [P i ]) which revealed that rapid decreases in [P i ] trigger force rises with slow kinetics, similar to those of calcium-induced force development and mechanically-induced force redevelopment at the same [P i ]. A possible explanation for this discrepancy came from imaging of individual sarcomeres in cardiac myofibrils, showing that the fast force decay upon increase in [P i ] results from so-called sarcomere 'give'. The slow force rise upon decrease in [P i ] was found to better reflect overall sarcomeres cross-bridge kinetics and its [P i ] dependence, suggesting that the force generation coupled to P i release cannot be separated from the rate-limiting transition. The reasons for the different conclusions achieved in fibre and myofibril studies are re-examined as the recent findings on cardiac myofibrils have fundamental consequences for the coupling between P i release, rate-limiting steps and force generation. The implications from P i -induced force kinetics of myofibrils are discussed in combination with historical and recent models of the cross-bridge cycle.

k-OptForce: integrating kinetics with flux balance analysis for strain design.

Directory of Open Access Journals (Sweden)

Anupam Chowdhury

2014-02-01

Full Text Available Computational strain design protocols aim at the system-wide identification of intervention strategies for the enhanced production of biochemicals in microorganisms. Existing approaches relying solely on stoichiometry and rudimentary constraint-based regulation overlook the effects of metabolite concentrations and substrate-level enzyme regulation while identifying metabolic interventions. In this paper, we introduce k-OptForce, which integrates the available kinetic descriptions of metabolic steps with stoichiometric models to sharpen the prediction of intervention strategies for improving the bio-production of a chemical of interest. It enables identification of a minimal set of interventions comprised of both enzymatic parameter changes (for reactions with available kinetics and reaction flux changes (for reactions with only stoichiometric information. Application of k-OptForce to the overproduction of L-serine in E. coli and triacetic acid lactone (TAL in S. cerevisiae revealed that the identified interventions tend to cause less dramatic rearrangements of the flux distribution so as not to violate concentration bounds. In some cases the incorporation of kinetic information leads to the need for additional interventions as kinetic expressions render stoichiometry-only derived interventions infeasible by violating concentration bounds, whereas in other cases the kinetic expressions impart flux changes that favor the overproduction of the target product thereby requiring fewer direct interventions. A sensitivity analysis on metabolite concentrations shows that the required number of interventions can be significantly affected by changing the imposed bounds on metabolite concentrations. Furthermore, k-OptForce was capable of finding non-intuitive interventions aiming at alleviating the substrate-level inhibition of key enzymes in order to enhance the flux towards the product of interest, which cannot be captured by stoichiometry-alone analysis

Unfolding Participation

DEFF Research Database (Denmark)

Saad-Sulonen, Joanna; Halskov, Kim; Eriksson, Eva

2015-01-01

The aim of the Unfolding Participation workshop is to outline an agenda for the next 10 years of participatory design (PD) and participatory human computer interaction (HCI) research. We will do that through a double strategy: 1) by critically interrogating the concept of participation (unfolding...... the concept itself), while at the same time, 2) reflecting on the way that participation unfolds across different participatory configurations. We invite researchers and practitioners from PD and HCI and fields in which information technology mediated participation is embedded (e.g. in political studies......, urban planning, participatory arts, business, science and technology studies) to bring a plurality of perspectives and expertise related to participation....

Many channel spectrum unfolding

International Nuclear Information System (INIS)

Najzer, M.; Glumac, B.; Pauko, M.

1980-01-01

The principle of the ITER unfolding code as used for the many channel spectrum unfolding is described. Its unfolding ability is tested on seven typical neutron spectra. The effect of the initial spectrum approximation upon the solution is discussed

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

Force-Induced Unravelling of DNA Origami.

Science.gov (United States)

Engel, Megan C; Smith, David M; Jobst, Markus A; Sajfutdinow, Martin; Liedl, Tim; Romano, Flavio; Rovigatti, Lorenzo; Louis, Ard A; Doye, Jonathan P K

2018-05-31

The mechanical properties of DNA nanostructures are of widespread interest as applications that exploit their stability under constant or intermittent external forces become increasingly common. We explore the force response of DNA origami in comprehensive detail by combining AFM single molecule force spectroscopy experiments with simulations using oxDNA, a coarse-grained model of DNA at the nucleotide level, to study the unravelling of an iconic origami system: the Rothemund tile. We contrast the force-induced melting of the tile with simulations of an origami 10-helix bundle. Finally, we simulate a recently-proposed origami biosensor, whose function takes advantage of origami behaviour under tension. We observe characteristic stick-slip unfolding dynamics in our force-extension curves for both the Rothemund tile and the helix bundle and reasonable agreement with experimentally observed rupture forces for these systems. Our results highlight the effect of design on force response: we observe regular, modular unfolding for the Rothemund tile that contrasts with strain-softening of the 10-helix bundle which leads to catastropic failure under monotonically increasing force. Further, unravelling occurs straightforwardly from the scaffold ends inwards for the Rothemund tile, while the helix bundle unfolds more nonlinearly. The detailed visualization of the yielding events provided by simulation allows preferred pathways through the complex unfolding free-energy landscape to be mapped, as a key factor in determining relative barrier heights is the extensional release per base pair broken. We shed light on two important questions: how stable DNA nanostructures are under external forces; and what design principles can be applied to enhance stability.

Structural basis and kinetics of force-induced conformational changes of an αA domain-containing integrin.

Directory of Open Access Journals (Sweden)

Xue Xiang

Full Text Available Integrin α(Lβ₂ (lymphocyte function-associated antigen, LFA-1 bears force upon binding to its ligand intercellular adhesion molecule 1 (ICAM-1 when a leukocyte adheres to vascular endothelium or an antigen presenting cell (APC during immune responses. The ligand binding propensity of LFA-1 is related to its conformations, which can be regulated by force. Three conformations of the LFA-1 αA domain, determined by the position of its α₇-helix, have been suggested to correspond to three different affinity states for ligand binding.The kinetics of the force-driven transitions between these conformations has not been defined and dynamically coupled to the force-dependent dissociation from ligand. Here we show, by steered molecular dynamics (SMD simulations, that the αA domain was successively transitioned through three distinct conformations upon pulling the C-terminus of its α₇-helix. Based on these sequential transitions, we have constructed a mathematical model to describe the coupling between the αA domain conformational changes of LFA-1 and its dissociation from ICAM-1 under force. Using this model to analyze the published data on the force-induced dissociation of single LFA-1/ICAM-1 bonds, we estimated the force-dependent kinetic rates of interstate transition from the short-lived to intermediate-lived and from intermediate-lived to long-lived states. Interestingly, force increased these transition rates; hence activation of LFA-1 was accelerated by pulling it via an engaged ICAM-1.Our study defines the structural basis for mechanical regulation of the kinetics of LFA-1 αA domain conformational changes and relates these simulation results to experimental data of force-induced dissociation of single LFA-1/ICAM-1 bonds by a new mathematical model, thus provided detailed structural and kinetic characterizations for force-stabilization of LFA-1/ICAM-1 interaction.

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.

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.

Experimental study of drying kinetics by forced convection of aromatic plants

Energy Technology Data Exchange (ETDEWEB)

Belghit, A; Boutaleb, B C [Laboratoire de Mecanique des Fluides et Energetique, Marrakech (Morocco). Faculte des Sciences Semlalia; Kouhila, M [Laboratoire d' Energie Solaire, Marrakech (Morocco). Ecole Normale Superieure

2000-08-01

This paper has the objectives to determine the isotherms of sorption and the drying kinetics of verbena, which is the most consumed aromatic plant in Morocco. The experiments undertaken consist of examining the effects of drying air velocity, temperature of drying air and air moisture content on the drying kinetics of verbena in a laboratory drying tunnel working by forced convection. The results verified, with good reproducibility, that temperature is the main factor in controlling the rate of drying. The expression of the drying rate is determined empirically from the characteristic curve of drying. (author)

Enthalpy-entropy compensation in protein unfolding

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

Enthalpy-entropy compensation was found to be a universal law in protein unfolding based on over 3 000 experimental data. Water molecular reorganization accompanying the protein unfolding was suggested as the origin of the enthalpy-entropy compensation in protein unfolding. It is indicated that the enthalpy-entropy compensation constitutes the physical foundation that satisfies the biological need of the small free energy changes in protein unfolding, without the sacrifice of the bio-diversity of proteins. The enthalpy-entropy compensation theory proposed herein also provides valuable insights into the Privalov's puzzle of enthalpy and entropy convergence in protein unfolding.

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.

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.

Molecular dynamics study of the nanosized droplet spreading: The effect of the contact line forces on the kinetic energy dissipation

Energy Technology Data Exchange (ETDEWEB)

Yoon, Hong Min [Department of Mechanical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Kondaraju, Sasidhar [Department of Mechanical Science, Indian Institute of Technology Bhubaneswar, Bhubaneswar, Odisha 751013 (India); Lee, Jung Shin [Department of Mechanical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Suh, Youngho; Lee, Joonho H. [Samsung Electronics, Mechatronics R& D Center, Hwaseong-si, Gyeonggi-do 445-330 (Korea, Republic of); Lee, Joon Sang, E-mail: joonlee@yonsei.ac.kr [Department of Mechanical Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of)

2017-07-01

Highlights: • Contact line forces, including friction and spreading forces are directly calculated. • Overall trends of variations in contact line forces during droplet spreading process show characteristics of contact line forces. • Detail relations of contact line forces and atomic kinetics in the contact line provide a clear evidence of the possible energy dissipation mechanism in droplet spreading process. - Abstract: Recent studies have revealed that contact line forces play an important role in the droplet spreading process. Despite their significance, the physics related to them has been studied only indirectly and the effect of contact line forces is still being disputed. We performed a molecular dynamics simulation and mimicked the droplet spreading process at the nanoscale. Based on the results of the simulation, the contact line forces were directly calculated. We found that the forces acting on the bulk and the contact line region showed different trends. Distinct positive and negative forces, contact line spreading, and friction forces were observed near the contact line. We also observed a strong dependency of the atomic kinetics in the contact line region on the variations in the contact line forces. The atoms of the liquid in the contact line region lost their kinetic energy due to the contact line friction force and became partially immobile on the solid surface. The results of the current study will be useful for understanding the role of the contact line forces on the kinetic energy dissipation in the contact line region.

Molecular dynamics study of the nanosized droplet spreading: The effect of the contact line forces on the kinetic energy dissipation

International Nuclear Information System (INIS)

Yoon, Hong Min; Kondaraju, Sasidhar; Lee, Jung Shin; Suh, Youngho; Lee, Joonho H.; Lee, Joon Sang

2017-01-01

Highlights: • Contact line forces, including friction and spreading forces are directly calculated. • Overall trends of variations in contact line forces during droplet spreading process show characteristics of contact line forces. • Detail relations of contact line forces and atomic kinetics in the contact line provide a clear evidence of the possible energy dissipation mechanism in droplet spreading process. - Abstract: Recent studies have revealed that contact line forces play an important role in the droplet spreading process. Despite their significance, the physics related to them has been studied only indirectly and the effect of contact line forces is still being disputed. We performed a molecular dynamics simulation and mimicked the droplet spreading process at the nanoscale. Based on the results of the simulation, the contact line forces were directly calculated. We found that the forces acting on the bulk and the contact line region showed different trends. Distinct positive and negative forces, contact line spreading, and friction forces were observed near the contact line. We also observed a strong dependency of the atomic kinetics in the contact line region on the variations in the contact line forces. The atoms of the liquid in the contact line region lost their kinetic energy due to the contact line friction force and became partially immobile on the solid surface. The results of the current study will be useful for understanding the role of the contact line forces on the kinetic energy dissipation in the contact line region.

Evidence for a Shared Mechanism in the Formation of Urea-Induced Kinetic and Equilibrium Intermediates of Horse Apomyoglobin from Ultrarapid Mixing Experiments

Science.gov (United States)

Mizukami, Takuya; Abe, Yukiko; Maki, Kosuke

2015-01-01

In this study, the equivalence of the kinetic mechanisms of the formation of urea-induced kinetic folding intermediates and non-native equilibrium states was investigated in apomyoglobin. Despite having similar structural properties, equilibrium and kinetic intermediates accumulate under different conditions and via different mechanisms, and it remains unknown whether their formation involves shared or distinct kinetic mechanisms. To investigate the potential mechanisms of formation, the refolding and unfolding kinetics of horse apomyoglobin were measured by continuous- and stopped-flow fluorescence over a time range from approximately 100 μs to 10 s, along with equilibrium unfolding transitions, as a function of urea concentration at pH 6.0 and 8°C. The formation of a kinetic intermediate was observed over a wider range of urea concentrations (0–2.2 M) than the formation of the native state (0–1.6 M). Additionally, the kinetic intermediate remained populated as the predominant equilibrium state under conditions where the native and unfolded states were unstable (at ~0.7–2 M urea). A continuous shift from the kinetic to the equilibrium intermediate was observed as urea concentrations increased from 0 M to ~2 M, which indicates that these states share a common kinetic folding mechanism. This finding supports the conclusion that these intermediates are equivalent. Our results in turn suggest that the regions of the protein that resist denaturant perturbations form during the earlier stages of folding, which further supports the structural equivalence of transient and equilibrium intermediates. An additional folding intermediate accumulated within ~140 μs of refolding and an unfolding intermediate accumulated in <1 ms of unfolding. Finally, by using quantitative modeling, we showed that a five-state sequential scheme appropriately describes the folding mechanism of horse apomyoglobin. PMID:26244984

How to Measure Load-Dependent Kinetics of Individual Motor Molecules Without a Force-Clamp

DEFF Research Database (Denmark)

Sung, Jongmin; Mortensen, Kim; Spudich, James A.

Molecular motors are responsible for numerous cellular processes from cargo transport to heart contraction. Their interactions with other cellular components are often transient and exhibit kinetics that depend on load. Here, we measure such interactions using a new method, Harmonic Force...... and efficient. The protocol accumulates statistics fast enough to deliver single-molecule results from single-molecule experiments. We demonstrate the method's performance by measuring the force-dependent kinetics of individual human beta-cardiac myosin molecules interacting with an actin filament...... at physiological ATP concentration. We show that a molecule's ADP release rate depends exponentially on the applied load. This points to Kramer's Brownian diffusion model of chemical reactions as explanation why muscle contracts with a velocity inversely proportional to external load....

Using ground reaction force to predict knee kinetic asymmetry following anterior cruciate ligament reconstruction.

Science.gov (United States)

Dai, B; Butler, R J; Garrett, W E; Queen, R M

2014-12-01

Asymmetries in sagittal plane knee kinetics have been identified as a risk factor for anterior cruciate ligament (ACL) re-injury. Clinical tools are needed to identify the asymmetries. This study examined the relationships between knee kinetic asymmetries and ground reaction force (GRF) asymmetries during athletic tasks in adolescent patients following ACL reconstruction (ACL-R). Kinematic and GRF data were collected during a stop-jump task and a side-cutting task for 23 patients. Asymmetry indices between the surgical and non-surgical limbs were calculated for GRF and knee kinetic variables. For the stop-jump task, knee kinetics asymmetry indices were correlated with all GRF asymmetry indices (P kinetic asymmetry indices were correlated with the peak propulsion vertical GRF and vertical GRF impulse asymmetry indices (P kinetic asymmetries and therefore may assist in optimizing rehabilitation outcomes and minimizing re-injury rates. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

How to measure load-dependent kinetics of individual motor molecules without a force clamp

DEFF Research Database (Denmark)

Sung, J.; Mortensen, Kim; Spudich, J.A.

2017-01-01

Single-molecule force spectroscopy techniques, including optical trapping, magnetic trapping, and atomic force microscopy, have provided unprecedented opportunities to understand biological processes at the smallest biological length scales. For example, they have been used to elucidate the molec......Single-molecule force spectroscopy techniques, including optical trapping, magnetic trapping, and atomic force microscopy, have provided unprecedented opportunities to understand biological processes at the smallest biological length scales. For example, they have been used to elucidate...... functions at the single molecule level, such as conformational changes and force-generation of individual motor proteins or force-dependent kinetics in molecular interactions. Here, we describe a new method, “Harmonic Force Spectroscopy (HFS).” With a conventional dual-beam optical trap and a simple...... concepts, experimental setup, step-by-step experimental protocol, theory, data analysis, and results....

Equilibrium amide hydrogen exchange and protein folding kinetics

International Nuclear Information System (INIS)

Bai Yawen

1999-01-01

The classical Linderstrom-Lang hydrogen exchange (HX) model is extended to describe the relationship between the HX behaviors (EX1 and EX2) and protein folding kinetics for the amide protons that can only exchange by global unfolding in a three-state system including native (N), intermediate (I), and unfolded (U) states. For these slowly exchanging amide protons, it is shown that the existence of an intermediate (I) has no effect on the HX behavior in an off-pathway three-state system (I↔U↔N). On the other hand, in an on-pathway three-state system (U↔I↔N), the existence of a stable folding intermediate has profound effect on the HX behavior. It is shown that fast refolding from the unfolded state to the stable intermediate state alone does not guarantee EX2 behavior. The rate of refolding from the intermediate state to the native state also plays a crucial role in determining whether EX1 or EX2 behavior should occur. This is mainly due to the fact that only amide protons in the native state are observed in the hydrogen exchange experiment. These new concepts suggest that caution needs to be taken if one tries to derive the kinetic events of protein folding from equilibrium hydrogen exchange experiments

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.

Non-specific binding of Na+ and Mg2+ to RNA determined by force spectroscopy methods

Science.gov (United States)

Bizarro, C. V.; Alemany, A.; Ritort, F.

2012-01-01

RNA duplex stability depends strongly on ionic conditions, and inside cells RNAs are exposed to both monovalent and multivalent ions. Despite recent advances, we do not have general methods to quantitatively account for the effects of monovalent and multivalent ions on RNA stability, and the thermodynamic parameters for secondary structure prediction have only been derived at 1M [Na+]. Here, by mechanically unfolding and folding a 20 bp RNA hairpin using optical tweezers, we study the RNA thermodynamics and kinetics at different monovalent and mixed monovalent/Mg2+ salt conditions. We measure the unfolding and folding rupture forces and apply Kramers theory to extract accurate information about the hairpin free energy landscape under tension at a wide range of ionic conditions. We obtain non-specific corrections for the free energy of formation of the RNA hairpin and measure how the distance of the transition state to the folded state changes with force and ionic strength. We experimentally validate the Tightly Bound Ion model and obtain values for the persistence length of ssRNA. Finally, we test the approximate rule by which the non-specific binding affinity of divalent cations at a given concentration is equivalent to that of monovalent cations taken at 100-fold concentration for small molecular constructs. PMID:22492710

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.

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.

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

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...

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.

Unfolding study of a trimeric membrane protein AcrB.

Science.gov (United States)

Ye, Cui; Wang, Zhaoshuai; Lu, Wei; Wei, Yinan

2014-07-01

The folding of a multi-domain trimeric α-helical membrane protein, Escherichia coli inner membrane protein AcrB, was investigated. AcrB contains both a transmembrane domain and a large periplasmic domain. Protein unfolding in sodium dodecyl sulfate (SDS) and urea was monitored using the intrinsic fluorescence and circular dichroism spectroscopy. The SDS denaturation curve displayed a sigmoidal profile, which could be fitted with a two-state unfolding model. To investigate the unfolding of separate domains, a triple mutant was created, in which all three Trp residues in the transmembrane domain were replaced with Phe. The SDS unfolding profile of the mutant was comparable to that of the wild type AcrB, suggesting that the observed signal change was largely originated from the unfolding of the soluble domain. Strengthening of trimer association through the introduction of an inter-subunit disulfide bond had little effect on the unfolding profile, suggesting that trimer dissociation was not the rate-limiting step in unfolding monitored by fluorescence emission. Under our experimental condition, AcrB unfolding was not reversible. Furthermore, we experimented with the refolding of a monomeric mutant, AcrBΔloop , from the SDS unfolded state. The CD spectrum of the refolded AcrBΔloop superimposed well onto the spectra of the original folded protein, while the fluorescence spectrum was not fully recovered. In summary, our results suggested that the unfolding of the trimeric AcrB started with a local structural rearrangement. While the refolding of secondary structure in individual monomers could be achieved, the re-association of the trimer might be the limiting factor to obtain folded wild-type AcrB. © 2014 The Protein Society.

Kinetically controlled thermal response of beta2-microglobulin amyloid fibrils.

Science.gov (United States)

Sasahara, Kenji; Naiki, Hironobu; Goto, Yuji

2005-09-23

Calorimetric measurements were carried out using a differential scanning calorimeter in the temperature range from 10 to 120 degrees C for characterizing the thermal response of beta2-microglobulin amyloid fibrils. The thermograms of amyloid fibril solution showed a remarkably large decrease in heat capacity that was essentially released upon the thermal unfolding of the fibrils, in which the magnitude of negative heat capacity change was not explicable in terms of the current accessible surface area model of protein structural thermodynamics. The heat capacity-temperature curve of amyloid fibrils prior to the fibril unfolding exhibited an unusual dependence on the fibril concentration and the heating rate. Particularly, the heat needed to induce the thermal response was found to be linearly dependent on the heating rate, indicating that its thermal response is under a kinetic control and precluding the interpretation in terms of equilibrium thermodynamics. Furthermore, amyloid fibrils of amyloid beta peptides also exhibited a heating rate-dependent exothermic process before the fibril unfolding, indicating that the kinetically controlled thermal response may be a common phenomenon to amyloid fibrils. We suggest that the heating rate-dependent negative change in heat capacity is coupled to the association of amyloid fibrils with characteristic hydration pattern.

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.

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

Directory of Open Access Journals (Sweden)

David S. Kliger

2009-04-01

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

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.

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.

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.

Advanced path sampling of the kinetic network of small proteins

NARCIS (Netherlands)

Du, W.

2014-01-01

This thesis is focused on developing advanced path sampling simulation methods to study protein folding and unfolding, and to build kinetic equilibrium networks describing these processes. In Chapter 1 the basic knowledge of protein structure and folding theories were introduced and a brief overview

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...

Improved free-energy landscape reconstruction of bacteriorhodopsin highlights local variations in unfolding energy.

Science.gov (United States)

Heenan, Patrick R; Yu, Hao; Siewny, Matthew G W; Perkins, Thomas T

2018-03-28

Precisely quantifying the energetics that drive the folding of membrane proteins into a lipid bilayer remains challenging. More than 15 years ago, atomic force microscopy (AFM) emerged as a powerful tool to mechanically extract individual membrane proteins from a lipid bilayer. Concurrently, fluctuation theorems, such as the Jarzynski equality, were applied to deduce equilibrium free energies (ΔG 0 ) from non-equilibrium single-molecule force spectroscopy records. The combination of these two advances in single-molecule studies deduced the free-energy of the model membrane protein bacteriorhodopsin in its native lipid bilayer. To elucidate this free-energy landscape at a higher resolution, we applied two recent developments. First, as an input to the reconstruction, we used force-extension curves acquired with a 100-fold higher time resolution and 10-fold higher force precision than traditional AFM studies of membrane proteins. Next, by using an inverse Weierstrass transform and the Jarzynski equality, we removed the free energy associated with the force probe and determined the molecular free-energy landscape of the molecule under study, bacteriorhodopsin. The resulting landscape yielded an average unfolding free energy per amino acid (aa) of 1.0 ± 0.1 kcal/mol, in agreement with past single-molecule studies. Moreover, on a smaller spatial scale, this high-resolution landscape also agreed with an equilibrium measurement of a particular three-aa transition in bacteriorhodopsin that yielded 2.7 kcal/mol/aa, an unexpectedly high value. Hence, while average unfolding ΔG 0 per aa is a useful metric, the derived high-resolution landscape details significant local variation from the mean. More generally, we demonstrated that, as anticipated, the inverse Weierstrass transform is an efficient means to reconstruct free-energy landscapes from AFM data.

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.

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.

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.

Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes

Directory of Open Access Journals (Sweden)

Jan David Kijlstra

2015-12-01

Full Text Available The quantitative analysis of cardiomyocyte function is essential for stem cell-based approaches for the in vitro study of human cardiac physiology and pathophysiology. We present a method to comprehensively assess the function of single human pluripotent stem cell-derived cardiomyocyte (hPSC-CMs through simultaneous quantitative analysis of contraction kinetics, force generation, and electrical activity. We demonstrate that statistical analysis of movies of contracting hPSC-CMs can be used to quantify changes in cellular morphology over time and compute contractile kinetics. Using a biomechanical model that incorporates substrate stiffness, we calculate cardiomyocyte force generation at single-cell resolution and validate this approach with conventional traction force microscopy. The addition of fluorescent calcium indicators or membrane potential dyes allows the simultaneous analysis of contractility and calcium handling or action potential morphology. Accordingly, our approach has the potential for broad application in the study of cardiac disease, drug discovery, and cardiotoxicity screening.

Single-Molecule Force Spectroscopy Trajectories of a Single Protein and Its Polyproteins Are Equivalent: A Direct Experimental Validation Based on A Small Protein NuG2.

Science.gov (United States)

Lei, Hai; He, Chengzhi; Hu, Chunguang; Li, Jinliang; Hu, Xiaodong; Hu, Xiaotang; Li, Hongbin

2017-05-22

Single-molecule force spectroscopy (SMFS) has become a powerful tool in investigating the mechanical unfolding/folding of proteins at the single-molecule level. Polyproteins made of tandem identical repeats have been widely used in atomic force microscopy (AFM)-based SMFS studies, where polyproteins not only serve as fingerprints to identify single-molecule stretching events, but may also improve statistics of data collection. However, the inherent assumption of such experiments is that all the domains in the polyprotein are equivalent and one SMFS trajectory of stretching a polyprotein made of n domains is equivalent to n trajectories of stretching a single domain. Such an assumption has not been validated experimentally. Using a small protein NuG2 and its polyprotein (NuG2) 4 as model systems, here we use optical trapping (OT) to directly validate this assumption. Our results show that OT experiments on NuG2 and (NuG2) 4 lead to identical parameters describing the unfolding and folding kinetics of NuG2, demonstrating that indeed stretching a polyprotein of NuG2 is equivalent to stretching single NuG2 in force spectroscopy experiments and thus validating the use of polyproteins in SMFS experiments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Static and kinetic friction force and surface roughness of different archwire-bracket sliding contacts.

Science.gov (United States)

Carrion-Vilches, Francisco J; Bermudez, María-Dolores; Fructuoso, Paula

2015-01-01

The aim of this study was to determine the static and kinetic friction forces of the contact bracket-archwire with different dental material compositions in order to select those materials with lower resistance to sliding. We carried out sliding friction tests by means of a universal testing machine following an experimental procedure as described in ASTM D1894 standard. We determined the static and kinetic friction forces under dry and lubricating conditions using an artificial saliva solution at 36.5ºC. The bracket-archwire pairs studied were: stainless steel-stainless steel; stainless steel-glass fiber composite; stainless steel-Nitinol 60; sapphire-stainless steel; sapphire-glass fiber composite; and sapphire-Nitinol 60. The best performance is obtained for Nitinol 60 archwire sliding against a stainless steel bracket, both under dry and lubricated conditions. These results are in agreement with the low surface roughness of Nitinol 60 with respect to the glass fiber composite archwire. The results described here contribute to establishing selection criteria for materials for dental archwire-brackets.

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)

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

Obtention of the ponderomotive force in the mark of the kinetic theory in the injection of high power in a plasma

International Nuclear Information System (INIS)

Gutierrez T, C.; Beltran P, M.

2006-01-01

To reach the quasi stationary work regime of a Tokamak, it is necessary to optimize the current generation by non inductive methods with the injection of radio-frequency waves (RF), such as the electron cyclotron waves, cyclotron ion, and in the inferior hybrid one. At the moment, the powers of the radiation sources are very big for what the such no-lineal effects as the ponderomotive force are very important. In the case of the electron cyclotron waves, in the mark of the lineal theory of waves propagation, using extraordinary waves (first and second harmonic), the problem of the singularity always arises in the exact resonance. One of the ways of eliminating this singularity is considering that the group of electrons under resonance conditions is big (quasi lineal theory) or introducing such non lineal effects such as the ponderomotive force. In the obtaining of the ponderomotive force under resonance conditions this indetermination arises also. In this work the kinetic theory to obtain the expression of the ponderomotive force in the cyclotron resonance of the electrons, where the Vlasov kinetic equation expands up to second order with regard to the electric field of the RF wave. The kinetic approach allows to the analysis of the ponderomotive force under resonance conditions considering the Landau integration method. (Author)

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.

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.

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.

Peripheral Protein Unfolding Drives Membrane Bending.

Science.gov (United States)

Siaw, Hew Ming Helen; Raghunath, Gokul; Dyer, R Brian

2018-06-20

Dynamic modulation of lipid membrane curvature can be achieved by a number of peripheral protein binding mechanisms such as hy-drophobic insertion of amphipathic helices and membrane scaffolding. Recently, an alternative mechanism was proposed in which crowding of peripherally bound proteins induces membrane curvature through steric pressure generated by lateral collisions. This effect was enhanced using intrinsically disordered proteins that possess high hydrodynamic radii, prompting us to explore whether membrane bending can be triggered by the folding-unfolding transition of surface-bound proteins. We utilized histidine-tagged human serum albumin bound to Ni-NTA-DGS containing liposomes as our model system to test this hypothesis. We found that reduction of the disulfide bonds in the protein resulted in unfolding of HSA, which subsequently led to membrane tubule formation. The frequency of tubule formation was found to be significantly higher when the proteins were unfolded while being localized to a phase-separated domain as opposed to randomly distributed in fluid phase liposomes, indicating that the steric pressure generated from protein unfolding is directly responsible for membrane deformation. Our results are critical for the design of peripheral membrane protein-immobilization strategies and open new avenues for exploring mechanisms of membrane bending driven by conformational changes of peripheral membrane proteins.

Transition paths in single-molecule force spectroscopy.

Science.gov (United States)

Cossio, Pilar; Hummer, Gerhard; Szabo, Attila

2018-03-28

In a typical single-molecule force spectroscopy experiment, the ends of the molecule of interest are connected by long polymer linkers to a pair of mesoscopic beads trapped in the focus of two laser beams. At constant force load, the total extension, i.e., the end-to-end distance of the molecule plus linkers, is measured as a function of time. In the simplest systems, the measured extension fluctuates about two values characteristic of folded and unfolded states, with occasional transitions between them. We have recently shown that molecular (un)folding rates can be recovered from such trajectories, with a small linker correction, as long as the characteristic time of the bead fluctuations is shorter than the residence time in the unfolded (folded) state. Here, we show that accurate measurements of the molecular transition path times require an even faster apparatus response. Transition paths, the trajectory segments in which the molecule (un)folds, are properly resolved only if the beads fluctuate more rapidly than the end-to-end distance of the molecule. Therefore, over a wide regime, the measured rates may be meaningful but not the transition path times. Analytic expressions for the measured mean transition path times are obtained for systems diffusing anisotropically on a two-dimensional free energy surface. The transition path times depend on the properties both of the molecule and of the pulling device.

The inverted chevron plot measured by NMR relaxation reveals a native-like unfolding intermediate in acyl-CoA binding protein

DEFF Research Database (Denmark)

Teilum, Kaare; Poulsen, F. M.; Akke, M.

2006-01-01

those from stopped-flow kinetics and define an "inverted chevron" plot. The combination of NMR relaxation and stopped-flow kinetic measurements allowed determination of k f and k u in the range from 0.48 M GuHCl to 1.28 M GuHCl. Individually, the stopped-flow and NMR data fit two-state models...... for folding. However, although the values of k f determined by the two methods agree, the values of k u do not. As a result, a combined analysis of all data does not comply with a two-state model but indicates that an unfolding intermediate exists on the native side of the dominant energy barrier...

Implementing atomic force microscopy (AFM) for studying kinetics of gold nanoparticle's growth

DEFF Research Database (Denmark)

Georgiev, P.; Bojinova, A.; Kostova, B.

2013-01-01

In a novel experimental approach Atomic Force Microscopy (AFM) was applied as a tool for studying the kinetics of gold nanoparticle growth. The gold nanoparticles were obtained by classical Turkevich citrate synthesis at two different temperatures. From the analysis of AFM images during...... the synthesis process the nanoparticle s' sizes were obtained. To demonstrate the applicability and the reliability of the proposed experimental approach we studied the nanoparticles growth at two different temperatures by spectrophotometric measurements and compared them with the results from AFM experimental...

Phonon forces and cold denaturatio

DEFF Research Database (Denmark)

Bohr, Jakob

2003-01-01

Protein unfolds upon temperature reduction as Well as upon In increase in temperature, These phenomena are called cold denaturation and hot denaturation, respectively. The contribution from quantum mode forces to denaturation is estimated using a simple phenomenological model describing the molec......Protein unfolds upon temperature reduction as Well as upon In increase in temperature, These phenomena are called cold denaturation and hot denaturation, respectively. The contribution from quantum mode forces to denaturation is estimated using a simple phenomenological model describing...... the molecule Is a continuum. The frequencies of the vibrational modes depend on the molecular dimensionality; hence, the zero-point energies for the folded and the denatured protein are estimated to differ by several electron volts. For a biomolecule such an energy is significant and may contribute to cold...... denaturing. This is consistent with the empirical observation that cold denaturation is exothermic anti hot denaturation endothermic....

The cumulative measure of a force: A unified kinetic theory for rigid-sphere and inverse-square force law interactions

Directory of Open Access Journals (Sweden)

Yongbin Chang

2011-09-01

Full Text Available By introducing a cutoff on the cumulative measure of a force, a unified kinetic theory is developed for both rigid-sphere and inverse-square force laws. The difference between the two kinds of interactions is characterized by a parameter, γ, which is 1 for rigid-sphere interactions and -3 for inverse-square force law interactions. The quantities governed by γ include the specific reaction rates, kernels, collision frequencies, arbitrarily high orders of transition moments, arbitrarily high orders of Fokker-Planck expansion (also called Kramers-Moyal expansion coefficients, and arbitrarily high orders of energy exchange rates. The cutoff constants are shown to be incomplete gamma functions of different orders. The widely used cutoff constant in plasma physics (usually known as Coulomb logarithm is found to be exactly the zeroth order of the incomplete gamma function. The well known Arrhenius reaction rate formula comes from the first order of the incomplete gamma functions, while the negative first order can be used for fitting the fusion reaction rate between deuterium and tritium.

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

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.

Structural and kinetic mapping of side-chain exposure onto the protein energy landscape.

Science.gov (United States)

Bernstein, Rachel; Schmidt, Kierstin L; Harbury, Pehr B; Marqusee, Susan

2011-06-28

Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated.

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.)

Counting Unfolding Events in Stretched Helices with Induced Oscillation by Optical Tweezers

Science.gov (United States)

Bacabac, Rommel Gaud; Otadoy, Roland

Correlation measures based on embedded probe fluctuations, single or paired, are now widely used for characterizing the viscoelastic properties of biological samples. However, more robust applications using this technique are still lacking. Considering that the study of living matter routinely demonstrates new and complex phenomena, mathematical and experimental tools for analysis have to catch up in order to arrive at newer insights. Therefore, we derive ways of probing non-equilibrium events in helical biopolymers provided by stretching beyond thermal forces. We generalize, for the first time, calculations for winding turn probabilities to account for unfolding events in single fibrous biopolymers and globular proteins under tensile stretching using twin optical traps. The approach is based on approximating the ensuing probe fluctuations as originating from a damped harmonic oscillator under oscillatory forcing.

Unfolding energetics and stability of banana lectin.

Science.gov (United States)

Gupta, Garima; Sinha, Sharmistha; Surolia, Avadhesha

2008-08-01

The unfolding pathway of banana lectin from Musa paradisiaca was determined by isothermal denaturation induced by the chaotrope GdnCl. The unfolding was found to be a reversible process. The data obtained by isothermal denaturation provided information on conformational stability of banana lectin. The high values of DeltaG of unfolding at various temperatures indicated the strength of intersubunit interactions. It was found that banana lectin is a very stable and denatures at high chaotrope concentrations only. The basis of the stability may be attributed to strong hydrogen bonds of the order 2.5-3.1 A at the dimeric interface along with the presence of water bridges. This is perhaps very unique example in proteins where subunit association is not a consequence of the predominance of hydrophobic interactions. (c) 2008 Wiley-Liss, Inc.

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.

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.

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 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.

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.

Quantum mode phonon forces between chainmolecules

DEFF Research Database (Denmark)

Bohr, Jakob

2001-01-01

bimolecular interaction is a truly many-body force that is temperature dependent and can be of the order of 1 eV. These phonon forces depend on molecular shape, composition, and density. They may therefore also be important for large molecular conformational changes, including the unfolding of chain molecules....... For the later case, a significant change in zero-point energy is found. This may be the underlying cause for cold denaturation of proteins. (C) 2001 John Wiley & Sons, Inc....

Kinetic evidence for a two-stage mechanism of protein denaturation by guanidinium chloride.

Science.gov (United States)

Jha, Santosh Kumar; Marqusee, Susan

2014-04-01

Dry molten globular (DMG) intermediates, an expanded form of the native protein with a dry core, have been observed during denaturant-induced unfolding of many proteins. These observations are counterintuitive because traditional models of chemical denaturation rely on changes in solvent-accessible surface area, and there is no notable change in solvent-accessible surface area during the formation of the DMG. Here we show, using multisite fluorescence resonance energy transfer, far-UV CD, and kinetic thiol-labeling experiments, that the guanidinium chloride (GdmCl)-induced unfolding of RNase H also begins with the formation of the DMG. Population of the DMG occurs within the 5-ms dead time of our measurements. We observe that the size and/or population of the DMG is linearly dependent on [GdmCl], although not as strongly as the second and major step of unfolding, which is accompanied by core solvation and global unfolding. This rapid GdmCl-dependent population of the DMG indicates that GdmCl can interact with the protein before disrupting the hydrophobic core. These results imply that the effect of chemical denaturants cannot be interpreted solely as a disruption of the hydrophobic effect and strongly support recent computational studies, which hypothesize that chemical denaturants first interact directly with the protein surface before completely unfolding the protein in the second step (direct interaction mechanism).

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.

Spatial distribution of mechanical forces and ionic flux in electro-kinetic instability near a permselective membrane

Science.gov (United States)

Magnico, Pierre

2018-01-01

This paper is devoted to the numerical investigation of electro-kinetic instability in a polarization layer next to a cation-exchange membrane. An analysis of some properties of the electro-kinetic instability is followed by a detailed description of the fluid flow structure and of the spatial distribution of the ionic flux. In this aim, the Stokes-Poisson-Nernst-Planck equation set is solved until the Debye length scale. The results show that the potential threshold of the marginal instability and the current density depend on the logarithm of the concentration at the membrane surface. The size of the stable vortices seems to be an increasing function of the potential drop. The fluid motion is induced by the electric force along the maximum concentration in the extended space charge (ESC) region and by the pressure force in the region around the inner edge of the ESC layer. Two spots of kinetic energy are located in the ESC region and between the vortices. The cationic motion, controlled by the electric field and the convection, presents counter-rotating vortices in the stagnation zone located in the fluid ejection region. The anion transport is also characterized by two independent layers which contain counter-rotating vortices. The first one is in contact with the stationary reservoir. In the second layer against the membrane, the convection, and the electric field control, the transversal motion, the Fickian diffusion, and the convection are dominant in the longitudinal direction. Finally, the longitudinal disequilibrium of potential and pressure along the membrane is analyzed.

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.

New force replica exchange method and protein folding pathways probed by force-clamp technique.

Science.gov (United States)

Kouza, Maksim; Hu, Chin-Kun; Li, Mai Suan

2008-01-28

We have developed a new extended replica exchange method to study thermodynamics of a system in the presence of external force. Our idea is based on the exchange between different force replicas to accelerate the equilibrium process. This new approach was applied to obtain the force-temperature phase diagram and other thermodynamical quantities of the three-domain ubiquitin. Using the C(alpha)-Go model and the Langevin dynamics, we have shown that the refolding pathways of single ubiquitin depend on which terminus is fixed. If the N end is fixed then the folding pathways are different compared to the case when both termini are free, but fixing the C terminal does not change them. Surprisingly, we have found that the anchoring terminal does not affect the pathways of individual secondary structures of three-domain ubiquitin, indicating the important role of the multidomain construction. Therefore, force-clamp experiments, in which one end of a protein is kept fixed, can probe the refolding pathways of a single free-end ubiquitin if one uses either the polyubiquitin or a single domain with the C terminus anchored. However, it is shown that anchoring one end does not affect refolding pathways of the titin domain I27, and the force-clamp spectroscopy is always capable to predict folding sequencing of this protein. We have obtained the reasonable estimate for unfolding barrier of ubiquitin, using the microscopic theory for the dependence of unfolding time on the external force. The linkage between residue Lys48 and the C terminal of ubiquitin is found to have the dramatic effect on the location of the transition state along the end-to-end distance reaction coordinate, but the multidomain construction leaves the transition state almost unchanged. We have found that the maximum force in the force-extension profile from constant velocity force pulling simulations depends on temperature nonlinearly. However, for some narrow temperature interval this dependence becomes

One Peptide Reveals the Two Faces of α-Helix Unfolding-Folding Dynamics.

Science.gov (United States)

Jesus, Catarina S H; Cruz, Pedro F; Arnaut, Luis G; Brito, Rui M M; Serpa, Carlos

2018-04-12

The understanding of fast folding dynamics of single α-helices comes mostly from studies on rationally designed peptides displaying sequences with high helical propensity. The folding/unfolding dynamics and energetics of α-helix conformations in naturally occurring peptides remains largely unexplored. Here we report the study of a protein fragment analogue of the C-peptide from bovine pancreatic ribonuclease-A, RN80, a 13-amino acid residue peptide that adopts a highly populated helical conformation in aqueous solution. 1 H NMR and CD structural studies of RN80 showed that α-helix formation displays a pH-dependent bell-shaped curve, with a maximum near pH 5, and a large decrease in helical content in alkaline pH. The main forces stabilizing this short α-helix were identified as a salt bridge formed between Glu-2 and Arg-10 and the cation-π interaction involving Tyr-8 and His-12. Thus, deprotonation of Glu-2 or protonation of His-12 are essential for the RN80 α-helix stability. In the present study, RN80 folding and unfolding were triggered by laser-induced pH jumps and detected by time-resolved photoacoustic calorimetry (PAC). The photoacid proton release, amino acid residue protonation, and unfolding/folding events occur at different time scales and were clearly distinguished using time-resolved PAC. The partial unfolding of the RN80 α-helix, due to protonation of Glu-2 and consequent breaking of the stabilizing salt bridge between Glu-2 and Arg-10, is characterized by a concentration-independent volume expansion in the sub-microsecond time range (0.8 mL mol -1 , 369 ns). This small volume expansion reports the cost of peptide backbone rehydration upon disruption of a solvent-exposed salt bridge, as well as backbone intrinsic expansion. On the other hand, RN80 α-helix folding triggered by His-12 protonation and subsequent formation of a cation-π interaction leads to a microsecond volume contraction (-6.0 mL mol -1 , ∼1.7 μs). The essential role of two

The Force Exerted by the Membrane Potential During Protein Import into the Mitochondrial Matrix

Science.gov (United States)

Shariff, Karim; Ghosal, Sandip; Matouschek, Andreas

2002-01-01

The electrostatic force exerted on a targeting sequence by the electrical potential across the inner mitochondrial membrane is calculated and found to vary from 1.4 pN to 2.2 pN (per unit elementary charge) as the radius of the inner membrane pore (assumed aqueous) is varied from 12 to 6.5 Angstroms, its measured range. Since the pore is not very much wider than the distance between water molecules, the full shielding effect of water may not be present; the extreme case of a nonaqueous pore gives a force of 3.1 pN per unit charge, which represents an upper limit. When applied to mitochondrial import experiments on the protein harness, these results imply that a force of 11 plus or minus 4 pN is sufficient to catalyze the unfolding of harness during import. Comparison of these results with unfolding forces measured using atomic force microscopy suggests that the two are not inconsistent.

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.

Tunneling Kinetics and Nonadiabatic Proton-Coupled Electron Transfer in Proteins: The Effect of Electric Fields and Anharmonic Donor-Acceptor Interactions.

Science.gov (United States)

Salna, Bridget; Benabbas, Abdelkrim; Russo, Douglas; Champion, Paul M

2017-07-20

A proper description of proton donor-acceptor (D-A) distance fluctuations is crucial for understanding tunneling in proton-coupled electron transport (PCET). The typical harmonic approximation for the D-A potential results in a Gaussian probability distribution, which does not appropriately reflect the electronic repulsion forces that increase the energetic cost of sampling shorter D-A distances. Because these shorter distances are the primary channel for thermally activated tunneling, the analysis of tunneling kinetics depends sensitively on the inherently anharmonic nature of the D-A interaction. Thus, we have used quantum chemical calculations to account for the D-A interaction and developed an improved model for the analysis of experimental tunneling kinetics. Strong internal electric fields are also considered and found to contribute significantly to the compressive forces when the D-A distance distribution is positioned below the van der Waals contact distance. This model is applied to recent experiments on the wild type (WT) and a double mutant (DM) of soybean lipoxygenase-1 (SLO). The compressive force necessary to prepare the tunneling-active distribution in WT SLO is found to fall in the ∼ nN range, which greatly exceeds the measured values of molecular motor and protein unfolding forces. This indicates that ∼60-100 MV/cm electric fields, aligned along the D-A bond axis, must be generated by an enzyme conformational interconversion that facilitates the PCET tunneling reaction. Based on the absolute value of the measured tunneling rate, and using previously calculated values of the electronic matrix element, the population of this tunneling-active conformation is found to lie in the range 10 -5 -10 -7 , indicating this is a rare structural fluctuation that falls well below the detection threshold of recent ENDOR experiments. Additional analysis of the DM tunneling kinetics leads to a proposal that a disordered (high entropy) conformation could be

Folding and unfolding pathway of chaperonin GroEL monomer and elucidation of thermodynamic parameters.

Science.gov (United States)

Puri, Sarita; Chaudhuri, Tapan K

2017-03-01

The conformation and thermodynamic stability of monomeric GroEL were studied by CD and fluorescence spectroscopy. GroEL denaturation with urea and dilution in buffer leads to formation of a folded GroEL monomer. The monomeric nature of this protein was verified by size-exclusion chromatography and native PAGE. It has a well-defined secondary and tertiary structure, folding activity (prevention of aggregation) for substrate protein and is resistant to proteolysis. Being a properly folded and reversibly refoldable, monomeric GroEL is amenable for the study of thermodynamic stability by unfolding transition methods. We present the equilibrium unfolding of monomeric GroEL as studied by urea and heat mediated unfolding processes. The urea mediated unfolding shows two transitions and a single transition in the heat mediated unfolding process. In the case of thermal unfolding, some residual structure unfolds at a higher temperature (70-75°C). The process of folding/unfolding is reversible in both cases. Analysis of folding/unfolding data provides a measure of ΔG NU H 2 O , T m , ΔH van and ΔS van of monomeric GroEL. The thermodynamic stability parameter ΔG NU H 2 O is similar with both CD and intrinsic fluorescence i.e. 7.10±1.0kcal/mol. The calculated T m , ΔH van and ΔS van from the thermal unfolding transition is 46±0.5°C, 43.3±0.1kcal/mol and 143.9±0.1cal/mol/k respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

The adsorption and unfolding kinetics determines the folding state of proteins at the air-water interface and thereby the equation of state

NARCIS (Netherlands)

Wierenga, P.A.; Egmond, M.R.; Voragen, A.G.J.; Jongh, H.H.J.de

2006-01-01

Unfolding of proteins has often been mentioned as an important factor during the adsorption process at air-water interfaces and in the increase of surface pressure at later stages of the adsorption process. This work focuses on the question whether the folding state of the adsorbed protein depends

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.

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.

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

Optimizing 1-μs-Resolution Single-Molecule Force Spectroscopy on a Commercial Atomic Force Microscope.

Science.gov (United States)

Edwards, Devin T; Faulk, Jaevyn K; Sanders, Aric W; Bull, Matthew S; Walder, Robert; LeBlanc, Marc-Andre; Sousa, Marcelo C; Perkins, Thomas T

2015-10-14

Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is widely used to mechanically measure the folding and unfolding of proteins. However, the temporal resolution of a standard commercial cantilever is 50-1000 μs, masking rapid transitions and short-lived intermediates. Recently, SMFS with 0.7-μs temporal resolution was achieved using an ultrashort (L = 9 μm) cantilever on a custom-built, high-speed AFM. By micromachining such cantilevers with a focused ion beam, we optimized them for SMFS rather than tapping-mode imaging. To enhance usability and throughput, we detected the modified cantilevers on a commercial AFM retrofitted with a detection laser system featuring a 3-μm circular spot size. Moreover, individual cantilevers were reused over multiple days. The improved capabilities of the modified cantilevers for SMFS were showcased by unfolding a polyprotein, a popular biophysical assay. Specifically, these cantilevers maintained a 1-μs response time while eliminating cantilever ringing (Q ≅ 0.5). We therefore expect such cantilevers, along with the instrumentational improvements to detect them on a commercial AFM, to accelerate high-precision AFM-based SMFS studies.

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)

Improving estimation of kinetic parameters in dynamic force spectroscopy using cluster analysis

Science.gov (United States)

Yen, Chi-Fu; Sivasankar, Sanjeevi

2018-03-01

Dynamic Force Spectroscopy (DFS) is a widely used technique to characterize the dissociation kinetics and interaction energy landscape of receptor-ligand complexes with single-molecule resolution. In an Atomic Force Microscope (AFM)-based DFS experiment, receptor-ligand complexes, sandwiched between an AFM tip and substrate, are ruptured at different stress rates by varying the speed at which the AFM-tip and substrate are pulled away from each other. The rupture events are grouped according to their pulling speeds, and the mean force and loading rate of each group are calculated. These data are subsequently fit to established models, and energy landscape parameters such as the intrinsic off-rate (koff) and the width of the potential energy barrier (xβ) are extracted. However, due to large uncertainties in determining mean forces and loading rates of the groups, errors in the estimated koff and xβ can be substantial. Here, we demonstrate that the accuracy of fitted parameters in a DFS experiment can be dramatically improved by sorting rupture events into groups using cluster analysis instead of sorting them according to their pulling speeds. We test different clustering algorithms including Gaussian mixture, logistic regression, and K-means clustering, under conditions that closely mimic DFS experiments. Using Monte Carlo simulations, we benchmark the performance of these clustering algorithms over a wide range of koff and xβ, under different levels of thermal noise, and as a function of both the number of unbinding events and the number of pulling speeds. Our results demonstrate that cluster analysis, particularly K-means clustering, is very effective in improving the accuracy of parameter estimation, particularly when the number of unbinding events are limited and not well separated into distinct groups. Cluster analysis is easy to implement, and our performance benchmarks serve as a guide in choosing an appropriate method for DFS data analysis.

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)

High-throughput single-molecule force spectroscopy for membrane proteins

Science.gov (United States)

Bosshart, Patrick D.; Casagrande, Fabio; Frederix, Patrick L. T. M.; Ratera, Merce; Bippes, Christian A.; Müller, Daniel J.; Palacin, Manuel; Engel, Andreas; Fotiadis, Dimitrios

2008-09-01

Atomic force microscopy-based single-molecule force spectroscopy (SMFS) is a powerful tool for studying the mechanical properties, intermolecular and intramolecular interactions, unfolding pathways, and energy landscapes of membrane proteins. One limiting factor for the large-scale applicability of SMFS on membrane proteins is its low efficiency in data acquisition. We have developed a semi-automated high-throughput SMFS (HT-SMFS) procedure for efficient data acquisition. In addition, we present a coarse filter to efficiently extract protein unfolding events from large data sets. The HT-SMFS procedure and the coarse filter were validated using the proton pump bacteriorhodopsin (BR) from Halobacterium salinarum and the L-arginine/agmatine antiporter AdiC from the bacterium Escherichia coli. To screen for molecular interactions between AdiC and its substrates, we recorded data sets in the absence and in the presence of L-arginine, D-arginine, and agmatine. Altogether ~400 000 force-distance curves were recorded. Application of coarse filtering to this wealth of data yielded six data sets with ~200 (AdiC) and ~400 (BR) force-distance spectra in each. Importantly, the raw data for most of these data sets were acquired in one to two days, opening new perspectives for HT-SMFS applications.

High-throughput single-molecule force spectroscopy for membrane proteins

International Nuclear Information System (INIS)

Bosshart, Patrick D; Casagrande, Fabio; Frederix, Patrick L T M; Engel, Andreas; Fotiadis, Dimitrios; Ratera, Merce; Palacin, Manuel; Bippes, Christian A; Mueller, Daniel J

2008-01-01

Atomic force microscopy-based single-molecule force spectroscopy (SMFS) is a powerful tool for studying the mechanical properties, intermolecular and intramolecular interactions, unfolding pathways, and energy landscapes of membrane proteins. One limiting factor for the large-scale applicability of SMFS on membrane proteins is its low efficiency in data acquisition. We have developed a semi-automated high-throughput SMFS (HT-SMFS) procedure for efficient data acquisition. In addition, we present a coarse filter to efficiently extract protein unfolding events from large data sets. The HT-SMFS procedure and the coarse filter were validated using the proton pump bacteriorhodopsin (BR) from Halobacterium salinarum and the L-arginine/agmatine antiporter AdiC from the bacterium Escherichia coli. To screen for molecular interactions between AdiC and its substrates, we recorded data sets in the absence and in the presence of L-arginine, D-arginine, and agmatine. Altogether ∼400 000 force-distance curves were recorded. Application of coarse filtering to this wealth of data yielded six data sets with ∼200 (AdiC) and ∼400 (BR) force-distance spectra in each. Importantly, the raw data for most of these data sets were acquired in one to two days, opening new perspectives for HT-SMFS applications

High-throughput single-molecule force spectroscopy for membrane proteins

Energy Technology Data Exchange (ETDEWEB)

Bosshart, Patrick D; Casagrande, Fabio; Frederix, Patrick L T M; Engel, Andreas; Fotiadis, Dimitrios [M E Mueller Institute for Structural Biology, Biozentrum of the University of Basel, CH-4056 Basel (Switzerland); Ratera, Merce; Palacin, Manuel [Institute for Research in Biomedicine, Barcelona Science Park, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona and Centro de Investigacion Biomedica en Red de Enfermedades Raras, E-08028 Barcelona (Spain); Bippes, Christian A; Mueller, Daniel J [BioTechnology Center, Technical University, Tatzberg 47, D-01307 Dresden (Germany)], E-mail: andreas.engel@unibas.ch, E-mail: dimitrios.fotiadis@mci.unibe.ch

2008-09-24

Atomic force microscopy-based single-molecule force spectroscopy (SMFS) is a powerful tool for studying the mechanical properties, intermolecular and intramolecular interactions, unfolding pathways, and energy landscapes of membrane proteins. One limiting factor for the large-scale applicability of SMFS on membrane proteins is its low efficiency in data acquisition. We have developed a semi-automated high-throughput SMFS (HT-SMFS) procedure for efficient data acquisition. In addition, we present a coarse filter to efficiently extract protein unfolding events from large data sets. The HT-SMFS procedure and the coarse filter were validated using the proton pump bacteriorhodopsin (BR) from Halobacterium salinarum and the L-arginine/agmatine antiporter AdiC from the bacterium Escherichia coli. To screen for molecular interactions between AdiC and its substrates, we recorded data sets in the absence and in the presence of L-arginine, D-arginine, and agmatine. Altogether {approx}400 000 force-distance curves were recorded. Application of coarse filtering to this wealth of data yielded six data sets with {approx}200 (AdiC) and {approx}400 (BR) force-distance spectra in each. Importantly, the raw data for most of these data sets were acquired in one to two days, opening new perspectives for HT-SMFS applications.

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

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.

Kinetic asymmetries between forward and drop jump landing tasks

Directory of Open Access Journals (Sweden)

Morgana Alves de Britto

2015-12-01

Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2015v17n6p661   Landing asymmetry is a risk factor for knee anterior cruciate ligament injury. The aim of this study was to identify kinetic asymmetries in healthy recreational athletes performing different jump-landing techniques. Twelve recreational athletes engaged in regular training underwent kinetic evaluation using two 3D force plates and were analyzed for: (a three-dimensional peak forces, (b time to peak vertical force, and (c initial phase asymmetries. All data were collected during performance of unilateral and bilateral trials of forward and drop jump tasks. Forward jump-landing tasks elicited greater kinetic asymmetry than drop-landing tasks. Regardless of jump-landing technique, the preferred leg experienced higher forces than the non-preferred leg. The initial landing phase showed more kinetic asymmetries than the later phase when peak vertical forces occur. It was concluded that when screening athletes for kinetic asymmetries that may predispose them to injury, forward jump-landing tasks and the early landing phase might show more kinetic asymmetries than drop jump-landing tasks and the late landing phase, respectively.

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.

pH regulation of the kinetic stability of the lipase from Thermomyces lanuginosus.

Science.gov (United States)

Wang, H; Andersen, K K; Sehgal, P; Hagedorn, J; Westh, P; Borch, K; Otzen, D E

2013-01-08

Thermomyces lanuginosus lipase (TlL) is a kinetically stable protein, resistant toward both denaturation and refolding in the presence of the ionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant decyl maltoside (DecM). We investigate the pH dependence of this kinetic stability. At pH 8, TlL remains folded and enzymatically active at multimillimolar surfactant concentrations but fails to refold from the acid urea-denatured state at submillimolar concentrations of SDS and DecM, indicating a broad concentration range of kinetic trapping or hysteresis. At pH 8, very few SDS molecules bind to TlL. The hysteresis SDS concentration range shrinks when moving to pH 4-6; in this pH range, SDS binds as micellelike clusters. Although hysteresis can be eliminated by reducing disulfide bonds, destabilizing the native state, and lowering the unfolding activation barrier, SDS sensitivity is not directly linked to intrinsic kinetic stability [its resistance to the general chemical denaturant guanidinium chloride (GdmCl)], because TlL unfolds more slowly in GdmCl at pH 6.0 than at pH 8.0. However, the estimated net charge drops from approximately -12 to approximately -5 between pH 8 and 6. SDS denatures TlL at pH 6.0 by nucleating via a critical number of bound SDS molecules on the surface of native TlL to form clusters. These results imply that SDS sensitivity is connected to the availability of appropriately charged regions on the protein. We suggest that conformational rigidity is a necessary but not sufficient feature of SDS resistance, because this has to be combined with sufficient negative electrostatic potential to avoid extensive SDS binding.

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)

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.

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.

Statolith sedimentation kinetics and force transduction to the cortical endoplasmic reticulum in gravity-sensing Arabidopsis columella cells.

Science.gov (United States)

Leitz, Guenther; Kang, Byung-Ho; Schoenwaelder, Monica E A; Staehelin, L Andrew

2009-03-01

The starch statolith hypothesis of gravity sensing in plants postulates that the sedimentation of statoliths in specialized statocytes (columella cells) provides the means for converting the gravitational potential energy into a biochemical signal. We have analyzed the sedimentation kinetics of statoliths in the central S2 columella cells of Arabidopsis thaliana. The statoliths can form compact aggregates with gap sizes between statoliths approaching sedimentation phase, the statoliths tend to move at a distance to the cortical endoplasmic reticulum (ER) boundary and interact only transiently with the ER. Statoliths moved by laser tweezers against the ER boundary experience an elastic lift force upon release from the optical trap. High-resolution electron tomography analysis of statolith-to-ER contact sites indicate that the weight of statoliths is sufficient to locally deform the ER membranes that can potentially activate mechanosensitive ion channels. We suggest that in root columella cells, the transduction of the kinetic energy of sedimenting statoliths into a biochemical signal involves a combination of statolith-driven motion of the cytosol, statolith-induced deformation of the ER membranes, and a rapid release of kinetic energy from the ER during reorientation to activate mechanosensitive sites within the central columella cells.

Explosive sport training and torque kinetics in children.

Science.gov (United States)

Dotan, Raffy; Mitchell, Cameron J; Cohen, Rotem; Gabriel, David; Klentrou, Panagiota; Falk, Bareket

2013-07-01

A high rate of force development (RFD) is often more important than maximal force in daily and sports activities. In children, resistance training has been shown to increase maximal force. It is unclear whether, or to what extent, can children improve RFD and force kinetics. For this study, we compared strength and force kinetics of boy gymnasts with those of untrained boys and untrained men. Eight boy gymnasts (age, 9.5 ± 1.2 y), 20 untrained boys (age, 10.1 ± 1.3 y), and 20 untrained men (age, 22.9 ± 4.4 y) performed maximal, explosive, isometric elbow flexions (EF) and knee flexions (KF). Peak torque (maximal voluntary contraction (MVC)), elapsed times to 10%-100% MVC, peak rate of torque development (RTDpk), and other kinetics parameters were determined. When gymnasts were compared with untrained boys, size-normalized EF MVC was 11%-20% higher, RTDpk was 32% higher, and times to 30% and 80% MVC were 16% and 55% shorter, respectively (p kinetics parameters were similar. These findings highlight the specificity of gymnastics training, which markedly elevated the torque kinetics of young, prepubertal boys to adult levels, but only moderately affected peak torque. It is suggested that neurologic adaptations, such as enhanced firing and activation rates or increased type II motor-unit recruitment, as well as changes in musculotendinous stiffness, could explain these findings.

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...

Analysis of thermoluminescence kinetics of Mg2SiO4:Tb compounds employing an interactive model

International Nuclear Information System (INIS)

Marcazzo, J.; Prokic, M.; Santiago, M.; Molina, P.; Caselli, E.

2009-01-01

The kinetics involved in the thermoluminescence (TL) of Mg 2 SiO 4 :Tb compounds has been investigated by unfolding glow curves employing both the General Order model and a model that takes into account interactions among traps. The dependence of the glow curve shape on dose is only correctly described if interaction among traps is included in the analysis.

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.

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.

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.

Scaling of the critical free length for progressive unfolding of self-bonded graphene

Energy Technology Data Exchange (ETDEWEB)

Kwan, Kenny; Cranford, Steven W., E-mail: s.cranford@neu.edu [Laboratory of Nanotechnology in Civil Engineering (NICE), Department of Civil and Environmental Engineering, Northeastern University, 400 Snell Engineering, 360 Huntington Avenue, Boston, Massachusetts 02115 (United States)

2014-05-19

Like filled pasta, rolled or folded graphene can form a large nanocapsule surrounding a hollow interior. Use as a molecular carrier, however, requires understanding of the opening of such vessels. Here, we investigate a monolayer sheet of graphene as a theoretical trial platform for such a nanocapsule. The graphene is bonded to itself via aligned disulfide (S-S) bonds. Through theoretical analysis and atomistic modeling, we probe the critical nonbonded length (free length, L{sub crit}) that induces fracture-like progressive unfolding as a function of folding radius (R{sub i}). We show a clear linear scaling relationship between the length and radius, which can be used to determine the necessary bond density to predict mechanical opening/closing. However, stochastic dissipated energy limits any exact elastic formulation, and the required energy far exceeds the dissociation energy of the S-S bond. We account for the necessary dissipated kinetic energy through a simple scaling factor (Ω), which agrees well with computational results.

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...

Conductive atomic force microscopy study of InAs growth kinetics on vicinal GaAs (110)

International Nuclear Information System (INIS)

Tejedor, Paloma; Diez-Merino, Laura; Beinik, Igor; Teichert, Christian

2009-01-01

Conductive atomic force microscopy has been used to investigate the effect of atomic hydrogen and step orientation on the growth behavior of InAs on GaAs (110) misoriented substrates. Samples grown by conventional molecular beam epitaxy exhibit higher conductivity on [110]-multiatomic step edges, where preferential nucleation of InAs nanowires takes place by step decoration. On H-terminated substrates with triangular terraces bounded by [115]-type steps, three-dimensional InAs clusters grow selectively at the terrace apices as a result of a kinetically driven enhancement in upward mass transport via AsH x intermediate species and a reduction in the surface free energy.

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

Dehydrogenation Kinetics and Modeling Studies of MgH2 Enhanced by Transition Metal Oxide Catalysts Using Constant Pressure Thermodynamic Driving Forces

Directory of Open Access Journals (Sweden)

Saidi Temitope Sabitu

2012-06-01

Full Text Available The influence of transition metal oxide catalysts (ZrO2, CeO2, Fe3O4 and Nb2O5 on the hydrogen desorption kinetics of MgH2 was investigated using constant pressure thermodynamic driving forces in which the ratio of the equilibrium plateau pressure (pm to the opposing plateau (pop was the same in all the reactions studied. The results showed Nb2O5 to be vastly superior to other catalysts for improving the thermodynamics and kinetics of MgH2. The modeling studies showed reaction at the phase boundary to be likely process controlling the reaction rates of all the systems studied.

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)

Documentation and localization of force-mediated filamin A domain perturbations in moving cells

Science.gov (United States)

Nakamura, Fumihiko; Song, Mia; Hartwig, John H.; Stossel, Thomas P.

2014-08-01

Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F-actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo.

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

Surface kinetic roughening caused by dental erosion: An atomic force microscopy study

Science.gov (United States)

Quartarone, Eliana; Mustarelli, Piercarlo; Poggio, Claudio; Lombardini, Marco

2008-05-01

Surface kinetic roughening takes place both in case of growth and erosion processes. Teeth surfaces are eroded by contact with acid drinks, such as those used to supplement mineral salts during sporting activities. Calcium-phosphate based (CPP-ACP) pastes are known to reduce the erosion process, and to favour the enamel remineralization. In this study we used atomic force microscopy (AFM) to investigate the surface roughening during dental erosion, and the mechanisms at the basis of the protection role exerted by a commercial CPP-ACP paste. We found a statistically significant difference (p<0.01) in the roughness of surfaces exposed and not exposed to the acid solutions. The treatment with the CPP-ACP paste determined a statistically significant reduction of the roughness values. By interpreting the AFM results in terms of fractal scaling concepts and continuum stochastic equations, we showed that the protection mechanism of the paste depends on the chemical properties of the acid solution.

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

Fluorescence lifetime components reveal kinetic intermediate states upon equilibrium denaturation of carbonic anhydrase II.

Science.gov (United States)

Nemtseva, Elena V; Lashchuk, Olesya O; Gerasimova, Marina A; Melnik, Tatiana N; Nagibina, Galina S; Melnik, Bogdan S

2017-12-21

In most cases, intermediate states of multistage folding proteins are not 'visible' under equilibrium conditions but are revealed in kinetic experiments. Time-resolved fluorescence spectroscopy was used in equilibrium denaturation studies. The technique allows for detecting changes in the conformation and environment of tryptophan residues in different structural elements of carbonic anhydrase II which in its turn has made it possible to study the intermediate states of carbonic anhydrase II under equilibrium conditions. The results of equilibrium and kinetic experiments using wild-type bovine carbonic anhydrase II and its mutant form with the substitution of leucine for alanine at position 139 (L139A) were compared. The obtained lifetime components of intrinsic tryptophan fluorescence allowed for revealing that, the same as in kinetic experiments, under equilibrium conditions the unfolding of carbonic anhydrase II ensues through formation of intermediate states.

Equilibrium unfolding of A. niger RNase: pH dependence of chemical and thermal denaturation.

Science.gov (United States)

Kumar, Gundampati Ravi; Sharma, Anurag; Kumari, Moni; Jagannadham, Medicherla V; Debnath, Mira

2011-08-01

Equilibrium unfolding of A. niger RNase with chemical denaturants, for example GuHCl and urea, and thermal unfolding have been studied as a function of pH using fluorescence, far-UV, near-UV, and absorbance spectroscopy. Because of their ability to affect electrostatic interactions, pH and chemical denaturants have a marked effect on the stability, structure, and function of many globular proteins. ANS binding studies have been conducted to enable understanding of the folding mechanism of the protein in the presence of the denaturants. Spectroscopic studies by absorbance, fluorescence, and circular dichroism and use of K2D software revealed that the enzyme has α + β type secondary structure with approximately 29% α-helix, 24% β-sheet, and 47% random coil. Under neutral conditions the enzyme is stable in urea whereas GuHCl-induced equilibrium unfolding was cooperative. A. niger RNase has little ANS binding even under neutral conditions. Multiple intermediates were populated during the pH-induced unfolding of A. niger RNase. Urea and temperature-induced unfolding of A. niger RNase into the molten globule-like state is non-cooperative, in contrast to the cooperativity seen with the native protein, suggesting the presence of two parts/domains, in the molecular structure of A. niger RNase, with different stability that unfolds in steps. Interestingly, the GuHCl-induced unfolding of the A state (molten globule state) of A. niger RNase is unique, because a low concentration of denaturant not only induces structural change but also facilitates transition from one molten globule like state (A(MG1)) into another (I(MG2)).

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)

pH regulation of the kinetic stability of the lipase from Thermomyces lanuginosus

DEFF Research Database (Denmark)

Wang, H.; Andersen, Kell Kleiner; Sehgal, P.

2013-01-01

Thermomyces lanuginosus lipase (TlL) is a kinetically stable protein, resistant toward both denaturation and refolding in the presence of the ionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant decyl maltoside (DecM). We investigate the pH dependence of this kinetic stability....... At pH 8, TlL remains folded and enzymatically active at multimillimolar surfactant concentrations but fails to refold from the acid urea-denatured state at submillimolar concentrations of SDS and DecM, indicating a broad concentration range of kinetic trapping or hysteresis. At pH 8, very few SDS...... molecules bind to TlL. The hysteresis SDS concentration range shrinks when moving to pH 4–6; in this pH range, SDS binds as micellelike clusters. Although hysteresis can be eliminated by reducing disulfide bonds, destabilizing the native state, and lowering the unfolding activation barrier, SDS sensitivity...

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.

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...

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.

Variability of grip kinetics during adult signature writing.

Directory of Open Access Journals (Sweden)

Bassma Ghali

Full Text Available Grip kinetics and their variation are emerging as important considerations in the clinical assessment of handwriting pathologies, fine motor rehabilitation, biometrics, forensics and ergonomic pen design. This study evaluated the intra- and inter-participant variability of grip shape kinetics in adults during signature writing. Twenty (20 adult participants wrote on a digitizing tablet using an instrumented pen that measured the forces exerted on its barrel. Signature samples were collected over 10 days, 3 times a day, to capture temporal variations in grip shape kinetics. A kinetic topography (i.e., grip shape image was derived per signature by time-averaging the measured force at each of 32 locations around the pen barrel. The normalized cross correlations (NCC of grip shape images were calculated within- and between-participants. Several classification algorithms were implemented to gauge the error rate of participant discrimination based on grip shape kinetics. Four different grip shapes emerged and several participants made grip adjustments (change in grip shape or grip height or rotated the pen during writing. Nonetheless, intra-participant variation in grip kinetics was generally much smaller than inter-participant force variations. Using the entire grip shape images as a 32-dimensional input feature vector, a K-nearest neighbor classifier achieved an error rate of 1.2±0.4% in discriminating among participants. These results indicate that writers had unique grip shape kinetics that were repeatable over time but distinct from those of other participants. The topographic analysis of grip kinetics may inform the development of personalized interventions or customizable grips in clinical and industrial applications, respectively.

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)

Principles and applications of force spectroscopy using atomic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Kyu; Kim, Woong; Park, Joon Won [Dept. of Chemistry, Pohang University of Science and Technology, Pohang (Korea, Republic of)

2016-12-15

Single-molecule force spectroscopy is a powerful technique for addressing single molecules. Unseen structures and dynamics of molecules have been elucidated using force spectroscopy. Atomic force microscope (AFM)-based force spectroscopy studies have provided picoNewton force resolution, subnanometer spatial resolution, stiffness of substrates, elasticity of polymers, and thermodynamics and kinetics of single-molecular interactions. In addition, AFM has enabled mapping the distribution of individual molecules in situ, and the quantification of single molecules has been made possible without modification or labeling. In this review, we describe the basic principles, sample preparation, data analysis, and applications of AFM-based force spectroscopy and its future.

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.

Statolith Sedimentation Kinetics and Force Transduction to the Cortical Endoplasmic Reticulum in Gravity-Sensing Arabidopsis Columella Cells[W][OA

Science.gov (United States)

Leitz, Guenther; Kang, Byung-Ho; Schoenwaelder, Monica E.A.; Staehelin, L. Andrew

2009-01-01

The starch statolith hypothesis of gravity sensing in plants postulates that the sedimentation of statoliths in specialized statocytes (columella cells) provides the means for converting the gravitational potential energy into a biochemical signal. We have analyzed the sedimentation kinetics of statoliths in the central S2 columella cells of Arabidopsis thaliana. The statoliths can form compact aggregates with gap sizes between statoliths approaching sedimentation phase, the statoliths tend to move at a distance to the cortical endoplasmic reticulum (ER) boundary and interact only transiently with the ER. Statoliths moved by laser tweezers against the ER boundary experience an elastic lift force upon release from the optical trap. High-resolution electron tomography analysis of statolith-to-ER contact sites indicate that the weight of statoliths is sufficient to locally deform the ER membranes that can potentially activate mechanosensitive ion channels. We suggest that in root columella cells, the transduction of the kinetic energy of sedimenting statoliths into a biochemical signal involves a combination of statolith-driven motion of the cytosol, statolith-induced deformation of the ER membranes, and a rapid release of kinetic energy from the ER during reorientation to activate mechanosensitive sites within the central columella cells. PMID:19276442

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

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...

Child–adult differences in the kinetics of torque development

Science.gov (United States)

DOTAN, RAFFY; MITCHELL, CAMERON; COHEN, ROTEM; GABRIEL, DAVID; KLENTROU, PANAGIOTA; FALK, BAREKET

2013-01-01

Children have lower size-normalised maximal voluntary force, speed, and power than adults. It has been hypothesised that these and other age-related performance differences are due to lesser type-II motor-unit utilisation in children. This should be manifested as slower force kinetics in explosive muscle contractions. The purpose of this study was to investigate the nature of child–adult force-kinetics differences and whether the latter could support that hypothesis. Untrained boys (n = 20) and men (n = 20) (10.1 ± 1.3 and 22.9 ± 4.4 years, respectively), performed maximal, explosive, isometric elbow flexions and knee extensions on a Biodex dynamometer. Peak torque (MVC), times to 10–100% MVC, and other kinetics parameters were determined. The boys’ body-mass-normalised knee extension MVC, peak rate of torque development, and %MVC at 100 ms were 26, 17 and 23% lower compared with the men and their times to 30% and 80% MVC were 24 and 48% longer, respectively. Elbow flexion kinetics showed similar or greater differences. The findings illuminate boys’ inherent disadvantage in tasks requiring speed or explosive force. It is demonstrated that the extent of the boys–men kinetics disparity cannot be explained by muscle-composition and/or musculo-tendinous-stiffness differences. We suggest therefore that the findings indirectly support children’s lower utilisation of type-II motor units. PMID:23320937

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.

Non-Linear Response to Periodic Forcing of Methane-Air Global and Detailed Kinetics in Continuous Stirred Tank Reactors Close to Extinction Conditions

Directory of Open Access Journals (Sweden)

Francesco Saverio Marra

2015-09-01

Full Text Available This paper focus on the behavior of a continuous stirred tank reactor (CSTR subject to perturbations of finite amplitude and frequency. Two main objectives are pursued: to determine the extinction line in the equivalence ratio (φ - residence time (τ plane, fixed the thermodynamic state conditions; and to characterize the response of the chemical system to periodic forcing of the residence time. Transient simulations of combustion of methane with air, using both global single-step and detailed chemical kinetic mechanisms, have been conducted and the corresponding asymptotic solutions analyzed. Results indicate very different dynamical behaviors, posing the issue of a proper choice of the kinetic scheme for the numerical study of combustion oscillations.

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.

Quantum fictitious forces

DEFF Research Database (Denmark)

Bialynicki-Birula, I; Cirone, M.A.; Dahl, Jens Peder

2002-01-01

We present Heisenberg's equation of motion for the radial variable of a free non-relativistic particle in D dimensions. The resulting radial force consists of three contributions: (i) the quantum fictitious force which is either attractive or repulsive depending on the number of dimensions, (ii......) a singular quantum force located at the origin, and (iii) the centrifugal force associated with non-vanishing angular momentum. Moreover, we use Heisenberg's uncertainty relation to introduce a lower bound for the kinetic energy of an ensemble of neutral particles. This bound is quadratic in the number...... of atoms and can be traced back to the repulsive quantum fictitious potential. All three forces arise for a free particle: "Force without force"....

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.

Compressive Force Spectroscopy: From Living Cells to Single Proteins.

Science.gov (United States)

Wang, Jiabin; Liu, Meijun; Shen, Yi; Sun, Jielin; Shao, Zhifeng; Czajkowsky, Daniel Mark

2018-03-23

One of the most successful applications of atomic force microscopy (AFM) in biology involves monitoring the effect of force on single biological molecules, often referred to as force spectroscopy. Such studies generally entail the application of pulling forces of different magnitudes and velocities upon individual molecules to resolve individualistic unfolding/separation pathways and the quantification of the force-dependent rate constants. However, a less recognized variation of this method, the application of compressive force, actually pre-dates many of these "tensile" force spectroscopic studies. Further, beyond being limited to the study of single molecules, these compressive force spectroscopic investigations have spanned samples as large as living cells to smaller, multi-molecular complexes such as viruses down to single protein molecules. Correspondingly, these studies have enabled the detailed characterization of individual cell states, subtle differences between seemingly identical viral structures, as well as the quantification of rate constants of functionally important, structural transitions in single proteins. Here, we briefly review some of the recent achievements that have been obtained with compressive force spectroscopy using AFM and highlight exciting areas of its future development.

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.

Discrete kinetic models from funneled energy landscape simulations.

Directory of Open Access Journals (Sweden)

Nicholas P Schafer

Full Text Available A general method for facilitating the interpretation of computer simulations of protein folding with minimally frustrated energy landscapes is detailed and applied to a designed ankyrin repeat protein (4ANK. In the method, groups of residues are assigned to foldons and these foldons are used to map the conformational space of the protein onto a set of discrete macrobasins. The free energies of the individual macrobasins are then calculated, informing practical kinetic analysis. Two simple assumptions about the universality of the rate for downhill transitions between macrobasins and the natural local connectivity between macrobasins lead to a scheme for predicting overall folding and unfolding rates, generating chevron plots under varying thermodynamic conditions, and inferring dominant kinetic folding pathways. To illustrate the approach, free energies of macrobasins were calculated from biased simulations of a non-additive structure-based model using two structurally motivated foldon definitions at the full and half ankyrin repeat resolutions. The calculated chevrons have features consistent with those measured in stopped flow chemical denaturation experiments. The dominant inferred folding pathway has an "inside-out", nucleation-propagation like character.

The interrelationship between ligand binding and thermal unfolding of the folate binding protein. The role of self-association and pH

DEFF Research Database (Denmark)

Holm, Jan; Babol, Linnea N.; Markova, Natalia

2014-01-01

The present study utilized a combination of DLS (dynamic light scattering) and DSC (differential scanning calorimetry) to address thermostability of high-affinity folate binding protein (FBP), a transport protein and cellular receptor for the vitamin folate. At pH7.4 (pI=7-8) ligand binding......, intermolecular forces involved in concentration-dependent multimerization thus contribute to the thermostability of holo-FBP. Hence, thermal unfolding and dissociation of holo-FBP multimers occur simultaneously consistent with a gradual decrease from octameric to monomeric holo-FBP (10μM) in DLS after a step-wise...

The fluorescence intensities ratio is not a reliable parameter for evaluation of protein unfolding transitions.

Science.gov (United States)

Žoldák, Gabriel; Jancura, Daniel; Sedlák, Erik

2017-06-01

Monitoring the fluorescence of proteins, particularly the fluorescence of intrinsic tryptophan residues, is a popular method often used in the analysis of unfolding transitions (induced by temperature, chemical denaturant, and pH) in proteins. The tryptophan fluorescence provides several suitable parameters, such as steady-state fluorescence intensity, apparent quantum yield, mean fluorescence lifetime, position of emission maximum that are often utilized for the observation of the conformational/unfolding transitions of proteins. In addition, the fluorescence intensities ratio at different wavelengths (usually at 330 nm and 350 nm) is becoming an increasingly popular parameter for the evaluation of thermal transitions. We show that, under certain conditions, the use of this parameter for the analysis of unfolding transitions leads to the incorrect determination of thermodynamic parameters characterizing unfolding transitions in proteins (e.g., melting temperature) and, hence, can compromise the hit identification during high-throughput drug screening campaigns. © 2017 The Protein Society.

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.

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...

α-Helix Unwinding as Force Buffer in Spectrins.

Science.gov (United States)

Takahashi, Hirohide; Rico, Felix; Chipot, Christophe; Scheuring, Simon

2018-03-27

Spectrins are cytoskeletal proteins located at the inner face of the plasma membrane, making connections between membrane anchors and the actin cortex, and between actin filaments. Spectrins share a common structure forming a bundle of 3 α-helices and play a major role during cell deformation. Here, we used high-speed force spectroscopy and steered molecular dynamics simulations to understand the mechanical stability of spectrin, revealing a molecular force buffering function. We find that spectrin acts as a soft spring at short extensions (70-100 Å). Under continuous external stretching, its α-helices unwind, leading to a viscous mechanical response over larger extensions (100-300 Å), represented by a constant-force plateau in force/extension curves. This viscous force buffering emerges from a quasi-equilibrium competition between disruption and re-formation of α-helical hydrogen bonds. Our results suggest that, in contrast to β-sheet proteins, which unfold in a catastrophic event, α-helical spectrins dominantly unwind, providing a viscous force buffer over extensions about 5 times their folded length.

Unfolding transitions in myosin give rise to the double-hyperbolic force-velocity relation in muscle

DEFF Research Database (Denmark)

Nielsen, Bjørn Gilbert

2003-01-01

This work presents an extension to a recent model of muscle contraction that was based on entropic elasticity (Nielsen 2002 J. Theor Biol. 219 99-119). By using entropic elasticity as the origin of muscle force, various possibilities emerge that can account for the presence of the double......-hyperbolic force-velocity relation in muscle that was observed by Edman (1988 J. Physiol. 404 301-21). In the present work, it will be argued that a slight change (elongation) of the contour length of the entropic springs involved in their high-force regions is sufficient to produce such a double...

Periodic and stochastic thermal modulation of protein folding kinetics.

Science.gov (United States)

Platkov, Max; Gruebele, Martin

2014-07-21

Chemical reactions are usually observed either by relaxation of a bulk sample after applying a sudden external perturbation, or by intrinsic fluctuations of a few molecules. Here we show that the two ideas can be combined to measure protein folding kinetics, either by periodic thermal modulation, or by creating artificial thermal noise that greatly exceeds natural thermal fluctuations. We study the folding reaction of the enzyme phosphoglycerate kinase driven by periodic temperature waveforms. As the temperature waveform unfolds and refolds the protein, its fluorescence color changes due to FRET (Förster resonant Energy Transfer) of two donor/acceptor fluorophores labeling the protein. We adapt a simple model of periodically driven kinetics that nicely fits the data at all temperatures and driving frequencies: The phase shifts of the periodic donor and acceptor fluorescence signals as a function of driving frequency reveal reaction rates. We also drive the reaction with stochastic temperature waveforms that produce thermal fluctuations much greater than natural fluctuations in the bulk. Such artificial thermal noise allows the recovery of weak underlying signals due to protein folding kinetics. This opens up the possibility for future detection of a stochastic resonance for protein folding subject to noise with controllable amplitude.

The Common Forces: Conservative or Nonconservative?

Science.gov (United States)

Keeports, David

2006-01-01

Of the forces commonly encountered when solving problems in Newtonian mechanics, introductory texts usually limit illustrations of the definitions of conservative and nonconservative forces to gravity, spring forces, kinetic friction and fluid resistance. However, at the expense of very little class time, the question of whether each of the common…

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 ...

Symmetry Relations in Chemical Kinetics Arising from Microscopic Reversibility

Science.gov (United States)

Adib, Artur B.

2006-01-01

It is shown that the kinetics of time-reversible chemical reactions having the same equilibrium constant but different initial conditions are closely related to one another by a directly measurable symmetry relation analogous to chemical detailed balance. In contrast to detailed balance, however, this relation does not require knowledge of the elementary steps that underlie the reaction, and remains valid in regimes where the concept of rate constants is ill defined, such as at very short times and in the presence of low activation barriers. Numerical simulations of a model of isomerization in solution are provided to illustrate the symmetry under such conditions, and potential applications in protein folding or unfolding are pointed out.

Analysis of a kinetic multi-segment foot model part II: kinetics and clinical implications.

Science.gov (United States)

Bruening, Dustin A; Cooney, Kevin M; Buczek, Frank L

2012-04-01

Kinematic multi-segment foot models have seen increased use in clinical and research settings, but the addition of kinetics has been limited and hampered by measurement limitations and modeling assumptions. In this second of two companion papers, we complete the presentation and analysis of a three segment kinetic foot model by incorporating kinetic parameters and calculating joint moments and powers. The model was tested on 17 pediatric subjects (ages 7-18 years) during normal gait. Ground reaction forces were measured using two adjacent force platforms, requiring targeted walking and the creation of two sub-models to analyze ankle, midtarsal, and 1st metatarsophalangeal joints. Targeted walking resulted in only minimal kinematic and kinetic differences compared with walking at self selected speeds. Joint moments and powers were calculated and ensemble averages are presented as a normative database for comparison purposes. Ankle joint powers are shown to be overestimated when using a traditional single-segment foot model, as substantial angular velocities are attributed to the mid-tarsal joint. Power transfer is apparent between the 1st metatarsophalangeal and mid-tarsal joints in terminal stance/pre-swing. While the measurement approach presented here is limited to clinical populations with only minimal impairments, some elements of the model can also be incorporated into routine clinical gait analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Kinetic Stability May Determine the Interaction Dynamics of the Bifunctional Protein DCoH1, the Dimerization Cofactor of the Transcription Factor HNF-1[alpha

Energy Technology Data Exchange (ETDEWEB)

Rho, H.; Jones, C.N.; Rose, R.B. (NCSU)

2010-12-07

The two disparate functions of DCoH1 (dimerization cofactor of HNF-1)/PCD (pterin-4a-carbinolamine dehydratase) are associated with a change in oligomeric state. DCoH dimers enhance the activity of the diabetes-associated transcription factor HNF-1{alpha} (hepatocyte nuclear factor-1{alpha}), while the PCD activity of DCoH1 homotetramers aids in aromatic amino acid metabolism. These complexes compete for the same interface of the DCoH dimer. Formation of the DCoH1/HNF-1{alpha} complex requires cofolding. The homotetramer of the DCoH1 paralogue, DCoH2, interacts with HNF-1{alpha} through simple mixing. To further investigate regulation of DCoH/HNF-1{alpha} complex formation, we measured the stability of the DCoH1 homotetramer through unfolding studies by intrinsic tryptophan fluorescence. DCoH2 unfolding is reversible. Surprisingly, the DCoH1 homotetramer is resistant to guanidine unfolding but refolds at a much lower guanidine concentration. We show that a point mutation at the DCoH1 tetramer interface, Thr 51 Ser, overcomes the dissociation barrier of the homotetramer and increases the interaction with HNF-1{alpha}. The 1.8 {angstrom} resolution crystal structure of DCoH1 T51S shows the presence of an ordered water molecule at the tetramer interface, as in DCoH2, which may destabilize the homotetramer. The equilibrium unfolding data were fit to a two-state model with no apparent intermediate. Folding intermediates were detectable by size exclusion chromatography. For wild-type DCoH1 the intermediates changed with time, suggesting a kinetic origin for the unfolding barrier of the homotetramer. We propose an unfolding pathway in which the tetramer unfolds slowly, but the dimer folds reversibly. Implications for regulation of DCoH1/HNF-1{alpha} complex formation are discussed.

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

Synthetic oligorotaxanes exert high forces when folding under mechanical load

Science.gov (United States)

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

2018-01-01

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

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.

Striking dynamics and kinetic properties of boxing and MMA gloves

Directory of Open Access Journals (Sweden)

Benjamin Lee

2014-08-01

Full Text Available With the growing popularity of Mixed Martial Arts (MMA as a competitive sport, questions regarding the dynamic response and properties of MMA gloves arise. High-energy impacts from punches are very similar to boxing yet MMA competition requires the use of 4 oz fingerless glove, compared to the larger full enclosure boxing glove. This work assessed the kinetic properties and strike dynamics of MMA gloves and compared findings with traditional boxing gloves. Gloves mounted on a molded fist were impacted repetitively on an instrumental anvil designed for impact, over a 5 hour period resulting in 10,000 continuous and consistent strikes. Kinetic data from impacts were sampled at the beginning of the data collection and subsequently every 30 minutes (every 1,000 strikes. MMA gloves produced 4-5 times greater peak force and 5 times faster load rate compared to the boxing glove. However, MMA gloves also showed signs of material fatigue, with peak force increasing by 35% and rate of loading increasing by 60% over the duration of the test. Boxing glove characteristics did deteriorate but to a lesser extent. In summary, the kinetic properties of MMA glove differed substantially from the boxing glove resulting in impacts characterized by higher peak forces and more rapid development of force. Material properties including stiffness and thickness play a role in the kinetic characteristics upon impact, and can be inferred to alter injury mechanisms of blunt force trauma.

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.

Hydrothermal Atomic Force Microscopy Investigation of Barite Growth: Role of Spectator Ions in Elementary Step Edge Growth Kinetics and Hillock Morphology [Supporting Information Only

Energy Technology Data Exchange (ETDEWEB)

Jindra, Sarah A. [Wright State Univ., Dayton, OH (United States); Bertagni, Angela L. [Wright State Univ., Dayton, OH (United States); Bracco, Jacquelyn N. [Wright State Univ., Dayton, OH (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Higgins, Steven R. [Wright State Univ., Dayton, OH (United States)

2017-09-25

Here, to better understand the role of spectator ions in barite growth, the kinetics of step edge growth on barite (001) surfaces were studied under various salt solutions. Hydrothermal atomic force microscopy (HAFM) was used to investigate the effect of background electrolytes (NaCl, NaBr, and NaNO₃) as a function of saturation index and ionic strength (I) on barite growth sourced at dislocations at 108 °C. Results demonstrate that hillock morphology is affected by I, as well as type of anion, where the prevalence of steps aligned on the [010] direction is highest under Cl^–. There is a modest increase in kinetic coefficient of 55–130% with a 10-fold increase in I for each salt. In comparing the kinetic coefficients of the salts at low ionic strength (0.01 M), there is a moderate difference, suggesting that the anion may play a role in barium attachment.

Static and kinetic frictional forces of silica-insert ceramic brackets with coated archwires in artificial saliva.

Science.gov (United States)

Shahabi, Mostafa; Salari, Soheil; Poosti, Maryam; Abtahi, Mostafa

2017-01-01

During sliding mechanics, the frictional force (FF) is an important counterforce to orthodontic tooth movement. The purpose of this in vitro study was to investigate the static and kinetic FFs of S silica-insert ceramic (SIC) brackets with Teflon-coated (TC) and conventional S stainless steel (SS) archwires. The target group of this study included 80 maxillary canine 0.022 inch slot SIC brackets. Forty SS brackets were used as the control. TC and conventional uncoated SS archwires of different dimensions (0.016, 0.018, 0.016 × 0.022, and 0.018 × 0.025 inch) were examined. All tests were carried out under artificial saliva injected condition. Scanning Electron Micrographs were prepared for two samples of coated and uncoated archwires. Analysis of variance and Tukey post hoc tests were used for statistical purposes (level of significance P brackets showed significantly lower levels of FFs than SS brackets. TC archwires had greater frictional values than conventional uncoated ones. They also exhibited an unusual behavior of increasing kinetic FFs with time. Indentation and delamination of coating were obvious under scanning electron microscopy observations. From the standpoint of friction, SIC brackets may serve well, even better than SS brackets, in sliding mechanics. The coating layer of the archwires may delaminate and lost, causing an impediment to tooth movement.

Probabilistic analysis for identifying the driving force of protein folding

Science.gov (United States)

Tokunaga, Yoshihiko; Yamamori, Yu; Matubayasi, Nobuyuki

2018-03-01

Toward identifying the driving force of protein folding, energetics was analyzed in water for Trp-cage (20 residues), protein G (56 residues), and ubiquitin (76 residues) at their native (folded) and heat-denatured (unfolded) states. All-atom molecular dynamics simulation was conducted, and the hydration effect was quantified by the solvation free energy. The free-energy calculation was done by employing the solution theory in the energy representation, and it was seen that the sum of the protein intramolecular (structural) energy and the solvation free energy is more favorable for a folded structure than for an unfolded one generated by heat. Probabilistic arguments were then developed to determine which of the electrostatic, van der Waals, and excluded-volume components of the interactions in the protein-water system governs the relative stabilities between the folded and unfolded structures. It was found that the electrostatic interaction does not correspond to the preference order of the two structures. The van der Waals and excluded-volume components were shown, on the other hand, to provide the right order of preference at probabilities of almost unity, and it is argued that a useful modeling of protein folding is possible on the basis of the excluded-volume effect.

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)

Thermal hysteresis kinetic effects of spin crossover nanoparticulated systems studied by FORC diagram method on an Ising-like model

International Nuclear Information System (INIS)

Atitoaie, Alexandru; Stoleriu, Laurentiu; Tanasa, Radu; Stancu, Alexandru; Enachescu, Cristian

2016-01-01

The scientific community is manifesting a high research interest on spin crossover compounds and their recently synthesized nanoparticles, due to their various appealing properties, such as the bistability between a diamagnetic low spin state and a paramagnetic high spin state (HS), inter-switchable by temperature or pressure changes, light irradiation or magnetic field. The utility of these compounds showing hysteresis covers a broad area of applications, from the development of more efficient designs of temperature and pressure sensors to automotive and aeronautic industries and even a new type of molecular actuators. We are proposing in this work a study regarding the kinetic effects and the distribution of reversible and irreversible components on the thermal hysteresis of spin crossover nanoparticulated systems. We are considering here tridimensional systems with different sizes and also systems of nanoparticles with a Gaussian size distribution. The correlations between the kinetics of the thermal hysteresis, the distributions of sizes and intermolecular interactions and the transition temperature distributions were established by using the FORC (First Order Reversal Curves) method using a Monte Carlo technique within an Ising-like system.

Thermal hysteresis kinetic effects of spin crossover nanoparticulated systems studied by FORC diagram method on an Ising-like model

Energy Technology Data Exchange (ETDEWEB)

Atitoaie, Alexandru, E-mail: atitoaie@phys-iasi.ro [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania); National Institute of Research and Development for Technical Physics, Iasi (Romania); Stoleriu, Laurentiu [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania); Tanasa, Radu [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania); Department of Engineering, University of Cambridge, CB2 1PZ Cambridge (United Kingdom); Stancu, Alexandru; Enachescu, Cristian [Department. of Physics, “Alexandru Ioan Cuza” University, 700506 Iasi (Romania)

2016-04-01

The scientific community is manifesting a high research interest on spin crossover compounds and their recently synthesized nanoparticles, due to their various appealing properties, such as the bistability between a diamagnetic low spin state and a paramagnetic high spin state (HS), inter-switchable by temperature or pressure changes, light irradiation or magnetic field. The utility of these compounds showing hysteresis covers a broad area of applications, from the development of more efficient designs of temperature and pressure sensors to automotive and aeronautic industries and even a new type of molecular actuators. We are proposing in this work a study regarding the kinetic effects and the distribution of reversible and irreversible components on the thermal hysteresis of spin crossover nanoparticulated systems. We are considering here tridimensional systems with different sizes and also systems of nanoparticles with a Gaussian size distribution. The correlations between the kinetics of the thermal hysteresis, the distributions of sizes and intermolecular interactions and the transition temperature distributions were established by using the FORC (First Order Reversal Curves) method using a Monte Carlo technique within an Ising-like system.

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)

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

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)

Determination of Model Kinetics for Forced Unsteady State Operation of Catalytic CH4 Oxidation

Directory of Open Access Journals (Sweden)

Effendy Mohammad

2016-01-01

Full Text Available The catalytic oxidation of methane for abating the emission vented from coal mine or natural gas transportation has been known as most reliable method. A reverse flow reactor operation has been widely used to oxidize this methane emission due to its capability for autothermal operation and heat production. The design of the reverse flow reactor requires a proper kinetic rate expression, which should be developed based on the operating condition. The kinetic rate obtained in the steady state condition cannot be applied for designing the reactor operated under unsteady state condition. Therefore, new approach to develop the dynamic kinetic rate expression becomes indispensable, particularly for periodic operation such as reverse flow reactor. This paper presents a novel method to develop the kinetic rate expression applied for unsteady state operation. The model reaction of the catalytic methane oxidation over Pt/-Al2O3 catalyst was used with kinetic parameter determined from laboratory experiments. The reactor used was a fixed bed, once-through operation, with a composition modulation in the feed gas. The switching time was set at 3 min by varying the feed concentration, feed flow rate, and reaction temperature. The concentrations of methane in the feed and product were measured and analysed using gas chromatography. The steady state condition for obtaining the kinetic rate expression was taken as a base case and as a way to judge its appropriateness to be applied for dynamic system. A Langmuir-Hinshelwood reaction rate model was developed. The time period during one cycle was divided into some segments, depending on the ratio of CH4/O2. The experimental result shows that there were kinetic regimes occur during one cycle: kinetic regime controlled by intrinsic surface reaction and kinetic regime controlled by external diffusion. The kinetic rate obtained in the steady state operation was not appropriate when applied for unsteady state operation

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

Kinetic energy dissipation in heavy-ion collisions

International Nuclear Information System (INIS)

Fedotov, S.I.; Jolos, R.V.; Kartavenko, V.G.

1979-01-01

Kinetic energy dissipation mechanism is considered in deep inelastic heavy-ion collisions. It is shown that the significant part of the kinetic energy loss can be explained by the excitation of the nuclear matter multipole vibrations. The main contribution of the energy dissipation is given by the time dependent heavy-ion interaction potential renormalized due to the nuclear excitations, rather than by the velocity proportional frictional forces

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)

Reversible unfolding of infectious prion assemblies reveals the existence of an oligomeric elementary brick.

Directory of Open Access Journals (Sweden)

Angélique Igel-Egalon

2017-09-01

Full Text Available Mammalian prions, the pathogens that cause transmissible spongiform encephalopathies, propagate by self-perpetuating the structural information stored in the abnormally folded, aggregated conformer (PrPSc of the host-encoded prion protein (PrPC. To date, no structural model related to prion assembly organization satisfactorily describes how strain-specified structural information is encoded and by which mechanism this information is transferred to PrPC. To achieve progress on this issue, we correlated the PrPSc quaternary structural transition from three distinct prion strains during unfolding and refolding with their templating activity. We reveal the existence of a mesoscopic organization in PrPSc through the packing of a highly stable oligomeric elementary subunit (suPrP, in which the strain structural determinant (SSD is encoded. Once kinetically trapped, this elementary subunit reversibly loses all replicative information. We demonstrate that acquisition of the templating interface and infectivity requires structural rearrangement of suPrP, in concert with its condensation. The existence of such an elementary brick scales down the SSD support to a small oligomer and provide a basis of reflexion for prion templating process and propagation.

Force-dominated non-equilibrium oxidation kinetics of tantalum

International Nuclear Information System (INIS)

Kar, Prasenjit; Wang, Ke; Liang, Hong

2008-01-01

Using a combined electrochemical and mechanical manipulation technique, we compared the equilibrium and non-equilibrium oxidation processes and states of tantalum. Experimentally, a setup was developed with an electrochemical system attached to a sliding mechanical configuration capable of friction force measurement. The surface chemistry of a sliding surface, i.e., tantalum, was modified through the electrolyte. The mechanically applied force was fixed and the dynamics of the surface was monitored in situ through a force sensor. The formation of non-equilibrium oxidation states of tantalum was found in oxidation limiting environment of acetic acid. An oxidative environment of deionized water saturated with KCl was used as comparison. We proposed a modified Arrhenius-Eyring equation in which the mechanical factor was considered. We found that the mechanical energy induced the non-stable-state reactions leading to metastable oxidation states of tantalum. This equation can be used to predict mechanochemical reactions that are important in many industrial applications

Are current atomistic force fields accurate enough to study proteins in crowded environments?

Directory of Open Access Journals (Sweden)

Drazen Petrov

2014-05-01

Full Text Available The high concentration of macromolecules in the crowded cellular interior influences different thermodynamic and kinetic properties of proteins, including their structural stabilities, intermolecular binding affinities and enzymatic rates. Moreover, various structural biology methods, such as NMR or different spectroscopies, typically involve samples with relatively high protein concentration. Due to large sampling requirements, however, the accuracy of classical molecular dynamics (MD simulations in capturing protein behavior at high concentration still remains largely untested. Here, we use explicit-solvent MD simulations and a total of 6.4 µs of simulated time to study wild-type (folded and oxidatively damaged (unfolded forms of villin headpiece at 6 mM and 9.2 mM protein concentration. We first perform an exhaustive set of simulations with multiple protein molecules in the simulation box using GROMOS 45a3 and 54a7 force fields together with different types of electrostatics treatment and solution ionic strengths. Surprisingly, the two villin headpiece variants exhibit similar aggregation behavior, despite the fact that their estimated aggregation propensities markedly differ. Importantly, regardless of the simulation protocol applied, wild-type villin headpiece consistently aggregates even under conditions at which it is experimentally known to be soluble. We demonstrate that aggregation is accompanied by a large decrease in the total potential energy, with not only hydrophobic, but also polar residues and backbone contributing substantially. The same effect is directly observed for two other major atomistic force fields (AMBER99SB-ILDN and CHARMM22-CMAP as well as indirectly shown for additional two (AMBER94, OPLS-AAL, and is possibly due to a general overestimation of the potential energy of protein-protein interactions at the expense of water-water and water-protein interactions. Overall, our results suggest that current MD force fields

Curvature force and dark energy

International Nuclear Information System (INIS)

Balakin, Alexander B; Pavon, Diego; Schwarz, Dominik J; Zimdahl, Winfried

2003-01-01

A curvature self-interaction of the cosmic gas is shown to mimic a cosmological constant or other forms of dark energy, such as a rolling tachyon condensate or a Chaplygin gas. Any given Hubble rate and deceleration parameter can be traced back to the action of an effective curvature force on the gas particles. This force self-consistently reacts back on the cosmological dynamics. The links between an imperfect fluid description, a kinetic description with effective antifriction forces and curvature forces, which represent a non-minimal coupling of gravity to matter, are established

Kinetic chain contributions to elbow function and dysfunction in sports.

Science.gov (United States)

Ben Kibler, W; Sciascia, Aaron

2004-10-01

The elbow functions in throwing and other athletic activities as a link in the kinetic chain of force development, regulation, and transfer. Efficient function, with maximal performance and minimal injury risk, requires optimum activation of all the link in the kinetic chain. Injury is often associated with alterations in force production or regulation capabilities in links that may be distant to the site of injury. Evaluation of injured athletes should include screening examinations for these areas, and treatment and conditioning should also include these areas.

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.

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

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 ...

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

Joint kinetic determinants of starting block performance in athletic sprinting.

Science.gov (United States)

Brazil, Adam; Exell, Timothy; Wilson, Cassie; Willwacher, Steffen; Bezodis, Ian N; Irwin, Gareth

2018-07-01

The aim of this study was to explore the relationships between lower limb joint kinetics, external force production and starting block performance (normalised average horizontal power, NAHP). Seventeen male sprinters (100 m PB, 10.67 ± 0.32 s) performed maximal block starts from instrumented starting blocks (1000 Hz) whilst 3D kinematics (250 Hz) were also recorded during the block phase. Ankle, knee and hip resultant joint moment and power were calculated at the rear and front leg using inverse dynamics. Average horizontal force applied to the front (r = 0.46) and rear (r = 0.44) block explained 86% of the variance in NAHP. At the joint level, many "very likely" to "almost certain" relationships (r = 0.57 to 0.83) were found between joint kinetic data and the magnitude of horizontal force applied to each block although stepwise multiple regression revealed that 55% of the variance in NAHP was accounted for by rear ankle moment, front hip moment and front knee power. The current study provides novel insight into starting block performance and the relationships between lower limb joint kinetic and external kinetic data that can help inform physical and technical training practices for this skill.

Hydrogen-exchange kinetics of the indole NH proton of the buried tryptophan in the constant fragment of the immunoglobulin light chain

International Nuclear Information System (INIS)

Kawata, Y.; Goto, Y.; Hamaguchi, K.; Hayashi, F.; Kobayashi, Y.; Kyogoku, Y.

1988-01-01

The constant fragment of the immunoglobulin light chain (type λ) has two trytophyl residues at positions 150 and 187. Trp-150 is buried in the interior, and Trp-187 lies on the surface of the molecule. The hydrogen-deuterium exchange kinetics of the indole NH proton Trp-150 were studied at various pH values at 25 0 C by 1 H nuclear magnetic resonance. Exchange rates were approximately first order in hydroxyl ion dependence above pH 8, were relatively independent of pH between pH 7 and 8, and decreased below pH 7. On the assumption that the exchange above pH 8 proceeds through local fluctuations of the protein molecule, the exchange rates between pH 7 and 8 through global unfolding were estimated. The exchange rate constant within this pH range at 25 0 C thus estimated was consistent with that of the global unfolding of the constant fragment under the same conditions as those reported previously. The activation energy for the exchange process at pH 7.8 was the same as that for the unfolding process by 2 M guanidine hydrochloride. The exchange rates of backbone NH protons were almost the same as that of the indole NH proton of Trp-150 at pH 7.l. These observations also indicated that the exchange between pH 7 and 8 occurs through global unfolding of the protein molecule and is rate-limited by the unfolding. At around pH 9, on the other hand, the activation energy for the exchange process of the indole NH proton of Trp-150 was smaller than that for the unfolding process, and the exchange rates differed according to the different signals of backbone NH protons. These findings together with the pH dependence of the rate constant indicated that exchange due to local fluctuations is predominant above pH 8

Writing forces associated with four pencil grasp patterns in grade 4 children.

Science.gov (United States)

Schwellnus, Heidi; Carnahan, Heather; Kushki, Azadeh; Polatajko, Helene; Missiuna, Cheryl; Chau, Tom

2013-01-01

OBJECTIVE. We investigated differences in handwriting kinetics, speed, and legibility among four pencil grasps after a 10-min copy task. METHOD. Seventy-four Grade 4 students completed a handwriting assessment before and after a copy task. Grip and axial forces were measured with an instrumented stylus and force-sensitive tablet. We used multiple linear regression to analyze the relationship between grasp pattern and grip and axial forces. RESULTS. We found no kinetic differences among grasps, whether considered individually or grouped by the number of fingers on the barrel. However, when grasps were grouped according to the thumb position, the adducted grasps exhibited higher mean grip and axial forces. CONCLUSION. Grip forces were generally similar across the different grasps. Kinetic differences resulting from thumb position seemed to have no bearing on speed and legibility. Interventions for handwriting difficulties should focus more on speed and letter formation than on grasp pattern. Copyright © 2013 by the American Occupational Therapy Association, Inc.

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.

Kinetics of conformational changes of fibronectin adsorbed onto model surfaces.

Science.gov (United States)

Baujard-Lamotte, L; Noinville, S; Goubard, F; Marque, P; Pauthe, E

2008-05-01

Fibronectin (FN), a large glycoprotein found in body fluids and in the extracellular matrix, plays a key role in numerous cellular behaviours. We investigate FN adsorption onto hydrophilic bare silica and hydrophobic polystyrene (PS) surfaces using Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) in aqueous medium. Adsorption kinetics using different bulk concentrations of FN were followed for 2h and the surface density of adsorbed FN and its time-dependent conformational changes were determined. When adsorption occurs onto the hydrophilic surface, FN molecules keep their native conformation independent of the adsorption conditions, but the amount of adsorbed FN increases with time and the bulk concentration. Although the protein surface density is the same on the hydrophobic PS surface, this has a strong impact on the average conformation of the adsorbed FN layer. Indeed, interfacial hydration changes induced by adsorption onto the hydrophobic surface lead to a decrease in unhydrated beta-sheet content and cause an increase in hydrated beta-strand and hydrated random domain content of adsorbed FN. This conformational change is mainly dependent on the bulk concentration. Indeed, at low bulk concentrations, the secondary structures of adsorbed FN molecules undergo strong unfolding, allowing an extended and hydrated conformation of the protein. At high bulk concentrations, the molecular packing reduces the unfolding of the stereoregular structures of the FN molecules, preventing stronger spreading of the protein.

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

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

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

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.

Dynamic prestress in a globular protein.

Directory of Open Access Journals (Sweden)

Scott A Edwards

Full Text Available A protein at equilibrium is commonly thought of as a fully relaxed structure, with the intra-molecular interactions showing fluctuations around their energy minimum. In contrast, here we find direct evidence for a protein as a molecular tensegrity structure, comprising a balance of tensed and compressed interactions, a concept that has been put forward for macroscopic structures. We quantified the distribution of inter-residue prestress in ubiquitin and immunoglobulin from all-atom molecular dynamics simulations. The network of highly fluctuating yet significant inter-residue forces in proteins is a consequence of the intrinsic frustration of a protein when sampling its rugged energy landscape. In beta sheets, this balance of forces is found to compress the intra-strand hydrogen bonds. We estimate that the observed magnitude of this pre-compression is enough to induce significant changes in the hydrogen bond lifetimes; thus, prestress, which can be as high as a few 100 pN, can be considered a key factor in determining the unfolding kinetics and pathway of proteins under force. Strong pre-tension in certain salt bridges on the other hand is connected to the thermodynamic stability of ubiquitin. Effective force profiles between some side-chains reveal the signature of multiple, distinct conformational states, and such static disorder could be one factor explaining the growing body of experiments revealing non-exponential unfolding kinetics of proteins. The design of prestress distributions in engineering proteins promises to be a new tool for tailoring the mechanical properties of made-to-order nanomaterials.

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

Validity of the Nintendo Wii Balance Board for Kinetic Gait Analysis

Directory of Open Access Journals (Sweden)

Ryo Eguchi

2018-02-01

Full Text Available The Nintendo Wii Balance Board (WBB has been suggested as an inexpensive, portable and accessible alternative to costly laboratory-grade force plates for measuring the vertical ground reaction force (vGRF and center of pressure (COP. Kinetic gait analysis provides important information for the rehabilitation of patients with gait disorders; however, the validity of the WBB for measuring kinetic gait parameters has not been evaluated. Therefore, the purpose of this study is to determine the accuracy of walking force measurements—which change dynamically in a short period of stance time—collected with the WBB. Three healthy adults were asked to walk 10 steps along both straight and curved paths in clockwise (CW and counterclockwise (CCW directions while measurements were taken using the WBB and the force plate. The accuracy of the vGRF, COP trajectory, and stance duration were evaluated using the root-mean-square error (RMSE, Pearson’s correlation coefficient and Bland–Altman plots (BAPs to compare the WBB and the force plate. The results of the vGRF showed high accuracy (r > 0.96 and %RMSE < 6.1% in the mean values, and the stance duration as defined by the vGRF and COP trajectory was equivalent to that of commercial instrumented insoles, which are used as an alternative to the force plates. From these results, we determined that the WBB may be used for kinetic gait analysis in clinical settings where lower accuracy is acceptable.

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.

The Kinetics of Swinging a Baseball Bat.

Science.gov (United States)

Crisco, Joseph J; Osvalds, Nikolas J; Rainbow, Michael J

2018-04-13

The purpose of this study was to compute the three-dimensional kinetics required to swing three youth baseball bats of varying moments of inertia (MOI). 306 swings by 22 male players (13-18 yrs.) were analyzed. Inverse dynamics with respect to the batter's hands were computed given the known kinematics and physical properties of the bats. We found that peak force increased with larger bat MOI and was strongly correlated with bat tip speed. In contrast, peak moments were weakly correlated with bat MOI and bat tip speed. Throughout the swing, the force applied to the bat was dominated by a component aligned with the long axis of the bat and directed away from the bat knob, while the moment applied to the bat was minimal until just prior to ball impact. These results indicate that players act to mostly "pull" the bat during their swing until just prior to ball impact, at which point they rapidly increase the moment on the bat. This kinetic analysis provides novel insight into the forces and moments used to swing baseball bats.

Hydrogen/deuterium exchange of multiply-protonated cytochrome c ions

International Nuclear Information System (INIS)

Wood, T.D.; Guan, Ziqiang; O'Connor, P.B.

1995-01-01

Low resolution measurements show gaseous multiply-protonated cytochrome c ions undergo hydrogen/deuterium (H/D) exchange with pseudo first-order kinetics at three distinct exchange levels, suggesting the co-existence of gaseous protein conformations. Although exchange levels first increase with increasing charge values, they decrease at the highest charge values, consistent with solution-phase behavior of cytochrome c, where the native structure unfolds with decreasing pH until folding into a compact A-state at lowest pH. High resolution measurements indicate the presence of at least six H/D exchange levels. Infrared (IR) laser heating and fast collisions via quadrupolar excitation (QE) increase H/D exchange levels (unfolding) while charge-stripping ions to lower charge values can increase or decrease H/D exchange levels (unfolding or folding). Wolynes has suggested studying proteins in vacuo could play an important role in delineating the contributions various forces play in the protein folding process, provided appropriate comparisons can be made between gas-phase and solution-phase structures

Obtention of the ponderomotive force in the mark of the kinetic theory in the injection of high power in a plasma; Obtencion de la fuerza ponderomotriz en el marco de la teoria cinetica en la inyeccion de alta potencia en un plasma

Energy Technology Data Exchange (ETDEWEB)

Gutierrez T, C.; Beltran P, M. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: cgt@nuclear.inin.mx

2006-07-01

To reach the quasi stationary work regime of a Tokamak, it is necessary to optimize the current generation by non inductive methods with the injection of radio-frequency waves (RF), such as the electron cyclotron waves, cyclo ion, and in the inferior hybrid one. At the moment, the powers of the radiation sources are very big for what the such no-lineal effects as the ponderomotive force are very important. In the case of the electron cyclotron waves, in the mark of the lineal theory of waves propagation, using extraordinary waves (first and second harmonic), the problem of the singularity always arises in the exact resonance. One of the ways of eliminating this singularity is considering that the group of electrons under resonance conditions is big (quasi lineal theory) or introducing such non lineal effects such as the ponderomotive force. In the obtaining of the ponderomotive force under resonance conditions this indetermination arises also. In this work the kinetic theory to obtain the expression of the ponderomotive force in the cyclotron resonance of the electrons, where the Vlasov kinetic equation expands up to second order with regard to the electric field of the RF wave. The kinetic approach allows to the analysis of the ponderomotive force under resonance conditions considering the Landau integration method. (Author)

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)

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

Spin force and torque in non-relativistic Dirac oscillator on a sphere

Science.gov (United States)

Shikakhwa, M. S.

2018-03-01

The spin force operator on a non-relativistic Dirac oscillator (in the non-relativistic limit the Dirac oscillator is a spin one-half 3D harmonic oscillator with strong spin-orbit interaction) is derived using the Heisenberg equations of motion and is seen to be formally similar to the force by the electromagnetic field on a moving charged particle. When confined to a sphere of radius R, it is shown that the Hamiltonian of this non-relativistic oscillator can be expressed as a mere kinetic energy operator with an anomalous part. As a result, the power by the spin force and torque operators in this case are seen to vanish. The spin force operator on the sphere is calculated explicitly and its torque is shown to be equal to the rate of change of the kinetic orbital angular momentum operator, again with an anomalous part. This, along with the conservation of the total angular momentum, suggests that the spin force exerts a spin-dependent torque on the kinetic orbital angular momentum operator in order to conserve total angular momentum. The presence of an anomalous spin part in the kinetic orbital angular momentum operator gives rise to an oscillatory behavior similar to the Zitterbewegung. It is suggested that the underlying physics that gives rise to the spin force and the Zitterbewegung is one and the same in NRDO and in systems that manifest spin Hall effect.

Unraveling protein-protein interactions in clathrin assemblies via atomic force spectroscopy.

Science.gov (United States)

Jin, Albert J; Lafer, Eileen M; Peng, Jennifer Q; Smith, Paul D; Nossal, Ralph

2013-03-01

Atomic force microscopy (AFM), single molecule force spectroscopy (SMFS), and single particle force spectroscopy (SPFS) are used to characterize intermolecular interactions and domain structures of clathrin triskelia and clathrin-coated vesicles (CCVs). The latter are involved in receptor-mediated endocytosis (RME) and other trafficking pathways. Here, we subject individual triskelia, bovine-brain CCVs, and reconstituted clathrin-AP180 coats to AFM-SMFS and AFM-SPFS pulling experiments and apply novel analytics to extract force-extension relations from very large data sets. The spectroscopic fingerprints of these samples differ markedly, providing important new information about the mechanism of CCV uncoating. For individual triskelia, SMFS reveals a series of events associated with heavy chain alpha-helix hairpin unfolding, as well as cooperative unraveling of several hairpin domains. SPFS of clathrin assemblies exposes weaker clathrin-clathrin interactions that are indicative of inter-leg association essential for RME and intracellular trafficking. Clathrin-AP180 coats are energetically easier to unravel than the coats of CCVs, with a non-trivial dependence on force-loading rate. Published by Elsevier Inc.

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.

Nanoparticle sizing: a comparative study using atomic force microscopy, transmission electron microscopy, and ferromagnetic resonance

International Nuclear Information System (INIS)

Lacava, L.M.; Lacava, B.M.; Azevedo, R.B.; Lacava, Z.G.M.; Buske, N.; Tronconi, A.L.; Morais, P.C.

2001-01-01

Atomic force microscopy (AFM), transmission electron microscopy (TEM), and ferromagnetic resonance (FMR) were used to unfold the nanoparticle size of a ferrofluid sample. Compared to TEM, the AFM method showed a nanoparticle diameter (D m ) reduction of 20% and standard deviation (σ) increase of 15%. The differences in D m and σ were associated with the AFM tip and the nanoparticle concentration on the substrate

Glycosylation and thermodynamic versus kinetic stability of horseradish peroxidase

DEFF Research Database (Denmark)

Tams, J.W.; Welinder, Karen G.

1998-01-01

Glycoprotein stability, glycoprotein unfolding, horseradish peroxidase, thermodynamic stability, kinetik stability......Glycoprotein stability, glycoprotein unfolding, horseradish peroxidase, thermodynamic stability, kinetik stability...

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.

Upper limb joint kinetic analysis during tennis serve: Assessment of competitive level on efficiency and injury risks.

Science.gov (United States)

Martin, C; Bideau, B; Ropars, M; Delamarche, P; Kulpa, R

2014-08-01

The aim of this work was to compare the joint kinetics and stroke production efficiency for the shoulder, elbow, and wrist during the serve between professionals and advanced tennis players and to discuss their potential relationship with given overuse injuries. Eleven professional and seven advanced tennis players were studied with an optoelectronic motion analysis system while performing serves. Normalized peak kinetic values of the shoulder, elbow, and wrist joints were calculated using inverse dynamics. To measure serve efficiency, all normalized peak kinetic values were divided by ball velocity. t-tests were used to determine significant differences between the resultant joint kinetics and efficiency values in both groups (advanced vs professional). Shoulder inferior force, shoulder anterior force, shoulder horizontal abduction torque, and elbow medial force were significantly higher in advanced players. Professional players were more efficient than advanced players, as they maximize ball velocity with lower joint kinetics. Since advanced players are subjected to higher joint kinetics, the results suggest that they appeared more susceptible to high risk of shoulder and elbow injuries than professionals, especially during the cocking and deceleration phases of the serve. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Revealing Abrupt and Spontaneous Ruptures of Protein Native Structure under picoNewton Compressive Force Manipulation.

Science.gov (United States)

Chowdhury, S Roy; Cao, Jin; He, Yufan; Lu, H Peter

2018-03-27

Manipulating protein conformations for exploring protein structure-function relationship has shown great promise. Although protein conformational changes under pulling force manipulation have been extensively studied, protein conformation changes under a compressive force have not been explored quantitatively. The latter is even more biologically significant and relevant in revealing protein functions in living cells associated with protein crowdedness, distribution fluctuations, and cell osmotic stress. Here we report our experimental observations on abrupt ruptures of protein native structures under compressive force, demonstrated and studied by single-molecule AFM-FRET spectroscopic nanoscopy. Our results show that the protein ruptures are abrupt and spontaneous events occurred when the compressive force reaches a threshold of 12-75 pN, a force amplitude accessible from thermal fluctuations in a living cell. The abrupt ruptures are sensitive to local environment, likely a general and important pathway of protein unfolding in living cells.

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)

Evolution of wave turbulence under "gusty" forcing.

Science.gov (United States)

Annenkov, S Y; Shrira, V I

2011-09-09

We consider nonlinear evolution of a random wave field under gusty forcing, fluctuating around a constant mean. Here the classical wave turbulence theory that assumes a proximity to stationarity is not applicable. We show by direct numerical simulation that the self-similarity of wave field evolution survives under fluctuating forcing. The wave field statistical characteristics averaged over fluctuations of forcing evolve as if there were a certain constant "effective wind." The results justify the use of the kinetic equations with forcing averaged over gusts as a good first approximation.

In situ measurement of the kinetic friction of ZnO nanowires inside a scanning electron microscope

Energy Technology Data Exchange (ETDEWEB)

Polyakov, Boris, E-mail: boriss.polakovs@ut.ee [Institute of Physics, University of Tartu, Riia st. 142, Tartu (Estonia); Institute of Solid State Physics, University of Latvia, Kengaraga st. 8, Riga (Latvia); Dorogin, Leonid M; Lohmus, Ants [Institute of Physics, University of Tartu, Riia st. 142, Tartu (Estonia); Romanov, Alexey E [Institute of Physics, University of Tartu, Riia st. 142, Tartu (Estonia); Ioffe Physical Technical Institute, RAS, Politehnicheskaja st. 26, St. Petersburg (Russian Federation); Lohmus, Rynno [Institute of Physics, University of Tartu, Riia st. 142, Tartu (Estonia)

2012-01-15

A novel method for measuring the kinetic friction force in situ was developed for zinc oxide nanowires on highly oriented pyrolytic graphite and oxidised silicon wafers. The experiments were performed inside a scanning electron microscope and used a nanomanipulation device as an actuator, which also had an atomic force microscope tip attached to it as a probe. A simple model based on the Timoshenko elastic beam theory was applied to interpret the elastic deformation of a sliding nanowire (NW) and to determine the distributed kinetic friction force.

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

Phenol oxidation by mushroom waste extracts: a kinetic and thermodynamic study.

Science.gov (United States)

Pigatto, Gisele; Lodi, Alessandra; Aliakbarian, Bahar; Converti, Attilio; da Silva, Regildo Marcio Gonçalves; Palma, Mauri Sérgio Alves

2013-09-01

Tyrosinase activity of mushroom extracts was checked for their ability to degrade phenol. Phenol oxidation kinetics was investigated varying temperature from 10 to 60 °C and the initial values of pH, enzyme activity and phenol concentration in the ranges 4.5-8.5, 1.43-9.54 U/mL and 50-600 mg/L, respectively. Thermodynamic parameters of phenol oxidation and tyrosinase reversible inactivation were estimated. Tyrosinase thermostability was also investigated through residual activity tests after extracts exposition at 20-50 °C, whose results allowed exploring the thermodynamics of enzyme irreversible thermoinactivation. This study is the first attempt to separate the effects of reversible unfolding and irreversible denaturation of tyrosinase on its activity. Extracts were finally tested on a real oil mill wastewater. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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.

Missense mutation Lys18Asn in dystrophin that triggers X-linked dilated cardiomyopathy decreases protein stability, increases protein unfolding, and perturbs protein structure, but does not affect protein function.

Directory of Open Access Journals (Sweden)

Surinder M Singh

Full Text Available Genetic mutations in a vital muscle protein dystrophin trigger X-linked dilated cardiomyopathy (XLDCM. However, disease mechanisms at the fundamental protein level are not understood. Such molecular knowledge is essential for developing therapies for XLDCM. Our main objective is to understand the effect of disease-causing mutations on the structure and function of dystrophin. This study is on a missense mutation K18N. The K18N mutation occurs in the N-terminal actin binding domain (N-ABD. We created and expressed the wild-type (WT N-ABD and its K18N mutant, and purified to homogeneity. Reversible folding experiments demonstrated that both mutant and WT did not aggregate upon refolding. Mutation did not affect the protein's overall secondary structure, as indicated by no changes in circular dichroism of the protein. However, the mutant is thermodynamically less stable than the WT (denaturant melts, and unfolds faster than the WT (stopped-flow kinetics. Despite having global secondary structure similar to that of the WT, mutant showed significant local structural changes at many amino acids when compared with the WT (heteronuclear NMR experiments. These structural changes indicate that the effect of mutation is propagated over long distances in the protein structure. Contrary to these structural and stability changes, the mutant had no significant effect on the actin-binding function as evident from co-sedimentation and depolymerization assays. These results summarize that the K18N mutation decreases thermodynamic stability, accelerates unfolding, perturbs protein structure, but does not affect the function. Therefore, K18N is a stability defect rather than a functional defect. Decrease in stability and increase in unfolding decrease the net population of dystrophin molecules available for function, which might trigger XLDCM. Consistently, XLDCM patients have decreased levels of dystrophin in cardiac muscle.

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)

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

Dynamic tunneling force microscopy for characterizing electronic trap states in non-conductive surfaces

Energy Technology Data Exchange (ETDEWEB)

Wang, R.; Williams, C. C., E-mail: clayton@physics.utah.edu [Department of Physics and Astronomy, University of Utah, Salt Lake City, Utah 84112 (United States)

2015-09-15

Dynamic tunneling force microscopy (DTFM) is a scanning probe technique for real space mapping and characterization of individual electronic trap states in non-conductive films with atomic scale spatial resolution. The method is based upon the quantum mechanical tunneling of a single electron back and forth between a metallic atomic force microscopy tip and individual trap states in completely non-conducting surface. This single electron shuttling is measured by detecting the electrostatic force induced on the probe tip at the shuttling frequency. In this paper, the physical basis for the DTFM method is unfolded through a physical model and a derivation of the dynamic tunneling signal as a function of several experimental parameters is shown. Experimental data are compared with the theoretical simulations, showing quantitative consistency and verifying the physical model used. The experimental system is described and representative imaging results are shown.

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.

Kinetic analysis of concurrent activation potentiation during back squats and jump squats.

Science.gov (United States)

Ebben, William P; Kaufmann, Clare E; Fauth, McKenzie L; Petushek, Erich J

2010-06-01

Concurrent activation potentiation enhances muscular force during open kinetic chain isometric and isokinetic exercises via remote voluntary contractions (RVCs). The purpose of this study was to evaluate the effect of RVCs on the performance of closed kinetic chain ground-based exercises. Subjects included 13 men (21.4+/-1.5 years) who performed the back squat and jump squat in 2 test conditions. The RVC condition included performing the test exercises while clenching the jaw on a mouth guard, forcefully gripping and pulling the barbell down into the trapezius, and performing a Valsalva maneuver. The normal condition (NO-RVC) included performing the test exercises without RVCs. Exercises were assessed with a force platform. Peak ground reaction force (GRF), rate of force development (RFD) during the first 100 milliseconds (RFD-100), RFD to peak GRF (RFD-P), and jump squat height (JH) were calculated from the force-time records. Data were analyzed using an analysis of variance. Results reveal that GRF and RFD-100 were higher in the RVC compared with the NO-RVC condition for both the back squat and jump squat (psquat (psquat (p=0.82). The JH was higher in the RVC compared to the NO-RVC condition for the jump squat (pkinetic chain exercises for most of the outcome variables assessed, yielding a 2.9-32.3% greater performance. Practitioners should encourage athletes to use RVCs to improve the acute training effect of exercises such as those used in this study.

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)

Symmetrical kinematics does not imply symmetrical kinetics in people with transtibial amputation using cycling model.

Science.gov (United States)

Childers, W Lee; Kogler, Géza F

2014-01-01

People with amputation move asymmetrically with regard to kinematics (joint angles) and kinetics (joint forces and moments). Clinicians have traditionally sought to minimize kinematic asymmetries, assuming kinetic asymmetries would also be minimized. A cycling model evaluated locomotor asymmetries. Eight individuals with unilateral transtibial amputation pedaled with 172 mm-length crank arms on both sides (control condition) and with the crank arm length shortened to 162 mm on the amputated side (CRANK condition). Pedaling kinetics and limb kinematics were recorded. Joint kinetics, joint angles (mean and range of motion [ROM]), and pedaling asymmetries were calculated from force pedals and with a motion capture system. A one-way analysis of variance with tukey post hoc compared kinetics and kinematics across limbs. Statistical significance was set to p Pedaling asymmetries did not differ and were 23.0% +/= 9.8% and 23.2% +/= 12% for the control and CRANK conditions, respectively. Our results suggest that minimizing kinematic asymmetries does not relate to kinetic asymmetries as clinically assumed. We propose that future research should concentrate on defining acceptable asymmetry.

Analysis of residuals from enzyme kinetic and protein folding experiments in the presence of correlated experimental noise.

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Kuzmic, Petr; Lorenz, Thorsten; Reinstein, Jochen

2009-12-01

Experimental data from continuous enzyme assays or protein folding experiments often contain hundreds, or even thousands, of densely spaced data points. When the sampling interval is extremely short, the experimental data points might not be statistically independent. The resulting neighborhood correlation invalidates important theoretical assumptions of nonlinear regression analysis. As a consequence, certain goodness-of-fit criteria, such as the runs-of-signs test and the autocorrelation function, might indicate a systematic lack of fit even if the experiment does agree very well with the underlying theoretical model. A solution to this problem is to analyze only a subset of the residuals of fit, such that any excessive neighborhood correlation is eliminated. Substrate kinetics of the HIV protease and the unfolding kinetics of UMP/CMP kinase, a globular protein from Dictyostelium discoideum, serve as two illustrative examples. A suitable data-reduction algorithm has been incorporated into software DYNAFIT [P. Kuzmic, Anal. Biochem. 237 (1996) 260-273], freely available to all academic researchers from http://www.biokin.com.

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

Science.gov (United States)

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

2014-05-14

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

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.

Kinetic chain abnormalities in the athletic shoulder.

Science.gov (United States)

Sciascia, Aaron; Thigpen, Charles; Namdari, Surena; Baldwin, Keith

2012-03-01

Overhead activities require the shoulder to be exposed to and sustain repetitive loads. The segmental activation of the body's links, known as the kinetic chain, allows this to occur effectively. Proper muscle activation is achieved through generation of energy from the central segment or core, which then transfers the energy to the terminal links of the shoulder, elbow, and hand. The kinetic chain is best characterized by 3 components: optimized anatomy, reproducible efficient motor patterns, and the sequential generation of forces. However, tissue injury and anatomic deficits such as weakness and/or tightness in the leg, pelvic core, or scapular musculature can lead to overuse shoulder injuries. These injuries can be prevented and maladaptations can be detected with a thorough understanding of biomechanics of the kinetic chain as it relates to overhead activity.

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).

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

Dynamically adjustable foot-ground contact model to estimate ground reaction force during walking and running.

Science.gov (United States)

Jung, Yihwan; Jung, Moonki; Ryu, Jiseon; Yoon, Sukhoon; Park, Sang-Kyoon; Koo, Seungbum

2016-03-01

Human dynamic models have been used to estimate joint kinetics during various activities. Kinetics estimation is in demand in sports and clinical applications where data on external forces, such as the ground reaction force (GRF), are not available. The purpose of this study was to estimate the GRF during gait by utilizing distance- and velocity-dependent force models between the foot and ground in an inverse-dynamics-based optimization. Ten males were tested as they walked at four different speeds on a force plate-embedded treadmill system. The full-GRF model whose foot-ground reaction elements were dynamically adjusted according to vertical displacement and anterior-posterior speed between the foot and ground was implemented in a full-body skeletal model. The model estimated the vertical and shear forces of the GRF from body kinematics. The shear-GRF model with dynamically adjustable shear reaction elements according to the input vertical force was also implemented in the foot of a full-body skeletal model. Shear forces of the GRF were estimated from body kinematics, vertical GRF, and center of pressure. The estimated full GRF had the lowest root mean square (RMS) errors at the slow walking speed (1.0m/s) with 4.2, 1.3, and 5.7% BW for anterior-posterior, medial-lateral, and vertical forces, respectively. The estimated shear forces were not significantly different between the full-GRF and shear-GRF models, but the RMS errors of the estimated knee joint kinetics were significantly lower for the shear-GRF model. Providing COP and vertical GRF with sensors, such as an insole-type pressure mat, can help estimate shear forces of the GRF and increase accuracy for estimation of joint kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.

Kinetic Analysis of Horizontal Plyometric Exercise Intensity.

Science.gov (United States)

Kossow, Andrew J; Ebben, William P

2018-05-01

Kossow, AJ, DeChiara, TG, Neahous, SM, and Ebben, WP. Kinetic analysis of horizontal plyometric exercise intensity. J Strength Cond Res 32(5): 1222-1229, 2018-Plyometric exercises are frequently performed as part of a strength and conditioning program. Most studies assessed the kinetics of plyometric exercises primarily performed in the vertical plane. The purpose of this study was to evaluate the multiplanar kinetic characteristics of a variety of plyometric exercises, which have a significant horizontal component. This study also sought to assess sex differences in the intensity progression of these exercises. Ten men and 10 women served as subjects. The subjects performed a variety of plyometric exercises including the double-leg hop, standing long jump, single-leg standing long jump, bounding, skipping, power skipping, cone hops, and 45.72-cm hurdle hops. Subjects also performed the countermovement jump for comparison. All plyometric exercises were evaluated using a force platform. Dependent variables included the landing rate of force development and landing ground reaction forces for each exercise in the vertical, frontal, and sagittal planes. A 2-way mixed analysis of variance with repeated-measures for plyometric exercise type demonstrated main effects for exercise type for all dependent variables (p ≤ 0.001). There was no significant interaction between plyometric exercise type and sex for any of the variable assessed. Bonferroni-adjusted pairwise comparisons identified a number of differences between the plyometric exercises for the dependent variables assessed (p ≤ 0.05). These findings should be used to guide practitioners in the progression of plyometric exercise intensity, and thus program design, for those who require significant horizontal power in their sport.

Comprehension of handwriting development: Pen-grip kinetics in handwriting tasks and its relation to fine motor skills among school-age children.

Science.gov (United States)

Lin, Yu-Chen; Chao, Yen-Li; Wu, Shyi-Kuen; Lin, Ho-Hsio; Hsu, Chieh-Hsiang; Hsu, Hsiao-Man; Kuo, Li-Chieh

2017-10-01

Numerous tools have been developed to evaluate handwriting performances by analysing written products. However, few studies have directly investigated kinetic performances of digits when holding a pen. This study thus attempts to investigate pen-grip kinetics during writing tasks of school-age children and explore the relationship between the kinetic factors and fine motor skills. This study recruited 181 children aged from 5 to 12 years old and investigated the effects of age on handwriting kinetics and the relationship between these and fine motor skills. The forces applied from the digits and pen-tip were measured during writing tasks via a force acquisition pen, and the children's fine motor performances were also evaluated. The results indicate that peak force and average force might not be direct indicators of handwriting performance for normally developing children at this age. Younger children showed larger force variation and lower adjustment frequency during writing, which might indicate they had poorer force control than the older children. Force control when handling a pen is significantly correlated with fine motor performance, especially in relation to the manual dexterity. A novel system is proposed for analysing school-age children's force control while handwriting. We observed the development of force control in relation to pen grip among the children with different ages in this study. The findings suggested that manipulation skill may be crucial when children are establishing their handwriting capabilities. © 2017 Occupational Therapy Australia.

Molecular Force Spectroscopy on Cells

Science.gov (United States)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

Science.gov (United States)

Andruchov, Oleg; Galler, Stefan

2008-03-01

This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

The kinetic energy of the vortex and pinning force in high-temperature superconductors

International Nuclear Information System (INIS)

Boiko, J.; Khar'kovskij Gosudarstvennyj Univ.; Majewski, P.; Aldinger, F.

1995-01-01

It is known that the total magnetic energy of the vortex consists of two parts: the kinetic energy, E k , which is connected with the supercurrents which circulate around the vortex, and its own magnetic energy, E mo , which is connected with the real magnetic field. Therefore, the characteristic linear spacing which corresponds to the maximum change of the kinetic energy is not related with the magnetic penetration depth, λ, but with another characteristic spacing R. Considering this fact, the idea of the nature of F p of different defects which are greater than ξ, but smaller than λ, can be modified. (orig.)

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

Kinetic Constrained Optimization of the Golf Swing Hub Path

Directory of Open Access Journals (Sweden)

Steven M. Nesbit

2014-12-01

Full Text Available This study details an optimization of the golf swing, where the hand path and club angular trajectories are manipulated. The optimization goal was to maximize club head velocity at impact within the interaction kinetic limitations (force, torque, work, and power of the golfer as determined through the analysis of a typical swing using a two-dimensional dynamic model. The study was applied to four subjects with diverse swing capabilities and styles. It was determined that it is possible for all subjects to increase their club head velocity at impact within their respective kinetic limitations through combined modifications to their respective hand path and club angular trajectories. The manner of the modifications, the degree of velocity improvement, the amount of kinetic reduction, and the associated kinetic limitation quantities were subject dependent. By artificially minimizing selected kinetic inputs within the optimization algorithm, it was possible to identify swing trajectory characteristics that indicated relative kinetic weaknesses of a subject. Practical implications are offered based upon the findings of the study.

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.

The similarity of attractive and repulsive forces on a lattice

Science.gov (United States)

Mirahmadi, Marjan-S.; Fatollahi, Amir H.; Khorrami, Mohammad

2015-07-01

On a lattice, as the momentum space is compact, the kinetic energy is bounded not only from below but also from above. It is shown that this somehow removes the distinction between repulsive and attractive forces. In particular, it is seen that a region with attractive force would appear forbidden for states with energies higher than a certain value, while repulsive forces could develop bound-states. An explicit transformation is introduced which transforms the spectrum of a system corresponding to a repulsive force, to that of a similar system corresponding to an attractive force. Explicit numerical examples are presented for discrete energies of bound-states of a particle experiencing repulsive force by a piecewise constant potential. Finally, the parameters of a specific one-dimensional (1D) translationally invariant system on continuum are tuned so that the energy of the system resembles the kinetic energy of a system on a 1D lattice. In particular, the parameters are tuned so that while the width of the first energy band and its position are kept finite, the gap between the first energy band and the next energy band goes to infinity, so that effectively only the first energy band is relevant.

Choose Wisely: Static or Kinetic Friction--The Power of Dimensionless Plots

Science.gov (United States)

Ludwigsen, Daniel; Svinarich, Kathryn

2009-01-01

Consider a problem of sliding blocks, one stacked atop the other, resting on a frictionless table. If the bottom block is pulled horizontally, nature makes a choice: if the applied force is small, static friction between the blocks accelerates the blocks together, but with a large force the blocks slide apart. In that case, kinetic friction still…

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)

Exploring the membrane fusion mechanism through force-induced disassembly of HIV-1 six-helix bundle

Energy Technology Data Exchange (ETDEWEB)

Gao, Kai [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Yong [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Lou, Jizhong, E-mail: jlou@ibp.ac.cn [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

2016-05-13

Enveloped virus, such as HIV-1, employs membrane fusion mechanism to invade into host cell. HIV-1 gp41 ectodomain uses six-helix bundle configuration to accomplish this process. Using molecular dynamic simulations, we confirmed the stability of this six-helix bundle by showing high occupancy of hydrogen bonds and hydrophobic interactions. Key residues and interactions important for the bundle integration were characterized by force-induced unfolding simulations of six-helix bundle, exhibiting the collapse order of these groups of interactions. Moreover, our results in some way concerted with a previous theory that the formation of coiled-coil choose a route which involved cooperative interactions between the N-terminal and C-terminal helix. -- Highlights: •Unfolding of HIV-1 gp41 six-helix bundle is studied by molecular dynamics simulations. •Specific interactions responsible for the stability of HIV-1 envelope post-fusion conformation were identified. •The gp41 six-helix bundle transition inducing membrane fusion might be a cooperative process of the three subunits.

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

Investigation of the heparin-thrombin interaction by dynamic force spectroscopy.

Science.gov (United States)

Wang, Congzhou; Jin, Yingzi; Desai, Umesh R; Yadavalli, Vamsi K

2015-06-01

The interaction between heparin and thrombin is a vital step in the blood (anti)coagulation process. Unraveling the molecular basis of the interactions is therefore extremely important in understanding the mechanisms of this complex biological process. In this study, we use a combination of an efficient thiolation chemistry of heparin, a self-assembled monolayer-based single molecule platform, and a dynamic force spectroscopy to provide new insights into the heparin-thrombin interaction from an energy viewpoint at the molecular scale. Well-separated single molecules of heparin covalently attached to mixed self-assembled monolayers are demonstrated, whereby interaction forces with thrombin can be measured via atomic force microscopy-based spectroscopy. Further these interactions are studied at different loading rates and salt concentrations to directly obtain kinetic parameters. An increase in the loading rate shows a higher interaction force between the heparin and thrombin, which can be directly linked to the kinetic dissociation rate constant (koff). The stability of the heparin/thrombin complex decreased with increasing NaCl concentration such that the off-rate was found to be driven primarily by non-ionic forces. These results contribute to understanding the role of specific and nonspecific forces that drive heparin-thrombin interactions under applied force or flow conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

Morphogenesis of Kinetic Reciprocal Frames

DEFF Research Database (Denmark)

Parigi, Dario; Sassone, Mario

2011-01-01

Kinetic structures in civil engineering and architecture gained considerable more attention in the very recent years as a practical solution to face time dependant performances. Realized projects are mostly bridges, retractable roofs, while in architecture the trend follows the category of intera......Kinetic structures in civil engineering and architecture gained considerable more attention in the very recent years as a practical solution to face time dependant performances. Realized projects are mostly bridges, retractable roofs, while in architecture the trend follows the category...... (RF) were studied in the past as a practical solution to span distances with shorter elements. Leonardo da Vinci discovered interesting RF patterns and studied three dimensional arch structures for bridges. RF are generally defined as structures that forms closed circuits of forces, and where elements...

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

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)

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

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.

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.

Force illusions and drifts observed during muscle vibration.

Science.gov (United States)

Reschechtko, Sasha; Cuadra, Cristian; Latash, Mark L

2018-01-01

We explored predictions of a scheme that views position and force perception as a result of measuring proprioceptive signals within a reference frame set by ongoing efferent process. In particular, this hypothesis predicts force illusions caused by muscle vibration and mediated via changes in both afferent and efferent components of kinesthesia. Healthy subjects performed accurate steady force production tasks by pressing with the four fingers of one hand (the task hand) on individual force sensors with and without visual feedback. At various times during the trials, subjects matched the perceived force using the other hand. High-frequency vibration was applied to one or both of the forearms (over the hand and finger extensors). Without visual feedback, subjects showed a drop in the task hand force, which was significantly smaller under the vibration of that forearm. Force production by the matching hand was consistently higher than that of the task hand. Vibrating one of the forearms affected the matching hand in a manner consistent with the perception of higher magnitude of force produced by the vibrated hand. The findings were consistent between the dominant and nondominant hands. The effects of vibration on both force drift and force mismatching suggest that vibration led to shifts in both signals from proprioceptors and the efferent component of perception, the referent coordinate and/or coactivation command. The observations fit the hypothesis on combined perception of kinematic-kinetic variables with little specificity of different groups of peripheral receptors that all contribute to perception of forces and coordinates. NEW & NOTEWORTHY We show that vibration of hand/finger extensors produces consistent errors in finger force perception. Without visual feedback, finger force drifted to lower values without a drift in the matching force produced by the other hand; hand extensor vibration led to smaller finger force drift. The findings fit the scheme with

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.

Nonconservative current-induced forces: A physical interpretation

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Tchavdar N. Todorov

2011-10-01

Full Text Available We give a physical interpretation of the recently demonstrated nonconservative nature of interatomic forces in current-carrying nanostructures. We start from the analytical expression for the curl of these forces, and evaluate it for a point defect in a current-carrying system. We obtain a general definition of the capacity of electrical current flow to exert a nonconservative force, and thus do net work around closed paths, by a formal noninvasive test procedure. Second, we show that the gain in atomic kinetic energy over time, generated by nonconservative current-induced forces, is equivalent to the uncompensated stimulated emission of directional phonons. This connection with electron–phonon interactions quantifies explicitly the intuitive notion that nonconservative forces work by angular momentum transfer.

Lower extremity kinetics in tap dance.

Science.gov (United States)

Mayers, Lester; Bronner, Shaw; Agraharasamakulam, Sujani; Ojofeitimi, Sheyi

2010-01-01

Tap dance is a unique performing art utilizing the lower extremities as percussion instruments. In a previous study these authors reported decreased injury prevalence among tap dancers compared to other dance and sports participants. No biomechanical analyses of tap dance exist to explain this finding. The purpose of the current pilot study was to provide a preliminary overview of normative peak kinetic and kinematic data, based on the hypothesis that tap dance generates relatively low ground reaction forces and joint forces and moments. Six professional tap dancers performed four common tap dance sequences that produced data captured by the use of a force platform and a five-camera motion analysis system. The mean vertical ground reaction force for all sequences was found to be 2.06+/-0.55 BW. Mean peak sagittal, frontal, and transverse plane joint moments (hip, knee, and ankle) ranged from 0.07 to 2.62 N.m/kg. These small ground reaction forces and joint forces and moments support our hypothesis, and may explain the relatively low injury incidence in tap dancers. Nevertheless, the analysis is highly complex, and other factors remain to be studied and clarified.

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

Directory of Open Access Journals (Sweden)

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

Body-force-driven multiplicity and stability of combined free and forced convection in rotating curved ducts: Coriolis force

Science.gov (United States)

Yang, T.; Wang, L.

A numerical study is made on the fully developed bifurcation structure and stability of forced convection in a rotating curved duct of square cross-section. Solution structure is determined as variation of a parameter that indicates the effect of rotation (Coriolis-force-driven multiplicity). Three solutions for the flows in a stationary curved duct obtained in the work of Yang and Wang [1] are used as initial solutions of continuation calculations to unfold the solution branches. Twenty-one solution branches are found comparing with five obtained by Selmi and Nandakumar [2]. Dynamic responses of the multiple solutions to finite random disturbances are examined by the direct transient computation. Results show that characteristics of physically realizable fully developed flows changes significantly with variation of effect of rotation. Fourteen sub-ranges are identified according to characteristics of physically realizable solutions. As rotation effect changes, possible physically realizable fully-developed flows can be stable steady 2-cell state, stable multi-cell state, temporal periodic oscillation between symmetric/asymmetric 2-cell/4-cell flows, temporal oscillation with intermittency, temporal chaotic oscillation and temporal oscillation with pseudo intermittency. Among these possible physically realizable fully developed flows, stable multi-cell state and stable steady 2-cell state exist as dual stable. And oscillation with pseudo intermittency is a new phenomenon. In addition to the temporal oscillation with intermittency, sudden shift from stationary stable solution to temporal chaotic oscillation is identified to be another way of onset of chaos.

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)

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.

Increasing Running Step Rate Reduces Patellofemoral Joint Forces

Science.gov (United States)

Lenhart, Rachel L.; Thelen, Darryl G.; Wille, Christa M.; Chumanov, Elizabeth S.; Heiderscheit, Bryan C.

2013-01-01

Purpose Increasing step rate has been shown to elicit changes in joint kinematics and kinetics during running, and has been suggested as a possible rehabilitation strategy for runners with patellofemoral pain. The purpose of this study was to determine how altering step rate affects internal muscle forces and patellofemoral joint loads, and then to determine what kinematic and kinetic factors best predict changes in joint loading. Methods We recorded whole body kinematics of 30 healthy adults running on an instrumented treadmill at three step rate conditions (90%, 100%, and 110% of preferred step rate). We then used a 3D lower extremity musculoskeletal model to estimate muscle, patellar tendon, and patellofemoral joint forces throughout the running gait cycles. Additionally, linear regression analysis allowed us to ascertain the relative influence of limb posture and external loads on patellofemoral joint force. Results Increasing step rate to 110% of preferred reduced peak patellofemoral joint force by 14%. Peak muscle forces were also altered as a result of the increased step rate with hip, knee and ankle extensor forces, and hip abductor forces all reduced in mid-stance. Compared to the 90% step rate condition, there was a concomitant increase in peak rectus femoris and hamstring loads during early and late swing, respectively, at higher step rates. Peak stance phase knee flexion decreased with increasing step rate, and was found to be the most important predictor of the reduction in patellofemoral joint loading. Conclusion Increasing step rate is an effective strategy to reduce patellofemoral joint forces and could be effective in modulating biomechanical factors that can contribute to patellofemoral pain. PMID:23917470

The effect of ankle bracing on knee kinetics and kinematics during volleyball-specific tasks.

Science.gov (United States)

West, T; Ng, L; Campbell, A

2014-12-01

The purpose of this study was to examine the effects of ankle bracing on knee kinetics and kinematics during volleyball tasks. Fifteen healthy, elite, female volleyball players performed a series of straight-line and lateral volleyball tasks with no brace and when wearing an ankle brace. A 14-camera Vicon motion analysis system and AMTI force plate were used to capture the kinetic and kinematic data. Knee range of motion, peak knee anterior-posterior and medial-lateral shear forces, and peak ground reaction forces that occurred between initial contact with the force plate and toe off were compared using paired sample t-tests between the braced and non-braced conditions (P volleyball tasks. However, ankle bracing was demonstrated to reduce knee lateral shear forces during all of the lateral movement volleyball tasks. Wearing the Active Ankle T2 brace will not impact knee joint range of motion and may in fact reduce shear loading to the knee joint in volleyball players. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kinetics and thermodynamics of the thermal inactivation and chaperone assisted folding of zebrafish dihydrofolate reductase.

Science.gov (United States)

Thapliyal, Charu; Jain, Neha; Rashid, Naira; Chaudhuri Chattopadhyay, Pratima

2018-01-01

The maintenance of thermal stability is a major issue in protein engineering as many proteins tend to form inactive aggregates at higher temperatures. Zebrafish DHFR, an essential protein for the survival of cells, shows irreversible thermal unfolding transition. The protein exhibits complete unfolding and loss of activity at 50 °C as monitored by UV-Visible, fluorescence and far UV-CD spectroscopy. The heat induced inactivation of zDHFR follows first-order kinetics and Arrhenius law. The variation in the value of inactivation rate constant, k with increasing temperatures depicts faster inactivation at elevated temperatures. We have attempted to study the chaperoning ability of a shorter variant of GroEL (minichaperone) and compared it with that of conventional GroEL-GroES chaperone system. Both the chaperone system prevented the aggregation and assisted in refolding of zDHFR. The rate of thermal inactivation was significantly retarded in the presence of chaperones which indicate that it enhances the thermal stability of the enzyme. As minichaperone is less complex, and does not require high energy co-factors like ATP, for its function as compared to conventional GroEL-GroES system, it can act as a very good in vitro as well as in vivo chaperone model for monitoring assisted protein folding phenomenon. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Biosimilarity under stress: A forced degradation study of Remicade® and Remsima™.

Science.gov (United States)

Pisupati, Karthik; Benet, Alexander; Tian, Yuwei; Okbazghi, Solomon; Kang, Jukyung; Ford, Michael; Saveliev, Sergei; Sen, K Ilker; Carlson, Eric; Tolbert, Thomas J; Ruotolo, Brandon T; Schwendeman, Steven P; Schwendeman, Anna

2017-10-01

Remsima™ (infliximab) is the first biosimilar monoclonal antibody (mAb) approved by the European Medical Agency and the US Food and Drug Administration. Remsima™ is highly similar to its reference product, Remicade®, with identical formulation components. The 2 products, however, are not identical; Remsima™ has higher levels of soluble aggregates, C-terminal lysine truncation, and fucosylated glycans. To understand if these attribute differences could be amplified during forced degradation, solutions and lyophilized powders of the 2 products were subjected to stress at elevated temperature (40-60°C) and humidity (dry-97% relative humidity). Stress-induced aggregation and degradation profiles were similar for the 2 products and resulted in loss of infliximab binding to tumor necrosis factor and FcγRIIIa. Appearances of protein aggregates and hydrolysis products were time- and humidity-dependent, with similar degradation rates observed for the reference and biosimilar products. Protein powder incubations at 40°C/97% relative humidity resulted in partial mAb unfolding and increased asparagine deamidation. Minor differences in heat capacity, fluorescence, levels of subvisible particulates, deamidation and protein fragments were observed in the 2 stressed products, but these differences were not statistically significant. The protein solution instability at 60°C, although quite significant, was also similar for both products. Despite the small initial analytical differences, Remicade® and Remsima™ displayed similar degradation mechanisms and kinetics. Thus, our results show that the 2 products are highly similar and infliximab's primary sequence largely defines their protein instabilities compared with the limited influence of small initial purity and glycosylation differences in the 2 products.

Optimizing Armed Forces Capabilities for Hybrid Warfare – New Challenge for Slovak Armed Forces

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Peter PINDJÁK

2015-09-01

Full Text Available The paper deals with the optimization of military capabilities of the Slovak Armed Forces for conducting operations in a hybrid conflict, which represents one of the possible scenarios of irregular warfare. Whereas in the regular warfare adversaries intend to eliminate the centers of gravity of each other, most often command and control structures, in irregular conflicts, the center of gravity shifts towards the will and cognitive perception of the target population. Hybrid warfare comprises a thoroughly planned combination of conventional military approaches and kinetic operations with subversive, irregular activities, including information and cyber operations. These efforts are often accompanied by intensified activities of intelligence services, special operation forces, and even mercenary and other paramilitary groups. The development of irregular warfare capabilities within the Slovak Armed Forces will require a progressive transformation process that may turn the armed forces into a modern and adaptable element of power, capable of deployment in national and international crisis management operations.

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.

Redistribution of Kinetic Energy in Turbulent Flows

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Alain Pumir

2014-10-01

Full Text Available In statistically homogeneous turbulent flows, pressure forces provide the main mechanism to redistribute kinetic energy among fluid elements, without net contribution to the overall energy budget. This holds true in both two-dimensional (2D and three-dimensional (3D flows, which show fundamentally different physics. As we demonstrate here, pressure forces act on fluid elements very differently in these two cases. We find in numerical simulations that in 3D pressure forces strongly accelerate the fastest fluid elements, and that in 2D this effect is absent. In 3D turbulence, our findings put forward a mechanism for a possibly singular buildup of energy, and thus may shed new light on the smoothness problem of the solution of the Navier-Stokes equation in 3D.

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...

Net joint kinetics in the limbs of pigs walking on concrete floor in dry and contaminated conditions

DEFF Research Database (Denmark)

Thorup, Vivi M.; Laursen, Bjarne; Jensen, Bente Rona

2008-01-01

In pigs (Sus scrofa), joint disorders are frequent leg problems, and inappropriate pigpen floors and slippery floor conditions may contribute to these problems. Therefore, this study first aimed to quantify the net joint kinetics (net joint moments and net joint reaction forces) in the forelimbs...... and hindlimbs of healthy pigs walking on solid concrete floors. Second, this study aimed to examine the effect of floor condition on the net joint kinetics. Kinematic (50-Hz video recordings) and kinetic (1-kHz force plate measurements) data were collected from 30 pigs and combined with body segment parameters...... from a cadaver study. Net joint kinetics was calculated by using a 2-dimensional inverse dynamic solution. Inverse dynamics have, to our knowledge, not been applied in pigs before. Dry, greasy, and wet floor conditions were tested with 10 pigs each. In the forelimbs, peak joint moment was less (P

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…

THE NECESSITY OF LAND FORCES BATTLEGROUPS TO DIVERSIFY THEIR STRUCTURE AND ACTION

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Ltc. Ilie MELINTE

2015-06-01

Full Text Available Given, on the one hand, the trends of military conflicts in the proximity of our country, and on the other hand the features the operating mode of the Land Forces brigades with the highest operational level, we consider it necessary to develop the principles envisaging the use of these large units in combat. The Romanian Land Forces brigades have gathered knowledge and experience on the unfolding of operations by participating, on various occasions, in international missions in operation theatres such as Kosovo, Afghanistan and Iraq, through a close study of the allied doctrines and of the NATO representative armies, by updating their document base and, last but not least, by intensifying combined arms and combined forces training both on a national and on a multinational level. Regarding the involvement of the operational units and large units in combat, in terms of taskorganising, we believe that they are able to act both in the classic format based on the current organization pattern and in the battlegroup format, especially set up for missions (Battlegroups - BGs.

Real-time hydrogen/deuterium exchange kinetics via supercharged electrospray ionization tandem mass spectrometry.

Science.gov (United States)

Sterling, Harry J; Williams, Evan R

2010-11-01

Amide hydrogen/deuterium exchange (HDX) rate constants of bovine ubiquitin in an ammonium acetate solution containing 1% of the electrospray ionization (ESI) "supercharging" reagent m-nitrobenzyl alcohol (m-NBA) were obtained using top-down, electron transfer dissociation (ETD) tandem mass spectrometry (MS). The supercharging reagent replaces the acid and temperature "quench" step in the conventional MS approach to HDX experiments by causing rapid protein denaturation to occur in the ESI droplet. The higher charge state ions that are produced with m-NBA are more unfolded, as measured by ion mobility, and result in higher fragmentation efficiency and higher sequence coverage with ETD. Single amino acid resolution was obtained for 44 of 72 exchangeable amide sites, and summed kinetic data were obtained for regions of the protein where adjacent fragment ions were not observed, resulting in an overall spatial resolution of 1.3 residues. Comparison of these results with previous values from NMR indicates that the supercharging reagent does not cause significant structural changes to the protein in the initial ESI solution and that scrambling or back-exchange is minimal. This new method for top-down HDX-MS enables real-time kinetic data measurements under physiological conditions, similar to those obtained using NMR, with comparable spatial resolution and significantly better sensitivity.

How metal films de-wet substrates-identifying the kinetic pathways and energetic driving forces

International Nuclear Information System (INIS)

McCarty, Kevin F; Hamilton, John C; Thuermer, Konrad; Jones, Frank; Talin, A Alec; Bartelt, Norman C; Sato, Yu; K Schmid, Andreas; Saa, Angela; Figuera, Juan de la; Stumpf, Roland

2009-01-01

We study how single-crystal chromium films of uniform thickness on W(110) substrates are converted to arrays of three-dimensional (3D) Cr islands during annealing. We use low-energy electron microscopy (LEEM) to directly observe a kinetic pathway that produces trenches that expose the wetting layer. Adjacent film steps move simultaneously uphill and downhill relative to the staircase of atomic steps on the substrate. This step motion thickens the film regions where steps advance. Where film steps retract, the film thins, eventually exposing the stable wetting layer. Since our analysis shows that thick Cr films have a lattice constant close to bulk Cr, we propose that surface and interface stress provide a possible driving force for the observed morphological instability. Atomistic simulations and analytic elastic models show that surface and interface stress can cause a dependence of film energy on thickness that leads to an instability to simultaneous thinning and thickening. We observe that de-wetting is also initiated at bunches of substrate steps in two other systems, Ag/W(110) and Ag/Ru(0001). We additionally describe how Cr films are converted into patterns of unidirectional stripes as the trenches that expose the wetting layer lengthen along the W[001] direction. Finally, we observe how 3D Cr islands form directly during film growth at elevated temperature. The Cr mesas (wedges) form as Cr film steps advance down the staircase of substrate steps, another example of the critical role that substrate steps play in 3D island formation.

Kinematic and kinetic analysis of overhand, sidearm and underhand lacrosse shot techniques.

Science.gov (United States)

Macaulay, Charles A J; Katz, Larry; Stergiou, Pro; Stefanyshyn, Darren; Tomaghelli, Luciano

2017-12-01

Lacrosse requires the coordinated performance of many complex skills. One of these skills is shooting on the opponents' net using one of three techniques: overhand, sidearm or underhand. The purpose of this study was to (i) determine which technique generated the highest ball velocity and greatest shot accuracy and (ii) identify kinematic and kinetic variables that contribute to a high velocity and high accuracy shot. Twelve elite male lacrosse players participated in this study. Kinematic data were sampled at 250 Hz, while two-dimensional force plates collected ground reaction force data (1000 Hz). Statistical analysis showed significantly greater ball velocity for the sidearm technique than overhand (P  0.05). Kinematic and kinetic variables were not significantly correlated to shot accuracy or velocity across all shot types; however, when analysed independently, the lead foot horizontal impulse showed a negative correlation with underhand ball velocity (P = 0.042). This study identifies the technique with the highest ball velocity, defines kinematic and kinetic predictors related to ball velocity and provides information to coaches and athletes concerned with improving lacrosse shot performance.

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

Thermodynamic and kinetic analysis of heterogeneous photocatalysis for semiconductor systems.

Science.gov (United States)

Liu, Baoshun; Zhao, Xiujian; Terashima, Chiaki; Fujishima, Akira; Nakata, Kazuya

2014-05-21

Since the report of the Honda-Fujishima effect, heterogeneous photocatalysis has attracted much attention around the world because of its potential energy and environmental applications. Although great progresses have been made in recent years, most were focused on preparing highly-active photocatalysts and investigating visible light utilization. In fact, we are still unclear on the thermodynamic and kinetic nature of photocatalysis to date, which sometimes leads to misunderstandings for experimental results. It is timely to give a review and discussion on the thermodynamics and kinetics of photocatalysis, so as to direct future researches. However, there is an absence of a detailed review on this topic until now. In this article, we tried to review and discuss the thermodynamics and kinetics of photocatalysis. We explained the thermodynamic driving force of photocatalysis, and distinguished the functions of light and heat in photocatalysis. The Langmuir-Hinshelwood kinetic model, the ˙OH oxidation mechanism, and the direct-indirect (D-I) kinetic model were reviewed and compared. Some applications of the D-I model to study photocatalytic kinetics were also discussed. The electron transport mode and its importance in photocatalysis were investigated. Finally, the intrinsic relation between the kinetics and the thermodynamics of photocatalytic reactions was discussed.

Kinetic theory in maximal-acceleration invariant phase space

International Nuclear Information System (INIS)

Brandt, H.E.

1989-01-01

A vanishing directional derivative of a scalar field along particle trajectories in maximal acceleration invariant phase space is identical in form to the ordinary covariant Vlasov equation in curved spacetime in the presence of both gravitational and nongravitational forces. A natural foundation is thereby provided for a covariant kinetic theory of particles in maximal-acceleration invariant phase space. (orig.)

Single-Molecule Stochastic Resonance

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K. Hayashi

2012-08-01

Full Text Available Stochastic resonance (SR is a well-known phenomenon in dynamical systems. It consists of the amplification and optimization of the response of a system assisted by stochastic (random or probabilistic noise. Here we carry out the first experimental study of SR in single DNA hairpins which exhibit cooperatively transitions from folded to unfolded configurations under the action of an oscillating mechanical force applied with optical tweezers. By varying the frequency of the force oscillation, we investigate the folding and unfolding kinetics of DNA hairpins in a periodically driven bistable free-energy potential. We measure several SR quantifiers under varied conditions of the experimental setup such as trap stiffness and length of the molecular handles used for single-molecule manipulation. We find that a good quantifier of the SR is the signal-to-noise ratio (SNR of the spectral density of measured fluctuations in molecular extension of the DNA hairpins. The frequency dependence of the SNR exhibits a peak at a frequency value given by the resonance-matching condition. Finally, we carry out experiments on short hairpins that show how SR might be useful for enhancing the detection of conformational molecular transitions of low SNR.

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

Progressive recruitment of muscle fibers is not necessary for the slow component of VO2 kinetics.

Science.gov (United States)

Zoladz, Jerzy A; Gladden, L Bruce; Hogan, Michael C; Nieckarz, Zenon; Grassi, Bruno

2008-08-01

The "slow component" of O2 uptake (VO2) kinetics during constant-load heavy-intensity exercise is traditionally thought to derive from a progressive recruitment of muscle fibers. In this study, which represents a reanalysis of data taken from a previous study by our group (Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, Gladden LB. J Physiol 538: 195-207, 2002) we evaluated the presence of a slow component-like response in the isolated dog gastrocnemius in situ (n=6) during 4 min of contractions at approximately 60-70% of peak VO2. In this preparation all muscle fibers are maximally activated by electrical stimulation from the beginning of the contraction period, and no progressive recruitment of fibers is possible. Muscle VO2 was calculated as blood flow multiplied by arteriovenous O2 content difference. The muscle fatigued (force decreased by approximately 20-25%) during contractions. Kinetics of adjustment were evaluated for 1) VO2, uncorrected for force development; 2) VO2 normalized for peak force; 3) VO2 normalized for force-time integral. A slow component-like response, described in only one muscle out of six when uncorrected VO2 was considered, was observed in all muscles when VO2/peak force and VO2/force-time were considered. The amplitude of the slow component-like response, expressed as a fraction of the total response, was higher for VO2/peak force (0.18+/-0.06, means+/-SE) and for VO2/force-time (0.22+/-0.05) compared with uncorrected VO2 (0.04+/-0.04). A progressive recruitment of muscle fibers may not be necessary for the development of the slow component of VO2 kinetics, which may be caused by the metabolic factors that induce muscle fatigue and, as a consequence, reduce the efficiency of muscle contractions.

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

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.

Casimir rack and pinion as a miniaturized kinetic energy harvester

Science.gov (United States)

Miri, MirFaez; Etesami, Zahra

2016-08-01

We study a nanoscale machine composed of a rack and a pinion with no contact, but intermeshed via the lateral Casimir force. We adopt a simple model for the random velocity of the rack subject to external random forces, namely, a dichotomous noise with zero mean value. We show that the pinion, even when it experiences random thermal torque, can do work against a load. The device thus converts the kinetic energy of the random motions of the rack into useful work.

Whole-Body Human Inverse Dynamics with Distributed Micro-Accelerometers, Gyros and Force Sensing

Directory of Open Access Journals (Sweden)

Claudia Latella

2016-05-01

Full Text Available Human motion tracking is a powerful tool used in a large range of applications that require human movement analysis. Although it is a well-established technique, its main limitation is the lack of estimation of real-time kinetics information such as forces and torques during the motion capture. In this paper, we present a novel approach for a human soft wearable force tracking for the simultaneous estimation of whole-body forces along with the motion. The early stage of our framework encompasses traditional passive marker based methods, inertial and contact force sensor modalities and harnesses a probabilistic computational technique for estimating dynamic quantities, originally proposed in the domain of humanoid robot control. We present experimental analysis on subjects performing a two degrees-of-freedom bowing task, and we estimate the motion and kinetics quantities. The results demonstrate the validity of the proposed method. We discuss the possible use of this technique in the design of a novel soft wearable force tracking device and its potential applications.

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)

Succinate overproduction: A case study of computational strain design using a comprehensive Escherichia coli kinetic model

Directory of Open Access Journals (Sweden)

Ali eKhodayari

2015-01-01

Full Text Available Computational strain design prediction accuracy has been the focus for many recent efforts through the selective integration of kinetic information into metabolic models. In general, kinetic model prediction quality is determined by the range and scope of genetic and/or environmental perturbations used during parameterization. In this effort, we apply the k-OptForce procedure on a kinetic model of E. coli core metabolism constructed using the Ensemble Modeling (EM method and parameterized using multiple mutant strains data under aerobic respiration with glucose as the carbon source. Minimal interventions are identified that improve succinate yield under both aerobic and anaerobic conditions to test the fidelity of model predictions under both genetic and environmental perturbations. Under aerobic condition, k-OptForce identifies interventions that match existing experimental strategies pointing at a number of unexplored flux redirections such as routing glyoxylate flux through the glycerate metabolism to improve succinate yield. Many of the identified interventions rely on the kinetic descriptions and would not be discoverable by a purely stoichiometric description. In contrast, under fermentative (anaerobic conditions, k-OptForce fails to identify key interventions including up-regulation of anaplerotic reactions and elimination of competitive fermentative products. This is due to the fact that the pathways activated under anaerobic conditions were not properly parameterized as only aerobic flux data were used in the model construction. This study shed light on the importance of condition-specific model parameterization and provides insight onto how to augment kinetic models so as to correctly respond to multiple environmental perturbations.

A model stomach system to investigate disintegration kinetics of solid foods during gastric digestion.

Science.gov (United States)

Kong, F; Singh, R P

2008-06-01

Knowledge of the disintegration kinetics of food particulates in the human stomach is essential for assessing the bioaccessibility of nutrients in solid foods and understanding stomach emptying. The objective of this study was to develop a model stomach system and to investigate the kinetics of food disintegration. Our system consisted mainly of a turntable and a jacketed glass chamber containing simulated gastric juice in which plastic beads were added to simulate food particulates as well as provide a suitable mechanical destructive force on food samples. The mechanical force on the samples was simultaneously measured using the load cell of a TA-XT2 texture analyzer. Cylindrical carrots and ham samples were used as representative foods. The system is capable of simulating the in vivo stomach in terms of providing a wide range of continuous and periodic forces comparable to those measured in vivo. The modified power exponential function of the form y(t)= 1 - (1 -e(-kt))(beta), where y(t) is the mass retention ratio at time t, provided a reasonable description for the disintegration performance of tested foods. The mass retention curve can be either a sigmoidal decay with an initial delay or an exponential decay, which are decided largely by the hardness of the foods during digestion and the extent of physical force acting on the foods. A good match was observed between the kinetics of food disintegration and in vivo stomach emptying.

Control over multiscale mixing in broadband-forced turbulence

NARCIS (Netherlands)

Kuczaj, Arkadiusz K.; Geurts, Bernardus J.

2008-01-01

The effects of explicit flow modulation on the dispersion of a passive scalar field are studied. Broadband forcing is applied to homogeneous isotropic turbulence to modulate the energy cascading and alter the kinetic energy spectrum. Consequently, a manipulation of turbulent flow can be achieved

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,

Kinetic constrained optimization of the golf swing hub path.

Science.gov (United States)

Nesbit, Steven M; McGinnis, Ryan S

2014-12-01

This study details an optimization of the golf swing, where the hand path and club angular trajectories are manipulated. The optimization goal was to maximize club head velocity at impact within the interaction kinetic limitations (force, torque, work, and power) of the golfer as determined through the analysis of a typical swing using a two-dimensional dynamic model. The study was applied to four subjects with diverse swing capabilities and styles. It was determined that it is possible for all subjects to increase their club head velocity at impact within their respective kinetic limitations through combined modifications to their respective hand path and club angular trajectories. The manner of the modifications, the degree of velocity improvement, the amount of kinetic reduction, and the associated kinetic limitation quantities were subject dependent. By artificially minimizing selected kinetic inputs within the optimization algorithm, it was possible to identify swing trajectory characteristics that indicated relative kinetic weaknesses of a subject. Practical implications are offered based upon the findings of the study. Key PointsThe hand path trajectory is an important characteristic of the golf swing and greatly affects club head velocity and golfer/club energy transfer.It is possible to increase the energy transfer from the golfer to the club by modifying the hand path and swing trajectories without increasing the kinetic output demands on the golfer.It is possible to identify relative kinetic output strengths and weakness of a golfer through assessment of the hand path and swing trajectories.Increasing any one of the kinetic outputs of the golfer can potentially increase the club head velocity at impact.The hand path trajectory has important influences over the club swing trajectory.

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.

Factors that influence ground reaction force profiles during counter movement jumping.

Science.gov (United States)

Eagles, Alexander N; Sayers, Mark G; Lovell, Dale I

2017-05-01

The purpose of this study was to examine how hip, knee and ankle kinetics and kinematics influence effective impulse production during countermovement jumps. Eighteen semi-professional soccer players (22.8±2.2 years) volunteered to participate in the study. Participants completed three maximal countermovement jumps on two force platforms (1000 Hz) that were linked to a nine camera infrared motion capture system (500 Hz). Kinetic and kinematic data revealed jumpers who fail to achieve uniform ground reaction force curves that result in optimal impulse production during their jump always display hip adduction and or hip internal rotation during the concentric phase of the countermovement jump. The variation of hip adduction and or internal rotation likely represents failed joint transition during the concentric phase of the countermovement jump and appears to account for a non-uniform force trace seen in these jumpers. The findings suggest rehabilitation and conditioning exercises for injury prevention and performance may benefit from targeting frontal and transverse plane movement.

Estimation of foot joint kinetics in three and four segment foot models using an existing proportionality scheme: Application in paediatric barefoot walking.

Science.gov (United States)

Deschamps, Kevin; Eerdekens, Maarten; Desmet, Dirk; Matricali, Giovanni Arnoldo; Wuite, Sander; Staes, Filip

2017-08-16

Recent studies which estimated foot segment kinetic patterns were found to have inconclusive data on one hand, and did not dissociate the kinetics of the chopart and lisfranc joint. The current study aimed therefore at reproducing independent, recently published three-segment foot kinetic data (Study 1) and in a second stage expand the estimation towards a four-segment model (Study 2). Concerning the reproducibility study, two recently published three segment foot models (Bruening et al., 2014; Saraswat et al., 2014) were reproduced and kinetic parameters were incorporated in order to calculate joint moments and powers of paediatric cohorts during gait. Ground reaction forces were measured with an integrated force/pressure plate measurement set-up and a recently published proportionality scheme was applied to determine subarea total ground reaction forces. Regarding Study 2, moments and powers were estimated with respect to the Instituto Ortopedico Rizzoli four-segment model. The proportionality scheme was expanded in this study and the impact of joint centre location on kinetic data was evaluated. Findings related to Study 1 showed in general good agreement with the kinetic data published by Bruening et al. (2014). Contrarily, the peak ankle, midfoot and hallux powers published by Saraswat et al. (2014) are disputed. Findings of Study 2 revealed that the chopart joint encompasses both power absorption and generation, whereas the Lisfranc joint mainly contributes to power generation. The results highlights the necessity for further studies in the field of foot kinetic models and provides a first estimation of the kinetic behaviour of the Lisfranc joint. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Local Order in the Unfolded State: Conformational Biases and Nearest Neighbor Interactions

Directory of Open Access Journals (Sweden)

Siobhan Toal

2014-07-01

Full Text Available The discovery of Intrinsically Disordered Proteins, which contain significant levels of disorder yet perform complex biologically functions, as well as unwanted aggregation, has motivated numerous experimental and theoretical studies aimed at describing residue-level conformational ensembles. Multiple lines of evidence gathered over the last 15 years strongly suggest that amino acids residues display unique and restricted conformational preferences in the unfolded state of peptides and proteins, contrary to one of the basic assumptions of the canonical random coil model. To fully understand residue level order/disorder, however, one has to gain a quantitative, experimentally based picture of conformational distributions and to determine the physical basis underlying residue-level conformational biases. Here, we review the experimental, computational and bioinformatic evidence for conformational preferences of amino acid residues in (mostly short peptides that can be utilized as suitable model systems for unfolded states of peptides and proteins. In this context particular attention is paid to the alleged high polyproline II preference of alanine. We discuss how these conformational propensities may be modulated by peptide solvent interactions and so called nearest-neighbor interactions. The relevance of conformational propensities for the protein folding problem and the understanding of IDPs is briefly discussed.

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.

Kinetics of diuron and amitrole adsorption from aqueous solution on activated carbons.

Science.gov (United States)

Fontecha-Cámara, M A; López-Ramón, M V; Pastrana-Martínez, L M; Moreno-Castilla, C

2008-08-15

A study was conducted on the adsorption kinetics of diuron and amitrole from aqueous solutions on activated carbons of different particle sizes and on an activated carbon fiber. Different kinetic models were applied to the experimental results obtained. A pseudo-second-order rate equation fitted the adsorption kinetics data better than a pseudo-first-order rate equation. Amitrole showed faster adsorption kinetics compared with diuron because of the smaller size of the former herbicide, despite its lower driving force for adsorption. Both reaction rate constants increased when the particle size decreased. The activated carbon fiber and the activated carbon of smallest particle size (0.03 mm) showed similar adsorption kinetics. The intraparticle diffusion rate constant increased with higher initial concentration of herbicides in solution and with lower particle size of the adsorbent. This is because the rise in initial concentration increased the amount adsorbed at equilibrium, and the reduction in particle size increased the number of collisions between adsorbate and adsorbent particles. Demineralization of the activated carbon with particle size of 0.5mm had practically no effect on the adsorption kinetics.

Individual differences in the forced swimming test and neurochemical kinetics in the rat brain.

Science.gov (United States)

Sequeira-Cordero, Andrey; Mora-Gallegos, Andrea; Cuenca-Berger, Patricia; Fornaguera-Trías, Jaime

2014-04-10

Individual differences in the forced swimming test (FST) could be associated with differential temporal dynamics of gene expression and neurotransmitter activity. We tested juvenile male rats in the FST and classified the animals into those with low and high immobility according to the amount of immobility time recorded in FST. These groups and a control group which did not undergo the FST were sacrificed either 1, 6 or 24 h after the test. We analyzed the expression of the CRF, CRFR1, BDNF and TrkB in the prefrontal cortex, hippocampus and nucleus accumbens as well as norepinephrine, dopamine, serotonin, glutamate, GABA and glutamine in the hippocampus and nucleus accumbens. Animals with low immobility showed significant reductions of BDNF expression across time points in both the prefrontal cortex and the nucleus accumbens when compared with non-swim control. Moreover, rats with high immobility only showed a significant decrease of BDNF expression in the prefrontal cortex 6h after the FST. Regarding neurotransmitters, only accumbal dopamine turnover and hippocampal glutamate content showed an effect of individual differences (i.e. animals with low and high immobility), whereas nearly all parameters showed significant differences across time points. Correlational analyses suggest that immobility in the FST, probably reflecting despair, is related to prefrontal cortical BDNF and to the kinetics observed in several other neurochemical parameters. Taken together, our results suggest that individual differences observed in depression-like behavior can be associated not only with changes in the concentrations of key neurochemical factors but also with differential time courses of such factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Force spectroscopy studies on protein-ligand interactions: a single protein mechanics perspective.

Science.gov (United States)

Hu, Xiaotang; Li, Hongbin

2014-10-01

Protein-ligand interactions are ubiquitous and play important roles in almost every biological process. The direct elucidation of the thermodynamic, structural and functional consequences of protein-ligand interactions is thus of critical importance to decipher the mechanism underlying these biological processes. A toolbox containing a variety of powerful techniques has been developed to quantitatively study protein-ligand interactions in vitro as well as in living systems. The development of atomic force microscopy-based single molecule force spectroscopy techniques has expanded this toolbox and made it possible to directly probe the mechanical consequence of ligand binding on proteins. Many recent experiments have revealed how ligand binding affects the mechanical stability and mechanical unfolding dynamics of proteins, and provided mechanistic understanding on these effects. The enhancement effect of mechanical stability by ligand binding has been used to help tune the mechanical stability of proteins in a rational manner and develop novel functional binding assays for protein-ligand interactions. Single molecule force spectroscopy studies have started to shed new lights on the structural and functional consequence of ligand binding on proteins that bear force under their biological settings. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Kinetic energy definition in velocity Verlet integration for accurate pressure evaluation

Science.gov (United States)

Jung, Jaewoon; Kobayashi, Chigusa; Sugita, Yuji

2018-04-01

In molecular dynamics (MD) simulations, a proper definition of kinetic energy is essential for controlling pressure as well as temperature in the isothermal-isobaric condition. The virial theorem provides an equation that connects the average kinetic energy with the product of particle coordinate and force. In this paper, we show that the theorem is satisfied in MD simulations with a larger time step and holonomic constraints of bonds, only when a proper definition of kinetic energy is used. We provide a novel definition of kinetic energy, which is calculated from velocities at the half-time steps (t - Δt/2 and t + Δt/2) in the velocity Verlet integration method. MD simulations of a 1,2-dispalmitoyl-sn-phosphatidylcholine (DPPC) lipid bilayer and a water box using the kinetic energy definition could reproduce the physical properties in the isothermal-isobaric condition properly. We also develop a multiple time step (MTS) integration scheme with the kinetic energy definition. MD simulations with the MTS integration for the DPPC and water box systems provided the same quantities as the velocity Verlet integration method, even when the thermostat and barostat are updated less frequently.

Kinetic energy definition in velocity Verlet integration for accurate pressure evaluation.

Science.gov (United States)

Jung, Jaewoon; Kobayashi, Chigusa; Sugita, Yuji

2018-04-28

In molecular dynamics (MD) simulations, a proper definition of kinetic energy is essential for controlling pressure as well as temperature in the isothermal-isobaric condition. The virial theorem provides an equation that connects the average kinetic energy with the product of particle coordinate and force. In this paper, we show that the theorem is satisfied in MD simulations with a larger time step and holonomic constraints of bonds, only when a proper definition of kinetic energy is used. We provide a novel definition of kinetic energy, which is calculated from velocities at the half-time steps (t - Δt/2 and t + Δt/2) in the velocity Verlet integration method. MD simulations of a 1,2-dispalmitoyl-sn-phosphatidylcholine (DPPC) lipid bilayer and a water box using the kinetic energy definition could reproduce the physical properties in the isothermal-isobaric condition properly. We also develop a multiple time step (MTS) integration scheme with the kinetic energy definition. MD simulations with the MTS integration for the DPPC and water box systems provided the same quantities as the velocity Verlet integration method, even when the thermostat and barostat are updated less frequently.

The Kinetic Chain Revisited: New Concepts on Throwing Mechanics and Injury.

Science.gov (United States)

Chu, Samuel K; Jayabalan, Prakash; Kibler, W Ben; Press, Joel

2016-03-01

The overhead throwing motion is a complex activity that is achieved through activation of the kinetic chain. The kinetic chain refers to the linkage of multiple segments of the body that allows for transfer of forces and motion. The lower extremities and core provide a base of support, generating energy that is transferred eventually through the throwing arm and hand, resulting in release of the ball. The kinetic chain requires optimal anatomy, physiology, and mechanics and is involved in all 6 phases of overhead throwing: windup, stride, arm cocking, acceleration, deceleration, and follow-through. Breaks or deficits in the kinetic chain can lead to injury or decreased performance. Through an understanding of the mechanics and pathomechanics seen in each phase of throwing, the clinician can better evaluate and screen for potential kinetic chain deficits in the overhead throwing athlete. The purpose of this article is to review the biomechanics of the overhead throwing motion, the role of the kinetic chain in throwing, and the clinical evaluation and management of abnormal throwing mechanics and related injuries. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Processes of aggression described by kinetic method

Science.gov (United States)

Aristov, V. V.; Ilyin, O.

2014-12-01

In the last decades many investigations have been devoted to theoretical models in new areas concerning description of different biological, sociological and historical processes. In the present paper we suggest a model of the Nazi Germany invasion of Poland, France and USSR based on the kinetic theory. We model this process with the Cauchy boundary problem for the two-element kinetic equations with spatial initial conditions. The solution of the problem is given in the form of traveling wave. The propagation velocity of a frontline depends on the quotient between initial forces concentrations. Moreover it is obtained that the general solution of the model can be expressed in terms of quadratures and elementary functions. Finally it is shown that the frontline velocities are complied with the historical data.

Processes of aggression described by kinetic method

International Nuclear Information System (INIS)

Aristov, V. V.; Ilyin, O.

2014-01-01

In the last decades many investigations have been devoted to theoretical models in new areas concerning description of different biological, sociological and historical processes. In the present paper we suggest a model of the Nazi Germany invasion of Poland, France and USSR based on the kinetic theory. We model this process with the Cauchy boundary problem for the two-element kinetic equations with spatial initial conditions. The solution of the problem is given in the form of traveling wave. The propagation velocity of a frontline depends on the quotient between initial forces concentrations. Moreover it is obtained that the general solution of the model can be expressed in terms of quadratures and elementary functions. Finally it is shown that the frontline velocities are complied with the historical data

Processes of aggression described by kinetic method

Energy Technology Data Exchange (ETDEWEB)

Aristov, V. V.; Ilyin, O. [Dorodnicyn Computing Centre of Russian Academy of Sciences, Vavilova str. 40, Moscow, 119333 (Russian Federation)

2014-12-09

In the last decades many investigations have been devoted to theoretical models in new areas concerning description of different biological, sociological and historical processes. In the present paper we suggest a model of the Nazi Germany invasion of Poland, France and USSR based on the kinetic theory. We model this process with the Cauchy boundary problem for the two-element kinetic equations with spatial initial conditions. The solution of the problem is given in the form of traveling wave. The propagation velocity of a frontline depends on the quotient between initial forces concentrations. Moreover it is obtained that the general solution of the model can be expressed in terms of quadratures and elementary functions. Finally it is shown that the frontline velocities are complied with the historical data.

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.

A thermostatted kinetic theory model for event-driven pedestrian dynamics

Science.gov (United States)

Bianca, Carlo; Mogno, Caterina

2018-06-01

This paper is devoted to the modeling of the pedestrian dynamics by means of the thermostatted kinetic theory. Specifically the microscopic interactions among pedestrians and an external force field are modeled for simulating the evacuation of pedestrians from a metro station. The fundamentals of the stochastic game theory and the thermostatted kinetic theory are coupled for the derivation of a specific mathematical model which depicts the time evolution of the distribution of pedestrians at different exits of a metro station. The perturbation theory is employed in order to establish the stability analysis of the nonequilibrium stationary states in the case of a metro station consisting of two exits. A general sensitivity analysis on the initial conditions, the magnitude of the external force field and the number of exits is presented by means of numerical simulations which, in particular, show how the asymptotic distribution and the convergence time are affected by the presence of an external force field. The results show how, in evacuation conditions, the interaction dynamics among pedestrians can be negligible with respect to the external force. The important role of the thermostat term in allowing the reaching of the nonequilibrium stationary state is stressed out. Research perspectives are underlined at the end of paper, in particular for what concerns the derivation of frameworks that take into account the definition of local external actions and the introduction of the space and velocity dynamics.

Monitoring the kinetics of the pH-driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance.

Science.gov (United States)

Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; McGinn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E P; Pentelute, B L; Collier, R John; Fisher, Mark T

2013-09-17

Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å β barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH-dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor, from the endosome to the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance and biolayer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from 7.5 to 5.0, mirroring acidification of the endosome. Once it had undergone the transition, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto electron microscopy grids, where PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early (pH 5.5) or late (pH 5.0) endosomal pH conditions. Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and the soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions.

Monitoring the kinetics of the pH driven transition of the anthrax toxin prepore to the pore by biolayer interferometry and surface plasmon resonance

Science.gov (United States)

Naik, Subhashchandra; Brock, Susan; Akkaladevi, Narahari; Tally, Jon; Mcginn-Straub, Wesley; Zhang, Na; Gao, Phillip; Gogol, E. P.; Pentelute, B. L.; Collier, R. John; Fisher, Mark T.

2013-01-01

Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and refolds during endosome acidification to generate an extended 100 Å beta barrel pore that inserts into the endosomal membrane. The PA pore facilitates the pH dependent unfolding and translocation of bound toxin enzymic components, lethal factor (LF) and/or edema factor (EF), from the endosome into the cytoplasm. We constructed immobilized complexes of the prepore with the PA-binding domain of LF (LFN) to monitor the real-time prepore to pore kinetic transition using surface plasmon resonance (SPR) and bio-layer interferometry (BLI). The kinetics of this transition increased as the solution pH was decreased from pH 7.5 to pH 5.0, mirroring acidification of the endosome. Once transitioned, the LFN-PA pore complex was removed from the BLI biosensor tip and deposited onto EM grids, where the PA pore formation was confirmed by negative stain electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the immobilized PA prepore, the transition to the pore state was observed only after the pH was lowered to early or late endosomal pH conditions (5.5 to 5.0 respectively). Once the pore formed, the soluble receptor readily dissociated from the PA pore. Separate binding experiments with immobilized PA pores and soluble receptor indicate that the receptor has a weakened propensity to bind to the transitioned pore. This immobilized anthrax toxin platform can be used to identify or validate potential antimicrobial lead compounds capable of regulating and/or inhibiting anthrax toxin complex formation or pore transitions. PMID:23964683

Development of a Wind Directly Forced Heat Pump and Its Efficiency Analysis

OpenAIRE

Jwo, Ching-Song; Chien, Zi-Jie; Chen, Yen-Lin; Chien, Chao-Chun

2013-01-01

The requirements of providing electric energy through the wind-forced generator to the heat pump for water cooling and hot water heating grow significantly by now. This study proposes a new technique to directly adopt the wind force to drive heat pump systems, which can effectively reduce the energy conversion losses during the processes of wind force energy converting to electric energy and electric energy converting to kinetic energy. The operation of heat pump system transfers between chil...

Stretched versus compressed exponential kinetics in α-helix folding

International Nuclear Information System (INIS)

Hamm, Peter; Helbing, Jan; Bredenbeck, Jens

2006-01-01

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

Optimization of the Kinetic Activation-Relaxation Technique, an off-lattice and self-learning kinetic Monte-Carlo method

International Nuclear Information System (INIS)

Joly, Jean-François; Béland, Laurent Karim; Brommer, Peter; Mousseau, Normand; El-Mellouhi, Fedwa

2012-01-01

We present two major optimizations for the kinetic Activation-Relaxation Technique (k-ART), an off-lattice self-learning kinetic Monte Carlo (KMC) algorithm with on-the-fly event search THAT has been successfully applied to study a number of semiconducting and metallic systems. K-ART is parallelized in a non-trivial way: A master process uses several worker processes to perform independent event searches for possible events, while all bookkeeping and the actual simulation is performed by the master process. Depending on the complexity of the system studied, the parallelization scales well for tens to more than one hundred processes. For dealing with large systems, we present a near order 1 implementation. Techniques such as Verlet lists, cell decomposition and partial force calculations are implemented, and the CPU time per time step scales sublinearly with the number of particles, providing an efficient use of computational resources.

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.

Atomic force microscopy and force spectroscopy on the assessment of protein folding and functionality.

Science.gov (United States)

Carvalho, Filomena A; Martins, Ivo C; Santos, Nuno C

2013-03-01

Atomic force microscopy (AFM) applied to biological systems can, besides generating high-quality and well-resolved images, be employed to study protein folding via AFM-based force spectroscopy. This approach allowed remarkable advances in the measurement of inter- and intramolecular interaction forces with piconewton resolution. The detection of specific interaction forces between molecules based on the AFM sensitivity and the manipulation of individual molecules greatly advanced the understanding of intra-protein and protein-ligand interactions. Apart from the academic interest in the resolution of basic scientific questions, this technique has also key importance on the clarification of several biological questions of immediate biomedical relevance. Force spectroscopy is an especially appropriate technique for "mechanical proteins" that can provide crucial information on single protein molecules and/or domains. Importantly, it also has the potential of combining in a single experiment spatial and kinetic measurements. Here, the main principles of this methodology are described, after which the ability to measure interactions at the single-molecule level is discussed, in the context of relevant protein-folding examples. We intend to demonstrate the potential of AFM-based force spectroscopy in the study of protein folding, especially since this technique is able to circumvent some of the difficulties typically encountered in classical thermal/chemical denaturation studies. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

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

Charge-Transfer Complexes Studied by Dynamic Force Spectroscopy

Directory of Open Access Journals (Sweden)

Jurriaan Huskens

2013-03-01

Full Text Available In this paper, the strength and kinetics of two charge-transfer complexes, naphthol-methylviologen and pyrene-methylviologen, are studied using dynamic force spectroscopy. The dissociation rates indicate an enhanced stability of the pyrene-methylviologen complex, which agrees with its higher thermodynamic stability compared to naphthol-methylviologen complex.

Kinetic quantification of plyometric exercise intensity.

Science.gov (United States)

Ebben, William P; Fauth, McKenzie L; Garceau, Luke R; Petushek, Erich J

2011-12-01

Ebben, WP, Fauth, ML, Garceau, LR, and Petushek, EJ. Kinetic quantification of plyometric exercise intensity. J Strength Cond Res 25(12): 3288-3298, 2011-Quantification of plyometric exercise intensity is necessary to understand the characteristics of these exercises and the proper progression of this mode of exercise. The purpose of this study was to assess the kinetic characteristics of a variety of plyometric exercises. This study also sought to assess gender differences in these variables. Twenty-six men and 23 women with previous experience in performing plyometric training served as subjects. The subjects performed a variety of plyometric exercises including line hops, 15.24-cm cone hops, squat jumps, tuck jumps, countermovement jumps (CMJs), loaded CMJs equal to 30% of 1 repetition maximum squat, depth jumps normalized to the subject's jump height (JH), and single leg jumps. All plyometric exercises were assessed with a force platform. Outcome variables associated with the takeoff, airborne, and landing phase of each plyometric exercise were evaluated. These variables included the peak vertical ground reaction force (GRF) during takeoff, the time to takeoff, flight time, JH, peak power, landing rate of force development, and peak vertical GRF during landing. A 2-way mixed analysis of variance with repeated measures for plyometric exercise type demonstrated main effects for exercise type and all outcome variables (p ≤ 0.05) and for the interaction between gender and peak vertical GRF during takeoff (p ≤ 0.05). Bonferroni-adjusted pairwise comparisons identified a number of differences between the plyometric exercises for the outcome variables assessed (p ≤ 0.05). These findings can be used to guide the progression of plyometric training by incorporating exercises of increasing intensity over the course of a program.

Unified Model of Dynamic Forced Barrier Crossing in Single Molecules

Energy Technology Data Exchange (ETDEWEB)

Friddle, R W

2007-06-21

Thermally activated barrier crossing in the presence of an increasing load can reveal kinetic rate constants and energy barrier parameters when repeated over a range of loading rates. Here we derive a model of the mean escape force for all relevant loading rates--the complete force spectrum. Two well-known approximations emerge as limiting cases; one of which confirms predictions that single-barrier spectra should converge to a phenomenological description in the slow loading limit.

Simultaneous measurement of static and kinetic friction of ZnO nanowires in situ with a scanning electron microscope.

Science.gov (United States)

Polyakov, Boris; Dorogin, Leonid M; Vlassov, Sergei; Kink, Ilmar; Romanov, Alexey E; Lohmus, Rynno

2012-11-01

A novel method for in situ measurement of the static and kinetic friction is developed and demonstrated for zinc oxide nanowires (NWs) on oxidised silicon wafers. The experiments are performed inside a scanning electron microscope (SEM) equipped with a nanomanipulator with an atomic force microscope tip as a probe. NWs are pushed by the tip from one end until complete displacement is achieved, while NW bending is monitored by the SEM. The elastic bending profile of a NW during the manipulation process is used to calculate the static and kinetic friction forces. Copyright © 2012 Elsevier Ltd. All rights reserved.

Transversal light forces in semiconductors

CERN Document Server

Lindberg, M

2003-01-01

The transversal light force is a well established effect in atomic and molecular systems that are exposed to spatially inhomogeneous light fields. In this paper it is shown theoretically that in an excited semiconductor, containing an electron-hole plasma or excitons, a similar light force exists, if the semiconductor is exposed to an ultrashort spatially inhomogeneous light field. The analysis is based on the equations of motion for the Wigner distribution functions of charge carrier populations and interband polarizations. The results show that, while the light force on the electron-hole plasma or the excitons does exist, its effects on the kinetic behaviour of the electron-hole plasma or the excitons are different compared to the situation in an atomic or molecular system. A detailed analysis presented here traces this difference back to the principal differences between atoms and molecules on the one hand and electron-hole plasmas or excitons on the other hand.

Massively Parallel Single-Molecule Manipulation Using Centrifugal Force

Science.gov (United States)

Wong, Wesley; Halvorsen, Ken

2011-03-01

Precise manipulation of single molecules has led to remarkable insights in physics, chemistry, biology, and medicine. However, two issues that have impeded the widespread adoption of these techniques are equipment cost and the laborious nature of making measurements one molecule at a time. To meet these challenges, we have developed an approach that enables massively parallel single- molecule force measurements using centrifugal force. This approach is realized in the centrifuge force microscope, an instrument in which objects in an orbiting sample are subjected to a calibration-free, macroscopically uniform force- field while their micro-to-nanoscopic motions are observed. We demonstrate high- throughput single-molecule force spectroscopy with this technique by performing thousands of rupture experiments in parallel, characterizing force-dependent unbinding kinetics of an antibody-antigen pair in minutes rather than days. Currently, we are taking steps to integrate high-resolution detection, fluorescence, temperature control and a greater dynamic range in force. With significant benefits in efficiency, cost, simplicity, and versatility, single-molecule centrifugation has the potential to expand single-molecule experimentation to a wider range of researchers and experimental systems.

Kinematic and kinetic characteristics of vertical jump: comparison between soccer and basketball players

Directory of Open Access Journals (Sweden)

Matheus Machado Gomes

2009-01-01

Full Text Available http://dx.doi.org/10.5007/1980-0037.2009v11n4p392   The aim of this study was to compare jump height and kinetic and kinematic com-ponents of countermovement vertical jumps between soccer and basketball players performed in two different arm swing conditions: with arm swing (WAS and without arm swing (NAS. Nine basketball players (21.2 ± 2.9 years; 101.64 ± 14.58 kg; 1.95 ± 0.06 m and nine soccer players (18.2 ± 0.7 years; 77.4 ± 7.58 kg; 1.81 ± 0.07 m performed 12 maximal countermo-vement vertical jumps, including 6 WAS jumps and 6 NAS jumps, on a force platform that recorded the ground reaction force (GRF. The vertical component of the GRF was used to estimate jump height and to calculate the kinematic (duration of eccentric phase, duration of concentric phase, and maximal downward displacement of center of mass and kinetic variables (mean power during the eccentric phase, mean power during the concentric, peak power, and peak force. The results showed no differences in jump height or in kinematic or kinetic variables between basketball and soccer players. In addition, the results showed that the participants of the two groups jumped higher in the WAS condition (0.41 m than in the NAS condition (0.36 m because of a higher peak power (WAS=276.8 W/kg0.67 and NAS=241.3 W/kg0.67 and a longer concentric phase duration (WAS=0.20 s/m0.5 and NAS=0.19 s/m0.5 during WAS jump. These results indicate that the basketball and soccer players studied here showed similar performance and the same kinematic and kinetic pattern in maximal vertical jumps and were comparably affected by the use of arm swing.

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)

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.

Kinetics of badminton lunges in four directions.

Science.gov (United States)

Hong, Youlian; Wang, Shao Jun; Lam, Wing Kai; Cheung, Jason Tak Man

2014-02-01

The lunge is the most fundamental skill in badminton competitions. Fifteen university-level male badminton players performed lunge maneuvers in four directions, namely, right-forward, left-forward, right-backward, and left-backward, while wearing two different brands of badminton shoes. The test compared the kinetics of badminton shoes in performing typical lunge maneuvers. A force plate and an insole measurement system measured the ground reaction forces and plantar pressures. These measurements were compared across all lunge maneuvers. The left-forward lunge generated significantly higher first vertical impact force (2.34 ± 0.52 BW) than that of the right-backward (2.06 ± 0.60 BW) and left-backward lunges (1.78 ± 0.44 BW); higher second vertical impact force (2.44 ± 0.51 BW) than that of the left-backward lunge (2.07 ± 0.38 BW); and higher maximum anterior-posterior shear force (1.48 ± 0.36 BW) than that of the left-backward lunge (1.18 ± 0.38 BW). Compared with other lunge directions, the left-forward lunge showed higher mean maximum vertical impact anterior-posterior shear forces and their respective maximum loading rates, and the plantar pressure at the total foot and heel regions. Therefore, the left-forward lunge is a critical maneuver for badminton biomechanics and related footwear research because of the high loading magnitude generated during heel impact.

Isometric Mid-Thigh Pull Performance Is Associated With Athletic Performance And Sprinting Kinetics In Division I Men And Women's Basketball Players.

Science.gov (United States)

Townsend, Jeremy R; Bender, David; Vantrease, William; Hudy, John; Huet, Kevin; Williamson, Cassie; Bechke, Emily; Serafini, Paul; Mangine, Gerald T

2017-07-31

To examine the relationships between isometric mid-thigh pull (IMTP) force, athletic performance measures, and sprint kinetics in Division I men's and women's basketball players. Twenty-three (male = 8, female = 15) division 1 basketball players completed a maximal 20-m sprint trial while tethered to a device which provided kinetic feedback (peak and average sprinting power, velocity and force). Additionally, one repetition-maximal (1RM) front squat, 1RM hang clean, vertical jump height, and agility (pro-agility and lane agility) tests were performed. Rate of force development (RFD) at 50ms, 100ms, 150ms, 200ms and 250ms of IMTP, as well as peak force (PF) were also collected. Pearson product-moment correlation analysis was used to examine the relationships between these measures. Significant (p training.

Atom-Pair Kinetics with Strong Electric-Dipole Interactions.

Science.gov (United States)

Thaicharoen, N; Gonçalves, L F; Raithel, G

2016-05-27

Rydberg-atom ensembles are switched from a weakly to a strongly interacting regime via adiabatic transformation of the atoms from an approximately nonpolar into a highly dipolar quantum state. The resultant electric dipole-dipole forces are probed using a device akin to a field ion microscope. Ion imaging and pair-correlation analysis reveal the kinetics of the interacting atoms. Dumbbell-shaped pair-correlation images demonstrate the anisotropy of the binary dipolar force. The dipolar C_{3} coefficient, derived from the time dependence of the images, agrees with the value calculated from the permanent electric-dipole moment of the atoms. The results indicate many-body dynamics akin to disorder-induced heating in strongly coupled particle systems.

Effect of knee and trunk angle on kinetic variables during the isometric midthigh pull: test-retest reliability.

Science.gov (United States)

Comfort, Paul; Jones, Paul A; McMahon, John J; Newton, Robert

2015-01-01

The isometric midthigh pull (IMTP) has been used to monitor changes in force, maximum rate of force development (mRFD), and impulse, with performance in this task being associated with performance in athletic tasks. Numerous postures have been adopted in the literature, which may affect the kinetic variables during the task; therefore, the aim of this investigation was to determine whether different knee-joint angles (120°, 130°, 140°, and 150°) and hip-joint angles (125° and 145°), including the subjects preferred posture, affect force, mRFD, and impulse during the IMTP. Intraclass correlation coefficients demonstrated high within-session reliability (r ≥ .870, P kinetic variables determined in all postures, excluding impulse measures during the 130° knee-flexion, 125° hip-flexion posture, which showed a low to moderate reliability (r = .666-.739, P .819, P kinetic variables. There were no significant differences in peak force (P > .05, Cohen d = 0.037, power = .408), mRFD (P > .05, Cohen d = 0.037, power = .409), or impulse at 100 ms (P > .05, Cohen d = 0.056, power = .609), 200 ms (P > .05, Cohen d = 0.057, power = .624), or 300 ms (P > .05, Cohen d = 0.061, power = .656) across postures. Smallest detectable differences demonstrated that changes in performance of >1.3% in peak isometric force, >10.3% in mRFD, >5.3% in impulse at 100 ms, >4.4% in impulse at 200 ms, and >7.1% in impulse at 300 ms should be considered meaningful, irrespective of posture.

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.

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.

Importance of the ion-pair interactions in the OPEP coarse-grained force field: parametrization and validation.

Science.gov (United States)

Sterpone, Fabio; Nguyen, Phuong H; Kalimeri, Maria; Derreumaux, Philippe

2013-10-08

We have derived new effective interactions that improve the description of ion-pairs in the OPEP coarse-grained force field without introducing explicit electrostatic terms. The iterative Boltzmann inversion method was used to extract these potentials from all atom simulations by targeting the radial distribution function of the distance between the center of mass of the side-chains. The new potentials have been tested on several systems that differ in structural properties, thermodynamic stabilities and number of ion-pairs. Our modeling, by refining the packing of the charged amino-acids, impacts the stability of secondary structure motifs and the population of intermediate states during temperature folding/unfolding; it also improves the aggregation propensity of peptides. The new version of the OPEP force field has the potentiality to describe more realistically a large spectrum of situations where salt-bridges are key interactions.

Kinetic Dissection of the Pre-existing Conformational Equilibrium in the Trypsin Fold*

Science.gov (United States)

Vogt, Austin D.; Chakraborty, Pradipta; Di Cera, Enrico

2015-01-01

Structural biology has recently documented the conformational plasticity of the trypsin fold for both the protease and zymogen in terms of a pre-existing equilibrium between closed (E*) and open (E) forms of the active site region. How such plasticity is manifested in solution and affects ligand recognition by the protease and zymogen is poorly understood in quantitative terms. Here we dissect the E*-E equilibrium with stopped-flow kinetics in the presence of excess ligand or macromolecule. Using the clotting protease thrombin and its zymogen precursor prethrombin-2 as relevant models we resolve the relative distribution of the E* and E forms and the underlying kinetic rates for their interconversion. In the case of thrombin, the E* and E forms are distributed in a 1:4 ratio and interconvert on a time scale of 45 ms. In the case of prethrombin-2, the equilibrium is shifted strongly (10:1 ratio) in favor of the closed E* form and unfolds over a faster time scale of 4.5 ms. The distribution of E* and E forms observed for thrombin and prethrombin-2 indicates that zymogen activation is linked to a significant shift in the pre-existing equilibrium between closed and open conformations that facilitates ligand binding to the active site. These findings broaden our mechanistic understanding of how conformational transitions control ligand recognition by thrombin and its zymogen precursor prethrombin-2 and have direct relevance to other members of the trypsin fold. PMID:26216877

Elastin-like Polypeptide Linkers for Single-Molecule Force Spectroscopy.

Science.gov (United States)

Ott, Wolfgang; Jobst, Markus A; Bauer, Magnus S; Durner, Ellis; Milles, Lukas F; Nash, Michael A; Gaub, Hermann E

2017-06-27

Single-molecule force spectroscopy (SMFS) is by now well established as a standard technique in biophysics and mechanobiology. In recent years, the technique has benefitted greatly from new approaches to bioconjugation of proteins to surfaces. Indeed, optimized immobilization strategies for biomolecules and refined purification schemes are being steadily adapted and improved, which in turn has enhanced data quality. In many previously reported SMFS studies, poly(ethylene glycol) (PEG) was used to anchor molecules of interest to surfaces and/or cantilever tips. The limitation, however, is that PEG exhibits a well-known trans-trans-gauche to all-trans transition, which results in marked deviation from standard polymer elasticity models such as the worm-like chain, particularly at elevated forces. As a result, the assignment of unfolding events to protein domains based on their corresponding amino acid chain lengths is significantly obscured. Here, we provide a solution to this problem by implementing unstructured elastin-like polypeptides as linkers to replace PEG. We investigate the suitability of tailored elastin-like polypeptides linkers and perform direct comparisons to PEG, focusing on attributes that are critical for single-molecule force experiments such as linker length, monodispersity, and bioorthogonal conjugation tags. Our results demonstrate that by avoiding the ambiguous elastic response of mixed PEG/peptide systems and instead building the molecular mechanical systems with only a single bond type with uniform elastic properties, we improve data quality and facilitate data analysis and interpretation in force spectroscopy experiments. The use of all-peptide linkers allows alternative approaches for precisely defining elastic properties of proteins linked to surfaces.

Kinetic Risk Factors of Running-Related Injuries in Female Recreational Runners.

Science.gov (United States)

Napier, Christopher; MacLean, Christopher L; Maurer, Jessica; Taunton, Jack E; Hunt, Michael A

2018-05-30

Our objective was to prospectively investigate the association of kinetic variables with running-related injury (RRI) risk. Seventy-four healthy female recreational runners ran on an instrumented treadmill while 3D kinetic and kinematic data were collected. Kinetic outcomes were vertical impact transient, average vertical loading rate, instantaneous vertical loading rate, active peak, vertical impulse, and peak braking force (PBF). Participants followed a 15-week half-marathon training program. Exposure time (hours of running) was calculated from start of program until onset of injury, loss to follow-up, or end of program. After converting kinetic variables from continuous to ordinal variables based on tertiles, Cox proportional hazard models with competing risks were fit for each variable independently, before analysis in a forward stepwise multivariable model. Sixty-five participants were included in the final analysis, with a 33.8% injury rate. PBF was the only kinetic variable that was a significant predictor of RRI. Runners in the highest tertile (PBF recreational runners and should be considered as a target for gait retraining interventions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Separation kinetics of an oil-in-water emulsion under enhanced gravity

NARCIS (Netherlands)

Krebs, T.; Schroën, C.G.P.H.; Boom, R.M.

2012-01-01

The breakup of crude oil emulsions to produce clean oil and water phases is an important task in crude oil processing. We have investigated the demulsification kinetics of a model oil-in-water emulsion in a centrifugal field to mimic the forces acting on emulsion droplets in oil/water separators

Kinetics of full scrum and staggered scrum engagement in under 19 ...

African Journals Online (AJOL)

Two hundred and eight male Rugby Union players from 13 high schools, whose ages ranged from 16 to 19 years, were used to examine the kinetics of the full scrum versus staggered scrum engagement techniques. Telemetric pressure transducers were used to measure the engagement and sustained forces acting on the ...

AND PI (π) FROM THE KINETIC MOLECULAR THEORY OF MATTER

African Journals Online (AJOL)

DJFLEX

This paper considers the possible physical origins of the important natural constants epsilon (e = 2.7182 ) and pi (π = 3.1415 ). They are suggested to originate from the kinetic molecular nature of matter. Epsilon (e) is suggested to be the ratio of the driving force on a randomly moving particle accelerated with a quantum of ...

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.

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.

Non-kinetic capabilities: complementing the kinetic prevalence to targeting

OpenAIRE

Ducheine, P.

2014-01-01

Targeting is used in military doctrine to describe a military operational way, using (military) means to influence a target (or addressee) in order to achieve designated political and/or military goals. The four factors italicized are used to analyse non-kinetic targeting, complementing our knowledge and understanding of the kinetic prevalence. Paradoxically, non-kinetic targeting is not recognized as a separate concept: kinetic and non-kinetic are intertwined facets of targeting. Kinetic tar...

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.

[Upper extremity kinetics and energy expenditure during walker-assisted gait in children with cerebral palsy].

Science.gov (United States)

Konop, Katherine A; Strifling, Kelly M B; Wang, Mei; Cao, Kevin; Eastwood, Daniel; Jackson, Scott; Ackman, Jeffrey; Altiok, Haluk; Schwab, Jeffrey; Harris, Gerald F

2009-01-01

We evaluated the relationships between upper extremity (UE) kinetics and the energy expenditure index during anterior and posterior walker-assisted gait in children with spastic diplegic cerebral palsy (CP). Ten children (3 boys, 7 girls; mean age 12.1 years; range 8 to 18 years) with spastic diplegic CP, who ambulated with a walker underwent gait analyses that included UE kinematics and kinetics. Upper extremity kinetics were obtained using instrumented walker handles. Energy expenditure index was obtained using the heart rate method (EEIHR) by subtracting resting heart rate from walking heart rate, and dividing by the walking speed. Correlations were sought between the kinetic variables and the EEIHR and temporal and stride parameters. In general, anterior walker use was associated with a higher EEIHR. Several kinetic variables correlated well with temporal and stride parameters, as well as the EEIHR. All of the significant correlations (r>0.80; pwalker use and involved joint reaction forces (JRF) rather than moments. Some variables showed multiple strong correlations during anterior walker use, including the medial JRF in the wrist, the posterior JRF in the elbow, and the inferior and superior JRFs in the shoulder. The observed correlations may indicate a relationship between the force used to advance the body forward within the walker frame and an increased EEIHR. More work is needed to refine the correlations, and to explore relationships with other variables, including the joint kinematics.

Integrated model of insulin and glucose kinetics describing both hepatic glucose and pancreatic insulin regulation

DEFF Research Database (Denmark)

Erlandsen, Mogens; Martinussen, Christoffer; Gravholt, Claus Højbjerg

2018-01-01

AbstractBackground and objectives Modeling of glucose kinetics has to a large extent been based on models with plasma insulin as a known forcing function. Furthermore, population-based statistical methods for parameter estimation in these models have mainly addressed random inter-individual varia......AbstractBackground and objectives Modeling of glucose kinetics has to a large extent been based on models with plasma insulin as a known forcing function. Furthermore, population-based statistical methods for parameter estimation in these models have mainly addressed random inter......-individual variations and not intra-individual variations in the parameters. Here we present an integrated whole-body model of glucose and insulin kinetics which extends the well-known two-compartment glucose minimal model. The population-based estimation technique allow for quantification of both random inter......- and intra-individual variation in selected parameters using simultaneous data series on glucose and insulin. Methods We extend the two-compartment glucose model into a whole-body model for both glucose and insulin using a simple model for the pancreas compartment which includes feedback of glucose on both...

Saturation mechanism of decaying ion temperature gradient driven turbulence with kinetic electrons

International Nuclear Information System (INIS)

Idomura, Yasuhiro

2016-01-01

We present full-f gyrokinetic simulations of the ion temperature gradient driven (ITG) turbulence including kinetic electrons. By comparing decaying ITG turbulence simulations with adiabatic and kinetic electron models, an impact of kinetic electrons on the ITG turbulence is investigated. It is found that significant electron transport occurs even in the ITG turbulence, and both ion and electron temperature profiles are relaxed. In steady states, both cases show upshifts of nonlinear critical ion temperature gradients from linear ones, while their saturation mechanisms are qualitatively different. In the adiabatic electron case, the ITG mode is stabilized by turbulence driven zonal flows. On the other hand, in the kinetic electron case, passing electrons transport shows fine resonant structures at mode rational surfaces, which generate corrugated density profiles. Such corrugated density profiles lead to fine radial electric fields following the neoclassical force balance relation. The resulting E × B shearing rate greatly exceeds the linear growth rate of the ITG mode. (author)

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

Kinematic and kinetic characteristics of vertical jump: comparison between soccer and basketball players

Directory of Open Access Journals (Sweden)

Matheus Machado Gomes

2009-09-01

Full Text Available The aim of this study was to compare jump height and kinetic and kinematic com-ponents of countermovement vertical jumps between soccer and basketball players performed in two different arm swing conditions: with arm swing (WAS and without arm swing (NAS. Nine basketball players (21.2 ± 2.9 years; 101.64 ± 14.58 kg; 1.95 ± 0.06 m and nine soccer players (18.2 ± 0.7 years; 77.4 ± 7.58 kg; 1.81 ± 0.07 m performed 12 maximal countermo-vement vertical jumps, including 6 WAS jumps and 6 NAS jumps, on a force platform that recorded the ground reaction force (GRF. The vertical component of the GRF was used to estimate jump height and to calculate the kinematic (duration of eccentric phase, duration of concentric phase, and maximal downward displacement of center of mass and kinetic variables (mean power during the eccentric phase, mean power during the concentric, peak power, and peak force. The results showed no differences in jump height or in kinematic or kinetic variables between basketball and soccer players. In addition, the results showed that the participants of the two groups jumped higher in the WAS condition (0.41 m than in the NAS condition (0.36 m because of a higher peak power (WAS=276.8 W/kg0.67 and NAS=241.3 W/kg0.67 and a longer concentric phase duration (WAS=0.20 s/m0.5 and NAS=0.19 s/m0.5 during WAS jump. These results indicate that the basketball and soccer players studied here showed similar performance and the same kinematic and kinetic pattern in maximal vertical jumps and were comparably affected by the use of arm swing.

How Chain Length and Charge Affect Surfactant Denaturation of Acyl Coenzyme A Binding Protein (ACBP)

DEFF Research Database (Denmark)

Andersen, Kell Kleiner; Otzen, Daniel

2009-01-01

maltoside (DDM). The aim has been to determine how surfactant chain length and micellar charge affect the denaturation mechanism. ACBP denatures in two steps irrespective of surfactant chain length, but with increasing chain length, the potency of the denaturant rises more rapidly than the critical micelle......Using intrinsic tryptophan fluorescence, equilibria and kinetics of unfolding of acyl coenzyme A binding protein (ACBP) have been investigated in sodium alkyl sulfate surfactants of different chain length (8-16 carbon atoms) and with different proportions of the nonionic surfactant dodecyl...... constants increases linearly with denaturant concentration below the cmc but declines at higher concentrations. Both shortening chain length and decreasing micellar charge reduce the overall kinetics of unfolding and makes the dependence of unfolding rate constants on surfactant concentration more complex...

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

Kinetics of sintering of uranium dioxide

International Nuclear Information System (INIS)

Soni, N.C.; Moorthy, V.K.

1978-01-01

The kinetics of sintering of UO 2 powders derived from ADU route and calcined at different temperatures was studied. The activation energy for sintering was found to depend on the calcination temperature, the density chosen and the sintering temperature range. The motive force for sintering is the excess free energy in the particle system. This exists in the powder compact in the form of surface energy and the excess lattice energy due to defects. The defects which can be eliminated at the operating temperature are responsible for the mobility and hence sintering. This concept of the motive force for sintering has been used to explain the difference in the activation energies observed in the present study. This would also explain phenomena such as attainment of limiting density, presence of optimum sintering temperature and the influence of calcination treatments on the sintering behaviour of powders. (author)

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)

A kinetic model of trp-cage folding from multiple biased molecular dynamics simulations.

Directory of Open Access Journals (Sweden)

Fabrizio Marinelli

2009-08-01

Full Text Available Trp-cage is a designed 20-residue polypeptide that, in spite of its size, shares several features with larger globular proteins.Although the system has been intensively investigated experimentally and theoretically, its folding mechanism is not yet fully understood. Indeed, some experiments suggest a two-state behavior, while others point to the presence of intermediates. In this work we show that the results of a bias-exchange metadynamics simulation can be used for constructing a detailed thermodynamic and kinetic model of the system. The model, although constructed from a biased simulation, has a quality similar to those extracted from the analysis of long unbiased molecular dynamics trajectories. This is demonstrated by a careful benchmark of the approach on a smaller system, the solvated Ace-Ala3-Nme peptide. For theTrp-cage folding, the model predicts that the relaxation time of 3100 ns observed experimentally is due to the presence of a compact molten globule-like conformation. This state has an occupancy of only 3% at 300 K, but acts as a kinetic trap.Instead, non-compact structures relax to the folded state on the sub-microsecond timescale. The model also predicts the presence of a state at Calpha-RMSD of 4.4 A from the NMR structure in which the Trp strongly interacts with Pro12. This state can explain the abnormal temperature dependence of the Pro12-delta3 and Gly11-alpha3 chemical shifts. The structures of the two most stable misfolded intermediates are in agreement with NMR experiments on the unfolded protein. Our work shows that, using biased molecular dynamics trajectories, it is possible to construct a model describing in detail the Trp-cage folding kinetics and thermodynamics in agreement with experimental data.

Monitoring ligand-receptor interactions by photonic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Jeney, Sylvia [M E Mueller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, Basel, 4056 (Switzerland); Mor, Flavio; Forro, Laszlo [Laboratory of Complex Matter Physics (LPMC), Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne (Switzerland); Koszali, Roland [Institute for Information and Communication Technologies (IICT), University of Applied Sciences of Western Switzerland (HEIG-VD), Rue Galilee 15, CH 1401 Yverdon-les-bains (Switzerland); Moy, Vincent T, E-mail: sylvia.jeney@unibas.ch, E-mail: vmoy@miami.edu [Department of Physiology and Biophysics, University of Miami Miller School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136 (United States)

2010-06-25

We introduce a method for the acquisition of single molecule force measurements of ligand-receptor interactions using the photonic force microscope (PFM). Biotin-functionalized beads, manipulated with an optical trap, and a streptavidin-functionalized coverslip were used to measure the effect of different pulling forces on the lifetime of individual streptavidin-biotin complexes. By optimizing the design of the optical trap and selection of the appropriate bead size, pulling forces in excess of 50 pN were achieved. Based on the amplitude of three-dimensional (3D) thermal position fluctuations of the attached bead, we were able to select for a bead-coverslip interaction that was mediated by a single streptavidin-biotin complex. Moreover, the developed experimental system was greatly accelerated by automation of data acquisition and analysis. In force-dependent kinetic measurements carried out between streptavidin and biotin, we observed that the streptavidin-biotin complex exhibited properties of a catch bond, with the lifetime increasing tenfold when the pulling force increased from 10 to 20 pN. We also show that silica beads were more appropriate than polystyrene beads for the force measurements, as tethers, longer than 200 nm, could be extracted from polystyrene beads.

Monitoring ligand-receptor interactions by photonic force microscopy

International Nuclear Information System (INIS)

Jeney, Sylvia; Mor, Flavio; Forro, Laszlo; Koszali, Roland; Moy, Vincent T

2010-01-01

We introduce a method for the acquisition of single molecule force measurements of ligand-receptor interactions using the photonic force microscope (PFM). Biotin-functionalized beads, manipulated with an optical trap, and a streptavidin-functionalized coverslip were used to measure the effect of different pulling forces on the lifetime of individual streptavidin-biotin complexes. By optimizing the design of the optical trap and selection of the appropriate bead size, pulling forces in excess of 50 pN were achieved. Based on the amplitude of three-dimensional (3D) thermal position fluctuations of the attached bead, we were able to select for a bead-coverslip interaction that was mediated by a single streptavidin-biotin complex. Moreover, the developed experimental system was greatly accelerated by automation of data acquisition and analysis. In force-dependent kinetic measurements carried out between streptavidin and biotin, we observed that the streptavidin-biotin complex exhibited properties of a catch bond, with the lifetime increasing tenfold when the pulling force increased from 10 to 20 pN. We also show that silica beads were more appropriate than polystyrene beads for the force measurements, as tethers, longer than 200 nm, could be extracted from polystyrene beads.

Acid-catalyzed kinetics of indium tin oxide etching

Energy Technology Data Exchange (ETDEWEB)