WorldWideScience

Sample records for volumetric colon unfolding

  1. Reversible projection technique for colon unfolding.

    Science.gov (United States)

    Yao, Jianhua; Chowdhury, Ananda S; Aman, Javed; Summers, Ronald M

    2010-12-01

    Colon unfolding provides an efficient way to navigate the colon in computed tomographic colonography (CTC). Most existing unfolding techniques only compute forward projections. When radiologists find abnormalities or conduct measurements on the unfolded view (which is often quicker and easier), it is difficult to locate the corresponding region on the 3-D view for further examination (which is more accurate and reliable). To address this, we propose a reversible projection technique for colon unfolding. The method makes use of advanced algorithms including rotation-minimizing frames, recursive ring sets, mesh skinning, and cylindrical projection. Both forward and reverse mapping can be computed for points on the colon surface. Therefore, it allows for detecting and measuring polyps on the unfolded view and mapping them back to the 3-D surface. We generated realistic colon simulation data incorporating most colon characteristics, such as curved centerline, variable distention, haustral folds, teniae coli, and colonic polyps. Our method was tested on both simulated data and data from 110 clinical CTC studies. The results showed submillimeter accuracy in simulated data and -0.23 ± 1.67 mm in the polyp measurement using clinical CTC data. The major contributions of our technique are: 1) the use of a recursive ring set method to solve the centerline and surface correspondence problem; 2) reverse transformation from the unfolded view to the 3-D view; and 3) quantitative validation using a realistic colon simulation and clinical CTC polyp measurement.

  2. 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......, urban planning, participatory arts, business, science and technology studies) to bring a plurality of perspectives and expertise related to participation.......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...

  3. Computer-aided detection of colonic polyps with level set-based adaptive convolution in volumetric mucosa to advance CT colonography toward a screening modality

    Science.gov (United States)

    Zhu, Hongbin; Duan, Chaijie; Pickhardt, Perry; Wang, Su; Liang, Zhengrong

    2009-01-01

    As a promising second reader of computed tomographic colonography (CTC) screening, the computer-aided detection (CAD) of colonic polyps has earned fast growing research interest. In this paper, we present a CAD scheme to automatically detect colonic polyps in CTC images. First, a thick colon wall representation, ie, a volumetric mucosa (VM) with several voxels wide in general, was segmented from CTC images by a partial-volume image segmentation algorithm. Based on the VM, we employed a level set-based adaptive convolution method for calculating the first- and second-order spatial derivatives more accurately to start the geometric analysis. Furthermore, to emphasize the correspondence among different layers in the VM, we introduced a middle-layer enhanced integration along the image gradient direction inside the VM to improve the operation of extracting the geometric information, like the principal curvatures. Initial polyp candidates (IPCs) were then determined by thresholding the geometric measurements. Based on IPCs, several features were extracted for each IPC, and fed into a support vector machine to reduce false positives (FPs). The final detections were displayed in a commercial system to provide second opinions for radiologists. The CAD scheme was applied to 26 patient CTC studies with 32 confirmed polyps by both optical and virtual colonoscopies. Compared to our previous work, all the polyps can be detected successfully with less FPs. At the 100% by polyp sensitivity, the new method yielded 3.5 FPs/dataset. PMID:20428331

  4. 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....

  5. Mechanics of collective unfolding

    CERN Document Server

    Caruel, M; Truskinovsky, L

    2015-01-01

    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 structure of the folding-u...

  6. Unfolding single- and multilayers

    Science.gov (United States)

    Llorens, Maria-Gema; Bons, Paul D.; Griera, Albert; Gomez-Rivas, Enrique

    2014-05-01

    When planar structures (e.g. sedimentary layers, veins, dykes, cleavages, etc.) are subjected to deformation, they have about equal chances to be shortened or stretched. The most common shortening and stretching structures are folds and boudinage, respectively. However, boudinage requires additional deformation mechanisms apart from viscous flow, like formation of fractures or strain localization. When folded layers are subjected to extension, they could potentially unfold back to straight layers. Although probably not uncommon, this would be difficult to recognize. Open questions are whether folded layers can unfold, what determines their mechanical behaviour and how we can recognize them in the field. In order to approach these questions, we present a series of numerical experiments that simulate stretching of previously folded single- and multi-layers in simple shear, using the two dimensional numerical modelling platform ELLE, including the finite element module BASIL that calculates viscous deformation. We investigate the parameters that affect a fold train once it rotates into the extensional field. The results show that the unfolding process strongly depends on the viscosity contrast between the layer and matrix (Llorens et al., 2013). Layers do not completely unfold when they experience softening before or during the stretching process or when other neighbouring competent layers prevent them from unfolding. The foliation refraction patterns are the main indicators of unfolded folds. Additionally, intrafolial folds and cusp-like folds adjacent to straight layers, as well as variations in fold amplitudes and limb lengths of irregular folds can also be used as indicators of stretching of a layer after shortening and folding. References: Llorens, M-.G., Bons, P.D., Griera, A. and Gomez-Rivas, E. 2013. When do folds unfold during progressive shear?. Geology, 41, 563-566.

  7. Volumetric Virtual Environments

    Institute of Scientific and Technical Information of China (English)

    HE Taosong

    2000-01-01

    Driven by fast development of both virtual reality and volume visualization, we discuss some critical techniques towards building a volumetric VR system, specifically the modeling, rendering, and manipulations of a volumetric scene.Techniques such as voxel-based object simplification, accelerated volume rendering,fast stereo volume rendering, and volumetric "collision detection" are introduced and improved, with the idea of demonstrating the possibilities and potential benefits of incorporating volumetric models into VR systems.

  8. Unfolding the Sulcus

    Science.gov (United States)

    Hohlfeld, Evan; Mahadevan, L.

    2011-03-01

    Sulci are localized furrows on the surface of soft materials that form by a compression-induced instability. We unfold this instability by breaking its natural scale and translation invariance, and compute a limiting bifurcation diagram for sulcfication showing that it is a scale-free, subcritical nonlinear instability. In contrast with classical nucleation, sulcification is continuous, occurs in purely elastic continua and is structurally stable in the limit of vanishing surface energy. During loading, a sulcus nucleates at a point with an upper critical strain and an essential singularity in the linearized spectrum. On unloading, it quasistatically shrinks to a point with a lower critical strain, explained by breaking of scale symmetry. At intermediate strains the system is linearly stable but nonlinearly unstable with no energy barrier. Simple experiments confirm the existence of these two critical strains.

  9. Protein Unfolding and Alzheimer's

    Science.gov (United States)

    Cheng, Kelvin

    2012-10-01

    Early interaction events of beta-amyloid (Aβ) proteins with neurons have been associated with the pathogenesis of Alzheimer's disease. Knowledge pertaining to the role of lipid molecules, particularly cholesterol, in modulating the single Aβ interactions with neurons at the atomic length and picosecond time resolutions, remains unclear. In our research, we have used atomistic molecular dynamics simulations to explore early molecular events including protein insertion kinetics, protein unfolding, and protein-induced membrane disruption of Aβ in lipid domains that mimic the nanoscopic raft and non-raft regions of the neural membrane. In this talk, I will summarize our current work on investigating the role of cholesterol in regulating the Aβ interaction events with membranes at the molecular level. I will also explain how our results will provide new insights into understanding the pathogenesis of Alzheimer's disease associated with the Aβ proteins.

  10. Slow Unfolding of Monomeric Proteins from Hyperthermophiles with Reversible Unfolding

    Directory of Open Access Journals (Sweden)

    Atsushi Mukaiyama

    2009-03-01

    Full Text Available Based on the differences in their optimal growth temperatures microorganisms can be classified into psychrophiles, mesophiles, thermophiles, and hyperthermophiles. Proteins from hyperthermophiles generally exhibit greater stability than those from other organisms. In this review, we collect data about the stability and folding of monomeric proteins from hyperthermophilies with reversible unfolding, from the equilibrium and kinetic aspects. The results indicate that slow unfolding is a general strategy by which proteins from hyperthermophiles adapt to higher temperatures. Hydrophobic interaction is one of the factors in the molecular mechanism of the slow unfolding of proteins from hyperthermophiles.

  11. Resolution of the unfolded state.

    Science.gov (United States)

    Beaucage, Gregory

    2008-03-01

    The unfolded states in proteins and nucleic acids remain weakly understood despite their importance to protein folding; misfolding diseases (Parkinson's & Alzheimer's); natively unfolded proteins (˜ 30% of eukaryotic proteins); and to understanding ribozymes. Research has been hindered by the inability to quantify the residual (native) structure present in an unfolded protein or nucleic acid. Here, a scaling model is proposed to quantify the degree of folding and the unfolded state (Beaucage, 2004, 2007). The model takes a global view of protein structure and can be applied to a number of analytic methods and to simulations. Three examples are given of application to small-angle scattering from pressure induced unfolding of SNase (Panick, 1998), from acid unfolded Cyt c (Kataoka, 1993) and from folding of Azoarcus ribozyme (Perez-Salas, 2004). These examples quantitatively show 3 characteristic unfolded states for proteins, the statistical nature of a folding pathway and the relationship between extent of folding and chain size during folding for charge driven folding in RNA. Beaucage, G., Biophys. J., in press (2007). Beaucage, G., Phys. Rev. E. 70, 031401 (2004). Kataoka, M., Y. Hagihara, K. Mihara, Y. Goto J. Mol. Biol. 229, 591 (1993). Panick, G., R. Malessa, R. Winter, G. Rapp, K. J. Frye, C. A. Royer J. Mol. Biol. 275, 389 (1998). Perez-Salas U. A., P. Rangan, S. Krueger, R. M. Briber, D. Thirumalai, S. A. Woodson, Biochemistry 43 1746 (2004).

  12. Neutron spectrum unfolding: Pt. 1; Theoretical

    Energy Technology Data Exchange (ETDEWEB)

    Matiullah (Centre for Nuclear Studies, Nilore, Islamabad (Pakistan)); Wiyaja, D.S. (PPTN - BATAN, Bandung (Indonesia)); Berzonis, M.A.; Bondars, H.; Lapenas, A.A. (Latvijskij Gosudarstvennyj Univ., Riga (USSR)); Kudo, K. (Electrotechnical Lab., Tsukuba, Ibaraki (Japan)); Majeed, A.; Durrani, S.A. (Birimingham Univ. (United Kingdom). School of Physics and Space Research)

    1991-01-01

    The use of the latest PC version of the computer code SAIPS in neutron spectrum unfolding is described. Guidelines for extending the use of SAIPS to unfold the spectrum from a CR-39-based spectrometer are presented. (author).

  13. Volumetric composition of nanocomposites

    DEFF Research Database (Denmark)

    Madsen, Bo; Lilholt, Hans; Mannila, Juha

    2015-01-01

    Detailed characterisation of the properties of composite materials with nanoscale fibres is central for the further progress in optimization of their manufacturing and properties. In the present study, a methodology for the determination and analysis of the volumetric composition of nanocomposites...... is presented, using cellulose/epoxy and aluminosilicate/polylactate nanocomposites as case materials. The buoyancy method is used for the accurate measurements of materials density. The accuracy of the method is determined to be high, allowing the measured nanocomposite densities to be reported with 5...... significant figures. The plotting of the measured nanocomposite density as a function of the nanofibre weight content is shown to be a first good approach of assessing the porosity content of the materials. The known gravimetric composition of the nanocomposites is converted into a volumetric composition...

  14. Enthalpy-entropy compensation in protein unfolding

    Institute of Scientific and Technical Information of China (English)

    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.

  15. Nanomechanics of Protein Unfolding outside Protease Nanopores

    Science.gov (United States)

    Luan, Binquan; Zhou, Ruhong

    Protein folding and unfolding have been the subject of active research for decades. Most of previous studies in protein unfolding were focused on temperature, chemical and/or force (such as in AFM) induced denaturations. Recent studies on the functional roles of proteasomes (such as ClpXP) revealed a novel unfolding process in cell, during which a target protein is mechanically unfolded and pulled into a confined, pore-like geometry for degradation. While the proteasome nanomachine has been extensively studied, the mechanism for unfolding proteins with the proteasome pore is still poorly understood. Here, we investigate the mechanical unfolding process of ubiquitin with (or really outside) an idealized proteasome pore, and compare such process with that in the AFM pulling experiment. Unexpectedly, the required force by a proteosome can be much smaller than that by the AFM. Simulation results also unveiled different nanomechanics, tearing fracture vs. shearing friction, in these two distinct types of mechanical unfoldings.

  16. Flexible Volumetric Structure

    Science.gov (United States)

    Cagle, Christopher M. (Inventor); Schlecht, Robin W. (Inventor)

    2014-01-01

    A flexible volumetric structure has a first spring that defines a three-dimensional volume and includes a serpentine structure elongatable and compressible along a length thereof. A second spring is coupled to at least one outboard edge region of the first spring. The second spring is a sheet-like structure capable of elongation along an in-plane dimension thereof. The second spring is oriented such that its in-plane dimension is aligned with the length of the first spring's serpentine structure.

  17. 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...

  18. Application of arrangement theory to unfolding models

    CERN Document Server

    Kamiya, Hidehiko; Tokushige, Norihide

    2010-01-01

    Arrangement theory plays an essential role in the study of the unfolding model used in many fields. This paper describes how arrangement theory can be usefully employed in solving the problems of counting (i) the number of admissible rankings in an unfolding model and (ii) the number of ranking patterns generated by unfolding models. The paper is mostly expository but also contains some new results such as simple upper and lower bounds for the number of ranking patterns in the unidimensional case.

  19. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  20. SVD-based unfolding: implementation and experience

    CERN Document Server

    AUTHOR|(CDS)2072546

    2011-01-01

    With the first year of data taking at the LHC by the experiments, unfolding methods for measured spectra are reconsidered with much interest. Here, we present a novel ROOT-based implementation of the Singular Value Decomposition approach to data unfolding, and discuss concrete analysis experience with this algorithm.

  1. A Linear Iterative Unfolding Method

    CERN Document Server

    Laszlo, Andras

    2011-01-01

    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 numerical ill-posedness of this task, various methods were invented which, given some assumptions on the initial probability distribution, try to regularize the problem. Most of these methods definitely introduce bias on 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. Convergence is proved under certain quite general conditions, which hold for p...

  2. 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.

  3. Quantitative Techniques in Volumetric Analysis

    Science.gov (United States)

    Zimmerman, John; Jacobsen, Jerrold J.

    1996-12-01

    Quantitative Techniques in Volumetric Analysis is a visual library of techniques used in making volumetric measurements. This 40-minute VHS videotape is designed as a resource for introducing students to proper volumetric methods and procedures. The entire tape, or relevant segments of the tape, can also be used to review procedures used in subsequent experiments that rely on the traditional art of quantitative analysis laboratory practice. The techniques included are: Quantitative transfer of a solid with a weighing spoon Quantitative transfer of a solid with a finger held weighing bottle Quantitative transfer of a solid with a paper strap held bottle Quantitative transfer of a solid with a spatula Examples of common quantitative weighing errors Quantitative transfer of a solid from dish to beaker to volumetric flask Quantitative transfer of a solid from dish to volumetric flask Volumetric transfer pipet A complete acid-base titration Hand technique variations The conventional view of contemporary quantitative chemical measurement tends to focus on instrumental systems, computers, and robotics. In this view, the analyst is relegated to placing standards and samples on a tray. A robotic arm delivers a sample to the analysis center, while a computer controls the analysis conditions and records the results. In spite of this, it is rare to find an analysis process that does not rely on some aspect of more traditional quantitative analysis techniques, such as careful dilution to the mark of a volumetric flask. Figure 2. Transfer of a solid with a spatula. Clearly, errors in a classical step will affect the quality of the final analysis. Because of this, it is still important for students to master the key elements of the traditional art of quantitative chemical analysis laboratory practice. Some aspects of chemical analysis, like careful rinsing to insure quantitative transfer, are often an automated part of an instrumental process that must be understood by the

  4. Pressure perturbation calorimetry of unfolded proteins.

    Science.gov (United States)

    Tsamaloukas, Alekos D; Pyzocha, Neena K; Makhatadze, George I

    2010-12-16

    We report the application of pressure perturbation calorimetry (PPC) to study unfolded proteins. Using PPC we have measured the temperature dependence of the thermal expansion coefficient, α(T), in the unfolded state of apocytochrome C and reduced BPTI. We have shown that α(T) is a nonlinear function and decreases with increasing temperature. The decrease is most significant in the low (2-55 °C) temperature range. We have also tested an empirical additivity approach to predict α(T) of unfolded state from the amino acid sequence using α(T) values for individual amino acids. A comparison of the experimental and calculated functions shows a very good agreement, both in absolute values of α(T) and in its temperature dependence. Such an agreement suggests the applicability of using empirical calculations to predict α(T) of any unfolded protein.

  5. 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...

  6. Data Unfolding Methods in High Energy Physics

    CERN Document Server

    Schmitt, Stefan

    2016-01-01

    A selection of unfolding methods commonly used in High Energy Physics is compared. The methods discussed here are: bin-by-bin correction factors, matrix inversion, template fit, Tikhonov regularisation and two examples of iterative methods. Two procedures to choose the strength of the regularisation are tested, namely the L-curve scan and a scan of global correlation coefficients. The advantages and disadvantages of the unfolding methods and choices of the regularisation strength are discussed using a toy example.

  7. Test Facility for Volumetric Absorber

    Energy Technology Data Exchange (ETDEWEB)

    Ebert, M.; Dibowski, G.; Pfander, M.; Sack, J. P.; Schwarzbozl, P.; Ulmer, S.

    2006-07-01

    Long-time testing of volumetric absorber modules is an inevitable measure to gain the experience and reliability required for the commercialization of the open volumetric receiver technology. While solar tower test facilities are necessary for performance measurements of complete volumetric receivers, the long-term stability of individual components can be tested in less expensive test setups. For the qualification of the aging effects of operating cycles on single elements of new absorber materials and designs, a test facility was developed and constructed in the framework of the KOSMOSOL project. In order to provide the concentrated solar radiation level, the absorber test facility is integrated into a parabolic dish system at the Plataforma Solar de Almeria (PSA) in Spain. Several new designs of ceramic absorbers were developed and tested during the last months. (Author)

  8. Fibronectin unfolding revisited: modeling cell traction-mediated unfolding of the tenth type-III repeat.

    Directory of Open Access Journals (Sweden)

    Elaine P S Gee

    Full Text Available Fibronectin polymerization is essential for the development and repair of the extracellular matrix. Consequently, deciphering the mechanism of fibronectin fibril formation is of immense interest. Fibronectin fibrillogenesis is driven by cell-traction forces that mechanically unfold particular modules within fibronectin. Previously, mechanical unfolding of fibronectin has been modeled by applying tensile forces at the N- and C-termini of fibronectin domains; however, physiological loading is likely focused on the solvent-exposed RGD loop in the 10(th type-III repeat of fibronectin (10FNIII, which mediates binding to cell-surface integrin receptors. In this work we used steered molecular dynamics to study the mechanical unfolding of 10FNIII under tensile force applied at this RGD site. We demonstrate that mechanically unfolding 10FNIII by pulling at the RGD site requires less work than unfolding by pulling at the N- and C- termini. Moreover, pulling at the N- and C-termini leads to 10FNIII unfolding along several pathways while pulling on the RGD site leads to a single exclusive unfolding pathway that includes a partially unfolded intermediate with exposed hydrophobic N-terminal beta-strands - residues that may facilitate fibronectin self-association. Additional mechanical unfolding triggers an essential arginine residue, which is required for high affinity binding to integrins, to move to a position far from the integrin binding site. This cell traction-induced conformational change may promote cell detachment after important partially unfolded kinetic intermediates are formed. These data suggest a novel mechanism that explains how cell-mediated forces promote fibronectin fibrillogenesis and how cell surface integrins detach from newly forming fibrils. This process enables cells to bind and unfold additional fibronectin modules - a method that propagates matrix assembly.

  9. Mechanics of forced unfolding of proteins.

    Science.gov (United States)

    Su, Tianxiang; Purohit, Prashant K

    2009-07-01

    We describe and solve a two-state kinetic model for the forced unfolding of proteins. The protein oligomer is modeled as a heterogeneous, freely jointed chain with two possible values of Kuhn length and contour length representing its folded and unfolded configurations. We obtain analytical solutions for the force-extension response of the protein oligomer for different types of loading conditions. We fit the analytical solutions for constant-velocity pulling to the force-extension data for ubiquitin and fibrinogen and obtain model parameters, such as Kuhn lengths and kinetic coefficients, for both proteins. We then predict their response under a linearly increasing force and find that our solutions for ubiquitin are consistent with a different set of experiments. Our calculations suggest that the refolding rate of proteins at low forces is several orders larger than the unfolding rate, and neglecting it can lead to lower predictions for the unfolding force, especially at high stretching velocities. By accounting for the refolding of proteins we obtain a critical force below which equilibrium is biased in favor of the folded state. Our calculations also suggest new methods to determine the distance of the transition state from the energy wells representing the folded and unfolded states of a protein.

  10. Neutron spectrum unfolding: Pt. 2; Experimental

    Energy Technology Data Exchange (ETDEWEB)

    Matiullah (Centre for Nuclear Studies, Nilore, Islamabad (Pakistan)); Wiyaja, D.S. (PPTN - BATAN, Bandung (Indonesia)); Berzonis, M.A.; Bondars, H.; Lapenas, A.A. (Latvijskij Gosudarstvennyj Univ., Riga (USSR)); Kudo, K. (Electrotechnical Lab., Tsukuba, Ibaraki (Japan)); Majeed, A.; Durrani, S.A. (Birimingham Univ. (United Kingdom). School of Physics and Space Research)

    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).

  11. 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.

  12. Chemical and thermal unfolding of calreticulin

    DEFF Research Database (Denmark)

    Duus, K.; Larsen, N.; Tran, T. A. T.;

    2013-01-01

    was found to obtain a molten structure in urea concentrations between 1-1.5 M urea, and to unfold/aggregate at high and low pH values. The results demonstrated that the fluorescent dye binding assay could measure the thermal stability of calreticulin in aqueous buffers with results comparable to melting...... assay, we have investigated the chemical and thermal stability of calreticulin. When the chemical stability of calreticulin was assessed, a midpoint for calreticulin unfolding was calculated to 3.0M urea using CD data at 222 nm. Using the fluorescent dye binding thermal shift assay, calreticulin...

  13. Colonic angiodysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vallee, C.; Legmann, P.; Garnier, T.; Levesque, M.; Favriel, J.M.

    1984-11-01

    The main clinical, endoscopic and radiographic findings in thirty documented cases of colonic angiodysplasia or vacular ectasia are described. We emphasise the association with colonic diverticulosis and cardiovascular pathology, describe the histological changes, summarize the present physiopathological hypothesis, and consider the various therapeutic approaches.

  14. Colonic locomotion

    NARCIS (Netherlands)

    Dodou, D.

    2006-01-01

    The most effective screening method for colonic cancer is colonoscopy. However, colonoscopy cannot be easily embraced by the population because of the related pain intensity. Robotic devices that pull themselves forward through the colon are a possible alternative. The main challenge for such device

  15. Zinc induces unfolding and aggregation of dimeric arginine kinase by trapping reversible unfolding intermediate.

    Science.gov (United States)

    Liu, Taotao; Wang, Xicheng

    2010-11-01

    Arginine kinase plays an important role in the cellular energy metabolism of invertebrates. Dimeric arginine kinase (dAK) is unique in some marine invertebrates. The effects of Zn²(+) on the unfolding and aggregation of dAK from the sea cucumber Stichopus japonicus were investigated. Our results indicated that Zn²(+) caused dAK inactivation accompanied by conformational unfolding, the exposure of hydrophobic surface, and aggregation. Kinetic studies showed the inactivation and unfolding of dAK followed biphasic kinetic courses. Zn²(+) can affect unfolding and refolding of dAK by trapping the reversible intermediate. Our study provides important information regarding the effect of Zn²(+) on metabolic enzymes in marine invertebrates.

  16. Volumetric Three-Dimensional Display Systems

    Science.gov (United States)

    Blundell, Barry G.; Schwarz, Adam J.

    2000-03-01

    A comprehensive study of approaches to three-dimensional visualization by volumetric display systems This groundbreaking volume provides an unbiased and in-depth discussion on a broad range of volumetric three-dimensional display systems. It examines the history, development, design, and future of these displays, and considers their potential for application to key areas in which visualization plays a major role. Drawing substantially on material that was previously unpublished or available only in patent form, the authors establish the first comprehensive technical and mathematical formalization of the field, and examine a number of different volumetric architectures. System level design strategies are presented, from which proposals for the next generation of high-definition predictable volumetric systems are developed. To ensure that researchers will benefit from work already completed, they provide: * Descriptions of several recent volumetric display systems prepared from material supplied by the teams that created them * An abstract volumetric display system design paradigm * An historical summary of 90 years of development in volumetric display system technology * An assessment of the strengths and weaknesses of many of the systems proposed to date * A unified presentation of the underlying principles of volumetric display systems * A comprehensive bibliography Beautifully supplemented with 17 color plates that illustrate volumetric images and prototype displays, Volumetric Three-Dimensional Display Systems is an indispensable resource for professionals in imaging systems development, scientific visualization, medical imaging, computer graphics, aerospace, military planning, and CAD/CAE.

  17. Chemical and thermal unfolding of calreticulin.

    Science.gov (United States)

    Duus, K; Larsen, N; Tran, T A T; Güven, E; Skov, L K; Jespersgaard, C; Gajhede, M; Houen, G

    2013-05-01

    Calreticulin is a soluble endoplasmic reticulum chaperone, which has a relatively low melting point due to its remarkable structure with a relatively high content of flexible structural elements. Using far ultraviolet circular dichroism (CD) spectroscopy and a fluorescent dye binding thermal shift assay, we have investigated the chemical and thermal stability of calreticulin. When the chemical stability of calreticulin was assessed, a midpoint for calreticulin unfolding was calculated to 3.0M urea using CD data at 222 nm. Using the fluorescent dye binding thermal shift assay, calreticulin was found to obtain a molten structure in urea concentrations between 1-1.5 M urea, and to unfold/aggregate at high and low pH values. The results demonstrated that the fluorescent dye binding assay could measure the thermal stability of calreticulin in aqueous buffers with results comparable to melting points obtained by other techniques.

  18. Spectral unfolding of fast neutron energy distributions

    Science.gov (United States)

    Mosby, Michelle; Jackman, Kevin; Engle, Jonathan

    2015-10-01

    The characterization of the energy distribution of a neutron flux is difficult in experiments with constrained geometry where techniques such as time of flight cannot be used to resolve the distribution. The measurement of neutron fluxes in reactors, which often present similar challenges, has been accomplished using radioactivation foils as an indirect probe. Spectral unfolding codes use statistical methods to adjust MCNP predictions of neutron energy distributions using quantified radioactive residuals produced in these foils. We have applied a modification of this established neutron flux characterization technique to experimentally characterize the neutron flux in the critical assemblies at the Nevada National Security Site (NNSS) and the spallation neutron flux at the Isotope Production Facility (IPF) at Los Alamos National Laboratory (LANL). Results of the unfolding procedure are presented and compared with a priori MCNP predictions, and the implications for measurements using the neutron fluxes at these facilities are discussed.

  19. Transition-Systems, Event Structures, and Unfoldings

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Rozenberg, Grzegorz; Thiagarajan, P.S.

    1995-01-01

    A subclass of transition systems called elementary transition systems can be identified with the help of axioms based on a structural notion called regions. Elementary transition systems have been shown to be the transition system model of a basic system model of net theory called elementary net ...... event structures. We then propose an operation of unfolding elementary transition systems into occurrence transition systems, We prove that it is "correct" in a strong categorical sense....

  20. A Constrained Unfolding Methodology for Product Positioning

    OpenAIRE

    Wayne DeSarbo; Rao, Vithala R

    1986-01-01

    This paper presents a recently developed unfolding methodology for analyzing preferential/dominance data that addresses the product positioning/repositioning decision problem of product (re)design and targeting by relating brand and consumer characteristics explicitly to perceptual brand locations and ideal points respectively. The methodology and associated algorithm are applied to a set of preference data for twelve models of residential communication devices. Various managerial implication...

  1. Thermal unfolding and aggregation of actin.

    Science.gov (United States)

    Levitsky, Dmitrii I; Pivovarova, Anastasiya V; Mikhailova, Valeria V; Nikolaeva, Olga P

    2008-09-01

    Actin is one of the most abundant proteins in nature. It is found in all eukaryotes and plays a fundamental role in many diverse and dynamic cellular processes. Also, actin is one of the most ubiquitous proteins because actin-like proteins have recently been identified in bacteria. Actin filament (F-actin) is a highly dynamic structure that can exist in different conformational states, and transitions between these states may be important in cytoskeletal dynamics and cell motility. These transitions can be modulated by various factors causing the stabilization or destabilization of actin filaments. In this review, we look at actin stabilization and destabilization as expressed by changes in the thermal stability of actin; specifically, we summarize and analyze the existing data on the thermal unfolding of actin as measured by differential scanning calorimetry. We also analyze in vitro data on the heat-induced aggregation of actin, the process that normally accompanies actin thermal denaturation. In this respect, we focus on the effects of small heat shock proteins, which can prevent the aggregation of thermally denatured actin with no effect on actin thermal unfolding. As a result, we have proposed a mechanism describing the thermal denaturation and aggregation of F-actin. This mechanism explains some of the special features of the thermal unfolding of actin filaments, including the effects of their stabilization and destabilization; it can also explain how small heat shock proteins protect the actin cytoskeleton from damage caused by the accumulation of large insoluble aggregates under heat shock conditions.

  2. Colonic Lipomas Mimicking Colon Cancer

    Directory of Open Access Journals (Sweden)

    Berna AYTAÇ

    2010-09-01

    Full Text Available Objective: Colonic lipomas are uncommon tumors of the gastrointestinal tract. Most of these tumors are asymptomatic and usually detected incidentally during colonoscopy or laparotomy and do not require treatment. Large lipomas are usually symptomatic and may mimic clinic manifestations of colonic carcinoma. Here we studied seven cases of submucosal and intramuscular colonic lipomas to evaluate the clinical features, diagnosis and treatment of this disease.Material and Method: Seven patients who were diagnosed with colonic lipoma between 1999 and 2006 were evaluated as regards age, gender, size of tumor, anatomic site, symptoms, location and treatment modality.Result: The mean age was 57.8± 14.7 years. Five patients were male and two were female. The size of the lipomas ranged from 1 to 5.5 cm and all were symptomatic except one patient. Five of the gastrointestinal lipomas were located submucosally and 2 intramurally. Five lipomas arose from the ascending colon, 1 from the hepatic flexure and 1 from the splenic flexure. Four large GI lipomas were removed by subtotal resection and one case underwent hemicolectomy while two pedunculated lipomas were resected by polypectomy. No recurrence was found after at least one year follow-up with endoscopic examination.Conclusion: Colonic lipomas may mimic malignancy with their clinical manifestations. Appropriate radiological and colonoscopic evaluation is essential to avoid unnecessary wide resections.

  3. A reduced volumetric expansion factor plot

    Science.gov (United States)

    Hendricks, R. C.

    1979-01-01

    A reduced volumetric expansion factor plot has been constructed for simple fluids which is suitable for engineering computations in heat transfer. Volumetric expansion factors have been found useful in correlating heat transfer data over a wide range of operating conditions including liquids, gases and the near critical region.

  4. Colon Polyps

    Science.gov (United States)

    ... whole grains. Reduce your fat intake. Limit alcohol consumption. Don't use tobacco. Stay physically active and maintain a healthy body weight. Talk to your doctor about calcium. Studies have shown that increasing your consumption of calcium may help prevent recurrence of colon ...

  5. Colon Cancer

    Centers for Disease Control (CDC) Podcasts

    2013-11-05

    In this podcast, Dr. Tom Frieden, CDC Director, discusses colon cancer and the importance of early detection.  Created: 11/5/2013 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 3/6/2014.

  6. Neutron spectrum unfolding using radial basis function neural networks.

    Science.gov (United States)

    Alvar, Amin Asgharzadeh; Deevband, Mohammad Reza; Ashtiyani, Meghdad

    2017-07-26

    Neutron energy spectrum unfolding has been the subject of research for several years. The Bayesian theory, Monte Carlo simulation, and iterative methods are some of the methods that have been used for neutron spectrum unfolding. In this study, the radial basis function (RBF), multilayer perceptron, and artificial neural networks (ANNs) were used for the unfolding of neutron spectrum, and a comparison was made between the networks' results. Both neural network architectures were trained and tested using the same data set for neutron spectrum unfolding from the response of LiI detectors with Eu impurity. Advantages of each ANN method in the unfolding of neutron energy spectrum were investigated, and the performance of the networks was compared. The results obtained showed that RBF neural network can be applied as an effective method for unfolding neutron spectrum, especially when the main target is the neutron dosimetry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. An introduction to the theory of unidimensional unfolding.

    Science.gov (United States)

    Kyngdon, Andrew

    2006-01-01

    Despite its 55 year presence in the field of mathematical psychology, the theory of unidimensional unfolding remains an enigma for many psychometricians and applied practitioners. This paper is the first of a three part series; and it aims to introduce unidimensional unfolding theory. The paper begins with a simple hypothetical example presenting an idealised distinction between responses to cumulative and unfolding dichotomous items. This followed by an accessible presentation of the theory of unidimensional unfolding as first articulated by Clyde H. Coombs (1950, 1964). The concept of the single peaked preference function (Coombs and Avrunin, 1977) which underpins unfolding theory is then presented. The article then progresses to the class of Rasch (1960) based IRT models developed by Andrich (1995) and Luo (2001). It was shown these models propose arguments not inconsistent with Coombs's (1964) original theory. The presumption of additive structure in psychological attributes was concluded to be the key weakness of the theories of unidimensional unfolding discussed.

  8. Protein unfolding pathways explored through molecular dynamics simulations.

    Science.gov (United States)

    Daggett, V; Levitt, M

    1993-07-20

    Herein we describe the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in solution at a variety of temperatures both with and without disulfide bonds. The reduced form of the protein unfolded at high temperature to an ensemble of conformations with all the properties of the molten globule state. In this account we outline the structural details of the actual unfolding process between the native and molten globule states. The first steps of unfolding involved expansion of the protein, which disrupted packing interactions. The solvent-accessible surface area also quickly increased. The unfolding was localized mostly to the turn and loop regions of the molecule, while leaving the secondary structure intact. Then, there was more gradual unfolding of the secondary structure and non-native turns became prevalent. This same trajectory was continued and more drastic unfolding occurred that resulted in a relatively compact state devoid of stable secondary structure.

  9. Learning about Colon Cancer

    Science.gov (United States)

    ... What do we know about heredity and colon cancer? Colon cancer, a malignant tumor of the large intestine, ... page Additional Resources for Information on Hereditary Colon Cancer Colon and Rectal Cancer Information [cancer.gov] The most ...

  10. Unfolding Implementation in Industrial Market Segmentation

    DEFF Research Database (Denmark)

    Bøjgaard, John; Ellegaard, Chris

    2011-01-01

    of implementing industrial market segmentation is discussed and unfolded in this article. Extant literature has identified segmentation implementation as a core challenge for marketers, but also one, which has received limited empirical attention. Future research opportunities are formulated in this article......Market segmentation is an important method of strategic marketing and constitutes a cornerstone of the marketing literature. It has undergone extensive scientific inquiry during the past 50 years. Reporting on an extensive review of the market segmentation literature, the challenging task...... for marketing management. Three key elements and challenges connected to execution of market segmentation are identified — organization, motivation, and adaptation....

  11. Unfolding of differential energy spectra in the MAGIC experiment

    CERN Document Server

    Albert, J; Anderhub, H; Antoranz, P; Armada, A; Asensio, M; Baixeras, C; Barrio, J A; Bartko, H; Bastieri, D; Becker, J; Bednarek, W; Berger, K; Bigongiari, C; Biland, A; Böck, R K; Bordas, P; Bosch-Ramon, V; Bretz, T; Britvitch, I; Camara, M; Carmona, E; Chilingarian, A; Ciprini, S; Coarasa, J A; Commichau, S; Contreras, J L; Cortina, J; Costado, M T; Curtef, V; Danielyan, V; Dazzi, F; De Angelis, A; Delgado, C; De los Reyes, R; De Lotto, B; Domingo-Santamaria, E; Dorner, D; Doro, M; Errando, M; Fagiolini, M; Ferenc, D; Fernández, E; Firpo, R; Flix, J; Fonseca, M V; Font, L; Fuchs, M; Galante, N; Garcia-Lopez, R J; Garczarczyk, M; Gaug, M; Giller, M; Göbel, F; Hakobyan, D; Hayashida, M; Hengstebeck, T; Herrero, A; Höhne, D; Hose, J; Hsu, C C; Jacon, P; Jogler, T; Kosyra, R; Kranich, D; Kritzer, R; Laille, A; Lindfors, E; Lombardi, S; Longo, F; López, J; López, M; Lorenz, E; Majumdar, P; Maneva, G; Mannheim, K; Mansutti, O; Mariotti, M; Martínez, M; Mazin, D; Merck, C; Meucci, M; Meyer, M; Miranda, J M; Mirzoyan, R; Mizobuchi, S; Moralejo, A; Nieto, D; Nilsson, K; Ninkovic, J; Ona-Wilhelmi, E; Otte, N; Oya, I; Panniello, M; Paoletti, R; Paredes, J M; Pasanen, M; Pascoli, D; Pauss, F; Pegna, R; Persic, M; Peruzzo, L; Piccioli, A; Puchades, N; Prandini, E; Raymers, A; Rhode, W; Ribó, M; Rico, J; Rissi, M; Robert, A; Rugamer, S; Saggion, A; Saitô, T; Sánchez, A; Sartori, P; Scalzotto, V; Scapin, V; Schmitt, R; Schweizer, T; Shayduk, M; Shinozaki, K; Shore, S N; Sidro, N; Sillanpää, A; Sobczynska, D; Stamerra, A; Stark, L S; Takalo, L; Temnikov, P; Tescaro, D; Teshima, M; Torres, D F; Turini, N; Vankov, H; Vitale, V; Wagner, R M; Wibig, T; Wittek, W; Zandanel, F; Zanin, R; Zapatero, J

    2007-01-01

    The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses.

  12. Universal convergence of the specific volume changes of globular proteins upon unfolding.

    Science.gov (United States)

    Schweiker, Katrina L; Fitz, Victoria W; Makhatadze, George I

    2009-11-24

    Both pressure and temperature are important environmental variables, and to obtain a complete understanding of the mechanisms of protein folding, it is necessary to determine how protein stability is dependent on these fundamental thermodynamic parameters. Although the temperature dependence of protein stability has been widely explored, the dependence of protein stability on pressure is not as well studied. In this paper, we report the results of the direct thermodynamic determination of the change in specific volume (DeltaV/V) upon protein unfolding, which defines the pressure dependence of protein stability, for five model proteins (ubiquitin, eglin c, ribonuclease A, lysozyme, and cytochrome c). We have shown that the specific volumetric changes upon unfolding for four of the proteins (ubiquitin, eglin c, ribonuclease A, and lysozyme) appear to converge to a common value at high temperatures. Analysis of various contributions to the change in volume upon protein unfolding allowed us to put forth the hypothesis that the change in volume due to hydration is very close to zero at this temperature, such that DeltaV/V is defined largely by the total volume of cavities and voids within a protein, and that this is a universal property of all small globular proteins without prosthetic groups. To test this hypothesis, additional experiments were performed with variants of eglin c that had site-directed substitutions at two buried positions, to create an additional cavity in the protein core. The results of these experiments, coupled with the structural analysis of cytochrome c showing a lower packing density compared to those of the other four proteins, provided further support for the hypothesis. Finally, we have shown that the deviation of the high-temperature DeltaV value of a given protein from the convergence value can be used to determine the size of the excess cavities in globular proteins.

  13. Unfolding spinor wave functions and expectation values of general operators: Introducing the unfolding-density operator

    Science.gov (United States)

    Medeiros, Paulo V. C.; Tsirkin, Stepan S.; Stafström, Sven; Björk, Jonas

    2015-01-01

    We show that the spectral weights Wm K ⃗(k ⃗) used for the unfolding of two-component spinor eigenstates | ψmK ⃗ SC>=|α >| ψmK ⃗ SC,α >+|β >| ψmK ⃗ SC,β > can be decomposed as the sum of the partial spectral weights WmK ⃗ μ(k ⃗) calculated for each component μ =α ,β independently, effortlessly turning a possibly complicated problem involving two coupled quantities into two independent problems of easy solution. Furthermore, we define the unfolding-density operator ρ̂K ⃗(k ⃗;ɛ ) , which unfolds the primitive cell expectation values φpc(k ⃗;ɛ ) of any arbitrary operator φ ̂ according to φpc(k ⃗;ɛ ) =Tr( ρ̂K ⃗(k ⃗;ɛ ) φ ̂) . As a proof of concept, we apply the method to obtain the unfolded band structures, as well as the expectation values of the Pauli spin matrices, for prototypical physical systems described by two-component spinor eigenfunctions.

  14. Mechanically unfolding proteins: The effect of unfolding history and the supramolecular scaffold

    Science.gov (United States)

    Zinober, Rebecca C.; Brockwell, David J.; Beddard, Godfrey S.; Blake, Anthony W.; Olmsted, Peter D.; Radford, Sheena E.; Smith, D. Alastair

    2002-01-01

    The mechanical resistance of a folded domain in a polyprotein of five mutant I27 domains (C47S, C63S I27)5is shown to depend on the unfolding history of the protein. This observation can be understood on the basis of competition between two effects, that of the changing number of domains attempting to unfold, and the progressive increase in the compliance of the polyprotein as domains unfold. We present Monte Carlo simulations that show the effect and experimental data that verify these observations. The results are confirmed using an analytical model based on transition state theory. The model and simulations also predict that the mechanical resistance of a domain depends on the stiffness of the surrounding scaffold that holds the domain in vivo, and on the length of the unfolded domain. Together, these additional factors that influence the mechanical resistance of proteins have important consequences for our understanding of natural proteins that have evolved to withstand force. PMID:12441375

  15. 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.

  16. The unfolded protein response protects from tau neurotoxicity in vivo.

    Directory of Open Access Journals (Sweden)

    Carin A Loewen

    Full Text Available The unfolded protein response is a critical system by which the cell handles excess misfolded protein in the secretory pathway. The role of the system in modulating the effects of aggregation prone cytosolic proteins has received less attention. We use genetic reporters to demonstrate activation of the unfolded protein response in a transgenic Drosophila model of Alzheimer's disease and related tauopathies. We then use loss of function genetic reagents to support a role for the unfolded protein response in protecting from tau neurotoxicity. Our findings suggest that the unfolded protein response can ameliorate the toxicity of tau in vivo.

  17. A Statistician’s View on Deconvolution and Unfolding

    CERN Document Server

    Panaretos, Victor M

    2011-01-01

    We briefly review some of the basic features of unfolding problems from the point of view of the statistician. To illustrate these, we mostly concentrate on the particular instance of unfolding called deconvolution. We discuss the issue of ill-posedness, the bias-variance trade-off, and regularisation tuning, placing emphasis on the important class of kernel density estimators. We also briefly consider basic aspects of the more general unfolding problem and men- tion some of the points that where raised during the discussion session of the unfolding workshop.

  18. Surfactant enhanced volumetric sweep efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Harwell, J.H.; Scamehorn, J.F.

    1989-10-01

    Surfactant-enhanced waterflooding is a novel EOR method aimed to improve the volumetric sweep efficiencies in reservoirs. The technique depends upon the ability to induce phase changes in surfactant solutions by mixing with surfactants of opposite charge or with salts of appropriate type. One surfactant or salt solution is injected into the reservoir. It is followed later by injection of another surfactant or salt solution. The sequence of injections is arranged so that the two solutions do not mix until they are into the permeable regions well away from the well bore. When they mix at this point, by design they form a precipitate or gel-like coacervate phase, plugging this permeable region, forcing flow through less permeable regions of the reservoir, improving sweep efficiency. The selectivity of the plugging process is demonstrated by achieving permeability reductions in the high permeable regions of Berea sandstone cores. Strategies were set to obtain a better control over the plug placement and the stability of plugs. A numerical simulator has been developed to investigate the potential increases in oil production of model systems. Furthermore, the hardness tolerance of anionic surfactant solutions is shown to be enhanced by addition of monovalent electrolyte or nonionic surfactants. 34 refs., 32 figs., 8 tabs.

  19. Laser Based 3D Volumetric Display System

    Science.gov (United States)

    1993-03-01

    Literature, Costa Mesa, CA July 1983. 3. "A Real Time Autostereoscopic Multiplanar 3D Display System", Rodney Don Williams, Felix Garcia, Jr., Texas...8217 .- NUMBERS LASER BASED 3D VOLUMETRIC DISPLAY SYSTEM PR: CD13 0. AUTHOR(S) PE: N/AWIU: DN303151 P. Soltan, J. Trias, W. Robinson, W. Dahlke 7...laser generated 3D volumetric images on a rotating double helix, (where the 3D displays are computer controlled for group viewing with the naked eye

  20. Unfolding in particle physics: a window on solving inverse problems

    Directory of Open Access Journals (Sweden)

    Spanò Francesco

    2013-07-01

    Full Text Available 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.

  1. THE UNFOLDING OF EQUIVARIANT BIFURCATION PROBLEMS WITH PARAMETERS SYMMETRY

    Institute of Scientific and Technical Information of China (English)

    高守平; 李养成

    2004-01-01

    In this paper versal unfolding theorem of multiparameter equivariant bifurcation problem with parameter symmetry is given. The necessary and sufficient condition that unfolding of multiparameter equivariant bifurcation problem with parameter symmetry factors through another is given. The corresponding results in [1]-[6] are generalized.

  2. Neutron spectrum unfolding using computer code SAIPS

    CERN Document Server

    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.

  3. Mimicking unfolding motion of a beetle hind wing

    Institute of Scientific and Technical Information of China (English)

    MUHAMMAD Azhar; PARK Hoon C; HWANG Do Y; BYUN Doyoung; GOO Nam S

    2009-01-01

    This paper presents an experimental research aiming to realize an artificial hind wing that can mimic the wing unfolding motion of Allomyrina dichotoma, an insect in coleopteran order. Based on the understanding of working principles of beetle wing folding/unfolding mechanisms, the hind wing unfolding motion is mimicked by a combination of creative ideas and state-of-art artificial muscle actuator. In this work, we devise two types of artificial wings and the successfully demonstrate that they can be unfolded by actuation of shape memory alloy wires to provide actuation force at the wing base and along the leading edge vein. The folding/unfolding mechanisms may provide an insight for portable nano/micro air vehicles with morphing wings.

  4. Should unfolded histograms be used to test hypotheses?

    CERN Document Server

    Cousins, Robert D; Sun, Yipeng

    2016-01-01

    In many analyses in high energy physics, attempts are made to remove the effects of detector smearing in data by techniques referred to as "unfolding" histograms, thus obtaining estimates of the true values of histogram bin contents. Such unfolded histograms are then compared to theoretical predictions, either to judge the goodness of fit of a theory, or to compare the abilities of two or more theories to describe the data. When doing this, even informally, one is testing hypotheses. However, a more fundamentally sound way to test hypotheses is to smear the theoretical predictions by simulating detector response and then comparing to the data without unfolding; this is also frequently done in high energy physics, particularly in searches for new physics. One can thus ask: to what extent does hypothesis testing after unfolding data materially reproduce the results obtained from testing by smearing theoretical predictions? We argue that this "bottom-line-test" of unfolding methods should be studied more commonl...

  5. On Inductive and Coinductive Proofs via Unfold/Fold Transformations

    Science.gov (United States)

    Seki, Hirohisa

    We consider a new application condition of negative unfolding, which guarantees its safe use in unfold/fold transformation of stratified logic programs. The new condition of negative unfolding is a natural one, since it is considered as a special case of replacement rule. The correctness of our unfold/fold transformation system in the sense of the perfect model semantics is proved. We then consider the coinductive proof rules proposed by Jaffar et al. We show that our unfold/fold transformation system, when used together with Lloyd-Topor transformation, can prove a proof problem which is provable by the coinductive proof rules by Jaffar et al. To this end, we propose a new replacement rule, called sound replacement, which is not necessarily equivalence-preserving, but is essential to perform a reasoning step corresponding to coinduction.

  6. Toward resolution of ambiguity for the unfolded state.

    Science.gov (United States)

    Beaucage, Gregory

    2008-07-01

    The unfolded states in proteins and nucleic acids remain weakly understood despite their importance in folding processes; misfolding diseases (Parkinson's and Alzheimer's); natively unfolded proteins (as many as 30% of eukaryotic proteins, according to Fink); and the study of ribozymes. Research has been hindered by the inability to quantify the residual (native) structure present in an unfolded protein or nucleic acid. Here, a scaling model is proposed to quantify the molar degree of folding and the unfolded state. The model takes a global view of protein structure and can be applied to a number of analytic methods and to simulations. Three examples are given of application to small-angle scattering from pressure-induced unfolding of SNase, from acid-unfolded cytochrome c, and from folding of Azoarcus ribozyme. These examples quantitatively show three characteristic unfolded states for proteins, the statistical nature of a protein folding pathway, and the relationship between extent of folding and chain size during folding for charge-driven folding in RNA.

  7. Nonequilibrium volumetric response of shocked polymers

    Energy Technology Data Exchange (ETDEWEB)

    Clements, B E [Los Alamos National Laboratory

    2009-01-01

    Polymers are well known for their non-equilibrium deviatoric behavior. However, investigations involving both high rate shock experiments and equilibrium measured thermodynamic quantities remind us that the volumetric behavior also exhibits a non-equilibrium response. Experiments supporting the notion of a non-equilibrium volumetric behavior will be summarized. Following that discussion, a continuum-level theory is proposed that will account for both the equilibrium and non-equilibrium response. Upon finding agreement with experiment, the theory is used to study the relaxation of a shocked polymer back towards its shocked equilibrium state.

  8. 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

  9. 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.

  10. Neutron spectrum unfolding using neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Vega C, H.R.; Hernandez D, V.M.; Manzanares A, E. [Universidad Autonoma de Zacatecas, A.P. 336, 98000 Zacatecas (Mexico)]. E-mail: rvega@cantera.reduaz.mx

    2004-07-01

    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)

  11. Analysis of distorted measurements -- parameter estimation and unfolding

    CERN Document Server

    Zech, Guenter

    2016-01-01

    1. Parameter inference from distorted measurements is discussed. 2. Smeared measurements are unfolded without explicit regularization. The corresponding results are unbiased and permit to fit parameters and to apply quantitative goodness-of-fit tests. 3. Common unfolding methods (iterative EM with early stopping, truncated SVD, ML fits with curvature, entropy and norm penalties) are tested and compared to each other with the regularization parameter adjusted to minimize the integrated square error (ISE) in all cases. Apart from histogram representations, spline approximations are considered. All simulations indicate that the EM method leads to smaller ISEs than the competing approaches. Especially promising is the EM unfolding to spline approximations. The studies are based on different distributions, event numbers, resolutions and enough independent simulations to obtain conclusive results. It is proposed to unfold data with the EM method to b-spline approximations and to supplement the results with histogra...

  12. 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.

  13. Unfolding of the spectrum for chaotic and mixed systems

    Science.gov (United States)

    Abul-Magd, Ashraf A.; Abul-Magd, Adel Y.

    2014-02-01

    Random Matrix Theory (RMT) is capable of making predictions for the spectral fluctuations of a physical system only after removing the influence of the level density by unfolding the spectra. When the level density is known, unfolding is done by using the integrated level density to transform the eigenvalues into dimensionless variables with unit mean spacing. When it is not known, as in most practical cases, one usually approximates the level staircase function by a polynomial. We here study the effect of unfolding procedure on the spectral fluctuation of two systems for which the level density is known asymptotically. The first is a time-reversal-invariant chaotic system, which is modeled in RMT by a Gaussian Orthogonal Ensemble (GOE). The second is the case of chaotic systems in which m quantum numbers remain almost undistorted in the early stage of the stochastic transition. The Hamiltonian of a system may be represented by a block diagonal matrix with m blocks of the same size, in which each block is a GOE. Unfolding is done once by using the asymptotic level densities for the eigenvalues of the m blocks and once by representing the integrated level density in terms of polynomials of different orders. We find that the spacing distribution of the eigenvalues shows a little sensitivity to the unfolding method. On the other hand, the variance of level number Σ2(L) is sensitive to the choice of the unfolding function. Unfolding that utilizes low order polynomials enhances Σ2(L) relative to the theoretical value, while the use of high order polynomial reduces it. The optimal value of the order of the unfolding polynomial depends on the dimension of the corresponding ensemble.

  14. Process conditions and volumetric composition in composites

    DEFF Research Database (Denmark)

    Madsen, Bo

    2013-01-01

    The obtainable volumetric composition in composites is linked to the gravimetric composition, and it is influenced by the conditions of the manufacturing process. A model for the volumetric composition is presented, where the volume fractions of fibers, matrix and porosity are calculated as a fun...... is increased. Altogether, the model is demonstrated to be a valuable tool for a quantitative analysis of the effect of process conditions. Based on the presented findings and considerations, examples of future work are mentioned for the further improvement of the model.......The obtainable volumetric composition in composites is linked to the gravimetric composition, and it is influenced by the conditions of the manufacturing process. A model for the volumetric composition is presented, where the volume fractions of fibers, matrix and porosity are calculated...... as a function of the fiber weight fraction, and where parameters are included for the composite microstructure, and the fiber assembly compaction behavior. Based on experimental data of composites manufactured with different process conditions, together with model predictions, different types of process related...

  15. Indexing Volumetric Shapes with Matching and Packing.

    Science.gov (United States)

    Koes, David Ryan; Camacho, Carlos J

    2015-04-01

    We describe a novel algorithm for bulk-loading an index with high-dimensional data and apply it to the problem of volumetric shape matching. Our matching and packing algorithm is a general approach for packing data according to a similarity metric. First an approximate k-nearest neighbor graph is constructed using vantage-point initialization, an improvement to previous work that decreases construction time while improving the quality of approximation. Then graph matching is iteratively performed to pack related items closely together. The end result is a dense index with good performance. We define a new query specification for shape matching that uses minimum and maximum shape constraints to explicitly specify the spatial requirements of the desired shape. This specification provides a natural language for performing volumetric shape matching and is readily supported by the geometry-based similarity search (GSS) tree, an indexing structure that maintains explicit representations of volumetric shape. We describe our implementation of a GSS tree for volumetric shape matching and provide a comprehensive evaluation of parameter sensitivity, performance, and scalability. Compared to previous bulk-loading algorithms, we find that matching and packing can construct a GSS-tree index in the same amount of time that is denser, flatter, and better performing, with an observed average performance improvement of 2X.

  16. First Passage Times, Lifetimes, and Relaxation Times of Unfolded Proteins

    Science.gov (United States)

    Dai, Wei; Sengupta, Anirvan M.; Levy, Ronald M.

    2015-01-01

    The dynamics of proteins in the unfolded state can be quantified in computer simulations by calculating a spectrum of relaxation times which describes the time scales over which the population fluctuations decay to equilibrium. If the unfolded state space is discretized we can evaluate the relaxation time of each state. We derive a simple relation that shows the mean first passage time to any state is equal to the relaxation time of that state divided by the equilibrium population. This explains why mean first passage times from state to state within the unfolded ensemble can be very long but the energy landscape can still be smooth (minimally frustrated). In fact, when the folding kinetics is two-state, all of the unfolded state relaxation times within the unfolded free energy basin are faster than the folding time. This result supports the well-established funnel energy landscape picture and resolves an apparent contradiction between this model and the recently proposed kinetic hub model of protein folding. We validate these concepts by analyzing a Markov State Model of the kinetics in the unfolded state and folding of the mini-protein NTL9 constructed from a 2.9 millisecond simulation provided by D. E. Shaw Research. PMID:26252709

  17. 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.

  18. The deconvolution of differential scanning calorimetry unfolding transitions.

    Science.gov (United States)

    Spink, Charles H

    2015-04-01

    This paper is a review of a process for deconvolution of unfolding thermal transitions measured by differential scanning calorimetry. The mathematical background is presented along with illustrations of how the unfolding data is processed to resolve the number of sequential transitions needed to describe an unfolding mechanism and to determine thermodynamic properties of the intermediate states. Examples of data obtained for a simple two-state unfolding of a G-quadruplex DNA structure derived from the basic human telomere sequence, (TTAGGG)4TT are used to present some of the basic issues in treating the DSC data. A more complex unfolding mechanism is also presented that requires deconvolution of a multistate transition, the unfolding of a related human telomere structure, (TTAGGG)12 TT. The intent of the discussion is to show the steps in deconvolution, and to present the data at each step to help clarify how the information is derived from the various mathematical manipulations. Copyright © 2014. Published by Elsevier Inc.

  19. Order Statistics Theory of Unfolding of Multimeric Proteins

    Science.gov (United States)

    Zhmurov, A.; Dima, R.I.; Barsegov, V.

    2010-01-01

    Dynamic force spectroscopy has become indispensable for the exploration of the mechanical properties of proteins. In force-ramp experiments, performed by utilizing a time-dependent pulling force, the peak forces for unfolding transitions in a multimeric protein (D)N are used to map the free energy landscape for unfolding for a protein domain D. We show that theoretical modeling of unfolding transitions based on combining the observed first (f1), second (f2), …, Nth (fN) unfolding forces for a protein tandem of fixed length N, and pooling the force data for tandems of different length, n1 molecular characteristics that determine the unfolding micromechanics. We present a simple method of estimation of the parent distribution, ψD(f), based on analyzing the force data for a tandem (D)n of arbitrary length n. Order statistics theory is exemplified through a detailed analysis and modeling of the unfolding forces obtained from pulling simulations of the monomer and oligomers of the all-β-sheet WW domain. PMID:20858442

  20. Unfolded protein response activation in cataracts.

    Science.gov (United States)

    Torres-Bernal, Beatriz E; Torres-Bernal, Luis Fernando; Gutiérrez-Campos, Rafael R; Kershenobich Stalnikowitz, David D; Barba-Gallardo, Luis Fernando; Chayet, Arturo A; Ventura-Juárez, Javier

    2014-10-01

    To analyze the expression of 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6 (ATF6), 2 factors in the unfolded protein response (UPR), in age-related and diabetes-associated cataract. Universidad Autónoma de Aguascalientes, Aguascalientes, México. Experimental study. The qualitative and quantitative expression of GRP78 and ATF6 were measured in surgical samples from 11 senile cataracts, 9 diabetic-associated cataracts, and 3 normal lenses. Both proteins were detected by immunofluorescence and immunogold-conjugated antibodies. Quantitative morphometry was used to analyze the differences in GRP78 and ATF6 between samples. The Mann-Whitney test was used for statistical analysis. Scanning electron microscopy showed the characteristic organization of fibers in normal lenses with regular alignment and interdigitation between them. On the other hand, lenses from eyes with senile or diabetic cataract showed the same pattern of misalignment and disorganization of the fibers. Both proteins were detected through immunofluorescence in senile and diabetic cataracts, but not in normal lenses. Immunogold-conjugated antibodies and transmission electron microscopy showed that GRP78 and ATF6 grains were 30% higher and 35% higher, respectively, in diabetic cataracts than in senile cataracts (P<.05). These data show for the first time in humans that GRP78 and ATF6 are present in lens fibers of senile cataracts and diabetic cataracts, establishing that the UPR may be important in the process of cataractogenesis. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  1. 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......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...... 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...

  2. Sequential protein unfolding through a carbon nanotube pore

    Science.gov (United States)

    Xu, Zhonghe; Zhang, Shuang; Weber, Jeffrey K.; Luan, Binquan; Zhou, Ruhong; Li, Jingyuan

    2016-06-01

    An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of the nanopore interface thus facilitate the formation of stable ``unfoldon'' motifs above the nanotube aperture that can exist in the absence of specific native contacts with the other secondary structure. Destruction of these unfoldons gives rise to distinct force peaks in our simulations, providing us with a sensitive probe for studying the kinetics of serial unfolding events. Our detailed analysis of nanopore-mediated protein unfolding events not only provides insight into how related processes might proceed in the cell, but also serves to deepen our understanding of structural arrangements which form the basis for protein conformational stability.An assortment of biological processes, like protein degradation and the transport of proteins across membranes, depend on protein unfolding events mediated by nanopore interfaces. In this work, we exploit fully atomistic simulations of an artificial, CNT-based nanopore to investigate the nature of ubiquitin unfolding. With one end of the protein subjected to an external force, we observe non-canonical unfolding behaviour as ubiquitin is pulled through the pore opening. Secondary structural elements are sequentially detached from the protein and threaded into the nanotube, interestingly, the remaining part maintains native-like characteristics. The constraints of

  3. Protein unfolding under isometric tension-what force can integrins generate, and can it unfold FNIII domains?

    Science.gov (United States)

    Erickson, Harold P

    2017-02-01

    Extracellular matrix fibrils of fibronectin (FN) are highly elastic, and are typically stretched three to four times their relaxed length. The mechanism of stretching has been controversial, in particular whether it involves tension-induced unfolding of FNIII domains. Recent studies have found that ∼5pN is the threshold isometric force for unfolding various protein domains. FNIII domains should therefore not be unfolded until the tension approaches 5pN. Integrins have been reported to generate forces ranging from 1 to >50pN, but I argue that studies reporting 1-2pN are the most convincing. This is not enough to unfold FNIII domains. Even if domains were unfolded, 2pN would only extend the worm-like-chain to about twice the length of the folded domain. Overall I conclude that stretching FN matrix fibrils involves primarily the compact to extended conformational change of FN dimers, with minimal contribution from unfolding FNIII domains. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding

    DEFF Research Database (Denmark)

    Mysling, Simon; Kristensen, Kristian Kølby; Larsson, Mikael

    2016-01-01

    Lipoprotein lipase (LPL) undergoes spontaneous inactivation via global unfolding and this unfolding is prevented by GPIHBP1 (Mysling et al., 2016). We now show: (1) that ANGPTL4 inactivates LPL by catalyzing the unfolding of its hydrolase domain; (2) that binding to GPIHBP1 renders LPL largely...

  5. Combined surface and volumetric occlusion shading

    KAUST Repository

    Schott, Matthias O.

    2012-02-01

    In this paper, a method for interactive direct volume rendering is proposed that computes ambient occlusion effects for visualizations that combine both volumetric and geometric primitives, specifically tube shaped geometric objects representing streamlines, magnetic field lines or DTI fiber tracts. The proposed algorithm extends the recently proposed Directional Occlusion Shading model to allow the rendering of those geometric shapes in combination with a context providing 3D volume, considering mutual occlusion between structures represented by a volume or geometry. © 2012 IEEE.

  6. Unfolding simulations of holomyoglobin from four mammals: identification of intermediates and β-sheet formation from partially unfolded states.

    Directory of Open Access Journals (Sweden)

    Pouria Dasmeh

    Full Text Available 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 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 (R g ~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 in terrestrial species. At 500 K, heme was lost within 1.0-3.7 ns. All four proteins displayed exponentially decaying helix structure within 20 ns. The C- and F-helices were lost quickly in all cases. Heme delayed helix loss, and sperm whale myoglobin exhibited highest retention of heme and D/E helices. Persistence of conformation (RMSD, secondary structure, and ellipticity between 2-11 ns was interpreted as intermediates of holoMb unfolding in all four species. The intermediates resemble those of apoMb notably in A and H helices, but differ substantially in the D-, E- and F-helices, which interact with heme. The identified mechanisms cast light on the role of metal/cofactor in poorly understood holoMb unfolding. We also observed β-sheet formation of several myoglobins at 500 K as seen experimentally, occurring after disruption of helices to a partially unfolded, globally disordered state; heme reduced this tendency and sperm-whale did not display any sheet propensity during the simulations.

  7. 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)

  8. MR volumetric assessment of endolymphatic hydrops

    Energy Technology Data Exchange (ETDEWEB)

    Guerkov, R.; Berman, A.; Jerin, C.; Krause, E. [University of Munich, Department of Otorhinolaryngology Head and Neck Surgery, Grosshadern Medical Centre, Munich (Germany); University of Munich, German Centre for Vertigo and Balance Disorders, Grosshadern Medical Centre, Marchioninistr. 15, 81377, Munich (Germany); Dietrich, O.; Flatz, W.; Ertl-Wagner, B. [University of Munich, Institute of Clinical Radiology, Grosshadern Medical Centre, Munich (Germany); Keeser, D. [University of Munich, Institute of Clinical Radiology, Grosshadern Medical Centre, Munich (Germany); University of Munich, German Centre for Vertigo and Balance Disorders, Grosshadern Medical Centre, Marchioninistr. 15, 81377, Munich (Germany); University of Munich, Department of Psychiatry and Psychotherapy, Innenstadtkliniken Medical Centre, Munich (Germany)

    2014-10-16

    We aimed to volumetrically quantify endolymph and perilymph spaces of the inner ear in order to establish a methodological basis for further investigations into the pathophysiology and therapeutic monitoring of Meniere's disease. Sixteen patients (eight females, aged 38-71 years) with definite unilateral Meniere's disease were included in this study. Magnetic resonance (MR) cisternography with a T2-SPACE sequence was combined with a Real reconstruction inversion recovery (Real-IR) sequence for delineation of inner ear fluid spaces. Machine learning and automated local thresholding segmentation algorithms were applied for three-dimensional (3D) reconstruction and volumetric quantification of endolymphatic hydrops. Test-retest reliability was assessed by the intra-class coefficient; correlation of cochlear endolymph volume ratio with hearing function was assessed by the Pearson correlation coefficient. Endolymph volume ratios could be reliably measured in all patients, with a mean (range) value of 15 % (2-25) for the cochlea and 28 % (12-40) for the vestibulum. Test-retest reliability was excellent, with an intra-class coefficient of 0.99. Cochlear endolymphatic hydrops was significantly correlated with hearing loss (r = 0.747, p = 0.001). MR imaging after local contrast application and image processing, including machine learning and automated local thresholding, enable the volumetric quantification of endolymphatic hydrops. This allows for a quantitative assessment of the effect of therapeutic interventions on endolymphatic hydrops. (orig.)

  9. Human pescadillo induces large-scale chromatin unfolding

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hao; FANG Yan; HUANG Cuifen; YANG Xiao; YE Qinong

    2005-01-01

    The human pescadillo gene encodes a protein with a BRCT domain. Pescadillo plays an important role in DNA synthesis, cell proliferation and transformation. Since BRCT domains have been shown to induce chromatin large-scale unfolding, we tested the role of Pescadillo in regulation of large-scale chromatin unfolding. To this end, we isolated the coding region of Pescadillo from human mammary MCF10A cells. Compared with the reported sequence, the isolated Pescadillo contains in-frame deletion from amino acid 580 to 582. Targeting the Pescadillo to an amplified, lac operator-containing chromosome region in the mammalian genome results in large-scale chromatin decondensation. This unfolding activity maps to the BRCT domain of Pescadillo. These data provide a new clue to understanding the vital role of Pescadillo.

  10. An empirical study into the theory of unidimensional unfolding.

    Science.gov (United States)

    Kyngdon, Andrew

    2006-01-01

    This article is the second in the series on unidimensional unfolding. Its aim was to test the quantitative component of Coombs's (1964) theory via an empirical application to subjective control in gambling behavior (Dickerson and Baron, 2000). It was found that approximately 96% of judgments upon bilateral stimulus pairs were as predicted by the theory of unidimensional unfolding. The double cancellation axiom of the theory of axiomatic conjoint measurement (ACM) (Krantz, Luce, Suppes and Tversky, 1971) was satisfied by the interstimulus midpoint order obtained from these judgments. These results supported previous unfolding studies on attitudes (Johnson, 2001; Michell, 1994). Exponential and linear relationships were found between the transformed scaling solutions of Coombs's (1964) theory and the SHCMpp (Andrich, 1995). The implications of these results were discussed. Additionally, the article presented both a formal theory of item construction (Michell, 1994) and an accessible demonstration of the Goode's algorithm scaling procedure.

  11. [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).

  12. Protein unfolding under force: crack propagation in a network.

    Science.gov (United States)

    de Graff, Adam M R; Shannon, Gareth; Farrell, Daniel W; Williams, Philip M; Thorpe, M F

    2011-08-03

    The mechanical unfolding of a set of 12 proteins with diverse topologies is investigated using an all-atom constraint-based model. Proteins are represented as polypeptides cross-linked by hydrogen bonds, salt bridges, and hydrophobic contacts, each modeled as a harmonic inequality constraint capable of supporting a finite load before breaking. Stereochemically acceptable unfolding pathways are generated by minimally overloading the network in an iterative fashion, analogous to crack propagation in solids. By comparing the pathways to those from molecular dynamics simulations and intermediates identified from experiment, it is demonstrated that the dominant unfolding pathways for 9 of the 12 proteins studied are well described by crack propagation in a network. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. Using the unfolding case study in midwifery education.

    Science.gov (United States)

    Carr, Katherine Camacho

    2015-01-01

    One of the challenges in teaching clinicians is helping health care provider students, including midwives, develop the critical thinking and clinical decision-making skills needed for various situations encountered in practice. Health care provider students need to master the required core knowledge and skills but also need to assess, analyze, judge, decide on action, act, and evaluate their actions. Lecture-heavy classroom teaching, which is usually delivered separately from clinical experiences in health care education, focuses on knowledge acquisition, often leaving knowledge application to trial and error. Case studies are commonly used by faculty with a problem-based learning approach, which is more analytic but sometimes static. The unfolding case study presents students with a patient scenario that changes over time and allows for discussion; lecture points as needed; and decision making as the situation or condition changes, reflecting what happens in real-life clinical practice. The use of the unfolding case study moves health care provider education from fact-based lecturing to situation-based discussion and decision making as a person's condition or situation changes. Use of the unfolding case facilitates collaborative learning, covers necessary content, and assists students to think beyond the facts and use their clinical imagination. Unfolding case studies require students to begin to grasp the nature of a clinical situation and adjust interventions as the clinical situation unfolds. Steps in developing and using an unfolding case study for midwifery students are presented, including 2 examples. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health.

  14. Flat Zipper-Unfolding Pairs for Platonic Solids

    CERN Document Server

    O'Rourke, Joseph

    2010-01-01

    We show that four of the five Platonic solids' surfaces may be cut open with a Hamiltonian path along edges and unfolded to a polygonal net each of which can "zipper-refold" to a flat doubly covered parallelogram, forming a rather compact representation of the surface. Thus these regular polyhedra have particular flat "zipper pairs." No such zipper pair exists for a dodecahedron, whose Hamiltonian unfoldings are "zip-rigid." This report is primarily an inventory of the possibilities, and raises more questions than it answers.

  15. Determination of heat capacity of unfolding for marginally stable proteins from a single temperature induced protein unfolding profile

    Energy Technology Data Exchange (ETDEWEB)

    Saini, Komal; Ahluwalia, Unnati [Department of Chemistry, Indian Institute of Technology, Delhi 110016 (India); Deep, Shashank, E-mail: sdeep@chemistry.iitd.ac.in [Department of Chemistry, Indian Institute of Technology, Delhi 110016 (India)

    2010-07-10

    A reliable estimation of heat capacity of denaturation ({Delta}C{sub p}) is necessary to calculate the free energy of unfolding of proteins. For marginally stable proteins, such as mutants of a protein or proteins at low pH or under denaturating conditions, the pre-transition region is not fully populated by the native state. Analysis of differential scanning calorimeter (DSC) data under such conditions may not yield a reliable value of {Delta}C{sub p} and other associated thermodynamic parameters of unfolding. Analysis of denaturation profiles of (a) cytochrome c at pH 2.5, 3 and 8 and (b) myoglobin at pH 4, show that an accurate value of {Delta}C{sub p} can be extracted from a single unfolding profile obtained spectroscopically by including low temperature data.

  16. Volumetric polymerization shrinkage of contemporary composite resins

    Directory of Open Access Journals (Sweden)

    Halim Nagem Filho

    2007-10-01

    Full Text Available The polymerization shrinkage of composite resins may affect negatively the clinical outcome of the restoration. Extensive research has been carried out to develop new formulations of composite resins in order to provide good handling characteristics and some dimensional stability during polymerization. The purpose of this study was to analyze, in vitro, the magnitude of the volumetric polymerization shrinkage of 7 contemporary composite resins (Definite, Suprafill, SureFil, Filtek Z250, Fill Magic, Alert, and Solitaire to determine whether there are differences among these materials. The tests were conducted with precision of 0.1 mg. The volumetric shrinkage was measured by hydrostatic weighing before and after polymerization and calculated by known mathematical equations. One-way ANOVA (a or = 0.05 was used to determine statistically significant differences in volumetric shrinkage among the tested composite resins. Suprafill (1.87±0.01 and Definite (1.89±0.01 shrank significantly less than the other composite resins. SureFil (2.01±0.06, Filtek Z250 (1.99±0.03, and Fill Magic (2.02±0.02 presented intermediate levels of polymerization shrinkage. Alert and Solitaire presented the highest degree of polymerization shrinkage. Knowing the polymerization shrinkage rates of the commercially available composite resins, the dentist would be able to choose between using composite resins with lower polymerization shrinkage rates or adopting technical or operational procedures to minimize the adverse effects deriving from resin contraction during light-activation.

  17. A SUBDIVISION SCHEME FOR VOLUMETRIC MODELS

    Institute of Scientific and Technical Information of China (English)

    GhulamMustafa; LiuXuefeng

    2005-01-01

    In this paper, a subdivision scheme which generalizes a surface scheme in previous papers to volume meshes is designed. The scheme exhibits significant control over shrink-age/size of volumetric models. It also has the ability to conveniently incorporate boundaries and creases into a smooth limit shape of models. The method presented here is much simpler and easier as compared to MacCracken and Joy's. This method makes no restrictions on the local topology of meshes. Particularly, it can be applied without any change to meshes of nonmanifold topology.

  18. Volumetric composition in composites and historical data

    DEFF Research Database (Denmark)

    Lilholt, Hans; Madsen, Bo

    2013-01-01

    guidance to the optimal combination of fibre content, matrix content and porosity content, in order to achieve the best obtainable properties. Several composite materials systems have been shown to be handleable with this model. An extensive series of experimental data for the system of cellulose fibres...... and polymer (resin) was produced in 1942 – 1944, and these data have been (re-)analysed by the volumetric composition model, and the property values for density, stiffness and strength have been evaluated. Good agreement has been obtained and some further observations have been extracted from the analysis....

  19. IMITATION OF STANDARD VOLUMETRIC ACTIVITY METAL SAMPLES

    Directory of Open Access Journals (Sweden)

    A. I. Zhukouski

    2016-01-01

    Full Text Available Due to the specific character of problems in the field of ionizing radiation spectroscopy, the R&D and making process of standard volumetric activity metal samples (standard samples for calibration and verification of spectrometric equipment is not only expensive, but also requires the use of highly qualified experts and a unique specific equipment. Theoretical and experimental studies performed have shown the possibility to use imitators as a set of alternating point sources of gamma radiation and metal plates and their use along with standard volumetric activity metal samples for calibration of scintillation-based detectors used in radiation control in metallurgy. Response functions or instrumental spectra of such spectrometer to radionuclides like 137Cs, 134Cs, 152Eu, 154Eu, 60Co, 54Mn, 232Th, 226Ra, 65Zn, 125Sb+125mTe, 106Ru+106Rh, 94Nb, 110mAg, 233U, 234U, 235U and 238U are required for calibration in a given measurement geometry. Standard samples in the form of a probe made of melt metal of a certain diameter and height are used in such measurements. However, the production of reference materials is costly and even problematic for such radionuclides as 94Nb, 125Sb+125mTe, 234U, 235U  etc. A recognized solution to solve this problem is to use the Monte-Carlo simulation method. Instrumental experimental and theoretical spectra obtained by using standard samples and their imitators show a high compliance between experimental spectra of real samples and the theoretical ones of their Monte-Carlo models, between spectra of real samples and the ones of their imitators and finally, between experimental spectra of real sample imitators and the theoretical ones of their Monte-Carlo models. They also have shown the adequacy and consistency of the approach in using a combination of metal scattering layers and reference point gamma-ray sources instead of standard volumetric activity metal samples. As for using several reference point gamma-ray sources

  20. Magnetic volumetric hologram memory with magnetic garnet.

    Science.gov (United States)

    Nakamura, Yuichi; Takagi, Hiroyuki; Lim, Pang Boey; Inoue, Mitsuteru

    2014-06-30

    Holographic memory is a promising next-generation optical memory that has a higher recording density and a higher transfer rate than other types of memory. In holographic memory, magnetic garnet films can serve as rewritable holographic memory media by use of magneto-optical effect. We have now demonstrated that a magnetic hologram can be recorded volumetrically in a ferromagnetic garnet film and that the signal image can be reconstructed from it for the first time. In addition, multiplicity of the magnetic hologram was also confirmed; the image could be reconstructed from a spot overlapped by other spots.

  1. Computerized Classification Testing under the Generalized Graded Unfolding Model

    Science.gov (United States)

    Wang, Wen-Chung; Liu, Chen-Wei

    2011-01-01

    The generalized graded unfolding model (GGUM) has been recently developed to describe item responses to Likert items (agree-disagree) in attitude measurement. In this study, the authors (a) developed two item selection methods in computerized classification testing under the GGUM, the current estimate/ability confidence interval method and the cut…

  2. Perceived Helpfulness and Unfolding Processes in Body-Oriented ...

    African Journals Online (AJOL)

    Christopher R Stones

    Research specific to this approach is being conducted by. Price .... the therapy as well as the unfolding of the therapeutic process (Elliott et al., ... benefits of increased emotional awareness, a more ..... described this as gaining the appreciation that it was ..... The tears I felt welling up-in gratitude toward a connection with.

  3. An Analysis of Lexical Cohesion in"How Empathy Unfolds"

    Institute of Scientific and Technical Information of China (English)

    朱玲霞

    2016-01-01

    This thesis aims to analyze the lexical cohesion in the text"How Empathy Unfolds" in the new standard college English textbook. This paper focuses on four kinds of lexical cohesive devices: repetition, synonymy, hyponymy and collocation. It is expected that these analyses can help readers gain a better and deeper comprehension of the structure and content of the text.

  4. Light-triggered β-hairpin folding and unfolding

    NARCIS (Netherlands)

    Schrader, Tobias E.; Schreier, Wolfgang J.; Cordes, Thorben; Koller, Florian O.; Babitzki, Galina; Denschlag, Robert; Renner, Christian; Löweneck, Markus; Dong, Shou-Liang; Moroder, Luis; Tavan, Paul; Zinth, Wolfgang

    2007-01-01

    A light-switchable peptide is transformed with ultrashort pulses from a β-hairpin to an unfolded hydrophobic cluster and vice versa. The structural changes are monitored by mid-IR probing. Instantaneous normal mode analysis with a Hamiltonian combining density functional theory with molecular

  5. High-pressure SANS and fluorescence unfolding study of calmodulin.

    Science.gov (United States)

    Gibrat, Gabriel; Hoa, Gaston Hui Bon; Craescu, Constantin T; Assairi, Liliane; Blouquit, Yves; Annighöfer, Burkhard; May, Roland P; Bellissent-Funel, Marie-Claire

    2014-09-01

    Apo-calmodulin, a small soluble mainly α protein, is a calcium-dependent protein activator. Calcium binding affects the calmodulin conformation but also its stability. Calcium free form unfolds between 40 and 80°C, whereas the calcium-saturated form is stable up to temperatures as high as 100°C, forbidding comparison of the thermal unfolding pathways of the two forms. Thus, this paper focuses especially on the conformation of pressure-induced unfolding states of both forms of calmodulin, by combining small-angle neutron scattering (SANS) with biophysical techniques such as tyrosines and ANS fluorescence. In contrast to heat denaturation (Gibrat et al., BBA, 2012), the pressure denaturation of calmodulin is reversible up to pressures of 3000bar (300MPa). A pressure-induced compact intermediate state has been found for the two calmodulin forms, but their unfolding pathways are different. A domain compaction and an increase of the ANS fluorescence of holo form have been evidenced. On the contrary, a domain dilatation and an ANS fluorescence decrease have been found for the apo form. The pressure induced an increase of the interdomain distance for both calmodulin forms, suggesting that the central linker of calmodulin is flexible in solution.

  6. Mathematical Knowledge for Teaching and Task Unfolding: An Exploratory Study

    Science.gov (United States)

    Charalambous, Charalambos Y.

    2010-01-01

    Although teachers' knowledge is thought to contribute to the selection and implementation of mathematical tasks, empirical evidence supporting this claim is scarce. To investigate this relationship and understand its nature, this exploratory study examines the unfolding of tasks in a series of lessons led by 2 elementary school teachers who…

  7. Effect of antimicrobial preservatives on partial protein unfolding and aggregation.

    Science.gov (United States)

    Hutchings, Regina L; Singh, Surinder M; Cabello-Villegas, Javier; Mallela, Krishna M G

    2013-02-01

    One-third of protein formulations are multi-dose. These require antimicrobial preservatives (APs); however, some APs have been shown to cause protein aggregation. Our previous work on a model protein cytochrome c indicated that partial protein unfolding, rather than complete unfolding, triggers aggregation. Here, we examined the relative strength of five commonly used APs on such unfolding and aggregation, and explored whether stabilizing the aggregation 'hot-spot' reduces such aggregation. All APs induced protein aggregation in the order m-cresol > phenol > benzyl alcohol > phenoxyethanol > chlorobutanol. All these enhanced the partial protein unfolding that includes a local region which was predicted to be the aggregation 'hot-spot'. The extent of destabilization correlated with the extent of aggregation. Further, we show that stabilizing the 'hot-spot' reduces aggregation induced by all five APs. These results indicate that m-cresol causes the most protein aggregation, whereas chlorobutanol causes the least protein aggregation. The same protein region acts as the 'hot-spot' for aggregation induced by different APs, implying that developing strategies to prevent protein aggregation induced by one AP will also work for others.

  8. Exploring early stages of the chemical unfolding of proteins at the proteome scale.

    Directory of Open Access Journals (Sweden)

    Michela Candotti

    Full Text Available After decades of using urea as denaturant, the kinetic role of this molecule in the unfolding process is still undefined: does urea actively induce protein unfolding or passively stabilize the unfolded state? By analyzing a set of 30 proteins (representative of all native folds through extensive molecular dynamics simulations in denaturant (using a range of force-fields, we derived robust rules for urea unfolding that are valid at the proteome level. Irrespective of the protein fold, presence or absence of disulphide bridges, and secondary structure composition, urea concentrates in the first solvation shell of quasi-native proteins, but with a density lower than that of the fully unfolded state. The presence of urea does not alter the spontaneous vibration pattern of proteins. In fact, it reduces the magnitude of such vibrations, leading to a counterintuitive slow down of the atomic-motions that opposes unfolding. Urea stickiness and slow diffusion is, however, crucial for unfolding. Long residence urea molecules placed around the hydrophobic core are crucial to stabilize partially open structures generated by thermal fluctuations. Our simulations indicate that although urea does not favor the formation of partially open microstates, it is not a mere spectator of unfolding that simply displaces to the right of the folded ←→ unfolded equilibrium. On the contrary, urea actively favors unfolding: it selects and stabilizes partially unfolded microstates, slowly driving the protein conformational ensemble far from the native one and also from the conformations sampled during thermal unfolding.

  9. Protein Unfolding Coupled to Ligand Binding: Differential Scanning Calorimetry Simulation Approach

    Science.gov (United States)

    Celej, Maria Soledad; Fidelio, Gerardo Daniel; Dassie, Sergio Alberto

    2005-01-01

    A comprehensive theoretical description of thermal protein unfolding coupled to ligand binding is presented. The thermodynamic concepts are independent of the method used to monitor protein unfolding but a differential scanning calorimetry is being used as a tool for examining the unfolding process.

  10. Disentangling volumetric and hydrational properties of proteins.

    Science.gov (United States)

    Voloshin, Vladimir P; Medvedev, Nikolai N; Smolin, Nikolai; Geiger, Alfons; Winter, Roland

    2015-02-05

    We used molecular dynamics simulations of a typical monomeric protein, SNase, in combination with Voronoi-Delaunay tessellation to study and analyze the temperature dependence of the apparent volume, Vapp, of the solute. We show that the void volume, VB, created in the boundary region between solute and solvent, determines the temperature dependence of Vapp to a major extent. The less pronounced but still significant temperature dependence of the molecular volume of the solute, VM, is essentially the result of the expansivity of its internal voids, as the van der Waals contribution to VM is practically independent of temperature. Results for polypeptides of different chemical nature feature a similar temperature behavior, suggesting that the boundary/hydration contribution seems to be a universal part of the temperature dependence of Vapp. The results presented here shine new light on the discussion surrounding the physical basis for understanding and decomposing the volumetric properties of proteins and biomolecules in general.

  11. All Photons Imaging Through Volumetric Scattering

    Science.gov (United States)

    Satat, Guy; Heshmat, Barmak; Raviv, Dan; Raskar, Ramesh

    2016-01-01

    Imaging through thick highly scattering media (sample thickness ≫ mean free path) can realize broad applications in biomedical and industrial imaging as well as remote sensing. Here we propose a computational “All Photons Imaging” (API) framework that utilizes time-resolved measurement for imaging through thick volumetric scattering by using both early arrived (non-scattered) and diffused photons. As opposed to other methods which aim to lock on specific photons (coherent, ballistic, acoustically modulated, etc.), this framework aims to use all of the optical signal. Compared to conventional early photon measurements for imaging through a 15 mm tissue phantom, our method shows a two fold improvement in spatial resolution (4db increase in Peak SNR). This all optical, calibration-free framework enables widefield imaging through thick turbid media, and opens new avenues in non-invasive testing, analysis, and diagnosis. PMID:27683065

  12. Unfolding features of bovine testicular hyaluronidase studied by fluorescence spectroscopy and fourier transformed infrared spectroscopy.

    Science.gov (United States)

    Pan, Nina; Cai, Xiaoqiang; Tang, Kai; Zou, Guolin

    2005-11-01

    Chemical unfolding of bovine testicular hyaluronidase (HAase) has been studied by fluorescence spectroscopy and Fourier transformed infrared spectroscopy (FTIR). Thermodynamic parameters were determined for unfolding HAase from changes in the intrinsic fluorescence emission intensity and the formations of several possible unfolding intermediates have been identified. This was further confirmed by representation of fluorescence data in terms of 'phase diagram'. The secondary structures of HAase have been assigned and semiquantitatively estimated from the FTIR. The occurrence of conformational change during chemical unfolding as judged by fluorescence and FTIR spectroscopy indicated that the unfolding of HAase may not follow the typical two-state model.

  13. A Technique for Volumetric CSG Based on Morphology

    DEFF Research Database (Denmark)

    Bærentzen, Jakob Andreas; Christensen, Niels Jørgen

    2001-01-01

    In this paper, a new technique for volumetric CSG is presented. The technique requires the input volumes to correspond to solids which fulfill a voxelization suitability criterion. Assume the CSG operation is union. The volumetric union of two such volumes is defined in terms of the voxelization...

  14. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  15. Colon capsule endoscopy

    Institute of Scientific and Technical Information of China (English)

    Ignacio Fernandez-Urien; Cristina Carretero; Ana Borda; Miguel Mu(n)oz-Navas

    2008-01-01

    Wireless capsule endoscopy has become the first imaging tool for small bowel examination.Recently,new capsule endoscopy applications have been developed,such as esophageal capsule endoscopy and colon capsule endoscopy.Clinical trials results have shown that colon capsule endoscopy is feasible,accurate and safe in patients suffering from colonic diseases.It could be a good alternative in patients refusing conventional colonoscopy or when it is contraindicated.Upcoming studies are needed to demonstrate its utilty for colon cancer screening and other indications such us ulcerative colitis.Comparative studies including both conventional and virtual colonoscopy are also required.

  16. High-irradiance reactors with unfolded aplanatic optics.

    Science.gov (United States)

    Feuermann, Daniel; Gordon, Jeffrey M

    2008-11-01

    Reconstituting the intense irradiance of short-arc discharge lamps at a remote target, at high radiative efficiency, represents a central challenge in the design of high-temperature chemical reactors, heightened by the need for high numerical aperture at both the target and the source. Separating the optical system from both the source and the reactor allows pragmatic operation, monitoring, and control. We explore near-field unfolded aplanats as feasible solutions and report measurements for a prototype that constitutes a double-ellipsoid mirror. We also propose compound unfolded aplanats that collect lamp emission over all angles (in lieu of light recycling optics) and irradiate the reactor over nearly its full circumference.

  17. Unfolding large-scale online collaborative human dynamics

    CERN Document Server

    Zha, Yilong; Zhou, Changsong

    2015-01-01

    Large-scale interacting human activities underlie all social and economic phenomena, but quantitative understanding of regular patterns and mechanism is very challenging and still rare. Self-organized online collaborative activities with precise record of event timing provide unprecedented opportunity. Our empirical analysis of the history of millions of updates in Wikipedia shows a universal double power-law distribution of time intervals between consecutive updates of an article. We then propose a generic model to unfold collaborative human activities into three modules: (i) individual behavior characterized by Poissonian initiation of an action, (ii) human interaction captured by a cascading response to others with a power-law waiting time, and (iii) population growth due to increasing number of interacting individuals. This unfolding allows us to obtain analytical formula that is fully supported by the universal patterns in empirical data. Our modeling approaches reveal "simplicity" beyond complex interac...

  18. An efficient method for unfolding kinetic pressure driven VISAR data

    Institute of Scientific and Technical Information of China (English)

    M.Hess; K.Peterson; A.Harvey-Thompson

    2015-01-01

    Velocity Interferometer System for Any Reflector(VISAR) [Barker and Hollenbach, J. Appl. Phys. 43, 4669(1972)]is a well-known diagnostic that is employed on many shock physics and pulsed-power experiments. With the VISAR diagnostic, the velocity on the surface of any metal flyer can be found. For most experiments employing VISAR, either a kinetic pressure [Grady, Mech. Mater. 29, 181(1998)] or a magnetic pressure [Lemke et al., Intl J. Impact Eng. 38,480(2011)] drives the motion of the flyer. Moreover, reliable prediction of the time-dependent pressure is often a critical component to understanding the physics of these experiments. Although VISAR can provide a precise measurement of a flyer’s surface velocity, the real challenge of this diagnostic implementation is using this velocity to unfold the timedependent pressure. The purpose of this paper is to elucidate a new method for quickly and reliably unfolding VISAR data.

  19. 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.

  20. Unfolding the band structure of GaAsBi

    Science.gov (United States)

    Maspero, R.; Sweeney, S. J.; Florescu, Marian

    2017-02-01

    Typical supercell approaches used to investigate the electronic properties of GaAs(1-x)Bi(x) produce highly accurate, but folded, band structures. Using a highly optimized algorithm, we unfold the band structure to an approximate E≤ft(\\mathbf{k}\\right) relation associated with an effective Brillouin zone. The dispersion relations we generate correlate strongly with experimental results, confirming that a regime of band gap energy greater than the spin-orbit-splitting energy is reached at around 10% bismuth fraction. We also demonstrate the effectiveness of the unfolding algorithm throughout the Brillouin zone (BZ), which is key to enabling transition rate calculations, such as Auger recombination rates. Finally, we show the effect of disorder on the effective masses and identify approximate values for the effective mass of the conduction band and valence bands for bismuth concentrations from 0-12%.

  1. Amyloid protein unfolding and insertion kinetics on neuronal membrane mimics

    Science.gov (United States)

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

    2010-03-01

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

  2. Clinical Application of the Sapphire Unfolder Lens Injection System

    Institute of Scientific and Technical Information of China (English)

    Weiai Guo; Danying Zheng; Zhenyu Li; Yiyong Qian; Zhenping Zhang

    2002-01-01

    Purpose: To summarize the clinical experience of 300 cases using the Sapphire unfloder intraocular lens (IOL) injection system.Methods: After the standard phacoemulsification, an AR40e IOL was implanted using the Sapphire Unfolder. The involved problems during and after the operation were observed and analyzed.Results:The complications occurred during the operation including the crack at the haptic-optic junction in 2 cases, slight kink in the haptic in 5 cases, IOL clamp into the cartridge in 2 cases, posterior capsular rupture in 2 cases and endothelium damage in the central small area in 4 cases. All the patients recovered successfully with IOLs in good position.Conclusion: IOL implantation with the Sapphire Unfolder led to no serious complications and got the satisfactory results.

  3. Folding/Unfolding Properties of Metal Foils in Transformable Structure

    Science.gov (United States)

    Daming, Nie; Zhen, Lu; Kaifeng, Zhang

    2017-01-01

    Transformable structures are widely applied in the aerospace, temporary facilities, etc. Compared to the structures made of polyester materials, the metal foil ones occupy many special advantages while have been rarely investigated. In this study, a series of transformable structures made of four different metal materials, 6065 Al, copper, TA1 and SUS 304 stainless steel, with thickness of 0.1 mm were prepared. Moreover, the folding (i.e., compressing the structure to the lowest height with external force) and unfolding (i.e., extending the structure to the largest height with external force) behaviors of these structures were exhibited and explained by experiments. Besides, the differences and corresponding mechanisms of various materials on the folding/unfolding properties of the structures were examined and discussed.

  4. Multiple unfolding pathways of leucine binding protein (LBP) probed by single-molecule force spectroscopy (SMFS).

    Science.gov (United States)

    Kotamarthi, Hema Chandra; Sharma, Riddhi; Narayan, Satya; Ray, Sayoni; Ainavarapu, Sri Rama Koti

    2013-10-02

    Experimental studies on the folding and unfolding of large multi-domain proteins are challenging, given the proteins' complex energy landscapes with multiple intermediates. Here, we report a mechanical unfolding study of a 346-residue, two-domain leucine binding protein (LBP) from the bacterial periplasm. Forced unfolding of LBP is a prerequisite for its translocation across the cytoplasmic membrane into the bacterial periplasm. During the mechanical stretching of LBP, we observe that 38% of the unfolding flux followed a two-state pathway, giving rise to a single unfolding force peak at ~70 pN with an unfolding contour length of 120 nm in constant-velocity single-molecule pulling experiments. The remaining 62% of the unfolding flux followed multiple three-state pathways, with intermediates having unfolding contour lengths in the range ~20-85 nm. These results suggest that the energy landscape of LBP is complex, with multiple intermediate states, and a large fraction of molecules go through intermediate states during the unfolding process. Furthermore, the presence of the ligand leucine increased the unfolding flux through the two-state pathway from 38% to 65%, indicating the influence of ligand binding on the energy landscape. This study suggests that unfolding through parallel pathways might be a general mechanism for the large two-domain proteins that are translocated to the bacterial periplasmic space.

  5. The Unfolded Protein Response and Chemical Chaperones Reduce Protein Misfolding and Colitis in Mice

    Science.gov (United States)

    CAO, STEWART SIYAN; ZIMMERMANN, ELLEN M.; CHUANG, BRANDY–MENGCHIEH; SONG, BENBO; NWOKOYE, ANOSIKE; WILKINSON, J. ERBY; EATON, KATHRYN A.; KAUFMAN, RANDAL J.

    2013-01-01

    BACKGROUND & AIMS Endoplasmic reticulum (ER) stress has been associated with development of inflammatory bowel disease. We examined the effects of ER stress–induced chaperone response and the orally active chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (PBA), which facilitate protein folding and reduce ER stress, in mice with colitis. METHODS We used dextran sulfate sodium (DSS) to induce colitis in mice that do not express the transcription factor ATF6α or the protein chaperone P58IPK. We examined the effects of TUDCA and PBA in cultured intestinal epithelial cells (IECs); in wild-type, P58IPK−/−, and Atf6α−/− mice with colitis; and in Il10−/− mice. RESULTS P58IPK−/− and Atf6α−/− mice developed more severe colitis following administration of DSS than wild-type mice. IECs from P58IPK−/− mice had excessive ER stress, and apoptotic signaling was activated in IECs from Atf6α−/− mice. Inflammatory stimuli induced ER stress signals in cultured IECs, which were reduced by incubation with TUDCA or PBA. Oral administration of either PBA or TUDCA reduced features of DSS-induced acute and chronic colitis in wild-type mice, the colitis that develops in Il10−/− mice, and DSS-induced colitis in P58IPK−/− and Atf6α−/− mice. Reduced signs of colonic inflammation in these mice were associated with significantly decreased ER stress in colonic epithelial cells. CONCLUSIONS The unfolded protein response induces expression of genes that encode chaperones involved in ER protein folding; these factors prevent induction of colitis in mice. Chemical chaperones such as TUDCA and PBA alleviate different forms of colitis in mice and might be developed for treatment of inflammatory bowel diseases. PMID:23336977

  6. Protein co-translocational unfolding depends on the direction of pulling

    Science.gov (United States)

    Rodriguez-Larrea, David; Bayley, Hagan

    2014-09-01

    Protein unfolding and translocation through pores occurs during trafficking between organelles, protein degradation and bacterial toxin delivery. In vivo, co-translocational unfolding can be affected by the end of the polypeptide that is threaded into the pore first. Recently, we have shown that co-translocational unfolding can be followed in a model system at the single-molecule level, thereby unravelling molecular steps and their kinetics. Here, we show that the unfolding kinetics of the model substrate thioredoxin, when pulled through an α-haemolysin pore, differ markedly depending on whether the process is initiated from the C terminus or the N terminus. Further, when thioredoxin is pulled from the N terminus, the unfolding pathway bifurcates: some molecules finish unfolding quickly, while others finish ~100 times slower. Our findings have important implications for the understanding of biological unfolding mechanisms and in the application of nanopore technology for the detection of proteins and their modifications.

  7. Unfolding Ubiquitin by force: water mediated H-bond destabilization

    Directory of Open Access Journals (Sweden)

    Germán Pabón

    2012-12-01

    Full Text Available Using the “pull and wait” (PNW simulation protocol at 300 K, we studied the unfolding by force of an ubiquitin molecule. PNW was implemented in the CHARMM program using an integration time step of 1 fs and a uniform dielectric constant of 1. The ubiquitin molecule, initially solvated, was put under mechanical stress, exerting forces from different directions. The rupture of five hydrogen bonds between parallel strands β1 and β5 takes place during the extension from 13 to 15 Å, defines a mechanical barrier for unfolding and dominates the point of maximum unfolding force. The simulations described here show that given adequate time, a small applied force can destabilize those five H-bonds relative to the bonds that can be created to water molecules; allowing the formation of stable H-bonds between a single water molecule and the donor and acceptor groups of the interstrand H-bonds. Thus, simulations run with PNW show that the force is not responsible for “ripping apart” the backbone H-bonds; it merely destabilizes them making them less stable than the H-bonds they can make with water. Additional simulations show that the force necessary to destabilize the H-bonds and allow them to be replaced by H-bonds to water molecules depends strongly on the pulling direction. By using a simulation protocol that allows equilibration at each extension we have been able to observe the details of the events leading to the unfolding of ubiquitin by mechanical force.

  8. 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....

  9. Thermodynamics of the temperature-induced unfolding of globular proteins.

    OpenAIRE

    Khechinashvili, N. N.; Janin, J.; Rodier, F.

    1995-01-01

    The heat capacity, enthalpy, entropy, and Gibbs energy changes for the temperature-induced unfolding of 11 globular proteins of known three-dimensional structure have been obtained by microcalorimetric measurements. Their experimental values are compared to those we calculate from the change in solvent-accessible surface area between the native proteins and the extended polypeptide chain. We use proportionality coefficients for the transfer (hydration) of aliphatic, aromatic, and polar groups...

  10. 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.

  11. 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.

  12. Assessing Mitochondrial Unfolded Protein Response in Mammalian Cells.

    Science.gov (United States)

    Durand, Fiona; Hoogenraad, Nicholas

    2017-01-01

    Mitochondria serve a key role in the supply of energy to cells in the form of ATP, the supply of essential cellular components such as phospholipids and heme, in apoptosis and as a mediator of cellular signaling pathways. Mitochondria have their own DNA, consisting of a small number of genes, but the majority of the total protein complement is encoded in the nucleus, synthesized in the cytosol, and is imported into the mitochondria in a largely, if not completely unfolded form. These proteins need to be folded into their functional form within the organelle with the concomitant requirement that the organelle has its own suite of molecular chaperones and complexes to degrade damaged proteins to avoid stress arising from accumulation of unfolded proteins. This mitochondrial unfolded protein response can also be induced in cells and protein regulation can be determined using western blot, luciferase reporter assay, and sensitive mass spectrometry techniques. In this chapter, we describe a method to induce mtUPR in mammalian cells and the three methods to analyze components involved in it.

  13. Numerical Simulation of Folding and Unfolding of Proteins

    CERN Document Server

    Kouza, Maksim

    2013-01-01

    The thesis examines in detail the folding and unfolding processes of a number of proteins including hbSBD, DDLNF4, single and multi Ubiquitin. Using simplified coarse-grained off-lattice Go model and CD experiments we have shown the two-state behavior of hbSBD protein. It was shown that refolding pathways of single Ubiquitin depend on what end is anchored to the surface. Namely, the fixation of the N-terminal changes refolding pathways but anchoring the C-terminal leaves them unchanged. Interestingly, the end fixation has no effect on multi-domain Ubiquitin. Using the Go modeling and all-atom models with explicit water, we have studied the mechanical unfolding mechanism of DDFLN4 in detail. We predict that, contrary to the AFM experiments, an additional unfolding peak would occur at the end-to-end $\\Delta R \\approx 1.5 $nm in the force-extension curve. Our study reveals the important role of non-native interactions which are responsible for a peak located at $\\Delta R \\approx 22 $nm. This peak can not be enco...

  14. Differential stability of the bovine prion protein upon urea unfolding

    Science.gov (United States)

    Julien, Olivier; Chatterjee, Subhrangsu; Thiessen, Angela; Graether, Steffen P; Sykes, Brian D

    2009-01-01

    Prion diseases, or transmissible spongiform encephalopathies, are a group of infectious neurological diseases associated with the structural conversion of an endogenous protein (PrP) in the central nervous system. There are two major forms of this protein: the native and noninfectious cellular form, PrPC; and the misfolded, infectious, and proteinase K-resistant form, PrPSc. The C-terminal domain of PrPC is mainly α-helical in structure, whereas PrPSc in known to aggregate into an assembly of β-sheets, forming amyloid fibrils. To identify the regions of PrPC potentially involved in the initial steps of the conversion to the infectious conformation, we have used high-resolution NMR spectroscopy to characterize the stability and structure of bovine recombinant PrPC (residues 121 to 230) during unfolding with the denaturant urea. Analysis of the 800 MHz 1H NMR spectra reveals region-specific information about the structural changes occurring upon unfolding. Our data suggest that the dissociation of the native β-sheet of PrPC is a primary step in the urea-induced unfolding process, while strong hydrophobic interactions between helices α1 and α3, and between α2 and α3, stabilize these regions even at very high concentrations of urea. PMID:19693935

  15. LEAKAGE OF COLONIC ANASTOMOSIS AFTER COLON RESECTION

    Institute of Scientific and Technical Information of China (English)

    Kanellos I; Pramateftakis MG

    2004-01-01

    Objective To present the diagnosis and management of anastomotic leakage after colon resection. Methods Early diagnosis and urgent therapeutic intervention are required in order to avert life-threatening conditions that may be caused by anastomotic leakage. Results The diagnosis of anastomotic leakage is based on clinical features, peripheral blood investigations and abdominal computed tomography (CT) scan. Major leaks are defined by symptoms of peritonitis and septicaemia due to leakage. Major leaks should be managed operatively. Minor leaks can be managed conservatively with successful outcomes. Conclusion Leakage of colonic anastomosis remains the most serious complication after colon resection. It is a major cause of postoperative morbidity and mortality. A high index of suspicion is required in order to detect early, nonspecific signs of a leakage and urgent surgical intervention is usually required to avert life-threatening events.

  16. CT findings of colonic complications associated with colon cancer.

    Science.gov (United States)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang-Jin

    2010-01-01

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

  17. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2010-04-15

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

  18. Cat scratch colon.

    Science.gov (United States)

    Ruiz-Rebollo, M Lourdes; Velayos-Jiménez, Benito; Prieto de Paula, José María; Alvarez Quiñones, María; González Hernández, José Manuel

    2011-01-01

    Over the past few years, we have read several publications regarding the term "cat scratch colon." This neologism was developed to define some bright red linear markings seen in the colonic mucosa that resemble scratches made by a cat. We would like to communicate a recent case attended at our institution.

  19. Cat Scratch Colon

    Directory of Open Access Journals (Sweden)

    M. Lourdes Ruiz-Rebollo

    2011-01-01

    Full Text Available Over the past few years, we have read several publications regarding the term “cat scratch colon.” This neologism was developed to define some bright red linear markings seen in the colonic mucosa that resemble scratches made by a cat. We would like to communicate a recent case attended at our institution.

  20. Colon cancer - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100157.htm Colon cancer - Series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The colon, or large intestine, is a muscular tube that ...

  1. Treatment Option Overview (Colon Cancer)

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colon Cancer Treatment (PDQ®)–Patient Version General Information About Colon Cancer Go to Health Professional Version Key Points Colon ...

  2. General Information about Colon Cancer

    Science.gov (United States)

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colon Cancer Treatment (PDQ®)–Patient Version General Information About Colon Cancer Go to Health Professional Version Key Points Colon ...

  3. Understanding your colon cancer risk

    Science.gov (United States)

    Colon cancer - prevention; Colon cancer - screening ... We do not know what causes colon cancer, but we do know some of the things that may increase the risk of getting it, such as: Age. Your risk increases ...

  4. Unfolding pathway of CotA-laccase and the role of copper on the prevention of refolding through aggregation of the unfolded state

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Andre T. [Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Av. da Republica, 2780-157 Oeiras (Portugal); Lopes, Carlos [Centre for Molecular and Structural Biomedicine, Institute for Biotechnology and Bioengineering, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Martins, Ligia O. [Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Av. da Republica, 2780-157 Oeiras (Portugal); Melo, Eduardo Pinho, E-mail: emelo@ualg.pt [Centre for Molecular and Structural Biomedicine, Institute for Biotechnology and Bioengineering, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer CotA-laccase unfolds with an intermediate state. Black-Right-Pointing-Pointer Copper stabilizes the native and the intermediate state. Black-Right-Pointing-Pointer Copper binding to the unfolded state prevents refolding through protein aggregation. Black-Right-Pointing-Pointer Copper incorporation in CotA-laccase occurs as a later step during folding. -- Abstract: Copper is a redox-active metal and the main player in electron transfer reactions occurring in multicopper oxidases. The role of copper in the unfolding pathway and refolding of the multicopper oxidase CotA laccase in vitro was solved using double-jump stopped-flow experiments. Unfolding of apo- and holo-CotA was described as a three-state process with accumulation of an intermediate in between the native and unfolded state. Copper stabilizes the native holo-CotA but also the intermediate state showing that copper is still bound to this state. Also, copper binds to unfolded holo-CotA in a non-native coordination promoting CotA aggregation and preventing refolding to the native structure. These results gather information on unfolding/folding pathways of multicopper oxidases and show that copper incorporation in vivo should be a tight controlled process as copper binding to the unfolded state under native conditions promotes protein aggregation.

  5. Direct observation of markovian behavior of the mechanical unfolding of individual proteins.

    Science.gov (United States)

    Cao, Yi; Kuske, Rachel; Li, Hongbin

    2008-07-01

    Single-molecule force-clamp spectroscopy is a valuable tool to analyze unfolding kinetics of proteins. Previous force-clamp spectroscopy experiments have demonstrated that the mechanical unfolding of ubiquitin deviates from the generally assumed Markovian behavior and involves the features of glassy dynamics. Here we use single molecule force-clamp spectroscopy to study the unfolding kinetics of a computationally designed fast-folding mutant of the small protein GB1, which shares a similar beta-grasp fold as ubiquitin. By treating the mechanical unfolding of polyproteins as the superposition of multiple identical Poisson processes, we developed a simple stochastic analysis approach to analyze the dwell time distribution of individual unfolding events in polyprotein unfolding trajectories. Our results unambiguously demonstrate that the mechanical unfolding of NuG2 fulfills all criteria of a memoryless Markovian process. This result, in contrast with the complex mechanical unfolding behaviors observed for ubiquitin, serves as a direct experimental demonstration of the Markovian behavior for the mechanical unfolding of a protein and reveals the complexity of the unfolding dynamics among structurally similar proteins. Furthermore, we extended our method into a robust and efficient pseudo-dwell-time analysis method, which allows one to make full use of all the unfolding events obtained in force-clamp experiments without categorizing the unfolding events. This method enabled us to measure the key parameters characterizing the mechanical unfolding energy landscape of NuG2 with improved precision. We anticipate that the methods demonstrated here will find broad applications in single-molecule force-clamp spectroscopy studies for a wide range of proteins.

  6. Soil volumetric water content measurements using TDR technique

    Directory of Open Access Journals (Sweden)

    S. Vincenzi

    1996-06-01

    Full Text Available A physical model to measure some hydrological and thermal parameters in soils will to be set up. The vertical profiles of: volumetric water content, matric potential and temperature will be monitored in different soils. The volumetric soil water content is measured by means of the Time Domain Reflectometry (TDR technique. The result of a test to determine experimentally the reproducibility of the volumetric water content measurements is reported together with the methodology and the results of the analysis of the TDR wave forms. The analysis is based on the calculation of the travel time of the TDR signal in the wave guide embedded in the soil.

  7. Iterative reconstruction of volumetric particle distribution

    Science.gov (United States)

    Wieneke, Bernhard

    2013-02-01

    For tracking the motion of illuminated particles in space and time several volumetric flow measurement techniques are available like 3D-particle tracking velocimetry (3D-PTV) recording images from typically three to four viewing directions. For higher seeding densities and the same experimental setup, tomographic PIV (Tomo-PIV) reconstructs voxel intensities using an iterative tomographic reconstruction algorithm (e.g. multiplicative algebraic reconstruction technique, MART) followed by cross-correlation of sub-volumes computing instantaneous 3D flow fields on a regular grid. A novel hybrid algorithm is proposed here that similar to MART iteratively reconstructs 3D-particle locations by comparing the recorded images with the projections calculated from the particle distribution in the volume. But like 3D-PTV, particles are represented by 3D-positions instead of voxel-based intensity blobs as in MART. Detailed knowledge of the optical transfer function and the particle image shape is mandatory, which may differ for different positions in the volume and for each camera. Using synthetic data it is shown that this method is capable of reconstructing densely seeded flows up to about 0.05 ppp with similar accuracy as Tomo-PIV. Finally the method is validated with experimental data.

  8. Sonography in Colonic Diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Mi Yun; Choi, Byung Hun; Kim, Keum Won; Kwon, Kwi Ryun; Lim, Myung Ah; Kim, Sung Soo; Choi, Chang Ho [Sunlin Presbyterian Hospital, Pohang (Korea, Republic of)

    1996-06-15

    To evaluate the sonographic findings and the diagnostic value of colonic diverticulitis. We evaluated the sonograms of 26 patients with colonic diverticulitis retrospectively. The final diagnosis was based on the pathologic interpretation of a surgical specimen (5 cases), clinical course (21 cases), on barium enema (12 cases) and colonoscopy (1 case). Twenty-five patients had acute diverticulitis in the cecum and 1 patient in the descending colon. On sonography, an oval or short tubular focus which protruded from the colonic wall was seen in 23 patients (88%) and the longest diameter were from 0.5 cm to 3 cm (mean 1.4cm). The lesions were echogenic in 8 cases and hypoechoic in 17 cases. Segmental thickening of the colonic wall was seen in 13 patients (50%), of these, protruding focus was seen in 92%. Pericolic abscess located inposterolateral and medial portion to the colon was seen in 11 patients (42%). Infiltration in pericolic fat(50%), enlargement of pericolic lymph nodes (27%) and small pericolic fluid (8%) were also seen. Our results show that ultrasonography is useful technique in the diagnosis of colonic diverticulitis and in the differentiation from acute appendicitis

  9. Retrocyclins neutralize bacterial toxins by potentiating their unfolding.

    Science.gov (United States)

    Kudryashova, Elena; Seveau, Stephanie; Lu, Wuyuan; Kudryashov, Dmitri S

    2015-04-15

    Defensins are a class of immune peptides with a broad range of activities against bacterial, fungal and viral pathogens. Besides exerting direct anti-microbial activity via dis-organization of bacterial membranes, defensins are also able to neutralize various unrelated bacterial toxins. Recently, we have demonstrated that in the case of human α- and β-defensins, this later ability is achieved through exploiting toxins' marginal thermodynamic stability, i.e. defensins act as molecular anti-chaperones unfolding toxin molecules and exposing their hydrophobic regions and thus promoting toxin precipitation and inactivation [Kudryashova et al. (2014) Immunity 41, 709-721]. Retrocyclins (RCs) are humanized synthetic θ-defensin peptides that possess unique cyclic structure, differentiating them from α- and β-defensins. Importantly, RCs are more potent against some bacterial and viral pathogens and more stable than their linear counterparts. However, the mechanism of bacterial toxin inactivation by RCs is not known. In the present study, we demonstrate that RCs facilitate unfolding of bacterial toxins. Using differential scanning fluorimetry (DSF), limited proteolysis and collisional quenching of internal tryptophan fluorescence, we show that hydrophobic regions of toxins normally buried in the molecule interior become more exposed to solvents and accessible to proteolytic cleavage in the presence of RCs. The RC-induced unfolding of toxins led to their precipitation and abrogated activity. Toxin inactivation by RCs was strongly diminished under reducing conditions, but preserved at physiological salt and serum concentrations. Therefore, despite significant structural diversity, α-, β- and θ-defensins employ similar mechanisms of toxin inactivation, which may be shared by anti-microbial peptides from other families.

  10. Investigating different analytical procedures to unfold neutron energy spectra, using HEPRO software to compare existing algorithms

    CERN Document Server

    Moghimzadeh Mohebi, A

    1999-01-01

    A system of programs is described which can be used for unfolding particle spectra from measured pulse height distribution, provided the corresponding response functions are known. There are two reasons for re-opening the question of unfolding: to discuss the properties of several unfolding algorithms and to describe a system of programs developed in the past to unfold neutron spectra. In the first part, least squares algorithms known from literature are described and discussed together with the MIEKE Monte Carlo unfolding code. The second part contains a detailed description of the codes, which are available on a diskette. In the discussion of examples it is shown that the MIEKE Monte Carlo code is well suited for unfolding neutron and photon induced pulse height distributions. For the resulting particle spectra a consistent uncertainty analysis can be performed.

  11. Characterizing volumetric deformation behavior of naturally occuring bituminous sand materials

    CSIR Research Space (South Africa)

    Anochie-Boateng, Joseph

    2009-05-01

    Full Text Available newly proposed hydrostatic compression test procedure. The test procedure applies field loading conditions of off-road construction and mining equipment to closely simulate the volumetric deformation and stiffness behaviour of oil sand materials. Based...

  12. Hyperspectral image classification based on volumetric texture and dimensionality reduction

    Science.gov (United States)

    Su, Hongjun; Sheng, Yehua; Du, Peijun; Chen, Chen; Liu, Kui

    2015-06-01

    A novel approach using volumetric texture and reduced-spectral features is presented for hyperspectral image classification. Using this approach, the volumetric textural features were extracted by volumetric gray-level co-occurrence matrices (VGLCM). The spectral features were extracted by minimum estimated abundance covariance (MEAC) and linear prediction (LP)-based band selection, and a semi-supervised k-means (SKM) clustering method with deleting the worst cluster (SKMd) bandclustering algorithms. Moreover, four feature combination schemes were designed for hyperspectral image classification by using spectral and textural features. It has been proven that the proposed method using VGLCM outperforms the gray-level co-occurrence matrices (GLCM) method, and the experimental results indicate that the combination of spectral information with volumetric textural features leads to an improved classification performance in hyperspectral imagery.

  13. Designing remote web-based mechanical-volumetric flow meter ...

    African Journals Online (AJOL)

    ... remote web-based mechanical-volumetric flow meter reading systems based on ... damage and also provides the ability to control and manage consumption. ... existing infrastructure of the telecommunications is used in data transmission.

  14. Molecular simulation of the reversible mechanical unfolding of proteins.

    Science.gov (United States)

    Rathore, Nitin; Yan, Qiliang; de Pablo, Juan J

    2004-03-22

    In this work we have combined a Wang-Landau sampling scheme [F. Wang and D. Landau, Phys. Rev. Lett. 86, 2050 (2001)] with an expanded ensemble formalism to yield a simple and powerful method for computing potentials of mean force. The new method is implemented to investigate the mechanical deformation of proteins. Comparisons are made with analytical results for simple model systems such as harmonic springs and Rouse chains. The method is then illustrated on a model 15-residue alanine molecule in an implicit solvent. Results for mechanical unfolding of this oligopeptide are compared to those of steered molecular dynamics calculations.

  15. Unfolding multicourse case study: developing students' administrative competencies.

    Science.gov (United States)

    Porter-Wenzlaffs, Linda J

    2013-01-01

    Providing students with learning opportunities that integrate disparate data into meaningful constructs can be a challenge for faculty. The author discusses an unfolding case study that provided simulated learning opportunities related to administrative student competencies, staged to increase in complexity and scope over time while affording multiple student evaluation opportunities. A hybrid delivery format was used, including Blackboard Learn e-technology, to support individual student assignments and small group collaboration, cloud technology for shared student document development, Excel budget manipulation, and face-to-face classroom interactions.

  16. Cluster algebras of finite mutation type via unfoldings

    CERN Document Server

    Felikson, Anna; Tumarkin, Pavel

    2010-01-01

    We complete classification of mutation-finite cluster algebras by extending the technique derived by Fomin, Shapiro, and Thurston to skew-symmetrizable case. We show that every mutation-finite skew-symmetrizable matrix admits an unfolding which embeds the mutation class of mutation-finite skew-symmetrizable matrix to the mutation class of some mutation-finite skew-symmetric matrix. In particular, this establishes a correspondence between almost all skew-symmetrizable mutation-finite cluster algebras and triangulated marked bordered surfaces.

  17. 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...... of in-depth examination of agreement variation, as a strategy for increasing the level of inter-rater agreement. By identifying and limiting the most important sources of disagreement, ultimately instrument reliability can be improved. Keywords: inter-rater, reliability, sources of disagreement, kappa...

  18. ARU – towards automatic unfolding of detector effects

    CERN Document Server

    Dembinski, H P

    2011-01-01

    This article presents the ARU algorithm, a general non-interactive algorithmfor the unfolding of detector effects (resolution effects, efficiency, non-linearresponse) from one-dimensional data distributions. ARU uses an unbinnedmaximum-likelihood fit with a weighted regularization term, based on the rel-ative information in the solution with respect to a reference distribution. Theoptimal regularization weight is found by minimizing the mean squared errorof the solution. The algorithm’s performance is demonstrated in a study of atoy data sets. The analysis shows that the bias on average is smaller than thestatistical uncertainties which are properly estimated by the fit.

  19. Natively unfolded domains in endocytosis: hooks, lines and linkers

    OpenAIRE

    Dafforn, Timothy R.; Smith, Corinne J I

    2004-01-01

    It is commonly assumed that a protein must adopt a tertiary structure to achieve its active native state and that regions of a protein that are devoid of α-helix or β-sheet structures are functionally inert. Although extended proline-rich regions are recognized as presenting binding motifs to, for example, Src homology 2 (SH2) and SH3 domains, the idea persists that natively unfolded regions in functional proteins are simply 'spacers' between the folded domains. Such a view has been challenge...

  20. 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.

  1. Unfolded protein response in plants: one master, many questions.

    Science.gov (United States)

    Ruberti, Cristina; Kim, Sang-Jin; Stefano, Giovanni; Brandizzi, Federica

    2015-10-01

    To overcome endoplasmic reticulum (ER) stress, ER-localized stress sensors actuate distinct downstream organelle-nucleus signaling pathways to invoke a cytoprotective response, known as the unfolded protein response (UPR). Compared to yeast and metazoans, plant UPR studies are more recent but nevertheless fascinating. Here we discuss recent discoveries in plant UPR, highlight conserved and unique features of the plant UPR as well as critical yet-open questions whose answers will likely make significant contributions to the understanding plant ER stress management.

  2. Increasing the volumetric efficiency of Diesel engines by intake pipes

    Science.gov (United States)

    List, Hans

    1933-01-01

    Development of a method for calculating the volumetric efficiency of piston engines with intake pipes. Application of this method to the scavenging pumps of two-stroke-cycle engines with crankcase scavenging and to four-stroke-cycle engines. The utility of the method is demonstrated by volumetric-efficiency tests of the two-stroke-cycle engines with crankcase scavenging. Its practical application to the calculation of intake pipes is illustrated by example.

  3. CT Findings of Colonic Complications Associated with Colon Cancer

    OpenAIRE

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang-Jin

    2010-01-01

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely oc...

  4. Activation foils unfolding for neutron spectrometry: Comparison of different deconvolution methods

    Energy Technology Data Exchange (ETDEWEB)

    Tripathy, S.P. [Radiation Safety Systems Division, BARC, Mumbai 400085 (India)], E-mail: sam.tripathy@gmail.com; Sunil, C. [Radiation Safety Systems Division, BARC, Mumbai 400085 (India); Nandy, M. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700064 (India); Sarkar, P.K. [Radiation Safety Systems Division, BARC, Mumbai 400085 (India); Variable Energy Cyclotron Centre, 1/AF Bidhan Nagar, Kolkata 700064 (India); Sharma, D.N. [Radiation Safety Systems Division, BARC, Mumbai 400085 (India); Mukherjee, B. [Deutsches Elektronen-Synchrotron, LLRF Group, D-22607 Hamburg (Germany)

    2007-12-21

    The results obtained from the activation foils measurement are unfolded using two different deconvolution methods such as BUNKI and genetic algorithm (GA). The spectra produced by these codes agree fairly with each other and are comparable with that measured previously for the same system using NE213 liquid scintillator and by unfolding the neutron-induced proton pulse height distribution using two different methods, viz. FERDOR and BUNKI. The details of various unfolding procedures used in this work are reported in this paper.

  5. Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation.

    Science.gov (United States)

    Dalby, Andrew; Shamsir, Mohd Shahir

    2015-01-01

    Molecular dynamics simulations have been used extensively to model the folding and unfolding of proteins. The rates of folding and unfolding should follow the Arrhenius equation over a limited range of temperatures. This study shows that molecular dynamic simulations of the unfolding of crambin between 500K and 560K do follow the Arrhenius equation. They also show that while there is a large amount of variation between the simulations the average values for the rate show a very high degree of correlation.

  6. Temperature, pressure, and electrochemical constraints on protein speciation: Group additivity calculation of the standard molal thermodynamic properties of ionized unfolded proteins

    Directory of Open Access Journals (Sweden)

    J. M. Dick

    2006-01-01

    Full Text Available Thermodynamic calculations can be used to quantify environmental constraints on the speciation of proteins, such as the pH and temperature dependence of ionization state, and the relative chemical stabilities of proteins in different biogeochemical settings. These calculations depend in part on values of the standard molal Gibbs energies of proteins and their ionization reactions as a function of temperature and pressure. Because these values are not generally available, we calculated values of the standard molal thermodynamic properties at 25°C and 1 bar as well as the revised Helgeson-Kirkham-Flowers equations of state parameters of neutral and charged zwitterionic reference model compounds including aqueous amino acids, polypeptides, and unfolded proteins. The experimental calorimetric and volumetric data for these species taken from the literature were combined with group additivity algorithms to calculate the properties and parameters of neutral and ionized sidechain and backbone groups in unfolded proteins. The resulting set of group contributions enables the calculation of the standard molal Gibbs energy, enthalpy, entropy, isobaric heat capacity, volume, and isothermal compressibility of unfolded proteins in a range of proton ionization states to temperatures and pressures exceeding 100°C and 1000 bar. This approach provides a useful frame of reference for thermodynamic studies of protein folding and complexation reactions. It can also be used to assign provisional values of the net charge and Gibbs energy of ionized proteins as a function of temperature and pH. Using these values, an Eh-pH diagram for a reaction representing the speciation of extracellular proteins from Pyrococcus furiosus and Bacillus subtilis was generated. The predicted predominance limits of these proteins correspond with the different electrochemical conditions of hydrothermal vents and soils. More comprehensive calculations of this kind may reveal pervasive

  7. Temperature, pressure, and electrochemical constraints on protein speciation: Group additivity calculation of the standard molal thermodynamic properties of ionized unfolded proteins

    Science.gov (United States)

    Dick, J. M.; Larowe, D. E.; Helgeson, H. C.

    2006-07-01

    Thermodynamic calculations can be used to quantify environmental constraints on the speciation of proteins, such as the pH and temperature dependence of ionization state, and the relative chemical stabilities of proteins in different biogeochemical settings. These calculations depend in part on values of the standard molal Gibbs energies of proteins and their ionization reactions as a function of temperature and pressure. Because these values are not generally available, we calculated values of the standard molal thermodynamic properties at 25°C and 1 bar as well as the revised Helgeson-Kirkham-Flowers equations of state parameters of neutral and charged zwitterionic reference model compounds including aqueous amino acids, polypeptides, and unfolded proteins. The experimental calorimetric and volumetric data for these species taken from the literature were combined with group additivity algorithms to calculate the properties and parameters of neutral and ionized sidechain and backbone groups in unfolded proteins. The resulting set of group contributions enables the calculation of the standard molal Gibbs energy, enthalpy, entropy, isobaric heat capacity, volume, and isothermal compressibility of unfolded proteins in a range of proton ionization states to temperatures and pressures exceeding 100°C and 1000 bar. This approach provides a useful frame of reference for thermodynamic studies of protein folding and complexation reactions. It can also be used to assign provisional values of the net charge and Gibbs energy of ionized proteins as a function of temperature and pH. Using these values, an Eh-pH diagram for a reaction representing the speciation of extracellular proteins from Pyrococcus furiosus and Bacillus subtilis was generated. The predicted predominance limits of these proteins correspond with the different electrochemical conditions of hydrothermal vents and soils. More comprehensive calculations of this kind may reveal pervasive chemical potential

  8. Colonic potassium handling

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Matos, Joana E.; Prætorius, Helle;

    2010-01-01

    regulated by hormones and adapts readily to changes in dietary K+ intake, aldosterone and multiple local paracrine agonists. In chronic renal insufficiency, colonic K+ secretion is greatly enhanced and becomes an important accessory K+ excretory pathway. During severe diarrheal diseases of different causes......, intestinal K+ losses caused by activated ion secretion may become life threatening. This topical review provides an update of the molecular mechanisms and the regulation of mammalian colonic K+ absorption and secretion. It is motivated by recent results, which have identified the K+ secretory ion channel...... in the apical membrane of distal colonic enterocytes. The directed focus therefore covers the role of the apical Ca2+ and cAMP-activated BK channel (KCa1.1) as the apparently only secretory K+ channel in the distal colon....

  9. Laparoscopic Colon Resection

    Science.gov (United States)

    ... thorough evaluation by a surgeon qualified in laparoscopic colon resection in consultation with your primary ... Olympic Blvd., Suite 600 Los Angeles, CA 90064 Tel: (310) 437-0544 Fax: (310) 437- ...

  10. Serial volumetric registration of pulmonary CT studies

    Science.gov (United States)

    Silva, José Silvestre; Silva, Augusto; Sousa Santos, Beatriz

    2008-03-01

    Detailed morphological analysis of pulmonary structures and tissue, provided by modern CT scanners, is of utmost importance as in the case of oncological applications both for diagnosis, treatment, and follow-up. In this case, a patient may go through several tomographic studies throughout a period of time originating volumetric sets of image data that must be appropriately registered in order to track suspicious radiological findings. The structures or regions of interest may change their position or shape in CT exams acquired at different moments, due to postural, physiologic or pathologic changes, so, the exams should be registered before any follow-up information can be extracted. Postural mismatching throughout time is practically impossible to avoid being particularly evident when imaging is performed at the limiting spatial resolution. In this paper, we propose a method for intra-patient registration of pulmonary CT studies, to assist in the management of the oncological pathology. Our method takes advantage of prior segmentation work. In the first step, the pulmonary segmentation is performed where trachea and main bronchi are identified. Then, the registration method proceeds with a longitudinal alignment based on morphological features of the lungs, such as the position of the carina, the pulmonary areas, the centers of mass and the pulmonary trans-axial principal axis. The final step corresponds to the trans-axial registration of the corresponding pulmonary masked regions. This is accomplished by a pairwise sectional registration process driven by an iterative search of the affine transformation parameters leading to optimal similarity metrics. Results with several cases of intra-patient, intra-modality registration, up to 7 time points, show that this method provides accurate registration which is needed for quantitative tracking of lesions and the development of image fusion strategies that may effectively assist the follow-up process.

  11. Volumetric optoacoustic monitoring of endovenous laser treatments

    Science.gov (United States)

    Fehm, Thomas F.; Deán-Ben, Xosé L.; Schaur, Peter; Sroka, Ronald; Razansky, Daniel

    2016-03-01

    Chronic venous insufficiency (CVI) is one of the most common medical conditions with reported prevalence estimates as high as 30% in the adult population. Although conservative management with compression therapy may improve the symptoms associated with CVI, healing often demands invasive procedures. Besides established surgical methods like vein stripping or bypassing, endovenous laser therapy (ELT) emerged as a promising novel treatment option during the last 15 years offering multiple advantages such as less pain and faster recovery. Much of the treatment success hereby depends on monitoring of the treatment progression using clinical imaging modalities such as Doppler ultrasound. The latter however do not provide sufficient contrast, spatial resolution and three-dimensional imaging capacity which is necessary for accurate online lesion assessment during treatment. As a consequence, incidence of recanalization, lack of vessel occlusion and collateral damage remains highly variable among patients. In this study, we examined the capacity of volumetric optoacoustic tomography (VOT) for real-time monitoring of ELT using an ex-vivo ox foot model. ELT was performed on subcutaneous veins while optoacoustic signals were acquired and reconstructed in real-time and at a spatial resolution in the order of 200μm. VOT images showed spatio-temporal maps of the lesion progression, characteristics of the vessel wall, and position of the ablation fiber's tip during the pull back. It was also possible to correlate the images with the temperature elevation measured in the area adjacent to the ablation spot. We conclude that VOT is a promising tool for providing online feedback during endovenous laser therapy.

  12. Treatment planning for volumetric modulated arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bedford, James L. [Joint Department of Physics, Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT (United Kingdom)

    2009-11-15

    Purpose: Volumetric modulated arc therapy (VMAT) is a specific type of intensity-modulated radiation therapy (IMRT) in which the gantry speed, multileaf collimator (MLC) leaf position, and dose rate vary continuously during delivery. A treatment planning system for VMAT is presented. Methods: Arc control points are created uniformly throughout one or more arcs. An iterative least-squares algorithm is used to generate a fluence profile at every control point. The control points are then grouped and all of the control points in a given group are used to approximate the fluence profiles. A direct-aperture optimization is then used to improve the solution, taking into account the allowed range of leaf motion of the MLC. Dose is calculated using a fast convolution algorithm and the motion between control points is approximated by 100 interpolated dose calculation points. The method has been applied to five cases, consisting of lung, rectum, prostate and seminal vesicles, prostate and pelvic lymph nodes, and head and neck. The resulting plans have been compared with segmental (step-and-shoot) IMRT and delivered and verified on an Elekta Synergy to ensure practicality. Results: For the lung, prostate and seminal vesicles, and rectum cases, VMAT provides a plan of similar quality to segmental IMRT but with faster delivery by up to a factor of 4. For the prostate and pelvic nodes and head-and-neck cases, the critical structure doses are reduced with VMAT, both of these cases having a longer delivery time than IMRT. The plans in general verify successfully, although the agreement between planned and measured doses is not very close for the more complex cases, particularly the head-and-neck case. Conclusions: Depending upon the emphasis in the treatment planning, VMAT provides treatment plans which are higher in quality and/or faster to deliver than IMRT. The scheme described has been successfully introduced into clinical use.

  13. Carbohydrate Markers in Colon Carcinoma

    Directory of Open Access Journals (Sweden)

    Sławomir Dariusz Szajda

    2008-01-01

    Full Text Available Spontaneously mutated multiple oncogenes and/or tumor suppressor genes in colon epithelial cell and its progeny, may cause proliferation out of control and create benign colon neoplasm (colon polyp. If additional mutations involve genes responsible for cell adhesion and movement, aberrant epithelial cells may become malignant (colon cancer and invade surrounding and remote tissues, creating secondary tumors called metastases.

  14. Adenocarcinoma in Colonic Interposition

    Directory of Open Access Journals (Sweden)

    Shahar Grunner

    2013-03-01

    Full Text Available A 59-year-old female with dysphagia presented to our clinic. In childhood, she underwent colonic interposition due to anastomotic stricture after a previous proximal gastrectomy for gastric ulcer perforation. Imaging studies revealed a space-occupying lesion obstructing the distal interposed colon. At surgery, completion gastrectomy with segmental colectomy was carried out, and Roux-en-Y coloenterostomy and enteroenterostomy were performed.

  15. Visualization and volumetric structures from MR images of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Parvin, B.; Johnston, W.; Robertson, D.

    1994-03-01

    Pinta is a system for segmentation and visualization of anatomical structures obtained from serial sections reconstructed from magnetic resonance imaging. The system approaches the segmentation problem by assigning each volumetric region to an anatomical structure. This is accomplished by satisfying constraints at the pixel level, slice level, and volumetric level. Each slice is represented by an attributed graph, where nodes correspond to regions and links correspond to the relations between regions. These regions are obtained by grouping pixels based on similarity and proximity. The slice level attributed graphs are then coerced to form a volumetric attributed graph, where volumetric consistency can be verified. The main novelty of our approach is in the use of the volumetric graph to ensure consistency from symbolic representations obtained from individual slices. In this fashion, the system allows errors to be made at the slice level, yet removes them when the volumetric consistency cannot be verified. Once the segmentation is complete, the 3D surfaces of the brain can be constructed and visualized.

  16. Soft bilateral filtering volumetric shadows using cube shadow maps

    Science.gov (United States)

    Ali, Hatam H.; Sunar, Mohd Shahrizal; Kolivand, Hoshang

    2017-01-01

    Volumetric shadows often increase the realism of rendered scenes in computer graphics. Typical volumetric shadows techniques do not provide a smooth transition effect in real-time with conservation on crispness of boundaries. This research presents a new technique for generating high quality volumetric shadows by sampling and interpolation. Contrary to conventional ray marching method, which requires extensive time, this proposed technique adopts downsampling in calculating ray marching. Furthermore, light scattering is computed in High Dynamic Range buffer to generate tone mapping. The bilateral interpolation is used along a view rays to smooth transition of volumetric shadows with respect to preserving-edges. In addition, this technique applied a cube shadow map to create multiple shadows. The contribution of this technique isreducing the number of sample points in evaluating light scattering and then introducing bilateral interpolation to improve volumetric shadows. This contribution is done by removing the inherent deficiencies significantly in shadow maps. This technique allows obtaining soft marvelous volumetric shadows, having a good performance and high quality, which show its potential for interactive applications. PMID:28632740

  17. The Ca(2+ influence on calmodulin unfolding pathway: a steered molecular dynamics simulation study.

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    Full Text Available The force-induced unfolding of calmodulin (CaM was investigated at atomistic details with steered molecular dynamics. The two isolated CaM domains as well as the full-length CaM were simulated in N-C-terminal pulling scheme, and the isolated N-lobe of CaM was studied specially in two other pulling schemes to test the effect of pulling direction and compare with relevant experiments. Both Ca(2+-loaded CaM and Ca(2+-free CaM were considered in order to define the Ca(2+ influence to the CaM unfolding. The results reveal that the Ca(2+ significantly affects the stability and unfolding behaviors of both the isolated CaM domains and the full-length CaM. In Ca(2+-loaded CaM, N-terminal domain unfolds in priori to the C-terminal domain. But in Ca(2+-free CaM, the unfolding order changes, and C-terminal domain unfolds first. The force-extension curves of CaM unfolding indicate that the major unfolding barrier comes from conquering the interaction of two EF-hand motifs in both N- and C- terminal domains. Our results provide the atomistic-level insights in the force-induced CaM unfolding and explain the observation in recent AFM experiments.

  18. The unfolded protein response and translation attenuation: a modelling approach.

    Science.gov (United States)

    Trusina, A; Tang, C

    2010-10-01

    Unfolded protein response (UPR) is a stress response to increased levels of unfolded proteins in the endoplasmic reticulum (ER). To deal with this stress, all eukaryotic cells share a well-conserved strategy--the upregulation of chaperons and proteases to facilitate protein folding and to degrade the misfolded proteins. For metazoans, however, an additional and seemingly redundant strategy has been evolved--translation attenuation (TA) of proteins targeted to the ER via the protein kinase PERK pathway. PERK is essential in secretory cells, such as the pancreatic β-cells, but not in non-secretory cell types. We have recently developed a mathematical model of UPR, focusing on the interplay and synergy between the TA arm and the conserved Ire1 arm of the UPR. The model showed that the TA mechanism is beneficial in highly fluctuating environment, for example, in the case where the ER stress changes frequently. Under highly variable levels of ER stress, tight regulation of the ER load by TA avoids excess amount of chaperons and proteases being produced. The model also showed that TA is of greater importance when there is a large flux of proteins through the ER. In this study, we further expand our model to investigate different types of ER stress and different temporal profiles of the stress. We found that TA is more desirable in dealing with the translation stress, for example, prolonged stimulation of proinsulin biosynthesis, than the chemical stress.

  19. Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway.

    Science.gov (United States)

    Millership, C; Phillips, J J; Main, E R G

    2016-05-08

    Repeat proteins are formed from units of 20-40 aa that stack together into quasi one-dimensional non-globular structures. This modular repetitive construction means that, unlike globular proteins, a repeat protein's equilibrium folding and thus thermodynamic stability can be analysed using linear Ising models. Typically, homozipper Ising models have been used. These treat the repeat protein as a series of identical interacting subunits (the repeated motifs) that couple together to form the folded protein. However, they cannot describe subunits of differing stabilities. Here we show that a more sophisticated heteropolymer Ising model can be constructed and fitted to two new helix deletion series of consensus tetratricopeptide repeat proteins (CTPRs). This analysis, showing an asymmetric spread of stability between helices within CTPR ensembles, coupled with the Ising model's predictive qualities was then used to guide reprogramming of the unfolding pathway of a variant CTPR protein. The designed behaviour was engineered by introducing destabilising mutations that increased the thermodynamic asymmetry within a CTPR ensemble. The asymmetry caused the terminal α-helix to thermodynamically uncouple from the rest of the protein and preferentially unfold. This produced a specific, highly populated stable intermediate with a putative dimerisation interface. As such it is the first step in designing repeat proteins with function regulated by a conformational switch. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. 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.

  1. A neutron spectrum unfolding code based on iterative procedures

    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

    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 {sup 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 {sup 241}AmBe neutron source on air, located at 150 cm from detector, is unfolded. (Author)

  2. 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.

  3. Improved volumetric imaging in tomosynthesis using combined multiaxial sweeps.

    Science.gov (United States)

    Gersh, Jacob A; Wiant, David B; Best, Ryan C M; Bennett, Marcus C; Munley, Michael T; King, June D; McKee, Mahta M; Baydush, Alan H

    2010-09-03

    This study explores the volumetric reconstruction fidelity attainable using tomosynthesis with a kV imaging system which has a unique ability to rotate isocentrically and with multiple degrees of mechanical freedom. More specifically, we seek to investigate volumetric reconstructions by combining multiple limited-angle rotational image acquisition sweeps. By comparing these reconstructed images with those of a CBCT reconstruction, we can gauge the volumetric fidelity of the reconstructions. In surgical situations, the described tomosynthesis-based system could provide high-quality volumetric imaging without requiring patient motion, even with rotational limitations present. Projections were acquired using the Digital Integrated Brachytherapy Unit, or IBU-D. A phantom was used which contained several spherical objects of varying contrast. Using image projections acquired during isocentric sweeps around the phantom, reconstructions were performed by filtered backprojection. For each image acquisition sweep configuration, a contrasting sphere is analyzed using two metrics and compared to a gold standard CBCT reconstruction. Since the intersection of a reconstructed sphere and an imaging plane is ideally a circle with an eccentricity of zero, the first metric presented compares the effective eccentricity of intersections of reconstructed volumes and imaging planes. As another metric of volumetric reconstruction fidelity, the volume of one of the contrasting spheres was determined using manual contouring. By comparing these manually delineated volumes with a CBCT reconstruction, we can gauge the volumetric fidelity of reconstructions. The configuration which yielded the highest overall volumetric reconstruction fidelity, as determined by effective eccentricities and volumetric contouring, consisted of two orthogonally-offset 60° L-arm sweeps and a single C-arm sweep which shared a pivot point with one the L-arm sweeps. When compared to a similar configuration that

  4. Prediction of change in protein unfolding rates upon point mutations in two state proteins.

    Science.gov (United States)

    Chaudhary, Priyashree; Naganathan, Athi N; Gromiha, M Michael

    2016-09-01

    Studies on protein unfolding rates are limited and challenging due to the complexity of unfolding mechanism and the larger dynamic range of the experimental data. Though attempts have been made to predict unfolding rates using protein sequence-structure information there is no available method for predicting the unfolding rates of proteins upon specific point mutations. In this work, we have systematically analyzed a set of 790 single mutants and developed a robust method for predicting protein unfolding rates upon mutations (Δlnku) in two-state proteins by combining amino acid properties and knowledge-based classification of mutants with multiple linear regression technique. We obtain a mean absolute error (MAE) of 0.79/s and a Pearson correlation coefficient (PCC) of 0.71 between predicted unfolding rates and experimental observations using jack-knife test. We have developed a web server for predicting protein unfolding rates upon mutation and it is freely available at https://www.iitm.ac.in/bioinfo/proteinunfolding/unfoldingrace.html. Prominent features that determine unfolding kinetics as well as plausible reasons for the observed outliers are also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 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.

  6. Unfolding Mixed-Symmetry Fields in AdS and the BMV Conjecture I. General Formalism

    CERN Document Server

    Boulanger, Nicolas; Sundell, Per

    2009-01-01

    We present some generalities of unfolded on-shell dynamics that are useful in analyzing the BMV conjecture for mixed-symmetry fields in constantly curved backgrounds. In particular we discuss the unfolded notion of local degrees of freedom in theories with and without gravity and with and without massive deformation parameters, using the language of Weyl zero-form modules and their duals.

  7. 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

  8. 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 can be applied to a range of experimental data and energy functions including the force fields used in molecular dynamics simulations....

  9. 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 equ

  10. The Application of an Unfolding Model of the PIRT Type to the Measurement of Attitude.

    Science.gov (United States)

    Andrich, David

    1988-01-01

    A simple probabilistic model for unfolding data collected by a direct response design in which responses were scored dichotomously was applied to the measurement of attitudes toward capital punishment. Responses conformed to the unfolding mechanism. Scale values of the statements were statistically equivalent to those of Thurstone's methods. (SLD)

  11. Using Data Augmentation and Markov Chain Monte Carlo for the Estimation of Unfolding Response Models

    Science.gov (United States)

    Johnson, Matthew S.; Junker, Brian W.

    2003-01-01

    Unfolding response models, a class of item response theory (IRT) models that assume a unimodal item response function (IRF), are often used for the measurement of attitudes. Verhelst and Verstralen (1993)and Andrich and Luo (1993) independently developed unfolding response models by relating the observed responses to a more common monotone IRT…

  12. Unfolding Case-Based Practicum Curriculum Infusing Crisis, Trauma, and Disaster Preparation

    Science.gov (United States)

    Greene, Catie A.; Williams, Amy E.; Harris, Pamela N.; Travis, Sterling P.; Kim, Sharon Y.

    2016-01-01

    The authors evaluated an unfolding case-based approach to a practicum in counseling course infusing crisis, trauma, and disaster preparation for changes in students' crisis self-efficacy across a semester. The course, informed by constructivist-developmental pedagogy and centered on the unfolding case, resulted in significant increases in…

  13. Mechanical unfolding of ribose binding protein and its comparison with other periplasmic binding proteins.

    Science.gov (United States)

    Kotamarthi, Hema Chandra; Narayan, Satya; Ainavarapu, Sri Rama Koti

    2014-10-01

    Folding and unfolding studies on large, multidomain proteins are still rare despite their high abundance in genomes of prokaryotes and eukaryotes. Here, we investigate the unfolding properties of a 271 residue, two-domain ribose binding protein (RBP) from the bacterial periplasm using single-molecule force spectroscopy. We observe that RBP predominately unfolds via a two-state pathway with an unfolding force of ∼80 pN and an unfolding contour length of ∼95 nm. Only a small population (∼15%) of RBP follows three-state pathways. The ligand binding neither increases the mechanical stability nor influences the unfolding flux of RBP through different pathways. The kinetic partitioning between two-state and three-state pathways, which has been reported earlier for other periplasmic proteins, is also observed in RBP, albeit to a lesser extent. These results provide important insights into the mechanical stability and unfolding processes of large two-domain proteins and highlight the contrasting features upon ligand binding. Protein structural topology diagrams are used to explain the differences in the mechanical unfolding behavior of RBP with other periplasmic binding proteins.

  14. 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...

  15. Aspects of volumetric efficiency measurement for reciprocating engines

    Directory of Open Access Journals (Sweden)

    Pešić Radivoje B.

    2013-01-01

    Full Text Available The volumetric efficiency significantly influences engine output. Both design and dimensions of an intake and exhaust system have large impact on volumetric efficiency. Experimental equipment for measuring of airflow through the engine, which is placed in the intake system, may affect the results of measurements and distort the real picture of the impact of individual structural factors. This paper deals with the problems of experimental determination of intake airflow using orifice plates and the influence of orifice plate diameter on the results of the measurements. The problems of airflow measurements through a multi-process Otto/Diesel engine were analyzed. An original method for determining volumetric efficiency was developed based on in-cylinder pressure measurement during motored operation, and appropriate calibration of the experimental procedure was performed. Good correlation between the results of application of the original method for determination of volumetric efficiency and the results of theoretical model used in research of influence of the intake pipe length on volumetric efficiency was determined. [Acknowledgments. The paper is the result of the research within the project TR 35041 financed by the Ministry of Science and Technological Development of the Republic of Serbia

  16. Congenital Pouch Colon

    Directory of Open Access Journals (Sweden)

    Vivek Gharpure

    2012-07-01

    Full Text Available Face The Examiner:QUESTIONS1. What are the diagnostic features of congenital pouch colon (CPC?Ans: A male patient with CPC often have a wide colovesical fistula and present with anorectal malformation and meconuria; on plain abdominal film, a single large bowel loop occupying more than 50% of the abdominal cavity is also a diagnostic sign. Girls (persistent cloaca/vestibular fistula/anteriorly placed anus etc. often present late with intractable constipation or multiple episodes of enterocolitis and persistent abdominal distension with common cloaca or anterior ectopic anus/ rectovestibular fistula. The congenital pouch colon can be identified as replacement of a part or entire colon in the configuration of pouch that lacks taenia coli, haustrations, appendices epiploicae, abnormal blood supply and a wide fistula with genitourinary system in a patient of anorectal malformation.

  17. Inflammation and colon cancer.

    Science.gov (United States)

    Terzić, Janos; Grivennikov, Sergei; Karin, Eliad; Karin, Michael

    2010-06-01

    The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.

  18. Recent trend of colonic diverticulosis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yae Soon; Lee, Sung Woo; Han, Chang Yul; Lee, Kwan Seh [Inje Medical College, Seoul (Korea, Republic of)

    1988-08-15

    Colonic Diverticulosis is once thought to be a rare disease in Korea compared with western countries, but the incidence has been increasing with passage of time. Authors reviewed 151 cases of colon study with new double contrast method performed from November, 1986 to March, 1987 at Paik Hospital Inje college. The results were as follow: 1. The colonic diverticulosis was found in 39 cases out of 151 colon study (25.8%). 2. Colonic Diverticulosis were located at right and transvercolon in 54% and left and sigmoid colon in 18%. 3. Increasing occurrence in younger age group predilection; 4th decade was observed.

  19. CT findings of colonic diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Shigeru; Ohba, Satoru [Nagoya City Univ. (Japan). Medical School; Mizutani, Masaru [and others

    1998-11-01

    Although colonic diverticulitis has no indication for operation, but in some mistaken cases were operated with a diagnosis of acute appendicitis. We evaluated the CT findings of colonic diverticulitis about 19 cases and of asymptomatic colonic diverticula about 15 cases retrospectively. Diagnosis was confirmed of barium enema and operation. CT are complementary methods of examination that can delineated the range of thickening of the colon and the extension of inflammatory changes around the colon. We also believe that CT findings of colonic diverticulitis are useful for differentiating from a diagnosis of appendicitis. (author)

  20. Unfolding and Refolding Embodiment into the Landscape of Ubiquitous Computing

    DEFF Research Database (Denmark)

    Schick, Lea; Malmborg, Lone

    2009-01-01

    how these are to an increasing extent focusing on sociality, context-awareness, relations, affects, connectedness, and collectivity we will examine how these new technological movements can change our perception of embodiment towards a distributed and shared one. By examining interactive textiles......This paper advocates the future of the body as a distributed and shared embodiment; an unfolded body that doesn’t end at one's skin, but emerges as intercorporeality between bodies and the technological environment. Looking at new tendencies within interaction design and ubiquitous computing to see...... as part of a future rising landscape of multi-sensory networks we will exemplify how the new technologies can shutter dichotomies and challenge traditional notions of embodiment and the subject. Finally, we show how this ‘new embodiment’ manifests Deleuze’s philosophy of the body as something unstable...

  1. Unfolded protein response in hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Shiu-Wan eChan

    2014-05-01

    Full Text Available Hepatitis C virus (HCV is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis and hepatocellular carcinoma. The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR, a cellular homeostatic response to endoplasmic reticulum (ER stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR.

  2. Unfolding Education for Sustainable Development as Didactic Thinking and Practice

    Directory of Open Access Journals (Sweden)

    Katrine Dahl Madsen

    2013-09-01

    Full Text Available 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 relation to ESD. The article draws on doctoral research involving interviews with researchers and teachers who have collaborated in ESD research and development projects at primary and secondary schools in two different countries, Denmark and Ireland. It is the teachers’ perspectives on the projects which form 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.

  3. Using unfolding case studies in a subject-centered classroom.

    Science.gov (United States)

    Day, Lisa

    2011-08-01

    The recently published report of the Carnegie Foundation's National Study of Nursing Education points out significant problems with classroom teaching in schools of nursing. This article suggests Palmer's idea of the subject-centered classroom as a way to transform nursing school classrooms into collaborative learning communities. For Palmer, the subject is the big idea of nursing practice-the nurse-patient/client/family/community relationship-that should take the lead in stimulating inquiry and discussion. The article goes on to describe how teachers can develop and use unfolding case studies to bring the subject to the center of the classroom. By doing so, the classroom becomes a place where students learn a sense of salience, develop their clinical imagination, and begin their formation as professional nurses.

  4. 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.

  5. Tannin-assisted aggregation of natively unfolded proteins

    Science.gov (United States)

    Zanchi, D.; Narayanan, T.; Hagenmuller, D.; Baron, A.; Guyot, S.; Cabane, B.; Bouhallab, S.

    2008-06-01

    Tannin-protein interactions are essentially physical: hydrophobic and hydrogen-bond-mediated. We explored the tannin-assisted protein aggregation on the case of β-casein, which is a natively unfolded protein known for its ability to form micellar aggregates. We used several tannins with specified length. Our SAXS results show that small tannins increase the number of proteins per micelle, but keeping their size constant. It leads to a tannin-assisted compactization of micelles. Larger tannins, with linear dimensions greater than the crown width of micelles, lead to the aggregation of micelles by a bridging effect. Experimental results can be understood within a model where tannins are treated as effective enhancers of hydrophobic attraction between specific sites in proteins.

  6. Nanoconfined circular and linear DNA - equilibrium conformations and unfolding kinetics

    CERN Document Server

    Alizadehheidari, M; Noble, C; Reiter-Schad, M; Nyberg, L K; Fritzsche, J; Mehlig, B; Tegenfeldt, J O; Ambjörnsson, T; Persson, F; Westerlund, F

    2016-01-01

    Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of DNA from the circular to linear configuration as a light-induced double strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to which extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA....

  7. The Unfolded Protein Response in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Kelsen, Steven G

    2016-04-01

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

  8. Haustral boundary contractions in the proximal 3-taeniated rabbit colon.

    Science.gov (United States)

    Chen, Ji-Hong; Yang, Zixian; Yu, Yuanjie; Huizinga, Jan D

    2016-02-01

    The rabbit proximal colon is similar in structure to the human colon. Our objective was to study interactions of different rhythmic motor patterns focusing on haustral boundary contractions, which create the haustra, using spatiotemporal mapping of video recordings. Haustral boundary contractions were seen as highly rhythmic circumferential ring contractions that propagated slowly across the proximal colon, preferentially but not exclusively in the anal direction, at ∼0.5 cycles per minute; they were abolished by nerve conduction blockers. When multiple haustral boundary contractions propagated in the opposite direction, they annihilated each other upon encounter. Ripples, myogenic propagating ring contractions at ∼9 cycles per min, induced folding and unfolding of haustral muscle folds, creating an anarchic appearance of contractile activity, with different patterns in the three intertaenial regions. Two features of ripple activity were prominent: frequent changes in propagation direction and the occurrence of dislocations showing a frequency gradient with the highest intrinsic frequency in the distal colon. The haustral boundary contractions showed an on/off/on/off pattern at the ripple frequency, and the contraction amplitude at any point of the colon showed waxing and waning. The haustral boundary contractions are therefore shaped by interaction of two pacemaker activities hypothesized to occur through phase-amplitude coupling of pacemaker activities from interstitial cells of Cajal of the myenteric plexus and of the submuscular plexus. Video evidence shows the unique role haustral folds play in shaping contractile activity within the haustra. Muscarinic agents not only enhance the force of contraction, they can eliminate one and at the same time induce another neurally dependent motor pattern.

  9. Unfolding the fast neutron spectra of a BC501A liquid scintillation detector using GRAVEL method

    CERN Document Server

    Chen, Yonghao; Lei, Jiarong; An, Li; Zhang, Xiaodong; Shao, Jianxiong; Zheng, Pu; Wang, Xinhua

    2013-01-01

    Accurate knowledge of the neutron energy spectra is useful in basic research and applications. The overall procedure of measuring and unfolding the fast neutron energy spectra with BC501A liquid scintillation detector is described. The recoil proton spectrum of Am-Be neutrons was obtained experimentally. With the NRESP7 code, the response matrix of detector was simulated. Combining the recoil proton spectrum and response matrix, the unfolding of neutron spectra was performed by GRAVEL iterative algorithm. A MatLab program based on the GRAVEL method was developed. The continuous neutron spectrum of Am-Be source and monoenergetic neutron spectrum of D-T source have been unfolded successfully and are in good agreement with their standard reference spectra. The unfolded Am-Be spectrum are more accurate than the spectra unfolded by artificial neural networks in recent years.

  10. Unfolding the fast neutron spectra of a BC501A liquid scintillation detector using GRAVEL method

    Science.gov (United States)

    Chen, YongHao; Chen, XiMeng; Lei, JiaRong; An, Li; Zhang, XiaoDong; Shao, JianXiong; Zheng, Pu; Wang, XinHua

    2014-10-01

    Accurate knowledge of the neutron energy spectra is useful in basic research and applications. The overall procedure of measuring and unfolding the fast neutron energy spectra with BC501A liquid scintillation detector is described. The recoil proton spectrum of 241Am-Be neutrons was obtained experimentally. With the NRESP7 code, the response matrix of detector was simulated. Combining the recoil proton spectrum and response matrix, the unfolding of neutron spectra was performed by GRAVEL iterative algorithm. A MatLab program based on the GRAVEL method was developed. The continuous neutron spectrum of 241Am-Be source and monoenergetic neutron spectrum of D-T source have been unfolded successfully and are in good agreement with their standard reference spectra. The unfolded 241Am-Be spectrum are more accurate than the spectra unfolded by artificial neural networks in recent years.

  11. A new neutron energy spectrum unfolding code using a two steps genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Shahabinejad, H., E-mail: shahabinejad1367@yahoo.com; Hosseini, S.A.; Sohrabpour, M.

    2016-03-01

    A new neutron spectrum unfolding code TGASU (Two-steps Genetic Algorithm Spectrum Unfolding) has been developed to unfold the neutron spectrum from a pulse height distribution which was calculated using the MCNPX-ESUT computational Monte Carlo code. To perform the unfolding process, the response matrices were generated using the MCNPX-ESUT computational code. Both one step (common GA) and two steps GAs have been implemented to unfold the neutron spectra. According to the obtained results, the new two steps GA code results has shown closer match in all energy regions and particularly in the high energy regions. The results of the TGASU code have been compared with those of the standard spectra, LSQR method and GAMCD code. The results of the TGASU code have been demonstrated to be more accurate than that of the existing computational codes for both under-determined and over-determined problems.

  12. 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.

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

    Science.gov (United States)

    De-Souza, Evandro A; Pimentel, Felipe S A; Machado, Caio M; Martins, Larissa S; da-Silva, Wagner S; Montero-Lomelí, Mónica; Masuda, Claudio A

    2014-01-01

    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.

  14. A new neutron energy spectrum unfolding code using a two steps genetic algorithm

    Science.gov (United States)

    Shahabinejad, H.; Hosseini, S. A.; Sohrabpour, M.

    2016-03-01

    A new neutron spectrum unfolding code TGASU (Two-steps Genetic Algorithm Spectrum Unfolding) has been developed to unfold the neutron spectrum from a pulse height distribution which was calculated using the MCNPX-ESUT computational Monte Carlo code. To perform the unfolding process, the response matrices were generated using the MCNPX-ESUT computational code. Both one step (common GA) and two steps GAs have been implemented to unfold the neutron spectra. According to the obtained results, the new two steps GA code results has shown closer match in all energy regions and particularly in the high energy regions. The results of the TGASU code have been compared with those of the standard spectra, LSQR method and GAMCD code. The results of the TGASU code have been demonstrated to be more accurate than that of the existing computational codes for both under-determined and over-determined problems.

  15. Correction of tuberous breasts using the unfolded subareolar gland flap.

    Science.gov (United States)

    Oroz-Torres, Javier; Pelay-Ruata, María-Josefa; Escolán-Gonzalvo, Nieves; Jordán-Palomar, Elena

    2014-08-01

    In this retrospective study, the authors present 12 years of experience using a modified Puckett's technique with a double unfolded strictly subareolar glandular flap for surgical correction of the deformity known as "tuberous breast." In 1976, Rees and Aston documented this congenital malformation of the mammary glands in women. Its cause is unknown, and it affects adolescent girls with varying severity uni- or bilaterally. The condition is characterized by a lack of development, primarily in the lower quadrants of the breast plus a rising of the inframammary fold, together with herniation and increased diameter of the areola. Many varied surgical techniques for correction of this malformation in its different degrees of severity have been documented in the available literature. This study examined the treatment of 42 breasts in 26 patients with a high percentage of full correction of the deformity. The advantages and achievements of the double unfolded strictly subareolar glandular flap include restructuring of the breast's lower pole in volume, length, and shape; reduction and even removal of the double-bubble effect as the flap covers the implant fitted; lowering of inframammary fold height; and correction of areola size and herniation. The procedure is performed through a hemi- or periareolar incision. The technique is versatile for managing the different variations of tuberous breasts, making it another interesting option for correction of the deformity. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  16. 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.

  17. The Unfolding of Equivariant Bifurcation Problems with Two Types of State Variables in the Presence of Parameter Symmetry

    Institute of Scientific and Technical Information of China (English)

    Deng Lan CUI; Yang Cheng LI

    2006-01-01

    The unfolding of equivariant bifurcation problems with two types of state variables under the action of group (ж) (Г, △) is discussed by using DA-algebraic tools. One of the main results is the equivariant versal unfolding theorem.

  18. A high volume, high throughput volumetric sorption analyzer

    Science.gov (United States)

    Soo, Y. C.; Beckner, M.; Romanos, J.; Wexler, C.; Pfeifer, P.; Buckley, P.; Clement, J.

    2011-03-01

    In this talk we will present an overview of our new Hydrogen Test Fixture (HTF) constructed by the Midwest Research Institute for The Alliance for Collaborative Research in Alternative Fuel Technology to test activated carbon monoliths for hydrogen gas storage. The HTF is an automated, computer-controlled volumetric instrument for rapid screening and manipulation of monoliths under an inert atmosphere (to exclude degradation of carbon from exposure to oxygen). The HTF allows us to measure large quantity (up to 500 g) of sample in a 0.5 l test tank, making our results less sensitive to sample inhomogeneity. The HTF can measure isotherms at pressures ranging from 1 to 300 bar at room temperature. For comparison, other volumetric instruments such as Hiden Isochema's HTP-1 Volumetric Analyser can only measure carbon samples up to 150 mg at pressures up to 200 bar. Work supported by the US DOD Contract # N00164-08-C-GS37.

  19. Volumetric (3D) compressive sensing spectral domain optical coherence tomography.

    Science.gov (United States)

    Xu, Daguang; Huang, Yong; Kang, Jin U

    2014-11-01

    In this work, we proposed a novel three-dimensional compressive sensing (CS) approach for spectral domain optical coherence tomography (SD OCT) volumetric image acquisition and reconstruction. Instead of taking a spectral volume whose size is the same as that of the volumetric image, our method uses a sub set of the original spectral volume that is under-sampled in all three dimensions, which reduces the amount of spectral measurements to less than 20% of that required by the Shan-non/Nyquist theory. The 3D image is recovered from the under-sampled spectral data dimension-by-dimension using the proposed three-step CS reconstruction strategy. Experimental results show that our method can significantly reduce the sampling rate required for a volumetric SD OCT image while preserving the image quality.

  20. Multiple sparse volumetric priors for distributed EEG source reconstruction.

    Science.gov (United States)

    Strobbe, Gregor; van Mierlo, Pieter; De Vos, Maarten; Mijović, Bogdan; Hallez, Hans; Van Huffel, Sabine; López, José David; Vandenberghe, Stefaan

    2014-10-15

    We revisit the multiple sparse priors (MSP) algorithm implemented in the statistical parametric mapping software (SPM) for distributed EEG source reconstruction (Friston et al., 2008). In the present implementation, multiple cortical patches are introduced as source priors based on a dipole source space restricted to a cortical surface mesh. In this note, we present a technique to construct volumetric cortical regions to introduce as source priors by restricting the dipole source space to a segmented gray matter layer and using a region growing approach. This extension allows to reconstruct brain structures besides the cortical surface and facilitates the use of more realistic volumetric head models including more layers, such as cerebrospinal fluid (CSF), compared to the standard 3-layered scalp-skull-brain head models. We illustrated the technique with ERP data and anatomical MR images in 12 subjects. Based on the segmented gray matter for each of the subjects, cortical regions were created and introduced as source priors for MSP-inversion assuming two types of head models. The standard 3-layered scalp-skull-brain head models and extended 4-layered head models including CSF. We compared these models with the current implementation by assessing the free energy corresponding with each of the reconstructions using Bayesian model selection for group studies. Strong evidence was found in favor of the volumetric MSP approach compared to the MSP approach based on cortical patches for both types of head models. Overall, the strongest evidence was found in favor of the volumetric MSP reconstructions based on the extended head models including CSF. These results were verified by comparing the reconstructed activity. The use of volumetric cortical regions as source priors is a useful complement to the present implementation as it allows to introduce more complex head models and volumetric source priors in future studies.

  1. Volumetric measurements of a spatially growing dust acoustic wave

    Science.gov (United States)

    Williams, Jeremiah D.

    2012-11-01

    In this study, tomographic particle image velocimetry (tomo-PIV) techniques are used to make volumetric measurements of the dust acoustic wave (DAW) in a weakly coupled dusty plasma system in an argon, dc glow discharge plasma. These tomo-PIV measurements provide the first instantaneous volumetric measurement of a naturally occurring propagating DAW. These measurements reveal over the measured volume that the measured wave mode propagates in all three spatial dimensional and exhibits the same spatial growth rate and wavelength in each spatial direction.

  2. Volumetric measurements of a spatially growing dust acoustic wave

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Jeremiah D. [Physics Department, Wittenberg University, Springfield, Ohio 45504 (United States)

    2012-11-15

    In this study, tomographic particle image velocimetry (tomo-PIV) techniques are used to make volumetric measurements of the dust acoustic wave (DAW) in a weakly coupled dusty plasma system in an argon, dc glow discharge plasma. These tomo-PIV measurements provide the first instantaneous volumetric measurement of a naturally occurring propagating DAW. These measurements reveal over the measured volume that the measured wave mode propagates in all three spatial dimensional and exhibits the same spatial growth rate and wavelength in each spatial direction.

  3. Volumetric Pricing of Agricultural Water Supplies: A Case Study

    Science.gov (United States)

    Griffin, Ronald C.; Perry, Gregory M.

    1985-07-01

    Models of water consumption by rice producers are conceptualized and then estimated using cross-sectional time series data obtained from 16 Texas canal operators for the years 1977-1982. Two alternative econometric models demonstrate that both volumetric and flat rate water charges are strongly and inversely related to agricultural water consumption. Nonprice conservation incentives accompanying flat rates are hypothesized to explain the negative correlation of flat rate charges and water consumption. Application of these results suggests that water supply organizations in the sample population converting to volumetric pricing will generally reduce water consumption.

  4. Spontaneous transverse colon volvulus.

    Science.gov (United States)

    Sana, Landolsi; Ali, Gassara; Kallel, Helmi; Amine, Baklouti; Ahmed, Saadaoui; Ali, Elouer Mohamed; Wajdi, Chaeib; Saber, Mannaï

    2013-01-01

    We report a case of spontaneous transverse colon volvulus in a young healthy woman. It constitutes an unusual case since it occurred in a young healthy woman with a subacute onset and no aetiological factor has been found. Its diagnosis is still challenging. Prompt recognition with emergency intervention constitutes the key to successful outcome.

  5. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  6. Stages of Colon Cancer

    Science.gov (United States)

    ... The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH. Purpose of This Summary This PDQ cancer information summary has current information about the treatment of colon cancer. It is meant to inform and help ...

  7. Carbohydrate Markers in Colon Carcinoma

    OpenAIRE

    Sławomir Dariusz Szajda; Anna Jankowska; Krzysztof Zwierz

    2008-01-01

    Spontaneously mutated multiple oncogenes and/or tumor suppressor genes in colon epithelial cell and its progeny, may cause proliferation out of control and create benign colon neoplasm (colon polyp). If additional mutations involve genes responsible for cell adhesion and movement, aberrant epithelial cells may become malignant (colon cancer) and invade surrounding and remote tissues, creating secondary tumors called metastases. Incidence of colorectal cancer dramatically increases at 50–65 ye...

  8. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... collection below explain colon cancer risk factors, screening tests, and treatments. There are also personal stories from ... Colon Cancer Risk Play Play Colon Cancer: Screening Tests Play Play Colon Cancer Screening Tests: Colonoscopy Play ...

  9. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A Resource for Patients Play Play Risk Factors for Colon Cancer Play Play Lowering Colon ...

  10. Understanding Antegrade Colonic Enema (ACE) Surgery

    Science.gov (United States)

    ... Enema (ACE) Surgery Understanding Antegrade Colonic Enema (ACE) Surgery Antegrade colonic enema surgery (ACE) or Malone antegrade ... Email Print What is antegrade colonic enema (ACE) surgery? Antegrade colonic enema surgery (ACE) or Malone antegrade ...

  11. Understanding Antegrade Colonic Enema (ACE) Surgery

    Science.gov (United States)

    ... Enema (ACE) Surgery Understanding Antegrade Colonic Enema (ACE) Surgery Antegrade colonic enema surgery (ACE) or Malone antegrade ... Full Article What is antegrade colonic enema (ACE) surgery? Antegrade colonic enema surgery (ACE) or Malone antegrade ...

  12. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... collection below explain colon cancer risk factors, screening tests, and treatments. There are also personal stories from ... Colon Cancer Risk Play Play Colon Cancer: Screening Tests Play Play Colon Cancer Screening Tests: Colonoscopy Play ...

  13. External coating of colonic anastomoses

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Achiam, Michael Patrick; Rosenberg, Jacob

    2012-01-01

    Colon anastomotic leakage remains both a frequent and serious complication in gastrointestinal surgery. External coating of colonic anastomoses has been proposed as a means to lower the rate of this complication. The aim of this review was to evaluate existing studies on external coating of colonic...

  14. Multiple unfolding intermediates of human placental alkaline phosphatase in equilibrium urea denaturation.

    Science.gov (United States)

    Hung, H C; Chang, G G

    2001-12-01

    Alkaline phosphatase is an enzyme with a typical alpha/beta hydrolase fold. The conformational stability of the human placental alkaline phosphatase was examined with the chemical denaturant urea. The red shifts of fluorescence spectra show a complex unfolding process involving multiple equilibrium intermediates indicating differential stability of the subdomains of the enzyme. None of these unfolding intermediates were observed in the presence of 83 mM NaCl, indicating the importance of ionic interactions in the stabilization of the unfolding intermediates. Guanidinium chloride, on the other hand, could stabilize one of the unfolding intermediates, which is not a salt effect. Some of the unfolding intermediates were also observed in circular dichroism spectroscopy, which clearly indicates steady loss of helical structure during unfolding, but very little change was observed for the beta strand content until the late stage of the unfolding process. The enzyme does not lose its phosphate-binding ability after substantial tertiary structure changes, suggesting that the substrate-binding region is more resistant to chemical denaturant than the other structural domains. Global analysis of the fluorescence spectral change demonstrated the following folding-unfolding process of the enzyme: N I(1) I(2) I(3) I(4) I(5) D. These discrete intermediates are stable at urea concentrations of 2.6, 4.1, 4.7, 5.5, 6.6, and 7.7 M, respectively. These intermediates are further characterized by acrylamide and/or potassium iodide quenching of the intrinsic fluorescence of the enzyme and by the hydrophobic probes, 1-anilinonaphthalene-8-sulfonic acid and 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid. The stepwise unfolding process was interpreted by the folding energy landscape in terms of the unique structure of the enzyme. The rigid central beta-strand domain is surrounded by the peripheral alpha-helical and coil structures, which are marginally stable toward a chemical

  15. Space-Time Transfinite Interpolation of Volumetric Material Properties.

    Science.gov (United States)

    Sanchez, Mathieu; Fryazinov, Oleg; Adzhiev, Valery; Comninos, Peter; Pasko, Alexander

    2015-02-01

    The paper presents a novel technique based on extension of a general mathematical method of transfinite interpolation to solve an actual problem in the context of a heterogeneous volume modelling area. It deals with time-dependent changes to the volumetric material properties (material density, colour, and others) as a transformation of the volumetric material distributions in space-time accompanying geometric shape transformations such as metamorphosis. The main idea is to represent the geometry of both objects by scalar fields with distance properties, to establish in a higher-dimensional space a time gap during which the geometric transformation takes place, and to use these scalar fields to apply the new space-time transfinite interpolation to volumetric material attributes within this time gap. The proposed solution is analytical in its nature, does not require heavy numerical computations and can be used in real-time applications. Applications of this technique also include texturing and displacement mapping of time-variant surfaces, and parametric design of volumetric microstructures.

  16. In Vivo Real Time Volumetric Synthetic Aperture Ultrasound Imaging

    DEFF Research Database (Denmark)

    Bouzari, Hamed; Rasmussen, Morten Fischer; Brandt, Andreas Hjelm;

    2015-01-01

    Synthetic aperture (SA) imaging can be used to achieve real-time volumetric ultrasound imaging using 2-D array transducers. The sensitivity of SA imaging is improved by maximizing the acoustic output, but one must consider the limitations of an ultrasound system, both technical and biological...

  17. Automatic segmentation of pulmonary segments from volumetric chest CT scans.

    NARCIS (Netherlands)

    Rikxoort, E.M. van; Hoop, B. de; Vorst, S. van de; Prokop, M.; Ginneken, B. van

    2009-01-01

    Automated extraction of pulmonary anatomy provides a foundation for computerized analysis of computed tomography (CT) scans of the chest. A completely automatic method is presented to segment the lungs, lobes and pulmonary segments from volumetric CT chest scans. The method starts with lung segmenta

  18. Volumetric T-spline Construction Using Boolean Operations

    Science.gov (United States)

    2013-07-01

    15213, USA 2 Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX 78712, USA 3 Department of Civil and...and S. Yau. Volumetric harmonic map. Communications in Information and Systems, 3(3):191–202, 2003. 12. C.A.R. Guerra . Simultaneous untangling and

  19. Volumetric motion quantification by 3D tissue phase mapped CMR

    Directory of Open Access Journals (Sweden)

    Lutz Anja

    2012-10-01

    Full Text Available Abstract Background The objective of this study was the quantification of myocardial motion from 3D tissue phase mapped (TPM CMR. Recent work on myocardial motion quantification by TPM has been focussed on multi-slice 2D acquisitions thus excluding motion information from large regions of the left ventricle. Volumetric motion assessment appears an important next step towards the understanding of the volumetric myocardial motion and hence may further improve diagnosis and treatments in patients with myocardial motion abnormalities. Methods Volumetric motion quantification of the complete left ventricle was performed in 12 healthy volunteers and two patients applying a black-blood 3D TPM sequence. The resulting motion field was analysed regarding motion pattern differences between apical and basal locations as well as for asynchronous motion pattern between different myocardial segments in one or more slices. Motion quantification included velocity, torsion, rotation angle and strain derived parameters. Results All investigated motion quantification parameters could be calculated from the 3D-TPM data. Parameters quantifying hypokinetic or asynchronous motion demonstrated differences between motion impaired and healthy myocardium. Conclusions 3D-TPM enables the gapless volumetric quantification of motion abnormalities of the left ventricle, which can be applied in future application as additional information to provide a more detailed analysis of the left ventricular function.

  20. Video-rate volumetric optical coherence tomography-based microangiography

    Science.gov (United States)

    Baran, Utku; Wei, Wei; Xu, Jingjiang; Qi, Xiaoli; Davis, Wyatt O.; Wang, Ruikang K.

    2016-04-01

    Video-rate volumetric optical coherence tomography (vOCT) is relatively young in the field of OCT imaging but has great potential in biomedical applications. Due to the recent development of the MHz range swept laser sources, vOCT has started to gain attention in the community. Here, we report the first in vivo video-rate volumetric OCT-based microangiography (vOMAG) system by integrating an 18-kHz resonant microelectromechanical system (MEMS) mirror with a 1.6-MHz FDML swept source operating at ˜1.3 μm wavelength. Because the MEMS scanner can offer an effective B-frame rate of 36 kHz, we are able to engineer vOMAG with a video rate up to 25 Hz. This system was utilized for real-time volumetric in vivo visualization of cerebral microvasculature in mice. Moreover, we monitored the blood perfusion dynamics during stimulation within mouse ear in vivo. We also discussed this system's limitations. Prospective MEMS-enabled OCT probes with a real-time volumetric functional imaging capability can have a significant impact on endoscopic imaging and image-guided surgery applications.

  1. VERSAL UNFOLDING OF EQUIVARIANT BIFURCATION PROBLEMS IN MORE GENERAL CASE UNDER TWO EQUIVALENT GROUPS

    Institute of Scientific and Technical Information of China (English)

    Li Yangcheng; He Wei

    2008-01-01

    For the unfolding of equivariant bifurcation problems with two types of state variables in the presence of parameter symmetry, the versa[ unfolding theorem with re-spect to left-right equivalence is obtained by using the related methods and techniques in the singularity theory of smooth map-germs. The corresponding results in [4, 9] can be considered as its special cases. A relationship between the versal unfolding w.r.t, left-right equivalence and the versal deformation w.r.t, contact equivalence is established.

  2. Comparison of Inactivation and Unfolding of Calf Intestinal Alkaline Phosphatase in Guanidinium Chloride Solution

    Institute of Scientific and Technical Information of China (English)

    张英侠; 闫淑莲; 刘永利; 席宏伟; 周海梦

    2002-01-01

    The changes in activity and unfolding of calf intestinal alkaline phosphatase (CIP) during denaturation in guanidinium chloride solutions of different concentrations were investigated using ultraviolet difference absorption spectra and fluorescence emission spectra. Unfolding and inactivation rate constants were measured and compared. The inactivation course is much faster than that of unfolding, which suggests that the active site of CIP containing two zinc ions and one magnesium ion is situated in a limited and flexible region of the enzyme molecule, which is more fragile to the denaturant than the protein as a whole.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Membrane proteins are vital for biological function, and their action is governed by structural properties critically depending on their interactions with the membranes. This has motivated considerable interest in studies of membrane protein folding and unfolding. Here the structural changes...... 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...

  4. 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)

  5. Sonographic Features of Colonic Diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yu Mee; Ko, Young Tae; Lim, Joo Won; Lee, Dong Ho; Yoon, Yup [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1996-06-15

    To evaluate sonographic features, location of diverticulum, and usefulness of sonography as a primary diagnostic tool. Sonographic findings of 28 patients with acute diverticulitis were reviewed. The diagnosis was made by surgery (11 patients), barium enema (20 patients), colonoscopy (3 patients), or CT (2 patients). There were 13 men and 15 women with ages ranging from 23 to 71 years old (mean, 33 years old). Sonographic abnormalities were seen in the cecum in 12 patients, both the cecum and ascending colon in seven, the ascending colon in six, the descending colon in two, and the transverse colon in one. On sonography, segmental thickening of the colonic wall was the most common finding, seen in 16 patients. The second most common finidngs were pericolic omental thickening and pericolic localized fluid collection (15 patients). Pericolic inflammatory mass of varying echogenicity (10 patients), out pouching hyper echoic foci beyond the lumen of the colon into or beyond the thickened wall (5 patients), contracture of the colon (5 patients), slightly thickened terminal ileum (1 patient), and local enlargement of ileocecal lymph node (1 patient) were also seen. Most diverticulitis occurred in the right colon. The useful sonographic findings in acute diverticulitis were echogenic foci of the diverticulum in the thickened colonic wall, focally and eccentrically thickened colonic wall, and localized omental thickening or fluid collection. In cases of pericecal fluid collection, appendicitis or colonic diverticulitis can be considered as a differential diagnosis

  6. Analysis of Changing Swarm Rate using Volumetric Strain

    Science.gov (United States)

    Kumazawa, T.; Ogata, Y.; Kimura, K.; Maeda, K.; Kobayashi, A.

    2015-12-01

    Near the eastern coast of Izu peninsula is an active submarine volcanic region in Japan, where magma intrusions have been observed many times. The forecast of earthquake swarm activities and eruptions are serious concern particularly in nearby hot spring resort areas. It is well known that temporal durations of the swarm activities have been correlated with early volumetric strain changes at a certain observation station of about 20 km distance apart. Therefore the Earthquake Research Committee (2010) investigated some empirical statistical relations to predict sizes of the swarm activity. Here we looked at the background seismicity rate changes during these swarm periods using the non-stationary ETAS model (Kumazawa and Ogata, 2013, 2014), and have found the followings. The modified volumetric strain data, by removing the effect of earth tides, precipitation and coseismic jumps, have significantly higher cross-correlations to the estimated background rates of the ETAS model than to the swarm rate-changes. Specifically, the background seismicity rate synchronizes clearer to the strain change by the lags around a half day. These relations suggest an enhanced prediction of earthquakes in this region using volumetric strain measurements. Hence we propose an extended ETAS model where the background rate is modulated by the volumetric strain data. We have also found that the response function to the strain data can be well approximated by an exponential functions with the same decay rate, but that their intersects are inversely proportional to the distances between the volumetric strain-meter and the onset location of the swarm. Our numerical results by the same proposed model show consistent outcomes for the various major swarms in this region.

  7. Nonobstructing Colonic Dilatation and Colon Perforations Following Renal Transplantation

    Science.gov (United States)

    Koneru, Baburao; Selby, Rick; O’Hair, Daniel P.; Tzakis, Andreas G.; Hakala, Thomas R.; Starzl, Thomas E.

    2010-01-01

    Nonobstructing colonic dilatation has not been commonly reported following renal transplantation, and colon perforations carry a high morbidity and mortality in this population. During a 7-year period, nonobstructing colonic dilatation developed in 13 adults 1 to 13 days after renal transplantation. Twelve (92%) of the 13 had poorly functioning allografts. Five (83%) of the 6 with and 2 (29%) of the 7 without colonoscopy had resolution of nonobstructing colonic dilatation. Of the seven right-sided colon perforations during this period, six were associated with nonobstructing colonic dilatation. An additional 4 patients had diverticular perforations in the left colon. Of a total of 11 patients with colon perforation, 7 had surgery within 24 hours of the perforation and 6 (86%) of these survived. Only 1 (25%) of the 4 having surgery more than 24 hours later survived. Six of the survivors retained functioning allografts. Nonobstructing colonic dilatation seems to be a potential complication of poor graft function after renal transplantation, and colonoscopy is effective in its treatment. In patients with colon perforations, early surgery and reduced immunosuppression are essential in decreasing mortality. PMID:2331220

  8. Decrease in membrane phospholipid unsaturation induces unfolded protein response.

    Science.gov (United States)

    Ariyama, Hiroyuki; Kono, Nozomu; Matsuda, Shinji; Inoue, Takao; Arai, Hiroyuki

    2010-07-16

    Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.

  9. Unfolding X-ray spectra using a flat panel detector.

    Science.gov (United States)

    Gallardo, Sergio; Juste, Belén; Pozuelo, Fausto; Ródenas, José; Querol, Andrea; Verdú, Gumersindo

    2013-01-01

    It is difficult to measure the energy spectrum of X-ray tubes due to the pile up effect produced by the high fluence of photons. Using attenuating materials, appropriate detector devices and the Monte Carlo method, primary X-ray spectrum of these devices can be estimated. In this work, a flat panel detector with a PMMA wedge has been used to obtain a dose curve corresponding to certain working conditions of a radiodiagnostic X-ray tube. The relation between the dose curve recorded by the flat panel and the primary X-ray spectrum is defined by a response function. Normally this function can be approximated by a matrix, which can be obtained by means of the Monte Carlo method. Knowing the measured dose curve and the response matrix, the primary X-ray spectrum can be unfolded. However, there are some problems that strongly affect the applicability of this method: i.e. technical features of the flat panel and inherent characteristics of the involved radiation physics (ill-posed problem). Both aspects are analyzed in this work, concluding that the proposed method can be applied with an acceptable accuracy for spectra without characteristic lines, for instance, tungsten anode in the 50-70 kVp range.

  10. An Unfolding Method for X-ray Spectro-Polarimetry

    CERN Document Server

    Kislat, Fabian; Zajczyk, Anna; Krawczynski, Henric

    2014-01-01

    X-ray polarimetry has great scientific potential and new experiments, such as X-Calibur, PoGOLite, XIPE, and GEMS, will not only be orders of magnitude more sensitive than previous missions, but also provide the capability to measure polarization over a wide energy range. However, the measured spectra depend on the collection area, detector responses, and, in case of balloon-borne experiments, the absorption of X-rays in the atmosphere, all of which are energy dependent. Combined with the typically steep source spectra, this leads to significant biases that need to be taken into account to correctly reconstruct energy-resolved polarization properties. In this paper, we present a method based on an iterative unfolding algorithm that makes it possible to simultaneously reconstruct the energy spectrum and the polarization properties as a function of true photon energy. We apply the method to a simulated X-Calibur data set and show that it is able to recover both the energy spectrum and the energy-dependent polar...

  11. The role of the unfolded protein response in diabetes mellitus.

    Science.gov (United States)

    Iwawaki, Takao; Oikawa, Daisuke

    2013-05-01

    The endoplasmic reticulum (ER) plays a key role in the synthesis and modification of secretory and membrane proteins in all eukaryotic cells. Under normal conditions, these proteins are correctly folded and assembled in the ER. However, when cells are exposed to environmental factors such as overproduction of ER proteins, viral infections, or glucose deprivation, the secretory and membrane proteins can accumulate in unfolded or misfolded forms in the lumen of the ER, and consequently, cause stress in the ER. To maintain cellular homeostasis, cells induce several responses to ER stress. In mammalian cells, ER stress responses are induced by a diversity of signal pathways. There are three ER-located transmembrane proteins that play important roles in mammalian ER stress responses: activating transcription factor 6, inositol-requiring protein 1, and protein kinase RNA-like endoplasmic reticulum kinase. ER stress is linked to various diseases, including diabetes. This review highlights the particular importance of ER stress-responsive molecules in insulin biosynthesis, glyconeogenesis, insulin resistance, glucose intolerance, and pancreatic β-cell apoptosis. An understanding of the pathogenic mechanism of diabetes from the aspect of ER stress is crucial in formulating therapeutic strategies.

  12. New insights into the unfolded protein response in stem cells.

    Science.gov (United States)

    Yang, Yanzhou; Cheung, Hoi Hung; Tu, JiaJie; Miu, Kai Kei; Chan, Wai Yee

    2016-08-16

    The unfolded protein response (UPR) is an evolutionarily conserved adaptive mechanism to increase cell survival under endoplasmic reticulum (ER) stress conditions. The UPR is critical for maintaining cell homeostasis under physiological and pathological conditions. The vital functions of the UPR in development, metabolism and immunity have been demonstrated in several cell types. UPR dysfunction activates a variety of pathologies, including cancer, inflammation, neurodegenerative disease, metabolic disease and immune disease. Stem cells with the special ability to self-renew and differentiate into various somatic cells have been demonstrated to be present in multiple tissues. These cells are involved in development, tissue renewal and certain disease processes. Although the role and regulation of the UPR in somatic cells has been widely reported, the function of the UPR in stem cells is not fully known, and the roles and functions of the UPR are dependent on the stem cell type. Therefore, in this article, the potential significances of the UPR in stem cells, including embryonic stem cells, tissue stem cells, cancer stem cells and induced pluripotent cells, are comprehensively reviewed. This review aims to provide novel insights regarding the mechanisms associated with stem cell differentiation and cancer pathology.

  13. Natively unfolded proteins: a point where biology waits for physics.

    Science.gov (United States)

    Uversky, Vladimir N

    2002-04-01

    The experimental material accumulated in the literature on the conformational behavior of intrinsically unstructured (natively unfolded) proteins was analyzed. Results of this analysis showed that these proteins do not possess uniform structural properties, as expected for members of a single thermodynamic entity. Rather, these proteins may be divided into two structurally different groups: intrinsic coils, and premolten globules. Proteins from the first group have hydrodynamic dimensions typical of random coils in poor solvent and do not possess any (or almost any) ordered secondary structure. Proteins from the second group are essentially more compact, exhibiting some amount of residual secondary structure, although they are still less dense than native or molten globule proteins. An important feature of the intrinsically unstructured proteins is that they undergo disorder-order transition during or prior to their biological function. In this respect, the Protein Quartet model, with function arising from four specific conformations (ordered forms, molten globules, premolten globules, and random coils) and transitions between any two of the states, is discussed.

  14. The Unfolded Protein Response in Amelogenesis and Enamel Pathologies

    Directory of Open Access Journals (Sweden)

    Steven J. Brookes

    2017-09-01

    Full Text Available During the secretory phase of their life-cycle, ameloblasts are highly specialized secretory cells whose role is to elaborate an extracellular matrix that ultimately confers both form and function to dental enamel, the most highly mineralized of all mammalian tissues. In common with many other “professional” secretory cells, ameloblasts employ the unfolded protein response (UPR to help them cope with the large secretory cargo of extracellular matrix proteins transiting their ER (endoplasmic reticulum/Golgi complex and so minimize ER stress. However, the UPR is a double-edged sword, and, in cases where ER stress is severe and prolonged, the UPR switches from pro-survival to pro-apoptotic mode. The purpose of this review is to consider the role of the ameloblast UPR in the biology and pathology of amelogenesis; specifically in respect of amelogenesis imperfecta (AI and fluorosis. Some forms of AI appear to correspond to classic proteopathies, where pathological intra-cellular accumulations of protein tip the UPR toward apoptosis. Fluorosis also involves the UPR and, while not of itself a classic proteopathic disease, shares some common elements through the involvement of the UPR. The possibility of therapeutic intervention by pharmacological modulation of the UPR in AI and fluorosis is also discussed.

  15. Giant colon lipoma.

    Science.gov (United States)

    Yaman, İsmail; Derici, Hayrullah; Demirpolat, Gülen

    2015-01-01

    Colon lipomas are rare, non-epithelial tumors. They are generally smaller than two centimeters and asymptomatic, they are incidentally diagnosed and do not require treatment. Large and symptomatic colon lipomas are rather rare. Its differential diagnosis is generally made by histopathological examination of the resected specimen. A fifty-year-old female patient presented with the symptoms of abdominal pain, swelling in the abdomen and loss of weight. During colonoscopy, there was a submucosal mass of 8×6 cm, which almost completely obstructed the lumen in the hepatic flexure and was covered by a mucosa that was sporadically ulcerated and necrotic in nature. In magnetic resonance imaging, an ovoid mass with a diameter of 8.5 cm at its widest dimension was detected, which had signal intensity similar to that of adipose tissue. Since the patient was symptomatic and differential diagnosis could not be made, she underwent laparoscopic right hemicolectomy. A submucosal lipoma was detected on histopathological examination of the specimen. The patient was discharged without any problems on post-operative day 7. Definite diagnosis of lipomas before surgery is challenging; they may be mistaken for malignancy, especially if the lesion is large and ulcerated. For large and symptomatic colon lipomas, surgery is required to both prevent complications and rule out malignancy.

  16. Neoplasia de colon

    Directory of Open Access Journals (Sweden)

    Alina Torreblanca Xiques

    2014-12-01

    Full Text Available El cáncer de colon es un tumor que se desarrolla por degeneración maligna de las células del intestino grueso, desde la válvula ileocecal hasta la flexura recto sigmoidea. Se presenta el caso de un paciente masculino, de 75 años, con astenia anorexia y pérdida de peso; al examen físico: mucosas hipocoloreadas, abdomen blando no doloroso a la palpación superficial ni profunda. Se palpa aumento de volumen a nivel de la fosa ilíaca derecha, fija, de consistencia dura, ruidos hidroaereos normales. Se realizaron exámenes hematológicos, radiológicos y endoscópicos para el diagnóstico. Se tuvo la confirmación diagnóstica por anatomía patológica de adenocarcinoma de colon derecho, bien diferenciado. Se aplicó tratamiento primario, consistente en una amplia resección quirúrgica del cáncer del colon y el drenaje linfático regional, posteriormente se aplicó quimioterapia. El paciente evolucionó satisfactoriamente

  17. 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.

  18. Using circular dichroism collected as a function of temperature to determine the thermodynamics of protein unfolding and binding interactions

    Science.gov (United States)

    Greenfield, Norma J.

    2009-01-01

    Circular dichroism (CD) is an excellent spectroscopic technique for following the unfolding and folding of proteins as a function of temperature. One of its principal applications is to determine the effects of mutations and ligands on protein and polypeptide stability If the change in CD as a function of temperature is reversible, analysis of the data may be used to determined the van't Hoff enthalpy (ΔH) and entropy (ΔS) of unfolding, the midpoint of the unfolding transition (TM) and the free energy (ΔG) of unfolding. Binding constants of protein-protein and protein-ligand interactions may also be estimated from the unfolding curves. Analysis of CD spectra obtained as a function of temperature is also useful to determine whether a protein has unfolding intermediates. Measurement of the spectra of five folded proteins and their unfolding curves at a single wavelength takes approximately eight hours. PMID:17406506

  19. Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes.

    Science.gov (United States)

    Finka, Andrija; Mattoo, Rayees U H; Goloubinoff, Pierre

    2016-06-01

    Molecular chaperones control the cellular folding, assembly, unfolding, disassembly, translocation, activation, inactivation, disaggregation, and degradation of proteins. In 1989, groundbreaking experiments demonstrated that a purified chaperone can bind and prevent the aggregation of artificially unfolded polypeptides and use ATP to dissociate and convert them into native proteins. A decade later, other chaperones were shown to use ATP hydrolysis to unfold and solubilize stable protein aggregates, leading to their native refolding. Presently, the main conserved chaperone families Hsp70, Hsp104, Hsp90, Hsp60, and small heat-shock proteins (sHsps) apparently act as unfolding nanomachines capable of converting functional alternatively folded or toxic misfolded polypeptides into harmless protease-degradable or biologically active native proteins. Being unfoldases, the chaperones can proofread three-dimensional protein structures and thus control protein quality in the cell. Understanding the mechanisms of the cellular unfoldases is central to the design of new therapies against aging, degenerative protein conformational diseases, and specific cancers.

  20. A Quasi-Metric Approach to Multidimensional Unfolding for Reducing the Occurrence of Degenerate Solutions.

    Science.gov (United States)

    Kim, Chulwan; Rangaswamy, Arvind; DeSarbo, Wayne S.

    1999-01-01

    Presents an approach to multidimensional unfolding that reduces the occurrence of degenerate solutions and conducts a Monte Carlo study to demonstrate the superiority of the new method to the ALSCAL and KYST nonmetric procedures for student preference data. (SLD)

  1. The unfolding of God’s revelation in Hebrews 1:1–2a

    Directory of Open Access Journals (Sweden)

    Albert Coetsee

    2016-04-01

    Full Text Available In the introduction to his sermon, the writer of Hebrews suggests that God’s revelation unfolded from his so-called ‘Old Testament’ revelation to his ‘New Testament’ revelation in his Son (Heb. 1:1–2a. By doing a thorough exegesis of Hebrews 1:1–2a, the author’s view of such an unfolding revelation is confirmed. From this conclusion, certain hermeneutical implications of the unfolding of God’s revelation are drawn for believers and scholars today. Among others, it is determined that God’s revelation is progressive, that his revelation in his Son is superior, climactic and final, and that God’s final revelation in his Son can only be understood within the context of his Old Testament revelation, and vice versa.Keywords: Hebrews; Hebrews 1:1-2a; unfolding; revelation; hermeneutics

  2. Protein unfolding versus β-sheet separation in spider silk nanocrystals

    Science.gov (United States)

    Alam, Parvez

    2014-03-01

    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.

  3. Human defensins facilitate local unfolding of thermodynamically unstable regions of bacterial protein toxins

    National Research Council Canada - National Science Library

    Kudryashova, Elena; Quintyn, Royston; Seveau, Stephanie; Lu, Wuyuan; Wysocki, Vicki H; Kudryashov, Dmitri S

    2014-01-01

    .... In this study, we showed that binding of neutrophil ?-defensin HNP1 to affected bacterial toxins caused their local unfolding, potentiated their thermal melting and precipitation, exposed new regions for proteolysis, and increased susceptibility...

  4. Thermal unfolding of myoglobin in the Landau-Ginzburg-Wilson approach

    Science.gov (United States)

    Peng, Xubiao; Sieradzan, Adam K.; Niemi, Antti J.

    2016-12-01

    The Landau-Ginzburg-Wilson paradigm is applied to model the low-temperature crystallographic C α backbone structure of sperm whale myoglobin. The Glauber protocol is employed to simulate its response to an increase in ambient temperature. The myoglobin is found to unfold from its native state by a succession of α -helical intermediates, fully in line with the observed folding and unfolding patterns in denaturation experiments. In particular, a molten globule intermediate is identified with experimentally correct attributes. A detailed, experimentally testable contact map is constructed to characterize the specifics of the unfolding pathway, including the formation of long-range interactions. The results reveal how the unfolding process of a protein is driven by the interplay between, and a successive melting of, its modular secondary structure components.

  5. Natively unfolded human prothymosin alpha adopts partially folded collapsed conformation at acidic pH.

    Science.gov (United States)

    Uversky, V N; Gillespie, J R; Millett, I S; Khodyakova, A V; Vasiliev, A M; Chernovskaya, T V; Vasilenko, R N; Kozlovskaya, G D; Dolgikh, D A; Fink, A L; Doniach, S; Abramov, V M

    1999-11-09

    Prothymosin alpha has previously been shown to be unfolded at neutral pH, thus belonging to a growing family of "natively unfolded" proteins. The structural properties and conformational stability of recombinant human prothymosin alpha were characterized at neutral and acidic pH by gel filtration, SAXS, circular dichroism, ANS fluorescence, (1)H NMR, and resistance to urea-induced unfolding. Interestingly, prothymosin alpha underwent a cooperative transition from the unfolded state into a partially folded conformation on lowering the pH. This conformation of prothymosin alpha is a compact denatured state, with structural properties different from those of the molten globule. The formation of alpha-helical structure by the glutamic acid-rich elements of the protein accompanied by the partial hydrophobic collapse is expected at lower pH due to the neutralization of the negatively charged residues. It is possible that such conformational changes may be associated with the protein function.

  6. Mechanical unfolding of RNA: From hairpins to structures with internal multiloops

    CERN Document Server

    Hyeon, Changbong

    2007-01-01

    Mechanical unfolding of RNA structures, ranging from hairpins to ribozymes, using laser optical tweezer (LOT) experiments have begun to reveal the features of the energy landscape that cannot be easily explored using conventional experiments. Upon application of constant force ($f$), RNA hairpins undergo cooperative transitions from folded to unfolded states whereas subdomains of ribozymes unravel one at a time. Here, we use a self-organized polymer (SOP) model and Brownian dynamics simulations to probe mechanical unfolding at constant force and constant-loading rate of four RNA structures of varying complexity. Our work shows (i) the response of RNA to force is largely determined by the native structure; (ii) only by probing mechanical unfolding over a wide range of forces can the underlying energy landscape be fully explored.

  7. Sequence-Specific Solvent Accessibilities of Protein Residues in Unfolded Protein Ensembles

    OpenAIRE

    Bernadó, Pau,; Blackledge, Martin; Sancho, Javier

    2006-01-01

    Protein stability cannot be understood without the correct description of the unfolded state. We present here an efficient method for accurate calculation of atomic solvent exposures for denatured protein ensembles. The method used to generate the ensembles has been shown to reproduce diverse biophysical experimental data corresponding to natively and chemically unfolded proteins. Using a data set of 19 nonhomologous proteins containing from 98 to 579 residues, we report average accessibiliti...

  8. Isoentropic and Isoenthalpic Temperatures of Protein Unfolding in Hydrophobic Interaction Chromatography

    Institute of Scientific and Technical Information of China (English)

    Yan YAN; Rui Xian LIU; Yin Mao WEI; Ye Hua SHEN; Xin Du GENG

    2006-01-01

    The thermal behaviors of five proteins in hydrophobic interaction chromatography (HIC) were investigated in the temperature range from 0 to 50℃. The thermodynamic parameters (△H°,△S°, △Cp°and △G°) of these proteins in the process of retention and unfolding were determined.The existence of enthalpy and entropy convergence with temperature was confirmed. The differences of the isoentropic and isoenthalpic temperatures for protein unfolding in HIC system from the traditional solution were elucidated.

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

    CERN Document Server

    Milke, Natalie; Klepser, Stefan; Mazin, Daniel; Blobel, Volker; Rhode, Wolfgang; 10.1016/j.nima.2012.08.105

    2012-01-01

    The unfolding program TRUEE is a software package for the numerical solution of inverse problems. The algorithm was fi?rst applied in the FORTRAN77 program RUN. RUN is an event-based unfolding algorithm which makes use of the Tikhonov regularization. It has been tested and compared to di?fferent 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.

  10. Long-Range Contacts in Unfolding of Two-State Proteins.

    Science.gov (United States)

    Samuel, Selvaraj; Balasubramanian, Harihar

    2017-01-01

    Predicting the unfolding rates of proteins remains complicated due to the intricacy present in the unfolding pathway of proteins and further it was observed that the experimental unfolding data were less while compared to folding kinetics. The aim of our present work is to show the variation in long-range contacts observed in various sequence separation bins belonging to all-α, all-β and mixed structural classes of 52 two-state proteins. In this work linear regression technique have been used and regression equations were developed using long-range contacts observed from various sequence separation bins. Also nine topological parameters developed from the 3-D structures of proteins are related with their experimental unfolding rates and their variation in correlation coefficient is observed before and after structural classification. The present work aims to show that long-range contacts formed between residues which are sequentially far and spatially close in the 3-D structure of proteins play a crucial role in the unfolding mechanism of proteins. Also importance of long-range contacts in various experimental and theoretical studies of protein folding along with NMR studies of the unfolded non-native states of proteins have been discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

    Heidarsson, Pétur O; Valpapuram, Immanuel; Camilloni, Carlo; Imparato, Alberto; Tiana, Guido; Poulsen, Flemming M; Kragelund, Birthe B; Cecconi, Ciro

    2012-10-17

    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 pulling axes, with transition states located almost halfway between the unfolded and folded states. Surprisingly, the deformability of ACBP is greater than that observed for the highly pliant molten globule intermediate states. Furthermore, when manipulated from the N- and C-termini, ACBP unfolds by populating a transition state that resembles that observed during chemical denaturation, both for structure and position along the reaction coordinate. Our data provide the first experimental evidence of a spontaneous-like mechanical unfolding pathway of a protein. The mechanical behavior of ACBP is discussed in terms of topology and helix propensity.

  12. Mode decomposition based on crystallographic symmetry in the band-unfolding method

    Science.gov (United States)

    Ikeda, Yuji; Carreras, Abel; Seko, Atsuto; Togo, Atsushi; Tanaka, Isao

    2017-01-01

    The band-unfolding method is widely used to calculate the effective band structures of a disordered system from its supercell model. The unfolded band structures show the crystallographic symmetry of the underlying structure, where the difference of chemical components and the local atomic relaxation are ignored. However, it has still been difficult to decompose the unfolded band structures into the modes based on the crystallographic symmetry of the underlying structure, and therefore detailed analyses of the unfolded band structures have been restricted. In this study, a procedure to decompose the unfolded band structures according to the small representations (SRs) of the little groups is developed. The decomposition is performed using the projection operators for SRs derived from the group representation theory. The current method is employed to investigate the phonon band structure of disordered face-centered-cubic Cu0.75Au0.25 , which has large variations of atomic masses and force constants among the atomic sites due to the chemical disorder. In the unfolded phonon band structure, several peculiar behaviors such as discontinuous and split branches are found in the decomposed modes corresponding to specific SRs. They are found to occur because different combinations of the chemical elements contribute to different regions of frequency.

  13. Ethanol cellular defense induce unfolded protein response in yeast

    Directory of Open Access Journals (Sweden)

    Elisabet eNavarro-Tapia

    2016-02-01

    Full Text Available Ethanol is a valuable industrial product and a common metabolite used by many cell types. However, this molecule produces high levels of cytotoxicity affecting cellular performance at several levels. In the presence of ethanol, cells must adjust some of their components, such as the membrane lipids to maintain homeostasis. In the case of microorganism as Saccharomyces cerevisiae, ethanol is one of the principal products of their metabolism and is the main stress factor during fermentation. Although many efforts have been made, mechanisms of ethanol tolerance are not fully understood and very little evidence is available to date for specific signaling by ethanol in the cell. This work studied two Saccharomyces cerevisiae strains, CECT10094 and Temohaya-MI26, isolated from flor wine and agave fermentation (a traditional fermentation from Mexico respectively, which differ in ethanol tolerance, in order to understand the molecular mechanisms underlying the ethanol stress response and the reasons for different ethanol tolerance. The transcriptome was analyzed after ethanol stress and, among others, an increased activation of genes related with the unfolded protein response (UPR and its transcription factor, Hac1p, was observed in the tolerant strain CECT10094. We observed that this strain also resist more UPR agents than Temohaya-MI26 and the UPR-ethanol stress correlation was corroborated observing growth of 15 more strains and discarding UPR correlation with other stresses as thermal or oxidative stress. Furthermore, higher activation of UPR pathway in the tolerant strain CECT10094 was observed using a UPR mCherry reporter. Finally, we observed UPR activation in response to ethanol stress in other S. cerevisiae ethanol tolerant strains as the wine strains T73 and EC1118. This work demonstrates that the UPR pathway is activated under ethanol stress occurring in a standard fermentation and links this response to an enhanced ethanol tolerance. Thus

  14. Unfolding the resident-invader dynamics of similar strategies.

    Science.gov (United States)

    Dercole, Fabio; Geritz, Stefan A H

    2016-04-01

    We investigate the competition between two groups of similar agents in the restricted, but classical context of unstructured populations varying in continuous time in an isolated, homogeneous, and constant abiotic environment. Individual behavioral and phenotypic traits are quantified by one-dimensional strategies and intra- as well as inter-specific interactions are described in the vicinity of a stationary regime. Some known results are revisited: invasion by a new strategy generically implies the substitution of the former resident; and resident-invader coexistence is possible close to singular strategies-the stationary points of the invasion fitness-and is generically protected-each of the two competing groups can invade the other. An (almost known) old conjecture is shown true: competition close to a singular strategy is "essentially Lotka-Volterra"-dominance of one strategy, protected coexistence at an intermediate equilibrium, and mutual exclusion are the generic outcomes. And the unfolding of the competition scenarios is completed with the analysis of three degenerate singular strategies-characterized by vanishing second-order fitness derivatives-near which resident-invader coexistence can be unprotected. Our approach is based on the series expansion of a generic demographic model, w.r.t. the small strategy difference between the two competing groups, and on known results on time-scale separation and bifurcation theories. The analysis is carried out up to third order and is extendable to any order. For each order, explicit genericity conditions under which higher orders can be neglected are derived and, interestingly, they are known prior to invasion. An important result is that degeneracies up to third-order are required to have more than one stable way of coexistence. Such degeneracies can be due to particular symmetries in the model formulation, and breaking the genericity conditions provides a direct way to draw biological interpretations. The developed

  15. ABCB10 depletion reduces unfolded protein response in mitochondria.

    Science.gov (United States)

    Yano, Masato

    2017-04-29

    Mitochondria have many functions, including ATP generation. The electron transport chain (ETC) and the coupled ATP synthase generate ATP by consuming oxygen. Reactive oxygen species (ROS) are also produced by ETC, and ROS damage deoxyribonucleic acids, membrane lipids and proteins. Recent analysis indicate that mitochondrial unfolded protein response (UPR(mt)), which enhances expression of mitochondrial chaperones and proteases to remove damaged proteins, is activated when damaged proteins accumulate in the mitochondria. In Caenorhabditis elegans, HAF-1, a putative ortholog of human ABCB10, plays an essential role in signal transduction from mitochondria to nuclei to enhance UPR(mt). Therefore, it is possible that ABCB10 has a role similar to that of HAF-1. However, it has not been reported whether ABCB10 is a factor in the signal transduction pathway to enhance UPR(mt). In this study, ABCB10 was depleted in HepG2 cells using small interfering RNA (siRNA), and the effect was examined. ABCB10 depletion upregulated ROS and the expression of ROS-detoxifying enzymes (SOD2, GSTA1, and GSTA2), and SESN3, a protein induced by ROS to protect the cell from oxidative stress. In addition, ABCB10 depletion significantly decreased expression of UPR(mt)-related mitochondrial chaperones (HSPD1 and DNAJA3), and a mitochondrial protease (LONP1). However, the putative activity of ABCB10 to export peptides from mitochondria was not lost by ABCB10 depletion. Altogether, these data suggest that ABCB10 is involved in UPR(mt) signaling pathway similar to that of HAF-1, although ABCB10 probably does not participate in peptide export from mitochondria. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Pulse sequence for dynamic volumetric imaging of hyperpolarized metabolic products

    Science.gov (United States)

    Cunningham, Charles H.; Chen, Albert P.; Lustig, Michael; Hargreaves, Brian A.; Lupo, Janine; Xu, Duan; Kurhanewicz, John; Hurd, Ralph E.; Pauly, John M.; Nelson, Sarah J.; Vigneron, Daniel B.

    2008-07-01

    Dynamic nuclear polarization and dissolution of a 13C-labeled substrate enables the dynamic imaging of cellular metabolism. Spectroscopic information is typically acquired, making the acquisition of dynamic volumetric data a challenge. To enable rapid volumetric imaging, a spectral-spatial excitation pulse was designed to excite a single line of the carbon spectrum. With only a single resonance present in the signal, an echo-planar readout trajectory could be used to resolve spatial information, giving full volume coverage of 32 × 32 × 16 voxels every 3.5 s. This high frame rate was used to measure the different lactate dynamics in different tissues in a normal rat model and a mouse model of prostate cancer.

  17. Nonrigid registration of volumetric images using ranked order statistics

    DEFF Research Database (Denmark)

    Tennakoon, Ruwan; Bab-Hadiashar, Alireza; Cao, Zhenwei

    2014-01-01

    Non-rigid image registration techniques using intensity based similarity measures are widely used in medical imaging applications. Due to high computational complexities of these techniques, particularly for volumetric images, finding appropriate registration methods to both reduce the computation...... burden and increase the registration accuracy has become an intensive area of research. In this paper we propose a fast and accurate non-rigid registration method for intra-modality volumetric images. Our approach exploits the information provided by an order statistics based segmentation method, to find...... the important regions for registration and use an appropriate sampling scheme to target those areas and reduce the registration computation time. A unique advantage of the proposed method is its ability to identify the point of diminishing returns and stop the registration process. Our experiments...

  18. Volumetric characterization of delamination fields via angle longitudinal wave ultrasound

    Science.gov (United States)

    Wertz, John; Wallentine, Sarah; Welter, John; Dierken, Josiah; Aldrin, John

    2017-02-01

    The volumetric characterization of delaminations necessarily precedes rigorous composite damage progression modeling. Yet, inspection of composite structures for subsurface damage remains largely focused on detection, resulting in a capability gap. In response to this need, angle longitudinal wave ultrasound was employed to characterize a composite surrogate containing a simulated three-dimensional delamination field with distinct regions of occluded features (shadow regions). Simple analytical models of the specimen were developed to guide subsequent experimentation through identification of optimal scanning parameters. The ensuing experiments provided visual evidence of the complete delamination field, including indications of features within the shadow regions. The results of this study demonstrate proof-of-principle for the use of angle longitudinal wave ultrasonic inspection for volumetric characterization of three-dimensional delamination fields. Furthermore, the techniques developed herein form the foundation of succeeding efforts to characterize impact delaminations within inhomogeneous laminar materials such as polymer matrix composites.

  19. Magnetic Resonance Image Segmentation and its Volumetric Measurement

    Directory of Open Access Journals (Sweden)

    Rahul R. Ambalkar

    2013-02-01

    Full Text Available Image processing techniques make it possible to extract meaningful information from medical images. Magnetic resonance (MR imaging has been widely applied in biological research and diagnostics because of its excellent soft tissue contrast, non-invasive character, high spatial resolution and easy slice selection at any orientation. The MRI-based brain volumetric is concerned with the analysis of volumes and shapes of the structural components of the human brain. It also provides a criterion, by which we recognize the presence of degenerative diseases and characterize their rates of progression to make the diagnosis and treatments as a easy task. In this paper we have proposed an automated method for volumetric measurement of Magnetic Resonance Imaging and used Self Organized Map (SOM clustering method for their segmentations. We have used the MRI data set of 61 slices of 256×256 pixels in DICOM standard format

  20. Two-dimensional random arrays for real time volumetric imaging

    DEFF Research Database (Denmark)

    Davidsen, Richard E.; Jensen, Jørgen Arendt; Smith, Stephen W.

    1994-01-01

    Two-dimensional arrays are necessary for a variety of ultrasonic imaging techniques, including elevation focusing, 2-D phase aberration correction, and real time volumetric imaging. In order to reduce system cost and complexity, sparse 2-D arrays have been considered with element geometries...... real time volumetric imaging system, which employs a wide transmit beam and receive mode parallel processing to increase image frame rate. Depth-of-field comparisons were made from simulated on-axis and off-axis beamplots at ranges from 30 to 160 mm for both coaxial and offset transmit and receive...... selected ad hoc, by algorithm, or by random process. Two random sparse array geometries and a sparse array with a Mills cross receive pattern were simulated and compared to a fully sampled aperture with the same overall dimensions. The sparse arrays were designed to the constraints of the Duke University...

  1. In Vivo Real Time Volumetric Synthetic Aperture Ultrasound Imaging

    DEFF Research Database (Denmark)

    Bouzari, Hamed; Rasmussen, Morten Fischer; Brandt, Andreas Hjelm

    2015-01-01

    . This paper investigates the in vivo applicability and sensitivity of volumetric SA imaging. Utilizing the transmit events to generate a set of virtual point sources, a frame rate of 25 Hz for a 90° x 90° field-of-view was achieved. Data were obtained using a 3.5 MHz 32 x 32 elements 2-D phased array......Synthetic aperture (SA) imaging can be used to achieve real-time volumetric ultrasound imaging using 2-D array transducers. The sensitivity of SA imaging is improved by maximizing the acoustic output, but one must consider the limitations of an ultrasound system, both technical and biological...... transducer connected to the experimental scanner (SARUS). Proper scaling is applied to the excitation signal such that intensity levels are in compliance with the U.S. Food and Drug Administration regulations for in vivo ultrasound imaging. The measured Mechanical Index and spatial-peak- temporal...

  2. COMPARISON OF VOLUMETRIC REGISTRATION ALGORITHMS FOR TENSOR-BASED MORPHOMETRY

    Science.gov (United States)

    Villalon, Julio; Joshi, Anand A.; Toga, Arthur W.; Thompson, Paul M.

    2015-01-01

    Nonlinear registration of brain MRI scans is often used to quantify morphological differences associated with disease or genetic factors. Recently, surface-guided fully 3D volumetric registrations have been developed that combine intensity-guided volume registrations with cortical surface constraints. In this paper, we compare one such algorithm to two popular high-dimensional volumetric registration methods: large-deformation viscous fluid registration, formulated in a Riemannian framework, and the diffeomorphic “Demons” algorithm. We performed an objective morphometric comparison, by using a large MRI dataset from 340 young adult twin subjects to examine 3D patterns of correlations in anatomical volumes. Surface-constrained volume registration gave greater effect sizes for detecting morphometric associations near the cortex, while the other two approaches gave greater effects sizes subcortically. These findings suggest novel ways to combine the advantages of multiple methods in the future. PMID:26925198

  3. Volumetric 3D display using a DLP projection engine

    Science.gov (United States)

    Geng, Jason

    2012-03-01

    In this article, we describe a volumetric 3D display system based on the high speed DLPTM (Digital Light Processing) projection engine. Existing two-dimensional (2D) flat screen displays often lead to ambiguity and confusion in high-dimensional data/graphics presentation due to lack of true depth cues. Even with the help of powerful 3D rendering software, three-dimensional (3D) objects displayed on a 2D flat screen may still fail to provide spatial relationship or depth information correctly and effectively. Essentially, 2D displays have to rely upon capability of human brain to piece together a 3D representation from 2D images. Despite the impressive mental capability of human visual system, its visual perception is not reliable if certain depth cues are missing. In contrast, volumetric 3D display technologies to be discussed in this article are capable of displaying 3D volumetric images in true 3D space. Each "voxel" on a 3D image (analogous to a pixel in 2D image) locates physically at the spatial position where it is supposed to be, and emits light from that position toward omni-directions to form a real 3D image in 3D space. Such a volumetric 3D display provides both physiological depth cues and psychological depth cues to human visual system to truthfully perceive 3D objects. It yields a realistic spatial representation of 3D objects and simplifies our understanding to the complexity of 3D objects and spatial relationship among them.

  4. Diverticulosis in total colonic aganglionosis

    Energy Technology Data Exchange (ETDEWEB)

    Ivancev, K.; Fork, T.; Haegerstrand, I.; Ivarsson, S.; Kullendorff, C.M.

    Two infants with total colonic aganglionosis (TCA) extending into the distal part of the ileum are described. Considerable diagnostic delay occurred with the correct diagnosis established first at 3 and 8 months, respectively. Radiologic findings compatible with TCA such as prolonged barium retention, reflux into ileum following barium enema, and foreshortening of colon were not clearly evident initially. Both patients demonstrated multiple acquired colon diverticula which increased both in number and size during the period of observation. These diverticula are probably a late manifestation of the spastic state of the anganglionic colon. Thus demonstration of diverticula supplies a strong evidence of TCA in infants with intestinal obstruction. (orig.).

  5. Using surface heave to estimate reservoir volumetric strain

    Energy Technology Data Exchange (ETDEWEB)

    Nanayakkara, A.S.; Wong, R.C.K. [Calgary Univ., AB (Canada)

    2008-07-01

    This paper presented a newly developed numerical tool for estimating reservoir volumetric strain distribution using surface vertical displacements and solving an inverse problem. Waterflooding, steam injection, carbon dioxide sequestration and aquifer storage recovery are among the subsurface injection operations that are responsible for reservoir dilations which propagate to the surrounding formations and extend to the surface resulting in surface heaves. Global positioning systems and surface tiltmeters are often used to measure the characteristics of these surface heaves and to derive valuable information regarding reservoir deformation and flow characteristics. In this study, Tikhonov regularization techniques were adopted to solve the ill-posed inversion problem commonly found in standard inversion techniques such as Gaussian elimination and least squares methods. Reservoir permeability was then estimated by inverting the volumetric strain distribution. Results of the newly developed numerical tool were compared with results from fully-coupled finite element simulation of fluid injection problems. The reservoir volumetric strain distribution was successfully estimated along with an approximate value for reservoir permeability.

  6. Volumetric Light-field Encryption at the Microscopic Scale

    Science.gov (United States)

    Li, Haoyu; Guo, Changliang; Muniraj, Inbarasan; Schroeder, Bryce C.; Sheridan, John T.; Jia, Shu

    2017-01-01

    We report a light-field based method that allows the optical encryption of three-dimensional (3D) volumetric information at the microscopic scale in a single 2D light-field image. The system consists of a microlens array and an array of random phase/amplitude masks. The method utilizes a wave optics model to account for the dominant diffraction effect at this new scale, and the system point-spread function (PSF) serves as the key for encryption and decryption. We successfully developed and demonstrated a deconvolution algorithm to retrieve both spatially multiplexed discrete data and continuous volumetric data from 2D light-field images. Showing that the method is practical for data transmission and storage, we obtained a faithful reconstruction of the 3D volumetric information from a digital copy of the encrypted light-field image. The method represents a new level of optical encryption, paving the way for broad industrial and biomedical applications in processing and securing 3D data at the microscopic scale.

  7. Volumetric Light-field Encryption at the Microscopic Scale

    Science.gov (United States)

    Li, Haoyu; Guo, Changliang; Muniraj, Inbarasan; Schroeder, Bryce C.; Sheridan, John T.; Jia, Shu

    2017-01-01

    We report a light-field based method that allows the optical encryption of three-dimensional (3D) volumetric information at the microscopic scale in a single 2D light-field image. The system consists of a microlens array and an array of random phase/amplitude masks. The method utilizes a wave optics model to account for the dominant diffraction effect at this new scale, and the system point-spread function (PSF) serves as the key for encryption and decryption. We successfully developed and demonstrated a deconvolution algorithm to retrieve both spatially multiplexed discrete data and continuous volumetric data from 2D light-field images. Showing that the method is practical for data transmission and storage, we obtained a faithful reconstruction of the 3D volumetric information from a digital copy of the encrypted light-field image. The method represents a new level of optical encryption, paving the way for broad industrial and biomedical applications in processing and securing 3D data at the microscopic scale. PMID:28059149

  8. Volumetric Light-field Encryption at the Microscopic Scale

    CERN Document Server

    Li, Haoyu; Muniraj, Inbarasan; Schroeder, Bryce C; Sheridan, John T; Jia, Shu

    2016-01-01

    We report a light-field based method that allows the optical encryption of three-dimensional (3D) volumetric information at the microscopic scale in a single 2D light-field image. The system consists of a microlens array and an array of random phase/amplitude masks. The method utilizes a wave optics model to account for the dominant diffraction effect at this new scale, and the system point-spread function (PSF) serves as the key for encryption and decryption. We successfully developed and demonstrated a deconvolution algorithm to retrieve spatially multiplexed discrete and continuous volumetric data from 2D light-field images. Showing that the method is practical for data transmission and storage, we obtained a faithful reconstruction of the 3D volumetric information from a digital copy of the encrypted light-field image. The method represents a new level of optical encryption, paving the way for broad industrial and biomedical applications in processing and securing 3D data at the microscopic scale.

  9. Volumetric Light-field Encryption at the Microscopic Scale.

    Science.gov (United States)

    Li, Haoyu; Guo, Changliang; Muniraj, Inbarasan; Schroeder, Bryce C; Sheridan, John T; Jia, Shu

    2017-01-06

    We report a light-field based method that allows the optical encryption of three-dimensional (3D) volumetric information at the microscopic scale in a single 2D light-field image. The system consists of a microlens array and an array of random phase/amplitude masks. The method utilizes a wave optics model to account for the dominant diffraction effect at this new scale, and the system point-spread function (PSF) serves as the key for encryption and decryption. We successfully developed and demonstrated a deconvolution algorithm to retrieve both spatially multiplexed discrete data and continuous volumetric data from 2D light-field images. Showing that the method is practical for data transmission and storage, we obtained a faithful reconstruction of the 3D volumetric information from a digital copy of the encrypted light-field image. The method represents a new level of optical encryption, paving the way for broad industrial and biomedical applications in processing and securing 3D data at the microscopic scale.

  10. COLONIC ADENOCARCINOMA WITH MALAKOPLAKIA OF COLON - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Chitrawati Bal

    2015-09-01

    Full Text Available The gastrointestinal tract is the most common site for malakoplakia outside the urinary tract. A variety of conditions co - exists with malakoplakia including inflammatory bowel disease, systemic lupus erythematosus, immunodeficiency and tuberculosis. Rarely, it is associated with colonic ad enocarcinoma or adenomas. We report a case of malakoplakia in association with colonic adenocarcinoma.

  11. An Act of Colonization

    DEFF Research Database (Denmark)

    Rasmussen, Anders Bo

    When Gideon Welles, U.S. Secretary of the Navy, sat down to write his diary entry on September 26, 1862, his thoughts turned once more to colonization. President Lincoln was an ardent proponent of colonization, “the government-promoted settlement of black Americans in Africa or some other location......” and based on the recurring cabinet discussions, Welles understood that “Great Britain, Denmark and perhaps other powers would take them [the black population].” Since at least 1860, Denmark had encouraged the American government to send the “quite uncivilized (…) Africans liberated” from slave ships to St...... and the United States signed an act on July 19, 1862, wherein the U.S. Navy agreed to unload “all negroes, mulattoes, or persons of color, delivered from on board vessels seized in the prosecution of the slave trade.” Yet, despite the two countries’ mutual interests in employing “laborers of African Extraction...

  12. Malacoplaquia intestinal Colonic malakoplakia

    Directory of Open Access Journals (Sweden)

    Jacinto José Frem Aun

    1998-04-01

    Full Text Available Malacoplakia is a chronic granulomatous disease of unknown origin. However immunodeficiency states (immunossuppressive medication, old people, renal transplantation, leukaemia, diabetes mellitus, malnutrition and others have been associated with patients with malacoplakia. An infectious cause of malakoplakia is suggested by the finding of coliform bacteria in the phagolysosomes of macrophages. The histologic study is characterized by a infiltrate of large macrophages (Hansenmann cells with pathognomonic inclusions containing siderocalcific structures (Michaelis-Gutmann bodies. Most of the cases reported in literature, involve the genitourinary tract, but other structures can be affected (brain, bone, adrenal glands, lymph nodes, intestine, and others. A 66-year-old man whith a abdominal mass, went to our hospital with a colonic tumour diagnosis. The patient was submitted to a surgery, with resection of the rigth colon. The disease was invading a portion of the retroperitoneal tissue that was removed. The histopatologic study showed the pathognomonic sign of malakoplakia (Hansenmann cells and Michaelis-Gutmann bodies. Norfloxacin have been used to the complementar treatment with total cure of the patient.

  13. Carbohydrate markers in colon carcinoma.

    Science.gov (United States)

    Szajda, Sławomir Dariusz; Jankowska, Anna; Zwierz, Krzysztof

    2008-01-01

    Spontaneously mutated multiple oncogenes and/or tumor suppressor genes in colon epithelial cell and its progeny, may cause proliferation out of control and create benign colon neoplasm (colon polyp). If additional mutations involve genes responsible for cell adhesion and movement, aberrant epithelial cells may become malignant (colon cancer) and invade surrounding and remote tissues, creating secondary tumors called metastases. Incidence of colorectal cancer dramatically increases at 50-65 year of age. In Europe in 2006 colorectal cancer consisted 12.9% of all cancers and caused 207,400 deaths. To laboratory detection and monitoring of colon cancer are used tumor markers. Tumor markers are substances produced by the body in response to cancer, or by cancer tissue itself. Glycoconjugate markers for colon cancer include aberrant: mucins covering the surface of the colon epithelial cells, cadherins, selectins and Ig-like adhesion molecules mediating cell-cell adhesion, integrins and integral membrane proteoglycans responsible for adhesion of colon epithelial cells to extracellular matrix, glycoconjugate components of ECM, as well as lysosomal membrane glycoproteins and exoglycosidases. Detection of colon cancer at early non malignant stage is crucial in its prevention and eradication. As colon cancer is the effect of accumulation many somatic mutations in oncogens, supressors, mismatch repair genes and many genes responsible for posttranslational modifications of proteins, multidirectional approach should be applied for its detection. A glycobiological approach to diagnosis and treatment of colorectal cancer should be directed to detection changes in glycosylation accompanying every step of colon cancer progression, and correlation between changes in glycosylation and tumor progression.

  14. Conformational properties of the unfolded state of Im7 in nondenaturing conditions.

    Science.gov (United States)

    Pashley, Clare L; Morgan, Gareth J; Kalverda, Arnout P; Thompson, Gary S; Kleanthous, Colin; Radford, Sheena E

    2012-02-17

    The unfolded ensemble in aqueous solution represents the starting point of protein folding. Characterisation of this species is often difficult since the native state is usually predominantly populated at equilibrium. Previous work has shown that the four-helix protein, Im7 (immunity protein 7), folds via an on-pathway intermediate. While the transition states and folding intermediate have been characterised in atomistic detail, knowledge of the unfolded ensemble under the same ambient conditions remained sparse. Here, we introduce destabilising amino acid substitutions into the sequence of Im7, such that the unfolded state becomes predominantly populated at equilibrium in the absence of denaturant. Using far- and near-UV CD, fluorescence, urea titration and heteronuclear NMR experiments, we show that three amino acid substitutions (L18A-L19A-L37A) are sufficient to prevent Im7 folding, such that the unfolded state is predominantly populated at equilibrium. Using measurement of chemical shifts, (15)N transverse relaxation rates and sedimentation coefficients, we show that the unfolded species of L18A-L19A-L37A deviates significantly from random-coil behaviour. Specifically, we demonstrate that this unfolded species is compact (R(h)=25 Å) relative to the urea-denatured state (R(h)≥30 Å) and contains local clusters of hydrophobic residues in regions that correspond to the four helices in the native state. Despite these interactions, there is no evidence for long-range stabilising tertiary interactions or persistent helical structure. The results reveal an unfolded ensemble that is conformationally restricted in regions of the polypeptide chain that ultimately form helices I, II and IV in the native state.

  15. The Intrinsic Dynamics and Unfolding Process of an Antibody Fab Fragment Revealed by Elastic Network Model

    Directory of Open Access Journals (Sweden)

    Ji-Guo Su

    2015-12-01

    Full Text Available Antibodies have been increasingly used as pharmaceuticals in clinical treatment. Thermal stability and unfolding process are important properties that must be considered in antibody design. In this paper, the structure-encoded dynamical properties and the unfolding process of the Fab fragment of the phosphocholine-binding antibody McPC603 are investigated by use of the normal mode analysis of Gaussian network model (GNM. Firstly, the temperature factors for the residues of the protein were calculated with GNM and then compared with the experimental measurements. A good result was obtained, which provides the validity for the use of GNM to study the dynamical properties of the protein. Then, with this approach, the mean-square fluctuation (MSF of the residues, as well as the MSF in the internal distance (MSFID between all pairwise residues, was calculated to investigate the mobility and flexibility of the protein, respectively. It is found that the mobility and flexibility of the constant regions are higher than those of the variable regions, and the six complementarity-determining regions (CDRs in the variable regions also exhibit relative large mobility and flexibility. The large amplitude motions of the CDRs are considered to be associated with the immune function of the antibody. In addition, the unfolding process of the protein was simulated by iterative use of the GNM. In our method, only the topology of protein native structure is taken into account, and the protein unfolding process is simulated through breaking the native contacts one by one according to the MSFID values between the residues. It is found that the flexible regions tend to unfold earlier. The sequence of the unfolding events obtained by our method is consistent with the hydrogen-deuterium exchange experimental results. Our studies imply that the unfolding behavior of the Fab fragment of antibody McPc603 is largely determined by the intrinsic dynamics of the protein.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-07

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

  17. Force-induced unfolding of fibronectin in the extracellular matrix of living cells.

    Directory of Open Access Journals (Sweden)

    Michael L Smith

    2007-10-01

    Full Text Available Whether mechanically unfolded fibronectin (Fn is present within native extracellular matrix fibrils is controversial. Fn extensibility under the influence of cell traction forces has been proposed to originate either from the force-induced lengthening of an initially compact, folded quaternary structure as is found in solution (quaternary structure model, where the dimeric arms of Fn cross each other, or from the force-induced unfolding of type III modules (unfolding model. Clarification of this issue is central to our understanding of the structural arrangement of Fn within fibrils, the mechanism of fibrillogenesis, and whether cryptic sites, which are exposed by partial protein unfolding, can be exposed by cell-derived force. In order to differentiate between these two models, two fluorescence resonance energy transfer schemes to label plasma Fn were applied, with sensitivity to either compact-to-extended conformation (arm separation without loss of secondary structure or compact-to-unfolded conformation. Fluorescence resonance energy transfer studies revealed that a significant fraction of fibrillar Fn within a three-dimensional human fibroblast matrix is partially unfolded. Complete relaxation of Fn fibrils led to a refolding of Fn. The compactly folded quaternary structure with crossed Fn arms, however, was never detected within extracellular matrix fibrils. We conclude that the resting state of Fn fibrils does not contain Fn molecules with crossed-over arms, and that the several-fold extensibility of Fn fibrils involves the unfolding of type III modules. This could imply that Fn might play a significant role in mechanotransduction processes.

  18. Explant cultures of human colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Barrett, L.A.; Jackson, F.E.

    1978-01-01

    Human colonic epithelium has been cultured as explants in a chemically defined medium for periods of 1 to 20 days. The viability of the explants was shown by the preservation of the ultrastructural features of the colonic epithelial cells and by active incorporation of radioactive precursors into...

  19. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... Search Category Cancer A-Z Colorectal Cancer Colon Cancer Videos Thanks to improvements in prevention, early detection, ... also personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A ...

  20. Get Tested for Colon Cancer: Here's How

    Science.gov (United States)

    ... Local Offices Close + - Text Size Get Tested for Colon Cancer [Video] This free video explains the most commonly ... re like most people, the thought of getting colon cancer or even going for a colon cancer test ...

  1. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... Search Search Category Cancer A-Z Colorectal Cancer Colon Cancer Videos Thanks to improvements in prevention, early detection, ... are also personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A ...

  2. Get Tested for Colon Cancer: Here's How

    Science.gov (United States)

    ... Search Search Category Cancer A-Z Colorectal Cancer Colon Cancer Videos Thanks to improvements in prevention, early detection, ... are also personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A ...

  3. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... Search Category Cancer A-Z Colorectal Cancer Colon Cancer Videos Thanks to improvements in prevention, early detection, ... also personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A ...

  4. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... How. Colon Cancer Treatments Play Play Colon Cancer Surgery: What You Need to Know Play Play Colon Cancer Surgery: Colostomies Play Play Advantages of Laparoscopic Colorectal Surgery ...

  5. Differences in the unfolding of procerain induced by pH, guanidine hydrochloride, urea, and temperature.

    Science.gov (United States)

    Dubey, Vikash Kumar; Jagannadham, M V

    2003-10-28

    The structural and functional aspects along with equilibrium unfolding of procerain, a cysteine protease from Calotropis procera, were studied in solution. The energetic parameters and conformational stability of procerain in different states were also estimated and interpreted. Procerain belongs to the alpha + beta class of proteins. At pH 2.0, procerain exists in a partially unfolded state with characteristics of a molten globule-like state, and the protein is predominantly a beta-sheet conformation and exhibits strong ANS binding. GuHCl and temperature denaturation of procerain in the molten globule-like state is noncooperative, contrary to the cooperativity seen with the native protein, suggesting the presence of two parts in the molecular structure of procerain, possibly domains, with different stability that unfolds in steps. Moreover, tryptophan quenching studies suggested the exposure of aromatic residues to solvent in this state. At lower pH, procerain unfolds to the acid-unfolded state, and a further decrease in the pH drives the protein to the A state. The presence of 0.5 M salt in the solvent composition directs the transition to the A state while bypassing the acid-unfolded state. GuHCl-induced unfolding of procerain at pH 3.0 seen by various methods is cooperative, but the transitions are noncoincidental. Besides, a strong ANS binding to the protein is observed at low concentrations of GuHCl, indicating the presence of an intermediate in the unfolding pathway. On the other hand, even in the presence of urea (8 M), procerain retains all the activity as well as structural parameters at neutral pH. However, the protein is susceptible to unfolding by urea at lower pH, and the transitions are cooperative and coincidental. Further, the properties of the molten globule-like state and the intermediate state are different, but both states have the same conformational stability. This indicates that these intermediates may be located on parallel folding routes

  6. Right colonic diverticulitis.

    Science.gov (United States)

    Lee, In Kyu

    2010-08-01

    Although right colonic diverticultis (RCD) has been reported to be a rare disease in Western countries, RCD is a common diagnosis, with an incidence per 2.9-17 case of appendicitis, in Korea. Many Western studies have reported that it is difficult to differentiate the presenting symptoms of RCD from those of appendicitis before surgery because the signs and symptoms are similar. However, performing a computed tomography scan after the application of the diagnostic criteria for RCD has increased the preoperative RCD diagnostic rate. Treatment strategies have been difficult to define for this condition due to its low preoperative diagnosis rate. However, recent reports have shown that conservative medical treatment of uncomplicated RCD can be recommended and that such treatment is effective due to the benign and self-limited natural history of RCD. Therefore, in this review, we discuss the controversies surrounding RCD management.

  7. Site-specific unfolding thermodynamics of a helix-turn-helix protein.

    Science.gov (United States)

    Amunson, Krista E; Ackels, Loren; Kubelka, Jan

    2008-07-01

    The thermal unfolding of a 40-residue helix-turn-helix subdomain of the P22 viral coat protein was investigated using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) with site-specific 13C isotopic labeling. Helix-turn-helix is the simplest alpha-helical structural motif that combines both secondary and tertiary structural elements. The CD of individual helical fragments reveals that the P22 subdomain is stabilized by tertiary interhelical interactions. Overall the temperature-dependent CD and FTIR data can be described by a three-state process with a partially folded intermediate. However, the analysis of the site-specific 13C IR signals reveals distinct unfolding thermodynamics for each of the labeled sites. The thermodynamic parameters of the thermal unfolding of each of the labeled segments were obtained using singular value decomposition in combination with target transformation and global fitting. The P22 subdomain unfolds from the N-terminus toward the helical segments near the turn. Our results show that as few as two 13C labeled residues can be detected in a 40 residue protein and provide local, site-specific structural information about protein unfolding, which is not resolved by standard, nonsite-specific spectroscopic probes.

  8. BIFURCATION AND UNIVERSAL UNFOLDING FOR A ROTATING SHAFT WITH UNSYMMETRICAL STIFFNESS

    Institute of Scientific and Technical Information of China (English)

    陈芳启; 吴志强; 陈予恕

    2002-01-01

    The 1/2 subharmonic resonance bifurcation and universal unfolding are studied for a rotating shaft with unsymmetrical stiffness. The bifurcation behavior of the response amplitude with respect to the detuning parameter was studied for this class of problems by Xiao et al. Obviously, it is highly important to research the bifurcation behavior of the response amplitude with respect to the unsymmetry of stiffness for this problem. Here, by means of the singularity theory, the bifurcation and universal unfolding of amplitude with respect to the unsymmetrical stiffness parameter are discussed. The results indicate that it is a high codimensional bifurcation problem with codimension 5, and the universal unfolding is given. From the mechanical background, we study four forms of two parameter unfoldings contained in the universal unfolding. The transition sets in the parameter plane and the bifurcation diagrams are plotted. The results obtained in this paper show rich bifurcation phenomena and provide some guidance for the analysis and design of dynamic buckling experiments of this class of system, especially, for the choice of system parameters.

  9. Temperature-induced unfolding behavior of proteins studied by tensorial elastic network model.

    Science.gov (United States)

    Srivastava, Amit; Granek, Rony

    2016-12-01

    Motivated by single molecule experiments and recent molecular dynamics (MD) studies, we propose a simple and computationally efficient method based on a tensorial elastic network model to investigate the unfolding pathways of proteins under temperature variation. The tensorial elastic network model, which relies on the native state topology of a protein, combines the anisotropic network model, the bond bending elasticity, and the backbone twist elasticity to successfully predicts both the isotropic and anisotropic fluctuations in a manner similar to the Gaussian network model and anisotropic network model. The unfolding process is modeled by breaking the native contacts between residues one by one, and by assuming a threshold value for strain fluctuation. Using this method, we simulated the unfolding processes of four well-characterized proteins: chymotrypsin inhibitor, barnase, ubiquitein, and adenalyate kinase. We found that this step-wise process leads to two or more cooperative, first-order-like transitions between partial denaturation states. The sequence of unfolding events obtained using this method is consistent with experimental and MD studies. The results also imply that the native topology of proteins "encrypts" information regarding their unfolding process. Proteins 2016; 84:1767-1775. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. 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.

  11. The study of unfoldable self-avoiding walks - Application to protein structure prediction software.

    Science.gov (United States)

    Guyeux, Christophe; Nicod, Jean-Marc; Philippe, Laurent; Bahi, Jacques M

    2015-08-01

    Self-avoiding walks (SAWs) are the source of very difficult problems in probability and enumerative combinatorics. They are of great interest as, for example, they are the basis of protein structure prediction (PSP) in bioinformatics. The authors of this paper have previously shown that, depending on the prediction algorithm, the sets of obtained walk conformations differ: For example, all the SAWs can be generated using stretching-based algorithms whereas only the unfoldable SAWs can be obtained with methods that iteratively fold the straight line. A deeper study of (non-)unfoldable SAWs is presented in this paper. The contribution is first a survey of what is currently known about these sets. In particular, we provide clear definitions of various subsets of SAWs related to pivot moves (unfoldable and non-unfoldable SAWs, etc.) and the first results that we have obtained, theoretically or computationally, on these sets. Then a new theorem on the number of non-unfoldable SAWs is demonstrated. Finally, a list of open questions is provided and the consequences on the PSP problem is proposed.

  12. Sequential unfolding of beta helical protein by single-molecule atomic force microscopy.

    Directory of Open Access Journals (Sweden)

    David Alsteens

    Full Text Available The parallel βhelix is a common fold among extracellular proteins, however its mechanical properties remain unexplored. In Gram-negative bacteria, extracellular proteins of diverse functions of the large 'TpsA' family all fold into long βhelices. Here, single-molecule atomic force microscopy and steered molecular dynamics simulations were combined to investigate the mechanical properties of a prototypic TpsA protein, FHA, the major adhesin of Bordetella pertussis. Strong extension forces were required to fully unfold this highly repetitive protein, and unfolding occurred along a stepwise, hierarchical process. Our analyses showed that the extremities of the βhelix unfold early, while central regions of the helix are more resistant to mechanical unfolding. In particular, a mechanically resistant subdomain conserved among TpsA proteins and critical for secretion was identified. This nucleus harbors structural elements packed against the βhelix that might contribute to stabilizing the N-terminal region of FHA. Hierarchical unfolding of the βhelix in response to a mechanical stress may maintain β-helical portions that can serve as templates for regaining the native structure after stress. The mechanical properties uncovered here might apply to many proteins with β-helical or related folds, both in prokaryotes and in eukaryotes, and play key roles in their structural integrity and functions.

  13. Effects of Glycerol in the Refolding and Unfolding of Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    欧文斌; 朴龙斗; 孟凡国; 周海梦

    2002-01-01

    The effects of glycerol in the refolding, reactivation, unfolding, and inactivation of guanidine- denatured creatine kinase were studied by observing the fluorescence emission spectra and the circular dichroism spectra, and by recovery and inactivation of enzymatic activity and aggregation. The results show that low concentrations of glycerol (<25%) improve the refolding yields of creatine kinase, but high glycerol concentrations decrease its recovery. Glycerol favors the secondary structural formation and inhibits aggregation of creatine kinase as proline does. These systematic observations further support the suggestion that low concentrations of glycerol possibly play a chaperone role in the refolding of creatine kinase. In addition, glycerol reduces the inactivation and unfolding rate of creatine kinase, increases the change in transition free energy of unfolding (ΔΔGu) and stabilizes its active conformation relative to the partially unfolded state with no glycerol. In the presence of glycerol, the inactivation and unfolding dynamics of creatine kinase are related to glycerol concentrations. Glycerol blocks the exposure of hydrophobic areas and the dissociation of dimers, and protects creatine kinase against guanidine denaturation in a concentration-dependent manner. This study suggests that glycerol as an energy substrate for metabolism and organic components in vivo, assists correct protein folding, maintains adequate rates of enzymatic catalysis and stabilizes the protein secondary and tertiary conformations.

  14. The Hydraulic Mechanism of the Unfolding of Hind Wings in Dorcus titanus platymelus (Order: Coleoptera

    Directory of Open Access Journals (Sweden)

    Jiyu Sun

    2014-04-01

    Full Text Available In most beetles, the hind wings are thin and fragile; when at rest, they are held over the back of the beetle. When the hind wing unfolds, it provides the necessary aerodynamic forces for flight. In this paper, we investigate the hydraulic mechanism of the unfolding process of the hind wings in Dorcus titanus platymelus (Oder: Coleoptera. The wing unfolding process of Dorcus titanus platymelus was examined using high speed camera sequences (400 frames/s, and the hydraulic pressure in the veins was measured with a biological pressure sensor and dynamic signal acquisition and analysis (DSA during the expansion process. We found that the total time for the release of hydraulic pressure during wing folding is longer than the time required for unfolding. The pressure is proportional to the length of the wings and the body mass of the beetle. A retinal camera was used to investigate the fluid direction. We found that the peak pressures correspond to two main cross-folding joint expansions in the hind wing. These observations strongly suggest that blood pressure facilitates the extension of hind wings during unfolding.

  15. Volumetric CT-images improve testing of radiological image interpretation skills

    Energy Technology Data Exchange (ETDEWEB)

    Ravesloot, Cécile J., E-mail: C.J.Ravesloot@umcutrecht.nl [Radiology Department at University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, Room E01.132 (Netherlands); Schaaf, Marieke F. van der, E-mail: M.F.vanderSchaaf@uu.nl [Department of Pedagogical and Educational Sciences at Utrecht University, Heidelberglaan 1, 3584 CS Utrecht (Netherlands); Schaik, Jan P.J. van, E-mail: J.P.J.vanSchaik@umcutrecht.nl [Radiology Department at University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, Room E01.132 (Netherlands); Cate, Olle Th.J. ten, E-mail: T.J.tenCate@umcutrecht.nl [Center for Research and Development of Education at University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht (Netherlands); Gijp, Anouk van der, E-mail: A.vanderGijp-2@umcutrecht.nl [Radiology Department at University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, Room E01.132 (Netherlands); Mol, Christian P., E-mail: C.Mol@umcutrecht.nl [Image Sciences Institute at University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht (Netherlands); Vincken, Koen L., E-mail: K.Vincken@umcutrecht.nl [Image Sciences Institute at University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht (Netherlands)

    2015-05-15

    Rationale and objectives: Current radiology practice increasingly involves interpretation of volumetric data sets. In contrast, most radiology tests still contain only 2D images. We introduced a new testing tool that allows for stack viewing of volumetric images in our undergraduate radiology program. We hypothesized that tests with volumetric CT-images enhance test quality, in comparison with traditional completely 2D image-based tests, because they might better reflect required skills for clinical practice. Materials and methods: Two groups of medical students (n = 139; n = 143), trained with 2D and volumetric CT-images, took a digital radiology test in two versions (A and B), each containing both 2D and volumetric CT-image questions. In a questionnaire, they were asked to comment on the representativeness for clinical practice, difficulty and user-friendliness of the test questions and testing program. Students’ test scores and reliabilities, measured with Cronbach's alpha, of 2D and volumetric CT-image tests were compared. Results: Estimated reliabilities (Cronbach's alphas) were higher for volumetric CT-image scores (version A: .51 and version B: .54), than for 2D CT-image scores (version A: .24 and version B: .37). Participants found volumetric CT-image tests more representative of clinical practice, and considered them to be less difficult than volumetric CT-image questions. However, in one version (A), volumetric CT-image scores (M 80.9, SD 14.8) were significantly lower than 2D CT-image scores (M 88.4, SD 10.4) (p < .001). The volumetric CT-image testing program was considered user-friendly. Conclusion: This study shows that volumetric image questions can be successfully integrated in students’ radiology testing. Results suggests that the inclusion of volumetric CT-images might improve the quality of radiology tests by positively impacting perceived representativeness for clinical practice and increasing reliability of the test.

  16. Personalized heterogeneous deformable model for fast volumetric registration.

    Science.gov (United States)

    Si, Weixin; Liao, Xiangyun; Wang, Qiong; Heng, Pheng Ann

    2017-02-20

    Biomechanical deformable volumetric registration can help improve safety of surgical interventions by ensuring the operations are extremely precise. However, this technique has been limited by the accuracy and the computational efficiency of patient-specific modeling. This study presents a tissue-tissue coupling strategy based on penalty method to model the heterogeneous behavior of deformable body, and estimate the personalized tissue-tissue coupling parameters in a data-driven way. Moreover, considering that the computational efficiency of biomechanical model is highly dependent on the mechanical resolution, a practical coarse-to-fine scheme is proposed to increase runtime efficiency. Particularly, a detail enrichment database is established in an offline fashion to represent the mapping relationship between the deformation results of high-resolution hexahedral mesh extracted from the raw medical data and a newly constructed low-resolution hexahedral mesh. At runtime, the mechanical behavior of human organ under interactions is simulated with this low-resolution hexahedral mesh, then the microstructures are synthesized in virtue of the detail enrichment database. The proposed method is validated by volumetric registration in an abdominal phantom compression experiments. Our personalized heterogeneous deformable model can well describe the coupling effects between different tissues of the phantom. Compared with high-resolution heterogeneous deformable model, the low-resolution deformable model with our detail enrichment database can achieve 9.4× faster, and the average target registration error is 3.42 mm, which demonstrates that the proposed method shows better volumetric registration performance than state-of-the-art. Our framework can well balance the precision and efficiency, and has great potential to be adopted in the practical augmented reality image-guided robotic systems.

  17. Volumetric measurements of pulmonary nodules: variability in automated analysis tools

    Science.gov (United States)

    Juluru, Krishna; Kim, Woojin; Boonn, William; King, Tara; Siddiqui, Khan; Siegel, Eliot

    2007-03-01

    Over the past decade, several computerized tools have been developed for detection of lung nodules and for providing volumetric analysis. Incidentally detected lung nodules have traditionally been followed over time by measurements of their axial dimensions on CT scans to ensure stability or document progression. A recently published article by the Fleischner Society offers guidelines on the management of incidentally detected nodules based on size criteria. For this reason, differences in measurements obtained by automated tools from various vendors may have significant implications on management, yet the degree of variability in these measurements is not well understood. The goal of this study is to quantify the differences in nodule maximum diameter and volume among different automated analysis software. Using a dataset of lung scans obtained with both "ultra-low" and conventional doses, we identified a subset of nodules in each of five size-based categories. Using automated analysis tools provided by three different vendors, we obtained size and volumetric measurements on these nodules, and compared these data using descriptive as well as ANOVA and t-test analysis. Results showed significant differences in nodule maximum diameter measurements among the various automated lung nodule analysis tools but no significant differences in nodule volume measurements. These data suggest that when using automated commercial software, volume measurements may be a more reliable marker of tumor progression than maximum diameter. The data also suggest that volumetric nodule measurements may be relatively reproducible among various commercial workstations, in contrast to the variability documented when performing human mark-ups, as is seen in the LIDC (lung imaging database consortium) study.

  18. Volumetric hemispheric ratio as a useful tool in personality psychology.

    Science.gov (United States)

    Montag, Christian; Schoene-Bake, Jan-Christoph; Wagner, Jan; Reuter, Martin; Markett, Sebastian; Weber, Bernd; Quesada, Carlos M

    2013-02-01

    The present study investigates the link between volumetric hemispheric ratios (VHRs) and personality measures in N=267 healthy participants using Eysenck's Personality Inventory-Revised (EPQ-R) and the BIS/BAS scales. A robust association between extraversion and VHRs was observed for gray matter in males but not females. Higher gray matter volume in the left than in the right hemisphere was associated with higher extraversion in males. The results are discussed in the context of positive emotionality and laterality of the human brain.

  19. AN ATTRIBUTION OF CAVITATION RESONANCE: VOLUMETRIC OSCILLATIONS OF CLOUD

    Institute of Scientific and Technical Information of China (English)

    ZUO Zhi-gang; LI Sheng-cai; LIU Shu-hong; LI Shuang; CHEN Hui

    2009-01-01

    In order to further verify the proposed theory of cavitation resonance, as well as to proceed the investigations into microscopic level, a series of studies are being carried out on the Warwick venturi. The analysis of the oscillation characteristics of the cavitation resonance has conclusively verified the macro-mechanism proposed through previous studies on other cavitating flows by the authors. The initial observations using high-speed photographic approach have revealed a new attribution of cavitation resonance. That is, the volumetric oscillation of cavitation cloud is associated with the cavitation resonance, which is a collective behaviour of the bubbles in the cloud.

  20. Synthesis of Volumetric Ring Antenna Array for Terrestrial Coverage Pattern

    Directory of Open Access Journals (Sweden)

    Alberto Reyna

    2014-01-01

    Full Text Available This paper presents a synthesis of a volumetric ring antenna array for a terrestrial coverage pattern. This synthesis regards the spacing among the rings on the planes X-Y, the positions of the rings on the plane X-Z, and uniform and concentric excitations. The optimization is carried out by implementing the particle swarm optimization. The synthesis is compared with previous designs by resulting with proper performance of this geometry to provide an accurate coverage to be applied in satellite applications with a maximum reduction of the antenna hardware as well as the side lobe level reduction.

  1. Synthesis of Volumetric Ring Antenna Array for Terrestrial Coverage Pattern

    Science.gov (United States)

    Reyna, Alberto; Panduro, Marco A.; Del Rio Bocio, Carlos

    2014-01-01

    This paper presents a synthesis of a volumetric ring antenna array for a terrestrial coverage pattern. This synthesis regards the spacing among the rings on the planes X-Y, the positions of the rings on the plane X-Z, and uniform and concentric excitations. The optimization is carried out by implementing the particle swarm optimization. The synthesis is compared with previous designs by resulting with proper performance of this geometry to provide an accurate coverage to be applied in satellite applications with a maximum reduction of the antenna hardware as well as the side lobe level reduction. PMID:24701150

  2. Estimation of volumetric breast density for breast cancer risk prediction

    Science.gov (United States)

    Pawluczyk, Olga; Yaffe, Martin J.; Boyd, Norman F.; Jong, Roberta A.

    2000-04-01

    Mammographic density (MD) has been shown to be a strong risk predictor for breast cancer. Compared to subjective assessment by a radiologist, computer-aided analysis of digitized mammograms provides a quantitative and more reproducible method for assessing breast density. However, the current methods of estimating breast density based on the area of bright signal in a mammogram do not reflect the true, volumetric quantity of dense tissue in the breast. A computerized method to estimate the amount of radiographically dense tissue in the overall volume of the breast has been developed to provide an automatic, user-independent tool for breast cancer risk assessment. The procedure for volumetric density estimation consists of first correcting the image for inhomogeneity, then performing a volume density calculation. First, optical sensitometry is used to convert all images to the logarithm of relative exposure (LRE), in order to simplify the image correction operations. The field non-uniformity correction, which takes into account heel effect, inverse square law, path obliquity and intrinsic field and grid non- uniformity is obtained by imaging a spherical section PMMA phantom. The processed LRE image of the phantom is then used as a correction offset for actual mammograms. From information about the thickness and placement of the breast, as well as the parameters of a breast-like calibration step wedge placed in the mammogram, MD of the breast is calculated. Post processing and a simple calibration phantom enable user- independent, reliable and repeatable volumetric estimation of density in breast-equivalent phantoms. Initial results obtained on known density phantoms show the estimation to vary less than 5% in MD from the actual value. This can be compared to estimated mammographic density differences of 30% between the true and non-corrected values. Since a more simplistic breast density measurement based on the projected area has been shown to be a strong indicator

  3. Volumetric 3D Display System with Static Screen

    Science.gov (United States)

    Geng, Jason

    2011-01-01

    Current display technology has relied on flat, 2D screens that cannot truly convey the third dimension of visual information: depth. In contrast to conventional visualization that is primarily based on 2D flat screens, the volumetric 3D display possesses a true 3D display volume, and places physically each 3D voxel in displayed 3D images at the true 3D (x,y,z) spatial position. Each voxel, analogous to a pixel in a 2D image, emits light from that position to form a real 3D image in the eyes of the viewers. Such true volumetric 3D display technology provides both physiological (accommodation, convergence, binocular disparity, and motion parallax) and psychological (image size, linear perspective, shading, brightness, etc.) depth cues to human visual systems to help in the perception of 3D objects. In a volumetric 3D display, viewers can watch the displayed 3D images from a completely 360 view without using any special eyewear. The volumetric 3D display techniques may lead to a quantum leap in information display technology and can dramatically change the ways humans interact with computers, which can lead to significant improvements in the efficiency of learning and knowledge management processes. Within a block of glass, a large amount of tiny dots of voxels are created by using a recently available machining technique called laser subsurface engraving (LSE). The LSE is able to produce tiny physical crack points (as small as 0.05 mm in diameter) at any (x,y,z) location within the cube of transparent material. The crack dots, when illuminated by a light source, scatter the light around and form visible voxels within the 3D volume. The locations of these tiny voxels are strategically determined such that each can be illuminated by a light ray from a high-resolution digital mirror device (DMD) light engine. The distribution of these voxels occupies the full display volume within the static 3D glass screen. This design eliminates any moving screen seen in previous

  4. Unfolding of event-by-event net-charge distributions in heavy-ion collision

    CERN Document Server

    Garg, P; Netrakanti, P K; Mohanty, A K; Mohanty, B

    2012-01-01

    We discuss a method to obtain the true event-by-event net-charge multiplicity distributions from a corresponding measured distribution which is subjected to detector effects such as finite particle counting efficiency. The approach is based on the Bayes method for unfolding of distributions. We are able to faithfully unfold back the measured distributions to match with their corresponding true distributions obtained for a widely varying underlying particle production mechanism, beam energy and collision centrality. Particularly the mean, variance, skewness, kurtosis, their products and ratios of net-charge distributions from the event generators are shown to be successfully unfolded from the measured distributions constructed to mimic a real experimental distribution. We demonstrate the necessity to account for detector effects before associating the higher moments of net-charge distributions with physical quantities or phenomena. The advantage of this approach being that one need not construct new observable...

  5. 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.

  6. Estimation of neutron spectrum in the low-level gamma spectroscopy system using unfolding procedure

    Science.gov (United States)

    Knežević, D.; Jovančević, N.; Krmar, M.

    2016-03-01

    The radiation resulting from neutron interactions with Ge nuclei in active volume of HPGe detectors is one of the main concerns in low-level gamma spectroscopy measurements [1,2]. It is usually not possible to measure directly spectrum of neutrons which strike detector. This paper explore the possibility of estimation of neutron spectrum using measured activities of certain Ge(n,γ) and Ge(n,n') reactions (obtained from low-level gamma measurements), available ENDF cross section data and unfolding procedures. In this work HPGe detector with passive shield made from commercial low background lead was used for the measurement. The most important objective of this study was to reconstruct muon induced neutron spectrum created in the shield of the HPGe detector. MAXED [3] and GRAVEL [4] algorithms for neutron spectra unfolding were used. The results of those two algorithms were compared and we analyzed the sensitivity of the unfolding procedure to the various input parameters.

  7. Unfolding and Folding of the Three-Helix Bundle Protein KIX in the Absence of Solvent

    Science.gov (United States)

    Schennach, Moritz; Schneeberger, Eva-Maria; Breuker, Kathrin

    2016-06-01

    Electron capture dissociation was used to probe the structure, unfolding, and folding of KIX ions in the gas phase. At energies for vibrational activation that were sufficiently high to cause loss of small molecules such as NH3 and H2O by breaking of covalent bonds in about 5% of the KIX (M + nH)n+ ions with n = 7-9, only partial unfolding was observed, consistent with our previous hypothesis that salt bridges play an important role in stabilizing the native solution fold after transfer into the gas phase. Folding of the partially unfolded ions on a timescale of up to 10 s was observed only for (M + nH)n+ ions with n = 9, but not n = 7 and n = 8, which we attribute to differences in the distribution of charges within the (M + nH)n+ ions.

  8. Attitudes, order and quantity: deterministic and direct probabilistic tests of unidimensional unfolding.

    Science.gov (United States)

    Kyngdon, Andrew; Richards, Ben

    2007-01-01

    This article is the final in the series on unidimensional unfolding. The investigations of Kyngdon (2006b) and Michell (1994) were extended to include direct probabilistic tests of the quantitative and ordinal components of unfolding theory with the multinomial Dirichlet model (Karabatsos 2005); and tests of the higher order axiomatic conjoint measurement (ACM, Krantz, Luce, Suppes and Tversky (KLST) 1971) condition of triple cancellation. Strong Dirichlet model support for both the ordinal and quantitative components of unfolding was only found in datasets that satisfied at least double cancellation. In contrast, the Item Response Theory (IRT) simple hyperbolic cosine model for pairwise preferences (SHCMpp, Andrich 1995) fitted all datasets. The paper concluded the SHCMpp is suited to the instrumental rather than scientific task (Michell 2000) of psychological measurement; with the caveat of the problematic chi square fit statistic. The paper also presents original work by the second author on coherent tests of triple cancellation.

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

    DEFF Research Database (Denmark)

    Heidarsson, Petur O.; Valpapuram, Immanuel; Camilloni, Carlo;

    2012-01-01

    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......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...

  10. RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria

    Science.gov (United States)

    Guo, Junjie U.; Bartel, David P.

    2017-01-01

    In vitro, some RNAs can form stable four-stranded structures known as G-quadruplexes. Although RNA G-quadruplexes have been implicated in post-transcriptional gene regulation and diseases, direct evidence for their formation in cells has been lacking. Here, we identified thousands of mammalian RNA regions that can fold into G-quadruplexes in vitro, but in contrast to previous assumptions, these regions were overwhelmingly unfolded in cells. Model RNA G-quadruplexes that were unfolded in eukaryotic cells were folded when ectopically expressed in Escherichia coli; however, they impaired translation and growth, which helps explain why we detected few G-quadruplex–forming regions in bacterial transcriptomes. Our results suggest that eukaryotes have a robust machinery that globally unfolds RNA G-quadruplexes, whereas some bacteria have instead undergone evolutionary depletion of G-quadruplex–forming sequences. PMID:27708011

  11. Unfolded Frequency Response and Model of a Multi-Tap Direct Sampling Mixer

    Institute of Scientific and Technical Information of China (English)

    PAN Yun; GE Ning; DONG Zaiwang

    2008-01-01

    A transform method was used to model a discrete time multi-tap direct sampling mixer. The method transforms the mixed filtering and down.sampling stages to separate cascade filtering and sampling stages to determine the unfolded frequency response which shows the anti-aliasing ability of the mixer. The transformation can also be applied to other mixed signal and multi-rate receiver systems to analyze their unfolded frequency responses. The transformed system architecture was used to calculate the unfolded frequency response of the multi-tap direct sampling mixer and compared with the mixer model without noise in the ad-vanced design system 2005A environment to further evaluate the frequency response. The simulations show that the -3 dB bandwidth is 3.0 MHz and the voltage gain is attenuated by 1.5 dB within a 1-MHz baseband bandwidth.

  12. Understanding disordered and unfolded proteins using single-molecule FRET and polymer theory

    Science.gov (United States)

    Hofmann, Hagen

    2016-12-01

    Understanding protein folding and the functional properties of intrinsically disordered proteins (IDPs) requires detailed knowledge of the forces that act in polypeptide chains. These forces determine the dimensions and dynamics of unfolded and disordered proteins and have been suggested to impact processes such as the coupled binding and folding of IDPs, or the rate of protein folding reactions. Much of the progress in understanding the physical and chemical properties of unfolded and intrinsically disordered polypeptide chains has been made possible by the recent developments in single-molecule fluorescence techniques. However, the interpretation of the experimental results requires concepts from polymer physics in order to be understood. Here, I review some of the theories used to describe the dimensions of unfolded polypeptide chains under varying solvent conditions together with their more recent application to experimental data.

  13. Web-based unfolding cases: a strategy to enhance and evaluate clinical reasoning skills.

    Science.gov (United States)

    Johnson, Gail; Flagler, Susan

    2013-10-01

    Clinical reasoning involves the use of both analytical and nonanalytical intuitive cognitive processes. Fostering student development of clinical reasoning skills and evaluating student performance in this cognitive arena can challenge educators. The use of Web-based unfolding cases is proposed as a strategy to address these challenges. Unfolding cases mimic real-life clinical situations by presenting only partial clinical information in sequential segments. Students receive immediate feedback after submitting a response to a given segment. The student's comparison of the desired and submitted responses provides information to enhance the development of clinical reasoning skills. Each student's set of case responses are saved for the instructor in an individual-student electronic file, providing a record of the student's knowledge and thinking processes for faculty evaluation. For the example case given, the approaches used to evaluate individual components of clinical reasoning are provided. Possible future uses of Web-based unfolding cases are described. Copyright 2013, SLACK Incorporated.

  14. Unfolding case studies as a formative teaching methodology for novice nursing students.

    Science.gov (United States)

    Kaylor, Sara K; Strickland, Haley P

    2015-02-01

    Nurse educators are challenged to incorporate evidence-based practice initiatives into content-laden curricula in a manner that supports learner-centered teaching environments. This article describes a technique for using unfolding case studies to include such initiatives in the teaching of novice nursing students, as opposed to summative evaluation of their knowledge. Modeled after Kolb's experiential learning theory, a framework for unfolding case studies is presented, which proposes that instead of faculty selecting scenarios for students, they should instead challenge students to directly and creatively develop their own. Small student groups used creative collaboration to create well-planned, complex case study scenarios that unfolded in surprising, realistic ways. This instructional method was met with positive student feedback; however, the authors suggest several recommendations for educators considering this approach. The authors found this framework to be a successful and effective strategy for undergraduate novice nursing students.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz R, J. M. [Escuela Politecnica Superior, Departamento de Electrotecnia y Electronica, Avda. Menendez Pidal s/n, Cordoba (Spain); Martinez B, M. R.; Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico); Gallego D, E.; Lorente F, A. [Universidad Politecnica de Madrid, Departamento de Ingenieria Nuclear, ETSI Industriales, C. Jose Gutierrez Abascal 2, 28006 Madrid (Spain); Mendez V, R.; Los Arcos M, J. M.; Guerrero A, J. E., E-mail: morvymm@yahoo.com.m [CIEMAT, Laboratorio de Metrologia de Radiaciones Ionizantes, Avda. Complutense 22, 28040 Madrid (Spain)

    2011-02-15

    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)

  16. Dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha induced by guanidine hydrochloride.

    Science.gov (United States)

    Kim, Y R; Hahn, J S; Hong, H; Jeong, W; Song, N W; Shin, H C; Kim, D

    1999-01-11

    The dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha (TNF-alpha) during denaturation at different guanidine hydrochloride (GdnHCl) concentrations (0-4.2 M) was investigated by steady-state fluorescence spectroscopy, potassium iodide (KI) fluorescence quenching, far-UV circular dichroism (CD), picosecond time-resolved fluorescence lifetime, and anisotropy decay measurements. We utilized the intrinsic fluorescence of Trp-28 and Trp-114 to characterize the conformational changes involved in the equilibrium unfolding pathway. The detailed unfolding pathway under equilibrium conditions was discussed with respect to motional dynamics and partially folded structures. At 0-0.9 M [GdnHCl], the rotational correlation times of 22-25 ns were obtained from fluorescence anisotropy decay measurements and assigned to those of trimeric states by hydrodynamic calculation. In this range, the solvent accessibility of Trp residues increased with increasing [GdnHCl], suggesting the slight expansion of the trimeric structure. At 1.2-2.1 M [GdnHCl], the enhanced solvent accessibility and the rotational degree of freedom of Trp residues were observed, implying the loosening of the internal structure. In this [GdnHCl] region, TNF-alpha was thought to be in soluble aggregates having distinct conformational characteristics from a native (N) or fully unfolded state (U). At 4.2 M [GdnHCl], TNF-alpha unfolded to a U-state. From these results, the equilibrium unfolding pathway of TNF-alpha, trimeric and all beta-sheet protein, could not be viewed from the simple two state model (N-->U).

  17. 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.

  18. 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.

  19. Floating volumetric image formation using a dihedral corner reflector array device.

    Science.gov (United States)

    Miyazaki, Daisuke; Hirano, Noboru; Maeda, Yuki; Yamamoto, Siori; Mukai, Takaaki; Maekawa, Satoshi

    2013-01-01

    A volumetric display system using an optical imaging device consisting of numerous dihedral corner reflectors placed perpendicular to the surface of a metal plate is proposed. Image formation by the dihedral corner reflector array (DCRA) is free from distortion and focal length. In the proposed volumetric display system, a two-dimensional real image is moved by a mirror scanner to scan a three-dimensional (3D) space. Cross-sectional images of a 3D object are displayed in accordance with the position of the image plane. A volumetric image is observed as a stack of the cross-sectional images. The use of the DCRA brings compact system configuration and volumetric real image generation with very low distortion. An experimental volumetric display system including a DCRA, a galvanometer mirror, and a digital micro-mirror device was constructed to verify the proposed method. A volumetric image consisting of 1024×768×400 voxels was formed by the experimental system.

  20. Colonic lymphangiomatosis associated with anemia

    Institute of Scientific and Technical Information of China (English)

    Woo Chul Chung; Hye-Kang Kim; Jin Young Yoo; Jeong Rok Lee; Kang-Moon Lee; Chang Nyol Paik; U-Im Jang; Jin Mo Yang

    2008-01-01

    lymphangioma is an uncommon malformation of lymphatic system.Multiple colonic lymphangioma named as lymphangiomatosis is considered an extremely rare disease.Although lymphangioma is a benign tumor and most colonic lymphangiomas do not cause symptoms and do not require treatment,resection of lymphangioma is necessary in the presence of symptoms such as abdominal pain,bleeding,intussusceptions.We report a case of colonic lymphangiomatosis in a man who presented with abdominal discomfort and anemia,which was diagnosed and treated with endoscopic snare polyperctomy.

  1. Vasohibin-1 suppresses colon cancer

    Science.gov (United States)

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo. PMID:25797264

  2. Diverticulosis of colon: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chang Yul [Paik Hospital, Seoul (Korea, Republic of)

    1972-12-15

    The authors reports 2 cases of diverticulosis involving the sacending colon and cecum: one, 55 year old, 85 kg Korean male admitted to Paik Hospital because of abdominal palm, constipation and tenderness in the right lower abdomen. The other, 48 year old, 78 kg male visited to our hospital for the routine examination. According to late European and American statistics, the colonic diverticulosis was discovered in late middle life about 20%, however, the incidence of colonic diverticulosis is rare in Korea. This paper presents a brief review of literature on the etiology, incidence and symptom.

  3. Space Colonization: Problems and Prospects

    Directory of Open Access Journals (Sweden)

    Krichevskiy S. V.

    2012-04-01

    Full Text Available Space colonization is the top priority of mankind and the strategic target of manned cosmonautics. It is necessary to comprehend the outcome of human space flights and to give a new impulse to space expansion, scientific and practical solving the problem of space colonization by human beings. The attention is also paid to key issues, potentials, restrictions, forecasts, and prospects of space colonization as well as to the transformation of a man into "a man of the future", "homo cosmicus", and "a universal man", to the formation of "space mankind".

  4. Sequential unfolding of the two-domain protein Pseudomonas stutzeri cytochrome c(4)

    DEFF Research Database (Denmark)

    Andersen, Niels Højmark; Jensen, Thomas Jon; Nørgaard, Allan

    2002-01-01

    F stutzeri cytochrome c. is a di-haem protein, composed of two globular domains each with His-Met coordinated haem. and a hydrogen bond network between the domains. The domain foldings are highly symmetric but with specific differences including structural differences of ligand coordination......, and different spin states of the oxidised haem groups. We have studied unfolding of oxidised P. stutzeri cyt c(4) induced thermally and by chemical denaturants Horse heart cyt c was a reference molecule. Isothermal unfolding induced by guanidinium chloride and acid was followed by Soret. alpha/beta. and 701-nm...

  5. Unfolding of event-by-event net-charge distributions in heavy-ion collisions

    CERN Document Server

    Garg, P; Netrakanti, P K; Mohanty, A K; Mohanty, B

    2013-01-01

    An unfolding method, based on Bayes theorem is presented to obtain true event-by-event net-charge multiplicity distribution from a corresponding measured distribution, which is subjected to detector artifacts. The unfolding is demonstrated to work for widely varying particle production mechanism, beam energy and collision centrality. Further the necessity of taking into account the detector effects is emphasized before comparing the experimental measurements to the theoretical calculations, particularly in case of higher moments. The advantage of this approach being that one need not construct new observable to cancel out detector effects which loose their ability to be connected to physical quantities calculable in standard theories.

  6. Measurement of accelerator neutron radiation field spectrum by Extended Range Neutron Multisphere Spectrometers and unfolding program

    CERN Document Server

    Li, Guanjia; Ma, Zhongjian; Guo, Siming; Yan, Mingyang; Shi, Haoyu; Xu, Chao

    2015-01-01

    This paper described a measurement of accelerator neutron radiation field at a transport beam line of Beijing-TBF. The experiment place was be selected around a Faraday Cup with a graphite target impacted by electron beam at 2.5GeV. First of all, we simulated the neutron radiation experiment by FLUKA. Secondly, we chose six appropriate ERNMS according to their neutron fluence response function to measure the neutron count rate. Then the U_M_G package program was be utilized to unfolding experiment data. Finally, we drew a comparison between the unfolding with the simulation spectrum and made an analysis about the result.

  7. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-01

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

  9. Unfolding-based corrector estimates for a reaction-diffusion system predicting concrete corrosion

    CERN Document Server

    Fatima, Tasnim; Ptashnyk, Mariya

    2011-01-01

    We use the periodic unfolding technique to derive corrector estimates for a reaction-diffusion system describing concrete corrosion penetration in the sewer pipes. The system, defined in a periodically-perforated domain, is semi-linear, partially dissipative, and coupled via a non-linear ordinary differential equation posed on the solid-water interface at the pore level. After discussing the solvability of the pore scale model, we apply the periodic unfolding techniques (adapted to treat the presence of perforations) not only to get upscaled model equations, but also to prepare a proper framework for getting a convergence rate (corrector estimates) of the averaging procedure.

  10. Volumetric display containing multiple two-dimensional color motion pictures

    Science.gov (United States)

    Hirayama, R.; Shiraki, A.; Nakayama, H.; Kakue, T.; Shimobaba, T.; Ito, T.

    2014-06-01

    We have developed an algorithm which can record multiple two-dimensional (2-D) gradated projection patterns in a single three-dimensional (3-D) object. Each recorded pattern has the individual projected direction and can only be seen from the direction. The proposed algorithm has two important features: the number of recorded patterns is theoretically infinite and no meaningful pattern can be seen outside of the projected directions. In this paper, we expanded the algorithm to record multiple 2-D projection patterns in color. There are two popular ways of color mixing: additive one and subtractive one. Additive color mixing used to mix light is based on RGB colors and subtractive color mixing used to mix inks is based on CMY colors. We made two coloring methods based on the additive mixing and subtractive mixing. We performed numerical simulations of the coloring methods, and confirmed their effectiveness. We also fabricated two types of volumetric display and applied the proposed algorithm to them. One is a cubic displays constructed by light-emitting diodes (LEDs) in 8×8×8 array. Lighting patterns of LEDs are controlled by a microcomputer board. The other one is made of 7×7 array of threads. Each thread is illuminated by a projector connected with PC. As a result of the implementation, we succeeded in recording multiple 2-D color motion pictures in the volumetric displays. Our algorithm can be applied to digital signage, media art and so forth.

  11. Volumetric three-dimensional display system with rasterization hardware

    Science.gov (United States)

    Favalora, Gregg E.; Dorval, Rick K.; Hall, Deirdre M.; Giovinco, Michael; Napoli, Joshua

    2001-06-01

    An 8-color multiplanar volumetric display is being developed by Actuality Systems, Inc. It will be capable of utilizing an image volume greater than 90 million voxels, which we believe is the greatest utilizable voxel set of any volumetric display constructed to date. The display is designed to be used for molecular visualization, mechanical CAD, e-commerce, entertainment, and medical imaging. As such, it contains a new graphics processing architecture, novel high-performance line- drawing algorithms, and an API similar to a current standard. Three-dimensional imagery is created by projecting a series of 2-D bitmaps ('image slices') onto a diffuse screen that rotates at 600 rpm. Persistence of vision fuses the slices into a volume-filling 3-D image. A modified three-panel Texas Instruments projector provides slices at approximately 4 kHz, resulting in 8-color 3-D imagery comprised of roughly 200 radially-disposed slices which are updated at 20 Hz. Each slice has a resolution of 768 by 768 pixels, subtending 10 inches. An unusual off-axis projection scheme incorporating tilted rotating optics is used to maintain good focus across the projection screen. The display electronics includes a custom rasterization architecture which converts the user's 3- D geometry data into image slices, as well as 6 Gbits of DDR SDRAM graphics memory.

  12. Myocardial kinematics based on tagged MRI from volumetric NURBS models

    Science.gov (United States)

    Tustison, Nicholas J.; Amini, Amir A.

    2004-04-01

    We present current research in which left ventricular deformation is estimated from tagged cardiac magnetic resonance imaging using volumetric deformable models constructed from nonuniform rational B-splines (NURBS). From a set of short and long axis images at end-diastole, the initial NURBS model is constructed by fitting two surfaces with the same parameterization to the set of epicardial and endocardial contours from which a volumetric model is created. Using normal displacements of the three sets of orthogonal tag planes as well as displacements of both tag line and contour/tag line intersection points, one can solve for the optimal homogeneous coordinates, in a least squares sense, of the control points of the NURBS model at a later time point using quadratic programming. After fitting to all time points of data, lofting the NURBS model at each time point creates a comprehensive 4-D NURBS model. From this model, we can extract 3-D myocardial displacement fields and corresponding strain maps, which are local measures of non-rigid deformation.

  13. Volumetric breast density affects performance of digital screening mammography.

    Science.gov (United States)

    Wanders, Johanna O P; Holland, Katharina; Veldhuis, Wouter B; Mann, Ritse M; Pijnappel, Ruud M; Peeters, Petra H M; van Gils, Carla H; Karssemeijer, Nico

    2017-02-01

    To determine to what extent automatically measured volumetric mammographic density influences screening performance when using digital mammography (DM). We collected a consecutive series of 111,898 DM examinations (2003-2011) from one screening unit of the Dutch biennial screening program (age 50-75 years). Volumetric mammographic density was automatically assessed using Volpara. We determined screening performance measures for four density categories comparable to the American College of Radiology (ACR) breast density categories. Of all the examinations, 21.6% were categorized as density category 1 ('almost entirely fatty') and 41.5, 28.9, and 8.0% as category 2-4 ('extremely dense'), respectively. We identified 667 screen-detected and 234 interval cancers. Interval cancer rates were 0.7, 1.9, 2.9, and 4.4‰ and false positive rates were 11.2, 15.1, 18.2, and 23.8‰ for categories 1-4, respectively (both p-trend density categories: 85.7, 77.6, 69.5, and 61.0% for categories 1-4, respectively (p-trend density, automatically measured on digital mammograms, impacts screening performance measures along the same patterns as established with ACR breast density categories. Since measuring breast density fully automatically has much higher reproducibility than visual assessment, this automatic method could help with implementing density-based supplemental screening.

  14. Volumetric properties of human islet amyloid polypeptide in liquid water.

    Science.gov (United States)

    Brovchenko, I; Andrews, M N; Oleinikova, A

    2010-04-28

    The volumetric properties of human islet amyloid polypeptide (hIAPP) in water were studied in a wide temperature range by computer simulations. The intrinsic density rho(p) and the intrinsic thermal expansion coefficient alpha(p) of hIAPP were evaluated by taking into account the difference between the volumetric properties of hydration and bulk water. The density of hydration water rho(h) was found to decrease almost linearly with temperature upon heating and its thermal expansion coefficient was found to be notably higher than that of bulk water. The peptide surface exposed to water is more hydrophobic and its rho(h) is smaller in conformation with a larger number of intrapeptide hydrogen bonds. The two hIAPP peptides studied (with and without disulfide bridge) show negative alpha(p), which is close to zero at 250 K and decreases to approximately -1.5 x 10(-3) K(-1) upon heating to 450 K. The analysis of various structural properties of peptides shows a correlation between the intrinsic peptide volumes and the number of intrapeptide hydrogen bonds. The obtained negative values of alpha(p) can be attributed to the shrinkage of the inner voids of the peptides upon heating.

  15. Volumetric verification of multiaxis machine tool using laser tracker.

    Science.gov (United States)

    Aguado, Sergio; Samper, David; Santolaria, Jorge; Aguilar, Juan José

    2014-01-01

    This paper aims to present a method of volumetric verification in machine tools with linear and rotary axes using a laser tracker. Beyond a method for a particular machine, it presents a methodology that can be used in any machine type. Along this paper, the schema and kinematic model of a machine with three axes of movement, two linear and one rotational axes, including the measurement system and the nominal rotation matrix of the rotational axis are presented. Using this, the machine tool volumetric error is obtained and nonlinear optimization techniques are employed to improve the accuracy of the machine tool. The verification provides a mathematical, not physical, compensation, in less time than other methods of verification by means of the indirect measurement of geometric errors of the machine from the linear and rotary axes. This paper presents an extensive study about the appropriateness and drawbacks of the regression function employed depending on the types of movement of the axes of any machine. In the same way, strengths and weaknesses of measurement methods and optimization techniques depending on the space available to place the measurement system are presented. These studies provide the most appropriate strategies to verify each machine tool taking into consideration its configuration and its available work space.

  16. The Volumetric Rate of Superluminous Supernovae at z~1

    CERN Document Server

    Prajs, S; Smith, M; Levan, A; Karpenka, N V; Edwards, T D P; Walker, C R; Wolf, W M; Balland, C; Carlberg, R; Howell, A; Lidman, C; Pain, R; Pritchet, C; Ruhlmann-Kleider, V

    2016-01-01

    We present a measurement of the volumetric rate of superluminous supernovae (SLSNe) at z~1, measured using archival data from the first four years of the Canada-France-Hawaii Telescope Supernova Legacy Survey (SNLS). We develop a method for the photometric classification of SLSNe to construct our sample. Our sample includes two previously spectroscopically-identified objects, and a further new candidate selected using our classification technique. We use the point-source recovery efficiencies from Perrett et.al. (2010) and a Monte Carlo approach to calculate the rate based on our SLSN sample. We find that the three identified SLSNe from SNLS give a rate of 91 (+76/-36) SNe/Yr/Gpc^3 at a volume-weighted redshift of z=1.13. This is equivalent to 2.2 (+1.8/-0.9) x10^-4 of the volumetric core collapse supernova rate at the same redshift. When combined with other rate measurements from the literature, we show that the rate of SLSNe increases with redshift in a manner consistent with that of the cosmic star formati...

  17. Calreticulin is a fine tuning molecule in epibrassinolide-induced apoptosis through activating endoplasmic reticulum stress in colon cancer cells.

    Science.gov (United States)

    Obakan-Yerlikaya, Pinar; Arisan, Elif Damla; Coker-Gurkan, Ajda; Adacan, Kaan; Ozbey, Utku; Somuncu, Berna; Baran, Didem; Palavan-Unsal, Narcin

    2017-06-01

    Epibrassinolide (EBR), a member of brassinostreoids plant hormones with cell proliferation promoting role in plants, is a natural polyhydroxysteroid with structural similarity to steroid hormones of vertebrates. EBR has antiproliferative and apoptosis-inducing effect in various cancer cells. Although EBR has been shown to affect survival and mitochondria-mediated apoptosis pathways in a p53-independent manner, the exact molecular targets of EBR are still under investigation. Our recent SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture) data showed that the most significantly altered protein after EBR treatment was calreticulin (CALR). CALR, a chaperone localized in endoplasmic reticulum (ER) lumen, plays role in protein folding and buffering Ca(2+) ions. The alteration of CALR may cause ER stress and unfolded protein response correspondingly the induction of apoptosis. Unfolded proteins are conducted to 26S proteasomal degradation following ubiquitination. Our study revealed that EBR treatment caused ER stress and UPR by altering CALR expression causing caspase-dependent apoptosis in HCT 116, HT29, DLD-1, and SW480 colon cancer cells. Furthermore, 48 h EBR treatment did not caused UPR in Fetal Human Colon cells (FHC) and Mouse Embryonic Fibroblast cells (MEF). In addition our findings showed that HCT 116 colon cancer cells lacking Bax and Puma expression still undergo UPR and related apoptosis. CALR silencing and rapamycin co-treatment prevented EBR-induced UPR and apoptosis, whereas 26S proteasome inhibition further increased the effect of EBR in colon cancer cells. All these findings showed that EBR is an ER stress and apoptotic inducer in colon cancer cells without affecting non-malignant cells. © 2017 Wiley Periodicals, Inc.

  18. Vasohibin-1 suppresses colon cancer

    National Research Council Canada - National Science Library

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown...

  19. Cholesterol metabolism and colon cancer.

    Science.gov (United States)

    Broitman, S A; Cerda, S; Wilkinson, J

    1993-01-01

    While epidemiologic and concordant experimental data indicate a direct relationship between dietary fat (and presumably caloric) intake and the development of colon cancer, the effect of dietary cholesterol on this disease is still not clear. However, there appears to be a developing literature concerning an inverse relationship between serum and plasma cholesterol levels, and the risk for colon cancer. Findings that low serum cholesterol levels are apparent as early as ten years prior to the detection of colon cancer implies that sub clinical disease is probably not involved initially in this process. The possibility of low serum cholesterol as a bio-marker was considered in epidemiologic studies which focused upon obese men with lower than normal serum cholesterol levels who were found to be at increased risk to colon cancer. While the relationship between low serum cholesterol and colonic or intestinal cholesterol metabolism is presently not understood, current genetic studies provide a promising though as yet unexplored potential association. Alterations which occur during the developmental progression of colonic cancer include changes in chromosome 5, which also carries two genes vital to the biosynthesis and regulation of systemic and cellular cholesterol metabolism, 3-hydroxy-3-methylglutaryl coenzyme A synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA R). Regulation of cholesterol metabolism in intestinal cells in vivo and in vitro varies from that seen in normal fibroblasts or hepatocytes in terms of exogenous sources of cholesterol and how these sources regulate internal synthesis. Colonic cancer cells have been used to assess small bowel enterocyte cholesterol metabolism, which has been possible because of their ability to differentiate in culture, however information regarding true colonic enterocyte cholesterol metabolism is relatively scarce. Colonic cancer cells have been shown to possess a diminished or nonexistent ability to use

  20. Spontaneous Perforation of Rectosigmoid Colon

    Directory of Open Access Journals (Sweden)

    Farhad Haj Sheikholeslami

    2010-12-01

    Full Text Available Spontaneous perforation of the sigmoid colon or rectom is definedas a sudden perforation of the colon in the absence of diseasessuch as tumors, diverticulosis or external injury. It is avery rare finding, and if neglected, results in severe peritonitisand high mortality. The causes of this rare condition are numerous,and in this case it might be due to the chronic constipationinduced by an anticholinergic antipsychotic.Iran J Med Sci 2010; 35(4: 339-341.

  1. (Un)folding mechanisms of the FBP28 WW domain in explicit solvent revealed by multiple rare event simulation methods

    NARCIS (Netherlands)

    Juraszek, J.; Bolhuis, P.G.

    2010-01-01

    We report a numerical study of the (un)folding routes of the truncated FBP28 WW domain at ambient conditions using a combination of four advanced rare event molecular simulation techniques. We explore the free energy landscape of the native state, the unfolded state, and possible intermediates, with

  2. Deconvoluting Protein (Unfolding Structural Ensembles Using X-Ray Scattering, Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation.

    Directory of Open Access Journals (Sweden)

    Alexandr Nasedkin

    Full Text Available The folding and unfolding of protein domains is an apparently cooperative process, but transient intermediates have been detected in some cases. Such (unfolding intermediates are challenging to investigate structurally as they are typically not long-lived and their role in the (unfolding reaction has often been questioned. One of the most well studied (unfolding pathways is that of Drosophila melanogaster Engrailed homeodomain (EnHD: this 61-residue protein forms a three helix bundle in the native state and folds via a helical intermediate. Here we used molecular dynamics simulations to derive sample conformations of EnHD in the native, intermediate, and unfolded states and selected the relevant structural clusters by comparing to small/wide angle X-ray scattering data at four different temperatures. The results are corroborated using residual dipolar couplings determined by NMR spectroscopy. Our results agree well with the previously proposed (unfolding pathway. However, they also suggest that the fully unfolded state is present at a low fraction throughout the investigated temperature interval, and that the (unfolding intermediate is highly populated at the thermal midpoint in line with the view that this intermediate can be regarded to be the denatured state under physiological conditions. Further, the combination of ensemble structural techniques with MD allows for determination of structures and populations of multiple interconverting structures in solution.

  3. [Lactobacilli and colon carcinoma--A review].

    Science.gov (United States)

    Wang, Shumei; Zhang, Lanwei; Shan, Yujuan

    2015-06-04

    Epidemiological studies showed that incidence of colon carcinoma is increased in the world. There are many difficulties to inhibit colon carcinoma because the causes of inducing colon carcinoma were various and interactive each other. Previous evidence supported the balance of the colonic microflora was critical in inhibiting colon carcinoma and the protection by colonic microflora could be improved by ingesting lactobacilli. Therefore, the biological functions and anticancer effects of lactobacilli attract attention of researchers. In this review we discussed the causes of colon carcinoma; the anticancer mechanisms of lactobacilli on the basis of our own studies. Eventually, we summarized the effects of anticancer of different components and metabolic products extracted from lactobacilli.

  4. pH-Dependent urea-induced unfolding of stem bromelain: unusual stability against urea at neutral pH.

    Science.gov (United States)

    Ahmad, B; Rathar, G M; Varshney, A; Khan, R H

    2009-12-01

    Equilibrium unfolding of stem bromelain (SB) with urea as a denaturant has been monitored as a function of pH using circular dichroism and fluorescence emission spectroscopy. Urea-induced denaturation studies at pH 4.5 showed that SB unfolds through a two-state mechanism and yields DeltaG (free energy difference between the fully folded and unfolded forms) of approximately 5.0 kcal/mol and C(m) (midpoint of the unfolding transition) of approximately 6.5 M at 25 degrees C. Very high concentration of urea (9.5 M) provides unusual stability to the protein with no more structural loss and transition to a completely unfolded state.

  5. Single-molecule spectroscopy of the temperature-induced collapse of unfolded proteins.

    Science.gov (United States)

    Nettels, Daniel; Müller-Späth, Sonja; Küster, Frank; Hofmann, Hagen; Haenni, Dominik; Rüegger, Stefan; Reymond, Luc; Hoffmann, Armin; Kubelka, Jan; Heinz, Benjamin; Gast, Klaus; Best, Robert B; Schuler, Benjamin

    2009-12-01

    We used single-molecule FRET in combination with other biophysical methods and molecular simulations to investigate the effect of temperature on the dimensions of unfolded proteins. With single-molecule FRET, this question can be addressed even under near-native conditions, where most molecules are folded, allowing us to probe a wide range of denaturant concentrations and temperatures. We find a compaction of the unfolded state of a small cold shock protein with increasing temperature in both the presence and the absence of denaturant, with good agreement between the results from single-molecule FRET and dynamic light scattering. Although dissociation of denaturant from the polypeptide chain with increasing temperature accounts for part of the compaction, the results indicate an important role for additional temperature-dependent interactions within the unfolded chain. The observation of a collapse of a similar extent in the extremely hydrophilic, intrinsically disordered protein prothymosin alpha suggests that the hydrophobic effect is not the sole source of the underlying interactions. Circular dichroism spectroscopy and replica exchange molecular dynamics simulations in explicit water show changes in secondary structure content with increasing temperature and suggest a contribution of intramolecular hydrogen bonding to unfolded state collapse.

  6. Pathways to schizophrenic psychosis: a LISREL-tested model of the unfolding of the schizophrenic prodrome

    NARCIS (Netherlands)

    Kampen, van D.

    2005-01-01

    In this article a literature-based model (the Schizotypic Syndrome Questionnaire [SSQ] model) is presented that gives a description of the temporal unfolding of the schizophrenic prodrome. As a guiding principle for the selection of the symptoms in the model, the hypothesis was held that the main pr

  7. The unfolded protein response mediates reversible tau phosphorylation induced by metabolic stress

    NARCIS (Netherlands)

    van der Harg, J. M.; Nolle, A.; Zwart, R.; Boerema, A. S.; van Haastert, E. S.; Strijkstra, A. M.; Hoozemans, J. J. M.; Scheper, W.

    2014-01-01

    The unfolded protein response (UPR) is activated in neurodegenerative tauopathies such as Alzheimer's disease (AD) in close connection with early stages of tau pathology. Metabolic disturbances are strongly associated with increased risk for AD and are a potent inducer of the UPR. Here, we demonstra

  8. Avoiding Degeneracy in Multidimensional Unfolding by Penalizing on the Coefficient of Variation

    Science.gov (United States)

    Busing, Frank M. T. A.; Groenen, Patrick J. K.; Heiser, Willem J.

    2005-01-01

    Multidimensional unfolding methods suffer from the degeneracy problem in almost all circumstances. Most degeneracies are easily recognized: the solutions are perfect but trivial, characterized by approximately equal distances between points from different sets. A definition of an absolutely degenerate solution is proposed, which makes clear that…

  9. Temperature induced structural transitions from native to unfolded aggregated states of tobacco etch virus protease

    Science.gov (United States)

    Zhu, Guo-Fei; Ren, Si-Yan; Xi, Lei; Du, Lin-Fang; Zhu, Xiao-Feng

    2015-02-01

    Tobacco etch virus protease (TEVp) is widely used to remove fusion tags from recombinant proteins because of its high and unique specificity. This work describes the conformational and the thermodynamic properties in the unfolding/refolding process of TEVp3M (three-point mutant: L56V/S135G/S219V) induced by temperature. With temperature increasing from 20 to 100 °C, the CD spectra showed a transition trend from α-helix to β-sheet, and the fluorescence emission, synchronous fluorescence, ANS and RLS spectroscopy consistently revealed that the temperature-induced unfolding process behaved in a three-state manner, for there was a relatively stable intermediate state observed around 50 °C. The reversibility of thermal unfolding of TEVp3M further showed that the transition from the native to the intermediate state was reversible (below 50 °C), however the transition from the intermediate to the unfolded state was irreversible (above 60 °C). Moreover, aggregates were observed above 60 °C as revealed by SDS-PAGE, Thioflavin-T fluorescence and Congo red absorbance.

  10. Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress

    Directory of Open Access Journals (Sweden)

    Emil Ylikallio

    2015-06-01

    General significance: sHSPs have important roles in prevention of protein aggregates that induce toxicity. We showed that C-terminal part of HSPB1 is critical for tolerance of unfolded protein stress, and when lacking causes axonal neuropathy in patients.

  11. Different thermal unfolding pathways of catalase in the presence of cationic surfactants.

    Science.gov (United States)

    Blanco, Elena; Ruso, Juan M; Prieto, Gerardo; Sarmiento, Félix

    2007-03-01

    In this paper we have corroborated the usefulness of spectroscopic techniques, such as UV-visible, in the study and thermodynamic characterization of the thermal unfolding of catalase as a function of the concentration and alkyl chain length of n-alkyltrimethylammonium bromides (CnTAB, n = 8, 10, and 12). For this reason, a thermodynamic model was used which included experimental data corresponding to the pre- and posttransition into the observable transition. It has been found that n-alkyltrimethylammonium bromides play two opposite roles in the folding and stability of catalase. They act as a structure stabilizer at a low molar concentration and as a destabilizer at a higher concentration. The maximum of the unfolding temperature has been found to decrease with the alkyl chain. The reason for this difference has been suggested to be the side chains involved. In the presence of C8TAB and C10TAB, Gibbs energies of unfolding (DeltaG(T)) decrease with concentration, whereas for C12TAB an increase has been observed. These findings can be explained by the fact that when differences in the hydrophobic nature of the surfactants exist, different pathways of unfolding may occur. Also, the presence of surfactants has been observed to affect the cold denaturation of catalase. Thermodynamic results suggest that the thermal denaturation of catalase in the presence of n-alkyltrimethylammonium bromides is a perfect transition between two states.

  12. Marginal Maximum A Posteriori Item Parameter Estimation for the Generalized Graded Unfolding Model

    Science.gov (United States)

    Roberts, James S.; Thompson, Vanessa M.

    2011-01-01

    A marginal maximum a posteriori (MMAP) procedure was implemented to estimate item parameters in the generalized graded unfolding model (GGUM). Estimates from the MMAP method were compared with those derived from marginal maximum likelihood (MML) and Markov chain Monte Carlo (MCMC) procedures in a recovery simulation that varied sample size,…

  13. Nucleic acid induced unfolding of recombinant prion protein globular fragment is pH dependent.

    Science.gov (United States)

    Bera, Alakesh; Nandi, Pradip K

    2014-12-01

    Nucleic acid can catalyze the conversion of α-helical cellular prion protein to β-sheet rich Proteinase K resistant prion protein oligomers and amyloid polymers in vitro and in solution. Because unfolding of a protein molecule from its ordered α-helical structure is considered to be a necessary step for the structural conversion to its β-sheet rich isoform, we have studied the unfolding of the α-helical globular 121-231 fragment of mouse recombinant prion protein in the presence of different nucleic acids at neutral and acid pH. Nucleic acids, either single or double stranded, do not have any significant effect on the secondary structure of the protein fragment at neutral pH; however the protein secondary structure is modified by the nucleic acids at pH 5. Nucleic acids do not show any significant effect on the temperature induced unfolding of the globular prion protein domain at neutral pH which, however, undergoes a gross conformational change at pH 5 as evidenced from the lowering of the midpoint of thermal denaturation temperatures, Tm, of the protein. The extent of Tm decrease shows a dependence on the nature of nucleic acid. The interaction of nucleic acid with the nonpolar groups exposed from the protein interior at pH 5 probably contributes substantially to the unfolding process of the protein. © 2014 The Protein Society.

  14. A cubic Henon-like map in the unfolding of degenerate homoclinic orbit with resonance

    NARCIS (Netherlands)

    Martens, M; Naudot, [No Value; Yang, JZ

    2005-01-01

    In this Note, we study the unfolding of a vector field that possesses a degenerate homoclinic (of inclination-flip type) to a hyperbolic equilibrium point where its linear part possesses a resonance. For the unperturbed system, the resonant term associated with the resonance vanishes. After suitable

  15. Order out of disorder: working cycle of an intrinsically unfolded chaperone.

    Science.gov (United States)

    Reichmann, Dana; Xu, Ying; Cremers, Claudia M; Ilbert, Marianne; Mittelman, Roni; Fitzgerald, Michael C; Jakob, Ursula

    2012-03-02

    The redox-regulated chaperone Hsp33 protects organisms against oxidative stress that leads to protein unfolding. Activation of Hsp33 is triggered by the oxidative unfolding of its own redox-sensor domain, making Hsp33 a member of a recently discovered class of chaperones that require partial unfolding for full chaperone activity. Here we address the long-standing question of how chaperones recognize client proteins. We show that Hsp33 uses its own intrinsically disordered regions to discriminate between unfolded and partially structured folding intermediates. Binding to secondary structure elements in client proteins stabilizes Hsp33's intrinsically disordered regions, and this stabilization appears to mediate Hsp33's high affinity for structured folding intermediates. Return to nonstress conditions reduces Hsp33's disulfide bonds, which then significantly destabilizes the bound client proteins and in doing so converts them into less-structured, folding-competent client proteins of ATP-dependent foldases. We propose a model in which energy-independent chaperones use internal order-to-disorder transitions to control substrate binding and release. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sourav Roy

    Full Text Available 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.

  17. Dynamic heterogeneity in the folding/unfolding transitions of FiP35

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Toshifumi, E-mail: mori@ims.ac.jp; Saito, Shinji, E-mail: shinji@ims.ac.jp [Institute for Molecular Science, Okazaki, Aichi 444-8585, Japan and School of Physical Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi 444-8585 (Japan)

    2015-04-07

    Molecular dynamics simulations have become an important tool in studying protein dynamics over the last few decades. Atomistic simulations on the order of micro- to milliseconds are becoming feasible and are used to study the state-of-the-art experiments in atomistic detail. Yet, analyzing the high-dimensional-long-temporal trajectory data is still a challenging task and sometimes leads to contradictory results depending on the analyses. To reveal the dynamic aspect of the trajectory, here we propose a simple approach which uses a time correlation function matrix and apply to the folding/unfolding trajectory of FiP35 WW domain [Shaw et al., Science 330, 341 (2010)]. The approach successfully characterizes the slowest mode corresponding to the folding/unfolding transitions and determines the free energy barrier indicating that FiP35 is not an incipient downhill folder. The transition dynamics analysis further reveals that the folding/unfolding transition is highly heterogeneous, e.g., the transition path time varies by ∼100 fold. We identify two misfolded states and show that the dynamic heterogeneity in the folding/unfolding transitions originates from the trajectory being trapped in the misfolded and half-folded intermediate states rather than the diffusion driven by a thermal noise. The current results help reconcile the conflicting interpretations of the folding mechanism and highlight the complexity in the folding dynamics. This further motivates the need to understand the transition dynamics beyond a simple free energy picture using simulations and single-molecule experiments.

  18. A strange attractor in the unfolding of an orbit-flip homoclinic orbit

    NARCIS (Netherlands)

    Naudot, [No Value

    2002-01-01

    An orbit-flip homoclinic orbit Gamma of a vector field defined on R-3 is a homoclinic orbit to an equilibrium point for which the one-dimensional unstable manifold of the equilibrium point is connected to the one-dimensional strong stable manifold. In this paper, we show that in a generic unfolding

  19. Markov Chain Monte Carlo Estimation of Item Parameters for the Generalized Graded Unfolding Model

    Science.gov (United States)

    de la Torre, Jimmy; Stark, Stephen; Chernyshenko, Oleksandr S.

    2006-01-01

    The authors present a Markov Chain Monte Carlo (MCMC) parameter estimation procedure for the generalized graded unfolding model (GGUM) and compare it to the marginal maximum likelihood (MML) approach implemented in the GGUM2000 computer program, using simulated and real personality data. In the simulation study, test length, number of response…

  20. VISAR Unfold Analysis of Load Current in MagLIF Experiments

    Science.gov (United States)

    Hess, Mark; McBride, Ryan; Martin, Matthew

    2013-10-01

    An accurate prediction of the load current is essential in the performance of MagLIF experiments on the Z-Machine at Sandia. At present, the most accurate diagnostic for measuring load current on the Z-machine is the well-established VISAR technique. The VISAR diagnostic measures the velocity of a thin aluminum foil placed near the load, which is subject to the magnetic pressure produced by the load current, using a laser interferometer. The load current unfold analysis is highly nonlinear due to the equation of state/conductivity models, along with the MHD equations governing the foil. Nevertheless, an accurate load current unfold from the VISAR measurement is possible using an MHD code, in conjunction with an optimization algorithm. We will review the VISAR unfold analysis, and show recent current unfolds of MagLIF experiments in comparison to load current measurements using B-dot probes. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  1. Quenching of Tryptophan Fluorescence in Unfolded Cytochrome "c": A Biophysics Experiment for Physical Chemistry Students

    Science.gov (United States)

    Schlamadinger, Diana E.; Kats, Dina I.; Kim, Judy E.

    2010-01-01

    Laboratory experiments that focus on protein folding provide excellent opportunities for undergraduate students to learn important topics in the expanding interdisciplinary field of biophysics. Here, we describe the use of Stern-Volmer plots to determine the extent of solvent accessibility of the single tryptophan residue (trp-59) in unfolded and…

  2. Statistical coil model of the unfolded state: resolving the reconciliation problem.

    Science.gov (United States)

    Jha, Abhishek K; Colubri, Andrés; Freed, Karl F; Sosnick, Tobin R

    2005-09-13

    An unfolded state ensemble is generated by using a self-avoiding statistical coil model that is based on backbone conformational frequencies in a coil library, a subset of the Protein Data Bank. The model reproduces two apparently contradicting behaviors observed in the chemically denatured state for a variety of proteins, random coil scaling of the radius of gyration and the presence of significant amounts of local backbone structure (NMR residual dipolar couplings). The most stretched members of our unfolded ensemble dominate the residual dipolar coupling signal, whereas the uniformity of the sign of the couplings follows from the preponderance of polyproline II and beta conformers in the coil library. Agreement with the NMR data substantially improves when the backbone conformational preferences include correlations arising from the chemical and conformational identity of neighboring residues. Although the unfolded ensembles match the experimental observables, they do not display evidence of native-like topology. By providing an accurate representation of the unfolded state, our statistical coil model can be used to improve thermodynamic and kinetic modeling of protein folding.

  3. Ethanol Effects Involve Non-canonical Unfolded Protein Response Activation in Yeast Cells

    Science.gov (United States)

    Navarro-Tapia, Elisabet; Pérez-Torrado, Roberto; Querol, Amparo

    2017-01-01

    The unfolded protein response (UPR) is a conserved intracellular signaling pathway that controls transcription of endoplasmic reticulum (ER) homeostasis related genes. Ethanol stress has been recently described as an activator of the UPR response in yeast Saccharomyces cerevisiae, but very little is known about the causes of this activation. Although some authors ensure that the UPR is triggered by the unfolded proteins generated by ethanol in the cell, there are studies which demonstrate that protein denaturation occurs at higher ethanol concentrations than those used to trigger the UPR. Here, we studied UPR after ethanol stress by three different approaches and we concluded that unfolded proteins do not accumulate in the ER under. We also ruled out inositol depletion as an alternative mechanism to activate the UPR under ethanol stress discarding that ethanol effects on the cell decreased inositol levels by different methods. All these data suggest that ethanol, at relatively low concentrations, does not cause unfolded proteins in the yeasts and UPR activation is likely due to other unknown mechanism related with a restructuring of ER membrane due to the effect of ethanol. PMID:28326077

  4. Avoiding Degeneracy in Multidimensional Unfolding by Penalizing on the Coefficient of Variation

    Science.gov (United States)

    Busing, Frank M. T. A.; Groenen, Patrick J. K.; Heiser, Willem J.

    2005-01-01

    Multidimensional unfolding methods suffer from the degeneracy problem in almost all circumstances. Most degeneracies are easily recognized: the solutions are perfect but trivial, characterized by approximately equal distances between points from different sets. A definition of an absolutely degenerate solution is proposed, which makes clear that…

  5. Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine.

    Science.gov (United States)

    Aubin-Tam, Marie-Eve; Olivares, Adrian O; Sauer, Robert T; Baker, Tania A; Lang, Matthew J

    2011-04-15

    All cells employ ATP-powered proteases for protein-quality control and regulation. In the ClpXP protease, ClpX is a AAA+ machine that recognizes specific protein substrates, unfolds these molecules, and then translocates the denatured polypeptide through a central pore and into ClpP for degradation. Here, we use optical-trapping nanometry to probe the mechanics of enzymatic unfolding and translocation of single molecules of a multidomain substrate. Our experiments demonstrate the capacity of ClpXP and ClpX to perform mechanical work under load, reveal very fast and highly cooperative unfolding of individual substrate domains, suggest a translocation step size of 5-8 amino acids, and support a power-stroke model of denaturation in which successful enzyme-mediated unfolding of stable domains requires coincidence between mechanical pulling by the enzyme and a transient stochastic reduction in protein stability. We anticipate that single-molecule studies of the mechanical properties of other AAA+ proteolytic machines will reveal many shared features with ClpXP.

  6. Rapid mapping of volumetric machine errors using distance measurements

    Energy Technology Data Exchange (ETDEWEB)

    Krulewich, D.A.

    1998-04-01

    This paper describes a relatively inexpensive, fast, and easy to execute approach to maping the volumetric errors of a machine tool, coordinate measuring machine, or robot. An error map is used to characterize a machine or to improve its accuracy by compensating for the systematic errors. The method consists of three steps: (1) models the relationship between volumetric error and the current state of the machine, (2) acquiring error data based on distance measurements throughout the work volume; and (3)fitting the error model using the nonlinear equation for the distance. The error model is formulated from the kinematic relationship among the six degrees of freedom of error an each moving axis. Expressing each parametric error as function of position each is combined to predict the error between the functional point and workpiece, also as a function of position. A series of distances between several fixed base locations and various functional points in the work volume is measured using a Laser Ball Bar (LBB). Each measured distance is a non-linear function dependent on the commanded location of the machine, the machine error, and the location of the base locations. Using the error model, the non-linear equation is solved producing a fit for the error model Also note that, given approximate distances between each pair of base locations, the exact base locations in the machine coordinate system determined during the non-linear filling procedure. Furthermore, with the use of 2048 more than three base locations, bias error in the measuring instrument can be removed The volumetric errors of three-axis commercial machining center have been mapped using this procedure. In this study, only errors associated with the nominal position of the machine were considered Other errors such as thermally induced and load induced errors were not considered although the mathematical model has the ability to account for these errors. Due to the proprietary nature of the projects we are

  7. Populated intermediates in the thermal unfolding of the human telomeric quadruplex.

    Science.gov (United States)

    Gray, Robert D; Buscaglia, Robert; Chaires, Jonathan B

    2012-10-10

    Thermal denaturation profiles of several model oligonucleotides of the human telomere DNA sequence including d[A(GGGTTA)(3)GGG] (Tel22) were determined using circular dichroism (CD), fluorescence of adenine → 2-aminopurine analogs, and fluorescence resonance energy transfer (FRET) to monitor the unfolding process at specific locations within the quadruplex. The resulting optical spectra vs temperature data matrices were analyzed by singular value decomposition (SVD) to ascertain the minimum number of species required to reproduce the unfolding spectral profiles. Global nonlinear least-squares fitting of the SVD amplitude vectors was used to estimate thermodynamic parameters and optical spectra of all species for a series of unfolding mechanisms that included one-, two-, and three-step sequential pathways F ⇌ I(n) ⇌ U, n = 0, 1, or 2) as well as two mechanisms with spectroscopically distinct starting structures (F(1) and F(2)). The CD and FRET data for Tel22 unfolding between 4 and 94 °C in 25 mM KCl were best described by a sequential unfolding model with two intermediates, while the 2-aminopurine analogs required one intermediate. The higher melting intermediate I(2) had a transition midpoint temperature (T(m)) of 61 °C and a CD spectrum with a maximum and minimum at ~265 and ~245 nm, respectively. The fluorescence emission spectra of the 2-aminopurine and FRET derivatives suggest greater solvent exposure of the 5'-AGGGTTA- segment in the intermediate compared to the folded state. The spectroscopic properties of the 61 °C intermediate suggest that it may be a triple helical structure.

  8. Design and characterization of a membrane protein unfolding platform in lipid bilayers.

    Directory of Open Access Journals (Sweden)

    Vincent G Nadeau

    Full Text Available Accurate measurement of membrane protein stability--and particularly how it may vary as a result of disease-phenotypic mutations--ideally requires a denaturant that can unfold a membrane-embedded structure while leaving the solubilizing environment unaffected. The steric trap method fulfills this requirement by using monovalent streptavidin (mSA molecules to unfold membrane proteins engineered with two spatially close biotin tags. Here we adapted this method to an 87-residue helix-loop-helix (hairpin construct derived from helices 3 and 4 in the transmembrane domain of the human cystic fibrosis transmembrane conductance regulator (CFTR, wherein helix-helix tertiary interactions are anticipated to confer a portion of construct stability. The wild type CFTR TM3/4 hairpin construct was modified with two accessible biotin tags for mSA-induced unfolding, along with two helix-terminal pyrene labels to monitor loss of inter-helical contacts by pyrene excimer fluorescence. A series of eight constructs with biotin tags at varying distances from the helix-terminal pyrene labels were expressed, purified and labeled appropriately; all constructs exhibited largely helical circular dichroism spectra. We found that addition of mSA to an optimized construct in lipid vesicles led to a complete and reversible loss in pyrene excimer fluorescence and mSA binding, and hence hairpin unfolding--results further supported by SDS-PAGE visualization of mSA bound and unbound species. While some dimeric/oligomeric populations persist that may affect quantitation of the unfolding step, our characterization of the design yields a promising prototype of a future platform for the systematic study of membrane protein folding in a lipid bilayer environment.

  9. Unfolding of a model protein on ion exchange and mixed mode chromatography surfaces.

    Science.gov (United States)

    Gospodarek, Adrian M; Hiser, Diana E; O'Connell, John P; Fernandez, Erik J

    2014-08-15

    Recent studies with proteins indicate that conformational changes and aggregation can occur during ion exchange chromatography (IEC). Such behavior is not usually expected, but could lead to decreased yield and product degradation from both IEC and multi mode chromatography (MMC) that has ligands of both hydrophobic and charged functionalities. In this study, we used hydrogen exchange mass spectrometry to investigate unfolding of the model protein BSA on IEC and MMC surfaces under different solution conditions at 25°C. Increased solvent exposure, indicating greater unfolding relative to that in solution, was found for protein adsorbed on cationic IEC and MMC surfaces in the pH range of 3.0 to 4.5, where BSA has decreased stability in solution. There was no effect of anionic surfaces at pH values in the range from 6.0 to 9.0. Differences of solvent exposure of whole molecules when adsorbed and in solution suggest that adsorbed BSA unfolds at lower pH values and may show aggregation, depending upon pH and the surface type. Measurements on digested peptides showed that classifications of stability can be made for various regions; these are generally retained as pH is changed. When salt was added to MMC systems, where electrostatic interactions would be minimized, less solvent exposure was seen, implying that it is the cationic moieties, rather than the hydrophobic ligands, which cause greater surface unfolding at low salt concentrations. These results suggest that proteins of lower stability may exhibit unfolding and aggregation during IEC and MMC separations, as they can with hydrophobic interaction chromatography.

  10. Precursory signatures of protein folding/unfolding: From time series correlation analysis to atomistic mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, P. J.; Lai, S. K., E-mail: sklai@coll.phy.ncu.edu.tw [Complex Liquids Laboratory, Department of Physics, National Central University, Chungli 320 Taiwan (China); Molecular Science and Technology Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan (China); Cheong, S. A. [Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371 (Singapore)

    2014-05-28

    Folded conformations of proteins in thermodynamically stable states have long lifetimes. Before it folds into a stable conformation, or after unfolding from a stable conformation, the protein will generally stray from one random conformation to another leading thus to rapid fluctuations. Brief structural changes therefore occur before folding and unfolding events. These short-lived movements are easily overlooked in studies of folding/unfolding for they represent momentary excursions of the protein to explore conformations in the neighborhood of the stable conformation. The present study looks for precursory signatures of protein folding/unfolding within these rapid fluctuations through a combination of three techniques: (1) ultrafast shape recognition, (2) time series segmentation, and (3) time series correlation analysis. The first procedure measures the differences between statistical distance distributions of atoms in different conformations by calculating shape similarity indices from molecular dynamics simulation trajectories. The second procedure is used to discover the times at which the protein makes transitions from one conformation to another. Finally, we employ the third technique to exploit spatial fingerprints of the stable conformations; this procedure is to map out the sequences of changes preceding the actual folding and unfolding events, since strongly correlated atoms in different conformations are different due to bond and steric constraints. The aforementioned high-frequency fluctuations are therefore characterized by distinct correlational and structural changes that are associated with rate-limiting precursors that translate into brief segments. Guided by these technical procedures, we choose a model system, a fragment of the protein transthyretin, for identifying in this system not only the precursory signatures of transitions associated with α helix and β hairpin, but also the important role played by weaker correlations in such protein

  11. Reversible heat inactivation of copper sites precedes thermal unfolding of molluscan (Rapana thomasiana) hemocyanin.

    Science.gov (United States)

    Idakieva, Krassimira; Meersman, Filip; Gielens, Constant

    2012-05-01

    Hemocyanin (Hc) is a type-3 copper protein, containing dioxygen-binding active sites consisting of paired copper atoms. In the present study the thermal unfolding of the Hc from the marine mollusc Rapana thomasiana (RtH) has been investigated by combining differential scanning calorimetry, Fourier transform infrared (FTIR) and UV-vis absorption spectroscopy. Two important stages in the unfolding pathway of the Hc molecule were discerned. A first event, with nonmeasurable heat absorption, occurring around 60°C, lowers the binding of dioxygen to the type-3 copper groups. This pretransition is reversible and is ascribed to a slight change in the tertiary structure. In a second stage, with midpoint around 80°C, the protein irreversibly unfolds with a loss of secondary structure and formation of amorphous aggregates. Experiments with the monomeric structural subunits, RtH1 and RtH2, indicated that the heterogeneity in the process of thermal denaturation can be attributed to the presence of multiple 50kDa functional units with different stability. In accordance, the irreversible unfolding of a purified functional unit (RtH2-e) occurred at a single transition temperature. At slightly alkaline pH (Tris buffer) the C-terminal β-sheet rich domain of the functional unit starts to unfold before the α-helix-rich N-terminal (copper containing) domain, triggering the collapse of the global protein structure. Even around 90°C some secondary structure is preserved as shown by the FTIR spectra of all investigated samples, confirming the high thermostability of molluscan Hc.

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

    Directory of Open Access Journals (Sweden)

    Laura U. Marks

    2011-04-01

    Full Text Available Why do certain images of history reach us, while others remain seemingly forgotten, in the infinite breadth of the past? Why do only certain events seem to matter? I suggest those experiences are not forgotten but enfolded. The contemporary politics of historiography can be conceptualized according to the relationship between Experience, Information, and Image; a triadic relationship I have proposed to understand the nature of the image in the information age. While Experience is infinite, the vast majority of experience lies latent. Few Images ever arise from it. In our age, those that do tend to be selected, or unfolded, by political and economic interests that deem them to be useful as Information. Nevertheless, anyone can unfold any aspect of Experience to become a public image, and artists (and others do so in order to allow other aspects of Experience to circulate, before they enfold, back into the matrix of history. I will show an animated diagram that illustrates this concept of history as a flow of unfolding and enfolding, influenced by concepts from Charles Sanders Peirce and Gilles Deleuze.   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

  13. Mechanical unfolding of two DIS RNA kissing complexes from HIV-1.

    Science.gov (United States)

    Li, Pan T X; Tinoco, Ignacio

    2009-03-13

    An RNA kissing complex formed by the dimerization initiation site plays a critical role in the survival and infectivity of human immunodeficiency virus. Two dimerization initiation site kissing sequences, Mal and Lai, have been found in most human immunodeficiency virus 1 variants. Formation and stability of these RNA kissing complexes depend crucially on cationic conditions, particularly Mg 2+. Using optical tweezers, we investigated the mechanical unfolding of single RNA molecules with either Mal-type (GUGCAC) or Lai-type (GCGCGC) kissing complexes under various ionic conditions. The force required to disrupt the kissing interaction of the two structures, the rip force, is sensitive to concentrations of KCl and MgCl2; addition of 3 mM MgCl2 to 100 mM KCl changes the rip force of Mal from 21 +/- 4 to 46 +/- 3 pN. From the rip force distribution, the kinetics of breaking the kissing interaction is calculated as a function of force and cation concentration. The two kissing complexes have distinct unfolding transition states, as shown by different values of deltaX(++), which is the distance from the folded structure to the unfolding transition state. The deltaX(++) of Mal is approximately 0.6 nm smaller than that of Lai, suggesting that fewer kissing base pairs are broken at the transition state of the former, consistent with observations that the Lai-type kissing complex is more stable and requires significantly more force to unfold than the Mal type. More importantly, neither K+ nor Mg 2+ significantly changes the position of the transition state along the reaction coordinate. However, increasing concentrations of cations increase the kinetic barrier. We derived a cation-specific parameter, m, to describe how the height of the kinetic barrier depends on the concentration of cations. Our results suggest that Mg 2+ greatly slows down the unfolding of the kissing complex but has moderate effects on the formation kinetics of the structure.

  14. Quantitative volumetric Raman imaging of three dimensional cell cultures

    Science.gov (United States)

    Kallepitis, Charalambos; Bergholt, Mads S.; Mazo, Manuel M.; Leonardo, Vincent; Skaalure, Stacey C.; Maynard, Stephanie A.; Stevens, Molly M.

    2017-03-01

    The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell-material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment. We demonstrate visualization and quantification of fine details in cell shape, cytoplasm, nucleus, lipid bodies and cytoskeletal structures in 3D with unprecedented biomolecular specificity for vibrational microspectroscopy.

  15. Optimization approaches to volumetric modulated arc therapy planning

    Energy Technology Data Exchange (ETDEWEB)

    Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bortfeld, Thomas; Craft, David [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Alber, Markus [Department of Medical Physics and Department of Radiation Oncology, Aarhus University Hospital, Aarhus C DK-8000 (Denmark); Bangert, Mark [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Heidelberg D-69120 (Germany); Bokrantz, Rasmus [RaySearch Laboratories, Stockholm SE-111 34 (Sweden); Chen, Danny [Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, Indiana 46556 (United States); Li, Ruijiang; Xing, Lei [Department of Radiation Oncology, Stanford University, Stanford, California 94305 (United States); Men, Chunhua [Department of Research, Elekta, Maryland Heights, Missouri 63043 (United States); Nill, Simeon [Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London SM2 5NG (United Kingdom); Papp, Dávid [Department of Mathematics, North Carolina State University, Raleigh, North Carolina 27695 (United States); Romeijn, Edwin [H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); Salari, Ehsan [Department of Industrial and Manufacturing Engineering, Wichita State University, Wichita, Kansas 67260 (United States)

    2015-03-15

    Volumetric modulated arc therapy (VMAT) has found widespread clinical application in recent years. A large number of treatment planning studies have evaluated the potential for VMAT for different disease sites based on the currently available commercial implementations of VMAT planning. In contrast, literature on the underlying mathematical optimization methods used in treatment planning is scarce. VMAT planning represents a challenging large scale optimization problem. In contrast to fluence map optimization in intensity-modulated radiotherapy planning for static beams, VMAT planning represents a nonconvex optimization problem. In this paper, the authors review the state-of-the-art in VMAT planning from an algorithmic perspective. Different approaches to VMAT optimization, including arc sequencing methods, extensions of direct aperture optimization, and direct optimization of leaf trajectories are reviewed. Their advantages and limitations are outlined and recommendations for improvements are discussed.

  16. Volumetric properties of water/AOT/isooctane microemulsions.

    Science.gov (United States)

    Du, Changfei; He, Wei; Yin, Tianxiang; Shen, Weiguo

    2014-12-23

    The densities of AOT/isooctane micelles and water/AOT/isooctane microemulsions with the molar ratios R of water to AOT being 2, 8, 10, 12, 16, 18, 20, 25, 30, and 40 were measured at 303.15 K. The apparent specific volumes of AOT and the quasi-component water/AOT at various concentrations were calculated and used to estimate the volumetric properties of AOT and water in the droplets and in the continuous oil phase, to discuss the interaction between the droplets, and to determine the critical micelle concentration and the critical microemulsion concentrations. A thermodynamic model was proposed to analysis the stability boundary of the microemulsion droplets, which confirms the maximum value of R being about 65 for the stable AOT/water/isooctane microemulsion droplets.

  17. Quantitative volumetric Raman imaging of three dimensional cell cultures

    KAUST Repository

    Kallepitis, Charalambos

    2017-03-22

    The ability to simultaneously image multiple biomolecules in biologically relevant three-dimensional (3D) cell culture environments would contribute greatly to the understanding of complex cellular mechanisms and cell–material interactions. Here, we present a computational framework for label-free quantitative volumetric Raman imaging (qVRI). We apply qVRI to a selection of biological systems: human pluripotent stem cells with their cardiac derivatives, monocytes and monocyte-derived macrophages in conventional cell culture systems and mesenchymal stem cells inside biomimetic hydrogels that supplied a 3D cell culture environment. We demonstrate visualization and quantification of fine details in cell shape, cytoplasm, nucleus, lipid bodies and cytoskeletal structures in 3D with unprecedented biomolecular specificity for vibrational microspectroscopy.

  18. In-line hologram segmentation for volumetric samples.

    Science.gov (United States)

    Orzó, László; Göröcs, Zoltán; Fehér, András; Tőkés, Szabolcs

    2013-01-01

    We propose a fast, noniterative method to segment an in-line hologram of a volumetric sample into in-line subholograms according to its constituent objects. In contrast to the phase retrieval or twin image elimination algorithms, we do not aim or require to reconstruct the complex wave field of all the objects, which would be a more complex task, but only provide a good estimate about the contribution of the particular objects to the original hologram quickly. The introduced hologram segmentation algorithm exploits the special inner structure of the in-line holograms and applies only the estimated supports and reconstruction distances of the corresponding objects as parameters. The performance of the proposed method is demonstrated and analyzed experimentally both on synthetic and measured holograms. We discussed how the proposed algorithm can be efficiently applied for object reconstruction and phase retrieval tasks.

  19. Three-Dimensional Volumetric Restoration by Structural Fat Grafting

    Science.gov (United States)

    Clauser, Luigi C.; Consorti, Giuseppe; Elia, Giovanni; Galié, Manlio; Tieghi, Riccardo

    2013-01-01

    The use of adipose tissue transfer for correction of maxillofacial defects was reported for the first time at the end of the 19th century. Structural fat grafting (SFG) was introduced as a way to improve facial esthetics and in recent years has evolved into applications in craniomaxillofacial reconstructive surgery. Several techniques have been proposed for harvesting and grafting the fat. However, owing to the damage of many adipocytes during these maneuvers, the results have not been satisfactory and have required several fat injection procedures for small corrections. The author's (L.C.) overview the application of SFG in the management of volumetric deficit in the craniomaxillofacial in patients treated with a long-term follow-up. PMID:24624259

  20. Semi-automatic volumetrics system to parcellate ROI on neocortex

    Science.gov (United States)

    Tan, Ou; Ichimiya, Tetsuya; Yasuno, Fumihiko; Suhara, Tetsuya

    2002-05-01

    A template-based and semi-automatic volumetrics system--BrainVol is build to divide the any given patient brain to neo-cortical and sub-cortical regions. The standard region is given as standard ROI drawn on a standard brain volume. After normalization between the standard MR image and the patient MR image, the sub-cortical ROIs' boundary are refined based on gray matter. The neo-cortical ROIs are refined by sulcus information that is semi-automatically marked on the patient brain. Then the segmentation is applied to 4D PET image of same patient for calculation of TAC (Time Activity Curve) by co-registration between MR and PET.

  1. Out-of-core clustering of volumetric datasets

    Institute of Scientific and Technical Information of China (English)

    GRANBERG Carl J.; LI Ling

    2006-01-01

    In this paper we present a novel method for dividing and clustering large volumetric scalar out-of-core datasets. This work is based on the Ordered Cluster Binary Tree (OCBT) structure created using a top-down or divisive clustering method. The OCBT structure allows fast and efficient sub volume queries to be made in combination with level of detail (LOD) queries of the tree. The initial partitioning of the large out-of-core dataset is done by using non-axis aligned planes calculated using Principal Component Analysis (PCA). A hybrid OCBT structure is also proposed where an in-core cluster binary tree is combined with a large out-of-core file.

  2. Volumetric Survey Speed: A Figure of Merit for Transient Surveys

    CERN Document Server

    Bellm, Eric C

    2016-01-01

    Time-domain surveys can exchange sky coverage for revisit frequency, complicating the comparison of their relative capabilities. By using different revisit intervals, a specific camera may execute surveys optimized for discovery of different classes of transient objects. We propose a new figure of merit, the instantaneous volumetric survey speed, for evaluating transient surveys. This metric defines the trade between cadence interval and snapshot survey volume and so provides a natural means of comparing survey capability. The related metric of areal survey speed imposes a constraint on the range of possible revisit times: we show that many modern time-domain surveys are limited by the amount of fresh sky available each night. We introduce the concept of "spectroscopic accessibility" and discuss its importance for transient science goals requiring followup observing. We present an extension of the control time algorithm for cases where multiple consecutive detections are required. Finally, we explore how surv...

  3. Volumetric optical coherence microscopy enabled by aberrated optics (Conference Presentation)

    Science.gov (United States)

    Mulligan, Jeffrey A.; Liu, Siyang; Adie, Steven G.

    2017-02-01

    Optical coherence microscopy (OCM) is an interferometric imaging technique that enables high resolution, non-invasive imaging of 3D cell cultures and biological tissues. Volumetric imaging with OCM suffers a trade-off between high transverse resolution and poor depth-of-field resulting from defocus, optical aberrations, and reduced signal collection away from the focal plane. While defocus and aberrations can be compensated with computational methods such as interferometric synthetic aperture microscopy (ISAM) or computational adaptive optics (CAO), reduced signal collection must be physically addressed through optical hardware. Axial scanning of the focus is one approach, but comes at the cost of longer acquisition times, larger datasets, and greater image reconstruction times. Given the capabilities of CAO to compensate for general phase aberrations, we present an alternative method to address the signal collection problem without axial scanning by using intentionally aberrated optical hardware. We demonstrate the use of an astigmatic spectral domain (SD-)OCM imaging system to enable single-acquisition volumetric OCM in 3D cell culture over an extended depth range, compared to a non-aberrated SD-OCM system. The transverse resolution of the non-aberrated and astigmatic imaging systems after application of CAO were 2 um and 2.2 um, respectively. The depth-range of effective signal collection about the nominal focal plane was increased from 100 um in the non-aberrated system to over 300 um in the astigmatic system, extending the range over which useful data may be acquired in a single OCM dataset. We anticipate that this method will enable high-throughput cellular-resolution imaging of dynamic biological systems over extended volumes.

  4. Marginal Space Deep Learning: Efficient Architecture for Volumetric Image Parsing.

    Science.gov (United States)

    Ghesu, Florin C; Krubasik, Edward; Georgescu, Bogdan; Singh, Vivek; Yefeng Zheng; Hornegger, Joachim; Comaniciu, Dorin

    2016-05-01

    Robust and fast solutions for anatomical object detection and segmentation support the entire clinical workflow from diagnosis, patient stratification, therapy planning, intervention and follow-up. Current state-of-the-art techniques for parsing volumetric medical image data are typically based on machine learning methods that exploit large annotated image databases. Two main challenges need to be addressed, these are the efficiency in scanning high-dimensional parametric spaces and the need for representative image features which require significant efforts of manual engineering. We propose a pipeline for object detection and segmentation in the context of volumetric image parsing, solving a two-step learning problem: anatomical pose estimation and boundary delineation. For this task we introduce Marginal Space Deep Learning (MSDL), a novel framework exploiting both the strengths of efficient object parametrization in hierarchical marginal spaces and the automated feature design of Deep Learning (DL) network architectures. In the 3D context, the application of deep learning systems is limited by the very high complexity of the parametrization. More specifically 9 parameters are necessary to describe a restricted affine transformation in 3D, resulting in a prohibitive amount of billions of scanning hypotheses. The mechanism of marginal space learning provides excellent run-time performance by learning classifiers in clustered, high-probability regions in spaces of gradually increasing dimensionality. To further increase computational efficiency and robustness, in our system we learn sparse adaptive data sampling patterns that automatically capture the structure of the input. Given the object localization, we propose a DL-based active shape model to estimate the non-rigid object boundary. Experimental results are presented on the aortic valve in ultrasound using an extensive dataset of 2891 volumes from 869 patients, showing significant improvements of up to 45

  5. The volumetric rate of superluminous supernovae at z ˜ 1

    Science.gov (United States)

    Prajs, S.; Sullivan, M.; Smith, M.; Levan, A.; Karpenka, N. V.; Edwards, T. D. P.; Walker, C. R.; Wolf, W. M.; Balland, C.; Carlberg, R.; Howell, D. A.; Lidman, C.; Pain, R.; Pritchet, C.; Ruhlmann-Kleider, V.

    2017-01-01

    We present a measurement of the volumetric rate of superluminous supernovae (SLSNe) at z ˜ 1.0, measured using archival data from the first four years of the Canada-France-Hawaii Telescope Supernova Legacy Survey (SNLS). We develop a method for the photometric classification of SLSNe to construct our sample. Our sample includes two previously spectroscopically identified objects, and a further new candidate selected using our classification technique. We use the point-source recovery efficiencies from Perrett et al. and a Monte Carlo approach to calculate the rate based on our SLSN sample. We find that the three identified SLSNe from SNLS give a rate of 91^{+76}_{-36} SNe yr-1 Gpc-3 at a volume-weighted redshift of z = 1.13. This is equivalent to 2.2^{+1.8}_{-0.9}× 10^{-4} of the volumetric core-collapse supernova rate at the same redshift. When combined with other rate measurements from the literature, we show that the rate of SLSNe increases with redshift in a manner consistent with that of the cosmic star formation history. We also estimate the rate of ultra-long gamma-ray bursts based on the events discovered by the Swift satellite, and show that it is comparable to the rate of SLSNe, providing further evidence of a possible connection between these two classes of events. We also examine the host galaxies of the SLSNe discovered in SNLS, and find them to be consistent with the stellar-mass distribution of other published samples of SLSNe.

  6. Volumetric analysis of corticocancellous bones using CT data

    Energy Technology Data Exchange (ETDEWEB)

    Krappinger, Dietmar; Linde, Astrid von; Rosenberger, Ralf; Blauth, Michael [Medical University Innsbruck, Department of Trauma Surgery and Sports Medicine, Innsbruck (Austria); Glodny, Bernhard; Niederwanger, Christian [Medical University Innsbruck, Department of Radiology I, Innsbruck (Austria)

    2012-05-15

    To present a method for an automated volumetric analysis of corticocancellous bones such as the superior pubic ramus using CT data and to assess the reliability of this method. Computed tomography scans of a consecutive series of 250 patients were analyzed. A Hounsfield unit (HU) thresholding-based reconstruction technique (''Vessel Tracking,'' GE Healthcare) was used. A contiguous space of cancellous bone with similar HU values between the starting and end points was automatically identified as the region of interest. The identification was based upon the density gradient to the adjacent cortical bone. The starting point was defined as the middle of the parasymphyseal corticocancellous transition zone on the axial slice showing the parasymphyseal superior pubic ramus in its maximum anteroposterior width. The end point was defined as the middle of the periarticular corticocancellous transition zone on the axial slice showing the quadrilateral plate as a thin cortical plate. The following parameters were automatically obtained on both sides: length of the center line, volume of the superior pubic ramus between the starting point and end point, minimum, maximum and mean diameter perpendicular to the center line, and mean cross-sectional area perpendicular to the center line. An automated analysis without manual adjustments was successful in 207 patients (82.8%). The center line showed a significantly greater length in female patients (67.6 mm vs 65.0 mm). The volume was greater in male patients (21.8 cm{sup 3} vs 19.4 cm{sup 3}). The intersite reliability was high with a mean difference between the left and right sides of between 0.1% (cross-sectional area) and 2.3% (volume). The method presented allows for an automated volumetric analysis of a corticocancellous bone using CT data. The method is intended to provide preoperative information for the use of intramedullary devices in fracture fixation and percutaneous cement augmentation techniques

  7. An Analysis Methodology for Stochastic Characteristic of Volumetric Error in Multiaxis CNC Machine Tool

    Directory of Open Access Journals (Sweden)

    Qiang Cheng

    2013-01-01

    Full Text Available Traditional approaches about error modeling and analysis of machine tool few consider the probability characteristics of the geometric error and volumetric error systematically. However, the individual geometric error measured at different points is variational and stochastic, and therefore the resultant volumetric error is aslo stochastic and uncertain. In order to address the stochastic characteristic of the volumetric error for multiaxis machine tool, a new probability analysis mathematical model of volumetric error is proposed in this paper. According to multibody system theory, a mean value analysis model for volumetric error is established with consideration of geometric errors. The probability characteristics of geometric errors are obtained by statistical analysis to the measured sample data. Based on probability statistics and stochastic process theory, the variance analysis model of volumetric error is established in matrix, which can avoid the complex mathematics operations during the direct differential. A four-axis horizontal machining center is selected as an illustration example. The analysis results can reveal the stochastic characteristic of volumetric error and are also helpful to make full use of the best workspace to reduce the random uncertainty of the volumetric error and improve the machining accuracy.

  8. Volumetric and two-dimensional image interpretation show different cognitive processes in learners

    NARCIS (Netherlands)

    van der Gijp, Anouk; Ravesloot, C.J.; van der Schaaf, Marieke F; van der Schaaf, Irene C; Huige, Josephine C B M; Vincken, Koen L; Ten Cate, Olle Th J; van Schaik, JPJ

    2015-01-01

    RATIONALE AND OBJECTIVES: In current practice, radiologists interpret digital images, including a substantial amount of volumetric images. We hypothesized that interpretation of a stack of a volumetric data set demands different skills than interpretation of two-dimensional (2D) cross-sectional imag

  9. Enfermedad Diverticular del Colon

    Directory of Open Access Journals (Sweden)

    Gonzalo López Escobar

    1991-06-01

    Full Text Available

    Los divertículos del colon han sido reconocidos por varios observadores desde hace más de un siglo, pero en su mayor parte se trataba de casos aislados, hoy se la considera como la enfermedad del siglo XX, la de la era moderna y de los países industrializados y de avanzada tecnología (5,18,33.

    Según el diccionario de la Real Academia Española (11, divertículo, del latín, diverticulum, quiere decir desviación de un camino; y desde el punto de vista anatómico, apéndice hueco y terminado en fondo de saco. (Gráfica No. 1.

    Goligher (17 lo define como la “posada al borde del camino, probablemente un lugar, a menudo, de mala reputación”.

    Historia

    Según Hackford (18, el proceso fué descrito brevemente por Littre a comienzos del siglo XVIII; pero se le atribuye a Cruveilhier la primera descripción como proceso patológico en 1849, quien, además, mencionó: “encontramos, no rara vez, en el sigmoide, entre las bandas de fibras musculares longitudinales, una serie de pequeños tumores piriformes oscuros, que están formados por hernias de la mucosa a través de brechas en la capa muscular” (17.

    Fleischman en 1815 hizo la primera observación de la enfermedad y empleó el término divertículo (45.

    Rokitansky en 1.849, habló de una enfermedad adquirida y consideró que su causa consistía en la constipación (45.

    Virchowen 1853 describió la perisigmoiditis (45.

    En 1859 Sidney Jones informó de una fístula colo-vesical debida a diverticulitis (5,45.

    Loomis en 1870 describe una peritonitis como resultante de una diverticulitis (45.

    En 1877 Ball describió la anatomía patológica de la enfermedad y presentó dos casos de fístula colovesical debidas a diverticulitis (9. Cripps en 1.888 popularizó la colostomía de desviación como tratamiento para la fístula colovesical(18...

  10. High Volumetric Energy Density Hybrid Supercapacitors Based on Reduced Graphene Oxide Scrolls.

    Science.gov (United States)

    Rani, Janardhanan R; Thangavel, Ranjith; Oh, Se-I; Woo, Jeong Min; Chandra Das, Nayan; Kim, So-Yeon; Lee, Yun-Sung; Jang, Jae-Hyung

    2017-07-12

    The low volumetric energy density of reduced graphene oxide (rGO)-based electrodes limits its application in commercial electrochemical energy storage devices that require high-performance energy storage capacities in small volumes. The volumetric energy density of rGO-based electrode materials is very low due to their low packing density. A supercapacitor with enhanced packing density and high volumetric energy density is fabricated using doped rGO scrolls (GFNSs) as the electrode material. The restacking of rGO sheets is successfully controlled through synthesizing the doped scroll structures while increasing the packing density. The fabricated cell exhibits an ultrahigh volumetric energy density of 49.66 Wh/L with excellent cycling stability (>10 000 cycles). This unique design strategy for the electrode material has significant potential for the future supercapacitors with high volumetric energy densities.

  11. Global segmentation and curvature analysis of volumetric data sets using trivariate B-spline functions.

    Science.gov (United States)

    Soldea, Octavian; Elber, Gershon; Rivlin, Ehud

    2006-02-01

    This paper presents a method to globally segment volumetric images into regions that contain convex or concave (elliptic) iso-surfaces, planar or cylindrical (parabolic) iso-surfaces, and volumetric regions with saddle-like (hyperbolic) iso-surfaces, regardless of the value of the iso-surface level. The proposed scheme relies on a novel approach to globally compute, bound, and analyze the Gaussian and mean curvatures of an entire volumetric data set, using a trivariate B-spline volumetric representation. This scheme derives a new differential scalar field for a given volumetric scalar field, which could easily be adapted to other differential properties. Moreover, this scheme can set the basis for more precise and accurate segmentation of data sets targeting the identification of primitive parts. Since the proposed scheme employs piecewise continuous functions, it is precise and insensitive to aliasing.

  12. The duct selective volumetric receiver: potential for different selectivity strategies and stability issues

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Casals, X. [Universidad Pontificia Comillas-ICAI, Madrid (Spain). Dept. de Fluidos y Calor; Ajona, J.I. [Departamento de Energia Solar, Viessemann, Poligono Industrial San Marcos, Getafe (Spain)

    1999-07-01

    Recently much theoretical and experimental work has been conducted on volumetric receivers. However, not much attention has been paid to the possibilities of using different selectivity mechanisms to minimize radiation thermal losses, which are the main ones at high operating temperature. In this paper we present a duct volumetric receiver model and its results, which allow the evaluation of different selectivity strategies such as: conventional {epsilon}/{alpha}, geometry, frontal absorption and diffuse/specular reflection. We propose a new concept of selective volumetric receivers based on a solar-specular/infrared-diffuse radiative behaviour and evaluate its potential for efficiency improvement. In recent work on volumetric receivers based on simplified models, it has been concluded that the duct volumetric receiver is inherently unstable when working with high solar flux. We didn't find any unstable receiver behaviour even at very high solar fluxes, and conclude that a substantial potential for efficiency improvement exists if selectivity mechanisms are properly combined. (author)

  13. Enhanced volumetric visualization for real time 4D intraoperative ophthalmic swept-source OCT.

    Science.gov (United States)

    Viehland, Christian; Keller, Brenton; Carrasco-Zevallos, Oscar M; Nankivil, Derek; Shen, Liangbo; Mangalesh, Shwetha; Viet, Du Tran; Kuo, Anthony N; Toth, Cynthia A; Izatt, Joseph A

    2016-05-01

    Current-generation software for rendering volumetric OCT data sets based on ray casting results in volume visualizations with indistinct tissue features and sub-optimal depth perception. Recent developments in hand-held and microscope-integrated intrasurgical OCT designed for real-time volumetric imaging motivate development of rendering algorithms which are both visually appealing and fast enough to support real time rendering, potentially from multiple viewpoints for stereoscopic visualization. We report on an enhanced, real time, integrated volumetric rendering pipeline which incorporates high performance volumetric median and Gaussian filtering, boundary and feature enhancement, depth encoding, and lighting into a ray casting volume rendering model. We demonstrate this improved model implemented on graphics processing unit (GPU) hardware for real-time volumetric rendering of OCT data during tissue phantom and live human surgical imaging. We show that this rendering produces enhanced 3D visualizations of pathology and intraoperative maneuvers compared to standard ray casting.

  14. [Colonic gallstone ileus: a rare cause of colonic obstruction].

    Science.gov (United States)

    Mazine, Khalid; Barsotti, Pierre; Elbouhaddouti, Hicham; Taleb, Khalid Ait

    2017-01-01

    Bile ileus with migration of the gallstone into the colon through cholecystocolonic fistula is rare. The diagnosis is difficult and often late. We here report the case of a 89-year old patient with a history of sigmoid diverticular disease presenting with colonic obstruction associated with bile ileus caused by migration of a large gallstone through cholecystocolonic fistula. Abdominal CT scan allowed the diagnosis. The patient underwent surgical extraction of the gallstone with sigmoidotomy followed by sigmoidostomy with subsequent recovery of the digestive continuity. The cholecystocolonic fistula wasn't identified.

  15. Volumetric and two-dimensional image interpretation show different cognitive processes in learners.

    Science.gov (United States)

    van der Gijp, Anouk; Ravesloot, Cécile J; van der Schaaf, Marieke F; van der Schaaf, Irene C; Huige, Josephine C B M; Vincken, Koen L; Ten Cate, Olle Th J; van Schaik, Jan P J

    2015-05-01

    In current practice, radiologists interpret digital images, including a substantial amount of volumetric images. We hypothesized that interpretation of a stack of a volumetric data set demands different skills than interpretation of two-dimensional (2D) cross-sectional images. This study aimed to investigate and compare knowledge and skills used for interpretation of volumetric versus 2D images. Twenty radiology clerks were asked to think out loud while reading four or five volumetric computed tomography (CT) images in stack mode and four or five 2D CT images. Cases were presented in a digital testing program allowing stack viewing of volumetric data sets and changing views and window settings. Thoughts verbalized by the participants were registered and coded by a framework of knowledge and skills concerning three components: perception, analysis, and synthesis. The components were subdivided into 16 discrete knowledge and skill elements. A within-subject analysis was performed to compare cognitive processes during volumetric image readings versus 2D cross-sectional image readings. Most utterances contained knowledge and skills concerning perception (46%). A smaller part involved synthesis (31%) and analysis (23%). More utterances regarded perception in volumetric image interpretation than in 2D image interpretation (Median 48% vs 35%; z = -3.9; P Cognitive processes in volumetric and 2D cross-sectional image interpretation differ substantially. Volumetric image interpretation draws predominantly on perceptual processes, whereas 2D image interpretation is mainly characterized by synthesis. The results encourage the use of volumetric images for teaching and testing perceptual skills. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

  16. RARE CASE OF COLONIC METASTASIS

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-04-01

    Full Text Available Colon cancer is the second most common type of cancer in females and the third in males worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this case report, an extremely rare case of colon adenocarcinoma with metastasis to the philtrum with extensive peritoneal and bowel involvement is presented. A 44 year old male presented with a change in bowel habits, melena and weight loss . Diagnosed to have carcinoma rectum underwent Abdominoperenial resection (APR two y ears back. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Now presented with swelling over philtrum . Fine needle aspiration (FNAC was done suggestive of adenocarcinoma. This case presented for its uncommon presentation.

  17. High- and low-temperature unfolding of human high-density apolipoprotein A-2.

    Science.gov (United States)

    Gursky, O; Atkinson, D

    1996-09-01

    Human plasma apolipoprotein A-2 (apoA-2) is the second major protein of the high-density lipoproteins that mediate the transport and metabolism of cholesterol. Using CD spectroscopy and differential scanning calorimetry, we demonstrate that the structure of lipid-free apoA-2 in neutral low-salt solutions is most stable at approximately 25 degrees C and unfolds reversibly both upon heating and cooling from 25 degrees C. High-temperature unfolding of apoA-2, monitored by far-UV CD, extends from 25-85 degrees C with midpoint Th = 56 +/- 2 degrees C and vant Hoff's enthalpy delta H(Th) = 17 +/- 2 kcal/mol that is substantially lower than the expected enthalpy of melting of the alpha-helical structure. This suggests low-cooperativity apoA-2 unfolding. The apparent free energy of apoA-2 stabilization inferred from the CD analysis of the thermal unfolding, delta G(app)(25 degrees) = 0.82 +/- 0.15 kcal/mol, agrees with the value determined from chemical denaturation. Enhanced low-temperature stability of apoA-2 observed upon increase in Na2HPO4 concentration from 0.3 mM to 50 mM or addition of 10% glycerol may be linked to reduced water activity. The close proximity of the heat and cold unfolding transitions, that is consistent with low delta G(app)(25 degrees), indicates that lipid-free apoA-2 has a substantial hydrophobic core but is only marginally stable under near-physiological solvent conditions. This suggests that in vivo apoA-2 transfer is unlikely to proceed via the lipid-free state. Low delta H(Th) and low apparent delta Cp approximately 0.52 kcal/mol.K inferred from the far-UV CD analysis of apoA-2 unfolding, and absence of tertiary packing interactions involving Tyr groups suggested by near-UV CD, are consistent with a molten globular-like state of lipid-free apoA-2.

  18. Medullary carcinoma of the colon

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Grauslund, Morten; Glenthøj, Anders

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic...... differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether...

  19. Neurological manifestation of colonic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Uzair Chaudhary

    2012-04-01

    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  20. Colon,rectum and anus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008303 MicroRNA expression profiling in hydrox-ycamptothecin-resistant human colon cancer cell line by microarray.TONG Jinlu(童锦禄), et al. Dept Gastroenterol, Renji Hosp, Med Sch, Shanghai Jiaotong Univ, Shanghai Instit Dig Dis, Shanghai 200001. Chin J Dig 2008;28(4):246-249.Objective To explore the role of a novel regulatory molecule-microRNA in the hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPTin order to provide a new reversal target for multidrug resistance.

  1. UNFOLDING OF MULTIPARAMETER EQUIVARIANT BIFURCATION PROBLEMS WITH TWO GROUPS OF STATE VARIABLES UNDER LEFT-RIGHT EQUIVALENT GROUP

    Institute of Scientific and Technical Information of China (English)

    GUO Rui-zhi; LI Yang-cheng

    2005-01-01

    Based on the left-right equivalent relation of smooth map-germs in singularity theory, the unfoldings of multiparameter equivariant bifurcation problems with respect to leftright equivalence are discussed. The state variables of such an equivariant bifurcation problem were divided into two groups, in which the first can vary independently, while the others depend on the first in the varying process. By applying related methods and techniques in the unfolding theory of smooth map-germs, the necessary and sufficient condition for an unfolding of a multiparameter equivariant bifurcation problem with two groups of state variables to be versal is obtained.

  2. Volumetric Spectroscopic Imaging of Glioblastoma Multiforme Radiation Treatment Volumes

    Energy Technology Data Exchange (ETDEWEB)

    Parra, N. Andres [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Maudsley, Andrew A. [Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida (United States); Gupta, Rakesh K. [Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana (India); Ishkanian, Fazilat; Huang, Kris [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Walker, Gail R. [Biostatistics and Bioinformatics Core Resource, Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, Florida (United States); Padgett, Kyle [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida (United States); Roy, Bhaswati [Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana (India); Panoff, Joseph; Markoe, Arnold [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Stoyanova, Radka, E-mail: RStoyanova@med.miami.edu [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States)

    2014-10-01

    Purpose: Magnetic resonance (MR) imaging and computed tomography (CT) are used almost exclusively in radiation therapy planning of glioblastoma multiforme (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI) can identify biochemical patterns associated with normal brain and tumor, predominantly by observation of choline (Cho) and N-acetylaspartate (NAA) distributions. In this study, volumetric 3-dimensional MRSI was used to map these compounds over a wide region of the brain and to evaluate metabolite-defined treatment targets (metabolic tumor volumes [MTV]). Methods and Materials: Volumetric MRSI with effective voxel size of ∼1.0 mL and standard clinical MR images were obtained from 19 GBM patients. Gross tumor volumes and edema were manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were defined (CTV{sub 46} and CTV{sub 60}, respectively). MTV{sub Cho} and MTV{sub NAA} were constructed based on volumes with high Cho and low NAA relative to values estimated from normal-appearing tissue. Results: The MRSI coverage of the brain was between 70% and 76%. The MTV{sub NAA} were almost entirely contained within the edema, and the correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast, a considerable fraction of MTV{sub Cho} was outside of the edema (median, 33%) and for some patients it was also outside of the CTV{sub 46} and CTV{sub 60}. These untreated volumes were greater than 10% for 7 patients (37%) in the study, and on average more than one-third (34.3%) of the MTV{sub Cho} for these patients were outside of CTV{sub 60}. Conclusions: This study demonstrates the potential usefulness of whole-brain MRSI for radiation therapy planning of GBM and revealed that areas of metabolically active tumor are not covered by standard RT volumes. The described integration of MTV into the RT system will pave the way to future clinical trials investigating outcomes in patients treated based on

  3. Volumetric capnography for the evaluation of chronic airways diseases

    Directory of Open Access Journals (Sweden)

    Veronez L

    2014-09-01

    Full Text Available Liliani de Fátima Veronez,1 Monica Corso Pereira,2 Silvia Maria Doria da Silva,2 Luisa Affi Barcaui,2 Eduardo Mello De Capitani,2 Marcos Mello Moreira,2 Ilma Aparecida Paschoalz2 1Department of Physical Therapy, University of Votuporanga (Educational Foundation of Votuporanga, Votuporanga, 2Department of Internal Medicine, School of Medical Sciences, State University of Campinas (UNICAMP, Campinas, Sao Paulo, BrazilBackground: Obstructive lung diseases of different etiologies present with progressive peripheral airway involvement. The peripheral airways, known as the silent lung zone, are not adequately evaluated with conventional function tests. The principle of gas washout has been used to detect pulmonary ventilation inhomogeneity and to estimate the location of the underlying disease process. Volumetric capnography (VC analyzes the pattern of CO2 elimination as a function of expired volume.Objective: To measure normalized phase 3 slopes with VC in patients with non-cystic fibrosis bronchiectasis (NCB and in bronchitic patients with chronic obstructive pulmonary disease (COPD in order to compare the slopes obtained for the groups.Methods: NCB and severe COPD were enrolled sequentially from an outpatient clinic (Hospital of the State University of Campinas. A control group was established for the NCB group, paired by sex and age. All subjects performed spirometry, VC, and the 6-Minute Walk Test (6MWT. Two comparisons were made: NCB group versus its control group, and NCB group versus COPD group. The project was approved by the ethical committee of the institution. Statistical tests used were Wilcoxon or Student’s t-test; P<0.05 was considered to be a statistically significant difference.Results: Concerning the NCB group (N=20 versus the control group (N=20, significant differences were found in body mass index and in several functional variables (spirometric, VC, 6MWT with worse results observed in the NCB group. In the comparison between

  4. Widespread Volumetric Brain Changes following Tooth Loss in Female Mice

    Science.gov (United States)

    Avivi-Arber, Limor; Seltzer, Ze'ev; Friedel, Miriam; Lerch, Jason P.; Moayedi, Massieh; Davis, Karen D.; Sessle, Barry J.

    2017-01-01

    Tooth loss is associated with altered sensory, motor, cognitive and emotional functions. These changes vary highly in the population and are accompanied by structural and functional changes in brain regions mediating these functions. It is unclear to what extent this variability in behavior and function is caused by genetic and/or environmental determinants and which brain regions undergo structural plasticity that mediates these changes. Thus, the overall goal of our research program is to identify genetic variants that control structural and functional plasticity following tooth loss. As a step toward this goal, here our aim was to determine whether structural magnetic resonance imaging (sMRI) is sensitive to detect quantifiable volumetric differences in the brains of mice of different genetic background receiving tooth extraction or sham operation. We used 67 adult female mice of 7 strains, comprising the A/J (A) and C57BL/6J (B) strains and a randomly selected sample of 5 of the 23 AXB-BXA strains (AXB1, AXB4, AXB24, BXA14, BXA24) that were produced from the A and B parental mice by recombinations and inbreeding. This panel of 25 inbred strains of genetically diverse inbred strains of mice is used for mapping chromosomal intervals throughout the genome that harbor candidate genes controlling the phenotypic variance of any trait under study. Under general anesthesia, 39 mice received extraction of 3 right maxillary molar teeth and 28 mice received sham operation. On post-extraction day 21, post-mortem whole-brain high-resolution sMRI was used to quantify the volume of 160 brain regions. Compared to sham operation, tooth extraction was associated with a significantly reduced regional and voxel-wise volumes of cortical brain regions involved in processing somatosensory, motor, cognitive and emotional functions, and increased volumes in subcortical sensorimotor and temporal limbic forebrain regions including the amygdala. Additionally, comparison of the 10 BXA14

  5. Hepatosplenic volumetric assessment at MDCT for staging liver fibrosis.

    Science.gov (United States)

    Pickhardt, Perry J; Malecki, Kyle; Hunt, Oliver F; Beaumont, Claire; Kloke, John; Ziemlewicz, Timothy J; Lubner, Meghan G

    2017-07-01

    To investigate hepatosplenic volumetry at MDCT for non-invasive prediction of hepatic fibrosis. Hepatosplenic volume analysis in 624 patients (mean age, 48.8 years; 311 M/313 F) at MDCT was performed using dedicated software and compared against pathological fibrosis stage (F0 = 374; F1 = 48; F2 = 40; F3 = 65; F4 = 97). The liver segmental volume ratio (LSVR) was defined by Couinaud segments I-III over segments IV-VIII. All pre-cirrhotic fibrosis stages (METAVIR F1-F3) were based on liver biopsy within 1 year of MDCT. LSVR and total splenic volumes increased with stage of fibrosis, with mean(±SD) values of: F0: 0.26 ± 0.06 and 215.1 ± 88.5 mm(3); F1: 0.25 ± 0.08 and 294.8 ± 153.4 mm(3); F2: 0.331 ± 0.12 and 291.6 ± 197.1 mm(3); F3: 0.39 ± 0.15 and 509.6 ± 402.6 mm(3); F4: 0.56 ± 0.30 and 790.7 ± 450.3 mm(3), respectively. Total hepatic volumes showed poor discrimination (F0: 1674 ± 320 mm(3); F4: 1631 ± 691 mm(3)). For discriminating advanced fibrosis (≥F3), the ROC AUC values for LSVR, total liver volume, splenic volume and LSVR/spleen combined were 0.863, 0.506, 0.890 and 0.947, respectively. Relative changes in segmental liver volumes and total splenic volume allow for non-invasive staging of hepatic fibrosis, whereas total liver volume is a poor predictor. Unlike liver biopsy or elastography, these CT volumetric biomarkers can be obtained retrospectively on routine scans obtained for other indications. • Regional changes in hepatic volume (LSVR) correlate well with degree of fibrosis. • Total liver volume is a very poor predictor of underlying fibrosis. • Total splenic volume is associated with the degree of hepatic fibrosis. • Hepatosplenic volume assessment is comparable to elastography for staging fibrosis. • Unlike elastography, volumetric analysis can be performed retrospectively.

  6. Volumetric and MGMT parameters in glioblastoma patients: Survival analysis

    Directory of Open Access Journals (Sweden)

    Iliadis Georgios

    2012-01-01

    Full Text Available Abstract Background In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O6-methylguanine methyltransferase related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. Methods We prospectively analyzed 65 patients suffering from glioblastoma (GBM who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy. The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA, for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. Results In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS (p = 0.023 and for preoperative necrosis on progression-free survival (PFS (p = 0.030. Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5% evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei was inversely associated with pre-operative tumor necrosis (p = 0.021. Conclusions Our findings implicate that volumetric parameters may have a significant role in

  7. Unfolded Drawings and Views for Irregular Spiral Surface Given Boundary Equations Based on CAD%Unfolded Drawings and Views for Irregular Spiral Surface Given Boundary Equations Based on CAD

    Institute of Scientific and Technical Information of China (English)

    SONG Yan; ZHANG Meng; SONG Juan

    2011-01-01

    Taking spiral chute as example, a method of unfolded drawings and views about irregular spiral surface is introduced. The surface is undevelopable and too complicated to get its views or to draw unfolded drawings by manual method. In this article, a series of the boundary equations of the spiral chute are derived by the movement rule of coal flow, and the solid and views of the spiral chute are generated based on redevelopment of SolidWorks. Unfolded drawing is drawn applying triangular development principle. The views and unfolded drawings not only are produced automatically, precisely and parameterized, but also involve more technological information. So it has an important significance on the irregular spiral surface's developments and processing.

  8. 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.

  9. 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.

  10. 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)

  11. Recent advances in understanding the control of secretory proteins by the unfolded protein response in plants.

    Science.gov (United States)

    Hayashi, Shimpei; Wakasa, Yuhya; Takaiwa, Fumio

    2013-04-29

    The membrane transport system is built on the proper functioning of the endoplasmic reticulum (ER). The accumulation of unfolded proteins in the ER lumen (ER stress) disrupts ER homeostasis and disturbs the transport system. In response to ER stress, eukaryotic cells activate intracellular signaling (named the unfolded protein response, UPR), which contributes to the quality control of secretory proteins. On the other hand, the deleterious effects of UPR on plant health and growth characteristics have frequently been overlooked, due to limited information on this mechanism. However, recent studies have shed light on the molecular mechanism of plant UPR, and a number of its unique characteristics have been elucidated. This study briefly reviews the progress of understanding what is happening in plants under ER stress conditions.

  12. Probing the role of hydration in the unfolding transitions of carbonmonoxy myoglobin and apomyoglobin.

    Science.gov (United States)

    Guo, Lin; Park, Jaeheung; Lee, Taegon; Chowdhury, Pramit; Lim, Manho; Gai, Feng

    2009-04-30

    We show that the equilibrium unfolding transition of horse carbonmonoxy myoglobin monitored by the stretching vibration of the CO ligand, a local environmental probe, is very sharp and, thus, quite different from those measured by global conformational reporters. In addition, the denatured protein exhibits an A(0)-like CO band. We hypothesize that this sharp transition reports penetration of water into the heme pocket of the protein. Parallel experiments on horse apomyoglobin, wherein an environment-sensitive fluorescent probe, nile red, was used, also reveals a similar putative hydration event. Given the importance of dehydration in protein folding and also the recent debate over the interpretation of probe-dependent unfolding transitions, these results have strong implications on the mechanism of protein folding.

  13. A novel neutron energy spectrum unfolding code using particle swarm optimization

    Science.gov (United States)

    Shahabinejad, H.; Sohrabpour, M.

    2017-07-01

    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.

  14. Shape-constrained uncertainty quantification in unfolding steeply falling elementary particle spectra

    CERN Document Server

    Kuusela, Mikael

    2015-01-01

    The high energy physics unfolding problem is an important statistical inverse problem arising in data analysis at the Large Hadron Collider at CERN. The problem arises in making nonparametric inferences about a particle spectrum from measurements smeared by the finite resolution of the particle detectors. Existing unfolding methodology has major practical limitations stemming from ad hoc discretization and regularization of the problem. As a result, confidence intervals derived using the current methods can have significantly lower coverage than expected. In this work, we regularize the problem by imposing physically justified shape constraints. We quantify the uncertainty by constructing a nonparametric confidence set for the true spectrum consisting of all spectra that satisfy the shape constraints and that predict observations within an appropriately calibrated level of fit to the data. Projecting that set produces simultaneous confidence intervals for all functionals of the spectrum, including averages wi...

  15. Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae.

    Science.gov (United States)

    Payne, Tom; Hanfrey, Colin; Bishop, Amy L; Michael, Anthony J; Avery, Simon V; Archer, David B

    2008-02-20

    Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR). Genome-wide analysis of translational regulation in response to the UPR-inducing agent dithiothreitol in Saccharomyces cerevisiae is reported. Microarray analysis, confirmed using qRT-PCR, identified transcript-specific translational regulation. Transcripts with functions in ribosomal biogenesis and assembly were translationally repressed. In contrast, mRNAs from known UPR genes, encoding the UPR transcription factor Hac1p, the ER-oxidoreductase Ero1p and the ER-associated protein degradation (ERAD) protein Der1p, were enriched in polysomal fractions, indicating translational up-regulation. Splicing of HAC1 mRNA is shown to be required for efficient ribosomal loading.

  16. Systematic detection of hidden complexities in the unfolding mechanism of a cytosine-rich DNA strand

    Science.gov (United States)

    Smiatek, Jens; Janssen-Müller, Daniel; Friedrich, Rudolf; Heuer, Andreas

    2014-01-01

    We investigate the unfolding pathway of a cytosine-rich DNA structure via molecular dynamics simulations. By the study of the essential dynamics, we are able to identify a hidden complexity in the description of the dynamics in terms of the first two eigenvectors which are used as collective variables. This complexity can be mainly explained by non-Gaussian fluctuations due to contributions arising from the disregarded set of eigenvectors. We introduce the local non-Gaussian parameter as a tool for the detection of hidden complexities. The usage of this parameter allows a fast and reliable investigation for the determination of the important minimal number of eigenvectors which is needed for a sufficient description of molecular unfolding motion.

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

    Science.gov (United States)

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

    2014-03-06

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

  18. 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.

  19. Homoclinic Bifurcations in Symmetric Unfoldings of a Singularity with Three-fold Zero Eigenvalue

    Institute of Scientific and Technical Information of China (English)

    Jian Hua SUN

    2005-01-01

    In this paper we study the singularity at the origin with three-fold zero eigenvalue for symmetric vector fields with nilpotent linear part and 3-jet C∞-equivalent to y(θ)/(θ)x+z(θ)/(θ)y+ax2y(θ)/(θ)zwith a ≠ 0. We first obtain several subfamilies of the symmetric versal unfoldings of this singularity by using the normal form and blow-up methods under some conditions, and derive the local and global bifurcation behavior, then prove analytically the existence of the Sil'nikov homoclinic bifurcation for some subfamilies of the symmetric versal unfoldings of this singularity, by using the generalized Mel'nikov methods of a homoclinic orbit to a hyperbolic or non-hyperbolic equilibrium in a highdimensional space.

  20. Dithiothreitol decreases the thermal stability and unfolding cooperativity of ribulose-1, 5-bisphosphate carboxylase/oxygenase

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Plant rubisco consists of eight large subunits (55 kD) encoded by chloroplast gene and eight small subunits (15 kD) encoded by nuclear gene. There are abundant cysteine residues that do not form disulfide bonds in native rubisco. Differential scanning calorimetry has been used to study some plant rubisco and suggested an irreversible two-state denaturation due to the high cooperativity in subunits. By comparing the data from circular dichroism, fluorescence, differential scanning calorimetry, SDS electrophoresis, and activity assays in the absence or presence of DTT, we suggest that the formation of disulfide bonds in subunits during the early thermal unfolding may increase the thermal stability and the thermal unfolding cooperativity of rubisco.

  1. Unfolding case studies in pre-registration nursing education: lessons learned.

    Science.gov (United States)

    West, Caryn; Usher, Kim; Delaney, Lori J

    2012-07-01

    Nursing education is undergoing radical change worldwide. There is criticism surrounding the content of education and the delivery. As a result, traditional methods of teaching and learning have been replaced by strategies that place greater emphasis on active learner interaction, critical thinking, and decision-making. Assisting pre-registration nurses to become competent and confident in clinical practice requires immersion in practice with sufficient support and coaching based on real life scenarios. Simulation via an unfolding case study approach is one way to provide interactive learning experiences where students acquire new skills that advance their clinical judgment with the aim of becoming safe, competent practitioners. Lessons learned from implementing an unfolding case study are discussed in this paper. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Statistical unfolding of elementary particle spectra: Empirical Bayes estimation and bias-corrected uncertainty quantification

    CERN Document Server

    Kuusela, Mikael

    2015-01-01

    We consider the high energy physics unfolding problem where the goal is to estimate the spectrum of elementary particles given observations distorted by the limited resolution of a particle detector. This important statistical inverse problem arising in data analysis at the Large Hadron Collider at CERN consists in estimating the intensity function of an indirectly observed Poisson point process. Unfolding typically proceeds in two steps: one first produces a regularized point estimate of the unknown intensity and then uses the variability of this estimator to form frequentist confidence intervals that quantify the uncertainty of the solution. In this paper, we propose forming the point estimate using empirical Bayes estimation which enables a data-driven choice of the regularization strength through marginal maximum likelihood estimation. Observing that neither Bayesian credible intervals nor standard bootstrap confidence intervals succeed in achieving good frequentist coverage in this problem due to the inh...

  4. An algorithm for automatic unfolding of one-dimensional data distributions

    Energy Technology Data Exchange (ETDEWEB)

    Dembinski, Hans P., E-mail: hans.dembinski@kit.edu; Roth, Markus

    2013-11-21

    We discuss a non-parametric algorithm to unfold detector effects from one-dimensional data distributions. Unfolding is performed by fitting a flexible spline model to the data using an unbinned maximum-likelihood method while employing a smooth regularisation that maximises the relative entropy of the solution with respect to an a priori guess. A regularisation weight is picked automatically such that it minimises the mean integrated squared error of the fit. The algorithm scales to large data sets by employing an adaptive binning scheme in regions of high density. An estimate of the uncertainty of the solution is provided and shown to be accurate by studying the frequentist properties of the algorithm in Monte-Carlo simulations. The simulations show that the regularisation bias decreases as the sample size increases.

  5. An algorithm for automatic unfolding of one-dimensional data distributions

    Science.gov (United States)

    Dembinski, Hans P.; Roth, Markus

    2013-11-01

    We discuss a non-parametric algorithm to unfold detector effects from one-dimensional data distributions. Unfolding is performed by fitting a flexible spline model to the data using an unbinned maximum-likelihood method while employing a smooth regularisation that maximises the relative entropy of the solution with respect to an a priori guess. A regularisation weight is picked automatically such that it minimises the mean integrated squared error of the fit. The algorithm scales to large data sets by employing an adaptive binning scheme in regions of high density. An estimate of the uncertainty of the solution is provided and shown to be accurate by studying the frequentist properties of the algorithm in Monte-Carlo simulations. The simulations show that the regularisation bias decreases as the sample size increases.

  6. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... factors, screening tests, and treatments. There are also personal stories from colon cancer survivors. Colon Cancer Prevention & ... Cancer: Don't Ignore Your Symptoms Play Play Personal Story: Lex Gilbert Play Play Personal Story: Karen ...

  7. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... Contrast Barium Enema(DCBE) Play Play Colon Cancer Treatments Play Play Colon Cancer Surgery: What You Need ... Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

  8. Treatment Options (by Stage) for Colon Cancer

    Science.gov (United States)

    ... Colorectal Cancer Colorectal Cancer Screening Research Colon Cancer Treatment (PDQ®)–Patient Version General Information About Colon Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  9. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... FOBT/FIT Play Play Colon Cancer Screening Tests: Flexible Sigmoidoscopy Play Play Colon Cancer Screening Tests: Double ... Select A Hope Lodge Close Please share your thoughts about your cancer.org website experience. If you ...

  10. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A Resource ... Cancer About Colorectal Cancer Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment ...

  11. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... Contrast Barium Enema(DCBE) Play Play Colon Cancer Treatments Play Play Colon Cancer Surgery: What You Need ... Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

  12. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A Resource ... Cancer About Colorectal Cancer Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment ...

  13. Breast and Colon Cancer Family Registries

    Science.gov (United States)

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  14. Vitamin D and colon cancer

    Institute of Scientific and Technical Information of China (English)

    Lidija; Klampfer

    2014-01-01

    Calcitriol, 1α, 25-dihydroxyvitamin D3(1,25(OH)2D3), the most active form of vitamin D, is a pleotropic hormone with a wide range of biological activities. Due to its ability to regulate calcium and phosphate metabolism, 1,25D3 plays a major role in bone health. In addition, 1,25D3 binds to the vitamin D receptor and thereby regulates the expression of a number of genes which control growth, differentiation and survival of cancer cells. In agreement, the levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models. Vitamin D3 has been estimated to lower the incidence of colorectal cancer by 50%, which is consistent with the inverse correlation between dietary vitamin D3 intake or sunlight exposure and human colorectal cancer. Several studies confirmed that increasing vitamin D3 lowers colon cancer incidence, reduces polyp recurrence, and that sufficient levels of vitamin D3 are associated with better overall survival of colon cancer patients. Vitamin D regulates the homeostasis of intestinal epithelium by modulating the oncogenic Wnt signaling pathway and by inhibiting tumor-promoting inflammation. Both activities contribute to the ability of 1,25D3 to prevent the development and progression of colon cancer.

  15. Colon,rectum and anus

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010344 Serotonin transporter expression in rats with chronic visceral hypersensitivity.SUN Chengcheng(孙程程),et al. Dept Gastroenterol,Peking Univ 1st Hosp,Beijing 100034.World Chin J Digestol 2010;18(14):1428-33. Objective To determine whether colonic serotonin transporter (SERT) expression is altered in rats with visceral hypersensitivity and to explore the

  16. Sustainable Intrapreneurship - The GSI Concept and Strategy - Unfolding Competitive Advantage via Fair Entrepreneurship

    OpenAIRE

    Anton, Roman

    2014-01-01

    Entrepreneurship and intrapreneurship are among the most important prerequisites and concepts of modern economics and free market theory. Intrapreneurship is defined here in its broadest definition, as grades of entrepreneurship within a given system or entity, such as a company, organization, sector, cluster, national or even global economy. Hereby, intrapreneuring is more than only providing some opportunity to some employees. The wider definition rather unfolds intrapreneuring into a new u...

  17. Folding and unfolding manual wheelchairs: an ergonomic evaluation of health-care workers.

    Science.gov (United States)

    White, Heather A; Lee Kirby, R

    2003-11-01

    The objective of this study was to test the hypotheses (i) that health-care workers vary greatly in the methods used to fold and unfold selected manual wheelchairs, and (ii) that many of the methods used include bent and twisted back postures that are known to be associated with a high risk of injury. We studied 20 health-care workers in a rehabilitation center. Subjects folded and unfolded two wheelchairs of cross-brace design, one with and one without a sling seat. As outcome measures, we used a questionnaire, time taken, visual analog scales of perceived exertion and back strain, folded width, videotape and Ovako Working Posture Analysis System (OWAS) back scores (1-4). Subjects used up to 14 different combinations of approach, hand placement and back posture to accomplish the tasks. The mean OWAS scores were in the 2.4-3.1 range and 49 (42%) of the 118 scores recorded were class 4 (back simultaneously "bent and twisted", considered to be associated with the highest risk of injury). We also observed methods that appeared to be safe and effective. Age, gender, profession, experience and seat condition did not generally influence the outcome measures. We conclude that health-care workers use a variety of methods to fold and unfold wheelchairs, many of which include bent and twisted back postures that may carry a risk of injury. Further study is needed to confirm this risk, to identify more ergonomically sound wheelchair designs and to develop better methods of carrying out the common and important task of folding and unfolding wheelchairs.

  18. Probing the Role of Hydration in the Unfolding Transitions of Carbonmonoxy Myoglobin and Apomyoglobin

    OpenAIRE

    GUO, LIN; Park, Jaeheung; Lee, Taegon; Chowdhury, Pramit; Lim, Manho; Gai, Feng

    2009-01-01

    We show that the equilibrium unfolding transition of horse carbonmonoxy myoglobin monitored by the stretching vibration of the CO ligand, a local environmental probe, is very sharp and, thus, quite different from those measured by global conformational reporters. In addition, the denatured protein exhibits an A0-like CO band. We hypothesize that this sharp transition reports penetration of water into the heme pocket of the protein. Parallel experiments on horse apomyoglobin, wherein an enviro...

  19. Adhesion, unfolding forces, and molecular elasticity of fibronectin coatings: An atomic force microscopy study.

    Science.gov (United States)

    Sumarokova, Maria; Iturri, Jagoba; Toca-Herrera, José L

    2017-10-07

    Fibronectin is an extracellular matrix protein that is involved in cell adhesion, growth, migration, differentiation, and wound healing. Fibronectin coatings are currently used in many laboratories for biomedical and biotechnology purposes. In this study we have investigated the adhesion and mechanical properties of fibronectin coatings. The coatings were also used to study the role of the residence time and the influence of the loading rate in nonspecific interactions. The results showed that the adhesion force between silica and fibronectin increased with loading rate delivering similar values for residence times of 1 and 2 s. Further analysis indicated that the distance to the transition state was about 0.5 nm. Moreover, the adhesion force did not vary with the loading rate for contact time of 0 s. The unfolding of fibronectin domains also depended of the Dwell time (no unfolding events were observed for zero residence time). Applied loads of 2 nN were able to stretch the fibronectin layer up to 200 nm and to unfold the three fibronectin domains, which were similar for a Dwell time of 1 and 2 s. However, the unfolding length increased with loading rate: below 2.5 µm s(-1) the obtained lengths matched the value of FN I (13.5 nm), while for higher speeds the measured values corresponded to the lengths of FN II (18 nm) and FN III (27 nm). This investigation has answered and opened new questions about the mechanical stability and function of fibronectin coatings. The results have also raised theoretical questions about the difference between specific and nonspecific interactions to be addressed in future work. © 2017 Wiley Periodicals, Inc.

  20. Quantitative evaluation of myoglobin unfolding in the presence of guanidinium hydrochloride and ionic liquids in solution.

    Science.gov (United States)

    Fiebig, Olivia C; Mancini, Emily; Caputo, Gregory; Vaden, Timothy D

    2014-01-16

    The use of ionic liquids in biochemical and biophysical applications has increased dramatically in recent years due to their interesting properties. We report results of a thermodynamic characterization of the chaotrope-induced denaturation of equine myoglobin in two different ionic liquid aqueous environments using a combined absorption/fluorescence spectroscopic approach. Denaturation by guanidinium hydrochloride was monitored by loss of heme absorptivity and limited unfolding structural information was obtained from Förster resonance energy transfer experiments. Results show that myoglobin unfolding is generally unchanged in the presence of ethylmethylimidazolium acetate (EMIAc) in aqueous solution up to 150 mM concentration but is facilitated by butylmethylimidazolium boron tetrafluoride (BMIBF4) in solution. The presence of 150 mM BMIBF4 alone does not induce unfolding but destabilizes the structure as observed by a decrease in threshold denaturant concentration for unfolding and an 80% decrease in the magnitude of ΔGunfolding from 44 kJ/mol in the absence of BMIBF4 to 8 kJ/mol in the presence of 150 mM BMIBF4. Thus, the BMIBF4 significantly destabilizes the myoglobin structure while the EMIAc does not, likely due to differences in anion interaction capabilities. This is confirmed with control studies using NaAc and LiBF4 solutions. EMIAc may be chosen as cosolvent additive with minimal effects on protein structure while BMIBF4 may be used as a supplement in protein folding experiments, potentially allowing access to proteins which have been traditionally difficult to denature as well as designing ionic liquids to match protein characteristics.

  1. Thermal stabilization of dihydrofolate reductase using monte carlo unfolding simulations and its functional consequences.

    Directory of Open Access Journals (Sweden)

    Jian Tian

    2015-04-01

    Full Text Available Design of proteins with desired thermal properties is important for scientific and biotechnological applications. Here we developed a theoretical approach to predict the effect of mutations on protein stability from non-equilibrium unfolding simulations. We establish a relative measure based on apparent simulated melting temperatures that is independent of simulation length and, under certain assumptions, proportional to equilibrium stability, and we justify this theoretical development with extensive simulations and experimental data. Using our new method based on all-atom Monte-Carlo unfolding simulations, we carried out a saturating mutagenesis of Dihydrofolate Reductase (DHFR, a key target of antibiotics and chemotherapeutic drugs. The method predicted more than 500 stabilizing mutations, several of which were selected for detailed computational and experimental analysis. We find a highly significant correlation of r=0.65-0.68 between predicted and experimentally determined melting temperatures and unfolding denaturant concentrations for WT DHFR and 42 mutants. The correlation between energy of the native state and experimental denaturation temperature was much weaker, indicating the important role of entropy in protein stability. The most stabilizing point mutation was D27F, which is located in the active site of the protein, rendering it inactive. However for the rest of mutations outside of the active site we observed a weak yet statistically significant positive correlation between thermal stability and catalytic activity indicating the lack of a stability-activity tradeoff for DHFR. By combining stabilizing mutations predicted by our method, we created a highly stable catalytically active E. coli DHFR mutant with measured denaturation temperature 7.2°C higher than WT. Prediction results for DHFR and several other proteins indicate that computational approaches based on unfolding simulations are useful as a general technique to discover

  2. Domain compatibility in Ire1 kinase is critical for the Unfolded Protein Response

    OpenAIRE

    Poothong, Juthakorn; Sopha, Pattarawut; Kaufman, Randal J.; Tirasophon, Witoon

    2010-01-01

    The unfolded phrotein response is a mechanism to cope with endoplasmic reticulum stress. In Saccharomyces cerevisiae, Ire1 senses the stress and mediates a signaling cascade to upregulate responsive genes through an unusual HAC1 mRNA splicing. The splicing requires interconnected activity (kinase and endoribonuclease) of Ire1 to cleave HAC1 mRNA at the non-canonical splice sites before translation into Hac1 transcription factor. Analysis of the truncated kinase domain from Ire1 homologs revea...

  3. 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)

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

    Science.gov (United States)

    Tischer, Alexander; Auton, Matthew

    2013-09-01

    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 ΔH0 and ΔCP0 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.

  5. Protein folding, unfolding and aggregation. Pressure induced intermediate states on the refolding pathway of horseradish peroxidase

    Science.gov (United States)

    Smeller, László; Fidy, Judit; Heremans, Karel

    2004-04-01

    We studied the refolding and aggregation of pressure unfolded proteins. Horseradish peroxidase was found to be very stable and no partially folded intermediates were populated during the refolding. However, the removal of the haem group or the Ca2+ ions or reduction of the disulfide bridge destabilized the protein, resulting in a significant amount of aggregation prone intermediate conformation. Substitution of the haem for fluorescent porphyrin however did not influence the refolding of the protein.

  6. Single-molecule force spectroscopy reveals the individual mechanical unfolding pathways of a surface layer protein.

    Science.gov (United States)

    Horejs, Christine; Ristl, Robin; Tscheliessnig, Rupert; Sleytr, Uwe B; Pum, Dietmar

    2011-08-05

    Surface layers (S-layers) represent an almost universal feature of archaeal cell envelopes and are probably the most abundant bacterial cell proteins. S-layers are monomolecular crystalline structures of single protein or glycoprotein monomers that completely cover the cell surface during all stages of the cell growth cycle, thereby performing their intrinsic function under a constant intra- and intermolecular mechanical stress. In gram-positive bacteria, the individual S-layer proteins are anchored by a specific binding mechanism to polysaccharides (secondary cell wall polymers) that are linked to the underlying peptidoglycan layer. In this work, atomic force microscopy-based single-molecule force spectroscopy and a polyprotein approach are used to study the individual mechanical unfolding pathways of an S-layer protein. We uncover complex unfolding pathways involving the consecutive unfolding of structural intermediates, where a mechanical stability of 87 pN is revealed. Different initial extensibilities allow the hypothesis that S-layer proteins adapt highly stable, mechanically resilient conformations that are not extensible under the presence of a pulling force. Interestingly, a change of the unfolding pathway is observed when individual S-layer proteins interact with secondary cell wall polymers, which is a direct signature of a conformational change induced by the ligand. Moreover, the mechanical stability increases up to 110 pN. This work demonstrates that single-molecule force spectroscopy offers a powerful tool to detect subtle changes in the structure of an individual protein upon binding of a ligand and constitutes the first conformational study of surface layer proteins at the single-molecule level.

  7. Colon Capsule Endoscopy: Review and Perspectives

    Directory of Open Access Journals (Sweden)

    David Friedel

    2016-01-01

    Full Text Available Colon capsule endoscopy utilizing PillCam COLON 2 capsule allows for visualization potentially of the entire colon and is currently approved for patients who cannot withstand the rigors of traditional optical colonoscopy (OC and associated sedation as well as those that had an OC that was incomplete for technical reasons other than a poor preparation. We will then describe the prior experience and current status of colon capsule endoscopy.

  8. Colonic urticaria pattern due to early ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, H.M.; Goldberg, H.I.; Axel, L.

    1981-05-15

    The unusual radiographic pattern of bleb-like mounds on the surface of the colon mucosa, previously described as colonic urticaria, was seen in 3 patients in whom no allergic state was present. This urticaria-like pattern was due to colonic distention in all 3, and represented only submucosal edema on the gross and microscopic specimens. We hypothesize that this pattern is due to early changes of ischemia caused by colon distention.

  9. Stability of Escherichia coli phosphoenolpyruvate carboxykinase against urea-induced unfolding and ligand effects.

    Science.gov (United States)

    Encinas, M V; Evangelio, J A; Andreu, J M; Goldie, H; Cardemil, E

    1998-07-15

    The urea-induced unfolding at pH 7.5 of Escherichia coli phosphoenolpyruvate (P-pyruvate) carboxykinase was studied by monitoring the enzyme activity, intrinsic protein fluorescence, circular dichroism spectra, and 1-anilino-8-naphthalenesulfonate binding. These studies were performed in the absence and presence of substrates and ligands. ATP or P-pyruvate plus MnCl2, or of the combined presence of ATP plus MnCl2 and oxalate, conferred great protection against urea-induced denaturation. The unfolding process showed the presence of at least one stable intermediate which is notably shifted to higher urea concentrations in the presence of substrates. This intermediate protein structure was inactive, contained less tertiary structure than the native protein and retained most of the original secondary structure. Hydrophobic surfaces were more exposed in the intermediate than in the native or unfolded species. Refolding experiments indicated that the secondary structure was completely recovered. Total recovery of tertiary structure and activity was obtained only from samples denatured at urea concentrations lower than those where the intermediate accumulates.

  10. Unfolding the neutron spectrum of a NE213 scintillator using artificial neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Sharghi Ido, A. [Radiation Application Department, Shahid Beheshti University, Tehran (Iran, Islamic Republic of); Bonyadi, M.R. [Electrical and Computer Engineering Faculty, Shahid Beheshti University, Tehran (Iran, Islamic Republic of); Etaati, G.R. [Nuclear Engineering and Physics Faculty, Amir Kabir University of Technology, Tehran (Iran, Islamic Republic of); Shahriari, M. [Radiation Application Department, Shahid Beheshti University, Tehran (Iran, Islamic Republic of)], E-mail: m-shahriari@sbu.ac.ir

    2009-10-15

    Artificial neural networks technology has been applied to unfold the neutron spectra from the pulse height distribution measured with NE213 liquid scintillator. Here, both the single and multi-layer perceptron neural network models have been implemented to unfold the neutron spectrum from an Am-Be neutron source. The activation function and the connectivity of the neurons have been investigated and the results have been analyzed in terms of the network's performance. The simulation results show that the neural network that utilizes the Satlins transfer function has the best performance. In addition, omitting the bias connection of the neurons improve the performance of the network. Also, the SCINFUL code is used for generating the response functions in the training phase of the process. Finally, the results of the neural network simulation have been compared with those of the FORIST unfolding code for both {sup 241}Am-Be and {sup 252}Cf neutron sources. The results of neural network are in good agreement with FORIST code.

  11. 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.

  12. Unfolding DNA condensates produced by DNA-like charged depletants: A force spectroscopy study

    Science.gov (United States)

    Lima, C. H. M.; Rocha, M. S.; Ramos, E. B.

    2017-02-01

    In this work, we have measured, by means of optical tweezers, forces acting on depletion-induced DNA condensates due to the presence of the DNA-like charged protein bovine serum albumin (BSA). The stretching and unfolding measurements performed on the semi-flexible DNA chain reveal (1) the softening of the uncondensed DNA contour length and (2) a mechanical behavior strikingly different from those previously observed: the force-extension curves of BSA-induced DNA condensates lack the "saw-tooth" pattern and applied external forces as high as ≈80 pN are unable to fully unfold the condensed DNA contour length. This last mechanical experimental finding is in agreement with force-induced "unpacking" detailed Langevin dynamics simulations recently performed by Cortini et al. on model rod-like shaped condensates. Furthermore, a simple thermodynamics analysis of the unfolding process has enabled us to estimate the free energy involved in the DNA condensation: the estimated depletion-induced interactions vary linearly with both the condensed DNA contour length and the BSA concentration, in agreement with the analytical and numerical analysis performed on model DNA condensates. We hope that future additional experiments can decide whether the rod-like morphology is the actual one we are dealing with (e.g. pulling experiments coupled with super-resolution fluorescence microscopy).

  13. On the formation of highly charged gaseous ions from unfolded proteins by electrospray ionization.

    Science.gov (United States)

    Konermann, Lars; Rodriguez, Antony D; Liu, Jiangjiang

    2012-08-07

    Electrospray ionization (ESI) of native proteins results in a narrow distribution of low protonation states. ESI for these folded species proceeds via the charged residue mechanism. In contrast, ESI of unfolded proteins yields a wide distribution of much higher charge states. The current work develops a model that can account for this effect. Recent molecular dynamics simulations revealed that ESI for unfolded polypeptide chains involves protein ejection from nanodroplets, representing a type of ion evaporation mechanism (IEM). We point out the analogies between this IEM, and the dissociation of gaseous protein complexes after collisional activation. The latter process commences with unraveling of a single subunit, in concert with Coulombically driven proton transfer. The subunit then separates from the residual complex as a highly charged ion. We propose that similar charge equilibration events accompany the IEM of unfolded proteins, thereby causing the formation of high ESI charge states. A bead chain model is used for examining how charge is partitioned as protein and droplet separate. It is shown that protein ejection from differently sized ESI droplets generates a range of protonation states. The predicted behavior agrees well with experimental data.

  14. Unfolding Thermodynamics of Cysteine-Rich Proteins and Molecular Thermal-Adaptation of Marine Ciliates

    Directory of Open Access Journals (Sweden)

    Giorgia Cazzolli

    2013-11-01

    Full Text Available Euplotes nobilii and Euplotes raikovi are phylogenetically closely allied species of marine ciliates, living in polar and temperate waters, respectively. Their evolutional relation and the sharply different temperatures of their natural environments make them ideal organisms to investigate thermal-adaptation. We perform a comparative study of the thermal unfolding of disulfide-rich protein pheromones produced by these ciliates. Recent circular dichroism (CD measurements have shown that the two psychrophilic (E. nobilii and mesophilic (E. raikovi protein families are characterized by very different melting temperatures, despite their close structural homology. The enhanced thermal stability of the E. raikovi pheromones is realized notwithstanding the fact that these proteins form, as a rule, a smaller number of disulfide bonds. We perform Monte Carlo (MC simulations in a structure-based coarse-grained (CG model to show that the higher stability of the E. raikovi pheromones is due to the lower locality of the disulfide bonds, which yields a lower entropy increase in the unfolding process. Our study suggests that the higher stability of the mesophilic E. raikovi phermones is not mainly due to the presence of a strongly hydrophobic core, as it was proposed in the literature. In addition, we argue that the molecular adaptation of these ciliates may have occurred from cold to warm, and not from warm to cold. To provide a testable prediction, we identify a point-mutation of an E. nobilii pheromone that should lead to an unfolding temperature typical of that of E. raikovi pheromones.

  15. 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...... that flexibility is limited to certain regions of the protein. Cleavage sites for α-lactalbumin and myoglobin correspond to regions identified in other studies as partially unfolded at low pH or in the presence of organic solvents. For Tnfn3, which does not form partially folded structures under other conditions...

  16. 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.

  17. Dataset of eye disease-related proteins analyzed using the unfolding mutation screen

    Science.gov (United States)

    McCafferty, Caitlyn L.; Sergeev, Yuri V.

    2016-01-01

    A number of genetic diseases are a result of missense mutations in protein structure. These mutations can lead to severe protein destabilization and misfolding. The unfolding mutation screen (UMS) is a computational method that calculates unfolding propensities for every possible missense mutation in a protein structure. The UMS validation demonstrated a good agreement with experimental and phenotypical data. 15 protein structures (a combination of homology models and crystal structures) were analyzed using UMS. The standard and clustered heat maps, and patterned protein structure from the analysis were stored in a UMS library. The library is currently composed of 15 protein structures from 14 inherited eye diseases including retina degenerations, glaucoma, and cataracts, and contains data for 181,110 mutations. The UMS protein library introduces 13 new human models of eye disease related proteins and is the first collection of the consistently calculated unfolding propensities, which could be used as a tool for the express analysis of novel mutations in clinical practice, next generation sequencing, and genotype-to-phenotype relationships in inherited eye disease. PMID:27922631

  18. Proteolytic degradation of ribonuclease A in the pretransition region of thermally and urea-induced unfolding.

    Science.gov (United States)

    Arnold, U; Ulbrich-Hofmann, R

    2001-01-01

    The method of limited proteolysis has proven to be appropriate for the determination of unfolding rate constants (k(U)) of ribonuclease A in the transition region of thermal denaturation [Arnold, U. & Ulbrich-Hofmann, R. (1997) Biochemistry 36, 2166-2172]. The aim of the present paper was to extend this procedure to the pretransition region of thermally and urea-induced denaturation where spectroscopic methods do not allow direct measurement of k(U). The results show that the approach can be applied successfully to denaturing (free energy of unfolding Delta G 30 kJ.mol(-1)), however, the determination of kU was not possible in this way as the proteolytic degradation of ribonuclease A by thermolysin or trypsin was no longer determined by global unfolding. Here, proteolysis proceeds via the native RNase A. In the presence of low concentrations of urea, the rate constants of proteolysis were, surprisingly, smaller than in the absence of urea. As the protease activity has been taken into account, this result points to a local stabilization of the RNase A molecule.

  19. Convergence and error propagation results on a linear iterative unfolding method

    CERN Document Server

    Laszlo, Andras

    2014-01-01

    Unfolding problems often arise in the context of signal processing, data analysis and experimental physics in general. It occurs when the probability distribution of a physical quantity is to be measured but it is randomized (smeared) by some well-described process, such as a non-ideal detector response or a well parametrized physical phenomenon. In such cases it is said that the original probability distribution of interest is folded by a known response function. The reconstruction of the original probability distribution from the measured one and from the response function is called unfolding, which is a delicate problem in signal or data processing. As the unfolding problem is numerically ill-posed, most methods have some relatively arbitrary control parameter on regularization. A large class of these methods, by construction, introduce bias which is difficult to quantify, furthermore sometimes it is difficult to show that the method is consistent, i.e.\\ that the bias tends to zero with respect to the cont...

  20. The Endoplasmic Reticulum Unfolded Protein Response in Neurodegenerative Disorders and Its Potential Therapeutic Significance

    Directory of Open Access Journals (Sweden)

    Paolo Remondelli

    2017-06-01

    Full Text Available In eukaryotic cells, the endoplasmic reticulum (ER is the cell compartment involved in secretory protein translocation and quality control of secretory protein folding. Different conditions can alter ER function, resulting in the accumulation of unfolded or misfolded proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated adaptive response known as the unfolded protein response (UPR that aims to restore proteostasis within the secretory pathway. Conversely, in prolonged cell stress or insufficient adaptive response, UPR signaling causes cell death. ER dysfunctions are involved and contribute to neuronal degeneration in several human diseases, including Alzheimer, Parkinson and Huntington disease and amyotrophic lateral sclerosis. The correlations between ER stress and its signal transduction pathway known as the UPR with neuropathological changes are well established. In addition, much evidence suggests that genetic or pharmacological modulation of UPR could represent an effective strategy for minimizing the progressive neuronal loss in neurodegenerative diseases. Here, we review recent results describing the main cellular mechanisms linking ER stress and UPR to neurodegeneration. Furthermore, we provide an up-to-date panoramic view of the currently pursued strategies for ameliorating the toxic effects of protein unfolding in disease by targeting the ER UPR pathway.

  1. Short chain polyethylene glycols unusually assist thermal unfolding of human serum albumin.

    Science.gov (United States)

    Samanta, Nirnay; Mahanta, Debasish Das; Hazra, Soumitra; Kumar, Gopinatha Suresh; Mitra, Rajib Kumar

    2014-09-01

    In the present study we have investigated the thermal stability of the globular transport protein human serum albumin (HSA), in the presence of two small chain polyethylene glycols (namely PEG 200 and PEG 400). Both near- and far-UV circular dichroism (CD) study reveal that addition of PEG moderately increases the α-helical content of the protein without abruptly changing its tertiary structure. The hydration structure at the protein surface experiences a notable change at 30% PEG (v/v) concentration as evidenced from compressibility and dynamic light scattering (DLS) measurements. Thermal denaturation of HSA in the presence of PEG has been studied by CD and fluorescence spectroscopy using the intrinsic fluorophore tryptophan and it has been found that addition of PEG makes the protein more prone towards unfolding, which is in contrary to what has been observed in case of larger molecular weight polymers. The energetics of the thermal unfolding process has been obtained using differential scanning calorimetry (DSC) measurements. Our study concludes that both the indirect excluded volume principle as well as interaction of the polymer at the protein surface is responsible for the observed change of the unfolding process.

  2. Sequence-Specific Solvent Accessibilities of Protein Residues in Unfolded Protein Ensembles

    Science.gov (United States)

    Bernadó, Pau; Blackledge, Martin; Sancho, Javier

    2006-01-01

    Protein stability cannot be understood without the correct description of the unfolded state. We present here an efficient method for accurate calculation of atomic solvent exposures for denatured protein ensembles. The method used to generate the ensembles has been shown to reproduce diverse biophysical experimental data corresponding to natively and chemically unfolded proteins. Using a data set of 19 nonhomologous proteins containing from 98 to 579 residues, we report average accessibilities for all residue types. These averaged accessibilities are considerably lower than those previously reported for tripeptides and close to the lower limit reported by Creamer and co-workers. Of importance, we observe remarkable sequence dependence for the exposure to solvent of all residue types, which indicates that average residue solvent exposures can be inappropriate to interpret mutational studies. In addition, we observe smaller influences of both protein size and protein amino acid composition in the averaged residue solvent exposures for individual proteins. Calculating residue-specific solvent accessibilities within the context of real sequences is thus necessary and feasible. The approach presented here may allow a more precise parameterization of protein energetics as a function of polar- and apolar-area burial and opens new ways to investigate the energetics of the unfolded state of proteins. PMID:17012314

  3. On the Roles of Substrate Binding and Hinge Unfolding in Conformational Changes of Adenylate Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Brokaw, Jason B.; Chu, Jhih-wei

    2010-11-17

    We characterized the conformational change of adenylate kinase (AK) between open and closed forms by conducting five all-atom molecular-dynamics simulations, each of 100 ns duration. Different initial structures and substrate binding configurations were used to probe the pathways of AK conformational change in explicit solvent, and no bias potential was applied. A complete closed-to-open and a partial open-to-closed transition were observed, demonstrating the direct impact of substrate-mediated interactions on shifting protein conformation. The sampled configurations suggest two possible pathways for connecting the open and closed structures of AK, affirming the prediction made based on available x-ray structures and earlier works of coarse-grained modeling. The trajectories of the all-atom molecular-dynamics simulations revealed the complexity of protein dynamics and the coupling between different domains during conformational change. Calculations of solvent density and density fluctuations surrounding AK did not show prominent variation during the transition between closed and open forms. Finally, we characterized the effects of local unfolding of an important hinge near Pro177 on the closed-to-open transition of AK and identified a novel mechanism by which hinge unfolding modulates protein conformational change. The local unfolding of Pro177 hinge induces alternative tertiary contacts that stabilize the closed structure and prevent the opening transition.

  4. 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)

  5. 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...

  6. Computational study of unfolding and regulation mechanism of preQ1 riboswitches.

    Directory of Open Access Journals (Sweden)

    Zhou Gong

    Full Text Available Riboswitches are novel RNA regulatory elements. Each riboswitch molecule consists of two domains: aptamer and express platform. The three-dimensional (3D structure of the aptamer domain, depending on ligand binding or not, controls that of the express platform, which then switches on or off transcriptional or translational process. Here we study the two types of preQ(1 riboswitch aptamers from T. Tengcongensis (denoted as Tte preQ(1 riboswitch for short below and Bacillus subtilis (denoted as Bsu preQ(1 riboswitch for short below, respectively. The free-state 3D structure of the Tte preQ(1 riboswitch is the same as its bound state but the Bsu preQ(1 riboswitch is not. Therefore, it is very interesting to investigate how these riboswitches realize their different regulation functions. We simulated the unfolding of these two aptamers through all-atom molecular dynamic simulation and found that they have similar unfolding or folding pathways and ligand-binding processes. The main difference between them is the folding intermediate states. The similarity and difference of their unfolding or folding dynamics may suggest their similar regulation mechanisms and account for their different functions, respectively. These results are also useful to understand the regulation mechanism of other riboswitches with free-state 3D structures similar to their bound states.

  7. VISAR Unfold Analysis of MagLIF Laser Blast Wave Experiments

    Science.gov (United States)

    Hess, Mark; Peterson, Kyle; Harvey-Thompson, Adam

    2015-06-01

    MagLIF (Magnetized Liner Inertial Fusion) is a fusion energy scheme, which utilizes a short laser pulse to preheat a fuel, and a magnetically driven cylindrical liner to compress the fuel to high energy density plasma conditions. Recently, a set of successful experiments have been performed to evaluate the effectiveness of our preheat process in MagLIF using the Z-Beamlet laser at Sandia. The fuel is preheated in the liner, with no compression from the Z-machine, and a VISAR diagnostic was fielded on the outer surface of the liner to measure velocity of the liner due to the pressure of the laser blast wave on the inner surface of the liner. In support of this program, we developed a fast unfold method of the VISAR data using semi-analytical techniques/numerical methods. The method incorporates appropriate boundary conditions at both edges of the VISAR foil, realistic EOS tables, and an additional pressure pulse time-delay feature for accurately unfolding the time-dependent pressure from the VISAR data. Our fully automated method can produce high-quality unfolds of the laser blast wave in under a minute. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's NNSA under Contract DE-AC04-94AL85000.

  8. 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.

  9. Characterization of ionizing radiation-induced unfolded protein response in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ju; Lee, Yoon Jin; Kang, Seong Man [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2013-04-15

    Misfolded or unfolded proteins within the endoplasmic reticulum (ER stress), viral infection, or amino acid deprivation induce eukaryotic translation initiation factor 2α phosphorylation (eIF2α) in eukaryotic cells, repressing global protein synthesis coincident with preferential translation of activating transcription factor 4 (ATF4). ATF4 is a transcriptional activator of genes involved in amino acid metabolism, cellular redox homeostasis, and regulation of apoptosis. When the eIF2α/ATF4 pathway is initiated by ER stress, the pathway is referred toas the unfolded protein response (UPR). In addition to DNA, proteins may be initial and important targets of ionizing radiation (IR), and the damaged protein can trigger ER stress pathway. Recent investigations suggested that IR induces ER stress followed by UPR in various cell types including intestinal epithelial cells. We conducted this study to determine whether IR can activate UPR in human vascular endothelial cells. Our data have shown that IR increased PERK-dependent eIF2α phosphorylation accompanied by induction in ATF4 protein levels in human vascular endothelial cells without alterations in expressions of XBP-1s and GRP78. Based on these data, we suggest that IR selectively activates PERK branch of unfolded protein response in human vascular endothelial cells.

  10. 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.

  11. 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.

  12. Folding and unfolding of a non-fluorescent mutant of green fluorescent protein

    Energy Technology Data Exchange (ETDEWEB)

    Wielgus-Kutrowska, Beata [Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Zwirki and Wigury 93, 02-089 (Poland); Narczyk, Marta [Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Zwirki and Wigury 93, 02-089 (Poland); Buszko, Anna [Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Zwirki and Wigury 93, 02-089 (Poland); Bzowska, Agnieszka [Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Zwirki and Wigury 93, 02-089 (Poland); Clark, Patricia L [Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556-5670 (United States)

    2007-07-18

    Green fluorescent protein (GFP), from the Pacific jellyfish A. victoria, has numerous uses in biotechnology and cell and molecular biology as a protein marker because of its specific chromophore, which is spontaneously created after proper protein folding. After formation, the chromophore is very stable and it remains intact during protein unfolding, meaning that the GFP unfolding process is not the reverse of the original folding reaction; i.e., the principles of microscopic reversibility do not apply. We have generated the mutant S65T/G67A-GFP, which is unable to efficiently form the cyclic chromophore, with the goal of investigating the folding, unfolding and competing aggregation of GFP under fully reversible conditions. Our studies have been performed in the presence of guanidinium hydrochloride (GdnHCl). The GFP conformation was monitored using intrinsic tryptophan fluorescence, and fluorescence of 1,1'-bis(4-anilino-5-naphthalenesulphonic acid) (bis-ANS). Light scattering was used to follow GFP aggregation. We conclude from these fluorescence measurements that S65T/G67A-GFP folding is largely reversible. During equilibrium folding, the first step is the formation of a molten globule, prone to aggregation.

  13. DIFFERENTIAL ANALYSIS OF VOLUMETRIC STRAINS IN POROUS MATERIALS IN TERMS OF WATER FREEZING

    Directory of Open Access Journals (Sweden)

    Rusin Z.

    2013-06-01

    Full Text Available The paper presents the differential analysis of volumetric strain (DAVS. The method allows measurements of volumetric deformations of capillary-porous materials caused by water-ice phase change. The VSE indicator (volumetric strain effect, which under certain conditions can be interpreted as the minimum degree of phase change of water contained in the material pores, is proposed. The test results (DAVS for three materials with diversified microstructure: clinker brick, calcium-silicate brick and Portland cement mortar were compared with the test results for pore characteristics obtained with the mercury intrusion porosimetry.

  14. Is there a role for the use of volumetric cone beam computed tomography in periodontics?

    Science.gov (United States)

    du Bois, A H; Kardachi, B; Bartold, P M

    2012-03-01

    Volumetric computed cone beam tomography offers a number of significant advantages over conventional intraoral and extraoral panoramic radiography, as well as computed tomography. To date, periodontal diagnosis has relied heavily on the assessment of both intraoral radiographs and extraoral panoramic radiographs. With emerging technology in radiology there has been considerable interest in the role that volumetric cone beam computed tomography might play in periodontal diagnostics. This narrative reviews the current evidence and considers whether there is a role for volumetric cone beam computed tomography in periodontics.

  15. Parkinson's disease: diagnostic utility of volumetric imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Wei-Che; Chen, Meng-Hsiang [Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Department of Diagnostic Radiology, Kaohsiung (China); Chou, Kun-Hsien [National Yang-Ming University, Brain Research Center, Taipei (China); Lee, Pei-Lin [National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China); Tsai, Nai-Wen; Lu, Cheng-Hsien [Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Department of Neurology, Kaohsiung (China); Chen, Hsiu-Ling [Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Department of Diagnostic Radiology, Kaohsiung (China); National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China); Hsu, Ai-Ling [National Taiwan University, Institute of Biomedical Electronics and Bioinformatics, Taipei (China); Huang, Yung-Cheng [Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Department of Nuclear Medicine, Kaohsiung (China); Lin, Ching-Po [National Yang-Ming University, Brain Research Center, Taipei (China); National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China)

    2017-04-15

    This paper aims to examine the effectiveness of structural imaging as an aid in the diagnosis of Parkinson's disease (PD). High-resolution T{sub 1}-weighted magnetic resonance imaging was performed in 72 patients with idiopathic PD (mean age, 61.08 years) and 73 healthy subjects (mean age, 58.96 years). The whole brain was parcellated into 95 regions of interest using composite anatomical atlases, and region volumes were calculated. Three diagnostic classifiers were constructed using binary multiple logistic regression modeling: the (i) basal ganglion prior classifier, (ii) data-driven classifier, and (iii) basal ganglion prior/data-driven hybrid classifier. Leave-one-out cross validation was used to unbiasedly evaluate the predictive accuracy of imaging features. Pearson's correlation analysis was further performed to correlate outcome measurement using the best PD classifier with disease severity. Smaller volume in susceptible regions is diagnostic for Parkinson's disease. Compared with the other two classifiers, the basal ganglion prior/data-driven hybrid classifier had the highest diagnostic reliability with a sensitivity of 74%, specificity of 75%, and accuracy of 74%. Furthermore, outcome measurement using this classifier was associated with disease severity. Brain structural volumetric analysis with multiple logistic regression modeling can be a complementary tool for diagnosing PD. (orig.)

  16. Volumetric Analysis of Regional Cerebral Development in Preterm Children

    Science.gov (United States)

    Kesler, Shelli R.; Ment, Laura R.; Vohr, Betty; Pajot, Sarah K.; Schneider, Karen C.; Katz, Karol H.; Ebbitt, Timothy B.; Duncan, Charles C.; Makuch, Robert W.; Reiss, Allan L.

    2011-01-01

    Preterm birth is frequently associated with both neuropathologic and cognitive sequelae. This study examined cortical lobe, subcortical, and lateral ventricle development in association with perinatal variables and cognitive outcome. High-resolution volumetric magnetic resonance imaging scans were acquired and quantified using advanced image processing techniques. Seventy-three preterm and 33 term control children ages 7.3-11.4 years were included in the study. Results indicated disproportionately enlarged parietal and frontal gray matter, occipital horn, and ventricular body, as well as reduced temporal and subcortical gray volumes in preterm children compared with control subjects. Birth weight was negatively correlated with parietal and frontal gray, as well as occipital horn volumes. Intraventricular hemorrhage was associated with reduced subcortical gray matter. Ventricular cerebrospinal fluid was negatively correlated with subcortical gray matter volumes but not with white matter volumes. Maternal education was the strongest predictor of cognitive function in the preterm group. Preterm birth appears to be associated with disorganized cortical development, possibly involving disrupted synaptic pruning and neural migration. Lower birth weight and the presence of intraventricular hemorrhage may increase the risk for neuroanatomic abnormality. PMID:15519112

  17. Volumetric microscale particle tracking velocimetry (PTV) in porous media

    Science.gov (United States)

    Guo, Tianqi; Aramideh, Soroush; Ardekani, Arezoo M.; Vlachos, Pavlos P.

    2016-11-01

    The steady-state flow through refractive-index-matched glass bead microchannels is measured using microscopic particle tracking velocimetry (μPTV). A novel technique is developed to volumetrically reconstruct particles from oversampled two-dimensional microscopic images of fluorescent particles. Fast oversampling of the quasi-steady-state flow field in the lateral direction is realized by a nano-positioning piezo stage synchronized with a fast CMOS camera. Experiments at different Reynolds numbers are carried out for flows through a series of both monodispersed and bidispersed glass bead microchannels with various porosities. The obtained velocity fields at pore-scale (on the order of 10 μm) are compared with direct numerical simulations (DNS) conducted in the exact same geometries reconstructed from micro-CT scans of the glass bead microchannels. The developed experimental method would serve as a new approach for exploring the flow physics at pore-scale in porous media, and also provide benchmark measurements for validation of numerical simulations.

  18. Buoyancy Driven Mixing with Continuous Volumetric Energy Deposition

    Science.gov (United States)

    Wachtor, Adam J.; Jebrail, Farzaneh F.; Dennisen, Nicholas A.; Andrews, Malcolm J.; Gore, Robert A.

    2014-11-01

    An experiment involving a miscible fluid pair is presented which transitioned from a Rayleigh-Taylor (RT) stable to RT unstable configuration through continuous volumetric energy deposition (VED) by microwave radiation. Initially a light, low microwave absorbing fluid rested above a heavier, more absorbing fluid. The alignment of the density gradient with gravity made the system stable, and the Atwood number (At) for the initial setup was approximately -0.12. Exposing the fluid pair to microwave radiation preferentially heated the bottom fluid, and caused its density to drop due to thermal expansion. As heating of the bottom fluid continued, the At varied from negative to positive, and after the system passed through the neutral stability point, At = 0, buoyancy driven mixing ensued. Continuous VED caused the At to continue increasing and further drive the mixing process. Successful VED mixing required careful design of the fluid pair used in the experiment. Therefore, fluid selection is discussed, along with challenges and limitations of data collection using the experimental microwave facility. Experimental and model predictions of the neutral stability point, and onset of buoyancy driven mixing, are compared, and differences with classical, constant At RT driven turbulence are discussed.

  19. FELIX 3D display: an interactive tool for volumetric imaging

    Science.gov (United States)

    Langhans, Knut; Bahr, Detlef; Bezecny, Daniel; Homann, Dennis; Oltmann, Klaas; Oltmann, Krischan; Guill, Christian; Rieper, Elisabeth; Ardey, Goetz

    2002-05-01

    The FELIX 3D display belongs to the class of volumetric displays using the swept volume technique. It is designed to display images created by standard CAD applications, which can be easily imported and interactively transformed in real-time by the FELIX control software. The images are drawn on a spinning screen by acousto-optic, galvanometric or polygon mirror deflection units with integrated lasers and a color mixer. The modular design of the display enables the user to operate with several equal or different projection units in parallel and to use appropriate screens for the specific purpose. The FELIX 3D display is a compact, light, extensible and easy to transport system. It mainly consists of inexpensive standard, off-the-shelf components for an easy implementation. This setup makes it a powerful and flexible tool to keep track with the rapid technological progress of today. Potential applications include imaging in the fields of entertainment, air traffic control, medical imaging, computer aided design as well as scientific data visualization.

  20. Toward a Philosophy and Theory of Volumetric Nonthermal Processing.

    Science.gov (United States)

    Sastry, Sudhir K

    2016-06-01

    Nonthermal processes for food preservation have been under intensive investigation for about the past quarter century, with varying degrees of success. We focus this discussion on two volumetrically acting nonthermal processes, high pressure processing (HPP) and pulsed electric fields (PEF), with emphasis on scientific understanding of each, and the research questions that need to be addressed for each to be more successful in the future. We discuss the character or "philosophy" of food preservation, with a question about the nature of the kill step(s), and the sensing challenges that need to be addressed. For HPP, key questions and needs center around whether its nonthermal effectiveness can be increased by increased pressures or pulsing, the theoretical treatment of rates of reaction as influenced by pressure, the assumption of uniform pressure distribution, and the need for (and difficulties involved in) in-situ measurement. For PEF, the questions include the rationale for pulsing, difficulties involved in continuous flow treatment chambers, the difference between electroporation theory and experimental observations, and the difficulties involved in in-situ measurement and monitoring of electric field distribution.