WorldWideScience

Sample records for macromolecular machines remodel

  1. Using support vector machines to improve elemental ion identification in macromolecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Morshed, Nader [University of California, Berkeley, CA 94720 (United States); Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Echols, Nathaniel, E-mail: nechols@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Adams, Paul D., E-mail: nechols@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); University of California, Berkeley, CA 94720 (United States)

    2015-05-01

    A method to automatically identify possible elemental ions in X-ray crystal structures has been extended to use support vector machine (SVM) classifiers trained on selected structures in the PDB, with significantly improved sensitivity over manually encoded heuristics. In the process of macromolecular model building, crystallographers must examine electron density for isolated atoms and differentiate sites containing structured solvent molecules from those containing elemental ions. This task requires specific knowledge of metal-binding chemistry and scattering properties and is prone to error. A method has previously been described to identify ions based on manually chosen criteria for a number of elements. Here, the use of support vector machines (SVMs) to automatically classify isolated atoms as either solvent or one of various ions is described. Two data sets of protein crystal structures, one containing manually curated structures deposited with anomalous diffraction data and another with automatically filtered, high-resolution structures, were constructed. On the manually curated data set, an SVM classifier was able to distinguish calcium from manganese, zinc, iron and nickel, as well as all five of these ions from water molecules, with a high degree of accuracy. Additionally, SVMs trained on the automatically curated set of high-resolution structures were able to successfully classify most common elemental ions in an independent validation test set. This method is readily extensible to other elemental ions and can also be used in conjunction with previous methods based on a priori expectations of the chemical environment and X-ray scattering.

  2. Epithelial Remodeling as Basis for Machine-Based Identification of Keratoconus

    Science.gov (United States)

    Silverman, Ronald H.; Urs, Raksha; RoyChoudhury, Arindam; Archer, Timothy J.; Gobbe, Marine; Reinstein, Dan Z.

    2014-01-01

    Purpose. To develop and evaluate automated computerized algorithms for differentiation of normal and keratoconus corneas based solely on epithelial and stromal thickness data. Methods. Maps of the corneal epithelial and stromal thickness were generated from Artemis-1 very high-frequency ultrasound arc-scans of 130 normal and 74 keratoconic subjects diagnosed by combined topography and tomography examination. Keratoconus severity was graded based on anterior curvature, minimum corneal thickness, and refractive error. Computer analysis of maps produced 161 features for one randomly selected eye per subject. Stepwise linear discriminant analysis (LDA) and neural network (NN) analysis were then performed to develop multivariate models based on combinations of selected features to correctly classify cases. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined for each classifier. Results. Stepwise LDA resulted in a six-variable model that provided an AUC of 100%, indicative of complete separation of keratoconic from normal corneas. Leave-one-out analysis resulted in 99.2% specificity and 94.6% sensitivity. Neural network analysis using the same six variables resulted in an AUC of 100% for the training set. Test set performance averaged over 10 trials gave a specificity of 99.5 ± 1.5% and sensitivity of 98.9 ± 1.9%. The LDA function values correlated with keratoconus severity grade. Conclusions. The results demonstrate that epithelial remodeling in keratoconus represents an independent means for differentiation of normal from advanced keratoconus corneas. PMID:24557351

  3. Macromolecular Prodrugs of Ribavirin

    DEFF Research Database (Denmark)

    Riber, Camilla Frich; Hinton, Tracey M; Gajda, Paulina

    2017-01-01

    The requirement for new antiviral therapeutics is an ever present need. Particularly lacking are broad spectrum antivirals that have low toxicity. We develop such agents based on macromolecular prodrugs whereby both the polymer chain and the drug released from the polymer upon cell entry have ant...

  4. Macromolecular Crystallization in Microgravity

    Science.gov (United States)

    Snell, Edward H.; Helliwell, John R.

    2004-01-01

    The key concepts that attracted crystal growers, macromolecular or solid state, to microgravity research is that density difference fluid flows and sedimentation of the growing crystals are greatly reduced. Thus, defects and flaws in the crystals can be reduced, even eliminated, and crystal volume can be increased. Macromolecular crystallography differs from the field of crystalline semiconductors. For the latter, crystals are harnessed for their electrical behaviors. A crystal of a biological macromolecule is used instead for diffraction experiments (X-ray or neutron) to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal of a biological macromolecule then the more molecular structure detail that can be extracted. This structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences with major potential in understanding disease pathologies. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry, and mathematics meet to enable insight to the basic fundamentals of life. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment, and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyze the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural

  5. Macromolecular crystallization in microgravity

    Energy Technology Data Exchange (ETDEWEB)

    Snell, Edward H [Biophysics Group, NASA Marshall Space Flight Center, Code XD42, Huntsville, AL 35812 (United States); Helliwell, John R [Department of Chemistry, The University of Manchester, Manchester, M13 9PL (United Kingdom)

    2005-04-01

    Density difference fluid flows and sedimentation of growing crystals are greatly reduced when crystallization takes place in a reduced gravity environment. In the case of macromolecular crystallography a crystal of a biological macromolecule is used for diffraction experiments (x-ray or neutron) so as to determine the three-dimensional structure of the macromolecule. The better the internal order of the crystal then the greater the molecular structure detail that can be extracted. It is this structural information that enables an understanding of how the molecule functions. This knowledge is changing the biological and chemical sciences, with major potential in understanding disease pathologies. In this review, we examine the use of microgravity as an environment to grow macromolecular crystals. We describe the crystallization procedures used on the ground, how the resulting crystals are studied and the knowledge obtained from those crystals. We address the features desired in an ordered crystal and the techniques used to evaluate those features in detail. We then introduce the microgravity environment, the techniques to access that environment and the theory and evidence behind the use of microgravity for crystallization experiments. We describe how ground-based laboratory techniques have been adapted to microgravity flights and look at some of the methods used to analyse the resulting data. Several case studies illustrate the physical crystal quality improvements and the macromolecular structural advances. Finally, limitations and alternatives to microgravity and future directions for this research are covered. Macromolecular structural crystallography in general is a remarkable field where physics, biology, chemistry and mathematics meet to enable insight to the fundamentals of life. As the reader will see, there is a great deal of physics involved when the microgravity environment is applied to crystallization, some of it known, and undoubtedly much yet to

  6. Microgravity and Macromolecular Crystallography

    Science.gov (United States)

    Kundrot, Craig E.; Judge, Russell A.; Pusey, Marc L.; Snell, Edward H.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    Macromolecular crystal growth has been seen as an ideal experiment to make use of the reduced acceleration environment provided by an orbiting spacecraft. The experiments are small, simply operated and have a high potential scientific and economic impact. In this review we examine the theoretical reasons why microgravity should be a beneficial environment for crystal growth and survey the history of experiments on the Space Shuttle Orbiter, on unmanned spacecraft, and on the Mir space station. Finally we outline the direction for optimizing the future use of orbiting platforms.

  7. CHD4 Is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex.

    Science.gov (United States)

    Low, Jason K K; Webb, Sarah R; Silva, Ana P G; Saathoff, Hinnerk; Ryan, Daniel P; Torrado, Mario; Brofelth, Mattias; Parker, Benjamin L; Shepherd, Nicholas E; Mackay, Joel P

    2016-07-22

    Chromatin remodeling enzymes act to dynamically regulate gene accessibility. In many cases, these enzymes function as large multicomponent complexes that in general comprise a central ATP-dependent Snf2 family helicase that is decorated with a variable number of regulatory subunits. The nucleosome remodeling and deacetylase (NuRD) complex, which is essential for normal development in higher organisms, is one such macromolecular machine. The NuRD complex comprises ∼10 subunits, including the histone deacetylases 1 and 2 (HDAC1 and HDAC2), and is defined by the presence of a CHD family remodeling enzyme, most commonly CHD4 (chromodomain helicase DNA-binding protein 4). The existing paradigm holds that CHD4 acts as the central hub upon which the complex is built. We show here that this paradigm does not, in fact, hold and that CHD4 is a peripheral component of the NuRD complex. A complex lacking CHD4 that has HDAC activity can exist as a stable species. The addition of recombinant CHD4 to this nucleosome deacetylase complex reconstitutes a NuRD complex with nucleosome remodeling activity. These data contribute to our understanding of the architecture of the NuRD complex.

  8. Accounting for large amplitude protein deformation during in silico macromolecular docking.

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-02-22

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  9. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-01-01

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success. PMID:21541061

  10. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Directory of Open Access Journals (Sweden)

    Chantal Prévost

    2011-02-01

    Full Text Available Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA.We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  11. Macromolecular architectures for organic photovoltaics.

    Science.gov (United States)

    Popere, Bhooshan C; Della Pelle, Andrea M; Poe, Ambata; Thayumanavan, S

    2012-03-28

    Research in the field of organic photovoltaics has gained considerable momentum in the last two decades owing to the need for developing low-cost and efficient energy harvesting systems. Elegant molecular architectures have been designed, synthesized and employed as active materials for photovoltaic devices thereby leading to a better molecular structure-device property relationship understanding. In this perspective, we outline new macromolecular scaffolds that have been designed within the purview of each of the three fundamental processes involving light harvesting, charge separation and charge transport.

  12. Emergent Property in Macromolecular Motion

    Institute of Scientific and Technical Information of China (English)

    吴嘉麟

    2003-01-01

    In this paper, the model of inverse cascade fractal super-blocks along one direction (in the positive or negative) in the 3-dimensional space is developed to describe the self-similar motion in macromolecular system. Microscopically the cohesive and dispersed states of the motion blocks are co-existent states with vastly different probability of occurrence.Experimental results and theoretical analysis show that the microscopic cohesive state energy and dispersed state energy of each motion block are respectively equal to the macroscopic glassy state energy kT8 and molten state energy kTm of the system. This singularity unveils topologically the nonintegrability, mathematically the anholonomy, and macroscopically the emergent property. This singularity also reveals that the glass, viscoelastic and melt states are three distinct emergent properties of macromolecular motion from a macroscopic viewpoint. The fractal concept of excluded volume is introduced to depict the random motion at various scales in the system. The Hausdorff dimensions of the excluded volune and the motion blocks are both found equal to 3/2.

  13. Data Mining of Macromolecular Structures.

    Science.gov (United States)

    van Beusekom, Bart; Perrakis, Anastassis; Joosten, Robbie P

    2016-01-01

    The use of macromolecular structures is widespread for a variety of applications, from teaching protein structure principles all the way to ligand optimization in drug development. Applying data mining techniques on these experimentally determined structures requires a highly uniform, standardized structural data source. The Protein Data Bank (PDB) has evolved over the years toward becoming the standard resource for macromolecular structures. However, the process selecting the data most suitable for specific applications is still very much based on personal preferences and understanding of the experimental techniques used to obtain these models. In this chapter, we will first explain the challenges with data standardization, annotation, and uniformity in the PDB entries determined by X-ray crystallography. We then discuss the specific effect that crystallographic data quality and model optimization methods have on structural models and how validation tools can be used to make informed choices. We also discuss specific advantages of using the PDB_REDO databank as a resource for structural data. Finally, we will provide guidelines on how to select the most suitable protein structure models for detailed analysis and how to select a set of structure models suitable for data mining.

  14. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair......, and gene regulation, at both transcriptional and translational levels. Udgivelsesdato: 1999-Jul...

  15. Liver-targeting macromolecular MRI contrast agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Macromolecular ligands with liver-targeting group (pyridoxamine, PM) PHEA-DTPA-PM and PAEA-DTPA-PM were prepared by the incorporation of different amount of diethylenetriaminepentaacetic acid monopyridoxamine group (DTPA-PM) into poly-a, b-[N-(2-hydroxyethyl)-L- aspartamide] (PHEA) and poly-a, b-[N-(2-aminoethyl)-L-aspartamide] (PAEA). The macromolecular ligands thus obtained were further complexed with gadolinium chloride to give macromolecular MRI contrast agents with different Gd(Ⅲ) contents. These macromolecular ligands and their gadolinium complexes were characterized by 1H NMR, IR, UV and elementary analysis. Relaxivity studies showed that these polyaspartamide gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of the liver in rats and experimental data of biodistribution in mice indicate that these macromolecular MRI contrast agents containing pyridoxamine exhibit liver-targeting property.

  16. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  17. Analysis of Tagish Lake macromolecular organic material

    OpenAIRE

    Gilmour, I; Pearson, V. K.; Sephton, M.A.

    2001-01-01

    Macromolecular material is, by far, the major organic component of meteorites. Flash pyrolysis GCMS has been used to investigate this organic component in Tagish Lake. It is more condensed, less susbtituted than Murchson.

  18. Automated data collection for macromolecular crystallography.

    Science.gov (United States)

    Winter, Graeme; McAuley, Katherine E

    2011-09-01

    An overview, together with some practical advice, is presented of the current status of the automation of macromolecular crystallography (MX) data collection, with a focus on MX beamlines at Diamond Light Source, UK.

  19. Macromolecular crowding: Macromolecules friend or foe.

    Science.gov (United States)

    Mittal, Shruti; Chowhan, Rimpy Kaur; Singh, Laishram Rajendrakumar

    2015-09-01

    Cellular interior is known to be densely crowded due to the presence of soluble and insoluble macromolecules, which altogether occupy ~40% of the total cellular volume. This results in altered biological properties of macromolecules. Macromolecular crowding is observed to have both positive and negative effects on protein folding, structure, stability and function. Significant data has been accumulated so far on both the aspects. However, most of the review articles so far have focused on the positive aspect of macromolecular crowding and not much attention has been paid on the deleterious aspect of crowding on macromolecules. In order to have a complete knowledge of the effect of macromolecular crowding on proteins and enzymes, it is important to look into both the aspects of crowding to determine its precise role under physiological conditions. To fill the gap in the understanding of the effect of macromolecular crowding on proteins and enzymes, this review article focuses on the deleterious influence of crowding on macromolecules. Macromolecular crowding is not always good but also has several deleterious effects on various macromolecular properties. Taken together, the properties of biological macromolecules in vivo appears to be finely regulated by the nature and level of the intracellular crowdedness in order to perform their biological functions appropriately. The information provided here gives an understanding of the role played by the nature and level of cellular crowdedness in intensifying and/or alleviating the burden of various proteopathies. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Energy transfer in macromolecular arrays

    Science.gov (United States)

    Andrews, David L.; Jenkins, Robert D.

    2003-11-01

    Macromolecular systems comprised of many light-sensitive centres (the photosynthetic unit, dendrimers, and other highly symmetric multichromophore arrays) are important structures offering challenges to theoreticians and synthetic chemists alike. Here we outline novel photophysical interactions predicted and observed in such arrays. Using the tools of molecular quantum electrodynamics (QED) we present quantum amplitudes for a variety of higher-order resonance energy transfer (RET) schemes associated with well-known nonlinear optical effects such as two- and three-photon absorption. The initial analysis is extended to account for situations where the participant donor species are identical and exist in a highly symmetric environment, leading to the possible formation of excitons. It emerges from the QED theory that such excitons are closely associated with the higher-order RET processes. General results are interpreted by analyzing particular molecular architectures which offer interesting features such as rate enhancement or limitation and exciton pathway quenching. Applications in the areas of photosynthesis, molecular logic gates and low-intensity fluorescence energy transfer are predicted.

  1. Characterization of cereulide synthetase, a toxin-producing macromolecular machine.

    Directory of Open Access Journals (Sweden)

    Diego A Alonzo

    Full Text Available Cereulide synthetase is a two-protein nonribosomal peptide synthetase system that produces a potent emetic toxin in virulent strains of Bacillus cereus. The toxin cereulide is a depsipeptide, as it consists of alternating aminoacyl and hydroxyacyl residues. The hydroxyacyl residues are derived from keto acid substrates, which cereulide synthetase selects and stereospecifically reduces with imbedded ketoreductase domains before incorporating them into the growing depsipeptide chain. We present an in vitro biochemical characterization of cereulide synthetase. We investigate the kinetics and side chain specificity of α-keto acid selection, evaluate the requirement of an MbtH-like protein for adenylation domain activity, assay the effectiveness of vinylsulfonamide inhibitors on ester-adding modules, perform NADPH turnover experiments and evaluate in vitro depsipeptide biosynthesis. This work also provides biochemical insight into depsipeptide-synthesizing nonribosomal peptide synthetases responsible for other bioactive molecules such as valinomycin, antimycin and kutzneride.

  2. Chromatin remodelling: the industrial revolution of DNA around histones.

    Science.gov (United States)

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  3. Effects of macromolecular crowding on genetic networks.

    Science.gov (United States)

    Morelli, Marco J; Allen, Rosalind J; Wolde, Pieter Rein ten

    2011-12-21

    The intracellular environment is crowded with proteins, DNA, and other macromolecules. Under physiological conditions, macromolecular crowding can alter both molecular diffusion and the equilibria of bimolecular reactions and therefore is likely to have a significant effect on the function of biochemical networks. We propose a simple way to model the effects of macromolecular crowding on biochemical networks via an appropriate scaling of bimolecular association and dissociation rates. We use this approach, in combination with kinetic Monte Carlo simulations, to analyze the effects of crowding on a constitutively expressed gene, a repressed gene, and a model for the bacteriophage λ genetic switch, in the presence and absence of nonspecific binding of transcription factors to genomic DNA. Our results show that the effects of crowding are mainly caused by the shift of association-dissociation equilibria rather than the slowing down of protein diffusion, and that macromolecular crowding can have relevant and counterintuitive effects on biochemical network performance.

  4. Chirality as a physical aspect of structure formation in biological macromolecular systems

    Science.gov (United States)

    Malyshko, E. V.; Tverdislov, V. A.

    2016-08-01

    A novel regularity of hierarchical structures is found in the formation of chiral biological macromolecular systems. The formation of structures with alternating chirality (helical structures) serves as an instrument of stratification. The ability of a carbon atom to form chiral compounds is an important factor that determined the carbon basis of living systems on the Earth as well as their development through a series of chiral bifurcations. In the course of biological evolution, the helical structures became basic elements of the molecular machines in the cell. The discreteness of structural levels allowed the mechanical degrees of freedom formation in the molecular machines in the cell.

  5. Macromolecular mimicry of nucleic acid and protein

    DEFF Research Database (Denmark)

    Nautrup Pedersen, Gitte; Nyborg, Jens; Clark, Brian F

    1999-01-01

    of the concept of macromolecular mimicry. Macromolecular mimicry has further been proposed among initiation and release factors, thereby adding a new element to the description of protein synthesis in bacteria. Such mimicry has also been observed in other biological processes such as autoimmunity, DNA repair......Although proteins and nucleic acids consist of different chemical components, proteins can mimic structures and possibly also functions of nucleic acids. Recently, structural mimicry was observed between two elongation factors in bacterial protein biosynthesis leading to the introduction...

  6. Force interacts with macromolecular structure in activation of TGF-β.

    Science.gov (United States)

    Dong, Xianchi; Zhao, Bo; Iacob, Roxana E; Zhu, Jianghai; Koksal, Adem C; Lu, Chafen; Engen, John R; Springer, Timothy A

    2017-02-02

    Integrins are adhesion receptors that transmit force across the plasma membrane between extracellular ligands and the actin cytoskeleton. In activation of the transforming growth factor-β1 precursor (pro-TGF-β1), integrins bind to the prodomain, apply force, and release the TGF-β growth factor. However, we know little about how integrins bind macromolecular ligands in the extracellular matrix or transmit force to them. Here we show how integrin αVβ6 binds pro-TGF-β1 in an orientation biologically relevant for force-dependent release of TGF-β from latency. The conformation of the prodomain integrin-binding motif differs in the presence and absence of integrin binding; differences extend well outside the interface and illustrate how integrins can remodel extracellular matrix. Remodelled residues outside the interface stabilize the integrin-bound conformation, adopt a conformation similar to earlier-evolving family members, and show how macromolecular components outside the binding motif contribute to integrin recognition. Regions in and outside the highly interdigitated interface stabilize a specific integrin/pro-TGF-β orientation that defines the pathway through these macromolecules which actin-cytoskeleton-generated tensile force takes when applied through the integrin β-subunit. Simulations of force-dependent activation of TGF-β demonstrate evolutionary specializations for force application through the TGF-β prodomain and through the β- and not α-subunit of the integrin.

  7. Statistics of Multiscale Fluctuations in Macromolecular Systems

    CERN Document Server

    Yukalov, V I

    2012-01-01

    An approach is suggested for treating multiscale fluctuations in macromolecular systems. The emphasis is on the statistical properties of such fluctuations. The approach is illustrated by a macromolecular system with mesoscopic fluctuations between the states of atomic orbitals. Strong-orbital and weak-orbital couplings fluctuationally arise, being multiscale in space and time. Statistical properties of the system are obtained by averaging over the multiscale fluctuations. The existence of such multiscale fluctuations causes phase transitions between strong-coupling and weak-coupling states. These transitions are connected with structure and size transformations of macromolecules. An approach for treating density and size multiscale fluctuations by means of classical statistical mechanics is also advanced.

  8. In situ macromolecular crystallography using microbeams.

    Science.gov (United States)

    Axford, Danny; Owen, Robin L; Aishima, Jun; Foadi, James; Morgan, Ann W; Robinson, James I; Nettleship, Joanne E; Owens, Raymond J; Moraes, Isabel; Fry, Elizabeth E; Grimes, Jonathan M; Harlos, Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S; Stuart, David I; Evans, Gwyndaf

    2012-05-01

    Despite significant progress in high-throughput methods in macromolecular crystallography, the production of diffraction-quality crystals remains a major bottleneck. By recording diffraction in situ from crystals in their crystallization plates at room temperature, a number of problems associated with crystal handling and cryoprotection can be side-stepped. Using a dedicated goniometer installed on the microfocus macromolecular crystallography beamline I24 at Diamond Light Source, crystals have been studied in situ with an intense and flexible microfocus beam, allowing weakly diffracting samples to be assessed without a manual crystal-handling step but with good signal to noise, despite the background scatter from the plate. A number of case studies are reported: the structure solution of bovine enterovirus 2, crystallization screening of membrane proteins and complexes, and structure solution from crystallization hits produced via a high-throughput pipeline. These demonstrate the potential for in situ data collection and structure solution with microbeams.

  9. Growth and dissolution of macromolecular Markov chains

    CERN Document Server

    Gaspard, Pierre

    2016-01-01

    The kinetics and thermodynamics of free living copolymerization are studied for processes with rates depending on k monomeric units of the macromolecular chain behind the unit that is attached or detached. In this case, the sequence of monomeric units in the growing copolymer is a kth-order Markov chain. In the regime of steady growth, the statistical properties of the sequence are determined analytically in terms of the attachment and detachment rates. In this way, the mean growth velocity as well as the thermodynamic entropy production and the sequence disorder can be calculated systematically. These different properties are also investigated in the regime of depolymerization where the macromolecular chain is dissolved by the surrounding solution. In this regime, the entropy production is shown to satisfy Landauer's principle.

  10. Growth and Dissolution of Macromolecular Markov Chains

    Science.gov (United States)

    Gaspard, Pierre

    2016-07-01

    The kinetics and thermodynamics of free living copolymerization are studied for processes with rates depending on k monomeric units of the macromolecular chain behind the unit that is attached or detached. In this case, the sequence of monomeric units in the growing copolymer is a kth-order Markov chain. In the regime of steady growth, the statistical properties of the sequence are determined analytically in terms of the attachment and detachment rates. In this way, the mean growth velocity as well as the thermodynamic entropy production and the sequence disorder can be calculated systematically. These different properties are also investigated in the regime of depolymerization where the macromolecular chain is dissolved by the surrounding solution. In this regime, the entropy production is shown to satisfy Landauer's principle.

  11. Dextran: A promising macromolecular drug carrier

    Directory of Open Access Journals (Sweden)

    Dhaneshwar Suneela

    2006-01-01

    Full Text Available Over the past three decades intensive efforts have been made to design novel systems able to deliver the drug more effectively to the target site. The ongoing intense search for novel and innovative drug delivery systems is predominantly a consequence of the well-established fact that the conventional dosage forms are not sufficiently effective in conveying the drug compound to its site of action and once in the target area, in releasing the active agent over a desired period of time. The potential use of macromolecular prodrugs as a means of achieving targeted drug delivery has attracted considerable interest in recent years. Macromolecules such as antibodies, lipoproteins, lectins, proteins, polypeptides, polysaccharides, natural as well as synthetic polymers offer potential applicabilities as high molecular weight carriers for various therapeutically active compounds. Dextrans serve as one of the most promising macromolecular carrier candidates for a wide variety of therapeutic agents due to their excellent physico-chemical properties and physiological acceptance. The present contribution attempts to review various features of the dextran carrier like its source, structural and physico-chemical characteristics, pharmacokinetic fate and its applications as macromolecular carrier with special emphasis on dextran prodrugs.

  12. Smoothing techniques for macromolecular global optimization

    Energy Technology Data Exchange (ETDEWEB)

    More, J.J.; Wu, Zhijun

    1995-09-01

    We study global optimization problems that arise in macromolecular modeling, and the solution of these problems via continuation and smoothing. Our results unify and extend the theory associated with the use of the Gaussian transform for smoothing. We show that the, Gaussian transform can be viewed as a special case of a generalized transform and that these generalized transforms share many of the properties of the Gaussian transform. We also show that the smoothing behavior of the generalized transform can be studied in terms of the Fourier transform and that these results indicate that the Gaussian transform has superior smoothing properties.

  13. Celebrating macromolecular crystallography: A personal perspective

    Directory of Open Access Journals (Sweden)

    Abad-Zapatero, Celerino

    2015-04-01

    Full Text Available The twentieth century has seen an enormous advance in the knowledge of the atomic structures that surround us. The discovery of the first crystal structures of simple inorganic salts by the Braggs in 1914, using the diffraction of X-rays by crystals, provided the critical elements to unveil the atomic structure of matter. Subsequent developments in the field leading to macromolecular crystallography are presented with a personal perspective, related to the cultural milieu of Spain in the late 1950’s. The journey of discovery of the author, as he developed professionally, is interwoven with the expansion of macromolecular crystallography from the first proteins (myoglobin, hemoglobin to the ‘coming of age’ of the field in 1971 and the discoveries that followed, culminating in the determination of the structure of the ribosomes at the turn of the century. A perspective is presented exploring the future of the field and also a reflection about the future generations of Spanish scientists.El siglo XX ha sido testigo del increíble avance que ha experimentado el conocimiento de la estructura atómica de la materia que nos rodea. El descubrimiento de las primeras estructuras atómicas de sales inorgánicas por los Bragg en 1914, empleando difracción de rayos X con cristales, proporcionó los elementos clave para alcanzar tal conocimiento. Posteriores desarrollos en este campo, que condujeron a la cristalografía macromolecular, se presentan aquí desde una perspectiva personal, relacionada con el contexto cultural de la España de la década de los 50. La experiencia del descubrimiento científico, durante mi desarrollo profesional, se integra en el desarrollo de la cristalografía macromolecular, desde las primeras proteínas (míoglobina y hemoglobina, hasta su madurez en 1971 que, con los posteriores descubrimientos, culmina con la determinación del la estructura del ribosoma. Asimismo, se explora el futuro de esta disciplina y se

  14. Remodeling A School Shop?

    Science.gov (United States)

    Baker, G. E.

    1970-01-01

    Presents guidelines for remodeling a school shop combining major considerations of funds, program changes, class management, and flexibility, with the needs of wiring, painting, and placement of equipment. (Author)

  15. Multiscale macromolecular simulation: role of evolving ensembles.

    Science.gov (United States)

    Singharoy, A; Joshi, H; Ortoleva, P J

    2012-10-22

    Multiscale analysis provides an algorithm for the efficient simulation of macromolecular assemblies. This algorithm involves the coevolution of a quasiequilibrium probability density of atomic configurations and the Langevin dynamics of spatial coarse-grained variables denoted order parameters (OPs) characterizing nanoscale system features. In practice, implementation of the probability density involves the generation of constant OP ensembles of atomic configurations. Such ensembles are used to construct thermal forces and diffusion factors that mediate the stochastic OP dynamics. Generation of all-atom ensembles at every Langevin time step is computationally expensive. Here, multiscale computation for macromolecular systems is made more efficient by a method that self-consistently folds in ensembles of all-atom configurations constructed in an earlier step, history, of the Langevin evolution. This procedure accounts for the temporal evolution of these ensembles, accurately providing thermal forces and diffusions. It is shown that efficiency and accuracy of the OP-based simulations is increased via the integration of this historical information. Accuracy improves with the square root of the number of historical timesteps included in the calculation. As a result, CPU usage can be decreased by a factor of 3-8 without loss of accuracy. The algorithm is implemented into our existing force-field based multiscale simulation platform and demonstrated via the structural dynamics of viral capsomers.

  16. Macromolecular recognition in the Protein Data Bank

    Energy Technology Data Exchange (ETDEWEB)

    Janin, Joël, E-mail: joel.janin@ibbmc.u-psud.fr [Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France); Institut de Biochimie et Biologie Moléculaire et Cellulaire, UMR8619, Bâtiment 430, Université Paris-Sud, 91405 Orsay (France); Rodier, Francis [Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France); Chakrabarti, Pinak [Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054 (India); Bahadur, Ranjit P. [Institut de Biochimie et Biologie Moléculaire et Cellulaire, UMR8619, Bâtiment 430, Université Paris-Sud, 91405 Orsay (France); Department of Biochemistry, Bose Institute, P-1/12 CIT Scheme VIIM, Calcutta 700 054 (India); Laboratoire d’Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette (France)

    2007-01-01

    X-ray structures in the PDB illustrate both the specific recognition of two polypeptide chains in protein–protein complexes and dimeric proteins and their nonspecific interaction at crystal contacts. Crystal structures deposited in the Protein Data Bank illustrate the diversity of biological macromolecular recognition: transient interactions in protein–protein and protein–DNA complexes and permanent assemblies in homodimeric proteins. The geometric and physical chemical properties of the macromolecular interfaces that may govern the stability and specificity of recognition are explored in complexes and homodimers compared with crystal-packing interactions. It is found that crystal-packing interfaces are usually much smaller; they bury fewer atoms and are less tightly packed than in specific assemblies. Standard-size interfaces burying 1200–2000 Å{sup 2} of protein surface occur in protease–inhibitor and antigen–antibody complexes that assemble with little or no conformation changes. Short-lived electron-transfer complexes have small interfaces; the larger size of the interfaces observed in complexes involved in signal transduction and homodimers correlates with the presence of conformation changes, often implicated in biological function. Results of the CAPRI (critical assessment of predicted interactions) blind prediction experiment show that docking algorithms efficiently and accurately predict the mode of assembly of proteins that do not change conformation when they associate. They perform less well in the presence of large conformation changes and the experiment stimulates the development of novel procedures that can handle such changes.

  17. Rotation-Induced Macromolecular Spooling of DNA

    Directory of Open Access Journals (Sweden)

    Tyler N. Shendruk

    2017-07-01

    Full Text Available Genetic information is stored in a linear sequence of base pairs; however, thermal fluctuations and complex DNA conformations such as folds and loops make it challenging to order genomic material for in vitro analysis. In this work, we discover that rotation-induced macromolecular spooling of DNA around a rotating microwire can monotonically order genomic bases, overcoming this challenge. We use single-molecule fluorescence microscopy to directly visualize long DNA strands deforming and elongating in shear flow near a rotating microwire, in agreement with numerical simulations. While untethered DNA is observed to elongate substantially, in agreement with our theory and numerical simulations, strong extension of DNA becomes possible by introducing tethering. For the case of tethered polymers, we show that increasing the rotation rate can deterministically spool a substantial portion of the chain into a fully stretched, single-file conformation. When applied to DNA, the fraction of genetic information sequentially ordered on the microwire surface will increase with the contour length, despite the increased entropy. This ability to handle long strands of DNA is in contrast to modern DNA sample preparation technologies for sequencing and mapping, which are typically restricted to comparatively short strands, resulting in challenges in reconstructing the genome. Thus, in addition to discovering new rotation-induced macromolecular dynamics, this work inspires new approaches to handling genomic-length DNA strands.

  18. Rotation-Induced Macromolecular Spooling of DNA

    Science.gov (United States)

    Shendruk, Tyler N.; Sean, David; Berard, Daniel J.; Wolf, Julian; Dragoman, Justin; Battat, Sophie; Slater, Gary W.; Leslie, Sabrina R.

    2017-07-01

    Genetic information is stored in a linear sequence of base pairs; however, thermal fluctuations and complex DNA conformations such as folds and loops make it challenging to order genomic material for in vitro analysis. In this work, we discover that rotation-induced macromolecular spooling of DNA around a rotating microwire can monotonically order genomic bases, overcoming this challenge. We use single-molecule fluorescence microscopy to directly visualize long DNA strands deforming and elongating in shear flow near a rotating microwire, in agreement with numerical simulations. While untethered DNA is observed to elongate substantially, in agreement with our theory and numerical simulations, strong extension of DNA becomes possible by introducing tethering. For the case of tethered polymers, we show that increasing the rotation rate can deterministically spool a substantial portion of the chain into a fully stretched, single-file conformation. When applied to DNA, the fraction of genetic information sequentially ordered on the microwire surface will increase with the contour length, despite the increased entropy. This ability to handle long strands of DNA is in contrast to modern DNA sample preparation technologies for sequencing and mapping, which are typically restricted to comparatively short strands, resulting in challenges in reconstructing the genome. Thus, in addition to discovering new rotation-induced macromolecular dynamics, this work inspires new approaches to handling genomic-length DNA strands.

  19. The role of macromolecular stability in desiccation tolerance

    NARCIS (Netherlands)

    Wolkers, W.F.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular st

  20. The role of macromolecular stability in desiccation tolerance.

    NARCIS (Netherlands)

    Wolkers, W.

    1998-01-01

    The work presented in this thesis concerns a study on the molecular interactions that play a role in the macromolecular stability of desiccation-tolerant higher plant organs. Fourier transform infrared microspectroscopy was used as the main experimental technique to assess macromolecular structures

  1. Echocardiographic evaluation of pressure overload-induced cardiac remodeling in mice using different ultrasound machines%小动物超声仪与临床用超声仪评价小鼠心脏重构的对比分析

    Institute of Scientific and Technical Information of China (English)

    赵静; 曾智; 颜亮; 纪丽景; 罗滔; 宾建平; 廖禹林

    2011-01-01

    目的 比较不同类型超声仪对小鼠压力负荷下心脏重构的评价结果.方法 C57 BL/6小鼠18只,随机分为假手术(sham)组和主动脉弓缩窄(TAC)组,每组9只.手术8周后,首先应用连接15L8高频探头的临床用西门子超声仪测定TAC组小鼠心功能,并比较清醒和麻醉状态下的差异.然后比较西门子超声仪和小动物用高分辨超声仪(Vevo770)对心功能评价的影响.结果 与清醒状态相比,异氟烷吸入麻醉小鼠的心率和左室短轴缩短率显著降低(P<0.001),而左室内径显著增加(P<0.05).但与相应的sham组比较,两种仪器都可以较敏感地反映TAC组的心脏重构.与西门子超声仪相比,小动物超声仪的分辨率明显增高,并可通过二尖瓣血流频谱图评价左室舒张功能,但暂不能在小鼠清醒状态下评价心功能.结论 麻醉本身会降低心功能,但在反映干预手段对心脏重构的影响程度上与清醒状态下有可比性.高分辨小动物超声仪在评价左室舒张功能方面优于西门子超声仪.%To compare the results of echocardiographic evaluation of pressure overload-induced cardiac remodeling in mice using different ultrasound machines. Methods Eighteen C57 BL/6 mice were randomly divided into the sham-operated and the transverse aortic constriction (TAC) groups (n=9). Eight weeks after the operation, the cardiac function of TAC group was evaluated using Siemens ultrasonic instrument with 15L8 probe and the differences between the awake and anesthetized states were compared. The heart rate, left ventricular (LV) dimensions, systolic and diastolic functions were measured in both sham-operated and TAC groups using the Siemens ultrasonic instrument and a high-resolution ultrasonic imaging system for small animals (Vevo 770). Results Compared with the mice in wakefulness, the anesthetized mice showed significantly decreased heart rate and LV fractional shortening (P<0.001) and markedly increased LV end

  2. Functional Sub-states by High-pressure Macromolecular Crystallography.

    Science.gov (United States)

    Dhaussy, Anne-Claire; Girard, Eric

    2015-01-01

    At the molecular level, high-pressure perturbation is of particular interest for biological studies as it allows trapping conformational substates. Moreover, within the context of high-pressure adaptation of deep-sea organisms, it allows to decipher the molecular determinants of piezophily. To provide an accurate description of structural changes produced by pressure in a macromolecular system, developments have been made to adapt macromolecular crystallography to high-pressure studies. The present chapter is an overview of results obtained so far using high-pressure macromolecular techniques, from nucleic acids to virus capsid through monomeric as well as multimeric proteins.

  3. When Machines Design Machines!

    DEFF Research Database (Denmark)

    2011-01-01

    Until recently we were the sole designers, alone in the driving seat making all the decisions. But, we have created a world of complexity way beyond human ability to understand, control, and govern. Machines now do more trades than humans on stock markets, they control our power, water, gas...... and food supplies, manage our elevators, microclimates, automobiles and transport systems, and manufacture almost everything. It should come as no surprise that machines are now designing machines. The chips that power our computers and mobile phones, the robots and commercial processing plants on which we...... depend, all are now largely designed by machines. So what of us - will be totally usurped, or are we looking at a new symbiosis with human and artificial intelligences combined to realise the best outcomes possible. In most respects we have no choice! Human abilities alone cannot solve any of the major...

  4. Perturbation-based Markovian transmission model for probing allosteric dynamics of large macromolecular assembling: a study of GroEL-GroES.

    Directory of Open Access Journals (Sweden)

    Hsiao-Mei Lu

    2009-10-01

    Full Text Available Large macromolecular assemblies are often important for biological processes in cells. Allosteric communications between different parts of these molecular machines play critical roles in cellular signaling. Although studies of the topology and fluctuation dynamics of coarse-grained residue networks can yield important insights, they do not provide characterization of the time-dependent dynamic behavior of these macromolecular assemblies. Here we develop a novel approach called Perturbation-based Markovian Transmission (PMT model to study globally the dynamic responses of the macromolecular assemblies. By monitoring simultaneous responses of all residues (>8,000 across many (>6 decades of time spanning from the initial perturbation until reaching equilibrium using a Krylov subspace projection method, we show that this approach can yield rich information. With criteria based on quantitative measurements of relaxation half-time, flow amplitude change, and oscillation dynamics, this approach can identify pivot residues that are important for macromolecular movement, messenger residues that are key to signal mediating, and anchor residues important for binding interactions. Based on a detailed analysis of the GroEL-GroES chaperone system, we found that our predictions have an accuracy of 71-84% judged by independent experimental studies reported in the literature. This approach is general and can be applied to other large macromolecular machineries such as the virus capsid and ribosomal complex.

  5. Sequential recovery of macromolecular components of the nucleolus.

    Science.gov (United States)

    Bai, Baoyan; Laiho, Marikki

    2015-01-01

    The nucleolus is involved in a number of cellular processes of importance to cell physiology and pathology, including cell stress responses and malignancies. Studies of macromolecular composition of the nucleolus depend critically on the efficient extraction and accurate quantification of all macromolecular components (e.g., DNA, RNA, and protein). We have developed a TRIzol-based method that efficiently and simultaneously isolates these three macromolecular constituents from the same sample of purified nucleoli. The recovered and solubilized protein can be accurately quantified by the bicinchoninic acid assay and assessed by polyacrylamide gel electrophoresis or by mass spectrometry. We have successfully applied this approach to extract and quantify the responses of all three macromolecular components in nucleoli after drug treatments of HeLa cells, and conducted RNA-Seq analysis of the nucleolar RNA.

  6. An upper limit for macromolecular crowding effects

    Directory of Open Access Journals (Sweden)

    Miklos Andrew C

    2011-05-01

    Full Text Available Abstract Background Solutions containing high macromolecule concentrations are predicted to affect a number of protein properties compared to those properties in dilute solution. In cells, these macromolecular crowders have a large range of sizes and can occupy 30% or more of the available volume. We chose to study the stability and ps-ns internal dynamics of a globular protein whose radius is ~2 nm when crowded by a synthetic microgel composed of poly(N-isopropylacrylamide-co-acrylic acid with particle radii of ~300 nm. Results Our studies revealed no change in protein rotational or ps-ns backbone dynamics and only mild (~0.5 kcal/mol at 37°C, pH 5.4 stabilization at a volume occupancy of 70%, which approaches the occupancy of closely packing spheres. The lack of change in rotational dynamics indicates the absence of strong crowder-protein interactions. Conclusions Our observations are explained by the large size discrepancy between the protein and crowders and by the internal structure of the microgels, which provide interstitial spaces and internal pores where the protein can exist in a dilute solution-like environment. In summary, microgels that interact weakly with proteins do not strongly influence protein dynamics or stability because these large microgels constitute an upper size limit on crowding effects.

  7. Macromolecular components of tomato fruit pectin.

    Science.gov (United States)

    Fishman, M L; Gross, K C; Gillespie, D T; Sondey, S M

    1989-10-01

    Chelate and alkaline-soluble pectin extracted from cell walls of pericarp tissue from mature green, turning, and red ripe (Lycopersicon esculentum Mill.) fruit (cv. Rutgers), were studied by high-performance size-exclusion chromatography. Computer-aided curve fitting of the chromatograms to a series of Gaussian-shaped components revealed that pectin from all fractions was composed of a linear combination of five macromolecular-sized species. The relative sizes of these macromolecules as obtained from their radii of gyration were 1:2:4:8:16. Dialysis against 0.05 M NaCl induced partial dissociation of the biopolymers. Apparently, the weight fraction of smaller sized species increased at the expense of larger ones. Also, the dissociation produced low-molecular-weight fragments. Behavior in the presence of 0.05 M NaCl led to the conclusion that cell wall pectin acted as if it were an aggregated mosaic, held together at least partially through noncovalent interactions.

  8. The solvent component of macromolecular crystals

    Energy Technology Data Exchange (ETDEWEB)

    Weichenberger, Christian X. [European Academy of Bozen/Bolzano (EURAC), Viale Druso 1, Bozen/Bolzano, I-39100 Südtirol/Alto Adige (Italy); Afonine, Pavel V. [Lawrence Berkeley National Laboratory (LBNL), 1 Cyclotron Road, Mail Stop 64R0121, Berkeley, CA 94720 (United States); Kantardjieff, Katherine [California State University, San Marcos, CA 92078 (United States); Rupp, Bernhard, E-mail: br@hofkristallamt.org [k.-k. Hofkristallamt, 991 Audrey Place, Vista, CA 92084 (United States); Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck (Austria)

    2015-04-30

    On average, the mother liquor or solvent and its constituents occupy about 50% of a macromolecular crystal. Ordered as well as disordered solvent components need to be accurately accounted for in modelling and refinement, often with considerable complexity. The mother liquor from which a biomolecular crystal is grown will contain water, buffer molecules, native ligands and cofactors, crystallization precipitants and additives, various metal ions, and often small-molecule ligands or inhibitors. On average, about half the volume of a biomolecular crystal consists of this mother liquor, whose components form the disordered bulk solvent. Its scattering contributions can be exploited in initial phasing and must be included in crystal structure refinement as a bulk-solvent model. Concomitantly, distinct electron density originating from ordered solvent components must be correctly identified and represented as part of the atomic crystal structure model. Herein, are reviewed (i) probabilistic bulk-solvent content estimates, (ii) the use of bulk-solvent density modification in phase improvement, (iii) bulk-solvent models and refinement of bulk-solvent contributions and (iv) modelling and validation of ordered solvent constituents. A brief summary is provided of current tools for bulk-solvent analysis and refinement, as well as of modelling, refinement and analysis of ordered solvent components, including small-molecule ligands.

  9. Immunoregulation of bone remodelling.

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-05-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also.

  10. Macromolecular networks and intelligence in microorganisms

    Directory of Open Access Journals (Sweden)

    Hans V Westerhoff

    2014-07-01

    Full Text Available Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of Information and Communication Technology (ICT: they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call intelligence. Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as human and brain out of the defining features of intelligence, all forms of life – from microbes to humans – exhibit some or all characteristics consistent with intelligence. We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo.

  11. Macromolecular networks and intelligence in microorganisms

    Science.gov (United States)

    Westerhoff, Hans V.; Brooks, Aaron N.; Simeonidis, Evangelos; García-Contreras, Rodolfo; He, Fei; Boogerd, Fred C.; Jackson, Victoria J.; Goncharuk, Valeri; Kolodkin, Alexey

    2014-01-01

    Living organisms persist by virtue of complex interactions among many components organized into dynamic, environment-responsive networks that span multiple scales and dimensions. Biological networks constitute a type of information and communication technology (ICT): they receive information from the outside and inside of cells, integrate and interpret this information, and then activate a response. Biological networks enable molecules within cells, and even cells themselves, to communicate with each other and their environment. We have become accustomed to associating brain activity – particularly activity of the human brain – with a phenomenon we call “intelligence.” Yet, four billion years of evolution could have selected networks with topologies and dynamics that confer traits analogous to this intelligence, even though they were outside the intercellular networks of the brain. Here, we explore how macromolecular networks in microbes confer intelligent characteristics, such as memory, anticipation, adaptation and reflection and we review current understanding of how network organization reflects the type of intelligence required for the environments in which they were selected. We propose that, if we were to leave terms such as “human” and “brain” out of the defining features of “intelligence,” all forms of life – from microbes to humans – exhibit some or all characteristics consistent with “intelligence.” We then review advances in genome-wide data production and analysis, especially in microbes, that provide a lens into microbial intelligence and propose how the insights derived from quantitatively characterizing biomolecular networks may enable synthetic biologists to create intelligent molecular networks for biotechnology, possibly generating new forms of intelligence, first in silico and then in vivo. PMID:25101076

  12. Macromolecular Topography Leaps into the Digital Age

    Science.gov (United States)

    Lovelace, J.; Bellamy, H.; Snell, E. H.; Borgstahl, G.

    2003-01-01

    A low-cost, real-time digital topography system is under development which will replace x-ray film and nuclear emulsion plates. The imaging system is based on an inexpensive surveillance camera that offers a 1000x1000 array of 8 im square pixels, anti-blooming circuitry, and very quick read out. Currently, the system directly converts x-rays to an image with no phosphor. The system is small and light and can be easily adapted to work with other crystallographic equipment. Preliminary images have been acquired of cubic insulin at the NSLS x26c beam line. NSLS x26c was configured for unfocused monochromatic radiation. Six reflections were collected with stills spaced from 0.002 to 0.001 degrees apart across the entire oscillation range that the reflections were in diffracting condition. All of the reflections were rotated to the vertical to reduce Lorentz and beam related effects. This particular CCD is designed for short exposure applications (much less than 1 sec) and so has a relatively high dark current leading to noisy raw images. The images are processed to remove background and other system noise with a multi-step approach including the use of wavelets, histogram, and mean window filtering. After processing, animations were constructed with the corresponding reflection profile to show the diffraction of the crystal volume vs. the oscillation angle as well as composite images showing the parts of the crystal with the strongest diffraction for each reflection. The final goal is to correlate features seen in reflection profiles captured with fine phi slicing to those seen in the topography images. With this development macromolecular topography finally comes into the digital age.

  13. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    2017-01-01

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance?

  14. Macromolecular Antioxidants and Dietary Fiber in Edible Seaweeds.

    Science.gov (United States)

    Sanz-Pintos, Nerea; Pérez-Jiménez, Jara; Buschmann, Alejandro H; Vergara-Salinas, José Rodrigo; Pérez-Correa, José Ricardo; Saura-Calixto, Fulgencio

    2017-02-01

    Seaweeds are rich in different bioactive compounds with potential uses in drugs, cosmetics and the food industry. The objective of this study was to analyze macromolecular antioxidants or nonextractable polyphenols, in several edible seaweed species collected in Chile (Gracilaria chilensis, Callophyllis concepcionensis, Macrocystis pyrifera, Scytosyphon lomentaria, Ulva sp. and Enteromorpha compressa), including their 1st HPLC characterization. Macromolecular antioxidants are commonly ignored in studies of bioactive compounds. They are associated with insoluble dietary fiber and exhibit significant biological activity, with specific features that are different from those of both dietary fiber and extractable polyphenols. We also evaluated extractable polyphenols and dietary fiber, given their relationship with macromolecular antioxidants. Our results show that macromolecular antioxidants are a major polyphenol fraction (averaging 42% to total polyphenol content), with hydroxycinnamic acids, hydroxybenzoic acids and flavonols being the main constituents. This fraction also showed remarkable antioxidant capacity, as determined by 2 complementary assays. The dietary fiber content was over 50% of dry weight, with some samples exhibiting the target proportionality between soluble and insoluble dietary fiber for adequate nutrition. Overall, our data show that seaweed could be an important source of commonly ignored macromolecular antioxidants. © 2017 Institute of Food Technologists®.

  15. Remodeling with the sun

    Energy Technology Data Exchange (ETDEWEB)

    Bodzin, S. [ed.

    1997-05-01

    Remodeling is the perfect time to improve daylighting, direct gain heating and shading with passive solar techniques. It can also provide the best opportunity to add solar water heating or even photoboltaics to a home. This article describes addition of such energy efficient plans to a home in terms of what is needed and what the benefits are: adding windows, North glass, east and west glass, south glass, daylighting, the roof, shingles and roofing tiles, walls and floors, solar hot water, photovoltaics. Two side bars discuss the sunplace: a passive solar room and angles and overhangs.

  16. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  17. Adverse Remodeling and Reverse Remodeling After Myocardial Infarction.

    Science.gov (United States)

    Bhatt, Ankeet S; Ambrosy, Andrew P; Velazquez, Eric J

    2017-08-01

    The purpose of this review it to summarize the current literature on remodeling after myocardial infarction, inclusive of pathophysiological considerations, imaging modalities, treatment strategies, and future directions. As patients continue to live longer after myocardial infarction (MI), the prevalence of post-MI heart failure continues to rise. Changes in the left ventricle (LV) after MI involve complex interactions between cellular and extracellular components, under neurohormonal regulation. Treatments to prevent adverse LV remodeling and promote reverse remodeling in the post-MI setting include early revascularization, pharmacotherapy aimed at neurohormonal blockade, and device-based therapies that address ventricular dyssynchrony. Despite varying definitions of adverse LV remodeling examined across multiple imaging modalities, the presence of an enlarged LV cavity and/or reduced ejection fraction is consistently associated with poor clinical outcomes. Advances in our knowledge of the neurohormonal regulation of adverse cardiac remodeling have been instrumental in generating therapies aimed at arresting adverse remodeling and promoting reserve remodeling. Further investigation into other specific mechanisms of adverse LV remodeling and pathways to disrupt these mechanisms is ongoing and may provide incremental benefit to current evidence-based therapies.

  18. Macromolecular crystallography beamline X25 at the NSLS.

    Science.gov (United States)

    Héroux, Annie; Allaire, Marc; Buono, Richard; Cowan, Matthew L; Dvorak, Joseph; Flaks, Leon; Lamarra, Steven; Myers, Stuart F; Orville, Allen M; Robinson, Howard H; Roessler, Christian G; Schneider, Dieter K; Shea-McCarthy, Grace; Skinner, John M; Skinner, Michael; Soares, Alexei S; Sweet, Robert M; Berman, Lonny E

    2014-05-01

    Beamline X25 at the NSLS is one of the five beamlines dedicated to macromolecular crystallography operated by the Brookhaven National Laboratory Macromolecular Crystallography Research Resource group. This mini-gap insertion-device beamline has seen constant upgrades for the last seven years in order to achieve mini-beam capability down to 20 µm × 20 µm. All major components beginning with the radiation source, and continuing along the beamline and its experimental hutch, have changed to produce a state-of-the-art facility for the scientific community.

  19. To Remodel or To Build?

    Science.gov (United States)

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  20. Machine Translation

    Institute of Scientific and Technical Information of China (English)

    张严心

    2015-01-01

    As a kind of ancillary translation tool, Machine Translation has been paid increasing attention to and received different kinds of study by a great deal of researchers and scholars for a long time. To know the definition of Machine Translation and to analyse its benefits and problems are significant for translators in order to make good use of Machine Translation, and helpful to develop and consummate Machine Translation Systems in the future.

  1. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  2. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  3. Generating triangulated macromolecular surfaces by Euclidean Distance Transform.

    Directory of Open Access Journals (Sweden)

    Dong Xu

    Full Text Available Macromolecular surfaces are fundamental representations of their three-dimensional geometric shape. Accurate calculation of protein surfaces is of critical importance in the protein structural and functional studies including ligand-protein docking and virtual screening. In contrast to analytical or parametric representation of macromolecular surfaces, triangulated mesh surfaces have been proved to be easy to describe, visualize and manipulate by computer programs. Here, we develop a new algorithm of EDTSurf for generating three major macromolecular surfaces of van der Waals surface, solvent-accessible surface and molecular surface, using the technique of fast Euclidean Distance Transform (EDT. The triangulated surfaces are constructed directly from volumetric solids by a Vertex-Connected Marching Cube algorithm that forms triangles from grid points. Compared to the analytical result, the relative error of the surface calculations by EDTSurf is <2-4% depending on the grid resolution, which is 1.5-4 times lower than the methods in the literature; and yet, the algorithm is faster and costs less computer memory than the comparative methods. The improvements in both accuracy and speed of the macromolecular surface determination should make EDTSurf a useful tool for the detailed study of protein docking and structure predictions. Both source code and the executable program of EDTSurf are freely available at http://zhang.bioinformatics.ku.edu/EDTSurf.

  4. Two-center-multipole expansion method: application to macromolecular systems

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Yakubovich, Alexander V.; Solov'yov, Andrey V.;

    2007-01-01

    We propose a theoretical method for the calculation of the interaction energy between macromolecular systems at large distances. The method provides a linear scaling of the computing time with the system size and is considered as an alternative to the well-known fast multipole method. Its...

  5. Understanding the chromatin remodeling code.

    Science.gov (United States)

    Ha, Misook

    2013-10-01

    Remodeling a chromatin structure enables the genetic elements stored in a genome to function in a condition-specific manner and predisposes the interactions between cis-regulatory elements and trans-acting factors. A chromatin signature can be an indicator of the activity of the underlying genetic elements. This paper reviews recent studies showing that the combination and arrangements of chromatin remodeling marks play roles as chromatin code affecting the activity of genetic elements. This paper also reviews recent studies inferring the primary DNA sequence contexts associated with chromatin remodeling that suggest interactions between genetic and epigenetic factors. We conclude that chromatin remodeling, which provides accurate models of gene expression and morphological variations, may help to find the biological marks that cannot be detected by genome-wide association study or genetic study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Simple machines

    CERN Document Server

    Graybill, George

    2007-01-01

    Just how simple are simple machines? With our ready-to-use resource, they are simple to teach and easy to learn! Chocked full of information and activities, we begin with a look at force, motion and work, and examples of simple machines in daily life are given. With this background, we move on to different kinds of simple machines including: Levers, Inclined Planes, Wedges, Screws, Pulleys, and Wheels and Axles. An exploration of some compound machines follows, such as the can opener. Our resource is a real time-saver as all the reading passages, student activities are provided. Presented in s

  7. Stochastic reaction–diffusion algorithms for macromolecular crowding

    Science.gov (United States)

    Sturrock, Marc

    2016-06-01

    Compartment-based (lattice-based) reaction–diffusion algorithms are often used for studying complex stochastic spatio-temporal processes inside cells. In this paper the influence of macromolecular crowding on stochastic reaction–diffusion simulations is investigated. Reaction–diffusion processes are considered on two different kinds of compartmental lattice, a cubic lattice and a hexagonal close packed lattice, and solved using two different algorithms, the stochastic simulation algorithm and the spatiocyte algorithm (Arjunan and Tomita 2010 Syst. Synth. Biol. 4, 35–53). Obstacles (modelling macromolecular crowding) are shown to have substantial effects on the mean squared displacement and average number of molecules in the domain but the nature of these effects is dependent on the choice of lattice, with the cubic lattice being more susceptible to the effects of the obstacles. Finally, improvements for both algorithms are presented.

  8. Controlled architecture for improved macromolecular memory within polymer networks.

    Science.gov (United States)

    DiPasquale, Stephen A; Byrne, Mark E

    2016-08-01

    This brief review analyzes recent developments in the field of living/controlled polymerization and the potential of this technique for creating imprinted polymers with highly structured architecture with macromolecular memory. As a result, it is possible to engineer polymers at the molecular level with increased homogeneity relating to enhanced template binding and transport. Only recently has living/controlled polymerization been exploited to decrease heterogeneity and substantially improve the efficiency of the imprinting process for both highly and weakly crosslinked imprinted polymers. Living polymerization can be utilized to create imprinted networks that are vastly more efficient than similar polymers produced using conventional free radical polymerization, and these improvements increase the role that macromolecular memory can play in the design and engineering of new drug delivery and sensing platforms.

  9. Isotope labeling for NMR studies of macromolecular structure and interactions

    Energy Technology Data Exchange (ETDEWEB)

    Wright, P.E. [Scripps Research Institute, La Jolla, CA (United States)

    1994-12-01

    Implementation of biosynthetic methods for uniform or specific isotope labeling of proteins, coupled with the recent development of powerful heteronuclear multidimensional NMR methods, has led to a dramatic increase in the size and complexity of macromolecular systems that are now amenable to NMR structural analysis. In recent years, a new technology has emerged that combines uniform {sup 13}C, {sup 15}N labeling with heteronuclear multidimensional NMR methods to allow NMR structural studies of systems approaching 25 to 30 kDa in molecular weight. In addition, with the introduction of specific {sup 13}C and {sup 15}N labels into ligands, meaningful NMR studies of complexes of even higher molecular weight have become feasible. These advances usher in a new era in which the earlier, rather stringent molecular weight limitations have been greatly surpassed and NMR can begin to address many central biological problems that involve macromolecular structure, dynamics, and interactions.

  10. Temperature-dependent macromolecular X-ray crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Weik, Martin, E-mail: martin.weik@ibs.fr; Colletier, Jacques-Philippe [CEA, IBS, Laboratoire de Biophysique Moléculaire, F-38054 Grenoble (France); CNRS, UMR5075, F-38027 Grenoble (France); Université Joseph Fourier, F-38000 Grenoble (France)

    2010-04-01

    The dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed. X-ray crystallography provides structural details of biological macromolecules. Whereas routine data are collected close to 100 K in order to mitigate radiation damage, more exotic temperature-controlled experiments in a broader temperature range from 15 K to room temperature can provide both dynamical and structural insights. Here, the dynamical behaviour of crystalline macromolecules and their surrounding solvent as a function of cryo-temperature is reviewed. Experimental strategies of kinetic crystallography are discussed that have allowed the generation and trapping of macromolecular intermediate states by combining reaction initiation in the crystalline state with appropriate temperature profiles. A particular focus is on recruiting X-ray-induced changes for reaction initiation, thus unveiling useful aspects of radiation damage, which otherwise has to be minimized in macromolecular crystallography.

  11. Refinement of macromolecular structures against neutron data with SHELXL2013.

    Science.gov (United States)

    Gruene, Tim; Hahn, Hinrich W; Luebben, Anna V; Meilleur, Flora; Sheldrick, George M

    2014-02-01

    Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [Acta Cryst. (1991), A47, 392-400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures.

  12. The vibron dressing in α-helicoidal macromolecular chains

    Institute of Scientific and Technical Information of China (English)

    D.(C)evizovi(c); S.Galovi(c); A.Reshetnyak; Z.Ivi(c)

    2013-01-01

    We present a study of the physical properties of the vibrational excitation in α-helicoidal macromolecular chains,caused by the interaction with acoustical and optical phonon modes.The influence of the temperature and the basic system parameters on the vibron dressing have been analyzed by employing the simple mean-field approach based on the variational extension of the Lang-Firsov unitary transformation.The applied approach predicts a region in system parameter space where one has an abrupt transition from a partially dressed (light and mobile) to a fully dressed (immobile) vibron state.We found that the boundary of this region depends on system temperature and the type of bond among structural elements in the macromolecular chain.

  13. A macromolecular model for the endothelial surface layer

    Science.gov (United States)

    Harden, James; Danova-Okpetu, Darina; Grest, Gary

    2006-03-01

    The endothelial surface layer (ESL) is a micron-scale macromolecular lining of the luminal side of blood vessels composed of proteoglycans, glycoproteins, polysaccharides and associated plasma proteins all in dynamic equilibrium. It has numerous physiological roles including the regulation of blood flow and microvascular permeability, and active participation in mechanotransduction and stress regulation, coagulation, cell adhesion, and inflammatory response. The dynamic structure and the mechanical properties of the ESL are crucial for many of its physiological properties. We present a topological model for the ESL composed of three basic macromolecular elements: branched proteoglycans, linear polysaccharide chains, and small plasma proteins. The model was studied using non-equilibrium molecular dynamics simulations and compared with scaling theories for associating tethered polymers. We discuss the observed dynamical and mechanical properties of the ESL captured by this model, and the possible physical insight it provides into the physiological behavior of the ESL.

  14. A Strategy for the Development of Macromolecular Nonlinear Optical Materials

    Science.gov (United States)

    1990-01-01

    obsolete. SECURITY CLASSIFICATION OF THIS PAGE STRATEGY FOR THE DEVELOPMENT OF MACROMOLECULAR NONLINEAR OPTICAL MATERIALS Braja K. Mandala , Jan-Chan...materials is significantly different from the conventional inorganic NLO materials. The extent of second order (quadratic) NLO effect such as second...is a criterion of paramount importance for a large second order electro-optic effect in organic materials 8 ,9 . The most common approach to obtain

  15. Facilitating structure determination: workshop on robotics andautomation in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Ralston, Corie; Cork, C.W.; McDermott, G.; Earnest, T.N.

    2006-03-28

    As part of the annual Advanced Light Source (ALS) andStanford Synchrotron Radiation Laboratory (SSRL) Users' Meeting inOctober of this year, the macromolecular crystallography staff at bothsynchrotrons held a joint hands-on workshop to address automation issuesin crystal mounting and data collection at the beamline. This paperdescribes the ALS portion of the workshop, while the accompanying paperreviews the SSRL workshop.

  16. Single-particle cryo-electron microscopy of macromolecular assemblies

    OpenAIRE

    Cheng, Kimberley

    2009-01-01

    In this thesis, single-particle cryo-electron microscopy (cryo-EM) was used to study the structure of three macromolecular assemblies: the two hemocyanin isoforms from Rapana thomasiana, the Pyrococcus furiosus chaperonin, and the ribosome from Escherichia coli. Hemocyanins are large respiratory proteins in arthropods and molluscs. Most molluscan hemocyanins exist as two distinct isoforms composed of related polypeptides. In most species the two isoforms differ in terms of their oligomeric st...

  17. Electric machine

    Science.gov (United States)

    El-Refaie, Ayman Mohamed Fawzi [Niskayuna, NY; Reddy, Patel Bhageerath [Madison, WI

    2012-07-17

    An interior permanent magnet electric machine is disclosed. The interior permanent magnet electric machine comprises a rotor comprising a plurality of radially placed magnets each having a proximal end and a distal end, wherein each magnet comprises a plurality of magnetic segments and at least one magnetic segment towards the distal end comprises a high resistivity magnetic material.

  18. What Macromolecular Crowding Can Do to a Protein

    Science.gov (United States)

    Kuznetsova, Irina M.; Turoverov, Konstantin K.; Uversky, Vladimir N.

    2014-01-01

    The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area. PMID:25514413

  19. REFMAC5 for the refinement of macromolecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Murshudov, Garib N., E-mail: garib@ysbl.york.ac.uk [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Skubák, Pavol [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Lebedev, Andrey A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Pannu, Navraj S. [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Steiner, Roberto A. [Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, London (United Kingdom); Nicholls, Robert A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Winn, Martyn D. [STFC Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Long, Fei; Vagin, Alexei A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom)

    2011-04-01

    The general principles behind the macromolecular crystal structure refinement program REFMAC5 are described. This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part of the CCP4 suite. REFMAC5 utilizes different likelihood functions depending on the diffraction data employed (amplitudes or intensities), the presence of twinning and the availability of SAD/SIRAS experimental diffraction data. To ensure chemical and structural integrity of the refined model, REFMAC5 offers several classes of restraints and choices of model parameterization. Reliable models at resolutions at least as low as 4 Å can be achieved thanks to low-resolution refinement tools such as secondary-structure restraints, restraints to known homologous structures, automatic global and local NCS restraints, ‘jelly-body’ restraints and the use of novel long-range restraints on atomic displacement parameters (ADPs) based on the Kullback–Leibler divergence. REFMAC5 additionally offers TLS parameterization and, when high-resolution data are available, fast refinement of anisotropic ADPs. Refinement in the presence of twinning is performed in a fully automated fashion. REFMAC5 is a flexible and highly optimized refinement package that is ideally suited for refinement across the entire resolution spectrum encountered in macromolecular crystallography.

  20. Macromolecular amplification of binding response in superaptamer hydrogels.

    Science.gov (United States)

    Bai, Wei; Gariano, Nicholas A; Spivak, David A

    2013-05-08

    It is becoming more important to detect ultralow concentrations of analytes for biomedical, environmental, and national security applications. Equally important is that new methods should be easy to use, inexpensive, portable, and if possible allow detection by the naked eye. By and large, detection of low concentrations of analytes cannot be achieved directly but requires signal amplification by catalysts, macromolecules, metal surfaces, or supramolecular aggregates. The rapidly progressing field of macromolecular signal amplification has been advanced using conjugated polymers, chirality in polymers, solvating polymers, and polymerization/depolymerization strategies. A new type of aptamer-based hydrogel with specific response to target proteins presented in this report demonstrates an additional category of macromolecular signal amplification. This superaptamer assembly provides the first example of using protein-specific aptamers to create volume-changing hydrogels with amplified response to the target protein. A remarkable aspect of these superaptamer hydrogels is that volume shrinking is visible to the naked eye down to femtomolar concentrations of protein. This extraordinary macromolecular amplification is attributed to a complex interplay between protein-aptamer supramolecular cross-links and the consequential reduction of excluded volume in the hydrogel. Specific recognition is even maintained in biological matrices such as urine and tears. Furthermore, the gels can be dried for long-term storage and regenerated for use without loss of activity. In practice, the ease of this biomarker detection method offers an alternative to traditional analytical techniques that require sophisticated instrumentation and highly trained personnel.

  1. Macromolecular Assemblage in the Design of a Synthetic AIDS Vaccine

    Science.gov (United States)

    Defoort, Jean-Philippe; Nardelli, Bernardetta; Huang, Wolin; Ho, David D.; Tam, James P.

    1992-05-01

    We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in liposome or micelle, was used to immunize mice and guinea pigs without any adjuvant and found to induce gp120-specific antibodies that neutralize virus infectivity in vitro, elicit cytokine production, and prime CD8^+ cytotoxic T lymphocytes in vivo. Our results show that the macromolecular assemblage approach bears immunological mimicry of the gp120 of HIV virus and may lead to useful vaccines against HIV infection.

  2. microRNAs and Cardiovascular Remodeling.

    Science.gov (United States)

    Ono, Koh

    2015-01-01

    Heart failure (HF) is associated with significant morbidity and mortality attributable largely to structural changes in the heart and with associated cardiac dysfunction. Remodeling is defined as alteration of the mass, dimensions, or shape of the heart (termed cardiac or ventricular remodeling) and vessels (vascular remodeling) in response to hemodynamic load and/or cardiovascular injury in association with neurohormonal activation. Remodeling may be described as physiologic or pathologic; alternatively, remodeling may be classified as adaptive or maladaptive. The importance of remodeling as a pathogenic mechanism has been controversial because factors leading to remodeling as well as the remodeling itself may be major determinants of patients' prognosis. The basic mechanisms of cardiovascular remodeling, and especially the roles of microRNAs in HF progression and vascular diseases, will be reviewed here.

  3. Recent Major Improvements to the ALS Sector 5 MacromolecularCrystallography Beamlines

    Energy Technology Data Exchange (ETDEWEB)

    Morton, Simon A.; Glossinger, James; Smith-Baumann, Alexis; McKean, John P.; Trame, Christine; Dickert, Jeff; Rozales, Anthony; Dauz,Azer; Taylor, John; Zwart, Petrus; Duarte, Robert; Padmore, Howard; McDermott, Gerry; Adams, Paul

    2007-07-01

    Although the Advanced Light Source (ALS) was initially conceived primarily as a low energy (1.9GeV) 3rd generation source of VUV and soft x-ray radiation it was realized very early in the development of the facility that a multipole wiggler source coupled with high quality, (brightness preserving), optics would result in a beamline whose performance across the optimal energy range (5-15keV) for macromolecular crystallography (MX) would be comparable to, or even exceed, that of many existing crystallography beamlines at higher energy facilities. Hence, starting in 1996, a suite of three beamlines, branching off a single wiggler source, was constructed, which together formed the ALS Macromolecular Crystallography Facility. From the outset this facility was designed to cater equally to the needs of both academic and industrial users with a heavy emphasis placed on the development and introduction of high throughput crystallographic tools, techniques, and facilities--such as large area CCD detectors, robotic sample handling and automounting facilities, a service crystallography program, and a tightly integrated, centralized, and highly automated beamline control environment for users. This facility was immediately successful, with the primary Multiwavelength Anomalous Diffraction beamline (5.0.2) in particular rapidly becoming one of the foremost crystallographic facilities in the US--responsible for structures such as the 70S ribosome. This success in-turn triggered enormous growth of the ALS macromolecular crystallography community and spurred the development of five additional ALS MX beamlines all utilizing the newly developed superconducting bending magnets ('superbends') as sources. However in the years since the original Sector 5.0 beamlines were built the performance demands of macromolecular crystallography users have become ever more exacting; with growing emphasis placed on studying larger complexes, more difficult structures, weakly diffracting or

  4. The Machine within the Machine

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    Although Virtual Machines are widespread across CERN, you probably won't have heard of them unless you work for an experiment. Virtual machines - known as VMs - allow you to create a separate machine within your own, allowing you to run Linux on your Mac, or Windows on your Linux - whatever combination you need.   Using a CERN Virtual Machine, a Linux analysis software runs on a Macbook. When it comes to LHC data, one of the primary issues collaborations face is the diversity of computing environments among collaborators spread across the world. What if an institute cannot run the analysis software because they use different operating systems? "That's where the CernVM project comes in," says Gerardo Ganis, PH-SFT staff member and leader of the CernVM project. "We were able to respond to experimentalists' concerns by providing a virtual machine package that could be used to run experiment software. This way, no matter what hardware they have ...

  5. Machine Learning

    CERN Document Server

    CERN. Geneva

    2017-01-01

    Machine learning, which builds on ideas in computer science, statistics, and optimization, focuses on developing algorithms to identify patterns and regularities in data, and using these learned patterns to make predictions on new observations. Boosted by its industrial and commercial applications, the field of machine learning is quickly evolving and expanding. Recent advances have seen great success in the realms of computer vision, natural language processing, and broadly in data science. Many of these techniques have already been applied in particle physics, for instance for particle identification, detector monitoring, and the optimization of computer resources. Modern machine learning approaches, such as deep learning, are only just beginning to be applied to the analysis of High Energy Physics data to approach more and more complex problems. These classes will review the framework behind machine learning and discuss recent developments in the field.

  6. Workshop on algorithms for macromolecular modeling. Final project report, June 1, 1994--May 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Leimkuhler, B.; Hermans, J.; Skeel, R.D.

    1995-07-01

    A workshop was held on algorithms and parallel implementations for macromolecular dynamics, protein folding, and structural refinement. This document contains abstracts and brief reports from that workshop.

  7. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available BACKGROUND: Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins. METHODOLOGY/PRINCIPAL FINDINGS: As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l. CONCLUSIONS/SIGNIFICANCE: We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of

  8. Bringing macromolecular machinery to life using 3D animation.

    Science.gov (United States)

    Iwasa, Janet H

    2015-04-01

    Over the past decade, there has been a rapid rise in the use of three-dimensional (3D) animation to depict molecular and cellular processes. Much of the growth in molecular animation has been in the educational arena, but increasingly, 3D animation software is finding its way into research laboratories. In this review, I will discuss a number of ways in which 3d animation software can play a valuable role in visualizing and communicating macromolecular structures and dynamics. I will also consider the challenges of using animation tools within the research sphere.

  9. BLOOD FLOW AND MACROMOLECULAR TRANSPORT IN CURVED BLOOD VESSELS

    Institute of Scientific and Technical Information of China (English)

    WEI Lan; WEN Gong-bi; TAN Wen-chang

    2006-01-01

    A numerical analysis of the steady/pulsatile flow and macromolecular (such as LDL and Albumin) transport in curved blood vessels was carried out. The computational results predict that the vortex of the secondary flow is time-dependent in the aortic arch.The concentration of macromolecule concentrates at the region of sharp curve, and the wall concentration at the outer part is higher than that at the inner part. Atherosclerosis and thrombosis are prone to develop in such regions with sharp flow.

  10. Machine Learning

    Energy Technology Data Exchange (ETDEWEB)

    Chikkagoudar, Satish; Chatterjee, Samrat; Thomas, Dennis G.; Carroll, Thomas E.; Muller, George

    2017-04-21

    The absence of a robust and unified theory of cyber dynamics presents challenges and opportunities for using machine learning based data-driven approaches to further the understanding of the behavior of such complex systems. Analysts can also use machine learning approaches to gain operational insights. In order to be operationally beneficial, cybersecurity machine learning based models need to have the ability to: (1) represent a real-world system, (2) infer system properties, and (3) learn and adapt based on expert knowledge and observations. Probabilistic models and Probabilistic graphical models provide these necessary properties and are further explored in this chapter. Bayesian Networks and Hidden Markov Models are introduced as an example of a widely used data driven classification/modeling strategy.

  11. Identifying and visualizing macromolecular flexibility in structural biology

    Directory of Open Access Journals (Sweden)

    Martina Palamini

    2016-09-01

    Full Text Available Structural biology comprises a variety of tools to obtain atomic resolution data for the investigation of macromolecules. Conventional structural methodologies including crystallography, NMR and electron microscopy often do not provide sufficient details concerning flexibility and dynamics, even though these aspects are critical for the physiological functions of the systems under investigation. However, the increasing complexity of the molecules studied by structural biology (including large macromolecular assemblies, integral membrane proteins, intrinsically disordered systems, and folding intermediates continuously demands in-depth analyses of the roles of flexibility and conformational specificity involved in interactions with ligands and inhibitors. The intrinsic difficulties in capturing often subtle but critical molecular motions in biological systems have restrained the investigation of flexible molecules into a small niche of structural biology. Introduction of massive technological developments over the recent years, which include time-resolved studies, solution X-ray scattering, and new detectors for cryo-electron microscopy, have pushed the limits of structural investigation of flexible systems far beyond traditional approaches of NMR analysis. By integrating these modern methods with powerful biophysical and computational approaches such as generation of ensembles of molecular models and selective particle picking in electron microscopy, more feasible investigations of dynamic systems are now possible. Using some prominent examples from recent literature, we review how current structural biology methods can contribute useful data to accurately visualize flexibility in macromolecular structures and understand its important roles in regulation of biological processes.

  12. Enzymes as Green Catalysts for Precision Macromolecular Synthesis.

    Science.gov (United States)

    Shoda, Shin-ichiro; Uyama, Hiroshi; Kadokawa, Jun-ichi; Kimura, Shunsaku; Kobayashi, Shiro

    2016-02-24

    The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysaccharides and functionalized polyesters. The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin. These polymerizations are "green" with several respects; nontoxicity of enzyme, high catalyst efficiency, selective reactions under mild conditions using green solvents and renewable starting materials, and producing minimal byproducts. Thus, the enzymatic polymerization is desirable for the environment and contributes to "green polymer chemistry" for maintaining sustainable society.

  13. Critical review and perspective of macromolecularly imprinted polymers.

    Science.gov (United States)

    Kryscio, David R; Peppas, Nicholas A

    2012-02-01

    Molecular recognition is a fundamental and ubiquitous process that is the driving force behind life. Natural recognition elements - including antibodies, enzymes, nucleic acids, and cells - exploit non-covalent interactions to bind to their targets with exceptionally strong affinities. Due to this unparalleled proficiency, scientists have long sought to mimic natural recognition pathways. One promising approach is molecularly imprinted polymers (MIPs), which are fully synthetic systems formed via the crosslinking of organic polymers in the presence of a template molecule, which results in stereo-specific binding sites for this analyte of interest. Macromolecularly imprinted polymers, those synthesized in the presence of macromolecule templates (>1500 Da), are of particular importance because they open up the field for a whole new set of robust diagnostic tools. Although the specific recognition of small-molecular-weight analytes is now considered routine, extension of these efficacious procedures to the protein regime has, thus far, proved challenging. This paper reviews the main approaches employed, highlights studies of interest with an emphasis on recent work, and offers suggestions for future success in the field of macromolecularly imprinted polymers.

  14. The macromolecular crystallography facility at the advanced light source

    Science.gov (United States)

    Earnest, Thomas; Padmore, Howard; Cork, Carl; Behrsing, Rolf; Kim, Sung-Hou

    1996-10-01

    Synchrotron radiation offers several advantages over the use of rotating anode sources for biological crystallography, which allow for the collection of higher-resolution data, substantially more rapid data collection, phasing by multiwavelength anomalous diffraction (MAD) techniques, and time-resolved experiments using polychromatic radiation (Laue diffraction). The use of synchrotron radiation is often necessary to record useful data from crystals which diffract weakly or have very large unit cells. The high brightness and stability characteristics of the advanced light source (ALS) at Lawrence Berkeley National Laboratory, along with the low emittance and long straight sections to accommodate insertion devices present in third generation synchrotrons like the ALS, lead to several advantages in the field of macromolecular crystallography. We are presently constructing a macromolecular crystallography facility at the ALS which is optimized for user-friendliness and high-throughput data collection, with advanced capabilities for MAD and Laue experiments. The X-rays will be directed to three branchlines. A well-equipped support lab will be available for biochemistry, crystal mounting and sample storage, as well as computer hardware and software available, along with staff support, allowing for the complete processing of data on site.

  15. MMDB and VAST+: tracking structural similarities between macromolecular complexes.

    Science.gov (United States)

    Madej, Thomas; Lanczycki, Christopher J; Zhang, Dachuan; Thiessen, Paul A; Geer, Renata C; Marchler-Bauer, Aron; Bryant, Stephen H

    2014-01-01

    The computational detection of similarities between protein 3D structures has become an indispensable tool for the detection of homologous relationships, the classification of protein families and functional inference. Consequently, numerous algorithms have been developed that facilitate structure comparison, including rapid searches against a steadily growing collection of protein structures. To this end, NCBI's Molecular Modeling Database (MMDB), which is based on the Protein Data Bank (PDB), maintains a comprehensive and up-to-date archive of protein structure similarities computed with the Vector Alignment Search Tool (VAST). These similarities have been recorded on the level of single proteins and protein domains, comprising in excess of 1.5 billion pairwise alignments. Here we present VAST+, an extension to the existing VAST service, which summarizes and presents structural similarity on the level of biological assemblies or macromolecular complexes. VAST+ simplifies structure neighboring results and shows, for macromolecular complexes tracked in MMDB, lists of similar complexes ranked by the extent of similarity. VAST+ replaces the previous VAST service as the default presentation of structure neighboring data in NCBI's Entrez query and retrieval system. MMDB and VAST+ can be accessed via http://www.ncbi.nlm.nih.gov/Structure.

  16. Macromolecular Crowding Enhances Thermal Stability of Rabbit Muscle Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    ZHU Jiang; HE Huawei; LI Sen

    2008-01-01

    The effect of dextran on the conformation (or secondary structure) and thermal stability of creatine kinase (CK) was studied using the far-ultraviolet (UV) circular dichroism (CD) spectra.The results showed that lower concentrations of dextran (less than 60 g/L) induced formation of the secondary CK structures.However,the secondary structure content of CK decreased when the dextran concentrations exceeded 60 g/L.Thermally induced transition curves were measured for CK in the presence of different concentrations of dextran by far-UV CD.The thermal transition curves were fitted to a two-state model by a nonlinear,least-squares method to obtain the transition temperature of the unfolding transition.An increase in the tran- sition temperature was observed with the increase of the dextran concentration.These observations qualita-tively accord with predictions of a previously proposed model for the effect of intermolecular excluded volume (macromolecular crowding) on protein stability and conformation.These findings imply that the effects of macromolecular crowding can have an important influence on our understanding of how protein folding oc-curs in vivo.

  17. PRIGo: a new multi-axis goniometer for macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Waltersperger, Sandro; Olieric, Vincent, E-mail: vincent.olieric@psi.ch; Pradervand, Claude [Paul Scherrer Institute, Villigen PSI (Switzerland); Glettig, Wayne [Centre Suisse d’Electronique et Microtechnique SA, Neuchâtel 2002 (Switzerland); Salathe, Marco; Fuchs, Martin R.; Curtin, Adrian; Wang, Xiaoqiang; Ebner, Simon; Panepucci, Ezequiel; Weinert, Tobias [Paul Scherrer Institute, Villigen PSI (Switzerland); Schulze-Briese, Clemens [Dectris Ltd, Baden 5400 (Switzerland); Wang, Meitian, E-mail: vincent.olieric@psi.ch [Paul Scherrer Institute, Villigen PSI (Switzerland)

    2015-05-09

    The design and performance of the new multi-axis goniometer PRIGo developed at the Swiss Light Source at Paul Scherrer Institute is described. The Parallel Robotics Inspired Goniometer (PRIGo) is a novel compact and high-precision goniometer providing an alternative to (mini-)kappa, traditional three-circle goniometers and Eulerian cradles used for sample reorientation in macromolecular crystallography. Based on a combination of serial and parallel kinematics, PRIGo emulates an arc. It is mounted on an air-bearing stage for rotation around ω and consists of four linear positioners working synchronously to achieve x, y, z translations and χ rotation (0–90°), followed by a ϕ stage (0–360°) for rotation around the sample holder axis. Owing to the use of piezo linear positioners and active correction, PRIGo features spheres of confusion of <1 µm, <7 µm and <10 µm for ω, χ and ϕ, respectively, and is therefore very well suited for micro-crystallography. PRIGo enables optimal strategies for both native and experimental phasing crystallographic data collection. Herein, PRIGo hardware and software, its calibration, as well as applications in macromolecular crystallography are described.

  18. Enhancing Endosomal Escape for Intracellular Delivery of Macromolecular Biologic Therapeutics.

    Science.gov (United States)

    Lönn, Peter; Kacsinta, Apollo D; Cui, Xian-Shu; Hamil, Alexander S; Kaulich, Manuel; Gogoi, Khirud; Dowdy, Steven F

    2016-09-08

    Bioactive macromolecular peptides and oligonucleotides have significant therapeutic potential. However, due to their size, they have no ability to enter the cytoplasm of cells. Peptide/Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), can promote uptake of macromolecules via endocytosis. However, overcoming the rate-limiting step of endosomal escape into the cytoplasm remains a major challenge. Hydrophobic amino acid R groups are known to play a vital role in viral escape from endosomes. Here we utilize a real-time, quantitative live cell split-GFP fluorescence complementation phenotypic assay to systematically analyze and optimize a series of synthetic endosomal escape domains (EEDs). By conjugating EEDs to a TAT-PTD/CPP spilt-GFP peptide complementation assay, we were able to quantitatively measure endosomal escape into the cytoplasm of live cells via restoration of GFP fluorescence by intracellular molecular complementation. We found that EEDs containing two aromatic indole rings or one indole ring and two aromatic phenyl groups at a fixed distance of six polyethylene glycol (PEG) units from the TAT-PTD-cargo significantly enhanced cytoplasmic delivery in the absence of cytotoxicity. EEDs address the critical rate-limiting step of endosomal escape in delivery of macromolecular biologic peptide, protein and siRNA therapeutics into cells.

  19. Structure and function insights into the NuRD chromatin remodeling complex.

    Science.gov (United States)

    Torchy, Morgan P; Hamiche, Ali; Klaholz, Bruno P

    2015-07-01

    Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. NuRD is a 1 MDa multi-subunit protein complex which comprises many different subunits, among which histone deacetylases HDAC1/2, ATP-dependent remodeling enzymes CHD3/4, histone chaperones RbAp46/48, CpG-binding proteins MBD2/3, the GATAD2a (p66α) and/or GATAD2b (p66β) and specific DNA-binding proteins MTA1/2/3. Here, we review the currently known crystal and NMR structures of these subunits, the functional data and their relevance for biomedical research considering the implication of NuRD subunits in cancer and various other diseases. The complexity of this macromolecular assembly, and its poorly understood mode of interaction with the nucleosome, the repeating unit of chromatin, illustrate that this complex is a major challenge for structure-function relationship studies which will be tackled best by an integrated biology approach.

  20. Machine testning

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with a laboratory exercise of 3 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercise includes a series of tests carried out by the student on a conventional and a numerically controled lathe, respectively. This document...

  1. Representational Machines

    DEFF Research Database (Denmark)

    Petersson, Dag; Dahlgren, Anna; Vestberg, Nina Lager

    to the enterprises of the medium. This is the subject of Representational Machines: How photography enlists the workings of institutional technologies in search of establishing new iconic and social spaces. Together, the contributions to this edited volume span historical epochs, social environments, technological...

  2. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  3. Adding machine and calculating machine

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In 1642 the French mathematician Blaise Pascal(1623-1662) invented a machine;.that could add and subtract. It had.wheels that each had: 1 to 10 marked off along its circumference. When the wheel at the right, representing units, made one complete circle, it engaged the wheel to its left, represents tens, and moved it forward one notch.

  4. Calcium remodeling in colorectal cancer.

    Science.gov (United States)

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2017-06-01

    Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca(2+) remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca(2+) entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca(2+) homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin

  5. PROFESSOR TEJ PAL SINGH: THE LEGEND OF INDIAN MACROMOLECULAR CRYSTALLOGRAPHY

    Directory of Open Access Journals (Sweden)

    Md. Imtaiyaz Hassan

    2013-12-01

    Full Text Available Professor Tej Pal Singh, an internationally recognized Indian scientist par excellence, is one of the pioneers of Indian macromolecular crystallography. He is a person of significant and enduring accomplishments as a teacher, scientist, administrator and family man. He has developed various methods to crystallize wide varieties of proteins. He has successfully determined crystal structures of lactoferrin, phospholipase A2, lactoperoxidase, peptidoglycan recognition proteins, disintegrin, zinc-α2-glycoprotein and several others including various protein-ligand and protein-protein complexes. He has a remarkably high number of structural entries in protein data bank. He received most of the prestigious awards and honors by Indian Government. This article covers most of his research and other achievements which will be a source of inspiration for young scientific community, motivation for peers and joy for his fellow colleagues and friends.

  6. Identification of macromolecular complexes in cryoelectron tomograms of phantom cells

    Science.gov (United States)

    Frangakis, Achilleas S.; Böhm, Jochen; Förster, Friedrich; Nickell, Stephan; Nicastro, Daniela; Typke, Dieter; Hegerl, Reiner; Baumeister, Wolfgang

    2002-01-01

    Electron tomograms of intact frozen-hydrated cells are essentially three-dimensional images of the entire proteome of the cell, and they depict the whole network of macromolecular interactions. However, this information is not easily accessible because of the poor signal-to-noise ratio of the tomograms and the crowded nature of the cytoplasm. Here, we describe a template matching algorithm that is capable of detecting and identifying macromolecules in tomographic volumes in a fully automated manner. The algorithm is based on nonlinear cross correlation and incorporates elements of multivariate statistical analysis. Phantom cells, i.e., lipid vesicles filled with macromolecules, provide a realistic experimental scenario for an assessment of the fidelity of this approach. At the current resolution of ≈4 nm, macromolecules in the size range of 0.5–1 MDa can be identified with good fidelity. PMID:12391313

  7. Detecting stoichiometry of macromolecular complexes in live cells using FRET

    Science.gov (United States)

    Ben-Johny, Manu; Yue, Daniel N.; Yue, David T.

    2016-01-01

    The stoichiometry of macromolecular interactions is fundamental to cellular signalling yet challenging to detect from living cells. Fluorescence resonance energy transfer (FRET) is a powerful phenomenon for characterizing close-range interactions whereby a donor fluorophore transfers energy to a closely juxtaposed acceptor. Recognizing that FRET measured from the acceptor's perspective reports a related but distinct quantity versus the donor, we utilize the ratiometric comparison of the two to obtain the stoichiometry of a complex. Applying this principle to the long-standing controversy of calmodulin binding to ion channels, we find a surprising Ca2+-induced switch in calmodulin stoichiometry with Ca2+ channels—one calmodulin binds at basal cytosolic Ca2+ levels while two calmodulins interact following Ca2+ elevation. This feature is curiously absent for the related Na channels, also potently regulated by calmodulin. Overall, our assay adds to a burgeoning toolkit to pursue quantitative biochemistry of dynamic signalling complexes in living cells. PMID:27922011

  8. An analysis of fractal geometry of macromolecular gelation

    Institute of Scientific and Technical Information of China (English)

    左榘; 陈天红; 冉少峰; 何炳林; 董宝中; 生文君; 杨恒林

    1996-01-01

    With fractal geometry theory and based on experiments, an analysis of fractal geometry behavior of gelation of macromolecules was carried out. Using the cross-linking copolymerization of styrene-divinylbenzene (DVB) as an example, through the determinations of the evolution of the molecular weight, size and the dependence of scattering intensity on the angle of macromolecules by employing laser and synchrotron small angle X-ray scattering, respectively, this chemical reaction was described quantitatively, its fractal behavior was analyzed and the fractal dimension was also measured. By avoiding the complex theories on gelation, this approach is based on modern physical techniques and theories to perform the analysis of the behavior of fractal geometry of macromolecular gelation and thus is able to reveal the rules of this kind of complicated gelation more essentially and profoundly.

  9. Revealing the macromolecular targets of complex natural products

    Science.gov (United States)

    Reker, Daniel; Perna, Anna M.; Rodrigues, Tiago; Schneider, Petra; Reutlinger, Michael; Mönch, Bettina; Koeberle, Andreas; Lamers, Christina; Gabler, Matthias; Steinmetz, Heinrich; Müller, Rolf; Schubert-Zsilavecz, Manfred; Werz, Oliver; Schneider, Gisbert

    2014-12-01

    Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The technique does not require three-dimensional target models and may be applied to structurally complex natural products. The algorithm dissects the natural products into fragments and infers potential pharmacological targets by comparing the fragments to synthetic reference drugs with known targets. We demonstrate that this approach results in confident predictions. In a prospective validation, we show that fragments of the potent antitumour agent archazolid A, a macrolide from the myxobacterium Archangium gephyra, contain relevant information regarding its polypharmacology. Biochemical and biophysical evaluation confirmed the predictions. The results obtained corroborate the practical applicability of the computational approach to natural product ‘de-orphaning’.

  10. Macromolecularly "Caged" Carbon Nanoparticles for Intracellular Trafficking via Switchable Photoluminescence.

    Science.gov (United States)

    Misra, Santosh K; Srivastava, Indrajit; Tripathi, Indu; Daza, Enrique; Ostadhossein, Fatemeh; Pan, Dipanjan

    2017-02-08

    Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counterionic macromolecular caging and decaging at the nanoscale. A negatively charged uncoated, "bare" CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant molecules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies. Results indicated for the first time that luminescence switchable CNPs can be synthesized for efficient intracellular tracking. This study further supports the origin of photoluminescence in CNP as a surface phenomenon correlated a function of characteristic charged macromolecules.

  11. On macromolecular refinement at subatomic resolution withinteratomic scatterers

    Energy Technology Data Exchange (ETDEWEB)

    Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.; Lunin, Vladimir Y.; Urzhumtsev, Alexandre

    2007-11-09

    A study of the accurate electron density distribution in molecular crystals at subatomic resolution, better than {approx} 1.0 {angstrom}, requires more detailed models than those based on independent spherical atoms. A tool conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8-1.0 {angstrom}, the number of experimental data is insufficient for the full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark datasets gave results comparable in quality with results of multipolar refinement and superior of those for conventional models. Applications to several datasets of both small- and macro-molecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

  12. Protein Coevolution and Isoexpression in Yeast Macromolecular Complexes

    Directory of Open Access Journals (Sweden)

    Laurence Ettwiller

    2007-01-01

    Full Text Available Previous studies in the yeast Saccharomyces cerevisiae have shown that genes encoding subunits of macromolecular complexes have similar evolutionary rates (K and expression levels (E. Besides, it is known that the expression of a gene is a strong predictor of its rate of evolution (i.e., E and K are correlated. Here we show that intracomplex variation of subunit expression correlates with intracomplex variation of their evolutionary rates (using two different measures of dispersion. However, a similar trend was observed for randomized complexes. Therefore, using a mathematical transformation, we created new variables capturing intracomplex variation of both E and K. The values of these new compound variables were smaller for real complexes than for randomized ones. This shows that proteins in complexes tend to have closer expressivities (E and K's simultaneously than in the randomly grouped genes. We speculate about the possible implications of this finding.

  13. [Progress in researches on synthetic antimicrobial macromolecular polymers].

    Science.gov (United States)

    Wei, Gang; Yang, Lihua; Chu, Liangyin

    2010-08-01

    Broad-spectrum antimicrobial peptides provide a new way to address the urgent growing problem of bacterial resistance. However, the limited natural resources and the high cost of extraction and purification of natural antimicrobial peptides can not meet the requirements of clinical application. In order to solve this problem, researchers have utilized two basic common structural features (amphiphilic and cationic) for designing and preparing synthetic antimicrobial macromolecular polymers. During the last decade, several kinds of amphiphilic polymers, including arylamide oligomers, phenylene ethynylenes, polymethacrylates, polynorbornenes as well as nylon-3 polymers have been synthesized. In this paper, the structures, antibacterial activities and selectivities of these polymers are reviewed, and the effects of molecular size, polarity and ratio of hydrophobic groups, positive charge density on antibacterial activity and selectivity are also summarized.

  14. Macromolecular Crystallization with Microfluidic Free-Interface Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Segelke, B

    2005-02-24

    Fluidigm released the Topaz 1.96 and 4.96 crystallization chips in the fall of 2004. Topaz 1.96 and 4.96 are the latest evolution of Fluidigm's microfluidics crystallization technologies that enable ultra low volume rapid screening for macromolecular crystallization. Topaz 1.96 and 4.96 are similar to each other but represent a major redesign of the Topaz system and have of substantially improved ease of automation and ease of use, improved efficiency and even further reduced amount of material needed. With the release of the new Topaz system, Fluidigm continues to set the standard in low volume crystallization screening which is having an increasing impact in the field of structural genomics, and structural biology more generally. In to the future we are likely to see further optimization and increased utility of the Topaz crystallization system, but we are also likely to see further innovation and the emergence of competing technologies.

  15. In-vacuum long-wavelength macromolecular crystallography.

    Science.gov (United States)

    Wagner, Armin; Duman, Ramona; Henderson, Keith; Mykhaylyk, Vitaliy

    2016-03-01

    Structure solution based on the weak anomalous signal from native (protein and DNA) crystals is increasingly being attempted as part of synchrotron experiments. Maximizing the measurable anomalous signal by collecting diffraction data at longer wavelengths presents a series of technical challenges caused by the increased absorption of X-rays and larger diffraction angles. A new beamline at Diamond Light Source has been built specifically for collecting data at wavelengths beyond the capability of other synchrotron macromolecular crystallography beamlines. Here, the theoretical considerations in support of the long-wavelength beamline are outlined and the in-vacuum design of the endstation is discussed, as well as other hardware features aimed at enhancing the accuracy of the diffraction data. The first commissioning results, representing the first in-vacuum protein structure solution, demonstrate the promising potential of the beamline.

  16. Extracting trends from two decades of microgravity macromolecular crystallization history

    Science.gov (United States)

    Judge, Russell A.; Snell, Edward H.; van der Woerd, Mark J.

    2005-01-01

    Since the 1980s hundreds of macromolecular crystal growth experiments have been performed in the reduced acceleration environment of an orbiting spacecraft. Significant enhancements in structural knowledge have resulted from X-ray diffraction of the crystals grown. Similarly, many samples have shown no improvement or degradation in comparison to those grown on the ground. A complex series of interrelated factors affect these experiments and by building a comprehensive archive of the results it was aimed to identify factors that result in success and those that result in failure. Specifically, it was found that dedicated microgravity missions increase the chance of success when compared with those where crystallization took place as a parasitic aspect of the mission. It was also found that the chance of success could not be predicted based on any discernible property of the macromolecule available to us.

  17. Large-volume protein crystal growth for neutron macromolecular crystallography.

    Science.gov (United States)

    Ng, Joseph D; Baird, James K; Coates, Leighton; Garcia-Ruiz, Juan M; Hodge, Teresa A; Huang, Sijay

    2015-04-01

    Neutron macromolecular crystallography (NMC) is the prevailing method for the accurate determination of the positions of H atoms in macromolecules. As neutron sources are becoming more available to general users, finding means to optimize the growth of protein crystals to sizes suitable for NMC is extremely important. Historically, much has been learned about growing crystals for X-ray diffraction. However, owing to new-generation synchrotron X-ray facilities and sensitive detectors, protein crystal sizes as small as in the nano-range have become adequate for structure determination, lessening the necessity to grow large crystals. Here, some of the approaches, techniques and considerations for the growth of crystals to significant dimensions that are now relevant to NMC are revisited. These include experimental strategies utilizing solubility diagrams, ripening effects, classical crystallization techniques, microgravity and theoretical considerations.

  18. NATO Advanced Study Institute on Evolving Methods for Macromolecular Gystallography

    CERN Document Server

    Read, Randy J

    2007-01-01

    X-ray crystallography is the pre-eminent technique for visualizing the structures of macromolecules at atomic resolution. These structures are central to understanding the detailed mechanisms of biological processes, and to discovering novel therapeutics using a structure-based approach. As yet, structures are known for only a small fraction of the proteins encoded by human and pathogenic genomes. To counter the myriad modern threats of disease, there is an urgent need to determine the structures of the thousands of proteins whose structure and function remain unknown. This volume draws on the expertise of leaders in the field of macromolecular crystallography to illuminate the dramatic developments that are accelerating progress in structural biology. Their contributions span the range of techniques from crystallization through data collection, structure solution and analysis, and show how modern high-throughput methods are contributing to a deeper understanding of medical problems.

  19. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  20. Genesis machines

    CERN Document Server

    Amos, Martyn

    2014-01-01

    Silicon chips are out. Today's scientists are using real, wet, squishy, living biology to build the next generation of computers. Cells, gels and DNA strands are the 'wetware' of the twenty-first century. Much smaller and more intelligent, these organic computers open up revolutionary possibilities. Tracing the history of computing and revealing a brave new world to come, Genesis Machines describes how this new technology will change the way we think not just about computers - but about life itself.

  1. Radiation damage to nucleoprotein complexes in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Bury, Charles; Garman, Elspeth F.; Ginn, Helen Mary [University of Oxford, South Parks Road, Oxford OX1 3QU (United Kingdom); Ravelli, Raimond B. G. [Maastricht University, PO Box 616, Maastricht 6200 MD (Netherlands); Carmichael, Ian [University of Notre Dame, Notre Dame, IN 46556 (United States); Kneale, Geoff; McGeehan, John E., E-mail: john.mcgeehan@port.ac.uk [University of Portsmouth, King Henry 1st Street, Portsmouth PO1 2DY (United Kingdom)

    2015-01-30

    Quantitative X-ray induced radiation damage studies employing a model protein–DNA complex revealed a striking partition of damage sites. The DNA component was observed to be far more resistant to specific damage compared with the protein. Significant progress has been made in macromolecular crystallography over recent years in both the understanding and mitigation of X-ray induced radiation damage when collecting diffraction data from crystalline proteins. In contrast, despite the large field that is productively engaged in the study of radiation chemistry of nucleic acids, particularly of DNA, there are currently very few X-ray crystallographic studies on radiation damage mechanisms in nucleic acids. Quantitative comparison of damage to protein and DNA crystals separately is challenging, but many of the issues are circumvented by studying pre-formed biological nucleoprotein complexes where direct comparison of each component can be made under the same controlled conditions. Here a model protein–DNA complex C.Esp1396I is employed to investigate specific damage mechanisms for protein and DNA in a biologically relevant complex over a large dose range (2.07–44.63 MGy). In order to allow a quantitative analysis of radiation damage sites from a complex series of macromolecular diffraction data, a computational method has been developed that is generally applicable to the field. Typical specific damage was observed for both the protein on particular amino acids and for the DNA on, for example, the cleavage of base-sugar N{sub 1}—C and sugar-phosphate C—O bonds. Strikingly the DNA component was determined to be far more resistant to specific damage than the protein for the investigated dose range. At low doses the protein was observed to be susceptible to radiation damage while the DNA was far more resistant, damage only being observed at significantly higher doses.

  2. The Chromodomains of the Chd1 Chromatin Remodeler Regulate DNA Access to the ATPase Motor

    Energy Technology Data Exchange (ETDEWEB)

    Hauk, G.; McKnight, J; Nodelman, I; Bowman, G

    2010-01-01

    Chromatin remodelers are ATP-driven machines that assemble, slide, and remove nucleosomes from DNA, but how the ATPase motors of remodelers are regulated is poorly understood. Here we show that the double chromodomain unit of the Chd1 remodeler blocks DNA binding and activation of the ATPase motor in the absence of nucleosome substrates. The Chd1 crystal structure reveals that an acidic helix joining the chromodomains can pack against a DNA-binding surface of the ATPase motor. Disruption of the chromodomain-ATPase interface prevents discrimination between nucleosomes and naked DNA and reduces the reliance on the histone H4 tail for nucleosome sliding. We propose that the chromodomains allow Chd1 to distinguish between nucleosomes and naked DNA by physically gating access to the ATPase motor, and we hypothesize that related ATPase motors may employ a similar strategy to discriminate among DNA-containing substrates.

  3. The remodeling transient and the calcium economy.

    Science.gov (United States)

    Aloia, J F; Arunabh-Talwar, S; Pollack, S; Yeh, J K

    2008-07-01

    The remodeling transient describes a change in bone mass that lasts one remodeling cycle following an intervention that disturbs the calcium economy. We demonstrated the transient in a study of the response of bone density to calcium/vitamin D3 supplementation and show the hazards of misinterpretation if the transient is not considered. The remodeling transient describes a change in bone mass that lasts for one remodeling cycle following an intervention that disturbs the calcium economy. We report an intervention with calcium and vitamin D supplementation in 208 postmenopausal African-American women where the remodeling transient was considered a priori in the study design. Both groups (calcium alone vs. calcium + 20 microg (800 IU) vitamin D3) were ensured a calcium intake in excess of 1200 mg/day. There were no differences between the two groups in changes in BMD over time. These BMD changes were therefore interpreted to reflect increased calcium intake in both groups but not any influence of vitamin D. A transient increase in bone mineral density was observed during the first year of study, followed by a decline. The remodeling period was estimated at about 9 months, which is similar to histomorphometric estimates. It is problematic to draw conclusions concerning interventions that influence the calcium economy without considering the remodeling transient in study design. Studies of agents that effect bone remodeling must be carried out for at least two remodeling cycles and appropriate techniques must be used in data analysis.

  4. Simulating Turing machines on Maurer machines

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2008-01-01

    In a previous paper, we used Maurer machines to model and analyse micro-architectures. In the current paper, we investigate the connections between Turing machines and Maurer machines with the purpose to gain an insight into computability issues relating to Maurer machines. We introduce ways to

  5. Environmentally Friendly Machining

    CERN Document Server

    Dixit, U S; Davim, J Paulo

    2012-01-01

    Environment-Friendly Machining provides an in-depth overview of environmentally-friendly machining processes, covering numerous different types of machining in order to identify which practice is the most environmentally sustainable. The book discusses three systems at length: machining with minimal cutting fluid, air-cooled machining and dry machining. Also covered is a way to conserve energy during machining processes, along with useful data and detailed descriptions for developing and utilizing the most efficient modern machining tools. Researchers and engineers looking for sustainable machining solutions will find Environment-Friendly Machining to be a useful volume.

  6. Machine Transliteration

    CERN Document Server

    Knight, K; Knight, Kevin; Graehl, Jonathan

    1997-01-01

    It is challenging to translate names and technical terms across languages with different alphabets and sound inventories. These items are commonly transliterated, i.e., replaced with approximate phonetic equivalents. For example, "computer" in English comes out as "konpyuutaa" in Japanese. Translating such items from Japanese back to English is even more challenging, and of practical interest, as transliterated items make up the bulk of text phrases not found in bilingual dictionaries. We describe and evaluate a method for performing backwards transliterations by machine. This method uses a generative model, incorporating several distinct stages in the transliteration process.

  7. Small artery remodelling in diabetes.

    Science.gov (United States)

    Rosei, Enrico Agabiti; Rizzoni, Damiano

    2010-05-01

    The aim of this article is to briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment. The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries of smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, although in some secondary forms of hypertension, a hypertrophic remodelling may be detected. Moreover, in non-insulin-dependent diabetes mellitus a hypertrophic remodelling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effect on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations of small resistance arteries with drugs blocking the renin-angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) was demonstrated. Alterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin-angiotensin system blockade seems to be effective in preventing/regressing alterations in microvascular structure.

  8. Machine Protection

    CERN Document Server

    Schmidt, R

    2014-01-01

    The protection of accelerator equipment is as old as accelerator technology and was for many years related to high-power equipment. Examples are the protection of powering equipment from overheating (magnets, power converters, high-current cables), of superconducting magnets from damage after a quench and of klystrons. The protection of equipment from beam accidents is more recent. It is related to the increasing beam power of high-power proton accelerators such as ISIS, SNS, ESS and the PSI cyclotron, to the emission of synchrotron light by electron–positron accelerators and FELs, and to the increase of energy stored in the beam (in particular for hadron colliders such as LHC). Designing a machine protection system requires an excellent understanding of accelerator physics and operation to anticipate possible failures that could lead to damage. Machine protection includes beam and equipment monitoring, a system to safely stop beam operation (e.g. dumping the beam or stopping the beam at low energy) and an ...

  9. Macromolecular crowding for tailoring tissue-derived fibrillated matrices.

    Science.gov (United States)

    Magno, Valentina; Friedrichs, Jens; Weber, Heather M; Prewitz, Marina C; Tsurkan, Mikhail V; Werner, Carsten

    2017-06-01

    Tissue-derived fibrillated matrices can be instrumental for the in vitro reconstitution of multiphasic extracellular microenvironments. However, despite of several advantages, the obtained scaffolds so far offer a rather narrow range of materials characteristics only. In this work, we demonstrate how macromolecular crowding (MMC) - the supplementation of matrix reconstitution media with synthetic or natural macromolecules in ways to create excluded volume effects (EVE) - can be employed for tailoring important structural and biophysical characteristics of kidney-derived fibrillated matrices. Porcine kidneys were decellularized, ground and the obtained extracellular matrix (ECM) preparations were reconstituted under varied MMC conditions. We show that MMC strongly influences the fibrillogenesis kinetics and impacts the architecture and the elastic modulus of the reconstituted matrices, with diameters and relative alignment of fibrils increasing at elevated concentrations of the crowding agent Ficoll400, a nonionic synthetic polymer of sucrose. Furthermore, we demonstrate how MMC modulates the distribution of key ECM molecules within the reconstituted matrix scaffolds. As a proof of concept, we compared different variants of kidney-derived fibrillated matrices in cell culture experiments referring to specific requirements of kidney tissue engineering approaches. The results revealed that MMC-tailored matrices support the morphogenesis of human umbilical vein endothelial cells (HUVECs) into capillary networks and of murine kidney stem cells (KSCs) into highly branched aggregates. The established methodology is concluded to provide generally applicable new options for tailoring tissue-specific multiphasic matrices in vitro. Tissue-derived fibrillated matrices can be instrumental for the in vitro reconstitution of multiphasic extracellular microenvironments. However, despite of several advantages, the obtained scaffolds so far offer a rather narrow range of materials

  10. NMR RELAXIVITY AND IMAGING OF NEUTRAL MACROMOLECULAR POLYESTER GADOLINIUM (Ⅲ) COMPLEXES

    Institute of Scientific and Technical Information of China (English)

    Kai-chao Yu; Hong-bing Hu; Mai-li Liu; Han-zhen Yuan; Chao-hui Ye; Ren-xi Zhuo

    1999-01-01

    Five neutral macromolecular polyester gadolinium (Ⅲ) complexes with pendant hydrophobic alkyl and aromatic functional groups were prepared. The longitudinal relaxation rates of these complexes were measured. One of these Gd (Ⅲ) complexes was chosen for the acute toxicity test and T1-weighted imaging measurement. Preliminary results showed that. compared with Gd-DTPA, the neutral macromolecular gadolinium (Ⅲ) complexes provide higher T1 relaxivity enhancement and longer function duration.

  11. Remodeling, Renovation, & Conversion of Educational Facilities.

    Science.gov (United States)

    Association of Physical Plant Administrators of Universities and Colleges, Washington, DC.

    Based on a series of workshops, this collection of papers provides a framework for thought--emphasizing planning within time, flexibility, and maintenance constraints--as well as a practical guide for actual engineering of remodeling/renovation/conversion projects. Is remodeling always less expensive than new construction? Should high initial…

  12. Analysis of machining and machine tools

    CERN Document Server

    Liang, Steven Y

    2016-01-01

    This book delivers the fundamental science and mechanics of machining and machine tools by presenting systematic and quantitative knowledge in the form of process mechanics and physics. It gives readers a solid command of machining science and engineering, and familiarizes them with the geometry and functionality requirements of creating parts and components in today’s markets. The authors address traditional machining topics, such as: single and multiple point cutting processes grinding components accuracy and metrology shear stress in cutting cutting temperature and analysis chatter They also address non-traditional machining, such as: electrical discharge machining electrochemical machining laser and electron beam machining A chapter on biomedical machining is also included. This book is appropriate for advanced undergraduate and graduate mechani cal engineering students, manufacturing engineers, and researchers. Each chapter contains examples, exercises and their solutions, and homework problems that re...

  13. A versatile microparticle-based immunoaggregation assay for macromolecular biomarker detection and quantification.

    Directory of Open Access Journals (Sweden)

    Haiyan Wu

    Full Text Available The rapid, sensitive and low-cost detection of macromolecular biomarkers is critical in clinical diagnostics, environmental monitoring, research, etc. Conventional assay methods usually require bulky, expensive and designated instruments and relative long assay time. For hospitals and laboratories that lack immediate access to analytical instruments, fast and low-cost assay methods for the detection of macromolecular biomarkers are urgently needed. In this work, we developed a versatile microparticle (MP-based immunoaggregation method for the detection and quantification of macromolecular biomarkers. Antibodies (Abs were firstly conjugated to MP through streptavidin-biotin interaction; the addition of macromolecular biomarkers caused the aggregation of Ab-MPs, which were subsequently detected by an optical microscope or optical particle sizer. The invisible nanometer-scale macromolecular biomarkers caused detectable change of micrometer-scale particle size distributions. Goat anti-rabbit immunoglobulin and human ferritin were used as model biomarkers to demonstrate MP-based immunoaggregation assay in PBS and 10% FBS to mimic real biomarker assay in the complex medium. It was found that both the number ratio and the volume ratio of Ab-MP aggregates caused by biomarker to all particles were directly correlated to the biomarker concentration. In addition, we found that the detection range could be tuned by adjusting the Ab-MP concentration. We envision that this novel MP-based immunoaggregation assay can be combined with multiple detection methods to detect and quantify macromolecular biomarkers at the nanogram per milliliter level.

  14. Role of thyroid hormones in ventricular remodeling.

    Science.gov (United States)

    Rajagopalan, Viswanathan; Gerdes, A Martin

    2015-04-01

    Cardiac remodeling includes alterations in molecular, cellular, and interstitial systems contributing to changes in size, shape, and function of the heart. This may be the result of injury, alterations in hemodynamic load, neurohormonal effects, electrical abnormalities, metabolic changes, etc. Thyroid hormones (THs) serve as master regulators for diverse remodeling processes of the cardiovascular system-from the prenatal period to death. THs promote a beneficial cardiomyocyte shape and improve contractility, relaxation, and survival via reversal of molecular remodeling. THs reduce fibrosis by decreasing interstitial collagen and reduce the incidence and duration of arrhythmias via remodeling ion channel expression and function. THs restore metabolic function and also improve blood flow both by direct effects on the vessel architecture and decreasing atherosclerosis. Optimal levels of THs both in the circulation and in cardiac tissues are critical for normal homeostasis. This review highlights TH-based remodeling and clinically translatable strategies for diverse cardiovascular disorders.

  15. JBluIce-EPICS control system for macromolecular crystallography.

    Energy Technology Data Exchange (ETDEWEB)

    Stepanov, S.; Makarov, O.; Hilgart, M.; Pothineni, S.; Urakhchin, A.; Devarapalli, S.; Yoder, D.; Becker, M.; Ogata, C.; Sanishvili, R.; Nagarajan, V.; Smith, J. L.; Fischetti, R. F. (Biosciences Division); (Univ. of Michigan)

    2011-01-01

    The trio of macromolecular crystallography beamlines constructed by the General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) in Sector 23 of the Advanced Photon Source (APS) have been in growing demand owing to their outstanding beam quality and capacity to measure data from crystals of only a few micrometres in size. To take full advantage of the state-of-the-art mechanical and optical design of these beamlines, a significant effort has been devoted to designing fast, convenient, intuitive and robust beamline controls that could easily accommodate new beamline developments. The GM/CA-CAT beamline controls are based on the power of EPICS for distributed hardware control, the rich Java graphical user interface of Eclipse RCP and the task-oriented philosophy as well as the look and feel of the successful SSRL BluIce graphical user interface for crystallography. These beamline controls feature a minimum number of software layers, the wide use of plug-ins that can be written in any language and unified motion controls that allow on-the-fly scanning and optimization of any beamline component. This paper describes the ways in which BluIce was combined with EPICS and converted into the Java-based JBluIce, discusses the solutions aimed at streamlining and speeding up operations and gives an overview of the tools that are provided by this new open-source control system for facilitating crystallographic experiments, especially in the field of microcrystallography.

  16. Patch-clamp detection of macromolecular translocation along nuclear pores

    Directory of Open Access Journals (Sweden)

    Bustamante J.O.

    1998-01-01

    Full Text Available The present paper reviews the application of patch-clamp principles to the detection and measurement of macromolecular translocation along the nuclear pores. We demonstrate that the tight-seal 'gigaseal' between the pipette tip and the nuclear membrane is possible in the presence of fully operational nuclear pores. We show that the ability to form a gigaseal in nucleus-attached configurations does not mean that only the activity of channels from the outer membrane of the nuclear envelope can be detected. Instead, we show that, in the presence of fully operational nuclear pores, it is likely that the large-conductance ion channel activity recorded derives from the nuclear pores. We conclude the technical section with the suggestion that the best way to demonstrate that the nuclear pores are responsible for ion channel activity is by showing with fluorescence microscopy the nuclear translocation of ions and small molecules and the exclusion of the same from the cisterna enclosed by the two membranes of the envelope. Since transcription factors and mRNAs, two major groups of nuclear macromolecules, use nuclear pores to enter and exit the nucleus and play essential roles in the control of gene activity and expression, this review should be useful to cell and molecular biologists interested in understanding how patch-clamp can be used to quantitate the translocation of such macromolecules into and out of the nucleus

  17. Timely deposition of macromolecular structures is necessary for peer review

    Energy Technology Data Exchange (ETDEWEB)

    Joosten, Robbie P. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Soueidan, Hayssam; Wessels, Lodewyk F. A. [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam (Netherlands); Perrakis, Anastassis, E-mail: a.perrakis@nki.nl [Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2013-12-01

    Deposition of crystallographic structures should be concurrent with or prior to manuscript submission for peer review, enabling validation and increasing reliability of the PDB. Most of the macromolecular structures in the Protein Data Bank (PDB), which are used daily by thousands of educators and scientists alike, are determined by X-ray crystallography. It was examined whether the crystallographic models and data were deposited to the PDB at the same time as the publications that describe them were submitted for peer review. This condition is necessary to ensure pre-publication validation and the quality of the PDB public archive. It was found that a significant proportion of PDB entries were submitted to the PDB after peer review of the corresponding publication started, and many were only submitted after peer review had ended. It is argued that clear description of journal policies and effective policing is important for pre-publication validation, which is key in ensuring the quality of the PDB and of peer-reviewed literature.

  18. Synchrotron radiation macromolecular crystallography: science and spin-offs

    Directory of Open Access Journals (Sweden)

    John R. Helliwell

    2015-03-01

    Full Text Available A current overview of synchrotron radiation (SR in macromolecular crystallography (MX instrumentation, methods and applications is presented. Automation has been and remains a central development in the last decade, as have the rise of remote access and of industrial service provision. Results include a high number of Protein Data Bank depositions, with an increasing emphasis on the successful use of microcrystals. One future emphasis involves pushing the frontiers of using higher and lower photon energies. With the advent of X-ray free-electron lasers, closely linked to SR developments, the use of ever smaller samples such as nanocrystals, nanoclusters and single molecules is anticipated, as well as the opening up of femtosecond time-resolved diffraction structural studies. At SR sources, a very high-throughput assessment for the best crystal samples and the ability to tackle just a few micron and sub-micron crystals will become widespread. With higher speeds and larger detectors, diffraction data volumes are becoming long-term storage and archiving issues; the implications for today and the future are discussed. Together with the rise of the storage ring to its current pre-eminence in MX data provision, the growing tendency of central facility sites to offer other centralized facilities complementary to crystallography, such as cryo-electron microscopy and NMR, is a welcome development.

  19. New concepts and applications in the macromolecular chemistry of fullerenes.

    Science.gov (United States)

    Giacalone, Francesco; Martín, Nazario

    2010-10-08

    A new classification on the different types of fullerene-containing polymers is presented according to their different properties and applications they exhibit in a variety of fields. Because of their interest and novelty, water-soluble and biodegradable C(60)-polymers are discussed first, followed by polyfullerene-based membranes where unprecedented supramolecular structures are presented. Next are compounds that involve hybrid materials formed from fullerenes and other components such as silica, DNA, and carbon nanotubes (CNTs) where the most recent advances have been achieved. A most relevant topic is still that of C(60)-based donor-acceptor (D-A) polymers. Since their application in photovoltaics D-A polymers are among the most realistic applications of fullerenes in the so-called molecular electronics. The most relevant aspects in these covalently connected fullerene/polymer hybrids as well as new concepts to improve energy conversion efficiencies are presented.The last topics disccused relate to supramolecular aspects that are in involved in C(60)-polymer systems and in the self-assembly of C(60)-macromolecular structures, which open a new scenario for organizing, by means of non-covalent interactions, new supramolecular structures at the nano- and micrometric scale, in which the combination of the hydrofobicity of fullerenes with the versatility of the noncovalent chemistry afford new and spectacular superstructures.

  20. Macromolecular metallurgy of binary mesocrystals via designed multiblock terpolymers.

    Science.gov (United States)

    Xie, Nan; Liu, Meijiao; Deng, Hanlin; Li, Weihua; Qiu, Feng; Shi, An-Chang

    2014-02-26

    Self-assembling block copolymers provide access to the fabrication of various ordered phases. In particular, the ordered spherical phases can be used to engineer soft mesocrystals with domain size at the 5-100 nm scales. Simple block copolymers, such as diblock copolymers, form a limited number of mesocrystals. However multiblock copolymers are capable to form more complex mesocrystals. We demonstrate that designed B1AB2CB3 multiblock terpolymers, in which the A- and C-blocks form spherical domains and the packing of these spheres can be controlled by changing the lengths of the middle and terminal B-blocks, self-assemble into various binary mesocrystals with space group symmetries of a large number of binary ionic crystals, including NaCl, CsCl, ZnS, α-BN, AlB2, CaF2, TiO2, ReO3, Li3Bi, Nb3Sn(A15), and α-Al2O3. This approach can be generalized to other terpolymers as well as to tetrapolymers to obtain ternary mesocrystals. Our study provides a new concept of macromolecular metallurgy for producing crystal phases in a mesoscale and thus makes multiblock copolymers a robust platform for the engineering of functional materials.

  1. Macromolecular Powder Diffraction: Ready for genuine biological problems.

    Science.gov (United States)

    Karavassili, Fotini; Margiolaki, Irene

    2016-01-01

    Knowledge of 3D structures of biological molecules plays a major role in both understanding important processes of life and developing pharmaceuticals. Among several methods available for structure determination, macromolecular X-ray powder diffraction (XRPD) has transformed over the past decade from an impossible dream to a respectable method. XRPD can be employed in biosciences for various purposes such as observing phase transitions, characterizing bulk pharmaceuticals, determining structures via the molecular replacement method, detecting ligands in protein-ligand complexes, as well as combining micro-sized single crystal crystallographic data and powder diffraction data. Studies using synchrotron and laboratory sources in some standard configuration setups are reported in this review, including their respective advantages and disadvantages. Methods presented here provide an alternative, complementary set of tools to resolve structural problems. A variety of already existing software packages for powder diffraction data processing and analysis, some of which have been adapted to large unit cell studies, are briefly described. This review aims to provide necessary elements of theory and current methods, along with practical explanations, available software packages and highlighted case studies.

  2. Canadian macromolecular crystallography facility: a suite of fully automated beamlines.

    Science.gov (United States)

    Grochulski, Pawel; Fodje, Michel; Labiuk, Shaunivan; Gorin, James; Janzen, Kathryn; Berg, Russ

    2012-06-01

    The Canadian light source is a 2.9 GeV national synchrotron radiation facility located on the University of Saskatchewan campus in Saskatoon. The small-gap in-vacuum undulator illuminated beamline, 08ID-1, together with the bending magnet beamline, 08B1-1, constitute the Canadian Macromolecular Crystallography Facility (CMCF). The CMCF provides service to more than 50 Principal Investigators in Canada and the United States. Up to 25% of the beam time is devoted to commercial users and the general user program is guaranteed up to 55% of the useful beam time through a peer-review process. CMCF staff provides "Mail-In" crystallography service to users with the highest scored proposals. Both beamlines are equipped with very robust end-stations including on-axis visualization systems, Rayonix 300 CCD series detectors and Stanford-type robotic sample auto-mounters. MxDC, an in-house developed beamline control system, is integrated with a data processing module, AutoProcess, allowing full automation of data collection and data processing with minimal human intervention. Sample management and remote monitoring of experiments is enabled through interaction with a Laboratory Information Management System developed at the facility.

  3. Exercise-induced cardiac remodeling.

    Science.gov (United States)

    Weiner, Rory B; Baggish, Aaron L

    2012-01-01

    Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

  4. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects...... without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile...

  5. Functional role of autophagy-mediated proteome remodeling in cell survival signaling and innate immunity.

    Science.gov (United States)

    Mathew, Robin; Khor, Sinan; Hackett, Sean R; Rabinowitz, Joshua D; Perlman, David H; White, Eileen

    2014-09-18

    Ras-driven cancer cells upregulate basal autophagy that degrades and recycles intracellular proteins and organelles. Autophagy-mediated proteome degradation provides free amino acids to support metabolism and macromolecular synthesis, which confers a survival advantage in starvation and promotes tumorigenesis. While the degradation of isolated protein substrates by autophagy has been implicated in controlling cellular function, the extent and specificity by which autophagy remodels the cellular proteome and the underlying functional consequences were unknown. Here we compared the global proteome of autophagy-functional and -deficient Ras-driven cancer cells, finding that autophagy affects the majority of the proteome yet is highly selective. While levels of vesicle trafficking proteins important for autophagy are preserved during starvation-induced autophagy, deleterious inflammatory response pathway components are eliminated even under basal conditions, preventing cytokine-induced paracrine cell death. This reveals the global, functional impact of autophagy-mediated proteome remodeling on cell survival and identifies critical autophagy substrates that mediate this process.

  6. Automation of printing machine

    OpenAIRE

    Sušil, David

    2016-01-01

    Bachelor thesis is focused on the automation of the printing machine and comparing the two types of printing machines. The first chapter deals with the history of printing, typesettings, printing techniques and various kinds of bookbinding. The second chapter describes the difference between sheet-fed printing machines and offset printing machines, the difference between two representatives of rotary machines, technological process of the products on these machines, the description of the mac...

  7. Airway remodeling in asthma: what really matters.

    Science.gov (United States)

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  8. Machines of life: catalogue, stochastic process modeling, probabilistic reverse engineering and the PIs- from Aristotle to Alberts

    CERN Document Server

    Chowdhury, Debashish

    2012-01-01

    Molecular machines consist of either a single protein or a macromolecular complex composed of protein and RNA molecules. Just like their macroscopic counterparts, each of these nano-machines has an engine that "transduces" input energy into an output form which is then utilized by its coupling to a transmission system for appropriate operations. The theory of heat engines, pioneered by Carnot, rests on the second law of equilibrium thermodynamics. However, the engines of molecular machines, operate under isothermal conditions far from thermodynamic equilibrium. Moreover, one of the possible mechanisms of energy transduction, popularized by Feynman and called Brownian ratchet, does not even have any macroscopic counterpart. But, {\\it molecular machine is not synonymous with Brownian ratchet}; a large number of molecular machines actually execute a noisy power stroke, rather than operating as Brownian ratchet. The man-machine analogy, a topic of intense philosophical debate in which many leading philosophers li...

  9. Machine musicianship

    Science.gov (United States)

    Rowe, Robert

    2002-05-01

    The training of musicians begins by teaching basic musical concepts, a collection of knowledge commonly known as musicianship. Computer programs designed to implement musical skills (e.g., to make sense of what they hear, perform music expressively, or compose convincing pieces) can similarly benefit from access to a fundamental level of musicianship. Recent research in music cognition, artificial intelligence, and music theory has produced a repertoire of techniques that can make the behavior of computer programs more musical. Many of these were presented in a recently published book/CD-ROM entitled Machine Musicianship. For use in interactive music systems, we are interested in those which are fast enough to run in real time and that need only make reference to the material as it appears in sequence. This talk will review several applications that are able to identify the tonal center of musical material during performance. Beyond this specific task, the design of real-time algorithmic listening through the concurrent operation of several connected analyzers is examined. The presentation includes discussion of a library of C++ objects that can be combined to perform interactive listening and a demonstration of their capability.

  10. DOMMINO 2.0: integrating structurally resolved protein-, RNA-, and DNA-mediated macromolecular interactions.

    Science.gov (United States)

    Kuang, Xingyan; Dhroso, Andi; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

    2016-01-01

    Macromolecular interactions are formed between proteins, DNA and RNA molecules. Being a principle building block in macromolecular assemblies and pathways, the interactions underlie most of cellular functions. Malfunctioning of macromolecular interactions is also linked to a number of diseases. Structural knowledge of the macromolecular interaction allows one to understand the interaction's mechanism, determine its functional implications and characterize the effects of genetic variations, such as single nucleotide polymorphisms, on the interaction. Unfortunately, until now the interactions mediated by different types of macromolecules, e.g. protein-protein interactions or protein-DNA interactions, are collected into individual and unrelated structural databases. This presents a significant obstacle in the analysis of macromolecular interactions. For instance, the homogeneous structural interaction databases prevent scientists from studying structural interactions of different types but occurring in the same macromolecular complex. Here, we introduce DOMMINO 2.0, a structural Database Of Macro-Molecular INteractiOns. Compared to DOMMINO 1.0, a comprehensive database on protein-protein interactions, DOMMINO 2.0 includes the interactions between all three basic types of macromolecules extracted from PDB files. DOMMINO 2.0 is automatically updated on a weekly basis. It currently includes ∼1,040,000 interactions between two polypeptide subunits (e.g. domains, peptides, termini and interdomain linkers), ∼43,000 RNA-mediated interactions, and ∼12,000 DNA-mediated interactions. All protein structures in the database are annotated using SCOP and SUPERFAMILY family annotation. As a result, protein-mediated interactions involving protein domains, interdomain linkers, C- and N- termini, and peptides are identified. Our database provides an intuitive web interface, allowing one to investigate interactions at three different resolution levels: whole subunit network

  11. Maternal uterine vascular remodeling during pregnancy.

    Science.gov (United States)

    Osol, George; Mandala, Maurizio

    2009-02-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  12. Advances in chromatin remodeling and human disease.

    Science.gov (United States)

    Cho, Kyoung Sang; Elizondo, Leah I; Boerkoel, Cornelius F

    2004-06-01

    Epigenetic factors alter phenotype without changing genotype. A primary molecular mechanism underlying epigenetics is the alteration of chromatin structure by covalent DNA modifications, covalent histone modifications, and nucleosome reorganization. Remodeling of chromatin structure regulates DNA methylation, replication, recombination, and repair as well as gene expression. As these functions would predict, dysfunction of the proteins that remodel chromatin causes an array of multi-system disorders and neoplasias. Insights from these diseases suggest that during embryonic and fetal life, environmental distortions of chromatin remodeling encode a 'molecular memory' that predispose the individual to diseases in adulthood.

  13. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  14. Non-contact luminescence lifetime cryothermometry for macromolecular crystallography.

    Science.gov (United States)

    Mykhaylyk, V B; Wagner, A; Kraus, H

    2017-05-01

    Temperature is a very important parameter when aiming to minimize radiation damage to biological samples during experiments that utilize intense ionizing radiation. A novel technique for remote, non-contact, in situ monitoring of the protein crystal temperature has been developed for the new I23 beamline at the Diamond Light Source, a facility dedicated to macromolecular crystallography (MX) with long-wavelength X-rays. The temperature is derived from the temperature-dependent decay time constant of luminescence from a minuscule scintillation sensor (luminescence lifetime thermometry is presented, the features of the detection method and the choice of temperature sensor are discussed, and it is demonstrated how the temperature monitoring system was integrated within the viewing system of the endstation used for the visualization of protein crystals. The thermometry system was characterized using a Bi4Ge3O12 crystal scintillator that exhibits good responsivity of the decay time constant as a function of temperature over a wide range (8-270 K). The scintillation sensor was calibrated and the uncertainty of the temperature measurements over the primary operation temperature range of the beamline (30-150 K) was assessed to be ±1.6 K. It has been shown that the temperature of the sample holder, measured using the luminescence sensor, agrees well with the expected value. The technique was applied to characterize the thermal performance of different sample mounts that have been used in MX experiments at the I23 beamline. The thickness of the mount is shown to have the greatest impact upon the temperature distribution across the sample mount. Altogether, these tests and findings demonstrate the usefulness of the thermometry system in highlighting the challenges that remain to be addressed for the in-vacuum MX experiment to become a reliable and indispensable tool for structural biology.

  15. A Compact X-Ray System for Macromolecular Crystallography. 5

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for macromolecular crystallography that combines a microfocus x-ray generator (40 gm FWHM spot size at a power level of 46.5Watts) and a 5.5 mm focal distance polycapillary optic. The Cu K(sub alpha) X-ray flux produced by this optimized system is 7.0 times above the X-ray flux previously reported. The X-ray flux from the microfocus system is also 3.2 times higher than that produced by the rotating anode generator equipped with a long focal distance graded multilayer monochromator (Green optic; CMF24-48-Cu6) and 30% less than that produced by the rotating anode generator with the newest design of graded multilayer monochromator (Blue optic; CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 Watts, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42,540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym) 5.0% for the data extending to 1.7A, and 4.8% for the complete set of data to 1.85A. The amplitudes of the reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  16. A Compact X-Ray System for Macromolecular Crystallography

    Science.gov (United States)

    Gubarev, Mikhail; Ciszak, Ewa; Ponomarev, Igor; Gibson, Walter; Joy, Marshall

    2000-01-01

    We describe the design and performance of a high flux x-ray system for a macromolecular crystallography that combines a microfocus x-ray generator (40 micrometer full width at half maximum spot size at a power level of 46.5 W) and a collimating polycapillary optic. The Cu Ka lpha x-ray flux produced by this optimized system through a 500,um diam orifice is 7.0 times greater than the x-ray flux previously reported by Gubarev et al. [M. Gubarev et al., J. Appl. Crystallogr. 33, 882 (2000)]. The x-ray flux from the microfocus system is also 2.6 times higher than that produced by a rotating anode generator equipped with a graded multilayer monochromator (green optic, Osmic Inc. CMF24-48-Cu6) and 40% less than that produced by a rotating anode generator with the newest design of graded multilayer monochromator (blue optic, Osmic, Inc. CMF12-38-Cu6). Both rotating anode generators operate at a power level of 5000 W, dissipating more than 100 times the power of our microfocus x-ray system. Diffraction data collected from small test crystals are of high quality. For example, 42 540 reflections collected at ambient temperature from a lysozyme crystal yielded R(sub sym)=5.0% for data extending to 1.70 A, and 4.8% for the complete set of data to 1.85 A. The amplitudes of the observed reflections were used to calculate difference electron density maps that revealed positions of structurally important ions and water molecules in the crystal of lysozyme using the phases calculated from the protein model.

  17. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  18. Simulations of trabecular remodeling and fatigue: is remodeling helpful or harmful?

    Science.gov (United States)

    van Oers, René F M; van Rietbergen, Bert; Ito, Keita; Huiskes, Rik; Hilbers, Peter A J

    2011-05-01

    Microdamage-targeted resorption is paradoxal, because it entails the removal of bone from a region that was already overloaded. Under continued intense loading, resorption spaces could potentially cause more damage than they remove. To investigate this problem, we incorporated damage algorithms in a computer-simulation model for trabecular remodeling. We simulated damage accumulation and bone remodeling in a trabecular architecture, for two fatigue regimens, a 'moderate' regimen, and an 'intense' regimen with a higher number of loading cycles per day. Both simulations were also performed without bone remodeling to investigate if remodeling removed or exacerbated the damage. We found that remodeling tends to remove damage under the 'moderate' fatigue regimen, but it exacerbates damage under the 'intense' regimen. This harmful effect of remodeling may play a role in the development of stress fractures.

  19. Electrical machines mathematical fundamentals of machine topologies

    CERN Document Server

    Gerling, Dieter

    2015-01-01

    Electrical Machines and Drives play a powerful role in industry with an ever increasing importance. This fact requires the understanding of machine and drive principles by engineers of many different disciplines. Therefore, this book is intended to give a comprehensive deduction of these principles. Special attention is given to the precise mathematical derivation of the necessary formulae to calculate machines and drives and to the discussion of simplifications (if applied) with the associated limits. The book shows how the different machine topologies can be deduced from general fundamentals, and how they are linked together. This book addresses graduate students, researchers, and developers of Electrical Machines and Drives, who are interested in getting knowledge about the principles of machine and drive operation and in detecting the mathematical and engineering specialties of the different machine and drive topologies together with their mutual links. The detailed - but nevertheless compact - mat...

  20. Laser machining of advanced materials

    CERN Document Server

    Dahotre, Narendra B

    2011-01-01

    Advanced materialsIntroductionApplicationsStructural ceramicsBiomaterials CompositesIntermetallicsMachining of advanced materials IntroductionFabrication techniquesMechanical machiningChemical Machining (CM)Electrical machiningRadiation machining Hybrid machiningLaser machiningIntroductionAbsorption of laser energy and multiple reflectionsThermal effectsLaser machining of structural ceramicsIntrodu

  1. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications...

  2. Raise the Floor When Remodeling Science Labs

    Science.gov (United States)

    Nation's Schools, 1972

    1972-01-01

    A new remodeling idea adopts the concept of raised floor covering gas, water, electrical, and drain lines. The accessible floor has removable panels set into an adjustable support frame 24 inches above a concrete subfloor. (Author)

  3. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud

    2012-01-01

    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  4. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography

    Directory of Open Access Journals (Sweden)

    Julian C.-H. Chen

    2017-01-01

    Full Text Available The Protein Crystallography Station (PCS, located at the Los Alamos Neutron Scattering Center (LANSCE, was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER for 13 years (2002–2014. The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallography in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  5. Fifteen years of the Protein Crystallography Station: the coming of age of macromolecular neutron crystallography.

    Science.gov (United States)

    Chen, Julian C-H; Unkefer, Clifford J

    2017-01-01

    The Protein Crystallography Station (PCS), located at the Los Alamos Neutron Scattering Center (LANSCE), was the first macromolecular crystallography beamline to be built at a spallation neutron source. Following testing and commissioning, the PCS user program was funded by the Biology and Environmental Research program of the Department of Energy Office of Science (DOE-OBER) for 13 years (2002-2014). The PCS remained the only dedicated macromolecular neutron crystallography station in North America until the construction and commissioning of the MaNDi and IMAGINE instruments at Oak Ridge National Laboratory, which started in 2012. The instrument produced a number of research and technical outcomes that have contributed to the field, clearly demonstrating the power of neutron crystallo-graphy in helping scientists to understand enzyme reaction mechanisms, hydrogen bonding and visualization of H-atom positions, which are critical to nearly all chemical reactions. During this period, neutron crystallography became a technique that increasingly gained traction, and became more integrated into macromolecular crystallography through software developments led by investigators at the PCS. This review highlights the contributions of the PCS to macromolecular neutron crystallography, and gives an overview of the history of neutron crystallography and the development of macromolecular neutron crystallography from the 1960s to the 1990s and onwards through the 2000s.

  6. Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

    Science.gov (United States)

    Marín-Yaseli, Margarita R; Cid, Cristina; Yagüe, Ana I; Ruiz-Bermejo, Marta

    2017-02-01

    Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed.

  7. The Chd Family of Chromatin Remodelers

    OpenAIRE

    Marfella, Concetta G.A.; Imbalzano, Anthony N.

    2007-01-01

    Chromatin remodeling enzymes contribute to the dynamic changes that occur in chromatin structure during cellular processes such as transcription, recombination, repair, and replication. Members of the chromodomain helicase DNA-binding (Chd) family of enzymes belong to the SNF2 superfamily of ATP-dependent chromatin remodelers. The Chd proteins are distinguished by the presence of two N-terminal chromodomains that function as interaction surfaces for a variety of chromatin components. Genetic,...

  8. Chromatin Modification and Remodeling in Heart Development

    Directory of Open Access Journals (Sweden)

    Paul Delgado-Olguín

    2006-01-01

    Full Text Available In organogenesis, cell types are specified from determined precursors as morphogenetic patterning takes place. These events are largely controlled by tissue-specific transcription factors. These transcription factors must function within the context of chromatin to activate or repress target genes. Recent evidence suggests that chromatin-remodeling and -modifying factors may have tissue-specific function. Here we review the potential roles for chromatin-remodeling and -modifying proteins in the development of the mammalian heart.

  9. The deleuzian abstract machines

    DEFF Research Database (Denmark)

    Werner Petersen, Erik

    2005-01-01

    production. In Kafka: Toward a Minor Literature, Deleuze and Guatari gave the most comprehensive explanation to the abstract machine in the work of art. Like the war-machines of Virilio, the Kafka-machine operates in three gears or speeds. Furthermore, the machine is connected to spatial diagrams...

  10. Bone remodeling as a spatial evolutionary game.

    Science.gov (United States)

    Ryser, Marc D; Murgas, Kevin A

    2017-04-07

    Bone remodeling is a complex process involving cell-cell interactions, biochemical signaling and mechanical stimuli. Early models of the biological aspects of remodeling were non-spatial and focused on the local dynamics at a fixed location in the bone. Several spatial extensions of these models have been proposed, but they generally suffer from two limitations: first, they are not amenable to analysis and are computationally expensive, and second, they neglect the role played by bone-embedded osteocytes. To address these issues, we developed a novel model of spatial remodeling based on the principles of evolutionary game theory. The analytically tractable framework describes the spatial interactions between zones of bone resorption, bone formation and quiescent bone, and explicitly accounts for regulation of remodeling by bone-embedded, mechanotransducing osteocytes. Using tools from the theory of interacting particle systems we systematically classified the different dynamic regimes of the spatial model and identified regions of parameter space that allow for global coexistence of resorption, formation and quiescence, as observed in physiological remodeling. In coexistence scenarios, three-dimensional simulations revealed the emergence of sponge-like bone clusters. Comparison between spatial and non-spatial dynamics revealed substantial differences and suggested a stabilizing role of space. Our findings emphasize the importance of accounting for spatial structure and bone-embedded osteocytes when modeling the process of bone remodeling. Thanks to the lattice-based framework, the proposed model can easily be coupled to a mechanical model of bone loading.

  11. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  12. Synthesis and characterization of miktoarm star copolymer of styrene and butadiene using multifunctional macromolecular initiator

    Institute of Scientific and Technical Information of China (English)

    Hai Yan Zhang; Xing Ying Zhang

    2009-01-01

    A new kind of multifunctional macromolecular initiator with Sn-C bonds and polydiene arms was synthesized by living anionic polymerization.At first,polydiene-stannum chloride(PD-SnCl3)was prepared by the reaction of n-butyl-Li(n-BuLi),stannic chloride(SnCl4)and diene.Then PD-SnCl3 was used to react with the dilithium initiator to prepare the multifunctional organic macromolecular initiators.The result suggested that the initiators had a remarkable yield by GPC,nearly 90%.By using these multifunctional macromolecular initiators,styrene and butadiene were effectively polymerized via anionic polymerization,which gave birth to novel miktoarm star copolymers.The relative molecular weight and polydispersity index,microstructure contents,copolymerization components,glass transition temperature(Tg)and morphology of the miktoarm star copolymers were investigated by GPC-UV,1H NMR,DSC and TEM,respectively.

  13. Use of Site-Specifically Tethered Chemical Nucleases to Study Macromolecular Reactions

    Directory of Open Access Journals (Sweden)

    Mukherjee Srabani

    2003-01-01

    Full Text Available During a complex macromolecular reaction multiple changes in molecular conformation and interactions with ligands may occur. X-ray crystallography may provide only a limited set of snapshots of these changes. Solution methods can augment such structural information to provide a more complete picture of a macromolecular reaction. We analyzed the changes in protein conformation and protein:nucleic acid interactions which occur during transcription initiation by using a chemical nuclease tethered to cysteines introduced site-specifically into the RNA polymerase of bacteriophage T7 (T7 RNAP. Changes in cleavage patterns as the polymerase steps through transcription reveal a series of structural transitions which mediate transcription initiation. Cleavage by tethered chemical nucleases is seen to be a powerful method for revealing the conformational dynamics of macromolecular reactions, and has certain advantages over cross-linking or energy transfer approaches.

  14. Macromolecular Hydrogen Sulfide Donors Trigger Spatiotemporally Confined Changes in Cell Signaling.

    Science.gov (United States)

    Ercole, Francesca; Mansfeld, Friederike M; Kavallaris, Maria; Whittaker, Michael R; Quinn, John F; Halls, Michelle L; Davis, Thomas P

    2016-01-11

    Hydrogen sulfide (H2S) is involved in a myriad of cell signaling processes that trigger physiological events ranging from vasodilation to cell proliferation. Moreover, disturbances to H2S signaling have been associated with numerous pathologies. As such, the ability to release H2S in a cellular environment and stimulate signaling events is of considerable interest. Herein we report the synthesis of macromolecular H2S donors capable of stimulating cell signaling pathways in both the cytosol and at the cell membrane. Specifically, copolymers having pendent oligo(ethylene glycol) and benzonitrile groups were synthesized, and the benzonitrile groups were subsequently transformed into primary aryl thioamide groups via thionation using sodium hydrosulfide. These thioamide moieties could be incorporated into a hydrophilic copolymer or a block copolymer (i.e., into either the hydrophilic or hydrophobic domain). An electrochemical sensor was used to demonstrate release of H2S under simulated physiological conditions. Subsequent treatment of HEK293 cells with a macromolecular H2S donor elicited a slow and sustained increase in cytosolic ERK signaling, as monitored using a FRET-based biosensor. The macromolecular donor was also shown to induce a small, fast and sustained increase in plasma membrane-localized PKC activity immediately following addition to cells. Studies using an H2S-selective fluorescent probe in live cells confirmed release of H2S from the macromolecular donor over physiologically relevant time scales consistent with the signaling observations. Taken together, these results demonstrate that by using macromolecular H2S donors it is possible to trigger spatiotemporally confined cell signaling events. Moreover, the localized nature of the observed signaling suggests that macromolecular donor design may provide an approach for selectively stimulating certain cellular biochemical pathways.

  15. Modeling stochastic kinetics of molecular machines at multiple levels: from molecules to modules.

    Science.gov (United States)

    Chowdhury, Debashish

    2013-06-04

    A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here.

  16. The Joint Structural Biology Group beam lines at the ESRF: Modern macromolecular crystallography

    CERN Document Server

    Mitchell, E P

    2001-01-01

    Macromolecular crystallography has evolved considerably over the last decade. Data sets in under an hour are now possible on high throughput beam lines leading to electron density and, possibly, initial models calculated on-site. There are five beam lines currently dedicated to macromolecular crystallography: the ID14 complex and BM-14 (soon to be superseded by ID-29). These lines handle over five hundred projects every six months and demand is increasing. Automated sample handling, alignment and data management protocols will be required to work efficiently with this demanding load. Projects developing these themes are underway within the JSBG.

  17. Aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes as revealed by microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu University, Matsumoto (Japan). Dept. of Anatomy and Cell Biology

    2007-07-01

    This mini-review reports aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes. We have observed the macromolecular synthesis, such as DNA, RNA and proteins, in the mitochondria of various mammalian cells by means of electron microscopic radioautography technique developed in our laboratory. The number of mitochondria per cell, number of labeled mitochondria per cell with 3H-thymidine, 3H-uridine and 3H-leucine, precursors for DNA, RNA and proteins, respectively, were counted and the labeling indices at various ages, from fetal to postnatal early days and several months to 1 and 2 years in senescence, were calculated, which showed variations due to aging. (author)

  18. THE STEADY/PULSATILE FLOW AND MACROMOLECULAR TRANSPORT IN T-BIFURCATION BLOOD VESSELS

    Institute of Scientific and Technical Information of China (English)

    李丁; 温功碧

    2003-01-01

    A numerical analysis of the steady and pulsatile, macromolecular( such as lowdensity lipopotein ( LDL ), Albumin ) transport in T-bifurcation was proposed. Theinfluence of Reynolds number and mass flow ratio etc. parameters on the velocity field andmass transport were calculated. The computational results predict that the blood flow factorsaffect the macromolecular distribution and the transport across the wall, it shows thathemodynamic play an important role in the process of atherosclerosis . The LDL and Albuminconcentration on the wall varies most greatly in flow bifurcation area where the wall shearstress varies greatly at the branching vessel and the atherosclerosis often appears there.

  19. Influence of protein crowder size on hydration structure and dynamics in macromolecular crowding

    Science.gov (United States)

    Wang, Po-hung; Yu, Isseki; Feig, Michael; Sugita, Yuji

    2017-03-01

    We investigate the effects of protein crowder sizes on hydration structure and dynamics in macromolecular crowded systems by all-atom MD simulations. The crowded systems consisting of only small proteins showed larger total surface areas than those of large proteins at the same volume fractions. As a result, more water molecules were trapped within the hydration shells, slowing down water diffusion. The simulation results suggest that the protein crowder size is another factor to determine the effect of macromolecular crowding and to explain the experimental kinetic data of proteins and DNAs in the presence of crowding agents.

  20. Phase Sensitive X-Ray Diffraction Imaging of Defects in Biological Macromolecular Crystals

    Science.gov (United States)

    Hu, Z. W.; Lai, B.; Chu, Y. S.; Cai, Z.; Mancini, D. C.; Thomas, B. R.; Chernov, A. A.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Characterization of defects and/or disorder in biological macromolecular crystals presents much greater challenges than in conventional small-molecule crystals. The lack of sufficient contrast of defects is often a limiting factor in x-ray diffraction topography of protein crystals. This has seriously hampered efforts to understand mechanisms and origins of formation of imperfections, and the role of defects as essential entities in the bulk of macromolecular crystals. In this report, we employ a phase sensitive x-ray diffraction imaging approach for augmenting the contrast of defects in protein crystals.

  1. Poly(isophthalic acid)(ethylene oxide) as a Macromolecular Modulator for Metal-Organic Polyhedra.

    Science.gov (United States)

    Chen, Teng-Hao; Wang, Le; Trueblood, Jonathan V; Grassian, Vicki H; Cohen, Seth M

    2016-08-03

    A new strategy was developed by using a polymer ligand, poly(isophthalic acid)(ethylene oxide), to modulate the growth of metal-organic polyhedra (MOP) crystals. This macromolecular modulator can effectively control the crystal habit of several different Cu24L24 (L = isophthalic acid derivatives) MOPs. The polymer also directed the formation of MOP structures under reaction conditions that only produce metal-organic frameworks in the absence of modulator. Moreover, the polymer also enabled the deposition of MOP crystals on glass surfaces. This macromolecular modulator strategy provides an innovative approach to control the morphology and assembly of MOP particles.

  2. Effect of macromolecular crowding on the rate of diffusion-limited enzymatic reaction

    Indian Academy of Sciences (India)

    Manish Agrawal; S B Santra; Rajat Anand; Rajaram Swaminathan

    2008-08-01

    The cytoplasm of a living cell is crowded with several macromolecules of different shapes and sizes. Molecular diffusion in such a medium becomes anomalous due to the presence of macromolecules and diffusivity is expected to decrease with increase in macromolecular crowding. Moreover, many cellular processes are dependent on molecular diffusion in the cell cytosol. The enzymatic reaction rate has been shown to be affected by the presence of such macromolecules. A simple numerical model is proposed here based on percolation and diffusion in disordered systems to study the effect of macromolecular crowding on the enzymatic reaction rates. The model qualitatively explains some of the experimental observations.

  3. Chromatin remodelling initiation during human spermiogenesis

    Directory of Open Access Journals (Sweden)

    Marieke De Vries

    2012-03-01

    During the last phase of spermatogenesis, spermiogenesis, haploid round spermatids metamorphose towards spermatozoa. Extensive cytoplasmic reduction and chromatin remodelling together allow a dramatic decrease of cellular, notably nuclear volume. DNA packing by a nucleosome based chromatin structure is largely replaced by a protamine based one. At the cytoplasmic level among others the acrosome and perinuclear theca (PNT are formed. In this study we describe the onset of chromatin remodelling to occur concomitantly with acrosome and PNT development. In spread human round spermatid nuclei, we show development of a DAPI-intense doughnut-like structure co-localizing with the acrosomal sac and sub acrosomal PNT. At this structure we observe the first gradual decrease of nucleosomes and several histones. Histone post-translational modifications linked to chromatin remodelling such as H4K8ac and H4K16ac also delineate the doughnut, that is furthermore marked by H3K9me2. During the capping phase of acrosome development, the size of the doughnut-like chromatin domain increases, and this area often is marked by uniform nucleosome loss and the first appearance of transition protein 2 and protamine 1. In the acrosome phase at nuclear elongation, chromatin remodelling follows the downward movement of the marginal ring of the acrosome. Our results indicate that acrosome development and chromatin remodelling are interacting processes. In the discussion we relate chromatin remodelling to the available data on the nuclear envelope and the linker of nucleoskeleton and cytoskeleton (LINC complex of spermatids, suggesting a signalling route for triggering chromatin remodelling.

  4. RNA interference and Register Machines (extended abstract

    Directory of Open Access Journals (Sweden)

    Masahiro Hamano

    2012-11-01

    Full Text Available RNA interference (RNAi is a mechanism whereby small RNAs (siRNAs directly control gene expression without assistance from proteins. This mechanism consists of interactions between RNAs and small RNAs both of which may be single or double stranded. The target of the mechanism is mRNA to be degraded or aberrated, while the initiator is double stranded RNA (dsRNA to be cleaved into siRNAs. Observing the digital nature of RNAi, we represent RNAi as a Minsky register machine such that (i The two registers hold single and double stranded RNAs respectively, and (ii Machine's instructions are interpreted by interactions of enzyme (Dicer, siRNA (with RISC com- plex and polymerization (RdRp to the appropriate registers. Interpreting RNAi as a computational structure, we can investigate the computational meaning of RNAi, especially its complexity. Initially, the machine is configured as a Chemical Ground Form (CGF, which generates incorrect jumps. To remedy this problem, the system is remodeled as recursive RNAi, in which siRNA targets not only mRNA but also the machine instructional analogues of Dicer and RISC. Finally, probabilistic termination is investigated in the recursive RNAi system.

  5. Machine tool structures

    CERN Document Server

    Koenigsberger, F

    1970-01-01

    Machine Tool Structures, Volume 1 deals with fundamental theories and calculation methods for machine tool structures. Experimental investigations into stiffness are discussed, along with the application of the results to the design of machine tool structures. Topics covered range from static and dynamic stiffness to chatter in metal cutting, stability in machine tools, and deformations of machine tool structures. This volume is divided into three sections and opens with a discussion on stiffness specifications and the effect of stiffness on the behavior of the machine under forced vibration c

  6. Adipose tissue remodeling in pathophysiology of obesity.

    Science.gov (United States)

    Lee, Mi-Jeong; Wu, Yuanyuan; Fried, Susan K

    2010-07-01

    Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodeling and highlight the influences of obesity, depot, and sex, as well as the relevance of rodent models to humans. A substantial literature now points to the importance of dynamic changes in adipocyte and immune cell turnover, angiogenesis, and extracellular matrix remodeling in regulating the expandability and functional integrity of this tissue. In obesity, the macrophages are recruited, surrounding dead adipocytes and polarized toward an inflammatory phenotype. The number of dead adipocytes is closely associated with the pathophysiological consequences of obesity, including insulin resistance and hepatic steatosis. Further, there are substantial depot, sex and species differences in the extent of remodeling. Adipose tissue undergoes a continuous remodeling process that normally maintains tissue health, but may spin out of control and lead to adipocyte death in association with the recruitment and activation of macrophages, and systemic insulin resistance.

  7. Molecular Aspects of Exercise-induced Cardiac Remodeling.

    Science.gov (United States)

    Bernardo, Bianca C; McMullen, Julie R

    2016-11-01

    Exercise-induced cardiac remodeling is typically an adaptive response associated with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers of cardiac remodeling include increased hemodynamic load, increased sympathetic activity, and the release of hormones and growth factors. Prolonged and strenuous exercise may lead to maladaptive exercise-induced cardiac remodeling including cardiac dysfunction and arrhythmia. In addition, this article describes novel therapeutic approaches for the treatment of heart failure that target mechanisms responsible for adaptive exercise-induced cardiac remodeling, which are being developed and tested in preclinical models.

  8. Design of Demining Machines

    CERN Document Server

    Mikulic, Dinko

    2013-01-01

    In constant effort to eliminate mine danger, international mine action community has been developing safety, efficiency and cost-effectiveness of clearance methods. Demining machines have become necessary when conducting humanitarian demining where the mechanization of demining provides greater safety and productivity. Design of Demining Machines describes the development and testing of modern demining machines in humanitarian demining.   Relevant data for design of demining machines are included to explain the machinery implemented and some innovative and inspiring development solutions. Development technologies, companies and projects are discussed to provide a comprehensive estimate of the effects of various design factors and to proper selection of optimal parameters for designing the demining machines.   Covering the dynamic processes occurring in machine assemblies and their components to a broader understanding of demining machine as a whole, Design of Demining Machines is primarily tailored as a tex...

  9. Applied machining technology

    CERN Document Server

    Tschätsch, Heinz

    2010-01-01

    Machining and cutting technologies are still crucial for many manufacturing processes. This reference presents all important machining processes in a comprehensive and coherent way. It includes many examples of concrete calculations, problems and solutions.

  10. Machining with abrasives

    CERN Document Server

    Jackson, Mark J

    2011-01-01

    Abrasive machining is key to obtaining the desired geometry and surface quality in manufacturing. This book discusses the fundamentals and advances in the abrasive machining processes. It provides a complete overview of developing areas in the field.

  11. Women, Men, and Machines.

    Science.gov (United States)

    Form, William; McMillen, David Byron

    1983-01-01

    Data from the first national study of technological change show that proportionately more women than men operate machines, are more exposed to machines that have alienating effects, and suffer more from the negative effects of technological change. (Author/SSH)

  12. Machine medical ethics

    CERN Document Server

    Pontier, Matthijs

    2015-01-01

    The essays in this book, written by researchers from both humanities and sciences, describe various theoretical and experimental approaches to adding medical ethics to a machine in medical settings. Medical machines are in close proximity with human beings, and getting closer: with patients who are in vulnerable states of health, who have disabilities of various kinds, with the very young or very old, and with medical professionals. In such contexts, machines are undertaking important medical tasks that require emotional sensitivity, knowledge of medical codes, human dignity, and privacy. As machine technology advances, ethical concerns become more urgent: should medical machines be programmed to follow a code of medical ethics? What theory or theories should constrain medical machine conduct? What design features are required? Should machines share responsibility with humans for the ethical consequences of medical actions? How ought clinical relationships involving machines to be modeled? Is a capacity for e...

  13. Brain versus Machine Control.

    Directory of Open Access Journals (Sweden)

    Jose M Carmena

    2004-12-01

    Full Text Available Dr. Octopus, the villain of the movie "Spiderman 2", is a fusion of man and machine. Neuroscientist Jose Carmena examines the facts behind this fictional account of a brain- machine interface

  14. Interplay between the bacterial nucleoid protein H-NS and macromolecular crowding in compacting DNA

    NARCIS (Netherlands)

    Wintraecken, C.H.J.M.

    2012-01-01

      In this dissertation we discuss H-NS and its connection to nucleoid compaction and organization. Nucleoid formation involves a dramatic reduction in coil volume of the genomic DNA. Four factors are thought to influence coil volume: supercoiling, DNA charge neutralization, macromolecular crow

  15. A kinetic type extended model for dense gases and macromolecular fluids

    Directory of Open Access Journals (Sweden)

    M. Cristina Carrisi

    2005-05-01

    Full Text Available Extended thermodynamics is an important theory which is appreciated from mathematicians and physicists. Following its ideas and considering the macroscopic approach with suggestions from the kinetic one, we find in this paper, the solution of an interesting model: the model for dense gases and macromolecular fluids.

  16. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    DEFF Research Database (Denmark)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.

    2017-01-01

    Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many...

  17. Isolation and chemical characterization of resistant macromolecular constituents in microalgae and marine sediments

    NARCIS (Netherlands)

    Gelin, F.

    1996-01-01

    The recognition of novel, insoluble and non-hydrolysable macromolecular constituents in protective tissues of fresh-water algae and higher plants has had a major impact on our understanding of the origin and fate of sedimentary organic matter (OM) in terrestrial and lacustrine deposits. The investig

  18. Researches, Publications and Achievements 2007-2011, Department of Macromolecular Science and Engineering

    OpenAIRE

    All teaching staffs at Department of Macromolecular Science and Engineering (19 members)

    2012-01-01

    Recent researches, publications and achievements are presented, which were made during these five years (2007-2011) by 19 members at Department of Macromolecular Science and Engineering. Listed publications include original papers, books, reviews and reports. Achievements such as invited lectures, patents, funds and financial supports, and awards are also listed.

  19. Synergy of DNA-bending nucleoid proteins and macromolecular crowd-condensing DNA

    NARCIS (Netherlands)

    Bessa Ramos, E.; Wintraecken, C.H.J.M.; Geerling, A.C.M.; Vries, de R.J.

    2007-01-01

    Many prokaryotic nucleoid proteins bend DNA and form extended helical protein-DNA fibers rather than condensed structures. On the other hand, it is known that such proteins (such as bacterial HU) strongly promote DNA condensation by macromolecular crowding. Using theoretical arguments, we show that

  20. The Postgraduate Study of Macromolecular Sciences at the University of Zagreb (1971-1980

    Directory of Open Access Journals (Sweden)

    Kunst, B.

    2008-07-01

    Full Text Available The postgraduate study of macromolecular sciences (PSMS was established at the University of Zagreb in 1971 as a university study in the time of expressed interdisciplinary permeation of natural sciences - physics, chemistry and biology, and application of their achievements in technologicaldisciplines. PSMS was established by a group of prominent university professors from the schools of Science, Chemical Technology, Pharmacy and Medicine, as well as from the Institute of Biology. The study comprised basic fields of macromolecular sciences: organic chemistry of synthetic macromolecules, physical chemistry of macromolecules, physics of macromolecules, biological macromolecules and polymer engineering with polymer application and processing, and teaching was performed in 29 lecture courses lead by 30 professors with their collaborators. PSMS ceased to exist with the change of legislation in Croatia in 1980, when the attitude prevailed to render back postgraduate studies to the university schools. During 9 years of existence of PSMS the MSci grade was awarded to 37 macromolecular experts. It was assessed that the PSMS some thirty years ago was an important example of modern postgraduate education as compared with the international postgraduate development. In concordance with the recent introduction of similar interdisciplinary studies in macromolecular sciences elsewhere in the world, the establishment of a modern interdisciplinary study in the field would be of importance for further development of these sciences in Croatia.

  1. Macromolecular Crowding Modulates Folding Mechanism of α/β Protein Apoflavodoxin

    Science.gov (United States)

    Homouz, D.; Stagg, L.; Wittungstafshede, P.; Cheung, M.

    2009-01-01

    Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.

  2. Hydropyrolysis: A new technique for the analysis of macromolecular material in meteorites

    Science.gov (United States)

    Sephton, Mark A.; Love, Gordon D.; Meredith, Will; Snape, Colin E.; Sun, Cheng-Gong; Watson, Jonathan S.

    2005-10-01

    The carbonaceous chondrite meteorites are fragments of asteroids that have remained relatively unprocessed since the formation of the Solar System 4.56 billion years ago. The major organic component in these meteorites is a macromolecular phase that is resistant to solvent extraction. The information contained within macromolecular material can be accessed by degradative techniques such as pyrolysis. Hydropyrolysis refers to pyrolysis assisted by high hydrogen gas pressures and a dispersed sulphided molybdenum catalyst. Hydropyrolysis of the Murchison macromolecular material successfully releases much greater quantities of hydrocarbons than traditional pyrolysis techniques (twofold greater than hydrous pyrolysis) including significant amounts of high molecular weight polyaromatic hydrocarbons (PAH) such as phenanthrene, carbazole, fluoranthene, pyrene, chrysene, perylene, benzoperylene and coronene units with varying degrees of alkylation. When hydropyrolysis products are collected using a silica trap immersed in liquid nitrogen, the technique enables the solubilisation and retention of compounds with a wide range of volatilities (i.e. benzene to coronene). This report describes the hydropyrolysis method and the information it can provide about meteorite macromolecular material constitution.

  3. A Universal Reactive Machine

    DEFF Research Database (Denmark)

    Andersen, Henrik Reif; Mørk, Simon; Sørensen, Morten U.

    1997-01-01

    Turing showed the existence of a model universal for the set of Turing machines in the sense that given an encoding of any Turing machine asinput the universal Turing machine simulates it. We introduce the concept of universality for reactive systems and construct a CCS processuniversal...

  4. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  5. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  6. Genetic backgrounds determine brown remodeling of white fat in rodents

    Directory of Open Access Journals (Sweden)

    Giulia Ferrannini

    2016-10-01

    Conclusion: Rodent genetic background determines the brown remodeling of different white fat depots. This study provides new insights into the role of genetic variation in fat remodeling in susceptibility to metabolic diseases.

  7. Asynchronized synchronous machines

    CERN Document Server

    Botvinnik, M M

    1964-01-01

    Asynchronized Synchronous Machines focuses on the theoretical research on asynchronized synchronous (AS) machines, which are "hybrids” of synchronous and induction machines that can operate with slip. Topics covered in this book include the initial equations; vector diagram of an AS machine; regulation in cases of deviation from the law of full compensation; parameters of the excitation system; and schematic diagram of an excitation regulator. The possible applications of AS machines and its calculations in certain cases are also discussed. This publication is beneficial for students and indiv

  8. Quantum machine learning.

    Science.gov (United States)

    Biamonte, Jacob; Wittek, Peter; Pancotti, Nicola; Rebentrost, Patrick; Wiebe, Nathan; Lloyd, Seth

    2017-09-13

    Fuelled by increasing computer power and algorithmic advances, machine learning techniques have become powerful tools for finding patterns in data. Quantum systems produce atypical patterns that classical systems are thought not to produce efficiently, so it is reasonable to postulate that quantum computers may outperform classical computers on machine learning tasks. The field of quantum machine learning explores how to devise and implement quantum software that could enable machine learning that is faster than that of classical computers. Recent work has produced quantum algorithms that could act as the building blocks of machine learning programs, but the hardware and software challenges are still considerable.

  9. Precision machine design

    CERN Document Server

    Slocum, Alexander H

    1992-01-01

    This book is a comprehensive engineering exploration of all the aspects of precision machine design - both component and system design considerations for precision machines. It addresses both theoretical analysis and practical implementation providing many real-world design case studies as well as numerous examples of existing components and their characteristics. Fast becoming a classic, this book includes examples of analysis techniques, along with the philosophy of the solution method. It explores the physics of errors in machines and how such knowledge can be used to build an error budget for a machine, how error budgets can be used to design more accurate machines.

  10. Retinal remodeling in human retinitis pigmentosa.

    Science.gov (United States)

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

  11. Revealing remodeler function: Varied and unique

    Science.gov (United States)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  12. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  13. Mechanisms of Airway Remodeling in Asthma

    Directory of Open Access Journals (Sweden)

    Etsuko Tagaya

    2007-01-01

    To date, many studies have identified candidate mechanisms and mediators for these observed structural changes, which are thus potential targets in the treatment of asthma. In this review, we describe the recent knowledge of the mechanisms and clinical implications of airway remodeling in asthma.

  14. Immune modulation of resistance artery remodelling.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2012-01-01

    Low-grade inflammation plays a role in cardiovascular disease. The innate and the adaptive immune responses participate in mechanisms that contribute to inflammatory responses. It has been increasingly appreciated that different subsets of lymphocytes and the cytokines they produce modulate the vascular remodelling that occurs in cardiovascular disease. Effector T cells such as T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (that produce interleukin-4), as well as Th17 (that produce interleukin-17), and T suppressor lymphocytes including regulatory T cells (Treg), which express the transcription factor forkhead box P3 (Foxp3), are involved in the remodelling of small arteries that occurs under the action of angiotensin II, deoxycorticosterone-salt and aldosterone-salt, as well as in models of hypertension such as the Dahl-salt-sensitive rat. The mechanism whereby the immune system is activated is unclear, but it has been suggested that neo-antigens may be generated by the elevation of blood pressure or other stimuli, leading to the activation of the immune response. Activated Th1 may contribute to vascular remodelling directly on blood vessels via effects of the cytokines produced or indirectly by actions on the kidney. The protective effect of Treg may be mediated similarly directly or via renal effects. These data offer promise for the discovery of new therapeutic targets to ameliorate vascular remodelling, which could lead to improved outcome in cardiovascular disease in humans.

  15. Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

    A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

  16. [Remodeling of cardiac gap junctions and arrhythmias].

    Science.gov (United States)

    Yu, Zhi-Bin; Sheng, Juan-Juan

    2011-12-25

    In the heart, gap junctions mediate electrical and chemical coupling between adjacent cardiomyocytes, forming the cell-to-cell pathways for orderly spread of the wave of electrical excitation responsible for a functional syncytium. Three principal connexins are expressed in cardiomyocytes, connexin 43 (CX43), CX40, and CX45. CX43 predominates in ventricular muscle cells. Most of the gap junctions, assembled from CX43, are located at the intercalated discs, often with larger junctional plaques at the disc periphery. The gap junctions are rarely distributed to the sides of the cardiomyocyte. The ischemia-reperfusion, cardiac hypertrophy, heart failure, hypercholesterolemia, and diabetes mellitus induce gap junction remodeling. The gap junction remodeling induced by above-mentioned diseases shows similar characteristics, including down-regulation of CX43, reduction in gap junction plaque size, increased heterogeneity and lateralization of gap junction distribution, and dephosphorylation of CX43. The elevated angiotensin II concentration in local myocardium may play an important role in the gap junction remodeling. The down-regulation of CX43 and lateralization of gap junction distribution alter anisotropic spread of the impulse of ventricular myocardium. The dephosphorylation of CX43 not only reduces electrical conductance, but also decreases permeability of chemicals between cardiomyocytes. The lateralization of gap junctions may increase the number of hemichannels formed by CX43. The opening of hemichannels induces ATP efflux and Na(+) influx, which forms a delayed after-depolarization. The gap junction remodeling in pathological condition produces arrhythmia substrate in the ventricles. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and arrhythmias were summarized.

  17. Perspex machine: VII. The universal perspex machine

    Science.gov (United States)

    Anderson, James A. D. W.

    2006-01-01

    The perspex machine arose from the unification of projective geometry with the Turing machine. It uses a total arithmetic, called transreal arithmetic, that contains real arithmetic and allows division by zero. Transreal arithmetic is redefined here. The new arithmetic has both a positive and a negative infinity which lie at the extremes of the number line, and a number nullity that lies off the number line. We prove that nullity, 0/0, is a number. Hence a number may have one of four signs: negative, zero, positive, or nullity. It is, therefore, impossible to encode the sign of a number in one bit, as floating-point arithmetic attempts to do, resulting in the difficulty of having both positive and negative zeros and NaNs. Transrational arithmetic is consistent with Cantor arithmetic. In an extension to real arithmetic, the product of zero, an infinity, or nullity with its reciprocal is nullity, not unity. This avoids the usual contradictions that follow from allowing division by zero. Transreal arithmetic has a fixed algebraic structure and does not admit options as IEEE, floating-point arithmetic does. Most significantly, nullity has a simple semantics that is related to zero. Zero means "no value" and nullity means "no information." We argue that nullity is as useful to a manufactured computer as zero is to a human computer. The perspex machine is intended to offer one solution to the mind-body problem by showing how the computable aspects of mind and, perhaps, the whole of mind relates to the geometrical aspects of body and, perhaps, the whole of body. We review some of Turing's writings and show that he held the view that his machine has spatial properties. In particular, that it has the property of being a 7D lattice of compact spaces. Thus, we read Turing as believing that his machine relates computation to geometrical bodies. We simplify the perspex machine by substituting an augmented Euclidean geometry for projective geometry. This leads to a general

  18. The RSC chromatin remodeling complex has a crucial role in the complete remodeler set for yeast PHO5 promoter opening.

    Science.gov (United States)

    Musladin, Sanja; Krietenstein, Nils; Korber, Philipp; Barbaric, Slobodan

    2014-04-01

    Although yeast PHO5 promoter chromatin opening is a founding model for chromatin remodeling, the complete set of involved remodelers remained unknown for a long time. The SWI/SNF and INO80 remodelers cooperate here, but nonessentially, and none of the many tested single or combined remodeler gene mutations could prevent PHO5 promoter opening. RSC, the most abundant and only remodeler essential for viability, was a controversial candidate for the unrecognized remodeling activity but unassessed in vivo. Now we show that remodels the structure of chromatin (RSC) is crucially involved in PHO5 promoter opening. Further, the isw1 chd1 double deletion also delayed chromatin remodeling. Strikingly, combined absence of RSC and Isw1/Chd1 or Snf2 abolished for the first time promoter opening on otherwise sufficient induction in vivo. Together with previous findings, we recognize now a surprisingly complex network of five remodelers (RSC, SWI/SNF, INO80, Isw1 and Chd1) from four subfamilies (SWI/SNF, INO80, ISWI and CHD) as involved in PHO5 promoter chromatin remodeling. This is likely the first described complete remodeler set for a physiological chromatin transition. RSC was hardly involved at the coregulated PHO8 or PHO84 promoters despite cofactor recruitment by the same transactivator and RSC's presence at all three promoters. Therefore, promoter-specific chromatin rather than transactivators determine remodeler requirements.

  19. Porosity Defect Remodeling and Tensile Analysis of Cast Steel

    Directory of Open Access Journals (Sweden)

    Linfeng Sun

    2016-02-01

    Full Text Available Tensile properties on ASTM A216 WCB cast steel with centerline porosity defect were studied with radiographic mapping and finite element remodeling technique. Non-linear elastic and plastic behaviors dependent on porosity were mathematically described by relevant equation sets. According to the ASTM E8 tensile test standard, matrix and defect specimens were machined into two categories by two types of height. After applying radiographic inspection, defect morphologies were mapped to the mid-sections of the finite element models and the porosity fraction fields had been generated with interpolation method. ABAQUS input parameters were confirmed by trial simulations to the matrix specimen and comparison with experimental outcomes. Fine agreements of the result curves between simulations and experiments could be observed, and predicted positions of the tensile fracture were found to be in accordance with the tests. Chord modulus was used to obtain the equivalent elastic stiffness because of the non-linear features. The results showed that elongation was the most influenced term to the defect cast steel, compared with elastic stiffness and yield stress. Additional visual explanations on the tensile fracture caused by void propagation were also given by the result contours at different mechanical stages, including distributions of Mises stress and plastic strain.

  20. Association Between Myocardial Mechanics and Ischemic LV Remodeling.

    Science.gov (United States)

    D'Elia, Nicholas; D'hooge, Jan; Marwick, Thomas H

    2015-12-01

    The outcomes associated with heart failure after myocardial infarction are still poor. Both global and regional left ventricular (LV) remodeling are associated with the progression of the post-infarct patient to heart failure, but although global remodeling can be accurately measured, regional LV remodeling has been more difficult to investigate. Preliminary evidence suggests that post-MI assessment of LV mechanics using stress and strain may predict global (and possibly regional) LV remodeling. A method of predicting both global and regional LV remodeling might facilitate earlier, targeted, and more extensive clinical intervention in those most likely to benefit from novel interventions such as cell therapy.

  1. Advances in electron microscopy: A qualitative view of instrumentation development for macromolecular imaging and tomography.

    Science.gov (United States)

    Schröder, Rasmus R

    2015-09-01

    Macromolecular imaging and tomography of ice embedded samples has developed into a mature imaging technology, in structural biology today widely referred to simply as cryo electron microscopy.(1) While the pioneers of the technique struggled with ill-suited instruments, state-of-the-art cryo microscopes are now readily available and an increasing number of groups are producing excellent high-resolution structural data of macromolecular complexes, of cellular organelles, or the morphology of whole cells. Instrumentation developers, however, are offering yet more novel electron optical devices, such as energy filters and monochromators, aberration correctors or physical phase plates. Here we discuss how current instrumentation has already changed cryo EM, and how newly available instrumentation - often developed in other fields of electron microscopy - may further develop the use and applicability of cryo EM to the imaging of single isolated macromolecules of smaller size or molecules embedded in a crowded cellular environment.

  2. Optimal cytoplasmatic density and flux balance model under macromolecular crowding effects.

    Science.gov (United States)

    Vazquez, Alexei

    2010-05-21

    Macromolecules occupy between 34% and 44% of the cell cytoplasm, about half the maximum packing density of spheres in three dimension. Yet, there is no clear understanding of what is special about this value. To address this fundamental question we investigate the effect of macromolecular crowding on cell metabolism. We develop a cell scale flux balance model capturing the main features of cell metabolism at different nutrient uptakes and macromolecular densities. Using this model we show there are two metabolic regimes at low and high nutrient uptakes. The latter regime is characterized by an optimal cytoplasmatic density where the increase of reaction rates by confinement and the decrease by diffusion slow-down balance. More important, the predicted optimal density is in the range of the experimentally determined density of Escherichia coli.

  3. Macromolecular crowding increases binding of DNA polymerase to DNA: an adaptive effect

    Energy Technology Data Exchange (ETDEWEB)

    Zimmerman, S.B.; Harrison, B.

    1987-05-01

    Macromolecular crowding extends the range of ionic conditions supporting high DNA polymerase reaction rates. Reactions tested were nick translation and gap-filling by DNA polymerase I of E. coli, nuclease and polymerase activities of the large fragment of that polymerase, and polymerization by the T4 DNA polymerase. For all of these reactions, high concentrations of nonspecific polymers increased enzymatic activity under otherwise inhibitory conditions resulting from relatively high ionic strength. The primary mechanism of the polymer effect seems to be to increase the binding of polymerase to DNA. They suggest that this effect of protein-DNA complexes is only one example of a general metabolic buffering action of crowded solutions on a variety of macromolecular interactions.

  4. The macromolecular crystallography beamline I911-3 at the MAX IV laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Ursby, Thomas, E-mail: thomas.ursby@maxlab.lu.se; Unge, Johan; Appio, Roberto [Lund University, POB 118, Lund SE-221 00 (Sweden); Logan, Derek T. [Lund University, POB 124, Lund SE-221 00 (Sweden); Fredslund, Folmer; Svensson, Christer; Larsson, Krister; Labrador, Ana [Lund University, POB 118, Lund SE-221 00 (Sweden); Thunnissen, Marjolein M. G. M. [Lund University, POB 124, Lund SE-221 00 (Sweden)

    2013-07-01

    The updated macromolecular crystallography beamline I911-3 at the MAX II storage ring is described. The macromolecular crystallography beamline I911-3, part of the Cassiopeia/I911 suite of beamlines, is based on a superconducting wiggler at the MAX II ring of the MAX IV Laboratory in Lund, Sweden. The beamline is energy-tunable within a range between 6 and 18 keV. I911-3 opened for users in 2005. In 2010–2011 the experimental station was completely rebuilt and refurbished such that it has become a state-of-the-art experimental station with better possibilities for rapid throughput, crystal screening and work with smaller samples. This paper describes the complete I911-3 beamline and how it is embedded in the Cassiopeia suite of beamlines.

  5. Romp: The Method of Choice for Precise Macromolecular Engineering and Synthesis of Smart Materials

    Science.gov (United States)

    Khosravi, Ezat; Castle, Thomas C.; Kujawa, Margaret; Leejarkpai, Jan; Hutchings, Lian R.; Hine, Peter J.

    The recent advances in olefin metathesis highlight the impact of Ring Opening Metathesis Polymerisation (ROMP) as a powerful technique for macromolecular engineering and synthesis of smart materials with well-defined structures. ROMP has attracted a considerable research attention recently particularly by industry largely due to the development of well-defined metal complexes as initiators and also because of the award of the Noble Prize for Chemistry in 2005 to three scientists (Chauvin, Grubbs, Schrock) for their contributions in this area. This chapter discusses several interesting examples in order to demonstrate that ROMP is a power tool in macromolecular engineering and that it allows the design and synthesis of polymers with novel topologies.

  6. Long-Wavelength X-Ray Diffraction and Its Applications in Macromolecular Crystallography.

    Science.gov (United States)

    Weiss, Manfred S

    2017-01-01

    For many years, diffraction experiments in macromolecular crystallography at X-ray wavelengths longer than that of Cu-K α (1.54 Å) have been largely underappreciated. Effects caused by increased X-ray absorption result in the fact that these experiments are more difficult than the standard diffraction experiments at short wavelengths. However, due to the also increased anomalous scattering of many biologically relevant atoms, important additional structural information can be obtained. This information, in turn, can be used for phase determination, for substructure identification, in molecular replacement approaches, as well as in structure refinement. This chapter reviews the possibilities and the difficulties associated with such experiments, and it provides a short description of two macromolecular crystallography synchrotron beam lines dedicated to long-wavelength X-ray diffraction experiments.

  7. 3DEM Loupe: Analysis of macromolecular dynamics using structures from electron microscopy.

    Science.gov (United States)

    Nogales-Cadenas, R; Jonic, S; Tama, F; Arteni, A A; Tabas-Madrid, D; Vázquez, M; Pascual-Montano, A; Sorzano, C O S

    2013-07-01

    Electron microscopy (EM) provides access to structural information of macromolecular complexes in the 3-20 Å resolution range. Normal mode analysis has been extensively used with atomic resolution structures and successfully applied to EM structures. The major application of normal modes is the identification of possible conformational changes in proteins. The analysis can throw light on the mechanism following ligand binding, protein-protein interactions, channel opening and other functional macromolecular movements. In this article, we present a new web server, 3DEM Loupe, which allows normal mode analysis of any uploaded EM volume using a user-friendly interface and an intuitive workflow. Results can be fully explored in 3D through animations and movies generated by the server. The application is freely available at http://3demloupe.cnb.csic.es.

  8. Clustering procedures for the optimal selection of data sets from multiple crystals in macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Foadi, James [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Aller, Pierre [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Alguel, Yilmaz; Cameron, Alex [Imperial College, London SW7 2AZ (United Kingdom); Axford, Danny; Owen, Robin L. [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Armour, Wes [Oxford e-Research Centre (OeRC), Keble Road, Oxford OX1 3QG (United Kingdom); Waterman, David G. [Research Complex at Harwell (RCaH), Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0FA (United Kingdom); Iwata, So [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom); Imperial College, London SW7 2AZ (United Kingdom); Evans, Gwyndaf, E-mail: gwyndaf.evans@diamond.ac.uk [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE (United Kingdom)

    2013-08-01

    A systematic approach to the scaling and merging of data from multiple crystals in macromolecular crystallography is introduced and explained. The availability of intense microbeam macromolecular crystallography beamlines at third-generation synchrotron sources has enabled data collection and structure solution from microcrystals of <10 µm in size. The increased likelihood of severe radiation damage where microcrystals or particularly sensitive crystals are used forces crystallographers to acquire large numbers of data sets from many crystals of the same protein structure. The associated analysis and merging of multi-crystal data is currently a manual and time-consuming step. Here, a computer program, BLEND, that has been written to assist with and automate many of the steps in this process is described. It is demonstrated how BLEND has successfully been used in the solution of a novel membrane protein.

  9. Machinability of advanced materials

    CERN Document Server

    Davim, J Paulo

    2014-01-01

    Machinability of Advanced Materials addresses the level of difficulty involved in machining a material, or multiple materials, with the appropriate tooling and cutting parameters.  A variety of factors determine a material's machinability, including tool life rate, cutting forces and power consumption, surface integrity, limiting rate of metal removal, and chip shape. These topics, among others, and multiple examples comprise this research resource for engineering students, academics, and practitioners.

  10. Pattern recognition & machine learning

    CERN Document Server

    Anzai, Y

    1992-01-01

    This is the first text to provide a unified and self-contained introduction to visual pattern recognition and machine learning. It is useful as a general introduction to artifical intelligence and knowledge engineering, and no previous knowledge of pattern recognition or machine learning is necessary. Basic for various pattern recognition and machine learning methods. Translated from Japanese, the book also features chapter exercises, keywords, and summaries.

  11. Support vector machines applications

    CERN Document Server

    Guo, Guodong

    2014-01-01

    Support vector machines (SVM) have both a solid mathematical background and good performance in practical applications. This book focuses on the recent advances and applications of the SVM in different areas, such as image processing, medical practice, computer vision, pattern recognition, machine learning, applied statistics, business intelligence, and artificial intelligence. The aim of this book is to create a comprehensive source on support vector machine applications, especially some recent advances.

  12. Machining of titanium alloys

    CERN Document Server

    2014-01-01

    This book presents a collection of examples illustrating the resent research advances in the machining of titanium alloys. These materials have excellent strength and fracture toughness as well as low density and good corrosion resistance; however, machinability is still poor due to their low thermal conductivity and high chemical reactivity with cutting tool materials. This book presents solutions to enhance machinability in titanium-based alloys and serves as a useful reference to professionals and researchers in aerospace, automotive and biomedical fields.

  13. STUDIES ON PAN MACROMOLECULAR SEMICONDUCTING FIBER 1. PREPARATION OF PAN CONDUCTING FIBER TREATED BY STANNIC CHLORIDE AND ITS SEMICONDUCTING BEHAVIOUR

    Institute of Scientific and Technical Information of China (English)

    WANG Dexi; CUI Dayuan; LUO Boliang; WANG Xiugang; WU Renjie

    1984-01-01

    The PAN fiber treated by Lewis acid (e.g. stannic chloride) could be transformed into a macromolecular conducting fiber by further thermal treatment. Depending on thermal treatment condition the resistance of the fiber varied from 103 to 1012 Ω and kept stable after hydrolysis. The fiber has enough strength to be processed by various means. This is a new kind of macromolecular semiconducting fiber having some characteristics similar to those of organic semiconductors.

  14. STUDY ON HYDROLYSIS OF MACROMOLECULAR GELATIN WITH ENZYMES IN COMBINATION MODE

    Institute of Scientific and Technical Information of China (English)

    Ya-qin Huang; Rui Guan; Ming-zhi Huang

    2004-01-01

    The enzymatic hydrolysis of macromolecular gelatin with AS1.398 neutral protease, bromelain and their combinations was studied by estimating the molecular weights of their hydrolytic products. It was discovered that the products hydrolyzed by using combination enzymes had lower molecular weight than those obtained by using single ones,and the kind of enzymes, their combination mode and addition sequence are effective ways to control the molecular weights of gelatin hydrolyzates.

  15. Porphyrin-Cored Polymer Nanoparticles: Macromolecular Models for Heme Iron Coordination.

    Science.gov (United States)

    Rodriguez, Kyle J; Hanlon, Ashley M; Lyon, Christopher K; Cole, Justin P; Tuten, Bryan T; Tooley, Christian A; Berda, Erik B; Pazicni, Samuel

    2016-10-03

    Porphyrin-cored polymer nanoparticles (PCPNs) were synthesized and characterized to investigate their utility as heme protein models. Created using collapsible heme-centered star polymers containing photodimerizable anthracene units, these systems afford model heme cofactors buried within hydrophobic, macromolecular environments. Spectroscopic interrogations demonstrate that PCPNs display redox and ligand-binding reactivity similar to that of native systems and thus are potential candidates for modeling biological heme iron coordination.

  16. CplexA: a Mathematica package to study macromolecular-assembly control of gene expression

    OpenAIRE

    Vilar, J. M. G.; Saiz, L

    2010-01-01

    Summary: Macromolecular assembly vertebrates essential cellular processes, such as gene regulation and signal transduction. A major challenge for conventional computational methods to study these processes is tackling the exponential increase of the number of configurational states with the number of components. CplexA is a Mathematica package that uses functional programming to efficiently compute probabilities and average properties over such exponentially large number of states from the en...

  17. Controlling Macromolecular Topology with Genetically Encoded SpyTag-SpyCatcher Chemistry

    OpenAIRE

    Zhang, Wen-Bin; Sun, Fei; Tirrell, David A.; Arnold, Frances H.

    2013-01-01

    Control of molecular topology constitutes a fundamental challenge in macromolecular chemistry. Here we describe the synthesis and characterization of artificial elastin-like proteins (ELPs) with unconventional nonlinear topologies including circular, tadpole, star, and H-shaped proteins using genetically encoded SpyTag–SpyCatcher chemistry. SpyTag is a short polypeptide that binds its protein partner SpyCatcher and forms isopeptide bonds under physiological conditions. Sequences encoding SpyT...

  18. Rotating electrical machines

    CERN Document Server

    Le Doeuff, René

    2013-01-01

    In this book a general matrix-based approach to modeling electrical machines is promulgated. The model uses instantaneous quantities for key variables and enables the user to easily take into account associations between rotating machines and static converters (such as in variable speed drives).   General equations of electromechanical energy conversion are established early in the treatment of the topic and then applied to synchronous, induction and DC machines. The primary characteristics of these machines are established for steady state behavior as well as for variable speed scenarios. I

  19. Chaotic Boltzmann machines.

    Science.gov (United States)

    Suzuki, Hideyuki; Imura, Jun-ichi; Horio, Yoshihiko; Aihara, Kazuyuki

    2013-01-01

    The chaotic Boltzmann machine proposed in this paper is a chaotic pseudo-billiard system that works as a Boltzmann machine. Chaotic Boltzmann machines are shown numerically to have computing abilities comparable to conventional (stochastic) Boltzmann machines. Since no randomness is required, efficient hardware implementation is expected. Moreover, the ferromagnetic phase transition of the Ising model is shown to be characterised by the largest Lyapunov exponent of the proposed system. In general, a method to relate probabilistic models to nonlinear dynamics by derandomising Gibbs sampling is presented.

  20. Tribology in machine design

    CERN Document Server

    Stolarski, Tadeusz

    1999-01-01

    ""Tribology in Machine Design is strongly recommended for machine designers, and engineers and scientists interested in tribology. It should be in the engineering library of companies producing mechanical equipment.""Applied Mechanics ReviewTribology in Machine Design explains the role of tribology in the design of machine elements. It shows how algorithms developed from the basic principles of tribology can be used in a range of practical applications within mechanical devices and systems.The computer offers today's designer the possibility of greater stringen

  1. Debugging the virtual machine

    Energy Technology Data Exchange (ETDEWEB)

    Miller, P.; Pizzi, R.

    1994-09-02

    A computer program is really nothing more than a virtual machine built to perform a task. The program`s source code expresses abstract constructs using low level language features. When a virtual machine breaks, it can be very difficult to debug because typical debuggers provide only low level machine implementation in formation to the software engineer. We believe that the debugging task can be simplified by introducing aspects of the abstract design into the source code. We introduce OODIE, an object-oriented language extension that allows programmers to specify a virtual debugging environment which includes the design and abstract data types of the virtual machine.

  2. Electrical machines & drives

    CERN Document Server

    Hammond, P

    1985-01-01

    Containing approximately 200 problems (100 worked), the text covers a wide range of topics concerning electrical machines, placing particular emphasis upon electrical-machine drive applications. The theory is concisely reviewed and focuses on features common to all machine types. The problems are arranged in order of increasing levels of complexity and discussions of the solutions are included where appropriate to illustrate the engineering implications. This second edition includes an important new chapter on mathematical and computer simulation of machine systems and revised discussions o

  3. Machine learning with R

    CERN Document Server

    Lantz, Brett

    2013-01-01

    Written as a tutorial to explore and understand the power of R for machine learning. This practical guide that covers all of the need to know topics in a very systematic way. For each machine learning approach, each step in the process is detailed, from preparing the data for analysis to evaluating the results. These steps will build the knowledge you need to apply them to your own data science tasks.Intended for those who want to learn how to use R's machine learning capabilities and gain insight from your data. Perhaps you already know a bit about machine learning, but have never used R; or

  4. Induction machine handbook

    CERN Document Server

    Boldea, Ion

    2002-01-01

    Often called the workhorse of industry, the advent of power electronics and advances in digital control are transforming the induction motor into the racehorse of industrial motion control. Now, the classic texts on induction machines are nearly three decades old, while more recent books on electric motors lack the necessary depth and detail on induction machines.The Induction Machine Handbook fills industry's long-standing need for a comprehensive treatise embracing the many intricate facets of induction machine analysis and design. Moving gradually from simple to complex and from standard to

  5. Metabolic remodeling in chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Jing WANG; Tao GUO

    2013-01-01

    Although the management of chronic heart failure (CHF) has made enormous progress over the past decades,CHF is still a tremendous medical and societal burden.Metabolic remodeling might play a crucial role in the pathophysiology of CHF.The characteristics and mechanisms of metabolic remodeling remained unclear,and the main hypothesis might include the changes in the availability of metabolic substrate and the decline of metabolic capability.In the early phases of the disease,metabolism shifts toward carbohydrate utilization from fatty acids (FAs) oxidation.Along with the progress of the disease,the increasing level of the hyperadrenergic state and insulin resistance cause the changes that shift back to a greater FA uptake and oxidation.In addition,a growing body of experimental and clinical evidence suggests that the improvement in the metabolic capability is likely to be more significant than the selection of the substrate.

  6. Chromatin remodeling in cardiovascular development and physiology.

    Science.gov (United States)

    Han, Pei; Hang, Calvin T; Yang, Jin; Chang, Ching-Pin

    2011-02-04

    Chromatin regulation provides an important means for controlling cardiac gene expression under different physiological and pathological conditions. Processes that direct the development of normal embryonic hearts and pathology of stressed adult hearts may share general mechanisms that govern cardiac gene expression by chromatin-regulating factors. These common mechanisms may provide a framework for us to investigate the interactions among diverse chromatin remodelers/modifiers and various transcription factors in the fine regulation of gene expression, essential for all aspects of cardiovascular biology. Aberrant cardiac gene expression, triggered by a variety of pathological insults, can cause heart diseases in both animals and humans. The severity of cardiomyopathy and heart failure correlates strongly with abnormal cardiac gene expression. Therefore, controlling cardiac gene expression presents a promising approach to the treatment of human cardiomyopathy. This review focuses on the roles of ATP-dependent chromatin-remodeling factors and chromatin-modifying enzymes in the control of gene expression during cardiovascular development and disease.

  7. In Vitro and In Vivo Evaluation of Microparticulate Drug Delivery Systems Composed of Macromolecular Prodrugs

    Directory of Open Access Journals (Sweden)

    Yoshiharu Machida

    2008-08-01

    Full Text Available Macromolecular prodrugs are very useful systems for achieving controlled drug release and drug targeting. In particular, various macromolecule-antitumor drug conjugates enhance the effectiveness and improve the toxic side effects. Also, polymeric micro- and nanoparticles have been actively examined and their in vivo behaviors elucidated, and it has been realized that their particle characteristics are very useful to control drug behavior. Recently, researches based on the combination of the concepts of macromolecular prodrugs and micro- or nanoparticles have been reported, although they are limited. Macromolecular prodrugs enable drugs to be released at a certain controlled release rate based on the features of the macromolecule-drug linkage. Micro- and nanoparticles can control in vivo behavior based on their size, surface charge and surface structure. These merits are expected for systems produced by the combination of each concept. In this review, several micro- or nanoparticles composed of macromolecule-drug conjugates are described for their preparation, in vitro properties and/or in vivo behavior.

  8. Macromolecular (pro)drugs with concurrent direct activity against the hepatitis C virus and inflammation.

    Science.gov (United States)

    Wohl, Benjamin M; Smith, Anton A A; Jensen, Bettina E B; Zelikin, Alexander N

    2014-12-28

    Macromolecular prodrugs (MPs) are a powerful tool to alleviate side-effects and improve the efficacy of the broad-spectrum antiviral agent ribavirin. In this work, we sought an understanding of what makes an optimal formulation within the macromolecular parameter space--nature of the polymer carrier, average molar mass, drug loading, or a good combination thereof. A panel of MPs based on biocompatible synthetic vinylic and (meth)acrylic polymers was tested in an anti-inflammatory assay with relevance to alleviating inflammation in the liver during hepatitis C infection. Pristine polymer carriers proved to have a pronounced anti-inflammatory activity, a notion which may prove significant in developing MPs for antiviral and anticancer treatments. With conjugated ribavirin, MPs revealed enhanced activity but also higher toxicity. Therapeutic windows and therapeutic indices were determined and discussed to reveal the most potent formulation and those with optimized safety. Polymers were also tested as inhibitors of replication of the hepatitis C viral RNA using a subgenomic viral replicon system. For the first time, negatively charged polymers are revealed to have an intracellular activity against hepatitis C virus replication. Concerted activity of the polymer and ribavirin afforded MPs which significantly increased the therapeutic index of ribavirin-based treatment. Taken together, the systematic investigation of the macromolecular space identified lead candidates with high efficacy and concurrent direct activity against the hepatitis C virus and inflammation.

  9. Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics

    Science.gov (United States)

    Moffatt, Ryan; Ma, Buyong; Nussinov, Ruth

    2016-01-01

    Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts. PMID:27124275

  10. Implementation of remote monitoring and diffraction evaluation systems at the Photon Factory macromolecular crystallography beamlines

    Science.gov (United States)

    Yamada, Yusuke; pHonda, Nobuo; Matsugaki, Naohiro; Igarashi, Noriyuki; Hiraki, Masahiko; Wakatsuki, Soichi

    2008-01-01

    Owing to recent advances in high-throughput technology in macromolecular crystallography beamlines, such as high-brilliant X-ray sources, high-speed readout detectors and robotics, the number of samples that can be examined in a single visit to the beamline has increased dramatically. In order to make these experiments more efficient, two functions, remote monitoring and diffraction image evaluation, have been implemented in the macromolecular crystallography beamlines at the Photon Factory (PF). Remote monitoring allows scientists to participate in the experiment by watching from their laboratories, without having to come to the beamline. Diffraction image evaluation makes experiments easier, especially when using the sample exchange robot. To implement these two functions, two independent clients have been developed that work specifically for remote monitoring and diffraction image evaluation. In the macromolecular crystallography beamlines at PF, beamline control is performed using STARS (simple transmission and retrieval system). The system adopts a client–server style in which client programs communicate with each other through a server process using the STARS protocol. This is an advantage of the extension of the system; implementation of these new functions required few modifications of the existing system. PMID:18421163

  11. Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics.

    Directory of Open Access Journals (Sweden)

    Tatiana Maximova

    2016-04-01

    Full Text Available Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts.

  12. Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination.

    Science.gov (United States)

    Wlodawer, Alexander; Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz

    2013-11-01

    The number of macromolecular structures deposited in the Protein Data Bank now approaches 100,000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation.

  13. Chromatin remodeling in cardiovascular development and physiology

    OpenAIRE

    Han, Pei; Hang, Calvin T.; Yang, Jin; Chang, Ching-Pin

    2011-01-01

    Chromatin regulation provides an important means of controlling cardiac gene expression under different physiological and pathological conditions. Processes that direct the development of normal embryonic hearts and pathology of stressed adult hearts may share general mechanisms that govern cardiac gene expression by chromatin-regulating factors. These common mechanisms may provide a framework for us to investigate the interactions among diverse chromatin remodelers/modifiers and various tran...

  14. Virtual machine vs Real Machine: Security Systems

    Directory of Open Access Journals (Sweden)

    Dr. C. Suresh Gnana Das

    2009-08-01

    Full Text Available This paper argues that the operating system and applications currently running on a real machine should relocate into a virtual machine. This structure enables services to be added below the operating system and to do so without trusting or modifying the operating system or applications. To demonstrate the usefulness of this structure, we describe three services that take advantage of it: secure logging, intrusion prevention and detection, and environment migration. In particular, we can provide services below the guest operating system without trusting or modifying it. We believe providing services at this layer are especially useful for enhancing security and mobility. This position paper describes the general benefits and challenges that arise from running most applications in a virtual machine, and then describes some example services and alternative ways to provide those services.

  15. Psoriatic architecture constructed by epidermal remodeling.

    Science.gov (United States)

    Iizuka, Hajime; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2004-08-01

    Epidermal remodeling is the concept that epidermal architecture is determined by a simple self-organizing mechanism; epidermal hyperproliferation constructs typical psoriatic architecture. This is based on the assumption that the enlargements in both the two-dimensional proliferative compartment (basal cell layer) and three-dimensional whole epidermal volume coexist. During this process, the dermal papillae become markedly, but passively, expanded by enlargement of the proliferative compartment. This creates a considerable shrinkage force against the crowded basal cell layer, which is forced to lose adherence to the dermal extracellular matrix (ECM). This results in anoikis, a type of apoptosis characterized by cell detachment, and, consequently, a markedly diminished epidermal turnover time in psoriasis. The papillary shrinkage force also explains the fact that dermal papillary height does not exceed a certain limit. At the cessation of hyperproliferation a normalisation remodeling takes place toward normal tissue architecture. Thus the concept of epidermal remodeling explains the self-organizing mechanism of the architectural change in psoriasis, which is essentially a reversible disorder depending on epidermal hyperproliferation.

  16. Bone Remodelling Markers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Patrice Fardellone

    2014-01-01

    Full Text Available Bone loss in rheumatoid arthritis (RA patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin, serum aminoterminal propeptide of type I collagen (PINP, serum carboxyterminal propeptide of type I collagen (ICTP, bone alkaline phosphatase (BAP, osteocalcin (OC, and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX, N-terminal telopeptide of type 1 collagen (I-NTX, pyridinolines (DPD and PYD, and tartrate-resistant acid phosphatase (TRAP. Bone resorption can be seen either in periarticular bone (demineralization and erosion or in the total skeleton (osteoporosis. Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

  17. Stepwise nucleosome translocation by RSC remodeling complexes.

    Science.gov (United States)

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-02-19

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome.

  18. Tissue Remodelling following Resection of Porcine Liver

    Directory of Open Access Journals (Sweden)

    Ingvild Engdal Nygård

    2015-01-01

    Full Text Available Aim. To study genes regulating the extracellular matrix (ECM and investigate the tissue remodelling following liver resection in porcine. Methods. Four pigs with 60% partial hepatectomy- (PHx- induced liver regeneration were studied over six weeks. Four pigs underwent sham surgery and another four pigs were used as controls of the normal liver growth. Liver biopsies were taken upon laparotomy, after three and six weeks. Gene expression profiles were obtained using porcine-specific oligonucleotide microarrays. Immunohistochemical staining was performed and a proliferative index was assessed. Results. More differentially expressed genes were associated with the regulation of ECM in the resection group compared to the sham and control groups. Secreted protein acidic and rich in cysteine (SPARC and collagen 1, alpha 2 (COL1A2 were both upregulated in the early phase of liver regeneration, validated by immunopositive cells during the remodelling phase of liver regeneration. A broadened connective tissue was demonstrated by Masson’s Trichrome staining, and an immunohistochemical staining against pan-Cytokeratin (pan-CK demonstrated a distinct pattern of migrating cells, followed by proliferating cell nuclear antigen (PCNA positive nuclei. Conclusions. The present study demonstrates both a distinct pattern of PCNA positive nuclei and a deposition of ECM proteins in the remodelling phase of liver regeneration.

  19. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  20. Stirling machine operating experience

    Energy Technology Data Exchange (ETDEWEB)

    Ross, B. [Stirling Technology Co., Richland, WA (United States); Dudenhoefer, J.E. [Lewis Research Center, Cleveland, OH (United States)

    1994-09-01

    Numerous Stirling machines have been built and operated, but the operating experience of these machines is not well known. It is important to examine this operating experience in detail, because it largely substantiates the claim that stirling machines are capable of reliable and lengthy operating lives. The amount of data that exists is impressive, considering that many of the machines that have been built are developmental machines intended to show proof of concept, and are not expected to operate for lengthy periods of time. Some Stirling machines (typically free-piston machines) achieve long life through non-contact bearings, while other Stirling machines (typically kinematic) have achieved long operating lives through regular seal and bearing replacements. In addition to engine and system testing, life testing of critical components is also considered. The record in this paper is not complete, due to the reluctance of some organizations to release operational data and because several organizations were not contacted. The authors intend to repeat this assessment in three years, hoping for even greater participation.

  1. Perpetual Motion Machine

    Directory of Open Access Journals (Sweden)

    D. Tsaousis

    2008-01-01

    Full Text Available Ever since the first century A.D. there have been relative descriptions of known devices as well as manufactures for the creation of perpetual motion machines. Although physics has led, with two thermodynamic laws, to the opinion that a perpetual motion machine is impossible to be manufactured, inventors of every age and educational level appear to claim that they have invented something «entirely new» or they have improved somebody else’s invention, which «will function henceforth perpetually»! However the fact of the failure in manufacturing a perpetual motion machine till now, it does not mean that countless historical elements for these fictional machines become indifferent. The discussion on every version of a perpetual motion machine on the one hand gives the chance to comprehend the inventor’s of each period level of knowledge and his way of thinking, and on the other hand, to locate the points where this «perpetual motion machine» clashes with the laws of nature and that’s why it is impossible to have been manufactured or have functioned. The presentation of a new «perpetual motion machine» has excited our interest to locate its weak points. According to the designer of it the machine functions with the work produced by the buoyant force

  2. Machine Intelligence and Explication

    NARCIS (Netherlands)

    Wieringa, Roelf J.

    1987-01-01

    This report is an MA ("doctoraal") thesis submitted to the department of philosophy, university of Amsterdam. It attempts to answer the question whether machines can think by conceptual analysis. Ideally. a conceptual analysis should give plausible explications of the concepts of "machine" and "inte

  3. Microsoft Azure machine learning

    CERN Document Server

    Mund, Sumit

    2015-01-01

    The book is intended for those who want to learn how to use Azure Machine Learning. Perhaps you already know a bit about Machine Learning, but have never used ML Studio in Azure; or perhaps you are an absolute newbie. In either case, this book will get you up-and-running quickly.

  4. Reactive Turing machines

    NARCIS (Netherlands)

    Baeten, J.C.M.; Luttik, B.; Tilburg, P.J.A. van

    2013-01-01

    We propose reactive Turing machines (RTMs), extending classical Turing machines with a process-theoretical notion of interaction, and use it to define a notion of executable transition system. We show that every computable transition system with a bounded branching degree is simulated modulo diverge

  5. Machine Intelligence and Explication

    NARCIS (Netherlands)

    Wieringa, Roel

    1987-01-01

    This report is an MA ("doctoraal") thesis submitted to the department of philosophy, university of Amsterdam. It attempts to answer the question whether machines can think by conceptual analysis. Ideally. a conceptual analysis should give plausible explications of the concepts of "machine" and "inte

  6. Coordinate measuring machines

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceability...

  7. Simple Machine Junk Cars

    Science.gov (United States)

    Herald, Christine

    2010-01-01

    During the month of May, the author's eighth-grade physical science students study the six simple machines through hands-on activities, reading assignments, videos, and notes. At the end of the month, they can easily identify the six types of simple machine: inclined plane, wheel and axle, pulley, screw, wedge, and lever. To conclude this unit,…

  8. Human Machine Learning Symbiosis

    Science.gov (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.

    2017-01-01

    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  9. Machine learning with R

    CERN Document Server

    Lantz, Brett

    2015-01-01

    Perhaps you already know a bit about machine learning but have never used R, or perhaps you know a little R but are new to machine learning. In either case, this book will get you up and running quickly. It would be helpful to have a bit of familiarity with basic programming concepts, but no prior experience is required.

  10. 15 CFR 700.31 - Metalworking machines.

    Science.gov (United States)

    2010-01-01

    ... Drilling and tapping machines Electrical discharge, ultrasonic and chemical erosion machines Forging..., power driven Machining centers and way-type machines Manual presses Mechanical presses, power...

  11. The effect of macromolecular crowding on the structure of the protein complex superoxide dismutase

    Science.gov (United States)

    Rajapaksha Mudalige, Ajith Rathnaweera

    Biological environments contain between 7 - 40% macromolecules by volume. This reduces the available volume for macromolecules and elevates the osmotic pressure relative to pure water. Consequently, biological macromolecules in their native environments tend to adopt more compact and dehydrated conformations than those in vitro. This effect is referred to as macromolecular crowding and constitutes an important physical difference between native biological environments and the simple solutions in which biomolecules are usually studied. We used small angle scattering (SAS) to measure the effects of macromolecular crowding on the size of a protein complex, superoxide dismutase (SOD). Crowding was induced using 400 MW polyethylene glycol (PEG), triethylene glycol (TEG), methyl-alpha-glucoside (alpha-MG) and trimethylamine N-oxide (TMAO). Parallel small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) allowed us to unambiguously attribute apparent changes in radius of gyration to changes in the structure of SOD. For a 40% PEG solution, we find that the volume of SOD was reduced by 9%. SAS coupled with osmotic pressure measurements allowed us to estimate a compressibility modulus for SOD. We believe this to be the first time the osmotic compressibility of a protein complex was measured. Molecular Dynamics (MD) simulations are widely used to obtain insights on biomolecular processes. However, it is not clear whether MD is capable of predicting subtle effects of macromolecular crowding. We used our experimentally observed compressibility of SOD to evaluate the ability of MD to predict macromolecular crowding. Effects of macromolecular crowding due to PEG on SOD were modeled using an all atom MD simulation with the CHARMM forcefield and the crystallographically resolved structures of SOD and PEG. Two parallel MD simulations were performed for SOD in water and SOD in 40% PEG for over 150~ns. Over the period of the simulation the SOD structure in 40

  12. LHC Report: machine development

    CERN Multimedia

    Rogelio Tomás García for the LHC team

    2015-01-01

    Machine development weeks are carefully planned in the LHC operation schedule to optimise and further study the performance of the machine. The first machine development session of Run 2 ended on Saturday, 25 July. Despite various hiccoughs, it allowed the operators to make great strides towards improving the long-term performance of the LHC.   The main goals of this first machine development (MD) week were to determine the minimum beam-spot size at the interaction points given existing optics and collimation constraints; to test new beam instrumentation; to evaluate the effectiveness of performing part of the beam-squeezing process during the energy ramp; and to explore the limits on the number of protons per bunch arising from the electromagnetic interactions with the accelerator environment and the other beam. Unfortunately, a series of events reduced the machine availability for studies to about 50%. The most critical issue was the recurrent trip of a sextupolar corrector circuit –...

  13. Micro-machining.

    Science.gov (United States)

    Brinksmeier, Ekkard; Preuss, Werner

    2012-08-28

    Manipulating bulk material at the atomic level is considered to be the domain of physics, chemistry and nanotechnology. However, precision engineering, especially micro-machining, has become a powerful tool for controlling the surface properties and sub-surface integrity of the optical, electronic and mechanical functional parts in a regime where continuum mechanics is left behind and the quantum nature of matter comes into play. The surprising subtlety of micro-machining results from the extraordinary precision of tools, machines and controls expanding into the nanometre range-a hundred times more precise than the wavelength of light. In this paper, we will outline the development of precision engineering, highlight modern achievements of ultra-precision machining and discuss the necessity of a deeper physical understanding of micro-machining.

  14. Introduction to machine learning.

    Science.gov (United States)

    Baştanlar, Yalin; Ozuysal, Mustafa

    2014-01-01

    The machine learning field, which can be briefly defined as enabling computers make successful predictions using past experiences, has exhibited an impressive development recently with the help of the rapid increase in the storage capacity and processing power of computers. Together with many other disciplines, machine learning methods have been widely employed in bioinformatics. The difficulties and cost of biological analyses have led to the development of sophisticated machine learning approaches for this application area. In this chapter, we first review the fundamental concepts of machine learning such as feature assessment, unsupervised versus supervised learning and types of classification. Then, we point out the main issues of designing machine learning experiments and their performance evaluation. Finally, we introduce some supervised learning methods.

  15. Machine Learning and Radiology

    Science.gov (United States)

    Wang, Shijun; Summers, Ronald M.

    2012-01-01

    In this paper, we give a short introduction to machine learning and survey its applications in radiology. We focused on six categories of applications in radiology: medical image segmentation, registration, computer aided detection and diagnosis, brain function or activity analysis and neurological disease diagnosis from fMR images, content-based image retrieval systems for CT or MRI images, and text analysis of radiology reports using natural language processing (NLP) and natural language understanding (NLU). This survey shows that machine learning plays a key role in many radiology applications. Machine learning identifies complex patterns automatically and helps radiologists make intelligent decisions on radiology data such as conventional radiographs, CT, MRI, and PET images and radiology reports. In many applications, the performance of machine learning-based automatic detection and diagnosis systems has shown to be comparable to that of a well-trained and experienced radiologist. Technology development in machine learning and radiology will benefit from each other in the long run. Key contributions and common characteristics of machine learning techniques in radiology are discussed. We also discuss the problem of translating machine learning applications to the radiology clinical setting, including advantages and potential barriers. PMID:22465077

  16. The basic anaesthesia machine.

    Science.gov (United States)

    Gurudatt, Cl

    2013-09-01

    After WTG Morton's first public demonstration in 1846 of use of ether as an anaesthetic agent, for many years anaesthesiologists did not require a machine to deliver anaesthesia to the patients. After the introduction of oxygen and nitrous oxide in the form of compressed gases in cylinders, there was a necessity for mounting these cylinders on a metal frame. This stimulated many people to attempt to construct the anaesthesia machine. HEG Boyle in the year 1917 modified the Gwathmey's machine and this became popular as Boyle anaesthesia machine. Though a lot of changes have been made for the original Boyle machine still the basic structure remains the same. All the subsequent changes which have been brought are mainly to improve the safety of the patients. Knowing the details of the basic machine will make the trainee to understand the additional improvements. It is also important for every practicing anaesthesiologist to have a thorough knowledge of the basic anaesthesia machine for safe conduct of anaesthesia.

  17. The basic anaesthesia machine

    Directory of Open Access Journals (Sweden)

    C L Gurudatt

    2013-01-01

    Full Text Available After WTG Morton′s first public demonstration in 1846 of use of ether as an anaesthetic agent, for many years anaesthesiologists did not require a machine to deliver anaesthesia to the patients. After the introduction of oxygen and nitrous oxide in the form of compressed gases in cylinders, there was a necessity for mounting these cylinders on a metal frame. This stimulated many people to attempt to construct the anaesthesia machine. HEG Boyle in the year 1917 modified the Gwathmey′s machine and this became popular as Boyle anaesthesia machine. Though a lot of changes have been made for the original Boyle machine still the basic structure remains the same. All the subsequent changes which have been brought are mainly to improve the safety of the patients. Knowing the details of the basic machine will make the trainee to understand the additional improvements. It is also important for every practicing anaesthesiologist to have a thorough knowledge of the basic anaesthesia machine for safe conduct of anaesthesia.

  18. Interactions between remodelling, architecture and tissue properties in cancellous bone

    OpenAIRE

    Linden, Jacqueline

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancellous bone. For this reason, the research presented in this thesis focussed on bone remodeling in cancellous bone. We used computer modeling, finite element calculations and in vivo labeled bone speci...

  19. Part Machinability Evaluation System

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In the early design period, estimation of the part or the whole product machinability is useful to consider the function and process request of the product at the same time so as to globally optimize the design decision. This paper presents a part machinability evaluation system, discusses the general restrictions of part machinability, and realizes the inspection of these restrictions with the relation between tool scan space and part model. During the system development, the expansibility and understandability were considered, and an independent restriction algorithm library and a general function library were set up. Additionally, the system has an interpreter and a knowledge manager.

  20. Fundamentals of machine design

    CERN Document Server

    Karaszewski, Waldemar

    2011-01-01

    A forum of researchers, educators and engineers involved in various aspects of Machine Design provided the inspiration for this collection of peer-reviewed papers. The resultant dissemination of the latest research results, and the exchange of views concerning the future research directions to be taken in this field will make the work of immense value to all those having an interest in the topics covered. The book reflects the cooperative efforts made in seeking out the best strategies for effecting improvements in the quality and the reliability of machines and machine parts and for extending

  1. Machine Tool Software

    Science.gov (United States)

    1988-01-01

    A NASA-developed software package has played a part in technical education of students who major in Mechanical Engineering Technology at William Rainey Harper College. Professor Hack has been using (APT) Automatically Programmed Tool Software since 1969 in his CAD/CAM Computer Aided Design and Manufacturing curriculum. Professor Hack teaches the use of APT programming languages for control of metal cutting machines. Machine tool instructions are geometry definitions written in APT Language to constitute a "part program." The part program is processed by the machine tool. CAD/CAM students go from writing a program to cutting steel in the course of a semester.

  2. Analysis of synchronous machines

    CERN Document Server

    Lipo, TA

    2012-01-01

    Analysis of Synchronous Machines, Second Edition is a thoroughly modern treatment of an old subject. Courses generally teach about synchronous machines by introducing the steady-state per phase equivalent circuit without a clear, thorough presentation of the source of this circuit representation, which is a crucial aspect. Taking a different approach, this book provides a deeper understanding of complex electromechanical drives. Focusing on the terminal rather than on the internal characteristics of machines, the book begins with the general concept of winding functions, describing the placeme

  3. Database machine performance

    Energy Technology Data Exchange (ETDEWEB)

    Cesarini, F.; Salza, S.

    1987-01-01

    This book is devoted to the important problem of database machine performance evaluation. The book presents several methodological proposals and case studies, that have been developed within an international project supported by the European Economic Community on Database Machine Evaluation Techniques and Tools in the Context of the Real Time Processing. The book gives an overall view of the modeling methodologies and the evaluation strategies that can be adopted to analyze the performance of the database machine. Moreover, it includes interesting case studies and an extensive bibliography.

  4. Virtual Machine Introspection

    Directory of Open Access Journals (Sweden)

    S C Rachana

    2014-06-01

    Full Text Available Cloud computing is an Internet-based computing solution which provides the resources in an effective manner. A very serious issue in cloud computing is security which is a major obstacle for the adoption of cloud. The most important threats of cloud computing are Multitenancy, Availability, Loss of control, Loss of Data, outside attacks, DOS attacks, malicious insiders, etc. Among many security issues in cloud, the Virtual Machine Security is one of the very serious issues. Thus, monitoring of virtual machine is essential. The paper proposes a Virtual Network Introspection [VMI] System to secure the Virtual machines from Distributed Denial of Service [DDOS] and Zombie attacks.

  5. Virtual Machine Introspection

    Directory of Open Access Journals (Sweden)

    S C Rachana

    2015-11-01

    Full Text Available Cloud computing is an Internet-based computing solution which provides the resources in an effective manner. A very serious issue in cloud computing is security which is a major obstacle for the adoption of cloud. The most important threats of cloud computing are Multitenancy, Availability, Loss of control, Loss of Data, outside attacks, DOS attacks, malicious insiders, etc. Among many security issues in cloud, the Virtual Machine Security is one of the very serious issues. Thus, monitoring of virtual machine is essential. The paper proposes a Virtual Network Introspection [VMI] System to secure the Virtual machines from Distributed Denial of Service [DDOS] and Zombie attacks.

  6. Machine Learning for Hackers

    CERN Document Server

    Conway, Drew

    2012-01-01

    If you're an experienced programmer interested in crunching data, this book will get you started with machine learning-a toolkit of algorithms that enables computers to train themselves to automate useful tasks. Authors Drew Conway and John Myles White help you understand machine learning and statistics tools through a series of hands-on case studies, instead of a traditional math-heavy presentation. Each chapter focuses on a specific problem in machine learning, such as classification, prediction, optimization, and recommendation. Using the R programming language, you'll learn how to analyz

  7. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  8. Pregnancy-induced remodeling of heart valves.

    Science.gov (United States)

    Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

    2015-11-01

    Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves.

  9. Electrical and myocardial remodeling in primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Mario eCurione

    2014-11-01

    Full Text Available Objective and design: primary aldosteronism (PA represents the most common cause of secondary hypertension. An higher risk of cardiovascular events has been reported in patients with PA than otherwise similar patients with essential hypertension (EH. At today few studies has been investigated the electrocardiographic changes in PA patients compared to EH patients.Methods: to investigate the electrocardiographic changes and heart remodeling in PA we enrolled 61 consecutive patients, 30 with PA (12 with aldosterone producing adenoma-APA and 18 with bilateral adrenal hyperplasia-IHA and 30 with EH. In all subjects electrelectrocardiographic parameters were evaluated from 12-lead electrocardiograms and heart remodeling with echocardiogram.Results: no significant differences in age, sex , body mass index (BMI and blood pressure were found in two groups. The P wave and PR interval duration were significantly prolonged in patientswith PA respect to EH (p< 0.003 and p< 0.002, respectively. First degree atrioventricular block was present in 16% patient with PA and only in 3.2% patients with EH. In PA patients the interventricular septum thickness (IVST correlated with left ventricular mass indecized (LVMi (r= 0.54; p< 0.04, and with PR duration (r= 0.51; p< 0.03. Left ventricular hypertrophy (LVH was present in 53% patients with PA and in 26% patients with EH (χ2 p<0.03.Conclusions: in this case-control study, patients with PA show more anatomic and electrical heart remodeling than those with EH. We hypothesize that in patients with PA these cardiac changes may play a role for the increased risk of future cardiovascular events.

  10. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling......-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope...

  11. Phospholipid remodeling and eicosanoid signaling in colon cancer cells.

    Science.gov (United States)

    Das, Siddhartha; Martinez, Leobarda Robles; Ray, Suparna

    2014-12-01

    Phospholipid remodeling and eicosanoid synthesis are central to lipid-based inflammatory reactions. Studies have revealed that membrane phospholipid remodeling by fatty acids through deacylation/reacylation reactions increases the risk of colorectal cancers (CRC) by allowing the cells to produce excess inflammatory eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Over the years, efforts have been made to understand the lipid remodeling pathways and to design anti-cancer drugs targeting the enzymes of eicosanoid biosynthesis. Here, we discuss the recent progress in phospholipid remodeling and eicosanoid biosynthesis in CRC.

  12. Myocardial Tissue Remodeling in Adolescent Obesity

    OpenAIRE

    Shah, Ravi V.; Abbasi, Siddique A.; Neilan, Tomas G; Hulten, Edward; Coelho‐Filho, Otavio; Hoppin, Alison; Levitsky, Lynne; de Ferranti, Sarah; Rhodes, Erinn T.; Traum, Avram; Goodman, Elizabeth; Feng, Henry; Heydari, Bobak; Harris, William S.; Hoefner, Daniel M.

    2013-01-01

    Background: Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue‐level markers within the myocardium that precede organ‐level alterations have not been described. Methods and Results: We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m2, including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years...

  13. CHD chromatin remodelers and the transcription cycle.

    Science.gov (United States)

    Murawska, Magdalena; Brehm, Alexander

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by "opening" or "closing" chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts.

  14. Some relations between quantum Turing machines and Turing machines

    CERN Document Server

    Sicard, A; Sicard, Andrés; Vélez, Mario

    1999-01-01

    For quantum Turing machines we present three elements: Its components, its time evolution operator and its local transition function. The components are related with deterministic Turing machines, the time evolution operator is related with reversible Turing machines and the local transition function is related with probabilistic and reversible Turing machines.

  15. Machining of hard-to-machine materials

    OpenAIRE

    2016-01-01

    Bakalářská práce se zabývá studiem obrábění těžkoobrobitelných materiálů. V první části jsou rozděleny těžkoobrobitelné materiály a následuje jejich analýza. V další části se práce zaměřuje na problematiku obrobitelnosti jednotlivých slitin. Závěrečná část práce je věnovaná experimentu, jeho statistickému zpracování a nakonec následnému vyhodnocení. This bachelor thesis studies the machining of hard-to-machine materials. The first part of the thesis considers hard-to-machine materials and ...

  16. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Science.gov (United States)

    Ó Conchúir, Shane; Barlow, Kyle A; Pache, Roland A; Ollikainen, Noah; Kundert, Kale; O'Meara, Matthew J; Smith, Colin A; Kortemme, Tanja

    2015-01-01

    The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks) to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  17. Enhanced delivery of the RAPTA-C macromolecular chemotherapeutic by conjugation to degradable polymeric micelles.

    Science.gov (United States)

    Blunden, Bianca M; Lu, Hongxu; Stenzel, Martina H

    2013-12-09

    Macromolecular ruthenium complexes are a promising avenue to better and more selective chemotherapeutics. We have previously shown that RAPTA-C [RuCl2(p-cymene)(PTA)], with the water-soluble 1,3,5-phosphaadamantane (PTA) ligand, could be attached to a polymer moiety via nucleophilic substitution of an available iodide with an amide in the PTA ligand. To increase the cell uptake of this macromolecule, we designed an amphiphilic block copolymer capable of self-assembling into polymeric micelles. The block copolymer was prepared by ring-opening polymerization of d,l-lactide (3,6-dimethyl-1,4-dioxane-2,5-dione) using a RAFT agent with an additional hydroxyl functionality, followed by the RAFT copolymerization of 2-hydroxyethyl acrylate (HEA) and 2-chloroethyl methacrylate (CEMA). The Finkelstein reaction and reaction with PTA led to polymers that can readily react with the dimer of RuCl2(p-cymene) to create a macromolecular RAPTA-C drug. RAPTA-C conjugation, micellization, and subsequent cytotoxicity and cell uptake of these polymeric moieties was tested on ovarian cancer A2780, A2780cis, and Ovcar-3 cell lines. Confocal microscopy images confirmed cell uptake of the micelles into the lysosome of the cells, indicative of an endocytic pathway. On average, a 10-fold increase in toxicity was found for the macromolecular drugs when compared to the RAPTA-C molecule. Furthermore, the cell uptake of ruthenium was analyzed and a significant increase was found for the micelles compared to RAPTA-C. Notably, micelles prepared from the polymer containing fewer HEA units had the highest cytotoxicity, the best cell uptake of ruthenium and were highly effective in suppressing the colony-forming ability of cells.

  18. A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design.

    Directory of Open Access Journals (Sweden)

    Shane Ó Conchúir

    Full Text Available The development and validation of computational macromolecular modeling and design methods depend on suitable benchmark datasets and informative metrics for comparing protocols. In addition, if a method is intended to be adopted broadly in diverse biological applications, there needs to be information on appropriate parameters for each protocol, as well as metrics describing the expected accuracy compared to experimental data. In certain disciplines, there exist established benchmarks and public resources where experts in a particular methodology are encouraged to supply their most efficient implementation of each particular benchmark. We aim to provide such a resource for protocols in macromolecular modeling and design. We present a freely accessible web resource (https://kortemmelab.ucsf.edu/benchmarks to guide the development of protocols for protein modeling and design. The site provides benchmark datasets and metrics to compare the performance of a variety of modeling protocols using different computational sampling methods and energy functions, providing a "best practice" set of parameters for each method. Each benchmark has an associated downloadable benchmark capture archive containing the input files, analysis scripts, and tutorials for running the benchmark. The captures may be run with any suitable modeling method; we supply command lines for running the benchmarks using the Rosetta software suite. We have compiled initial benchmarks for the resource spanning three key areas: prediction of energetic effects of mutations, protein design, and protein structure prediction, each with associated state-of-the-art modeling protocols. With the help of the wider macromolecular modeling community, we hope to expand the variety of benchmarks included on the website and continue to evaluate new iterations of current methods as they become available.

  19. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Coquel

    2013-04-01

    Full Text Available Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian. Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on

  20. D3, the new diffractometer for the macromolecular crystallography beamlines of the Swiss Light Source

    Energy Technology Data Exchange (ETDEWEB)

    Fuchs, Martin R., E-mail: mfuchs@bnl.gov [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Brookhaven National Laboratory, Mail Stop 745, Upton, NY 11973 (United States); Pradervand, Claude; Thominet, Vincent; Schneider, Roman; Panepucci, Ezequiel; Grunder, Marcel; Gabadinho, Jose; Dworkowski, Florian S. N.; Tomizaki, Takashi; Schneider, Jörg; Mayer, Aline; Curtin, Adrian; Olieric, Vincent; Frommherz, Uli; Kotrle, Goran; Welte, Jörg; Wang, Xinyu; Maag, Stephan [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Schulze-Briese, Clemens [DECTRIS Ltd, Neuenhoferstrasse 107, 5400 Baden (Switzerland); Wang, Meitian [Paul Scherrer Institute, 5232 Villigen PSI (Switzerland)

    2014-02-04

    A new diffractometer for microcrystallography has been developed for the three macromolecular crystallography beamlines of the Swiss Light Source. A new diffractometer for microcrystallography has been developed for the three macromolecular crystallography beamlines of the Swiss Light Source. Building upon and critically extending previous developments realised for the high-resolution endstations of the two undulator beamlines X06SA and X10SA, as well as the super-bend dipole beamline X06DA, the new diffractometer was designed to the following core design goals. (i) Redesign of the goniometer to a sub-micrometer peak-to-peak cylinder of confusion for the horizontal single axis. Crystal sizes down to at least 5 µm and advanced sample-rastering and scanning modes are supported. In addition, it can accommodate the new multi-axis goniometer PRIGo (Parallel Robotics Inspired Goniometer). (ii) A rapid-change beam-shaping element system with aperture sizes down to a minimum of 10 µm for microcrystallography measurements. (iii) Integration of the on-axis microspectrophotometer MS3 for microscopic sample imaging with 1 µm image resolution. Its multi-mode optical spectroscopy module is always online and supports in situ UV/Vis absorption, fluorescence and Raman spectroscopy. (iv) High stability of the sample environment by a mineral cast support construction and by close containment of the cryo-stream. Further features are the support for in situ crystallization plate screening and a minimal achievable detector distance of 120 mm for the Pilatus 6M, 2M and the macromolecular crystallography group’s planned future area detector Eiger 16M.

  1. Optimized beamline design for macromolecular crystallography at the Cornell High Energy Synchrotron Source (CHESS) (abstract)

    Science.gov (United States)

    Schildkamp, Wilfried; Bilderback, Donald; Moffat, Keith

    1989-07-01

    The A1 station on the CHESS wiggler beamline has been the workhorse for most macromolecular crystallographic experiments. This station is equipped with a fixed energy focusing germanium (111) monochromator and a focusing total reflection mirror. Our macromolecular crystallographers made full use of the high flux of more than 1012 photons/s/mm2 and the stable beam conditions, both in position and energy resolution. As a result, the A1 station was heavily oversubscribed. CHESS is presently expanding its capabilities and a new diffraction station for macromolecular crystallography is under construction. This beamline will be powered by a 24-pole hybrid permanent magnet wiggler with a critical energy of 25 keV. A focusing monochromator, which handles a specific heat load of 10 W/mm2, will have a range of tunability which covers all relevant absorption edges from 7 to 15 keV using a Ge(111) crystal. The energy resolution and the focusing properties remain constant within a factor of 2 over the entire tunability range. We expect a brilliance of about 1013 photons/s/mm2/mrad2/0.1% bandpass. The diffraction station will be equipped with an oscillation camera which can be used with x-ray film of 5×5 or 8×10 in. size or alternatively with Kodak storage phosphors. A wide variety of clamp-on accessories, like crystal coolers, fast shutters, helium pathways, polarimeter, etc. are available. The station will contain a beampipe system, which can also be used for small angle scattering experiments with sample-to-detector distances of up to 3000 mm. The entire diffraction station, its control area, a biological preparation area, and a darkroom are to be embedded in a biological safety containment of the level BL3. This will allow diffraction studies of virulent strains of viruses and other biohazards, which could not previously be studied at synchrotron radiation sources before without causing major disruption to the normal laboratory procedure.

  2. Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect.

    Science.gov (United States)

    Coquel, Anne-Sophie; Jacob, Jean-Pascal; Primet, Mael; Demarez, Alice; Dimiccoli, Mariella; Julou, Thomas; Moisan, Lionel; Lindner, Ariel B; Berry, Hugues

    2013-04-01

    Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results provide evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3D individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion-aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular

  3. Machine (bulk) harvest

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This is a summary of machine harvesting activities on Neal Smith National Wildlife Refuge between 1991 and 2008. Information is provided for each year about...

  4. Machine Vision Handbook

    CERN Document Server

    2012-01-01

    The automation of visual inspection is becoming more and more important in modern industry as a consistent, reliable means of judging the quality of raw materials and manufactured goods . The Machine Vision Handbook  equips the reader with the practical details required to engineer integrated mechanical-optical-electronic-software systems. Machine vision is first set in the context of basic information on light, natural vision, colour sensing and optics. The physical apparatus required for mechanized image capture – lenses, cameras, scanners and light sources – are discussed followed by detailed treatment of various image-processing methods including an introduction to the QT image processing system. QT is unique to this book, and provides an example of a practical machine vision system along with extensive libraries of useful commands, functions and images which can be implemented by the reader. The main text of the book is completed by studies of a wide variety of applications of machine vision in insp...

  5. Tests of Machine Intelligence

    CERN Document Server

    Legg, Shane

    2007-01-01

    Although the definition and measurement of intelligence is clearly of fundamental importance to the field of artificial intelligence, no general survey of definitions and tests of machine intelligence exists. Indeed few researchers are even aware of alternatives to the Turing test and its many derivatives. In this paper we fill this gap by providing a short survey of the many tests of machine intelligence that have been proposed.

  6. Metalworking and machining fluids

    Science.gov (United States)

    Erdemir, Ali; Sykora, Frank; Dorbeck, Mark

    2010-10-12

    Improved boron-based metal working and machining fluids. Boric acid and boron-based additives that, when mixed with certain carrier fluids, such as water, cellulose and/or cellulose derivatives, polyhydric alcohol, polyalkylene glycol, polyvinyl alcohol, starch, dextrin, in solid and/or solvated forms result in improved metalworking and machining of metallic work pieces. Fluids manufactured with boric acid or boron-based additives effectively reduce friction, prevent galling and severe wear problems on cutting and forming tools.

  7. mlpy: Machine Learning Python

    CERN Document Server

    Albanese, Davide; Merler, Stefano; Riccadonna, Samantha; Jurman, Giuseppe; Furlanello, Cesare

    2012-01-01

    mlpy is a Python Open Source Machine Learning library built on top of NumPy/SciPy and the GNU Scientific Libraries. mlpy provides a wide range of state-of-the-art machine learning methods for supervised and unsupervised problems and it is aimed at finding a reasonable compromise among modularity, maintainability, reproducibility, usability and efficiency. mlpy is multiplatform, it works with Python 2 and 3 and it is distributed under GPL3 at the website http://mlpy.fbk.eu.

  8. Human-machine interactions

    Science.gov (United States)

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  9. Machine Learning with Distances

    Science.gov (United States)

    2015-02-16

    and demonstrated their usefulness in experiments. 1 Introduction The goal of machine learning is to find useful knowledge behind data. Many machine...212, 172]. However, direct divergence approximators still suffer from the curse of dimensionality. A possible cure for this problem is to combine them...obtain the global optimal solution or even a good local solution without any prior knowledge . For this reason, we decided to introduce the unit-norm

  10. mlpy: Machine Learning Python

    OpenAIRE

    Albanese, Davide; Visintainer, Roberto; Merler, Stefano; Riccadonna, Samantha; Jurman, Giuseppe; Furlanello, Cesare

    2012-01-01

    mlpy is a Python Open Source Machine Learning library built on top of NumPy/SciPy and the GNU Scientific Libraries. mlpy provides a wide range of state-of-the-art machine learning methods for supervised and unsupervised problems and it is aimed at finding a reasonable compromise among modularity, maintainability, reproducibility, usability and efficiency. mlpy is multiplatform, it works with Python 2 and 3 and it is distributed under GPL3 at the website http://mlpy.fbk.eu.

  11. The "macromolecular tourist": universal temperature dependence of thermal diffusion in aqueous colloidal suspensions.

    Science.gov (United States)

    Iacopini, S; Rusconi, R; Piazza, R

    2006-01-01

    By performing measurements on a large class of macromolecular and colloidal systems, we show that thermophoresis (particle drift induced by thermal gradients) in aqueous solvents displays a distinctive universal dependence on temperature. For systems of particles interacting via temperature-independent forces, this behavior is strictly related to the solvent thermal expansivity, while an additional, T-independent term is needed to account for the behavior of "thermophilic" (migrating to the warmth) particles. The former relation between thermophoresis and thermal expansion may be exploited to envisage other fruitful studies of colloidal diffusion in inhomogeneous fluids.

  12. Simulation of macromolecular liquids with the adaptive resolution molecular dynamics technique

    Science.gov (United States)

    Peters, J. H.; Klein, R.; Delle Site, L.

    2016-08-01

    We extend the application of the adaptive resolution technique (AdResS) to liquid systems composed of alkane chains of different lengths. The aim of the study is to develop and test the modifications of AdResS required in order to handle the change of representation of large molecules. The robustness of the approach is shown by calculating several relevant structural properties and comparing them with the results of full atomistic simulations. The extended scheme represents a robust prototype for the simulation of macromolecular systems of interest in several fields, from material science to biophysics.

  13. INFLUENCE OF THE SOLVENT SWELLING ON MACROMOLECULAR CHOLESTERIC LIQUID CRYSTALLINE STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    Jia Zeng; Yong Huang

    1999-01-01

    Ethyl-cyanoethyl cellulose [(E-CE)C]/cross-linked polyacrylic acid [PAA] molecular composites with cholesteric order were prepared. It was found that the macromolecular cholesteric structure was changed with the swelling of PAA in the composites. The selective reflection of the cholesteric phase shifted to the longer wavelength and the X-ray diffraction angle shifted to the high angle direction during swelling, which suggested that the cholesteric pitch and the number of the layers of ordered (E-CE)C chains in the cholesteric phase were increased.

  14. A vibrating membrane bioreactor (VMBR): Macromolecular transmission-influence of extracellular polymeric substances

    DEFF Research Database (Denmark)

    Beier, Søren; Jonsson, Gunnar Eigil

    2009-01-01

    The vibrating membrane bioreactor (VMBR) system facilitates the possibility of conducting a separation of macromolecules (BSA) from larger biological components (yeast cells) with a relatively high and stable macromolecular transmission at sub-critical flux. This is not possible to achieve...... for a static non-vibrating membrane module. A BSA transmission of 74% has been measured in the separation of 4g/L BSA from 8 g/L dry weight yeast cells in suspension at sub-critical flux (20L/(m(2) h)). However, this transmission is lower than the 85% BSA transmission measured for at pure 4g/L BSA solution...

  15. Specific remodeling of splenic architecture by cytomegalovirus.

    Science.gov (United States)

    Benedict, Chris A; De Trez, Carl; Schneider, Kirsten; Ha, Sukwon; Patterson, Ginelle; Ware, Carl F

    2006-03-01

    Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  16. Vascular remodeling underlies rebleeding in hemophilic arthropathy.

    Science.gov (United States)

    Bhat, Vikas; Olmer, Merissa; Joshi, Shweta; Durden, Donald L; Cramer, Thomas J; Barnes, Richard Fw; Ball, Scott T; Hughes, Tudor H; Silva, Mauricio; Luck, James V; Moore, Randy E; Mosnier, Laurent O; von Drygalski, Annette

    2015-11-01

    Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

  17. Epithelial Cell Apoptosis and Lung Remodeling

    Institute of Scientific and Technical Information of China (English)

    Kazuyoshi Kuwano

    2007-01-01

    Lung epithelium is the primary site of lung damage in various lung diseases. Epithelial cell apoptosis has been considered to be initial event in various lung diseases. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. The other pathway triggered by stresses such as drugs, radiation, infectious agents and reactive oxygen species is mediated by mitochondria. Endoplasmic reticulum has also been shown to be the organelle to mediate apoptosis.Epithelial cell death is followed by remodeling processes, which consist of epithelial and fibroblast activation,cytokine production, activation of coagulation pathway, neoangiogenesis, re-epithelialization and fibrosis.Epithelial and mesenchymal interaction plays important roles in these processes. Further understanding of apoptosis signaling and its regulation by novel strategies may lead to effective treatments against various lung diseases. We review the recent advances in the understanding of apoptosis signaling and discuss the involvement of apoptosis in lung remodeling.

  18. Specific remodeling of splenic architecture by cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Chris A Benedict

    2006-03-01

    Full Text Available Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21. The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  19. ECG manifestations of left ventricular electrical remodeling.

    Science.gov (United States)

    Estes, E Harvey

    2012-01-01

    Research and thinking about the electrocardiographic manifestations of left ventricular hypertrophy has been constrained by a limited conceptual model of the process: heart disease produces chamber enlargement (increased mass), which in turn produces an altered electrocardiogram. The process is much more complex than can be represented in this simple model. A more robust and intricate model is proposed, in which heart (and vascular) disease causes structural changes, electrical changes, biochemical changes, and others, all of which interact to produce electrical remodeling of ventricular myocardium. This electrical remodeling results in a variety of ECG changes. All of these changes interact, leading to an altered clinical course, and to premature death. It is suggested that research, based on this model, can provide new clues to the processes involved, and improve the prediction of clinical outcomes. New directions in research, in recording equipment, and in organizational activities are suggested to test this new model, and to improve the usefulness of the electrocardiogram as a research and diagnostic tool.

  20. Airway remodelling in the transplanted lung.

    Science.gov (United States)

    Kuehnel, Mark; Maegel, Lavinia; Vogel-Claussen, Jens; Robertus, Jan Lukas; Jonigk, Danny

    2017-03-01

    Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities. Although recent years have seen considerable advances in identifying and categorizing these subgroups on the basis of clinical, functional and histomorphological changes, as well as susceptibility to medicinal treatment, this process is far from over. Since the actual pathophysiological mechanisms governing airway remodelling are still only poorly understood, diagnosis and therapy of chronic lung allograft dysfunction presents a major challenge to clinicians, radiologists and pathologists alike. Here, we review and discuss the current state of the literature on chronic lung allograft dysfunction and shed light on classification systems, corresponding clinical and morphological changes, key cellular players and underlying molecular pathways, as well as on emerging diagnostic and therapeutic approaches.

  1. Adipose Tissue Remodeling as Homeostatic Inflammation

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    2011-01-01

    Full Text Available Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

  2. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  3. System and method for investigating arterial remodeling.

    Science.gov (United States)

    Rachev, Alexander; Dominguez, Zachary; Vito, Raymond

    2009-10-01

    Organ culture systems are used to study remodeling of arteries and to fabricate tissue engineered vascular grafts. Investigations to date focused on changes in geometry and mechanical response of arteries or constructs associated with controlled sustained alterations in the global load parameters such as the arterial pressure, flow, or axial stretch. A new experimental paradigm is proposed, which is based on the simultaneous independent control of local mechanical parameters such as mean strain or stress in the arterial wall and flow-induced shear at the intima. An organ culture system and methodology were developed, which controls pressure, flow, and axial length of a specimen in order to maintain the local mechanical parameters at prescribed values. The operation of the system is illustrated by maintenance of elevated axial medial stress in porcine carotid artery, while keeping the mean circumferential stress and flow-induced shear stress at baseline values. Previously unknown aspects of remodeling that might be revealed by the novel approach are discussed.

  4. [Semiology for gluteal remodeling by lipofilling].

    Science.gov (United States)

    Ho Quoc, C; Mojallal, A

    2012-12-01

    Gluteal augmentation is a consultation request for many patients. The most common surgical techniques performed for gluteal augmentation employ gluteal implants. However, the results can be frustrating. Liposuction is one of the most common surgical procedures in aesthetic surgery. This surgical procedure can provide some complications. Fat grafting is an effective and predictable way to remodel the buttocks. To get better results, it's important to understand gluteal compartments with a descriptive study. The aim of this study is to describe gluteal semiology for buttocks remodeling with fat grafting. We have described gluteal semiology with our review of literature. We have analyzed fat compartments of gluteal region: volume, links between every compartments, connections with major gluteal muscle and with the skin. We have also analyzed shape and volume of the buttocks. We have described 11 aesthetic subunits, the volume and the shape of the buttocks, and the skin laxity. We did an important literature review to understand the most important gluteal zones to improve for patients' satisfaction. Our gluteal semiology description is very useful to understand liposuction/lipoinjection of gluteal areas. Fat grafting may be a reliable technique, simple and safe procedure. Surgery for correction of the buttocks may involve more than projection and volume. However, these must be in a balanced proportion with the rest of the body. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. EVALUATION OF MACHINE TOOL QUALITY

    Directory of Open Access Journals (Sweden)

    Ivan Kuric

    2011-12-01

    Full Text Available Paper deals with aspects of quality and accuracy of machine tools. As the accuracy of machine tools has key factor for product quality, it is important to know the methods for evaluation of quality and accuracy of machine tools. Several aspects of diagnostics of machine tools are described, such as aspects of reliability.

  6. An HTS machine laboratory prototype

    DEFF Research Database (Denmark)

    Mijatovic, Nenad; Jensen, Bogi Bech; Træholt, Chresten

    2012-01-01

    This paper describes Superwind HTS machine laboratory setup which is a small scale HTS machine designed and build as a part of the efforts to identify and tackle some of the challenges the HTS machine design may face. One of the challenges of HTS machines is a Torque Transfer Element (TTE) which...

  7. Machining of fiber reinforced composites

    Science.gov (United States)

    Komanduri, Ranga; Zhang, Bi; Vissa, Chandra M.

    Factors involved in machining of fiber-reinforced composites are reviewed. Consideration is given to properties of composites reinforced with boron filaments, glass fibers, aramid fibers, carbon fibers, and silicon carbide fibers and to polymer (organic) matrix composites, metal matrix composites, and ceramic matrix composites, as well as to the processes used in conventional machining of boron-titanium composites and of composites reinforced by each of these fibers. Particular attention is given to the methods of nonconventional machining, such as laser machining, water jet cutting, electrical discharge machining, and ultrasonic assisted machining. Also discussed are safety precautions which must be taken during machining of fiber-containing composites.

  8. Machining of Metal Matrix Composites

    CERN Document Server

    2012-01-01

    Machining of Metal Matrix Composites provides the fundamentals and recent advances in the study of machining of metal matrix composites (MMCs). Each chapter is written by an international expert in this important field of research. Machining of Metal Matrix Composites gives the reader information on machining of MMCs with a special emphasis on aluminium matrix composites. Chapter 1 provides the mechanics and modelling of chip formation for traditional machining processes. Chapter 2 is dedicated to surface integrity when machining MMCs. Chapter 3 describes the machinability aspects of MMCs. Chapter 4 contains information on traditional machining processes and Chapter 5 is dedicated to the grinding of MMCs. Chapter 6 describes the dry cutting of MMCs with SiC particulate reinforcement. Finally, Chapter 7 is dedicated to computational methods and optimization in the machining of MMCs. Machining of Metal Matrix Composites can serve as a useful reference for academics, manufacturing and materials researchers, manu...

  9. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  10. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  11. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer

    1992-01-01

    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

  12. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  13. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  14. Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

    NARCIS (Netherlands)

    Rubbens, M.P.; Mol, A.; Marion, M.H. van; Hanemaaijer, R.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechan

  15. Macromolecular liquids

    Energy Technology Data Exchange (ETDEWEB)

    Safinya, C.R.; Safran, S.A. (Exxon Research and Engineering Co., Annandale, NJ (US)); Pincus, P.A. (Univ. of California at Santa Barbara, Santa Barbara, CA (US))

    1990-01-01

    Liquids include a broad range of material systems which are of high scientific and technological interest. Generally speaking, these are partially ordered or disordered phases where the individual molecular species have organized themselves on length scales which are larger than simple fluids, typically between 10 Angstroms and several microns. The specific systems reported on in this book include membranes, microemulsions, micelles, liquid crystals, colloidal suspensions, and polymers. They have a major impact on a broad spectrum of technological industries such as displays, plastics, soap and detergents, chemicals and petroleum, and pharmaceuticals.

  16. Non-conventional electrical machines

    CERN Document Server

    Rezzoug, Abderrezak

    2013-01-01

    The developments of electrical machines are due to the convergence of material progress, improved calculation tools, and new feeding sources. Among the many recent machines, the authors have chosen, in this first book, to relate the progress in slow speed machines, high speed machines, and superconducting machines. The first part of the book is dedicated to materials and an overview of magnetism, mechanic, and heat transfer.

  17. Fast Method for Computing Chemical Potentials and Liquid-Liquid Phase Equilibria of Macromolecular Solutions.

    Science.gov (United States)

    Qin, Sanbo; Zhou, Huan-Xiang

    2016-08-25

    Chemical potential is a fundamental property for determining thermodynamic equilibria involving exchange of molecules, such as between two phases of molecular systems. Previously, we developed the fast Fourier transform (FFT)-based method for Modeling Atomistic Protein-crowder interactions (FMAP) to calculate excess chemical potentials according to the Widom insertion. Intermolecular interaction energies were expressed as correlation functions and evaluated via FFT. Here, we extend this method to calculate liquid-liquid phase equilibria of macromolecular solutions. Chemical potentials are calculated by FMAP over a wide range of molecular densities, and the condition for coexistence of low- and high-density phases is determined by the Maxwell equal-area rule. When benchmarked on Lennard-Jones fluids, our method produces an accurate phase diagram at 18% of the computational cost of the current best method. Importantly, the gain in computational speed increases dramatically as the molecules become more complex, leading to many orders of magnitude in speed up for atomistically represented proteins. We demonstrate the power of FMAP by reporting the first results for the liquid-liquid coexistence curve of γII-crystallin represented at the all-atom level. Our method may thus open the door to accurate determination of phase equilibria for macromolecular mixtures such as protein-protein mixtures and protein-RNA mixtures, that are known to undergo liquid-liquid phase separation, both in vitro and in vivo.

  18. A NEW UNSTEADY THREE DIMENSIONAL MODEL FOR MACROMOLECULAR TRANSPORT AND WATER FILTRATION ACROSS THE ARTERIAL WALL

    Institute of Scientific and Technical Information of China (English)

    黄浩; 温功碧

    2001-01-01

    A new unsteady three-dimensional convective-diffusive mathematical model for the transportation of macromolecules and water across the arterial wall was proposed . After the formation of leaky junctions due to the mitosis of endothelial cell of the arterial wall, the macromolecular transport happens surrounding the leaky cells. The arterial wall was divided into four layers: the endothelial layer, the subendothelial intima, the internal elastic lamina and the media for the convenience of research. The time-dependent concentration growth,the effect of the shape of endothelial cell and the effect of physiological parameters were analyzed. The analytical solution of velocity field and pressure field of water flow across the arterial wall were obtained; and concentration distribution of three macromolecules ; LDL,HRP and Albumin, were calculated with numerical simulation method. The new theory predicts, the maximum and distribution areas of time dependent concentration with round shape endothelial cell are both larger than that with ellipse-shape endothelial cell. The model also predicts the concentration growth is much alike that of a two-dimensional model and it shows that the concentration reaches its peak at the leaky junction where atherosclerotic formation frequently occurs and falls down rapidly in a limited area beginning from its earlier time growth to the state when macromolecular transfer approaches steadily. These predictions of the new model are in agreement with the experimental observation for the growth and concentration distribution of LDL and Albumin.

  19. A brief history of macromolecular crystallography, illustrated by a family tree and its Nobel fruits.

    Science.gov (United States)

    Jaskolski, Mariusz; Dauter, Zbigniew; Wlodawer, Alexander

    2014-09-01

    As a contribution to the celebration of the year 2014, declared by the United Nations to be 'The International Year of Crystallography', the FEBS Journal is dedicating this issue to papers showcasing the intimate union between macromolecular crystallography and structural biology, both in historical perspective and in current research. Instead of a formal editorial piece, by way of introduction, this review discusses the most important, often iconic, achievements of crystallographers that led to major advances in our understanding of the structure and function of biological macromolecules. We identified at least 42 scientists who received Nobel Prizes in Physics, Chemistry or Medicine for their contributions that included the use of X-rays or neutrons and crystallography, including 24 who made seminal discoveries in macromolecular sciences. Our spotlight is mostly, but not only, on the recipients of this most prestigious scientific honor, presented in approximately chronological order. As a summary of the review, we attempt to construct a genealogy tree of the principal lineages of protein crystallography, leading from the founding members to the present generation. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  20. Resolving macromolecular structures from electron cryo-tomography data using subtomogram averaging in RELION.

    Science.gov (United States)

    Bharat, Tanmay A M; Scheres, Sjors H W

    2016-11-01

    Electron cryo-tomography (cryo-ET) is a technique that is used to produce 3D pictures (tomograms) of complex objects such as asymmetric viruses, cellular organelles or whole cells from a series of tilted electron cryo-microscopy (cryo-EM) images. Averaging of macromolecular complexes found within tomograms is known as subtomogram averaging, and this technique allows structure determination of macromolecular complexes in situ. Subtomogram averaging is also gaining in popularity for the calculation of initial models for single-particle analysis. We describe herein a protocol for subtomogram averaging from cryo-ET data using the RELION software (http://www2.mrc-lmb.cam.ac.uk/relion). RELION was originally developed for cryo-EM single-particle analysis, and the subtomogram averaging approach presented in this protocol has been implemented in the existing workflow for single-particle analysis so that users may conveniently tap into existing capabilities of the RELION software. We describe how to calculate 3D models for the contrast transfer function (CTF) that describe the transfer of information in the imaging process, and we illustrate the results of classification and subtomogram averaging refinement for cryo-ET data of purified hepatitis B capsid particles and Saccharomyces cerevisiae 80S ribosomes. Using the steps described in this protocol, along with the troubleshooting and optimization guidelines, high-resolution maps can be obtained in which secondary structure elements are resolved subtomogram.

  1. Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction

    Science.gov (United States)

    Wakabayashi, Ayako; Kumagai, Yoshihiro; Watari, Eiji; Shimizu, Masumi; Utsuyama, Masanori; Hirokawa, Katsuiku; Takahashi, Hidemi

    2006-01-01

    Oral administration of a certain dose of antigen can generally induce immunological tolerance against the same antigen. In this study, we showed the temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral blood of mice after the oral administration of OVA. Furthermore, we detected 45 000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based on this observation, we examined whether the injection of intact OVA into the portal or peripheral vein induces immunological tolerance against OVA. We found that the intravenous injection of intact OVA did not induce immunological tolerance but rather enhanced OVA-specific antibody production in some subclasses, suggesting that OVA antigens via the gastrointestinal tract but not intact OVA may contribute to establish immunological tolerance against OVA. Therefore, we examined the effects of digesting intact OVA in the gastrointestinal tract on the induction of oral tolerance. When mice were orally administered or injected into various gastrointestinal organs, such as the stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA-specific antibody production and delayed-type hypersensitivity (DTH) response were significantly enhanced in mice injected into the ileum or colon, compared with orally administered mice. These results suggest that although macromolecular OVA antigens are detected after oral administration of OVA in tolerant-mouse serum, injection of intact OVA cannot contribute to tolerance induction. Therefore, some modification of macromolecular OVA in the gastrointestinal tract and ingestion may be essential for oral tolerance induction. PMID:16796692

  2. Assessing physio-macromolecular effects of lactic acid on Zygosaccharomyces bailii cells during microaerobic fermentation.

    Science.gov (United States)

    Kuanyshev, Nurzhan; Ami, Diletta; Signori, Lorenzo; Porro, Danilo; Morrissey, John P; Branduardi, Paola

    2016-08-01

    The ability of Zygosaccharomyces bailii to grow at low pH and in the presence of considerable amounts of weak organic acids, at lethal condition for Saccharomyces cerevisiae, increased the interest in the biotechnological potential of the yeast. To understand the mechanism of tolerance and growth effect of weak acids on Z. bailii, we evaluated the physiological and macromolecular changes of the yeast exposed to sub lethal concentrations of lactic acid. Lactic acid represents one of the important commodity chemical which can be produced by microbial fermentation. We assessed physiological effect of lactic acid by bioreactor fermentation using synthetic media at low pH in the presence of lactic acid. Samples collected from bioreactors were stained with propidium iodide (PI) which revealed that, despite lactic acid negatively influence the growth rate, the number of PI positive cells is similar to that of the control. Moreover, we have performed Fourier Transform Infra-Red (FTIR) microspectroscopy analysis on intact cells of the same samples. This technique has been never applied before to study Z. bailii under this condition. The analyses revealed lactic acid induced macromolecular changes in the overall cellular protein secondary structures, and alterations of cell wall and membrane physico-chemical properties.

  3. Influence of macromolecular architecture on necking in polymer extrusion film casting process

    Energy Technology Data Exchange (ETDEWEB)

    Pol, Harshawardhan; Banik, Sourya; Azad, Lal Busher; Doshi, Pankaj; Lele, Ashish [CSIR-National Chemical Laboratory, Pune, Maharashtra (India); Thete, Sumeet [Purdue University, West Lafayette, Indiana (United States)

    2015-05-22

    Extrusion film casting (EFC) is an important polymer processing technique that is used to produce several thousand tons of polymer films/coatings on an industrial scale. In this research, we are interested in understanding quantitatively how macromolecular chain architecture (for example long chain branching (LCB) or molecular weight distribution (MWD or PDI)) influences the necking and thickness distribution of extrusion cast films. We have used different polymer resins of linear and branched molecular architecture to produce extrusion cast films under controlled experimental conditions. The necking profiles of the films were imaged and the velocity profiles during EFC were monitored using particle tracking velocimetry (PTV) technique. Additionally, the temperature profiles were captured using an IR thermography and thickness profiles were calculated. The experimental results are compared with predictions of one-dimensional flow model of Silagy et al{sup 1} wherein the polymer resin rheology is modeled using molecular constitutive equations such as the Rolie-Poly (RP) and extended Pom Pom (XPP). We demonstrate that the 1-D flow model containing the molecular constitutive equations provides new insights into the role of macromolecular chain architecture on film necking.{sup 1}D. Silagy, Y. Demay, and J-F. Agassant, Polym. Eng. Sci., 36, 2614 (1996)

  4. X-ray Diffraction of Cotton Treated with Neutralized Vegetable Oil-based Macromolecular Crosslinkers

    Directory of Open Access Journals (Sweden)

    James W. Rawlins, Ph.D.

    2010-03-01

    Full Text Available Maleinized soybean oil (MSO has been investigated as a flexible, macromolecular crosslinker for cotton fabrics. The ability of MSO to penetrate crystalline cellulose and crosslink aligned cellulose chains upon cure has been in question. This study compares the penetration capability of MSO to dimethyloldihydroxyethyleneurea (DMDHEU, which is the commercial standard for durable press finishing and is an efficient cellulose crosslinker. X-ray diffraction was employed to characterize changes in the crystalline morphology upon heating un-mercerized cotton fabrics treated with aqueous DMDHEU and soybean oil derivatives. Displacement of characteristic interplanar spacings and the genesis/elimination of diffraction intensities from quintessential planes were evidence of structural modification. The penetration of ammonia neutralized MSO (acid value 230.00 mg KOH/g into the microstructure of cotton cellulose is similar to that of DMDHEU in terms of expanding the interplanar spacings of characteristic planes. Moreover, polymorphism of cotton and mercerized cotton occurred upon treatment with aqueous solutions of MSO. These findings suggest that macromolecular reagents can diffuse into cellulose fibrils if they are sufficiently hydrated or enshrouded by more favored penetrants.

  5. MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments.

    Science.gov (United States)

    Gabadinho, José; Beteva, Antonia; Guijarro, Matias; Rey-Bakaikoa, Vicente; Spruce, Darren; Bowler, Matthew W; Brockhauser, Sandor; Flot, David; Gordon, Elspeth J; Hall, David R; Lavault, Bernard; McCarthy, Andrew A; McCarthy, Joanne; Mitchell, Edward; Monaco, Stéphanie; Mueller-Dieckmann, Christoph; Nurizzo, Didier; Ravelli, Raimond B G; Thibault, Xavier; Walsh, Martin A; Leonard, Gordon A; McSweeney, Sean M

    2010-09-01

    The design and features of a beamline control software system for macromolecular crystallography (MX) experiments developed at the European Synchrotron Radiation Facility (ESRF) are described. This system, MxCuBE, allows users to easily and simply interact with beamline hardware components and provides automated routines for common tasks in the operation of a synchrotron beamline dedicated to experiments in MX. Additional functionality is provided through intuitive interfaces that enable the assessment of the diffraction characteristics of samples, experiment planning, automatic data collection and the on-line collection and analysis of X-ray emission spectra. The software can be run in a tandem client-server mode that allows for remote control and relevant experimental parameters and results are automatically logged in a relational database, ISPyB. MxCuBE is modular, flexible and extensible and is currently deployed on eight macromolecular crystallography beamlines at the ESRF. Additionally, the software is installed at MAX-lab beamline I911-3 and at BESSY beamline BL14.1.

  6. Translational diffusion of macromolecular assemblies measured using transverse-relaxation-optimized pulsed field gradient NMR.

    Science.gov (United States)

    Horst, Reto; Horwich, Arthur L; Wüthrich, Kurt

    2011-10-19

    In structural biology, pulsed field gradient (PFG) NMR spectroscopy for the characterization of size and hydrodynamic parameters of macromolecular solutes has the advantage over other techniques that the measurements can be recorded with identical solution conditions as used for NMR structure determination or for crystallization trials. This paper describes two transverse-relaxation-optimized (TRO) (15)N-filtered PFG stimulated-echo (STE) experiments for studies of macromolecular translational diffusion in solution, (1)H-TRO-STE and (15)N-TRO-STE, which include CRINEPT and TROSY elements. Measurements with mixed micelles of the Escherichia coli outer membrane protein X (OmpX) and the detergent Fos-10 were used for a systematic comparison of (1)H-TRO-STE and (15)N-TRO-STE with conventional (15)N-filtered STE experimental schemes. The results provide an extended platform for evaluating the NMR experiments available for diffusion measurements in structural biology projects involving molecular particles with different size ranges. An initial application of the (15)N-TRO-STE experiment with very long diffusion delays showed that the tedradecamer structure of the 800 kDa Thermus thermophilus chaperonin GroEL is preserved in aqueous solution over the temperature range 25-60 °C.

  7. Translational diffusion of macromolecular assemblies measured using transverse relaxation-optimized PFG-NMR

    Science.gov (United States)

    Horst, Reto; Horwich, Arthur L.

    2012-01-01

    In structural biology, pulsed field gradient (PFG) NMR for characterization of size and hydrodynamic parameters of macromolecular solutes has the advantage over other techniques that the measurements can be recorded with identical solution conditions as used for NMR structure determination or for crystallization trials. This paper describes two transverse relaxation-optimized (TRO) 15N-filtered PFG stimulated-echo (STE) experiments for studies of macromolecular translational diffusion in solution, 1H-TRO-STE and 15N-TRO-STE, which include CRINEPT and TROSY elements. Measurements with mixed micelles of the Escherichia coli outer membrane protein X (OmpX) and the detergent Fos-10 were used for a systematic comparison of 1H-TRO-STE and 15N-TRO-STE with conventional 15N-filtered STE experimental schemes. The results provide an extended platform for evaluating the NMR experiments available for diffusion measurements in structural biology projects with molecular particles of different size ranges. An initial application of the 15N-TRO-STE experiment with very long diffusion delays showed that the tedradecamer structure of the 800 kDa Thermus thermophilus chaperonin GroEL is preserved in aqueous solution over the temperature range 25–60°C. PMID:21919531

  8. Macromolecular Crowding Studies of Amino Acids Using NMR Diffusion Measurements and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Amninder S Virk

    2015-02-01

    Full Text Available Molecular crowding occurs when the total concentration of macromolecular species in a solution is so high that a considerable proportion of the volume is physically occupied and therefore not accessible to other molecules. This results in significant changes in the solution properties of the molecules in such systems. Macromolecular crowding is ubiquitous in biological systems due to the generally high intracellular protein concentrations. The major hindrance to understanding crowding is the lack of direct comparison of experimental data with theoretical or simulated data. Self-diffusion is sensitive to changes in the molecular weight and shape of the diffusing species, and the available diffusion space (i.e., diffusive obstruction. Consequently, diffusion measurements are a direct means for probing crowded systems including the self-association of molecules. In this work, nuclear magnetic resonance measurements of the self-diffusion of four amino acids (glycine, alanine, valine and phenylalanine up to their solubility limit in water were compared directly with molecular dynamics simulations. The experimental data were then analyzed using various models of aggregation and obstruction. Both experimental and simulated data revealed that the diffusion of both water and the amino acids were sensitive to the amino acid concentration. The direct comparison of the simulated and experimental data afforded greater insights into the aggregation and obstruction properties of each amino acid.

  9. Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

    Directory of Open Access Journals (Sweden)

    Iborra Francisco J

    2007-04-01

    Full Text Available Abstract Background The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. Results The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin scattered within domains rich in fast components (protein/RNA. Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. Conclusion I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon.

  10. Left Atrial Reverse Remodeling: Mechanisms, Evaluation, and Clinical Significance.

    Science.gov (United States)

    Thomas, Liza; Abhayaratna, Walter P

    2017-01-01

    The left atrium is considered a biomarker for adverse cardiovascular outcomes, particularly in patients with left ventricular diastolic dysfunction and atrial fibrillation in whom left atrial (LA) enlargement is of prognostic importance. LA enlargement with a consequent decrease in LA function represents maladaptive structural and functional "remodeling" that in turn promotes electrical remodeling and a milieu conducive for incident atrial fibrillation. Medical and nonmedical interventions may arrest this pathophysiologic process to the extent that subsequent reverse remodeling results in a reduction in LA size and improvement in LA function. This review examines cellular and basic mechanisms involved in LA remodeling, evaluates the noninvasive techniques that can assess these changes, and examines potential mechanisms that may initiate reverse remodeling.

  11. The redox state of transglutaminase 2 controls arterial remodeling

    DEFF Research Database (Denmark)

    van den Akker, Jeroen; VanBavel, Ed; van Geel, Remon

    2011-01-01

    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates......, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG......2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited...

  12. Vessel remodelling, pregnancy hormones and extravillous trophoblast function.

    Science.gov (United States)

    Chen, Jessie Z-J; Sheehan, Penelope M; Brennecke, Shaun P; Keogh, Rosemary J

    2012-02-26

    During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia.

  13. MX1: a bending-magnet crystallography beamline serving both chemical and macromolecular crystallography communities at the Australian Synchrotron

    Energy Technology Data Exchange (ETDEWEB)

    Cowieson, Nathan Philip; Aragao, David; Clift, Mark; Ericsson, Daniel J.; Gee, Christine; Harrop, Stephen J.; Mudie, Nathan; Panjikar, Santosh; Price, Jason R.; Riboldi-Tunnicliffe, Alan; Williamson, Rachel; Caradoc-Davies, Tom, E-mail: tom.caradoc-davies@synchrotron.org.au [Australian Synchrotron, 800 Blackburn Road, Clayton, Victoria 3168 (Australia)

    2015-01-01

    The macromolecular crystallography beamline MX1 at the Australian Synchrotron is described. MX1 is a bending-magnet crystallography beamline at the 3 GeV Australian Synchrotron. The beamline delivers hard X-rays in the energy range from 8 to 18 keV to a focal spot at the sample position of 120 µm FWHM. The beamline endstation and ancillary equipment facilitate local and remote access for both chemical and biological macromolecular crystallography. Here, the design of the beamline and endstation are discussed. The beamline has enjoyed a full user program for the last seven years and scientific highlights from the user program are also presented.

  14. Machinability evaluation of machinable ceramics with fuzzy theory

    Institute of Scientific and Technical Information of China (English)

    YU Ai-bing; ZHONG Li-jun; TAN Ye-fa

    2005-01-01

    The property parameters and machining output parameters were selected for machinability evaluation of machinable ceramics. Based on fuzzy evaluation theory, two-stage fuzzy evaluation approach was applied to consider these parameters. Two-stage fuzzy comprehensive evaluation model was proposed to evaluate machinability of machinable ceramic materials. Ce-ZrO2/CePO4 composites were fabricated and machined for evaluation of machinable ceramics. Material removal rates and specific normal grinding forces were measured. The parameters concerned with machinability were selected as alternative set. Five grades were chosen for the machinability evaluation of machnable ceramics. Machinability grades of machinable ceramics were determined through fuzzy operation. Ductile marks are observed on Ce-ZrO2/CePO4 machined surface. Five prepared Ce-ZrO2/CePO4 composites are classified as three machinability grades according to the fuzzy comprehensive evaluation results. The machinability grades of Ce-ZrO2/CePO4 composites are concerned with CePO4 content.

  15. MACHINE MOTION EQUATIONS

    Directory of Open Access Journals (Sweden)

    Florian Ion Tiberiu Petrescu

    2015-09-01

    Full Text Available This paper presents the dynamic, original, machine motion equations. The equation of motion of the machine that generates angular speed of the shaft (which varies with position and rotation speed is deduced by conservation kinetic energy of the machine. An additional variation of angular speed is added by multiplying by the coefficient dynamic D (generated by the forces out of mechanism and or by the forces generated by the elasticity of the system. Kinetic energy conservation shows angular speed variation (from the shaft with inertial masses, while the dynamic coefficient introduces the variation of w with forces acting in the mechanism. Deriving the first equation of motion of the machine one can obtain the second equation of motion dynamic. From the second equation of motion of the machine it determines the angular acceleration of the shaft. It shows the distribution of the forces on the mechanism to the internal combustion heat engines. Dynamic, the velocities can be distributed in the same way as forces. Practically, in the dynamic regimes, the velocities have the same timing as the forces. Calculations should be made for an engine with a single cylinder. Originally exemplification is done for a classic distribution mechanism, and then even the module B distribution mechanism of an Otto engine type.

  16. Chondromodulin I Is a Bone Remodeling Factor

    Science.gov (United States)

    Nakamichi, Yuko; Shukunami, Chisa; Yamada, Takashi; Aihara, Ken-ichi; Kawano, Hirotaka; Sato, Takashi; Nishizaki, Yuriko; Yamamoto, Yoko; Shindo, Masayo; Yoshimura, Kimihiro; Nakamura, Takashi; Takahashi, Naoyuki; Kawaguchi, Hiroshi; Hiraki, Yuji; Kato, Shigeaki

    2003-01-01

    Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage and its functions in cultured chondrocytes as a major regulator in cartilage development. Here, we generated mice deficient in ChM-I by targeted disruption of the ChM-I gene. No overt abnormality was detected in endochondral bone formation during embryogenesis and cartilage development during growth stages of ChM-I−/− mice. However, a significant increase in bone mineral density with lowered bone resorption with respect to formation was unexpectedly found in adult ChM-I−/− mice. Thus, the present study established that ChM-I is a bone remodeling factor. PMID:12509461

  17. Multiscale Bone Remodelling with Spatial P Systems

    CERN Document Server

    Cacciagrano, Diletta; Merelli, Emanuela; Tesei, Luca; 10.4204/EPTCS.40.6

    2010-01-01

    Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as ...

  18. Renovascular hypertension causes cerebral vascular remodeling

    Institute of Scientific and Technical Information of China (English)

    Yamei Tang; Xiangpen Li; Yi Li; Qingyu Shen; Xiaoming Rong; Ruxun Huang; Ying Peng

    2011-01-01

    Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

  19. Small artery remodeling in hypertension and diabetes.

    Science.gov (United States)

    Rizzoni, Damiano; Agabiti Rosei, Enrico

    2006-04-01

    The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small artery smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, whereas in some secondary forms of hypertension and in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling may be detected. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients. Various antihypertensive drugs seem to have different effects on vascular structure. A complete normalization of small resistance artery structure was demonstrated in hypertensive patients, after prolonged and effective therapy with angiotensin-converting enzyme inhibitors, angiotensin II-receptor blockers, and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard.

  20. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts

    OpenAIRE

    Kemi, Ole J.; Hoydal, Morten A; MacQuaide, Niall; Haram, Per M; Koch, Lauren G.; Steven L Britton; Ellingsen, Oyvind; Smith, Godfrey L.; Wisloff, Ulrik

    2011-01-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T-tubule density. Thus, the T-tubules adapted to the physiologi...

  1. Dynamics of cyclic machines

    CERN Document Server

    Vulfson, Iosif

    2015-01-01

    This book focuses on modern methods of oscillation analysis in machines, including cyclic action mechanisms (linkages, cams, steppers, etc.). It presents schematization techniques and mathematical descriptions of oscillating systems, taking into account the variability of the parameters and nonlinearities, engineering evaluations of dynamic errors, and oscillation suppression methods. The majority of the book is devoted to the development of new methods of dynamic analysis and synthesis for cyclic machines that form regular oscillatory systems with multiple duplicate modules.  There are also sections examining aspects of general engineering interest (nonlinear dissipative forces, systems with non-stationary constraints, impacts and pseudo-impacts in clearances, etc.)  The examples in the book are based on the widely used results of theoretical and experimental studies as well as engineering calculations carried out in relation to machines used in the textile, light, polygraphic and other industries. Particu...

  2. Chatter and machine tools

    CERN Document Server

    Stone, Brian

    2014-01-01

    Focussing on occurrences of unstable vibrations, or Chatter, in machine tools, this book gives important insights into how to eliminate chatter with associated improvements in product quality, surface finish and tool wear. Covering a wide range of machining processes, including turning, drilling, milling and grinding, the author uses his research expertise and practical knowledge of vibration problems to provide solutions supported by experimental evidence of their effectiveness. In addition, this book contains links to supplementary animation programs that help readers to visualise the ideas detailed in the text. Advancing knowledge in chatter avoidance and suggesting areas for new innovations, Chatter and Machine Tools serves as a handbook for those desiring to achieve significant reductions in noise, longer tool and grinding wheel life and improved product finish.

  3. Machines and Metaphors

    Directory of Open Access Journals (Sweden)

    Ángel Martínez García-Posada

    2016-10-01

    Full Text Available The edition La ley del reloj. Arquitectura, máquinas y cultura moderna (Cátedra, Madrid, 2016 registers the useful paradox of the analogy between architecture and technique. Its author, the architect Eduardo Prieto, also a philosopher, professor and writer, acknowledges the obvious distance from machines to buildings, so great that it can only be solved using strange comparisons, since architecture does not move nor are the machines habitable, however throughout the book, from the origin of the metaphor of the machine, with clarity in his essay and enlightening erudition, he points out with certainty some concomitances of high interest, drawing throughout history a beautiful cartography of the fruitful encounter between organics and mechanics.

  4. Machine Learning Markets

    CERN Document Server

    Storkey, Amos

    2011-01-01

    Prediction markets show considerable promise for developing flexible mechanisms for machine learning. Here, machine learning markets for multivariate systems are defined, and a utility-based framework is established for their analysis. This differs from the usual approach of defining static betting functions. It is shown that such markets can implement model combination methods used in machine learning, such as product of expert and mixture of expert approaches as equilibrium pricing models, by varying agent utility functions. They can also implement models composed of local potentials, and message passing methods. Prediction markets also allow for more flexible combinations, by combining multiple different utility functions. Conversely, the market mechanisms implement inference in the relevant probabilistic models. This means that market mechanism can be utilized for implementing parallelized model building and inference for probabilistic modelling.

  5. Machine Learning for Security

    CERN Document Server

    CERN. Geneva

    2015-01-01

    Applied statistics, aka ‘Machine Learning’, offers a wealth of techniques for answering security questions. It’s a much hyped topic in the big data world, with many companies now providing machine learning as a service. This talk will demystify these techniques, explain the math, and demonstrate their application to security problems. The presentation will include how-to’s on classifying malware, looking into encrypted tunnels, and finding botnets in DNS data. About the speaker Josiah is a security researcher with HP TippingPoint DVLabs Research Group. He has over 15 years of professional software development experience. Josiah used to do AI, with work focused on graph theory, search, and deductive inference on large knowledge bases. As rules only get you so far, he moved from AI to using machine learning techniques identifying failure modes in email traffic. There followed digressions into clustered data storage and later integrated control systems. Current ...

  6. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts.

    Science.gov (United States)

    Kemi, Ole J; Hoydal, Morten A; Macquaide, Niall; Haram, Per M; Koch, Lauren G; Britton, Steven L; Ellingsen, Oyvind; Smith, Godfrey L; Wisloff, Ulrik

    2011-09-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P hypertrophy. Next, we studied T-tubules in a rat model of metabolic syndrome with pressure overload-induced concentric left ventricle hypertrophy, evidenced by 15% (P Exercise training further increased cardiomyocyte volume by 8% (P eccentric and concentric hypertrophy and 55% (P Exercise training reversed 50% (P hypertrophy, whereas the T-tubule density increased by 40% (P hypertrophy associated with conserved T-tubule spacing (~1.8-1.9 µm), whereas in pathologic hypertrophy, T-tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T-tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T-tubules; exercise training reverses the remodeling and partly corrects the T-tubule density.

  7. Advanced Analysis of Nontraditional Machining

    CERN Document Server

    Tsai, Hung-Yin

    2013-01-01

    Nontraditional machining utilizes thermal, chemical, electrical, mechanical and optical sources of energy to form and cut materials. Advanced Analysis of Nontraditional Machining explains in-depth how each of these advanced machining processes work, their machining system components, and process variables and industrial applications, thereby offering advanced knowledge and scientific insight. This book also documents the latest and frequently cited research results of a few key nonconventional machining processes for the most concerned topics in industrial applications, such as laser machining, electrical discharge machining, electropolishing of die and mold, and wafer processing for integrated circuit manufacturing. This book also: Fills the gap of the advanced knowledge of nonconventional machining between industry and research Documents latest and frequently cited research of key nonconventional machining processes for the most sought after topics in industrial applications Demonstrates advanced multidisci...

  8. Machining strategy choice: performance VIEWER

    CERN Document Server

    Tapie, Laurent; Anselmetti, Bernard

    2009-01-01

    Nowadays high speed machining (HSM) machine tool combines productivity and part quality. So mould and die maker invested in HSM. Die and mould features are more and more complex shaped. Thus, it is difficult to choose the best machining strategy according to part shape. Geometrical analysis of machining features is not sufficient to make an optimal choice. Some research show that security, technical, functional and economical constrains must be taken into account to elaborate a machining strategy. During complex shape machining, production system limits induce feed rate decreases, thus loss of productivity, in some part areas. In this paper we propose to analyse these areas by estimating tool path quality. First we perform experiments on HSM machine tool to determine trajectory impact on machine tool behaviour. Then, we extract critical criteria and establish models of performance loss. Our work is focused on machine tool kinematical performance and numerical controller unit calculation capacity. We implement...

  9. Electrical machines diagnosis

    CERN Document Server

    Trigeassou, Jean-Claude

    2013-01-01

    Monitoring and diagnosis of electrical machine faults is a scientific and economic issue which is motivated by objectives for reliability and serviceability in electrical drives.This book provides a survey of the techniques used to detect the faults occurring in electrical drives: electrical, thermal and mechanical faults of the electrical machine, faults of the static converter and faults of the energy storage unit.Diagnosis of faults occurring in electrical drives is an essential part of a global monitoring system used to improve reliability and serviceability. This diagnosis is perf

  10. Refrigerating machine oil

    Energy Technology Data Exchange (ETDEWEB)

    Nozawa, K.

    1981-03-17

    Refrigerating machine oil to be filled in a sealed motorcompressor unit constituting a refrigerating cycle system including an electric refrigerator, an electric cold-storage box, a small-scaled electric refrigerating show-case, a small-scaled electric cold-storage show-case and the like, is arranged to have a specifically enhanced property, in which smaller initial driving power consumption of the sealed motor-compressor and easier supply of the predetermined amount of the refrigerating machine oil to the refrigerating system are both guaranteed even in a rather low environmental temperature condition.

  11. Machine shop basics

    CERN Document Server

    Miller, Rex

    2004-01-01

    Use the right tool the right wayHere, fully updated to include new machines and electronic/digital controls, is the ultimate guide to basic machine shop equipment and how to use it. Whether you're a professional machinist, an apprentice, a trade student, or a handy homeowner, this fully illustrated volume helps you define tools and use them properly and safely. It's packed with review questions for students, and loaded with answers you need on the job.Mark Richard Miller is a Professor and Chairman of the Industrial Technology Department at Texas A&M University in Kingsville, T

  12. Electrical machines & their applications

    CERN Document Server

    Hindmarsh, J

    1984-01-01

    A self-contained, comprehensive and unified treatment of electrical machines, including consideration of their control characteristics in both conventional and semiconductor switched circuits. This new edition has been expanded and updated to include material which reflects current thinking and practice. All references have been updated to conform to the latest national (BS) and international (IEC) recommendations and a new appendix has been added which deals more fully with the theory of permanent-magnets, recognising the growing importance of permanent-magnet machines. The text is so arra

  13. Clojure for machine learning

    CERN Document Server

    Wali, Akhil

    2014-01-01

    A book that brings out the strengths of Clojure programming that have to facilitate machine learning. Each topic is described in substantial detail, and examples and libraries in Clojure are also demonstrated.This book is intended for Clojure developers who want to explore the area of machine learning. Basic understanding of the Clojure programming language is required, but thorough acquaintance with the standard Clojure library or any libraries are not required. Familiarity with theoretical concepts and notation of mathematics and statistics would be an added advantage.

  14. Perpetual Motion Machine

    OpenAIRE

    D. Tsaousis

    2008-01-01

    Ever since the first century A.D. there have been relative descriptions of known devices as well as manufactures for the creation of perpetual motion machines. Although physics has led, with two thermodynamic laws, to the opinion that a perpetual motion machine is impossible to be manufactured, inventors of every age and educational level appear to claim that they have invented something «entirely new» or they have improved somebody else’s invention, which «will function henceforth perpetuall...

  15. Man - Machine Communication

    CERN Document Server

    Petersen, Peter; Nielsen, Henning

    1984-01-01

    This report describes a Man-to-Machine Communication module which together with a STAC can take care of all operator inputs from the touch-screen, tracker balls and mechanical buttons. The MMC module can also contain a G64 card which could be a GPIB driver but many other G64 cards could be used. The soft-ware services the input devices and makes the results accessible from the CAMAC bus. NODAL functions for the Man Machine Communication is implemented in the STAC and in the ICC.

  16. Machine Fault Signature Analysis

    Directory of Open Access Journals (Sweden)

    Pratesh Jayaswal

    2008-01-01

    Full Text Available The objective of this paper is to present recent developments in the field of machine fault signature analysis with particular regard to vibration analysis. The different types of faults that can be identified from the vibration signature analysis are, for example, gear fault, rolling contact bearing fault, journal bearing fault, flexible coupling faults, and electrical machine fault. It is not the intention of the authors to attempt to provide a detailed coverage of all the faults while detailed consideration is given to the subject of the rolling element bearing fault signature analysis.

  17. Design of rotating electrical machines

    CERN Document Server

    Pyrhonen , Juha; Hrabovcova , Valeria

    2013-01-01

    In one complete volume, this essential reference presents an in-depth overview of the theoretical principles and techniques of electrical machine design. This timely new edition offers up-to-date theory and guidelines for the design of electrical machines, taking into account recent advances in permanent magnet machines as well as synchronous reluctance machines. New coverage includes: Brand new material on the ecological impact of the motors, covering the eco-design principles of rotating electrical machinesAn expanded section on the design of permanent magnet synchronous machines, now repo

  18. Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes.

    Science.gov (United States)

    Brea, Roberto J; Rudd, Andrew K; Devaraj, Neal K

    2016-08-02

    Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.

  19. The redox state of transglutaminase 2 controls arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Jeroen van den Akker

    Full Text Available While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2, the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub cellular localization, substrates, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited by a TG2 inhibitor and by the nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21 proteins were identified as TG2 cross-linking substrates, including fibronectin, collagen and nidogen. Inward remodeling induced by low blood flow was associated with the upregulation of several anti-oxidant proteins, notably glutathione-S-transferase, and selenoprotein P. In conclusion, these results show that a reduced state induces smooth muscle membrane-bound TG2 activity. Inward remodeling results from the cross-linking of vicinal matrix proteins, causing a stiffening of the arterial wall.

  20. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  1. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Science.gov (United States)

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC.

  2. Machine speech and speaking about machines

    Energy Technology Data Exchange (ETDEWEB)

    Nye, A. [Univ. of Wisconsin, Whitewater, WI (United States)

    1996-12-31

    Current philosophy of language prides itself on scientific status. It boasts of being no longer contaminated with queer mental entities or idealist essences. It theorizes language as programmable variants of formal semantic systems, reimaginable either as the properly epiphenomenal machine functions of computer science or the properly material neural networks of physiology. Whether or not such models properly capture the physical workings of a living human brain is a question that scientists will have to answer. I, as a philosopher, come at the problem from another direction. Does contemporary philosophical semantics, in its dominant truth-theoretic and related versions, capture actual living human thought as it is experienced, or does it instead reflect, regardless of (perhaps dubious) scientific credentials, pathology of thought, a pathology with a disturbing social history.

  3. Probing the Interplay of Size, Shape, and Solution Environment in Macromolecular Diffusion Using a Simple Refraction Experiment

    Science.gov (United States)

    Mankidy, Bijith D.; Coutinho, Cecil A.; Gupta, Vinay K.

    2010-01-01

    The diffusion coefficient of polymers is a critical parameter in biomedicine, catalysis, chemical separations, nanotechnology, and other industrial applications. Here, measurement of macromolecular diffusion in solutions is described using a visually instructive, undergraduate-level optical refraction experiment based on Weiner's method. To…

  4. Macromolecular crowding meets oxygen tension in human mesenchymal stem cell culture - A step closer to physiologically relevant in vitro organogenesis

    Science.gov (United States)

    Cigognini, Daniela; Gaspar, Diana; Kumar, Pramod; Satyam, Abhigyan; Alagesan, Senthilkumar; Sanz-Nogués, Clara; Griffin, Matthew; O’Brien, Timothy; Pandit, Abhay; Zeugolis, Dimitrios I.

    2016-01-01

    Modular tissue engineering is based on the cells’ innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes. PMID:27478033

  5. Errors in macromolecular synthesis after stress : a study of the possible protective role of the small heat shock proteins

    NARCIS (Netherlands)

    Marin Vinader, L.

    2006-01-01

    The general goal of this thesis was to gain insight in what small heat shock proteins (sHsps) do with respect to macromolecular synthesis during a stressful situation in the cell. It is known that after a non-lethal heat shock, cells are better protected against a subsequent more severe heat shock,

  6. An optimal strategy for X-ray data collection on macromolecular crystals with position-sensitive detectors

    NARCIS (Netherlands)

    Vicković, Ivan; Kalk, Kor H.; Drenth, Jan; Dijkstra, Bauke W.

    1994-01-01

    X-ray data collection on macromolecular crystals is preferably done with minimum exposure time and high completeness. A Fortran procedure - DCS - has been written in the environment of the MADNES program to predict the completeness of data before the start of actual data collection. In addition, the

  7. Probing the Interplay of Size, Shape, and Solution Environment in Macromolecular Diffusion Using a Simple Refraction Experiment

    Science.gov (United States)

    Mankidy, Bijith D.; Coutinho, Cecil A.; Gupta, Vinay K.

    2010-01-01

    The diffusion coefficient of polymers is a critical parameter in biomedicine, catalysis, chemical separations, nanotechnology, and other industrial applications. Here, measurement of macromolecular diffusion in solutions is described using a visually instructive, undergraduate-level optical refraction experiment based on Weiner's method. To…

  8. Macromolecular crowding meets oxygen tension in human mesenchymal stem cell culture - A step closer to physiologically relevant in vitro organogenesis

    Science.gov (United States)

    Cigognini, Daniela; Gaspar, Diana; Kumar, Pramod; Satyam, Abhigyan; Alagesan, Senthilkumar; Sanz-Nogués, Clara; Griffin, Matthew; O'Brien, Timothy; Pandit, Abhay; Zeugolis, Dimitrios I.

    2016-08-01

    Modular tissue engineering is based on the cells’ innate ability to create bottom-up supramolecular assemblies with efficiency and efficacy still unmatched by man-made devices. Although the regenerative potential of such tissue substitutes has been documented in preclinical and clinical setting, the prolonged culture time required to develop an implantable device is associated with phenotypic drift and/or cell senescence. Herein, we demonstrate that macromolecular crowding significantly enhances extracellular matrix deposition in human bone marrow mesenchymal stem cell culture at both 20% and 2% oxygen tension. Although hypoxia inducible factor - 1α was activated at 2% oxygen tension, increased extracellular matrix synthesis was not observed. The expression of surface markers and transcription factors was not affected as a function of oxygen tension and macromolecular crowding. The multilineage potential was also maintained, albeit adipogenic differentiation was significantly reduced in low oxygen tension cultures, chondrogenic differentiation was significantly increased in macromolecularly crowded cultures and osteogenic differentiation was not affected as a function of oxygen tension and macromolecular crowding. Collectively, these data pave the way for the development of bottom-up tissue equivalents based on physiologically relevant developmental processes.

  9. Proceedings of a one-week course on exploiting anomalous scattering in macromolecular structure determination (EMBO'07)

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, M.S.; Shepard, W.; Dauter, Z.; Leslie, A.; Diederichs, K.; Evans, G.; Svensson, O.; Schneider, T.; Bricogne, G.; Dauter, Z.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Leslie, A.; Kabsch, W.; Flensburg, C.; Terwilliger, T.; Lamzin, V.; Read, R.; Panjikar, S.; Pannu, N.S.; Dauter, Z.; Weiss, M.S.; McSweeney, S

    2007-07-01

    This course, which was directed to young scientists, illustrated both theoretical and practical aspects of macromolecular crystal structure solution using synchrotron radiation. Some software dedicated to data collection, processing and analysis were presented. This document gathers only the slides of the presentations.

  10. Lipase-catalyzed Regioselective Synthesis of Vinyl Ester Derivatives of Thiamphenicol: Novel Thiamphenicol Monomers for Preparation of Macromolecular Antibiotic

    Institute of Scientific and Technical Information of China (English)

    Yu Zhen SHI; Zhi Chun CHEN; Na WANG; Qi WU; Xian Fu LIN

    2005-01-01

    Three polymerizable vinyl thiamphenicol esters with different acyl donor carbon chain length (C4, C6, C10) were regioselectivly synthesized by Lipozyme(R) (immobilized from mucor miehei) in acetone at 50 ℃ for 12 h to give 73%, 81%, 63% yield, respectively. The products were valuable monomers for preparation of macromolecular antibiotic.

  11. Force Spectroscopy of Individual Stimulus-Responsive Poly(ferrocenyldimethylsilane) Chains: Towards a Redox-Driven Macromolecular Motor

    NARCIS (Netherlands)

    Zou, Shan; Hempenius, Mark A.; Schönherr, Holger; Vancso, G. Julius

    2006-01-01

    Progress in the development of a redox-driven macromolecular motor and the characterization of its redox-mechanical cycle using electrochemical AFM-based single-molecule force spectroscopy (SMFS) is described. The elasticities of individual neutral and oxidized poly(ferrocenyldimethylsilane) (PFS) m

  12. Hybrid machining processes perspectives on machining and finishing

    CERN Document Server

    Gupta, Kapil; Laubscher, R F

    2016-01-01

    This book describes various hybrid machining and finishing processes. It gives a critical review of the past work based on them as well as the current trends and research directions. For each hybrid machining process presented, the authors list the method of material removal, machining system, process variables and applications. This book provides a deep understanding of the need, application and mechanism of hybrid machining processes.

  13. Cybernetic anthropomorphic machine systems

    Science.gov (United States)

    Gray, W. E.

    1974-01-01

    Functional descriptions are provided for a number of cybernetic man machine systems that augment the capacity of normal human beings in the areas of strength, reach or physical size, and environmental interaction, and that are also applicable to aiding the neurologically handicapped. Teleoperators, computer control, exoskeletal devices, quadruped vehicles, space maintenance systems, and communications equipment are considered.

  14. ARM : abstract rewriting machine

    NARCIS (Netherlands)

    J.F.T. Kamperman; H.R. Walters (Pum)

    1993-01-01

    textabstractTerm rewriting is frequently used as implementation technique for algebraic specifications. In this paper we present the abstract term rewriting machine (ARM), which has an extremely compact instruction set and imposes no restrictions on the implemented TRSs. Apart from standard

  15. A "Living" Machine

    Institute of Scientific and Technical Information of China (English)

    N.R.Bogatyrev

    2004-01-01

    Biomimetics (or bionics) is the engineering discipline that constructs artificial systems using biological principles. The ideal final result in biomimetics is to create a living machine. But what are the desirable and non-desirable properties of biomimetic product? Where can natural prototypes be found? How can technical solutions be transferred from nature to technology? Can we use living nature like LEGO bricks for construction our machines? How can biology help us? What is a living machine? In biomimetic practice only some "part" (organ, part of organ, tissue) of the observed whole organism is utilized. A possible template for future super-organism extension for biomimetic methods might be drawn from experiments in holistic ecological agriculture (ecological design, permaculture, ecological engineering, etc. ). The necessary translation of these rules to practical action can be achieved with the Russian Theory of Inventive Problem Solving (TRIZ), specifically adjusted to biology. Thus, permaculture, reinforced by a TRIZ conceptual framework, might provide the basis for Super-Organismic Bionics, which is hypothesized as necessary for effective ecological engineering. This hypothesis is supported by a case study-the design of a sustainable artificial nature reserve for wild pollinators as a living machine.

  16. Of machines and men ...

    CERN Multimedia

    CERN; Daniel Boileau

    1990-01-01

    Engineering and construction at LEP. Committed work and physicists motivation to work on this type of machine. With Guido Altarelli Theory Division Physicist, Ugo Amaldi Delphi Experiment Spokesman, Oscar Barbalat Head of Industry and Technology Liaison Office, Jonathan Ellis Head of Theory Division.

  17. Technology Time Machine 2012

    DEFF Research Database (Denmark)

    Lehner, Wolfgang; Fettweis, Gerhard; Fitzek, Frank

    2013-01-01

    The IEEE Technology Time Machine (TTM) is a unique event for industry leaders, academics, and decision making government officials who direct R&D activities, plan research programs or manage portfolios of research activities. This report covers the main topics of the 2nd Symposium of future...

  18. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...

  19. Laser machining of explosives

    Science.gov (United States)

    Perry, Michael D.; Stuart, Brent C.; Banks, Paul S.; Myers, Booth R.; Sefcik, Joseph A.

    2000-01-01

    The invention consists of a method for machining (cutting, drilling, sculpting) of explosives (e.g., TNT, TATB, PETN, RDX, etc.). By using pulses of a duration in the range of 5 femtoseconds to 50 picoseconds, extremely precise and rapid machining can be achieved with essentially no heat or shock affected zone. In this method, material is removed by a nonthermal mechanism. A combination of multiphoton and collisional ionization creates a critical density plasma in a time scale much shorter than electron kinetic energy is transferred to the lattice. The resulting plasma is far from thermal equilibrium. The material is in essence converted from its initial solid-state directly into a fully ionized plasma on a time scale too short for thermal equilibrium to be established with the lattice. As a result, there is negligible heat conduction beyond the region removed resulting in negligible thermal stress or shock to the material beyond a few microns from the laser machined surface. Hydrodynamic expansion of the plasma eliminates the need for any ancillary techniques to remove material and produces extremely high quality machined surfaces. There is no detonation or deflagration of the explosive in the process and the material which is removed is rendered inert.

  20. Electrical Discharge Machining.

    Science.gov (United States)

    Montgomery, C. M.

    The manual is for use by students learning electrical discharge machining (EDM). It consists of eight units divided into several lessons, each designed to meet one of the stated objectives for the unit. The units deal with: introduction to and advantages of EDM, the EDM process, basic components of EDM, reaction between forming tool and workpiece,…

  1. The Answer Machine.

    Science.gov (United States)

    Feldman, Susan

    2000-01-01

    Discusses information retrieval systems and the need to have them adapt to user needs, integrate information in any format, reveal patterns and trends in information, and answer questions. Topics include statistics and probability; natural language processing; intelligent agents; concept mapping; machine-aided indexing; text mining; filtering;…

  2. Massively collaborative machine learning

    NARCIS (Netherlands)

    Rijn, van J.N.

    2016-01-01

    Many scientists are focussed on building models. We nearly process all information we perceive to a model. There are many techniques that enable computers to build models as well. The field of research that develops such techniques is called Machine Learning. Many research is devoted to develop comp

  3. Recent Advances on Permanent Magnet Machines

    Institute of Scientific and Technical Information of China (English)

    诸自强

    2012-01-01

    This paper overviews advances on permanent magnet(PM) brushless machines over last 30 years,with particular reference to new and novel machine topologies.These include current states and trends for surface-mounted and interior PM machines,electrically and mechanically adjusted variable flux PM machines including memory machine,hybrid PM machines which uniquely integrate PM technology into induction machines,switched and synchronous reluctance machines and wound field machines,Halbach PM machines,dual-rotor PM machines,and magnetically geared PM machines,etc.The paper highlights their features and applications to various market sectors.

  4. Motherhood and the Machine

    Directory of Open Access Journals (Sweden)

    Miglena Nikolchina

    2014-12-01

    Full Text Available In her conceptualization of the human as defined by the capacity for revolt Kristeva unavoidably touches upon issues of robotization, technology, and the virtual. The concepts of animal and machine, however, although they do appear occasionally and in important ways, are never at the focus of her inquiries and are absent in her “New Forms of Revolt.” Yet these two concepts to a large extent define the field of contemporary philosophical debates of the human giving rise to three major theoretical orientations. On the one hand, there is the trend which tries to come to terms with technological novelties and the merging of human and machine that they imply. This trend unfolds under the rubric of “transhuman” or “posthuman” and of the “enhancement” of man. The second trend predominates in animal studies. Mostly in an ethical perspective but also ontologically, this trend, to which Derrida’s later writing made a significant contribution, questions the idea of the “human exception” and the rigorous distinction between man and animal on which this exception rests. While apparently antagonistic, both trends align the human with the animal and oppose it to technology. The third trend collapses the distinctions on which the previous two rely through the lens of biopolitics: drawing on Heidegger, Kojève, and Foucault, it regards contemporary technological transformations as amounting to the animalization of man.  The human disappears in the animal, in the machine, or in the indistinguishability of the two, confirming what Agamben has described as the inoperativeness of the anthropological machine. The present text turns to Kristeva’s conceptions of motherhood and revolt as introducing a powerful inflection in this tripartite field. Remarkably, it is precisely new sagas of rebellious machines like Battlestar “Galactica” that foreground the relevance of Kristeva’s approach.

  5. A mixed method for measuring low-frequency acoustic properties of macromolecular materials

    Institute of Scientific and Technical Information of China (English)

    LIU; Hongwei; YAO; Lei; ZHAO; Hong; ZHANG; Jichuan; XUE; Zhaohong

    2006-01-01

    A mixed method for measuring low-frequency acoustic properties of macromolecular materials is presented.The dynamic mechanical parameters of materials are first measured by using Dynamic Mechanical Thermal Apparatus(DMTA) at low frequencies,usually less than 100 Hz; then based on the Principles of Time-Temperature Super position (TTS),these parameters are extended to the frequency range that acousticians are concerned about,usually from hundreds to thousands of hertz; finally the extended dynamic mechanical parameters are transformed into acoustic parameters with the help of acoustic measurement and inverse analysis.To test the feasibility and accuracy,we measure a kind of rubber sample in DMTA and acquire the basic acoustic parameters of the sample by using this method.While applying the basic parameters to calculating characteristics of the sample in acoustic pipe,a reasonable agreement of sound absorption coefficients is obtained between the calculations and measurements in the acoustic pipe.

  6. Site-selective electroless nickel plating on patterned thin films of macromolecular metal complexes.

    Science.gov (United States)

    Kimura, Mutsumi; Yamagiwa, Hiroki; Asakawa, Daisuke; Noguchi, Makoto; Kurashina, Tadashi; Fukawa, Tadashi; Shirai, Hirofusa

    2010-12-01

    We demonstrate a simple route to depositing nickel layer patterns using photocross-linked polymer thin films containing palladium catalysts, which can be used as adhesive interlayers for fabrication of nickel patterns on glass and plastic substrates. Electroless nickel patterns can be obtained in three steps: (i) the pattern formation of partially quaterized poly(vinyl pyridine) by UV irradiation, (ii) the formation of macromolecular metal complex with palladium, and (iii) the nickel metallization using electroless plating bath. Metallization is site-selective and allows for a high resolution. And the resulting nickel layered structure shows good adhesion with glass and plastic substrates. The direct patterning of metallic layers onto insulating substrates indicates a great potential for fabricating micro/nano devices.

  7. Reliable and efficient solution of genome-scale models of Metabolism and macromolecular Expression

    Science.gov (United States)

    Ma, Ding; Yang, Laurence; Fleming, Ronan M. T.; Thiele, Ines; Palsson, Bernhard O.; Saunders, Michael A.

    2017-01-01

    Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many orders of magnitude. Data values also have greatly varying magnitudes. Standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME models have 70,000 constraints and variables and will grow larger). We have developed a quadruple-precision version of our linear and nonlinear optimizer MINOS, and a solution procedure (DQQ) involving Double and Quad MINOS that achieves reliability and efficiency for ME models and other challenging problems tested here. DQQ will enable extensive use of large linear and nonlinear models in systems biology and other applications involving multiscale data.

  8. Phenix - a comprehensive python-based system for macromolecular structure solution

    Energy Technology Data Exchange (ETDEWEB)

    Terwilliger, Thomas C [Los Alamos National Laboratory; Hung, Li - Wei [Los Alamos National Laboratory; Adams, Paul D [UC BERKELEY; Afonine, Pavel V [UC BERKELEY; Bunkoczi, Gabor [UNIV OF CAMBRIDGE; Chen, Vincent B [DUKE UNIV; Davis, Ian [DUKE UNIV; Echols, Nathaniel [LBNL; Headd, Jeffrey J [DUKE UNIV; Grosse Kunstleve, Ralf W [LBNL; Mccoy, Airlie J [UNIV OF CAMBRIDGE; Moriarty, Nigel W [LBNL; Oeffner, Robert [UNIV OF CAMBRIDGE; Read, Randy J [UNIV OF CAMBRIDGE; Richardson, David C [DUKE UNIV; Richardson, Jane S [DUKE UNIV; Zwarta, Peter H [LBNL

    2009-01-01

    Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages, and the repeated use of interactive three-dimensional graphics. Phenix has been developed to provide a comprehensive system for crystallographic structure solution with an emphasis on automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand, and finally the development of a framework that allows a tight integration between the algorithms.

  9. Syntheses of Macromolecular Ruthenium Compounds: A New Approach for the Search of Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Andreia Valente

    2014-03-01

    Full Text Available The continuous rising of the cancer patient death rate undoubtedly shows the pressure to find more potent and efficient drugs than those in clinical use. These agents only treat a narrow range of cancer conditions with limited success and are associated with serious side effects caused by the lack of selectivity. In this frame, innovative syntheses approaches can decisively contribute to the success of “smart compounds” that might be only selective and/or active towards the cancer cells, sparing the healthy ones. In this scope, ruthenium chemistry is a rising field for the search of proficient metallodrugs by the use of macromolecular ruthenium complexes (dendrimers and dendronized polymers, coordination-cage and protein conjugates, nanoparticles and polymer-“ruthenium-cyclopentadienyl” conjugates that can take advantage of the singularities of tumor cells (vs. healthy cells.

  10. Dependence of Protein Folding Stability and Dynamics on the Density and Composition of Macromolecular Crowders

    Science.gov (United States)

    Mittal, Jeetain; Best, Robert B.

    2010-01-01

    We investigate the effect of macromolecular crowding on protein folding, using purely repulsive crowding particles and a self-organizing polymer model of protein folding. We find that the variation in folding stability with crowder size for typical α-, β-, and α/β-proteins is well described by an adaptation of the scaled particle theory. The native state, the transition state, and the unfolded protein are treated as effective hard spheres, with the folded and transition state radii independent of the size and concentration of the crowders. Remarkably, we find that, as the effective unfolded state radius is very weakly dependent on the crowder concentration, it can also be approximated by a single size. The same model predicts the effect of crowding on the folding barrier and therefore refolding rates with no adjustable parameters. A simple extension of the scaled-particle theory model, assuming additivity, can also describe the behavior of mixtures of crowding particles. PMID:20338853

  11. Integration and global analysis of isothermal titration calorimetry data for studying macromolecular interactions.

    Science.gov (United States)

    Brautigam, Chad A; Zhao, Huaying; Vargas, Carolyn; Keller, Sandro; Schuck, Peter

    2016-05-01

    Isothermal titration calorimetry (ITC) is a powerful and widely used method to measure the energetics of macromolecular interactions by recording a thermogram of differential heating power during a titration. However, traditional ITC analysis is limited by stochastic thermogram noise and by the limited information content of a single titration experiment. Here we present a protocol for bias-free thermogram integration based on automated shape analysis of the injection peaks, followed by combination of isotherms from different calorimetric titration experiments into a global analysis, statistical analysis of binding parameters and graphical presentation of the results. This is performed using the integrated public-domain software packages NITPIC, SEDPHAT and GUSSI. The recently developed low-noise thermogram integration approach and global analysis allow for more precise parameter estimates and more reliable quantification of multisite and multicomponent cooperative and competitive interactions. Titration experiments typically take 1-2.5 h each, and global analysis usually takes 10-20 min.

  12. C1 Polymerization: a unique tool towards polyethylene-based complex macromolecular architectures

    KAUST Repository

    Wang, De

    2017-05-09

    The recent developments in organoborane initiated C1 polymerization (chain grows by one atom at a time) of ylides opens unique horizons towards well-defined/perfectly linear polymethylenes (equivalent to polyethylenes, PE) and PE-based complex macromolecular architectures. The general mechanism of C1 polymerization (polyhomologation) involves the formation of a Lewis complex between a methylide (monomer) and a borane (initiator), followed by migration/insertion of a methylene into the initiator and after oxidation/hydrolysis to afford OH-terminated polyethylenes. This review summarizes efforts towards conventional and newly discovered borane-initiators and ylides (monomers), as well as a combination of polyhomologation with other polymerization methods. Initial efforts dealing with C3 polymerization and the synthesis of the first C1/C3 copolymers are also given. Finally, some thoughts for the future of these polymerizations are presented.

  13. Mix and Inject: Reaction Initiation by Diffusion for Time-Resolved Macromolecular Crystallography

    Directory of Open Access Journals (Sweden)

    Marius Schmidt

    2013-01-01

    Full Text Available Time-resolved macromolecular crystallography unifies structure determination with chemical kinetics, since the structures of transient states and chemical and kinetic mechanisms can be determined simultaneously from the same data. To start a reaction in an enzyme, typically, an initially inactive substrate present in the crystal is activated. This has particular disadvantages that are circumvented when active substrate is directly provided by diffusion. However, then it is prohibitive to use macroscopic crystals because diffusion times become too long. With small micro- and nanocrystals diffusion times are adequately short for most enzymes and the reaction can be swiftly initiated. We demonstrate here that a time-resolved crystallographic experiment becomes feasible by mixing substrate with enzyme nanocrystals which are subsequently injected into the X-ray beam of a pulsed X-ray source.

  14. Phase behaviour of macromolecular liquid crystalline materials. Computational studies at the molecular level

    CERN Document Server

    Stimson, L M

    2003-01-01

    Molecular simulations provide an increasingly useful insight into the static and dynamic characteristics of materials. In this thesis molecular simulations of macro-molecular liquid crystalline materials are reported. The first liquid crystalline material that has been investigated is a side chain liquid crystal polymer (SCLCP). In this study semi-atomistic molecular dynamics simulations have been conducted at a range of temperatures and an aligning potential has been applied to mimic the effect of a magnetic field. In cooling the SCLCP from an isotropic melt, microphase separation was observed yielding a domain structure. The application of a magnetic field to this structure aligns the domains producing a stable smectic mesophase. This is the first study in which mesophases have been observed using an off-lattice model of a SCLCP. The second material that has been investigated is a dendrimer with terminal mesogenic functionalization. Here, a multi-scale approach has been taken with Monte Carlo studies of a s...

  15. Phase transitions of macromolecular microsphere composite hydrogels based on the stochastic Cahn–Hilliard equation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiao, E-mail: lixiao1228@163.com; Ji, Guanghua, E-mail: ghji@bnu.edu.cn; Zhang, Hui, E-mail: hzhang@bnu.edu.cn

    2015-02-15

    We use the stochastic Cahn–Hilliard equation to simulate the phase transitions of the macromolecular microsphere composite (MMC) hydrogels under a random disturbance. Based on the Flory–Huggins lattice model and the Boltzmann entropy theorem, we develop a reticular free energy suit for the network structure of MMC hydrogels. Taking the random factor into account, with the time-dependent Ginzburg-Landau (TDGL) mesoscopic simulation method, we set up a stochastic Cahn–Hilliard equation, designated herein as the MMC-TDGL equation. The stochastic term in the equation is constructed appropriately to satisfy the fluctuation-dissipation theorem and is discretized on a spatial grid for the simulation. A semi-implicit difference scheme is adopted to numerically solve the MMC-TDGL equation. Some numerical experiments are performed with different parameters. The results are consistent with the physical phenomenon, which verifies the good simulation of the stochastic term.

  16. Functionalization of Planet-Satellite Nanostructures Revealed by Nanoscopic Localization of Distinct Macromolecular Species

    KAUST Repository

    Rossner, Christian

    2016-09-26

    The development of a straightforward method is reported to form hybrid polymer/gold planet-satellite nanostructures (PlSNs) with functional polymer. Polyacrylate type polymer with benzyl chloride in its backbone as a macromolecular tracer is synthesized to study its localization within PlSNs by analyzing the elemental distribution of chlorine. The functionalized nanohybrid structures are analyzed by scanning transmission electron microscopy, electron energy loss spectroscopy, and spectrum imaging. The results show that the RAFT (reversible addition-fragmentation chain transfer) polymers\\' sulfur containing end groups are colocalized at the gold cores, both within nanohybrids of simple core-shell morphology and within higher order PlSNs, providing microscopic evidence for the affinity of the RAFT group toward gold surfaces. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA., Weinheim.

  17. Machine learning in image steganalysis

    CERN Document Server

    Schaathun, Hans Georg

    2012-01-01

    "The only book to look at steganalysis from the perspective of machine learning theory, and to apply the common technique of machine learning to the particular field of steganalysis; ideal for people working in both disciplines"--

  18. New Applications of Learning Machines

    DEFF Research Database (Denmark)

    Larsen, Jan

    * Machine learning framework for sound search * Genre classification * Music separation * MIMO channel estimation and symbol detection......* Machine learning framework for sound search * Genre classification * Music separation * MIMO channel estimation and symbol detection...

  19. New Applications of Learning Machines

    DEFF Research Database (Denmark)

    Larsen, Jan

    * Machine learning framework for sound search * Genre classification * Music separation * MIMO channel estimation and symbol detection......* Machine learning framework for sound search * Genre classification * Music separation * MIMO channel estimation and symbol detection...

  20. Hinged Shields for Machine Tools

    Science.gov (United States)

    Lallande, J. B.; Poland, W. W.; Tull, S.

    1985-01-01

    Flaps guard against flying chips, but fold away for tool setup. Clear plastic shield in position to intercept flying chips from machine tool and retracted to give operator access to workpiece. Machine shops readily make such shields for own use.

  1. PURY: a database of geometric restraints of hetero compounds for refinement in complexes with macromolecular structures.

    Science.gov (United States)

    Andrejasic, Miha; Praaenikar, Jure; Turk, Dusan

    2008-11-01

    The number and variety of macromolecular structures in complex with ;hetero' ligands is growing. The need for rapid delivery of correct geometric parameters for their refinement, which is often crucial for understanding the biological relevance of the structure, is growing correspondingly. The current standard for describing protein structures is the Engh-Huber parameter set. It is an expert data set resulting from selection and analysis of the crystal structures gathered in the Cambridge Structural Database (CSD). Clearly, such a manual approach cannot be applied to the vast and ever-growing number of chemical compounds. Therefore, a database, named PURY, of geometric parameters of chemical compounds has been developed, together with a server that accesses it. PURY is a compilation of the whole CSD. It contains lists of atom classes and bonds connecting them, as well as angle, chirality, planarity and conformation parameters. The current compilation is based on CSD 5.28 and contains 1978 atom classes and 32,702 bonding, 237,068 angle, 201,860 dihedral and 64,193 improper geometric restraints. Analysis has confirmed that the restraints from the PURY database are suitable for use in macromolecular crystal structure refinement and should be of value to the crystallographic community. The database can be accessed through the web server http://pury.ijs.si/, which creates topology and parameter files from deposited coordinates in suitable forms for the refinement programs MAIN, CNS and REFMAC. In the near future, the server will move to the CSD website http://pury.ccdc.cam.ac.uk/.

  2. A 3D image filter for parameter-free segmentation of macromolecular structures from electron tomograms.

    Directory of Open Access Journals (Sweden)

    Rubbiya A Ali

    Full Text Available 3D image reconstruction of large cellular volumes by electron tomography (ET at high (≤ 5 nm resolution can now routinely resolve organellar and compartmental membrane structures, protein coats, cytoskeletal filaments, and macromolecules. However, current image analysis methods for identifying in situ macromolecular structures within the crowded 3D ultrastructural landscape of a cell remain labor-intensive, time-consuming, and prone to user-bias and/or error. This paper demonstrates the development and application of a parameter-free, 3D implementation of the bilateral edge-detection (BLE algorithm for the rapid and accurate segmentation of cellular tomograms. The performance of the 3D BLE filter has been tested on a range of synthetic and real biological data sets and validated against current leading filters-the pseudo 3D recursive and Canny filters. The performance of the 3D BLE filter was found to be comparable to or better than that of both the 3D recursive and Canny filters while offering the significant advantage that it requires no parameter input or optimisation. Edge widths as little as 2 pixels are reproducibly detected with signal intensity and grey scale values as low as 0.72% above the mean of the background noise. The 3D BLE thus provides an efficient method for the automated segmentation of complex cellular structures across multiple scales for further downstream processing, such as cellular annotation and sub-tomogram averaging, and provides a valuable tool for the accurate and high-throughput identification and annotation of 3D structural complexity at the subcellular level, as well as for mapping the spatial and temporal rearrangement of macromolecular assemblies in situ within cellular tomograms.

  3. A 3D image filter for parameter-free segmentation of macromolecular structures from electron tomograms.

    Science.gov (United States)

    Ali, Rubbiya A; Landsberg, Michael J; Knauth, Emily; Morgan, Garry P; Marsh, Brad J; Hankamer, Ben

    2012-01-01

    3D image reconstruction of large cellular volumes by electron tomography (ET) at high (≤ 5 nm) resolution can now routinely resolve organellar and compartmental membrane structures, protein coats, cytoskeletal filaments, and macromolecules. However, current image analysis methods for identifying in situ macromolecular structures within the crowded 3D ultrastructural landscape of a cell remain labor-intensive, time-consuming, and prone to user-bias and/or error. This paper demonstrates the development and application of a parameter-free, 3D implementation of the bilateral edge-detection (BLE) algorithm for the rapid and accurate segmentation of cellular tomograms. The performance of the 3D BLE filter has been tested on a range of synthetic and real biological data sets and validated against current leading filters-the pseudo 3D recursive and Canny filters. The performance of the 3D BLE filter was found to be comparable to or better than that of both the 3D recursive and Canny filters while offering the significant advantage that it requires no parameter input or optimisation. Edge widths as little as 2 pixels are reproducibly detected with signal intensity and grey scale values as low as 0.72% above the mean of the background noise. The 3D BLE thus provides an efficient method for the automated segmentation of complex cellular structures across multiple scales for further downstream processing, such as cellular annotation and sub-tomogram averaging, and provides a valuable tool for the accurate and high-throughput identification and annotation of 3D structural complexity at the subcellular level, as well as for mapping the spatial and temporal rearrangement of macromolecular assemblies in situ within cellular tomograms.

  4. Transition modes in Ising networks: an approximate theory for macromolecular recognition.

    Science.gov (United States)

    Keating, S; Di Cera, E

    1993-07-01

    For a statistical lattice, or Ising network, composed of N identical units existing in two possible states, 0 and 1, and interacting according to a given geometry, a set of values can be found for the mean free energy of the 0-->1 transition of a single unit. Each value defines a transition mode in an ensemble of nu N = 3N - 2N possible values and reflects the role played by intermediate states in shaping the energetics of the system as a whole. The distribution of transition modes has a number of intriguing properties. Some of them apply quite generally to any Ising network, regardless of its dimension, while others are specific for each interaction geometry and dimensional embedding and bear on fundamental aspects of analytical number theory. The landscape of transition modes encapsulates all of the important thermodynamic properties of the network. The free energy terms defining the partition function of the system can be derived from the modes by simple transformations. Classical mean-field expressions can be obtained from consideration of the properties of transition modes in a rather straightforward way. The results obtained in the analysis of the transition mode distributions have been used to develop an approximate treatment of the problem of macromolecular recognition. This phenomenon is modeled as a cooperative process that involves a number of recognition subsites across an interface generated by the binding of two macromolecular components. The distribution of allowed binding free energies for the system is shown to be a superposition of Gaussian terms with mean and variance determined a priori by the theory. Application to the analysis of the biologically interaction of thrombin with hirudin has provided some useful information on basic aspects of the interaction, such as the number of recognition subsites involved and the energy balance for binding and cooperative coupling among them. Our results agree quite well with information derived independently

  5. Design of Sugarcane Peeling Machine

    Directory of Open Access Journals (Sweden)

    Ge Xinfeng

    2015-02-01

    Full Text Available In order to solve the problem that appeared in hand peeling sugarcane, the sugarcane peeling machine is designed, the sugarcane peeling machine includes motor, groove wheel, cutting room, slider crank mechanism, reducer (including belt drive, chain drive and so on. The designed sugarcane peeling machine is simulated, the results show that the sugarcane peeling machine can peel sugarcane successfully with convenient, fast and uniform.

  6. Automatically-Programed Machine Tools

    Science.gov (United States)

    Purves, L.; Clerman, N.

    1985-01-01

    Software produces cutter location files for numerically-controlled machine tools. APT, acronym for Automatically Programed Tools, is among most widely used software systems for computerized machine tools. APT developed for explicit purpose of providing effective software system for programing NC machine tools. APT system includes specification of APT programing language and language processor, which executes APT statements and generates NC machine-tool motions specified by APT statements.

  7. Automatically-Programed Machine Tools

    Science.gov (United States)

    Purves, L.; Clerman, N.

    1985-01-01

    Software produces cutter location files for numerically-controlled machine tools. APT, acronym for Automatically Programed Tools, is among most widely used software systems for computerized machine tools. APT developed for explicit purpose of providing effective software system for programing NC machine tools. APT system includes specification of APT programing language and language processor, which executes APT statements and generates NC machine-tool motions specified by APT statements.

  8. Feature Recognition for Virtual Machining

    OpenAIRE

    Xú, Shixin; Anwer, Nabil; Qiao, Lihong

    2014-01-01

    International audience; Virtual machining uses software tools to simulate machining processes in virtual environments ahead of actual production. This paper proposes that feature recognition techniques can be applied in the course of virtual machining, such as identifying some process problems, and presenting corresponding correcting advices. By comparing with the original CAD model, form errors of the machining features can be found. And then corrections are suggested to process designers. T...

  9. The Neural Support Vector Machine

    NARCIS (Netherlands)

    Wiering, Marco; van der Ree, Michiel; Embrechts, Mark; Stollenga, Marijn; Meijster, Arnold; Nolte, A; Schomaker, Lambertus

    2013-01-01

    This paper describes a new machine learning algorithm for regression and dimensionality reduction tasks. The Neural Support Vector Machine (NSVM) is a hybrid learning algorithm consisting of neural networks and support vector machines (SVMs). The output of the NSVM is given by SVMs that take a

  10. The Neural Support Vector Machine

    NARCIS (Netherlands)

    Wiering, Marco; van der Ree, Michiel; Embrechts, Mark; Stollenga, Marijn; Meijster, Arnold; Nolte, A; Schomaker, Lambertus

    2013-01-01

    This paper describes a new machine learning algorithm for regression and dimensionality reduction tasks. The Neural Support Vector Machine (NSVM) is a hybrid learning algorithm consisting of neural networks and support vector machines (SVMs). The output of the NSVM is given by SVMs that take a centr

  11. Gap Junction Remodeling in Skin Repair Following Wounding and Disease

    National Research Council Canada - National Science Library

    Jared M. Churko; Dale W. Laird

    2013-01-01

    In the present review, we provide an overview of connexin expression during skin development and remodeling in wound healing, and reflect on how loss- or gain-of-function connexin mutations may change...

  12. Modeling and remodeling of human extraction sockets.

    Science.gov (United States)

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Bozzi, Leopoldo; Liljenberg, Birgitta; Lindhe, Jan

    2008-07-01

    The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

  13. Cutaneous remodeling and photorejuvenation using radiofrequency devices

    Directory of Open Access Journals (Sweden)

    Elsaie Mohamed

    2009-01-01

    Full Text Available Radio frequency (RF is electromagnetic radiation in the frequency range of 3-300GHz. The primary effects of RF energy on living tissue are considered to be thermal. The goal of the new devices based on these frequency ranges is to heat specific layers of the skin. The directed use of RF can induce dermal heating and cause collagen degeneration. Wound healing mechanisms promote the remodeling of collagen and wound contraction, which ultimately clinically enhances the appearance of mild to moderate skin laxity. Preliminary studies have reported efficacy in the treatment of laxity that involves the periorbital area and jowls. Because RF energy is not dependent on specific chromophore interaction, epidermal melanin is not at risk of destruction and treatment of all skin types is possible. As such, radiofrequency-based systems have been used successfully for nonablative skin rejuvenation, atrophic scar revision and treatment of unwanted hair, vascular lesions and inflammatory acne. The use of RF is becoming more popular, although a misunderstanding exists regarding the mechanisms and limitations of its actions. This concise review serves as an introduction and guide to many aspects of RF in the non ablative rejuvenation of skin.

  14. Prediction of Machine Tool Condition Using Support Vector Machine

    Science.gov (United States)

    Wang, Peigong; Meng, Qingfeng; Zhao, Jian; Li, Junjie; Wang, Xiufeng

    2011-07-01

    Condition monitoring and predicting of CNC machine tools are investigated in this paper. Considering the CNC machine tools are often small numbers of samples, a condition predicting method for CNC machine tools based on support vector machines (SVMs) is proposed, then one-step and multi-step condition prediction models are constructed. The support vector machines prediction models are used to predict the trends of working condition of a certain type of CNC worm wheel and gear grinding machine by applying sequence data of vibration signal, which is collected during machine processing. And the relationship between different eigenvalue in CNC vibration signal and machining quality is discussed. The test result shows that the trend of vibration signal Peak-to-peak value in surface normal direction is most relevant to the trend of surface roughness value. In trends prediction of working condition, support vector machine has higher prediction accuracy both in the short term ('One-step') and long term (multi-step) prediction compared to autoregressive (AR) model and the RBF neural network. Experimental results show that it is feasible to apply support vector machine to CNC machine tool condition prediction.

  15. Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

    OpenAIRE

    Cowling, Belinda S; Anne Toussaint; Jean Muller; Jocelyn Laporte

    2012-01-01

    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Too...

  16. A Boltzmann machine for the organization of intelligent machines

    Science.gov (United States)

    Moed, Michael C.; Saridis, George N.

    1989-01-01

    In the present technological society, there is a major need to build machines that would execute intelligent tasks operating in uncertain environments with minimum interaction with a human operator. Although some designers have built smart robots, utilizing heuristic ideas, there is no systematic approach to design such machines in an engineering manner. Recently, cross-disciplinary research from the fields of computers, systems AI and information theory has served to set the foundations of the emerging area of the design of intelligent machines. Since 1977 Saridis has been developing an approach, defined as Hierarchical Intelligent Control, designed to organize, coordinate and execute anthropomorphic tasks by a machine with minimum interaction with a human operator. This approach utilizes analytical (probabilistic) models to describe and control the various functions of the intelligent machine structured by the intuitively defined principle of Increasing Precision with Decreasing Intelligence (IPDI) (Saridis 1979). This principle, even though resembles the managerial structure of organizational systems (Levis 1988), has been derived on an analytic basis by Saridis (1988). The purpose is to derive analytically a Boltzmann machine suitable for optimal connection of nodes in a neural net (Fahlman, Hinton, Sejnowski, 1985). Then this machine will serve to search for the optimal design of the organization level of an intelligent machine. In order to accomplish this, some mathematical theory of the intelligent machines will be first outlined. Then some definitions of the variables associated with the principle, like machine intelligence, machine knowledge, and precision will be made (Saridis, Valavanis 1988). Then a procedure to establish the Boltzmann machine on an analytic basis will be presented and illustrated by an example in designing the organization level of an Intelligent Machine. A new search technique, the Modified Genetic Algorithm, is presented and proved

  17. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

    Directory of Open Access Journals (Sweden)

    Chi-Li Chiu

    2013-01-01

    Full Text Available Extracellular matrix (ECM remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7, which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3. We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments.

  18. KyoT2 downregulates airway remodeling in asthma.

    Science.gov (United States)

    Hu, Mei; Ou-Yang, Hai-Feng; Han, Xing-Peng; Ti, Xin-Yu; Wu, Chang-Gui

    2015-01-01

    The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.

  19. Effect of Ovariectomy on Stimulating Intracortical Remodeling in Rats

    Directory of Open Access Journals (Sweden)

    Chun Lei Li

    2014-01-01

    Full Text Available Objective. Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles. Materials and Methods. Sixteen 12-week-old Spraque-Dawly (SD female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT and histomorphometric assessments. Results. Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm3, P<0.001 and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%, P<0.001 in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats. Conclusion. For the first time, to the authors’ knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process.

  20. Engineering molecular machines

    Science.gov (United States)

    Erman, Burak

    2016-04-01

    Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

  1. Boosting Support Vector Machines

    Directory of Open Access Journals (Sweden)

    Elkin Eduardo García Díaz

    2006-11-01

    Full Text Available En este artículo, se presenta un algoritmo de clasificación binaria basado en Support Vector Machines (Máquinas de Vectores de Soporte que combinado apropiadamente con técnicas de Boosting consigue un mejor desempeño en cuanto a tiempo de entrenamiento y conserva características similares de generalización con un modelo de igual complejidad pero de representación más compacta./ In this paper we present an algorithm of binary classification based on Support Vector Machines. It is combined with a modified Boosting algorithm. It run faster than the original SVM algorithm with a similar generalization error and equal complexity model but it has more compact representation.

  2. Quo vadis, Intelligent Machine?

    Directory of Open Access Journals (Sweden)

    Rosemarie Velik

    2010-09-01

    Full Text Available Artificial Intelligence (AI is a branch of computer science concerned with making computers behave like humans. At least this was the original idea. However, it turned out that this is no task easy to be solved. This article aims to give a comprehensible review on the last 60 years of artificial intelligence taking a philosophical viewpoint. It is outlined what happened so far in AI, what is currently going on in this research area, and what can be expected in future. The goal is to mediate an understanding for the developments and changes in thinking in course of time about how to achieve machine intelligence. The clear message is that AI has to join forces with neuroscience and other brain disciplines in order to make a step towards the development of truly intelligent machines.

  3. Introduction to Machine Protection

    CERN Document Server

    Schmidt, R

    2016-01-01

    Protection of accelerator equipment is as old as accelerator technology and was for many years related to high-power equipment. Examples are the protection of powering equipment from overheating (magnets, power converters, high-current cables), of superconducting magnets from damage after a quench and of klystrons. The protection of equipment from beam accidents is more recent, although there was one paper that discussed beam-induced damage for the SLAC linac (Stanford Linear Accelerator Center) as early as in 1967. It is related to the increasing beam power of high-power proton accelerators, to the emission of synchrotron light by electron-positron accelerators and to the increase of energy stored in the beam. Designing a machine protection system requires an excellent understanding of accelerator physics and operation to anticipate possible failures that could lead to damage. Machine protection includes beam and equipment monitoring, a system to safely stop beam operation (e.g. dumping the beam or stopping ...

  4. Technological requirements of profile machining

    Institute of Scientific and Technical Information of China (English)

    PARK Sangchul; CHUNG Yunchan

    2006-01-01

    The term ‘profile machining’is used to refer to the milling of vertical surfaces described by profile curves. Profile machining requires higher precision (1/1000 mm) than regular 3D machining (1/100 mm) with the erosion of sharp vertices should being especially avoided. Although, profile machining is very essential for making trimming and flangedies, it seldom brought into focus. This paper addresses the technological requirements of profile machining including machining width and depth control,minimizing toolware, and protecting sharp vertices. Issues of controller alarms are also addressed.

  5. Machining fiber-reinforced composites

    Science.gov (United States)

    Komanduri, Ranga

    1993-04-01

    Compared to high tool wear and high costs of tooling of fiber-reinforced composites (FRCs), noncontact material-removal processes offer attractive alternative. Noncontact machining methods can also minimize dust, noise, and extensive plastic deformation and consequent heat generation associated with conventional machining of FRCs, espacially those with an epoxy matrix. The paper describes the principles involved in and the details of machining of FRCs by laser machining, water jet-cutting and abrasive water jet-cutting, and electrical discharge machining of composites, as well as the limitations of each method.

  6. Future database machine architectures

    OpenAIRE

    Hsiao, David K.

    1984-01-01

    There are many software database management systems available on many general-purpose computers ranging from micros to super-mainframes. Database machines as backened computers can offload the database management work from the mainframe so that we can retain the same mainframe longer. However, the database backend must also demonstrate lower cost, higher performance, and newer functionality. Some of the fundamental architecture issues in the design of high-performance and great-capacity datab...

  7. Machine Learning at Scale

    OpenAIRE

    Izrailev, Sergei; Stanley, Jeremy M.

    2014-01-01

    It takes skill to build a meaningful predictive model even with the abundance of implementations of modern machine learning algorithms and readily available computing resources. Building a model becomes challenging if hundreds of terabytes of data need to be processed to produce the training data set. In a digital advertising technology setting, we are faced with the need to build thousands of such models that predict user behavior and power advertising campaigns in a 24/7 chaotic real-time p...

  8. Cost of photochemical machining

    OpenAIRE

    Roy, Rajkumar; Allen, David; Zamora, Oscar

    2004-01-01

    Photochemical machining (PCM), also known as photoetching, photofabrication or photochemical milling, is a non-traditional manufacturing method based on the combination of photoresist imaging and chemical etching. PCM uses techniques similar to those employed for the production of printed circuit boards and silicon integrated circuits. The PCM industry plays a valuable worldwide role in the production of metal precision parts and decorative items. Parts produced by PCM are t...

  9. Austempered Ductile Iron Machining

    Science.gov (United States)

    Pilc, Jozef; Šajgalík, Michal; Holubják, Jozef; Piešová, Marianna; Zaušková, Lucia; Babík, Ondrej; Kuždák, Viktor; Rákoci, Jozef

    2015-12-01

    This article deals with the machining of cast iron. In industrial practice, Austempered Ductile Iron began to be used relatively recently. ADI is ductile iron that has gone through austempering to get improved properties, among which we can include strength, wear resistance or noise damping. This specific material is defined also by other properties, such as high elasticity, ductility and endurance against tenigue, which are the properties, that considerably make the tooling characteristic worse.

  10. Quantum Virtual Machine (QVM)

    Energy Technology Data Exchange (ETDEWEB)

    2016-11-18

    There is a lack of state-of-the-art HPC simulation tools for simulating general quantum computing. Furthermore, there are no real software tools that integrate current quantum computers into existing classical HPC workflows. This product, the Quantum Virtual Machine (QVM), solves this problem by providing an extensible framework for pluggable virtual, or physical, quantum processing units (QPUs). It enables the execution of low level quantum assembly codes and returns the results of such executions.

  11. Agent Based Computing Machine

    Science.gov (United States)

    2005-12-09

    be used in Phase 2 to accomplish the following enhancements. Due to the speed and support of MPI for C/C++ on Beowulf clusters , these languages could...1.7 ABC Machine Formal Definition 24 1.8 Computational Analysis 31 1.9 Programming Concepts 34 1.10 Cluster Mapping 38 1.11 Phase 1 Results 43 2...options for hardware implementation are explored including an emulation with a high performance cluster , a high performance silicon chip and the

  12. Magnetic Electrochemical Finishing Machining

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    How to improve the finishing efficiency and surface roughness have been all along the objective of research in electrochemical polishing. However, the research activity, i.e. during electrochemical polishing, directly introduce the magnetic field to study how the magnetic field influences on the finishing efficiency, quality and the electrochemical process in the field of finishing machining technology, is insufficient. When introducing additional magnetic field in the traditional electrochemical pol...

  13. FMS precision machining

    Energy Technology Data Exchange (ETDEWEB)

    Burnham, M.W.

    1980-01-01

    In evaluating the technical obstacles and accuracy limits to producing a Precision Flexible Manufacturing System, a current system is subjected to an error budget analysis. It is noted that to make complex part geometries with tolerances in the lower thousandths range, machining to tenths is required for process control. Actual parts made to tenths are illustrated, along with a discussion of the requirements for automation and for process control.

  14. Machine on Trial

    Science.gov (United States)

    2012-06-01

    front of the Judge, how did we come to justify the ethical use of such a machine? The Judge called for a recess so that he could further educate ...commerce, where money would change hands, or for the purposes of controlling critical systems.”29 The initial group that set up the ARPANET did not... EBook of Fundamental Principals of the Metaphysic of Morals, May, 2004 [ EBook #5682 translated by Thomas Kingsmill Abbott, 12. http://manybooks.net

  15. Electrochemical Discharge Machining Process

    Directory of Open Access Journals (Sweden)

    Anjali V. Kulkarni

    2007-09-01

    Full Text Available Electrochemical discharge machining process is evolving as a promising micromachiningprocess. The experimental investigations in the present work substantiate this trend. In the presentwork, in situ, synchronised, transient temperature and current measurements have been carriedout. The need for the transient measurements arose due to the time-varying nature of the dischargeformation and time varying circuit current. Synchronised and transient measurements revealedthe discrete nature of the process. It also helped in formulating the basic mechanism for thedischarge formation and the material removal in the process. Temperature profile on workpieceand in electrochemical discharge machining cell is experimentally measured using pyrometer,and two varieties of K-type thermocouples. Surface topography of the discharge-affected zoneson the workpiece has been carried out using scanning electron microscope. Measurements andsurface topographical studies reveal the potential use of this process for machining in micronregime. With careful experimental set-up design, suitable supply voltage and its polarity, theprocess can be applied for both micromachining and micro-deposition. It can be extended formachining and or deposition of wide range of materials.

  16. Introduction: Minds, Bodies, Machines

    Directory of Open Access Journals (Sweden)

    Deirdre Coleman

    2008-10-01

    Full Text Available This issue of 19 brings together a selection of essays from an interdisciplinary conference on 'Minds, Bodies, Machines' convened last year by Birkbeck's Centre for Nineteenth-Century Studies, University of London, in partnership with the English programme, University of Melbourne and software developers Constraint Technologies International (CTI. The conference explored the relationship between minds, bodies and machines in the long nineteenth century, with a view to understanding the history of our technology-driven, post-human visions. It is in the nineteenth century that the relationship between the human and the machine under post-industrial capitalism becomes a pervasive theme. From Blake on the mills of the mind by which we are enslaved, to Carlyle's and Arnold's denunciation of the machinery of modern life, from Dickens's sooty fictional locomotive Mr Pancks, who 'snorted and sniffed and puffed and blew, like a little labouring steam-engine', and 'shot out […]cinders of principles, as if it were done by mechanical revolvency', to the alienated historical body of the late-nineteenth-century factory worker under Taylorization, whose movements and gestures were timed, regulated and rationalised to maximize efficiency; we find a cultural preoccupation with the mechanisation of the nineteenth-century human body that uncannily resonates with modern dreams and anxieties around technologies of the human.

  17. Machine Learning in Medicine.

    Science.gov (United States)

    Deo, Rahul C

    2015-11-17

    Spurred by advances in processing power, memory, storage, and an unprecedented wealth of data, computers are being asked to tackle increasingly complex learning tasks, often with astonishing success. Computers have now mastered a popular variant of poker, learned the laws of physics from experimental data, and become experts in video games - tasks that would have been deemed impossible not too long ago. In parallel, the number of companies centered on applying complex data analysis to varying industries has exploded, and it is thus unsurprising that some analytic companies are turning attention to problems in health care. The purpose of this review is to explore what problems in medicine might benefit from such learning approaches and use examples from the literature to introduce basic concepts in machine learning. It is important to note that seemingly large enough medical data sets and adequate learning algorithms have been available for many decades, and yet, although there are thousands of papers applying machine learning algorithms to medical data, very few have contributed meaningfully to clinical care. This lack of impact stands in stark contrast to the enormous relevance of machine learning to many other industries. Thus, part of my effort will be to identify what obstacles there may be to changing the practice of medicine through statistical learning approaches, and discuss how these might be overcome.

  18. Behind the machines

    CERN Document Server

    Laëtitia Pedroso

    2010-01-01

    One of the first things we think about when someone mentions physics is the machines. But behind the machines, there are the men and women who design, build and operate them. In an exhibition at the Thinktank planetarium’s art gallery in Birmingham (UK), Claudia Marcelloni and her husband Neal Hartman—she is a photographer and Outreach Officer for ATLAS, while he is an engineer working on the ATLAS pixel detector—explore the human side of scientists.   The exhibition at the Thinktank Planetarium art gallery, Birmingham (UK). It all began two years ago with the publication of Exploring the mystery of matter, a book about ATLAS. “A Norwegian physicist friend, Heidi Sandaker, saw my photographs and suggested that I display them in a museum. I thought this was an interesting idea, except that the photos consisted entirely of depictions of machinery, with human beings completely absent. For me, showing the people who are behind the machines and the fascination ...

  19. Soft computing in machine learning

    CERN Document Server

    Park, Jooyoung; Inoue, Atsushi

    2014-01-01

    As users or consumers are now demanding smarter devices, intelligent systems are revolutionizing by utilizing machine learning. Machine learning as part of intelligent systems is already one of the most critical components in everyday tools ranging from search engines and credit card fraud detection to stock market analysis. You can train machines to perform some things, so that they can automatically detect, diagnose, and solve a variety of problems. The intelligent systems have made rapid progress in developing the state of the art in machine learning based on smart and deep perception. Using machine learning, the intelligent systems make widely applications in automated speech recognition, natural language processing, medical diagnosis, bioinformatics, and robot locomotion. This book aims at introducing how to treat a substantial amount of data, to teach machines and to improve decision making models. And this book specializes in the developments of advanced intelligent systems through machine learning. It...

  20. Machine Translation Effect on Communication

    DEFF Research Database (Denmark)

    Jensen, Mika Yasuoka; Bjørn, Pernille

    2011-01-01

    Intercultural collaboration facilitated by machine translation has gradually spread in various settings. Still, little is known as for the practice of machine-translation mediated communication. This paper investigates how machine translation affects intercultural communication in practice. Based...... determines communication process largely, our data indicates communication relies more on a dynamic process where participants establish common ground than on reproducibility and grammatical accuracy.......Intercultural collaboration facilitated by machine translation has gradually spread in various settings. Still, little is known as for the practice of machine-translation mediated communication. This paper investigates how machine translation affects intercultural communication in practice. Based...... on communication in which multilingual communication system is applied, we identify four communication types and its’ influences on stakeholders’ communication process, especially focusing on establishment and maintenance of common ground. Different from our expectation that quality of machine translation results...

  1. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Gulshan B., E-mail: gbsharma@ucalgary.ca [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States); University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4 (Canada); Robertson, Douglas D., E-mail: douglas.d.robertson@emory.edu [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States)

    2013-07-01

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  2. Cardiac remodeling indicators in adolescent athletes

    Directory of Open Access Journals (Sweden)

    Joaquim Castanheira

    Full Text Available Summary Objective: The idea that different sports and physical training type results in different cardiac adaptations has been widely accepted. However, this remodelling process among different sport modalities is still not fully understood. Thus, the current study aims to investigate the heart morphology variation associated with a set of different modalities characterized by distinct models of preparation and different methods and demands of training and completion. Method: The sample comprises 42 basketball players, 73 roller hockey players, 28 judo athletes and 21 swimmers. Anthropometry was assessed by a single and experienced anthropometrist and the same technician performed the echocardiographic exams. Analysis of variance was used to study age, body size and echocardiograph parameters as well as different sport athlete's comparison. Results: Basketball players are taller (F=23.448; p<0.001; ES-r=0.553, heavier (F=6.702; p<0.001; ES-r=0.334 and have a greater body surface area (F=11.896; p<0.001; ES-r=0.427. Basketball and hockey players have larger left auricle diameters compared with judo athletes (F=3.865; p=0.011; ES-r=0.316. Interventricular end-diastolic septal thickness (F=7.287; p<0.001; ES-r=0.347 and left ventricular posterior wall thickness (F=8.038; p<0.001; ES-r=0.362 of the judokas are smaller compared to the mean values of other sports participants. In addition, relative left parietal ventricular wall thickness is lower among swimmers compared with judokas (F=4.127; p=0.008; ES-r=0.268. Conclusion: The major contributors to changes in heart morphology are for the most part associated with sport-specific training and competition and the specific dynamics and adaptive mechanisms imposed by each sport.

  3. In vitro analysis of PDZ-dependent CFTR macromolecular signaling complexes.

    Science.gov (United States)

    Wu, Yanning; Wang, Shuo; Li, Chunying

    2012-08-13

    has been shown to be of functional significance, suggesting that PDZ scaffold proteins may facilitate formation of CFTR macromolecular signaling complexes for specific/selective and efficient signaling in cells(16-18). Multiple biochemical assays have been developed to study CFTR-involving protein interactions, such as co-immunoprecipitation, pull-down assay, pair-wise binding assay, colorimetric pair-wise binding assay, and macromolecular complex assembly assay(16-19,28,29). Here we focus on the detailed procedures of assembling a PDZ motif-dependent CFTR-containing macromolecular complex in vitro, which is used extensively by our laboratory to study protein-protein or domain-domain interactions involving CFTR(16-19,28,29).

  4. Solid-state NMR in macromolecular systems: insights on how molecular entities move.

    Science.gov (United States)

    Hansen, Michael Ryan; Graf, Robert; Spiess, Hans Wolfgang

    2013-09-17

    The function of synthetic and natural macromolecularsystems critically depends on the packing and dynamics of the individual components of a given system. Not only can solid-state NMR provide structural information with atomic resolution, but it can also provide a way to characterize the amplitude and time scales of motions over broad ranges of length and time. These movements include molecular dynamics, rotational and translational motions of the building blocks, and also the motion of the functional species themselves, such as protons or ions. This Account examines solid-state NMR methods for correlating dynamics and function in a variety of chemical systems. In the early days, scientists thought that the rotationalmotions reflected the geometry of the moving entities. They described these phenomena as jumps about well-defined axes, such as phenyl flips, even in amorphous polymers. Later, they realized that conformational transitions in macromolecules happen in a much more complex way. Because the individual entities do not rotate around well-defined axes, they require much less space. Only recently researchers have appreciated the relative importance of large angle fluctuations of polymers over rotational jumps. Researchers have long considered that cooperative motions might be at work, yet only recently they have clearly detected these motions by NMR in macromolecular and supramolecular systems. In correlations of dynamics and function, local motions do not always provide the mechanism of long-range transport. This idea holds true in ion conduction but also applies to chain transport in polymer melts and semicrystalline polymers. Similar chain motions and ion transport likewise occur in functional biopolymers, systems where solid-state NMR studies are also performed. In polymer science, researchers have appreciated the unique information on molecular dynamics available from advanced solid-state NMR at times, where their colleagues in the biomacromolecular

  5. Macromolecular composition of terrestrial and marine organic matter in sediments across the East Siberian Arctic Shelf

    Science.gov (United States)

    Sparkes, Robert B.; Doğrul Selver, Ayça; Gustafsson, Örjan; Semiletov, Igor P.; Haghipour, Negar; Wacker, Lukas; Eglinton, Timothy I.; Talbot, Helen M.; van Dongen, Bart E.

    2016-10-01

    Mobilisation of terrestrial organic carbon (terrOC) from permafrost environments in eastern Siberia has the potential to deliver significant amounts of carbon to the Arctic Ocean, via both fluvial and coastal erosion. Eroded terrOC can be degraded during offshore transport or deposited across the wide East Siberian Arctic Shelf (ESAS). Most studies of terrOC on the ESAS have concentrated on solvent-extractable organic matter, but this represents only a small proportion of the total terrOC load. In this study we have used pyrolysis-gas chromatography-mass spectrometry (py-GCMS) to study all major groups of macromolecular components of the terrOC; this is the first time that this technique has been applied to the ESAS. This has shown that there is a strong offshore trend from terrestrial phenols, aromatics and cyclopentenones to marine pyridines. There is good agreement between proportion phenols measured using py-GCMS and independent quantification of lignin phenol concentrations (r2 = 0.67, p < 0.01, n = 24). Furfurals, thought to represent carbohydrates, show no offshore trend and are likely found in both marine and terrestrial organic matter. We have also collected new radiocarbon data for bulk OC (14COC) which, when coupled with previous measurements, allows us to produce the most comprehensive 14COC map of the ESAS to date. Combining the 14COC and py-GCMS data suggests that the aromatics group of compounds is likely sourced from old, aged terrOC, in contrast to the phenols group, which is likely sourced from modern woody material. We propose that an index of the relative proportions of phenols and pyridines can be used as a novel terrestrial vs. marine proxy measurement for macromolecular organic matter. Principal component analysis found that various terrestrial vs. marine proxies show different patterns across the ESAS, and it shows that multiple river-ocean transects of surface sediments transition from river-dominated to coastal-erosion-dominated to marine

  6. Chemiluminescence-imaging detection of DNA on a solid-phase membrane by using a peroxidase-labeled macromolecular probe.

    Science.gov (United States)

    Azam, Md Golam; Yamasuji, Mutsumi; Krawczyk, Tomasz; Shibata, Takayuki; Kabashima, Tsutomu; Kai, Masaaki

    2015-07-01

    We have developed a novel method for sensitive chemiluminescence (CL)-imaging detection of DNA by using a macromolecular probe synthesized by attaching multiple molecules of horseradish peroxidase (HRP) and biotin in dextran backbone. The probe formed a macromolecular assembly by binding to streptavidin which specifically recognized biotinylated complementary DNA, which was hybridized to a target DNA on a solid-phase membrane. This methodology was applied to CL-imaging detection of a synthetic telomere DNA (TTAGGG)10 and human telomere DNA by using the CL probe comprising of dextranT2000 (MW=ca. 2000kDa) bonded to approximately 42 molecules of HRP and 210 molecules of biotin. The human telomere DNA in a small number of buccal mucous cells (ca. 70 cell numbers) of cheek tissue was quantitatively determined by the proposed CL detection method that afforded approximately 10 times higher sensitivity than that of the conventional CL method using commercially available HRP-avidin probe.

  7. Distribution and enzymatic activity of heterotrophic bacteria decomposing selected macromolecular compounds in a Baltic Sea sandy beach

    Science.gov (United States)

    Podgórska, B.; Mudryk, Z. J.

    2003-03-01

    The potential capability to decompose macromolecular compounds, and the level of extracellular enzyme activities were determined in heterotrophic bacteria isolated from a sandy beach in Sopot on the Southern Baltic Sea coast. Individual isolates were capable of hydrolysing a wide spectrum of organic macromolecular compounds. Lipids, gelatine, and DNA were hydrolyzed most efficiently. Only a very small percentage of strains were able to decompose cellulose, and no pectinolytic bacteria were found. Except for starch-hydrolysis, no significant differences in the intensity of organic compound decomposition were recorded between horizontal and vertical profiles of the studied beach. Of all the studied extracellular enzymes, alkaline phosphatase, esterase lipase, and leucine acrylaminidase were most active; in contrast, the activity α-fucosidase, α-galactosidase and β-glucouronidase was the weakest. The level of extracellular enzyme activity was similar in both sand layers.

  8. On the vibron dressing in the one-dimensional macromolecular chains caused by the interaction with acoustic phonon modes

    CERN Document Server

    Cevizovic, Dalibor; Galovic, Slobodanka; Ivic, Zoran

    2012-01-01

    We present a study of the physical properties of the vibrational excitation in the one-dimensional macromolecular chains, caused by the interaction with acoustical phonon modes. The influence of the temperature and the basic system parameters on the vibron dressing has been analyzed by employing the simple mean--field approach based on the variational extension of the Lang--Firsov unitary transformation. Applied approach predicts a region in system parameter space where it is possible of the coexistence of the partially dressed (light and mobile) and fully dressed (immobile) vibron states. We found that the boundary of this region depends on system temperature and type of bond among structure elements in macromolecular chain.

  9. Mineral mining machines

    Energy Technology Data Exchange (ETDEWEB)

    Mc Gaw, B.H.

    1984-01-01

    A machine for mining minerals is patented. It is a cutter loader with a drum actuating element of the worm type equipped with a multitude of cutting teeth reinforced with tungsten carbide. A feature of the patented machine is that all of the cutting teeth and holders on the drum have the identical design. This is achieved through selecting a slant angle for the cutting teeth which is the mean between the slant angle of the conventional radial teeth and the slant angle of the advance teeth. This, in turn, is provided thanks to the corresponding slant of the holders relative to the drum and (or) the slant of the cutting part of the teeth relative to their stems. Thus, the advance teeth projecting beyond the surface of the drum on the face side and providing upper and lateral clearances have the same angle of attack as the radial teeth, that is, from 20 to 35 degrees. A series of modifications of the cutting teeth is patented. One of the designs allows the cutting tooth to occupy a varying position relative to the drum, from the conventional vertical to an inverted, axially projecting position. In the last case the tooth in the extraction process provides the upper and lateral clearances for the drum on the face side. Among the different modifications of the cutting teeth, a design is proposed which provides for the presence of a stem which is shaped like a truncated cone. This particular stem is designed for use jointly with a wedge which unfastens the teeth and is placed in a holder. The latter is completed in a transverse slot thanks to which the rear end of the stem is compressed, which simplifies replacement of a tooth. Channels are provided in the patented machine for feeding water to the worm spiral, the holders and the cutting teeth themselves in order to deal with dust.

  10. Advanced Machine learning Algorithm Application for Rotating Machine Health Monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Kanemoto, Shigeru; Watanabe, Masaya [The University of Aizu, Aizuwakamatsu (Japan); Yusa, Noritaka [Tohoku University, Sendai (Japan)

    2014-08-15

    The present paper tries to evaluate the applicability of conventional sound analysis techniques and modern machine learning algorithms to rotating machine health monitoring. These techniques include support vector machine, deep leaning neural network, etc. The inner ring defect and misalignment anomaly sound data measured by a rotating machine mockup test facility are used to verify the above various kinds of algorithms. Although we cannot find remarkable difference of anomaly discrimination performance, some methods give us the very interesting eigen patterns corresponding to normal and abnormal states. These results will be useful for future more sensitive and robust anomaly monitoring technology.

  11. Diamond Measuring Machine

    Energy Technology Data Exchange (ETDEWEB)

    Krstulic, J.F.

    2000-01-27

    The fundamental goal of this project was to develop additional capabilities to the diamond measuring prototype, work out technical difficulties associated with the original device, and perform automated measurements which are accurate and repeatable. For this project, FM and T was responsible for the overall system design, edge extraction, and defect extraction and identification. AccuGem provided a lab and computer equipment in Lawrence, 3D modeling, industry expertise, and sets of diamonds for testing. The system executive software which controls stone positioning, lighting, focusing, report generation, and data acquisition was written in Microsoft Visual Basic 6, while data analysis and modeling were compiled in C/C++ DLLs. All scanning parameters and extracted data are stored in a central database and available for automated analysis and reporting. The Phase 1 study showed that data can be extracted and measured from diamond scans, but most of the information had to be manually extracted. In this Phase 2 project, all data required for geometric modeling and defect identification were automatically extracted and passed to a 3D modeling module for analysis. Algorithms were developed which automatically adjusted both light levels and stone focus positioning for each diamond-under-test. After a diamond is analyzed and measurements are completed, a report is printed for the customer which shows carat weight, summarizes stone geometry information, lists defects and their size, displays a picture of the diamond, and shows a plot of defects on a top view drawing of the stone. Initial emphasis of defect extraction was on identification of feathers, pinpoints, and crystals. Defects were plotted color-coded by industry standards for inclusions (red), blemishes (green), and unknown defects (blue). Diamonds with a wide variety of cut quality, size, and number of defects were tested in the machine. Edge extraction, defect extraction, and modeling code were tested for

  12. Tribology in machine design

    CERN Document Server

    Stolarski, T A

    1990-01-01

    Tribology in Machine Design aims to promote a better appreciation of the increasingly important role played by tribology at the design stage in engineering. This book shows how algorithms developed from the basic principles of tribology can be used in a range of practical applications. The concept of tribodesign is introduced in Chapter 1. Chapter 2 is devoted to a brief discussion of the basic principles of tribology, including some concepts and models of lubricated wear and friction under complex kinematic conditions. Elements of contact mechanics, presented in Chapter 3, are confined to the

  13. Quantum adiabatic machine learning

    CERN Document Server

    Pudenz, Kristen L

    2011-01-01

    We develop an approach to machine learning and anomaly detection via quantum adiabatic evolution. In the training phase we identify an optimal set of weak classifiers, to form a single strong classifier. In the testing phase we adiabatically evolve one or more strong classifiers on a superposition of inputs in order to find certain anomalous elements in the classification space. Both the training and testing phases are executed via quantum adiabatic evolution. We apply and illustrate this approach in detail to the problem of software verification and validation.

  14. Daphne machine project

    Energy Technology Data Exchange (ETDEWEB)

    Vignola, G. and Daphne Project Team [Istituto Nazionale di Fisica Nucleare, Frascati (Italy)

    1996-07-01

    Daphne, a high luminosity e{sup +}/e{sup -} {Phi} factory, is presently under construction in Frascati. The beginning of the collider commissioning is scheduled by winter 1997, with a short term luminosity goal L=1.3 10{sup 32} cm{sup -2} sec{sup -1}. Daphne shall be the first of the new generation of very high luminosity colliders, called factories, to come in operation. Other factories under construction are PEP-II and KEK-B: first collision, for both machines, is planned for 1998.

  15. CENTRIFUGAL CASTING MACHINE

    Science.gov (United States)

    Shuck, A.B.

    1958-04-01

    A device is described that is specifically designed to cast uraniumn fuel rods in a vacuunn, in order to obtain flawless, nonoxidized castings which subsequently require a maximum of machining or wastage of the expensive processed material. A chamber surrounded with heating elements is connected to the molds, and the entire apparatus is housed in an airtight container. A charge of uranium is placed in the chamber, heated, then is allowed to flow into the molds While being rotated. Water circulating through passages in the molds chills the casting to form a fine grained fuel rod in nearly finished form.

  16. Electrical machines with Matlab

    CERN Document Server

    Gonen, Turan

    2011-01-01

    Basic ConceptsDistribution SystemImpact of Dispersed Storage and GenerationBrief Overview of Basic Electrical MachinesReal and Reactive Powers in Single-Phase AC CircuitsThree-Phase CircuitsThree-Phase SystemsUnbalanced Three-Phase LoadsMeasurement of Average Power in Three-Phase CircuitsPower Factor CorrectionMagnetic CircuitsMagnetic Field of Current-Carrying ConductorsAmpère's Magnetic Circuital LawMagnetic CircuitsMagnetic Circuit with Air GapBrief Review of FerromagnetismMagnetic Core LossesHow to Determine Flux for a Given MMFPermanent MagnetsTransformersTransformer ConstructionBrief Rev

  17. 08B1-1: an automated beamline for macromolecular crystallography experiments at the Canadian Light Source.

    Science.gov (United States)

    Fodje, Michel; Grochulski, Pawel; Janzen, Kathryn; Labiuk, Shaunivan; Gorin, James; Berg, Russ

    2014-05-01

    Beamline 08B1-1 is a recently commissioned bending-magnet beamline at the Canadian Light Source. The beamline is designed for automation and remote access. Together with the undulator-based beamline 08ID-1, they constitute the Canadian Macromolecular Crystallography Facility. This paper describes the design, specifications, hardware and software of beamline 08B1-1. A few scientific results using data obtained at the beamline will be highlighted.

  18. A facile metal-free "grafting-from" route from acrylamide-based substrate toward complex macromolecular combs

    KAUST Repository

    Zhao, Junpeng

    2013-01-01

    High-molecular-weight poly(N,N-dimethylacrylamide-co-acrylamide) was used as a model functional substrate to investigate phosphazene base (t-BuP 4)-promoted metal-free anionic graft polymerization utilizing primary amide moieties as initiating sites. The (co)polymerization of epoxides was proven to be effective, leading to macromolecular combs with side chains being single- or double-graft homopolymer, block copolymer and statistical copolymer. © 2013 The Royal Society of Chemistry.

  19. Machining of Complex Sculptured Surfaces

    CERN Document Server

    2012-01-01

    The machining of complex sculptured surfaces is a global technological topic in modern manufacturing with relevance in both industrialized and emerging in countries particularly within the moulds and dies sector whose applications include highly technological industries such as the automotive and aircraft industry. Machining of Complex Sculptured Surfaces considers new approaches to the manufacture of moulds and dies within these industries. The traditional technology employed in the manufacture of moulds and dies combined conventional milling and electro-discharge machining (EDM) but this has been replaced with  high-speed milling (HSM) which has been applied in roughing, semi-finishing and finishing of moulds and dies with great success. Machining of Complex Sculptured Surfaces provides recent information on machining of complex sculptured surfaces including modern CAM systems and process planning for three and five axis machining as well as explanations of the advantages of HSM over traditional methods ra...

  20. Learning thermodynamics with Boltzmann machines

    Science.gov (United States)

    Torlai, Giacomo; Melko, Roger G.

    2016-10-01

    A Boltzmann machine is a stochastic neural network that has been extensively used in the layers of deep architectures for modern machine learning applications. In this paper, we develop a Boltzmann machine that is capable of modeling thermodynamic observables for physical systems in thermal equilibrium. Through unsupervised learning, we train the Boltzmann machine on data sets constructed with spin configurations importance sampled from the partition function of an Ising Hamiltonian at different temperatures using Monte Carlo (MC) methods. The trained Boltzmann machine is then used to generate spin states, for which we compare thermodynamic observables to those computed by direct MC sampling. We demonstrate that the Boltzmann machine can faithfully reproduce the observables of the physical system. Further, we observe that the number of neurons required to obtain accurate results increases as the system is brought close to criticality.

  1. Experimental study on aortic remodeling in sinoaortic denervated rats

    Institute of Scientific and Technical Information of China (English)

    MIAO Chao-yu; TAO Xia; GUAN Yun-feng; YANG You-cai; CHU Zheng-xu; SU Ding-feng

    2001-01-01

    Objective: To study the aortic remodeling produced by chronic sinoaortic denervation (SAD) and its time course, and to study the role of humoral factor in the SAD-induced aortic remodeling. Methods: In rats with chronic SAD or sham operation, the aortic structure was measured by computer-assisted image analysis, the aortic function by isolated artery preparation, and angiotensin Ⅱ concentration by radioimmunoassay. Results and Conclusion: The aortic structural remodeling developed progressively at 4, 8, 16 and 32 weeks after SAD. Aortic structural remodeling after SAD expressed mainly as aortic hypertrophy due to SMC growth and collagen accumulation. The aortic contraction elicited by norepinephrine (NE) was progressively increased 8, 16 and 32 weeks after SAD. The aortic relaxation elicited by acetylcholine (ACh) was depressed 8, 16 and 32 weeks after SAD. In addition, in 32-week SAD rats the NE-induced contraction was not increased by endothelial denudation. These indicated that the increased contraction and depressed relaxation after SAD were related to the change of endothelium and/or the change of interaction between endothelium and SMC. In 10-week SAD rats, plasma angiotensin Ⅱ concentration remained unchanged, whereas aortic angiotensin Ⅱ concentration was significantly increased, suggesting that activation of tissue renin-angiotensin system may be involved in SAD-induced aortic remodeling.

  2. Chromatin dynamics: interplay between remodeling enzymes and histone modifications.

    Science.gov (United States)

    Swygert, Sarah G; Peterson, Craig L

    2014-08-01

    Chromatin dynamics play an essential role in regulating the accessibility of genomic DNA for a variety of nuclear processes, including gene transcription and DNA repair. The posttranslational modification of the core histones and the action of ATP-dependent chromatin remodeling enzymes represent two primary mechanisms by which chromatin dynamics are controlled and linked to nuclear events. Although there are examples in which a histone modification or a remodeling enzyme may be sufficient to drive a chromatin transition, these mechanisms typically work in concert to integrate regulatory inputs, leading to a coordinated alteration in chromatin structure and function. Indeed, site-specific histone modifications can facilitate the recruitment of chromatin remodeling enzymes to particular genomic regions, or they can regulate the efficiency or the outcome of a chromatin remodeling reaction. Conversely, chromatin remodeling enzymes can also influence, and sometimes directly modulate, the modification state of histones. These functional interactions are generally complex, frequently transient, and often require the association of myriad additional factors. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Wall tissue remodeling regulates longitudinal tension in arteries.

    Science.gov (United States)

    Jackson, Zane S; Gotlieb, Avrum I; Langille, B Lowell

    2002-05-03

    Changes in blood pressure or flow induce arterial remodeling that normalizes mechanical loads that are imposed on arterial tissue. Arteries are also under substantial longitudinal stretch (axial strain) that may be altered by growth or atrophy of tissues to which they are attached. We therefore tested whether axial strain is also regulated in a negative feedback manner through arterial remodeling. Axial strain in rabbit carotid arteries was increased from 62+/-2% to 97+/-2% without altering other mechanical loads on wall tissues. Strain was reduced within 3 days and completely normalized by 7 days. Remodeling involved tissue elaboration, endothelial cell replication rates were increased by >50-fold and smooth muscle cell replication rates were increased by >15-fold, and substantially elevated DNA, elastin, and collagen contents were recorded. Also, increased rates of apoptosis were indicated by degradation of DNA into oligonucleosomes, and matrix remodeling was reflected in enlarged fenestrae in the internal elastic lamina and increased expression and activation of gelatinases, especially matrix metalloproteinase-2. Intriguingly, reduced axial strain was not normalized, presumably because remodeling processes, apart from cell contraction, are ineffective in decreasing strain, and arterial smooth muscle orientation precludes large effects of contraction on axial strain.

  4. Unremodeled and remodeled cardiolipin are functionally indistinguishable in yeast.

    Science.gov (United States)

    Baile, Matthew G; Sathappa, Murugappan; Lu, Ya-Wen; Pryce, Erin; Whited, Kevin; McCaffery, J Michael; Han, Xianlin; Alder, Nathan N; Claypool, Steven M

    2014-01-17

    After biosynthesis, an evolutionarily conserved acyl chain remodeling process generates a final highly homogeneous and yet tissue-specific molecular form of the mitochondrial lipid cardiolipin. Hence, cardiolipin molecules in different organisms, and even different tissues within the same organism, contain a distinct collection of attached acyl chains. This observation is the basis for the widely accepted paradigm that the acyl chain composition of cardiolipin is matched to the unique mitochondrial demands of a tissue. For this hypothesis to be correct, cardiolipin molecules with different acyl chain compositions should have distinct functional capacities, and cardiolipin that has been remodeled should promote cardiolipin-dependent mitochondrial processes better than its unremodeled form. However, functional disparities between different molecular forms of cardiolipin have never been established. Here, we interrogate this simple but crucial prediction utilizing the best available model to do so, Saccharomyces cerevisiae. Specifically, we compare the ability of unremodeled and remodeled cardiolipin, which differ markedly in their acyl chain composition, to support mitochondrial activities known to require cardiolipin. Surprisingly, defined changes in the acyl chain composition of cardiolipin do not alter either mitochondrial morphology or oxidative phosphorylation. Importantly, preventing cardiolipin remodeling initiation in yeast lacking TAZ1, an ortholog of the causative gene in Barth syndrome, ameliorates mitochondrial dysfunction. Thus, our data do not support the prevailing hypothesis that unremodeled cardiolipin is functionally distinct from remodeled cardiolipin, at least for the functions examined, suggesting alternative physiological roles for this conserved pathway.

  5. Unremodeled and Remodeled Cardiolipin Are Functionally Indistinguishable in Yeast*

    Science.gov (United States)

    Baile, Matthew G.; Sathappa, Murugappan; Lu, Ya-Wen; Pryce, Erin; Whited, Kevin; McCaffery, J. Michael; Han, Xianlin; Alder, Nathan N.; Claypool, Steven M.

    2014-01-01

    After biosynthesis, an evolutionarily conserved acyl chain remodeling process generates a final highly homogeneous and yet tissue-specific molecular form of the mitochondrial lipid cardiolipin. Hence, cardiolipin molecules in different organisms, and even different tissues within the same organism, contain a distinct collection of attached acyl chains. This observation is the basis for the widely accepted paradigm that the acyl chain composition of cardiolipin is matched to the unique mitochondrial demands of a tissue. For this hypothesis to be correct, cardiolipin molecules with different acyl chain compositions should have distinct functional capacities, and cardiolipin that has been remodeled should promote cardiolipin-dependent mitochondrial processes better than its unremodeled form. However, functional disparities between different molecular forms of cardiolipin have never been established. Here, we interrogate this simple but crucial prediction utilizing the best available model to do so, Saccharomyces cerevisiae. Specifically, we compare the ability of unremodeled and remodeled cardiolipin, which differ markedly in their acyl chain composition, to support mitochondrial activities known to require cardiolipin. Surprisingly, defined changes in the acyl chain composition of cardiolipin do not alter either mitochondrial morphology or oxidative phosphorylation. Importantly, preventing cardiolipin remodeling initiation in yeast lacking TAZ1, an ortholog of the causative gene in Barth syndrome, ameliorates mitochondrial dysfunction. Thus, our data do not support the prevailing hypothesis that unremodeled cardiolipin is functionally distinct from remodeled cardiolipin, at least for the functions examined, suggesting alternative physiological roles for this conserved pathway. PMID:24285538

  6. Minor groove binder distamycin remodels chromatin but inhibits transcription.

    Directory of Open Access Journals (Sweden)

    Parijat Majumder

    Full Text Available The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as "chromatin remodeling". In a eukaryotic cell, a fine balance between condensed and de-condensed states of chromatin helps to maintain an optimum level of gene expression. DNA binding small molecules have the potential to perturb such equilibrium. We present herein the study of an oligopeptide antibiotic distamycin, which binds to the minor groove of B-DNA. Chromatin mobility assays and circular dichroism spectroscopy have been employed to study the effect of distamycin on chromatosomes, isolated from the liver of Sprague-Dawley rats. Our results show that distamycin is capable of remodeling both chromatosomes and reconstituted nucleosomes, and the remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes. This hints at a possible corkscrew type motion of the DNA with respect to the histone octamer. Our results indicate that distamycin in spite of remodeling chromatin, inhibits transcription from both DNA and chromatin templates. Therefore, the DNA that is made accessible due to remodeling is either structurally incompetent for transcription, or bound distamycin poses a roadblock for the transcription machinery to advance.

  7. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  8. A decade of user operation on the macromolecular crystallography MAD beamline ID14-4 at the ESRF.

    Science.gov (United States)

    McCarthy, Andrew A; Brockhauser, Sandor; Nurizzo, Didier; Theveneau, Pascal; Mairs, Trevor; Spruce, Darren; Guijarro, Matias; Lesourd, Marc; Ravelli, Raimond B G; McSweeney, Sean

    2009-11-01

    ID14-4 at the ESRF is the first tunable undulator-based macromolecular crystallography beamline that can celebrate a decade of user service. During this time ID14-4 has not only been instrumental in the determination of the structures of biologically important molecules but has also contributed significantly to the development of various instruments, novel data collection schemes and pioneering radiation damage studies on biological samples. Here, the evolution of ID14-4 over the last decade is presented, and some of the major improvements that were carried out in order to maintain its status as one of the most productive macromolecular crystallography beamlines are highlighted. The experimental hutch has been upgraded to accommodate a high-precision diffractometer, a sample changer and a large CCD detector. More recently, the optical hutch has been refurbished in order to improve the X-ray beam quality on ID14-4 and to incorporate the most modern and robust optical elements used at other ESRF beamlines. These new optical elements will be described and their effect on beam stability discussed. These studies may be useful in the design, construction and maintenance of future X-ray beamlines for macromolecular crystallography and indeed other applications, such as those planned for the ESRF upgrade.

  9. A decade of user operation on the macromolecular crystallography MAD beamline ID14-4 at the ESRF

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, Andrew A., E-mail: andrewmc@embl.fr; Brockhauser, Sandor [European Molecular Biology Laboratory, 6 rue Jules Horowitz, BP 181, 38042 Grenoble (France); Unit of Virus Host Cell Interactions, UJF-EMBL-CNRS, UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9 (France); Nurizzo, Didier; Theveneau, Pascal; Mairs, Trevor; Spruce, Darren; Guijarro, Matias; Lesourd, Marc [European Synchrotron Radiation Facility, 6 rue Jules Horowitz, BP 220, 38042 Grenoble (France); Ravelli, Raimond B. G. [European Molecular Biology Laboratory, 6 rue Jules Horowitz, BP 181, 38042 Grenoble (France); McSweeney, Sean [European Synchrotron Radiation Facility, 6 rue Jules Horowitz, BP 220, 38042 Grenoble (France)

    2009-11-01

    The improvement of the X-ray beam quality achieved on ID14-4 by the installation of new X-ray optical elements is described. ID14-4 at the ESRF is the first tunable undulator-based macromolecular crystallography beamline that can celebrate a decade of user service. During this time ID14-4 has not only been instrumental in the determination of the structures of biologically important molecules but has also contributed significantly to the development of various instruments, novel data collection schemes and pioneering radiation damage studies on biological samples. Here, the evolution of ID14-4 over the last decade is presented, and some of the major improvements that were carried out in order to maintain its status as one of the most productive macromolecular crystallography beamlines are highlighted. The experimental hutch has been upgraded to accommodate a high-precision diffractometer, a sample changer and a large CCD detector. More recently, the optical hutch has been refurbished in order to improve the X-ray beam quality on ID14-4 and to incorporate the most modern and robust optical elements used at other ESRF beamlines. These new optical elements will be described and their effect on beam stability discussed. These studies may be useful in the design, construction and maintenance of future X-ray beamlines for macromolecular crystallography and indeed other applications, such as those planned for the ESRF upgrade.

  10. Machine learning with R cookbook

    CERN Document Server

    Chiu, Yu-Wei

    2015-01-01

    If you want to learn how to use R for machine learning and gain insights from your data, then this book is ideal for you. Regardless of your level of experience, this book covers the basics of applying R to machine learning through to advanced techniques. While it is helpful if you are familiar with basic programming or machine learning concepts, you do not require prior experience to benefit from this book.

  11. Machine learning in healthcare informatics

    CERN Document Server

    Acharya, U; Dua, Prerna

    2014-01-01

    The book is a unique effort to represent a variety of techniques designed to represent, enhance, and empower multi-disciplinary and multi-institutional machine learning research in healthcare informatics. The book provides a unique compendium of current and emerging machine learning paradigms for healthcare informatics and reflects the diversity, complexity and the depth and breath of this multi-disciplinary area. The integrated, panoramic view of data and machine learning techniques can provide an opportunity for novel clinical insights and discoveries.

  12. Autocoding State Machine in Erlang

    DEFF Research Database (Denmark)

    Guo, Yu; Hoffman, Torben; Gunder, Nicholas

    2008-01-01

    This paper presents an autocoding tool suit, which supports development of state machine in a model-driven fashion, where models are central to all phases of the development process. The tool suit, which is built on the Eclipse platform, provides facilities for the graphical specification...... of a state machine model. Once the state machine is specified, it is used as input to a code generation engine that generates source code in Erlang....

  13. Temperature sensitivity of soil microbial communities: An application of macromolecular rate theory to microbial respiration

    Science.gov (United States)

    Alster, Charlotte J.; Koyama, Akihiro; Johnson, Nels G.; Wallenstein, Matthew D.; Fischer, Joseph C.

    2016-06-01

    There is compelling evidence that microbial communities vary widely in their temperature sensitivity and may adapt to warming through time. To date, this sensitivity has been largely characterized using a range of models relying on versions of the Arrhenius equation, which predicts an exponential increase in reaction rate with temperature. However, there is growing evidence from laboratory and field studies that observe nonmonotonic responses of reaction rates to variation in temperature, indicating that Arrhenius is not an appropriate model for quantitatively characterizing temperature sensitivity. Recently, Hobbs et al. (2013) developed macromolecular rate theory (MMRT), which incorporates thermodynamic temperature optima as arising from heat capacity differences between isoenzymes. We applied MMRT to measurements of respiration from soils incubated at different temperatures. These soils were collected from three grassland sites across the U.S. Great Plains and reciprocally transplanted, allowing us to isolate the effects of microbial community type from edaphic factors. We found that microbial community type explained roughly 30% of the variation in the CO2 production rate from the labile C pool but that temperature and soil type were most important in explaining variation in labile and recalcitrant C pool size. For six out of the nine soil × inoculum combinations, MMRT was superior to Arrhenius. The MMRT analysis revealed that microbial communities have distinct heat capacity values and temperature sensitivities sometimes independent of soil type. These results challenge the current paradigm for modeling temperature sensitivity of soil C pools and understanding of microbial enzyme dynamics.

  14. Interaction of wall shear stress magnitude and gradient in the prediction of arterial macromolecular permeability.

    Science.gov (United States)

    LaMack, Jeffrey A; Himburg, Heather A; Li, Xue-Mei; Friedman, Morton H

    2005-04-01

    Large spatial shear stress gradients have anecdotally been associated with early atherosclerotic lesion susceptibility in vivo and have been proposed as promoters of endothelial cell dysfunction in vitro. Here, experiments are presented in which several measures of the fluid dynamic shear stress, including its gradient, at the walls of in vivo porcine iliac arteries, are correlated against the transendothelial macromolecular permeability of the vessels. The fluid dynamic measurements are based on postmortem vascular casts, and permeability is measured from Evans blue dye (EBD) uptake. Time-averaged wall shear stress (WSS), as well as a new parameter termed maximum gradient stress (MGS) that describes the spatial shear stress gradient due to flow acceleration at a given point, are mapped for each artery and compared on a point-by-point basis to the corresponding EBD patterns. While there was no apparent relation between MGS and EBD uptake, a composite parameter, WSS(-0.11) MGS(0.044), was highly correlated with permeability. Notwithstanding the small exponents, the parameter varied widely within the region of interest. The results suggest that sites exposed to low wall shear stresses are more likely to exhibit elevated permeability, and that this increase is exacerbated in the presence of large spatial shear stress gradients.

  15. Macromolecular crowding and the steady-state kinetics of malate dehydrogenase.

    Science.gov (United States)

    Poggi, Christopher G; Slade, Kristin M

    2015-01-20

    To understand how macromolecular crowding affects enzyme activity, we quantified the Michaelis-Menten kinetics of mitochondrial malate dehydrogenase (MDH) in the presence of hen egg white (HEW), lysozyme, bovine serum albumin (BSA), gum arabic, poly(vinylpyrrolidone) (PVP), and dextrans of various molecular weights. Although crowding tended to decrease Km and Vmax values, the magnitude depended on the crowding agent, reaction direction, and isozyme (mitochondrial porcine heart or thermophlic TaqMDH from Thermus flavus). Crowding slowed oxaloacetate reduction more significantly than malate oxidation, which may suggest that mitochondrial enzymes have evolved to function optimally under the crowded constraints in which they are immersed. Since direct comparisons of neutral to charged crowders are underrepresented in the literature, we performed these studies and found that neutral crowding agents lowered Vmax values more than charged crowders of similar size. The exception was hen egg white, a mixture of charged proteins that caused the largest observed decreases in both Km and Vmax. Finally, the data provide insight about the mechanism by corroborating MDH subunit dependence.

  16. Effect of the macromolecular architecture of biodegradable polyurethanes on the controlled delivery of ocular drugs.

    Science.gov (United States)

    da Silva, Gisele Rodrigues; da Silva Cunha, Armando; Ayres, Eliane; Oréfice, Rodrigo L

    2009-02-01

    Controlled delivery of drugs is a major issue in the treatment of ocular diseases, such as in the treatment of uveitis. In this study, dexamethasone acetate, an important type of corticoid used in the treatment of some uveitis, was incorporated into biodegradable polyurethanes (PU) having different macromolecular architectures. The biodegradable polyurethanes were obtained by preparing PU aqueous dispersions having poly(caprolactone) and/or poly(ethylene glycol) as soft segments. The drug was incorporated into the polymer by dissolving it in the PU aqueous dispersion. FTIR results showed the presence of the drug in the polymer with its original chemical structure. Small angle X-ray scattering (SAXS) results were explored to show that the incorporation of dexamethasone acetate led to the modification of the nanostructure of the polyurethane having only poly(caprolactone) as the soft segment, while the drug did not change significantly the microphase separated structure of PU having both poly(caprolactone) and poly(ethylene glycol) as soft segments. The evaluation of the release of the drug in vitro demonstrated that the obtained biodegradable polyurethanes were well succeeded in delivering dexamethasone acetate at an almost constant rate for 53 weeks. The presence of poly(ethylene glycol) together with poly(caprolactone) as soft segment in biodegradable PU was able to increase the rate of dexamethasone acetate release when compared to the rate of drug release from PU having only poly(caprolactone).

  17. Influence of temperature and macromolecular mobility on sorption of TCE on humic acid coated mineral surfaces.

    Science.gov (United States)

    Bell, Katherine Young; LeBoeuf, Eugene J

    2013-01-01

    This study demonstrates differences in sorptive capacity of volatile organic compound (VOC) trichloroethylene (TCE) onto natural organic matter (NOM) coated and uncoated mineral surfaces above and below the NOM glass transition temperature. TCE sorption isotherms for dry NOM-mineral systems below the NOM glass transition temperature (T(g)) demonstrated sorption behavior characteristic of micropore filling, with sorption capacities reduced relative to uncoated mineral matrices. Such differences were not entirely associated with differences in surface areas of the coated and uncoated mineral matrices, but were likely associated with either a blockage of pore space available to the VOC or a kinetic limitation that does not allow the VOC access to the internal porosity of the model soil within the time periods of the experiment. TCE sorption in dry NOM-mineral matrices above the T(g), however, was described in terms of sorption within a more fluid, macromolecular dissolution medium that does not hinder access to mineral surfaces. Such observations have potential important implications for modeling the fate and transport of VOCs in soils and sediment systems.

  18. IMAGINE: first neutron protein structure and new capabilities for neutron macromolecular crystallography

    Energy Technology Data Exchange (ETDEWEB)

    Munshi, Parthapratim [ORNL; Myles, Dean A A [ORNL; Robertson, Lee [ORNL; Stoica, Alexandru Dan [ORNL; Crow, Lowell [ORNL; Kovalevskyi, Andrii Y [ORNL; Koritsanszky, Tibor S [ORNL; Chakoumakos, Bryan C [ORNL; Blessing, Robert [Hauptman-Woodward Medical Research Institute; Meilleur, Flora [ORNL

    2013-01-01

    We report the first high resolution neutron protein structure of perdeuterated rubredoxin from Pyrococcus furiosus (PfRd) determined using the new IMAGINE macromolecular neutron crystallography instrument at the Oak Ridge National Laboratory. Neutron diffraction data extending to 1.65 resolution were collected from a relatively small 0.7 mm3 PfRd crystal using 2.5 days (60 h) of beam time. The refined structure contains 371 out of 391, or 95%, of the deuterium atoms of the protein, and 58 solvent molecules. The IMAGINE instrument is designed to provide neutron data at or near atomic resolutions (1.5 ) from crystals with volume < 1.0 mm3 and with unit cell edges < 100 . Beam line features include elliptical focusing mirrors that deliver 3x107 n s-1 cm-2 into a 3.5 x 2.0 mm2 focal spot at the sample position, and variable short and long wavelength cutoff optics that provide automated exchange between multiple wavelength configurations ( min=2.0 , 2.8 , 3.3 - max =3.0 , 4.0 , 4.5 , ~20 ). Notably, the crystal used to collect this PfRd data is 5-10 times smaller than has been previously reported.

  19. Enzyme activity determination on macromolecular substrates by isothermal titration calorimetry: application to mesophilic and psychrophilic chitinases.

    Science.gov (United States)

    Lonhienne, T; Baise, E; Feller, G; Bouriotis, V; Gerday, C

    2001-02-09

    Isothermal titration calorimetry has been applied to the determination of the kinetic parameters of chitinases (EC 3.2.1.14) by monitoring the heat released during the hydrolysis of chitin glycosidic bonds. Experiments were carried out using two different macromolecular substrates: a soluble polymer of N-acetylglucosamine and the insoluble chitin from crab shells. Different experimental temperatures were used in order to compare the thermodependence of the activity of two chitinases from the psychrophile Arthrobacter sp. TAD20 and of chitinase A from the mesophile Serratia marcescens. The method allowed to determine unequivocally the catalytic rate constant k(cat), the activation energy (E(a)) and the thermodynamic activation parameters (DeltaG(#), DeltaH(#), DeltaS(#)) of the chitinolytic reaction on the soluble substrate. The catalytic activity has also been determined on insoluble chitin, which displays an effect of substrate saturation by chitinases. On both substrates, the thermodependence of the activity of the psychrophilic chitinases was lower than that observed with the mesophilic counterpart.

  20. Chemical composition and structural features of the macromolecular components of plantation Acacia mangium wood.

    Science.gov (United States)

    Pinto, Paula C; Evtuguin, Dmitry V; Pascoal Neto, Carlos

    2005-10-05

    The wood of Acacia mangium, a prominent fast-growing plantation species used in the pulp-and-paper industry and, so far, poorly investigated for its chemical structure, was submitted to a detailed characterization of its main macromolecular components. Lignin (28% wood weight) isolated by mild acidolysis and characterized by permanganate oxidation, 1H and 13C NMR, and GPC, showed a very low content of syringylpropane-derived units (S:G:H of 48:49:3), a high degree of condensation, a low content of beta-O-4 ( approximately 0.40-0.43 per C6) structures, and a Mw of 2230. Glucuronoxylan (14% wood weight) isolated by alkaline (KOH) or by dimethyl sulfoxide extraction was characterized by methylation analysis, 1H NMR, and GPC. About 10% of the xylopyranose (Xylp) units constituting the linear backbone were substituted at O-2 with 4-O-methylglucuronic acid residues. Almost half of the Xylp units (45%) were O-2 (18%), O-3 (24%) or O-2,3 (3%) acetylated. X-ray diffraction analysis of cellulose (46% wood weight), isolated according to the Kürschner-Hoffer method, showed a degree of crystallinity of 67.6%.